Sense of purpose and social-emotional-behavioral skills during university
(2025) Personality and Individual Differences, 233, art. no. 112870, .
Beatty, J.F.a , Hill, P.L.a , Spengler, M.b
Abstract
Past research has demonstrated that university students with a stronger sense of purpose tend to fare better than their peers. However, work is needed to investigate the mechanisms and skills that may underlie these associations. The current studies employed two university student samples (total n = 412) and comprehensively investigated associations between sense of purpose and social-emotional-behavioral skills, using multiple purpose measures. Associations were relatively similar across measures and samples, and results suggested that sense of purpose was most robustly positively associated with self-management skills. Sense of purpose also was associated with better student wellbeing (life satisfaction, college satisfaction, and student connectedness), though it was inconsistently associated with reported likelihood of degree completion. Sense of purpose largely remained a significant correlate of student wellbeing, even when accounting for SEB skill domains, although some associations between purpose and wellbeing were reduced in magnitude. © 2024 The Authors
Author Keywords
Academic performance; Sense of purpose; Social-emotional-behavioral skills; University
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Psychology Department, Medical School Berlin, Berlin, Germany
Document Type: Article
Publication Stage: Final
Source: Scopus
Derived psychoactive cannabis product perceptions and use among a sample of US young adults
(2025) Addictive Behaviors, 160, art. no. 108180, .
LoParco, C.R.a , Rossheim, M.E.b , Cui, Y.a , McCready, D.M.a , Romm, K.F.c , Wang, Y.a e , Yang, Y.T.d e , Cavazos-Rehg, P.A.f , Berg, C.J.a g
a Department of Prevention and Community Health, Milken Institute School of Public Health, George Washington University, Washington, DC, United States
b Department of Health Administration and Health Policy, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, United States
c TSET Health Promotion Research Center, Stephenson Cancer Center
d Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
e Center for Health Policy and Media Engagement, School of Nursing, George Washington University, Washington, DC, United States
f Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
g George Washington Cancer Center, George Washington University, Washington, DC, United States
Abstract
Aims: To characterize derived psychoactive cannabis product (DPCP) perceptions and use among US young adults. Methods: We analyzed 2023 survey data among 4,031 young adults (ages 18–34), comprising ∼ 50 % reporting past-month cannabis use. Multivariable regressions examined sociodemographics, cannabis use, and DPCP risk perceptions in relation to: 1) past-month DPCP use (yes/no), 2) past-month number of DPCP use days, and 3) among those reporting no past-month DPCP use, future likelihood of DPCP use. Results: In this sample (Mage = 26.3, 59.8 % female, 64.9 % White, 19.4 % Hispanic), DPCP awareness (67.5 %), lifetime use (41.7 %), and past-month use (24.4 %) differed by past-month cannabis use versus nonuse (87.0 % vs 48.8 %, 68.7 % vs 15.9 %, 45.6 % vs 4.2 %, respectively). Those aware learned about them mainly from friends/family (44.5 %) and believed DPCPs were required to be tested and approved to be safe (70.3 %) or were approved by the US Food and Drug Administration (59.0 %). Those who ever used DPCPs most often used delta-8 (69.7 %) and delta-9 (44.4 %) THC and for curiosity (55.5 %), belief of federal legality (34.1 %), and friends’ suggestion (34.0 %). Correlates of past-month DPCP use, using more frequently, and higher likelihood of future use were: lower DPCP perceived harm and higher perceived addictiveness. Living where non-medical cannabis was illegal, higher perceived social acceptability, being Black (vs. White), and past-month cannabis use were also correlated with past-month use (but not frequency) and future likelihood of use. Conclusions: Efforts are needed to better understand DPCPs’ risks and correct consumer misperceptions. Relatedly, DPCP regulation, including marketing and distribution, is crucial. © 2024 Elsevier Ltd
Author Keywords
Delta-8 thc; Derived psychoactive cannabis products; Hemp-derived cannabinoids; Perceived risk; Policy
Document Type: Article
Publication Stage: Final
Source: Scopus
An exploratory graphical analysis of the Montgomery-Åsberg Depression Rating Scale pre- and post-treatment using pooled antidepressant trial secondary data
(2025) Journal of Affective Disorders, 368, pp. 584-590.
Byrne, D.a , Ghoshal, A.b , Boland, F.a , Brannick, S.c , Carney, R.M.d , Cuijpers, P.e , Dima, A.L.f , Freedland, K.E.d , Guerin, S.g , Hevey, D.h , Kathuria, B.i , McDarby, V.j , Wallace, E.k l , Doyle, F.a
a RCSI University of Medicine and Health Sciences, School of Population Health, Dublin, Ireland
b Princess Margaret Cancer Centre, University Health NetworkON, Canada
c Aware, Dublin, Ireland
d Department of Psychiatry, Washington University School of Medicine, St Louis, United States
e Department of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
f Health Psychology and Health Services, Sant Joan de Déu Research Institute, Barcelona, Spain
g School of Psychology, University College Dublin, Dublin, Ireland
h School of Psychology, Trinity College Dublin, Dublin, Ireland
i Medical Affairs, Novartis Ireland Ltd., Dublin, Ireland
j Psychological Society of Ireland (PSI), Dublin, Ireland
k Department of General Practice, University College Cork, Cork, Ireland
l RCSI University of Medicine and Health Sciences, Department of General Practice, Dublin, Ireland
Abstract
Background: The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) is a commonly used measure of depression in antidepressant clinical trials. Numerous studies have adopted classical test theory perspectives to assess the psychometric properties of this scale, finding generally positive results. However, its network configural structure and stability is unexplored across different time-points and treatment groups. Aims: To assess the network structure and stability of the MADRS in clinical settings pre- and post-treatment, and to determine a configurally invariant and stable model across time-points and treatment groups (placebo and intervention). Method: Individual participant data for 6440 participants from 14 clinical trials of major depressive disorder was obtained from the data repository Vivli.org. Exploratory Graphical Analysis (EGA) was used to identify empirical models pre-treatment (baseline) and post-treatment (8-week outcome). Bootstrapping techniques were applied to obtain optimised configurally invariant models. Results: Empirical models presented with performance issues at baseline and for the placebo group at outcome. An abbreviated 8-item single-community model was found to be stable and configurally invariant across time-points and treatment groups. Symptoms such as low mood and lassitude showed most centrality across all models. Limitations: Metric invariance could not be explored due to research environment limitations. Conclusions: An 8-item one-community variant of the MADRS may provide optimal performance when conducting network analyses of antidepressant clinical trial outcomes. Findings suggest that interventions targeting low mood and lassitude might be most efficacious in treating depression among clinical trial participants. Further considerations of the potential impact on trial design and analysis should be explored. © 2024 The Authors
Author Keywords
Depression; MADRS; Network analysis; Psychometrics; RCT
Document Type: Article
Publication Stage: Final
Source: Scopus
Associations between Parenting and Cognitive and Language Abilities at 2 Years of Age Depend on Prenatal Exposure to Disadvantage
(2025) Journal of Pediatrics, 276, art. no. 114289, .
Leverett, S.D.a b , Brady, R.G.a , Tooley, U.A.b , Lean, R.E.b , Tillman, R.b , Wilson, J.b , Ruscitti, M.b , Triplett, R.L.c , Alexopoulos, D.c , Gerstein, E.D.d , Smyser, T.A.b , Warner, B.e , Luby, J.L.b , Smyser, C.D.c , Rogers, C.E.b , Barch, D.M.b f g
a Division of Biology & Biomedical Sciences, Neurosciences Program, Washington University in Saint Louis, St Louis, MO
b Department of Psychiatry, Washington University in Saint Louis, St Louis, MO
c Department of Neurology, Washington University in Saint Louis, St Louis, MO
d Department of Psychological Sciences, University of Missouri-St. Louis, St Louis, MO
e Department of Pediatrics, Washington University in Saint Louis, St Louis, MO
f Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO
g Department of Radiology, Washington University in St. Louis, St Louis, MO
Abstract
Objective: To investigate whether parenting or neonatal brain volumes mediate associations between prenatal social disadvantage (PSD) and cognitive/language abilities and whether these mechanisms vary by level of disadvantage. Study design: Pregnant women were recruited prospectively from obstetric clinics in St Louis, Missouri. PSD encompassed access to social (eg, education) and material (eg, income to needs, health insurance, area deprivation, and nutrition) resources during pregnancy. Neonates underwent brain magnetic resonance imaging. Mother-child dyads (n = 202) returned at age 1 year for parenting observations and at age 2 years for cognition/language assessments (Bayley Scales of Infant and Toddler Development, Third Edition). Generalized additive and mediation models tested hypotheses. Results: Greater PSD associated nonlinearly with poorer cognitive/language scores. Associations between parenting and cognition/language were moderated by disadvantage, such that supportive and nonsupportive parenting behaviors related only to cognition/language in children with lesser PSD. Parenting mediation effects differed by level of disadvantage: both supportive and nonsupportive parenting mediated PSD-cognition/language associations in children with lesser disadvantage, but not in children with greater disadvantage. PSD-associated reductions in neonatal subcortical grey matter (β = 0.19; q = 0.03), white matter (β = 0.23; q = 0.02), and total brain volume (β = 0.18; q = 0.03) were associated with lower cognition, but did not mediate the associations between PSD and cognition. Conclusions: Parenting moderates and mediates associations between PSD and early cognition and language, but only in families with less social disadvantage. These findings, although correlational, suggest that there may be a critical threshold of disadvantage, below which mediating or moderating factors become less effective, highlighting the importance of reducing disadvantage as primary prevention. © 2024 The Author(s)
Author Keywords
brain structure; development; parenting; socioeconomic status
Document Type: Article
Publication Stage: Final
Source: Scopus
Life After Neonatal Seizures: Characterizing the Longitudinal Parent Experience
(2024) Pediatric Neurology, 161, pp. 76-83.
Field, N.K.a , Franck, L.S.b , Shellhaas, R.A.c , Glass, H.C.d e , Young, K.A.a , Dhar, S.f , Hamlett, A.g , Pilon, B.h , Means, K.i , Soul, J.S.j , Massey, S.L.k , Wusthoff, C.J.l , Chu, C.J.m , Thomas, C.n , Rogers, E.d , Berl, M.M.o , Benedetti, G.M.p , Anwar, T.q , Lemmon, M.E.r , Neonatal Seizure Registrys
a Duke University School of Medicine, Durham, North Carolina, United States
b Department of Family Health Care Nursing, University of California, San Francisco, San Francisco, California, United States
c Division of Pediatric Neurology, Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, United States
d Department of Pediatrics, UCSF Benioff Children’s Hospital, University of California, San Francisco, San Francisco, California, United States
e Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, California, United States
f Trinity College, Duke University, Durham, North Carolina, United States
g NSR Parent Partner, Duke University Medical Center, Durham, North Carolina, United States
h NSR Parent Partner, Executive Director – Hope for HIE, West BloomfieldMichigan, United States
i NSR Parent Partner, Cincinnati Children’s Hospital Medical Center, Fort Thomas, KY, United States
j Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts, United States
k Departments of Neurology and Pediatrics, Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States
l Departments of Neurology and Pediatrics, Stanford University, Palo Alto, California, United States
m Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, United States
n Department of Pediatrics, University of Cincinnati and Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States
o Departments of Psychiatry and Behavioral Sciences, Children’s Research Institute, Children’s National Hospital, George Washington University, Washington, District of Columbia, United States
p Division of Pediatric Neurology, Department of Pediatrics, C.S. Mott Children’s Hospital and the University of Michigan, Ann Arbor, MI, United States
q Departments of Neurology and Pediatrics, Children’s National Hospital and The George Washington University School of Medicine, Washington, District of Columbia, United States
r Departments of Pediatrics and Population Health Sciences, Duke University School of Medicine, Durham, NC, USA, Duke-Margolis Center for Health Policy, Washington, District of Columbia, United States
Abstract
Background: Parents of neonates with seizures report persistent symptoms of depression, anxiety, and posttraumatic stress. We aimed to characterize the parent experience of caring for children impacted by neonatal seizures, including longitudinal assessment across childhood. Methods: This prospective, observational, multicenter study was conducted at Neonatal Seizure Registry (NSR) sites in partnership with the NSR Parent Advisory Panel. Parents completed surveys at discharge; 12, 18, and 24 months; and 3, 4, 5, 7, and 8 years. Surveys included demographic information and open-ended questions targeting parent experience. A conventional content analysis approach was used. Results: A total of 320 caregivers completed at least one open-ended question, with the majority of respondents at discharge (n = 142), 12 months (n = 169), 18 months (n = 208), and 24 months (n = 245). We identified the following three primary themes. (1) Personal Burden of Care: Parents experienced emotional distress, financial strain, physical demands, and fears for their child’s unknown outcome; (2) Managing Day-to-Day Life: Parents described difficulties navigating their parenting role, including managing their child’s challenging behaviors and understanding their child’s needs amid neurodevelopmental impairment; (3) My Joys as a Parent: Parents valued bonding with their child, being a caregiver, and watching their child’s personality grow. Conclusions: Parents of children impacted by neonatal seizures face persistent challenges, which are interwoven with the joys of being a parent. Our findings suggest that future interventions should promote resiliency, address caregivers’ psychosocial needs longitudinally, and provide enhanced support for parents caring for children with medical complexity. © 2024 Elsevier Inc.
Author Keywords
Burden of care; Children with medical complexity; Epilepsy; Neurology; Pediatrics; Qualitative research
Document Type: Article
Publication Stage: Final
Source: Scopus
CYP1B1-RMDN2 Alzheimer’s disease endophenotype locus identified for cerebral tau PET
(2024) Nature Communications, 15 (1), art. no. 8251, .
Nho, K.a b c d , Risacher, S.L.a c , Apostolova, L.G.a c e f , Bice, P.J.a c , Brosch, J.R.c e , Deardorff, R.c e , Faber, K.f g , Farlow, M.R.c e , Foroud, T.c f g , Gao, S.c h , Rosewood, T.a b c , Kim, J.P.a b c , Nudelman, K.c f g , Yu, M.a c , Aisen, P.i , Sperling, R.j , Hooli, B.k , Shcherbinin, S.k , Svaldi, D.k , Jack, C.R., Jr.l , Jagust, W.J.m , Landau, S.m , Vasanthakumar, A.n , Waring, J.F.n , Doré, V.o p , Laws, S.M.q , Masters, C.L.r , Porter, T.q , Rowe, C.C.p r , Villemagne, V.L.p s , Dumitrescu, L.t u , Hohman, T.J.t u , Libby, J.B.t , Mormino, E.v , Buckley, R.F.j , Johnson, K.j w , Yang, H.-S.j x , Petersen, R.C.y , Ramanan, V.K.y , Ertekin-Taner, N.z aa , Vemuri, P.l , Cohen, A.D.s , Fan, K.-H.ab , Kamboh, M.I.ab , Lopez, O.L.s ac , Bennett, D.A.ad , Ali, M.ae , Benzinger, T.af , Cruchaga, C.ae ag , Hobbs, D.af , De Jager, P.L.ah , Fujita, M.ah , Jadhav, V.f ai , Lamb, B.T.c f ai , Tsai, A.P.v ai aj , Castanho, I.ak al , Mill, J.ak , Weiner, M.W.am an , Saykin, A.J.a b c e f , for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)ao , the Department of Defense Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI)ao , the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Study (A4 Study) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN)ao , the Australian Imaging, Biomarker & Lifestyle Study (AIBL)ao
a Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, United States
b Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, United States
c Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, United States
d Department of BioHealth Informatics, Indiana University, Indianapolis, United States
e Department of Neurology, Indiana University School of Medicine, Indianapolis, United States
f Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United States
g National Centralized Repository for Alzheimer’s Disease and Related Dementias, Indiana University School of Medicine, Indianapolis, United States
h Department of Biostatistics, Indiana University School of Medicine, Indianapolis, United States
i Department of Neurology, Keck School of Medicine, University of Southern California, San Diego, United States
j Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, United States
k Eli Lilly and Company, Indianapolis, United States
l Department of Radiology, Mayo Clinic, Rochester, United States
m UC Berkeley Helen Wills Neuroscience Institute, University of California – Berkeley, Berkeley, United States
n Genomics Research Center, AbbVie, North Chicago, United States
o CSIRO Health and Biosecurity, Melbourne, Australia
p Department of Molecular Imaging & amp; Therapy, Austin Health, Heidelberg, Australia
q Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
r Florey Institute of Neuroscience and Mental Health and The University of Melbourne, Parkville, Australia
s Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, United States
t Vanderbilt Memory & amp; Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, United States
u Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, United States
v Department of Neurology & amp; Neurological Sciences, Stanford University, Stanford, United States
w Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, United States
x Center for Alzheimer’s Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
y Department of Neurology, Mayo Clinic, Rochester, United States
z Department of Neurology, Mayo Clinic, Jacksonville, United States
aa Department of Neuroscience, Mayo Clinic, Jacksonville, United States
ab Department of Human Genetics, University of Pittsburgh, Pittsburgh, United States
ac Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, United States
ad Department of Neurological Sciences, Rush Medical College, Rush University, Chicago, United States
ae Department of Psychiatry, Washington University, St. Louis, United States
af Department of Radiology, Washington University School of Medicine, St. Louis, United States
ag NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, United States
ah Center for Translational and Computational Neuroimmunology, Department of Neurology and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical CenterNY, United States
ai Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, United States
aj Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, United States
ak Department for Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom
al Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States
am Departments of Radiology, Medicine, and Psychiatry, University of California-San Francisco, San Francisco, United States
an Department of Veterans Affairs Medical Center, San Francisco, United States
Abstract
Determining the genetic architecture of Alzheimer’s disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. rs2113389 is associated with higher CYP1B1 expression and methylation levels. Mouse model studies provide additional functional evidence for a relationship between CYP1B1 and tau deposition but not amyloid beta. These results provide insight into the genetic basis of cerebral tau deposition and support novel pathways for therapeutic development in AD. © The Author(s) 2024.
Document Type: Article
Publication Stage: Final
Source: Scopus
Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models
(2024) Nature Communications, 15 (1), art. no. 8118, .
Havel, V.a , Kruegel, A.C.a , Bechand, B.a , McIntosh, S.b , Stallings, L.b , Hodges, A.b , Wulf, M.G.a , Nelson, M.c d e , Hunkele, A.f g , Ansonoff, M.h , Pintar, J.E.h i , Hwu, C.a , Ople, R.S.g j , Abi-Gerges, N.k , Zaidi, S.A.l m , Katritch, V.l m , Yang, M.n , Javitch, J.A.c d e , Majumdar, S.f g j , Hemby, S.E.b , Sames, D.a o
a Department of Chemistry, Columbia University, New York, NY 10027, United States
b Department of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, United States
c Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY 10032, United States
d Department of Psychiatry, Columbia University, New York, NY 10032, United States
e Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, United States
f Department of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
g Center for Clinical Pharmacology, University of Health Sciences & Pharmacy at St Louis and Washington University School of Medicine, St Louis, MO 63110, United States
h Department of Neuroscience and Cell Biology, Rutgers University, Piscataway, NJ 08854, United States
i Rutgers Addiction Research Center, Brain Health Institute, Rutgers University, Piscataway, NJ 08854, United States
j Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, United States
k AnaBios Corporation, 1155 Island Ave, Suite 200, San Diego, CA 92101, United States
l Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, United States
m Department of Chemistry, Bridge Institute, Michelson Center for Convergent Sciences, University of Southern California, Los Angeles, CA 90089, United States
n Mouse Neurobehavioral Core facility, Columbia University Irving Medical Center, New York, NY 10032, United States
o The Zuckerman Mind Brain Behavior Institute at Columbia University, New York, NY, United States
Abstract
Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids – termed oxa-iboga – defined as benzofuran-containing iboga analogs and created via structural editing of the iboga skeleton. The oxa-iboga compounds lack the proarrhythmic adverse effects of ibogaine and noribogaine in primary human cardiomyocytes and show superior efficacy in animal models of opioid use disorder in male rats. They act as potent kappa opioid receptor agonists in vitro and in vivo, but exhibit atypical behavioral features compared to standard kappa opioid agonists. Oxa-noribogaine induces long-lasting suppression of morphine, heroin, and fentanyl intake after a single dose or a short treatment regimen, reversal of persistent opioid-induced hyperalgesia, and suppression of opioid drug seeking in rodent relapse models. As such, oxa-iboga compounds represent mechanistically distinct iboga analogs with therapeutic potential. © The Author(s) 2024.
Document Type: Article
Publication Stage: Final
Source: Scopus
Adynamic spoken language in corpus callosum dysgenesis
(2024) Cortex, 180, pp. 42-54.
Barker, M.S.a b , Knight, J.L.a , Dean, R.J.c , Richards, L.J.b c , Robinson, G.A.a b
a Neuropsychology Research Unit, School of Psychology, The University of Queensland, St Lucia, Brisbane, QLD, Australia
b Queensland Brain Institute, The University of Queensland, St Lucia, Brisbane, Australia
c Department of Neuroscience, Washington University in St Louis School of Medicine, St LouisMO, United States
Abstract
Corpus callosum dysgenesis (CCD) is a congenital brain malformation that occurs when the development of the corpus callosum is disrupted, either partially or completely. The cognitive outcomes in individuals with CCD vary greatly, but generally the neuropsychological profile is characterised by slow processing speed, poor transfer of interhemispheric sensory-motor information, and impaired complex problem solving. Core language skills are often preserved in CCD, but there is some evidence that complex language may be impaired. Thus, the current study sought to examine whether spontaneous speech output was reduced in a cohort of individuals with CCD compared to age-matched controls. We further explored a series of factors that may be contributing to poor spontaneous speech in CCD, such as difficulties generating, selecting, and sequencing ideas for expression, as well as apathy and slowed processing speed. A cohort of 25 individuals with CCD and 39 neurotypical controls were enrolled in this study. Participants completed a picture description task to measure spontaneous speech output, alongside a series of cognitive and language baseline tests. Verbal and nonverbal fluency tasks gauged idea generation and sequencing, and sentence-level selection tasks measured idea selection. We found that, despite having largely intact core language skills, individuals with CCD produced significantly less spontaneous speech on the picture description task than controls. This language profile may be described as “adynamic”. Further, we found that poor spontaneous speech output in CCD was related to problems generating ideas for expression, as individuals with CCD performed below controls on the verbal and nonverbal fluency tasks. Exploratory analyses revealed that apathy and slowed processing speed may be contributing factors. Adynamia in CCD is a novel finding that may be an intervention target for improving communication skills in this population. © 2024 The Authors
Author Keywords
Adynamia; Apathy; Corpus callosum dysgenesis; Spontaneous speech; Verbal fluency
Document Type: Article
Publication Stage: Final
Source: Scopus
Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases
(2024) Genetics in Medicine, 26 (11), art. no. 101219, .
Alstrup, M.a b , Cesca, F.c d , Krawczun-Rygmaczewska, A.c d , López-Menéndez, C.e f , Pose-Utrilla, J.e f , Castberg, F.C.g h , Bjerager, M.O.h , Finnila, C.i , Kruer, M.C.j k , Bakhtiari, S.j k , Padilla-Lopez, S.j k , Manwaring, L.l , Keren, B.m , Afenjar, A.n , Galatolo, D.o , Scalise, R.o , Santorelli, F.M.o , Shillington, A.p q , Vezain, M.r , Martinovic, J.s , Stevens, C.t , Gowda, V.K.u , Srinivasan, V.M.u , Thiffault, I.v w x , Pastinen, T.v w , Baranano, K.y , Lee, A.z , Granadillo, J.z , Glassford, M.R.p aa , Keegan, C.E.aa , Matthews, N.ab , Saugier-Veber, P.r ac , Iglesias, T.e f , Østergaard, E.b ad
a Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark
b Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
c Department of Life Sciences, University of Trieste, Trieste, Italy
d IIT Center for Synaptic Neuroscience and Technology, Genova, Italy
e Instituto de Investigaciones Biomédicas Sols-Morreale. Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
f Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III. Madrid, Spain
g Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
h Department of Pediatrics, North Zealand Hospital, Hilleroed, Denmark
i Hudson Alpha Institute for Biotechnology, Huntsville, AL, United States
j Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children’s Hospital, Phoenix, AZ, United States
k Departments of Child Health, Neurology, and Cellular & Molecular Medicine, Program in Genetics, University of Arizona College of Medicine–Phoenix, Phoenix, AZ, United States
l Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
m Département de génétique, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
n APHP. Sorbonne Université, Centre de Référence Malformations et maladies congénitales du cervelet et déficiences intellectuelles de causes rares, UF de génétique clinique, Hôpital Trousseau, Paris, France
o Molecular Medicine and Neurogenetics, IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy
p Department of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
q Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States
r Univ Rouen Normandie, Inserm, Normandie Univ, Rouen, U1245, France
s Department of Fetal Pathology, AP-HP Antoine Beclere Hospital, University Paris Saclay, Clamart, France
t Department of Pediatrics, University of Tennessee College of Medicine, Chattanooga, TN, United States
u Department of Pediatric Neurology, Indira Gandhi institute of child health, Bangalore, India
v Genomic Medicine Center, Children’s Mercy Research Institute, Kansas City, MO, United States
w University of Missouri Kansas City School of Medicine, Kansas City, MO, United States
x Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, MO, United States
y Johns Hopkins University, The Johns Hopkins Hospital, Baltimore, MD, United States
z Department of Pediatrics, Division of Genetics and Genomics, Washington University, Saint Louis, MO, United States
aa Department of Pediatrics, Division of Genetics, Metabolism, and Genomic Medicine, University of Michigan, Ann Arbor, MI, United States
ab WVU Medicine Children’s Hospital, Division of Genetics, Morgantown, WV, United States
ac CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Rouen, France
ad Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Abstract
Purpose: Spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising 8 with SINO and 4 with an autosomal recessive condition attributed to biallelic KIDINS220 variants. Methods: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed the clinical and molecular data of our cohort and previously reported individuals and, based on functional experiments, reached a better understanding of the pathogenesis behind the KIDINS220-related disease. Results: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. A total of 92% had their diagnosis within 3 years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact, and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted. Conclusion: Our study provides further insights into the clinical spectrum, etiology, and predicted functional impact of KIDINS220 variants. © 2024 American College of Medical Genetics and Genomics
Author Keywords
Intellectual disability; KIDINS220; Obesity; Spastic paraplegia; Ventriculomegaly
Funding details
Ministerio de Ciencia, Innovación y UniversidadesMCIU
Ministerio de Ciencia e InnovaciónMCIN
Instituto de Salud Carlos IIIISCIII
Centro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasCIBERNED
European Regional Development FundERDF
Ministero dell’Istruzione, dell’Università e della RicercaMIURJ53D23010800006, 20224YX5ZX, CUP J53D23010800006
Ministero dell’Istruzione, dell’Università e della RicercaMIUR
Agencia Estatal de InvestigaciónAEICB06/05/1122
Agencia Estatal de InvestigaciónAEI
European CommissionECMCIN /AEI/ 10.13039/501100011033, M4.C2.1.1, PID2020-115218RB-I00
European CommissionEC
Document Type: Article
Publication Stage: Final
Source: Scopus
Measuring cognitive effort using tabular transformer-based language models of electronic health record-based audit log action sequences
(2024) Journal of the American Medical Informatics Association: JAMIA, 31 (10), pp. 2228-2235.
Kim, S.a b , Warner, B.C.c , Lew, D.b , Lou, S.S.b d , Kannampallil, T.b c d
a Roy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63110, United States
b Institute for Informatics, Data Science and Biostatistics (I2DB), Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Computer Science and Engineering, Washington University St. Louis, St. Louis, United States
d Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
OBJECTIVES: To develop and validate a novel measure, action entropy, for assessing the cognitive effort associated with electronic health record (EHR)-based work activities. MATERIALS AND METHODS: EHR-based audit logs of attending physicians and advanced practice providers (APPs) from four surgical intensive care units in 2019 were included. Neural language models (LMs) were trained and validated separately for attendings’ and APPs’ action sequences. Action entropy was calculated as the cross-entropy associated with the predicted probability of the next action, based on prior actions. To validate the measure, a matched pairs study was conducted to assess the difference in action entropy during known high cognitive effort scenarios, namely, attention switching between patients and to or from the EHR inbox. RESULTS: Sixty-five clinicians performing 5 904 429 EHR-based audit log actions on 8956 unique patients were included. All attention switching scenarios were associated with a higher action entropy compared to non-switching scenarios (P < .001), except for the from-inbox switching scenario among APPs. The highest difference among attendings was for the from-inbox attention switching: Action entropy was 1.288 (95% CI, 1.256-1.320) standard deviations (SDs) higher for switching compared to non-switching scenarios. For APPs, the highest difference was for the to-inbox switching, where action entropy was 2.354 (95% CI, 2.311-2.397) SDs higher for switching compared to non-switching scenarios. DISCUSSION: We developed a LM-based metric, action entropy, for assessing cognitive burden associated with EHR-based actions. The metric showed discriminant validity and statistical significance when evaluated against known situations of high cognitive effort (ie, attention switching). With additional validation, this metric can potentially be used as a screening tool for assessing behavioral action phenotypes that are associated with higher cognitive burden. CONCLUSION: An LM-based action entropy metric-relying on sequences of EHR actions-offers opportunities for assessing cognitive effort in EHR-based workflows. © The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Author Keywords
audit log; clinical workflow; cognitive effort; entropy; language model
Document Type: Article
Publication Stage: Final
Source: Scopus
HiMAL: Multimodal Hierarchical Multi-task Auxiliary Learning framework for predicting Alzheimer’s disease progression
(2024) JAMIA Open, 7 (3), art. no. ooae087, .
Kumar, S.a b , Yu, S.C.b , Michelson, A.b c , Kannampallil, T.a b d , Payne, P.R.O.a b
a Department of Computer Science and Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
b Institute for Informatics Data Science and Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, United States
c Division of Pulmonary and Critical Care, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Objective: We aimed to develop and validate a novel multimodal framework Hierarchical Multi-task Auxiliary Learning (HiMAL) framework, for predicting cognitive composite functions as auxiliary tasks that estimate the longitudinal risk of transition from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD). Materials and Methods: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer’s Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal explanations regarding risk of disease progression were provided to interpret the predicted cognitive decline. Results: Out of 634 MCI patients (mean [IQR] age: 72.8 [67-78], 60% male), 209 (32%) progressed to AD. HiMAL showed better prediction performance compared to all state-of-the-art longitudinal single-modality singe-task baselines (AUROC = 0.923 [0.915-0.937]; AUPRC = 0.623 [0.605-0.644]; all P <. 05). Ablation analysis highlighted that imaging and cognition scores with maximum contribution towards prediction of disease progression. Discussion: Clinically informative model explanations anticipate cognitive decline 6 months in advance, aiding clinicians in future disease progression assessment. HiMAL relies on routinely collected electronic health records (EHR) variables for proximal (6 months) prediction of AD onset, indicating its translational potential for point-of-care monitoring and managing of high-risk patients. © 2024 The Author(s).
Author Keywords
Alzheimer’s disease progression; hierarchical; model explainability; multimodal; multitask auxiliary learning
Document Type: Article
Publication Stage: Final
Source: Scopus
Social support and the association between post-traumatic stress disorder and risk for long-term prescription opioid use
(2024) Pain, 165 (10), pp. 2379-2386.
Sullivan, M.D.a , Wilson, L.b , Amick, M.b , Miller-Matero, L.R.c , Chrusciel, T.b d e , Salas, J.b d , Zabel, C.c , Lustman, P.J.f , Ahmedani, B.c , Carpenter, R.W.g , Scherrer, J.F.b d h
a Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, United States
b Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
c Center for Health Policy and Health Services Research and Behavioral Health Services, Henry Ford Health, One Ford Place, Detroit, MI, United States
d Advanced HEAlth Data (AHEAD) Research Institute, Saint Louis University School of Medicine, St. Louis, MO, United States
e Department of Health and Clinical Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO, United States
f Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
g Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, United States
h Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St. Louis, MO, United States
Abstract
Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. Eligible participants were $18 years and had completed a new period of prescription opioid use lasting 30 to 90 days. Bivariate associations between cohort characteristics and each key variable was assessed using x2 tests for categorical variables and t-tests for continuous variables. Interaction between PTSD and emotional support was assessed by a priori stratification on low vs high emotional support. Participants (n 5 808) were 53.6 (SD 6 11.6) years of age, 69.8% female, 69.6% White, and 26.4% African American. Overall, 17.2% had probable PTSD. High emotional support was significantly (P, 0.0001) more common among those without probable PTSD. Prescription opioid use at 6-month follow-up was significantly (P 5 0.0368) more common among patients with vs without probable PTSD. In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio 5 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio 5 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use. © 2024 International Association for the Study of Pain.
Author Keywords
Cohort; Epidemiology; Opioid; Pain; Psychiatry
Document Type: Article
Publication Stage: Final
Source: Scopus
Elevated VCP ATPase Activity Correlates With Disease Onset in Multisystem Proteinopathy-1
(2024) Neurology: Genetics, 10 (5), art. no. e200191, .
Robinson, S.E.a , Findlay, A.R.a , Li, S.b , Wang, F.b , Schiava, M.b , Daw, J.a b , Diaz-Manera, J.b , Chou, T.-F.c , Weihl, C.C.a
a Department of Neurology, Washington University, St. Louis, MO, United States
b John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle Hospitals NHS Foundation Trusts, United Kingdom
c Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
Abstract
Objectives Multisystem proteinopathy-1 (MSP1) is a late onset disease with >50 pathogenic variants in p97/VCP. MSP1 patients have multiple phenotypes that include inclusion body myopathy, Paget disease of the bone, amyotrophic lateral sclerosis, and frontotemporal dementia. There have been no clear genotype-phenotype correlations. We sought to identify genotype-phenotype correlations and associate these with VCP intrinsic ATPase activity. Methods Patients with MSP1 were identified from the literature and the Cure VCP patient registry. Age at onset and at loss of ambulation were collated. VCP intrinsic ATPase activity was evaluated from recombinant purified protein. Results Among the 5 most common pathogenic VCP variants in MSP1 patients, R155C patients had the earliest average age at onset (38.15 ± 9.78). This correlated with higher ATPase activity. Evaluation of 5 variants confirmed an inverse correlation between age at onset and ATPase activity (r = −0.94, p = 0.01). Discussion Previous studies have reported that VCP pathogenic variants are “hyperactive.” Whether this elevation in VCP ATPase activity is relevant to disease is unclear. Our study supports that in vitro VCP activity correlates with disease onset and may guide the prognosis of patients with rare or unreported variants. Moreover, it suggests that inhibition of VCP ATPase activity in MSP1 may be therapeutic. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Funding details
National Institutes of HealthNIHR01 AG031867, K24 AR073317
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Final
Source: Scopus
Manifested U-Waves Prior to Seizure Attacks in a Patient Who Had Remote Subarachnoid Hemorrhage: A Case Report
(2024) Annals of Noninvasive Electrocardiology, 29 (5), art. no. e70014, .
Kaneko, N.a , Watanabe, M.b , Mori, S.c , Turker, I.d , Okamoto, K.e , Urabe, T.b , Ai, T.f
a Department of Laboratory Medicine, Juntendo University Urayasu Hospital, Chiba, Japan
b Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan
c Department of Emergency Medicine, Tokyo Women’s Medical University, Shinjuku, Japan
d Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Chiba, Japan
f Department of Clinical Laboratory Medicine, Juntendo University Urayasu Hospital, Chiba, Japan
Abstract
Sudden unexpected death in epilepsy (SUDEP) refers to unpredictable demise of a person following a seizure. Electroencephalograms can directly measure electrical activity in the brain; however, it cannot predict when seizures will occur. The use of electrocardiograms (ECGs) to monitor changes in brain electrical activity has gained attention, recently. In this case report, we retrospectively reviewed ECGs taken before and after seizure activity in a 75-year-old male who had a remote subarachnoid hemorrhage. Interestingly, U-waves appeared prior to his seizures and disappeared afterward, which suggests ECGs can be used to predict epilepsy in a certain population. © 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.
Author Keywords
ECG; repolarization; seizure; U-wave
Document Type: Article
Publication Stage: Final
Source: Scopus
Structure-function coupling in highly sampled individual brains
(2024) Cerebral Cortex, 34 (9), art. no. bhae361, .
Rajesh, A.a , Seider, N.A.b , Newbold, D.J.c , Adeyemo, B.d , Marek, S.b , Greene, D.J.e , Snyder, A.Z.a c , Shimony, J.S.a c , Laumann, T.O.b , Dosenbach, N.U.F.a b d f g , Gordon, E.M.a
a Department of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
c Department of Neurology, New York Langone Medical Center, 550 First Avenue, New York, NY 10016, United States
d Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States
e Department of Cognitive Science, University of California San Diego, 9500 Gilman Dr La JollaCA 92037, United States
f Department of Biomedical Engineering, Washington University, 1 Brookings Drive, St. Louis, MO 63130, United States
g Program in Occupational Therapy, Washington University, 4444 Forest Park Ave, St. Louis, MO 63108, United States
Abstract
Structural connectivity (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to SC may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-Averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 min of diffusion-weighted MRI for SC and 360 min of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-To-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas. © 2024 The Author(s). Published by Oxford University Press. All rights reserved.
Author Keywords
dense sampling; diffusion imaging; functional imaging; individual; structure-function coupling
Funding details
Intellectual and Developmental Disabilities Research CenterIDDRC
Hope Center for Neurological Disorders, Washington University in St. Louis
Dysphonia InternationalNSDA
Mallinckrodt Institute of Radiology, School of Medicine, Washington University in St. LouisMIR
MH122066, NS088590, NS129521, MH124567, MH121276
National Institutes of HealthNIHMH096773, MH100019, NS110332, MH129616
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Final
Source: Scopus
Men of Mexican ethnicity, alcohol use, and help-seeking: “I can quit on my own.”
(2024) Journal of Substance Use and Addiction Treatment, 163, art. no. 209359, .
Robles, E.H.a , Castro, Y.b , Najera, S.c , Cardoso, J.d , Gonzales, R.e , Mallonee, J.f , Segovia, J.a , Salazar-Hinojosa, L.a , De Vargas, C.g , Field, C.c
a Worden School of Social Service, Our Lady of the Lake University, United States
b Steve Hicks School of Social Work, The University of Texas at Austin, United States
c Department of Psychology, The University of Texas at El Paso, United States
d Department of Psychology, Hastings College, United States
e St. Louis School of Medicine, Washington University, United States
f Department of Social Work, The University of Texas at El Paso, United States
g Department of Psychiatry, Texas Tech University Health Sciences Center El Paso, United States
Abstract
Introduction: Hispanics report higher rates of problematic alcohol use compared to non-Hispanic Whites while also reporting lower rates of alcohol treatment utilization compared to non-Hispanics. The study employs Anderson’s Behavioral Model of Healthcare Utilization Model to guide the exploration of alcohol use, help-seeking and healthcare utilization. Methods: The present qualitative study explored help-seeking and alcohol treatment utilization for Hispanic men of Mexican ethnicity. A total of 27 participants (Mage = 35.7, SD = 10.82) completed a semi-structured interview that explored the treatment experiences and underlying psychological mechanisms that shaped their help-seeking. Results: Through a thematic content analysis, the following themes emerged: 1) perceiving need with subthemes of familismo, role as protector and provider, and positive face; 2) predisposing beliefs on help-seeking; and 3) treatment experiences and elements of patient satisfaction with subthemes of monetized treatment, respect, and perceiving professional stigma. Conclusions: The findings in this article may assist in improving strategies for increasing alcohol treatment utilization among men of Mexican ethnicity. By exploring beliefs, values, and experiences health researchers can develop culturally informed intervention strategies. © 2024 Elsevier Inc.
Author Keywords
Alcohol use; Disparities; Help-seeking; Men of Mexican ethnicity; Qualitative health study
Document Type: Article
Publication Stage: Final
Source: Scopus
Evaluating preferences for medication formulation and treatment model among people who use opioids non-medically: A web-based cross-sectional study
(2024) Journal of Substance Use and Addiction Treatment, 163, art. no. 209383, .
Saunders, E.C.a , Budney, A.J.a , Cavazos-Rehg, P.b , Scherer, E.a , Bell, K.a , John, D.c , Marsch, L.A.a
a Center for Technology and Behavioral Health, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c New York Medical College, United States
Abstract
Introduction: Over the past decade, treatment for opioid use disorder has expanded to include long-acting injectable and implantable formulations of medication for opioid use disorder (MOUD), and integrated treatment models systematically addressing both behavioral and physical health. Patient preference for these treatment options has been underexplored. Gathering data on OUD treatment preferences is critical to guide the development of patient-centered treatment for OUD. This cross-sectional study assessed preferences for long-acting MOUD and integrated treatment using an online survey. Methods: An online Qualtrics survey assessed preferences for MOUD formulation and integrated treatment models. The study recruited participants (n = 851) in October and November 2019 through advertisements or posts on Facebook, Google AdWords, Reddit, and Amazon Mechanical Turk (mTurk). Eligible participants scored a two or higher on the opioid pain reliever or heroin scales of the Tobacco, Alcohol Prescription Medication and other Substance Use (TAPS) Tool. Structured survey items obtained patient preference for MOUD formulation and treatment model. Using stated preference methods, the study assessed preference via comparison of preferred options for MOUD and treatment model. Results: In the past year, 824 (96.8 %) participants reported non-prescribed use of opioid pain relievers (mean TAPS score = 2.72, SD = 0.46) and 552 (64.9 %) reported heroin or fentanyl use (mean TAPS score = 2.73, SD = 0.51). Seventy-four percent of participants (n = 631) reported currently or previously receiving OUD treatment, with 407 (48.4 %) receiving MOUD. When asked about preferences for type of MOUD formulation, 452 (53.1 %) preferred a daily oral formulation, 115 (13.5 %) preferred an implant, 114 (13.4 %) preferred a monthly injection and 95 (11.2 %) preferred a weekly injection. Approximately 8.8 % (n = 75) would not consider MOUD regardless of formulation. The majority of participants (65.2 %, n = 555) preferred receiving treatment in a specialized substance use treatment program distinct from their medical care, compared with receiving care in an integrated model (n = 296, 34.8 %). Conclusions: Though most participants expressed willingness to try long-acting MOUD formulations, the majority preferred short-acting formulations. Likewise, the majority preferred non-integrated treatment in specialty substance use settings. Reasons for these preferences provide insight on developing effective educational tools for patients and suggesting targets for intervention to develop a more acceptable treatment system. © 2024 Elsevier Inc.
Author Keywords
Integrated treatment; Medication for opioid use disorder; Patient preference; Treatment models; Web-based recruitment
Document Type: Article
Publication Stage: Final
Source: Scopus
Diversity of Intraspecific Patterns of Brain Region Size Covariation in Fish
(2024) Integrative and Comparative Biology, 64 (2), pp. 506-519.
Axelrod, C.J.a , Urquhart, E.M.b , Mahabir, P.N.c , Carlson, B.A.b , Gordon, S.P.a
a Department of Ecology and Evolution, Cornell University, E145, 215 Tower Rd Dale R. Corson Hall, Ithaca, NY 14853, United States
b Department of Biology, Washington University in St. Louis, St. Louis, MO 63105, United States
c Department of Integrative Biology, University of Guelph, Guelph, ON N1G 2W1, Canada
Abstract
Synopsis Traits often do not evolve in isolation or vary independently of other traits. Instead, they can be affected by covariation, both within and across species. However, the importance of within-species trait covariation and, critically, the degree to which it varies between species has yet to be thoroughly studied. Brain morphology is a trait of great ecological and behavioral importance, with regions that are hypothesized to vary in size based on behavioral and cognitive demands. Sizes of brain regions have also been shown to covary with each other across various taxa. Here, we test the degree to which covariation in brain region sizes within species has been conserved across 10 teleost fish species. These 10 species span five orders, allowing us to examine how phylogenetic proximity influences similarities in intraspecific trait covariation. Our results showed a trend that similar patterns of brain region size covariation occur in more closely related species. Interestingly, there were certain brain region pairs that showed similar levels of covariation across all species regardless of phylogenetic distance, such as the telencephalon and optic tectum, while others, such as the olfactory bulb and the hypothalamus, varied more independently. Ultimately, the patterns of brain region covariation shown here suggest that evolutionary mechanisms or constraints can act on specific brain regions independently, and that these constraints can change over evolutionary time. © The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
Alterations of tau and Camk2 in acute stroke and effects of a multicomponent drug
(2024) Science of Traditional Chinese Medicine, 2 (2), pp. 148-157.
Wu, Y.a b c , Zhou, R.a , Wang, M.a , Xu, J.a , Zhang, Y.a , Wei, J.a , Yang, H.b
a Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
b Beijing Key Lab. of Traditional Chinese Med. Basic Res. on Prev. and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
c Washington University, St. Louis, MO, United States
Abstract
Background Stroke is one of the leading causes of death around the world. The sequelae of ischemic stroke cause drastic effects on the quality of life for patients. Sanwujiaowan (SWJW) is a mixture prepared with 5 herbal medicines (Aconiti Lateralis Radix Praeparata, Aconiti Kusnezoffii Radix, Polygoni Multiflori Radix, Aconiti Radix, and Olibanum), with a long history of application in treating the sequelae of stroke. Objectives To provide evidence and decipher the mechanism of SWJW in alleviating stroke. Materials and Methods In this article, we expanded the indicators of SWJW by an integrated strategy based on signature metabolomics, target proteins, and bioinformatics and probed into the mechanism of SWJW intervention in ischemic stroke in a rat model. Results The results indicated that SWJW protected rats from nerve damage during the acute phase of ischemic stroke by regulating tau phosphorylation via the PI3K/Akt pathway. Conclusions This study, for the first time, proved that the reduction of phosphorylated tau was harmful for the neural function in the acute phase of ischemic stroke. Meanwhile, the pathological changes of phosphorylated tau proteins were detected in stroke and recalled by SWJW. This finding may provide a new reference for formulating treatment strategies for the acute phase of ischemic stroke. © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Author Keywords
Bioinformatics; Ischemic stroke; Metabolomics; Proteomics; SWJW; Tau
Document Type: Article
Publication Stage: Final
Source: Scopus
Head and Neck Injuries among Powered Scooter Users between 2010 and 2019
(2024) Facial Plastic Surgery, 40 (5), pp. 640-647.
Trapp, L.P.a , Sukumar, N.b , Cristel, R.T.c , Yu, J.d
a Department of Otolaryngology, University of Illinois at Chicago, Chicago, IL, United States
b Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, MO, United States
c Department of Facial Plastic & Reconstructive Surgery, Synergi Facial Surgery, Chesterfield, MO, United States
d Department of Otolaryngology, Kaiser Permanente, Seattle, WA, United States
Abstract
Powered scooters, including electric scooters (e-scooters), have become an increasingly available and popular mode of personal transportation, but the health risks of these devices are poorly explored. We aim to quantify the increase in frequency of powered scooter-associated head and neck region injuries occurring yearly from 2010 to 2019, and to compare the frequency and severity of injury with those involving unpowered scooters. Here we present a retrospective cross-sectional study of all patients with head and neck injuries associated with powered and unpowered scooters seen in emergency departments reporting to the National Electronic Injury Surveillance System (NEISS) database from January 1, 2010 to December 31, 2019. During this time frame, a total of 1,620 injuries associated with powered scooters and a total of 5,675 injuries associated with unpowered scooters were reported to the NEISS. The database estimates these to reflect a nationwide total of 54,036 powered scooter-related injuries and 168,265 unpowered scooter-related injuries. Powered scooter injuries have increased for both children and adults since 2014, and estimated powered scooter injuries (16,243) surpassed estimated unpowered scooter injuries (14,124) when including all age groups for the first time in 2019. In 2019, adults are estimated to have nearly twice as many powered scooter-related head and neck injuries as children (10,884 vs. 5,359, respectively). In 2019, a higher proportion of powered scooter-related injuries involving adults were severe injuries when compared with those involving children (13.3 vs. 5.2%, respectively). Interestingly, unpowered scooters still cause many more estimated injuries in children than powered scooters did during 2019 (11,953 vs. 5,083). We find that powered scooters are now associated with a greater number and severity of head and neck injuries among the adult population than the pediatric population. But unpowered scooters still cause more head and neck injuries than powered scooters in the pediatric population. © 2024. Thieme. All rights reserved.
Author Keywords
e-scooter; head and neck injury; trauma
Document Type: Article
Publication Stage: Final
Source: Scopus
Survey of the Landscape of Society Practice Guidelines for Genetic Testing of Neurodevelopmental Disorders
(2024) Annals of Neurology, .
Srivastava, S.a , Cole, J.J.b , Cohen, J.S.c d , Chopra, M.a , Smith, H.S.e , Deardorff, M.A.f , Pedapati, E.g , Corner, B.h , Anixt, J.S.g , Jeste, S.i , Sahin, M.a , Gurnett, C.A.j , Campbell, C.A.k , the Intellectual and Developmental Disabilities Research Center (IDDRC) Workgroup on Advocating for Access to Genomic Testingl
a Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
b Department of Pediatrics, University of Colorado, Children’s Hospital Colorado, Aurora, CO, United States
c Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD, United States
d Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
e Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, United States
f Departments of Pathology and Pediatrics, Keck School of Medicine of USC, Children’s Hospital Los Angeles, Los Angeles, CA, United States
g Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital, Cincinnati, OH, United States
h Department of Pediatrics and Genetics, Vanderbilt University Medical Center, Nashville, TN, United States
i Department of Neurology, Keck School of Medicine of USC, Children’s Hospital Los Angeles, Los Angeles, CA, United States
j Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
k Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, United States
Abstract
Genetic testing of patients with neurodevelopmental disabilities (NDDs) is critical for diagnosis, medical management, and access to precision therapies. Because genetic testing approaches evolve rapidly, professional society practice guidelines serve an essential role in guiding clinical care; however, several challenges exist regarding the creation and equitable implementation of these guidelines. In this scoping review, we assessed the current state of United States professional societies’ guidelines pertaining to genetic testing for unexplained global developmental delay, intellectual disability, autism spectrum disorder, and cerebral palsy. We describe several identified shortcomings and argue the need for a unified, frequently updated, and easily-accessible cross-specialty society guideline. ANN NEUROL 2024. © 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
Loss-of-Function Variants in CUL3 Cause a Syndromic Neurodevelopmental Disorder
(2024) Annals of Neurology, .
Blackburn, P.R.a , Ebstein, F.b c , Hsieh, T.-C.d , Motta, M.e , Radio, F.C.e , Herkert, J.C.f , Rinne, T.g , Thiffault, I.h i , Rapp, M.j , Alders, M.k , Maas, S.k , Gerard, B.l , Smol, T.m , Vincent-Delorme, C.n , Cogné, B.c o , Isidor, B.c o , Vincent, M.c o , Bachmann-Gagescu, R.p q , Rauch, A.p , Joset, P.r , Ferrero, G.B.s , Ciolfi, A.e , Husson, T.t u , Guerrot, A.-M.u , Bacino, C.v , Macmurdo, C.w , Thompson, S.S.w , Rosenfeld, J.A.v x , Faivre, L.y z , Mau-Them, F.T.z aa , Deb, W.c o , Vignard, V.c o , Agrawal, P.B.ab ac , Madden, J.A.ab ac , Goldenberg, A.u , Lecoquierre, F.u , Zech, M.ad ae af , Prokisch, H.ad ae af , Necpál, J.ag ah , Jech, R.ai , Winkelmann, J.aj ak al am , Koprušáková, M.T.an , Konstantopoulou, V.ao , Younce, J.R.ap , Shinawi, M.aq ar , Mighton, C.as at , Fung, C.au av , Morel, C.F.au aw , Lerner-Ellis, J.ax ay az , DiTroia, S.ba , Barth, M.bb bc , Bonneau, D.bb , Krapels, I.bd be , Stegmann, A.P.A.bd be , van der Schoot, V.bd be , Brunet, T.bf bg , Bußmann, C.bh , Mignot, C.bi , Zampino, G.bj bk , Wortmann, S.B.bl , Mayr, J.A.bl , Feichtinger, R.G.bl , Courtin, T.bm , Ravelli, C.bn , Keren, B.bi , Ziegler, A.bc bo , Hasadsri, L.bp , Pichurin, P.N.bq , Klee, E.W.bq br bs , Grand, K.bt , Sanchez-Lara, P.A.bt , Krüger, E.b , Bézieau, S.c o , Klinkhammer, H.d bu , Krawitz, P.M.d , Eichler, E.E.bv bw , Tartaglia, M.e , Küry, S.c o , Wang, T.bx by bz ca
a Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, United States
b Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany
c Nantes Université, CHU Nantes, CNRS, INSERM, l’institut du Thorax, Nantes, France
d Institute of Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany
e Molecular Genetics and Functional Genomics, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
f Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
g Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
h Center for Pediatric Genomic Medicine, Children’s Mercy Hospital, Kansas City, MO, United States
i Department of Pathology and Laboratory Medicine, Children’s Mercy Hospitals, Kansas City, MO, United States
j Department of Pediatrics-Clinical Genetics and Metabolism, Children’s Hospital Colorado, Aurora, CO, United States
k Amsterdam University Medical Center, University of Amsterdam, Department of Clinical Genetics, Amsterdam, Netherlands
l Unité de Biologie et de Génétique Moléculaire, Center Hospitalier Universitaire de Strasbourg, Strasbourg, France
m Univ Lille, CHU Lille, RADEME Team, Institut de Génétique Médicale, Lille, France
n Department of Clinical Genetics, Hôpital Jeanne de Flandre, CHU Lille, Lille, France
o Nantes Université, CHU de Nantes, Service de Génétique Médicale, Nantes, France
p Institute of Medical Genetics, University of Zurich, Schlieren, Switzerland
q Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
r Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
s Department of Clinical and Biological Sciences, San Luigi Gonzaga University Hospital, University of Torino, Turin, Italy
t Department of Research, Center Hospitalier du Rouvray, Rouen, France
u Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Rouen, France
v Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
w Division of Medical Genetics, Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, TX, United States
x Baylor Genetics, Houston, TX, United States
y Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD CHU, Dijon, France
z INSERM UMR1231, équipe GAD, Université de Bourgogne-Franche Comté, Dijon, France
aa Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France
ab Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston, MA, United States
ac Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine and Holtz Children’s Hospital, Jackson Health System, Miami, FL, United States
ad Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany
ae Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany
af Institute for Advanced Study, Technical University of Munich, Garching, Germany
ag Department of Neurology, Zvolen Hospital, Zvolen, Slovakia
ah Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
ai Department of Neurology, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic
aj Institute of Neurogenomics, Helmholtz Zentrum Muenchen, Neuherberg, Germany
ak Neurogenetics, Technische Universitaet Muenchen, Munich, Germany
al Institute of Human Genetics, Klinikum rechts der Isar der TUM, Munich, Germany
am Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
an Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovakia
ao Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
ap Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
aq Division of Genetics and Genomic Medicine, St. Louis Children’s Hospital, St. Louis, MO, United States
ar Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
as Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
at Genomics Health Services and Policy Research Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, Canada
au The Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Sinai Health System, Toronto, Canada
av Department of Molecular Genetics, University of Toronto, Toronto, Canada
aw Department of Medicine, University of Toronto, Toronto, Canada
ax Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, Canada
ay Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
az Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada
ba Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United States
bb Department of Biochemistry and Genetics, University Hospital of Angers, Angers, France
bc Mitovasc Unit, UMR CNRS 6015-INSERM 1083, Angers, France
bd Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, Netherlands
be Department of Clinical Genetics and School for Oncology and Developmental Biology, Maastricht UMC, Maastricht, Netherlands
bf Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
bg Dr. v. Hauner Children’s Hospital, Department of Pediatric Neurology and Developmental Medicine, LMU—University of Munich, Munich, Germany
bh Department of Neuropediatrics, ATOS Klinik Heidelberg, Heidelberg, Germany
bi Département de Génétique, AP-HP-Sorbonne Université, Hôpital Trousseau & Groupe Hospitalier Pitié-Salpêtrière, Paris, France
bj Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
bk Dipartimento di Scienze Della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
bl University Children’s Hospital, Paracelsus Medical University (PMU), Salzburg, Austria
bm Center for Molecular and Chromosomal Genetics, AP-HP-Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
bn Department of Pediatric Neurology and Neurogenetic Referral Center, AP-HP-Sorbonne Université, Armand Trousseau Hospital, Paris, France
bo Department of Biochemistry and Genetics, Angers University Hospital and UMR CNRS, Angers, France
bp Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
bq Department of Clinical Genomics, Mayo Clinic, Rochester, MN, United States
br Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, MN, United States
bs Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United States
bt Department of Pediatrics, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, United States
bu Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
bv Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, United States
bw Howard Hughes Medical Institute, University of Washington, Seattle, WA, United States
bx Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China
by Neuroscience Research Institute, Peking University, Beijing, China
bz Key Laboratory for Neuroscience, Ministry of Education of China & National Health Commission of China, Beijing, China
ca Autism Research Center, Peking University Health Science Center, Beijing, China
Abstract
Objective: De novo variants in cullin-3 ubiquitin ligase (CUL3) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype–phenotype correlation, and investigate the underlying pathogenic mechanism. Methods: Genetic data and detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells. Results: We assembled a cohort of 37 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 35 have loss-of-function (LoF) and 2 have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugates in vitro. Notably, we show that 4E-BP1 (EIF4EBP1), a prominent substrate of CUL3, fails to be targeted for proteasomal degradation in patient-derived cells. Interpretation: Our study further refines the clinical and mutational spectrum of CUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism. ANN NEUROL 2024. © 2024 American Neurological Association.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Molecular characterization of gliomas and glioneuronal tumors amid Noonan syndrome: cancer predisposition examined
(2024) Frontiers in Oncology, 14, art. no. 1453309, .
Shatara, M.a , Schieffer, K.M.b c d , Melas, M.b , Varga, E.A.b , Thomas, D.c e , Bucknor, B.A.b , Costello, H.M.b , Wheeler, G.b , Kelly, B.J.b , Miller, K.E.b d , Rodriguez, D.P.f , Mathew, M.T.b c d , Lee, K.b c d , Crotty, E.g , Leary, S.g , Paulson, V.A.h , Cole, B.h , Abdelbaki, M.S.a , Finlay, J.L.i , Lazow, M.A.d i , Salloum, R.d i , Fouladi, M.d i , Boué, D.R.c e , Mardis, E.R.b d , Cottrell, C.E.b c d
a The Division of Hematology and Oncology, St. Louis Children’s Hospital, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
c Department of Pathology, The Ohio State University, Columbus, OH, United States
d Department of Pediatrics, The Ohio State University, Columbus, OH, United States
e Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
f The Department of Radiology, Nationwide Children’s Hospital, Columbus, OH, United States
g Division of Pediatric Hematology, Oncology, Bone Marrow Transplant and Cellular Therapy, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA, United States
h Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States
i The Division of Hematology/Oncology, and Bone Marrow Transplantation, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, United States
Abstract
Introduction: In the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease. Methods: Within an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease–germline comparator exome analysis, RNA sequencing, and tumor classification by DNA methylation analysis was performed. Results: Through the implementation of paired analysis, this study identified 4 of 314 (1.3%) individuals who harbored a germline PTPN11 variant associated with NS, of which 3 individuals were diagnosed with a glioma or glioneuronal tumor. Furthermore, we extend this study through collaboration with a peer institution to identify two additional individuals with NS and a glioma or glioneuronal tumor. Notably, in three of five (60%) individuals, paired genomic profiling led to a previously unrecognized diagnosis of Noonan syndrome despite an average age of cancer diagnosis of 16.8 years. The study of the disease-involved tissue identified signaling pathway dysregulation through somatic alteration of genes involved in cellular proliferation, survival, and differentiation. Discussion: Comparative pathologic findings are presented to enable an in-depth examination of disease characteristics. This comprehensive analysis highlights the association of gliomas and glioneuronal tumors with RASopathies and the potential therapeutic challenges and importantly demonstrates the utility of genomic profiling for the identification of germline cancer predisposition. Copyright © 2024 Shatara, Schieffer, Melas, Varga, Thomas, Bucknor, Costello, Wheeler, Kelly, Miller, Rodriguez, Mathew, Lee, Crotty, Leary, Paulson, Cole, Abdelbaki, Finlay, Lazow, Salloum, Fouladi, Boué, Mardis and Cottrell.
Author Keywords
cancer predisposition; genomic profiling; germline; glioma; glioneuronal tumor; next-generation sequencing; Noonan syndrome; PTPN11
Document Type: Article
Publication Stage: Final
Source: Scopus
Do Ethnic Identity, Familial, and Community Contexts Impact the Association Between Adverse Childhood Experiences and Psychopathology Among Latinx Adolescents?
(2024) Journal of the American Academy of Child and Adolescent Psychiatry, .
Garcia, A.R.a , Barnhart, S.a , López, D.J.b , Karcher, N.R.c
a University of Kentucky, Lexington, Kentucky, United States
b Boston University, Boston, Massachusetts, United States
c Washington University, St. Louis, Missouri, United States
Abstract
Objective: Few studies have explored the interplay of how individual identity, parental, familial, and contextual factors impact associations between Latinx adolescent adversities and psychopathology. This study aimed to examine whether these factors mediate the relationship between adversities and psychopathology in Latinx youth. Method: Latinx youth (n = 2,411) data from the Adolescent Brain Cognitive Development (ABCD) Study were used to examine path models with adverse childhood experiences (ACEs) as the predictor and either youth- or caregiver-rated internalizing/externalizing scores over 4 timepoints as the outcome (ages 9-13 years). Models examined 3 potential mediators: (1) ethnic identity, (2) familial context (comprising parental monitoring, family conflict, and caregiver acceptance), and (3) community cohesion. Models were conducted separately for internalizing and externalizing symptoms. Results: Greater adversity was associated with greater youth- and caregiver-rated internalizing/externalizing psychopathology over time. Greater adversity was associated with lower family functioning and lower ethnic identity, and greater family functioning was associated with lower psychopathology. Family functioning mediated associations between adversity and psychopathology over time (youth-reported internalizing: 95% CI = 0.012-0.019; youth-reported externalizing: 95% CI = 0.020-0.028). In contrast, there was not strong evidence for ethnic identity and community cohesion mediating associations between adversities and psychopathology over time. Conclusion: Unlike previous studies, ethnic identity did not influence the relationship between ACEs and psychopathology over time. Additional research is needed to identify whether possible tensions rise as Latinx youth acculturate into US culture and achieve optimal levels of ethnic identity formation. Providers need to assess specific Latinx parental and familial contexts that may interfere with youth identity formation. © 2024 American Academy of Child and Adolescent Psychiatry
Author Keywords
Adolescent Brain Cognitive Development Study; adverse childhood experiences; child psychopathology; Latinx youth; trauma
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors
(2024) Molecular Imaging and Biology, .
Nandi, A.a , Nakano, M.b , Brašić, J.R.a c d , Brinson, Z.S.e , Kitzmiller, K.f , Mathur, A.a , Mohamed, M.g , Roberts, J.h , Wong, D.F.a i , Kuwabara, H.a
a Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, JHOC Room 3243, 601 N. Caroline St, Baltimore, MD 21287, United States
b Clinical Science Division, R & amp;D, Janssen Pharmaceutical K.K, Tokyo, Japan
c Department of Psychiatry, New York City Health + Hospitals/Bellevue, New York, NY, United States
d Department of Psychiatry, New York University Grossman School of Medicine, New York University Langone Health, New York, NY, United States
e Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States
f Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, United States
g Radiology, Ain Shams University, Cairo, Egypt
h Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
i Lab of CNS Neuropsychopharmacology And Multimodal Imaging (CNAMI), Mallinckrodt Institute of Radiology, Washington University in St Louis, St Louis, MO, United States
Abstract
Purpose: Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BPND) in rodent PET studies. Procedures: PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BPND in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT. Results: The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BPND in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter. Conclusions: The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BPND in proportion to errors of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners. © The Author(s), under exclusive licence to World Molecular Imaging Society 2024.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
When is context used to guide prospective memory monitoring?
(2024) Psychonomic Bulletin and Review, .
Ball, B.H.a , Peper, P.a , Bugg, J.M.b
a Department of Psychology, University of Texas, at Arlington, TX, 501 Nedderman Drive, Arlington, Austin, 76109, United States
b Department of Psychological and Brain Sciences, Washington University in Saint Louis, St. Louis, MO 63130, United States
Abstract
Monitoring the environment for prospective memory (PM) targets can be attentionally demanding, such as searching for a pharmacy to pick up medication while driving in traffic. It is therefore optimal to increase monitoring in contexts when the probability of encountering a PM target is high (e.g., business plaza) and decrease monitoring in contexts when the probability is low (e.g., residential area), referred to as strategic monitoring. In some instances, though, identifying whether the context is appropriate for monitoring can be attentionally demanding. For example, when contextual information varies unpredictably, it may be easier to continuously monitor rather than dynamically increase and decrease monitoring on a moment-by-moment basis. The current study extends previous research by showing that participants strategically monitor when the ongoing task automatically orients attention to contextual information (i.e., focal context cues), regardless of the difficulty of checking for PM targets (Experiment 1). In contrast, when ongoing task processing does not orient attention to contextual information (i.e., nonfocal context cues), participants only strategically monitor when the demands of target checking are high (Experiment 2). These findings suggest that the decision to utilize context to adjust monitoring is driven by a cost–benefit analysis that weighs the perceived efforts of context identification relative to the expected benefit of not having to check for PM targets on half of the trials. When the perceived effort of identifying context on each trial is outweighed by the benefit of reducing target checking on a subset of trials, strategic monitoring occurs. © The Psychonomic Society, Inc. 2024.
Author Keywords
Attention; Context; Effort; Prospective memory; Strategic monitoring
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
A modular chemigenetic calcium indicator for multiplexed in vivo functional imaging
(2024) Nature Methods, .
Farrants, H.a , Shuai, Y.a , Lemon, W.C.a , Monroy Hernandez, C.b , Zhang, D.a , Yang, S.a , Patel, R.a , Qiao, G.c , Frei, M.S.d e , Plutkis, S.E.a , Grimm, J.B.a , Hanson, T.L.a , Tomaska, F.a f , Turner, G.C.a , Stringer, C.a , Keller, P.J.a , Beyene, A.G.a , Chen, Y.b , Liang, Y.c , Lavis, L.D.a , Schreiter, E.R.a
a Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, United States
b Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
c Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
d Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg, Germany
e Department of Pharmacology, University of California San Diego, La Jolla, CA, United States
f Department of Electrical and Computer Engineering, Center for BioEngineering, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, United States
Abstract
Genetically encoded fluorescent calcium indicators allow cellular-resolution recording of physiology. However, bright, genetically targetable indicators that can be multiplexed with existing tools in vivo are needed for simultaneous imaging of multiple signals. Here we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several that efficiently label the brain in animals. When bound to a near-infrared dye-ligand, WHaloCaMP shows a 7× increase in fluorescence intensity and a 2.1-ns increase in fluorescence lifetime upon calcium binding. We use WHaloCaMP1a to image Ca2+ responses in vivo in flies and mice, to perform three-color multiplexed functional imaging of hundreds of neurons and astrocytes in zebrafish larvae and to quantify Ca2+ concentration using fluorescence lifetime imaging microscopy (FLIM). © The Author(s) 2024.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Cross-Sectional and Prospective Associations between Parkinsonism and Parkinson’s Disease with Frailty in Latin America
(2024) Movement Disorders Clinical Practice, .
Kim, D.J.a b , Khan, N.b , Llibre-Rodriguez, J.J.c , Jiang, M.d , Rodriguez-Salgado, A.M.e , Acosta, I.f g , Sosa, A.L.f g , Acosta, D.h , Jimenez-Velasquez, I.Z.i , Guerra, M.j , Salas, A.k , Sánchez, N.D.d , López-Contreras, R.l , Hesse, H.m , Tanner, C.n , Llibre-Guerra, J.J.o , Prina, M.a b
a Health Service and Population Research Department, Institute of Health Service and Population Research Department, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
b Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
c Dementia Research Unit, Medical University of Havana, Havana, Cuba
d Institute of Public Health, Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland
e Global Brain Health Institute, University of San Francisco California, San Francisco, CA, United States
f Laboratory of the Dementias, National Institute of Neurology and Neurosurgery, Mexico, Mexico
g National Autonomous University of Mexico, Mexico, Mexico
h Universidad Nacional Pedro Henriquez Ureña (UNPHU), Internal Medicine Department, Geriatric Section, Santo Domingo, Dominican Republic
i Internal Medicine Department, Geriatrics Program, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
j Instituto de la Memoria Depresion y Enfermedades de Riesgo IMEDER, Lima, Peru
k Medicine Department, Caracas University Hospital, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela
l Memory Clinic, Neurology Service, Salvadoran Social Security Institute, San Salvador, El Salvador
m Observatorio Covid-19, Universidad Tecnológica Centroamericana, Tegucigalpa, Honduras
n Department of Neurology, Weill Institute for Neurosciences, University of California-San Francisco, San Francisco, CA, United States
o Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Abstract
Background: Little is known about the relationship between parkinsonism or Parkinson’s disease (PD) and frailty in Latin America. Objective: The study aimed to determine the cross-sectional and prospective associations between parkinsonism and PD with frailty in a large multi-country cohort in Latin America. Frailty was assessed using three different models to explore which definitions are more appropriate to screen for frailty in a PD population. Methods: 12,865 older adults (aged ≥65 years) from the 10/66 population-based cohort study in six Latin American countries were analyzed. Logistic regression models assessed the cross-sectional association between parkinsonism/PD with baseline frailty. Individual country analyses were combined via fixed-effect meta-analysis. In non-frail participants who were followed up for 4 years, Cox proportional hazards regression models assessed the prospective association between parkinsonism/PD with incident frailty accounting for competing risk of mortality. Results: At baseline, the prevalence of parkinsonism and PD was 7% and 2%, respectively, and the prevalence of frailty varied across the three models with rates of 18% for frailty phenotype, 20% for frailty index and 30% for multidimensional frailty model. PD was associated with baseline and incident frailty after accounting for age, sex, and education: odds ratios and 95% confidence intervals (95% CI) for frailty were 2.49 (95% CIs 1.87–3.31), 2.42 (95% CIs 1.80–3.25), and 1.57 (95% CIs 1.16–2.21), and cause-specific hazard ratios were 1.66 (95% CIs 1.07–2.56), 1.78 (95% CIs 1.05–3.03), and 1.58 (95% CIs 0.91–2.74). Similar results were found for parkinsonism. Conclusion: Parkinsonism and PD were cross-sectionally and prospectively associated with frailty in Latin America. Routine screening for frailty in PD patients may aid earlier detection of those at greater risk of adverse outcomes. © 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Author Keywords
epidemiology; frailty; Latin America; Parkinson’s disease
Funding details
Fondo Nacional de Ciencia Tecnología e InnovaciónFONACIT
Universidad Central de VenezuelaUCV
World Health OrganizationWHO
Alzheimer’s AssociationAA24HPE‐1287320, IIRG–04–1286
Alzheimer’s AssociationAA
Wellcome TrustWTGR080002, GR066133
Wellcome TrustWT
K01AG073526
Michael J. Fox Foundation for Parkinson’s ResearchMJFFMJFF‐020770
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
Document Type: Article
Publication Stage: Article in Press
Source: Scopus