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Article ; Online: Association between Neuroligin-1 polymorphism and plasma glutamine levels in individuals with autism spectrum disorder.

Lee, In-Hee / Walker, Douglas I / Lin, Yufei / Smith, Matthew Ryan / Mandl, Kenneth D / Jones, Dean P / Kong, Sek Won

2023 Volume 95, Page(s) 104746

Abstract: Background: Unravelling the relationships between candidate genes and autism spectrum disorder (ASD) phenotypes remains an outstanding challenge. Endophenotypes, defined as inheritable, measurable quantitative traits, might provide intermediary links ... ...

Abstract	Background: Unravelling the relationships between candidate genes and autism spectrum disorder (ASD) phenotypes remains an outstanding challenge. Endophenotypes, defined as inheritable, measurable quantitative traits, might provide intermediary links between genetic risk factors and multifaceted ASD phenotypes. In this study, we sought to determine whether plasma metabolite levels could serve as endophenotypes in individuals with ASD and their family members. Methods: We employed an untargeted, high-resolution metabolomics platform to analyse 14,342 features across 1099 plasma samples. These samples were collected from probands and their family members participating in the Autism Genetic Resource Exchange (AGRE) (N = 658), compared with neurotypical individuals enrolled in the PrecisionLink Health Discovery (PLHD) program at Boston Children's Hospital (N = 441). We conducted a metabolite quantitative trait loci (mQTL) analysis using whole-genome genotyping data from each cohort in AGRE and PLHD, aiming to prioritize significant mQTL and metabolite pairs that were exclusively observed in AGRE. Findings: Within the AGRE group, we identified 54 significant associations between genotypes and metabolite levels (P < 5.27 × 10 Interpretation: Our findings suggest that plasma glutamine levels could potentially serve as an endophenotype, thus establishing a link between the genetic risk associated with NLGN1 and the severity of RRB in ASD. This identified association could facilitate the development of novel therapeutic targets, assist in selecting specific cohorts for clinical trials, and provide insights into target symptoms for future ASD treatment strategies. Funding: This work was supported by the National Institute of Health (grant numbers: R01MH107205, U01TR002623, R24OD024622, OT2OD032720, and R01NS129188) and the PrecisionLink Biobank for Health Discovery at Boston Children's Hospital.
MeSH term(s)	Child ; Humans ; Autism Spectrum Disorder/blood ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/metabolism ; Endophenotypes ; Genotype ; Glutamine/blood ; Polymorphism, Single Nucleotide
Chemical Substances	Glutamine (0RH81L854J) ; neuroligin 1
Language	English
Publishing date	2023-08-04
Publishing country	Netherlands
Document type	Clinical Study ; Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104746
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Article ; Online: Cross-national comparisons of later-life cognitive function using data from the Harmonized Cognitive Assessment Protocol (HCAP): Considerations and recommended best practices.

Kobayashi, Lindsay C / Jones, Richard N / Briceño, Emily M / Rentería, Miguel Arce / Zhang, Yuan / Meijer, Erik / Langa, Kenneth M / Lee, Jinkook / Gross, Alden L

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 3, Page(s) 2273–2281

Abstract: The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational ... ...

Abstract	The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross-national comparisons of risk factor associations using HCAP data. Because existing and planned HCAP studies provide cognition data representing an estimated 75% of the global population ≥65 years of age, these recommended best practices will support high-quality comparative analyses of cognitive aging around the world. The principles described in this perspective are applicable to any researcher aiming to integrate or compare harmonized data on cognitive outcomes and their risk and protective factors across diverse populations.
MeSH term(s)	Humans ; Cognition ; Risk Factors
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13694
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Article ; Online: Comprehensive characterization of putative genetic influences on plasma metabolome in a pediatric cohort.

Lee, In-Hee / Smith, Matthew Ryan / Yazdani, Azam / Sandhu, Sumiti / Walker, Douglas I / Mandl, Kenneth D / Jones, Dean P / Kong, Sek Won

Human genomics

2022 Volume 16, Issue 1, Page(s) 67

Abstract: Background: The human exposome is composed of diverse metabolites and small chemical compounds originated from endogenous and exogenous sources, respectively. Genetic and environmental factors influence metabolite levels, while the extent of genetic ... ...

Abstract	Background: The human exposome is composed of diverse metabolites and small chemical compounds originated from endogenous and exogenous sources, respectively. Genetic and environmental factors influence metabolite levels, while the extent of genetic contributions across metabolic pathways is not yet known. Untargeted profiling of human metabolome using high-resolution mass spectrometry (HRMS) combined with genome-wide genotyping allows comprehensive identification of genetically influenced metabolites. As such previous studies of adults discovered and replicated genotype-metabotype associations. However, these associations have not been characterized in children. Results: We conducted the largest genome by metabolome-wide association study to date of children (N = 441) using 619,688 common genetic variants and 14,342 features measured by HRMS. Narrow-sense heritability (h Conclusion: Comprehensive profiling of plasma metabolome across age groups combined with genome-wide genotyping revealed a wide range of genetic influence on diverse chemical species and metabolic pathways. The developmental trajectory of a biological system is shaped by gene-environment interaction especially in early life. Therefore, continuous efforts on generating metabolomics data in diverse human tissue types across age groups are required to understand gene-environment interaction toward healthy aging trajectories.
MeSH term(s)	Humans ; Child ; Metabolomics ; Genomics
Language	English
Publishing date	2022-12-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2147618-4
ISSN	1479-7364 ; 1479-7364
ISSN (online)	1479-7364
ISSN	1479-7364
DOI	10.1186/s40246-022-00440-w
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Article ; Online: A generic approach to construct pseudo components for oil weathering models.

Geng, Xiaolong / Barker, Christopher H / MacFadyen, Amy / Boufadel, Michel C / Thrift-Viveros, Dalina L / Jones, Robert K / O'Connor, Caitlin / Lee, Kenneth

Journal of hazardous materials

2023 Volume 459, Page(s) 132160

Abstract: Oil weathering models are essential for predicting the behavior of spilled oil in the environment. Most models use a "Pseudo Component" (PC) approach to represent the wide range of compounds found in petroleum products. Within the approach, rather than ... ...

Abstract	Oil weathering models are essential for predicting the behavior of spilled oil in the environment. Most models use a "Pseudo Component" (PC) approach to represent the wide range of compounds found in petroleum products. Within the approach, rather than modeling each individual compound in an oil, a manageable number of PCs are developed that represent whole classes of compounds. However, previous studies focused mainly on traditional crude oils and did not develop a generic approach to create an optimal set of PCs for a variety of oils. In developing the updates to the NOAA oil weathering model, we propose herein a generic approach to construct PCs using oil distillation data to capture the complexity of oil evaporative weathering. We validated our approach with 899 oils from the Automated Data Inquiry for Oil Spills (ADIOS) oil library and found that an optimal set of sixteen PCs should be used. These PCs include two with low boiling point (below 144 °C), one with a high boiling point (above 400 °C), and thirteen constructed within a middle range of boiling points with a temperature resolution of 20 °C. Our simulation tests suggested that this set of sixteen PCs adequately characterizes oil evaporation processes for a wide variety of oils.
Language	English
Publishing date	2023-07-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2023.132160
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Article ; Online: Lifetime occupational skill and later-life cognitive function among older adults in the United States, Mexico, India, and South Africa.

Kobayashi, Lindsay C / O'Shea, Brendan Q / Wixom, Caroline / Jones, Richard N / Langa, Kenneth M / Weir, David / Lee, Jinkook / Wong, Rebeca / Gross, Alden L

Alzheimer's & dementia : the journal of the Alzheimer's Association

2023 Volume 20, Issue 3, Page(s) 1933–1943

Abstract: Introduction: We conducted a cross-national comparison of the association between main lifetime occupational skills and later-life cognitive function across four economically and socially distinct countries.: Methods: Data were from population-based ... ...

Abstract	Introduction: We conducted a cross-national comparison of the association between main lifetime occupational skills and later-life cognitive function across four economically and socially distinct countries. Methods: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women. Results: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa. Discussion: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association. Highlights: No studies have examined cross-national differences in the association of occupational skill with cognition. We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa. The association of occupational skill with cognitive function varies by country and gender.
MeSH term(s)	Male ; Humans ; Female ; United States/epidemiology ; Aged ; Middle Aged ; Aged, 80 and over ; South Africa/epidemiology ; Mexico/epidemiology ; Cognition ; Aging/psychology ; Occupations
Language	English
Publishing date	2023-12-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13665
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Article: Harmonization of Later-Life Cognitive Function Across National Contexts: Results from the Harmonized Cognitive Assessment Protocols (HCAPs).

Gross, Alden L / Li, Chihua / Briceno, Emily M / Rentería, Miguel Arce / Jones, Richard N / Langa, Kenneth M / Manly, Jennifer J / Nichols, Emma L / Weir, David / Wong, Rebeca / Berkman, Lisa / Lee, Jinkook / Kobayashi, Lindsay C

medRxiv : the preprint server for health sciences

2023

Abstract: Background: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonize general and ... ...

Abstract	Background: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonize general and domain-specific cognitive scores from HCAPs across six countries, and evaluate precision and criterion validity of the resulting harmonized scores. Methods: We statistically harmonized general and domain-specific cognitive function across the six publicly available HCAP partner studies in the United States, England, India, Mexico, China, and South Africa (N=21,141). We used an item banking approach that leveraged common cognitive test items across studies and tests that were unique to studies, as identified by a multidisciplinary expert panel. We generated harmonized factor scores for general and domain- specific cognitive function using serially estimated graded-response item response theory (IRT) models. We evaluated precision of the factor scores using test information plots and criterion validity using age, gender, and educational attainment. Findings: IRT models of cognitive function in each country fit well. We compared measurement reliability of the harmonized general cognitive function factor across each cohort using test information plots; marginal reliability was high (r> 0·90) for 93% of respondents across six countries. In each country, general cognitive function scores were lower with older ages and higher with greater levels of educational attainment. Interpretation: We statistically harmonized cognitive function measures across six large, population-based studies of cognitive aging in the US, England, India, Mexico, China, and South Africa. Precision of the estimated scores was excellent. This work provides a foundation for international networks of researchers to make stronger inferences and direct comparisons of cross-national associations of risk factors for cognitive outcomes. Funding: National Institute on Aging (R01 AG070953, R01 AG030153, R01 AG051125, U01 AG058499; U24 AG065182; R01AG051158).
Language	English
Publishing date	2023-06-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.09.23291217
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Article ; Online: Harmonisation of later-life cognitive function across national contexts: results from the Harmonized Cognitive Assessment Protocols.

Gross, Alden L / Li, Chihua / Briceño, Emily M / Arce Rentería, Miguel / Jones, Richard N / Langa, Kenneth M / Manly, Jennifer J / Nichols, Emma / Weir, David / Wong, Rebeca / Berkman, Lisa / Lee, Jinkook / Kobayashi, Lindsay C

The lancet. Healthy longevity

2023 Volume 4, Issue 10, Page(s) e573–e583

Abstract	Background: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonise general and domain-specific cognitive scores from HCAP studies across six countries, and evaluate reliability and criterion validity of the resulting harmonised scores. Methods: We statistically harmonised general and domain-specific cognitive function scores across publicly available HCAP partner studies in China, England, India, Mexico, South Africa, and the USA conducted between October, 2015 and January, 2020. Participants missing all cognitive test items in a given HCAP were excluded. We used an item banking approach that leveraged common cognitive test items across studies and tests that were unique to studies. We generated harmonised factor scores to represent a person's relative functioning on the latent factors of general cognitive function, memory, executive function, orientation, and language using confirmatory factor analysis. We evaluated the marginal reliability, or precision, of the factor scores using test information plots. Criterion validity of factor scores was assessed by regressing the scores on age, gender, and educational attainment in a multivariable analysis adjusted for these characteristics. Findings: We included 21 144 participants from the six HCAP studies of interest (11 480 women [54·3%] and 9664 [45·7%] men), with a median age of 69 years (IQR 64-76). Confirmatory factor analysis models of cognitive function in each country fit well: 31 (88·6%) of 35 models had adequate or good fit to the data (comparative fit index ≥0·90, root mean square error of approximation ≤0·08, and standardised root mean residual ≤0·08). Marginal reliability of the harmonised general cognitive function factor was high (>0·9) for 19 044 (90·1%) of 21 144 participant scores across the six countries. Marginal reliability of the harmonised factor was above 0·85 for 19 281 (91·2%) of 21 142 participant factor scores for memory, 7805 (41·0%) of 19 015 scores for executive function, 3446 (16·3%) of 21 103 scores for orientation, and 4329 (20·5%) of 21 113 scores for language. In each country, general cognitive function scores were lower with older age and higher with greater levels of educational attainment. Interpretation: We statistically harmonised cognitive function measures across six large population-based studies of cognitive ageing. These harmonised cognitive function scores empirically reflect comparable domains of cognitive function among older adults across the six countries, have high reliability, and are useful for population-based research. This work provides a foundation for international networks of researchers to make improved inferences and direct comparisons of cross-national associations of risk factors for cognitive outcomes in pooled analyses. Funding: US National Institute on Aging.
MeSH term(s)	Male ; Humans ; Female ; Aged ; Reproducibility of Results ; Cognition ; Educational Status ; Executive Function ; Risk Factors
Language	English
Publishing date	2023-10-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2666-7568
ISSN (online)	2666-7568
DOI	10.1016/S2666-7568(23)00170-8
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Article ; Online: Biomechanical analysis of wheelchair athletes with paraplegia during cross-training exercises.

Jones, Carrie / Schnorenberg, Alyssa J / Garlanger, Kristin / Leonardis, Joshua M / Kortes, Sam / Riebe, Justin / Plesnik, Justin / Lee, Kenneth / Slavens, Brooke A

The journal of spinal cord medicine

2021 Volume 45, Issue 6, Page(s) 882–897

Abstract: Context: Extreme conditioning programs (ECPs), such as CrossFit ... ® ... , are a relatively new method of fitness with rapid growth in individuals with paraplegia. However, it is unknown if wheelchair users are at an additional risk of musculoskeletal ...

Abstract	Context: Extreme conditioning programs (ECPs), such as CrossFit<sup>®</sup>, are a relatively new method of fitness with rapid growth in individuals with paraplegia. However, it is unknown if wheelchair users are at an additional risk of musculoskeletal injury during these exercises. Biomechanical characterization is necessary to determine the safety and efficacy of ECPs as an exercise modality for wheelchair users with paraplegia. Objective: To characterize the three-dimensional (3-D) thorax and upper extremity joint kinematics of paraplegic wheelchair athletes during exercises commonly prescribed as part of ECPs. Design: Observational study. Participants: Three male wheelchair athletes, average age of 37.1 ± 4.6 years, with spinal cord injury levels of T8, L2, and T10, with varying exercise experience. Methods: 3-D movement was acquired using motion capture during the performance of four exercises: battle ropes, sled pull, overhead press, and sledgehammer swing. A custom upper extremity inverse kinematics model was applied to compute 3-D joint angles. Outcome measures: 3-D peak thorax, glenohumeral, elbow, and wrist joint angles and ranges of motion (ROM), Visual Analog Scale (VAS), and Borg Scale of Perceived Exertion. Results: Large joint motions were required for the exercises, at times demanding extreme shoulder and/or wrist flexion and extension, abduction, and external rotation, which are concerning for injury risk in wheelchair users. Participants, however, were able to perform the exercises pain free. Conclusion: These quantitative findings highlight that wheelchair athletes may be exposed to potentially injurious positions during common ECP exercises. These findings provide insight that may lead to improved clinical guidelines for prescription and training of exercise regimens, particularly involving ECPs, for wheelchair users.
MeSH term(s)	Humans ; Male ; Adult ; Wheelchairs ; Para-Athletes ; Shoulder Joint ; Spinal Cord Injuries ; Paraplegia/etiology ; Biomechanical Phenomena
Language	English
Publishing date	2021-06-08
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223949-5
ISSN	2045-7723 ; 1079-0268
ISSN (online)	2045-7723
ISSN	1079-0268
DOI	10.1080/10790268.2021.1928868
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Article: The "other" forms of diabetes in children.

Jones, Kenneth Lee

Adolescent medicine: state of the art reviews

2010 Volume 21, Issue 1, Page(s) 120–8, x

Abstract: The large majority of children with diabetes seen by any pediatrician or in any pediatric diabetes clinic will fall into the two major categories of type 1 (T1DM) and, more recently in adolescents, type 2 (T2DM). But one has only to look at the diabetes ... ...

Abstract	The large majority of children with diabetes seen by any pediatrician or in any pediatric diabetes clinic will fall into the two major categories of type 1 (T1DM) and, more recently in adolescents, type 2 (T2DM). But one has only to look at the diabetes classifications currently proposed by the American Diabetes Association or the World Health Organization to see that these forms account for only two of the many forms of diabetes listed. The goal of this chapter is to discuss, very briefly, the other classes of diabetes which occur in children and are of importance to physicians caring for adolescents.
MeSH term(s)	Adolescent ; Child ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/etiology ; Diagnosis, Differential ; Drug-Related Side Effects and Adverse Reactions/complications ; Glucokinase/deficiency ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Humans
Chemical Substances	HNF1A protein, human ; Hepatocyte Nuclear Factor 1-alpha ; Glucokinase (EC 2.7.1.2)
Language	English
Publishing date	2010-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2398471-5
ISSN	1934-4287
ISSN	1934-4287
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Article ; Online: Oil biodegradation in permeable marine sediments: Effects of benthic pore-water advection and solute exchange.

Geng, Xiaolong / Barker, Christopher H / MacFadyen, Amy / Boufadel, Michel C / Lee, Kenneth / Thrift-Viveros, Dalina L / Jones, Robert / O'Connor, Caitlin

Journal of hazardous materials

2022 Volume 436, Page(s) 129211

Abstract: Oil spills have been recognized as among the worst kinds of environmental disasters, causing severe coastal ecological and economic damages. Although benthic flow and solute fluxes are known to have strong impacts on fate and transport of oil deposited ... ...

Abstract	Oil spills have been recognized as among the worst kinds of environmental disasters, causing severe coastal ecological and economic damages. Although benthic flow and solute fluxes are known to have strong impacts on fate and transport of oil deposited within marine sediments, their endogenous mechanisms still remain to be uncovered. In this paper, simulations of flow and solute transport processes along with hydrocarbon biodegradation were conducted in a cylindrical benthic chamber system to investigate influences of benthic hydrodynamics on oil biodegradation in permeable marine sediments. Results show that ripple-flow interactions create subsurface recirculation cells whereby seawater infiltrates into the benthic sediments at ripple troughs while groundwater discharges near the crests. It results in a spatially varied oil biodegradation rate in marine sediments. Significant oil biodegradation occurs near sediment ripple troughs due to direct oxygen recharge, while biodegradation of oil deposited uphill becomes slow due to limited oxygen replenishment. Oil biodegradation decreases subsurface oxygen content, and consequently impedes discharge of oxygen from benthic sediments. Our results reveal a dynamic interaction between oil biodegradation and benthic flow and solute transport processes, which has strong implications for predicting oil persistence and biodegradation within marine sediments and its associated impacts on benthic biogeochemical processes.
MeSH term(s)	Biodegradation, Environmental ; Geologic Sediments/chemistry ; Oxygen ; Petroleum ; Petroleum Pollution/analysis ; Water ; Water Pollutants, Chemical/analysis
Chemical Substances	Petroleum ; Water Pollutants, Chemical ; Water (059QF0KO0R) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-05-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1491302-1
ISSN	1873-3336 ; 0304-3894
ISSN (online)	1873-3336
ISSN	0304-3894
DOI	10.1016/j.jhazmat.2022.129211
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