bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obsessive-Compulsive Disorder and Risk of Parkinson Disease: A Nationwide Longitudinal Study
Authors: Liou Ying-Jay , Bai Ya-Mei , Chen Mu-Hong , Cheng Chih-Ming , Chen Tzeng-Ji , Tsai Shih-Jen 
Published: August 2022

ABSTRACT

Objective
Several small-scale studies have suggested a biological link between obsessive-compulsive disorder (OCD) and Parkinson disease (PD). However, the temporal association of OCD and subsequent PD remained unclear.

Methods
Here, we used Taiwan National Health Insurance Research Database and included the data of 28,722 patients with OCD (International Classification of Diseases, Ninth Revision, Clinical Modification code: 300.3) and 287,220 matched controls between 2001 and 2009. They were followed until the end of 2011 to identify diagnosis of new-onset PD (International Classification of Diseases, Ninth Revision, Clinical Modification code: 332.0). The frequency of psychiatric outpatient visits for OCD per year (<5, 5–10, and >10) was identified as a proxy of OCD severity.

Results
Using the stratified Cox regression model, the hazard ratio of developing PD among patients with OCD was 2.70 (95% confidence interval = 1.74–4.18) compared with matched controls. Among patients with OCD, those with >10 psychiatric outpatient visits per year for OCD (hazard ratio = 3.18, 95% confidence interval = 2.06–4.93) were more likely to develop PD during the follow-up period compared with those with <5 psychiatric outpatient visits per years for OCD.

Conclusions
OCD was found to be an independent risk factor for PD. The mechanisms underlying the temporal association between OCD and subsequent PD require further investigation.
Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV
Authors: Ghanooni Delaram , Carrico Adam W. , Williams Renessa , Glynn Tiffany R. , Moskowitz Judith T. , Pahwa Savita , Pallikkuth Suresh , Roach Margaret E. , Dilworth Samantha , Aouizerat Bradley E. , Flentje Annesa 
Published: August 2022

ABSTRACT

Objective
Sexual minority men (e.g., gay, bisexual, and other men who have sex with men) experience stigma and sexual minority stress, which are theorized to drive negative health outcomes. Sexual minority men with treated HIV display persistent immune dysregulation, which could be amplified by sexual minority stress responses to potentiate cellular aging.

Methods
This cross-sectional study included 52 sexual minority men living with HIV who had undetectable viral load (<40 copies/mL) and biologically confirmed recent methamphetamine use. Participants completed measures assessing sexual minority stress and openness about sexual minority status (i.e., outness). DNA methylation–derived outcomes included the following: the extrinsic epigenetic age acceleration clock, telomere length, naive CD4+ T-helper cells, and naive CD8+ T-cytotoxic/suppressor cells.

Results
After adjusting for negative affect and recent stimulant use, higher sexual minority stress was associated with a faster extrinsic epigenetic age acceleration clock (β = 0.29, p = .030), shorter telomere length (β = −0.43, p = .002), and fewer naive CD4+ (β = −0.57, p < .001) and naive CD8+ T cells (β = −0.57, p < .001). Greater outness was associated with higher naive CD4+ (β = 0.32, p = .030) and naive CD8+ T cells (β = 0.38, p = .008) as well as lower plasma interleukin 6 (β = −0.33, p = .027).

Conclusions
Sexual minority stress processes are associated with markers of cellular aging and inflammation in methamphetamine-using sexual minority men living with HIV. Longitudinal research should elucidate biobehavioral mechanisms linking sexual minority stress processes with accelerated cellular aging in those with and without HIV.
Reliable energy-based antibody humanization and stabilization
Authors: Tennenhouse Ariel , Khmelnitsky Lev , Khalaila Razi , Yeshaya Noa , Noronha Ashish , Lindzen Moshit , Makowski Emily , Zaretsky Ira , Sirkis Yael Fridmann , Galon-Wolfenson Yael , Tessier Peter M. , Abramson Jakub , Yarden Yosef , Fass Deborah , Fleishman Sarel J. 
Published: August 2022

AbstractHumanization is an essential step in developing animal-derived antibodies into therapeutics, and approximately one third of approved antibodies have been humanized. Conventional humanization approaches graft the complementarity-determining regions (CDRs) of the animal antibody onto several homologous human frameworks. This process, however, often drastically lowers stability and antigen binding, demanding iterative mutational fine-tuning to recover the original antibody properties. Here, we present Computational hUMan AntiBody design (CUMAb), a web-accessible method that starts from an experimental or model antibody structure, systematically grafts the animal CDRs on thousands of human frameworks, and uses Rosetta atomistic simulations to rank the designs by energy and structural integrity (http://CUMAb.weizmann.ac.il). CUMAb designs of five independent antibodies exhibit similar affinities to the parental animal antibody, and some designs show marked improvement in stability. Surprisingly, nonhomologous frameworks are often preferred to the highest-homology ones, and several CUMAb designs that use different human frameworks and differ by dozens of mutations are functionally equivalent. Thus, CUMAb presents a general and streamlined approach to optimizing antibody stability and expressibility while increasing humanness.
Rapid waning of protection induced by prior BA.1/BA.2 infection against BA.5 infection
Authors: Malato João , Ribeiro Ruy M. , Fernandes Eugénia , Leite Pedro Pinto , Casaca Pedro , Antunes Carlos , Fonseca Válter R. , Gomes Manuel Carmo , Graca Luis 
Published: August 2022

AbstractSARS-CoV-2 omicron subvariants BA.1 and BA.2 became dominant in many countries in early 2022. These subvariants are now being displaced by BA.4 and BA.5. While natural infection with BA.1/BA.2 provides some protection against BA.4/BA.5 infection, the duration of this protection remains unknown.We used the national Portuguese COVID-19 registry to investigate the waning of protective immunity conferred by prior BA.1/BA.2 infection towards BA.5. We divided the individuals infected during the period of BA.1/BA.2 dominance (>90% of sample isolates) in successive 15-day intervals and determined the risk of subsequent infection with BA.5 over a fixed period.Compared with uninfected people, one previous infection conferred substantial protection against BA.5 re-infection at 3 months (RR=0.12; 95% CI: 0.11-0.12). However, although still significant, the protection was reduced by two-fold at 5 months post-infection (RR=0.24; 0.23-0.24).These results should be interpreted in the context of vaccine breakthrough infections, as the vaccination coverage in the individuals included in the analyses is >98% since the end of 2021.This waning of protection following BA.1/BA.2 infection highlights the need to assess the stability and durability of immune protection induced with the adapted vaccines (based on BA.1) over time.
Neighbourhood deprivation across eight decades and late-life cognitive function in the Lothian Birth Cohort 1936: A life-course study
Authors: Baranyi Gergő , Conte Federica , Deary Ian J. , Shortt Niamh , Thompson Catharine Ward , Cox Simon R. , Pearce Jamie 
Published: August 2022

ABSTRACTIntroductionAlthough neighbourhood may predict late-life cognitive function, studies mostly relies on measurements at a single time point, with few investigations applying a life-course approach. Further, it is unclear whether the associations between neighbourhood and cognitive tests scores relate to specific cognitive domains or general ability. This study explored how neighbourhood deprivation across eight decades contributes to late-life cognitive function.MethodsData were drawn from the Lothian Birth Cohort 1936 (n=1091) with cognitive function measured through 10 tests at ages 70, 73, 76, 79 and 82. Participants’ residential history was gathered with ‘lifegrid’ questionnaires and linked to neighbourhood deprivation in childhood, young adulthood, and mid-to-late adulthood. Associations were tested with latent growth curve models for levels and slopes of general (g) and domain-specific abilities (visuospatial ability, memory, and processing speed), life-course associations were explored with path analysis.ResultsHigher mid-to-late adulthood neighbourhood deprivation was associated with lower age 70 levels (β=-0.113, 95%CI: −0.205, −0.021) and faster decline of g over 12 years (β=-0.160, 95%CI: −0.290, −0.031). Initially-apparent findings with domain-specific cognitive functions (e.g. processing speed) were due to their shared variance with g. Path analyses suggested that childhood neighbourhood disadvantage is indirectly linked to late-life cognitive function through education and selective residential mobility.ConclusionsTo our knowledge, we provide the most comprehensive assessment of the relationship between life-course neighbourhood deprivation and cognitive ageing. Living in advantaged areas in mid-to-late adulthood may contribute to better cognitive function and slower decline, whereas advantaged childhood neighbourhood environment likely affects functioning through cognitive reserves.
Aerodigestoscopy (ADS): A retrospective examination of the feasibility, safety, and comfort of a new procedure for the evaluation of physiological disorders of the aerodigestive tract
Authors: Arnold Robert J. , Bausek Nina , Gaskill Christopher S. , Johnson Lawrence F. , Aldarondo Sigfredo , Aull Cody , Midani Malik , Midani Tarek , Midani Ramiz , Brown Ashton S. , Wallace Alana 
Published: August 2022

AbstractLimited access to comprehensive assessment of physiological disorders of the upper aerodigestive tract by different specialties represents a barrier to care in rural healthcare settings, which may lead to misdiagnosis, underdiagnosis, and increased associated mortality. No single differential diagnostic exam for the comprehensive assessment of all functions of the upper aerodigestive tract is available to bridge this gap. We present a single procedure for assessment of physiological functions of the upper aerodigestive tract including swallow, voice, respiration, and cough while also screening for gastric retention and obstructive sleep apnea which might contribute to these disorders. Our procedure, called Aerodigestoscopy (ADS), represents a procedure incorporating other established exams as integral components to evaluate patients with aerodigestive disorders. Patients who might particularly benefit from our ADS diagnostic algorithm are those in a rural community referred by other health professionals due to complaints of aerodigestive symptoms and signs. We present a brief overview of how the procedure was developed, what it includes, and retrospective safety data from over 18,000 ADS procedures performed over the last 10 years, demonstrating safety and feasibility of this procedure.
An atlas of thyroid hormone receptors target genes in mouse tissues
Authors: Zekri Yanis , Guyot Romain , Flamant Frédéric 
Published: August 2022

AbstractWe gathered in a single database available RNA-seq and ChIP-seq data to better characterize the target genes of the thyroid hormone receptors in several cell types. This database can serve as a resource to analyze the mode of action of the hormone. Also, it is an easy-handling convenient tool to obtain information on specific genes in regards to T3 regulation, or extract larger list of genes of interest based on the users’ criteria. Overall, this atlas is a unique compilation of recent sequencing data focusing on thyroid hormones, their receptors, mode of action, targets and roles which may profit researchers within the field. A preliminary analysis indicates extensive variations in the repertoire of target genes which transcription is upregulated by chromatin-bound nuclear receptor. Although it has a major influence, chromatin accessibility is not the only parameter that determines the cellular selectivity of hormonal response.
Loss of protein stability and function caused by P228L variation in NADPH-cytochrome P450 reductase linked to lower testosterone levels
Authors: Velazquez Maria Natalia Rojas , Noebauer Mathias , Pandey Amit V. 
Published: August 2022

AbstractCytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolizing cytochromes P450 located in the endoplasmic reticulum. Mutations in POR cause a broad range of metabolic disorders. The POR variant rs17853284 (P228L) identified by genome sequencing has been linked to lower testosterone levels and reduced P450 activities. We expressed POR wild type and the P228L variant in bacteria, purified the proteins, and performed protein stability and catalytic functional studies. Variant P228L affected the stability of the protein as evidenced by lower unfolding temperatures and higher sensitivity to urea denaturation. A significant reduction of model electron acceptors was observed with POR P228L while activities of CYP3A4 were reduced by 25%, and activities of CYP3A5, and CYP2C9 were reduced by more than 40% compared to WT POR. The 17,20 lyase activity of CYP17A1 responsible for production of main androgen precursor dehydroepiandrosterone, was reduced to 27% of WT in presence of P228L variant of POR. Based on in silico and in vitro studies we predict that the change of proline to leucine may change the rigidity of the protein, causing conformational changes in POR, leading to altered electron transfer to redox partners. A single amino acid change can affect protein stability and cause a severe reduction in POR activity. Molecular characterization of individual POR mutations is crucial for a better understanding of the impact on different redox partners of POR.
Elucidating the unknown transcriptional responses and PHR1 mediated biotic and abiotic stress tolerance during phosphorus-limitation
Authors: Scheible Wolf-Rűdiger , Pandey-Pant Pooja , Pant Bikram D. , Krom Nick , Allen Randy D. , Mysore Kirankumar S. 
Published: August 2022

AbstractPhosphorus (P) limitation in the majority of world soils is a major constraint for plant growth and crop productivity. RNA sequencing was used to discover novel P-responsive gene transcripts (PRGT) in leaves and roots of Arabidopsis. Hisat StringTie and Cufflinks TopHat transcript assembler were used to analyze reads and identify 1,074 PRGTs with a >5-fold altered abundance during P-limitation. Interestingly, 60% of these transcripts were not previously reported. Among the novel PRGT, 106 were from unannotated genes, and some were among the most P-responsive, includingAt2g36727which encodes a novel microRNA. Annotated novel PRGTs encode for transcription factors, microRNAs, small signaling peptides, long non-coding RNAs, defense-related proteins, and transporters, along with proteins involved in many biological processes. We identified several genes that undergo alternative splicing during P-limitation, including a novelmiR399resistant splice variant ofPHOSPHATE2(PHO2.2). Several novel P-responsive genes were regulated byPHOSPHATE STARVATION RESPONSE1(PHR1),PHR1-LIKE 1(PHL1) andPHO2. We discovered that P-limited plants show increased resistance to pathogens and drought stress mediated by PHR1-PHL1. Identification of novel P-responsive transcripts and the discovery of the influence of P-limitation on biotic and abiotic stress adds a significant component to our understanding of plant P-signaling.HighlightPhosphorus limitation elicits the expression of several novel genes including many previously unannotated genes, noncoding RNAs, small peptides and alternatively spliced RNAs, and leads to enhanced disease and drought tolerance.
Deep learning for satellite image forecasting of vegetation greenness
Authors: Kladny Klaus-Rudolf , Milanta Marco , Mraz Oto , Hufkens Koen , Stocker Benjamin D. 
Published: August 2022

AbstractThe advent of abundant Earth observation data enables the development of novel predictive methods for forecasting climate impacts on the state and health of terrestrial ecosystems. Here, we target the spatial and temporal variations of land surface reflectance and vegetation greenness, measuring the density of green vegetation and active foliage area, conditioned on current and past climate and the local topography. We train two alternative recurrent deep learning models that rely on convolutional layers for forecasting the spatially resolved deviation of surface reflectance across a heterogeneous landscape from a specified initial state (Baseline Framework). We demonstrate efficiency of the Baseline Framework with respect to training convergence speed. Using data from diverse ecosystems and land cover types across Europe and following a standardized model evaluation framework (EarthNet2021 Challenge), results indicate increased performance in predicting surface greenness during drought events of the models presented here, compared to currently published benchmarks. Our results demonstrate how deep learning methods enable early-warning of vegetation responses to the impacts of climatic extreme events, such as the drought-related loss of green foliage.
Non-invasive fecal DNA yields whole genome and metagenomic data for species conservation
Authors: de Flamingh A. , Ishida Y. , Pečnerová P. , Vilchis S. , Siegismund H.R. , van Aarde R.J. , Malhi R.S. , Roca A.L. 
Published: August 2022

AbstractNon-invasive biological samples benefit studies that investigate rare, elusive, endangered, and/or dangerous species. Integrating genomic techniques that use non-invasive biological samples with advances in computational approaches can benefit and inform wildlife conservation and management. Here we present a molecular pipeline that uses non-invasive fecal DNA samples to generate low- to medium-coverage genomes (e.g., >90% of the complete nuclear genome at 6X coverage) and metagenomic sequences, combining in a novel fashion widely available and accessible DNA collection cards with commonly used DNA extraction and library building approaches. DNA preservation cards are easy to transport and can be stored non-refrigerated, avoiding cumbersome and/or costly sample methods. The genomic library construction and shotgun sequencing approach did not require enrichment or targeted DNA amplification. The utility and potential of the data generated by this pipeline was demonstrated by the application of genome-scale analysis and metagenomics to zoo and free-ranging African savanna elephants (Loxodonta africana). Fecal samples collected from free-ranging individuals contained an average of 12.41% (5.54-21.65%) endogenous elephant DNA. Clustering of these elephants with others from the same geographic region was demonstrated by a principal component analysis of genetic variation using nuclear genome-wide SNPs. Metagenomic analyses generated compositional taxon classifications that included Loxodonta, green plants, fungi, arthropods, bacteria, viruses and archaea, showcasing the utility of our approach for addressing complementary questions based on host-associated DNA, e.g., pathogen and parasite identification. The molecular pipeline presented here extends applications beyond what has previously been shown for target-enriched datasets and contributes towards the expansion and application of genomic techniques to conservation science and practice.
The Hydroxyproline O-arabinosyltransferase FIN4 is required for tomato pollen intine development
Authors: Jaffri Syeda Roop Fatima , Scheer Holly , MacAlister Cora A. 
Published: August 2022

AbstractThe pollen grain cell wall is a highly specialized structure composed of distinct layers formed through complex developmental pathways. The production of the innermost intine layer, composed of cellulose, pectin and other polymers, is particularly poorly understood. Here we demonstrate an important and specific role for the hydroxyproline O-arabinosyltransferase (HPAT) FIN4 in tomato intine development. HPATs are plant-specific enzymes which initiate glycosylation of certain cell wall structural proteins and signaling peptides. FIN4 was expressed throughout pollen development in both the developing pollen and surrounding tapetal cells. A fin4 mutant with a partial deletion of the catalytic domain displayed significantly reduced male fertility in vivo and compromised pollen hydration and germination in vitro. However, fin4 pollen that successfully germinated formed morphologically normal pollen tubes with the same growth rate as the wild-type pollen. When we examined mature fin4 pollen, we found they were cytologically normal, and formed morphologically normal exine, but produced significantly thinner intine. During intine deposition at the late stages of pollen development we found fin4 pollen had altered polymer deposition, including reduced cellulose and increased detection of pectin, specifically homogalacturonan with both low and high degrees of methylesterification. Therefore, FIN4 plays an important role in intine formation and, in turn pollen hydration and germination and the process of intine formation involves dynamic changes in the developing pollen cell wall.
High-dimensional profiling of pediatric immune responses to solid organ transplantation
Authors: Rao Mahil , Amouzgar Meelad , Harden James T. , Lapasaran M. Gay , Trickey Amber , Armstrong Brian , Odim Jonah , Debnam Tracia , Esquivel Carlos O. , Bendall Sean C. , Martinez Olivia M. , Krams Sheri M. 
Published: August 2022

AbstractSolid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼25% of allograft recipients experience acute rejection within the first 12 months after transplant. Our ability to detect rejection early and to develop less toxic immunosuppressive agents is hampered by an incomplete understanding of the immune changes associated with rejection, particularly in the pediatric population. Here we used high-dimensional single-cell proteomic technologies (CyTOF) to generate the first detailed, multi-lineage analysis of the peripheral blood immune composition of pediatric solid organ transplant recipients. We report that the organ transplanted impacts the immune composition post-transplant. When taking these allograft-specific differences into account, we further observed that differences in the proportion of subsets of CD8 and CD4 T cells were significantly associated with allograft health. Together, these data form the basis for mechanistic studies into the pathobiology of rejection to develop less invasive tools to identify early rejection and new immunosuppressive agents with greater specificity and less toxicity.