bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating shared genetic architecture between obesity and multiple sclerosis
Authors: Zeng Ruijie , Jiang Rui , Huang Wentao , Wang Jiaxuan , Zhang Lijun , Ma Yuying , Wu Yanjun , Meng Meijun , Leung Felix W , Lian Qizhou , Sha Weihong , Chen Hao 
Published: December 2022

AbstractBackground and aimsObservational studies have suggested a complex relationship between obesity and multiple sclerosis (MS). However, the role of genetic factors in the comorbidity and whether obesity exist consistent shared genetic relationships with MS, remains unclear. Our study aims to investigate the extent of shared genetic architecture underlying obesity and MS.MethodsBased on genome-wide association studies (GWAS) summary statistics, we investigate the genetic correlation by the linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). The casualty was identified by using bidirectional Mendelian randomization. Linkage disequilibrium score regression in specifically expressed genes (LDSC-SEG) and multi-marker analysis of GenoMic annotation (MAGMA) were utilized to investigate single-nucleotide polymorphisms (SNP) enrichment in the tissue and cell-type levels. We then identified shared risk SNPs using cross-trait meta-analyses and Heritability Estimation from Summary Statistics (ρ-HESS). We further explore the potential functional genes for BMI and MS using summary-data-based Mendelian randomization (SMR).ResultWe found significantly positive genetic correlation and 18 novel shared genetic SNPs were identified in cross-trait meta-analyses. We found the causality of BMI on MS using Mendelian randomization, but slight inconsistent evidence for the causality of MS on BMI. We observed tissue-specific level SNP heritability enrichment for BMI in 9 tissues and MS in 4 tissues, and in cell-type-specific level SNP heritability enrichment 12 consistent cell types were identified for BMI and MS in brain, spleen, lung and whole blood.ConclusionOur study identifies the genetical correlation and shared risk SNPs between BMI and MS. These findings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trials.
Sample average treatment effect on the treated analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma
Authors: Mitra Amit Kumar , Mukherjee Ujjal Kumar , Mazumder Suman , Madhira Vithal , Bergquist Timothy , Shao Yu Raymond , Liu Feifan , Song Qianqian , Su Jing , Kumar Shaji , Bates Benjamin A. , Sharafeldin Noha , Topaloglu Umit 
Published: December 2022

AbstractPatients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS’ National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date).Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the propensity score matching (PSM) method.As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma.To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.
Genetic modification of inflammation and clonal hematopoiesis-associated cardiovascular risk
Authors: Yu Zhi , Fidler Trevor P. , Ruan Yunfeng , Vlasschaert Caitlyn , Nakao Tetsushi , Uddin Md Mesbah , Mack Taralynn , Niroula Abhishek , Heimlich J. Brett , Zekavat Seyedeh M. , Gibson Christopher J. , Griffin Gabriel K. , Wang Yuxuan , Peloso Gina M. , Heard-Costa Nancy , Levy Daniel , Vasan Ramachandran S. , Aguet François , Ardlie Kristin , Taylor Kent D. , Rich Stephen S. , Rotter Jerome I. , Libby Peter , Jaiswal Siddhartha , Ebert Benjamin L. , Bick Alexander G. , Tall Alan R. , Natarajan Pradeep 
Published: December 2022

AbstractClonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data of blood DNA and modeled both as a composite and for common drivers (DNMT3A,TET2,ASXL1,andJAK2) separately. We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identifyIL1RAPas a potential key molecule for CHIP-associated CVD risk across genes and increasedAIM2gene expression leading to heightenedJAK2- andASXL1-associated CVD risks. We show that CRISPR- inducedAsxl1mutated murine macrophages have a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVD protective effect ofIL10expression inASXL1CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides new evidence to support gene-specific strategies to address CHIP-associated CVD risk.
A multi-parameter optimization in middle-down analysis of monoclonal antibodies by LC-MS/MS
Authors: Dhenin Jonathan , Dupré Mathieu , Druart Karen , Krick Alain , Mauriac Christine , Chamot-Rooke Julia 
Published: December 2022

ABSTRACTIn antibody-based drug research, regulatory agencies request a complete characterization of antibody proteoforms covering both the amino acid sequence and all post-translational modifications. The usual mass spectrometry-based approach to achieve this goal is bottom-up proteomics, which relies on the digestion of antibodies, but does not allow the diversity of proteoforms to be assessed. Middle-down and top-down approaches have recently emerged as attractive alternatives but are not yet mastered and thus used in routine by many analytical chemistry laboratories. The work described here aims at providing guidelines to achieve the best sequence coverage for the fragmentation of intact light and heavy chains generated from a simple reduction of intact antibodies using Orbitrap mass spectrometry. Three parameters were found crucial to this aim: the use of an electron-based activation technique, the multiplex selection of precursor ions of different charge states and the combination of replicates.
Cell type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behaviour in fragile X syndrome model mice
Authors: Longo Francesco , Aryal Sameer , Anastasiades Paul , Maltese Marta , Baimel Corey , Albanese Federica , Tabor Joanna , Zhu Jeffrey D , Oliveira Mauricio M , Gastaldo Denise , Bagni Claudia , Santini Emanuela , Tritsch Nicolas X , Carter Adam G , Klann Eric 
Published: December 2022

SummaryIndividuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviours (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissected the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. We found that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum revealed differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings represent the first evidence of a cell-type specific impact of the loss of FMRP on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS.HighlightsDysregulated striatal protein synthesis underlies altered synaptic plasticity and RRBs displayed by FXS model miceFXS model mice exhibit cell type-specific molecular, morphological, and synaptic changes in the dorsolateral striatumSelective deletion ofFmr1from dSNPs in mice alters translation and causes repetitive behaviorTRAP-Seq indicates that there is altered binding of >120 mRNAs to ribosomes in dSNPs ofFmr1KO miceG-protein signaling (RGS) 4 translation is significantly reduced in dSPNs in FXS model miceTreatment of FXS model mice with VU0152100, a positive allosteric modulator of the M4 muscarinic receptor that is upstream of RGS4, can reverse RRBs
Microbiome, resistome and mobilome of chlorine-free drinking water treatment systems
Authors: Calderón-Franco David , Corbera-Rubio Francesc , Cuesta-Sanz Marcos , Pieterse Brent , de Ridder David , van Loosdrecht Mark C. M. , van Halem Doris , Laureni Michele , Weissbrodt David G. 
Published: December 2022

ABSTRACTDrinking water treatment plants (DWTPs) are designed to remove physical, chemical, and biological contaminants. However, until recently, the role of DWTPs in minimizing the cycling of antibiotic resistance determinants has got limited attention. In particular, the risk of selecting antibiotic-resistant bacteria (ARB) is largely overlooked in chlorine-free DWTPs where biological processes are applied. Here, we combined high-throughput quantitative PCR and metagenomics to analyze the abundance and dynamics of microbial communities, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) across the treatment trains of two chlorine-free DWTPs involving dune-based and reservoir-based systems. The microbial diversity of the water being treated increased after all biological unit operations, namely rapid and slow sand filtration (SSF), and granular activated carbon filtration. Both DWTPs reduced the concentration of ARGs and MGEs in the water by about 2.5 log gene copies mL-1, despite their relative increase in the disinfection sub-units (SSF in dune-based and UV treatment in reservoir-based DWTPs). The total microbial concentration was also reduced (2.5 log units), and none of the DWTPs were enriched for antibiotic resistant bacteria. Our findings highlight the effectiveness of chlorine-free DWTPs in supplying safe drinking water while reducing the concentration of antibiotic resistance determinants. To the best of our knowledge, this is the first study that monitors the presence and dynamics of antibiotic resistance determinants in chlorine-free DWTPs.
Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants
Authors: Vaid Roshan , Mendez Akram , Thombare Ketan , Burgos-Panadero Rebeca , Robinot Rémy , Fonseca Barbara F , Gandasi Nikhil R , Ringlander Johan , Baig Mohammad Hassan , Dong Jae-June , Cho Jae Yong , Reinius Björn , Chakrabarti Lisa A , Nystrom Kristina , Mondal Tanmoy 
Published: December 2022

ABSTRACTHost-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics.N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers and erasers. We found that infection with SARS-CoV-2 variants caused a loss of m6A in cellular RNAs, whereas m6A was detected abundantly in viral RNA. METTL3, the m6A methyltransferase, showed an unusual cytoplasmic localization post-infection. The B.1.351 variant had a less pronounced effect on METTL3 localization and loss of m6A than the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2 infected cells. Further, transcripts with m6A modification were preferentially down-regulated post-infection. Inhibition of the export protein XPO1 resulted in the restoration of METTL3 localization, recovery of m6A on cellular RNA, and increased mRNA expression. Stress granule formation, which was compromised by SARS-CoV-2 infection, was restored by XPO1 inhibition and accompanied by a reduced viral infectionin vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m6A-dependent manner.
Quantifying Drift-Fitness Balance Using an Agent-Based Biofilm Model of Identical Heterotrophs Under Low Nutrient Conditions
Authors: Weaver Joseph Earl 
Published: December 2022

AbstractBoth deterministic and stochastic forces shape biofilm communities, but the balance between those forces is variable. Quantifying the balance is both desirable and challenging. For example, negative drift selection, a stochastic force, can be thought of as an organism experiencing ‘bad luck’ and manipulating ‘luck’ as a factor in real world systems is difficult. We used an agent-based model to manipulate luck by controlling seed values governing random number generation. We determined which organism among identical competitors experienced the greatest negative drift selection, gave it a deterministic growth advantage, and re-ran the simulation with the same seed. This enabled quantifying the growth advantage required to overcome drift,e.g., a 50% chance to thrive may require a 10-20% improved growth rate. Further, we found that crowding intensity affected that balance. At moderate spacings, there were wide ranges where neither drift nor growth dominated. Those ranges shrank at extreme spacings; close and loose crowding respectively favoured drift and growth. We explain how these results may partially illuminate two conundrums: the difference between taxa and functional stability in wastewater treatment plans and the difference between equivalent and total community size in neutral community assembly models.
Proposed three-phenylalanine motif involved in magnetoreception signaling of an Actinopterygii protein expressed in mammalian cells
Authors: Ricker Brianna , Mitra Sunayana , Castellanos E. Alejandro , Grady Connor J. , Pelled Galit , Gilad Assaf A. 
Published: December 2022

SummaryStudies at the cellular and molecular level of magnetoreception – sensing and responding to magnetic fields – is a relatively new research area. As it appears that different mechanisms of magnetoreception in animals evolved from different origins, many questions about the mechanisms remain left open. Here we present new information regarding the Electromagnetic Perceptive Gene (EPG) fromKryptopterus vitreolusthat may serve as part of the foundation to understanding and applying magnetoreception. Using HaloTag coupled with fluorescent ligands and phosphatidylinositol specific phospholipase C (PI-PLC) we show that EPG is associated to the membrane via glycosylphosphatidylinositol (GPI) anchor. EPG’s function of increasing intracellular calcium was also used to generate an assay using GCaMP6m to observe the function of EPG and to compare its function with homologous proteins. It was also revealed that EPG relies on a motif of three phenylalanine residues in order to function – stably swapping these residues using site directed mutagenesis resulted in a loss of function in EPG. This information not only expands upon our current understanding of magnetoreception but may provide a foundation and template to continue characterizing and discovering more within the field.Graphical AbstractIn BriefEPG is a magnetoreceptive GPI anchored protein. Critical to its function is a three-phenylalanine motif which allows EPG to sense and respond to EMF. When expressed in mammalian cell, an increase in intracellular calcium is observed using GCaMP6m. This work represents progress towards understanding magnetoreception for use in future technologies.HighlightsEPG is associated to the cell membrane via glycosylphosphatidylinositol anchoringIn mammalian cells, EPG increases intracellular calcium upon EMF stimulationHomologs of EPG from the uPAR/Ly6 family show different responses to EMFA three-phenylalanine motif in EPG is critical to its magnetoreceptive ability
Biochemistry-informed design selects potent siRNAs against SARS-CoV-2
Authors: Houbron Élisabeth , Mockly Sophie , Rafasse Sophia , Gros Nathalie , Muriaux Delphine , Seitz Hervé 
Published: December 2022

ABSTRACTRNA interference (RNAi) offers an efficient way to repress genes of interest, and it is widely used in research settings. Clinical applications emerged more recently, with 5 approved siRNAs (the RNA guides of the RNAi effector complex) against human diseases. The development of siRNAs against the SARS-CoV-2 virus could therefore provide the basis of novel COVID-19 treatments, while being easily adaptable to future variants or to other, unrelated viruses. Because the biochemistry of RNAi is very precisely described, it is now possible to design siRNAs with high predicted activity and specificity using only computational tools. While previous siRNA design algorithms tended to rely on simplistic strategies (raising fully complementary siRNAs against targets of interest), our approach uses the most up-to-date mechanistic description of RNAi to allow mismatches at tolerable positions and to force them at beneficial positions, while optimizing siRNA duplex asymmetry. Our pipeline proposes 8 siRNAs against SARS-CoV-2, andex vivoassessment confirms the high antiviral activity of 6 out of 8 siRNAs, also achieving excellent variant coverage (with several 3-siRNA combinations recognizing each correctly-sequenced variant as of September 2022). Our approach is easily generalizable to other viruses as long as a variant genome database is available. With siRNA delivery procedures being currently improved, RNAi could therefore become an efficient and versatile antiviral therapeutic strategy.
Better understanding of technology effects in adoption of predictive supply chain business analytics among SMEs: fresh insights from developing countries
Authors: AL-Shboul Moh'd Anwer 
Published: December 2022

PurposeThis study contributes to the supply chain management (SCM) literature differently. It offers insightful information about the use and adoption of technologies for small and medium-sized enterprises (SMEs) in developing countries. Some challenges regarding the predictive supply chain business analytics (SCBA) tools and their prediction remain unexplored and require addressing and examination in developing economies. Therefore, this study examines the substantial roles of relative advantage (RA) and compatibility (Comp.) in using technology in predictive SCBA adoption among SMEs in developing countries.Design/methodology/approachThis paper performed a quantitative survey-based study to analyze the substantial role of RA and Comp. with the aim of using predictive SCBA adoption. To this end, the author conducted an online survey through which 262 SMEs from developing countries (i.e. Jordan, Kingdom of Saudi Arabia (KSA), the United Arab Emirates (UAE), Egypt, Turkey and Qatar) only responded by email.FindingsThe partial least squares structural equation modeling (PLS-SEM) clearly shows a significant relationship between RA and predictive SCBA adoption. Still, Comp. does not significantly affect the use of predictive SCBA adoption.Originality/valueSuch findings of this study can provide insightful implications for stakeholders and policymakers regarding the importance of using predictive SCBA adoption in SMEs in developing countries.
Travel behaviour differences among Indonesian youth in Generations Y and Z: pre-, during and post-travel
Authors: Damanik Janianton , Priyambodo Tri Kuntoro , Wibowo Moh Edi , Pitanatri Putu Diah Sastri , Wachyuni Suci Sandi 
Published: December 2022

Purpose
This study aims to explore the differences in the travel behaviour of Indonesian youth of Generations Y and Z in the pre-, during and post-travel stages and their associated use of information and communication technology.

Design/methodology/approach
Data were gathered through a questionnaire that was distributed via the internet for six weeks; 569 people provided their full responses. Chi-square tests and linear regression were used for data analysis.

Findings
These generations use digital media and word of mouth differently when searching for travel information. The differences are also apparent in the pre-, during and post-travel stages. Generation Z tends to use digital media and share travel experiences through a certain social media platform more frequently than Generation Y.

Research limitations/implications
This study covers the travel history prior to and during the COVID-19 pandemic and equalises the situation in these two periods. The number of samples was relatively small to capture the current population of both generations.

Practical implications
This study promotes a new understanding of the travel behaviours of the two generations based on the stages of the travel examined. The findings suggest that the travel industry can distinguish between promotional media and types of services to serve each of the generational cohorts more effectively.

Originality/value
To the best of the authors’ knowledge, this is the first study to reveal differences in travel behaviour between Generations Y and Z in Indonesia.