bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact on mental health of young Asian Americans due to acts of discrimination and hate crimes during COVID-19
Authors: Gawash Ahmed , Lo David F. , Nghiem Brianna , Rofail Priscilla , Basu Sayan 
Published: January 2023

AbstractThis article is an examination of the acts of discriminiation and hate crimes against the Asian American community and how their mental health has been impacted. The historical examination of acts against the Asian American community stem from acts against the Asian American community during both the yellow peril and the Roosevelt Era. Alongside current day institutionalized policies that are propagated by the media, the resurrection of historical tropes further act to seclude Asian Americans from mainstream society. These acts of seclusion further drive mental health inequality in Asian American society that include, but are not limited to: anxiety, depression, and psychological stress. These mental health inequalities are further subdivided into different ethnic groups that worsen as data is collected from older generations. More recently, COVID-19 has brought forth an upsurge in hate crimes that has only worsened the ability of Asian American youth to fully develop a racial identity; the upsurge in hate crimes is also coupled with invalidation of interethnic differences and invalidation of their discriminatory experiences. The synthesis of current day research will aid in the understanding of the mental health inequality in the Asian American community and aid in further studies that can address these plights.Purpose StatementThe purpose of this paper is to investigate how acts of discrimination and hate crimes against the Asian community have impacted the mental health of young Asian Americans. This review seeks to explore the many effects of race-based discrimiation specifically for Asian Americans during and after the COVID-19 (coronavirus pandemic) such as: general feelings of inclusivity, physiological responses as a result of increasing racist encounters, and incidences of mental health experiences. Overall, the paper highlights how these characteristics manifest within the Asian American population and what measures and interventions can be done to protect Asian American from the negative consequences of hate.
Solving the Variable-Particle Size Quandary of Bone Mills. Development of an Automated Milling System to Generate Graft Particles of Definite Sizes
Authors: Chandra R Viswa 
Published: January 2023

ABSTRACTThere are situations where block grafts have to be milled to convert them into particulate grafts of definite sizes. The objectives of this study were to evaluate the quality of graft particles generated in two sizes from a custom-built automated milling system (AMS) and their biocompatibility in an animal model. A Monetite block was milled in an AMS to generate small (SS group; 0.5-0.8 mm) and medium size (MS group; 1.0-1.2 mm) particles. Measures of particle count, Feret’s diameter (dF), particle distribution and size were recorded. Biocompatibility of particles was tested in a rabbit tibial defect model. The average particle size was significantly smaller in the SS group than the MS group (0.68±0.39vs1.10±0. 79 mm;p≤0.001). There were significant to highly significant differences between SS and MS groups in measures of particle count (p≤0.001), dF(p=0.02)and size (p≤0.001). SS and MS groups had maximum percentage of particles in the 0.6-1mm (71%) and >1mm (70%) ranges respectively. The mineralized tissue volumes across SS, MS when compared to an autogenous block were 68.92±35.66%, 66.29±29.21% and 89.83±19.91% (p=0.003)respectively. The device was able to generate small and medium-size graft particles which were distinct from each other.
Structural insights into ligand-recognition, activation, and signaling-bias at the complement C5a receptor, C5aR1
Authors: Saha Shirsha , Maharana Jagannath , Yadav Manish K. , Sarma Parishmita , Singh Vinay , Mohapatra Samanwita , Soni Chahat , Saha Sayantan , Mishra Sudha , Ganguly Manisankar , Chami Mohamed , Banerjee Ramanuj , Shukla Arun K. 
Published: January 2023

AbstractActivation of the complement cascade is a critical part of our innate immune response against invading pathogens, and it operates in a concerted fashion with the antibodies and phagocytic cells towards the clearance of pathogens. The complement peptide C5a, generated during the activation of complement cascade, is a potent inflammatory molecule, and increased levels of C5a are implicated in multiple inflammatory disorders including the advanced stages of COVID-19 pathophysiology. The proximal step in C5a-mediated cellular and physiological responses is its interaction with two different seven transmembrane receptors (7TMRs) known as C5aR1 and C5aR2. Despite a large body of functional data on C5a-C5aR1 interaction, direct visualization of their interaction at high-resolution is still lacking, and it represents a significant knowledge gap in our current understanding of complement receptor activation and signaling. Here, we present cryo-EM structures of C5aR1 activated by its natural agonist C5a, and a G-protein-biased synthetic peptide ligand C5apep, in complex with heterotrimeric G-proteins. The C5a-C5aR1 structure reveals the ligand binding interface involving the N-terminus and extracellular loops of the receptor, and we observe that C5a exhibits a significant conformational change upon its interaction with the receptor compared to the basal conformation. On the other hand, the structural details of C5apep-C5aR1 complex provide a molecular basis to rationalize the ability of peptides, designed based on the carboxyl-terminus sequence of C5a, to act as potent agonists of the receptor, and also the mechanism underlying their biased agonism. In addition, these structural snapshots also reveal activation-associated conformational changes in C5aR1 including outward movement of TM6 and a dramatic rotation of helix 8, and the interaction interface for G-protein-coupling. In summary, this study provides previously lacking molecular basis for the complement C5a recognition and activation of C5aR1, and it should facilitate structure-based discovery of novel lead molecules to target C5aR1 in inflammatory disorders.
HLA allele-calling using whole-exome sequencing identifies 129 novel associations in 11 autoimmune diseases: a multi-ancestry analysis in the UK Biobank
Authors: Butler-Laporte Guillaume , Farjoun Joseph , Nakanishi Tomoko , Lu Tianyuan , Abner Erik , Chen Yiheng , Hultström Michael , Metspalu Andres , Milani Lili , Mägi Reedik , Nelis Mari , Hudjashov Georgi ,   Estonian Biobank Research Team, Yoshiji Satoshi , Ilboudo Yann , Liang Kevin YH , Su Chen-Yang , Willet Julian DS , Esko Tõnu , Zhou Sirui , Forgetta Vincenzo , Taliun Daniel , Richards J Brent 
Published: January 2023

AbstractThe human leukocyte antigen (HLA) region on chromosome 6 is strongly associated with many immune-mediated and infection-related diseases. Due to its highly polymorphic nature and complex linkage disequilibrium patterns, traditional genetic association studies of single nucleotide polymorphisms (SNPs) do not perform well in this region. Instead, the field has adopted the assessment of the association of HLA alleles (i.e., entire HLA gene haplotypes) with disease. Often based on genotyping arrays, these association studies impute HLA alleles, decreasing accuracy and thus statistical power for rare alleles and in non-European ancestries. Here, we use whole-exome sequencing (WES) from 454,824 UK Biobank participants to directly call HLA alleles using the HLA- HD algorithm. We show this method is more accurate than imputing HLA alleles and harness the improved statistical power to identify 360 associations for 11 auto-immune phenotypes (at least 129 likely novel), leading to better insights into the specific coding polymorphisms that underlie these diseases. We show that HLA alleles with synonymous variants, often overlooked in HLA studies, can significantly influence these phenotypes. Lastly, we show that HLA sequencing may improve polygenic risk scores accuracy across ancestries. These findings allow better characterization of the role of the HLA region in human disease.
T492I mutation alters SARS-CoV-2 properties via modulating viral non-structural proteins
Authors: Lin Xiaoyuan , Sha Zhou , Trimpert Jakob , Kunec Dusan , Jiang Chen , Xiong Yan , Xu BinBin , Zhu Zhenglin , Xue Weiwei , Wu Haibo 
Published: January 2023

ABSTRACTThe historically dominant SARS-CoV-2 Delta variants and the currently dominant Omicron variants carry a T492I substitution within the non-structural protein 4 (NSP4). Based on a combination ofin silicoanalyses, we predicted that the T492I mutation increases the transmissibility and adaptability of the virus. We confirmed this hypothesis by performing competition experiments in hamsters and in human airway tissue culture models. Furthermore, we show that the T492I mutation also increases the replication capacity and infectiveness of the virus, and improves its ability to evade antibody neutralization induced by previous variants. Mechanistically, the T492I mutation increases cleavage efficiency of the viral main protease NSP5 by enhancing enzyme-substrate binding, resulting in increased production of nearly all non-structural proteins processed by NSP5. Importantly, T492I mutation suppresses the viral RNA associated chemokines in monocytic macrophages, which may contribute to the attenuated pathogenicity of Omicron variants. Our results highlight the importance of the NSP4 mutation in the evolutionary dynamics of SARS-CoV-2 and identify a novel target for the development of broad-spectrum antiviral agents.
NGS method for parallel processing of high quality, damaged or fragmented input material using target enrichment
Authors: Lyander Anna , Gellerbring Anna , Hägglund Moa , Elhami Keyvan , Wirta Valtteri 
Published: January 2023

ABSTRACTNext-generation sequencing (NGS) has been increasingly popular in genomics studies over the last decade and is now commonly used in clinical applications for precision diagnostics. Many disease areas typically involve different kinds of sample specimens, sample qualities and quantities. The quality of the DNA can range from intact, high molecular weight molecules to degraded, damaged and very short molecules. The differences in quality and quantity pose challenges for downstream molecular analyses. To overcome the challenge with the need of different molecular methods for different types of samples, we have developed a joint procedure for preparing enriched DNA libraries from high molecular weight DNA and DNA from formalin-fixed, paraffin-embedded tissue, fresh frozen tissue material, as well as cell-free DNA.
Nucleoside Diphosphate Kinases 1 and 2 regulate a protective liver response to a high-fat diet
Authors: Iuso Domenico , Garcia-Saez Isabel , Couté Yohann , Yamaryo-Botté Yoshiki , Erba Elisabetta Boeri , Adrait Annie , Zeaiter Nour , Tokarska-Schlattner Malgorzata , Jilkova Zuzana Macek , Boussouar Fayçal , Barral Sophie , Signor Luca , Couturier Karine , Hajmirza Azadeh , Chuffart Florent , Vitte Anne-Laure , Bargier Lisa , Puthier Denis , Decaens Thomas , Rousseaux Sophie , Botté Cyrille , Schlattner Uwe , Petosa Carlo , Khochbin Saadi 
Published: January 2023

SUMMARYDe novolipogenesis (DNL), the process whereby cells synthesize fatty acids from acetyl-coenzyme A (acetyl-CoA), is deregulated in diverse pathologies, including cancer. Here we report that DNL is negatively regulated by Nucleoside Diphosphate Kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently discovered to bind co-enzyme A (CoA). We show that NME1 additionally binds acetyl-CoA and that ligand recognition involves a unique binding mode dependent on the CoA/acetyl-CoA 3’ phosphate. We report thatNme2knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells NME2 mediates a gene transcriptional response to HFD leading to DNL repression and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling acetyl-CoA usage between the competing paths of histone acetylation and DNL.
Thor-Ribo-Seq: ribosome profiling tailored for low input with RNA-dependent RNA amplification
Authors: Mito Mari , Shichino Yuichi , Iwasaki Shintaro 
Published: January 2023

AbstractTranslation regulation plays a pivotal role in the diversification of gene expression and the response to intra- and extracellular environmental cues. Ribosome profiling (or Ribo-Seq) serves as a sensitive, quantitative, comprehensive, and data-rich technique to survey ribosome traversal across the cellular transcriptome. However, due to the intricacy of library preparation, applications to low input have presented analytic challenges. To overcome this issue, here we developed Thor-Ribo-Seq, a ribosome profiling method tailored for low input. Thor-Ribo-Seq harnesses RNA-templated RNA transcription to linearly amplify ribosome footprints, assessing ribosome traversal at codon resolution with limited artifacts. This highly sensitized ribosome profiling approach provides a versatile option to investigate the translatome in precious samples.
Linear versus Nonlinear Muscle Networks: A Case Study to Decode Hidden Synergistic Patterns During Dynamic Lower-limb Tasks
Authors: O’Keeffe Rory , Rathod Vaibhavi , Shirazi Seyed Yahya , Mehrdad Sarmad , Edwards Alexis , Rao Smita , Atashzar S. Farokh 
Published: January 2023

AbstractThis paper, for the first time, compares the behaviors of nonlinear versus linear muscle networks in decoding hidden peripheral synergistic neural patterns during dynamic functional tasks. In this paper, we report a case study during which one healthy subject conducts a series of four lower limb repetitive tasks. Specifically, the paper focuses on tasks that involve the right knee joint, including walking, sit-tostand, stepping, and drop-jump. Twelve muscles were recorded using the Delsys Trigno system. The linear muscle network was generated using coherence analysis, and the nonlinear network was generated using Spearman’s correlation. The results show that the degree, clustering coefficient, and global efficiency of the muscle network have the highest value among tasks in the linear domain for the walking task, while a low linear synergistic network behavior for the sit-to-stand is observed. On the other hand, the results show that the nonlinear functional muscle network decodes high connectivity (degree) and clustering coefficient and efficiency for the sit-tostand when compared with other tasks. We have also developed a two-dimensional functional connectivity plane composed of linear and nonlinear features and shown that it can span the lower-limb dynamic task space. The results of this paper for the first time highlight the importance of observing both linear and nonlinear connectivity patterns, especially for complex dynamic tasks. It should also be noted that through a simultaneous EEG recording (using BrainVision System), we have shown that, indeed, cortical activity may indirectly explain highly-connected nonlinear muscle network for the sit-to-stand task, highlighting the importance of nonlinear muscle network as a neurophysiological window of observation beyond the periphery.
Acute Kidney Injury, the Present on Admission indicator (POA) and sex disparities: Observational study of inpatient real world data in a Swiss tertiary health care system
Authors: Triep Karen , Musy Sarah , Simon Michael , Endrich Olga 
Published: January 2023

AbstractBackgroundRegarding kidney disease, sex differences in epidemiology and clinical relevance have been reported. Related to absolute and relative changes of baseline creatinine, different criteria for staging may induce under-or over-diagnosis related to sex. At the largest Swiss provider of inpatient acute health care, a clinic decision support algorithm ensures exact staging of kidney disease (2012 KDIGO Clinical Practice Guideline). Coding of the indicator “Present On Admission” was introduced at this institution in 2018 to flag post-admission conditions.ObjectiveWe hypothesized sex differences in health care associated acute kidney injury. Defined indicators and the distribution of stages in acute kidney injury were analysed using the POA flag. Sex differences were reported.MethodsRetrospective observational study. Routinely collected health data, Insel Group, Berne, Switzerland, 2019 and 2020 (121’757 cases) on the patient history and intensive care treatment duration, comorbidity levels, coded diagnoses, age and sex. Software and statistic: program R, version 4.1.1, standard deviation; median, interquartile range; prop.test; standardized mean difference.ResultsThe reporting of post-admission diagnoses was associated with more interhospital transfers, intensive care stays, scores of severity and treatment intensity, mechanical ventilation, age, number of diagnoses, complexity level of the related cases and mortality. A weaker association could be observed for the female population. However, mortality was higher (stage III acute kidney injury 41.6%).ConclusionUsing the POA-flag the results reflect the clinical situation of complications and comorbidities evolving unexpectedly. As our results show sex differences, i.e. a lower morbidity of female patients for each stage, but a higher mortality, a deeper evaluation of the implied sex differences in staging of kidney disease should follow.The general results confirm the necessity of a diagnosis-onset reporting in health statistic.
Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: a population-based cohort study in UK Biobank
Authors: Zhang Yuchen , Sun Yitang , Yu Qi , Song Suhang , Brenna J. Thomas , Shen Ye , Ye Kaixiong 
Published: January 2023

AbstractBackgroundCirculating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.MethodsWe investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6,461 died during follow-up, including 2,794 from cancer and 1,668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.ResultsRisk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend< 0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15-38%) higher total mortality, 14% (95% CI, 0-31%) higher cancer mortality, and 31% (95% CI, 10-55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.ConclusionsUsing a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Prediction of Long COVID Based on Severity of Initial COVID-19 Infection: Differences in predictive feature sets between hospitalized versus non-hospitalized index infections
Authors: Socia Damien , Larie Dale , Feuerwerker Sol , An Gary , Cockrell Chase 
Published: January 2023

AbstractLong COVID is recognized as a significant consequence of SARS-COV2 infection. While the pathogenesis of Long COVID is still a subject of extensive investigation, there is considerable potential benefit in being able to predict which patients will develop Long COVID. We hypothesize that there would be distinct differences in the prediction of Long COVID based on the severity of the index infection, and use whether the index infection required hospitalization or not as a proxy for developing predictive models. We divide a large population of COVID patients drawn from the United States National Institutes of Health (NIH) National COVID Cohort Collaborative (N3C) Data Enclave Repository into two cohorts based on the severity of their initial COVID-19 illness and correspondingly trained two machine learning models: the Long COVID after Severe Disease Model (LCaSDM) and the Long COVID after Mild Disease Model (LCaMDM). The resulting models performed well on internal validation/testing, with a F1 score of 0.94 for the LCaSDM and 0.82 for the LCaMDM. There were distinct differences in the top 10 features used by each model, possibly reflecting the differences in type and amount of pathophysiological data between the hospitalized and non-hospitalized patients and/or reflecting different pathophysiological trajectories in the development of Long COVID. Of particular interest was the importance of Plant Hardiness Zone in the feature set for the LCaMDM, which may point to a role of climate and/or sunlight in the progression to Long COVID. Future work will involve a more detailed investigation of the potential role of climate and sunlight, as well as refinement of the predictive models as Long COVID becomes increasingly parsed into distinct clinical phenotypes.
Specificity Guides Interpretation: On H3K4 Methylation at Enhancers and Broad Promoters
Authors: Shah Rohan N. , Ruthenburg Alexander J. 
Published: January 2023

AbstractIn 2018, we used internally calibrated chromatin immunoprecipitation (ICeChIP) to find that many of the most commonly used antibodies against H3K4 methylforms had significant off-target binding, which compromised the findings of at least eight literature paradigms that used these antibodies for ChIP-seq (Shah et al., 2018). In many cases, we were able to recapitulate the prior findings in K562 cells with the original, low-quality antibody, only to find that the models did not hold up to scrutiny with highly specific reagents and quantitative calibration.In a recent preprint originally prepared as a Letter to the Editor of Molecular Cell, though they agree with our overarching conclusions, Pekowska and colleagues take issue with analyses presented for two relatively minor points of the paper (Pekowska et al., 2023). We are puzzled by the assertion that these two points constitute the “bulk” of our findings, nor is it clear which components of our “analytical design” they find problematic. We feel their critique, however mild, is misguided.