bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in Dietary Intake Exist Among U.S. Adults by Diabetic Status Using NHANES 2009-2016
Authors: Lin Luotao , Zhu Fengqing , Delp Edward J. , Eicher-Miller Heather A. 
Published: May 2022

AbstractObjectivesInsulin takers’ diets have rarely been described although insulin dosing is highly dependent on dietary intake. The objective of this paper was to determine the most frequently consumed food or beverage items, food subcategories, and food categories, and those that contributed most to total energy intake among U.S. insulin takers, those with type 2 diabetes (T2D) not taking insulin and those without diabetes; the groups were also compared at the broad food category level.MethodsThe Laboratory tests and questionnaires of the NHANES 2009–2016 classified 774 insulin takers, 2,758 T2D not taking insulin, and 17,796 participants without diabetes. USDA assigned 8-digit food codes identifying each food item and its membership to a category and subcategory of foods were used to categorize foods based on the WWEIA categories. Raw and weighted frequency and energy contributions of each food item, food subcategory, and food category were calculated and ranked. Comparisons among groups by broad food category used the Rao–Scott modified chi-square test.ResultsDiet soft drinks ranked as the 4th and 7th most consumed food subcategory in insulin takers and T2D not taking insulin, respectively. Soft drinks ranked as the 8th and 6th most consumed food subcategory in T2D not taking insulin and those without diabetes, and contributed 5th and 2nd most to energy, respectively. Protein foods represented 4 of the top 10 highest energy contributing food subcategories among insulin takers, 3 of the top 10 food subcategories among those with T2D not taking insulin, and only 1 subcategory among those without diabetes. Insulin takers had higher consumption frequency of grains, and lower consumption frequency of sweets and alcohol, and a larger share of energy comprising protein, vegetables, and grains, and a smaller share of energy comprising beverages and alcohol compared to participants without diabetes.ConclusionsDifferences in dietary intake exist among U.S. adults by diabetic status. Insulin takers are likely to consume more protein foods and less regular soft drinks compared to other 2 groups. Lists of the most frequently reported foods and foods contributing most to energy may be helpful for nutrition education, prescribing diets, and digital-based dietary assessment for insulin takers.
Molecular Phylogenetics of HIV-1 Subtypes in African Populations: A Case Study of Sub-Saharan African Countries
Authors: Obura Hesborn Omwandho , Mlay Clement Dastan , Moyo Lindani , Karumbo Brenda Muthoni , Omar Kauthar Mwanamkuu , Sinza Erick Masunge , Rotich Gladys Jerono , Mudaki Wilson , Kamau Brenda Muthoni , Awe Olaitan I. , Dillman Allissa 
Published: May 2022

AbstractDespite advances in antiretroviral therapy that have revolutionized HIV-1 disease management, effective control of the HIV-1 infection pandemic remains elusive. Increased HIV-1 infection rates and genetic diversity in Sub-Saharan African countries pose a challenge in HIV-1 clinical management. This study provides a picture of HIV-1 genetic diversity and its implications for HIV-1 disease spread and the effectiveness of therapies in Africa. Whole-genome sequences of HIV-1 were obtained from Genbank using the accession numbers from 10 African countries with high HIV-1 prevalence. Alignment composed of the query and reference sequences retrieved from the Los Alamos database. The alignment file was viewed and curated in Aliview. Phylogenetic analysis was done by constructing a phylogenetic tree using the maximum likelihood method implemented in IQ-TREE. The clustering pattern of the studied countries showed both homogeneous clustering and heterogeneous clustering with all Zambia sequences clustering with HIV-1 subtype-C indicating local distribution of only subtype-C. Sequences from nine countries showed heterogeneous clustering along with different subtypes as well as individual clustering of the sequences away from references suggesting cross border genetic exchange. Sequences from Kenya and Nigeria clustered with almost all the HIV-1 subtypes suggesting high HIV-1 genetic diversity in Kenya and Nigeria as compared to other African countries. Our results indicate that there is the presence of subtype-specific HIV-1 polymorphisms and interactions during border movements.
Spatial Transcriptomics-correlated Electron Microscopy
Authors: Androvic Peter , Schifferer Martina , Anderson Katrin Perez , Cantuti-Castelvetri Ludovico , Ji Hao , Liu Lu , Besson-Girard Simon , Knoferle Johanna , Simons Mikael , Gokce Ozgun 
Published: May 2022

AbstractCurrent spatial transcriptomics methods identify cell states in a spatial context but lack morphological information. Scanning electron microscopy, in contrast, provides structural details at nanometer resolution but lacks molecular decoding of the diverse cellular states. To address this, we correlated MERFISH spatial transcriptomics with large area volume electron microscopy using adjacent tissue sections. We applied our technology to characterize the damage-associated microglial identities in mouse brain, allowing us, for the first time, to link the morphology of foamy microglia and interferon-response microglia with their transcriptional signatures.
Aiolos modulates the TFH and CD4-CTL differentiation programs via reciprocal regulation of the Zfp831/TCF-1/Bcl-6 axis and CD25
Authors: Read Kaitlin A. , Jones Devin M. , Pokhrel Srijana , Hales Emily D.S. , Varkey Aditi , Tuazon Jasmine A. , Eisele Caprice D. , Abdouni Omar , Saadey Abbey , Warren Robert T. , Powell Michael D. , Boss Jeremy M. , Hemann Emily A. , Yount Jacob S. , Ghoneim Hazem E. , Lio Chan-Wang J. , Freud Aharon G. , Collins Patrick L. , Oestreich Kenneth J. 
Published: May 2022

AbstractEffective immunity to influenza virus and other respiratory viruses requires the generation of CD4+ T cell subsets that coordinate multiple aspects of the immune response. These subsets include T follicular helper (TFH) and T helper 1 (TH1) cells, which promote humoral and cell-mediated responses, respectively. A third population, CD4+ cytotoxic T lymphocytes (CD4-CTLs) facilitates clearance of infection via mechanisms normally associated with CD8+ T cells. Here, we identify the transcription factor Aiolos as a regulator of TFH and CD4-CTL responses. We demonstrate that Aiolos deficiency compromises TFH differentiation and antibody production during influenza virus infection. Conversely, we find that CD4+ T cells acquire a cytotoxic-like program in the absence of Aiolos, including increased expression of the CTL-associated transcription factors Eomes and Blimp-1. We further show that while Aiolos positively regulates the TFH transcriptional regulators Zfp831, TCF-1 and Bcl-6, it also directly represses expression of IL-2Rα and IL-2/STAT5-driven expression of the cytotoxic gene program. Thus, our findings identify Aiolos as a pivotal regulator of TFH and CD4-CTL differentiation and highlight its potential as a target for manipulating CD4+ T cell humoral and cytotoxic responses.
The TERT promoter is polycomb-repressed in neuroblastoma cells with long telomeres
Authors: Graham Mindy Kim , Xu Beisi , Davis Christine , Meeker Alan K. , Heaphy Christopher M. , Yegnasubramaian Srinivasan , Dyer Michael A. , Zeineldin Maged 
Published: May 2022

AbstractAcquiring a telomere maintenance mechanism is one of the hallmarks of high-risk neuroblastoma and commonly occurs by expressing telomerase (TERT). Telomerase-negative neuroblastoma has, characteristically, long telomeres and most utilize the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. Conversely, no discernable telomere maintenance mechanism is detected in a fraction of neuroblastoma with long telomeres, representing a phenomenon referred to as ever-shorter telomeres. Here, we show that, unlike most cancers, DNA of the TERT promoter is broadly hypomethylated in neuroblastoma. In telomerase-positive neuroblastoma cells, the hypomethylated DNA promoter is approximately 1.5-kb in length and is bound by hypermethylated TERT gene body and upstream intergenic sequences. The TERT locus shows active chromatin marks including H3K4me3, H3K27Ac, H3K14Ac, RNA PolII and BRD4 with low enrichment for the repressive mark, H3K27me3. Strikingly, in neuroblastoma with long telomeres, the hypomethylated region spans the entire TERT locus, including multiple nearby genes with enrichment for the repressive H3K27me3 chromatin mark. Furthermore, subtelomeric regions showed enrichment of repressive chromatin marks in neuroblastomas with long telomeres relative to those with short telomeres. These repressive marks were even more evident at the genic loci, suggesting a telomere position effect. Inhibiting H3K27 methylation by the EZH2 inhibitor, Tazemetostat, induced the expression of TERT, particularly in cell lines with long telomeres and H3K27me3 marks in the promoter region. Taken together, these data suggest that epigenetic regulation of TERT expression differs in neuroblastoma depending on the telomere maintenance status, and H3K27 methylation is important in repressing TERT expression in neuroblastoma with long telomeres.
Ter-Seq: A high-throughput method to stabilize transient ternary complexes and measure associated kinetics
Authors: Chattopadhyay Gopinath , Ahmed Shahbaz , Srilatha Nonavinakere Seetharam , Ashok Apana , Varadarajan Raghavan 
Published: May 2022

AbstractRegulation of biological processes by proteins often involves the formation of transient, multimeric complexes whose characterisation is mechanistically important but challenging. The bacterial toxin CcdB binds and poisons DNA Gyrase. The corresponding antitoxin CcdA extracts CcdB from its complex with Gyrase through formation of a transient ternary complex, thus rejuvenating Gyrase. We describe a high throughput methodology called Ter-Seq to stabilize probable ternary complexes and measure associated kinetics using the CcdA-CcdB-GyrA14 ternary complex as a model system. The method involves screening a YSD saturation mutagenesis library of one partner (CcdB) for mutants that show enhanced ternary complex formation. We also isolated CcdB mutants that were either resistant or sensitive to rejuvenation, and used SPR with purified proteins to validate the kinetics measured using surface display. Positions where CcdB mutations lead to slower rejuvenation rates are largely involved in CcdA-binding, though there were several notable exceptions. Mutations at these positions reduce the affinity towards CcdA, thereby slowing down the rejuvenation process. Mutations at GyrA14-interacting positions significantly enhanced rejuvenation rates, either due to reduced affinity or complete loss of CcdB binding to GyrA14. We examined the effect of different parameters (CcdA affinity, GyrA14 affinity, surface accessibilities, evolutionary conservation) on the rate of rejuvenation. Finally, we further validated the Ter-Seq results by monitoring kinetics of ternary complex formation for individual CcdB mutants in solution by FRET studies.
Evaluating the impact on health outcomes of an event that resulted in a delay in contact tracing of COVID-19 cases
Authors: Findlater Lucy , Pierotti Livia , Turner Charlie , Wensley Adrian , Chen Cong , Seaman Shaun , Samartsidis Pantelis , Charlett Andre , Anderson Charlotte , Hughes Gareth , Hickman Matt , Edeghere Obaghe , Oliver Isabel 
Published: May 2022

AbstractObjectiveIn September 2020, records of 15,861 SARS-CoV-2 cases failed to upload from the Second Generation Laboratory Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, resulting in a delay in the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on health outcomes: transmission events, hospitalisations, and mortality. Previously, a modelling study had suggested a substantial impact.DesignObservational studySettingEngland.PopulationIndividuals testing positive for SARS-CoV-2 and their reported contacts.Main outcome measuresSecondary attack rates (SARs), hospitalisations, and deaths amongst primary and secondary contacts were calculated, compared to all other concurrent, unaffected cases. SGSS records affected by the event were matched to CTAS records and successive contacts and cases were identified.ResultsThe initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared to the control group (3 days). This was associated with lower completion of contact tracing of primary cases in the delay group: 80% (95%CI: 79-81%) in the delay group and 83% (95%CI: 83-84%) in the control group. There was some evidence to suggest an increase in transmission to non-household contacts amongst those affected by the delay. The SAR for non-household contacts was higher amongst secondary contacts in the delay group than the control group (delay group: 7.9%, 95%CI:6.4% to 9.2%; control group: 5.9%, 95%CI: 5.3% to 6.6%). There was no evidence of a difference between the delay and control groups in the odds of hospitalisation (crude odds ratio: 1.1 (95%CI: 0.9 to 1.2) or death (crude odds ratio: 0.7 (0.1 to 4.0)) amongst secondary contacts.ConclusionsThe delay in contact tracing had a limited impact on population health outcomes.Strengths and limitations of the studyShows empirical data on the health impact of an event leading to a delay in contact tracing so can test hypotheses generated by models of the potential impact of a delay in contact tracingEstimates the extent of further transmission and odds of increased mortality or hospitalisation in up to the third generation of cases affected by the eventThe event acts as a natural experiment to describe the possible impact of contact tracing, comparing a group affected by chance by delayed contact tracing to a control group who experienced no delayContact tracing was not completed for all individuals, so the study might not capture all affected contacts or transmissions
SARS-CoV-2 Variants of Concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron coincident with consecutive pandemic waves in Pakistan
Authors: Nasir Asghar , Aamir Uzma Bashir , Kanji Akbar , Samreen Azra , Ansar Zeeshan , Ghanchi Najia K. , Bukhari Ali Raza , Masood Kiran Iqbal , Islam Nazneen , Ghani Samina , Syed M. Asif , Wassan Mansoor , Mahmood Syed Faisal , Hasan Zahra 
Published: May 2022

AbstractIdentification and monitoring of SARS-CoV-2 Variants of Concern/Interest (VOC/VOIs) is essential to guide public health measures. We report the surveillance of VOCs circulating in Karachi during the pandemic between April 2021 and February 2022. We screened 2150 SARS-CoV-2 PCR positive samples received at the AKUH Clinical Laboratories. VOC was identified using a PCR-based approach targeting lineage-specific mutations using commercially available assays. Of the SARS-CoV-2 PCR positive samples, 81.7% had VOC/VOI, while 18.3% were undetermined. Alpha variants were predominant at 82.5% and 40.3% of the cases in April and May 2021. Beta variants increased in May (29%) and June (42%) and then reduced to 6% by July. Gamma variant cases were at 14.5% and 9% in May and June, respectively. Delta variants first detected in May, increased to comprise 66% of all variants by July, remaining dominant in August, September, October, and November 2021 at 88%, 91%, 91% and 85% respectively. Omicron (BA.1) variants emerged in December, rising to 42% of cases with an increase to 81% by January 2022 and then reducing to 45% in February 2022. Delta variant prevalence was coincident with increased hospital admissions and mortality. The Omicron variant surge was associated with increased daily infections but limited COVID-19 severity. We highlight the predominance of the VOCs identified through a rapid PCR based approach. As this is important to inform a public health response, we propose that a mutation targeted approach can be a rapid, lower cost solution to aid tracking of known VOCs during pandemic waves.
Predicting Age-Related Macular Degeneration Progression with Contrastive Attention and Time-Aware LSTM
Authors: Yin Changchang , Moroi Sayoko E. , Zhang Ping 
Published: May 2022

ABSTRACTAge-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. Identifying patients at high risk of progression to late AMD, the sight-threatening stage, is critical for clinical actions, including medical interventions and timely monitoring. Recently, deep-learning-based models have been developed and achieved superior performance for late AMD prediction. However, most existing methods are limited to the color fundus photography (CFP) from the last ophthalmic visit and do not include the longitudinal CFP history and AMD progression during the previous years’ visits. Patients in different AMD subphenotypes might have various speeds of progression in different stages of AMD disease. Capturing the progression information during the previous years’ visits might be useful for the prediction of AMD progression. In this work, we propose a Contrastive-Attention-based Time-aware Long Short-Term Memory network (CAT-LSTM) to predict AMD progression. First, we adopt a convolutional neural network (CNN) model with a contrastive attention module (CA) to extract abnormal features from CFPs. Then we utilize a time-aware LSTM (T-LSTM) to model the patients’ history and consider the AMD progression information. The combination of disease progression, genotype information, demographics, and CFP features are sent to T-LSTM. Moreover, we leverage an auto-encoder to represent temporal CFP sequences as fixed-size vectors and adopt k-means to cluster them into subphenotypes. We evaluate the proposed model based on real-world datasets, and the results show that the proposed model could achieve 0.925 on area under the receiver operating characteristic (AUROC) for 5-year late-AMD prediction and outperforms the state-of-the-art methods by more than 3%, which demonstrates the effectiveness of the proposed CAT-LSTM. After analyzing patient representation learned by an auto-encoder, we identify 3 novel subphenotypes of AMD patients with different characteristics and progression rates to late AMD, paving the way for improved personalization of AMD management. The code of CAT-LSTM can be found at GitHub1.CCS CONCEPTS• Applied computing → Health informatics; • Computing methodologies → Neural networks.ACM Reference FormatChangchang Yin, Sayoko E. Moroi, and Ping Zhang. 2018. Predicting Age-Related Macular Degeneration Progression with Contrastive Attention and Time-Aware LSTM. In Proceedings of SIGKDD 2022. ACM, New York, NY, USA, 11 pages. https://doi.org/10.1145/1122445.1122456
Nerve pathology is prevented by linker proteins in mouse models for LAMA2-related muscular dystrophy
Authors: Reinhard Judith R. , Porrello Emanuela , Lin Shuo , Pelczar Pawel , Previtali Stefano C. , Rüegg Markus A. 
Published: May 2022

ABSTRACTLAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is caused by mutations in the LAMA2 gene encoding laminin-α2, the long chain of several heterotrimeric laminins. Laminins are essential components of the extracellular matrix that interface with underlying cells. The pathology of LAMA2 MD patients is dominated by the severe muscular dystrophy but also involves other tissues. In the dyW/dyW mouse model for LAMA2 MD, amelioration of muscle function by skeletal muscle-specific expression of the two linker proteins, mini-agrin and αLNNd, is sufficient to greatly increase survival. In such survivors, the phenotype is dominated by the hindlimb paralysis. We now show that ubiquitous expression of the two linker proteins in dyW/dyW mice improves muscle function and prevents hindlimb paralysis. The same ameliorating effect of the linker proteins was seen in dy3K/dy3K mice, which represent the most severe mouse model of LAMA2 MD. In summary, these data show that the two linker proteins can compensate the loss of laminin-α2 in many, if not all tissues affected in LAMA2 MD.
Study of the glycome of synovial mast cells in normal tissues, osteoarthritis and rheumatoid arthritis reveals MGAT5 activity in these and endochondral cells
Authors: McClure Sheena F , McClure John 
Published: May 2022

ABSTRACTMast cells and angiogenesis play roles in the synovium of both osteoarthritis and rheumatoid disease but precise mechanisms are unclear. In a study of the glycome of human synovial biopsies from normal, osteoarthritic and rheumatoid disease cases mast cell numbers were increased in both osteoarthritic and rheumatoid disease synovial samples (the latter more than the former). Both mast cells and endothelial cells expressed receptors for the lectinPhaseolus vulgarisleukagglutinin (lPHA). Endothelial cells only expressed receptors forPsophocarpus tetragonolobus(PTL-II). Mast cells and angiogenesis are, therefore, likely to have a common pathogenetic mechanism in osteoarthritis and rheumatoid synovitis, the difference being one of degree. lPHA receptor expression in both mast cells and endothelial cells indicates βl,6N–acetylglucosaminyl (GlcNAc) – transferase V (GnTaseV/MGAT5) activity. This provides a linkage between mast cells and endothelial cell proliferation. Endothelial cells show core 1 O-glycosylation (positive PTL-II staining) which is probably necessary for the formation of competent tubular structures and for continuing vascular integrity.
A Microfluidic Chip for LAMP-based Multiplex Detection of Pathogen
Authors: Guan Jingyi , Wang Yunhua , Jin Jing , Zheng Guoxia 
Published: May 2022

AbstractEarly diagnosis of bacterial causing the disease is important for treatment of patent and preventing the spread of pathogen. Utilizing of POCT devices to detect the pathogens on-site will accelerate the diagnosis of infectious disease. By using loop-mediated-amplification, we developed a microfluidic chip for multiplex detection of three bacterial, where the samples were driven by negative pressure were loaded quickly. The performance of the device was preliminarily evaluated. The specificities of the detections were demonstrated. And the LOD for Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were measured as 17.15, 5.67 and 16.47 ng/μL, respectively. The results demonstrated the feasibility of the method.
GRHL2 enhances phosphorylated estrogen receptor DNA-binding and regulates ER-mediated transcriptional activation and repression
Authors: Reese Rebecca M. , Helzer Kyle T. , Allen Kaelyn O. , Zheng Christy , Solodin Natalia , Alarid Elaine T. 
Published: May 2022

ABSTRACTPhosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) is induced by estrogen and is the most abundant post-translational mark associated with a transcriptionally active receptor. Cistromic analysis of pS118-ER from our group found enrichment of the GRHL2 motif near pS118-ER binding sites. In this report we use cistromic and transcriptomic analyses to interrogate the relationship between GRHL2 and pS118-ER. We found that GRHL2 is bound to chromatin at pS118-ER/GRHL2 co-occupancy sites prior to ligand treatment, and GRHL2 binding is required for maximal pS118-ER recruitment. pS118-ER/GRHL2 co-occupancy sites were enriched at active enhancers marked by H3K27ac and H3K4me1, along with FOXA1 and p300. Transcriptomic analysis yielded four subsets of ER/GRHL2 co-regulated genes revealing that GRHL2 can both enhance and antagonize E2-mediated ER transcriptional activity. Gene ontology analysis identified several coregulated genes involved in cell migration. Accordingly, knockdown of GRHL2 combined with estrogen treatment resulted in increased cell migration but no change in proliferation. These results support a model in which GRHL2 binds to select enhancers and facilitates pS118-ER recruitment to chromatin which then results in differential activation and repression of genes that control ER-positive breast cancer cell migration.