bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial protection against Omicron in children and adolescents by BNT162b2
Authors: Amir Ofra , Goldberg Yair , Mandel Micha , Bar-On Yinon M. , Bodenheimer Omri , Freedman Laurence , Ash Nachman , Alroy-Preis Sharon , Huppert Amit , Milo Ron 
Published: May 2022

AbstractBACKGROUNDThe BNT162b2 (Pfizer-BioNTech) 2-dose vaccine for children and the BNT162b2 3rd dose for adolescents were approved shortly before the Omicron outbreak in Israel. The effects of these vaccines on the rates of Omicron confirmed infection are not yet clear.METHODSWe extracted data for the Omicron-dominated (sub-lineage BA.1) period December 26, 2021 through January 8, 2022. We compared rates of confirmed Covid-19 infection between children 5-10 years old 14-35 days after receiving the 2nd dose to an internal control group of children 3-7 days after receiving the 1st dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents 12-15 years old 14-60 days after receiving a booster dose to an internal control group of adolescents 3-7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure.RESULTSIn the 5-10 age group, the estimated rate of confirmed infection was 2.3 fold (95% CI, 2.0 to 2.5) lower in the 2nd dose group than in the internal control group. In adolescents, the third dose decreased confirmed infection rates by 3.3-fold (95% CI, 2.8 to 4.0).CONCLUSIONSA recent 2-dose BNT162b2 vaccination in children and a recent booster dose in adolescents reduced the rate of confirmed infection compared to the respective internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as PIMS and long-COVID.
Endline Assessment of a Community-Based Program on Hypertension and Diabetes Management in Brazil
Authors: Flor Luisa Sorio , Wilson Shelley , Amorim Welma Wildes , Barone Mark TU , Bezerra Vanessa Moraes , Bhatt Paurvi , Bouskela Maria A Loguercio , Camarda Joseph N , Cimini Christiane CR , Cortes Matheus L , Daly Jessica , Endlich Patrick W , Fullman Nancy , Harris Katie Panhorst , Kochergin Clavdia N , Lima Marcia Maria Oliveira , Louzado José A , Maia Junia X , Marcolino Milena S , McNellan Claire R , de Medeiros Danielle Souto , Mistro Sostenes , Ng Marie , Oliveira Joao AQ , Oliveira Marcio Galvão , Phillips Bryan K , de O e Almeida Pinto Vânia S , Ribeiro Antonio Luiz P , Rumel Davi , Silva Kelle Oliveira , Soares Daniela Arruda , Thomson Blake , Gakidou Emmanuela 
Published: May 2022

AbstractBackgroundBrazil HealthRise community-based program focused on improving technologies for care coordination, developing the local workforce, and identifying and educating individuals with hypertension and diabetes.ObjectivesTo assess the impact of HealthRise on hypertension and diabetes management among patients in the region of Teófilo Otoni (TO) and in the city of Vitória da Conquista (VC).MethodsGrantees routinely collected patient-level clinical in intervention areas from March 2017 to December 2018; endline qualitative interviews were conducted with patients, providers, administrators, and policymakers in both intervention and comparison sites. Paired t-tests were employed to measure the potential impact of the program on reducing systolic blood pressure (SBP) and hemoglobin A1c (HbA1c) between baseline and endline, and on increasing the percentage of enrollees meeting clinical targets (SBP < 140 mmHg for hypertension; < 8% HbA1c for diabetes). We analyzed qualitative data using thematic coding.ResultsAcross sites, 2,764 hypertension patients and 244 diabetes patients were followed through endline. Participants experienced reductions in SBP in TO (−1.9 mmHg [−3.1;−0.7]) and VC (−4,2 mmHg [−5.2;−3.1]); more hypertension patients met treatment targets in these locations (TO: +3.9 percentage-points [0.4;7.2]; VC: +10.5 percentage-points [7.81;13.2]) by endline. HbA1c decreased in TO (−0.6 [−0.9;−0.4]) and VC (−0.9 [−1.4;−0.5]), and more individuals presented HbA1c < 8% by endline (TO: +10.2 percentage-points [3.8, 16.6]; VC: +25 percentage-points [12.2, 37.8]). Qualitative data pointed to overall enthusiasm for new technologies and care routine implemented by HealthRise, but challenges regarding program implementation, integration with other levels of care, and social determinants of health persisted.ConclusionsProgram showed positive effects on hypertension and diabetes outcomes. Community-based health interventions can help bridge healthcare gaps, but their full impact will remain limited until multisectoral policies and actions address underlying structural and social determinants of health more effectively.
Sox6 expression and aneurysms of the thoracic and abdominal aorta
Authors: Carmona-Berrio David , Adarve-Rengifo Isabel , Marshall Andrea G. , Vue Zer , Hall Duane D. , Miller-Fleming Tyne W. , Actkins Ky’Era V. , Beasley Heather K. , Almonacid Paula M. , Barturen-Larrea Pierina , Wells Quinn S. , Lopez Marcos G. , Garza-Lopez Edgar , Dai Dao-Fu , Shao Jianqiang , Neikirk Kit , Billings Federic T. , Curci John A. , Cox Nancy J. , Gama Vivian , Hinton Antentor , Gomez Jose A. 
Published: May 2022

AbstractBackgroundAbdominal and thoracic aortic aneurysms (AAA; TAA) remain a large cause of deaths worldwide. This is in part a result of the lack of prognostic markers or early warning signs, leading to undiagnosed aortic aneurysms. Sox6 has been found to function as a regulator of renin expression controlling the rate limiting step in the renin angiotensin aldosterone system. We hypothesized that the transcription factor Sox6 may serve as an important regulator of mechanisms contributing to hypertension induced aortic aneurysms.MethodsOur approach includes mRNA analysis, immunohistology staining, and protein expression studies in human samples from patients affected with AAA and TAA. In vivo, we use Angiotensin (II) to induce AAA in mice with a tamoxifen inducible Cre to specifically knock out Sox6 in smooth muscle cells. Additionally, we utilize large-scale biobank data linking de-identified medical records with genotype information to perform phenotype and laboratory-wide association scans to assess the effects of SOX6 expression in a clinical cohort.ResultsIn a large biobank population, SOX6 gene expression is associated with aortic aneurysm in humans of European ancestry. Protein expression of Sox6 and TNFα was upregulated in tissue from patients affected by AAA and TAA. Moreover, we found that knocking out Sox6 in smooth muscle cells protected mice from hypertension-induced AAA, suggesting that Sox6 may be a molecular target in aortic aneurysms.ConclusionsThe data presented here suggest that the transcription factor Sox6 functions in the development of abdominal aortic aneurysms, and hypertension-induced rupture.Clinical PerspectiveUsing electronic health records and biobank samples, we found that the transcription factor SOX6 is associated with abdominal and thoracic aortic aneurysm and its expression is upregulated in tissue from patients affected by those diseases.Laboratory-wide association study (LabWAS) provides several clinical laboratory measurements associated with aortic aneurysm diagnosis that may be potential biomarkers for the disease.Mice with smooth muscle-specific Sox6 knock out attenuated hypertension-induced abdominal aortic aneurysm. These novel mice may be useful tools to elucidate the mechanisms associated with abdominal aortic aneurysm.
Small RNA sequencing reveals snoRNAs and piRNA-019825 as novel players in diabetic kidney disease
Authors: ’t Hart LM , de Klerk JA , Bouland GA , Peerlings JHD , Blom M.T. , Cramer SJ , Bijkerk R , Beulens JWJ , Slieker RC 
Published: May 2022

AbstractIntroductionMicro- and macrovascular complications are common among persons with type 2 diabetes. Recently there has been growing interest to investigate the potential of circulating small non-coding RNAs (sncRNAs) as contributors to the development of diabetic complications. In this study we investigate to what extent circulating sncRNAs levels associate with prevalent diabetic kidney disease (DKD) in persons with type 2 diabetes.MethodsPlasma sncRNAs levels were determined using small RNA-seq, allowing detection of miRNAs, snoRNAs, piRNAs, tRNA-fragments and various other sncRNA classes. We tested for differentially expressed sncRNAs in persons with type 2 diabetes, with DKD (n=69) or without DKD (n=405). In secondary analyses, we also tested the association with eGFR, albuminuria (UACR) and the plasma proteome.ResultsIn total seven sncRNAs were negatively associated with prevalent DKD (all PFDR≤0.05). Including one microRNA (miR-143-5p), five snoRNAs (U8, SNORD118, SNORD24, SNORD107, SNORD87) and a piRNA (piR-019825|DQ597218). Proteomic analyses showed that the seven sncRNAs, and especially the piRNA piR-019825, were associated with plasma levels of 24 proteins of which several have known associations with kidney function including TNF sR-I (TNFRFS1A), DAN (NBL1) and cystatin C (CST3).ConclusionWe have identified novel small non-coding RNAs, primarily from classes other than microRNAs, that are associated with diabetic kidney disease. Our results shows that the involvement of small non-coding RNAs in DKD goes beyond the already known microRNAs and also involves other classes of sncRNA, in particular snoRNAs and the piRNA piR-019825, that have never been studied before in relation to kidney function.
Evaluation of triage checklist for mild COVID-19 outpatients in predicting subsequent emergency department visits and hospitalization during isolation period
Authors: Tanaka Yasuhiro , Yamamoto Kazuko , Morimoto Shimpei , Nabeshima Takeshi , Matsushima Kayoko , Ishimoto Hiroshi , Ashizawa Nobuyuki , Hirayama Tatsuro , Takeda Kazuaki , Gyotoku Hiroshi , Iwanaga Naoki , Takemoto Shinnosuke , Fukahori Susumu , Takazono Takahiro , Yamaguchi Hiroyuki , Kido Takashi , Sakamoto Noriho , Hosogaya Naoki , Akabame Shogo , Sugimoto Takashi , Yamanashi Hirotomo , Matsui Kosuke , Izumida Mai , Fujita Ayumi , Tashiro Masato , Tanaka Takeshi , Ariyoshi Koya , Furumoto Akitsugu , Morita Kouichi , Izumikawa Koichi , Yanagihara Katsunori , Mukae Hiroshi 
Published: May 2022

ABSTRACTBackground and objectiveLimited evidence exists regarding the outcomes of patients with coronavirus disease 2019 (COVID-19) who are not hospitalized. This study aimed to assess the outcomes for mild COVID-19 patients in terms of emergency department (ED) visits and hospital admission given initial outpatient triage evaluation and to identify the triage factors affecting these outcomes.MethodsThis retrospective cohort study investigated adult COVID-19 Japanese patients who were triaged at Nagasaki University Hospital between April 1, 2021, and May 31, 2021. A triage checklist with 30 factors was used to identify patients requiring hospitalization. Patients recommended for isolation were followed up for later ED visit or hospital admission.ResultsOverall, 338 COVID-19 patients (mean age, 44.7; 45% women) visited the clinic at an average of 5.4 days after symptom onset. Thirty-six patients (10.6%) were hospitalized from triage, and the rest were recommended for isolation. Seventy-two non-hospitalized patients (23.8%) visited ED during their isolation period, and 30 (9.9%) were hospitalized after ED evaluation. The mean duration to ED visit and hospitalization after symptom onset were 8.8 and 9.7 days, respectively. Checklist factors associated with hospitalization during the isolation period were age > 50 years, obesity with BMI > 25, underlying hypertension, tachycardia with HR > 100/min or blood pressure >135 mmHg at triage, and >□3-day delay in hospital visit after symptom onset.ConclusionClinicians should be wary of COVID-19 patients with above risk factors and prompt them to seek follow-up assessment by a medical professional.SUMMARY AT A GLANCEOverall, 338 patients with mild COVID-19 were retrospectively followed up. Factors such as age >□50 years, BMI□> □25, underlying hypertension, high blood pressure and tachycardia at triage, and delayed visit after symptom onset were associated with emergency department visit and hospitalization during the isolation period.
Expected endpoints from future chikungunya vaccine trial sites informed by serological data and modeling
Authors: Tran Quan Minh , Soda James , Siraj Amir , Moore Sean , Clapham Hannah , Perkins T. Alex 
Published: May 2022

AbstractIn recent decades, there has been an increased interest in developing a vaccine for chikungunya. However, due to its unpredictable transmission, planning for a chikungunya vaccine trial is challenging. To inform decision making on the selection of sites for a vaccine efficacy trial, we developed a new framework for projecting the expected number of endpoint events at a given site. In this framework, we first accounted for population immunity using serological data collated from a systematic review and used it to estimate parameters related to the timing and size of past outbreaks, as predicted by an SIR transmission model. Then, we used that model to project the infection attack rate of a hypothetical future outbreak, in the event that one were to occur at the time of a future trial. This informed projections of how many endpoint events could be expected if a trial were to take place at that site. Our results suggest that some sites may have sufficient transmission potential and susceptibility to support future vaccine trials, in the event that an outbreak were to occur at those sites. In general, we conclude that sites that have experienced outbreaks within the past 10 years may be poorer targets for chikungunya vaccine efficacy trials in the near future. Our framework also generates projections of the numbers of endpoint events by age, which could inform study participant recruitment efforts.
Cardiac-Gated Spectroscopic Photoacoustic Imaging for Ablation-Induced Necrotic Lesion Visualization: In Vivo Demonstration in a Beating Heart
Authors: Gao Shang , Ashikaga Hiroshi , Suzuki Masahito , Mansi Tommaso , Kim Young-Ho , Ghesu Florin-Cristian , Kang Jeeun , Boctor Emad M. , Halperin Henry R. , Zhang Haichong K. 
Published: May 2022

AbstractRadiofrequency (RF) ablation is a minimally invasive therapy for heart arrhythmia, including atrial fibrillation (A-fib), which creates lesions using an electric current to isolate the heart from abnormal electrical signals. However, conventional RF procedures do not involve intraoperative monitoring of the area and extent of ablation-induced necrosis, making the assessment of the procedure completeness challenging. Previous studies have suggested that spectroscopic photoacoustic (sPA) imaging is capable of differentiating ablated tissue from its non-ablated counterpart based on PA spectrum variation. Here, we aim to demonstrate the applicability of sPA imaging in an in vivo environment, where the cardiac motion presents, and introduce a framework for mapping the necrotic lesion using cardiac-gated sPA imaging. We computed the degree of necrosis, or necrotic extent (NE), by dividing the quantified ablated tissue contrast by the total contrast from both ablated and non-ablated tissues, visualizing it as continuous colormap to highlight the necrotic area and extent. To compensate for tissue motion during the cardiac cycle, we applied the cardiac-gating on sPA data, based on the image similarity. The in vivo validation of the concept was conducted in a swine model. As a result, the ablation-induced necrotic lesion at the surface of the beating heart was successfully depicted throughout the cardiac cycle through cardiac-gated sPA (CG-sPA) imaging. The results suggest that the introduced CG-sPA imaging system has great potential to be incorporated into clinical workflow to guide ablation procedures intraoperatively.
SCAMPP+FastTree: Improving Scalability for Likelihood-based Phylogenetic Placement
Authors: Chu Gillian , Warnow Tandy 
Published: May 2022

AbstractPhylogenetic placement is the problem of placing “query” sequences into an existing tree (called a “backbone tree”), and is useful in both microbiome analysis and to update large evolutionary trees. The most accurate phylogenetic placement method to date is the maximum likelihood-based method pplacer, which uses RAxML to estimate numeric parameters on the backbone tree and then adds the given query sequence to the edge that maximizes the probability that the resulting tree generates the query sequence. Unfortunately, pplacer fails to return valid outputs on many moderately large datasets, and so is limited to backbone trees with at most ∼10,000 leaves. In TCBB 2022, Wedell et al. introduced SCAMPP, a technique to enable pplacer to run on larger backbone trees. SCAMPP operates by finding a small “placement subtree” specific to each query sequence, within which the query sequence are placed using pplacer. That approach matched the scalability and accuracy of APPLES-2, the previous most scalable method. In this study, we explore a different aspect of pplacer’s strategy: the technique used to estimate numeric parameters on the backbone tree. We confirm anecdotal evidence that using FastTree instead of RAxML to estimate numeric parameters on the backbone tree enables pplacer to scale to much larger backbone trees, almost (but not quite) matching the scalability of APPLES-2 and pplacer-SCAMPP. We then evaluate the combination of these two techniques – SCAMPP and the use of FastTree. We show that this combined approach, pplacer-SCAMPP-FastTree, has the same scalability as APPLES-2, improves on the scalability of pplacer-FastTree, and achieves better accuracy than the comparably scalable methods. Availability:https://github.com/gillichu/PLUSplacer-taxtastic.
A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage
Authors: Argenty Jérémy , Rouquié Nelly , Bories Cyrielle , Mélique Suzanne , Duplan Valérie , Saoudi Abdelhadi , Fazilleau Nicolas , Lesourne Renaud 
Published: May 2022

AbstractThe ability to proliferate is a common feature of most T-cell populations. However, proliferation follows different cell-cycle dynamics and is coupled to different functional outcomes according to T-cell subsets. Whether the mitotic machineries supporting these qualitatively distinct proliferative responses are identical remains unknown. Here, we show that disruption of the microtubule-associated protein LIS1 leads to proliferative defects associated with a blockade of T-cell development after β-selection and of peripheral CD4+ T cell expansion after antigen priming. In contrast, cell divisions in CD8+ T cells occurred independently of LIS1 following T-cell antigen receptor stimulation, although LIS1 was required for proliferation elicited by pharmacological activation. In thymocytes and CD4+ T cells, LIS1-deficiency did not affect signaling events leading to activation but led to an interruption of proliferation after the initial round of division and to p53-induced cell death. Proliferative defects resulted from a mitotic failure, characterized by the presence of extra-centrosomes and the formation of multipolar spindles, causing abnormal chromosomes congression during metaphase and separation during telophase. LIS1 was required to stabilize dynein/dynactin complexes, which promote chromosome attachment to mitotic spindles and ensure centrosome integrity. Together, these results suggest that proliferative responses are supported by distinct mitotic machineries across T-cell subsets.
A generalizable framework to comprehensively predict epigenome, chromatin organization, and transcriptome
Authors: Zhang Zhenhao , Feng Fan , Qiu Yiyang , Liu Jie 
Published: May 2022

AbstractMany deep learning approaches have been proposed to predict epigenetic profiles, chromatin organization, and transcription activity. While these approaches achieve satisfactory performance in predicting one modality from another, the learned representations are not generalizable across predictive tasks or across cell types. In this paper, we propose a deep learning approach named EPCOT which employs a pre-training and fine-tuning framework, and comprehensively predicts epigenome, chromatin organization, transcriptome, and enhancer activity in one framework. EPCOT is the first framework proposed to predict all of these genomic modalities and performs well in individual modality prediction, which is also generalizable to new cell and tissue types. EPCOT also maps from DNA sequence and chromatin accessibility profiles to generic representations which are generalizable across different modalities. Interpreting EPCOT model also provides biological insights including mapping between different genomic modalities, identifying TF sequence binding patterns, and analyzing cell-type specific TF impacts on enhancer activity.
Accurate inference of genome-wide spatial expression with iSpatial
Authors: Zhang Chao , Chen Renchao , Zhang Yi 
Published: May 2022

ABSTRACTSpatially resolved transcriptomic analyses can reveal molecular insights underlying tissue structure and context-dependent cell-cell or cell-environment interaction. Due to the current technical limitation, obtaining genome-wide spatial transcriptome at single-cell resolution is challenging. Here we developed a new algorithm named iSpatial to derive spatial pattern of the entire transcriptome by integrating spatial transcriptomic and single-cell RNA-seq datasets. Compared to other existing methods, iSpatial has higher accuracy in predicting gene expression and their spatial distribution. Furthermore, it reduces false-positive and false-negative signals in the original datasets. By testing iSpatial with multiple spatial transcriptomic datasets, we demonstrate its wide applicability to datasets from different tissues and by different techniques. Thus, we innovated a computational approach to reveal spatial organization of the entire transcriptome at single cell resolution without the need of new technology development. With numerous high quality datasets available in the public domain, iSpatial provides a unique way for understanding the structure, function of complex tissues and disease processes.HIGHLIGHTSiSpatial infers genome-wide spatial gene expression pattern by integrating spatial transcriptomic and scRNA-seq dataiSpatial outperforms existing approaches in inferring spatial gene expression patternsiSpatial reduces false-positive/negative signals of the original spatial transcriptomeiSpatial is applicable to spatial transcriptomic datasets from different tissues and techniques
The allosteric mechanism leading to an open-groove lipid conductive state of the TMEM16F scramblase
Authors: Khelashvili George , Kots Ekaterina , Cheng Xiaolu , Levine Michael V , Weinstein Harel 
Published: May 2022

ABSTRACTTMEM16F is a Ca2+-activated phospholipid scramblase in the TMEM16 family of membrane proteins. Unlike other TMEM16s exhibiting a membrane-exposed hydrophilic groove that serves as a translocation pathway for lipids, the experimentally determined structures of TMEM16F shows the groove in a closed conformation even under conditions of maximal scramblase activity. Here we describe the analysis of ∼400 µs all-atom ensemble molecular dynamics (MD) simulations of the TMEM16F dimer that revealed an allosteric mechanism leading to an open-groove state of the protein that is competent for lipid scrambling. The grove opens into a continuous hydrophilic conduit that is highly similar in structure to that seen in other activated scramblases. The allosteric pathway connects this opening to an observed destabilization of the Ca2+ ion bound at the distal site near the dimer interface, to the dynamics of specific protein regions that produces the open-groove state seen in our MD simulations to scramble phospholipids.