bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal HIV care outcomes by gender identity in the United States
Authors: Lesko Catherine R. , Edwards Jessie K. , Hanna David B. , Mayor Angel M. , Silverberg Michael J. , Horberg Michael , Rebeiro Peter F. , Moore Richard D. , Rich Ashleigh J. , McGinnis Kathleen A. , Buchacz Kate , Crane Heidi M. , Rabkin Charles S. , Althoff Keri N. , Poteat Tonia C. 
Published: July 2022

Objective:
Describe engagement in HIV care over time after initial engagement in HIV care, by gender identity.

Design:
Observational, clinical cohort study of people with HIV engaged in routine HIV care across the United States.

Methods:
We followed people with HIV who linked to and engaged in clinical care (attending ≥2 visits in 12 months) in cohorts in the North American Transgender Cohort Collaboration, 2000–2018. Within strata of gender identity, we estimated the 7-year (84-month) restricted mean time spent: lost-to-clinic (stratified by pre/postantiretroviral therapy (ART) initiation); in care prior to ART initiation; on ART but not virally suppressed; virally suppressed (≤200 copies/ml); or dead (pre/post-ART initiation).

Results:
Transgender women (N = 482/101 841) spent an average of 35.5 out of 84 months virally suppressed (this was 30.5 months for cisgender women and 34.4 months for cisgender men). After adjustment for age, race, ethnicity, history of injection drug use, cohort, and calendar year, transgender women were significantly less likely to die than cisgender people. Cisgender women spent more time in care not yet on ART, and less time on ART and virally suppressed, but were less likely to die compared with cisgender men. Other differences were not clinically meaningful.

Conclusions:
In this sample, transgender women and cisgender people spent similar amounts of time in care and virally suppressed. Additional efforts to improve retention in care and viral suppression are needed for all people with HIV, regardless of gender identity.
The Ideal Nasion in Chinese: A Preference Analysis of the General Population
Authors: Liang Xuebing , Sun Sijie , Ma Hengyuan , Gu Tianyi , Guo Haoyue , Zhao Zhao , Wang Keming 
Published: July 2022

Augmentation rhinoplasty has gained popularity in China in the past decades and nasion profile is a key variable in aesthetic outcomes. The nasion is the deepest portion of the nasofrontal groove and its aesthetic preferences vary between different ethnic groups. At the time of this writing, there is limited research about ideal nasion measurements in the Chinese population. Therefore, we conducted an online survey of plastic surgeons and the public through social media. Participants were asked to rank nasion images according to their preferences. Images were created from a 3-dimensional scan of a Chinese Han female and modified to show various dimensions of nasion height, position, and forehead height. Nasion preferences were compared by age, sex, ethnicity, occupation, and whether had a history of plastic surgery. There were 777 respondents, including 461 (59.3%) women and 74 (9.5%) plastic surgeons. Nasion height of 8 and 10 mm ranked highest among all demographic groups. All respondents preferred nasion position to be level with the center of the pupil and forehead height of 4 mm above the nasion. Our study showed that the ideal Chinese nasion is in line with baseline ethnic characteristics. Therefore, plastic surgeons must be aware of these nasion preferences to guide preoperative discussions and achieve satisfactory outcomes.
A Novel Tumor Staging System Incorporating Tumor Regression Grade (TRG) With Lymph Node Status (ypN-Category) Results in Better Prognostication Than ypTNM Stage Groups After Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma
Authors: Wong Ian Y.H. , Chung Jason C.Y. , Zhang Rui Qi , Gao X. , Lam K.O. , Kwong Dora L.W. , Chao Y.K. , Law Simon Y.K. 
Published: July 2022

Objective:
This study aims at constructing a staging system incorporating tumor regression grade and ypN-category (TRG-N) in patients with neoadjuvant therapy before esophagectomy. It is hypothesized that this would prognosticate better than the current American Joint Committee on Cancer (AJCC) postneoadjuvant therapy (ypTNM) stage groups.

Background:
Conventional pathological T-category is defined by the depth of invasion, and may lose prognostic relevance after neoadjuvant therapy. TRG defines treatment response by the degree of tumor regression, and when combined with ypN-category may be more prognostic than AJCC postneoadjuvant therapy (ypTNM) stage groups.

Methods:
A training cohort of 210 patients with esophageal squamous cell carcinoma and who had had neoadjuvant therapy before esophagectomy were studied. A validation cohort comprised 107 patients from another hospital. Resected esophagi were assessed by ypT-category and TRG, the latter assigned according to the Becker 4-tier system. These categories were grouped with ypN-category into a TRG-N system. Patients’ survival was compared between the current AJCC postneoadjuvant therapy (ypTNM) stage groups and this TRG-N system.

Results:
In the training cohort, 5-year survival rates according to ypTNM stage I, II, IIIA, IIIB, and IVA were 53%, 39.4%, 47%, 18.3%, and 0%, respectively. For TRG-N stages I, II, III, and IV, the respective figures were 59.6%, 43.5%, 23.8%, and 15.6%. TRG-N stage showed better fit in survival than ypTNM stage groups, indicated by lower Akaike Information Criteria (AIC) and Bayesian Information Criterion values. Similar results were found in the validation cohort. Multivariate analysis showed that TRG-N stage (P=0.02), age (P=0.006), and sex (P=0.005) were independent prognostic factors.

Conclusion:
TRG-N stage shows better prognostication than the AJCC postneoadjuvant therapy (ypTNM) stage groups.
“#LongCOVID affects children too”: A Twitter analysis of healthcare workers’ sentiment and discourse about Long COVID in children and young people in the UK
Authors: Martin Sam , Chepo Macarena , Déom Noémie , Khalid Ahmad Firas , Vindrola-Padros Cecilia 
Published: July 2022

ABSTRACTAimsWith a social media analysis of the discourse surrounding the prevalence of Long COVID in children and young people (CYP), this study aims to explore healthcare workers’ perceptions concerning Long COVID in CYP in the UK between January 2021 and January 2022. This will allow to contribute to the emerging knowledge on Long COVID and identify critical areas and future directions for researchers and policymakers.DesignA mixed methods approach with a discourse, keywords, sentiment, and image analysis, using Pulsar™ and Infranodus.SettingA discussion of the experience of Long COVID in CYP in the UK shared on Twitter between 1 January 2021 and 31 January 2022.ParticipantsA sample of health workers with Twitter accounts whose bio has them identifying themselves as HCWs.ResultsWe obtained 2588 tweets. HCW were responsive to announcements issued by authorities regarding the management of COVID-19 in the UK. The most frequent feelings were negative. The main themes were uncertainty about the future, policies and regulations, managing and addressing COVID-19 and Long COVID in CYP, vaccination, using Twitter to share scientific literature and management strategies, and clinical and personal experiences.ConclusionsThe perceptions described on Twitter by HCW concerning the presence of Long COVID in CYP appear to be a relevant and timely issue and responsive to the declarations and guidelines issued by health authorities over time. We recommend further support and training strategies for health workers and school staff regarding the manifestations and treatment of Long COVID in CYP.Strengths and limitations of this study–Our online analysis of Long COVID contributes towards an emerging understanding of reported experiential, emotional and practical dimensions of Long COVID in CYP specifically, as well as questions of vaccine hesitancy in CYP with Long COVID.–We identify key policy areas that need considered attention and focus, such as: a) the provision of psychosocial support with access to quality mental health resources to alleviate the impact that Long COVID can have on the mental health of CYP; and b) the development of clear Long COVID pandemic recovery policies that are informed from a health equity perspective and how this affects CYP living with Long COVID.–This is one of few studies to collect healthcare workers’ perceptions regarding Long COVID in CYP in the UK, using information from Twitter.–This study is limited to the perception of those who identified as healthcare workers via their online biographies, and so is not representative of the general UK or the global population.
The expression levels of NOS2, HMOX1 and VEGFC in cumulus cells are markers of oocyte maturation and fertilization rate
Authors: Barragán Montserrat , Cornet-Bartolomé David , Molina Natalia , Vassena Rita 
Published: July 2022

ABSTRACTPurposeWe aim to study whether the expression of genes related to hypoxia and ageing in cumulus cells (CC) is associated to reproductive results in in vitro fertilization cycles.MethodsCumulus cells (CC) were collected after ovum pick-up (OPU) from 94 women recruited undergoing controlled ovarian stimulation from 2018 to 2021; total RNA was extracted and reverse transcribed to cDNA using random hexamers. 14 genes affected by ageing in humans, and expressed in CC, were selected for testing. Expression levels of these genes were detected by qPCR and normalized against TATA-box binding protein (TBP) in CC. Expression levels were plotted against woman age, AFC, MII rate at OPU (MR), and fertilization rates (FR) and non-parametric Spearman’s correlation was applied.ResultsFrom the initial list of 423 candidate genes, we tested 14 genes related to hypoxia response via HIF1alpha activation, oxidative stress response, and angiogenic response. The expression of CLU, NOS2 and TXNIP had a positive correlation with age (rs=0.25, p=0.014; rs=0.31, p=0.0027; and rs=0.24, p=0.03; respectively). Additionally, NOS2 and HMOX1 expression correlated positively with the retrieval of immature oocytes (rs = 0.23228, p = 0.03242; rs = 0.38827, p = 0.01212; respectively). Moreover, VEGFC levels decreased overall with increasing fertilization rate, independently of age (rs=-0.29, p=0.026).ConclusionWe found that the fertilization potential of a cohort of oocytes is related to the ability of CC to respond to oxidative stress and hypoxia, pointing at NOS2, HMOX1 and VEGFC expression as markers for oocyte maturation and fertilization success.
TIST: Transcriptome and Histopathological Image Integrative Analysis for Spatial Transcriptomics
Authors: Shan Yiran , Zhang Qian , Guo Wenbo , Wu Yanhong , Miao Yuxin , Xin Hongyi , Lian Qiuyu , Gu Jin 
Published: July 2022

AbstractSequencing-based spatial transcriptomics (ST) is an emerging technique to study in situ gene expression patterns at the whole-genome scale. In addition to transcriptomic data, the technique usually generates matched histopathological images for the same tissue sample. ST data analysis is complicated by severe technical noise; matched histopathological images with high spatial continuity and resolution introduce complementary cellular phenotypical information and provide a chance to mitigate the noise in ST data. Hence, we propose a novel ST data analysis method called transcriptome and histopathological image integrative analysis for spatial transcriptomics (TIST), which integrates the information from sequencing-based ST data and histopathological images. TIST uses a Markov random field (MRF) model to learn the macroscopic cellular features from histopathological images and devises a random-walk-based strategy to integrate the extracted image features, the transcriptomic features and the location information for spatial cluster (SC) identification and gene expression enhancement. We tested TIST both on simulated datasets and on 33 real datasets; we found that TIST achieved superior performance on multiple tasks, which illustrates the utility of this method in facilitating the discovery of biological insights from sequencing-based ST data.
Top-Down Ion Mobility Separations of Isomeric Proteoforms
Authors: Berthias Francis , Thurman Hayden A. , Wijegunawardena Gayani , Wu Haifan , Shvartsburg Alexandre A. , Jensen Ole N. 
Published: July 2022

ABSTRACTContinuing advances in proteomics highlight the ubiquity and biological importance of proteoforms - the proteins with varied sequence, splicing, or distribution of post-translational modifications (PTMs). The preeminent example is histones, where the PTM pattern encodes the combinatorial language controlling the DNA transcription central to life. While the proteoforms with distinct PTM compositions are distinguishable by mass, the isomers with permuted PTMs (“localization variants”) commonly coexisting in cells generally require separation before mass-spectrometric (MS) analyses. That was accomplished on the bottom-up and middle-down levels using chromatography or ion mobility spectrometry (IMS), but proteolytic digestion obliterates the crucial PTM connectivity information. Here we demonstrate baseline IMS resolution of intact isomeric proteoforms, specifically the acetylated H4 histones (11.3 kDa). The variants with a single acetyl moiety on five alternative lysine residues (K5, K8, K12, K16, K20) known for distinct functionalities in vivo were constructed by two-step native chemical ligation and separated using trapped IMS at the resolving power up to 350 on the Bruker TIMS/ToF platform. Full resolution for several pairs was confirmed using binary mixtures and by unique fragments in tandem MS employing collision-induced dissociation. This novel capability for top-down proteoform characterization is poised to open major new avenues in proteomics and epigenetics.
An Agent-Based Model for COVID-19 in Bangladesh
Authors: Farheen Farhanaz , Shamil Md Salman , Rahman Jony Sheikh Saifur , Ahmad Zafar , Sojib Kawsar Hosain , Chowdhury Anir , Niaz Arifin SM , Sania Ayesha , Rahman M. Sohel 
Published: July 2022

AbstractBackgroundThe COVID-19 pandemic, that has resulted in millions of deaths and hundreds of millions of cases worldwide, continues to affect the lives, health and economy of various countries including Bangladesh. Despite the high proportion of asymptomatic cases and relatively low mortality, the virus’s spread had been a significant public health problem for densely populated Bangladesh. With the healthcare system at stress, understanding the disease dynamics in the unique Bangladesh context became essential to guide policy decisions.MethodsWith a goal to capture the COVID-19 disease dynamics, we developed two stochastic Agent-Based Models (ABMs) considering the key characteristics of COVID-19 in Bangladesh, which vastly differ from the developed countries. We have implemented our ABMs extending the popular (but often inadequate) SIR model, where the infected population is sub-divided into Asymptomatic, Mild Symptomatic and Severe Symptomatic populations. One crucial issue in Bangladesh is the lack of enough COVID-19 tests as well as unwillingness of people to do the tests resulting in much less number of official positive cases than the actual reality. Although not directly relevant to the epidemiological process, our model attempts to capture this crucial aspect while calibrating against official daily test-positive cases. Our first model, ABM-BD, divides the population into age-groups that interact among themselves based on an aggregated Contact Matrix. Thus ABM-BD considers aggregate agents and avoids direct agent level interactions as the number of agents are prohibitively large in our context. We also implement a scaled down model, ABM-SD, that is capable of simulating agent level interactions.ResultsABM-BD was quite well-calibrated for Dhaka: the Mean Absolute Percentage Error (MAPE) between official and forecasted cases was 1.845 approximately during the period between April 4, 2020 and March 31, 2021. After an initial model validation, we conducted a number of experiments - including retrospective scenario analysis, and hypothetical future scenario analysis. For example, ABM-BD has demonstrated the trade off between a strict lockdown with low infections and a relaxed lockdown with reduced burden on the economy. Leveraging the true agent level interaction capability of ABD-SD, we have also successfully analyzed the relative severity of different strains thereby (confidently) capturing the effect of different virus mutations.ConclusionsOur models have adequately captured the COVID-19 disease transmission dynamics in Bangladesh. This is a useful tool to forecast the impact of interventions to assist policymakers in planning appropriate COVID response. Our models will be particularly useful in a resource constrained setting in countries like Bangladesh where the population size is huge.
Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022
Authors: Scotch Matthew , Lauer Kimberly , Wieben Eric D. , Cherukuri Yesesri , Cunningham Julie M , Klee Eric W , Harrington Jonathan J. , Lau Julie S , McDonough Samantha J , Mutawe Mark , O’Horo John C. , Rentmeester Chad E. , Schlicher Nicole R , White Valerie T , Schneider Susan K , Vedell Peter T , Wang Xiong , Yao Joseph D , Pritt Bobbi S , Norgan Andrew P 
Published: July 2022

AbstractSARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread, and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020-2022 and use Bayesian phylodynamics to describe county and regional spread in Minnesota.The earliest introduction into Minnesota was to Hennepin County from a domestic source around January 22, 2020; six weeks before the first confirmed case in the state. This led to the virus spreading to Northern Minnesota, and eventually, the rest of the state. International introductions were most abundant in Hennepin (home to the Minneapolis/St. Paul International (MSP) airport) totaling 45 (out of 107) over the two-year period. Southern Minnesota counties were most common for domestic introductions with 19 (out of 64), potentially driven by bordering states such as Iowa and Wisconsin as well as Illinois which is nearby. Hennepin also was, by far, the most dominant source of in-state transmissions to other Minnesota locations (n=772) over the two-year period.We also analyzed the diversity of the location source of SARS-CoV-2 viruses in each county and noted the timing of state-wide policies as well as trends in clinical cases. Neither the number of clinical cases or major policy decisions, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, appeared to have impact on virus diversity across each individual county.ImportanceWe analyzed over 22,000 SARS-CoV-2 genomes of patient samples tested at Mayo Clinic Laboratories during a two-year period in the COVID-19 pandemic that included Alpha, Delta, and Omicron VoCs to examine the roles and relationships of Minnesota virus transmission.We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after its initial introduction with the virus in early 2020 from an international source, while other counties acted as transmission “sinks”. In addition, major policies such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, did not appear to have an impact on virus diversity across individual counties.
Adaptive phototaxis ofChlamydomonasand the evolutionary transition to multicellularity in Volvocine green algae
Authors: Leptos Kyriacos C , Chioccioli Maurizio , Furlan Silvano , Pesci Adriana I , Goldstein Raymond E 
Published: July 2022

AbstractA fundamental issue in biology is the nature of evolutionary transitions from unicellular to multicellular organisms. Volvocine algae are models for this transition, as they span from the unicellular biflagellateChlamydomonasto multicellular species ofVolvoxwith up to 50,000Chlamydomonas-like cells on the surface of a spherical extracellular matrix. The mechanism of phototaxis in these species is of particular interest since they lack a nervous system and intercellular connections; steering is a consequence of the response of individual cells to light. Studies ofVolvoxandGonium, a 16-cell organism with a plate-like structure, have shown that the flagellar response to changing illumination of the cellular photosensor is adaptive, with a recovery time tuned to the rotation period of the colony around its primary axis. Here, combining high-resolution studies of the flagellar photoresponse with 3D tracking of freely-swimming cells, we show that such tuning also underlies phototaxis ofChlamydomonas. A mathematical model is developed based on the rotations around an axis perpendicular to the flagellar beat plane that occur through the adaptive response to oscillating light levels as the organism spins. Exploiting a separation of time scales between the flagellar photoresponse and phototurning, we develop an equation of motion that accurately describes the observed photoalignment. In showing that the adaptive time scale is tuned to the organisms’ rotational period across three orders of magnitude in cell number, our results suggest a unified picture of phototaxis in green algae in which the asymmetry in torques that produce phototurns arise from the individual flagella ofChlamydomonas, the flagellated edges ofGoniumand the flagellated hemispheres ofVolvox.
Drug repurposing for therapeutic discovery against human metapneumovirus infection
Authors: Van Den Bergh Annelies , Guillon Patrice , von Itzstein Mark , Bailly Benjamin , Dirr Larissa 
Published: July 2022

AbstractHuman metapneumovirus (HMPV) is recognised as an important cause of pneumonia in infants, elderly, and immunocompromised individuals worldwide. The absence of an antiviral treatment or vaccine strategy against HMPV infection creates a high burden on the global health care system. Drug repurposing has become increasingly attractive for the treatment of emerging and endemic diseases as it requires less research and development costs than traditional drug discovery. In this study, we developed anin vitromedium-throughput screening assay that allows for the identification of novel anti-HMPV drugs candidates. Out of ∼2400 compounds, we identified eleven candidates with a dose-dependent inhibitory activity against HMPV infection. Additionally, we further described the mode of action of five anti-HMPV candidates with lowin vitrocytotoxicity. Two entry inhibitors, Evans Blue and aurintricarboxylic acid, and three post-entry inhibitors, mycophenolic acid, mycophenolate mofetil, and 2,3,4-trihydroxybenzaldehyde, were identified. Among them, the mycophenolic acid series displayed the highest levels of inhibition, due to the blockade of intracellular guanosine synthesis. Importantly, MPA has significant potential for drug repurposing as inhibitory levels are achieved below the approved human oral dose. Our drug-repurposing strategy proved to be useful for the rapid discovery of novel hit candidates to treat HMPV infection and provide promising novel templates for drug design.HighlightsThere is currently no treatment against acute HMPV infection.We developed a medium-throughput screening for drug repurposing against HMPV infection.Evaluation of a large drug library identified 5 candidates with low μM to nM IC50values against HMPV growth.The approved drug mycophenolic acid (MPA) is a nM inhibitor of HMPVin vitroinfectionHuman MPA plasma levels upon oral dosing are 10x higher than MPA IC50against HMPVin vitroinfection.