bluuebunny/crossref_metadata_2025_split huggingface dataset:
The natural history of chronic widespread pain in patients with axial spondyloarthritis: a cohort study with clinical and self-tracking data
Authors: Soni Anushka , Nishtala Revathi , Ng Stanley , Barnett Rosemarie , Chyou Te-yuan , Cavill Charlotte , Sengupta Raj 
Published: December 2022

Abstract

Objectives
This study investigates longitudinal patterns, predictors and long-term impact of pain in axial spondyloarthritis (axSpA), using clinical and self-tracking data.

Methods
The presence of multisite pain (MSP), affecting at least six of nine body regions using a Margolis pain drawing, and subsequent chronic widespread pain (CWP), MSP at more than one timepoint, was assessed in a cohort of axSpA patients. Incident MSP (MSP at two consecutive visits or more), intermittent MSP (MSP at two or more non-consecutive visits) and persistent MSP (MSP at each visit) were described. Demographic, clinical and self-tracking measures were compared for the CWP vs non-CWP groups using Students t test, Wilcoxon–Mann–Whitney and χ2 test for normal, non-normal and categorical data, respectively. Predictors of CWP were evaluated using logistic regression modelling.

Results
A total of 136 patients, mean clinical study duration of 120 weeks (range 27–277 weeks) were included, with sufficient self-tracking data in 97 patients. Sixty-eight (50%) patients reported MSP during at least one clinical visit: eight (6%) incident MSP; 16 (12%) persistent MSP; and 44 (32%) intermittent MSP. Forty-six (34%) of the cohort had CWP. All baseline measures of disease activity, function, quality of life, sleep disturbance, fatigue and overall activity impairment were significant predictors of the development of CWP. BASDAI and BASFI scores were significantly higher in those with CWP and self-tracking data revealed significantly worse pain, fatigue, sleep quality and stress.

Conclusions
The development of CWP is predicted by higher levels of disease activity and burden at baseline. It also impacts future disease activity and wellbeing.
Genome Resource for the Verticillium Wilt Resistant Gossypium hirsutum Cultivar Zhongzhimian No. 2
Authors: Li Ran , Zhang Yong-Jun , Ma Xi-Yue , Li Song-Ke , Klosterman Steven J. , Chen Jie-Yin , Subbarao Krishna V. , Dai Xiao-Feng 
Published: December 2022

Verticillium wilt, caused by the fungal pathogen Verticillium dahliae, is the major cause of disease-related yield losses in cotton ( Gossypium hirsutum). Despite these losses, the major cultivars of G. hirsutum remain highly susceptible to Verticillium wilt. The lack of understanding on the genetic basis for Verticillium wilt resistance may further hinder progress in deploying elite cultivars with proven resistance, such as the wilt resistant G. hirsutum cultivar Zhongzhimian No. 2. To help remedy this knowledge gap, we sequenced the whole genome of Zhongzhimian No. 2 and assembled it from a combination of PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture technologies. The final assembly of the genome was 2.33 Gb, encoding 95,327 predicted coding sequences. The GC content was 34.39% with 99.2% of the bases anchored to 26 pseudo-chromosomes that ranged from 53.8 to 127.7 Mb. This resource will help gain a detailed understanding of the genomic features governing high yield and Verticillium wilt resistance in this cultivar. Comparative genomics will be particularly helpful, since there are several published genomes of other Gossypium species. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Increased insulin resistance due to Long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection
Authors: Al-Hakeim Hussein Kadhem , Al-Rubaye Haneen Tahseen , Jubran Abdulsahib S. , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael 
Published: December 2022

AbstractBackgroundSome months after the remission of acute COVID-19 infection, some people show depressive symptoms, which are predicted by increased peak body temperature (PBT) and lowered blood oxygen saturation (SpO2). Nevertheless, no data indicate whether Long COVID is associated with increased insulin resistance (IR) in association with depressive symptoms and immune, oxidative, and nitrosative (IO&NS) processes.MethodsWe used the homeostasis Model Assessment 2 (HOMA2) calculator©to compute β-cell function, insulin sensitivity and resistance (HOMA2-IR) and measured the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HAMD) in 86 Long COVID patients and 39 controls. We examined the associations between the HOMA2 indices and PBT and SpO2 during acute infection, and depression, IO&NS biomarkers (C-reactive protein, NLRP3 activation, myeloperoxidase, and advanced oxidation protein products) 3-4 months after the acute infection.ResultsLong COVID is accompanied by increased HOMA2-IR, fasting blood glucose, and insulin levels. We found that 33.7% of the patients versus 0% of the controls had HOMA2-IR values >1.8, suggesting IR. PBT, but not SpO2, during acute infection significantly predicted IR, albeit with a small effect size. Increased IR was significantly associated with depressive symptoms as assessed with the BDI and HAMD above and beyond the effects of IO&NS pathways. There were no significant associations between increased IR and the activated IO&NS pathways during Long COVID.ConclusionLong COVID is associated with new-onset IR in a subset of patients. Increased IR may contribute to the onset of depressive symptoms due to Long COVID by enhancing overall neurotoxicity.
Durability of immune responses to the booster mRNA vaccination against COVID-19
Authors: Arunachalam Prabhu S. , Lai Lilin , Samaha Hady , Feng Yupeng , Hu Mengyun , Hui Harold Sai-yin , Wali Bushra , Ellis Madison , Huerta Christopher , Bechnack Kareem , Bechnack Sarah , Lee Matthew , Litvack Matthew , Losada Cecilia , Grifoni Alba , Sette Alessandro , Zarnitsyna Veronika I. , Rouphael Nadine , Suthar Mehul S. , Pulendran Bali 
Published: December 2022

AbstractWaning immunity to vaccination represents a major challenge in vaccinology. Whether booster vaccination improves the durability of immune responses is unknown. Here we show, using a cohort of 55 adult vaccinees who received the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine against SARS-CoV-2, that a booster (i.e., 3rdimmunization) dose at 6 - 10 months increased the half-life of serum neutralizing antibody (nAb) titers to 76 days from 56 - 66 days estimated after the primary two-dose vaccination series. A second booster dose (i.e., 4thimmunization) more than a year after the primary vaccination increased the half-life further to 88 days. However, despite this modestly improved durability in nAb responses against the Wuhan strain, there was a loss in neutralization capacity against Omicron subvariants, especially the recently emerged variants, BA.2.75.2 and BQ.1.1 (35 and 50-fold drop in titers respectively, relative to the ancestral (WA.1) strain. While only 55 – 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (3rddose), the response declined to below the detection limit in almost all individuals by 6 months. Notably, even against BA.1 and BA.5, the titers declined rapidly in a third of the vaccinees and were below the detection limit at 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. Collectively, our data show that the durability of immune responses improves following subsequent booster immunizations; however, the emergence of immune evasive variants reduces the effectiveness of booster doses in preventing infection.
A retrospective case - control study for assessing the risk factors for development of Diabetic Kidney Disease among people with Type 2 Diabetes in Tamil Nadu and Puducherry
Authors: Saji Sneha , Suresh Srividya , MC Deepak , Krishnaswamy Sampath Kumar , Asirvatham Arthur Joseph , Kumar Manoj , George Melvin , Kumaraswamy Subramaniyan , Krishnamoorthy Narayanan , Raman Gopinath , Kannan Arun , Mehta Ratnesh Bhai 
Published: December 2022

AbstractObjectiveTo understand the associated risk factors in the progression of Diabetic Kidney Disease among the Type 2 Diabetes individuals living in the state of Tamil Nadu and Puducherry.Research design and methodsClinical and socio-demographic data was collected, digitized, and analyzed for 482 participants diagnosed either with Diabetic Kidney Disease (DKD) or Type 2 Diabetes (T2D). The study was analyzed by using descriptive statistical analysis SAS version 9.4.ResultsOut of 482 participants, 422 fulfilled the eligibility criteria. Gender, age, T2D duration, and comorbidity are the major risk factors that are found to be associated with DKD in population understudy. We also found inclination towards usage of insulin among DKD participants rather than oral diabetic medications. Metformin (Biguanides) was the most used oral diabetic medication among the T2D participants followed by DPP-4 inhibitors and Sulphonylureas.ConclusionTogether, these data describe the risk pattern among participants diagnosed with DKD at regional level that is integral in early and proper management of the disease.
Multicenter analysis of immunosuppressive medications on the subsequent risk of malignancy in solid organ transplant recipients
Authors: Shaw Reid , Haque Ali R. , Fitzsimons Jack , Hamidi Adam , O’Connor Timothy E. , Roloff Gregory W. , Bemiss Bradford C. , Kallwitz Eric R. , Hagen Patrick A. , Berg Stephanie 
Published: December 2022

AbstractSolid organ transplant is a curative treatment for end organ disease. However, the immunosuppressive therapy required to prevent graft rejection increases the likelihood of developing a subsequent malignancy. This retrospective cohort study from a multi-center academic hospital system investigated solid organ transplantation, immunosuppression, and the risk of subsequent malignancy. Of the 5,591 patients and 6,142 transplanted organs studied, there were 517 subsequent malignancies identified. Skin cancer was the most common type of malignancy to be diagnosed, whereas liver cancer was the first malignancy to present at a median time of one-year post-transplant. Subsequent malignancy was proportionally more often diagnosed in non-Hispanic White transplant recipients compared to other racial groups. Heart and lung transplant recipients had relatively higher rates of subsequent malignancy than liver and kidney transplant recipients, but this finding was not significant upon adjusting for immunosuppressive medications. Multivariate cox proportional hazard analysis and random forest variable importance calculations identified statistically significant correlations with sirolimus and azathioprine and high rates of malignancy after transplant, while tacrolimus was associated with low rates of post-transplant neoplasia.
Are fewer cases of diabetes mellitus diagnosed in the months after SARS-CoV-2 infection?
Authors: Reddy Neha V , Yeh Hsin-Chieh , Tronieri Jena S , Stürmer Til , Buse John B , Reusch Jane E , Johnson Steven G , Wong Rachel , Moffitt Richard , Wilkins Kenneth J , Harper Jeremy , Bramante Carolyn T ,   the N3C and RECOVER Consortiums
Published: December 2022

AbstractLong-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include an increased incidence of diabetes. Our objective was to describe the temporal relationship between new diagnoses of diabetes mellitus and SARS-CoV-2 infection in a nationally representative database. There appears to be a sharp increase in diabetes diagnoses in the 30 days surrounding SARS-CoV-2 infection, followed by a decrease in new diagnoses in the post-acute period, up to 360 days after infection. These results underscore the need for further investigation, as understanding the timing of new diabetes onset after COVID-19 has implications regarding potential etiology and screening and treatment strategies.
Decreased Viral Load, Symptom Reduction, and Prevention of Respiratory Syncytial Virus Infection with MVA-BN-RSV Vaccine
Authors: Jordan Elke , Kabir Golam , Schultz Stephanie , Silbernagl Günter , Schmidt Darja , Jenkins Victoria A. , Weidenthaler Heinz , Stroukova Daria , Martin Barbara K. , De Moerlooze Laurence 
Published: December 2022

ABSTRACTBackgroundRespiratory syncytial virus (RSV) causes significant disease burden in infants and older adults. Most vaccines in development focus on the virus’s F protein. MVA-BN-RSV is a novel vectored vaccine encoding internal and external proteins from both RSV subtypes.MethodsIn a phase 2a trial, participants aged 18 to 50 years selected for low RSV titers were randomized to receive MVA-BN-RSV or placebo, then challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes and virus cultivation, and RSV symptoms were collected throughout quarantine. Antibody titers and cellular markers were assessed before and after vaccination and challenge.ResultsOf 74 participants randomized, 36 received MVA-BN-RSV and 37 received placebo; 31 and 32, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (p=0.017) for MVA-BN-RSV (median=0.00) compared to placebo (median=49.05). Total symptom scores also were lower with MVA-BN-RSV. Vaccine efficacy in preventing infection confirmed by viral culture was 88.5% (CI: 14.8%; 98.5%). Immunoglobulin A and G in serum increased about 4-fold after MVA-BN-RSV vaccination, which was greater than the placebo response to challenge, and neutralizing antibody titer increased about 2-fold. Cellular responses were robust, particularly to the internal RSV proteins. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination.ConclusionMVA-BN-RSV vaccination resulted in lower viral load and was effective against laboratory-confirmed symptomatic infection. Humoral and cellular responses support broad immunogenicity of the vaccine. No safety issues were identified with vaccination.Clinical Trial Registry NumberNCT04752644
Echocardiographic progression of calcific aortic valve disease in patients with preexisting aortic valve sclerosis
Authors: Shamekhi Jasmin , Uehre Carina , Al-Kassou Baravan , Weber Marcel , Sedaghat Alexander , Sugiura Atsushi , Wilde Nihal , Adam Matti , Veulemans Verena , Kelm Malte , Baldus Stephan , Nickenig Georg , Zimmer Sebastian 
Published: December 2022

AbstractObjectiveWe aimed to evaluate echocardiographic parameters to predict CAVD progression.BackgroundCalcific aortic valve disease (CAVD) ranges from aortic valve sclerosis (ASc) with no functional impairment of the aortic valve to severe aortic stenosis (AS). It remains uncertain, which patients with ASc are at particular high risk of developing AS.MethodsWe included a total of 153 patients with visual signs of ASc and peak flow velocity (Vmax.) below 2.5m/s at baseline echocardiography. Progression of CAVD to AS was defined as an increase of the Vmax. ≥ 2.5m/s with a delta of ≥ 0.1m/s; stable ASc complied with a Vmax. below 2.5m/s and a delta < 0.1m/s. Finally, we compared clinical and echocardiographic parameters between these two groups.ResultsThe mean age at baseline was 73.5 (± 8.2) years and 66.7% were of male gender. After a mean follow-up of 1463 days, 57 patients developed AS, while 96 patients remained in the ASc group. The AS group showed significantly more calcification (p < 0.001) and thickening (p < 0.001) of the aortic valve cusps at baseline, although hemodynamics showed no evidence of AS in both groups (ASc group: Vmax. 1.6 ± 0.3 m/s versus AS group: Vmax. 1.9 ± 0.3 m/s; p < 0.001). Advanced calcification (OR (95% CI): 4.8 (1.5 − 15.9); p = 0.009) and a cusp thickness > 0.26cm (OR (95% CI): 16.6 (5.4 – 50.7); p < 0.001) were independent predictors for the development of AS.ConclusionThe acquisition of simple echocardiographic parameter may help to identify patients at particular high risk of developing AS.
BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant BRCA-mutant ovarian cancer
Authors: Gupta Nitasha , Huang Tzu-Ting , Nair Jayakumar R. , An Daniel , Zurcher Grant , Lampert Erika J. , McCoy Ann , Cimino-Mathews Ashley , Swisher Elizabeth M. , Radke Marc R. , Lockwood Christina M , Reichel Jonathan B. , Chiang Chih-Yuan , Wilson Kelli M. , Cheng Ken Chih-Chien , Nousome Darryl , Lee Jung-Min 
Published: December 2022

AbstractPARP inhibitors (PARPis) have changed the treatment paradigm inBRCA-mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for novel therapeutic strategies. Using high-throughput drug screens, we identified ATR/CHK1 pathway inhibitors as cytotoxic, and further validated monotherapy activity of the CHK1 inhibitor (CHK1i), prexasertib, in PARPi-resistantBRCA-mutant HGSC cells and animal models. As a proof-of-concept trial, we conducted a phase II study of prexasertib inBRCA-mutant HGSC patients. The treatment was well-tolerated but yielded an objective response rate of 6% (1/17; 1 PR) in patients with prior PARPi treatment. Exploratory biomarker analyses revealed that replication stress and fork stabilization were associated with clinical benefit to CHK1i. In particular, overexpression ofBLM, andCCNE1overexpression or copy number gain/amplification were seen in patients deriving durable benefit from CHK1i. Our findings suggest replication fork–related biomarkers should be further evaluated for CHK1i sensitivity in HGSC.One Sentence SummaryOverexpression of RecQ helicase BLM is a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistantBRCA-mutant ovarian cancer.
A systematic review of low-dose interleukin-2 for the treatment of systemic lupus erythematosus
Authors: Bader Lara , Boyman Onur , Raeber Miro E. 
Published: December 2022

AbstractBackgroundLow-dose interleukin-2 (IL-2) shows promise as a treatment for restoring functional and numerical deficits of regulatory T (Treg) cells in patients with various autoimmune diseases. Several clinical trials testing low-dose IL-2 in systemic lupus erythematosus (SLE) have been completed, with a comprehensive review of these trials currently lacking.ObjectiveWe aimed to conduct a systematic synthesis of findings from clinical trials regarding the clinical efficacy and safety of using low-dose IL-2 in patients with SLE. Furthermore, we intended to determine the sensitivity of different responder indices for IL-2-induced clinical improvement in SLE.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched the Scopus and MEDLINE databases for articles reporting trials testing low-dose IL-2 in patients with SLE published between January 2010 and September 2022. To evaluate the risk of bias, we applied a modified version of the Downs and Black assessment tool.ResultsWe retrieved 1,018 articles, six of which we analyzed including four open-label studies and two randomized controlled trials following a detailed review process. The studies included a total of 230 patients, of which 150 received low dose IL-2 and 80 received placebo. Although the open-label studies demonstrated an expansion of Treg cells that coincided with a clinical response, the predefined primary endpoints for clinical efficacy were not achieved in the randomized controlled trials. In general, treatment with low-dose IL-2 appears to be safe and tolerated well.ConclusionLow-dose IL-2 therapy appears to be a promising strategy for treating SLE; however, larger trials are still necessary to assess clinical responses in patients with such a heterogeneous disease.
Death, Inequality, and the Pandemic in the Nation’s Capital
Authors: Alva Maria L. , Illa Srujana S. , Haber Jaren 
Published: December 2022

AbstractAbrupt changes in mortality rates and life expectancy allow us to understand how shocks like COVID-19 can exacerbate health inequalities across groups. We look at Washington, D.C., a major city with a diverse population and long-standing socio-economic divisions, to describe the all-cause mortality trends from 2015 to 2021 by age, sex, race, and ward of residence. We report differences in cause-specific mortality pre- and post-COVID-19 outbreak and estimate the Years of Life Lost (YLL) attributable to COVID-19. We compute death rates using information from death certificates and the Census, and we calculate YLL using the life table approach, comparing the life expectancy of people with and without COVID-19. We find that in 2020 and 2021, there were respectively 1,128 and 629 excess deaths (158 per 100K and 94 per 100K) compared to the annual average over the previous five years, and 689 and 363 deaths in 2020 and 2021, respectively (97 per 100K and 54 per 100K) listing COVID-19 as a cause of death. Death rates in 2020 and 2021, compared to the five previous years, were higher for men than women by about 12pp and 5pp and occurred almost entirely among residents 45 and older. Excess deaths between 2020 and 2021 were higher for Black and Hispanic residents by about 286 and 97 per 100K, respectively—with the highest proportional increase (almost twofold) for Hispanics in 2020. YLL was highest for Hispanic males and lowest for White females.Significance StatementThe leading causes of death in DC were historically heart disease and cancer. In 2020, the leading cause of death was COVID. Accidental and violent deaths increased dramatically and disproportionately by race. Racial disparities in COVID and non-COVID deaths indicate that these correlate with socioeconomic conditions.Life expectancy in the United States decreased for the first time in 2020 due to COVID-19. In the nation’s capital, the decline in life expectancy was more significant for Hispanic and non-Hispanic Black than White people, widening the already large difference in life expectancy among these groups.