bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCL-2 expression promotes immunosuppression in chronic lymphocytic leukemia by enhancing regulatory T cell differentiation and cytotoxic T cell exhaustion
Authors: Liu Lu , Cheng Xianfeng , Yang Hui , Lian Senlin , Jiang Yuegen , Liang Jinhua , Chen Xiao , Mo Suo , Shi Yu , Zhao Sishu , Li Jianyong , Jiang Runqiu , Yang Dong-Hua , Wu Yujie 
Published: February 2022

AbstractBackgroundChronic lymphocytic leukemia (CLL) results in increased susceptibility to infections. T cell dysfunction is not associated with CLL in all patients; therefore, it is important to identify CLL patients with T cell defects. The role of B-cell lymphoma-2 (BCL-2) in CLL has been explored; however, few studies have examined its role in T cells in CLL patients. Herein, we have investigated the regulatory role of BCL-2 in T cells in the CLL tumor microenvironment.MethodsThe expression of BCL-2 in T cells was evaluated using flow cytometry. The regulatory roles of BCL-2 were investigated using single-cell RNA sequencing (scRNA-seq) and verified using multi-parameter flow cytometry on CD4 and CD8 T cells. The clinical features of BCL-2 expression in T cells in CLL were also explored.ResultsWe found a significant increase in BCL-2 expression in the T cells of CLL patients (n = 266). Single cell RNA sequencing (scRNA-seq) indicated that BCL-2+CD4+T cells had the gene signature of increased regulatory T cells (Treg); BCL-2+CD8+T cells showed the gene signature of exhausted cytotoxic T lymphocytes (CTL); and increased expression of BCL-2 was associated with T cell activation and cellular adhesion. The results from scRNA-seq were verified in peripheral T cells from 70 patients with CLL, wherein BCL-2+CD4+T cells were enriched with Tregs and had higher expression of interleukin-10 and transforming growth factor-β than BCL-2−CD4+T cells. BCL-2 expression in CD8+T cells was associated with exhausted cells (PD-1+Tim-3+) and weak expression of granzyme B and perforin. T cell–associated cytokine profiling revealed a negative association between BCL-2+T cells and T cell activation. Decreased frequencies and recovery functions of BCL-2+T cells were observed in CLL patients in complete remission after treatment with venetoclax.ConclusionBCL-2 expression in the T cells of CLL patients is associated with immunosuppression via promotion of Treg abundance and CTL exhaustion.
Progressive, refractory macrophage activation syndrome as the initial presentation of anti-MDA5 antibody positive juvenile dermatomyositis: a case report and literature review
Authors: Stewart J. Alex , Price Theresa , Moser Sam , Mullikin Dolores , Bryan Angela 
Published: February 2022

Abstract
Background
Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis.

Case presentation
We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings.

Conclusions
JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient’s clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.
Patient and health facility attributes associated with retention and virologic suppression in private for-profit health facilities in Nigeria
Authors: Aina Muyi , Yesufu Zeena , Salisu Abdulateef , Ezeanolue Echezona , Mensah Charles , Dakum Patrick 
Published: February 2022

Abstract
Background
In Nigeria, private for-profit health facilities present an opportunity to achieve the UNAIDS 95-95-95 HIV targets because of their reach and patronage. However, little is known about determinants of outcomes in these facilities. This study describes patient outcomes and the patient and health facility characteristics associated with these outcomes in adults receiving HIV treatment in private facilities in the Federal Capital Territory (FCT), Benue and Nasarawa states in north-central Nigeria.

Methods
A retrospective longitudinal analysis of program data collected between 2013 and 2019 was done. Patient attributes and outcomes were compared across the two states and FCT. Incidence rates were determined for all cause exit, mortality and loss to follow up (LTFU). Cox proportional hazard models were used to identify associations between patient and facility attributes and these outcomes. Bivariate and multivariate logistic regression models were used to determine the factors associated with viral suppression among the study participants.

Results
Of the 22,010 study subjects, 42.7%, 22.2% and 35.1%, respectively, were in Benue, FCT and Nasarawa. Almost a third (31.8%) had received antiretroviral treatment (ART) for less than a year at censoring. Incidence rates for all-cause exit, mortality and loss to follow up (LTFU) were 17.2 (95% CI 16.8, 17.5), 2.1 (95% CI 2.0, 2.2), and 11.2 (95% CI 10.8, 11.8) per 100 person years respectively. Males had higher risks of death (HR = 1.47, 95% CI 1.25–1.73), and LTFU (HR = 1.08, 95% CI 1.00–1.16). Age at ART start showed a dose–response association with both mortality and LTFU. Care at model facilities (OR = 2.16, p < 0.001), Zidovudine (AZT)-based regimens (OR = 2.00, p < 0.001), and lowest quartile baseline CD4 + count (OR = 2.40, p < 0.001) were associated with regimen switch. 75.6% of subjects were viral suppressed. Male gender (OR = 0.84, p = 0.025); AZT-based regimen (OR = 0.72, p < 0.001), age in the bottom quartile (OR = 0.71, p = 0.002) were associated with virally suppression.

Conclusion
Private for-profit facilities are a major provider of HIV and other health services in Nigeria. With appropriate technical support and engagement, they can help accelerate efforts to achieve epidemic control of HIV in Nigeria, and contribute to achievement of UNAIDS 95-95-95 target by 2030.
Promotion of early and exclusive breastfeeding in neonatal care units in rural Rwanda: a pre- and post-intervention study
Authors: Gato Saidath , Biziyaremye Francois , Kirk Catherine M. , De Sousa Chiquita Palha , Mukuralinda Alain , Habineza Hamissy , Asir Maya , de Silva Himali , Manirakiza Marie Louise , Karangwa Egide , Nshimyiryo Alphonse , Tugume Alex , Beck Kathryn 
Published: February 2022

Abstract
Background
Early initiation of breastfeeding after birth and exclusive breastfeeding for the first six months improves child survival, nutrition and health outcomes. However, only 42% of newborns worldwide are breastfed within the first hour of life. Small and sick newborns are at greater risk of not receiving breastmilk and often require additional support for feeding. This study compares breastfeeding practices in Rwandan neonatal care units (NCUs) before and after the implementation of a package of interventions aimed to improve breastfeeding.

Methods
This pre-post intervention study was conducted at two district hospital NCUs in rural Rwanda from October–December 2017 (pre-intervention) and September 2018–March 2019 (post-intervention). Only newborns admitted before their second day of life (DOL) were included. Data were extracted from patient charts for clinical and demographic characteristics, feeding, and patient outcomes. Exclusive breastfeeding at discharge was based on last recorded infant feeding on the day of discharge. Logistic regression analysis was used to evaluate factors associated with exclusive breastfeeding at discharge.

Results
Pre-intervention, 255 newborns were admitted in the NCUs and 793 were admitted in post-intervention. Exclusive breastfeeding on the day of birth (DOL0) increased from 5.4% (12/255) to 35.9% (249/793). At discharge, exclusive breastfeeding increased from 69.6% (149/214) to 87.0% (618/710). The mortality rate decreased from 16.1% (41/255) to 10.5% (83/793). Factors associated with greater odds of exclusive breastfeeding at discharge included admission during the post-intervention period (aOR 4.91; 95% CI 1.99, 12.11), and admission for infection (aOR 2.99; 95% CI 1.13, 7.93). Home deliveries (aOR 0.15; 95% CI 0.05, 0.47), preterm delivery (aOR 0.36; 95% CI 0.15, 0.87) and delayed first breastmilk feed (aOR 0.04 for DOL3 vs. DOL0; 95% CI 0.01, 0.35) reduced odds of exclusive breastfeeding at discharge.

Conclusions
Expansion and adoption of evidenced-based guidelines, using innovative approaches, aimed at the unique needs of small and sick newborns may help to improve earlier initiation of breastfeeding, decrease mortality, and improve exclusive breastfeeding on discharge from hospital among small and sick newborns. These interventions should be replicated in similar settings to determine their effectiveness.
The effects of l-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit (ICU): study protocol for a double blind, randomized, placebo-controlled clinical trial
Authors: Keshani Mahdi , Alikiaii Babak , Askari Gholamreza , Yahyapoor Farveh , Ferns Gordon A. , Bagherniya Mohammad 
Published: February 2022

Abstract
Background
Sepsis is a common cause for admission to the intensive care unit (ICU), and its incidence has been increasing. It is associated with a significant increase in serum inflammatory biomarkers such as C-reactive protein (CRP) and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). Sepsis is also associated with pathophysiological changes that include fluid accumulation in the lungs, eventually leading to acute respiratory distress syndrome (ARDS), tissue edema, hypotension, and acute kidney injury (AKI). Conventional therapies include antibiotics, but these may have important adverse effects, so novel therapeutic approaches are required. In animal studies, l-carnitine improves antioxidant status, and in some clinical trials, it has been shown to reduce inflammation. It has also been shown to improve respiratory distress and help maintain coenzyme A homeostasis, metabolic flexibility, promoting the normal function of the tricarboxylic acid (TCA) cycle, and oxidation of fatty acids by peroxisomes. We aim to determine the effects of very high doses of l-carnitine on inflammatory factors, oxidative stress, and clinical outcomes of patients with sepsis in ICU.

Method and design
In this double-blind, randomized controlled clinical trial, we will use block randomization of 60 patients with sepsis, aged between 20 and 65 years from Al-Zahra Hospital, Isfahan, Iran. The intervention group (n = 30) will receive three capsules of l-carnitine (each capsule contains 1000 mg l-carnitine; totally 3000 mg/day) for 7 days, and a control group (n = 30) will receive a placebo with the same dose and for the same duration in addition to usual care. At baseline, scores for clinical and nutritional status (Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), and NUTRIC Score) will be assessed. At beginning and end point of the study, inflammatory markers (CRP, erythrocyte sedimentation rate (ESR)), oxidative stress status (total oxidative stress (TOS), total antioxidant capacity (TAC)), and clinical variables will be evaluated also. The mortality rate will be assessed within 28 days of the beginning of the intervention.

Discussion
Because of the anti-inflammatory and antioxidant properties of l-carnitine, it is possible that using a high dose of 3000 mg daily of this nutritional supplement may reduce inflammation and oxidative stress and improve subsequent mortality of critically ill patients with sepsis.

Trial registration
Iranian Registry of Clinical Trials IRCT20201129049534N1. Registered on 2 May 2021.
Systematic review of quantitative preference studies of treatments for rheumatoid arthritis among patients and at-risk populations
Authors: Simons Gwenda , Caplan Joshua , DiSantostefano Rachael L. , Veldwijk Jorien , Englbrecht Matthias , Bywall Karin Schölin , Kihlbom Ulrik , Raza Karim , Falahee Marie 
Published: February 2022

AbstractTreatments used for rheumatoid arthritis (RA) are under investigation for their efficacy to prevent RA in at risk groups. It is therefore important to understand treatment preferences of those at risk. We systematically reviewed quantitative preference studies of drugs to treat, or prevent RA, to inform the design of further studies and trials of RA prevention. Stated preference studies for RA treatment or prevention were identified through a search of five databases. Study characteristics and results were extracted, and the relative importance of different types of treatment attributes was compared across populations. Twenty three studies were included 20 of RA treatments (18 of patients; 2 of the general public) and 3 prevention studies with first-degree relatives (FDRs). Benefits, risks, administration method and cost (when included) were important determinants of treatment choice. A benefit was more important than a risk attribute in half of the studies of RA treatment that included a benefit attribute and 2/3 studies of RA prevention. There was variability in the relative importance of attributes across the few prevention studies. In studies with non-patient participants, attributes describing confidence in treatment effectiveness/safety were more important determinants of choice than in studies with patients. Most preference studies relating to RA are of treatments for established RA. Few studies examine preferences for treatments to prevent RA. Given intense research focus on RA prevention, additional preference studies in this context are needed. Variation in treatment preferences across different populations is not well understood and direct comparisons are needed.
LncRNA HOTAIR facilitates high glucose-induced mesangial cell proliferation, fibrosis and oxidative stress in diabetic nephropathy via regulating miR-147a/WNT2B axis
Authors: Wang Xin , Wang Wei , HuangFu Weizhong , Liu Zhonghua , Zhao Feng 
Published: February 2022

Abstract
Background
Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of many disease progression. However, the role of lncRNA HOX transcript antisense RNA (HOTAIR) in diabetic nephropathy (DN) remains unclear.

Methods
High glucose (HG)-induced human mesangial cells (HMC) was used to construct DN cell models in vitro. HMC proliferation was evaluated by CCK8 assay and EDU staining. Protein levels of proliferation markers, fibrosis markers, and wingless-type family member 2B (WNT2B) were measured using western blot analysis. HMC oxidative stress was assessed by determining the levels of oxygen species and malondialdehyde, as well as superoxide dismutase activity. Relative expression levels of lncRNA HOTAIR, microRNA (miR)-147a, and WNT2B were examined using quantitative real-time PCR. The interaction between miR-147a and lncRNA HOTAIR or WNT2B was confirmed by dual-luciferase reporter assay and RIP assay.

Results
Our data showed that lncRNA HOTAIR knockdown could inhibit the proliferation, fibrosis, and oxidative stress in HG-induced HMC. LncRNA HOTAIR could serve as a sponge of miR-147a. The inhibition effect of lncRNA HOTAIR silencing on the biological functions of HG-induced HMC could be reversed by miR-147a inhibitor. WNT2B was targeted by miR-147a, and its overexpression also overturned the suppressive effect of miR-147a on the proliferation, fibrosis, and oxidative stress of HG-induced HMC.

Conclusion
In total, our research pointed out that lncRNA HOTAIR could mediate miR-147a/WNT2B axis to promote DN progression.
Isokinetic muscle strength cannot be related to the odds ratio of musculoskeletal injuries in young elite wrestlers
Authors: Hoseini Alireza , Zarei Mostafa , Nobari Hadi , Hovanloo Fariborz , Abbasi Hamed , Pérez-Gómez Jorge 
Published: February 2022

Abstract
Background
Wrestling is considered one of the oldest sports in the world. There is a high rate of injuries in Wrestling. To prevent injuries, it is necessary to identify the risk factors. Despite the functional importance of strength in wrestling, few studies have investigated the relationship between isokinetic strength and the rate of injuries in the sport.

Objectives
The objective of the present study was to investigate the relationship between the isokinetic strength of elite wrestlers and the rate of injuries prospectively.

Method
A total of 72 young wrestlers with at least 2 years of experience in the Tehran Wrestling Premier League participated in this study. Before the start of the competition season, the isokinetic strength of flexor and extensor muscles of the knee and shoulder were measured at different velocities by an isokinetic dynamometer. The injuries and training hours of these wrestlers were then recorded for nine months.

Results
The study results showed no significant relationship between isokinetic strength of flexor and extensor muscles of the knee or shoulder at different angular speeds of 60, 180, and 300°/s. There was neither significant between the ratio of the strength flexor/extensor for knee and/or shoulder in young elite wrestlers with injuries.

Conclusion
Isokinetic strength of lower and upper limb muscles alone cannot predict wrestlers' injuries. Therefore, the use of these tests is not recommended to evaluate the risk of injury in this population.
Towards a culture of open scholarship: the role of pedagogical communities
Authors: Azevedo Flávio , Liu Meng , Pennington Charlotte R. , Pownall Madeleine , Evans Thomas Rhys , Parsons Sam , Elsherif Mahmoud Medhat , Micheli Leticia , Westwood Samuel J. ,   Framework for Open, Reproducible Research Training (FORRT)
Published: February 2022

AbstractThe UK House of Commons Science and Technology Committee has called for evidence on the roles that different stakeholders play in reproducibility and research integrity. Of central priority are proposals for improving research integrity and quality, as well as guidance and support for researchers. In response to this, we argue that there is one important component of research integrity that is often absent from discussion: the pedagogical consequences of how we teach, mentor, and supervise students through open scholarship. We justify the need to integrate open scholarship principles into research training within higher education and argue that pedagogical communities play a key role in fostering an inclusive culture of open scholarship. We illustrate these benefits by presenting theFramework for Open and Reproducible Research Training (FORRT), an international grassroots community whose goal is to provide support, resources, visibility, and advocacy for the adoption of principled, open teaching and mentoring practices, whilst generating conversations about the ethics and social impact of higher-education pedagogy. Representing a diverse group of early-career researchers and students across specialisms, we advocate for greater recognition of and support for pedagogical communities, and encourage all research stakeholders to engage with these communities to enable long-term, sustainable change.
Physical activity specifically evokes release of cell-free DNA from granulocytes thereby affecting liquid biopsy
Authors: Neuberger Elmo W. I. , Sontag Stephanie , Brahmer Alexandra , Philippi Keito F. A. , Radsak Markus P. , Wagner Wolfgang , Simon Perikles 
Published: February 2022

AbstractPhysical activity impacts immune homeostasis and leads to rapid and marked increase in cell-free DNA (cfDNA). However, the origin of cfDNA during exercise remains elusive and it is unknown if physical activity could improve or interfere with methylation based liquid biopsy. We analyzed the methylation levels of four validated CpGs representing cfDNA from granulocytes, lymphocytes, monocytes, and non-hematopoietic cells, in healthy individuals in response to exercise, and in patients with hematological malignancies under resting conditions. The analysis revealed that physical activity almost exclusively triggered DNA release from granulocytes, highlighting the relevance as a pre-analytical variable which could compromise diagnostic accuracy.
Graphical Abstract
A protocol for a scoping review to map the assessment approaches in optometry education programmes globally
Authors: van Staden Diane , Chetty Verusia , Munsamy Alvin Jeffrey 
Published: February 2022

Abstract
Background
The training of optometrists aims to prepare practitioners with critical thinking skills who utilise their education and experience to solve clinical problems in real-life practice. Professional competencies should inform assessment, and as such, assessment methods for learning should encompass a wide range of approaches. The objective of this scoping review is therefore to map assessment approaches utilised within optometry education programmes globally.

Methods
This study is a scoping review based on the PRISMA methodology. The review will be guided by the following research question, “What are the assessment approaches that inform optometry training globally?”. This was validated by the Population-Concept-Context framework according to the methodology for Joanna Briggs Institution Scoping Reviews. Relevant peer-reviewed studies and grey literature conducted during the last 10 years will be identified from electronic databases including CINAHL, PubMed, PROquest and ERIC. The search strings using keywords such as “Optometry students and staff”, “Assessments” and “Optometry education” will be conducted using Boolean logic. An independent reviewer will conduct all title screening, two independent reviewers will conduct abstract and full article screening, followed by data extraction. Thereafter, a thematic analysis will be conducted. The Mixed Method Appraisal Tool version 2018 will be used for quality appraisal of mapped studies.

Discussion
The review will document evidence of assessment approaches utilised in optometry training globally. Considering the exit level competencies required in the basic job function of an optometrist, a coherence in assessment approaches and relevant rationale for these would be expected, if the accredited (regulated) training programmes follow a competency-based model.