bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling up the “24/7 BHU” strategy to provide round-the-clock maternity care in Punjab, Pakistan: a theory-driven, coproduced implementation study
Authors: Salway Sarah , Mumtaz Zubia , Bhatti Afshan , Barnes Amy , Dawson Jeremy , Jhangri Gian Singh 
Published: December 2022

Abstract
Background
Pakistan’s maternal mortality rate remains persistently high at 186/100,000 live births. The country’s government-run first-level healthcare facilities, the basic health units (BHUs), are an important source of maternity care for rural women. However,BHUsonly operate on working days from 8:00 am to 2:00 pm. Recognizing that this severely constrains access to maternity services, the government is implementing the “24/7 BHU” initiative to upgrade BHUs to provide round-the-clock care. Although based on a successful pilot project, initial reports reveal challenges in scaling up the initiative. This implementation research project aims to address a key concern of the Government of Punjab: How can the 24/7 BHU initiative be successfully implemented at scale to provide high-quality, round-the-clock skilled maternity care in rural Punjab?

Methods
The project consists of two overlapping work packages (WP). WP1 includes three modules generating data at the directorate, district and BHU levels. Module 1 uses document analysis and policy-maker interviews to explicateprogrammetheory and begin to build a system model. Module 2 compares government-collected data with data generated from a survey of 1500 births to assess BHU performance. Module 3 uses institutional ethnographies in 4–5 BHUs in three districts to provide a detailed system for understanding and identifying processes that influence scale-up. WP2 includes two modules. First, two workshops and regular meetings with stakeholders integrate WP1 findings, identify feasible changes and establish priorities. Next, “change ideas” are selected for testing in one district and 2–3 BHUs through carefully documented pilots using the PDSA (plan–do–study–act) improvement approach. An integrated knowledge translation approach will engage key policy and practice stakeholders throughout the project.

Discussion
This theory-driven implementation research project willcoproducesignificant new understandings of the wider system in which the 24/7 BHU initiative is being implemented, and actionable knowledge that will highlight ways the implementation processes might be modified to enable BHUs to meet service provision goals. This study will also produce insights that will be relevant for other South Asian and low- and middle-income countries (LMICs) that experience similar challenges of programme scale-up and delivery of maternal health services to remote and marginalized communities.
Knowledge of HIV/AIDS among married women in Bangladesh: analysis of three consecutive multiple indicator cluster surveys (MICS)
Authors: Hasan Mohammad Nayeem , Tambuly Sumi , Trisha Kaniz Fatema , Haque Md. Ashiqul , Chowdhury Muhammad Abdul Baker , Uddin Md Jamal 
Published: December 2022

AbstractMarried women have a higher risk of contracting human immunodeficiency virus (HIV) or develop acquired immune deficiency syndrome (AIDS) than men. Knowledge of HIV/AIDS contributes significantly to describing the prevalence and consequences of such virus/disease. The study aimed to investigate the level of HIV/AIDS knowledge and the socio-demographic variables that influence HIV/AIDS knowledge among married women in Bangladesh. We used three waves of Multiple Indicator Cluster Survey (MICS), which included 33,843, 20,727, and 29,724 married women from 2006, 2012, and 2019 MICS. A score was prepared through their interrogation to determine the level of knowledge and logistic regression models were used for analyzing the data. This study found that the prevalence of knowledge level of HIV/AIDS in different questions increased from 55.20% in 2006 to 58.69% in 2019. In our study, respondents having highest education had 4.03 (95% CI 3.50–4.64) times more chance to obtain “High Score” in 2019 MICS which is 5.30 times in 2012 MICS (95% CI 4.41–6.37) and 2.58 times in 2006 MICS (95% CI 2.28–2.93) compared to illiterate married women. Moreover, respondents from urban area were 1.13 times more likely to obtain “High Score” in 2019 MICS which is 1.14 times in 2012 MICS and 1.16 times in 2006 MICS, respectively than the rural married women. This study also found respondent’s age, division, mass media access, and wealth status have played an important role in HIV/AIDS knowledge. Although a significant proportion of women had adequate knowledge of HIV/AIDS, more knowledge is still required to protect against such viruses/diseases. Thus, we advocate for the implementation of educational program in the curriculum, counselling, particularly in rural areas, and mass media access to ensure quality knowledge throughout the country.
Suppression of porcine hemagglutinating encephalomyelitis virus replication by resveratrol
Authors: Liu Yuzhu , Song Deguang , Liu Xueli , Wang Yuanqi , Wang Gaili , Lan Yungang 
Published: December 2022

Abstract
Background
Porcine hemagglutinating encephalomyelitis virus (PHEV), a member of the genus Betacoronavirus, is the causative agent of neurological disease in pigs. No effective therapeutics are currently available for PHEV infection. Resveratrol has been shown to exert neuroprotective and antiviral effects. Here resveratrol was investigated for its ability to inhibit PHEV replication in nerve cells and central nervous system tissues.

Methods
Anti-PHEV effect of resveratrol was evaluated using an in vitro cell-based PHEV infection model and employing a mouse PHEV infection model. The collected cells or tissues were used for quantitative PCR analysis, western blot analysis, or indirect immunofluorescence assay. The supernatants were collected to quantify viral loads by TCID50 assay in vitro. EC50 and CC50 were determined by dose–response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral versus cytotoxic activity.

Results
Our results showed that resveratrol treatment reduced PHEV titer in a dose-dependent manner, with a 50% inhibition concentration of 6.24 μM. A reduction of > 70% of viral protein expression and mRNA copy number and a 19-fold reduction of virus titer were achieved when infected cells were treated with 10 µM resveratrol in a pre-treatment assay. Quantitative PCR analysis and TCID50 assay results revealed that the addition of 10 μM resveratrol to cells after adsorption of PHEV significantly reduced 56% PHEV mRNA copy number and eightfold virus titer. 10 µM resveratrol treatment reduced 46% PHEV mRNA copy number and fourfold virus titer in virus inactivation assay. Moreover, the in vivo data obtained in this work also demonstrated that resveratrol inhibited PHEV replication, and anti-PHEV activities of resveratrol treatment via intranasal installation displayed better than oral gavage.

Conclusion
These results indicated that resveratrol exerted antiviral effects under various drug treatment and virus infection conditions in vitro and holds promise as a treatment for PHEV infection in vivo.
Neoadjuvant radiotherapy for resectable retroperitoneal sarcoma: a meta-analysis
Authors: Li Xiangji , Dong Ruihan , Xiao Mengmeng , Min Li , Luo Chenghua 
Published: December 2022

AbstractBackgroundNeoadjuvant radiotherapy (NRT) for resectable retroperitoneal sarcoma (RPS) has been shown to be systematically feasible. Whether NRT has equivalent or better clinical effects compared to surgery alone for RPS patients remains controversial.MethodsWe performed a systematic literature search of PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane library databases for studies in humans with defined search terms. Articles were independently assessed by 2 reviewers, and only randomized controlled trials and cohort studies were included. The hazard ratios (HRs) of overall survival (OS), recurrence-free survival (RFS), and local recurrence (LR) were extracted from included studies. Heterogeneity among study-specific HRs was assessed by the Q statistic and I2statistic. Overall HR was assessed by random-effects or fixed-effects models. Publication bias was tested by Begg’s tests, and the quality of each study was assessed with the Newcastle Ottawa Scale.ResultsA total of 12 eligible studies with 7778 resectable RPS patients were finally included in this study. The pooled analysis revealed the distinct advantages of NRT as compared to surgery alone, including longer OS (HR = 0.81,P < 0.001), longer RFS (HR = 0.58,P = 0.04), and lower LR (HR = 0.70,P = 0.03). No evidence of publication bias was observed.ConclusionNRT is likely to be beneficial for resectable RPS patients in terms of OS and RFS.However, more multicenter clinical trials are needed to confirm these findings.
The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy for unresectable rectal cancer (SUNRISE): interim analysis of a randomized phase II trial
Authors: Liu Wen-Yang , Shi Jin-Ming , Li Ning , Wang Xin , Gao Yuan-Hong , Chi Yihebali , Sun Yong-Kun , Zhao Qing , Zhu Yong-Jian , Chen Hong-Da , Fang Hui , Lu Ning-Ning , Qi Shu-Nan , Chen Bo , Wang Shu-Lian , Song Yong-Wen , Liu Yue-Ping , Li Ye-Xiong , Liu Zheng , Zhou Hai-Tao , Liang Jian-Wei , Wang Xi-Shan , Zhang Hai-Zeng , Tang Yuan , Jin Jing 
Published: December 2022

Abstract
Purpose
The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis.

Methods and materials
Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments.

Results
From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group.

Conclusion
Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.
The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic
Authors: Stafford Fergus , Krishnan Neesha , Richardson Ebony , Butters Alexandra , Hespe Sophie , Burns Charlotte , Gray Belinda , Medi Caroline , Nowak Natalie , Isbister Julia C. , Raju Hariharan , Richmond David , Ryan Mark P. , Singer Emma S. , Sy Raymond W. , Yeates Laura , Bagnall Richard D. , Semsarian Christopher , Ingles Jodie 
Published: December 2022

Abstract
Background
The diagnostic yield of genetic testing for inherited cardiac diseases is up to 40% and is primarily indicated for screening of at-risk relatives. Here, we evaluate the role of genomics in diagnosis and management among consecutive individuals attending a specialised clinic and identify those with the highest likelihood of having a monogenic disease.

Methods
A retrospective audit of 1697 consecutive, unrelated probands referred to a specialised, multidisciplinary clinic between 2002 and 2020 was performed. A concordant clinical and genetic diagnosis was considered solved. Cases were classified as likely monogenic based on a score comprising a positive family history, young age at onset, and severe phenotype, whereas low-scoring cases were considered to have a likely complex aetiology. The impact of a genetic diagnosis was evaluated.

Results
A total of 888 probands fulfilled the inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%) and suspicious variants of uncertain significance (VUS) in 73 (8%). Research-focused efforts identified 46 (5%) variants, missed by conventional genetic testing. Where a variant was identified, this changed or clarified the final diagnosis in a clinically useful way for 51 (13%). The yield of suspicious VUS across ancestry groups ranged from 15 to 20%, compared to only 10% among Europeans. Even when the clinical diagnosis was uncertain, those with the most monogenic disease features had the greatest diagnostic yield from genetic testing.

Conclusions
Research-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease.
Axl regulated survival/proliferation network and its therapeutic intervention in mouse models of glomerulonephritis
Authors: Zhen Yuxuan , Ren Yan , Medvedovic Mario , Adams David E. , Wang Diping , Shao Wen-Hai 
Published: December 2022

Abstract
Background
Lupus nephritis (LN) is the most common and serious complication of systemic lupus erythematosus (SLE). LN pathogenesis is not fully understood. Axl receptor tyrosine kinase is upregulated and contributes to the pathogenic progress in LN. We have reported that Axl disruption attenuates nephritis development in mice.

Methods
In this study, we analyzed the gene expression profiles with RNA-seq using renal cortical samples from nephritic mice. Axl-KO mice were bred onto a B6.lpr spontaneous lupus background, and renal disease development was followed and compared to the Axl-sufficient B6.lpr mice. Finally, anti-glomerular basement membrane (anti-GBM) Ab-induced nephritic mice were treated with Axl small molecule inhibitor, R428, at different stages of nephritis development. Blood urine nitrogen levels and renal pathologies were evaluated.

Results
Transcriptome analysis revealed that renal Axl activation contributed to cell proliferation, survival, and motility through regulation of the Akt, c-Jun, and actin pathways. Spontaneous lupus-prone B6.lpr mice with Axl deficiency showed significantly reduced kidney damages and decreased T cell infiltration compared to the renal damage and T cell infiltration in Axl-sufficient B6.lpr mice. The improved kidney function was independent of autoAb production. Moreover, R428 significantly reduced anti-GBM glomerulonephritis at different stages of GN development compared to the untreated nephritic control mice. R428 administration reduced inflammatory cytokine (IL-6) production, T cell infiltration, and nephritis disease activity.

Conclusions
Results from this study emphasize the important role of Axl signaling in LN and highlight Axl as an attractive target in LN.
Changing epidemiology of acute kidney injury in critically ill patients with COVID-19: a prospective cohort
Authors: Lumlertgul Nuttha , Baker Eleanor , Pearson Emma , Dalrymple Kathryn V. , Pan Jacqueline , Jheeta Anup , Weerapolchai Kittisak , Wang Yanzhong , Leach Richard , Barrett Nicholas A. , Ostermann Marlies 
Published: December 2022

Abstract
Background
Acute kidney injury (AKI) is common in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to explore the changes in AKI epidemiology between the first and the second COVID wave in the United Kingdom (UK).

Methods
This was an observational study of critically ill adult patients with COVID-19 in an expanded tertiary care intensive care unit (ICU) in London, UK. Baseline characteristics, organ support, COVID-19 treatments, and patient and kidney outcomes up to 90 days after discharge from hospital were compared.

Results
A total of 772 patients were included in the final analysis (68% male, mean age 56 ± 13.6). Compared with wave 1, patients in wave 2 were older, had higher body mass index and clinical frailty score, but lower baseline serum creatinine and C-reactive protein (CRP). The proportion of patients receiving invasive mechanical ventilation (MV) on ICU admission was lower in wave 2 (61% vs 80%; p < 0.001). AKI incidence within 14 days of ICU admission was 76% in wave 1 and 51% in wave 2 (p < 0.001); in wave 1, 32% received KRT compared with 13% in wave 2 (p < 0.001). Patients in wave 2 had significantly lower daily cumulative fluid balance (FB) than in wave 1. Fewer patients were dialysis dependent at 90 days in wave 2 (1% vs. 4%; p < 0.001).

Conclusions
In critically ill adult patients admitted to ICU with COVID-19, the risk of AKI and receipt of KRT significantly declined in the second wave. The trend was associated with less MV, lower PEEP and lower cumulative FB.
Trial registration: NCT04445259.
Interventions to treat and prevent postpartum depression: a protocol for systematic review of the literature and parallel network meta-analyses
Authors: Monks David Thomas , Ankalagi Basavaraj , Singh Preet Mohinder , Carter Ebony , Doering Michelle , Guard Meg , Lenze Shannon 
Published: December 2022

Abstract
Introduction
Postpartum depression has costly consequences for the mother, baby, and society. Numerous pharmacological and non-pharmacological interventions are available for the prevention and treatment of postpartum depression. To date, no attempt has been made to synthesize the evidence from comparisons of interventions both within and across these categories.

Methods
We will perform a systematic review of the literature and perform network meta-analysis of interventions to (a) prevent and (b) treat postpartum depression. This review will include studies of primiparous or multiparous women during pregnancy or within 12 months of delivery of their baby that assess either interventions initiated during pregnancy or within 1 year of childbirth. Comparators will be other eligible interventions or control conditions. The outcome of interests will be related to the antidepressant efficacy of the interventions as well as their acceptability. The published literature will be searched in Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. The search will use a combination of standardized terms and keywords for postpartum depression, a sensitive search filter to limit for randomized controlled trials, and a librarian-created “humans” filter. The search results will be uploaded to the Covidence online systematic review platform (Veritas Health Information Ltd., Victoria, Australia) where two review team members will independently screen articles. We will extract data to include year of publication, language, country, participants (number, demographic data, eligibility criteria, psychiatric symptoms, and co-morbidities), characteristics of the intervention and control conditions, and reported outcomes. Risk of bias for each study will be assessed independently by two review authors using the RoB 2: A revised Cochrane risk of bias tool for randomized trials. Network meta-analysis will be performed using a Bayesian hierarchical model supplemented with a Markov chain Monte Carlo approach.

Discussion
Postpartum depression is a devastating disease with long-lasting consequences. Given the numerous available interventions to both prevent and treat postpartum depression and the great number of studies comparing them, it is imperative that clinicians and patients are provided with an assessment of their comparative efficacy and acceptability.

Systematic review registration
Prospero registration (CRD42022303247).
Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer’s disease protects against mitochondrial dysfunction and mitigates brain pathology
Authors: Verma Ankit , Shteinfer-Kuzmine Anna , Kamenetsky Nikita , Pittala Srinivas , Paul Avijit , Nahon Crystal Edna , Ouro Alberto , Chalifa-Caspi Vered , Pandey Swaroop Kumar , Monsonego Alon , Vardi Noga , Knafo Shira , Shoshan-Barmatz Varda 
Published: December 2022

AbstractBackgroundAlzheimer's disease (AD) exhibits mitochondrial dysfunctions associated with dysregulated metabolism, brain inflammation, synaptic loss, and neuronal cell death. As a key protein serving as the mitochondrial gatekeeper, the voltage-dependent anion channel-1 (VDAC1) that controls metabolism and Ca2+homeostasis is positioned at a convergence point for various cell survival and death signals. Here, we targeted VDAC1 with VBIT-4, a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity, and mitochondria dysfunction.MethodsTo address the multiple pathways involved in AD, neuronal cultures and a 5 × FAD mouse model of AD were treated with VBIT-4. We addressed multiple topics related to the disease and its molecular mechanisms using immunoblotting, immunofluorescence, q-RT-PCR, 3-D structural analysis and several behavioral tests.ResultsIn neuronal cultures, amyloid-beta (Aβ)-induced VDAC1 and p53 overexpression and apoptotic cell death were prevented by VBIT-4. Using an AD-like 5 × FAD mouse model, we showed that VDAC1 was overexpressed in neurons surrounding Aβ plaques, but not in astrocytes and microglia, and this was associated with neuronal cell death. VBIT-4 prevented the associated pathophysiological changes including neuronal cell death, neuroinflammation, and neuro-metabolic dysfunctions. VBIT-4 also switched astrocytes and microglia from being pro-inflammatory/neurotoxic to neuroprotective phenotype. Moreover, VBIT-4 prevented cognitive decline in the 5 × FAD mice as evaluated using several behavioral assessments of cognitive function. Interestingly, VBIT-4 protected against AD pathology, with no significant change in phosphorylated Tau and only a slight decrease in Aβ-plaque load.ConclusionsThe study suggests that mitochondrial dysfunction with its gatekeeper VDAC1 is a promising target for AD therapeutic intervention, and VBIT-4 is a promising drug candidate for AD treatment.