bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges of being a maternity service leader during the COVID-19 pandemic: a descriptive analysis of the journey
Authors: Tan Annie , Wilson Alyce N. , Bucknall Tracey , Digby Robin , Vogel Joshua P. , Homer Caroline SE. 
Published: April 2023

Abstract
Background
In Australia, maternity care services provide care for pregnant and postpartum women and their newborns. The COVID-19 pandemic forced these services to quickly adapt and develop policies and procedures for dealing with transmission in health care facilities, as well as work under public health measures to counter its spread within the community. Despite well-documented responses and adaptations by healthcare systems, no studies have examined the experiences of maternity service leaders through the pandemic. This study aimed to explore the experiences of maternity service leaders, to understand their perspectives on what happened in health services and what was required of a leader during the COVID-19 pandemic in one Australian state.

Methods
A longitudinal qualitative study collected data from 11 maternity care leaders during the pandemic in the state of Victoria. Leaders participated in a series of interviews over the 16-month study period, with a total of 57 interviews conducted. An inductive approach to developing codes allowed for semantic coding of the data, then a thematic analysis was conducted to explore patterned meaning across the dataset.

Results
One overarching theme, ‘challenges of being a maternity service leader during the pandemic’, encompassed participant’s experiences. Four sub-themes described the experiences of these leaders: (1) needing to be a rapid decision-maker, (2) needing to adapt and alter services, (3) needing to filter and translate information, and (4) the need to support people. At the beginning of the pandemic, the challenges were most acute with slow guideline development, rapid communications from the government and an urgent need to keep patients and staff safe. Over time, with knowledge and experience, leaders were able to quickly adjust and respond to policy change.

Conclusion
Maternity service leaders played an important role in preparing and adapting services in accordance with government directives and guidelines while also developing strategies tailored to their own health service requirements. These experiences will be invaluable in designing high quality and responsive systems for maternity care in future crises.
Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia
Authors: Cai Yiqing , Chen Xiaomin , Lu Tiange , Yu Zhuoya , Hu Shunfeng , Liu Jiarui , Zhou Xiangxiang , Wang Xin 
Published: April 2023

Abstract
Background
As an essential regulator of type I interferon (IFN) response, TMEM173 participates in immune regulation and cell death induction. In recent studies, activation of TMEM173 has been regarded as a promising strategy for cancer immunotherapy. However, transcriptomic features of TMEM173 in B-cell acute lymphoblastic leukemia (B-ALL) remain elusive.

Methods
Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were applied to determine the mRNA and protein levels of TMEM173 in peripheral blood mononuclear cells (PBMCs). TMEM173 mutation status was assessed by Sanger sequencing. Single-cell RNA sequencing (scRNA-seq) analysis was performed to explore the expression of TMEM173 in different types of bone marrow (BM) cells.

Results
The mRNA and protein levels of TMEM173 were increased in PBMCs from B-ALL patients. Besides, frameshift mutation was presented in TMEM173 sequences of 2 B-ALL patients. ScRNA-seq analysis identified the specific transcriptome profiles of TMEM173 in the BM of high-risk B-ALL patients. Specifically, expression levels of TMEM173 in granulocytes, progenitor cells, mast cells, and plasmacytoid dendritic cells (pDCs) were higher than that in B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs). Subset analysis further revealed that TMEM173 and pyroptosis effector gasdermin D (GSDMD) restrained in precursor-B (pre-B) cells with proliferative features, which expressed nuclear factor kappa-B (NF-κB), CD19, and Bruton’s tyrosine kinase (BTK) during the progression of B-ALL. In addition, TMEM173 was associated with the functional activation of NK cells and DCs in B-ALL.

Conclusions
Our findings provide insights into the transcriptomic features of TMEM173 in the BM of high-risk B-ALL patients. Targeted activation of TMEM173 in specific cells might provide new therapeutic strategies for B-ALL patients.
Expression characteristics and their functional role of IGFBP gene family in pan-cancer
Authors: Liu Yingnan , Shen Shixuan , Yan Ziwei , Yan Lirong , Ding Hanxi , Wang Ang , Xu Qian , Sun Liping , Yuan Yuan 
Published: April 2023

Abstract
Background
Insulin-like growth factor binding proteins (IGFBPs) are critical regulators of the biological activities of insulin-like growth factors. The IGFBP family plays diverse roles in different types of cancer, which we still lack comprehensive and pleiotropic understandings so far.

Methods
Multi-source and multi-dimensional data, extracted from The Cancer Genome Atlas (TCGA), Oncomine, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA) was used for bioinformatics analysis by R language. Immunohistochemistry and qRT-PCR were performed to validate the results of the database analysis results. Bibliometrics and literature review were used for summarizing the research progress of IGFBPs in the field of tumor.

Results
The members of IGFBP gene family are differentially expressed in various cancer types. IGFBPs expression can affect prognosis of different cancers. The expression of IGFBPs expression is associated with multiple signal transduction pathways. The expression of IGFBPs is significantly correlated with tumor mutational burden, microsatellite instability, tumor stemness and tumor immune microenvironment. The qRT-PCR experiments verified the lower expression of IGFBP2 and IGFBP6 in gastric cancer and the lower expression of IGFBP6 in colorectal cancer. Immunohistochemistry validated a marked downregulation of IGFBP2 protein in gastric cancer tissues. The keywords co-occurrence analysis of IGFBP related publications in cancer showed relative research have been more concentrating on the potential of IGFBPs as tumor diagnostic and prognostic markers and developing cancer therapies.

Conclusions
These findings provide frontier trend of IGFBPs related research and new clues for identifying novel therapeutic targets for various cancers.
Transcriptome profiling of a synergistic volumetric muscle loss repair strategy
Authors: Roberts Kevin , Kim John Taehwan , Huynh Tai , Schluns Jacob , Dunlap Grady , Hestekin Jamie , Wolchok Jeffrey C 
Published: April 2023

AbstractVolumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in severe functional deficits that have defied clinical repair strategies. In this manuscript we pair the early in vivo functional response induced by differing volumetric muscle loss tissue engineering repair strategies that are broadly representative of those explored by the field (scaffold alone, cells alone, or scaffold + cells) to the transcriptomic response induced by each intervention. We demonstrate that an implant strategy comprising allogeneic decellularized skeletal muscle scaffolds seeded with autologous minced muscle cellular paste (scaffold + cells) mediates a pattern of increased expression for several genes known to play roles in axon guidance and peripheral neuroregeneration, as well as several other key genes related to inflammation, phagocytosis, and extracellular matrix regulation. The upregulation of several key genes in the presence of both implant components suggests a unique synergy between scaffolding and cells in the early period following intervention that is not seen when either scaffolds or cells are used in isolation; a finding that invites further exploration of the interactions that could have a positive impact on the treatment of volumetric muscle loss.
Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder
Authors: Dmochowski Roger R. , Rovner Eric S. , Kennelly Michael J. , Newman Diane K. , Abedinzadeh Laleh , Snyder Daniel , Thomas Elizabeth , Haag-Molkenteller Cornelia , Rosenberg Matt T. 
Published: April 2023

Abstract
Background
Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective β3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence.

Methods
This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence.

Discussion
OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting.
Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.
Protocol for developing a dashboard for interactive cohort analysis of oral health-related data
Authors: Sharma Vinay , Cassetti Oscar , Winning Lewis , O’Sullivan Michael , Crowe Michael 
Published: April 2023

Abstract
Introduction
A working knowledge of data analytics is becoming increasingly important in the digital health era. Interactive dashboards are a useful, accessible format for presenting and disseminating health-related information to a wide audience. However, many oral health researchers receive minimal data visualisation and programming skills.

Objectives
The objective of this protocols paper is to demonstrate the development of an analytical, interactive dashboard, using oral health-related data from multiple national cohort surveys.

Methods
The package was used within the R Studio framework to create the structure-elements of the dashboard and interactivity was added with the package. Data sources derived from the national longitudinal study of children in Ireland and the national children’s food survey. Variables for input were selected based on their known associations with oral health. The data were aggregated using tidyverse packages such as and summarised using and with specific functions created to generate bar-plots and tables.

Results
The dashboard layout is structured by the YAML (YAML Ain’t Markup Language) metadata in the R Markdown document and the syntax from Flexdashboard. Survey type, wave of survey and variable selector were set as filter options. Shiny’s render functions were used to change input to automatically render code and update output. The deployed dashboard is openly accessible at https://dduh.shinyapps.io/dduh/. Examples of how to interact with the dashboard for selected oral health variables are illustrated.

Conclusion
Visualisation of national child cohort data in an interactive dashboard allows viewers to dynamically explore oral health data without requiring multiple plots and tables and sharing of extensive documentation. Dashboard development requires minimal non-standard R coding and can be quickly created with open-source software.
There’s no time for no stress! Exploring the relationship between pharmacy student stress and time use
Authors: Minshew Lana M. , Bensky Hannah P. , Zeeman Jacqueline M. 
Published: April 2023

Abstract
Background
Health professions students experience significantly more stress than students 20 years ago. While prior studies have explored student time use and other studies have begun to explore factors influencing student stress, little is known about the relationship between student time use and stress. As more efforts are employed to promote student wellness and better understand student stress, it is imperative to recognize the implications of time as a finite resource. Thus, it is important to understand if and how time use relates to student stress so the two can be better managed.

Methods
A mixed methods approach exploring the challenge-hindrance stressor framework was used to collect and analyze student stress and time use. First, second, and third year pharmacy students were invited to participate. Participants completed the Perceived Stress Scale (PSS10), a week-long daily time logging activity, and daily stress questionnaire. After the week-long daily time logging, students participated in a semi-structured focus group. Descriptive statistics were used to analyze quantitative data, and inductive coding along with creation of summary reports were created for the qualitative data.

Results
Students reported moderate stress on the PSS10, and spending the majority of their time on activities of daily life and academic activities. Students shared that academics, co-curriculars, and working for pay increased their stress, whereas discretionary activities such as socializing and exercising alleviated stress. Finally, students reported feeling overwhelmed due to too little time to complete all necessary activities daily, including limited time to invest in discretionary activities to support their wellbeing.

Conclusions
Increased stress levels among students is a concerning trend that affects students’ mental health and therefore limits their ability to perform to their greatest potential. Better understanding of the relationship between time use and stress is critical to improve the quality of life of students in the health professions. These findings provide critical insight into factors contributing towards student stress that can inform curricular strategies that support wellness within health professions education.
Submersion and hypoxia inhibit alveolar epithelial Na+ transport through ERK/NF-κB signaling pathway
Authors: Zhou Wei , Hou Yapeng , Yu Tong , Wang Tingyu , Ding Yan , Nie Hongguang 
Published: April 2023

Abstract
Background
Hypoxia is associated with many respiratory diseases, partly due to the accumulation of edema fluid and mucus on the surface of alveolar epithelial cell (AEC), which forms oxygen delivery barriers and is responsible for the disruption of ion transport. Epithelial sodium channel (ENaC) on the apical side of AEC plays a crucial role to maintain the electrochemical gradient of Na+ and water reabsorption, thus becomes the key point for edema fluid removal under hypoxia. Here we sought to explore the effects of hypoxia on ENaC expression and the further mechanism related, which may provide a possible treatment strategy in edema related pulmonary diseases.

Methods
Excess volume of culture medium was added on the surface of AEC to simulate the hypoxic environment of alveoli in the state of pulmonary edema, supported by the evidence of increased hypoxia-inducible factor-1 expression. The protein/mRNA expressions of ENaC were detected, and extracellular signal-regulated kinase (ERK)/nuclear factor κB (NF-κB) inhibitor was applied to explore the detailed mechanism about the effects of hypoxia on epithelial ion transport in AEC. Meanwhile, mice were placed in chambers with normoxic or hypoxic (8%) condition for 24 h, respectively. The effects of hypoxia and NF-κB were assessed through alveolar fluid clearance and ENaC function by Ussing chamber assay.

Results
Hypoxia (submersion culture mode) induced the reduction of protein/mRNA expression of ENaC, whereas increased the activation of ERK/NF-κB signaling pathway in parallel experiments using human A549 and mouse alveolar type 2 cells, respectively. Moreover, the inhibition of ERK (PD98059, 10 µM) alleviated the phosphorylation of IκB and p65, implying NF-κB as a downstream pathway involved with ERK regulation. Intriguingly, the expression of α-ENaC could be reversed by either ERK or NF-κB inhibitor (QNZ, 100 nM) under hypoxia. The alleviation of pulmonary edema was evidenced by the administration of NF-κB inhibitor, and enhancement of ENaC function was supported by recording amiloride-sensitive short-circuit currents.

Conclusions
The expression of ENaC was downregulated under hypoxia induced by submersion culture, which may be mediated by ERK/NF-κB signaling pathway.
Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis
Authors: Runge Manuela , Stahlfeld Anne , Ambrose Monique , Toh Kok Ben , Rahman Semiu , Omoniwa Omowunmi F. , Bever Caitlin A. , Oresanya Olusola , Uhomoibhi Perpetua , Galatas Beatriz , Tibenderana James K. , Gerardin Jaline 
Published: April 2023

AbstractBackgroundA recent WHO recommendation for perennial malaria chemoprevention (PMC) encourages countries to adapt dose timing and number to local conditions. However, knowledge gaps on the epidemiological impact of PMC and possible combination with the malaria vaccine RTS,S hinder informed policy decisions in countries where malaria burden in young children remains high.MethodsThe EMOD malaria model was used to predict the impact of PMC with and without RTS,S on clinical and severe malaria cases in children under the age of two years (U2). PMC and RTS,S effect sizes were fit to trial data. PMC was simulated with three to seven doses (PMC-3-7) before the age of eighteen months and RTS,S with three doses, shown to be effective at nine months. Simulations were run for transmission intensities of one to 128 infectious bites per person per year, corresponding to incidences of < 1 to 5500 cases per 1000 population U2. Intervention coverage was either set to 80% or based on 2018 household survey data for Southern Nigeria as a sample use case. The protective efficacy (PE) for clinical and severe cases in children U2 was calculated in comparison to no PMC and no RTS,S.ResultsThe projected impact of PMC or RTS,S was greater at moderate to high transmission than at low or very high transmission. Across the simulated transmission levels, PE estimates of PMC-3 at 80% coverage ranged from 5.7 to 8.8% for clinical, and from 6.1 to 13.6% for severe malaria (PE of RTS,S 10–32% and 24.6–27.5% for clinical and severe malaria, respectively. In children U2, PMC with seven doses nearly averted as many cases as RTS,S, while the combination of both was more impactful than either intervention alone. When operational coverage, as seen in Southern Nigeria, increased to a hypothetical target of 80%, cases were reduced beyond the relative increase in coverage.ConclusionsPMC can substantially reduce clinical and severe cases in the first two years of life in areas with high malaria burden and perennial transmission. A better understanding of the malaria risk profile by age in early childhood and on feasible coverage by age, is needed for selecting an appropriate PMC schedule in a given setting.
Sublobar resection versus lobectomy in the treatment of synchronous multiple primary lung cancer
Authors: Niu Niu , Zhou Liang , Zhao Junjie , Ma Xingjie , Yang Fan , Qi Weibo 
Published: April 2023

Abstract
Objective
Although synchronous multiple primary lung cancers (sMPLCs) are common in clinical practice, the choice of surgical modalities for the main lesion is still at the stage of exploration. This study is designed to analyze the prognosis of sMPLCs and single primary lung cancers with similar tumor stages and to explore whether sublobar resection has a similar prognosis as lobectomy for sMPLCs.

Methods
One-hundred forty-one cases of sMPLCs were selected, including the following: 65 cases underwent lobectomy for main lesions, and 76 cases underwent sublobar resection for main lesions. One thousand one hundred forty-four cases of single primary lung cancer were matched at 1:1 by propensity score matching. Then, the patients with sMPLCs were divided into a lobectomy group and a sublobar group according to the first tumor stage. Ninety-eight cases of patients with sMPLCs were matched. The short-term perioperative effect, 5-year disease-free survival (DFS) rate, and 5-year overall survival (OS) rate between the two groups were compared.

Results
There was no significant difference in OS between sMPLCs and single primary lung cancer after lobectomy (77.1% vs. 77.2%, P = 0.157) and sublobar resection (98.7% vs. 90.7%, P = 0.309). There was no significant difference in OS (86.7% vs. 83.9%, P = 0.482) or DFS (67.6 vs. 87.7%, P = 0.324) between the lobectomy group and sublobar group with sMPLCs. The sublobar resection group obtained a lower incidence of postoperative complications (40.8% vs. 16.3%, P = 0.007) and shorter postoperative hospital stay (11.22 vs. 9.27, P = 0.049).

Conclusion
The prognosis of patients with sMPLCs generally depends on the main tumor state, which has no statistical difference regardless of sublobar resection or lobectomy, and the perioperative period of sublobar resection is safer than that of lobectomy.