bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: a systematic review and meta-analysis
Authors: Finnerty James Patrick , Ponnuswamy Aravind , Dutta Prosjenjit , Abdelaziz Ammar , Kamil Hafiz 
Published: December 2021

Abstract
Background
Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF.

Study design and methods
A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies.

Results
13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was − 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were − 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71.

Interpretation
Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy.

Trial Registration PROSPERO, registration number CRD42021266046.
Chloroplast genome sequencing based on genome skimming for identification of Eriobotryae Folium
Authors: Li Fang , Xie Xuena , Huang Rong , Tian Enwei , Li Chan , Chao Zhi 
Published: December 2021

Abstract
Background
Whole chloroplast genome (cpDNA) sequence is becoming widely used in the phylogenetic studies of plant and species identification, but in most cases the cpDNA were acquired from silica gel dried fresh leaves. So far few reports have been available to describe cpDNA acquisition from crude drugs derived from plant materials, the DNA of which usually was seriously damaged during their processing. In this study, we retrieved cpDNA from the commonly used crude drug Eriobotryae Folium (Pipaye in Chinese, which is the dried leaves of Eriobotrya japonica, PPY) using genome skimming technique.

Results
We successfully recovered cpDNA sequences and rDNA sequences from the crude drug PPY, and bioinformatics analysis showed a high overall consistency between the cpDNA obtained from the crude drugs and fresh samples. In the ML tree, each species formed distinct monophyletic clades based on cpDNA sequence data, while the phylogenetic relationships between Eriobotrya species were poorly resolved based on ITS and ITS2.

Conclusion
Our results demonstrate that both cpDNA and ITS/ITS2 are effective for identifying PPY and its counterfeits derived from distantly related species (i.e. Dillenia turbinata and Magnolia grandiflora), but cpDNA is more effective for distinguishing the counterfeits derived from the close relatives of Eriobotrya japonica, suggesting the potential of genome skimming for retrieving cpDNA from crude drugs used in Traditional Chinese Medicine for their identification.
Menstrual characteristics, menstrual anxiety and school attendance among adolescents in Uganda: a longitudinal study
Authors: Tanton Clare , Nakuya Kevin , Kansiime Catherine , Hytti Laura , Torondel Belen , Francis Suzanna C. , Namirembe Prossy , Nakalema Shamirah , Nalugya Ruth , Musoke Saidat Namuli , Neema Stella , Ross David A. , Bonell Chris , Seeley Janet , Weiss Helen A. 
Published: December 2021

Abstract
Background
Qualitative data show negative impacts of menstruation on health and education in many settings, but there are few longitudinal quantitative studies of the impact of menstruation. We analyse associations with menstrual anxiety and school attendance in a study of Ugandan secondary school students.

Methods
Data were from a longitudinal pilot study of a menstrual health intervention (MENISCUS), conducted in two secondary schools in Entebbe sub-district, Uganda. Self-completed menstrual-related data, including menstrual anxiety, were collected from 232 participants pre- and post-intervention. A sub-cohort of 100 randomly-selected post-menarcheal girls were asked to self-complete daily diaries during 10 months of follow-up, with data on menstrual flow, pain, and school attendance. We used multivariable logistic regression to estimate associations with menstrual anxiety among all girls at baseline, and random-effects logistic regression to estimate associations of menstrual characteristics with school non-attendance for 3 months pre-intervention in the sub-cohort, adjusting for within-girl clustering.

Results
Overall, 130/222 (58.6%) of menstruating girls reported being anxious about their next period. Menstrual anxiety was higher in those not living with their mother (adjusted odds ratio (OR) = 1.91; 95% confidence interval (CI) 1.01–3.60), believing menstrual myths (aOR = 1.83; 0.95–3.50 for not agreeing that it is healthy for a girl to run, dance or cycle during her period; aOR = 1.97; 1.04–3.73 for agreeing that when a girl has her period she is unclean), lower menstrual confidence (aOR = 2.49; 1.33–4.65 for avoiding physical activity during her period; aOR = 1.68; 0.89–3.17 for not feeling comfortable to talk to other girls about her period; aOR = 2.89; 1.28–6.54 for agreeing that boys/girls tease them about their periods; and aOR = 2.27; 1.21–4.27 for worrying about being teased during her period). Those with lower knowledge about menstruation were less likely to report anxiety (aOR = 0.44; 0.23–0.84). During the pre-intervention period of the sub-cohort, school non-attendance was associated with menstrual pain, with 21.7% of girls missing school on days when they reported pain vs. 8.3% on days when no pain was reported (aOR = 3.82; 1.66–8.77).

Conclusions
Menstruation causes substantial anxiety in Ugandan schoolgirls, and menstrual pain is associated with missing school on period-days. Menstrual health interventions should address socio-cultural aspects of menstruation to reduce anxiety, and provide education on pain management strategies to support school attendance.
Validation of Internal structure of Self-Directed Learning Readiness Scale among Indian Medical Students using factor analysis and the Structural equation Modelling Approach
Authors: Kumar Archana Prabu , Omprakash Abirami , Mani Prabu Kumar Chokkalingam , Swaminathan Narasimman , Maheshkumar K. , Maruthy K. N. , Sathiyasekaran B. W. C. , Vijayaraghavan P. V. , Padmavathi R 
Published: December 2021

AbstractBackgroundThe Self-Directed Learning Readiness Scale (SDLRS) is a tool that helps in the assessment of the readiness of the students to pursue Self-Directed Learning (SDL). There are no documented studies on the validation of internal structure of the SDLRS among Indian medical students. Hence, the objective of this study is to validate the internal structure of SDLRS among Indian medical students using factor analysis and the Structural Equation Modelling (SEM) approach.MethodsWe administered Fisher’s 40-item SDLRS to 750 students after receiving the ethics clearance and the author’s permission and taking written informed consent from all the study participants (response rate: 92%). The exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and Cronbach’s alpha were performed using SPSS version 25 and the Lavaan package of R version 3.1.2.ResultsThe values of the comparative fit index (CFI), standardised root-mean-square residual (SRMR), and root mean square error of approximation (RMSEA) were ≥ 0.9, ≤ 0.08, and ≤ 0.08, respectively, for a model fit to be acceptable. EFA showed that except for Q2 (loading score: 0.210), Q12 (loading score: 0.384), Q13 (loading score: 0.362), and Q25 (loading score: -0.219), all the items loaded well. After the exclusion of the aforementioned items, the factor loading scores for the items in the self-management, desire for learning, and self-control factors ranged from 0.405 to 0.753 (Cronbach α: 0.775), 0.396 to 0.616 (Cronbach α: 0.730), and 0.427 to 0.556 (Cronbach α: 0.799), respectively. The updated model was used for CFA, which displayed a good model fit.ConclusionsThe resultant model consisting of 36 items is shown to have internal structure validity for Indian version of SDLRS, which can be used to assess medical students.
For-profit hospitals as anchor institutions in the United States: a study of organizational stability
Authors: Franz Berkeley , Cronin Cory E. , Rodriguez Vanessa , Choyke Kelly , Simon Janet E. , Hall Maxwell T. 
Published: December 2021

Abstract
Background
Anchor institutions, by definition, have a long-term presence within their local communities, but it is uncertain as to whether for-profit hospitals meet this definition; most research on anchor institutions to date has been limited to nonprofit organizations such as hospitals and universities. Accordingly, this study aims to determine whether for-profit hospitals are stable enough to fulfill the role of anchor institutions through a long-term presence in communities which may help to stabilize local economies.

Methods
This longitudinal study analyzes national, secondary data between 2008 and 2017 compiled from the Dartmouth Atlas of Health Care, the American Hospital Association Annual Survey, and County Health Rankings. We use descriptive statistics to calculate the number of closures and mergers of hospitals of different ownership type, as well as staffing levels. Using logistic regression, we also assessed whether for-profit hospitals had higher odds of closing and merging, controlling for both organization and community factors.

Results
We found for-profit hospitals to be less stable than their public and nonprofit hospital counterparts, experiencing disproportionately more closures and mergers over time, with a multivariable analysis indicating a statistically significant difference. Furthermore, for-profit hospitals have fewer full-time employees relative to their size than hospitals of other ownership types, as well as lower total payroll expenditures.

Conclusions
Study findings suggest that for-profit hospitals operate more efficiently in terms of expenses, but this also may translate into a lower level of economic contributions to the surrounding community through employment and purchasing initiatives. For-profit hospitals may also not have the stability required to serve as long-standing anchor institutions. Future studies should consider whether for-profit hospitals make other types of community investments to offset these deficits and whether policy changes can be employed to encourage anchor activities from local businesses such as hospitals.
Nanoscale characterization of drug-induced microtubule filament dysfunction using super-resolution microscopy
Authors: Rozario Ashley M. , Duwé Sam , Elliott Cade , Hargreaves Riley B. , Moseley Gregory W. , Dedecker Peter , Whelan Donna R. , Bell Toby D. M. 
Published: December 2021

Abstract
Background
The integrity of microtubule filament networks is essential for the roles in diverse cellular functions, and disruption of its structure or dynamics has been explored as a therapeutic approach to tackle diseases such as cancer. Microtubule-interacting drugs, sometimes referred to as antimitotics, are used in cancer therapy to target and disrupt microtubules. However, due to associated side effects on healthy cells, there is a need to develop safer drug regimens that still retain clinical efficacy. Currently, many questions remain open regarding the extent of effects on cellular physiology of microtubule-interacting drugs at clinically relevant and low doses. Here, we use super-resolution microscopies (single-molecule localization and optical fluctuation based) to reveal the initial microtubule dysfunctions caused by nanomolar concentrations of colcemid.

Results
We identify previously undetected microtubule (MT) damage caused by clinically relevant doses of colcemid. Short exposure to 30–80 nM colcemid results in aberrant microtubule curvature, with a trend of increased curvature associated to increased doses, and curvatures greater than 2 rad/μm, a value associated with MT breakage. Microtubule fragmentation was detected upon treatment with ≥ 100 nM colcemid. Remarkably, lower doses (< 20 nM after 5 h) led to subtle but significant microtubule architecture remodelling characterized by increased curvature and suppression of microtubule dynamics.

Conclusions
Our results support the emerging hypothesis that microtubule-interacting drugs induce non-mitotic effects in cells, and establish a multi-modal imaging assay for detecting and measuring nanoscale microtubule dysfunction. The sub-diffraction visualization of these less severe precursor perturbations compared to the established antimitotic effects of microtubule-interacting drugs offers potential for improved understanding and design of anticancer agents.
Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations
Authors: Wang Chaohong , Tang Junxiang , Tong Keting , Huang Daoqi , Tu Huayu , Li Qingnan , Zhu Jiansheng 
Published: December 2021

Abstract
Purpose
The aim of this study was to assess the detection efficiency and clinical application value of non-invasive prenatal testing (NIPT) for foetal copy number variants (CNVs) in clinical samples from 39,002 prospective cases.

Methods
A total of 39,002 pregnant women who received NIPT by next-generation sequencing (NGS) with a sequencing depth of 6 M reads in our centre from January 2018 to April 2020 were enrolled. Chromosomal microarray analysis (CMA) was further used to diagnose suspected chromosomal aneuploidies and chromosomal microdeletion/microduplication for consistency assessment.

Results
A total of 473 pregnancies (1.213%) were positive for clinically significant foetal chromosome abnormalities by NIPT. This group comprised 99 trisomy 21 (T21, 0.254%), 30 trisomy 18 (T18, 0.077%), 25 trisomy 13 (T13, 0.064%), 155 sex chromosome aneuploidy (SCA, 0.398%), 69 rare trisomy (0.177%), and 95 microdeletion/microduplication syndrome (MMS, 0.244%) cases. Based on follow-up tests, the positive predictive values (PPVs) for the T21, T18, T13, SCA, rare trisomy, and MMS cases were calculated to be 88.89%, 53.33%, 20.00%, 40.22%, 4.88%, and 49.02%, respectively. In addition, the PPVs of CNVs of < 5 Mb, 5–10 Mb, and > 10 Mb were 54.55%, 38.46%, and 40.00%, respectively. Among the 95 cases with suspected CNVs, 25 were diagnosed as true positive and 26 cases as false positive; follow-up prenatal diagnosis by CMA was not performed for 44 cases. Moreover, among the 25 true positive cases, 10 were pathogenic, 3 were likely pathogenic, and 12 were of uncertain significance.

Conclusion
NIPT is not only suitable for screening T21, T18, T13, and SCA but also has potential significance for CNV detection. As combined with ultrasound, extended NIPT is effective for screening MMS. However, NIPT should not be recommended for whole-chromosome aneuploidy screening.
Transcriptome sequencing reveals a lncRNA–mRNA interaction network in extramammary Paget’s disease
Authors: Zheng Da-chao , Shen Yan-ting , Wei Zi-wei , Wan Xiang , Xie Min-kai , Yao Hai-jun , Wang Zhong 
Published: December 2021

Abstract
Background
Extramammary Paget’s disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA–mRNA interaction network in extramammary Paget’s disease.

Methods
High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA–mRNA interaction network, which was finally confirmed in vitro.

Results
Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA–mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT–PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes.

Conclusion
These findings suggest that the lncRNA–mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.
Changes in the role of explanatory factors for socioeconomic inequalities in physical performance: a comparative study of three birth cohorts
Authors: Klokgieters Silvia S. , Kok Almar A. L. , Visser Marjolein , van Groenou Marjolein I. Broese , Huisman Martijn 
Published: December 2021

Abstract
Background
Due to societal changes and changes in the availability of health promoting factors, explanatory factors of socioeconomic inequalities in health (SIH) may change with time. We investigate differences in the relative importance of behavioural, social and psychological factors for explaining inequalities in physical performance between three birth cohorts.

Methods
Data came from N = 988, N = 1002, and N = 1023 adults aged 55–64 years, collected in 1992, 2002 and 2012 as part of the Longitudinal Aging Study Amsterdam. Physical performance was measured by three performance tests. We included lifestyle factors (physical activity, smoking, alcohol use and Body Mass Index (BMI)); social factors (network size, network complexity, divorce, social support); and psychological factors (mastery, self-efficacy and neuroticism). In multi-group mediation models, we tested whether the strength of indirect effects from socioeconomic position (SEP) via the explanatory factors to health differed between birth cohorts. Stronger indirect effects indicate an increase in the importance; weaker indirect effects indicate a decrease in importance.

Results
Absolute SIH were present and similar across cohorts. The strength of indirect effects of SEP on physical performance through smoking, binge alcohol use, emotional support and mastery increased across cohorts. The indirect effects of BMI, network size, self-efficacy and neuroticism were similar across cohorts.

Conclusions
Inequalities in smoking, binge alcohol use, emotional support and mastery may have become more important for explaining SIH in recent cohorts of middle-aged adults. Policies that aim to reduce socioeconomic inequalities may need to adapt their targets of intervention to changing mechanisms in order to reduce SIH.
Access to primary healthcare Services in Conflict-Affected Fragile States: a subnational descriptive analysis of educational and wealth disparities in Cameroon, Democratic Republic of Congo, Mali, and Nigeria
Authors: Ramadan Marwa , Tappis Hannah , Uribe Manuela Villar , Brieger William 
Published: December 2021

AbstractBackgroundMeasuring and improving equitable access to care is a necessity to achieve universal health coverage. Pre-pandemic estimates showed that most conflict-affected and fragile situations were off-track to meet the Sustainable Development Goals on health and equity by 2030. Yet, there is a paucity of studies examining health inequalities in these settings. This study addresses the literature gap by applying a conflict intensity lens to the analysis of disparities in access to essential Primary Health Care (PHC) services in four conflict-affected fragile states: Cameroon, Democratic Republic of Congo, Mali and Nigeria.MethodsFor each studied country, disparities in geographic and financial access to care were compared across education and wealth strata in areas with differing levels of conflict intensity. The Demographic Health Survey (DHS) and the Uppsala Conflict Data Program were the main sources of information on access to PHC and conflict events, respectively. To define conflict intensity, household clusters were linked to conflict events within a 50-km distance. A cut-off of more than two conflict-related deaths per 100,000 population was used to differentiate medium or high intensity conflict from no or low intensity conflict. We utilized three measures to assess inequalities: an absolute difference, a concentration index, and a multivariate logistic regression coefficient. Each disparity measure was compared based on the intensity of conflict the year the DHS data was collected.ResultsWe found that PHC access varied across subnational regions in the four countries studied; with more prevalent financial than geographic barriers to care. The magnitude of both educational and wealth disparities in access to care was higher with geographic proximity to medium or high intensity conflict. A higher magnitude of wealth rather than educational disparities was also likely to be observed in the four studied contexts. Meanwhile, only Nigeria showed statistically significant interaction between conflict intensity and educational disparities in access to care.ConclusionBoth educational and wealth disparities in access to PHC services can be exacerbated by geographic proximity to organized violence. This paper provides additional evidence that, despite limitations, household surveys can contribute to healthcare assessment in conflict-affected and fragile settings.