bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a performance-based financing scheme in Malawi and resulting externalities on the quality of care of non-incentivized services
Authors: Brenner Stephan , Favaretti Caterina , Lohmann Julia , Chinkhumba Jobiba , Muula Adamson S. , De Allegri Manuela 
Published: May 2021

Abstract
Background
Countries in Africa progressively implement performance-based financing schemes to improve the quality of care provided by maternal, newborn and child health services. Beyond its direct effects on service provision, evidence suggests that performance-based financing can also generate positive externalities on service utilization, such as increased use of those services that reached higher quality standards after effective scheme implementation. Little, however, is known about externalities generated within non-incentivized health services, such as positive or negative effects on the quality of services within the continuum of maternal care.

Methods
We explored whether a performance-based financing scheme in Malawi designed to improve the quality of childbirth service provision resulted positive or negative externalities on the quality of non-targeted antenatal care provision. This non-randomized controlled pre-post-test study followed the phased enrolment of facilities into a performance-based financing scheme across four districts over a two-year period. Effects of the scheme were assessed by various composite scores measuring facilities’ readiness to provide quality antenatal care, as well as the quality of screening, prevention, and education processes offered during observed antenatal care consultations.

Results
Our study did not identify any statistically significant effects on the quality of ANC provision attributable to the implemented performance-based financing scheme. Our findings therefore suggest not only the absence of positive externalities, but also the absence of any negative externalities generated within antenatal care service provision as a result of the scheme implementation in Malawi.

Conclusions
Prior research has shown that the Malawian performance-based financing scheme was sufficiently effective to improve the quality of incentivized childbirth service provision. Our findings further indicate that scheme implementation did not affect the quality of non-incentivized but clinically related antenatal care services. While no positive externalities could be identified, we also did not observe any negative externalities attributable to the scheme’s implementation. While performance-based incentives might be successful in improving targeted health care processes, they have limited potential in producing externalities – neither positive nor negative – on the provision quality of related non-incentivized services.
Radiographic features and prognosis of early- and late-onset non-small cell lung cancer immune checkpoint inhibitor-related pneumonitis
Authors: Huang Aiben , Xu Yang , Zang Xuelei , Wu Chongchong , Gao Jie , Sun Xiaoli , Xie Mei , Ma Xidong , Deng Hui , Song Jialin , Ren Fangping , Pang Li , Qian Jin , Yu Zhaofeng , Wan Shiyu , Chen Yuanyuan , Pan Lei , Zhuang Guanglei , Liu Sanhong , Xue Xinying 
Published: May 2021

Abstract
Background
Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis.

Methods
We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP.

Results
CIP had an incidence of 4.7%, a median onset time of 10 weeks, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥ 3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥ 3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05).

Conclusion
Early-onset CIP cases were higher in the Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in CTCAE grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP.
Significance of KDM6A mutation in bladder cancer immune escape
Authors: Chen Xingxing , Lin Xuehua , Pang Guofu , Deng Jian , Xie Qun , Zhang Zhengrong 
Published: May 2021

Abstract
Background
Bladder cancer (BC) is the fourth most prevalent neoplasm in men and is associated with high tumour recurrence rates, leading to major treatment challenges. Lysine-specific demethylase 6A (KDM6A) is frequently mutated in several cancer types; however, its effects on tumour progression and clinical outcome in BC remain unclear. Here, we explored the potential role of KDM6A in regulating the antitumor immune response.

Methods
We mined The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for somatic mutation and clinical data in patients with BC.

Results
We found frequent mutations in 12 genes in both cohorts, including TP53, KDM6A, CSMD3, MUC16, STAG2, PIK3CA, ARID1A, RB1, EP300, ERBB2, ERBB3, and FGFR3. The frequency o KDM6A mutations in the TCGA and ICGC datasets was 25.97 and 24.27%, respectively. In addition, KDM6A mutation was associated with a lower number of tumour-infiltrating immune cells (TIICs) and indicated a state of immune tolerance. KDM6A mutation was associated with lower KDM6A mRNA level compared with that in samples carrying the wild-type gene. Further, survival analysis showed that the prognosis of patients with low KDM6A expression was worse than that with high KDM6A expression. Using the CIBERSORT algorithm, Tumor Immune Estimation Resource site, and Gene Set Enrichment Analysis, we found that KDM6A mutation downregulated nine signalling pathways that participate in the immune system and attenuated the tumour immune response.

Conclusion
Overall, we conclude that KDM6A mutation is frequent in BC and promotes tumour immune escape, which may serve as a novel biomarker to predict the immune response.
Breast lesions excised via vacuum-assisted system: could we get any clues for B3 lesions before excision biopsy?
Authors: Zheng Liang , Zheng Fufu , Xing Zhaomin , Zhang Yunjian , Li Yongxin , Xu Hongbiao , Lai Yuanhui , Li Jie , Wang Wenjian 
Published: May 2021

Abstract
Background
The purpose of this study was to determine the validity of the ultrasound features as well as patient characteristics assigned to B3 (uncertain malignant potential) breast lesions before vacuum-assisted excision biopsy (VAEB).

Methods
This study population consisted of 2245 women with breast-nodular abnormalities, which were conducted ultrasound-guided VAEB (US-VAEB). Patient’s clinical and anamnestic data and lesion-related ultrasonic feature variables of B3 captured before US-VAEB were compared with those of benign or malignant cases, using histopathological results as a benchmark.

Results
The proportions of benign, B3 and malignant breast lesions diagnosed post-US-VAEB were 88.5, 8.2 and 3.4% respectively. B3 high frequent occurred in BI-RADS-US grade 3 (7.7%), grade 4a (11.0%) and grade 4b (9.1%). The overall malignancy underestimation rate of B3 was 4.4% (8/183). Malignant lesions were found mostly in the range of BI-RADS grade 4b (27.3%), grade 4c (33.3%) and grade 5 (100%). Multivariate binary logistic regression analyses (B3 vs benign) showed that non-menopausal patients (95% CI 1.628–8.616, P = 0.002), single (95% CI 1.370–2.650, P = 0.000) or vascularity (95% CI 1.745–4.150, P = 0.000) nodules in ultrasonic features were significant risk factors for B3 occurrences. In addition, patients elder than 50 years (95% CI 3.178–19.816, P = 0.000), unclear margin (95% CI 3.571–14.119, P = 0.000) or suspicious calcification (95% CI 4.010–30.733, P = 0.000) lesions were significantly associated with higher risks of malignant potentials for B3 cases (malignant vs B3).

Conclusion
The results of this study indicate that ultrasound findings and patients’ characteristics might provide valuable information for distinguishing B3 lesions from benign breast abnormalities before VAEB, and help to reduce malignancy underestimation of B3.
Pooled CRISPR screening in pancreatic cancer cells implicates co-repressor complexes as a cause of multiple drug resistance via regulation of epithelial-to-mesenchymal transition
Authors: Ramaker Ryne C. , Hardigan Andrew A. , Gordon Emily R. , Wright Carter A. , Myers Richard M. , Cooper Sara J. 
Published: May 2021

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) patients suffer poor outcomes, including a five-year survival of below 10%. Poor outcomes result in part from therapeutic resistance that limits the impact of cytotoxic first-line therapy. Novel therapeutic approaches are needed, but currently no targeted therapies exist to treat PDAC.MethodsTo assess cellular resistance mechanisms common to four cytotoxic chemotherapies (gemcitabine, 5-fluorouracil, irinotecan, and oxaliplatin) used to treat PDAC patients, we performed four genome-wide CRISPR activation (CRISPRact) and CRISPR knock-out (CRISPRko) screens in two common PDAC cell lines (Panc-1 and BxPC3). We used pathway analysis to identify gene sets enriched among our hits and conducted RNA-sequencing and chromatin immunoprecipitation-sequencing (ChIP-seq) to characterize top hits from our screen. We used scratch assays to assess changes in cellular migration with HDAC1 overexpression.ResultsOur data revealed activation of ABCG2,a well-described efflux pump, as the most consistent mediator of resistance in each of our screens. CRISPR-mediated activation of genes involved in transcriptional co-repressor complexes also conferred resistance to multiple drugs. Expression of many of these genes, including HDAC1, is associated with reduced survival in PDAC patients. Up-regulation of HDAC1 in vitro increased promoter occupancy and expression of several genes involved in the epithelial-to-mesenchymal transition (EMT). These cells also displayed phenotypic changes in cellular migration consistent with activation of the EMT pathway. The expression changes resulting from HDAC1 activation were also observed with activation of several other co-repressor complex members. Finally, we developed a publicly available analysis tool, PancDS, which integrates gene expression profiles with our screen results to predict drug sensitivity in resected PDAC tumors and cell lines.ConclusionOur results provide a comprehensive resource for identifying cellular mechanisms of drug resistance in PDAC, mechanistically implicate HDAC1, and co-repressor complex members broadly, in multi-drug resistance, and provide an analytical tool for predicting treatment response in PDAC tumors and cell lines.
Profiles of total worker health® in United States small businesses
Authors: Schwatka Natalie V. , Dally Miranda , Shore Erin , Dexter Lynn , Tenney Liliana , Brown Carol E. , Newman Lee S. 
Published: May 2021

Abstract
Background
The Total Worker Health® (TWH) approach is a best practice method to protect and promote worker safety, health, and well-being. Central to this approach is leadership support and health and safety climates that support day-to-day use of health and safety policies and programs. There is some research that supports these relationships, but there is limited research amongst small businesses. Furthermore, it remains to be shown what role TWH business strategies, as reflected by organizational policies and programs, play in this process. The purpose of this study is to characterize small businesses by their organizations’ TWH approach and assess the relationship of these approaches to employee health and safety behaviors.

Methods
We utilized cross-sectional data from 97 businesses participating in the Small+Safe+Well study. We collected data using a business assessment tool, Healthy Workplace Assessment™, and an employee assessment tool, Employee Health and Safety Culture Survey. We used latent profile analysis at the business level to identify subgroups of businesses based on a set of characteristics from these assessments. Linear regression analysis at the employee level was used to determine profile association with employee safety and health behaviors.

Results
There were two profiles characterized by the lowest (33% of all businesses) and highest (9%) levels of the indicators. There were also two profiles with higher scores on two of the different foci on either TWH business strategies (27%) or leadership and climate (31%). Employees working for a business with a profile that focused on leadership and climate, in addition to having a business strategy, reported the best safety and health behaviors.

Conclusions
Our study demonstrates that employee engagement in TWH will be highest when businesses have a strategy for how they implement a TWH approach and when they demonstrate leadership commitment to these strategies and foster positive safety and health climates. Our results offer suggestions on how to use TWH assessments to develop interventions for small businesses. More research is needed to understand whether small businesses can improve upon their profile overtime, whether these changes depend on contextual factors, and whether TWH interventions can help them improve their profile.
Feasibility pilot of an adapted parenting program embedded within the Thai public health system
Authors: McCoy Amalee , Lachman Jamie M. , Ward Catherine L. , Tapanya Sombat , Poomchaichote Tassawan , Kelly Jane , Mukaka Mavuto , Cheah Phaik Yeong , Gardner Frances 
Published: May 2021

Abstract
Background
This feasibility pilot of the Parenting for Lifelong Health for Young Children program in Thailand aimed to: 1) explore the feasibility of study evaluation approaches; 2) assess the feasibility of delivering an adapted program; 3) report indicative effects on child maltreatment and related outcomes; and 4) examine intervention content associated with key mechanisms of change perceived by caregivers and facilitators.

Method
Sixty primary caregivers of children aged 2–9 years were recruited for an 8-week parenting program embedded within the local health system. Mixed-methods approaches included quantitative caregiver-report and observational data from standardized instruments, and qualitative data from individual and group interviews with caregivers and program facilitators. Analyses involved Wilcoxon signed-rank tests, paired t-tests, Friedman’s ANOVA, and thematic analysis.

Results
Participants reported that most (65%) were grandparents or great-grandparents. Study retention and response rates were high, and enrolled caregivers attended an average of 93% of sessions. Primary outcomes showed caregiver-reported pre-post reductions in overall child maltreatment (d = − 0.58, p < 0.001), as well as reductions in physical (d = − 0.58, p < 0.001) and emotional abuse (d = − 0.40, p < 0.001). Combined caregiver report and observational assessments using the HOME Inventory showed reductions in abusive and harsh parenting (d = − 0.52, p < 0.001). Secondary outcomes demonstrated decreases in child neglect; dysfunctional parenting; poor child monitoring and supervision; parental sense of inefficacy; child behavior problems; daily report on child problem behavior; parent overall depression, anxiety, and stress; and attitudes supporting physical punishment and harsh discipline. There were increases in overall positive parenting, daily positive parenting behavior, as well as HOME Inventory assessments on parent-child relationships. Thematic analyses from interviews and focus group data identified six key program themes associated with strengthened parent-child relationships, reduced child behavior problems, improved attitudes and strategies toward discipline, and improved management of parental stress.

Conclusions
This study represents one of few evaluations to test the feasibility of an evidence-based parenting program embedded within routine public health service delivery in a low- or middle-income country. Findings show preliminary effectiveness in reducing child maltreatment, improvements on 22 of 24 secondary outcomes, and perceived mechanisms of change that support quantitative findings. Prospects are promising for program scalability, pending randomized controlled trial results.

Trial registration
11/01/2019, ClinicalTrials.gov, ID# NCT03539341.
“I don’t feel safe sitting in my own yard”: Chicago resident experiences with urban rats during a COVID-19 stay-at-home order
Authors: Murray Maureen H. , Byers Kaylee A. , Buckley Jacqueline , Magle Seth B. , Maffei Dorothy , Waite Preeya , German Danielle 
Published: May 2021

Abstract
Background
Encounters with rats in urban areas increase risk of human exposure to rat-associated zoonotic pathogens and act as a stressor associated with psychological distress. The frequency and nature of human-rat encounters may be altered by social distancing policies to mitigate the COVID-19 pandemic. For example, restaurant closures may reduce food availability for rats and promote rat activity in nearby residential areas, thus increasing public health risks during a period of public health crisis. In this study, we aimed to identify factors associated with increased perceived exposure to rats during a stay-at-home order, describe residents’ encounters with rats relevant to their health and well-being, and identify factors associated with increased use of rodent control.

Methods
Urban residents in Chicago, a large city with growing concerns about rats and health disparities, completed an online questionnaire including fixed response and open-ended questions during the spring 2020 stay-at-home order. Analyses included ordinal multivariate regression, spatial analysis, and thematic analysis for open-ended responses.

Results
Overall, 21% of respondents (n = 835) reported an increase in rat sightings around their homes during the stay-at-home order and increased rat sightings was positively associated with proximity to restaurants, low-rise apartment buildings, and rat feces in the home (p ≤ 0.01). Many respondents described feeling unsafe using their patio or yard, and afraid of rats entering their home or spreading disease. Greater engagement with rodent control was associated with property ownership, information about rat control, and areas with lower incomes (p ≤ 0.01).

Conclusions
More frequent rat encounters may be an unanticipated public health concern during periods of social distancing, especially in restaurant-dense areas or in low-rise apartment buildings. Rat presence may also limit residents’ ability to enjoy nearby outdoor spaces, which otherwise might buffer stress experienced during a stay-at-home order. Proactive rat control may be needed to mitigate rat-associated health risks during future stay-at-home orders.
Authentication of differential gene expression in oral squamous cell carcinoma using machine learning applications
Authors: Pratama Rian , Hwang Jae Joon , Lee Ji Hye , Song Giltae , Park Hae Ryoun 
Published: May 2021

Abstract
Background
Recently, the possibility of tumour classification based on genetic data has been investigated. However, genetic datasets are difficult to handle because of their massive size and complexity of manipulation. In the present study, we examined the diagnostic performance of machine learning applications using imaging-based classifications of oral squamous cell carcinoma (OSCC) gene sets.

Methods
RNA sequencing data from SCC tissues from various sites, including oral, non-oral head and neck, oesophageal, and cervical regions, were downloaded from The Cancer Genome Atlas (TCGA). The feature genes were extracted through a convolutional neural network (CNN) and machine learning, and the performance of each analysis was compared.

Results
The ability of the machine learning analysis to classify OSCC tumours was excellent. However, the tool exhibited poorer performance in discriminating histopathologically dissimilar cancers derived from the same type of tissue than in differentiating cancers of the same histopathologic type with different tissue origins, revealing that the differential gene expression pattern is a more important factor than the histopathologic features for differentiating cancer types.

Conclusion
The CNN-based diagnostic model and the visualisation methods using RNA sequencing data were useful for correctly categorising OSCC. The analysis showed differentially expressed genes in multiwise comparisons of various types of SCCs, such as KCNA10, FOSL2, and PRDM16, and extracted leader genes from pairwise comparisons were FGF20, DLC1, and ZNF705D.
Antlerogenic stem cells extract accelerate chronic wound healing: a preliminary study
Authors: Kmiecik Janusz , Kulus Michał Jerzy , Popiel Jarosław , Cekiera Agnieszka , Cegielski Marek 
Published: May 2021

Abstract
Background
Chronic wounds constitute a significant medical and social problem. Chronic wound treatment may be supported by various techniques, such as negative pressure therapy, phototherapy or stem cells therapy, yet most of those supporting therapies need more evidence to be used for standard wound care. Current study covers the use of sonicated Antlerogenic Stem Cells (ASC) extract on chronic wounds.

Methods
Study was performed on 20 dermatological patients with venous leg ulcers, divided into two groups – treated with and without ASC extract respectively. The area and circumference of the wounds during the follow-up visits were measured on the wound imprint. Dynamics of wound healing was determined and compared between control and study group; statistics includes changes in absolute values (wound area, circumference), as well as relative (percentage of wound decrease, circumference/area ratio) and their change in time. For the purpose of Ki-67 immunohistochemical staining, sections were sampled from the wound edge at distinct check-points during therapy. Results of both groups were compared with Student test or Mann-Whitney test, depending on results distribution.

Results
Besides Ki-67 expression, all tested wound healing parameters (including relative and absolute wound decrease and changes in circumference/area ratio) were statistically significant more favorable in experimental group.

Conclusion
ASC extract significantly supported standard chronic wound treatment. Due to small population of study the results should be considered preliminary, yet promising for further research.