bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating a research training programme for frontline health workers in conflict-affected and fragile settings in the middle east
Authors: Naal Hady , Daou Tracy , Brome Dayana , Mansour Rania , Sittah Ghassan Abu , Giannou Christos , Steiger Enrique , Saleh Shadi 
Published: April 2023

Abstract
Background
Health Research Capacity Building (HRCB) is key to improving research production among health workers in LMICs to inform related policies and reduce health disparities in conflict settings. However, few HRCB programmes are available in the MENA region, and few evaluations of HRCB globally are reported in the literature.

Methods
Through a qualitative longitudinal design, we evaluated the first implementation of the Center for Research and Education in the Ecology of War (CREEW) fellowship. Semi-structured interviews were conducted with fellows (n = 5) throughout the programme at key phases during their completion of courses and at each research phase. Additional data was collected from supervisors and peers of fellows at their organizations. Data were analysed using qualitative content analysis and presented under pre-identified themes.

Results
Despite the success of most fellows in learning on how to conduct research on AMR in conflict settings and completing the fellowship by producing research outputs, important challenges were identified. Results are categorized under predefined categories of (1) course delivery, (2) proposal development, (3) IRB application, (4) data collection, (5) data analysis, (6) manuscript write-up, (7) long-term effects, and (8) mentorship and networking.

Conclusion
The CREEW model, based on this evaluation, shows potential to be replicable and scalable to other contexts and other health-related topics. Detailed discussion and analysis are presented in the manuscript and synthesized recommendations are highlighted for future programmes to consider during the design, implementation, and evaluation of such programmes.
Shiftwork sleep disorder and associated factors among nurses working at public hospitals in Harari Regional state and Dire Dawa Administration, Eastern Ethiopia: a cross-sectional study
Authors: Abate Henok , Letta Shiferaw , Worku Teshager , Tesfaye Dejene , Amare Eldana , Mechal Ayalnesh 
Published: April 2023

Abstract
Background
Shiftwork sleep disorder is one of the most common health-related effects of Shiftwork, particularly among healthcare workers. It is a chronic condition that is directly related to a person’s work schedule. In Ethiopia, although a mental health strategy is in place, little attention is given to studies that focus on shiftwork sleep disorders among nurses. This study aimed to determine the magnitude of shiftwork sleep disorder and associated factors among nurses working at public hospitals in Harari Regional State and the Dire Dawa Administration.

Methods
Institutional based cross-sectional study was conducted from June 1–30, 2021 among 392 nurses selected by a simple random sampling technique. A structured interviewer-guided self-administered questionnaire was used for data collection. The International Classification of Sleep Disorders 3rd edition (ICSD-3), Bargen Insomnia Scale (BIS) and Epworth Sleepiness Scale were used to assess shift-work sleep disorder. The data were entered into EpiData and exported to SPSS for analysis. Bivariable logistic regression was used to see the association between the outcome and the explanatory variables. Bivariate and Multivariate analyses were performed, and AOR with 95% CI was used to measure the strength of the association. Those variables with a p-values of < 0.05 were considered as statistically significant.

Results
In this study, the magnitude of shiftwork sleep disorder among nurses was 30.4% (95% CI: 25.4–34.5). Being female (AOR = 2.4, 95% CI: 1.3, 4.2), working an average number of nights > 11 per month in the last 12 months (AOR = 2.5, 95% CI: 1.3, 3.8), and khat use in the last 12 months (AOR = 4.9, 95% CI: 2.9, 8.7) were significantly associated with the shiftwork sleep disorder.

Conclusions
The study revealed that about one-third of the nurses had a shiftwork sleep disorder implying a high burden of the problem among nurses in the study setting, which endangers nurses, patients, and the healthcare system. Being female, working an average number of nights > 11 per month in the last 12 months, and khat use showed statistically significantly associated with the shiftwork sleep disorder. Early detection of shiftwork sleep disorder, having a policy on khat use and considering rest/recovery while scheduling work time should be addressed to prevent shiftwork sleep disorder.
Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever
Authors: Ioannidis Lisa J. , Studniberg Stephanie I. , Eriksson Emily M. , Suwarto Suhendro , Denis Dionisius , Liao Yang , Shi Wei , Garnham Alexandra L. , Sasmono R. Tedjo , Hansen Diana S. 
Published: April 2023

Abstract
Background
Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems.

Methods
To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia.

Results
After a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease.

Conclusions
Our results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value.
Predicting long-term prognosis after percutaneous coronary intervention in patients with new onset ST-elevation myocardial infarction: development and external validation of a nomogram model
Authors: Ye Zongwei , Xu Yanan , Tang Long , Wu Min , Wu Bing , Zhu Tongjian , Wang Jun 
Published: April 2023

Abstract
Background
The triglyceride glucose (TyG) index is a well-established biomarker for insulin resistance (IR) that shows correlation with poor outcomes in patients with coronary artery disease. We aimed to integrate the TyG index with clinical data in a prediction nomogram for the long-term prognosis of new onset ST-elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI) .

Methods
This retrospective study included new-onset STEMI patients admitted at two heart centers for emergency PCI from December 2015 to March 2018 in development and independent validation cohorts. Potential risk factors were screened applying least absolute shrinkage and selection operator (LASSO) regression. Multiple Cox regression was employed to identify independent risk factors for prediction nomogram construction. Nomogram performance was assessed based on receiver operating characteristic curve analysis, calibration curves, Harrell’s C-index and decision curve analysis (DCA).

Results
In total, 404 patients were assigned to the development cohort and 169 to the independent validation cohort. The constructed nomogram included four clinical variables: age, diabetes mellitus, current smoking, and TyG index. The Harrell’s C-index values for the nomogram were 0.772 (95% confidence interval [CI]: 0.721–0.823) in the development cohort and 0.736 (95%CI: 0.656–0.816) in the independent validation cohort. Significant correlation was found between the predicted and actual outcomes in both cohorts, indicating that the nomogram is well calibrated. DCA confirmed the clinical value of the development prediction nomogram.

Conclusions
Our validated prediction nomogram based on the TyG index and electronic health records data was shown to provide accurate and reliable discrimination of new-onset STEMI patients at high- and low-risk for major adverse cardiac events at 2, 3 and 5 years following emergency PCI.
A pandemic within a pandemic? Admission to COVID-19 wards in hospitals is associated with increased prevalence of antimicrobial resistance in two African settings
Authors: Elton Linzy , Abdel Hamid Muzamil Mahdi , Tembo John , Elbadawi Hana , Maluzi Kwitaka , Abdelraheem Mohammed H. , Cullip Teresa , Kabanda Caren , Roulston Kerry , Honeyborne Isobella , Thomason Margaret J , Elhag Kamal , Mohammed Alaelddin , Adam Abdelsalam , Mulonga Kangwa , Sikakena Kapatiso , Matibula Peter , Kabaso Mwewa , Nakazwe Ruth , Fwoloshi Sombo , Zumla Alimuddin , McHugh Timothy D 
Published: April 2023

Abstract
Background
Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19.

Methods
Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences.

Results
109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more β-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001).

Conclusions
Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted.
In situ forming ROS-scavenging hybrid hydrogel loaded with polydopamine-modified fullerene nanocomposites for promoting skin wound healing
Authors: Chen Xuan , Zhang Yihui , Yu Wei , Zhang Wenkai , Tang Haozheng , Yuan Wei-En 
Published: April 2023

Abstract
Background
Excessive oxidative stress at the wound sites always leads to a prolonged healing and even causes chronic inflammatory wounds. Therefore, antioxidative dressings with multiple features are desired to improve wound healing performance. Herein, we fabricated a ROS-scavenging hybrid hydrogel by incorporating mussel-inspired fullerene nanocomposites (C60@PDA) into gelatin methacryloyl (GelMA) hydrogel.

Results
The developed C60@PDA/GelMA hydrogel showed a sustainable free radical scavenging ability, and eliminated ROS to protect cells against external oxidative stress damage. Besides, the hydrogel presented favorable cytocompatibility, hemocompatibility, and antibacterial ability in vitro. Furthermore, in a mouse full-thickness wound defect model, the in situ forming hybrid hydrogel accelerated wound closure by 38.5% and 42.9% on day 3 and day 7 over the control. Histological results demonstrated that hybrid hydrogels effectively enhanced wound healing on re-epithelialization, collagen deposition and angiogenesis.

Conclusion
Collectively, the C60@PDA/GelMA hydrogel could be a promising dressing for promoting cutaneous wound repair.
Women who use drugs: engagement in practices of harm reduction care
Authors: Austin Tamar , Lavalley Jennifer , Parusel Sylvia , Collins Alexandra B. , Olding Michelle , Boyd Jade 
Published: April 2023

Abstract
Background
Harm reduction services that employ or are operated by people who use drugs are an effective means of mitigating overdose risks and other drug-related harms. However, stereotypes portraying people who use criminalized drugs as incapable caregivers persist. This is especially true for women who use drugs, and to a greater extent racialized women, who are characterized as having diverged from traditional ideals of womanhood as a result of drug-user stigma and the intersections of gender- and class-based and racist stereotypes. In an effort to identify and understand how women who use drugs practise care through harm reduction, we explored the experiences of women accessing a low-threshold supervised consumption site exclusively for women (transgender and non-binary inclusive) in Vancouver, Canada.

Methods
Data were drawn from research conducted from May 2017 to June 2018 exploring women’s experiences accessing the supervised consumption site during an overdose crisis. Data included forty-five semistructured interviews with women recruited from the site, analysed thematically to explore practices of care through harm reduction.

Findings
Participants reported engaging in both formal and informal care. Acts of care included interventions that both aligned with and deviated from conventional understandings of care practices, including overdose reversal and education, overdose supervision/care, and assisted injection.

Conclusion
The boundary between formal and informal harm reduction care is fluid. Women who use drugs engage in harm reduction across these borders with acts of care that align with or fill the gaps in current harm reduction services in order to meet the needs of drug-using communities, challenging negative stereotypes of women who use drugs. However, these caregiving practices can increase risks to care providers’ physical, mental, and emotional health and wellness. Increased financial, social, and institutional supports, including safer supply, assisted injection, and community resources, are needed to better support women as they continue to engage in harm reduction care.
Cross-platform comparison of immune signatures in immunotherapy-treated patients with advanced melanoma using a rank-based scoring approach
Authors: Mao Yizhe , Gide Tuba N. , Adegoke Nurudeen A. , Quek Camelia , Maher Nigel , Potter Alison , Patrick Ellis , Saw Robyn P. M. , Thompson John F. , Spillane Andrew J. , Shannon Kerwin F. , Carlino Matteo S. , Lo Serigne N. , Menzies Alexander M. , da Silva Inês Pires , Long Georgina V. , Scolyer Richard A. , Wilmott James S. 
Published: April 2023

Abstract
Background
Gene expression profiling is increasingly being utilised as a diagnostic, prognostic and predictive tool for managing cancer patients. Single-sample scoring approach has been developed to alleviate instability of signature scores due to variations from sample composition. However, it is a challenge to achieve comparable signature scores across different expressional platforms.

Methods
The pre-treatment biopsies from a total of 158 patients, who have received single-agent anti-PD-1 (n = 84) or anti-PD-1 + anti-CTLA-4 therapy (n = 74), were performed using NanoString PanCancer IO360 Panel. Multiple immune-related signature scores were measured from a single-sample rank-based scoring approach, singscore. We assessed the reproducibility and the performance in reporting immune profile of singscore based on NanoString assay in advance melanoma. To conduct cross-platform analyses, singscores between the immune profiles of NanoString assay and the previous orthogonal whole transcriptome sequencing (WTS) data were compared through linear regression and cross-platform prediction.

Results
singscore-derived signature scores reported significantly high scores in responders in multiple PD-1, MHC-1-, CD8 T-cell-, antigen presentation-, cytokine- and chemokine-related signatures. We found that singscore provided stable and reproducible signature scores among the repeats in different batches and cross-sample normalisations. The cross-platform comparisons confirmed that singscores derived via NanoString and WTS were comparable. When singscore of WTS generated by the overlapping genes to the NanoString gene set, the signatures generated highly correlated cross-platform scores (Spearman correlation interquartile range (IQR) [0.88, 0.92] and r2 IQR [0.77, 0.81]) and better prediction on cross-platform response (AUC = 86.3%). The model suggested that Tumour Inflammation Signature (TIS) and Personalised Immunotherapy Platform (PIP) PD-1 are informative signatures for predicting immunotherapy-response outcomes in advanced melanoma patients treated with anti-PD-1-based therapies.

Conclusions
Overall, the outcome of this study confirms that singscore based on NanoString data is a feasible approach to produce reliable signature scores for determining patients’ immune profiles and the potential clinical utility in biomarker implementation, as well as to conduct cross-platform comparisons, such as WTS.
Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer
Authors: Liu Lilong , Mo Min , Chen Xuehan , Chao Dongchen , Zhang Yufan , Chen Xuewei , Wang Yang , Zhang Nan , He Nan , Yuan Xi , Chen Honglei , Yang Jing 
Published: April 2023

Abstract
Background
Lipid metabolic reprogramming in colon cancer shows a potential impact on tumor immune microenvironment and is associated with response to immunotherapy. Therefore, this study aimed to develop a lipid metabolism-related prognostic risk score (LMrisk) to provide new biomarkers and combination therapy strategies for colon cancer immunotherapy.

Methods
Differentially expressed lipid metabolism-related genes (LMGs) including cytochrome P450 (CYP) 19A1 were screened to construct LMrisk in TCGA colon cancer cohort. The LMrisk was then validated in three GEO datasets. The differences of immune cell infiltration and immunotherapy response between LMrisk subgroups were investigated via bioinformatic analysis. These results were comfirmed by in vitro coculture of colon cancer cells with peripheral blood mononuclear cells, human colon cancer tissue microarray analysis, multiplex immunofluorescence staining and mouse xenograft models of colon cancer.

Results
Six LMGs including CYP19A1, ALOXE3, FABP4, LRP2, SLCO1A2 and PPARGC1A were selected to establish the LMrisk. The LMrisk was positively correlated with the abundance of macrophages, carcinoma-associated fibroblasts (CAFs), endothelial cells and the levels of biomarkers for immunotherapeutic response including programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden and microsatellite instability, but negatively correlated with CD8+ T cell infiltration levels. CYP19A1 protein expression was an independent prognostic factor, and positively correlated with PD-L1 expression in human colon cancer tissues. Multiplex immunofluorescence analyses revealed that CYP19A1 protein expression was negatively correlated with CD8+ T cell infiltration, but positively correlated with the levels of tumor-associated macrophages, CAFs and endothelial cells. Importantly, CYP19A1 inhibition downregulated PD-L1, IL-6 and TGF-β levels through GPR30-AKT signaling, thereby enhancing CD8+ T cell-mediated antitumor immune response in vitro co-culture studies. CYP19A1 inhibition by letrozole or siRNA strengthened the anti-tumor immune response of CD8+ T cells, induced normalization of tumor blood vessels, and enhanced the efficacy of anti-PD-1 therapy in orthotopic and subcutaneous mouse colon cancer models.

Conclusion
A risk model based on lipid metabolism-related genes may predict prognosis and immunotherapeutic response in colon cancer. CYP19A1-catalyzed estrogen biosynthesis promotes vascular abnormality and inhibits CD8+ T cell function through the upregulation of PD-L1, IL-6 and TGF-β via GPR30-AKT signaling. CYP19A1 inhibition combined with PD-1 blockade represents a promising therapeutic strategy for colon cancer immunotherapy.
Large-scale genome sequencing redefines the genetic footprints of high-altitude adaptation in Tibetans
Authors: Zheng Wangshan , He Yaoxi , Guo Yongbo , Yue Tian , Zhang Hui , Li Jun , Zhou Bin , Zeng Xuerui , Li Liya , Wang Bin , Cao Jingxin , Chen Li , Li Chunxia , Li Hongyan , Cui Chaoying , Bai Caijuan , Baimakangzhuo  , Qi Xuebin , Ouzhuluobu  , Su Bing 
Published: April 2023

AbstractBackgroundTibetans are genetically adapted to high-altitude environments. Though many studies have been conducted, the genetic basis of the adaptation remains elusive due to the poor reproducibility for detecting selective signatures in the Tibetan genomes.ResultsHere, we present whole-genome sequencing (WGS) data of 1001 indigenous Tibetans, covering the major populated areas of the Qinghai–Tibetan Plateau in China. We identify 35 million variants, and more than one-third of them are novel variants. Utilizing the large-scale WGS data, we construct a comprehensive map of allele frequency and linkage disequilibrium and provide a population-specific genome reference panel, referred to as 1KTGP. Moreover, with the use of a combined approach, we redefine the signatures of Darwinian-positive selection in the Tibetan genomes, and we characterize a high-confidence list of 4320 variants and 192 genes that have undergone selection in Tibetans. In particular, we discover four new genes,TMEM132C,ATP13A3,SANBR, andKHDRBS2, with strong signals of selection, and they may account for the adaptation of cardio-pulmonary functions in Tibetans. Functional annotation and enrichment analysis indicate that the 192 genes with selective signatures are likely involved in multiple organs and physiological systems, suggesting polygenic and pleiotropic effects.ConclusionsOverall, the large-scale Tibetan WGS data and the identified adaptive variants/genes can serve as a valuable resource for future genetic and medical studies of high-altitude populations.