bluuebunny/crossref_metadata_2025_split huggingface dataset:
A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships
Authors: Lohia Ruchi , Fox Nathan , Gillis Jesse 
Published: November 2022

Abstract
Background
Chromatin contacts are essential for gene-expression regulation; however, obtaining a high-resolution genome-wide chromatin contact map is still prohibitively expensive owing to large genome sizes and the quadratic scale of pairwise data. Chromosome conformation capture (3C)-based methods such as Hi-C have been extensively used to obtain chromatin contacts. However, since the sparsity of these maps increases with an increase in genomic distance between contacts, long-range or trans-chromatin contacts are especially challenging to sample.

Results
Here, we create a high-density reference genome-wide chromatin contact map using a meta-analytic approach. We integrate 3600 human, 6700 mouse, and 500 fly Hi-C experiments to create species-specific meta-Hi-C chromatin contact maps with 304 billion, 193 billion, and 19 billion contacts in respective species. We validate that meta-Hi-C contact maps are uniquely powered to capture functional chromatin contacts in both cis and trans. We find that while individual dataset Hi-C networks are largely unable to predict any long-range coexpression (median 0.54 AUC), meta-Hi-C networks perform comparably in both cis and trans (0.65 AUC vs 0.64 AUC). Similarly, for long-range expression quantitative trait loci (eQTL), meta-Hi-C contacts outperform all individual Hi-C experiments, providing an improvement over the conventionally used linear genomic distance-based association. Assessing between species, we find patterns of chromatin contact conservation in both cis and trans and strong associations with coexpression even in species for which Hi-C data is lacking.

Conclusions
We have generated an integrated chromatin interaction network which complements a large number of methodological and analytic approaches focused on improved specificity or interpretation. This high-depth “super-experiment” is surprisingly powerful in capturing long-range functional relationships of chromatin interactions, which are now able to predict coexpression, eQTLs, and cross-species relationships. The meta-Hi-C networks are available at https://labshare.cshl.edu/shares/gillislab/resource/HiC/.
Brief Educational Workshops in Secondary Schools Trial (BESST): protocol for a school-based cluster randomised controlled trial of open-access psychological workshop programme for 16–18-year-olds
Authors: Lisk Stephen , Carter Ben , James Kirsty , Stallard Paul , Deighton Jessica , Yarrum Jynna , Fonagy Peter , Day Crispin , Byford Sarah , Shearer James , Weaver Timothy , Sclare Irene , Evans Claire , Farrelly Maria , Ho Pin-Cheng , Brown June ,   BESST Study Collaborators
Published: November 2022

Abstract
Anxiety and depression are increasingly prevalent in adolescents, often causing daily distress and negative long-term outcomes. Despite the significant and growing burden, less than 25% of those with probable diagnosis of anxiety and depression are receiving help in England. Significant barriers to help-seeking exist in this population, with a scarcity of easily accessible, effective, and cost-effective interventions tailored specially for this age group. One intervention that has been shown to be feasible to deliver and with the promise of reducing stress in this age group is a school-based stress workshop programme for 16–18-year-olds (herein called DISCOVER). The next step is to rigorously assess the effectiveness, and cost-effectiveness, of the DISCOVER intervention in a fully powered cluster randomised controlled trial (cRCT). If found to be clinically and cost-effective, DISCOVER could be scaled up as a service model UK-wide and have a meaningful impact on the mental health of adolescents across the country.Trial registration: ISRCTN registry ISRCTN90912799. Registered with ISRCTN 28 May 2020.
The Workwell trial: protocol for the process evaluation of a randomised controlled trial of job retention vocational rehabilitation for employed people with inflammatory arthritis
Authors: Hammond Alison , Radford Kathryn A. , Ching Angela , Prior Yeliz , O’Brien Rachel , Woodbridge Sarah , Culley June , Parker Jennifer , Holland Paula 
Published: November 2022

Abstract
Background
The Workwell trial is a multi-centre randomised controlled trial with the aims of evaluating the effectiveness and cost-effectiveness of job retention vocational rehabilitation for employed people with inflammatory arthritis, who are experiencing work difficulties due to their arthritis. Vocational rehabilitation is delivered by health service occupational therapists, who have received additional training in providing this Workwell intervention. A process evaluation will be undertaken alongside the main trial to investigate implementation fidelity; understand key stakeholders’ perspectives of the intervention and the social and structural context in which the intervention is provided; and explore issues related to future implementation in clinical practice. This protocol describes the aims, objectives, and methodology of the Workwell trial process evaluation.

Methods
This mixed methods process evaluation will follow the Medical Research Council’s Guidance on process evaluations for complex interventions. It will be underpinned by the conceptual framework for implementation fidelity (CFIF) and normalisation process theory (NPT). We will analyse treatment records, work assessments, and treatment notes to ascertain implementation fidelity. Semi-structured interviews with trial participants, their employer/line managers, treating therapists, and their therapy service managers will be undertaken to explore perceptions of the intervention, contextual factors, and potential for future implementation in practice. Interview topic guides will be informed by NPT. Therapists’ views about Workwell training will be explored via questionnaires following training, and interviews and focus groups following treatment delivery to inform future implementation. Quantitative data will be analysed descriptively. Qualitative data will be analysed using thematic analysis. NPT will guide data analysis and interpretation. Findings from the different elements of this embedded design process evaluation will be reported separately and then the elements integrated. The process evaluation data will be analysed independently of the Workwell trial outcome evaluation. The process evaluation data will then be reviewed in the light of the trial findings.

Discussion
Few trials of job retention vocational rehabilitation in arthritis have included process evaluations. This process evaluation will assist in understanding factors influencing trial outcomes and identifying potential contextual barriers and facilitators for the potential implementation of Workwell vocational rehabilitation into clinical services.

Trial registration
ClinicalTrials.gov NCT03942783. Registered on 08 May 2019. ISRCTN Registry ISRCTN61762297. Registered on 13 May 2019. Retrospectively registered.
A new version of $( p,q ) $-Hermite–Hadamard’s midpoint and trapezoidal inequalities via special operators in $( p,q ) $-calculus
Authors: Sitthiwirattham Thanin , Ali Muhammad Aamir , Budak Hüseyin , Etemad Sina , Rezapour Shahram 
Published: November 2022

AbstractIn this paper, we conduct a research on a new version of the$( p,q ) $(p,q)-Hermite–Hadamard inequality for convex functions in the framework of postquantum calculus. Moreover, we derive several estimates for$(p,q)$(p,q)-midpoint and$(p,q)$(p,q)-trapezoidal inequalities for special$( p,q ) $(p,q)-differentiable functions by using the notions of left and right$(p,q ) $(p,q)-derivatives. Our newly obtained inequalities are extensions of some existing inequalities in other studies. Lastly, we consider some mathematical examples for some$(p,q)$(p,q)-functions to confirm the correctness of newly established results.
Vaccination coverage in Italian children and antimicrobial resistance: an ecological analysis
Authors: Maugeri Andrea , Barchitta Martina , Agodi Antonella 
Published: November 2022

Abstract
Background
Although a general consensus that vaccines could be a complementary strategy against antimicrobial resistance (AMR), there is still the need for studies investigating the relationship between childhood vaccination coverage and AMR proportions in the overall population.

Methods
We performed an ecological analysis of available Italian data (vaccination coverages, AMR proportions, number of isolates tested, and antibiotic use) to evaluate the relationships between vaccination coverages in children and AMR proportions in the last 2 decades.

Results
After adjusting for covariates, we showed that AMR proportions decreased with increasing vaccination coverages, especially for some combinations of vaccines, pathogens, and antimicrobials. Vaccination coverages for pertussis, diphtheria, and tetanus were inversely related to proportions of E. coli resistant to fluoroquinolones and third generation cephalosporins, K. pneumoniae resistant to carbapenems and third generation cephalosporins, and P. aeruginosa resistant to piperacillin and tazobactam. Polio vaccination coverage was inversely related to proportions of E. coli and K. pneumoniae resistant to third generation cephalosporins.

Conclusions
These results, however, should be interpreted cautiously due to the ecological nature of our analysis. For this reason, further studies designed ad hoc should be encouraged to measure the impact of increasing childhood vaccination coverage on AMR.
The optimal neoadjuvant chemotherapy regimen for locally advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and Bayesian network meta-analysis
Authors: Wang Tongya , Li Changyang , Li Xiang , Zhai Jing , Wang Shoulin , Shen Lizong 
Published: November 2022

AbstractBackgroundNeoadjuvant chemotherapy (NAC) for locally advanced gastric and gastroesophageal junction adenocarcinoma (LAGC) has been recommended in several guidelines. However, there is no global consensus about the optimum of NAC regimens. We aimed to determine the optimal NAC regimen for LAGC.MethodsA systematic review and Bayesian network meta-analysis was performed. The literature search was conducted from inception to June 2022. The odds ratio (OR) value and 95% confidence interval (95% CI) were used for assessment of R0 resection rate and pathological complete response rate (pCR) as primary outcomes. The hazard ratio (HR) value and 95% CI were interpreted for the assessment of overall survival (OS) and disease-free survival (DFS) as second outcomes. The risk ratio (RR) value and 95% CI were used for safety assessment.ResultsTwelve randomized controlled trials were identified with 3846 eligible participants. The network plots for R0 resectability, OS, and DFS constituted closed loops. The regimens of TPF (taxane and platinumplusfluoropyrimidine), ECF (epirubicin and cisplatinplusfluorouracil), and PF (platinumplusfluoropyrimidine) showed a meaningful improvement of R0 resectability, as well as OS and/or DFS, compared with surgery (including surgery-alone and surgerypluspostoperative adjuvant chemotherapy). Importantly, among these regimens, TPF regimen showed significant superiority in R0 resection rate (versusECF regimen), OS (versusECF regimen), DFS (versusPF and ECF regimens), and pCR (versusPF regimen).ConclusionsThe taxane-based triplet regimen of TPF is likely the optimal neoadjuvant chemotherapy regimen for LAGC patients.
Sex differences in heart: from basics to clinics
Authors: Prajapati Chandra , Koivumäki Jussi , Pekkanen-Mattila Mari , Aalto-Setälä Katriina 
Published: November 2022

AbstractSex differences exist in the structure and function of human heart. The patterns of ventricular repolarization in normal electrocardiograms (ECG) differ in men and women: men ECG pattern displays higher T-wave amplitude and increased ST angle. Generally, women have longer QT duration because of reduced repolarization reserve, and thus, women are more susceptible for the occurrence of torsades de pointes associated with drugs prolonging ventricular repolarization. Sex differences are also observed in the prevalence, penetrance and symptom severity, and also in the prognosis of cardiovascular disease. Generally, women live longer, have less clinical symptoms of cardiac diseases, and later onset of symptoms than men. Sex hormones also play an important role in regulating ventricular repolarization, suggesting that hormones directly influence various cellular functions and adrenergic regulation. From the clinical perspective, sex-based differences in heart physiology are widely recognized, but in daily practice, cardiac diseases are often underdiagnosed and untreated in the women. The underlying mechanisms of sex differences are, however, poorly understood. Here, we summarize sex-dependent differences in normal cardiac physiology, role of sex hormones, and differences in drug responses. Furthermore, we also discuss the importance of human induced pluripotent stem cell-derived cardiomyocytes in further understanding the mechanism of differences in women and men.
The association between the body height and cardiovascular diseases: a retrospective analysis of 657,310 outpatients in Germany
Authors: Krieg Sarah , Kostev Karel , Luedde Mark , Krieg Andreas , Luedde Tom , Roderburg Christoph , Loosen Sven H. 
Published: November 2022

Abstract
Background
Cardiovascular disease (CVD) represents the leading cause of death worldwide. The identification of individuals at increased risk of CVD is essential to reduce its morbidity and mortality globally. Based on existing data on a potential association between the individual body height and the risk for CVD, we investigated this association in a large cohort of outpatients in Germany.

Methods
A total of 657,310 adult outpatients with available body height data from the Disease Analyzer (IQVIA) database were included in Germany between 2019 and 2021. The prevalence of common CVD diagnoses (hypertension, coronary heart disease, atrial fibrillation and flutter, heart failure, ischemic stroke, and venous thromboembolism) was evaluated as a function of the patients’ body height stratified by age and sex.

Results
In both sexes, the prevalence of hypertension, coronary heart disease, heart failure, and ischemic stroke was higher among patients of smaller body height. In contrast, the prevalence of atrial fibrillation and venous thromboembolism was higher in taller patients. In age- and BMI-adjusted logistic regression analyses, an increased body height was negatively associated with coronary heart disease (OR = 0.91 in women and OR = 0.87 in men per 10-cm increase in height) and strongly positively associated with atrial fibrillation (OR = 1.25 in women and men) and venous thromboembolism (OR = 1.23 in women and OR = 1.24 in men).

Conclusion
We present the first data from a large cohort of outpatients in Germany providing strong evidence for an association between the body height and common CVD. These data should stimulate a discussion as to how far the body height should be implemented as a parameter in stratification tools to assess CVD risk in order to further reduce cardiovascular morbidity and mortality in the future.
Ethnobotanical study of medicinal plants used in Artuma Fursi district, Amhara Regional State, Ethiopia
Authors: Yimam Mohammed , Yimer Siraj Mammo , Beressa Tamirat Bekele 
Published: November 2022

Abstract
Introduction
Indigenous people of different ethnic groups in Ethiopia are noticeably reliant on traditional medicinal plants for their healthcare due to their effective medicinal values. The study was aimed to document different herbal medicinal plants used and the associated knowledge of herbal medicine in the communities of the Artuma Fursi district.

Methodology
Ethnobotanical data were collected through semi-structured interviews, field observations, focused group discussions with the informants selected from the study area. Key informants were selected by purposive sampling technique, while the rest, were selected by random sampling techniques. The collected data were analyzed using descriptive statistics; paired comparison, preference ranking, and informant consensus factor.

Results
A total of 86 informants participated in the collection of the ethnobotanical data. A total of 92 medicinal plants were collected and identified. Fabaceae was the highest family cited (11.9%). The study revealed that leaves (31.1%), seeds (19.8%), and roots (12.26%) were the most cited plant parts used for the preparation of herbal medicine by the respondents. The most common method of preparation of herbal medicines was pounding (21.6%) and the most common route of administration was oral route (53.7%). The majority of the medications (60.3%) were prepared without the additive. Charcoal production was the major threat to medicinal plants in the study area.

Conclusion
Artuma Fursi district is rich in medicinal plant and the associated indigenous knowledge. The documented knowledge will be helpful for further research in the drug development process.
Preparation of Superactive Prolactin Receptor Antagonists
Authors: Solomon Gili , Oclon Ewa , Hayouka Zvi , Gertler Arieh 
Published: November 2022

Abstract
Most breast cancer deaths are caused by malignant estrogen receptor–positive breast tumors that later recur as metastatic disease. Prolactin (PRL) has been documented as a factor promoting breast cancer development and metastasis. We therefore developed superactive prolactin receptor (PRLR) antagonists aimed at blocking PRL action. We purified 12 novel mutants to homogeneity as monomers, and the most potent antagonist was over 95-fold more active than the previously reported weak antagonist, the mutant Del 1-9 human PRL G129R. This enhanced antagonistic activity resulted mostly from prolonged interaction with the extracellular domain (ECD) of PRLR. All mutants were properly refolded, as indicated by interaction with human PRLR-ECD and by circular dichroism analysis. We then prepared monopegylated variants of the most active mutants to extend their biological half-life in vivo.
White Enclosures
Authors: Rexhepi Piro 
Published: November 2022

For all its history of intersecting empires, the Balkans has been rarely framed as a global site of race and coloniality. This, as Piro Rexhepi argues in White Enclosures is not surprising, given the perception of the Balkans as colorblind and raceless, a project that spans post-Ottoman racial formations, transverses Socialist modernity and is negotiated anew in the process of postsocialist Euro-Atlantic integration. Connecting severed colonial histories from the vantage point of body politic, Rexhepi turns to the borderland zones of the Balkans to trace past and present geopolitical attempts of walling whiteness. From efforts to straighten the sexualities of post-Ottoman Muslim subjects, to Yugoslav nonaligned solidarities between Muslims of the second and third world, to Roma displacement and contemporary emergence of refugee carceral technologies along the Balkan Route, Rexhepi points not only to the epistemic erasures that maintain the fantasy of whiteness but also to the disruption emanating from the solidarities between queer- and transpeople that fold the Balkans back into global efforts to resist the politics of racial capitalism.
Prognostic Value of Preoperative Serological Biomarkers in Patients Undergoing Curative-Intent Cytoreductive Surgery for Colorectal Cancer Peritoneal Metastases
Authors: El Asmar Antoine , Delcourt Martin , Kamden Leonel , Khaled Charif , Bohlok Ali , Moreau Michel , Sclafani Francesco , Donckier Vincent , Liberale Gabriel 
Published: November 2022

Abstract
Background
Cytoreductive surgery (CRS) for peritoneal metastases of colorectal cancer (PMCRC) is associated with a high risk of postoperative morbidity, thus making patient selection of upmost importance. Further to data showing an association between preoperative serological biomarkers and patient outcome in various solid tumors, in this study we aim to evaluate their prognostic value in patients with PMCRC treated with curative intent.

Patients and Methods
This is a retrospective study including patients with PMCRC treated by complete CRS ± HIPEC at our institution between 2011 and 2020. Preoperative serological biomarkers, along with other standard clinicopathological variables, were studied to determine their prognostic value.

Results
A total of 94 out of 108 patients met the inclusion criteria. Forty-three patients (46%) presented with synchronous PM. The median peritoneal cancer index (PCI) was 6. On univariate analysis, a higher neutrophil-to-lymphocyte ratio (NLR) was associated with poor prognosis in terms of overall survival (OS) [cutoff 3.567, hazard ratio (HR) 2.8 (1.4–5.3), p = 0.002], whereas a higher platelet-to-lymphocyte ratio (PLR) predicted favorable prognosis in terms of disease-free survival (DFS) [cutoff 185.4, HR 1.9 (1.07–3.53), p = 0.030]. On multivariate analysis, NLR > 3.567, positive lymph nodes (LNs), and PCI > 7 were independent predictive factors for worse OS, whereas NLR > 3.567 and positive LNs were significantly associated with worse DFS. PLR > 185.4 was associated with better DFS.

Conclusion
High preoperative NLR (> 3.567) and PLR (> 185.4) can predict outcome of patients with PMCRC treated by complete CRS ± HIPEC.
Association of pre-diabetes and type 2 diabetes mellitus with intracranial plaque characteristics in patients with acute ischemic stroke
Authors: Li Rui-Ying , Yu Jia-Wei , Chen Xiao-Hui , Han Qiao-Qiao , Ge Hong , Li Cheng , Ju Shenghong , Zhao Deng-Ling 
Published: November 2022

Objectives: To investigate the association of pre-diabetes(i.e., the early stages of glucometabolic disturbance) and Type 2 diabetes mellitus (T2DM) with intracranial plaque characteristics in patients with acute ischemic stroke using three-dimensional high-resolution MR imaging. Methods: One hundred and forty-three symptomatic patients with acute ischemic stroke attribute to intracranial atherosclerotic plaque were prospectively enrolled. All participants were further divided into three groups: normal glucose metabolism(non-diabetes) group(n = 41), pre-diabetes group(n = 45), and T2DM group(n = 57) according to glucometabolic status. Culprit plaque characteristics (such as plaque burden, normalized wall index and enhancement ratio), total plaque number, and global plaque enhancement score were analyzed and compared among the three glucometabolic groups. The association between pre-diabetes and T2DM with intracranial plaque characteristics was assessed by logistic regression and multivariate linear regression. Results: Plaque number was higher in patients with pre-diabetes and T2DM compared with those with non-diabetes(3.71 ± 1.83 and 3.75 ± 1.71 vs 2.24 ± 1.46, p = 0.006). Multivariate logistic regression showed a significant association of multiple intracranial plaques with pre-diabetes(OR 3.524, 95% CI 1.082 ~ 11.479, p = 0.037), T2DM(OR 3.760, 95% CI 1.098 ~ 12.872, p = 0.035) and luminal stenotic rate. Both pre-diabetes and T2DM were significantly associated with culprit plaque enhancement ratio(β = 0.527 and β = 0.536; respectively; p < 0.001) and global plaque enhancement score(β = 0.264 and β = 0.373; respectively; p < 0.05). Conclusions: Patients with pre-diabetes and T2DM had similar intracranial atherosclerotic plaque vulnerability, as demonstrated by multiple plaques, increased culprit plaque enhancement ratio and global plaque enhancement score. Advances in knowledge: Pre-diabetes might be a risk factor for intracranial plaque vulnerability. It is necessary to monitor a slight increase in blood glucose in non-diabetes patients with acute ischemic stroke.