bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized targeted therapy prescription in colorectal cancer using algorithmic analysis of RNA sequencing data
Authors: Sorokin Maxim , Zolotovskaia Marianna , Nikitin Daniil , Suntsova Maria , Poddubskaya Elena , Glusker Alexander , Garazha Andrew , Moisseev Alexey , Li Xinmin , Sekacheva Marina , Naskhletashvili David , Seryakov Alexander , Wang Ye , Buzdin Anton 
Published: October 2022

Abstract
Background:
Overall survival of advanced colorectal cancer (CRC) patients remains poor, and gene expression analysis could potentially complement detection of clinically relevant mutations to personalize CRC treatments.

Methods:
We performed RNA sequencing of formalin-fixed, paraffin-embedded (FFPE) cancer tissue samples of 23 CRC patients and interpreted the data obtained using bioinformatic method Oncobox for expression-based rating of targeted therapeutics. Oncobox ranks cancer drugs according to the efficiency score calculated using target genes expression and molecular pathway activation data. The patients had primary and metastatic CRC with metastases in liver, peritoneum, brain, adrenal gland, lymph nodes and ovary. Two patients had mutations in NRAS, seven others had mutated KRAS gene. Patients were treated by aflibercept, bevacizumab, bortezomib, cabozantinib, cetuximab, crizotinib, denosumab, panitumumab and regorafenib as monotherapy or in combination with chemotherapy, and information on the success of totally 39 lines of therapy was collected.

Results:
Oncobox drug efficiency score was effective biomarker that could predict treatment outcomes in the experimental cohort (AUC 0.77 for all lines of therapy and 0.91 for the first line after tumor sampling). Separately for bevacizumab, it was effective in the experimental cohort (AUC 0.87) and in 3 independent literature CRC datasets, n = 107 (AUC 0.84–0.94). It also predicted progression-free survival in univariate (Hazard ratio 0.14) and multivariate (Hazard ratio 0.066) analyses. Difference in AUC scores evidences importance of using recent biosamples for the prediction quality.

Conclusion:
Our results suggest that RNA sequencing analysis of tumor FFPE materials may be helpful for personalizing prescriptions of targeted therapeutics in CRC.
Can the level of HbA1C predict diabetic retinopathy among type II diabetic patients?
Authors: Setareh Javad , Hoseinzade Ghazale , Khoundabi Batoul , Kamali Mahsa , Ebrahimi Ata , Fazlollahpour-Naghibi Andarz , Zareei Mohammad , Mohamaditabar Mona , Makaremi Ali 
Published: October 2022

Abstract
Background
Hemoglobin A1C (HbA1C) test is the best care evaluation measurement due to a strong correlation between the test results and diabetic complications. So, this cross-sectional study aimed to assess whether the level of HbA1C can predict Diabetic Retinopathy (DR) among Type 2 diabetes mellitus (T2DM) in the Iranian population.

Method
One hundred sixty-eight diabetic patients were selected via the convenience sampling method. Data were collected by research made questionnaire scale and laboratory test had been done. To estimate the cut off point for some variables statistical tests, formal measures of classification performance, model evaluation criteria and a decision Tree were used.

Results
The prevalence of DR was 29.8%. The Receiver Operating Characteristic (ROC) curve and decision tree showed the optimal cut-off point for the HbA1C variable that separates the patient with and without DR is HbA1C = 8.15.

Conclusion
Current study showed an appropriate cutoff point for detecting the development of DR among diabetic patients. So, this cutoff point can be used as guide evidence in several clinical judgments on the Iranian population.
Association of metabolic comorbidity with myocardial infarction in individuals with a family history of cardiovascular disease: a prospective cohort study
Authors: An Seokyung , Moon Sungji , Park Sue K. 
Published: October 2022

Abstract
Background
The association between metabolic comorbidity and myocardial infarction (MI) among individuals with a family history of cardiovascular disease (CVD) is yet to be elucidated. We aimed to examine the combined effects of metabolic comorbidities, including diabetes mellitus, hypertension, and dyslipidemia, with a family history of CVD in first-degree on the risk of incident MI.

Methods
This cohort study consisted of 81,803 participants aged 40–89 years without a previous history of MI at baseline from the Korean Genome and Epidemiology Study. We performed Cox proportional hazard regression analysis to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for MI and early-onset MI risk associated with metabolic comorbidity in individuals with a family history of CVD.

Results
During a median follow-up of 5 years, 1,075 and 479 cases of total and early-onset MI were reported, respectively. According to the disease score, among individuals who had a positive family history of CVD, the HRs for MI were 1.92 (95% CI: 1.47–2.51) in individuals with one disease, 2.75 (95% CI: 2.09–3.61) in those with two diseases, and 3.74 (95% CI: 2.45–5.71) in those with three diseases at baseline compared to individuals without a family history of CVD and metabolic diseases. Similarly, an increase of the disease score among individuals with a positive family history of CVD was associated with an increase in early-onset MI risk.

Conclusion
Metabolic comorbidity was significantly associated with an increased risk of MI among individuals with a family history of CVD.
Mental and physical health and well-being of Canadian employees who were working from home during the COVID-19 pandemic
Authors: Somasundram Kumara G. , Hackney Amy , Yung Marcus , Du Bronson , Oakman Jodi , Nowrouzi-Kia Behdin , Yazdani Amin 
Published: October 2022

Abstract
Background
The COVID-19 pandemic has drastically changed various aspects of our lives, including how we work. Since the start of the pandemic, numerous organizations in Canada have mandated their employees to work from home (WFH) on a full-time basis. The rapid rise in the number of remote workers and the possibility for WFH continuing in the future signifies the importance of understanding the health and well-being of employees working from home over the course of the pandemic in Canada. We present the findings of two surveys (initial and 6-month follow-up) to examine the health and well-being of WFH employees during the COVID-19 pandemic in Canada. We analyzed the changes in mental and physical health and well-being of employees who were working from home between two time points during the pandemic.

Methods
Initial survey was completed between October 2020 and December 2020 (n = 1617); follow-up survey was completed between May 2021 and June 2021 (n = 382). We calculated the frequencies for survey questions involving demographics, WFH preferences, workstation setup training, employment situation, provision of hardware technologies, provision and usage of software technologies, and organization’s return to work plan. We conducted Wilcoxon signed-rank tests to analyze the within-individual changes in mental and physical health and well-being of the 382 respondents who completed both the initial and follow-up surveys.

Results
Our analyses showed significant changes in various aspects of employee mental and physical health and well-being. Burnout, stress, general mental health, and job insecurity levels significantly decreased between the two time periods. Work-related sedentary behaviour reduced over time; however, the average proportion of time spent sitting during work hours was more than 80% in both surveys. Employees received more help and feedback from their colleagues and experienced a better sense of community with their co-workers over time.

Conclusion
The findings can inform workers and organizations on the changes in mental and physical health and well-being of employees working from home during the pandemic. By understanding the changes in worker health and well-being, employers can develop effective strategies and implement policies that help protect employees’ health and well-being.
Association between sociodemographic status and cardiovascular risk factors burden in community populations: implication for reducing cardiovascular disease burden
Authors: Cai Anping , Nie Zhiqiang , Ou Yanqiu , Wang Jiabin , Chen Yanshuang , Lu Zhisheng , Liang Yanhua , Zhou Yingling , Feng Yingqing 
Published: October 2022

Abstract
Background:
We aimed to evaluate the burden of cardiovascular (CV) risk factors in the community populations of Guangdong Province and its association with sociodemographic status (SDS).

Method:
The data were from the community populations of Guangdong Province who have participated in the China PEACE Million Persons Project between 2016 and 2020 (n = 102,358, women 60.5% and mean age 54.3 years). The prevalence of CV risk factors (smoking, drinking, overweight/obesity, hypertension, dyslipidemia and diabetes mellitus) and its association with SDS (age, sex and socioeconomic status [SES]) was evaluated cross-sectionally.

Results:
The prevalence of overweight/obesity was 48.9%, hypertension 39.9%, dyslipidemia 18.6%, smoking 17.2%, diabetes mellitus 16.1% and drinking 5.3%. Even in young adults (aged 35–44), nearly 60% had at least 1 CV risk factor. Overweight/obesity often coexisted with other risk factors, including smoking, hypertension, dyslipidemia and diabetes mellitus. The proportion of people with no risk factor decreased with increasing age. Women were more likely than men to have no CV risk factor (29.4% vs. 12.7%). People with ≥ high school degree were more likely than those with < high school to have no risk factor (28.5% vs. 20.4%), and farmers were less likely than non-farmers to have no risk factor (20.8% vs. 23.1%).

Conclusion:
The burden of CV risk factors is high and varied by SDS in the community populations of Guangdong Province. Cost-effective and targeted interventions are needed to reduce the burden of CV risk factors at the population level.
Preoperative plasma D-Dimer level is correlated with peritoneal cancer index of patients with pseudomyxoma peritonei
Authors: Feng Jing , Qi Changhai , Lu Yiyan , Wei Hongjiang , Liang Guowei , Ma Ruiqing , Bai Mingjian 
Published: October 2022

Abstract
Purpose
Accurate assessment of preoperative tumor burden contribute to formulate a scientific surgical plan for patients with pseudomyxoma peritonei (PMP). Present study aimed to assess whether the preoperative plasma D-Dimer level could reflect tumor burden for PMP patients.

Methods
A total of 253 PMP patients were included between June 1, 2013 and March 1, 2022. According to the peritoneal cancer index (PCI), all participants were divided into extensive (PCI ≥ 28) and none-extensive (PCI < 28) subgroups. The D-Dimer and tumor markers were compared between the two subgroups. The correlation between the abovementioned biomarkers and PCI will be calculated, and further compared with each other. Two-sided P value less than 0.05 is considered statistically significant.

Results
The level of D-Dimer (ng/ml) between extensive and none-extensive subgroup were 600 (328, 1268) vs. 339 (128, 598), Z = -5.425, p < 0.001. The Spearman correlation between D-Dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), CA 19 − 9 and PCI were 0.487, 0.509, 0.469, and 0.499, respectively (all p < 0.001). The correlation coefficients were compared with each other according to Meng, Rosenthal and Rubin’s method, however, there was no significant difference.

Conclusion
Preoperative plasma D-Dimer could moderately reflect tumor burden for PMP. In the future, a multivariate prediction model will be developed to help surgeons to formulate a more precise surgical plan for the PMP patients.
Improving midwifery educators’ capacity to teach emergency obstetrics and newborn care in Kenya universities: a pre-post study
Authors: Shikuku Duncan N , Jebet Joyce , Nandikove Peter , Tallam Edna , Ogoti Evans , Nyaga Lucy , Mutsi Hellen , Bashir Issak , Okoro Dan , Bar Zeev Sarah , Ameh Charles 
Published: October 2022

Abstract
Background:
International Confederation of Midwives and World Health Organization recommend core competencies for midwifery educators for effective theory and practical teaching and practice. Deficient curricula and lack of skilled midwifery educators are important factors affecting the quality of graduates from midwifery programmes. The objective of the study was to assess the capacity of university midwifery educators to deliver the updated competency-based curriculum after the capacity strengthening workshop in Kenya.

Methods:
The study used a quasi-experimental (pre-post) design. A four-day training to strengthen the capacity of educators to deliver emergency obstetrics and newborn care (EmONC) within the updated curriculum was conducted for 30 midwifery educators from 27 universities in Kenya. Before-after training assessments in knowledge, two EmONC skills and self-perceived confidence in using different teaching methodologies to deliver the competency-based curricula were conducted. Wilcoxon signed-rank test was used to compare the before-after knowledge and skills mean scores. McNemar test was used to compare differences in the proportion of educators’ self-reported confidence in applying the different teaching pedagogies. P-values < 0.05 were considered statistically significant.

Findings:
Thirty educators (7 males and 23 females) participated, of whom only 11 (37%) had participated in a previous hands-on basic EmONC training – with 10 (91%) having had the training over two years beforehand. Performance mean scores increased significantly for knowledge (60.3% − 88. %), shoulder dystocia management (51.4 – 88.3%), newborn resuscitation (37.9 − 89.1%), and overall skill score (44.7 − 88.7%), p < 0.0001. The proportion of educators with confidence in using different stimulatory participatory teaching methods increased significantly for simulation (36.7 – 70%, p = 0.006), scenarios (53.3 – 80%, p = 0.039) and peer teaching and support (33.3 – 63.3%, p = 0.022). There was improvement in use of lecture method (80 – 90%, p = 0.289), small group discussions (73.3 – 86.7%, p = 0.344) and giving effective feedback (60 – 80%, p = 0.146), although this was not statistically significant.

Conclusion:
Training improved midwifery educators’ knowledge, skills and confidence to deliver the updated EmONC-enhanced curriculum. To ensure that midwifery educators maintain their competence, there is need for structured regular mentoring and continuous professional development. Besides, there is need to cascade the capacity strengthening to reach more midwifery educators for a competent midwifery workforce.
Public-access defibrillation and favorable neurological outcome after out-of-hospital cardiac arrest during the COVID-19 pandemic in Japan
Authors: Matsuyama Tasuku , Kiyohara Kosuke , Kitamura Tetsuhisa , Nishiyama Chika , Kiguchi Takeyuki , Iwami Taku 
Published: October 2022

Abstract
Background
Early public-access defibrillation (PAD) effectively improves the outcomes of out-of-hospital cardiac arrests (OHCA), but several strategies implemented to prevent the spread of coronavirus disease 2019 (COVID-19) could decrease the availability of PAD and worsen outcomes after OHCA. Previous studies have reported conflicting findings, and there is a paucity of nationwide observations. This study aims to investigate the impact of COVID-19 on PAD and OHCA outcomes using a nationwide OHCA registry in Japan, where PAD is well-documented.

Methods
This secondary analysis of the All-Japan Utstein Registry, a prospective population-based nationwide registry of OHCA patients, included patients aged ≥ 18 years with bystander-witnessed OHCA and an initial shockable rhythm who were transported to medical facilities between January 1, 2005, and December 31, 2020. The analytical parameters of this study were the proportion of patients who underwent PAD and patients with one-month survival with favorable neurological outcomes, defined as a cerebral performance category score of 1 or 2. We compared the data between 2019 and 2020 using a multivariable logistic regression analysis.

Results
During the study period, 1,930,273 OHCA patients were registered; of these, 78,302 were eligible for the analysis. Before the COVID-19 pandemic, the proportion of OHCA patients who underwent PAD and demonstrated favorable neurological outcomes increased gradually from 2005 to 2019 (P for trend < 0.001). The proportion of patient who had PAD were 17.7% (876/4959) in 2019 and 15.1% (735/4869) in 2020, respectively. The proportion of patient who displayed favorable neurological outcomes were 25.1% (1245/4959) in 2019 and 22.8% (1109/4869) in 2020, respectively. After adjusting for potential confounders, a significant reduction in the proportion of PAD was observed compared to that in 2019 (adjusted odds ratio [AOR], 0.86; 95% confidence interval [CI], 0.76–0.97), while no significant reduction was observed in favorable neurological outcomes (AOR, 0.97; 95% CI 0.87–1.07).

Conclusion
The proportion of PAD clearly decreased in 2020, probably due to the COVID-19 pandemic in Japan. In contrast, no significant reduction was observed in favorable neurological outcomes.
Association of haemoglobin glycation index with outcomes in patients with acute coronary syndrome: results from an observational cohort study in China
Authors: Li Jiayu , Xin Yanguo , Li Jingye , Zhou Li , Qiu Hui , Shen Aidong , Chen Hui , Li Hongwei 
Published: October 2022

Abstract
Background
The hemoglobin glycation index (HGI) is the difference between measured and estimated glycation of hemoglobin. However, there is limited evidence to investigate the HGI and the clinical outcomes of acute coronary syndrome patients. This study aimed to evaluate the association between HGI and the clinical outcomes of acute coronary syndrome (ACS) in a China cohort.

Method
This single-center retrospective study was carried out in the Cardiovascular Center of Beijing Friendship Hospital, a total of 11004 consecutive patients with ACS from Dec 2012–Dec 2020 were enrolled in this study. Patients were divided into quintiles according to their HGI levels. The incidence of major adverse cardiac and cerebrovascular events (MACCEs) was recorded.

Result
HGI were divided into five quintiles quintiles: −0.906 (−7.188, −0.663), −0.491 (−0.663, −0.343), −0.196 (−0.342, −0.039), 0.170 (−0.039, 0.485), and 1.156 (0.485, 7.875), respectively.
Competing risk regression revealed that HGI was positively related to all-cause death, CV death, and composite MACCEs. Multivariate Cox proportional hazards regression analysis indicated that hypertension (HR:1.109, P = 0.013), previous stroke (HR:1.208, P < 0.001), past PCI (HR: 1.268, P < 0.001), age (HR: 1.011, P < 0.001), BMI (HR: 0.987, P = 0.012), heart rate (HR: 1.004, P = 0.001), NSTEMI (HR: 1.205, P < 0.001), WBC (HR: 1.020, P = 0.008), eGFR (HR: 0.993, P < 0.001), HDL-C (HR: 0.809, P = 0.002), LVEF (HR:0.240, P < 0.001), LM/three-vessel or proximal LAD involved (HR: 1.208 P < 0.001; HR:0.914, P = 0.019, respectively), and antiplatelet agents during hospitalization (HR:0.806, P = 0.020) independently predicted the incidence of MACCEs in ACS patients. Restricted cubic spline indicated a U-shaped association between the HGI and risk of MACCEs.

Conclusion
Both low HGI and high HGI was associated with an increased risk of adverse outcomes in patients with acute coronary syndrome, compared with moderate HGI.
Genome-wide DNA methylation analysis of extreme phenotypes in the identification of novel epigenetic modifications in diabetic retinopathy
Authors: Yang Shaopeng , Guo Xiao , Cheng Weijing , Seth Ishith , Bulloch Gabriella , Chen Yifan , Shang Xianwen , Zhu Zhuoting , Huang Wenyong , Wang Wei 
Published: October 2022

Abstract
Background
Aberrant epigenetic modifications such as DNA methylation may contribute to the pathogenesis of DR. We aimed at elucidating the role of novel DNA methylation modifications in diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) using an extreme phenotypic design.

Methods/results
Two consecutive studies were conducted. A cross-sectional study using an extreme phenotypic design was conducted to identify rare methylation modifications that might contribute to DR pathogenesis. A 2-year longitudinal nested case–control study was conducted to validate the results and assess whether these novel methylation modifications could be used as biomarkers for predicting DR onset. A large number of differentially methylated CpG sites were identified in the cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known genes were replicated in the longitudinal study. Higher methylation of cg12869254 significantly correlated with macular RNFL thinning in the superior and nasal subregions, and that of cg04026387 correlated with reduced deep capillary plexus VD in the superior and inferior subregions after adjusting for covariates.

Conclusions
Cg12869254 and cg04026387 hypermethylation may complement the known risk factors that contribute to the pathogenesis of DR and as novel biomarkers for disease prediction.
Exponential stability for a class of set dynamic equations on time scales
Authors: Jia Keke , Hong Shihuang , Cao Xiaoyu , Yue Jieqing 
Published: October 2022

AbstractWe first present a new definition for some form of exponential stability of solutions, including H-exponential stability, H-exponentially asymptotic stability, H-uniformly exponential stability, and H-uniformly exponentially asymptotic stability for a class of set dynamic equations on time scales. Employing Lyapunov-like functions on time scales, we provide the sufficient conditions for the exponential stability of the trivial solution for such set dynamic equations.
Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p
Authors: Yang Xiaoqi , Wang Shuhua , Zhang Xianjun , Gao Xiangbin , Xu Pengfei 
Published: October 2022

Abstract
Background
Circ-NT5C2 has been confirmed to be highly expressed and associated to the progression of osteosarcoma (OS). However, the behind mechanism of circ-NT5C2 involvement in OS remains unclear.

Methods
The expression of circ-NT5C2, miR-488-3p and FZD4 was measured by quantitative real-time PCR, and the protein expression of E-cadherin, N-cadherin and FZD4 was detected by western blot. Cell counting kit 8 assay, colony formation assay and 5-ethynyl-2-deoxyuridine assay were performed to assess the cell proliferation. The cell apoptosis was measured by flow cytometry and Caspase3/Caspase9 Activity Assay Kits. Cell migration and invasion were detected by transwell assay. Dual-luciferase reporter assay and RIP assay were carried out to determine the binding relation among circ-NT5C2, miR-488-3p and FZD4. Animal experiment and immunohistochemistry analysis were conducted to explore the role of circ-NT5C2 in tumor growth in vivo.

Results
Comparing with controls, the expression of circ-NT5C2 and FZD4 was upregulated and miR-488-3p expression was downregulated in OS tumor tissues and cells. Circ-NT5C2 overexpression facilitated the cell proliferation and motility and induced cell apoptosis of OS cells, whereas circ-NT5C2 knockdown had the opposite effect. Besides, we also found and confirmed that circ-NT5C2 regulated cell malignant behaviors via modulating miR-488-3p/FZD4 axis in OS. Moreover, circ-NT5C2 silencing repressed the growth of xenografts in vivo.

Conclusion
Circ-NT5C2 upregulated FZD4 expression via sponging miR-488-3p, thus facilitating cell malignant behaviors in OS.