bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant POLQ and POLZ/REV3L DNA polymerases may contribute to the favorable survival of patients with tumors with POLE mutations outside the exonuclease domain
Authors: Huang Fangjin , Tanaka Hisashi , Knudsen Beatrice S. , Rutgers Joanne K. 
Published: August 2020

Abstract
Background
Mutations in the exonuclease domain of POLE, a DNA polymerase associated with DNA replication and repair, lead to cancers with ultra-high mutation rates. Most studies focus on intestinal and uterine cancers with POLE mutations. These cancers exhibit a significant immune cell infiltrate and favorable prognosis. We questioned whether loss of function of other DNA polymerases can cooperate to POLE to generate the ultramutator phenotype.

Methods
We used cases and data from 15 cancer types in The Cancer Genome Atlas to investigate mutation frequencies of 14 different DNA polymerases. We tested whether tumor mutation burden, patient outcome (disease-free survival) and immune cell infiltration measured by ESTIMATE can be attributed to mutations in POLQ and POLZ/REV3L.

Results
Thirty six percent of colorectal, stomach and endometrial cancers with POLE mutations carried additional mutations in POLQ (E/Q), POLZ/REV3L (E/Z) or both DNA polymerases (E/Z/Q). The mutation burden in these tumors was significantly greater compared to POLE-only (E) mutant tumors (p < 0.001). In addition, E/Q, E/Z, and E/Q/Z mutant tumors possessed an increased frequency of mutations in the POLE exonuclease domain (p = 0.013). Colorectal, stomach and endometrial E/Q, E/Z, and E/Q/Z mutant tumors within TCGA demonstrated 100% disease-free survival, even if the POLE mutations occurred outside the exonuclease domain (p = 0.003). However, immune scores in these tumors were related to microsatellite instability (MSI) and not POLE mutation status. This suggests that the host immune response may not be the sole mechanism for prolonged disease-free survival of ultramutated tumors in this cohort.

Conclusion
Results in this study demonstrate that mutations in POLQ and REV3L in POLE mutant tumors should undergo further investigation to determine whether POLQ and REV3L mutations contribute to the ultramutator phenotype and favorable outcome of patients with POLE mutant tumors.
Delayed diagnoses of mitochondrial cytopathies in patients presenting with end stage kidney disease: two case reports
Authors: Roper Tayeba , Harber Mark , Jones Gareth , Pitceathly Robert D. S. , Salama Alan D. 
Published: August 2020

Abstract
Background
Up to one third of patients on renal replacement programmes have an unknown cause of kidney disease, and the diagnosis may only be established following renal transplantation when the disease recurs or if new extra-renal symptoms develop.

Case presentation
We present two patients who presented with progressive chronic kidney disease of unknown cause. Both patients underwent successful renal transplantation but subsequently developed multisystem abnormalities, and were ultimately diagnosed with mitochondrial cytopathy 10–15 years following transplantation.

Conclusions
Mitochondrial cytopathies are rare inborn errors of metabolism that should be considered in adults with renal impairment, especially in those with a family history of kidney or other multisystem disease. The widespread availability of genetic testing provides the potential for earlier diagnoses, thereby enhancing management decisions, anticipation of complications, avoidance of mitotoxic drugs, and informed prognosis prediction.
Men, trans/masculine, and non-binary people’s experiences of pregnancy loss: an international qualitative study
Authors: Riggs Damien W. , Pearce Ruth , Pfeffer Carla A. , Hines Sally , White Francis Ray , Ruspini Elisabetta 
Published: August 2020

Abstract
Background
Growing numbers of men, trans/masculine, and non-binary people are becoming gestational parents, yet very little is known about experiences of pregnancy loss among this diverse population.

Methods
The study employed a cross sectional design. Interviews were undertaken with a convenience sample of 51 trans/masculine and non-binary people who had undertaken at least one pregnancy, living in either Australia, the United States, Canada, or the European Union (including the United Kingdom). Participants were recruited by posts on Facebook and Twitter, via researcher networks, and by community members. 16 (31.2%) of the participants had experienced a pregnancy loss and are the focus of this paper. Thematic analysis was used to analyse interview responses given by these 16 participants to a specific question asking about becoming pregnant and a follow up probe question about pregnancy loss.

Results
Thematic analysis of interview responses given by the 16 participants led to the development of 10 themes: (1) pregnancy losses count as children, (2) minimizing pregnancy loss, (3) accounting for causes of pregnancy loss, (4) pregnancy loss as devastating, (5) pregnancy loss as having positive meaning, (6) fears arising from a pregnancy loss, (7) experiences of hospitals enacting inclusion, (8) lack of formal support offered, (9) lack of understanding from family, and (10) importance of friends.

Conclusions
The paper concludes by outlining specific recommendations for clinical practice. These include the importance of focusing on the emotions attached to pregnancy loss, the need for targeted support services for men, trans/masculine, and non-binary people who undertake a pregnancy (including for their partners), and the need for ongoing training for hospital staff so as to ensure the provision of trans-affirming medical care.
Nomogram model for predicting cause-specific mortality in patients with stage I small-cell lung cancer: a competing risk analysis
Authors: Li Jianjie , Zheng Qiwen , Zhao Xinghui , Zhao Jun , An Tongtong , Wu Meina , Wang Yuyan , Zhuo Minglei , Zhong Jia , Yang Xue , Jia Bo , Chen Hanxiao , Dong Zhi , Wang Jingjing , Chi Yujia , Zhai Xiaoyu , Wang Ziping 
Published: August 2020

Abstract
Background
The five-year cumulative incidence rate in patients diagnosed with stage I small-cell lung cancer (SCLC) who were instructed to undergo surgery was from 40 to 60%.The death competition influence the accuracy of the classical survival analyses. The aim of the study is to investigate the mortality of stage I small-cell lung cancer (SCLC) patients in the presence of competing risks according to a proportional hazards model, and to establish a competing risk nomogram to predict probabilities of both cause-specific death and death resulting from other causes.

Methods
The study subjects were patients diagnosed with stage I SCLC according to ICD-O-3. First, the cumulative incidence functions (CIFs) of cause-specific death, as well as of death resulting from other causes, were calculated. Then, a proportional hazards model for the sub-distribution of competing risks and a monogram were constructed to evaluate the probability of mortality in stage I SCLC patients.

Results
1811 patients were included in this study. The five-year probabilities of death due to specific causes and other causes were 61.5 and 13.6%, respectively. Tumor size, extent of tumor, surgery, and radiotherapy were identified as the predictors of death resulting from specific causes in stage I SCLC. The results showed that surgery could effectively reduce the cancer-specific death, and the one-year cumulative incidence dropped from 34.5 to 11.2%. Like surgery, chemotherapy and radiotherapy improved the one-year survival rate.

Conclusions
We constructed a predictive model for stage I SCLC using the data from the SEER database. The proportional sub-distribution models of competing risks revealed the predictors of death resulting from both specific causes and other causes. The competing risk nomogram that we built to predict the prognosis showed good reliability and could provide beneficial and individualized predictive information for stage I SCLC patients.
Molecular evidence of IGFBP-3 dependent and independent VD3 action and its nonlinear response on IGFBP-3 induction in prostate cancer cells
Authors: Igarashi Ko , Yui Yoshihiro , Watanabe Kenta , Kumai Jun , Nishizawa Yasuko , Miyaura Chisato , Inada Masaki , Sasagawa Satoru 
Published: August 2020

Abstract
Background
Clinical trials have been conducted to clarify the beneficial effects of VD3 (1α,25-dihydroxy vitamin D3, also known as calcitriol) treatment in prostate cancer. However, the molecular mechanisms underlying these effects are not fully understood. Recent studies on IGFBP-3 have indicated its intracellular functions in cell growth and apoptosis. The aim of this study was to confirm the benefits of low-dose VD3 treatment and clarify the molecular mechanisms underlying these beneficial effects in prostate cancer cells.

Methods
The molecular effects of simultaneous treatment of LNCaP cells and their genetically modified cell lines with low concentration of docetaxel and VD3 were biologically and biochemically analyzed. To further determine the effects of VD3 treatment on IGFBP-3 induction system, cells were temporarily treated with VD3 in combination with a transcriptional inhibitor or protein synthesis inhibitor. Bcl-2 protein and its mRNA behavior were also observed in Igfbp-3 expression-modified LNCaP cells to determine the involvement of IGFBP-3 in the suppression of Bcl-2 by VD3 treatment.

Results
Changes in IGFBP-3 expression levels in LNCaP cells indicated that it mediated the inhibition of cell growth induced by VD3 treatment. IGFBP-3 was also found to be a mediator of the enhanced cytotoxicity of prostate cancer cells to VD3 in combination with the anti-cancer drug. We further identified the distinct property of the IGFBP-3 induction system, wherein temporal VD3 stimulation-induced prolonged IGFBP-3 expression and VD3 treatment-induced increase in IGFBP-3 expression were optimized based on the protein concentration rather than the mRNA concentration. Meanwhile, Bcl-2 expression was down-regulated by VD3 treatment in an IGFBP-3-independent manner.

Conclusion
These findings indicate the molecular mechanisms of IGFBP-3 induction stimulated by VD3 and IGFBP-3 independent Bcl-2 suppression by VD3 treatment in prostate cancer cells. The results could prompt a re-evaluation of VD3 usage in therapy for patients with prostate cancer.
Protocol for expanded indications of endoscopic submucosal dissection for early gastric cancer in China: a multicenter, ambispective, observational, open-cohort study
Authors: Zheng Zhi , Yin Jie , Li Ziyu , Ye Yingjiang , Wei Bo , Wang Xin , Tian Yantao , Li Mengyi , Zhang Qian , Zeng Na , Xu Rui , Chen Guangyong , Zhang Jie , Li Peng , Cai Jun , Yao Hongwei , Zhang Jun , Zhang Zhongtao , Zhang Shutian 
Published: August 2020

Abstract
Background
The main treatment methods for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD) and radical gastrectomy. However, appropriate treatment for patients who exceed the absolute indications for ESD remains unestablished. In China, evidence-based medicine for the expanding indications of ESD and accurate diagnostic staging for EGC patients are lacking. Thus, clinical studies involving Chinese patients with EGC are necessary to select appropriate treatment options and promote China’s expanded indications for ESD and diagnostic staging scheme.

Methods
This is a multicenter, ambispective, observational, open-cohort study that is expected to enroll 554 patients with EGC. The study was launched in May 2018 and is scheduled to end in March 2022. All enrolled patients should meet the inclusion criteria. Case report forms and electronic data capture systems are used to obtain clinical data, which includes demographic information, results of perioperative blood- and auxiliary examinations, surgical information, results of postoperative pathology, and the outcomes of postoperative recovery and follow-up. Patients are followed up every 6 months after surgery for a minimum of 5 years. The primary endpoint is the rate of lymph node metastasis (LNM), whereas the secondary endpoints include the following: consistency, sensitivity, and specificity of the results of preoperative examinations and postoperative pathology; cut-off values for LNM; logistic regression model of expanded indications for ESD; and incidence of postoperative complications within the 30-day and 5-year relapse-free survival rates.

Discussion
This study will explore and evaluate expanded indications for ESD that match the characteristics of the Chinese population in patients with EGC and will introduce a related staging procedure and examination scheme that is appropriate for China. Ethical approval was obtained from all participating centers. The findings are expected to be disseminated through publications or presentations and will facilitate clinical decision-making in EGC.

Trial registration
The name of the registry is ChiCTR. It was registered on May 9, 2018, with the registration number (ChiCTR1800016084). The clinical trial was launched in May 2018 and will end in March 2022, with enrollment to be completed by December 2021. Trial status: Ongoing.
Neutrophil-to-lymphocyte ratio and scoring system for predicting coronary artery lesions of Kawasaki disease
Authors: Chang Ling-Sai , Lin Yi-Ju , Yan Jia-Huei , Guo Mindy Ming-Huey , Lo Mao-Hung , Kuo Ho-Chang 
Published: August 2020

AbstractBackgroundKawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD.MethodsWe retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL.ResultsDuring the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696.ConclusionsIdentifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.
The experience of loneliness among young people with depression: a qualitative meta-synthesis of the literature
Authors: Achterbergh Louis , Pitman Alexandra , Birken Mary , Pearce Eiluned , Sno Herman , Johnson Sonia 
Published: August 2020

Abstract
Background
Young people have a higher prevalence of loneliness than other age groups, and they are also at risk of depression. Quantitative studies describe a bidirectional association between loneliness and depression, but there is limited understanding of how these influence each other. Little is known about the experience of loneliness among young people with depression. Qualitative approaches may help understand the relationship between loneliness and depression among young people, and how to intervene to improve outcomes. We aimed to conduct a meta-synthesis to understand the complex inter-relationship between loneliness and depression among young depressed people by synthesising evidence from a systematic review of qualitative studies.

Methods
We conducted a meta-synthesis of qualitative studies capturing experiences of loneliness among young people with depression. We systematically searched six electronic databases for selected search terms, critically appraised eligible studies, and analysed the data from included studies using the approach of thematic synthesis. We used feedback from an inter-disciplinary research workshop to improve reflexivity.

Results
Our inclusion criteria identified fourteen studies. Our analysis identified four themes: (1) social withdrawal due to poor mental health, (2) non-disclosure of depression contributing to social distance, (3) the desire to connect, and (4) paradoxes of loneliness and depression. These themes illustrated a range of pathways between depression and loneliness, and a sense of how these might be mutually reinforcing. Our findings suggest that where depressed individuals engage in certain behaviours (withdrawing; not confiding) for a range of reasons, this can lead to feelings of loneliness, an awareness of which worsens their mood, thus perpetuating their depression.

Conclusions
Young people with depression experience loneliness as an insurmountable distance between themselves and others. Our findings identified non-disclosure of depression, and the debilitating nature of the depressive symptomatology, as factors perpetuating a vicious cycle of loneliness and depression. They suggest that approaches to tackling the problem might include helping young people communicate about their depression to trusted friends and educating their social networks in how to support them. The wider research literature suggests that cognitive interventions may have a role in shifting maladaptive cognitions about their social world.
Factors associated with resilience among non-local medical workers sent to Wuhan, China during the COVID-19 outbreak
Authors: Lin Jing , Ren Yun-Hong , Gan Hai-Jie , Chen Ying , Huang Ying-Fan , You Xue-Mei 
Published: August 2020

Abstract
Background
To investigate the resilience of non-local medical workers sent to support local medical workers in treating the outbreak of 2019 novel coronavirus disease (COVID-19).

Methods
In February 2020, non-local medical workers who had been sent to Wuhan as support staff to respond to the COVID-19 outbreak were asked to complete an online survey composed of the Connor Davidson Resilience Scale (CD-RISC), Hospital Anxiety Depression Scale (HADS) and Simplified Coping Style Questionnaire (SCSQ).

Results
Survey responses from 114 non-local medical workers were analyzed. CD-RISC scores were high (67.03 ± 13.22). The resilience level was highest for physicians (73.48 ± 11.49), followed by support staff, including health care assistants, technicians (67.78 ± 12.43) and nurses (64.86 ± 13.46). Respondents differed significantly in the levels of education, training/support provided by the respondent’s permanent hospital (where he or she normally works), and in their feelings of being adequately prepared and confident to complete tasks (P < 0.05). Resilience correlated negatively with anxiety (r = −.498, P < 0.01) and depression (r = −.471, P < 0.01) but positively with active coping styles (r = .733, P < 0.01). Multiple regression analysis showed that active coping (β = 1.314, p < 0.05), depression (β = −.806, p < 0.05), anxiety (β = − 1.091, p < 0.05), and training/support provided by the respondent’s permanent hospital (β = 3.510, p < 0.05) were significant associated with resilience.

Conclusion
Our data show that active coping, depression, anxiety, and training/support provided by the respondent’s permanent hospital are associated with resilience. Managers of medical staff should use these data to develop psychosocial interventions aimed at reinforcing the resilience of medical workers during highly stressful and prolonged medical emergencies, as seen during the COVID-19 outbreak.
Evaluating the effect of village health workers on hospital admission rates and their economic impact in the Kingdom of Bhutan
Authors: Hauc Sacha C. , Tshering Dolley , Feliciano Josemari , Atayde Agata M. P. , Aboukhater Layla M. , Dorjee Kinley , Dukpa Tshering , Rinchen Pema , Yoezer Neema , Luc Casey M. , Adhikari Rup N. , Lhamo Kezang , Khoshnood Kaveh 
Published: August 2020

Abstract
Background
Village health workers (VHWs) in Bhutan play an all-encompassing role in supporting the health of their communities. Recent reports from the Bhutan Ministry of Health have indicated a sharp reduction in the number of working VHWs. As such, our work attempts to estimate the cost saved and the number of averted hospital admissions onto the Bhutanese healthcare system and the individuals who are served by these health workers.

Methods
We utilized a dataset from the Bhutan Ministry of Health which encompassed over 95% of all reported disease cases within the nation. We examined the impact that VHWs have on hospital admission rates for eight diseases of interest by using multiple multivariate logistic regression models. Our model allowed us to estimate the potential disease cases averted when the average number of VHWs per health center is increased by one unit. Lastly, we utilized the 2011 “A Costing of Healthcare Services in Bhutan” to estimate the cost saved attributed to VHWs.

Results
An average one unit increase of VHWs per health center is associated with a decrease in hospital and clinic admission for diarrhea, dysentery, wound care, depression/anxiety, dental caries, and skin infection, while a non-significant increase was observed for scabies and conjunctivitis. These findings translate to 4604 outpatient visits averted, with $28,637 saved, and 78 inpatient visits averted, with $10,711 saved. These values sum to a total of 4682 yearly averted admissions at health centers, with a total cost savings of $39,348 yearly. Additionally, we estimated a yearly savings of $13,348 in transportation costs and a total of $20,960 saved in wages to the community members that VHWs serve.

Conclusions
VHWs serve as a source of cost-savings for the Kingdom of Bhutan and also act as an economic buffer for more vulnerable communities. The cost-savings associated with these health workers is likely to become more pertinent as the nation begins to develop and healthcare costs increase. It is imperative that proper action be taken to retain these health workers as every VHW who leaves the program increases healthcare costs onto the Bhutanese government.