bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of personalized invitation letters on research participation among general practitioners: a randomized trial
Authors: Hennrich Patrick , Arnold Christine , Wensing Michel 
Published: November 2021

Abstract
Background
Participation of general practitioners is crucial for health care studies. However, recruiting them is an ongoing challenge and participation rates of general practitioners around the globe are often low. One feasible and cost-efficient approach to potentially enhance participation rates among general practitioners are personalized invitation letters, since they may increase one’s attention to and appreciation of a study. Still, evidence whether this method actually affects participation is scarce and ambiguous in relation to physicians.

Methods
We undertook a randomized trial in a sample of general practitioners from three German states in the context of a large, observational study on physicians’ coordination and uptake of recommended cardiovascular ambulatory care. An intervention group (n = 757 general practitioners) received a personalized invitation to participate in the observational study, the control group (n = 754 general practitioners) received a generic invitation. Both groups were blinded to group assignment. Eventual participation rates as well as the number and types of responses overall were compared between arms. Besides the main intervention, sociodemographic and geographical context factors were considered as well.

Results
The overall participation rate among physicians was 2.6% (2.8% in the intervention group and 2.4% in the control group). No statistically significant effect of personalization on participation of physicians was found (relative risk to participate when receiving a personalized invitation of 1.17 [95%-CI: 0.62, 2.21]). However, the number of responses to the invitation varied significantly between the geographical regions.

Conclusions
Personalization of first written contact alone did not improve research participation among general practitioners, which was overall very low.

Trial registration
The study in which the trial was embedded has been registered prospectively at the German Clinical Trials Register (DRKS) under registration number DRKS00019219.
Altered cytokine profiles in relapsed paucibacillary leprosy: a case report
Authors: Sameshima Tomoyuki , Maeda Yumi , Mukai Tetsu , Goto Masamichi 
Published: November 2021

Abstract
Background
Individuals with relapses of leprosy should be monitored carefully, however, with respect to paucibacillary (PB) leprosy, it is sometimes difficult to make a definitive diagnosis of relapse, because the bacillary index is often negative. To evaluate the usefulness of cytokine profiling in a patient with relapsed PB leprosy who tested negative for anti-phenolic glycolipid-I antibodies, we analyzed the Mycobacterium leprae protein-induced cytokine expression in peripheral blood mononuclear cells of the patient.

Case presentation
An 89-year-old-male relapsed PB patient, first treated for leprosy over 50 years prior, was examined. In April 2012, he noticed three skin lesions consisting of annular erythema in the thighs. Slit skin smear tests were negative, and skin biopsies revealed a pathology of indeterminate-to-borderline tuberculoid leprosy. He received 600 mg of rifampicin once per month and 75 mg of dapsone daily for 12 months. The annular erythemas disappeared after starting treatment. Before treatment, and 6 and 12 months after starting treatment, the Th1/Th2 cytokine profiles in the supernatant of mononuclear cells from the patient before and after stimulation with Mycobacterium leprae soluble protein (MLS) were examined using a Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II. The CBA Enhanced Sensitivity Flex Set system was applied to detect small amounts of cytokines in the serum just before treatment and one year before relapse. In the culture supernatant, just before treatment, increases in IFN-γ level and the IFN-γ/IL-10 ratio and a decreased IL-6 level were observed without stimulation. Upon stimulation with MLS, just before treatment, both the IFN-γ and TNF levels increased markedly, and twelve months after starting treatment, the IFN-γ and TNF levels decreased greatly. In the serum, just before treatment, increases in IFN-γ and TNF levels and the IFN-γ/IL-10 ratio were evident compared with those measured one year before relapse.

Conclusions
Cytokine profiling using culture supernatants and serum samples may be useful for the diagnosis of relapsed PB leprosy.
Patient experiences of switching from Efavirenz- to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda
Authors: Twimukye Adelline , Laker Miriam , Odongpiny Eva Agnes Laker , Ajok Florence , Onen Henry , Kalule Ivan , Kajubi Phoebe , Seden Kay , Owarwo Noela , Kiragga Agnes , Armstrong-Hough Mari , Katahoire Anne , Mujugira Andrew , Lamorde Mohammed , Castelnuovo Barbara 
Published: November 2021

Abstract
Background
In 2019, the World Health Organisation (WHO) recommended Dolutegravir (DTG) as the preferred first-line antiretroviral treatment (ART) for all persons with HIV. ART regimen switches may affect HIV treatment adherence. We sought to describe patient experiences switching from EFV to DTG-based ART in Kampala, Uganda.

Methods
Between July and September 2019, we purposively sampled adults living with HIV who had switched to DTG at the Infectious Diseases Institute HIV clinic. We conducted in-depth interviews with adults who switched to DTG, to explore their preparation to switch and experiences on DTG. Interviews were audio-recorded, transcribed and analysed thematically using Atlas ti version 8 software.

Results
We interviewed 25 adults: 18 (72%) were women, and the median age was 35 years (interquartile range [IQR] 30–40). Median length on ART before switching to DTG was 67 months (IQR 51–125). Duration on DTG after switching was 16 months (IQR 10–18). Participants reported accepting provider recommendations to switch to DTG mainly because they anticipated that swallowing a smaller pill once a day would be more convenient. While most participants initially felt uncertain about drug switching, their providers offer of frequent appointments and a toll-free number to call in the event of side effects allayed their anxiety. At the same time, participants said they felt rushed to switch to the new ART regimen considering that they had been on their previous regimen(s) for several years and the switch to DTG happened during a routine visit when they had expected their regular prescription. Some participants felt unprepared for new adverse events associated with DTG and for the abrupt change in treatment schedule. Most participants said they needed additional support from their health providers before and after switching to DTG.

Conclusion and recommendations
Adults living with HIV stable on an EFV-based regimen but were switched to DTG in a program-wide policy change found the duration between counselling and drug switching inadequate. DTG was nonetheless largely preferred because of the small pill size, once daily dosing, and absence of EFV-like side effects. Community-engaged research is needed to devise acceptable ways to prepare participants for switching ART at scale.
Components of quality of life in hemodialysis patients from family caregivers’ perspective: a qualitative study
Authors: Hejazi Sima Sadat , Hosseini Meimanat , Ebadi Abbas , Alavi Majd Hamid 
Published: November 2021

Abstract
Background
Patients with end-stage kidney disease experience serious complications which affect their lives. Few studies have investigated the patients’ quality of life qualitatively from the perspective of family caregivers as the closest individuals to the patients. The family caregivers are directly involved in the patients’ disease progression and observe the changes, problems, and complications of disease and hemodialysis. This study aimed to explain the components of quality of life in hemodialysis patients from the family caregivers’ perspective.

Methods
In this qualitative inductive content analysis, 16 family caregivers of hemodialysis patients, presenting to the teaching hospitals of Tehran, Iran, were enrolled via maximum-variation purposive sampling; sampling continued until reaching data saturation. The data collection method included in-depth semi-structured interviews. Also, an inductive content analysis was carried out based on Elo and Kyngas’ method.

Results
A total of 311 codes, 19 subcategories, eight generic categories, and three main categories were extracted in this study. The main (and the generic categories) included mental and psychological problems (depressive mood, incompatibility and reduced tolerance, mental exhaustion, and deprivation of basic needs), social disruption (social isolation and social threats), and physical problems (general complications and disabilities and defects in the normal functioning of organs).

Conclusion
Family caregivers can be valuable information sources for formal caregivers to plan treatment for chronically ill patients who are mainly cared for at home. The present results can help us increase the existing knowledge on the impact of end-stage kidney disease and hemodialysis on the patients’ quality of life. It seems that addressing the issues related to quality of life, mentioned by the caregivers, can positively affect the patients’ quality of life and even reduce the caregivers’ burden.
Using genetics to understand the role of kidney function in COVID-19: a mendelian randomization study
Authors: Zhao Jie V. , Schooling C. Mary 
Published: November 2021

AbstractBackgroundKidney dysfunction occurs in severe COVID-19, and is a predictor of COVID-19 mortality. Whether kidney dysfunction causes severe COVID-19, and hence is a target of intervention, or whether it is a symptom, is unclear because conventional observational studies are open to confounding. To obtain unconfounded estimates, we used Mendelian randomization to examine the role of kidney function in severe COVID-19.MethodsWe used genome-wide significant, uncorrelated genetic variants to predict kidney function, in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), and then assessed whether people with genetically instrumented higher eGFR or lower UACR, an indication of better kidney function, had a lower risk of severe COVID-19 (8779 cases, 1,001,875 controls), using the largest available cohorts with extensive genotyping. For comprehensiveness, we also examined their role in COVID-19 hospitalization (24,274 cases, 2,061,529 controls) and all COVID-19 (1,12,612 cases, 2,474,079 controls).ResultsGenetically instrumented higher eGFR was associated with lower risk of severe COVID-19 (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.83, 0.98) but not related to COVID-19 hospitalization or infection. Genetically instrumented UACR was not related to COVID-19.ConclusionsKidney function appears to be one of the key targets for severe COVID-19 treatment. Use of available medications to improve kidney function, such as antihypertensives, might be beneficial for COVID-19 treatment, with relevance to drug repositioning.
Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data
Authors: Li Jia-yi , Huang Xuan-zhang , Gao Peng , Song Yong-xi , Chen Xiao-wan , Lv Xing-er , Fu Yv , Xiao Qiong , Ye Shi-yv , Wang Zhen-ning 
Published: November 2021

Abstract
Background
Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD).

Methods
The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan–Meier curves.

Results
The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177–0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205–0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results.

Conclusions
Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.
The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis
Authors: Ba He , Liu Lei , Peng Qiang , Chen Jie , Zhu Yao-dong 
Published: November 2021

Abstract
Background
The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low.

Methods
PubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups.

Results
A total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52–0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48–0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84–3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69–1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78–1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49–0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable.

Conclusions
The efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.
Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
Authors: Zheng Qunhao , Wang Zhiping , Zhang Mengyan , Yu Yilin , Chen Rui , Lu Tianzhu , Liu Lingyun , Ma Jiayu , Liu Tianxiu , Zheng Hongying , Li Hui , Li Jiancheng 
Published: November 2021

Abstract
Background
Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD.

Methods
Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan–Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC).

Results
SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297–2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = − 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell.

Conclusion
Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.
Achieving integrated self-directed Cancer aftercare (ASICA) for melanoma: how a digital intervention to support total skin self-examination was used by people treated for cutaneous melanoma
Authors: Reilly Felicity , Contstable Lynda , Brant William , Rahman Kaz , Durrani Amer , Burrows Nigel , Proby Charlotte , Allan Julia , Johnston Marie , Johnston Derek , Walter Fiona , Murchie Peter 
Published: November 2021

AbstractBackgroundMelanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial.MethodsThis paper reports on process evaluation. Data on participants’ demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants’ demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved.ResultsOf 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up.ConclusionMelanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool.Trial registrationClinicalTrials.gov,NCT03328247. Registered on 1 November 2017
MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
Authors: Pan Hongli , Pan Zhenhua , Guo Fengjie , Meng Fanrong , Zu Lingling , Fan Yaguang , Li Yang , Li Mengjie , Du Xinxin , Zhang Xiuwen , Shao Yi , Wei Mingming , Li Xuebing , Zhou Qinghua 
Published: November 2021

Abstract
Background
MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC.

Methods
The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP).

Results
miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3′untranslated region (3′UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What’s more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4.

Conclusions
These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.