bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do the patient education program and nurse-led telephone follow-up improve treatment adherence in hemodialysis patients? A randomized controlled trial
Authors: Arad Mansour , Goli Rasoul , Parizad Naser , Vahabzadeh Davoud , Baghaei Rahim 
Published: April 2021

Abstract
Background
End-Stage Renal Disease (ESRD) is the final and permanent stage of Chronic Kidney Disease (CKD). Hemodialysis (HD) is the most common treatment for CKD. To have desirable therapeutic outcomes, patients have to adhere to a specific therapeutic regimen that reduces the hospitalization rate and side-effects of HD. The present study aimed to determine the effects of the patient education program and nurse-led telephone follow-up on adherence to the treatment in hemodialysis patients.

Methods
This is a randomized controlled trial in which a total of 66 patients were recruited using convenience sampling and then randomly assigned to two groups of control (n = 33) and intervention (n = 33). Data were collected using a demographic questionnaire, the laboratory results record sheet, and the End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ), which included four dimensions of HD attendance, medication use, fluid restrictions, and diet recommendations. The intervention group received a patient education program and nurse-led follow-up services through telephone communication and the Short Message Service (SMS) for 3 months. All participants filled in the questionnaire before and after the intervention. Data were analyzed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA).

Results
The results showed a significant difference in the mean scores of HD attendance, medication use, fluid restrictions, and diet recommendations between the two groups immediately, 1 month, and 3 months after the intervention (p < .001). The results also indicated a significant difference in the mean scores of four dimensions during the four-time points of measurement in the intervention group (P < 0.0005). Therefore, the level of treatment adherence in the intervention group was higher than in the control group. Moreover, there was a significant difference in the mean score of laboratory values between the two groups after the intervention, except for the level of serum sodium (P = 0.130).

Conclusion
Implementation of the patient education program and nurse-led follow-up can lead to better adherence to hemodialysis in four dimensions of HD attendance, medication use, fluid restrictions, and dietary recommendations in HD patients.

Trial registration
IRCT registration number: IRCT20190127042512N1; Registration date: 2020-09-12; Registration timing: retrospectively registered: Last update: 2020-09-12.
The role of digital clinical decision support tool in improving quality of intrapartum and postpartum care: experiences from two states of India
Authors: Usmanova Gulnoza , Lalchandani Kamlesh , Srivastava Ashish , Joshi Chandra Shekhar , Bhatt Deepak Chandra , Bairagi Anand Kumar , Jain Yashpal , Afzal Mohammed , Dhoundiyal Rashmi , Benawri Jyoti , Chaudhary Tarun , Mishra Archana , Wadhwa Rajni , Sridhar Pompy , Bahl Nupur , Gaikwad Pratibha , Sood Bulbul 
Published: April 2021

Abstract
Background
Computerized clinical decision support (CDSS) –digital information systems designed to improve clinical decision making by providers – is a promising tool for improving quality of care. This study aims to understand the uptake of ASMAN application (defined as completeness of electronic case sheets), the role of CDSS in improving adherence to key clinical practices and delivery outcomes.

Methods
We have conducted secondary analysis of program data (government data) collected from 81 public facilities across four districts each in two sates of Madhya Pradesh and Rajasthan. The data collected between August –October 2017 (baseline) and the data collected between December 2019 – March 2020 (latest) was analysed. The data sources included: digitized labour room registers, case sheets, referral and discharge summary forms, observation checklist and complication format. Descriptive, univariate and multivariate and interrupted time series regression analyses were conducted.

Results
The completeness of electronic case sheets was low at postpartum period (40.5%), and in facilities with more than 300 deliveries a month (20.9%). In multivariate logistic regression analysis, the introduction of technology yielded significant improvement in adherence to key clinical practices. We have observed reduction in fresh still births rates and asphyxia, but these results were not statistically significant in interrupted time series analysis. However, our analysis showed that identification of maternal complications has increased over the period of program implementation and at the same time referral outs decreased.

Conclusions
Our study indicates CDSS has a potential to improve quality of intrapartum care and delivery outcome. Future studies with rigorous study design is required to understand the impact of technology in improving quality of maternity care.
Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation
Authors: Vidal Amanda Ferreira , Ferraz Rafaella Sousa , El-Husny Antonette , Silva Caio Santos , Vinasco-Sandoval Tatiana , Magalhães Leandro , Raiol-Moraes Milene , Barra Williams Fernandes , Pereira Cynthia Lara Brito Lins , de Assumpção Paulo Pimentel , de Brito Leonardo Miranda , Vialle Ricardo Assunção , Santos Sidney , Ribeiro-dos-Santos Ândrea , Ribeiro-dos-Santos André M. 
Published: April 2021

Abstract
Background
Next generation sequencing (NGS) has been a handy tool in clinical practice, mainly due to its efficiency and cost-effectiveness. It has been widely used in genetic diagnosis of several inherited diseases, and, in clinical oncology, it may enhance the discovery of new susceptibility genes and enable individualized care of cancer patients. In this context, we explored a pan-cancer panel in the investigation of germline variants in Brazilian patients presenting clinical criteria for hereditary cancer syndromes or familial history.

Methods
Seventy-one individuals diagnosed or with familial history of hereditary cancer syndromes were submitted to custom pan-cancer panel including 16 high and moderate penetrance genes previously associated with hereditary cancer syndromes (APC, BRCA1, BRCA2, CDH1, CDKN2A, CHEK2, MSH2, MSH6, MUTYH, PTEN, RB1, RET, TP53, VHL, XPA and XPC). All pathogenic variants were validated by Sanger sequencing.

Results
We identified a total of eight pathogenic variants among 12 of 71 individuals (16.9%). Among the mutation-positive subjects, 50% were diagnosed with breast cancer and had mutations in BRCA1, CDH1 and MUTYH. Notably, 33.3% were individuals diagnosed with polyposis or who had family cases and harbored pathogenic mutations in APC and MUTYH. The remaining individuals (16.7%) were gastric cancer patients with pathogenic variants in CDH1 and MSH2. Overall, 54 (76.05%) individuals presented at least one variant uncertain significance (VUS), totalizing 81 VUS. Of these, seven were predicted to have disease-causing potential.

Conclusion
Overall, analysis of all these genes in NGS-panel allowed the identification not only of pathogenic variants related to hereditary cancer syndromes but also of some VUS that need further clinical and molecular investigations. The results obtained in this study had a significant impact on patients and their relatives since it allowed genetic counselling and personalized management decisions.
A bibliometric analysis of researches on flap endonuclease 1 from 2005 to 2019
Authors: Wei Qiaochu , Shen Jiming , Wang Dongni , Han Xu , Shi Jing , Zhao Lei , Teng Yuee 
Published: April 2021

Abstract
Background
Flap endonuclease 1 (FEN1) is a structure-specific nuclease that plays a role in a variety of DNA metabolism processes. FEN1 is important for maintaining genomic stability and regulating cell growth and development. It is associated with the occurrence and development of several diseases, especially cancers. There is a lack of systematic bibliometric analyses focusing on research trends and knowledge structures related to FEN1.

Purpose
To analyze hotspots, the current state and research frontiers performed for FEN1 over the past 15 years.

Methods
Publications were retrieved from the Web of Science Core Collection (WoSCC) database, analyzing publication dates ranging from 2005 to 2019. VOSviewer1.6.15 and Citespace5.7 R1 were used to perform a bibliometric analysis in terms of countries, institutions, authors, journals and research areas related to FEN1. A total of 421 publications were included in this analysis.

Results
Our findings indicated that FEN1 has received more attention and interest from researchers in the past 15 years. Institutes in the United States, specifically the Beckman Research Institute of City of Hope published the most research related to FEN1. Shen BH, Zheng L and Bambara Ra were the most active researchers investigating this endonuclease and most of this research was published in the Journal of Biological Chemistry. The main scientific areas of FEN1 were related to biochemistry, molecular biology, cell biology, genetics and oncology. Research hotspots included biological activities, DNA metabolism mechanisms, protein-protein interactions and gene mutations. Research frontiers included oxidative stress, phosphorylation and tumor progression and treatment.

Conclusion
This bibliometric study may aid researchers in the understanding of the knowledge base and research frontiers associated with FEN1. In addition, emerging hotspots for research can be used as the subjects of future studies.
Downregulated ZNF132 predicts unfavorable outcomes in breast Cancer via Hypermethylation modification
Authors: Liu Zhao , Liu Jiaxin , Liu Ruimiao , Xue Man , Zhang Weifan , Zhao Xinhui , Zhu Jiang , Xia Peng 
Published: April 2021

Abstract
Background
An important mechanism that promoter methylation-mediated gene silencing for gene inactivation is identified in human tumorigenesis. Methylated genes have been found in breast cancer (BC) and beneficial biomarkers for early diagnosis. Prognostic assessment of breast cancer remain little known. Zinc finger protein 132 (ZNF132) is downregulated by promoter methylation in prostate cancer and esophageal squamous cell carcinoma. However, no study provides information on the status of ZNF132, analyzes diagnosis and prognostic significance of ZNF132 in BC.

Methods
In the present study, the expression of ZNF132 mRNA and protein level was determined based on the Cancer Genome Atlas (TCGA) RNA-Seq database and clinical samples analysis and multiple cancer cell lines verification. P rognostic significance of ZNF132 in BC was assessed using the Kaplan-Meier plotter. Molecular mechanisms exploration of ZNF132 in BC was performed using the multiple bioinformatic tools. Hypermethylated status of ZNF132 in BC cell lines was confirmed via Methylation specific polymerase chain reaction (MSP) analysis.

Results
The expression of ZNF132 both the mRNA and protein levels was downregulated in BC tissues. These results were obtained based on TCGA database and clinical sample analysis. Survival analysis from the Kaplan-Meier plotter revealed that the lower level of ZNF132 was associated with a shorter Relapse Free Survival (RFS) time. Receiver operating characteristic curve (ROC) of 0.887 confirmed ZNF132 had powerful sensitivity and specificity to distinguish between BC and adjacent normal tissues. Bioinformatic analysis showed that 6% ((58/960)) alterations of ZNF132 were identified from cBioPortal. ZNF132 participated in multiple biological pathways based on the Gene Set Enrichment Analysis (GSEA) database including the regulation of cell cycle and glycolysis. Finally, MSP analysis demonstrated that ZNF132 was hypermethylated in a panel of breast cancer cell lines and 5-aza-2′-deoxycytidine (5-Aza-dC) treatment restored ZNF132 expression in partial cell lines.

Conclusions
Results revealed that hypermethylation of ZNF132 contributed to its downregulated expression and could be identified as a new diagnostic and prognostic marker in BC.
Identification of PIK3CA multigene mutation patterns associated with superior prognosis in stomach cancer
Authors: Yu Yu , Xie Zhuoming , Zhao Mingxin , Lian Xiaohua 
Published: April 2021

Abstract
Background
PIK3CA is the second most frequently mutated gene in cancers and is extensively studied for its role in promoting cancer cell resistance to chemotherapy or targeted therapy. However, PIK3CA functions have mostly been investigated at a lower-order genetic level, and therapeutic strategies targeting PIK3CA mutations have limited effects. Here, we explore crucial factors interacting with PIK3CA mutations to facilitate a significant marginal survival effect at the higher-order level and identify therapeutic strategies based on these marginal factors.

Methods
Mutations in stomach adenocarcinoma (STAD), breast adenocarcinoma (BRCA), and colon adenocarcinoma (COAD) samples from The Cancer Genome Atlas (TCGA) database were top-selected and combined for Cox proportional-hazards model analysis to calculate hazard ratios of mutation combinations according to overall survival data and define criteria to acquire mutation combinations with considerable marginal effects. We next analyzed the PIK3CA + HMCN1 + LRP1B mutation combination with marginal effects in STAD patients by Kaplan-Meier, transcriptomic differential, and KEGG integrated pathway enrichment analyses. Lastly, we adopted a connectivity map (CMap) to find potentially useful drugs specifically targeting LRP1B mutation in STAD patients.

Results
Factors interacting with PIK3CA mutations in a higher-order manner significantly influenced patient cohort survival curves (hazard ratio (HR) = 2.93, p-value = 2.63 × 10− 6). Moreover, PIK3CA mutations interacting with higher-order combination elements distinctly differentiated survival curves, with or without a marginal factor (HR = 0.26, p-value = 6.18 × 10− 8).
Approximately 3238 PIK3CA-specific higher-order mutational combinations producing marginal survival effects were obtained. In STAD patients, PIK3CA + HMCN1 mutation yielded a substantial beneficial survival effect by interacting with LRP1B (HR = 3.78 × 10− 8, p-value = 0.0361) and AHNAK2 (HR = 3.86 × 10− 8, p-value = 0.0493) mutations. We next identified 208 differentially expressed genes (DEGs) induced by PIK3CA + HMCN1 compared with LRP1B mutation and mapped them to specific KEGG modules. Finally, small-molecule drugs such as geldanamycin (connectivity score = − 0.4011) and vemurafenib (connectivity score = − 0.4488) were selected as optimal therapeutic agents for targeting the STAD subtype with LRP1B mutation.

Conclusions
Overall, PIK3CA-induced marginal survival effects need to be analyzed. We established a framework to systematically identify crucial factors responsible for marginal survival effects, analyzed mechanisms underlying marginal effects, and identified related drugs.
Predictive factors of toxicity of TPF induction chemotherapy for locally advanced head and neck cancers
Authors: Bernadach Maureen , Lapeyre Michel , Dillies Anne-Françoise , Miroir Jessica , Casile Melanie , Moreau Juliette , Molnar Ioana , Ginzac Angeline , Pham-Dang Nathalie , Saroul Nicolas , Durando Xavier , Biau Julian 
Published: April 2021

AbstractBackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.
Second primary malignancies after ocular adnexal lymphoma diagnosis
Authors: Loya Asad , Ramachandran Vignesh , Ayaz Talha , Weng Christina Y. 
Published: April 2021

AbstractBackgroundAlthough studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated this risk in patients with lymphoma originating within the ocular adnexa. We conducted a retrospective study to assess incidence of secondary malignancies in patients with a prior diagnosis of ocular adnexal lymphoma (OAL) and to determine latency periods and age-groups at increased risk for SPM occurrence.MethodsRetrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results (SEER) 9 database. Patients with an initial primary malignancy diagnosis of OAL between 1973 and 2015 were included in the study. Standardized incidence ratios (SIR) and excess absolute risks (EAR) compared to a SEER reference population with similar sex, race, age, and calendar year were computed for SPMs. Excess absolute risk is per 10,000 individuals; alpha of 0.05 was used.ResultsOf 1834 patients with primary ocular adnexal lymphoma, 279 developed a secondary malignancy during average follow-up of 110.03 months (+/− 88.46), denoting higher incidence than expected (SIR 1.20; 95% CI, 1.07 to 1.35; EAR 30.56). Amongst the primary lymphoma cohort, 98.7% (1810/1834) of patients had non-Hodgkin’s lymphoma and amongst those that developed secondary malignancies, 99.6% (278/279) had non-Hodgkin’s lymphoma. Patients exhibited increased incidence of lymphohematopoietic and non-lymphohematopoietic second malignancies and no secondary malignancies of the eye or orbit. Patients had increased incidence of secondary malignancies in the first year (SIR 2.07; 95% CI, 1.49 to 2.79; EAR 150.37) and 1–5 years following lymphoma diagnosis (SIR 1.24; 95% CI, 1.01 to 1.51; EAR 34.89). Patients with various OAL subtypes demonstrated differing patterns of site-specific and overall SPM risk.ConclusionsPatients with prior diagnosis of ocular adnexal lymphoma possess increased risk of hematologic and non-hematologic secondary malignancies. Risk of secondary malignancy could vary by lymphoma subtype. Patients with ocular adnexal lymphoma may benefit from regular surveillance to promote early detection of second primary malignancies.
ILC-OPI: impulsive lifestyle counselling versus cognitive behavioral therapy to improve retention of patients with opioid use disorders and externalizing behavior: study protocol for a multicenter, randomized, controlled, superiority trial
Authors: Hesse Morten , Thylstrup Birgitte , Karsberg Sidsel Helena , Pedersen Michael Mulbjerg , Pedersen Mads Uffe 
Published: April 2021

Abstract
Background
Substance use disorders show a high comorbidity with externalizing behavior difficulties, creating treatment challenges, including difficulties with compliance, a high risk of conflict, and a high rate of offending post-treatment. Compared with people with other substance use disorders those with opioid use disorders have the highest risk of criminal activity, but studies on the evidence base for psychosocial treatment in opioid agonist treatment (OAT) are scarce. The Impulsive Lifestyle Counselling (ILC) program may be associated with better retention and outcomes among difficult-to-treat patients with this comorbidity.

Methods
The study is a multicenter, randomized, controlled, superiority clinical trial. Participants will be a total of 137 hard-to-treat individuals enrolled in opioid agonist treatment (OAT). Participants will be randomized to either a standard treatment (14 sessions of individual manual-based cognitive behavioral therapy and motivational interviewing (MOVE-I)) or six sessions of ILC followed by nine sessions of MOVE-I. All participants will receive personalized text reminders prior to each session and vouchers for attendance, as well as medication as needed. The primary outcome is retention in treatment. Secondary measures include severity of drug use and days of criminal offending for profit three and nine months post-randomization. A secondary aim is, through a case-control study, to investigate whether participants in the trial differ from patients receiving treatment as usual in municipalities where ILC and MOVE-I have not been implemented in OAT. This will be done by comparing number of offences leading to conviction 12 months post-randomization recorded in the national criminal justice register and number of emergency room contacts 12 months post-randomization recorded in the national hospital register.

Discussion
This is the first randomized, controlled clinical trial in OAT to test the effectiveness of ILC against a standardized comparison with structural elements to increase the likelihood of exposure to the elements of treatment. Results obtained from this study may have important clinical, social, and economic implications for publicly funded treatment of opioid use disorder.

Trial registration
ISRCTN, ISRCTN19554367, registered on 04/09/2020.