bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-immune profiling of CT-26 and Colon 26 syngeneic mouse models reveals mechanism of anti-PD-1 response
Authors: Sato Yosuke , Fu Yu , Liu Hong , Lee Min Young , Shaw Michael H. 
Published: November 2021

Abstract
Background
Immune checkpoint blockade (ICB) therapies have changed the paradigm of cancer therapies. However, anti-tumor response of the ICB is insufficient for many patients and limited to specific tumor types. Despite many preclinical and clinical studies to understand the mechanism of anti-tumor efficacy of ICB, the mechanism is not completely understood. Harnessing preclinical tumor models is one way to understand the mechanism of treatment response.

Methods
In order to delineate the mechanisms of anti-tumor activity of ICB in preclinical syngeneic tumor models, we selected two syngeneic murine colorectal cancer models based on in vivo screening for sensitivity with anti-PD-1 therapy. We performed tumor-immune profiling of the two models to identify the potential mechanism for anti-PD-1 response.

Results
We performed in vivo screening for anti-PD-1 therapy across 23 syngeneic tumor models and found that CT-26 and Colon 26, which are murine colorectal carcinoma derived from BALB/c mice, showed different sensitivity to anti-PD-1. CT-26 tumor mice were more sensitive to the anti-PD-1 antibody than Colon 26, while both models show similarly sensitivity to anti-CTLA4 antibody. Immune-profiling showed that CT-26 tumor tissue was infiltrated with more immune cells than Colon 26. Genomic/transcriptomic analyses highlighted thatWnt pathway was one of the potential differences between CT-26 and Colon 26, showing Wnt activity was higher in Colon 26 than CT-26. .

Conclusions
CT-26 and Colon 26 syngeneic tumor models showed different sensitivity to anti-PD-1 therapy, although both tumor cells are murine colorectal carcinoma cell lines from BALB/c strain. By characterizing the mouse cells lines and tumor-immune context in the tumor tissues with comprehensive analysis approaches, we found that CT-26 showed “hot tumor” profile with more infiltrated immune cells than Colon 26. Further pathway analyses enable us to propose a hypothesis that Wnt pathway could be one of the major factors to differentiate CT-26 from Colon 26 model and link to anti-PD-1 response. Our approach to focus on preclinical tumor models with similar genetic background but different sensitivity to anti-PD-1 therapy would contribute to illustrating the potential mechanism of anti-PD-1 response and to generating a novel concept to synergize current anti-PD-1 therapies for cancer patients.
A novel ferroptosis-related lncRNA signature for prognosis prediction in gastric cancer
Authors: Wei Jianming , Zeng Ye , Gao Xibo , Liu Tong 
Published: November 2021

Abstract
Background
Gastric cancer (GC) is a common malignant cancer with a poor prognosis. Ferroptosis has been shown to play crucial roles in GC development. Long non-coding RNAs (lncRNAs) is also associated with tumor progression in GC. This study aimed to screen the prognostic ferroptosis-related lncRNAs and to construct a prognostic risk model for GC.

Methods
Ferroptosis-related lncRNAs from The Cancer Genome Atlas (TCGA) GC expression data was downloaded. First, single factor Cox proportional hazard regression analysis was used to select seven prognostic ferroptosis-related lncRNAs from TCGA database. And then, the selected lncRNAs were further included in the multivariate Cox proportional hazard regression analysis to establish the prognostic model. A nomogram was constructed to predict individual survival probability. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the risk model.

Results
We constructed a prognostic ferroptosis-related lncRNA signature in this study. Kaplan-Meier curve analysis revealed a significantly better prognosis for the low-risk group than for the high-risk group (P = 2.036e-05). Multivariate Cox proportional risk regression analysis demonstrated that risk score was an independent prognostic factor [hazard ratio (HR) = 1.798, 95% confidence interval (CI) =1.410–2.291, P < 0.001]. A nomogram, receiver operating characteristic curve, and principal component analysis were used to predict individual prognosis. Finally, the expression levels of AP003392.1, AC245041.2, AP001271.1, and BOLA3-AS1 in GC cell lines and normal cell lines were tested by qRT-PCR.

Conclusions
This risk model was shown to be a novel method for predicting prognosis for GC patients.
Risk and protective factors of drug abuse among adolescents: a systematic review
Authors: Nawi Azmawati Mohammed , Ismail Rozmi , Ibrahim Fauziah , Hassan Mohd Rohaizat , Manaf Mohd Rizal Abdul , Amit Noh , Ibrahim Norhayati , Shafurdin Nurul Shafini 
Published: November 2021

Abstract
Background
Drug abuse is detrimental, and excessive drug usage is a worldwide problem. Drug usage typically begins during adolescence. Factors for drug abuse include a variety of protective and risk factors. Hence, this systematic review aimed to determine the risk and protective factors of drug abuse among adolescents worldwide.

Methods
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was adopted for the review which utilized three main journal databases, namely PubMed, EBSCOhost, and Web of Science. Tobacco addiction and alcohol abuse were excluded in this review. Retrieved citations were screened, and the data were extracted based on strict inclusion and exclusion criteria. Inclusion criteria include the article being full text, published from the year 2016 until 2020 and provided via open access resource or subscribed to by the institution. Quality assessment was done using Mixed Methods Appraisal Tools (MMAT) version 2018 to assess the methodological quality of the included studies. Given the heterogeneity of the included studies, a descriptive synthesis of the included studies was undertaken.

Results
Out of 425 articles identified, 22 quantitative articles and one qualitative article were included in the final review. Both the risk and protective factors obtained were categorized into three main domains: individual, family, and community factors. The individual risk factors identified were traits of high impulsivity; rebelliousness; emotional regulation impairment, low religious, pain catastrophic, homework completeness, total screen time and alexithymia; the experience of maltreatment or a negative upbringing; having psychiatric disorders such as conduct problems and major depressive disorder; previous e-cigarette exposure; behavioral addiction; low-perceived risk; high-perceived drug accessibility; and high-attitude to use synthetic drugs. The familial risk factors were prenatal maternal smoking; poor maternal psychological control; low parental education; negligence; poor supervision; uncontrolled pocket money; and the presence of substance-using family members. One community risk factor reported was having peers who abuse drugs. The protective factors determined were individual traits of optimism; a high level of mindfulness; having social phobia; having strong beliefs against substance abuse; the desire to maintain one’s health; high paternal awareness of drug abuse; school connectedness; structured activity and having strong religious beliefs.

Conclusion
The outcomes of this review suggest a complex interaction between a multitude of factors influencing adolescent drug abuse. Therefore, successful adolescent drug abuse prevention programs will require extensive work at all levels of domains.
Generating cause of death information to inform health policy: implementation of an automated verbal autopsy system in the Solomon Islands
Authors: Reeve Matthew , Chowdhury Hafizur , Mahesh Pasyodun Koralage Buddhika , Jilini Gregory , Jagilly Rooney , Kamoriki Baakai , Ruskin Rodley , McLaughlin Deirdre , Lopez Alan D. 
Published: November 2021

Abstract
Background
Good quality cause of death (COD) information is fundamental for formulating and evaluating public health policy; yet most deaths in developing countries, including the Solomon Islands, occur at home without medical certification of cause of death (MCCOD). As a result, COD data in such contexts are often of limited use for policy and planning. Verbal autopsies (VAs) are a cost-effective way of generating reliable COD information in populations lacking comprehensive MCCOD coverage, but this method has not previously been applied in the Solomon Islands. This study describes the establishment of a VA system to estimate the cause specific mortality fractions (CSMFs) for community deaths that are not medically certified in the Solomon Islands.

Methods
Automated VA methods (SmartVA) were introduced into the Solomon Islands in 2016. Trained data collectors (nurses) conducted VAs on eligible deaths to December 2020 using electronic tablet devices and VA responses were analysed using the Tariff 2.0 automated diagnostic algorithm. CSMFs were generated for both non-inpatient deaths in hospitals (i.e. ‘dead on/by arrival’) and community deaths.

Results
VA was applied to 914 adolescent-and-adult deaths with a median (IQR) age of 62 (45–75) years, 61% of whom were males. A specific COD could be diagnosed for more than 85% of deaths. The leading causes of death for both sexes combined were: ischemic heart disease (16.3%), stroke (13.5%), diabetes (8.1%), pneumonia (5.7%) and chronic-respiratory disease (4.8%). Stroke was the top-ranked cause for females, and ischaemic heart disease the leading cause for males. The CSMFs from the VAs were similar to Global Burden of Disease (GBD) estimates. Overall, non-communicable diseases (NCDs) accounted for 73% of adult deaths; communicable, maternal and nutritional conditions 15%, and injuries 12%. Six of the ten leading causes reported for facility deaths in the Solomon Islands were also identified as leading causes of community deaths based on the VA diagnoses.

Conclusions
NCDs are the leading cause of adult deaths in the Solomon Islands. Automated VA methods are an effective means of generating reliable COD information for community deaths in the Solomon Islands and should be routinely incorporated into the national mortality surveillance system.
The recurrence of prolactinoma after withdrawal of dopamine agonist: a systematic review and meta-analysis
Authors: Zou Yunzhi , Li Depei , Gu Jiayu , Chen Siyu , Wen Xia , Dong Jiajun , Jiang Xiaobing 
Published: November 2021

Abstract
Background
Prolactinoma is the major cause of hyperprolactinemia, and dopamine agonists (DAs) are generally the first-line treatment for them. Several studies have reviewed the recurrent rate of hyperprolactinemia after DAs withdrawal. However, few of them have concerned the recurrence risk of prolactinoma following the withdrawal of DAs.

Methods
Three medical databases, PubMed, EMBASE and Cochrane library, were retrieved up to February, 14, 2021 to identify studies related to recurrence of prolactinoma and withdrawal of DAs. Statistical analyses including meta-analysis, sensitivity analysis, meta-regression, funnel plot and Egger test were performed through software R.

Results
A total of 3225 studies were retrieved from the three data bases, and 13 studies consisted of 616 patients and 19 arms were finally included in this systematic analysis. There was no significant heterogeneity among the included studies, and fixed effect model was thus used. The pooled recurrence proportion of prolactinoma after withdrawal of DA was 2% with a 95% confidence interval (CI) of 1–3%.

Conclusion
Our study showed a very low recurrent rate of prolactinomas after DAs withdrawal. Much more prospective studies with larger cases and longer follow-up period are encouraged to confirm our finding.

Trial registration
Registration numberCRD42021245888 (PROSPERO).
“One size does not fit all” – lessons learned from a multiple-methods study of a resident wellness curriculum across sites and specialties
Authors: Chaukos Deanna , Zebrowski Jonathan P. , Benson Nicole M. , Celik Alper , Chad-Friedman Emma , Teitelbaum Aviva , Bernstein Carol , Cook Rebecca , Genfi Afia , Denninger John W. 
Published: November 2021

Abstract
Background
There is growing recognition that wellness interventions should occur in context and acknowledge complex contributors to wellbeing, including individual needs, institutional and cultural barriers to wellbeing, as well as systems issues which propagate distress. The authors conducted a multiple-methods study exploring contributors to wellbeing for junior residents in diverse medical environments who participated in a brief resilience and stress-reduction curriculum, the Stress Management and Resiliency Training Program for Residents (SMART-R).

Methods
Using a waitlist-controlled design, the curriculum was implemented for post-graduate year (PGY)-1 or PGY-2 residents in seven residency programs across three sites. Every three months, residents completed surveys, including the Perceived Stress Scale-10, General Self-Efficacy Questionnaire, a mindfulness scale (CAMSR), and a depression screen (PHQ-2). Residents also answered free-text reflection questions about psychological wellbeing and health behaviors.

Results
The SMART-R intervention was not significantly associated with decreased perceived stress. Linear regression modeling showed that depression was positively correlated with reported stress levels, while male sex and self-efficacy were negatively correlated with stress. Qualitative analysis elucidated differences in these groups: Residents with lower self-efficacy, those with a positive depression screen, and/or female residents were more likely to describe experiencing lack of control over work. Residents with higher self-efficacy described more positive health behaviors. Residents with a positive depression screen were more self-critical, and more likely to describe negative personal life events.

Conclusions
This curriculum did not significantly modify junior residents’ stress. Certain subpopulations experienced greater stress than others (female residents, those with lower self-efficacy, and those with a positive depression screen). Qualitative findings from this study highlight universal stressful experiences early in residency, as well as important differences in experience of the learning environment among subgroups. Tailored wellness interventions that aim to support diverse resident sub-groups may be higher yield than a “one size fits all” approach.

Trial registration
NCT02621801, Registration date: December 4, 2015 – Retrospectively registered.
Assessing the quality of electronic medical records as a platform for resident education
Authors: Hung Hsuan , Kueh Ling-Ling , Tseng Chin-Chung , Huang Han-Wei , Wang Shu-Yen , Hu Yu-Ning , Lin Pao-Yen , Wang Jiun-Ling , Chen Po-Fan , Liu Ching-Chuan , Roan Jun-Neng 
Published: November 2021

Abstract
Background
Previous studies have assessed note quality and the use of electronic medical record (EMR) as a part of medical training. However, a generalized and user-friendly note quality assessment tool is required for quick clinical assessment. We held a medical record writing competition and developed a checklist for assessing the note quality of participants’ medical records. Using the checklist, this study aims to explore note quality between residents of different specialties and offer pedagogical implications.

Methods
The authors created an inpatient checklist that examined fundamental EMR requirements through six note types and twenty items. A total of 149 records created by residents from 32 departments/stations were randomly selected. Seven senior physicians rated the EMRs using a checklist. Medical records were grouped as general medicine, surgery, paediatric, obstetrics and gynaecology, and other departments. The overall and group performances were analysed using analysis of variance (ANOVA).

Results
Overall performance was rated as fair to good. Regarding the six note types, discharge notes (0.81) gained the highest scores, followed by admission notes (0.79), problem list (0.73), overall performance (0.73), progress notes (0.71), and weekly summaries (0.66). Among the five groups, other departments (80.20) had the highest total score, followed by obstetrics and gynaecology (78.02), paediatrics (77.47), general medicine (75.58), and surgery (73.92).

Conclusions
This study suggested that duplication in medical notes and the documentation abilities of residents affect the quality of medical records in different departments. Further research is required to apply the insights obtained in this study to improve the quality of notes and, thereby, the effectiveness of resident training.
Healthcare professionals’ perceptions on medication communication challenges and solutions – text mining and manual content analysis - cross-sectional study
Authors: Syyrilä Tiina , Vehviläinen-Julkunen Katri , Härkänen Marja 
Published: November 2021

AbstractBackgroundCommunication challenges contribute to medication incidents in hospitals, but it is unclear how communication can be improved. The aims of this study were threefold: firstly, to describe the most common communication challenges related to medication incidents as perceived by healthcare professionals across specialized hospitals for adult patients; secondly, to consider suggestions from healthcare professionals with regard to improving medication communication; and thirdly, to explore how text mining compares to manual analysis when analyzing the free-text content of survey data.MethodsThis was a cross-sectional, descriptive study. A digital survey was sent to professionals in two university hospital districts in Finland from November 1, 2019, to January 31, 2020. In total, 223 professionals answered the open-ended questions; respondents were primarily registered nurses (77.7 %), physicians (8.6 %), and pharmacists (7.3 %). Text mining and manual inductive content analysis were employed for qualitative data analysis.ResultsThe communication challenges were: (1) inconsistent documentation of prescribed and administered medication; (2) failure to document orally given prescriptions; (3) nurses’ unawareness of prescriptions (given outside of ward rounds) due to a lack of oral communication from the prescribers; (4) breaks in communication during care transitions to non-communicable software; (5) incomplete home medication reconciliation at admission and discharge; (6) medication lists not being updated during the inpatient period due to a lack of clarity regarding the responsible professional; and (7) work/environmental factors during medication dispensation and the receipt of verbal prescriptions.Suggestions for communication enhancements included: (1) structured digital prescriptions; (2) guidelines and training on how to use documentation systems; (3) timely documentation of verbal prescriptions and digital documentation of administered medication; (4) communicable software within and between organizations; (5) standardized responsibilities for updating inpatients’ medication lists; (6) nomination of a responsible person for home medication reconciliation at admission and discharge; and (7) distraction-free work environment for medication communication. Text mining and manual analysis extracted similar primary results.ConclusionsNon-communicable software, non-standardized medication communication processes, lack of training on standardized documentation, and unclear responsibilities compromise medication safety in hospitals. Clarification is needed regarding interdisciplinary medication communication processes, techniques, and responsibilities. Text mining shows promise for free-text analysis.
Pragmatic pharmacoeconomic analyses by using post-market adverse drug reaction reports: an illustration using infliximab, adalimumab, and the Canada vigilance adverse reaction database
Authors: Maity Tuhin , Longo Christopher 
Published: November 2021

Abstract
Background
The prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT). However, trial conditions do not always reflect the real-world applications of pharmaceutical products; hence, they may not accurately portray the actual risks of ADRs associated with them. The objective of this study is two-fold: (a) demonstrate whether and how post-market and RCT ADR data could lead to different conclusions for a set of drugs of interest, and (b) evaluate the potential economic impact of the post-market ADRs associated with those drugs.

Methods
We selected two TNF-α inhibitor biologics, infliximab and adalimumab, and used the Canada Vigilance Adverse Reaction (CVAR) online database as a source of post-market ADR data. Adverse reaction data from RCTs were obtained from ClinicalTrials.gov. Direct healthcare costs associated with adverse reactions were obtained from Canadian Institute for Health Information (CIHI) or Interactive Health Data Application, Alberta. We calculated post-market ADR rates and compared them with those found in the randomized controlled trials of these two drugs. Using the post-market data, we estimated the costs associated with serious ADRs from three perspectives: patient, health system, and societal.

Results
For both drugs, the post-market and RCT data exhibited significantly different adverse reaction rates for several different clinical outcomes. As a general trend, more serious adverse reactions, such as death, appeared to have a higher rate in post-market applications compared to the clinical trials. The estimated average annual economic burden of the severe adverse reaction outcomes ranged from $10 million to $20 million for infliximab and $6 million to $19 million for adalimumab.

Conclusions
The frequency and severity of post-market adverse reactions associated with pharmaceutical products may significantly differ from those detected in the clinical trials. Despite possible methodological differences, this is due to the fact that post-market data reflect the externalities of the real-world that are absent in RCTs. The economic burden of adverse reactions can be substantial, and the cost calculated using post-market data is better reflective of the cost of ADRs in the real-world.