bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refractory suffering at the end of life and the assisted dying debate: An interview study with palliative care nurses and doctors
Authors: Gustad Kristine Espegren , Askjer Åsta , Nortvedt Per , Fredheim Olav Magnus S , Magelssen Morten 
Published: July 2020

Background How often does refractory suffering, which is suffering due to symptoms that cannot be adequately controlled, occur at the end of life in modern palliative care? What are the causes of such refractory suffering? Should euthanasia be offered for refractory suffering at the end of life? We sought to shed light on these questions through interviews with palliative care specialists. Methods Semi-structured interviews with six nurses and six doctors working in palliative care in five Norwegian hospitals. Transcripts were analysed with systematic text condensation, a qualitative analysis framework. Results Informants find that refractory suffering is rare, and that with palliative sedation satisfactory symptom control can nearly always be achieved at the end of life. However, the process of reaching adequate symptom control can be protracted, and there can be significant suffering in the meantime. Both somatic, psychological, social and existential factors can contribute to refractory suffering and potentiate each other. However, informants also place significant weight on factors pertaining to the organization of palliative care services as contributing to insufficient symptom control. Conclusions If refractory suffering is indeed rare, then this arguably weakens a common prima facie argument for the legalization of assisted dying. However, the process of reaching adequate symptom control can be protracted and involve significant suffering. The experiences of palliative care clinicians constitute important empirical premises for the assisted dying debate. The study points to several areas in which palliative care can be improved.
Estimating the number of preventable cardiovascular disease events in the United States using the EMPA-REG OUTCOME trial results and National Health and Nutrition Examination Survey
Authors: Wong Nathan D , Fan Wenjun , Pak Jonathan 
Published: July 2020

Aim: We examined eligibility and preventable cardiovascular disease events in US adults with diabetes mellitus from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). Methods: We identified adults with diabetes mellitus eligible for EMPA-REG OUTCOME based on trial eligibility criteria available from the National Health and Nutrition Examination Surveys, 2007–2016. We estimated composite cardiovascular disease endpoints, as well as all-cause deaths, death from cardiovascular disease and hospitalizations for heart failure from trial treatment and placebo event rates, the difference indicating the preventable events. Results: Among 29,629 US adults aged ⩾18 years (representing 231.9 million), 4672 (27.3 million) had diabetes mellitus, with 342 (1.86 million) meeting eligibility criteria of EMPA-REG OUTCOME. We estimated from trial primary endpoint event rates of 10.5% and 12.1% in the empagliflozin and placebo groups, respectively, that based on the ‘treatment’ of our 1.86 million estimated EMPA-REG OUTCOME eligible subjects, 12,066 (95% confidence interval: 10,352–13,780) cardiovascular disease events could be prevented annually. Estimated annual preventable deaths from any cause, cardiovascular causes and hospitalizations from heart failure were 17,078 (95% confidence interval: 14,652–19,504), 14,479 (95% confidence interval: 12,422–16,536) and 9467 (95% confidence interval: 8122–10,812), respectively. Conclusion: Empagliflozin, if provided to EMPA-REG OUTCOME eligible US adults, may prevent many cardiovascular disease events, cardiovascular and total deaths, as well as heart failure hospitalizations.
Endovascular treatment of complex middle cerebral artery aneurysms using TuBridge flow diverters
Authors: Liang Feng , Yang Yibing , Luo Lijuan , Liao Bingye , Zhang Guofeng , Ou Siqi , Xiao Weiping , Guo Ning , Qi Tiewei 
Published: July 2020

Background The safety and efficacy of the TuBridge flow diverter in treating middle cerebral artery aneurysms remains unknown. In this study, we report our preliminary experience treating complex middle cerebral artery aneurysms using the TuBridge flow diverter. Methods A prospectively maintained database of intracranial aneurysms treated with the TuBridge flow diverter was retrospectively reviewed, and patients with middle cerebral artery aneurysms were included in this study. Demographics, aneurysm features, complications, and clinical and angiographic outcomes were assessed. Evaluation of the angiographic results included occlusion grade of aneurysm (O’Kelly–Marotta grading scale), patency of jailed branch(es), and in-stent stenosis. Results Eight patients with eight middle cerebral artery aneurysms were included in this study. The mean aneurysm size was 11.8 ± 6.8 mm. There were no procedure-related complications and there was no morbidity or mortality at a mean follow-up of 11.3 ± 3.6 months. All patients had follow-up angiograms at a mean of 7.5 ± 4.0 months after surgery. Of the eight patients, there was 1 (12.5%) O’Kelly–Marotta grading scale A, 3 (37.5%) O’Kelly–Marotta grading scale B, 1 (12.5%) O’Kelly–Marotta grading scale C, and 3 (37.5%) O’Kelly–Marotta grading scale D. Of the seven patients with jailed branch, the blood flow of jailed branch was unchanged in 4 (57.1%), decreased in 2 (28.6%), and occluded in 1 (14.3%). In-stent stenosis was mild in 2 (25%) patients and moderate in 1 (12.5%) patient. Conclusion Midterm results suggest that endovascular treatment of middle cerebral artery aneurysms using the TuBridge flow diverter is safe and associated with good outcomes. The TuBridge flow diverter may be an option for complex middle cerebral artery aneurysms that are difficult to treat with either clipping or coiling.
The impact of Behçet’s disease on intimate relationships in women: A qualitative study
Authors: Sweeting Fay , Arden-Close Emily 
Published: July 2020

Objective Behçet’s disease is a rare and incurable condition where the body’s immune system attacks healthy tissue. Behçet’s can cause blood clots and ulcerations to form in every organ and system in the body, including deep and painful genital ulceration. The psychological impact of the disease on intimacy and relationships is unexplored. This study aimed to explore how the disease impacts on female patients’ intimate partner relationships. Methods Participants were seven female, UK patients with Behçet’s disease who were in committed relationships. In depth, semi-structured interviews lasting approximately 80 minutes were conducted via video conferencing about participants’ sexual functioning and intimate relationships. Data was analysed using Interpretative Phenomenological Analysis. Results Patients’ sexual relationships and intimacy were impacted by issues due to lack of knowledge of symptoms (misdiagnosis of herpes), issues due to symptoms (genital manifestations, painful sex, exhaustion), difficulties communicating with medical professionals, medication, partner support, and support from fellow Behçet’s patients. Discussion Female Behçet’s patients are at risk of developing psychological problems with intimacy due to symptoms, lack of knowledge of symptoms, and negative impacts of medication. Intimacy needs to be discussed in medical consultations so these issues can be addressed before a lack of intimacy negatively impacts relationships.
Adverse Events Related to Cartiva Hemiarthroplasty of First Metatarsal: An Analysis of Reports to the United States Food and Drug Administration
Authors: Metikala Sreenivasulu , Mahmoud Karim , O’Connor Kathryn M. , Chao Wen , Wapner Keith L. , Farber Daniel C. 
Published: July 2020

Background: The results supporting Cartiva, a synthetic cartilage implant (Wright Medical) in hallux rigidus have come from limited institutions creating observational bias. Complications experienced in community centers are not routinely included in the published literature. To look at a broader range of potential complications, we reviewed the United States Food and Drug Administration’s (FDA) voluntary device database and compared that data with published literature. Methods: The Manufacturer and User Facility Device Experience (MAUDE) database of the FDA was retrospectively reviewed between July 2016 and October 2019 using the product code: PNW, assigned for Cartiva. Results: A total of 49 events have been reported and implant subsidence was the most common with 16 reports. Others include fragmentation (9), infection (4), bone erosion (3), foreign body reaction (1) and unspecified (16). Thirty-five events mentioned further surgeries at a mean interval of 4.75 months. Conclusions: The analysis of the MAUDE database disclosed certain device-related dysfunctions that have been underreported in the published literature. Because of the voluntary nature of reporting, the true incidence of each complication is unknown with this data representing a baseline. The MAUDE database could be further strengthened by a more robust reporting mechanism or mandatory reporting of device-related complications. Levels of Evidence: Level IV: Case series from large database analysis
Let bees be bees
Authors: Johnson Norman A. 
Published: July 2020

AbstractThomas Seeley reviews a half century of research, mostly conducted by himself and his colleagues on the ecology, evolution, and natural history of wild honey bees. He provides insights into how bees reproduce, how they forage, and how they defend the colony. The final chapter, “Darwinian beekeeping” discusses how ecological and evolutionary principles can be incorporated into the practice of beekeeping.
Comparison of different bacteriological testing strategies and factors for bacteriological confirmation among pulmonary TB patients: a retrospective study in Tianjin, China, 2017–2018
Authors: Zhang Guoqin , Zhang Yuhua , Chen Mingting , Zhang Fan 
Published: July 2020

Abstract
Background
Bacteriological confirmation (BC) proportion among notified pulmonary TB patients in China is among the lowest in the world. This study was to understand the yield of BC using different testing strategies and patient-level factors associated with BC among pulmonary TB patients in Tianjin, China during 2017–2018.

Methods
A retrospective study was conducted, enrolling pulmonary TB patients reported to National TB Information Management System (TBIMS) in Tianjin during 2017–2018. BC was defined as a positive result by any of the followings: smear microscopy, culture, or nucleic acid amplification test. Individual characteristics were compared between patients with positive and negative bacteriological results using contingency tables and χ2 test. Multivariable logistic regression was applied to analyze factors associated with BC, calculating adjusted odds ratios (aOR) and 95% confidence intervals (CI) (α = 0.05).

Results
Of 6364 reported patients, 4181 (65.7%) were bacteriologically confirmed. Positivity proportion was 43.1% (2746/6364) for smear microscopy, 57.7% (3380/5853) for culture, 61.7% (1608/2605) for Xpert® MTB/RIF assay (Xpert) and 73.4% (1824/2484) for combination of the three. The unemployed (aOR = 1.5, 95% CI: 1.0–2.2) and farmers (aOR = 1.7, 95% CI: 1.1–2.8) compared with students; diagnosis by inpatient hospitals compared with TB clinics (aOR = 3.4, 95% CI: 2.6–4.4); having symptoms for ≥2 weeks (aOR = 1.4, 95% CI: 1.1–1.8); cough (aOR = 2.2, 95% CI: 1.8–2.8); blood sputum (aOR = 1.5, 95% CI: 1.0–2.2); cavitation on chest X-ray (aOR = 3.3, 95% CI: 2.5–4.3); bilateral lung lobes affected (aOR = 1.7, 95% CI: 1.4–2.2) were factors associated with BC.

Conclusions
Combination test was an effective way to improve BC among pulmonary TB patients. Being unemployed, farmers, having prolonged symptoms, and more severe in TB condition were factors associated with BC. We recommend combination of tests to improve BC for pulmonary TB patients, especially who are in early stage of the disease or with conditions tend to be bacteriologically negative.
Binary Tönnis classification: simplified modification demonstrates better inter- and intra-observer reliability as well as agreement in surgical management of hip pathology
Authors: Shapira Jacob , Chen Jeffrey W. , Bheem Rishika , Rosinsky Philip J. , Maldonado David R. , Lall Ajay C. , Domb Benjamin G. 
Published: July 2020

Abstract
Background
The traditional Tönnis Classification System has inherent drawbacks as it is vulnerable to the subjectivity of a four-grade system. A two-grade classification could potentially be more reliable. The purpose of this study is to (1) compare the inter-observer and intra-observer reliability of the traditional Tönnis Classification System and a simplified Binary Tönnis Classification System for hip osteoarthritis and to (2) evaluate the clinical applicability of both systems. Our hypothesis is that the proposed Binary Tönnis Classification System will have better reliability and agreement for surgical decision-making.

Methods
Forty consecutive patients were selected to participate in this study. Patients were included in this study if they were between 35 and 60 years old. Patients were excluded if they had prior hip surgeries or conditions. All radiographs were randomized and blinded by a non-observer. Five fellowship-trained hip surgeons from a single center, in a fully crossed design, analyzed and graded all the radiographs utilizing the traditional Tönnis Classification System and the proposed Binary Tönnis Classification System. Intra- and inter-observer reliability values for both the systems were calculated using the Cohen’s κ coefficient. A multi-rater κ was calculated using the weighted Fleiss method.

Results
The study sample contained 40 anterosuperior hip radiographs. For the traditional Tönnis Classification System, the weighted κ showed a fair inter-observer reliability (κ = 0.474) and excellent intra-observer reliability (κ mean = 0.866). For the proposed Binary Tönnis Classification System, both inter-observer and intra-observer reliability demonstrated excellent values, (κ = 0.858 and 0.928, respectively). On average, the Binary Tönnis Classification System correctly captured 87% of cases. When the traditional Tönnis Classification System was dichotomized, the capture rate was 84%.

Conclusion
A simplified binary Tönnis Classification System demonstrates better reliability and clinical implementation than the traditional Tönnis Classification System.
Stopping renin-angiotensin system blockers after acute kidney injury and risk of adverse outcomes: parallel population-based cohort studies in English and Swedish routine care
Authors: Bidulka Patrick , Fu Edouard L. , Leyrat Clémence , Kalogirou Fotini , McAllister Katherine S. L. , Kingdon Edward J. , Mansfield Kathryn E. , Iwagami Masao , Smeeth Liam , Clase Catherine M. , Bhaskaran Krishnan , van Diepen Merel , Carrero Juan-Jesus , Nitsch Dorothea , Tomlinson Laurie A. 
Published: July 2020

AbstractBackgroundThe safety of restarting angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) after acute kidney injury (AKI) is unclear. There is concern that previous users do not restart ACEI/ARB despite ongoing indications. We sought to determine the risk of adverse events after an episode of AKI, comparing prior ACEI/ARB users who stop treatment to those who continue.MethodsWe conducted two parallel cohort studies in English and Swedish primary and secondary care, 2006–2016. We used multivariable Cox regression to estimate hazard ratios (HR) for hospital admission with heart failure (primary analysis), AKI, stroke, or death within 2 years after hospital discharge following a first AKI episode. We compared risks of admission between people who stopped ACEI/ARB treatment to those who were prescribed ACEI/ARB within 30 days of AKI discharge. We undertook sensitivity analyses, including propensity score-matched samples, to explore the robustness of our results.ResultsIn England, we included 7303 people with AKI hospitalisation following recent ACEI/ARB therapy for the primary analysis. Four thousand three (55%) were classified as stopping ACEI/ARB based on no prescription within 30 days of discharge. In Sweden, we included 1790 people, of whom 1235 (69%) stopped treatment. In England, no differences were seen in subsequent risk of heart failure (HR 1.10; 95% confidence intervals (CI) 0.93–1.30), AKI (HR 0.90; 95% CI 0.77–1.05), or stroke (HR 0.99; 95% CI 0.71–1.38), but there was an increased risk of death (HR 1.27; 95% CI 1.15–1.41) in those who stopped ACEI/ARB compared to those who continued. Results were similar in Sweden: no differences were seen in risk of heart failure (HR 0.91; 95% CI 0.73–1.13) or AKI (HR 0.81; 95% CI 0.54–1.21). However, no increased risk of death was seen (HR 0.94; 95% CI 0.78–1.13) and stroke was less common in people who stopped ACEI/ARB (HR 0.56; 95% CI 0.34–0.93). Results were similar across all sensitivity analyses.ConclusionsPrevious ACEI/ARB users who continued treatment after an episode of AKI did not have an increased risk of heart failure or subsequent AKI compared to those who stopped the drugs.
Integration analysis of long non-coding RNA (lncRNA) role in tumorigenesis of colon adenocarcinoma
Authors: Poursheikhani Arash , Abbaszadegan Mohammad Reza , Nokhandani Negin , Kerachian Mohammad Amin 
Published: July 2020

Abstract
Background
Colon adenocarcinoma (COAD) is one of the most common gastrointestinal cancers globally. Molecular aberrations of tumor suppressors and/or oncogenes are the main contributors to tumorigenesis. However, the exact underlying mechanisms of COAD pathogenesis are clearly not known yet. In this regard, there is an urgent need to indicate promising potential diagnostic and prognostic biomarkers in COAD patients.

Methods
In the current study, level 3 RNA-Seq and miR-Seq data and corresponding clinical data of colon adenocarcinoma (COAD) were retrieved from the TCGA database. The “limma” package in R software was utilized to indicate the differentially expressed genes. For in silico functional analysis, GO and KEGG signaling pathways were conducted. PPI network was constructed based on the STRING online database by Cytoscape 3.7.2. A ceRNA network was also constructed by “GDCRNATools” package in R software. Kaplan-Meier survival analysis (log-rank test) and ROC curve analysis were used to indicate the diagnostic and prognostic values of the biomarkers.

Results
The differential expression data demonstrated that 2995 mRNAs, 205 lncRNAs, and 345 miRNAs were differentially expressed in COAD. The GO and KEGG pathway analysis indicated that the differentially expressed mRNAs were primarily enriched in canonical processes in cancer. The PPI network showed that the CDKN2A, CCND1, MYC, E2F, CDK4, BRCA2, CDC25B, and CDKN1A proteins were the critical hubs. In addition, the Kaplan-Meier analysis revealed that 215 mRNAs, 14 lncRNAs, and 39 miRNAs were associated with overall survival time in the patients. Also, the ceRNA network data demonstrated that three lncRNAs including MIR17HG, H19, SNHG1, KCNQ1OT1, MALAT1, GAS5, SNHG20, OR2A1-AS1, and MAGI2-AS3 genes were involved in the development of COAD.

Conclusions
Our data suggested several promising lncRNAs in the diagnosis and prognosis of patients with COAD.
DNA methylation data-based molecular subtype classification and prediction in patients with gastric cancer
Authors: Lian Qixin , Wang Bo , Fan Lijun , Sun Junqiang , Wang Guilai , Zhang Jidong 
Published: July 2020

Abstract
Background
Genetic and epigenetic alterations have been indicated to be closely correlated with the carcinogenesis, DNA methylation is one of most frequently occurring molecular behavior that take place early during this complicated process in gastric cancer (GC).

Methods
In this study, 398 samples were collected from the cancer genome atlas (TCGA) database and were analyzed, so as to mine the specific DNA methylation sites that affected the prognosis for GC patients. Moreover, the 23,588 selected CpGs that were markedly correlated with patient prognosis were used for consistent clustering of the samples into 6 subgroups, and samples in each subgroup varied in terms of M, Stage, Grade, and Age. In addition, the levels of methylation sites in each subgroup were calculated, and 347 methylation sites (corresponding to 271 genes) were screened as the intrasubgroup specific methylation sites. Meanwhile, genes in the corresponding promoter regions that the above specific methylation sites were located were performed signaling pathway enrichment analysis.

Results
The specific genes were enriched to the biological pathways that were reported to be closely correlated with GC; moreover, the subsequent transcription factor enrichment analysis discovered that, these genes were mainly enriched into the cell response to transcription factor B, regulation of MAPK signaling pathways, and regulation of cell proliferation and metastasis. Eventually, the prognosis prediction model for GC patients was constructed using the Random Forest Classifier model, and the training set and test set data were carried out independent verification and test.

Conclusions
Such specific classification based on specific DNA methylation sites can well reflect the heterogeneity of GC tissues, which contributes to developing the individualized treatment and accurately predicting patient prognosis.
Reshaping the role of m6A modification in cancer transcriptome: a review
Authors: Yang Guanqun , Sun Zhigang , Zhang Nan 
Published: July 2020

AbstractN6-methyl-adenosine(m6A) modification emerges as an abundant and dynamic regulation throughout the Eukaryotic transcriptome. Dysregulation of the m6A regulators has increasingly been found in many neoplasms. It is reasonable to believe that m6A changes the fate of cancer cells and subsequently affected all aspects of cancer progression. In view of the context-dependent role of m6A modification, we emphasize a dual effect of m6A in a particular tumor model, that is, m6A plays a promoting role or a suppressing role in different stages of cancer. This novel sight is compared to the older view that a particular m6A regulator acts as a consistent role in cancer progression.