bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights from a general practice service evaluation supporting a lower carbohydrate diet in patients with type 2 diabetes mellitus and prediabetes: a secondary analysis of routine clinic data including HbA1c, weight and prescribing over 6 years
Authors: Unwin David , Khalid Ali Ahsan , Unwin Jen , Crocombe Dominic , Delon Christine , Martyn Kathy , Golubic Rajna , Ray Sumantra 
Published: November 2020

BackgroundIn a single general practice (GP) surgery in England, there was an eightfold increase in the prevalence of type 2 diabetes (T2D) in three decades with 57 cases and 472 cases recorded in 1987 and 2018, respectively. This mirrors the growing burden of T2D on the health of populations round the world along with healthcare funding and provision more broadly. Emerging evidence suggests beneficial effects of carbohydrate-restricted diets on glycaemic control in T2D, but its impact in a ‘real-world’ primary care setting has not been fully evaluated.MethodsAdvice on a lower carbohydrate diet was offered routinely to patients with newly diagnosed and pre-existing T2D or prediabetes between 2013 and 2019, in the Norwood GP practice with 9800 patients. Conventional ‘one-to-one’ GP consultations were used, supplemented by group consultations, to help patients better understand the glycaemic consequences of their dietary choices with a particular focus on sugar, carbohydrates and foods with a higher Glycaemic Index. Those interested were computer coded for ongoing audit to compare ‘baseline’ with ‘latest follow-up’ for relevant parameters.ResultsBy 2019, 128 (27%) of the practice population with T2D and 71 people with prediabetes had opted to follow a lower carbohydrate diet for a mean duration of 23 months. For patients with T2D, the median (IQR) weight dropped from of 99.7 (86.2, 109.3) kg to 91.4 (79, 101.1) kg, p<0.001, while the median (IQR) HbA1c dropped from 65.5 (55, 82) mmol/mol to 48 (43, 55) mmol/mol, p<0.001. For patients with prediabetes, the median (IQR) HbA1c dropped from 44 (43, 45) mmol/mol to 39 (38, 41) mmol/mol, p<0.001. Drug-free T2D remission occurred in 46% of participants. In patients with prediabetes, 93% attained a normal HbA1c. Since 2015, there has been a relative reduction in practice prescribing of drugs for diabetes leading to a T2D prescribing budget £50 885 per year less than average for the area.ConclusionsThis approach to lower carbohydrate dietary advice for patients with T2D and prediabetes was incorporated successfully into routine primary care over 6 years. There were statistically significant improvements in both groups for weight, HbA1c, lipid profiles and blood pressure as well as significant drug budget savings. These results suggest a need for more empirical research on the effects of lower carbohydrate diet and long-term glycaemic control while recording collateral impacts to other metabolic health outcomes.
SOX2 promotes resistance of melanoma with PD-L1 high expression to T-cell-mediated cytotoxicity that can be reversed by SAHA
Authors: Wu Ruiyan , Wang Caiqin , Li Zhiming , Xiao Jian , Li Chunyan , Wang Xuemin , Kong Pengfei , Cao Jianghua , Huang Fuxue , Li Zhiling , Huang Yun , Chen Yuhong , Li Xuan , Yang Dong , Zhang Hailiang , Mai Jia , Feng Gongkan , Deng Rong , Zhu Xiaofeng 
Published: November 2020

BackgroundImmune checkpoint inhibitors (ICIs) induce better tumor regression in melanoma with programmed cell death 1 ligand 1 (PD-L1) high expression, but there has been an upsurge of failed responses. In this study, we aimed to explore the additional mechanisms possibly accounting for ICIs resistance and interventional strategies to overcome the resistance in melanoma with PD-L1 high expression.MethodsMelanoma xenografts and cytotoxicity assays were used to investigate function of SOX2 in regulating antitumor immunity. The activity of the janus kinase-signal transducer and activator of transcriptions (JAK-STAT) pathway was investigated by western blots, quantitative PCR and luciferase assay. Epigenetic compounds library screen was employed to identify inhibitors that could decrease SOX2 level. The effect of histone deacetylase inhibitor SAHA in antitumor immunity alone or in combination with immunotherapy was also determined in vitro and in vivo. Prognostic impact of SOX2 was analyzed using transcriptional profiles and clinical data download from the Gene Expression Omnibus and The Cancer Genome Atlas repository.ResultsWe uncovered a role of SOX2 in attenuating the sensitivity of melanoma cells to CD8+ T-cell killing. Mechanistically, SOX2 inhibited phosphatases suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase non-receptor type 1 (PTPN1) transcription, induced duration activation of the JAK-STAT pathway and thereby overexpression of interferon stimulated genes resistance signature (ISG.RS). By targeting the SOX2-JAK-STAT signaling, SAHA promoted the antitumor efficacy of IFNγ or anti-PD-1 in vitro and in vivo. Moreover, SOX2 was an independent prognostic factor for poor survival and resistant to anti-PD-1 therapy in melanoma with PD-L1 high expression.ConclusionsOur data unveiled an additional function of SOX2 causing immune evasion of CD8+ T-cell killing through alleviating the JAK-STAT pathway and ISG.RS expression. We also provided a rationale to explore a novel combination of ICIs with SAHA clinically, especially in melanoma with PD-L1 and SOX2 high expression.
Cellular responses to flow diverters in a tissue-engineered aneurysm model
Authors: Liu Wenjing , Dai Daying , Ding Yong-Hong , Liu Yang , Temnyk Kristen , Shen Tiffany W , Cardinal Kristen O'Halloran , Kallmes David F , Kadirvel Ramanathan 
Published: November 2020

BackgroundNotwithstanding the widespread implementation of flow diverters (FDs) in the treatment of intracranial aneurysms, the exact mechanism of action of these devices remains elusive. We aimed to advance the understanding of cellular responses to FD implantation using a 3D tissue-engineered in vitro aneurysm model.MethodsAneurysm-like blood vessel mimics (aBVMs) were constructed by electrospinning polycaprolactone nanofibers onto desired aneurysm-like geometries. aBVMs were seeded with human aortic smooth muscle cells (SMCs) followed by human aortic endothelial cells (ECs). FDs were then deployed in the parent vessel of aBVMs covering the aneurysm neck and were cultivated for 7, 14, or 28 days (n=3 for each time point). The EC and SMC coverage in the neck was measured semi-quantitatively.ResultsAt day 7, the device segment in contact with the parent vessel was partially endothelialized. Also, the majority of device struts, but not pores, at the parent vessel and neck interface were partially covered with ECs and SMCs, while device struts in the middle of the neck lacked cell coverage. At 14 days, histology verified a neointimal-like lining had formed, partially covering both the struts and pores in the center of the neck. At 28 days, the majority of the neck was covered with a translucent neointimal-like layer. A higher degree of cellular coverage was seen on the struts and pores at the neck at 28 days compared with both 7 and 14 days.ConclusionaBVMs can be a valuable alternative tool for evaluating the healing mechanisms of endovascular aneurysm devices.
Occupational standing and change in the Ankle-Brachial Index: the Jackson Heart Study
Authors: Friel Ciaran P , Duran Andrea T , Abdalla Marwah , Unkart Jonathan T , Bellettiere John , Sims Mario , Correa Adolfo , Shimbo Daichi , Diaz Keith M 
Published: November 2020

BackgroundA growing interest in reducing occupational sitting has resulted in public health efforts to encourage intermittent standing in workplaces. However, concerns have been raised that standing for prolonged periods may expose individuals to new health hazards, including lower limb atherosclerosis. These concerns have yet to be corroborated or refuted. The purpose of this study was to investigate the association between occupational standing and adverse changes in the Ankle-Brachial Index (ABI).MethodsWe studied 2121 participants from the Jackson Heart Study, a single-site community-based study of African-Americans residing in Jackson, MS. Occupational standing (‘never/seldom’, ‘sometimes’, ‘often/always’) was self-reported at baseline (2000–2004). ABI was measured at baseline and again at follow-up (2009–2013).ResultsOver a median follow-up of 8 years, 247 participants (11.6%) exhibited a significant decline in ABI (eg, ABI decline >0.15). In multivariable-adjusted models, higher occupational standing was not significantly associated with ABI decline (occupational standing sometimes vs never/seldom: OR 1.05; 95% CI 0.67, 1.66; occupational standing often/always vs never/seldom: OR 1.22; 95% CI 0.77, 1.94). Similarly, higher occupational standing was not associated with low ABI at follow-up reflective of peripheral artery disease (ABI <0.90) or high ABI at follow-up reflective of incompressible vessels (ABI >1.40).ConclusionsIn this community-based study of African-Americans, we found no evidence that occupational standing is deleteriously associated with adverse changes in ABI over a median follow-up of 8.0 years. These findings do not provide evidence implicating occupational standing as a risk factor for lower limb atherosclerosis.
A ternary Cahn–Hilliard–Navier–Stokes model for two-phase flow with precipitation and dissolution
Authors: Rohde Christian , von Wolff Lars 
Published: November 2020

We consider the incompressible flow of two immiscible fluids in the presence of a solid phase that undergoes changes in time due to precipitation and dissolution effects. Based on a seminal sharp interface model a phase-field approach is suggested that couples the Navier–Stokes equations and the solid’s ion concentration transport equation with the Cahn–Hilliard evolution for the phase fields. The model is shown to preserve the fundamental conservation constraints and to obey the second law of thermodynamics for a novel free energy formulation. An extended analysis for vanishing interfacial width reveals that in this limit the sharp interface model is recovered, including all relevant transmission conditions. Notably, the new phase-field model is able to realize Navier-slip conditions for solid–fluid interfaces in the limit.
The one-phase fractional Stefan problem
Authors: del Teso Félix , Endal Jørgen , Vázquez Juan Luis 
Published: November 2020

We study the existence and properties of solutions and free boundaries of the one-phase Stefan problem with fractional diffusion posed in [Formula: see text]. In terms of the enthalpy [Formula: see text], the evolution equation reads [Formula: see text], while the temperature is defined as [Formula: see text] for some constant [Formula: see text] called the latent heat, and [Formula: see text] stands for the fractional Laplacian with exponent [Formula: see text]. We prove the existence of a continuous and bounded selfsimilar solution of the form [Formula: see text] which exhibits a free boundary at the change-of-phase level [Formula: see text]. This level is located at the line (called the free boundary) [Formula: see text] for some [Formula: see text]. The construction is done in 1D, and its extension to [Formula: see text]-dimensional space is shown. We also provide well-posedness and basic properties of very weak solutions for general bounded data [Formula: see text] in several dimensions. The temperatures [Formula: see text] of these solutions are continuous functions that have finite speed of propagation, with possible free boundaries. We obtain estimates on the growth in time of the support of [Formula: see text] for solutions with compactly supported initial temperatures. Besides, we show the property of conservation of positivity for [Formula: see text] so that the support never recedes. On the contrary, the enthalpy [Formula: see text] has infinite speed of propagation and we obtain precise estimates on the tail. The limits [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] are also explored, and we find interesting connections with well-studied diffusion problems. Finally, we propose convergent monotone finite-difference schemes and include numerical experiments aimed at illustrating some of the obtained theoretical results, as well as other interesting phenomena.
A Case–Control Study to Evaluate Environmental and Lifestyle Risk Factors for Esophageal Cancer in Tanzania
Authors: Mmbaga Elia J. , Mushi Beatrice P. , Deardorff Katrina , Mgisha William , Akoko Larry O. , Paciorek Alan , Hiatt Robert A. , Buckle Geoffrey C. , Mwaiselage Julius , Zhang Li , Van Loon Katherine 
Published: November 2020

Abstract

Background:
East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC).

Methods:
We conducted an incident case–control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran–Mantel–Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone.

Results:
Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41–4.68], former smoking (OR 2.45; 95% CI, 1.46–4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01–2.77), daily spicy chilies (OR 1.62; 1.04–2.52), and daily salted foods (OR 2.02; 95% CI, 1.06–3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16–0.80), fruit (OR 0.47; 95% CI, 0.27–0.82), and smoked fish (OR 0.31; 95% CI, 0.15–0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16–11.73), Northern-Lake (OR 2.40; 95% CI, 1.46–3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56–6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone.

Conclusions:
Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania.

Impact:
These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa.
See related commentary by McCormack et al., p. 248
Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway
Authors: Støer Nathalie C. , Botteri Edoardo , Thoresen G. Hege , Karlstad Øystein , Weiderpass Elisabete , Friis Søren , Pottegård Anton , Andreassen Bettina K. 
Published: November 2020

AbstractBackground:Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk.Methods:This registry-based, nested case–control study, 1:10 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose–response trends.Results:We found 145 associations among 1,230 drug–cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug–cancer combinations are presented in this article and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk.Conclusions:This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies.Impact:DWAS studies are robust and important tools to define new drug–cancer hypotheses.See related commentary by Wang and Gadalla, p. 597
Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors
Authors: Sha Dan , Jin Zhaohui , Budczies Jan , Kluck Klaus , Stenzinger Albrecht , Sinicrope Frank A. 
Published: November 2020

AbstractTumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, varies across malignancies. Panel sequencing–based estimates of TMB have largely replaced whole-exome sequencing–derived TMB in the clinic. Retrospective evidence suggests that TMB can predict the efficacy of immune checkpoint inhibitors, and data from KEYNOTE-158 led to the recent FDA approval of pembrolizumab for the TMB-high tumor subgroup. Unmet needs include prospective validation of TMB cutoffs in relationship to tumor type and patient outcomes. Furthermore, standardization and harmonization of TMB measurement across test platforms are important to the successful implementation of TMB in clinical practice.Significance:Evaluation of TMB as a predictive biomarker creates the need to harmonize panel-based TMB estimation and standardize its reporting. TMB can improve the predictive accuracy for immunotherapy outcomes, and has the potential to expand the candidate pool of patients for treatment with immune checkpoint inhibitors.
The effectiveness of practicum-based worksheet based on salt hydrolysis material viewed from the aspect of laboratory skills and interpersonal intelligence learners
Authors: Astuti Elsa Ari , Wardani Sri , Kadarwati Sri , Kasmui Kasmui 
Published: November 2020

This study aims to determine the effectiveness of a practicum worksheet (LKPPD) based on guided inquiry and the response of learners as users. The effectiveness of LKPPD is seen from aspects of laboratory skills and students' interpersonal intelligence on hydrolysis material. This type of research is qualitative and quantitative. Data collected by interview, observation, and questionnaire. The results showed that LKPPD that has been developed is effective because 76% of students have laboratory skills with very high category and 96.5% of students have interpersonal intelligence with a minimum category high. In addition, this LKPPD received a positive response from learners as users with a percentage score of 77.9%.
Developing instruments of teacher’s perception of critical thinking in elementary school
Authors: Rahmawati Eni , Harun Harun 
Published: November 2020

This study aims to develop the teacher's perceptions of critical thinking in science learning in elementary schools. The samples in this study were 50 elementary school teachers in Central Java. Selection of samples employed convenience sampling. The instruments in this study used a modified Likert Scale. The validity tests used in this research were content validity and construct validity. Content validity was measured using CVR (Content Validity Ratio) and construct validity was measured using EFA (Exploratory Factor Analysis). By using SPSS, reliability estimation was obtained with the Cronbach Alpha formula 0.83 and it can be stated that the instruments for evaluating teacher perceptions of critical thinking in science learning are reliable.
Institutional Red Blood Cell Transfusion Rates Are Correlated Following Endovascular and Surgical Cardiovascular Procedures: Evidence That Local Culture Influences Transfusion Decisions
Authors: Apostolidou Eirini , Kolte Dhaval , Kennedy Kevin F. , Beale Charles E. , Abbott J. Dawn , Ehsan Afshin , Gurm Hitinder S. , Carson Jeffrey L. , Mamdani Shafiq , Aronow Herbert D. 
Published: November 2020

Background
The relationship between local hospital culture and transfusion rates following endovascular and surgical cardiovascular procedures has not been well studied.

Methods and Results

Patients undergoing coronary revascularization, aortic valve replacement, lower extremity peripheral vascular intervention, or carotid artery revascularization from up to 852 US hospitals in the Nationwide Readmissions Database were identified. Crude and risk‐standardized red blood cell transfusion rates were determined for each procedure. Pearson correlation coefficients were calculated between respective procedural transfusion rates. Median odds ratios were estimated to reflect between‐hospital variability in red blood cell transfusion rates following the same procedure for a given patient. There was wide variation in red blood cell transfusion rates across different procedures, from 2% following carotid endarterectomy to 29% following surgical aortic valve replacement. For surgical and endovascular modalities, transfusion rates at the same hospital were highly correlated for aortic valve replacement (
r
=0.67;
P
<0.001), moderately correlated for coronary revascularization (
r
=0.56;
P
<0.001) and peripheral vascular intervention (
r
=0.51;
P
<0.001), and weakly correlated for carotid artery revascularization (
r
=0.19,
P
<0.001). Median odds ratios were all >2, highest for coronary artery bypass graft surgery and surgical aortic valve replacement, indicating substantial site variation in transfusion rates.

Conclusions
After adjustment for patient‐related factors, wide variation in red blood cell transfusion rates remained across surgical and endovascular procedures employed for the same cardiovascular condition. Transfusion rates following these procedures are highly correlated at individual hospitals and vary widely across hospitals. In aggregate, these findings suggest that local institutional culture significantly influences the decision to transfuse following invasive cardiovascular procedures and highlight the need for randomized data to inform such decisions.