bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Outcomes Associated With Utilization of Education, Case Management, and Advanced Practice Pharmacy Services by American Indian and Alaska Native Peoples With Diabetes
Authors: O’Connell Joan , Reid Margaret , Rockell Jennifer , Harty Kathleen , Perraillon Marcelo , Manson Spero 
Published: March 2021

Background:
The burden of diabetes is exceptionally high among American Indian and Alaska Native (AI/AN) peoples. The Indian Health Service (IHS) and Tribal health programs provide education, case management, and advanced practice pharmacy (ECP) services for AI/ANs with diabetes to improve their health outcomes.

Objective:
The objective of this study was to evaluate patient outcomes associated with ECP use by AI/AN adults with diabetes.

Research Design:
This observational study included the analysis of IHS data for fiscal years (FY) 2011–2013. Using propensity score models, we assessed FY2013 patient outcomes associated with FY2012 ECP use, controlling for FY2011 baseline characteristics.

Subjects:
AI/AN adults with diabetes who used IHS and Tribal health services (n=28,578).

Measures:
We compared health status and hospital utilization outcomes for ECP users and nonusers.

Results:
Among adults with diabetes, ECP users, compared with nonusers, had lower odds of high systolic blood pressure [odds ratio (OR)=0.85, P<0.001] and high low-density lipoprotein cholesterol (OR=0.89, P<0.01). Among adults with diabetes absent cardiovascular disease (CVD) at baseline, 3 or more ECP visits, compared with no visits, was associated with lower odds of CVD onset (OR=0.79, P<0.05). Among adults with diabetes and CVD, any ECP use was associated with lower odds of end-stage renal disease onset (OR=0.60, P<0.05). ECP users had lower odds of 1 or more hospitalizations (OR=0.80, P<0.001).

Conclusions:
Findings on positive patient outcomes associated with ECP use by adults with diabetes may inform IHS and Tribal policies, funding, and enhancements to ECP services to reduce disparities between AI/ANs and other populations in diabetes-related morbidity and mortality.
High Expression of PRSS3 Indicates Unfavorable Clinical Outcomes in Colon Adenocarcinoma
Authors: Zhang Quanyi , Wang Jihai , Huang Di , Liu Gang 
Published: March 2021

Introduction:
Serine proteases have been implicated as key drivers and facilitators of cancer malignancy. Protease, serine, 3 (PRSS3), which belongs to the serine proteases family, is reported to be abundantly expressed in a variety of types of tumor and contributes to the initiation and development of cancers. However, the clinical role of PRSS3 in colon adenocarcinoma (CAC) was not clarified yet. In the present study, we explored the potential effect of PRSS3 in CAC and whether it is related to the poor survival of CAC patients.

Materials and Methods:
The mRNA and protein levels of PRSS3 were examined in CAC samples and connective noncancerous colon samples through quantitative real-time polymerase chain reaction assay and immunohistochemistry staining. Univariate and multivariate analyses were performed to estimate the prognostic role of PRSS3 in enrolled CAC patients.

Results:
PRSS3 expression in CAC samples was significantly increased compared with connective noncancerous samples. Moreover, a higher level of PRSS3 was found to be correlated with the larger tumor size, advanced T stage, and positive lymph node metastasis. In addition, PRSS3 was also defined as an unfavorable prognosis factor for CAC patients.

Conclusions:
High expression of PRSS3 was significantly related to the unfavorable clinical features and poor prognosis in CAC patients. It suggested that PRSS3 might serve as a novel prognostic indicator and potential drug target for CAC treatment.
Preparation for Hand Surgery Fellowship: A Comparison of Resident Training Pathways
Authors: Drinane James J. , Drolet Brian , Roth Malcolm Z. , Eberlin Kyle R. 
Published: March 2021

Background:
Hand surgery is a unique subspecialty in which one can train after completion of either a plastic, orthopedic, or general surgical residency. This study compared hand surgery experience in residency among these different training pathways.

Methods:
The Accreditation Council for Graduate Medical Education case logs of graduating residents in general surgery, orthopedics, and plastic surgery were evaluated for years 2009 through 2018. Cases were grouped according to the Accreditation Council for Graduate Medical Education–defined categories for hand surgery. Comparisons between specialties were made using a one-tail analysis of variance with a 95 percent confidence interval.

Results:
There were 19,159 total residents studied: 11,189 general surgery, 7290 orthopedic, and 1040 plastic surgery. General surgery performed the fewest total hand surgeries per individual resident, while plastic surgery performed the most. Plastic surgery performed more operations than orthopedics in all categories studied including tendon, nerve, amputation, soft tissue, fracture, vascular cases, with p < 0.01 for each category.

Conclusions:
There are significant differences in the preparation of resident trainees for entry into a hand surgery fellowship, and the lack of uniform exposure to hand surgery represents an opportunity for improvement. Fellowship directors and the tripartite specialty board should embrace the differences among general surgery, orthopedic, and plastic surgery graduates early in the fellowship year and address the expected differences. Trainees’ education should be optimized on an individualized basis with targeted education, additional educational courses, and encouraging trainees to seek out clinical challenges to foster their continued professional growth.
Vitamin K2 protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila
Authors: Lin Xiaohui , Wen Xueyi , Wei Zaiwa , Guo Keyi , Shi Fang , Huang Tingting , Wang Wenjing , Zheng Jinou 
Published: March 2021

Objective
Alzheimer disease is characterized by progressive decline in cognitive function due to neurodegeneration induced by accumulation of Aβ and hyperphosphorylated tau protein. This study was conducted to explore the protective effect of vitamin K2 against Aβ42-induced neurotoxicity.

Methods
Alzheimer disease transgenic Drosophila model used in this study was amyloid beta with the arctic mutation expressed in neurons. Alzheimer disease flies were treated with vitamin K2 for 28 days after eclosion. Aβ42 level in brain was detected by ELISA. Autophagy-related genes and NDUFS3, the core subunit of mitochondrial complex I, were examined using real-Time PCR (RT-PCR) and western blot analysis.

Results
Vitamin K2 improved climbing ability (P = 0.0105), prolonged lifespan (P < 0.0001) and decreased Aβ42 levels (P = 0.0267), upregulated the expression of LC3 and Beclin1(P = 0.0012 and P = 0.0175, respectively), increased the conversion of LC3I to LC3II (P = 0.0206) and decreased p62 level (P =0.0115) in Alzheimer disease flies. In addition, vitamin K2 upregulated the expression of NDUFS3 (P = 0.001) and increased ATP production (P = 0.0033) in Alzheimer disease flies.

Conclusion
It seems that vitamin K2 protect against Aβ42-induced neurotoxicity by activation of autophagy and rescue mitochondrial dysfunction, which suggests that it may be a potential valuable therapeutic approach for Alzheimer disease.
Genome-wide study of DNA methylation in Amyotrophic Lateral Sclerosis identifies differentially methylated loci and implicates metabolic, inflammatory and cholesterol pathways
Authors: Hop Paul J. , Zwamborn Ramona A.J. , Hannon Eilis , Shireby Gemma L. , Nabais Marta F. , Walker Emma M. , van Rheenen Wouter , van Vugt Joke J.F.A. , Dekker Annelot M. , Westeneng Henk-Jan , Tazelaar Gijs H.P. , van Eijk Kristel R. , Moisse Matthieu , Baird Denis , Khleifat Ahmad Al , Iacoangeli Alfredo , Ticozzi Nicola , Ratti Antonia , Cooper-Knock Jonathan , Morrison Karen E. , Shaw Pamela J. , Basak A. Nazli , Chiò Adriano , Calvo Andrea , Moglia Cristina , Canosa Antonio , Brunetti Maura , Grassano Maurizio , Gotkine Marc , Lerner Yossef , Zabari Michal , Vourc’h Patrick , Corcia Philippe , Couratier Philippe , Mora Pardina Jesus S. , Salas Teresa , Dion Patrick , Ross Jay P. , Henderson Robert D. , Mathers Susan , McCombe Pamela A. , Needham Merrilee , Nicholson Garth , Rowe Dominic B. , Pamphlett Roger , Mather Karen A. , Sachdev Perminder S. , Furlong Sarah , Garton Fleur C. , Henders Anjali K. , Lin Tian , Ngo Shyuan T. , Steyn Frederik J. , Wallace Leanne , Williams Kelly L. ,   BIOS Consortium,   Brain MEND Consortium, Neto Miguel Mitne , Cauchi Ruben J. , Blair Ian P. , Kiernan Matthew C. , Drory Vivian , Povedano Monica , de Carvalho Mamede , Pinto Susana , Weber Markus , Rouleau Guy , Silani Vincenzo , Landers John E. , Shaw Christopher E. , Andersen Peter M. , McRae Allan F. , van Es Michael A. , Pasterkamp R. Jeroen , Wray Naomi R. , McLaughlin Russell L. , Hardiman Orla , Kenna Kevin P. , Tsai Ellen , Runz Heiko , Al-Chalabi Ammar , van den Berg Leonard H. , Damme Philip Van , Mill Jonathan , Veldink Jan H. 
Published: March 2021

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study (EWAS) meta-analysis in 10,462 samples (7,344 ALS patients and 3,118 controls), representing the largest case-control study of DNA methylation for any disease to date. We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We show that DNA-methylation-based proxies for HDL-cholesterol, BMI, white blood cell (WBC) proportions and alcohol intake were independently associated with ALS. Integration of these results with our latest GWAS showed that cholesterol biosynthesis was causally related to ALS. Finally, we found that DNA methylation levels at several DMPs and blood cell proportion estimates derived from DNA methylation data, are associated with survival rate in patients, and could represent indicators of underlying disease processes.
Epicardial adipose tissue thickness is associated with increased COVID-19 severity and mortality
Authors: Mehta Roopa , Bello-Chavolla Omar Yaxmehen , Mancillas-Adame Leonardo , Rodriguez-Flores Marcela , Pedraza Natalia Ramírez , Encinas Bethsabel Rodríguez , Pérez Carrión Carolina Isabel , Jasso Ávila María Isabel , Valladares-García Jorge Carlos , Vanegas-Cedillo Pablo Esteban , Juárez Diana Hernández , Vargas-Vázquez Arsenio , Antonio-Villa Neftali Eduardo , Chapa-Ibarguengoitia Monica , Almeda-Valdés Paloma , Elias-Lopez Daniel , Galindo-Fraga Arturo , Gulias-Herrero Alfonso , de Leon Alfredo Ponce , Sifuentes-Osornio José , Aguilar-Salinas Carlos A. 
Published: March 2021

ABSTRACTBACKGROUNDIncreased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes.METHODSWe included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes.RESULTSEAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95%CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4C severity score, independent of obesity. EAT mediated 13.1% (95%CI 3.67-28.0%) and 5.1% (95%CI 0.19-14.0%) of the effect of age and 19.4% (95%CI 4.67-63.0%) and 12.8% (95%CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19.CONCLUSIONEAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.
The Effect of Famotidine on Hospitalized Patients with COVID-19: a Systematic Review and Meta-analysis
Authors: Chiu Leonard , Shen Max , Chow Ronald , Lo Chun-Han , Chiu Nicholas , Chen Austin , Shin Hyun Joon , Prsic Elizabeth Horn , Hur Chin , Lebwohl Benjamin 
Published: March 2021

ABSTRACTIntroductionFamotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with COVID-19. The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.MethodsFive databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.ResultsFour studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death - HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.ConclusionBased on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further RCTs may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.
Improved Prediction of COVID-19 Transmission and Mortality Using Google Search Trends for Symptoms in the United States
Authors: Alruily Meshrif , Ezz Mohamed , Mostafa Ayman Mohamed , Yanes Nacim , Abbas Mostafa , EL-Manzalawy Yasser 
Published: March 2021

ABSTRACTAccurate forecasting of emerging infectious diseases can guide public health officials in making appropriate decisions related to the allocation of public health resources. Due to the exponential spread of the COVID-19 infection worldwide, several computational models for forecasting the transmission and mortality rates of COVID-19 have been proposed in the literature. To accelerate scientific and public health insights into the spread and impact of COVID-19, Google released the Google COVID-19 search trends symptoms open-access dataset. Our objective is to develop 7 and 14 -day-ahead forecasting models of COVID-19 transmission and mortality in the US using the Google search trends for COVID-19 related symptoms. Specifically, we propose a stacked long short-term memory (SLSTM) architecture for predicting COVID-19 confirmed and death cases using historical time series data combined with auxiliary time series data from the Google COVID-19 search trends symptoms dataset. Considering the SLSTM networks trained using historical data only as the base models, our base models for 7 and 14 -day-ahead forecasting of COVID cases had the mean absolute percentage error (MAPE) values of 6.6% and 8.8%, respectively. On the other side, our proposed models had improved MAPE values of 3.2% and 5.6%, respectively. For 7 and 14 -day-ahead forecasting of COVID-19 deaths, the MAPE values of the base models were 4.8% and 11.4%, while the improved MAPE values of our proposed models were 4.7% and 7.8%, respectively. We found that the Google search trends for “pneumonia,” “shortness of breath,” and “fever” are the most informative search trends for predicting COVID-19 transmission. We also found that the search trends for “hypoxia” and “fever” were the most informative trends for forecasting COVID-19 mortality.
Reporting results of diagnostic NGS-based testing – user-centered redesign of the clinical report
Authors: Agafonov Oleg , Vik Sigrun , Kjølås Kaja O. , Alagaratnam Sharmini 
Published: March 2021

1AbstractThe transition of next-generation sequencing (NGS) from the research environment to clinical diagnostics has proven difficult, with exome and whole genome sequencing at various stages of implementation in Nordic hospitals. The clinical genomics report details key findings from the interpretation of NGS data and represents the core hand-off between specialized clinical genomics laboratories and the broader healthcare community. However, these text-heavy reports can be difficult to read: critical information may be scattered around the report, and vital information such as limitations of the test may not always be present. Misunderstanding of results, limitations or key findings can lead to incorrect therapeutic decisions, directly impacting patient management.We applied the principles of user-centred design to redesign clinical reports to respond to user needs, while also incorporating existing recommendations and guidelines. We performed several rounds of needs gathering, first with producers of clinical genetics reports, then with clinicians with various level of experience in genetic testing. Based on the insights from a workshop and interviews, we created prototypes of reports which were evaluated in comparison to a set of simulated reports representing those currently in clinical production. Our results showed that the majority of evaluators found the redesigned reports to be clearer and easier to process, demonstrating the value of this approach.
Quit attempts and tobacco abstinence in primary care patients: long-term follow-up of a pragmatic, two-arm cluster randomised controlled trial on brief stop-smoking advice (ABC versus 5As method)
Authors: Kastaun Sabrina , Viechtbauer Wolfgang , Leve Verena , Hildebrandt Jaqueline , Funke Christian , Klosterhalfen Stephanie , Lubisch Diana , Reddemann Olaf , Raupach Tobias , Wilm Stefan , Kotz Daniel 
Published: March 2021

ABSTRACTWe developed a 3.5-h-training for general practitioners (GPs) in delivering brief stop-smoking advice according to different methods (ABC, 5As). In a pragmatic, cluster randomised controlled trial our training proved effective in increasing GP-delivered rates of such advice. In this follow-up analysis we examined the effect of ABC and 5As on patient-reported quit attempts and point prevalence abstinence at weeks 4, 12, and 26 following GP consultation.Follow-up data were collected by questionnaires delivered to 1,937 smoking patients recruited before or after the training in which 69 GPs participated. At week 26, ∼70% of the patients were lost to follow-up. All 1,937 smoking patients were included in an intention-to-treat analysis. Multiple imputation was used to impute missing outcome data of each follow-up and few missing data of potential confounders.While the receipt of brief GP advice compared to no advice was associated with a two-fold increase in patients’ attempts to quit at each follow-up and abstinence at week 26, quit attempts and abstinence rates did not differ significantly from pre- to post-training or between patients from the ABC versus the 5As group.We previously reported that our training increases patient-reported rates of GP-delivered stop-smoking advice. The present follow-up analysis did not show that patients more often attempted or achieved to quit when they received advice from a trained vs. untrained GP. Future training studies should take contextual factors into account – such as access to free evidence-based cessation treatment – which might hamper the transfer of GPs’ effective advice into patients’ behaviour change.TRIAL REGISTRATIONGerman Clinical Trials Register, prior to the first patient in (DRKS00012786, www.drks.de/drks_web/setLocale_EN.do).
Molecular Epidemiology of SARS-CoV-2 in Cyprus
Authors: Richter Jan , Fanis Pavlos , Tryfonos Christina , Koptides Dana , Krashias George , Bashiardes Stavros , Hadjisavvas Andreas , Loizidou Maria , Oulas Anastasis , Alexandrou Denise , Kalakouta Olga , Panayiotidis Mihalis I. , Spyrou George M. , Christodoulou Christina 
Published: March 2021

AbstractWhole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of COVID-19 were identified on March 9, 2020 and since then 33,567 confirmed cases and 230 deaths were documented. In this study, viral whole genome sequencing was performed on 133 SARS-CoV-2 positive samples collected between March 2020 and January 2021. Phylogenetic analysis was conducted to evaluate the genomic diversity of circulating SARS-CoV-2 lineages in Cyprus. 15 different lineages were identified that clustered into three groups associated with the spring, summer and autumn/winter wave of SARS-CoV2 incidence in Cyprus, respectively. The majority of the Cypriot samples belonged to the B.1.258 lineage first detected in September that spread rapidly and largely dominated the autumn/winter wave with a peak prevalence of 86% during the months of November and December. The B.1.1.7 UK variant (VOC-202012/01) was identified for the first time at the end of December and spread rapidly reaching 37% prevalence within one month. Overall, we describe the changing pattern of circulating SARS-CoV-2 lineages in Cyprus since the beginning of the pandemic until the end of January 2021. These findings highlight the role of importation of new variants through travel towards the emergence of successive waves of incidence in Cyprus and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures.