Miracle-dz/UniFAR-FTUs huggingface dataset:
Flipping the Classroom in Graduate Medical Education: A Systematic Review.

Background Flipped classroom (FC) instruction has become increasingly common in graduate medical education (GME). Objective The purpose of this study was to profile the use of FC in the GME setting and assess the current status of research quality. Methods We conducted a systematic literature search of major health and social science databases from July 2017 to July 2018. Articles were screened to ensure they described use of the FC method in an Accreditation Council for Graduate Medical Education-accredited residency program and included research outcomes. Resulting articles were analyzed, described, and evaluated for research quality using the Kirkpatrick framework and the Medical Education Research Study Quality Instrument (MERSQI). Results Twenty-two articles were identified, all of which were recently published. Five were only indirectly related to FC methods. Most studies reported Kirkpatrick-level outcomes. Studies involving resident learner opinions were generally positive. Pre-posttest studies resulted in large positive improvements in knowledge or skills attainment. Control group study results ranged from large positive (1.56) to negative effects (-0.51). Average MERSQI scores of 12.1 (range, 8.5-15.5) were comparable to GME research norms. Conclusions Varying methods for implementing and studying the FC in GME has led to variable results. While residents expressed a positive attitude toward FC learning, shortcomings were reported. Approximately half of the studies comparing the flipped to the traditional classroom reported better achievement under the FC design. As indicated by the MERSQI score, studies captured by this review, on average, were as rigorous as typical research on residency education.
Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study

Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III (GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide a conformational rationale for the different antigenic epitopes identified for these PS. We find that side chains stabilize the proximal βdGlc(1→6)βdGlcNAc backbone linkage, restricting rotation and creating a well-defined conformational epitope at the branch point. This agrees with the glycotope structure recognized by an anti-GBSIII PS functional monoclonal antibody. We find the same dominant solution conformation for GBSIII and Pn14 PS: aside from the branch point, the backbone is very flexible with a “zig-zag” conformational habit, rather than the helix previously proposed for GBSIII PS. This suggests a common strategy for bacterial evasion of the host immune system: a flexible backbone that is less perceptible to the immune system, combined with conformationally-defined branch points presenting human-mimic epitopes. This work demonstrates how small structural features such as side chains can alter the conformation of a polysaccharide by restricting rotation around backbone linkages.
EUS: A one-stop shop approach for pancreatic head masses: Dream or reality?

217 Address for correspondence Dr. Alberto Larghi, Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy. E-mail: alberto.larghi@yahoo.it Received: 2018-09-18; Accepted: 2018-11-16; Published online: 2019-02-20 The approach to the head of the pancreas (HOP) masses causing distal biliary obstruction has rapidly changed over the last decade. In patients with unresectable disease, tissue confirmation and biliary drainage are required to allow for chemotherapy administration. EUS‐guided fine‐needle tissue acquisition (EUS‐TA), when available, is now considered the best method to reach a definitive diagnosis. [1] The choice of the biliary stent to be placed by endoscopic retrograde cholangiography (ERC) is based on the predictable survival of the patient, being 4 months the cutoff to decide between a plastic stent (<4‐month survival) and a self‐expandable metal stent (SEMS) (>4‐month survival). [2]
The Planning, Implementation, and Evaluation of California's Inaugural Food Waste Prevention Week

Supplemental Digital Content is Available in the Text. Preventing food waste can divert food from landfills to feed people, combat climate change, preserve natural resources, and save money. In February 2017, the Nutrition Policy Institute and the Public Health Alliance of Southern California initiated a multisector collaboration among California state agencies to raise awareness about food waste. After development and distribution of a Communications Guide, Food Waste Prevention Week was launched successfully in March 2018, with official support from California's Governor, Secretary of Agriculture, Superintendent of Public Instruction, and other leaders. The multiagency shared messaging campaign was estimated to reach millions, based on unique page views via social and traditional media. In a follow-up survey, partners expressed satisfaction with Food Waste Prevention Week and interest in participating in future efforts. Organizing leaders across multiple sectors to raise awareness about food waste is possible; such efforts can contribute to driving behavioral and structural changes to reduce food waste.
Biobanking: Objectives, Requirements, and Future Challenges—Experiences from the Munich Vascular Biobank

Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine.
Mechanical stretch upregulates connexin43 in human trabecular meshwork cells

Primary open angle glaucoma (POAG) patients have hallmark increases in intraocular pressure (IOP) and noted dysfunction of the trabecular meshwork (TM). Connexin43 (Cx43) is a gap junction widely expressed on the TM that is important for intercellular communication. The human gene is known as gap junction alpha‐1 (GJA1). Since the role of Cx43 in the TM is not fully understood, we set out to determine the effect of excess mechanical stretch on cultured human trabecular meshwork cells (hTMCs) and to specifically investigate the effect of stretch on Cx43 expression and function.
Cardiac Biomarkers in the Emergency Department: The Role of Soluble ST2 (sST2) in Acute Heart Failure and Acute Coronary Syndrome—There is Meat on the Bone

Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated with an increased risk of adverse left ventricular remodeling. Therefore, sST2 could represent a useful tool that could help the risk stratification and diagnostic and therapeutic work-up of patients admitted to an emergency department. With this review, based on recent literature, we have built sST2-assisted flowcharts applicable to three very common clinical scenarios of the emergency department: Acute heart failure, type 1, and type 2 acute myocardial infarction. In particular, we combined sST2 levels together with clinical and instrumental evaluation in order to offer a practical tool for emergency medicine physicians.
Enhanced cerebral perfusion during brief exposures to cyclic intermittent hypoxemia.

Cerebral vasodilation and increased cerebral oxygen extraction help maintain cerebral oxygen uptake in the face of hypoxemia. This study examined cerebrovascular responses to intermittent hypoxemia in eight healthy men breathing 10% O2 for 5 cycles, each 6 min, interspersed with 4 min of room air breathing. Hypoxia exposures raised heart rate ( P < 0.01) without altering arterial pressure, and increased ventilation ( P < 0.01) by expanding tidal volume. Arterial oxygen saturation ([Formula: see text]) and cerebral tissue oxygenation ([Formula: see text]) fell ( P < 0.01) less appreciably in the first bout (from 97.0 ± 0.3% and 72.8 ± 1.6% to 75.5 ± 0.9% and 54.5 ± 0.9%, respectively) than the fifth bout (from 94.9 ± 0.4% and 70.8 ± 1.0% to 66.7 ± 2.3% and 49.2 ± 1.5%, respectively). Flow velocity in the middle cerebral artery ( VMCA) and cerebrovascular conductance increased in a sigmoid fashion with decreases in [Formula: see text] and [Formula: see text]. These stimulus-response curves shifted leftward and upward from the first to the fifth hypoxia bouts; thus, the centering points fell from 79.2 ± 1.4 to 74.6 ± 1.1% ( P = 0.01) and from 59.8 ± 1.0 to 56.6 ± 0.3% ( P = 0.002), and the minimum VMCA increased from 54.0 ± 0.5 to 57.2 ± 0.5 cm/s ( P = 0.0001) and from 53.9 ± 0.5 to 57.1 ± 0.3 cm/s ( P = 0.0001) for the [Formula: see text]- VMCA and [Formula: see text]- VMCA curves, respectively. Cerebral oxygen extraction increased from prehypoxia 0.22 ± 0.01 to 0.25 ± 0.02 in minute 6 of the first hypoxia bout, and remained elevated between 0.25 ± 0.01 and 0.27 ± 0.01 throughout the fifth hypoxia bout. These results demonstrate that cerebral vasodilation combined with enhanced cerebral oxygen extraction fully compensated for decreased oxygen content during acute, cyclic hypoxemia. NEW & NOTEWORTHY Five bouts of 6-min intermittent hypoxia (IH) exposures to 10% O2 progressively reduce arterial oxygen saturation ([Formula: see text]) to 67% without causing discomfort or distress. Cerebrovascular responses to hypoxemia are dynamically reset over the course of a single IH session, such that threshold and saturation for cerebral vasodilations occurred at lower [Formula: see text] and cerebral tissue oxygenation ([Formula: see text]) during the fifth vs. first hypoxia bouts. Cerebral oxygen extraction is augmented during acute hypoxemia, which compensates for decreased arterial O2 content.
Cross-species amplification and development of new microsatellite loci for Taxus wallichiana (Taxaceae).

PREMISE OF THE STUDY Previously published and newly developed microsatellite primers for Taxus species were screened for their potential transfer to Taxus wallichiana and to characterize the genetic diversity and population structure of this species. METHODS AND RESULTS Twenty microsatellite markers that successfully PCR amplified showed polymorphisms when tested on T. wallichiana. Ten of these were obtained by cross-species amplification. The remaining 10 markers were developed in the current study. These markers were characterized on 58 individuals from two T. wallichiana populations from China. Overall, the number of alleles per locus ranged from two to twelve. No significant linkage disequilibrium (LD) was detected between the comparisons of these loci. CONCLUSIONS The polymorphic microsatellite markers screened in this study will be useful for further investigations of the conservation genetics of the endangered species T. wallichiana.
Medical decision making and the counting of uncertainty.

In economic theory, homo economicus is a concept used to explain decision making as a rational exercise.1 The “economic man,” to use the term often associated with the work of the utilitarian philosopher John Stuart Mills, is someone who makes decisions by carefully weighing the benefits and costs of his or her options and then deciding on a course of action that maximizes his or her utility. Although now considered overly simplistic, this idea is often implicit in how we as clinicians have traditionally approached medical decision making. In the case of statins for the primary prevention of cardiovascular diseases, the choice is frequently framed in terms of the tradeoff between the potential benefit of preventing a future heart attack or stroke (ie, utility) and the side effects and inconveniences of taking a medication (ie, disutility). Thus, the recently released 2013 American Heart Association/American College of Cardiology guideline on the treatment of blood cholesterol reminds us that, in addition to calculating estimated atherosclerotic cardiovascular disease risk to determine statin eligibility, we should engage with patients “in a discussion…to consider the potential for ASCVD [atherosclerotic cardiovascular disease] benefit and for adverse effects, for drug-drug interactions, and patient preferences for treatment. ”2 However, although much of the debate over the current guidelines has focused on the accuracy of risk estimation,3,4 the evidence base is limited for how to engage with patients during the decision-making process to assess their disutility for taking statin therapy. Article see p 2539 The reason is in part that, although the proportion of patients who report side effects can be measured, it is difficult to assign a numeric value to the aspect of disutility resulting from having to take a medication daily. In this issue of Circulation , Fontana and …
GABAA receptor family: overview on structural characterization.

The pentameric γ-aminobutyric acid type A receptors are ion channels activated by ligands, which intervene in the rapid inhibitory transmission in the mammalian CNS. Due to their rich pharmacology and therapeutic potential, it is essential to understand their structure and function thoroughly. This deep characterization was hampered by the lack of experimental structural information for many years. Thus, computational techniques have been extensively combined with experimental data, in order to undertake the study of γ-aminobutyric acid type A receptors and their interaction with drugs. Here, we review the exciting journey made to assess the structures of these receptors and outline major outcomes. Finally, we discuss the brand-new structure of the α1β2γ2 subtype and the amazing advances it brings to the field.
Expression of SNAIL in accompanying PanIN is a key prognostic indicator in pancreatic ductal adenocarcinomas

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, mainly because of its invasive and metastatic characteristics. Pancreatic intraepithelial neoplasia (PanIN) is one of the major precursor lesions of PDAC. Although epithelial‐to‐mesenchymal transition (EMT) is known to play an important role for these malignant behaviors, the association between PanIN and EMT has not been clearly understood. Therefore, we explored possible molecules for regulation of EMT immunohistochemically. Using surgically resected specimens from 71 PDAC patients, expressions of SNAIL, SLUG, TWIST1, and ZEB1 were investigated in high‐grade PanIN (HG‐PanIN) and PDAC. Results demonstrated that PDAC accompanied by SNAIL‐positive HG‐PanIN showed a significantly better relapse‐free survival (RFS) (median survival time (MST) of 11.3 months vs 4.4 months, P < 0.001) and overall survival overall survival (OS) (MST of 25.2 months vs 13.6 months, P < 0.001). In PDAC accompanied by SLUG‐positive HG‐PanIN, RFS and OS (P = 0.09 and P = 0.05) tended to have a better prognosis. In contrast, we could not find any significant prognostic benefits in the expression of TWIST1 or ZEB1 in PDAC accompanied by HG‐PanIN. Our present results suggest that (1) EMT may play an important role in the development of PDAC from HG‐PanIN, and (2) SNAIL may predict a distinct subgroup that shows a better prognosis.
Deep Learning for Prediction of AMD Progression: A Pilot Study.

Purpose To develop and assess a method for predicting the likelihood of converting from early/intermediate to advanced wet age-related macular degeneration (AMD) using optical coherence tomography (OCT) imaging and methods of deep learning. Methods Seventy-one eyes of 71 patients with confirmed early/intermediate AMD with contralateral wet AMD were imaged with OCT three times over 2 years (baseline, year 1, year 2). These eyes were divided into two groups: eyes that had not converted to wet AMD (n = 40) at year 2 and those that had (n = 31). Two deep convolutional neural networks (CNN) were evaluated using 5-fold cross validation on the OCT data at baseline to attempt to predict which eyes would convert to advanced AMD at year 2: (1) VGG16, a popular CNN for image recognition was fine-tuned, and (2) a novel, simplified CNN architecture was trained from scratch. Preprocessing was added in the form of a segmentation-based normalization to reduce variance in the data and improve performance. Results Our new architecture, AMDnet, with preprocessing, achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89 at the B-scan level and 0.91 for volumes. Results for VGG16, an established CNN architecture, with preprocessing were 0.82 for B-scans/0.87 for volumes versus 0.66 for B-scans/0.69 for volumes without preprocessing. Conclusions A CNN with layer segmentation-based preprocessing shows strong predictive power for the progression of early/intermediate AMD to advanced AMD. Use of the preprocessing was shown to improve performance regardless of the network architecture.
Breakdown of a Brassica rapa subsp. sylvestris Single Dominant Blackleg Resistance Gene in B. napus Rapeseed by Leptosphaeria maculans Field Isolates in Australia.

Blackleg, caused by Leptosphaeria maculans, is a major disease of oilseed rape (Brassica napus) grown in Canada, Europe, and Australia. Cv. Surpass 400 was released in Australia in 2000 as the most resistant cultivar to L. maculans. It carries a single dominant resistance gene from B. rapa subsp. sylvestris. This cultivar usually shows a hypersensitive response to L. maculans characterized by small, dark brown lesions that are necrotic, localized, and without pycnidia on cotyledons, leaves, and stems. However, in 2001 on a Western Australian experimental farm, a small proportion of the lesions on the lower stem and crown region of cv. Surpass 400 were typical of those observed in susceptible cultivars, which were brown, necrotic lesions with a darker margin, but they contained fewer pycnidia. Forty seedlings of cv. Surpass 400 and susceptible cv. Westar were inoculated with pycnidiospore suspensions (106/ml) of each of 18 isolates taken from lesions on cv. Surpass 400. All 18 isolates caused collapse of cotyledons of susceptible cv. Westar. Four of these isolates caused large cotyledon lesions with some pycnidia on cv. Surpass 400. Three of these four isolates were subsequently inoculated onto 60 seedlings per isolate, at each of the four cotyledon lobes of each seedling of the two cultivars. Inoculated plants were assessed for disease severity on cotyledons and transplanted to the field 14 days after inoculation. The cotyledons of inoculated cv. Surpass 400 showed characteristic large, necrotic lesions with pycnidia, while the cotyledons of cv. Westar had collapsed and contained a mass of pycnidia. Blackleg disease severity in the crown region of the stem was assessed at 2 weeks before harvest. Fifty-four percent of the cv. Surpass 400 transplanted inoculated plants subsequently developed susceptible symptoms of crown cankers on stems. These symptoms were deep, girdling, brown lesions on the plant crowns with some pycnidia. One hundred percent of cv. Westar plants were infected and dead at this stage. This confirmed the ability of these field isolates to overcome the single dominant resistance gene present in cv. Surpass 400. To our knowledge, this is the first report of breakdown of a single dominant B. rapa subsp. sylvestris gene based resistance to blackleg in oilseed rape in the field.
The fish oil story remains fishy.

There is substantial evidence, mostly observational, that diets that include fish reduce the risk of coronary heart disease.1,–,4 Yet, a major question remains as to whether this benefit is due entirely to the omega-3, or long-chain, n-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and/or other nutrient contents in fish. An alternative explanation is that people who consume more fish are already consuming a heart-healthy diet. Although an effect of omega-3 fatty acids on cardiac sudden death has been suggested,5,–,7 minimal evidence exists to support their use in the setting of an acute myocardial infarction (AMI). Article see p 2152 The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)–Prevenzione was a trial in patients surviving a recent (<3 months earlier) AMI.5 In that trial, 11 323 patients were randomly assigned to 1-g supplements of n-3 polyunsaturated fatty acids, vitamin E (300 mg/d), both, or no treatment on top of the optimal pharmacological treatment and lifestyle advice at the time. Survival curves for n-3 polyunsaturated fatty acid treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (risk reduction, 0.59; 95% confidence interval, 0.36 to 0.97; P =0.037), and the reduction in risk of sudden death was particularly relevant and statistically significant at 4 months (risk reduction, 0.47; 95% confidence interval, 0.219 to 0.995; P =0.048). Although this study was implemented 10 years ago, it set the stage for the OMEGA Trial, a double-blind, randomized, placebo-controlled trial of earlier administration of omega-3 fatty acids in patients with AMI who were receiving more recent and aggressive state-of-the-art and guidelines-based therapy. The OMEGA Trial8 set …