Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update.

PURPOSE To provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) with driver alterations. A guideline update for systemic therapy for patients with stage IV NSCLC without driver alterations was published separately. METHODS The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel updated recommendations based on a systematic review of randomized controlled trials (RCTs) from December 2015 to January 2020 and meeting abstracts from ASCO 2020. RESULTS This guideline update reflects changes in evidence since the previous update. Twenty-seven RCTs, 26 observational studies, and one meta-analysis provide the evidence base (total 54). Outcomes of interest included efficacy and safety. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations, when possible, following other existing high-quality testing guidelines. Most patients should receive targeted therapy for these alterations: Targeted therapies against ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions should be offered to patients, either as initial or second-line therapy when not given in the first-line setting. New or revised recommendations include the following: Osimertinib is the optimal first-line treatment for patients with activating epidermal growth factor receptor mutations (exon 19 deletion, exon 21 L858R, and exon 20 T790M); alectinib or brigatinib is the optimal first-line treatment for patients with anaplastic lymphoma kinase fusions. For the first time, to our knowledge, the guideline includes recommendations regarding RET, MET, and NTRK alterations. Chemotherapy is still an option at most stages.Additional information is available at www.asco. org/thoracic-cancer-guidelines.
Death following extreme temperature exposure: Histological, biochemical and immunohistochemical markers

Introduction Defining extreme temperatures as the cause of death remains challenging. It is mostly based on circumstantial, macroscopic and microscopic features. Methods We retrospectively compared groups of cases of fatal hypothermia, fatal hyperthermia and non-extreme temperature-related deaths. We analysed specific histological findings, focusing on samples from the liver, pancreas and kidney. Results Between 1 January 2013 and 31 December 2016, 15 autopsies were performed for deaths related to extreme temperatures. They included 11 cases of fatal hypothermia (group A), four cases of fatal hyperthermia (group B) and eight controls (group C). Perinuclear hepatocyte vacuolisation was observed in seven cases of hypothermia, one case of hyperthermia and four controls. Pancreatic cytoarchitecture was well preserved in two cases of hypothermia, one case of hyperthermia and two controls. No particular microscopic feature was found in pancreatic samples. Renal epithelial tubular cell vacuolisation was observed in seven cases of hypothermia and one case of hyperthermia, while it was absent in all controls. Chromogranin A (CgA) was markedly positive in the pancreatic tissue of five cases of fatal hypothermia and one control, and mildly positive in one case of fatal hyperthermia. No significant p-values were observed for any comparisons (p > 0.05), except when hypothermia cases group were compared to the control group for the Armanni–Ebstein phenomenon test (p = 0.0078). Conclusions Although our study did not find a specific microscopic marker, hepatocyte vacuolisation, the Armanni–Ebstein phenomenon and pancreatic CgA positivity, taken together, may be useful tools to confirm hypo- and hyperthermia-related deaths, in addition to circumstantial and macroscopic findings.
Clinical manifestations in patients with antiphospholipid antibodies: Beyond thrombosis and pregnancy loss

The clinical spectrum of the antiphospholipid syndrome (APS) encompasses additional manifestations other than thrombosis and pregnancy morbidity, which may potentially affect every organ and system. The pathophysiology of APS indeed cannot be explained exclusively by a prothrombotic state and the “extra-criteria” manifestations of the syndrome should be attributed to other mechanisms, such as inflammation, complement and platelet activation. In this case-series, we report patients with uncommon clinical APS presentations, to highlight relevant peculiarities of the syndrome, potentially paving the way for a further update of clinical as well as laboratory manifestations of this complex immunological condition.
Paucity of Entorhinal Cortex Pathology of the Alzheimer's Type in SuperAgers with Superior Memory Performance.

Advancing age is typically associated with declining memory capacity and increased risk of Alzheimer's disease (AD). Markers of AD such as amyloid plaques (AP) and neurofibrillary tangles (NFTs) are commonly found in the brains of cognitively average elderly but in more limited distribution than in those at the mild cognitive impairment and dementia stages of AD. Cognitive SuperAgers are individuals over age 80 who show superior memory capacity, at a level consistent with individuals 20-30 years their junior. Using a stereological approach, the current study quantitated the presence of AD markers in the memory-associated entorhinal cortex (ERC) of seven SuperAgers compared with six age-matched cognitively average normal control individuals. Amyloid plaques and NFTs were visualized using Thioflavin-S histofluorescence, 6E10, and PHF-1 immunohistochemistry. Unbiased stereological analysis revealed significantly more NFTs in ERC in cognitively average normal controls compared with SuperAgers (P < 0.05) by a difference of ~3-fold. There were no significant differences in plaque density. To highlight relative magnitude, cases with typical amnestic dementia of AD showed nearly 100 times more entorhinal NFTs than SuperAgers. The results suggest that resistance to age-related neurofibrillary degeneration in the ERC may be one factor contributing to preserved memory in SuperAgers.
Characterization of age-related macular degeneration in Indian donor eyes

Purpose: The purpose of this study was to test the reliability of fundus stereomicroscopy in postmortem eyes to assign severity of age-related macular degeneration (AMD) using the Minnesota grading and confirmation by histology using Alabama and Sarks grading scales and to assess the incidence of AMD pathology in donor eyes from a South Indian population. Methods: Eyes (199) from 153 donors (55–95 years) after obtaining fundus images were processed for histology. Fundus images were graded according to the Minnesota grading system based on drusen size, area of depigmentation, and atrophy. At least one eye from each donor displaying the AMD phenotypes were subjected to histological examination. The fundus grading was correlated with histology and the stages of AMD assigned for early AMD by the Alabama AMD grading system and for both early and advanced AMD by the Sarks classification. Results: Stereoscopic examination of the fundus found that 10 of the 153 donors had features of early AMD and 3 advanced AMD. Following histological examination, one of the early AMD eyes was reclassified as advanced AMD. Early AMD features that were observed on histology included soft drusen (>63 μm), basal laminar deposits, photoreceptor outer segment degeneration, disorganization of retinal pigment epithelium (RPE), Bruch's membrane thickening. Advanced AMD features observed in histology are extensive atrophy of RPE, choroidal neovascularization and disciform scar formation. Conclusion: Identification of either early or advanced AMD using stereomicroscopic assessment (SMA) showed high sensitivity and specificity. However, misclassification between AMD stages can occur when only SMA is used.
Improving Diabetes Education in Mexican American Older Adults

Lack of culturally sensitive, age-specific diabetes education in Mexican American older aged people may contribute to deficits in diabetes knowledge, self-management, and glycemic control. This quality improvement initiative applied evidence-based, culturally competent, age-specific education to improve health outcomes. A one-group, pretest/posttest design guided this project in a primary care community clinic. Mexican American adults >60 years, with type 2 diabetes mellitus (T2DM; N = 12) received 3 months of biweekly innovative classes including: healthy Mexican foods; family involvement; Spanish interpreter using simultaneous earphone technology; and interactive, bilingual, large-print materials. Paired sample t tests compared diabetes knowledge, self-management, and A1C levels. There was a significant improvement in preeducation and posteducation outcomes: knowledge, t(11) = −7.969, p = . 000; d = 2.32, self-management, t(11) = −7.930, p = . 000; d = 2.43, and A1C levels, t(11) = 6.434, p = . 000; d = 0.78. Culturally competent, language-friendly innovation, age-specific T2DM education can positively impact knowledge, self-management behaviors, and glycemic values in older aged Mexican American people.
Effect of Therapeutic Ultrasound on the Release of Insulin, Glucagon, and Alpha‐Amylase from Ex Vivo Pancreatic Models

Our previously published studies showed the potential of therapeutic ultrasound (US) as a novel non‐pharmacological alternative for the treatment of secretory deficiencies in type 2 diabetes. Despite showing enhanced insulin release from beta cells, these studies did not explore the potential effects of US treatment on other cells in the islets of Langerhans such as glucagon‐secreting alpha cells or acinar cells of the exocrine pancreas.
Proteolytic activity among psychrotrophic bacteria isolated from refrigerated raw milk

Psychrotrophic bacteria were isolated from refrigerated raw milk from a processing plant in Southern Brazil. Psychrotrophic counts were between 4.9 and 7.8 log cfu/mL, and 5.3 to 7.2 log cfu/mL, for samples collected at the truck and the milk storage silo, respectively. Among the bacterial isolates, 90% were Gram-negative. Most strains presented low proteolytic activity, but strains of Burkholderia cepacia, Klebsiella oxytoca and Aeromonas sp. showed higher than 20 U/mL on azocasein as substrate. Crude proteases from selected strains were resistant to conventional heat treatments and caused coagulation of UHT milk after 5 days storage at room temperature.
Ultralow friction regime from the in situ production of a richer fullerene-like nanostructured carbon in sliding contact

Hitherto, among carbon-based thin films, fullerene-like hydrogenated carbon (FL-C:H) films exhibit unique ultralow friction and wear in open or humid air, but the mechanisms responsible for the friction regime are still not clear. Here, we provide definitive experimental evidences obtained from the wear tracks and debris of FL-C:H films, and show that FL-C:H films’ surface undergoes gradual transformation into a richer and more stable fullerene-like nanostructure, due to the increasing content of pentagonal and heptagonal carbon rings in addition to the six-membered graphene rings, as a result of thermal and strain effects from the repeated friction. The sliding-induced in situ promotion of the FL structures at frictional contact leads to ultralow friction and wear in open air. The results establish an excellent low friction and wear regime for the structural film, and develop the lubrication mechanisms of carbon-based films.
Rheological and curing behavior of reactive blending. II. Natural rubber‐g‐poly(methyl methacrylate)–cassava starch

Graft copolymers of natural rubber (NR) and methyl methacrylate (MMA) were prepared using cumene hydroperoxide and tetraethylene pentamine as redox initiators via the semibatch emulsion polymerization technique. Various molar percentage ratios of NR/MMA were studied in the grafting reaction (i.e., 95/5, 90/10, 80/20, 70/30, and 60/40). The graft copolymer with a 70/30 molar ratio was selected and used to prepare rubber blends with cassava starch. The starch was used at levels of 0, 20, 40, and 60 phr. Another set of rubber blends was prepared for comparison purposes. The NR-g-poly(MMA) (PMMA, 75 phr) was blended with 25 phr of NR air dried sheets (ADS) and a given level of the cassava starch. We found that the Mooney viscosity, shear stress, and shear viscosity increased with an increasing concentration of cassava starch. This may be attributed to the chemical interactions between the polar groups of the NR-g-PMMA and the cassava starch. The blends were later compounded using a compounding formulation according to ASTM D 3184-89. A similar short delay onset of vulcanization (i.e., approximately 1 min) was observed for the whole set of compounds under study. However, different curing characteristics were observed for the blends of NR-g-PMMA–cassava starch and NR-g-PMMA–ADS–cassava starch. The NR-g-PMMA–cassava starch compounds exhibited two-stage curing characteristics. The curing curve had a slight reversion at a testing time of approximately 8 min. The shear modulus then abruptly increased with an increasing testing time in the range of 20–60 min. The curing curves for NR-g-PMMA–ADS–cassava starch blends exhibited a single curing stage with a shear modulus that increased slightly with the testing time was increased from 20 to 60 min. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1453–1463, 2003
‘A Way to Know’ Your Stress: Acceptability and Meaning of Hair Sample Collection for Cortisol Analysis From African-American and Latina Women in a Digital Storytelling Study

Obtaining biological samples for research purposes from members of marginalized communities demands careful social and ethical consideration. This paper aims to discuss how feasibility and acceptability translate into methodological and ethical considerations for collecting hair samples in a study comprised of young, pregnant Latinx and African-American women participating in a digital storytelling intervention (DST). Transcripts from two focus groups with Healthy Families home visitor staff (N =10) and follow-up interviews with DST participants (N = 8) were analyzed through qualitative content analysis for hair sampling acceptability. Responses regarding the feasibility of obtaining a hair sample were generally positive amongst Healthy Families home visitor staff participating in the two focus groups, though responses overall were more favorable with the pregnant women participants who were interviewed post-DST intervention. Home visitors emphasized clear communication to participants around the reasoning for obtaining biological samples. Social and ethical considerations for communication of biomarker data to participants, as well as the intersection of lay knowledge of stress and participants' perspectives on providing a hair sample for cortisol analysis, is discussed.
Effect of sex/gender on obesity traits in Canadian first year university students: The GENEiUS study

Background While weight gain during first year of university has been well documented in North America, literature on sex-specific effects is scarce and inconsistent. The objective of this investigation was to explore sex-specific changes in obesity traits during first year of university at McMaster University (Ontario, Canada). Methods 245 first-year students (80.4% females) were followed longitudinally with data collected early in the academic year and towards the end of the year. Obesity parameters including weight, waist and hip circumferences, BMI, and waist to hip ratio were investigated. The Mann-Whitney U test and the Wilcoxon signed-rank test were used for pairwise comparison of traits in the absence of adjustments. Additionally, the repeated-measures ANOVA test was used with covariate adjustments to investigate the interaction between sex and time. Results Overall sample trends indicated a significant increase in mean weight by 1.55 kg (95% CI: 1.24–1.86) over the school year (p<0.001). This was accompanied by significant gains in BMI, and waist and hip circumferences (p<0.001) in the overall sample. At baseline, males presented with higher body weight, BMI, waist and hip circumferences, and WHR, as compared to their females counterparts (p<0.01). Additionally, sex-stratified analysis indicated significant gains in weight, BMI, and waist and hip circumferences in both males and females (p<0.01). However, a comparison of the magnitude of change over time between the two sex groups revealed no significant difference for any of the investigated traits (p>0.05). Conclusion While our study confirms significant weight gain in both male and female first year university students in Ontario, Canada, it does not show sex specific differences within this context. Our investigation highlights the importance of accounting for sex and gender in health research and supports the need of further studies in this area.
Safety and efficacy of transvenous lead extraction in octogenarians using powered extraction sheaths

In the aging population equipped with cardiac implantable electronic devices, an increasing number of octogenarians require lead extractions. This patient population is often considered as a high‐risk group for surgical procedures. We, therefore, investigated the safety and efficacy of transvenous lead extraction in octogenarians using powered extraction sheaths.
A Comparative Study of Polydioxanone (PDS) and Polyglactin (Vicryl) in Hypospadias Repair

Background: Hypospadias is a fairly common problem, and it is the most common genital congenital anomaly. Objective: This study was carried out to compare polyglactin and polydioxanone in hypospadias repair by assessing the rate of complications, especially urethrocutaneous fistula (UCF) formation. Patients and Methods: This is a prospective observational cross-sectional hospital-based study carried out at the Department of Paediatric Surgery, Ribat University Hospital, from June 2015 to November 2016. In Group A, there were 55 patients who underwent repair using polyglactin, and in Group B, there were 50 patients who underwent repair using polydioxanone. All patients were operated by the same surgeon. Results: The mean age of Group A was 5.7 ± 4.3 years and 5.1 ± 3.9 years in Group B. Meatal advancement and glanuloplasty incorporated operation was done in 47.6%, Tubularized incised plate urethroplasty in (31.4%), Theirsch-Duplay in 20% and Mathieu's repair in 1%. The complication rate was 34% in Group A and 10.9% in Group B. The most frequent complication was UCF, as 19 patients (18.1%) of the study candidates developed UCF; most of them were in Group A (14 patients) and 5 patients in Group B. Another significant complication was meatal stenosis, which occurred in 11 patients (10.5%): 9 in Group A and 2 in Group B. Conclusion: Polydioxanone (PDS) is satisfactory in hypospadias repair as it is associated with better outcome, especially UCF, which is most common and most difficult to treat complication.
Evaluation of Optimal Diastolic Blood Pressure Range Among Adults With Treated Systolic Blood Pressure Less Than 130 mm Hg

Key Points Question What are the safe and optimal diastolic blood pressure (DBP) ranges among adults with treated systolic blood pressure (SBP) of less than 130 mm Hg? Findings In this cohort study of 7515 patients from 2 randomized clinical trials who had treated SBP of less than 130 mm Hg, a DBP of less than 60 mm Hg was associated with increased cardiovascular risk and a DBP between 70 and 80 mm Hg was associated with lower cardiovascular risk. Meaning The findings suggest that a DBP of less than 60 mm Hg may be harmful and a DBP between 70 and 80 mm Hg is an optimal target for patients with treated SBP of less than 130 mm Hg; this topic merits further study.
Effect of treatment with carvacrol and aerobic training on cardiovascular function in spontaneously hypertensive rats

What is the central question of this study? Can two non‐drug therapies, carvacrol and aerobic physical training, together have additive effects on the reduction of cardiovascular risks and control of arterial hypertension? What is the main finding and its importance? The oral use of carvacrol (20 mg/kg/day) can control sustained hypertension in spontaneously hypertensive rats, and when this use is associated with aerobic physical training, there is a more pronounced effect on the reduction of blood pressure values, making these therapies an adjunct option in the drug treatment of hypertension.
Evaluation of a Conical Mill for Screening of Direct Compression Formulations

AbstractSuitability of a Quadro Comil™ for screening of direct compression tablet masses was evaluated with respect to alteration of particle size distribution and blending efficiency. Air jet sieving was qualijied for determination of a particle size of spraydried lactose and microcrystalline cellulose. Using a full 31 × 23 factorial design not only effects of single processing parameters (output screen size, impeller shape, velocity of the mill, and type of powder), but also their respective combinations were investigated in terms of impact on particle size and flow properties (angle of repose, bulk and tapped densities). Particle sizes before and after passing the Comil were found to be normally distributed. The results indicate that the process does not allow any of the powder characteristics studied beyond normal batch-to batch variability. This refers in particular to the proportion of fines. For evaluation of the deagglomeration effectiveness, a 23 design was implemented with iron oxide as a model .
Evaluation of two automated low-cost RNA extraction protocols for SARS-CoV-2 detection

Background Two automatable in-house protocols for high-troughput RNA extraction from nasopharyngeal swabs for SARS-CoV-2 detection have been evaluated. Methods One hundred forty one SARS-CoV-2 positive samples were collected during a period of 10-days. In-house protocols were based on extraction with magnetic beads and designed to be used with either the Opentrons OT-2 (OT-2in-house) liquid handling robot or the MagMAXTM Express-96 system (MMin-house). Both protocols were tested in parallel with a commercial kit that uses the MagMAXTM system (MMkit). Nucleic acid extraction efficiencies were calculated from a SARS-CoV-2 DNA positive control. Results No significant differences were found between both in-house protocols and the commercial kit in their performance to detect positive samples. The MMkit was the most efficient although the MMin-house presented, in average, lower Cts than the other two. In-house protocols allowed to save between 350€ and 400€ for every 96 extracted samples compared to the commercial kit. Conclusion The protocols described harness the use of easily available reagents and an open-source liquid handling system and are suitable for SARS-CoV-2 detection in high throughput facilities.