Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling drug response using network-based personalized treatment prediction (NetPTP) with applications to inflammatory bowel disease

For many prevalent complex diseases, treatment regimens are frequently ineffective. For example, despite multiple available immunomodulators and immunosuppressants, inflammatory bowel disease (IBD) remains difficult to treat. Heterogeneity in the disease across patients makes it challenging to select the optimal treatment regimens, and some patients do not respond to any of the existing treatment choices. Drug repurposing strategies for IBD have had limited clinical success and have not typically offered individualized patient-level treatment recommendations. In this work, we present NetPTP, a Network-based Personalized Treatment Prediction framework which models measured drug effects from gene expression data and applies them to patient samples to generate personalized ranked treatment lists. To accomplish this, we combine publicly available network, drug target, and drug effect data to generate treatment rankings using patient data. These ranked lists can then be used to prioritize existing treatments and discover new therapies for individual patients. We demonstrate how NetPTP captures and models drug effects, and we apply our framework to individual IBD samples to provide novel insights into IBD treatment.
Safety and Angiographic Efficacy of Intra-Arterial Fibrinolytics as Adjunct to Mechanical Thrombectomy: Results from the INFINITY Registry

Background and Purpose Data on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse. Methods INtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months. Results Of 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9). Conclusions Administration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.
Effects of Streamwise Pressure Gradient on Turbulent Spot Development

A pressure distribution representative of a controlled diffusion compressor blade suction surface is imposed on a flat plate. Boundary layer transition in this situation is investigated by triggering a wave packet which evolves into a turbulent spot. The development from wave packet to turbulent spot is observed and the interactions of the turbulent spot with the ongoing natural transition aad the ensuing turbulent boundary layer are examined. Under this steeply diffusing pressure distribution strong amplification of primary instabilities prevails. Breakdown to turbulence is instigated near the center line and propagates transversely along the wave packet until the turbulent region dominates. An extensive calmed region is present behind the spot which persists well into the surrounding turbulent layer. Celerities of spot leading and trailing edges are presented, as is the spanwise spreading half-angle. Corresponding measurements for spots under a wide range of imposed pressure gradients are compiled and the present results are compared with those of other authors. Resulting correlations for spot propagation parameters are provided for use in computational modeling of the transition region under variable pressure gradients.Copyright © 1995 by ASME
Trainee engagement with reflection in online portfolios: A qualitative study highlighting the impact of the Bawa-Garba case on professional development

Abstract Background Reflection is an essential tool for postgraduate medical training, yet fear of exposing incompetence is a known barrier for engagement with reflection. In the UK, this fear may have been amplified by the case of Dr Bawa-Garba, whose reflective e-portfolio entries informed a General Medical Council investigation resulting in the loss of her licence to practice. Aim To identify themes GP trainees commonly explore in e-portfolio entries, and whether their reflective e-portfolio entries have changed following the Bawa-Garba case. Method A phenomenological approach was applied. Semi-structured interviews continued to data saturation in a purposive sample of trainees (7) and trainers (4) recruited from a South Yorkshire GP training scheme. Transcript data were assigned to a coding framework with iterative thematic analysis. Results Dominant emergent themes were ‘difficulty’ and ‘challenge’. All trainees described reluctance to submit significant event analyses (SEAs) on mistakes and near misses for fear of jeopardising their careers. International medical graduates were disproportionately affected by the challenges reflection posed. Conclusion Following the Bawa-Garba case, trainees are disengaging with SEAs to reduce the risk of self-incrimination. Further guidance with which trainees can navigate their reflective e-portfolios is required to retain the value of reflection as a tool for professional development.
Ohmic contact formation mechanism of Ta∕Al∕Mo∕Au and Ti∕Al∕Mo∕Au metallizations on AlGaN∕GaN HEMTs

A comparative study of Ta∕Al∕Mo∕Au and Ti∕Al∕Mo∕Au metallizations for AlGaN∕GaN high electron mobility transistors is presented. By the optimization of surface treatment schemes and annealing temperature, contact resistances of 0.172 and 0. 228Ωmm, and specific contact resistivities of 2.96×10−7 and 1.09×10−6Ωcm2 were obtained for Ti∕Al∕Mo∕Au and Ta∕Al∕Mo∕Au, respectively. Auger electron spectroscopy (AES), x-ray diffraction (XRD), and transmission electron microscopy (TEM) were utilized to study microstructural changes occurring in the metallization layers as a result of heat treatment. Results indicate dynamic systems of severe intermixing between atoms from the metallization layers and epilayers resulting in changes in surface morphology, as determined by atomic force microscopy (AFM). The formation of intermetallics and interfacial compounds was observed. The combined effect of surface treatment and annealing-induced reaction is proposed as the mechanisms for low-resistance Ohmic contact formation.
Circadian hepatocyte clocks keep synchrony in the absence of a master pacemaker in the suprachiasmatic nucleus or other extrahepatic clocks

In this study, Sinturel et al. sought to show that the suprachiasmatic nucleus (SCN) synchronizes peripheral circadian oscillators. By using long-term bioluminescence recordings in freely moving mice, they show that the SCN is indeed required for maintaining synchrony between organs and that circadian oscillations persist in the livers of mice devoid of an SCN or oscillators in cells other than hepatocytes.
Put MY mask on first: Mothers’ reactions to prioritizing health behaviours as a function of self-compassion and fear of self-compassion

Self-compassion predicts mothers’ engagement in health behaviours yet some mothers fear self-compassion. We examined relationships between both self-compassion and fear of self-compassion with mothers’ reactions to prioritizing health behaviours. Mothers rated their self-compassion, fear of self-compassion, read a scenario about prioritizing health behaviours and rated adjectives describing themselves if they behaved as described in the scenario. Self-compassion was positively related to positive reactions to engaging in health behaviours in the midst of motherhood. Fear of self-compassion led to negative reactions. This research provides insight into why some mothers feel better about incorporating health behaviours into their lives than others.
Trends in food consumption by degree of processing and diet quality over 17 years: results from the Framingham Offspring Study

Abstract Ultraprocessed foods provide the majority of energy content in the American diet, yet little is known regarding consumption trends over time. We determined trends in diet processing level and diet quality from 1991 to 2008 within the prospective Framingham Offspring Cohort. Dietary intakes were collected by FFQ quadrennially 1991–2008 (total of four examinations). The analytical sample included 2893 adults with valid dietary data for ≥3 examinations (baseline mean age = 54 years). Based on the NOVA framework, we classified foods as: unprocessed/minimally processed foods; processed culinary ingredients (salt/sugar/fats/oils); and processed foods and ultraprocessed foods. We evaluated diet quality using the Dietary Guidelines for Americans Adherence Index (DGAI) 2010. Trends in consumption of foods within each processing level (servings/d) and diet quality over the four examinations were evaluated using mixed effects models with subject-specific random intercepts. Analyses were stratified by sex, BMI (<25 kg/m2, 25–29·9 kg/m2, ≥30 kg/m2) and smoking status. Over 17 years of follow-up, ultraprocessed food consumption decreased from 7·5 to 6·0 servings/d and minimally processed food consumption decreased from 11·9 to 11·3 servings/d (P trend < 0·001). Changes in intakes of processed foods, culinary ingredients and culinary preparations were minimal. Trends were similar by sex, BMI and smoking status. DGAI-2010 score increased from 60·1 to 61·5, P < 0·001. The current study uniquely describes trends in diet processing level in an ageing US population, highlighting the longstanding presence of ultraprocessed foods in the American diet. Given the poor nutritional quality of ultraprocessed foods, public health efforts should be designed to limit their consumption.
Long‐term in vitro expansion ensures increased yield of central memory T cells as perspective for manufacturing challenges

Adoptive T cell therapy (ATT) has revolutionized the treatment of cancer patients. A sufficient number of functional T cells are indispensable for ATT efficacy; however, several ATT dropouts have been reported due to T cell expansion failure or lack of T cell persistence in vivo. With the aim of providing ATT also to those patients experiencing insufficient T cell manufacturing via standard protocol, we evaluated if minimally manipulative prolongation of in vitro expansion (long‐term [LT] >3 weeks with IL‐7 and IL‐15 cytokines) could result in enhanced T cell yield with preserved T cell functionality. The extended expansion resulted in a 39‐fold increase of murine CD8+ T central memory cells (Tcm). LT expanded CD8+ and CD4+ Tcm cells retained a gene expression profile related to Tcm and T memory stem cells (Tscm). In vivo transfer of LT expanded Tcm revealed persistence and antitumor capacity. We confirmed our in vitro findings on human T cells, on healthy donors and diffuse large B cell lymphoma patients, undergoing salvage therapy. Our study demonstrates the feasibility of an extended T cell expansion as a practicable alternative for patients with insufficient numbers of T cells after the standard manufacturing process thereby increasing ATT accessibility.
Malaria and helminth co-infections in children living in endemic countries: A systematic review with meta-analysis

Background Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries. Methodology/Principal findings We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in endemic countries. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane’s Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger’s test (bias if p<0.1). Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence of Plasmodium-helminth co-infections of 17.7% (95% CI 12.7–23.2%). Summary estimates from 14 studies showed a lower odds of P. falciparum infection in children co-infected with Schistosoma spp (OR: 0.65; 95%CI: 0.37–1.16). Similar lower odds of P. falciparum infection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28–0.64). When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk of P. falciparum infection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03–1.65). A subset of 16 studies showed that the odds of anaemia were higher in children co-infected with Plasmodium and STH than in children with Plasmodium infection alone (OR = 1.20; 95% CI: 0.59–2.45), and were almost equal in children co-infected with Plasmodium-Schistosoma spp or Plasmodium infection alone (OR = 0.97, 95% CI: 0.30–3.14). Conclusions/Significance The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.
SIMULATION OF GRAVITY DOMINATED DNAPL INSTABILITIES IN SATURATED POROUS MEDUIM USING A PORE SCALE MODEL

Summary. In this study we present a pore-scale network model to simulate gravity dominated displacement of a wetting fluid (water) by a lower-viscosity DNAPL (trichloroethylene) in homogenous porous media. A typical geometric representation of the network model includes a regular cubic lattice structure with pore bodies corresponding to the vertices of the lattice, and pore throats connecting the pore bodies. Both size distributions of the pores bodies and pores throats are determined by a probabilistic approach that computes the distribution of the volume of the voids in packed spheres. The model is used to simulate laboratory experiments conducted on a glass column having a length of 68 cm and 10 cm of diameter, filled with medium quartz sand. The calculated arrival times of the DNAPL front are compared with those measured using optic fiber probes placed at 8 points of the control section of the experimental device. Furthermore, the mean pressure of TCE measured during the experiment at the column inlet section was compared to the transient pressure predicted by the pore-throat-model. Globally, the numerical results obtained were in good agreement with the measurements.
Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer

Purpose: PIK3CA mutations are common in breast cancer and promote tumor progression and treatment resistance. We conducted a phase I/II trial of alpelisib (α-specific PI3K inhibitor) plus nab-paclitaxel in patients with HER2-negative metastatic breast cancer (MBC). Patients and Methods: Eligible patients had HER2-negative MBC with any number of prior chemotherapies. Phase I was 3+3 dose-escalation design with three dose levels of alpelisib (250, 300, and 350 mg) daily plus nab-paclitaxel 100 mg/m2 administered on days 1, 8, and 15 every 28 days. Phase II was according to Simon's two-stage design. PIK3CA mutations in tumor/circulating tumor DNA (ctDNA) were assessed. Primary endpoints were recommended phase II dose (RP2D) and objective response rate (ORR). Additional endpoints included safety, pharmacokinetics, progression-free survival (PFS), and association of PIK3CA mutation with outcomes. Results: A total of 43 patients were enrolled (phase I, n = 13 and phase II, n = 30). A total of 84% had visceral disease and 84% had prior taxane. No dose-limiting toxicities occurred in phase I. RP2D was alpelisib 350 mg daily plus nab-paclitaxel 100 mg/m2 on days 1, 8, and 15. Hyperglycemia (grade 3, 26% and grade 4, 0%), neutropenia (grade 3, 23% and grade 4, 7%), diarrhea (grade 3, 5% and grade 4, 0%), and rash (grade 3, 7% and grade 4, 0%) were the most common adverse events. Among 42 evaluable patients, ORR was 59% (complete response, 7% and partial response, 52%), 21% of whom had response lasting >12 months; median PFS was 8.7 months. A total of 40% of patients demonstrated tumor and/or ctDNA PIK3CA mutation; patients with tumor/ctDNA mutation demonstrated better PFS compared with those without mutation (11.9 vs. 7.5 months; HR, 0.44; P = 0.027). Patients with normal metabolic status had longer PFS compared with prediabetic/diabetic patients (12 vs. 7.5 months; P = 0.014). No pharmacokinetics interactions were detected. Conclusions: The alpelisib plus nab-paclitaxel combination was well tolerated and shows encouraging efficacy, especially in patients with PIK3CA-mutated tumor/ctDNA. The impact of metabolic status on response to this combination merits further investigation.
Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients

Supplemental Digital Content is available in the text. Introduction and Aim: Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. Methods: We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. Result: From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I 2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). Conclusion: Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.
Dilatation of the Endolymphatic Space in the Ampulla of the Posterior Semicircular Canal: A New Clinical Finding Detected on Magnetic Resonance Imaging

Objectives: To investigate the clinical features of ears with dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal on magnetic resonance imaging. Study Design: Retrospective study. Setting: A university hospital. Methods: This study included 1,842 ears from 934 patients who underwent 3-T magnetic resonance imaging with gadolinium to investigate the presence of endolymphatic hydrops. Age, sex distribution, hearing thresholds on pure-tone audiometry, and vestibular symptoms were compared between cases of unilateral and bilateral dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal. Results: Forty-eight ears (17 men and 14 women; mean age 49.9 yrs) showed dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal. Age and the rate of chronic sensorineural hearing loss were significantly higher in the unilateral group (14 ears) than in the bilateral group (34 ears). The average hearing thresholds and rates of vestibular symptoms reported did not differ between unilateral and bilateral cases, but some patients showed positional nystagmus. Conclusions: Dilatation of the endolymphatic space in the ampulla was observed selectively in the posterior semicircular canal, though its pathogenesis was not clear. Such dilatation is not usually accompanied by vestibular endolymphatic hydrops, and it may be a cause of vertigo and dizziness.
A Systematic Review of Seizure-Freedom Rates in Patients With Benign Epilepsy of Childhood With Centrotemporal Spikes Receiving Antiepileptic Drugs

Objectives The objective of this study was to evaluate seizure remission rates in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) receiving antiepileptic drugs. Methods PubMed and Web of Science were searched for studies on pharmacotherapy in patients with BECTS using free search terms or Medical Subject Headings. Only studies that used seizure-freedom rates as an indicator for pharmaceutical efficacy were considered. Different antiepileptic drugs were compared using the Fisher exact test for seizure-freedom rates. Results A total of 19 studies were included, 6 of them being randomized controlled trials. The randomized controlled trials included a total of 308 patients and covered sulthiame (n = 52), topiramate (n = 45), levetiracetam (n = 43), oxcarbazepine (n = 31), carbamazepine (n = 68), and clobazam (n = 18) as well as placebo (n = 35) and untreated control groups (n = 16). Treatment success rates were significantly higher in those children treated with sulthiame, levetiracetam, and clobazam compared with the children treated with carbamazepine, oxcarbazepine, or topiramate. Conclusions The available literature suggests the use of sulthiame, levetiracetam, or clobazam as first-line agents for the treatment of BECTS.