Miracle-dz/UniFAR-FTUs huggingface dataset:
Hierarchical improvement of regional tissue oxygenation after packed red blood cell transfusion

Background It is well established that counter-regulation to hypoxia follows a hierarchical pattern, with brain-sparing in preference to peripheral tissues. In contrast, it is unknown if the same hierarchical sequence applies to recovery from hypoxia after correction of anemia with packed red blood cell transfusion (PRBCT). Objective To understand the chronology of cerebral and splanchnic tissue oxygenation resulting after correction of anemia by PRBCT in preterm infants using near-infrared spectroscopy (NIRS). Design Prospective cohort study. Setting Neonatal intensive care. Patients included Haemodynamically stable infants: <32 weeks gestation, <37weeks postmenstrual age, <1500 grams birth weight; and ≥120 mL/kg/day feeds tolerated. Intervention PRBCT at 15 mL/Kg over 4 hours. Main outcome measures Transfusion-associated changes were determined by comparing the 4-hour mean pre-transfusion cerebral and splanchnic fractional tissue oxygen extraction (FTOEc0; FTOEs0) with hourly means during (FTOEc1-4; FTOEs1-4) and for 24 hours after PRBCT completion (FTOEc5-28; FTOEs5-28). Results Of 30 enrolled infants, 14[46.7%] male; median[IQR] birth weight, 923[655–1064]g; gestation, 26.4[25.5–28.1]weeks; enrolment weight, 1549[1113–1882]g; and postmenstrual age, 33.6[32.4–35]weeks, 1 infant was excluded because of corrupted NIRS data. FTOEc significantly decreased during and for 24 hours after PRBCT (p < 0.001), indicating prompt improvement in cerebral oxygenation. In contrast, FTOEs showed no significant changes during and after PRBCT (p>0.05), indicating failure of improvement in splanchnic oxygenation. Conclusion Improvement in regional oxygenation after PRBCT follows the same hierarchical pattern with a prompt improvement of cerebral but not splanchnic tissue oxygenation. We hypothesise that this hierarchical recovery may indicate continued splanchnic hypoxia in the immediate post-transfusion period and vulnerability to transfusion-associated necrotizing enterocolitis (TANEC). Our study provides a possible mechanistic underpinning for TANEC and warrants future randomised controlled studies to stratify its prevention.
Treatments for relapsed-refractory diffuse large B-cell lymphoma: comparison of overall survival outcomes observed with four novel agents.

OBJECTIVE Tafasitamab, loncastuximab, tesirine, polatuzumab, and selinexor have been proposed for the treatment of relapsed/refractory B-cell lymphomas. We studied the patterns of overall survival (OS) for these four agents. PATIENTS AND METHODS: We reconstructed patient-level data from the published Kaplan-Meier OS graphs. For this purpose, we used an artificial intelligence technique (the Shiny method). Reconstructed survival curves were then subjected to standard statistics to perform between-treatment comparisons, and hazard ratios (HRs) and 95% confidence intervals (CI) were estimated. RESULTS Using tafasitamab plus lenalidomide as a common comparator, our analysis of OS yielded the following results: a) Polatuzumab vedotin vs. tafasitamab + lenalidomide: HR=1.60 (95%CI, 0.94-2.74, p=0.0831); b) Selinexor vs. tafasitamab + lenalidomide: HR=2.28 (95%CI, 1.54-3.38, p<0.001); c) Loncastuximab tesirine vs. tafasitamab + lenalidomide: HR=2.35 (95%CI, 1.55-3.56, p<0.001). All three values favored tafasitamab + lenalidomide. CONCLUSIONS These comparative OS results represent the original findings. Although these comparisons were indirect, our analysis offered a useful synthesis of the outcomes reported thus far for these four treatments.
Electrical conductivity of doped porous glasses as possible sensors for oxygen

Corresponding author: renata@vms.huji. ac.ilWe are proposing Rubpy complex incorporated in a number of porous sol–gel thin films asa sensor for oxygen. The principle is based on the following fact: triplet oxygen reacts withthe excited states of Rubpy resulting in decay of luminescence of the complex due to tripletquenching. The decrease of fluorescence is proportional to the amount of absorbed oxygen. Wediscuss here several sol–gel matrices with doped by deposited as thin films on ITOconducting glass. The absorption and emission spectra of the complex, and electrical conductivityof the doped films show how the fluorescence can be excited either by optical or electronic means.The decrease of fluorescence indicates the concentration of oxygen.Keywords: Rubpy complex, porous glasses, sensors for oxygen, fluorescence, electrical conductivity.
Novel polymeric phases proposed by cold-pressing SiC tubes

A detailed structural evolution behavior of SiC single-wall nanotubes (SiC SWNTs) under high-pressure is studied by using density functional theory. We proposed four new polymeric phases (hP4-SiC, hP48-SiC, oI32-SiC and oA40-SiC), which possess the high stability, outstanding electronic and mechanical properties. The hP4-SiC, hP48-SiC and oA40-SiC are indirect band gap semiconductors, while the oI32-SiC is direct band gap semiconductor. The exhibited suitable band gap (∼3.1 eV) allows hP4-SiC, hP48-SiC, oI32-SiC and oA40-SiC as the potential blue-laser diodes materials. The Si–C bond in four new structures is the strong covalent bond in sp3 hybridization, which results in their high stability and hardness. The exhibited high decomposition temperature and high hardness make them as the potential high temperature abrasive materials. The stacking way of different rings in structures and atomic arrangement configurations of C and Si atoms in rings induce the anisotropic stiffness of polymeric structures. The analysis of x-ray diffraction, Raman and infrared radiation spectra is performed for a guideline of their synthesis in experiment. These results would help to understand the structural evolution of SiC SWNTs under high pressure and contribute to develop the high hardness and temperature materials.
Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients.

OBJECTIVE The occurrence of side effects related to the use of combined oral contraceptives (COCs) - or even the fear of them - often affects patients' compliance and their quality of life. Such adverse effects include both physical and psychological alterations. Therapies based on COCs are related to lower levels of vitamins and minerals, including vitamins B, C and E, zinc, magnesium, and selenium. This review gathers scientific evidence about the effectiveness of the administration of specific micronutrients to address nutritional needs and recover adverse conditions. MATERIALS AND METHODS We reviewed literature searching through different databases (MEDLINE, Scopus, Google Scholar). We used different keywords, including micronutrients, COCs, side effects, B vitamins, vitamin C, vitamin E, vitamin D, zinc, magnesium, selenium and Centella Asiatica. We narrowed the search down to English literature, including both preclinical and clinical studies. The outcome of database search was to highlight beneficial effects of specific micronutrients on the evaluated side reactions. RESULTS Based on the collected evidence, dietary supplementations of specific micronutrients, whose depletion occurs during COC treatments, have significant beneficial effects. By acting on different aspects and pathways, such supplementation prevents and counteracts discomforts and side effects related to COC treatments. CONCLUSIONS Considering the wide use of OCs, taking appropriate dietary supplements could be an effective approach in clinical practice, tailoring therapies and improving both safety and tolerability.
Assessment of pesticide safety knowledge and practices in Vietnam: A cross-sectional study of smallholder farmers in the Mekong Delta

Abstract Over the past three decades, the Vietnamese Mekong Delta has experienced a significant increase in agricultural productivity, partly achieved through increased agrochemical use. To abate negative effects on human and environmental health, several national programs were launched to enhance safer pesticide use. This study aimed to assess the patterns and relationships of official sustainable agriculture educational programs, pesticide safety knowledge, and practices of smallholder farmers in the Mekong Delta. A cross-sectional survey was conducted with 400 smallholder farmers from three communes in Thoi Lai district (Can Tho province) from March to May 2020. Twenty-four questions on pesticide safety knowledge and practices were used to identify traits using latent class analysis. Adjusted generalized linear regression was used to assess determinants of pesticide safety knowledge and estimate associations of pesticide safety knowledge with pesticide practices. 96.2% of participants have used at least one WHO class II pesticide during the past year while the use of specific personal protective equipment was limited mainly due to unavailability (37.0%) or discomfort (83.0%). High education (Odds Ratio (OR), 95% Confidence Interval; 3.84, 1.70–9.45), exposure to official educational programs (1.87, 1.13–3.12), peer-to-peer knowledge exchange (3.58, 2.18–6.00), and learning from governmental extension services (2.31, 1.14–4.98) were positively associated with increased pesticide safety knowledge. Compared to poor practices, pesticide safety knowledge was increasingly positively associated with intermediate (1.65, 1.02–2.66) and good pesticide practices (8.96, 2.58–31.12). These findings highlight the importance of school education and educational programs, access to PPE, and addressing discomforts of PPE to improve the protection of farmers from pesticide exposures. Simultaneously, pesticide market authorization processes should be reconsidered to promote the authorization of less toxic products. Further in-depth studies on the nature of pesticides used, nonuse of personal protective equipment, and effectiveness of educational programs will further define leverage points for safer pesticide use.
Psychometric properties of the Short Warwick-Edinburgh Mental Well-Being Scale in a sample of Danish schoolchildren

Aim: The aims of this this study was to examine the psychometric properties, including internal consistency and construct validity, of the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) in a sample of Danish schoolchildren aged 10–16 years. Method: A total of 1155 schoolchildren (54% girls) aged 10–16 years (Mage=12 years, SD=1.3) responded to an electronic questionnaire as part of the Danish SELFCARE study. To examine the internal consistency and construct validity of the SWEMWBS, we performed descriptive statistics, reliability and correlation analyses in Stata as well as confirmatory factor analysis (CFA) in Mplus. Correlations between scores on the SWEMWBS and scores on scales from the Strengths and Difficulties Questionnaire (SDQ) were calculated using Spearman’s rank correlation coefficients. The analysis was conducted on the general study population and in subgroups divided by sex and class (age groups). Results: CFA confirmed SWEMWBS one-dimensional factor structure, and the model fit the data well (CFI=0.984, TLI=0.97, RMSEA=0.062 and SRMR=0.021). The scale showed satisfactory internal consistency (ɑ=0.78) and composite reliability (ω=0.82). In addition, the scale was shown to have acceptable construct validity. Thus, correlations between scores on the SWEMWBS and SDQ subscales were in line with expectations. Corresponding results were found for subgroups divided by sex and class (age groups). Conclusions: Our study indicates that the Danish translation of the SWEMWBS is valid for measuring well-being among Danish schoolchildren aged 10–16 years. This construct validation study is among the first to validate the SWEMWBS in younger populations.
Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S–specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19–vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1. 1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1. 1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1. 1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs. Description COVID-19 mRNA vaccines induce poor anti-Omicron mucosal immunity, but this immunity can be boosted with an intranasal immunization. Breathing stronger immunity with COVID-19 vaccines Many intramuscular SARS-CoV-2 mRNA–vaccinated people still experience breakthrough Omicron subvariant infection. Despite the Omicron subvariants’ immune evasion, T and B cells induced from the vaccine still provide some protection; thus, it is unclear why so many breakthrough infections occur. Here, Tang et al. looked in the blood and bronchoalveolar lavage (BAL) fluid of unvaccinated, COVID-19 convalescent, and SARS-CoV-2 mRNA–vaccinated people. Immune responses in the PBMCs were comparable between the two groups, but the mRNA vaccine did not induce Omicron BA.1–specific neutralizing antibodies and T cells in the lung. In a mouse model, boosting mRNA-vaccinated mice intranasally improved SARS-CoV-2 immunity in the lung. Thus, an intranasal vaccine boosting strategy will be critical to protect people against emerging variants of concern.
Alzheimer’s disease: a scoping review of biomarker research and development for effective disease diagnosis

ABSTRACT Introduction Alzheimer’s disease (AD) is regarded as the foremost reason for neurodegeneration that prominently affects the geriatric population. Characterized by extracellular accumulation of amyloid-beta (Aβ), intracellular aggregation of hyperphosphorylated tau (p-tau), and neuronal degeneration that causes impairment of memory and cognition. Amyloid/tau/neurodegeneration (ATN) classification is utilized for research purposes and involves amyloid, tau, and neuronal injury staging through MRI, PET scanning, and CSF protein concentration estimations. CSF sampling is invasive, and MRI and PET scanning requires sophisticated radiological facilities which limit its widespread diagnostic use. ATN classification lacks effectiveness in preclinical AD. Areas Covered This publication intends to collate and review the existing biomarker profile and the current research and development of a new arsenal of biomarkers for AD pathology from different biological samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments. Expert Opinion It is an accepted observation that AD-related pathological changes occur over a long period of time before the first symptoms are observed providing ample opportunity for detection of biological alterations in various biological samples that can aid in early diagnosis and modify treatment outcomes.
Genetic determinants associated with response to clozapine in schizophrenia: an umbrella review

Objective Clozapine response varies widely from person to person, which may be due to inter-individual genetic variability. This umbrella review aims to summarize the current evidence on associations between pharmacodynamic genes and response to clozapine treatment. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology, a systematic literature search was conducted in the PubMed and EMBASE databases from inception to November 2021 to identify systematic reviews and meta-analyses of studies that examined genetic determinants of clozapine response. The quality of the reviews was assessed with the AMSTAR-2 tool. Results From a total of 128 records, 10 studies representing nine systematic reviews and one meta-analysis met our inclusion criteria. The overall quality of the included studies was poor. All systematic reviews concluded that the results of primary studies were largely negative or conflicting. Most evidence was found for an association with clozapine response and rs6313 and rs6314 within HTR2A and rs1062613 within HTR3A in the serotonergic system. Conclusions Conclusive evidence for associations between genetic variants and clozapine response is still lacking. Hypothesis-generating genetic studies in large, well-characterized study populations are urgently needed to obtain more consistent and clinically informative results. Future studies may also include multi-omics approaches to identify novel genetic determinants associated with clozapine response.
Diaphragm Electromyography Versus Ultrasonography in the Prediction of Mechanical Ventilation Liberation Outcome

BACKGROUND: ICU-acquired diaphragm paresis occurs in about 25% of patients after prolonged mechanical ventilation. Diaphragm function can be evaluated via several approaches including monitoring of electrical activity of diaphragm (electromyography [EMG]) or ultrasound (US) measurements. We aimed to assess the usefulness of diaphragm EMG indices in predicting liberation outcome in comparison with diaphragm US measurements. METHODS: We included consecutive subjects invasively ventilated for > 48 h for acute respiratory failure and who were considered ready to undergo a spontaneous breathing trial (SBT). Exclusion criteria were age < 18 y, pregnancy, tracheostomy, or patients with confirmed neuromuscular diseases. To start the SBT, we set pressure support to 0 cm H2O and PEEP to 5 cm H2O. During the initial 5 min of SBT, mean values of Δ electrical activity of the diaphragm (ΔEAdi) (EAdi peak − EAdi minimal), tidal volume (VT), and breathing frequency were measured. Neuroventilatory efficiency was calculated as VT divided by ΔEAdi. Rapid shallow breathing index was calculated as breathing frequency divided by VT. US examination of the diaphragm and assessment of diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) were recorded 30 min after initiation of SBT. RESULTS: Twenty-four subjects were included; DTF predicted weaning failure with area under the curve 0.96 and P value < . 001 with sensitivity 100% and specificity 94% for the cutoff value ≤ 15%. DE for the cutoff ≤ 1.56 cm showed sensitivity 75% and specificity 69%, whereas ΔEAdi with cutoff value ≤ 4 μV showed sensitivity 25% and specificity 100%. Neuroventilatory efficiency with cutoff value ≤ 29 mL/μV showed sensitivity 50% and specificity 81%. All 3 parameters showed nonsignificant results with area under the curve 0.73, 0.56, and 0.62 and P values . 08, . 65, and . 34, respectively. CONCLUSIONS: Diaphragm EMG indices were inferior to diaphragm ultrasonography in prediction of mechanical ventilation liberation outcome.
Structure and thermodynamics of the CD2AP-SH3 domains and their interaction with ubiquitin

33 Biological context 33 Methods and results 34 Discussion and conclusions 41 Acknowledgements 41 References 42 Chapter 3 Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP 45 Abstract 47 Introduction 47 Results 49 Discussion 62 Materials and methods 66 Acknowledgements 69 References 70 Chapter 4 Accurate characterization of weak macromolecular interactions by titration of NMR residual dipolar couplings: application to the CD2AP SH3-C:ubiquitin complex 75 Abstract 77 Introduction 77 Theoretical aspects 79 Materials and methods 81 Results and discussion 83 Conclusions 96 Acknowledgements 96 References 97 Supporting information 101 Methods 101 Supplementary tables 105 Supplementary figures 107 References 113 Chapter 5 Distinct ubiquitin binding modes exhibited by the SH3 domains of CD2AP. Molecular determinants and functional implications 115 Abstract 117 Introduction 117 Experimental procedures 119 Results 122 Discussion 133 Acknowledgements 138 References 139117 Introduction 117 Experimental procedures 119 Results 122 Discussion 133 Acknowledgements 138 References 139 Chapter 6 Final Discussion 143 Chapter 7 Resumen y conclusiones/Summary and conclusions 155 Resumen y conclusiones 157 Summary and conclusions 160
Learning to Solve Soft-Constrained Vehicle Routing Problems with Lagrangian Relaxation

Vehicle Routing Problems (VRPs) in real-world applications often come with various constraints, therefore bring additional computational challenges to exact solution methods or heuristic search approaches. The recent idea to learn heuristic move patterns from sample data has become increasingly promising to reduce solution developing costs. However, using learning-based approaches to address more types of constrained VRP remains a challenge. The difficulty lies in controlling for constraint violations while searching for optimal solutions. To overcome this challenge, we propose a Reinforcement Learning based method to solve soft-constrained VRPs by incorporating the Lagrangian relaxation technique and using constrained policy optimization. We apply the method on three common types of VRPs, the Travelling Salesman Problem with Time Windows (TSPTW), the Capacitated VRP (CVRP) and the Capacitated VRP with Time Windows (CVRPTW), to show the generalizability of the proposed method. After comparing to existing RL-based methods and open-source heuristic solvers, we demonstrate its competitive performance in finding solutions with a good balance in travel distance, constraint violations and inference speed.
Improved mixing for the convex polygon triangulation flip walk

We prove that the well-studied triangulation flip walk on a convex point set mixes in time O(n^3 log^3 n), the first progress since McShine and Tetali's O(n^5 log n) bound in 1997. In the process we give lower and upper bounds of respectively Omega(1/(sqrt n log n)) and O(1/sqrt n) -- asymptotically tight up to an O(log n) factor -- for the expansion of the associahedron graph K_n. The upper bound recovers Molloy, Reed, and Steiger's Omega(n^{3/2}) bound on the mixing time of the walk. To obtain these results, we introduce a framework consisting of a set of sufficient conditions under which a given Markov chain mixes rapidly. This framework is a purely combinatorial analogue that in some circumstances gives better results than the projection-restriction technique of Jerrum, Son, Tetali, and Vigoda. In particular, in addition to the result for triangulations, we show quasipolynomial mixing for the k-angulation flip walk on a convex point set, for fixed k>= 4.