Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn’s Disease Intestinal Mucosa: Analysis From the CELEST Study

Abstract Background Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn’s disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST. Methods Seventy-four patients consented to this optional substudy. Ileal and colonic biopsies were collected during endoscopy at screening and week 12 or 16. RNA isolated from 226 samples was analyzed by RNAseq, with additional qPCR analysis. Additional biopsies from patients with Crohn's disease receiving anti-tumor necrosis factor (anti-TNF; n = 34) and healthy controls (n = 10) were used for qPCR. Single-cell RNAseq public profiles were used to evaluate treatment effects on specific cellular subsets, associations with endoscopic improvement, and indirect comparisons with the anti-TNF-treated cohort. Results In involved areas of mucosa with endoscopic remission after upadacitinib treatment, 1156 and 76 protein-coding genes were significantly regulated (false discovery rate < 0.05) at week 12/16 in colonic and ileal biopsies, respectively (60 overlapped), compared with baseline. Upadacitinib did not significantly affect transcriptomes of noninvolved intestinal areas. CELEST patients (mostly anti-TNF-refractory) showed baseline differences in gene expression compared with a separate cohort of biologic-naïve patients. Notably, upadacitinib reversed overexpression of inflammatory fibroblast and interferon-γ effector signature markers. Conclusions Upadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier: NCT02365649)
Image Processing of Conventional Computer Tomography Images for Segmentation of the Human Cochlea

Against the background of increasing numbers of indications for Cochlea implants (CIs), there is an increasing need for a CI outcome prediction tool to assist the process of deciding on the best possible treatment solution for each individual patient prior to intervention. The hearing outcome depends on several features in cochlear structure, the influence of which is not entirely known as yet. In preparation for surgical planning a preoperative CT scan is recorded. The overall goal is the feature extraction and prediction of the hearing outcome only based on this conventional CT data. Therefore, the aim of our research work for this paper is the preprocessing of the conventional CT data and a following segmentation of the human cochlea. The great challenge is the very small size of the cochlea in combination with a fairly bad resolution. For a better distinction between cochlea and surrounding tissue, the data has to be rotated in a way the typical cochlea shape is observable. Afterwards, a segmentation can be performed which enables a feature detection. We can show the effectiveness of our method compared to results in literature which were based on CT data with a much higher resolution. A further study with a much larger amount of data is planned.
Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors

Circadian rhythm is heritable, and paternal circadian disruption affects offspring health via stress hormones in the seminal fluid. Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes.
NAD+ homeostasis in human health and disease

Depletion of nicotinamide adenine dinucleotide (NAD+), a central redox cofactor and the substrate of key metabolic enzymes, is the causative factor of a number of inherited and acquired diseases in humans. Primary deficiencies of NAD+ homeostasis are the result of impaired biosynthesis, while secondary deficiencies can arise due to other factors affecting NAD+ homeostasis, such as increased NAD+ consumption or dietary deficiency of its vitamin B3 precursors. NAD+ depletion can manifest in a wide variety of pathological phenotypes, ranging from rare inherited defects, characterized by congenital malformations, retinal degeneration, and/or encephalopathy, to more common multifactorial, often age‐related, diseases. Here, we discuss NAD+ biochemistry and metabolism and provide an overview of the etiology and pathological consequences of alterations of the NAD+ metabolism in humans. Finally, we discuss the state of the art of the potential therapeutic implications of NAD+ repletion for boosting health as well as treating rare and common diseases, and the possibilities to achieve this by means of the different NAD+‐enhancing agents.
Prognostic value of prealbumin, N-terminal pro-B-type natriuretic peptide, heart type fatty acid binding protein, and cardiac troponin I in elderly patients for heart failure and poor outcomes

Objectives This study aimed to investigate the prognostic value of serum prealbumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), heart type fatty acid binding protein (hFABP), and cardiac troponin I (cTnI) for heart failure and cardiac death in elderly patients. Methods We studied 426 consecutive patients with New York Heart Association classes I to IV who were recruited between February 2014 and 2018. Cardiac mortality was the primary end point. Receiver operator characteristic curves were created to analyze predictive values. Results When prealbumin, NT-proBNP, hFABP, and cTnI were combined, the areas under the receiver operator characteristic curve reached 0.930 and 0.903 for heart failure and cardiac death, respectively. Prealbumin, NT-proBNP, hFABP, and cTnI levels changed differently during therapy in patients in different prognosis groups. These parameters improved in patients who did not develop major adverse cardiovascular events (MACEs), but were unchanged or deteriorated in patients with MACEs. Multivariate Cox regression analysis showed that these parameters were significant independent risk factors for MACEs and cardiac death. Conclusions Our study shows that serum prealbumin, NT-proBNP, hFABP, and cTnI levels are significant prognostic factors for elderly patients with poor cardiac function. These parameters are more accurate for prognosis when used together.
Self-consistent dielectric functions of materials: Toward accurate computation of Casimir–van der Waals forces

Accurate determination of dielectric function in the vacuum UV range enables the precise computation of Casimir-vdW forces. Research on theoretical calculation of Casimir–van der Waals (vdW) forces is characterized by a great number of inconsistencies and conflicting reports with widely differing results for many known materials, including water, contradicting experimental measurements. Despite its importance for conceptual advances in both fundamental aspects and practical applications, a universal framework for the accurate determination of Casimir-vdW forces is lacking. Here, we propose a universal theoretical platform for computing Casimir-vdW forces, accounting for the electronic dielectric constant, optical bandgap, density, and chemical composition. Using this methodology, we determine the dielectric function for 55 materials, over a wide range of photon energies, covering an extensive list of common metals, organic and inorganic semiconductors, and insulators. Internal consistency of the compiled data is validated using optical sum rules and Kramers-Kronig relations. We demonstrate that the calculated vdW forces based on these data match remarkably well with the experimentally measured vdW forces.
Arsenic speciation, the abundance of arsenite-oxidizing bacteria and microbial community structures in groundwater, surface water, and soil from a gold mine

Abstract The arsenic speciation, the abundance of arsenite-oxidizing bacteria, and microbial community structures in the groundwater, surface water, and soil from a gold mining area were explored using the PHREEQC model, cloning-ddPCR of the aioA gene, and high-throughput sequencing of the 16S rRNA gene, respectively. The analysis of the aioA gene showed that arsenite-oxidizing bacteria retrieved from groundwater, surface water, and soil were associated with Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria. In groundwaters from the mining area, there were relatively high ratios of aioA/total 16S rRNA gene copies and the dominance of As5+, which suggested the presence and activity of arsenite-oxidizing bacteria. Metagenomic analysis revealed that the majority of the soil and surface water microbiomes were Proteobacteria, Actinobacteria, Bacteroidetes, and Chloroflexi, whereas the groundwater microbiomes were dominated exclusively by Betaproteobacteria and Alphaproteobacteria. Geochemical factors influencing the microbial structure in the groundwater were As, residence time, and groundwater flowrate, while those showing a positive correlation to the microbial structure in the surface water were TOC, ORP, and DO. This study provides insights into the groundwater, surface water, and soil microbiomes from a gold mine and expands the current understanding of the diversity and abundance of arsenite-oxidizing bacteria, playing a vital role in global As cycling.
COVID-NURSE: evaluation of a fundamental nursing care protocol compared with care as usual on experience of care for noninvasively ventilated patients in hospital with the SARS-CoV-2 virus—protocol for a cluster randomised controlled trial

Introduction Patient experience of nursing care is correlated with safety, clinical effectiveness, care quality, treatment outcomes and service use. Effective nursing care includes actions to develop nurse–patient relationships and deliver physical and psychosocial care to patients. The high risk of transmission of the SARS-CoV-2 virus compromises nursing care. No evidence-based nursing guidelines exist for patients infected with SARS-CoV-2, leading to potential variations in patient experience, outcomes, quality and costs. Methods and analysis we aim to recruit 840 in-patient participants treated for infection with the SARS-CoV-2 virus from 14 UK hospitals, to a cluster randomised controlled trial, with embedded process and economic evaluations, of care as usual and a fundamental nursing care protocol addressing specific areas of physical, relational and psychosocial nursing care where potential variation may occur, compared with care as usual. Our coprimary outcomes are patient-reported experience (Quality from the Patients’ Perspective; Relational Aspects of Care Questionnaire); secondary outcomes include care quality (pressure injuries, falls, medication errors); functional ability (Barthell Index); treatment outcomes (WHO Clinical Progression Scale); depression Patient Health Questionnaire-2 (PHQ-2), anxiety General Anxiety Disorder-2 (GAD-2), health utility (EQ5D) and nurse-reported outcomes (Measure of Moral Distress for Health Care Professionals). For our primary analysis, we will use a standard generalised linear mixed-effect model adjusting for ethnicity of the patient sample and research intensity at cluster level. We will also undertake a planned subgroup analysis to compare the impact of patient-level ethnicity on our primary and secondary outcomes and will undertake process and economic evaluations. Ethics and dissemination Research governance and ethical approvals are from the UK National Health Service Health Research Authority Research Ethics Service. Dissemination will be open access through peer-reviewed scientific journals, study website, press and online media, including free online training materials on the Open University’s FutureLearn web platform. Trial registration number ISRCTN13177364; Pre-results.
Manipulating phloem transport affects wood formation but not local nonstructural carbon reserves in an evergreen conifer.

How variations in carbon supply affect wood formation remains poorly understood in particular in mature forest trees. To elucidate how carbon supply affects carbon allocation and wood formation, we attempted to manipulate carbon supply to the cambial region by phloem girdling and compression during the mid- and late-growing season and measured effects on structural development, CO2 efflux, and nonstructural carbon reserves in stems of mature white pines. Wood formation and stem CO2 efflux varied with location relative to treatment (i.e., above or below the restriction). We observed up to twice as many tracheids formed above versus below the treatment after the phloem transport manipulation, whereas cell-wall area decreased only slightly below the treatments, and cell size did not change relative to the control. Nonstructural carbon reserves in the xylem, needles, and roots were largely unaffected by the treatments. Our results suggest that low and high carbon supply affects wood formation, primarily through a strong effect on cell proliferation, and respiration, but local nonstructural carbon concentrations appear to be maintained homeostatically. This contrasts with reports of a decoupling of source activity and wood formation at the whole-tree or ecosystem level, highlighting the need to better understand organ-specific responses, within-tree feedbacks, as well as phenological and ontogenetic effects on sink-source dynamics. This article is protected by copyright. All rights reserved.
Maternal microbiome in preeclampsia pathophysiology and implications on offspring health

Preeclampsia is a devastating hypertensive pregnancy disorder that currently affects 2%–8% of pregnancies worldwide. It is associated with maternal and fetal mortality and morbidity and adverse health outcomes both in mom and offspring beyond pregnancy. The pathophysiology is not completely understood, and there are no approved therapies to specifically treat for the disease, with only few therapies approved to manage symptoms. Recent advances suggest that aberrations in the composition of the microbiome may play a role in the pathogenesis of various diseases including preeclampsia. The maternal and uteroplacental environments greatly influence the long‐term health outcomes of the offspring through developmental programming mechanisms. The current review summarizes recent developments on the role of the microbiome in adverse pregnancy outcomes with a focus on preeclampsia. It also discusses the potential role of the maternal microbiome in fetal programming; explores gut‐targeted therapeutics advancement and their implications in the treatment of preeclampsia.
Preliminary Qualitative Evaluation of Patient-Related Perspectives Related to the Implementation of a Predictive Algorithm in a Telehealth System for COPD

The aim of the present study was to evaluate patient-related perspectives from a five-week test of the implementation of a COPD prediction algorithm. The test intended to discover and avoid potential errors prior to testing the COPD prediction algorithm in a two-armed randomized controlled trial (RCT). The COPD prediction algorithm aims to predict exacerbations in COPD based on home measurements. In the present study, the algorithm was implemented in a currently deployed telehealth system. Five weeks after implementation, six interviews were conducted, including five interviews with patients with COPD and one interview with a specialized COPD nurse. The participants were overall satisfied with the telehealth system including the COPD prediction algorithm. However, technical issues must be addressed before the COPD prediction algorithm is ready to be tested in the RCT. Moreover, communication with the monitoring nurses should be clearer based on the COPD nurse's experiences. In conclusion, the participants were satisfied with the integration of the COPD prediction algorithm in the telehealth system. The identification of technical issues shows the importance of including a technical test period in a similar trial setup.
The Frequency of Intermittently Scanned Glucose and Diurnal Variation of Glycemic Metrics

Background: The relation between the frequency of intermittently scanned continuous glucose monitoring (isCGM) and diurnal variation of time in range (TIR) and time below range (TBR) is unknown. Method: A total of 163 persons with type 1 diabetes who used isCGM had glucose data for 60 days downloaded. Mean TIR and median TBR were calculated for 15-minute periods and presented for daytime and nighttime. The values for tertiles of scanning frequency were compared. Results: The 1st tertile (n = 53) of the population scanned <10 times; the 2nd tertile (n = 56) 10-13 times, and the 3rd tertile (n = 54) >13 per 24 hours. TIR (%, mean ± (SD)) increased significantly from the 1st to the 3rd scan tertile both during the day (43.8 ± 14.8, 52.0 ± 12.3, 62.1 ± 12.8) and the night (44.5 ± 17.3, 52.3 ± 18.5, 64.0 ± 13.9; P < .0001). In contrast, TBR (median, (IQR)) was not significantly associated with scan tertiles during daytime (3.5% (1.1-7.8), 4.4% (1.8-6.1), 3.5% (2.1-6.1); P = . 85) or nighttime (3.8% (1.4-13.7), 5.0% (1.6-9.6), 5.7% (3.6-10.9); P = . 24). In a multiple regression model, a 50% increase in 24-hour scanning frequency was associated with a 7.8 percentage point increase in TIR (95% CI, 5.6-10.0). Conclusions: Increased scanning frequency was associated with a higher TIR both during daytime and nighttime with no change in TBR.
COVID-19: The significance of platelets, mitochondria, vitamin D, serotonin and the gut microbiota.

We provide a brief review of the significance of platelets, mitochondria, vitamin D, serotonin and the gutmicrobiome in COVID-19. We hypothesize that hyperactive platelets and mitochondrial dysfunction, as well as low vitamin D level, gut dysbiosis and increased serum serotonin produced by enterochromaffin cells, may all represent important aspects in the pathophysiology of COVID-19.
Coagulation parameters may predict clinical outcomes in patients with septic acute kidney injury.

BACKGROUND Acute kidney injury (AKI) and coagulation disorders are common complications of sepsis that affect its prognosis. However, the relationship between coagulation function and the prognosis of septic AKI has not been fully elucidated. MATERIALS AND METHODS In this retrospective study, clinical data from patients with septic AKI admitted to the First Affiliated Hospital of Guangxi Medical University from June 2016 to March 2019 were analyzed. Based on clinical outcomes within 60 days, septic AKI patients were divided into a survival and non-survival group, and the survivors were divided into a recovered and non-recovered group depending on renal function. RESULTS A total of 338 septic AKI patients were enrolled and followed up; 86 patients died, and 124 patients' renal function did not recover. The all-cause mortality rate in the septic AKI group was higher than in the non-AKI group by 1 : 1 propensity score matching (25.4 vs. 18.9%). The recovery rate for renal function was 50.8% (128/252), and 228 patients (67.5%) had at least one abnormal coagulation index. Logistic analysis indicated that male sex, advanced age, multiple organ dysfunction syndrome, thrombocytopenia, and an increased international standardized ratio (INR) were independent risk factors for all-cause mortality in septic AKI. Concomitant heart disease and prolonged activated partial thrombin time (APTT) were independent risk factors for renal function non-recovery among survivors. Kaplan-Meier curves showed that the cumulative survival rate was lower, and the mean survival time was shorter, in the abnormal coagulation parameter group compared to the normal coagulation parameter group (all p < 0.05). CONCLUSION Many patients with septic AKI have a poor prognosis. Coagulation disorders, including thrombocytopenia, increased INR, and prolonged APTT might predict poor clinical outcomes in patients with septic AKI.
Early-stage bone regeneration of hyaluronic acid supplemented with porous 45s5 bioglass-derived granules: an injectable system

In the present study, an injectable bone substitute system which utilized porous bioglass (BG)-derived granules supplemented with hyaluronic acid (Hya), was evaluated. Hya plays ultimate role in wound healing, promoting cell motility. The BG were synthesized by a simple and low sintering temperature process without any foreign phase incorporation. Furthermore, the physical properties in the porous scaffold were optimized to investigate the in vitro and in vivo performance. The porous BG60 scaffolds system showed excellent bioactivity in an in vitro simulated body fluid test in which the ions dissolved from the composite materials influenced apatite growth, countered the acidic pH, and increased material degradation. In an in vitro study with pre-osteoblasts cells (MC3T3-E1), the porous scaffold supported cell adhesion and proliferation. A post-implantation study conducted in femoral defects showed implant degradation and surprisingly fast bone formation just after 2 weeks of implantation. Initial in vivo degradation of Hya promotes releasing ions which regulates the bone forming cells, clues to tissue repair, and regeneration. On the other hand it also prevent the scattering of BG granule after grafting at implant site. The faster dissolution of the porous BG scaffold increased the resorption of the composite material and hence, facilitated bone tissue regeneration. Our findings suggest that the porous BG scaffold could potentially be used as an injectable bone substitute for fast, early bone regeneration applications.