Miracle-dz/UniFAR-FTUs huggingface dataset:
The SARS-CoV-2 receptor and other key components of the Renin-Angiotensin-Aldosterone System related to COVID-19 are expressed in enterocytes in larval zebrafish

ABSTRACT People with underlying conditions, including hypertension, obesity, and diabetes, are especially susceptible to negative outcomes after infection with coronavirus SARS-CoV-2, which causes COVID-19. Hypertension and respiratory inflammation are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from rapidly dropping blood pressure via Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II, counteracting its chronic effects, and serves as the SARS-CoV-2 receptor. Ace, the coronavirus, and COVID-19 comorbidities all regulate Ace2, but we do not yet understand how. To exploit zebrafish (Danio rerio) to help understand the relationship of the RAAS to COVID-19, we must identify zebrafish orthologs and co-orthologs of human RAAS genes and understand their expression patterns. To achieve these goals, we conducted genomic and phylogenetic analyses and investigated single cell transcriptomes. Results showed that most human RAAS genes have one or more zebrafish orthologs or co-orthologs. Results identified a specific type of enterocyte as the specific site of expression of zebrafish orthologs of key RAAS components, including Ace, Ace2, Slc6a19 (SARS-CoV-2 co-receptor), and the Angiotensin-related peptide cleaving enzymes Anpep (receptor for the common cold coronavirus HCoV-229E), and Dpp4 (receptor for the Middle East Respiratory Syndrome virus, MERS-CoV). Results identified specific vascular cell subtypes expressing Ang II receptors, apelin, and apelin receptor genes. These results identify genes and cell types to exploit zebrafish as a disease model for understanding mechanisms of COVID-19. Summary: Genomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics shows that they act in a specialized intestinal cell type.
Studies on Reactions of 3‐Benzoyl‐4‐hydroxypyrido[3,2‐e]‐1,2‐thiazines with Primary Amines and N‐Methylhydrazine.

Reaction of the appropriate 3-benzoyl-4-hydroxypyrido[3,2-e]-1,2-thiazine-1,1-dioxides 2 bearing a methyl or a 3-(4-arylpiperazin- 1-yl)propyl group at the nitrogen atom of the thiazine ring with primary amines resulted in enamines of type (E)-3. The related products 8 were obtained by alkylation of 3-phenylpyrazolo[4,3-c]pyrido[3,2-e]-1,2-thiazine-5,5-dioxide 7 with the corresponding 1-aryl-4-(3-chloropropyl)piperazines 9. The structures ofthe new heterocycles 3 and 8, synthesized for pharmaceutical purposes, and of the model compounds 4-6, prepared for comparison of spectral properties, were proven through elemental, IR, 1 H NMR and, in some cases (3d, 8a), X-ray data.
What Are the Burden, Causes, and Costs of Early Hospital Readmissions After Kidney Transplantation?

Introduction: Kidney transplant recipients are at risk for complications resulting in early hospital readmission. This study sought to determine the incidences, risk factors, causes, and financial costs of early readmissions. Design: This single-centre cohort study included 1461 kidney recipients from 1 Jul 2004 to 31 Dec 2012, with at least 1-year follow-up. Early readmission was defined as hospitalization within 30 or 90-days postdischarge from transplant admission. Associations between various parameters and 30 and 90-days posttransplant were determined using multivariable Cox proportional hazards models. The hospital-associated costs of were assessed. Results: The rates of early readmission were 19.4% at 30 days and 26.8% at 90 days posttransplant. Mean cost per 30-day readmission was 11 606 CAD. Infectious complications were the most common reasons and resulted in the greatest cost burden. Factors associated with 30 and 90-days in multivariable models were recipient history of chronic lung disease (hazard ratio or HR 1.78 [95%CI: 1.14, 2.76] and HR 1.68 [1.14, 2.48], respectively), median time on dialysis (HR 1.07 [95% CI: 1.01, 1.13]and HR 1.06 [95% CI: 1.01, 1.11], respectively), being transplanted preemptively (HR 1.75 [95% CI: 1.07, 2.88] and HR 1.66 [95% CI: 1.07, 2.57], respectively), and having a transplant hospitalization lasting of and more than 11 days (HR 1.52 [95% CI: 1.01, 2.27] and HR 1.65 [95% CI: 1.16, 2.34], respectively). Discussion: Early hospital readmission after transplantation was common and costly. Strategies to reduce the burden of early hospital readmissions are needed for all patients.
Urinary Pharmacokinetics of 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol after Controlled Oral Δ9-Tetrahydrocannabinol Administration

vitally important for optimizing therapeutic usage and to determine the impact of positive tests on detection programs. In this study, gas chromatography-mass spectrometry (limit of quantitation = 2.5 ng/mL) was used to monitor the excretion of total 11-nor-9-carboxy-A%tetrahydrocannabinol (THCCOOH) in 4381 urine voids collected from seven participants throughout a controlled clinical study of multiple oral doses of THC. The National Institute on Drug Abuse Institutional Review Board approved the study and each participant provided informed consent. Seven participants received 0, 0.39, 0.47, 7.5, and 14.8 mg THC/day for five days in this double blind, placebo-controlled, randomized protocol conducted on a closed research ward. No significant differences (P_ 15 ng/mL. An average of only 2.9  1.6%, 2.5  2.7%, 1.5  1.4%, and 0.6  0.5% of the THC in the 0.39, 0.47, 7.5, and 14.8 rag/day doses, respectively, was excreted as THCCOOH in the urine over each 14-day dosing session. This study demonstrated that the terminal urinary elimination tl a of THCCOOH following oral administration was approximately two to three days for doses ranging from 0.39 to 14.8 mg/d. These data also demonstrate that the apparent urinary elimination t,/2 of THCCOOH prior to reaching a ng/mL concentration is significantly shorter than the terminal urinary
Basic Medical Training for Refugees via Collaborative Blended Learning: Quasi-Experimental Design

Background Globally, there is an excess of 68.5 million people who have been forced to leave their homes and seek sanctuary elsewhere because of poverty, persecution, conflict, violence, and human rights violations. Although international humanitarian responses usually focus on ensuring that the basic needs of these people are being met, there is growing attention on the role that development-oriented interventions can play in the longer term. Higher education in a refugee context is one such intervention that can equip refugees with the knowledge and skills they need to serve their communities and move forward. Objective This study aims to evaluate the outcomes and effectiveness of the University of Geneva InZone-Raft Basic Medical Training Course in the Kakuma refugee camp in Kenya compared with a previous incarnation of the same course in the Dadaab refugee camp in Kenya. Methods We used a quasi-experimental design to compare the posttest scores of both inequivalent student groups: control group (n=18) and intervention group (n=16). Factors that influenced refugee students’ knowledge acquisition, the amount of knowledge they acquired, and their academic outcomes were assessed, and the pedagogical evolution of the project is presented. Results We found that the Kakuma intervention course yielded better outcomes and was more effective in terms of learning than the Dadaab control course. Of the 16 students who took part in the intervention course, 10 (63%) completed the program successfully and received accreditation from the University of Geneva. We observed that they received new knowledge well and scored higher on all learning modalities than those in the control course. Comparison of written and oral examinations between the courses showed statistical significance for the intervention group in written and oral exams (two-tailed: P=.006 and P=.05; one-tailed: P=.003 and P=.03, respectively). The Kakuma course was not effective in addressing electricity and internet access problems, nor in reducing the challenge of tight deadlines in the syllabus. Pedagogical adjustments to the intervention course improved student involvement, with higher participation rates in quizzes (10/11, 91%), and overall satisfaction and learning. Conclusions The intervention group—with an improved mode of delivery, better contextualized content, and further interaction—reached a higher level of medical knowledge acquisition and developed more complex questions on medical topics than the control group. The positive outcome of this project shows that given the right resources and support, refugees can contribute to the improvement and development of health care in their communities. Nonetheless, a more focused effort is necessary to meet the educational needs of refugee learners and better understand their living conditions.
Dementia-friendly intervention for hospitalized older adults with cognitive impairments: results of the Italian Dementia-Friendly Hospital Trial (IDENTITÀ)

Abstract Objective: To evaluate whether a short training focused on improving dementia care practices of the hospital staff was able to counteract functional loss and to decrease negative outcomes at discharge among hospitalized older adults with cognitive impairment. Method: Sixty-eight hospitalized participants aged 65 and over with cognitive impairment were included in the study, allocated in the control group (n = 34) and intervention group (n = 34). The intervention consisted of a short training of the hospital staff aimed at improving the management of patients with cognitive impairment. Participants were evaluated within 48 h of hospital admission and at discharge using a battery of tests including Barthel Index, Mini-Mental State Examination, and Hospital Anxiety and Depression Scale. Results: The intervention group demonstrated shorter hospital length of stay and a maintenance of the functional status at discharge compared to the control group. We observed no differences in cognitive ability between the two groups, and a trend towards a decrease of anxious symptoms in the intervention group compared to the control group. Conclusion: The results suggest that an intervention, focused on improving dementia care practices in healthcare staff, has the potential to improve the outcomes for hospitalized older adults with cognitive impairment.
miRNA-independent function of long noncoding pri-miRNA loci

Significance The human genome contains many thousands of genes that produce a large diversity of long noncoding RNAs (lncRNAs). Some lncRNA genes produce microRNAs (miRNAs), which are regulators of protein expression. It has been unclear whether lncRNA genes that produce miRNAs, termed lnc-pri-miRNAs, have important function independent of their miRNAs. We find multiple lnc-pri-miRNA genes that regulate cell proliferation even when miRNA production machinery is knocked down. lnc-pri-miRNA LOC646329 produces miR-29a/b1, and the function of LOC646329 in cell proliferation can be genetically and phenotypically separated from its cognate miRNAs. The miRNA-independent function of LOC646329 and other lnc-pri-miRNAs relates to their activation of genes in physical proximity. These results shed light on the function and intermingled complexity of the noncoding genome. Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1–independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms.
Event-Triggered Resilient L∞ Control for Markov Jump Systems Subject to Denial-of-Service Jamming Attacks

In this article, the event-triggered resilient $\mathcal {L}_{\infty }$ control problem is concerned for the Markov jump systems in the presence of denial-of-service (DoS) jamming attacks. First, a fixed lower bound-based event-triggering scheme (ETS) is presented in order to avoid the Zeno problem caused by exogenous disturbance. Second, when DoS jamming attacks are involved, the transmitted data are blocked and the old control input is kept by using the zero-order holder (ZOH). On the basis of this process, the effect of DoS attacks on ETS is further discussed. Next, by utilizing the state-feedback controller and multiple Lyapunov functions method, some criteria incorporating the restriction of DoS jamming attacks are proposed to guarantee the $\mathcal {L}_{\infty }$ control performance of the event-triggered Markov closed-loop jump system. In particular, the bounded transition rates rather than the exact ones are taken into account. That is appropriate for the practical environment in which transition rates of the Markov process are difficult to measure accurately. Correspondingly, some criteria are proposed to obtain state-feedback gains and event-triggering parameters simultaneously. Finally, we provide two examples to show the effectiveness of the proposed method.
Improved CO 2 separation performance of Matrimid®5218 membrane by addition of low molecular weight polyethylene glycol

Polyethylene glycols have received worldwide attention as a highly permeable CO 2 ‐philic polymer in carbon dioxide separation applications. In this study, we investigated the influence of a low molecular weight polyethylene glycol (PEG 200) on physicochemical, morphological, and gas separation properties of Matrimid®5218 as a novel polymer blend. Both symmetric and asymmetric Matrimid flat sheet membranes with 0–20 wt. % PEG were prepared via a dense film‐casting method. The miscibility of blends at low PEG concentrations (3–5 wt.%) was confirmed by differential scanning calorimetry (DSC) and polarized light microscopy (PLM). Moreover, the blends were partially miscible at higher PEG concentrations (10–20 wt.%). Matrimid/PEG molecular interactions were further studied by FTIR and XRD analysis. SEM images indicated an impressive influence of PEG on the symmetric structure of Matrimid membrane. An asymmetric structure with a dense thin skin layer and a highly porous sub‐layer was observed for the blends containing 10–20 wt. % PEG. The CO 2 permeability and CO 2 /CH 4 selectivity of the best‐yield CO 2 ‐selective blend membrane (Matrimid/PEG (95:5)) incvreased about 25% (from 7.68 to 9.62 Barrer) and 15% (from 35 to 40) compared to pure Matrimid, respectively. Furthermore studying the plasticization pressures of the membranes revealed that the more PEG content in blend the less the plasticization pressure obtained. © 2015 Society of Chemical Industry and John Wiley & Sons, Ltd
Associations Between Elevated Systolic Blood Pressure and Outcomes in Critically Ill Patients: A Retrospective Cohort Study and Propensity Analysis

Supplemental Digital Content is available in the text ABSTRACT Introduction: Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. Methods: This study was a retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC) III database, which includes more than 1,000,000 SBP records from 12,820 patients. Associations of cumulative times at four SBP ranges (<100 mm Hg, 100–120 mm Hg, 120–140 mm Hg, and ≥140 mm Hg) with mortality (12-, 3-, 1-month mortality and in-hospital mortality) were evaluated. Restricted cubic splines and multivariable Cox regression models were employed to assess associations between mortality and cumulative times at SBP levels (4 levels: <2, 2–12, 12–36, and ≥36 h) over 72 h of ICU admission. Additionally, 120 mm Hg to 140 mm Hg was subdivided into <12 h (Group L) and ≥12 h (Group M) subsets and subjected to propensity-score matching and subgroup analyses. Results: At 120 mm Hg to 140 mm Hg, level-4 SBP was associated with lower adjusted risks of mortality at 12 months (OR, 0.71; CI, 0.61–0.81), 3 months (OR, 0.72; CI, 0.61–0.85), and 1 month (OR, 0.61; CI, 0.48–0.79) and in the hospital (OR, 0.71; CI, 0.58–0.88) than level-1 SBP. The cumulative times at the other 3 SBP ranges (<100 mm Hg, 100–120 mm Hg, and ≥140 mm Hg) were not independent risk predictors of prognosis. Furthermore, Group M had lower 12-month mortality than Group L, which remained in the propensity-score matched and subgroup analyses. Conclusions: SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.
Maternal First-Trimester Cow-Milk Intake Is Positively Associated with Childhood General and Abdominal Visceral Fat Mass and Lean Mass but Not with Other Cardiometabolic Risk Factors at the Age of 10 Years

ABSTRACT Background Higher maternal cow-milk intake during pregnancy is associated with higher fetal growth measures and higher birth weight. Objective The aim of this study was to assess the associations of maternal milk intake during pregnancy with body fat measures and cardiometabolic risk factors at the age of 10 y. Methods In a population-based cohort of Dutch mothers and their children (n = 2466) followed from early pregnancy onwards, we assessed maternal first-trimester milk intake (milk and milk drinks) by food-frequency questionnaire. Maternal milk intake was categorized into 0–0.9, 1–1.9, 2–2.9, 3–3.9, 4–4.9, and ≥5 glasses/d, with 1 glass equivalent to 150 mL milk. For children at the age of 10 y, we calculated BMI and obtained detailed measures of body and organ fat by DXA and MRI. We also measured blood pressure and lipid, insulin, and glucose concentrations. Data were analyzed using linear and logistic regression models. Results Compared with children whose mothers consumed 0–0.9 glass of milk/d during their pregnancy, those whose mothers consumed ≥5 glasses of milk/d had a 0.29 SD (95% CI: 0.10, 0.48) higher BMI, 0.27 SD (95% CI: 0.08, 0.47) higher fat mass, 0.26 SD (95% CI: 0.07, 0.46) higher lean mass, 0.30 SD (95% CI: 0.09, 0.50) higher android-to-gynoid fat mass ratio and 0.38 SD (95% CI: 0.09, 0.67) higher abdominal visceral fat mass. After correction for multiple comparisons, groups of maternal milk intake were not associated with pericardial fat mass index, liver fat fraction, blood pressure, or lipid, insulin, or glucose concentrations (P values >0.0125). Conclusions Our results suggest that maternal first-trimester milk intake is positively associated with childhood general and abdominal visceral fat mass and lean mass, but not with other cardiometabolic risk factors.
Personalized collection of plasma from healthy donors: A randomized controlled trial of a novel technology‐enabled nomogram

Source plasma is essential to support the growing demand for plasma‐derived medicinal products. Supply is short, with donor availability further limited by the coronavirus disease 2019 (COVID‐19) pandemic. This study examined whether a novel, personalized, technology‐based nomogram was noninferior with regard to significant hypotensive adverse events (AEs) in healthy donors.
Becoming the temporary surgeon: A grounded theory examination of anaesthetists performing emergency front of neck access in inter-disciplinary simulation-based training

The time-critical ‘can’t intubate, can’t oxygenate’ [CICO] emergency post-induction of anaesthesia is rare, but one which, should it occur, requires Anaesthetists to perform rapid emergency front of neck access [FONA] to the trachea, restoring oxygenation, and preventing death or brain hypoxia. The UK Difficult Airway Society [DAS] has directed all Anaesthetists to be trained with surgical cricothyroidotomy [SCT] as the primary emergency FONA method, sometimes referred to as ‘Cric’ as a shorthand. We present a longitudinal analysis using a classical approach to Grounded Theory methodology of ten Specialist Trainee Anaesthetists’ data during a 6-month training programme delivered jointly by Anaesthetists and Surgeons. We identified with a critical realist ontology and an objectivist epistemology meaning data interpretation was driven by participants’ narratives and accepted as true accounts of their experience. Our theory comprises three themes: ‘Identity as an Anaesthetist’; ‘The Role of a Temporary Surgeon’; and ‘Training to Reconcile Identities’, whereby training facilitated the psychological transition from a ‘bloodless Doctor’ (Anaesthetist) to becoming a ‘temporary Surgeon’. The training programme enabled Specialist Trainees to move between the role of control and responsibility (Identity as an Anaesthetist), through self-described ‘failure’ and into a role of uncertainty about one’s own confidence and competence (The Role of a Temporary Surgeon), and then return to the Anaesthetist’s role once the airway had been established. Understanding the complexity of an intervention and providing a better insight into the training needs of Anaesthetic trainees, via a Grounded Theory approach, allows us to evaluate training programmes against the recognised technical and non-technical needs of those being trained.
Natural Glycoforms of Human Interleukin 6 Show Atypical Plasma Clearance

Abstract A library of glycoforms of human interleukin 6 (IL‐6) comprising complex and mannosidic N‐glycans was generated by semisynthesis. The three segments were connected by sequential native chemical ligation followed by two‐step refolding. The central glycopeptide segments were assembled by pseudoproline‐assisted Lansbury aspartylation and subsequent enzymatic elongation of complex N‐glycans. Nine IL‐6 glycoforms were synthesized, seven of which were evaluated for in vivo plasma clearance in rats and compared to non‐glycosylated recombinant IL‐6 from E. coli. Each IL‐6 glycoform was tested in three animals and reproducibly showed individual serum clearances depending on the structure of the N‐glycan. The clearance rates were atypical, since the 2,6‐sialylated glycoforms of IL‐6 cleared faster than the corresponding asialo IL‐6 with terminal galactoses. Compared to non‐glycosylated IL‐6 the plasma clearance of IL‐6 glycoforms was delayed in the presence of larger and multibranched N‐glycans in most cases