Miracle-dz/UniFAR-FTUs huggingface dataset:
OP-ICVA210086 1..5

OBJECTIVES: Treatment of severe acute respiratory distress syndrome (ARDS) induced by severe acute respiratory syndrome coronavirus 2 has been heavily debated. Our goal was to describe our findings in patients with severe ARDS due to severe coronavirus disease 2019 (sCOVID-19) treated with venovenous extracorporeal membrane oxygenation (vv-ECMO). METHODS: We retrospectively examined all patients treated with vv-ECMO for severe ARDS due to acute respiratory syndrome coronavirus 2. RESULTS: In total, 13 patients were treated with vv-ECMO in our medical centre. The mean patient age was 48.1 years. Most patients were obese (69%) and male (85%). All patients were mechanically ventilated before ECMO. The mean time from intubation to proning was 16.6 h; the time from start of prone therapy to vv-ECMO implantation was 155.1 h. The mean total ECMO run time was 358 h. Significant reduction of positive end-expiratory pressure (P = 0.02), peak pressure (P = 0.001) and minute volume (P = 0.03) could be achieved after implantation of vv-ECMO. All patients showed an inflammatory response. Overall mortality was 30.7%: 1 patient died of mesenteric ischaemia; 3 patients died of multiple organ failure. A worse prognosis was seen in patients with highly elevated concentrations of interleukin-6. Presented at the 34th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 8–10 October 2020. M EC H A N IC A L C IR C U LA TO R Y SU P P O R T VC The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Interactive Cardiovascular and Thoracic Surgery (2021) 1–5 ORIGINAL ARTICLE doi:10.1093/icvts/ivab087 CONCLUSIONS: The use of vv-ECMO in patients with sCOVID-19-induced ARDS is safe and associated with improved respiratory ventilation settings. The rate of immune system involvement plays a pivotal role in the development and outcome of sCOVID-19.
Incidence and risk factors for urinary tract infections in the first year after renal transplantation

Background The most common infections among renal transplant patients are urinary tract infections (UTI). Our main objective in this study is to determine the incidence of UTIs in patients who have undergone renal transplantation in our hospital, to identify the causative microbiological agents, risk factors and determine the effects of UTI on short-term graft survival. Methods Urinary tract infections, which developed within the first year of renal transplantation, were investigated. Patients were compared regarding demographic, clinical, laboratory characteristics and graft survival. Results 102 patients were included in our study. Fifty-three patients (53%) were male and 49 (48%) were female. Sixty-seven urinary tract infection attacks in 21 patients (20.5%) were recorded. Age (p = 0.004; 95% Confidence Interval [CI]: 1.032–1.184), longer indwelling urinary catheter stay time (p = 0.039; 95% Confidence Interval [CI]: 1.013–1.661) and urologic complications (p = 0.006; 95% Confidence Interval [CI]: 0.001–0.320) were found as risk factors for UTI development in the first year of transplantation. Escherichia coli and Klebsiella pneumoniae were the most frequently isolated microorganisms. Of these bacteria, 63.2% were found to be extended spectrum beta lactamase (ESBL) positive. Multidrug resistant microorganisms (MDROs) were more frequent in male patients (32 episodes in males vs. 14 episodes in females, p = <0.001). UTI had no negative impact on short-term graft survival. Conclusion Our study results represent the high incidence of UTI with MDROs in KT recipients. Infection control methods should be applied even more vigorously especially in male transplant patients since a higher incidence of UTI caused by resistant microorganisms was reported in male patients.
Integrative analysis reveals unique structural and functional features of the Smc5/6 complex

Significance Structural maintenance of chromosomes (SMC) complexes are essential for chromosome organization and functions. Within this family of complexes, the Smc5/6 complex has unique roles in regulating DNA replication and repair; however, our understanding of its structural organization is limited. Our integrative study presented here reveals several distinct features of the Smc5/6 complex. Unlike other SMCs, the long filamentous region of Smc5/6 does not fold back; rather, it associates with unique, coevolved subunits of the complex, including the Nse2 SUMO ligase and the Nse5/6 subcomplex. We also present a cryoelectron microscopy structure of the Nse5/6 subcomplex and evidence for its involvement in Nse2-mediated sumoylation. Our findings thus provide insights into Smc5/6 structural anatomy and functions. Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for the distinct functions of Smc5/6 is poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 holo-complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that the Smc5/6 complex possesses several unique features, while sharing some architectural characteristics with other SMC complexes. In contrast to arm-folded structures of cohesin and condensin, Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5/Nse6 subcomplex, with the latter also serving as a linchpin connecting distal parts of the complex. Our 3.0-Å resolution cryoelectron microscopy structure of the Nse5/Nse6 core further reveals a clasped-hand topology and a dimeric interface important for cell growth. Finally, we provide evidence that Nse5/Nse6 uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative study identifies distinct structural features of the Smc5/6 complex and functional cooperation among its coevolved unique subunits.
Effects of High-Fat Diet on Carcinogen-Induced Pancreatic Cancer and Intestinal Microbiota in C57BL/6 Wild-Type Mice

Objectives High-fat diet has been considered a risk factor for the development of pancreatic cancer. It is also shown to significantly impact composition and dysbiosis of gut microbiota in both humans and animals. However, there is little information on the effect of high-fat diet on the development of pancreatic cancer or upon the gut microbiota of patients with pancreatic cancer in humans or animal models. Methods In this study, the effect of high-fat diet on cancer pathology and the gut microbiota was investigated by a carcinogen-induced pancreatic cancer mouse model. Results Compared with carcinogen alone, mice with high-fat diet and carcinogen showed more obvious pathological changes in pancreatic tissue; increased levels of proinflammatory cytokine tumor necrosis factor-α, interleukin-6, interleukin-10, and carbohydrate antigen 242; and increased expression of cancer-associated biomarkers mucin-4 and claudin-4 in pancreatic tissue. Moreover, there is a significant change in the gut microbiota between the carcinogen group and the carcinogen with high-fat diet group. We identified that Johnsonella ignava especially existed in the carcinogen with high-fat diet group, which may contribute to pancreatic cancer development. Conclusions Our results revealed that high-fat diet changed the composition of the gut microbiota and was involved in carcinogen-induced pancreatic cancer progression.
Psychometric properties of the Child Eating Behavior Questionnaire (CEBQ) in school age children with overweight and obesity: A proposed three‐factor structure

Obesity in youth is a significant public health concern, with eating behaviors being a major contributor. The Child Eating Behavior Questionnaire (CEBQ) was developed to evaluate the appetitive characteristics of young children, across a myriad of eating domains. Despite the breadth of its use, the psychometric properties of the measure in children with overweight/obesity (OW/OB), particularly treatment seeking youth, remains largely unexplored.
STUDYING STRUCTURAL, OPTICAL, ELECTRICAL, AND SENSING PROPERTIES OF NANOCRYSTALLINE SnO2:Cu FILMS PREPARED BY SOL–GEL METHOD FOR CO GAS SENSOR APPLICATION AT LOW TEMPERATURE

Nanocrystalline SnO2 and SnO2:Cu thin films derived from SnCl2⋅2H2O precursors have been prepared on glass substrates using sol–gel dip-coating technique. The deposited film was 300±20nm thick and the films were annealed in air at 500∘C for 1h. Structural, optical and sensing properties of the films were studied under different preparation conditions, such as Cu-doping concentration of 2%, 4% and 6wt. %. X-ray diffraction studies show the polycrystalline nature with tetragonal rutile structure of SnO2 and Cu:SnO2 thin films. The films have highly preferred orientation along (110). The crystallite size of the prepared samples reduced with increasing Cu-doping concentrations and the addition of Cu as dopants changed the structural properties of the thin films. Surface morphology was determined through scanning electron microscopy and atomic force microscopy. Results show that the particle size decreased as doping concentration increased. The films have moderate optical transmission (up to 82.4% at 800nm), and the transmittance, absorption coefficient and energy gap at different Cu-doping concentration were measured and calculated. Results show that Cu-doping decreased the transmittance and energy gap whereas it increased the absorption coefficient. Two peaks were noted with Cu-doping concentration of 0–6wt. %; the first peak was positioned exactly at 320nm ultraviolet emission and the second was positioned at 430–480nm. Moreover, emission bands were noticed in the photoluminescence spectra of Cu:SnO2. The electrical properties of SnO2 films include DC electrical conductivity, showing that the films have two activation energies, namely, Ea1 and Ea2, which increase as Cu-doping concentration increases. Cudoped nanocrystalline SnO2 gas-sensing material has better sensitivity to CO gas compared with pure SnO2.
Inhibition of CDK4/6 promotes CD8 T-cell memory formation.

CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8 T cells during early stages of activation. Mice receiving tumor-specific CD8 T cells treated with CDK4/6 inhibitors displayed increased T cell persistence and immunologic memory. CDK4/6 inhibition upregulated Mxd4, a negative regulator of Myc, in both mouse and human CD8 T cells. Silencing of Mxd4 or Myc in mouse CD8 T cells demonstrated the importance of this axis for memory formation. We used single cell transcriptional profiling and TCR clonotype tracking to evaluate recently activated human CD8 T cells in breast cancer patients before and during treatment with either palbociclib or abemaciclib. CDK4/6 inhibitor therapy in humans increases the frequency of CD8 memory precursors and downregulates their expression of MYC target genes, suggesting that CDK4/6 inhibitors in cancer patients may augment long-term protective immunity.
The Impact of Maternal Preeclampsia and Hyperglycemia on the Cardiovascular Health of the Offspring: A Systematic Review and Meta-Analysis

Abstract Objectives The objective of this review was to assess the impact of maternal preeclampsia or hyperglycemia on the body composition and cardiovascular health in the offspring. Study Design We conducted a systematic review utilizing PubMed, EBSCO, CINAHLPlus, Cochrane Library, and Web of Science to include all studies assessing the impact of preeclampsia/eclampsia and/or gestational/pregestational diabetes mellitus on the health of the offspring (children <10 years of age). The health measures included anthropometry, cardiac dimensions and function, and vascular function. We performed a meta-analysis using Review Manager software and computed net risk ratio (RR) with 95% confidence interval (CI) for dichotomous data and mean difference (MD) with 95% CI for continuous data. Results There were 6,376 studies in total, of which 45 were included in the review and 40 in the meta-analysis. The results demonstrated higher birth weight (MD: 0.12 kg; 95% CI: 0.06–0.18) and systolic and diastolic blood pressure (BP; MD: 5.98 mmHg; 95% CI: 5.64–6.32 and MD: 3.27 mmHg; 95% CI: 0.65–5.89, respectively) in the offspring of mothers with gestational diabetes compared to controls. In contrast, the offspring of mothers with preeclampsia had lower birth weight (MD: −0.41 kg; 95% CI: −0.7 to −0.11); however, they had increased systolic (MD: 2.2 mmHg; 95% CI: 1.28–3.12) and diastolic BP (MD: 1.41 mmHg; 95% CI: 0.3–2.52) compared to controls. There is lack of data to conduct a meta-analysis of cardiac morphology, functional, and vascular imaging parameters. Conclusion These findings suggest that the in-utero milieu can have a permanent impact on the body composition and vascular health of the offspring. Future work warrants multicenter prospective studies to understand the mechanism and the actual effect of exposure to maternal hyperglycemia and high BP on the cardiovascular health of the offspring and long-term outcomes. Key Points Adverse in-utero exposures may have an impact on cardiovascular risk in children. Maternal hyperglycemia/preeclampsia lead to changes in birthweight and BP. Limited echocardiographic and vascular imaging data in these cohorts necessitates future work.
Myelodysplastic syndrome and immunotherapy novel to next in-line treatments

ABSTRACT Patients with Myelodysplastic syndromes (MDS) have few therapy options for sustainable responses in the frontline setting, and even less after hypomethylating agent (HMA) failure in relapsed and refractory setting. The only potential cure is an allogeneic hematopoietic stem cell transplant which is an unrealistic option for the majority of MDS patients. Immunotherapy with checkpoint inhibition, CAR-T cells, and vaccine therapy few have shown promise in a variety cancer and have now been tested in patients with MDS. Most trials have focused on AML patients and included small numbers of MDS patients. Until now, a dedicated review of immunotherapy outcomes in MDS patients has been lacking. Thus, herein we review outcomes of MDS patients after immunotherapies on a variety of clinical trials reported to date.
A Single Supratherapeutic Dose of Atogepant Does Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized, Single‐Dose, Phase 1 Crossover Trial

Atogepant is a selective, oral calcitonin gene–related peptide receptor antagonist in development for preventive treatment of migraine. This randomized, double‐blind, phase 1 crossover study evaluated the cardiac repolarization effect of a single supratherapeutic (300 mg) atogepant dose vs placebo in healthy adults. Moxifloxacin 400 mg was the open‐label active control. The primary end point was a change from baseline in Fridericia‐corrected QT intervals (ΔQTcF). Sixty participants were randomized to atogepant 300 mg, placebo, and moxifloxacin; 59 (98.3%) completed all interventions. Assay sensitivity was confirmed: lower 90% confidence interval limit for QTcF interval change from baseline (ΔΔQTcF) for moxifloxacin was >5 millisecond vs placebo at prespecified 2‐, 3‐, and 4‐hour time points. Following single‐dose atogepant 300 mg, mean atogepant ΔΔQTcF and upper 90% confidence interval limits were lower than the 10‐millisecond threshold at all time points. Atogepant mean peak plasma concentration was 3197 ng/mL, area under the concentration‐time curve from time 0 to time t was 16 640 ng • h/mL, area under the concentration‐time curve from time 0 to 24 hours was 16 607 ng • h/mL, and median time to peak plasma concentration was 2.1 hours. The incidence of adverse events was low; no serious adverse events or elevations of liver enzymes were reported. Overall, a single supratherapeutic dose of atogepant was safe and did not impact cardiac repolarization in healthy participants.
HIF‐1α is necessary for activation and tumour‐promotion effect of cancer‐associated fibroblasts in lung cancer

Cancer‐associated fibroblasts (CAFs) activation is crucial for the establishment of a tumour promoting microenvironment, but our understanding of CAFs activation is still limited. In this study, we found that hypoxia‐inducible factor‐1α (HIF‐1α) was highly expressed in CAFs of human lung cancer tissues and mouse spontaneous lung tumour. Accordingly, enhancing the expression of HIF‐1α in fibroblasts via hypoxia induced the conversion of normal fibroblasts into CAFs. HIF‐1α‐specific inhibitor or HIF‐1α knockout (KO) significantly attenuated CAFs activation, which was manifested by the decreased expression of COL1A2 and α‐SMA. In vivo, during tumour formation, the expression of Ki‐67 and proliferating cell nuclear antigen (PCNA) in the tumour tissue with HIF‐1α KO fibroblasts was significantly lower than that of normal fibroblasts. Moreover, HIF‐1α in fibroblasts could activate the NF‐κB signalling pathway and enhance a subsequent secretion of CCL5, thus promoting the tumour growth. In conclusion, our results suggest that HIF‐1α is essential for the activation and tumour‐promotion function of CAFs in lung cancer (LC). And targeting HIF‐1α expression on CAFs may be a promising strategy for LC therapy.
Midterm Outcome of Subtalar Joint Revision Arthrodesis

Background: The outcomes of revision subtalar arthrodesis have received relatively little focus in research compared with primary subtalar arthrodesis outcomes. This study aimed to assess the midterm clinical and radiologic results of subtalar joint revision arthrodesis and to analyze the risk factors that might influence the outcome of this procedure. Methods: We performed a retrospective review of 20 patients after subtalar joint revision arthrodesis for malunion, using interposition of iliac crest bone graft. The mean age was 55.75 years and the average follow-up lasted for 48.93 months. Eighty-five percent of the patients had at least 1 risk factor identified prior to revision. Patients’ satisfaction and functional outcomes were evaluated with the American Orthopaedic Foot & Ankle Society Scale (AOFAS), the Foot and Ankle Outcome Score (FAOS), the Foot Function Index (FFI), and dynamic pedobarography. Results: A fusion rate of 80% was recorded whereas 20% of the cases ended with a painful pseudarthrosis requiring additional surgery. Pedobarographic measurements demonstrated that loading has a propensity toward the lateral column, but no substantial effect on the gait of patients. In this group, the following patient-reported outcomes were observed: 70% of the patients were satisfied, 20% of the patients found the result fair, and 10% were not satisfied with the results. Compared with the preoperative evaluation, postoperative functional scores showed significant improvement on the FOAS, AOFAS, and FFI outcome scales. Conclusion: Revision arthrodesis of the subtalar joint remains a challenging issue with a relatively high rate of nonunion, especially in a population of patients with multiple risk factors. Level of Evidence: Level IV, retrospective case series.
Cortical and trabecular bone structure of the hominoid capitate

Morphological variation in the hominoid capitate has been linked to differences in habitual locomotor activity due to its importance in movement and load transfer at the midcarpal joint proximally and carpometacarpal joints distally. Although the shape of bones and their articulations are linked to joint mobility, the internal structure of bones has been shown experimentally to reflect, at least in part, the loading direction and magnitude experienced by the bone. To date, it is uncertain whether locomotor differences among hominoids are reflected in the bone microarchitecture of the capitate. Here, we apply a whole‐bone methodology to quantify the cortical and trabecular architecture (separately and combined) of the capitate across bipedal (modern Homo sapiens), knuckle‐walking (Pan paniscus, Pan troglodytes, Gorilla sp.), and suspensory (Pongo sp.) hominoids (n = 69). It is hypothesized that variation in bone microarchitecture will differentiate these locomotor groups, reflecting differences in habitual postures and presumed loading force and direction. Additionally, it is hypothesized that trabecular and cortical architecture in the proximal and distal regions, as a result of being part of mechanically divergent joints proximally and distally, will differ across these portions of the capitate. Results indicate that the capitate of knuckle‐walking and suspensory hominoids is differentiated from bipedal Homo primarily by significantly thicker distal cortical bone. Knuckle‐walking taxa are further differentiated from suspensory and bipedal taxa by more isotropic trabeculae in the proximal capitate. An allometric analysis indicates that size is not a significant determinate of bone variation across hominoids, although sexual dimorphism may influence some parameters within Gorilla. Results suggest that internal trabecular and cortical bone is subjected to different forces and functional adaptation responses across the capitate (and possibly other short bones). Additionally, while separating trabecular and cortical bone is normal protocol of current whole‐bone methodologies, this study shows that when applied to carpals, removing or studying the cortical bone separately potentially obfuscates functionally relevant signals in bone structure.
Dysregulation of miR-374a is involved in the progression of diabetic retinopathy and regulates the proliferation and migration of retinal microvascular endothelial cells

ABSTRACT Clinical relevance microRNAs (miRNAs) have been reported to be involved in the progression of various diseases. Background This study evaluated the expression and clinical value of miR-374a in diabetic retinopathy (DR) patients and analysed the effects of miR-374a on the progression of DR. Methods Subjects were divided into four groups: healthy control, type 2 diabetes mellitus without DR (NDR), proliferation DR (PDR) and non-proliferation DR (NPDR). Real-time polymerase chain reaction (qRT-PCR) was detected in the serum miR-374a levels of the subjects. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-374a in DR patients. Pearson correlation was used to analyse the correlation between miRNA and clinical indicators of patients. High glucose (HG) in treatment of human retinal microvascular endothelial cells (HRMECs). The effects of miR-374a on cell proliferation and migration induced by HG were detected. Results Serum miR-374a was progressively accelerated in patients with NDR, NPDR and PDR than in healthy controls. Moreover, miR-374a can significantly distinguish between NDR and DR patients. Among DR patients, miR-374a can differentiate PDR patients from NPDR patients. Serum miR-374a was positively correlated with diabetes duration, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), and homoeostasis model assessment of insulin resistance (HOMA-IR) in DR patients. HG-induced proliferation and migration of HRMECs was inhibited by reduction of miR-374a. Conclusion Dysregulation of miR-374a is involved in the progression of DR and serves a regulatory role in retinal, which can be used as a promising diagnostic biomarker for DR.