Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice.

Obesity is the only known modifiable risk factor for multiple myeloma (MM), an incurable cancer of bone marrow plasma cells. The mechanism linking the two is unknown. Obesity is associated with an increased risk of sleep apnea, which results in chronic intermittent hypoxia (CIH), and drives solid tumor aggressiveness. Given the link between CIH and solid tumor progression, we tested the hypothesis that CIH drives the proliferation of MM cells in culture and their engraftment and progression in vivo. Malignant mouse 5TGM1 cells were cultured in CIH, static hypoxia, or normoxia as a control in custom, gas-permeable plates. Typically MM-resistant C57BL/6J mice were exposed to 10 h/day CIH (AHI = 12/h), static hypoxia, or normoxia for 7 days, followed by injection with 5TGM1 cells and an additional 28 days of exposure. CIH and static hypoxia slowed the growth of 5TGM1 cells in culture. CIH-exposed mice developed significantly more MM than controls (67 vs. 12%, P = 0.005), evidenced by hindlimb paralysis, gammopathy, bone lesions, and bone tumor formation. Static hypoxia was not a significant driver of MM progression and did not reduce survival (P = 0.117). Interestingly, 5TGM1 cells preferentially engrafted in the bone marrow and promoted terminal disease in CIH mice, despite a lower tumor burden, compared with the positive controls. These first experiments in the context of hematological cancer demonstrate that CIH promotes MM through mechanisms distinct from solid tumors and that sleep apnea may be a targetable risk factor in patients with or at risk for blood cancer.
Revealing signatures of planets migrating in protoplanetary discs with ALMA multiwavelength observations

Recent observations show that rings and gaps are ubiquitous in protoplanetary discs. These features are often interpreted as being due to the presence of planets; however, the effect of planetary migration on the observed morphology has not been investigated hitherto. In this work we investigate whether multiwavelength mm/submm observations can detect signatures of planet migration, using 2D dusty hydrodynamic simulations to model the structures generated by migrating planets and synthesising ALMA continuum observations at 0.85 and 3 mm. We identify three possible morphologies for a migrating planet: a slowly migrating planet is associated with a single ring outside the planet's orbit, a rapidly migrating planet is associated with a single ring inside the planet's orbit while a planet migrating at intermediate speed generates one ring on each side of the planet's orbit. We argue that multiwavelength data can distinguish multiple rings produced by a migrating planet from other scenarios for creating multiple rings, such as multiple planets or discs with low viscosity. The signature of migration is that the outer ring has a lower spectral index, due to larger dust grains being trapped there. Of the recent ALMA observations revealing protoplanetary discs with multiple rings and gaps, we suggest that Elias 24 is the best candidate for a planet migrating in the intermediate speed regime.
Calcitonin gene-related peptide regulates FOSL2 expression and cell proliferation of BMSCs via mmu_circRNA_003795

Circular RNAs (circRNAs) are a class of non-coding RNAs that may have important regulatory potency in various biological processes. However, the role of circRNAs and their potential functions in bone marrow mesenchymal stem cells of mice (BMSCs) are still ambiguous. The current study aims to examine the expression of circRNAs and to investigate their effects on FOS like 2 AP-1 transcription factor subunit (FOSL2) expression following stimulation of BMSCs with calcitonin gene-related peptide (CGRP). RNA generated from BMSCs stimulated with or without CGRP was used in a microarray to detect expression of circRNAs. There were 58 significantly differentially expressed circRNAs following CGRP treatment, with 44 circRNAs downregulated and 14 upregulated. Bioinformatics analysis and regulatory networks were used to identify the potential interactions between circRNAs and microRNAs (miRs). mmu_circRNA_003795 was significantly increased in the CGRP-stimulated BMSCs compared with the blank control. Silencing of mmu_circRNA_003795, significantly increased the expression of mmu_miR-504-3p, whereas FOSL2 expression and cell proliferation were decreased. Furthermore, silencing of mmu_mir-504-3p using an miR inhibitor led to increased FOSL2 expression. Additionally, silencing of mmu_circRNA_003795 using small interfering RNA induced marked alterations in the cell cycle of BMSCs. The results demonstrated that mmu_circRNA_003795 can indirectly regulate FOSL2 expression via sponging of miR-504-3p, resulting in alterations in BMSC proliferation.
Effects of whole-body vibration exercise on functions required for bowling performance of male bowling player

The focus of this research is to examine the impact of 8 weeks of whole body vibration (WBV) exercise on physical factors by conducting an experiment on 17 male bowling players registered in Korea Bowling Association. Strength of truncus and lower-limb and balance were mea-sured as the physical factors and the impact of WBV exercise on each variable was examined. There was significant increase between groups in flexor-weight ratio of truncus at 60°/sec according to performance after applying WBV exercise. There was significant difference in groups before bowling event in pre and posttest as well as after bowling event in pre and posttest. There was significant difference of extensor-weight ratio in groups after bowling event in pre and posttest. There was significant increase at 60°/sec in flexor-ratio of both left and right lower-limb strength according to performance after applying WBV exercise. There was significant difference between groups before bowling event in pre and posttest as well as after bowling event in pre and posttest. Extensor-weight ratio showed significant difference between groups only before bowling event in pre and posttest. There was significant difference between groups in both left and right balance according to performance after applying WBV exercise. There was significant difference in before bowling event in pre and posttest as well as after bowling event in pre and posttest.
Universal gradient descent

In this book we collect many different and useful facts around gradient descent method. First of all we consider gradient descent with inexact oracle. We build a general model of optimized function that include composite optimization approach, level's methods, proximal methods etc. Then we investigate primal-dual properties of the gradient descent in general model set-up. At the end we generalize method to universal one.
The T-SPOT.TB assay used for screening and monitoring of latent tuberculosis infection in patients with Behçet’s disease pre- and post-anti-TNF treatment: A retrospective study

Background: Patients undergoing anti-tumor necrosis factor (TNF) treatment are more susceptible to latent tuberculosis infection (LTBI). The aim of the current study was to determine the rate of active tuberculosis (TB) in patients with Behçet’s disease (BD) pre- and post-anti-TNF treatment and to evaluate the long-term efficacy of LTBI screening as primary prophylaxis in China. Methods: This retrospective study included BD patients eligible for anti-TNF therapy at a single institution in Fudan University, China. On the basis of the results of T-SPOT.TB assay, chest radiograph, and history of exposure to TB, patients were screened and regularly followed up at 3-months interval. Results: Eighty-nine BD patients with mean disease duration of 87.5 ± 86.1 months were included. Their median duration of anti-TNF therapy was 10.6 months; 51 patients were treated with Infliximab, 38 with Etanercept, and four with Adalimumab. While 84 patients received a consecutive single anti-TNF drug therapy, five patients switched to a second drug. Twelve patients demonstrated positive results in LTBI screening: three had history of TB exposure and nine were solely T-SPOT.TB-positive patients. Before anti-TNF treatment, LTBI treatment was initiated in 11 patients, and one patient refused treatment. With a median follow-up period of 27.9 months, we observed only one case (1.1%) of intestinal TB during Infliximab treatment. Conclusion: Regardless of anti-TNF treatment, long-term screening via T-SPOT.TB assay might represent a more sensitive approach to identify BD patients with LTBI. As a secondary prophylaxis, the LTBI treatment is effective in a country with high risk of TB.
Preoperative colonoscopy in patients with a supposed primary ovarian cancer

Abstract The final diagnosis of ovarian cancer is based on surgery and pathological verification. Therefore patients who are presented to surgery may be described only as supposed ovarian cancer. According to the literature the diagnosis of ovarian cancer is confirmed only in 2/3 of them. The rest are that which mimic ovarian cancer. One of them is colorectal cancer. Colonoscopy is a gold standard in its diagnostics. On the other hand, ovarian cancer may disturb the bowel patency and makes the bowel resection or stoma necessary. The main aim was to find out the distribution of bowel patency disturbances in ovarian cancer patients during preoperative colonoscopy and to assess their predictive value with respect to the bowel resection or stoma and the additional aim to identify the pathologies which mimic the ovarian cancer. In a prospective study among 104 patients with supposed ovarian cancer, primary ovarian cancer was diagnosed in 68 patients. The rest of them suffered from colorectal cancer found at colonoscopy (N = 6), ovarian benign pathology (N = 8), ovarian borderline tumor (N = 5), and other nonandexal malignant diseases (N = 17). In ovarian cancer group dominated serous carcinoma and fedération international de gynécologie et d’obstétrique stage 3 (N = 33). During preoperative colonoscopy in ovarian cancer patients, the complete obstruction was found in 27.9%, and relative risk of bowel resection or stoma was in them 4.29 and 4.38, respectively. Another colonoscopic finding was limited patency caused by extrinsic compression (29%) which is connected with relative risk of bowel resection or stoma 3.16 and 3.21 accordingly. The last colonoscopy finding was described as moderate limited patency of unknown origin (20.6%) and the relative risk of bowel resection or stoma was 5.14 and 4.17, respectively. Colonoscopy enables the diagnoses of colorectal cancer one of the diseases which mimic ovarian cancer in patients supposed to have this diseases. Bowel patency disturbances found at colonoscopy are a potential risk factor to intestine resection or ostomy. Colonoscopy is not fully noninvasive procedure and its obligatory use in patients supposed to have ovarian cancer should be limited to the cases with specific symptoms, and tumor marker pattern. Preoperative computed tomography, dedicated to bowel examination, candidates as an alternative to colonoscopy, but not completely.
A Novel Risk Calculator Predicts 90-Day Readmission Following Total Joint Arthroplasty

Background: A reliable prediction tool for 90-day adverse events not only would provide patients with valuable estimates of their individual risk perioperatively, but would also give health-care systems a method to enable them to anticipate and potentially mitigate postoperative complications. Predictive accuracy, however, has been challenging to achieve. We hypothesized that a broad range of patient and procedure characteristics could adequately predict 90-day readmission after total joint arthroplasty (TJA). Methods: The electronic medical records on 10,155 primary unilateral total hip (4,585, 45%) and knee (5,570, 55%) arthroplasties performed at a single institution from June 2013 to January 2018 were retrospectively reviewed. In addition to 90-day readmission status, >50 candidate predictor variables were extracted from these records with use of structured query language (SQL). These variables included a wide variety of preoperative demographic/social factors, intraoperative metrics, postoperative laboratory results, and the 30 standardized Elixhauser comorbidity variables. The patient cohort was randomly divided into derivation (80%) and validation (20%) cohorts, and backward stepwise elimination identified important factors for subsequent inclusion in a multivariable logistic regression model. Results: Overall, subsequent 90-day readmission was recorded for 503 cases (5.0%), and parameter selection identified 17 variables for inclusion in a multivariable logistic regression model on the basis of their predictive ability. These included 5 preoperative parameters (American Society of Anesthesiologists [ASA] score, age, operatively treated joint, insurance type, and smoking status), duration of surgery, 2 postoperative laboratory results (hemoglobin and blood-urea-nitrogen [BUN] level), and 9 Elixhauser comorbidities. The regression model demonstrated adequate predictive discrimination for 90-day readmission after TJA (area under the curve [AUC]: 0.7047) and was incorporated into static and dynamic nomograms for interactive visualization of patient risk in a clinical or administrative setting. Conclusions: A novel risk calculator incorporating a broad range of patient factors adequately predicts the likelihood of 90-day readmission following TJA. Identifying at-risk patients will allow providers to anticipate adverse outcomes and modulate postoperative care accordingly prior to discharge. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Comparison of Collapsibility of the Human Upper Airway During Anesthesia and During Sleep

BACKGROUND: The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea–hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared. METHODS: Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m2) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep. RESULTS: Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02–0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, −0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs −2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32–5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs −1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, −0.95 to 7.96]; P = .087). CONCLUSIONS: These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.
Structure-Specific Endonucleases and the Resolution of Chromosome Underreplication

Complete genome duplication in every cell cycle is fundamental for genome stability and cell survival. However, chromosome replication is frequently challenged by obstacles that impede DNA replication fork (RF) progression, which subsequently causes replication stress (RS). Cells have evolved pathways of RF protection and restart that mitigate the consequences of RS and promote the completion of DNA synthesis prior to mitotic chromosome segregation. If there is entry into mitosis with underreplicated chromosomes, this results in sister-chromatid entanglements, chromosome breakage and rearrangements and aneuploidy in daughter cells. Here, we focus on the resolution of persistent replication intermediates by the structure-specific endonucleases (SSEs) MUS81, SLX1-SLX4 and GEN1. Their actions and a recently discovered pathway of mitotic DNA repair synthesis have emerged as important facilitators of replication completion and sister chromatid detachment in mitosis. As RS is induced by oncogene activation and is a common feature of cancer cells, any advances in our understanding of the molecular mechanisms related to chromosome underreplication have important biomedical implications.
A novel pathogenic variant in OFD1 results in X‐linked Joubert syndrome with orofaciodigital features and pituitary aplasia

Orofaciodigital syndrome type I and X‐linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first report of a newborn male with a novel hemizygous variant in OFD1 gene c.515T>C, (p.Leu172Pro) resulting in X‐linked Joubert syndrome and orofaciodigital features with complete pituitary gland aplasia and subsequent severe hypoplasia of peripheral endocrine glands. This clinical report expands the phenotypic spectrum of endocrine system involvement in OFD1‐related disorders and suggests that OFD1 gene may be related to pituitary gland development.
An overview of the physical and biochemical transformation of cocoa seeds to beans and to chocolate: Flavor formation

Abstract Chocolate is a widely consumed product worldwide due to its exquisite flavor, which comes from the unique and fascinating cocoa flavor. This flavor depends on little controllable variables such as the genotype and the agroecological niche, and on the other side, on postharvest operations: (1) cocoa transformation from seeds to beans that comprises cocoa seeds preconditioning, fermentation, and drying, and (2) the production of chocolate from the bean in which roasting is highlighted. Postharvest transformation operations are critically important because during these, cocoa flavor is formed, allowing the differentiation of two categories: bulk and specialty cocoa. In this sense, this article presents an overview of cocoa postharvest operations, the variables and phenomena that influence and control the physical and biochemical transformation from seeds to cocoa beans, and their relation to the formation of chocolate flavor. Moreover, research perspectives in terms of control and management of postharvest practices in order to obtain cocoa with differentiated and specialty characteristics “from bean to bar” are discussed.
Nano illumination microscopy: a technique based on scanning with an array of individually addressable nanoLEDs.

In lensless microscopy, spatial resolution is usually provided by the pixel density of current digital cameras, which are reaching a hard-to-surpass pixel size / resolution limit over 1 µm. As an alternative, the dependence of the resolving power can be moved from the detector to the light sources, offering a new kind of lensless microscopy setups. The use of continuously scaled-down Light-Emitting Diode (LED) arrays to scan the sample allows resolutions on order of the LED size, giving rise to compact and low-cost microscopes without mechanical scanners or optical accessories. In this paper, we present the operation principle of this new approach to lensless microscopy, with simulations that demonstrate the possibility to use it for super-resolution, as well as a first prototype. This proof-of-concept setup integrates an 8 × 8 array of LEDs, each 5 × 5 μm2 pixel size and 10 μm pitch, and an optical detector. We characterize the system using Electron-Beam Lithography (EBL) pattern. Our prototype validates the imaging principle and opens the way to improve resolution by further miniaturizing the light sources.
Impact of Antibiotic Therapy in the Microbiological Yield of Healthcare–Associated Ventriculitis and Meningitis

Abstract The impact of antibiotic therapy on the diagnosis of healthcare–associated ventriculitis and meningitis (HCAVM) is unknown. Antibiotics were administered before obtaining cerebrospinal fluid (CSF) in 217 out of 326 (66%) patients with HCAVM, and they impacted the sensitivity of the cerebrospinal fluid Gram stain and culture (P ≤ .004).
Rubric-based debriefing to enhance nursing students’ critical thinking via simulation

Introduction Debriefing plays a vital role in effective simulation-based learning by providing feedback to students to foster their development of critical thinking in the learning. Objectives We evaluated the effects of rubric-based debriefing on students’ critical thinking, level of confidence in performing tasks and communication. Method This is a quasi-experimental study. Final year nursing undergraduates (n=204) of a local university participated in the study. In the intervention group, students performed two 20 min simulation sessions individually with simulated patients followed by a 15 min individual rubric-based debriefing between the two sessions and had a 5 min of that at the end. In the control group, students performed the same simulation sessions followed by a 20 min individual rubric-based debriefing at the end. The primary outcome was comparing the critical thinking of students between two groups, which was assessed by The Northeastern Illinois University Critical Thinking Rubric. The qualitative data were collected by an open-ended question. Results Based on generalised estimating equation models, the intervention effect over time was found to be statistically significant (β=2.06, 95% CI 1.04 to 3.08) in enhancing students’ critical thinking. No statistically significant differences were reported in the self-perceived confidence levels between the intervention group and control group. Qualitative data reflected positive feedback from students on simulation activities. Conclusions This is the first study to provide evidence that a rubric-based debriefing enhances students’ critical thinking in simulation learning.
Involvement of a Response Regulator VdSsk1 in Stress Response, Melanin Biosynthesis and Full Virulence in Verticillium dahliae

Verticillium dahliae causes vascular wilt disease on over 200 plant species worldwide. This fungus forms melanized microsclerotia which help it to survive under adverse conditions and these structures are vital to the disease spread. Here, we identified and characterized a V. dahliae homolog to of the Saccharomyces cerevisiae Ssk1, a response regulator of the two-component system. Herein, we demonstrated that the VdSsk1 deletion strains were more sensitive to various stresses, including oxidative stress conferred by H2O2 and sodium nitroprusside dihydrate, while the mutants confered higher resistance to fungicides such as fludioxonil and iprodione. Furthermore, disruption of VdSsk1 resulted in significant downregulation of melanin biosynthesis-related genes but did not affect microsclerotial development. Phosphorylation of VdHog1 was not detected in the VdSsk1 deletion strains under the treatment of sorbitol, indicating that phosphorylation of VdHog1 is dependent on VdSsk1. Finally, we demonstrated that VdSsk1 is required for full virulence. Taken together, this study suggests that VdSsk1 modulates stress response, melanin biosynthesis and virulence of V. dahliae.