Miracle-dz/UniFAR-FTUs huggingface dataset:
Muscle-Saturated Bioactive Lipids Are Increased with Aging and Influenced by High-Intensity Interval Training

Ceramide and diacylglycerol are linked to insulin resistance in rodents, but in humans the data are inconsistent. Insulin resistance is frequently observed with aging, but the role of ceramide and diacylglycerol is not clarified. Training improves metabolic health and, therefore, we aimed to elucidate the influence of age and high-intensity interval training (HIIT) on ceramide and diacylglycerol content in muscle. Fourteen young (33 ± 1) and 22 older (63 ± 1) overweight to obese subjects performed 6 weeks HIIT three times a week. Maximal oxygen uptake and body composition were measured and muscle biopsies and fasting blood samples were obtained. Muscle ceramide and diacylglycerol were measured by gas-liquid chromatography and proteins in insulin signaling, lipid and glucose metabolism were measured by Western blotting. Content of ceramide and diacylglycerol total, saturated, C16:0 and C18:0 fatty acids and C18:1 ceramide were higher in older compared to young. HIIT reduced saturated and C18:0 ceramides, while the content of the proteins involved in glucose (GLUT4, glycogen synthase, hexokinase II, AKT) and lipid metabolism (adipose triglyceride lipase, fatty acid binding protein) were increased after HIIT. We demonstrate a higher content of saturated ceramide and diacylglycerol fatty acids in the muscle of older subjects compared to young. Moreover, the content of saturated ceramides was reduced and muscle glucose metabolism improved at protein level after HIIT. This study highlights an increased content of saturated ceramides in aging which could be speculated to influence insulin sensitivity.
Synthetic Lethality in Lung Cancer—From the Perspective of Cancer Genomics

Cancer is a genetic disease, and this concept is now widely exploited by both scientists and clinicians to develop new genotype-selective anticancer therapeutics. Although the quest of cancer genomics is in its dawn, recognition of the widespread applicability of genetic interactions with biological processes of tumorigenesis is propelling research throughout academic fields. Lung cancer is the most common cause of cancer death worldwide, with an estimated 1.6 million deaths each year. Despite the development of targeted therapies that inhibit oncogenic mutations of lung cancer cases, continued research into new therapeutic approaches is required for untreatable lung cancer patients, and the development of therapeutic modalities has proven elusive. The “synthetic lethal” approach holds the promise of delivering a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. We highlight the potential challenges in synthetic lethal anticancer therapeutics that target untreatable genetic alterations in lung cancer. We also discuss both challenges and opportunities regarding the application of new synthetic lethal interactions in lung cancer.
Epilepsy Disease and Nose-to-Brain Delivery of Polymeric Nanoparticles: An Overview

Epilepsy is the fourth most common global neurological problem, which can be considered a spectrum disorder because of its various causes, seizure types, its ability to vary in severity and the impact from person to person, as well as its range of co-existing conditions. The approaches to drug therapy of epilepsy are directed at the control of symptoms by chronic administration of antiepileptic drugs (AEDs). These AEDs are administered orally or intravenously but alternative routes of administration are needed to overcome some important limits. Intranasal (IN) administration represents an attractive route because it is possible to reach the brain bypassing the blood brain barrier while the drug avoids first-pass metabolism. It is possible to obtain an increase in patient compliance for the easy and non-invasive route of administration. This route, however, has some drawbacks such as mucociliary clearance and the small volume that can be administered, in fact, only drugs that are efficacious at low doses can be considered. The drug also needs excellent aqueous solubility or must be able to be formulated using solubilizing agents. The use of nanomedicine formulations able to encapsulate active molecules represents a good strategy to overcome several limitations of this route and of conventional drugs. The aim of this review is to discuss the innovative application of nanomedicine for epilepsy treatment using nose-to-brain delivery with particular attention focused on polymeric nanoparticles to load drugs.
Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.
Phase stability of three-dimensional bulk and two-dimensional monolayer As1−xSbx solid solutions from first principles

The mixing thermodynamics of both three-dimensional bulk and two-dimensional mono-layered alloys of As1−xSbx as a function of alloy composition and temperature are explored using a first-principles cluster-expansion method, combined with canonical Monte-Carlo simulations. We observe that, for the bulk phase, As1−xSbx alloy can exhibit not only chemical ordering of As and Sb atoms at x = 0.5 to form an ordered compound of AsSb stable upon annealing up to K, but also a miscibility gap at 475 K T 550 K in which two disordered solid solutions of As1−xSbx of different alloy compositions thermodynamically coexist. At T > 550 K, a single-phase solid solution of bulk As1−xSbx is predicted to be stable across the entire composition range. These results clearly explain the existing uncertainties in the alloying behavior of bulk As1−xSbx alloy, as previously reported in the literature, and also found to be in qualitative and quantitative agreement with the experimental observations. Interestingly, the alloying behavior of As1−xSbx is considerably altered, as the dimensionality of the material reduces from the three-dimensional bulk state to the two-dimensional mono-layered state—for example, a single-phase solid solution of monolayer As1−xSbx is predicted to be stable over the whole composition range at T > 250 K. This distinctly highlights an influence of the reduced dimensionality on the alloying behavior of As1−xSbx.
A virome-wide clonal integration analysis platform for discovering cancer viral etiology

Oncoviral infection is responsible for 12%–15% of cancer in humans. Convergent evidence from epidemiology, pathology, and oncology suggests that new viral etiologies for cancers remain to be discovered. Oncoviral profiles can be obtained from cancer genome sequencing data; however, widespread viral sequence contamination and noncausal viruses complicate the process of identifying genuine oncoviruses. Here, we propose a novel strategy to address these challenges by performing virome-wide screening of early-stage clonal viral integrations. To implement this strategy, we developed VIcaller, a novel platform for identifying viral integrations that are derived from any characterized viruses and shared by a large proportion of tumor cells using whole-genome sequencing (WGS) data. The sensitivity and precision were confirmed with simulated and benchmark cancer data sets. By applying this platform to cancer WGS data sets with proven or speculated viral etiology, we newly identified or confirmed clonal integrations of hepatitis B virus (HBV), human papillomavirus (HPV), Epstein-Barr virus (EBV), and BK Virus (BKV), suggesting the involvement of these viruses in early stages of tumorigenesis in affected tumors, such as HBV in TERT and KMT2B (also known as MLL4) gene loci in liver cancer, HPV and BKV in bladder cancer, and EBV in non-Hodgkin's lymphoma. We also showed the capacity of VIcaller to identify integrations from some uncharacterized viruses. This is the first study to systematically investigate the strategy and method of virome-wide screening of clonal integrations to identify oncoviruses. Searching clonal viral integrations with our platform has the capacity to identify virus-caused cancers and discover cancer viral etiologies.
A Preventive Model for Hamstring Injuries in Professional Soccer: Learning Algorithms

Abstract Hamstring strain injury (HSI) is one of the most prevalent and severe injury in professional soccer. The purpose was to analyze and compare the predictive ability of a range of machine learning techniques to select the best performing injury risk factor model to identify professional soccer players at high risk of HSIs. A total of 96 male professional soccer players underwent a pre-season screening evaluation that included a large number of individual, psychological and neuromuscular measurements. Injury surveillance was prospectively employed to capture all the HSI occurring in the 2013/2014 season. There were 18 HSIs. Injury distribution was 55.6% dominant leg and 44.4% non-dominant leg. The model generated by the SmooteBoostM1 technique with a cost-sensitive ADTree as the base classifier reported the best evaluation criteria (area under the receiver operating characteristic curve score=0.837, true positive rate=77.8%, true negative rate=83.8%) and hence was considered the best for predicting HSI. The prediction model showed moderate to high accuracy for identifying professional soccer players at risk of HSI during pre-season screenings. Therefore, the model developed might help coaches, physical trainers and medical practitioners in the decision-making process for injury prevention.
Lesions Responsible for Impaired Visual Perception in Poststroke Patients Using Voxel‐Based Lesion Symptom Mapping

We aimed to clarify the clinical characteristics that affect visual perception (VP) and elucidate lesion locations correlated with impaired VP. We reviewed 61 patients with stroke. Clinical assessments of a motor‐free VP test were used to evaluate VP after stroke. Regression analyses were performed to examine predictors of impaired VP. We generated statistical maps of lesions related to impaired VP using voxel‐based lesion symptom mapping (VLSM). The group of patients who had right hemispheric lesions had significantly low VP function. In a regression model, impaired VP was predicted by cognitive function, age, lesion volume, and right hemispheric lesion. Using VLSM, we found lesion location associated with impaired VP after adjusting for age, lesion volume, and Korean version of mini mental status exam. The results showed a lesion pattern with predominant distribution in the right parietal lobe and deep white matter. Age, lesion volume, and cognitive impairment affected the results of VP tests. Even after adjustments, we found that lesions responsible for impaired VP were located in the right parietal lobe and deep white matter. This result confirmed right hemispheric dominance for VP using VLSM. Clin. Anat. 32:689–696, 2019. © 2019 Wiley Periodicals, Inc.
Detail Preserved Surface Reconstruction from Point Cloud

In this paper, we put forward a new method for surface reconstruction from image-based point clouds. In particular, we introduce a new visibility model for each line of sight to preserve scene details without decreasing the noise filtering ability. To make the proposed method suitable for point clouds with heavy noise, we introduce a new likelihood energy term to the total energy of the binary labeling problem of Delaunay tetrahedra, and we give its s-t graph implementation. Besides, we further improve the performance of the proposed method with the dense visibility technique, which helps to keep the object edge sharp. The experimental result shows that the proposed method rivalled the state-of-the-art methods in terms of accuracy and completeness, and performed better with reference to detail preservation.
A Mathematical Model of dP/dt Max for the Evaluation of the Dynamic Control of Heart Contractility in Septic Shock

Objective: Septic shock (SS) patients often show elevated heart rate (HR) despite resuscitation, and this condition is considered an early manifestation of myocardial dysfunction due to an impairment of autonomic nervous system (ANS). We aimed at proposing a mathematical model to assess the autonomic control of ventricular contractility (VC) and HR to track changes in heart functionality during an experimental animal model of SS and resuscitation. Methods: SS was induced in six adult swine by polymicrobial peritonitis. We analyzed the beat-to-beat variability of the maximum positive time derivative of left ventricular pressure (dP/dt max), heart period (HP), and aortic blood pressure (ABP). We identified the transfer functions relating fluctuations in ABP and HP to dP/dt max to characterize the static and dynamic properties of the arterial baroreflex and the force-frequency relation mechanisms, respectively. Standard indices of autonomic dysfunction have also been considered as HR variability (HRV) and baroreflex sensitivity (BRS). Results: During baseline, the baroreflex is predominant in controlling VC with a gain value of −5.8 (−7.5,−3) s−1, compared to −1.2 (−1.9,−0.5) mmHg/s ms−1 of the force–frequency autoregulation. During shock, both mechanisms increase their extent in VC control (higher gains and slightly faster dynamics for the baroreflex). After resuscitation, the physiological control of VC is not restored and all the animals still exhibit high HR and reduced HRV and BRS. Conclusion: A condition of cardiovascular inefficiency is persistent after resuscitation and this could be due to autonomic dysfunction. Significance: The ANS in SS is crucial to restore homeostasis. Our model could be used to evaluate the efficacy of treatments on VC and related control mechanisms.
SIGMAR1/Sigma-1 receptor ablation impairs autophagosome clearance

ABSTRACT Autophagosome-lysosome fusion is a common critical step in various forms of macroautophagy/autophagy including mitophagy, the selective degradation of mitochondria. Regulations of this fusion process remain poorly defined. Here we have determined the role of SIGMAR1, a unique endoplasmic reticulum membrane protein. Knockout of Sigmar1 impaired mitochondrial clearance without altering the PINK1-PRKN/Parkin signaling, in mouse retinal explants and cultured cells treated with carbonyl cyanide m-chlorophenyl hydrazone (CCCP) for induction of mitophagy. SIGMAR1 depletion also caused accumulation of autophagosome markers LC3-II and SQSTM1, but did not change the levels of BECN1 and ATG7, proteins associated with autophagosome biogenesis. Lysosomal pH and protease activities were not negatively affected. However, sigmar1 knockout partially compromised autophagosome-lysosome fusion in CCCP-treated NSC34 cells, as revealed by reduced GFP fluorescence quenching of GFP-RFP-LC3-II puncta and co-localization of lysosomes with mitochondria. Furthermore, SIGMAR1 co-immunoprecipitated with ATG14, STX17, and VAMP8 (but not SNAP29), proteins key to autophagosome-lysosome membrane fusion. Re-expressing SIGMAR1 in the null background rescued clearance of mitochondria and autophagosomes. In summary, we started out finding that sigmar1 knockout impaired the clearance of mitochondria and autophagosomes, and then narrowed down the SIGMAR1 modulation to the autophagosome-lysosome fusion step. This study may shed new light on understanding autophagy-associated cyto-protection and disease mechanisms. Abbreviations: APEX2, a genetically engineered peroxidase; BiFC, bimolecule fluorescence complementation; CCCP, a mitophagy inducing compound; CRISPR, clustered regularly interspaced short palindromic repeats; EM, electron microscopy; ER, endoplasmic reticulum; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; SIGMAR1, sigma non-opioid intracellular receptor 1.
Preservation of Residual Hearing After Cochlear Implant Surgery With Deep Insertion Electrode Arrays.

OBJECTIVE To evaluate the hearing preservation (HP) in cochlear implant (CI) recipients who did not fulfill the criteria for electric acoustic stimulation (EAS). STUDY DESIGN Prospective study SETTING:: Tertiary academic hospital. PATIENTS Adults undergoing CI with deep insertion electrode arrays who had measurable residual hearing (RH) before surgery. INTERVENTION Demographic data, surgical technique, pure-tone average, and radiological findings were evaluated. MAIN OUTCOME MEASURE Pre- and postoperative pure-tone audiometry. A preservation study was therefore performed for the whole range of frequencies (THP), and for low frequencies (LFHP). RESULTS From the total 25 patients who underwent the surgical procedure, 6 of them (26.08%) did not retain any RH and 17 of them (73.91%) had some degree of HP. A clear association was observed between the use of the atraumatic technique (AT) and the percentage of some degree of HP. In patients who underwent the AT, LFHP was 72.79% and THP was 70.40%. In patients who did not undergo the technique, LFHP was 31.48% (p: 0.003) and THP was 23.50% (p: 0.002). LFHP was complete or partial (more than 25% of initial RH) in 92.3% of patients who underwent AT and in 50% of those who did not. Radiological findings showed that complete insertion is not associated with poorer HP. CONCLUSION If the appropriate technique is used, preservation of RH is feasible after cochlear implant surgery with deep insertion electrode arrays.
Effects of Fresh Watermelon Consumption on the Acute Satiety Response and Cardiometabolic Risk Factors in Overweight and Obese Adults

Although some studies have demonstrated the beneficial effects of watermelon supplementation on metabolic diseases, no study has explored the potential mechanism by which watermelon consumption improves body weight management. The objective of this study was to evaluate the effects of fresh watermelon consumption on satiety, postprandial glucose and insulin response, and adiposity and body weight change after 4 weeks of intervention in overweight and obese adults. In a crossover design, 33 overweight or obese subjects consumed watermelon (2 cups) or isocaloric low-fat cookies daily for 4 weeks. Relative to cookies, watermelon elicited more (p < 0.05) robust satiety responses (lower hunger, prospective food consumption and desire to eat and greater fullness). Watermelon consumption significantly decreased body weight, body mass index (BMI), systolic blood pressure and waist-to-hip ratio (p ≤ 0.05). Cookie consumption significantly increased blood pressure and body fat (p < 0.05). Oxidative stress was lower at four week of watermelon intervention compared to cookie intervention (p = 0.034). Total antioxidant capacity increased with watermelon consumption (p = 0.003) in blood. This study shows that reductions in body weight, body mass index (BMI), and blood pressure can be achieved through daily consumption of watermelon, which also improves some factors associated with overweight and obesity (clinicaltrials.gov, NCT03380221).
A checkpoint-oriented cell cycle simulation model

ABSTRACT Modeling and in silico simulations are of major conceptual and applicative interest in studying the cell cycle and proliferation in eukaryotic cells. In this paper, we present a cell cycle checkpoint-oriented simulator that uses agent-based simulation modeling to reproduce the dynamics of a cancer cell population in exponential growth. Our in silico simulations were successfully validated by experimental in vitro supporting data obtained with HCT116 colon cancer cells. We demonstrated that this model can simulate cell confluence and the associated elongation of the G1 phase. Using nocodazole to synchronize cancer cells at mitosis, we confirmed the model predictivity and provided evidence of an additional and unexpected effect of nocodazole on the overall cell cycle progression. We anticipate that this cell cycle simulator will be a potential source of new insights and research perspectives. Graphical abstract This figure describes the input biological data (doubling time and cell cycle distribution) and the two main outputs of the simulator. The simulator offers several tools to analyze cell cycle progression/distribution and provides a virtual dynamic view of the cell cycle parameters. Moreover, the simulator allows testing hypotheses, such as challenging the cell cycle checkpoints.
Design, Implementation, and Evaluation of an Integrative Pain Management Program in a Primary Care Safety-Net Clinic.

OBJECTIVE To design, implement, and evaluate a comprehensive Integrative Pain Management Program (IPMP) for patients with chronic pain in a safety-net primary care clinic. DESIGN We used a quality improvement "Plan Do Study Act" (PDSA) framework to design, refine, and evaluate an integrative chronic pain program. SETTING An urban federally qualified health center located in a community with high rates of chronic pain, substance use, and opioid overdose. SUBJECTS Eligible participants included individuals with pain for greater than 3 months who were prescribed opioid therapy. OUTCOME MEASURES We designed IPMP using a PDSA framework that promotes continuous evaluation and adaptation of the program to meet the needs of the clinical system. We assessed feasibility and acceptability with program referrals and attendance and evaluated program satisfaction. RESULTS The IPMP delivered a 12-week group-based intervention that involved group support, education on pain etiology and treatments, movement-based interventions, mindfulness-based therapies, acupuncture, and massage therapy. One hundred forty-six patients were referred to IPMP; 58 individuals participated in one of the first three cohorts of the program. Sixty-two percent of participants attended at least half of the sessions. Staff and participants reported high levels of satisfaction with IPMP and demand for longitudinal services. CONCLUSIONS An IPMP delivered within a safety-net primary care clinic could be implemented in a way feasible and acceptable to staff and participants with the support of the local health care system. The application of a PDSA cycle allowed for rigorous implementation and evaluation of a multimodal pain program. Quality improvement frameworks are a strategy to improve and expand the delivery of high-quality patient-centered integrative pain treatments.