Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial Involvement in Cisplatin Resistance

Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.
Stapes piston insertion depth and clinical correlations

Abstract Background: The insertion of the stapes piston within the vestibule provides the physical basis for a successful stapedotomy. An insertion depth of 0.5 mm is recommended to avoid the dislocation of the stapes prosthesis (e.g. sneezing). Aims: The objective of this study is to analyze the depth of stapes prosthesis insertion and its correlation with clinical outcome. Material and methods: We observed in a retrospective case series 39 otosclerosis patients after a stapedotomy and a postoperative performed flat panel tomography/cone beam CT. The evaluation included the radiologically found depth of prosthesis insertion within the vestibule, the vestibule depth, and the correlation with the bone conduction (BC) threshold, vertigo, and tinnitus. Results: Insertion depth varied between 0.2 and 1.6 mm (mean 0.74 mm). The ratio of insertion depth versus the vestibule depth was between 8% and 59% (mean 26.6%). We observed no correlation between the insertion depth, the length of the prosthesis, the ratio of insertion depth/vestibule depth, postoperative BC, appearance of vertigo, or tinnitus. Conclusions and significance: In our group, we observed no significant relation between insertion depth of the stapes piston, postoperative vertigo, tinnitus, or decrease of the BC.
Shifting brain circuits in pain chronicity

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long‐term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome‐CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age‐ and sex‐matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory‐emotional changes in adult CRPS and rFC patterns from sensory‐sensory alterations in pediatric populations to a sensory‐emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well‐known differences between child and adult pain vulnerability and resilience.
Pediatric Pulmonology

Funding information Clalit Health Services, Grant/Award Number: none; Clalit Research Institute Abstract Background: Recurrent asthma‐like symptoms are common in infants, but few population studies describe diagnostic and treatment practice. Methods: Using the electronic data repository of Clalit Health Services, the largest integrated health care provider in Israel, we evaluated children born 2005–2012, who before 3 years of age had >3 episodes of asthma‐like symptoms and/or >2 bronchodilator purchases within a year. We described health care utilization and the odds ratio for subsequent utilization after 3 and 12 months’ controller therapy. The primary outcome measure was respiratory‐related doctor visits. Linear and categorical regression analysis measured overall effectiveness of therapy. Results: Among 689 171 infants, 262 900 (38.1%) had > 3 asthma‐like episodes/year during at least 1 year. Of those, 26 108 (10%) purchased controller therapy: 20 316 (77.8%) inhaled corticosteroids (ICS) with or without leukotriene receptor antagonists (LTRA), and 5792 (22.2%) LTRA alone. For these 26 108 over 3 months there were 93 845 respiratory‐related doctor visits, 3110 hospital admissions, 5568 diagnoses of pneumonia, 9960 chest X‐rays, 37 127 purchases for oral steroids, and 45 142 for antibiotics courses. Healthcare utilization decreased following ICS ± LTRA and LTRA alone, respectively, as follows: doctor visits 7% and 3%, chest X‐rays 16% and 17%, bronchodilators 20% and 11%, systemic steroids 17% and 12%, and antibiotics by 35% and 22%, (P < .001 for all). Twelve months’ therapy remained effective. Conclusions: Asthma‐like symptoms are common in infants. Health care utilization is very high and physician practices should be reassessed. Following controller therapy, health care utilization decreased. Yet controllers were prescribed in only a minority of eligible children.
Simultaneous Enrichment Analysis of all Possible Gene-sets: Unifying Self-Contained and Competitive Methods

Abstract Studying sets of genomic features is increasingly popular in genomics, proteomics and metabolomics since analyzing at set level not only creates a natural connection to biological knowledge but also offers more statistical power. Currently, there are two gene-set testing approaches, self-contained and competitive, both of which have their advantages and disadvantages, but neither offers the final solution. We introduce simultaneous enrichment analysis (SEA), a new approach for analysis of feature sets in genomics and other omics based on a new unified null hypothesis, which includes the self-contained and competitive null hypotheses as special cases. We employ closed testing using Simes tests to test this new hypothesis. For every feature set, the proportion of active features is estimated, and a confidence bound is provided. Also, for every unified null hypotheses, a \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$P$\end{document}-value is calculated, which is adjusted for family-wise error rate. SEA does not need to assume that the features are independent. Moreover, users are allowed to choose the feature set(s) of interest after observing the data. We develop a novel pipeline and apply it on RNA-seq data of dystrophin-deficient mdx mice, showcasing the flexibility of the method. Finally, the power properties of the method are evaluated through simulation studies.
Maladaptive neurovisceral interactions in patients with Internet gaming disorder: A study of heart rate variability and functional neural connectivity using the graph theory approach

Heart rate variability (HRV) can be used to represent the regulatory adaptive system and is a proxy for neurovisceral integration. Consistent with the view that, like other addictions, Internet gaming disorder (IGD) involves disrupted regulatory function, the present study hypothesized that IGD patients would show (a) decreased HRV, (b) ineffective functional neural connectivity, and (c) differential patterns of association between HRV and functional neural connectivity relative to healthy controls (HCs). The present study included 111 young adults (53 IGD patients and 58 age‐ and sex‐matched HCs) who underwent simultaneous recordings with an electrocardiogram and electroencephalogram during a resting state. Heart rate (HR), HRV, and functional neural connectivity were calculated using the graph theory approach. Compared with the HCs, the IGD patients exhibited elevated HR and decreased HRV based on the high frequency (HF), which reflects suppression of parasympathetic and/or vagal tone. The IGD patients also exhibited a heightened theta band characteristic path length (CPL) compared with HCs, indicating decreased efficacy of the functional network. Furthermore, IGD patients exhibited negative correlations between the standard deviation of the normal‐to‐normal interval index (SDNNi) and theta and delta CPL values, which were not observed in HCs. In conclusion, the present findings suggest that IGD patients might have maladaptive brain‐body integration features involving disruptions of the autonomic nervous system and brain function.
Heterogeneity-Aware Multicast for MANETs

Multicast is an essential group communication service and an important building block for many applications in MANETs, including data dissemination, service discovery, publishsubscribe, among others. Therefore, it has been widely studied and many solutions can be found in the literature. However, most existing multicast protocols are tailored to a specific type of mobility pattern and therefore are unable to excel in face of heterogeneous mobility conditions. This thesis proposes and evaluates HAMP, a Heterogeneity-Aware Multicast Protocol for MANETs that combines the efficiency of structured approaches and the robustness of floodingbased schemes. HAMP dynamically adapts its forwarding mechanism according to locally observed mobility conditions. If much mobility is observed in the neighborhood the node starts forwarding multicast traffic using a scoped flooding technique. As local network conditions stabilize the node reverts to a structured mesh-based operation. HAMP was implemented as a combination of a mesh-based protocol that uses a floodingbased technique. However, the main idea of combining structured and unstructured approaches in the same protocol can be also applied to other forwarding schemes. Experimental results obtained using the NS-2 network simulator confirm that HAMP successfully combines the robustness of flooding with the efficiency of mesh-based routing. Palavras Chave Keywords
Sheath-run artificial muscles

Getting the most out of muscles Materials that convert electrical, chemical, or thermal energy into a shape change can be used to form artificial muscles. Such materials include bimetallic strips or host-guest materials or coiled fibers or yarns (see the Perspective by Tawfick and Tang). Kanik et al. developed a polymer bimorph structure from an elastomer and a semicrystalline polymer where the difference in thermal expansion enabled thermally actuated artificial muscles. Iterative cold stretching of clad fibers could be used to tailor the dimensions and mechanical response, making it simple to produce hundreds of meters of coiled fibers. Mu et al. describe carbon nanotube yarns in which the volume-changing material is placed as a sheath outside the twisted or coiled fiber. This configuration can double the work capacity of tensile muscles. Yuan et al. produced polymer fiber torsional actuators with the ability to store energy that could be recovered on heating. Twisting mechanical deformation was applied to the fibers above the glass transition temperature and then stored via rapid quenching. Science, this issue p. 145, p. 150, p. 155; see also p. 125 A sheath on a coiled yarn drives actuation with high work-per-cycle and power densities during contraction. Although guest-filled carbon nanotube yarns provide record performance as torsional and tensile artificial muscles, they are expensive, and only part of the muscle effectively contributes to actuation. We describe a muscle type that provides higher performance, in which the guest that drives actuation is a sheath on a twisted or coiled core that can be an inexpensive yarn. This change from guest-filled to sheath-run artificial muscles increases the maximum work capacity by factors of 1.70 to 2.15 for tensile muscles driven electrothermally or by vapor absorption. A sheath-run electrochemical muscle generates 1.98 watts per gram of average contractile power—40 times that for human muscle and 9.0 times that of the highest power alternative electrochemical muscle. Theory predicts the observed performance advantages of sheath-run muscles.
Effect of intrapartum antibiotics on the intestinal microbiota of infants: a systematic review

Introduction The use of intrapartum antibiotic prophylaxis (IAP) has become common practice in obstetric medicine and is used in up to 40% of deliveries. Despite its benefits, the risks associated with exposing large numbers of infants to antibiotics, especially long-term effects on health through changes in the microbiota, remain unclear. This systematic review summarises studies that have investigated the effect of IAP on the intestinal microbiota of infants. Methods A systematic search in Ovid MEDLINE was used to identify original studies that investigated the effect of IAP on the intestinal microbiota in infants. Studies were excluded if: they included preterm infants, the antibiotic regimen was not specified, antibiotics were used for indications other than prophylaxis, probiotics were given to mothers or infants, or antibiotics were given to infants. Results We identified six studies, which investigated a total of 272 infants and included 502 stool samples collected up to 3 months of age. In all the studies, IAP was given for group B streptococcus (GBS) colonisation. Infants who were exposed to GBS IAP had a lower bacterial diversity, a lower relative abundance of Actinobacteria, especially Bifidobacteriaceae, and a larger relative abundance of Proteobacteria in their intestinal microbiota compared with non-exposed infants. Conflicting results were reported for the phyla Bacteroidetes and Firmicutes. Conclusions GBS IAP has profound effects on the intestinal microbiota of infants by diminishing beneficial commensals. Such changes during the early-life ‘critical window’ during which the intestinal microbiota and the immune response develop concurrently may have an important influence on immune development. The potential long-term adverse consequences of this on the health of children warrant further investigation.
Epidemiology investigation and analysis of patients with hemodialysis in Sichuan province of China

Abstract Objectives: To investigate the incidence, pathogenesis, as well as mortality rate and causes of end-stage renal disease patients with hemodialysis (ESRD-HD) in Sichuan province of China. Methods: In this retrospective descriptive study, all the data were exported from the Chinese National Renal Data System (CNRDS). The demographic and pathogenic information from 01 January 2011 to 31 December 2016 were statistically analyzed. Results: According to the data from CNRDS, the incidence of ESRD-HD was high in Sichuan province. From 2011 to 2016, the annual incidence rate of ESRD-HD was 61.84, 73.75, 78.04, 66.04, 72.61, and 60.98 per million population (pmp). Male ESRD-HD patients were higher than female patients (1.5:1). The major causes of ESRD-HD in Sichuan province from 2011 to 2016 were chronic glomerulonephritis and diabetic nephropathy. The annual mortality rate of ESRD-HD was 113.20, 91.25, 73.02, 68.56, 68.57, and 58.39 per 1000 person-years. The descending rate of mortality was parallel in both males and females. The mortality rate was observed to be higher in the elderly group (age ≥ 60). The major cause of mortality was cardiovascular diseases (24.48%). Conclusions: In Sichuan province, the incidence of ESRD-HD annually was gradually descending. The elderly and male patients had higher incidence of ESRD-HD. The annual mortality rate of ESRD-HD was declining year by year, and elderly patients aged ≥ 60 contributed to the highest mortality rates. The major cause of death was cardiovascular diseases. This could contribute to a better understanding of ESRD-HD in southwest of China, thus providing better treatment for ESRD in the future.
The Interpeduncular Angle: A Practical and Objective Marker for the Detection and Diagnosis of Intracranial Hypotension on Brain MRI

MRIs of 30 patients with intracranial hypotension and 30 age-matched controls were evaluated by 2 neuroradiologists for classic findings of intracranial hypotension and the interpeduncular angle. Group analysis was performed with a Student t test, and receiver operating characteristic analysis was used to identify an ideal angle threshold to maximize sensitivity and specificity. The interpeduncular angle had excellent interobserver reliability (intraclass correlation coefficient value = 0.833) and was significantly lower in the intracranial hypotension group compared with the control group (25.3° versus 56.3°). There was significant correlation between the interpeduncular angle and the presence of brain stem slumping. With a threshold of 40.5°, sensitivity and specificity were 80% and 96.7%, respectively. BACKGROUND AND PURPOSE: Classic findings of intracranial hypotension on MR imaging, such as brain stem slumping, can be variably present and, at times, subjective, potentially making the diagnosis difficult. We hypothesize that the angle between the cerebral peduncles correlates with the volume of interpeduncular cistern fluid and is decreased in cases of intracranial hypotension. We aimed to investigate its use as an objective assessment for intracranial hypotension. MATERIALS AND METHODS: Brain MRIs of 30 patients with intracranial hypotension and 30 age-matched controls were evaluated by 2 fellowship-trained neuroradiologists for classic findings of intracranial hypotension and the interpeduncular angle. Group analysis was performed with a Student t test, and receiver operating characteristic analysis was used to identify an ideal angle threshold to maximize sensitivity and specificity. Interobserver reliability was assessed for classic findings of intracranial hypotension using the Cohen κ value, and the interpeduncular angle, using the intraclass correlation. RESULTS: The interpeduncular angle had excellent interobserver reliability (intraclass correlation coefficient value = 0.833) and was significantly lower in the intracranial hypotension group compared with the control group (25.3° versus 56.3°; P < .001). There was significant correlation between the interpeduncular angle and the presence of brain stem slumping (P < .001) and in cases with ≥3 classic features of intracranial hypotension (P = .01). With a threshold of 40.5°, sensitivity and specificity were 80% and 96.7%, respectively. CONCLUSIONS: The interpeduncular angle is a sensitive and specific measure of intracranial hypotension and is a reliably reproducible parameter on routine clinical MR imaging.
Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2019

Main Recommendations ESGE recommends a low fiber diet on the day preceding colonoscopy. Strong recommendation, moderate quality evidence. ESGE recommends the use of enhanced instructions for bowel preparation. Strong recommendation, moderate quality evidence. ESGE suggests adding oral simethicone to bowel preparation. Weak recommendation, moderate quality evidence. ESGE recommends split-dose bowel preparation for elective colonoscopy. Strong recommendation, high quality evidence. ESGE recommends, for patients undergoing afternoon colonoscopy, a same-day bowel preparation as an acceptable alternative to split dosing. Strong recommendation, high quality evidence. ESGE recommends to start the last dose of bowel preparation within 5 hours of colonoscopy, and to complete it at least 2 hours before the beginning of the procedure. Strong recommendation, moderate quality evidence. ESGE recommends the use of high volume or low volume PEG-based regimens as well as that of non-PEG-based agents that have been clinically validated for routine bowel preparation. In patients at risk for hydroelectrolyte disturbances, the choice of laxative should be individualized.Strong recommendation, moderate quality evidence.
Evidence-based treatment of Tourette’s disorder and chronic tic disorders

ABSTRACT Introduction: Chronic Tic Disorders and Tourette’s Disorder (collectively referred to as TD) are characterized by sudden, rapid, and repetitive motor movements or vocalizations called tics. Children, adolescents, and adults with TD often experience co-occurring psychiatric symptoms and impairments in multiple domains. As a result of tics and other symptoms, patients with TD can develop negative self-views, require considerable accommodations, and experience a poor quality of life. Therefore, the efficient and effective management of TD bears considerable importance. Areas covered: This expert review evaluated the empirical support for behavioral and pharmacological interventions based on the results of randomized controlled trials (RCTs). Behavioral interventions evaluated include habit reversal training (HRT), comprehensive behavioral intervention for tics (CBIT), and exposure response prevention (ERP). Reviewed pharmacological interventions included alpha-2 agonists, antipsychotics, and anticonvulsants. Expert opinion: This review identified several efficacious behavioral and pharmacological interventions for TD. However, several gaps in the management of TD include: (1) the access/availability of behavioral interventions, (2) novel and more efficacious treatment approaches, and (3) the development of more comprehensive interventions to manage TD. In order to advance the treatment of TD, additional research is necessary to efficiently, effectively, and comprehensively develop and evaluate new treatments for patients with TD.