Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipidomic Analysis Reveals Specific Differences between Fibroblast and Keratinocyte Ceramide Profile of Patients with Psoriasis Vulgaris

Ceramides are important lipid metabolites for primal skin functions. There is increasing evidence that alteration of the profile and metabolism of ceramides is associated with skin diseases, such as psoriasis vulgaris. Most studies have reported alteration in ceramide content in the stratum corneum, but these have been scarcely reported for other skin layers. In the present work, we aimed to explore changes in the ceramide profile of fibroblasts and keratinocytes in patients with psoriasis vulgaris and healthy subjects. Using the reversed-phase liquid chromatography-quadrupole-time-of-flight-tandem-mass spectrometry (RPLC-QTOF-MS/MS) platform, we identified ceramide containing non-hydroxy fatty acid ([N]), α-hydroxy fatty acid ([A]), and esterified ω-hydroxy fatty acid ([EO]) and 3 sphingoid bases, dihydrosphingosine ([DS]), sphingosine ([S]), and phytosphingosine ([P]). We found that in the keratinocytes of patients with psoriasis, CER[NS], CER[NP], CER[AS], CER[ADS], CER[AP] and CER[EOS] tended to be expressed at higher relative levels, whereas CER[NDS] tended to be expressed with lower levels than in healthy subjects. In the case of fibroblasts, significant differences were observed, mainly in the three ceramide classes (CER[AS], CER[ADS] and CER[EOS]), which were expressed at significantly higher levels in patients with psoriasis. The most significant alteration in the fibroblasts involved elevated levels of CER[EOS] that contained ester-linked fatty acids. Our findings provide insights into the ceramide profile in the dermis and epidermis of patients with psoriasis and contribute for the research in this field, focusing on the role of keratinocyte-fibroblast crosstalk in the development of psoriasis vulgaris.
The Reflux Symptom Index and Symptom Overlap in Dysphonic Patients

The Reflux Symptom Index (RSI) is a validated quality‐of‐life instrument that quantifies symptoms associated with laryngopharyngeal reflux (LPR). Many dysphonic patients are managed empirically for reflux. In this study, we examine responses to the RSI in patients with dysphonia attributable to a variety of pathologies.
Oral HPV16 Prevalence in Oral Potentially Malignant Disorders and Oral Cavity Cancers

The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p < 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.
Kinase Inhibitor Treatment of Patients with Advanced Cancer Results in High Tumor Drug Concentrations and in Specific Alterations of the Tumor Phosphoproteome

Identification of predictive biomarkers for targeted therapies requires information on drug exposure at the target site as well as its effect on the signaling context of a tumor. To obtain more insight in the clinical mechanism of action of protein kinase inhibitors (PKIs), we studied tumor drug concentrations of protein kinase inhibitors (PKIs) and their effect on the tyrosine-(pTyr)-phosphoproteome in patients with advanced cancer. Tumor biopsies were obtained from 31 patients with advanced cancer before and after 2 weeks of treatment with sorafenib (SOR), erlotinib (ERL), dasatinib (DAS), vemurafenib (VEM), sunitinib (SUN) or everolimus (EVE). Tumor concentrations were determined by LC-MS/MS. pTyr-phosphoproteomics was performed by pTyr-immunoprecipitation followed by LC-MS/MS. Median tumor concentrations were 2–10 µM for SOR, ERL, DAS, SUN, EVE and >1 mM for VEM. These were 2–178 × higher than median plasma concentrations. Unsupervised hierarchical clustering of pTyr-phosphopeptide intensities revealed patient-specific clustering of pre- and on-treatment profiles. Drug-specific alterations of peptide phosphorylation was demonstrated by marginal overlap of robustly up- and downregulated phosphopeptides. These findings demonstrate that tumor drug concentrations are higher than anticipated and result in drug specific alterations of the phosphoproteome. Further development of phosphoproteomics-based personalized medicine is warranted.
Improved Physical Performance and Decreased Muscular and Oxidative Damage With Postlunch Napping After Partial Sleep Deprivation in Athletes.

PURPOSE To investigate the effects of napping after partial sleep deprivation (PSD) on reaction time, mood, and biochemical response to repeated-sprint exercise in athletes. METHODS Nine male judokas performed 4 test sessions in a counterbalanced and randomized order. Participants accomplished 1 control session after a normal sleep night (NSN) and 3 after PSD with (1) no nap, (2) ∼20-min nap (N20), and (3) ∼90-min nap (N90) opportunities. Test sessions included the running-based anaerobic sprint test, reaction time, Hooper index, and Epworth Sleepiness Scale. Muscle-damage biomarkers and antioxidant status were evaluated before and after exercise. RESULTS PSD decreased maximum (P < .001, d = 1.12), mean (P < .001, d = 1.33), and minimum (P < .001, d = 1.15) powers compared with NSN. However, N20 and N90 enhanced maximum power compared with PSD (P < .05, d = 0.54; P < .001, d = 1.06, respectively). Minimum power and mean power increased only after N90 (P < .001, d = 1.63; P < .001, d = 1.16, respectively). Epworth Sleepiness Scale increased after PSD (P < .001, d = 0.86) and decreased after N20 (P < .001, d = 1.36) and N90 (P < .001, d = 2.07). N20 reduced multiple-choice reaction time (P < .001, d = 0.61). Despite performance decrement, PSD increased postexercise aspartate aminotransferase (P < .001, d = 4.16) and decreased glutathione peroxidase (P < .001, d = 4.02) compared with NSN. However, the highest performances after N90 were accompanied with lesser aspartate aminotransferase (P < .001, d = 1.74) and higher glutathione peroxidase (P < .001, d = 0.86) compared with PSD. CONCLUSIONS Napping could be preventive against performance degradation caused by sleep loss. A short nap opportunity could be more beneficial when the subsequent effort is brief and requires frequent decision making. However, a longer nap opportunity could be preventive against muscle and oxidative damage, even for higher performances.
APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid

APOE4 exacerbates α-synuclein pathology in a synucleinopathy mouse model, and APOE4 genotype associates with increased α-synuclein pathology in humans. APOE4 beyond amyloid Although several genetic risk factors for neurodegenerative disorders have been identified, often the mechanistic aspect is not clear. Now, Zhao et al. and Davis et al. investigated whether apolipoprotein E4 (APOE4) genotype, a major genetic risk factor for neurodegenerative diseases, affected α-synuclein pathology in mouse models and Parkinson’s disease (PD) patients. Zhao et al. generated a mouse model of α-synucleinopathy and showed that APOE4 exacerbated α-synuclein pathology in the absence of amyloid. Davis et al. used a mouse model of PD and analyzed cognition in patients with PD to demonstrate that APOE4 directly regulated α-synuclein pathology and was associated with faster cognitive decline. These results provide insight into the mechanisms linking APOE genotype to neurodegenerative disorders. The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease mainly by driving amyloid-β pathology. Recently, APOE4 has also been found to be a genetic risk factor for Lewy body dementia (LBD), which includes dementia with Lewy bodies and Parkinson’s disease dementia. How APOE4 drives risk of LBD and whether it has a direct effect on α-synuclein pathology are not clear. Here, we generated a mouse model of synucleinopathy using an adeno-associated virus gene delivery of α-synuclein in human APOE-targeted replacement mice expressing APOE2, APOE3, or APOE4. We found that APOE4, but not APOE2 or APOE3, increased α-synuclein pathology, impaired behavioral performances, worsened neuronal and synaptic loss, and increased astrogliosis at 9 months of age. Transcriptomic profiling in APOE4-expressing α-synuclein mice highlighted altered lipid and energy metabolism and synapse-related pathways. We also observed an effect of APOE4 on α-synuclein pathology in human postmortem brains with LBD and minimal amyloid pathology. Our data demonstrate a pathogenic role of APOE4 in exacerbating α-synuclein pathology independent of amyloid, providing mechanistic insights into how APOE4 increases the risk of LBD.
Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection

Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut’s metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut’s microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.
Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses

Patients with chronic kidney disease (CKD) have altered physiologic processes, which result in different treatment outcomes compared with the general population. We aimed to systematically evaluate the efficacy of clinical interventions in reducing mortality of patients with CKD. We searched PubMed, MEDLINE, Embase, and Cochrane Database of Systematic Reviews for meta-analyses of randomized controlled trials (RCT) or observational studies (OS) studying the effect of treatment on all-cause mortality of patients with CKD. The credibility assessment was based on the random-effects summary estimate, heterogeneity, 95% prediction intervals, small study effects, excess significance, and credibility ceilings. Ninety-two articles yielded 130 unique meta-analyses. Convincing evidence from OSs supported mortality reduction with three treatments: angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers for patients not undergoing dialysis, warfarin for patients with atrial fibrillation not undergoing dialysis, and (at short-term) percutaneous coronary intervention compared to coronary artery bypass grafting for dialysis patients. Two treatment comparisons were supported by highly credible evidence from RCTs in terms of all-cause mortality. These were high-flux hemodialysis (HD) versus low-flux HD as a maintenance HD method and statin versus less statin or placebo for patients not undergoing dialysis. Most significant associations identified in OSs failed to be replicated in RCTs. Associations of high credibility from RCTs were in line with current guidelines. Given the heterogeneity of CKD, it seems hard to assume mortality reductions based on findings from OSs.
Extent of Mucosal Inflammation in Ulcerative Colitis Influences the Clinical Remission Induced by Vedolizumab

Randomized controlled clinical trials and real-life observations indicate that less than 50% of patients with Crohn’s disease (CD) or ulcerative colitis (UC) respond to vedolizumab, a humanized monoclonal antibody that blocks the α4β7 integrin. Since α4β7-expressing lymphocytes mainly infiltrate the left colon, we assessed whether localization of CD and UC influences vedolizumab-induced remission. One hundred and eighty-one patients (74 CD and 107 UC) receiving vedolizumab in 3 referral centers were retrospectively evaluated for clinical remission at week 14. Demographic and clinical characteristics were compared between remitters and non-responders, and multivariable multinomial analysis was performed to identify predictors of remission. Remission was achieved in 17 CD (23%) and 34 UC (32%) patients, respectively. In CD, localization of the lesions did not influence clinical remission. In UC, the remitters had more frequently a distal/left-sided colitis (21/34, 62%) as compared to the non-responders (9/47, 19%), and extensive colitis was more frequent in the non-responders (38/47, 81%) than in the remitters (13/34, 38%). The multivariable multinomial analysis showed that distal/left-sided colitis was associated with a higher probability of clinical remission while extensive colitis was inversely associated with induction of remission. Data indicate that UC patients with distal or left-sided colitis are more likely to achieve remission than patients with extensive colitis following vedolizumab treatment.
Geographical distribution of at fault drivers involved in fatal traffic collisions in Tehran, Iran

OBJECTIVES According to Traffic Police, about 35% of deaths and more than 50% of injuries caused by traffic collision in the roads of Tehran are among drivers and car occupants. This study was conducted to determine areas with the highest number of traffic collisions and perform spatial analysis of traffic collisions involving drivers in Tehran during April 2014 to March 2017. METHODS The present study was a cross-sectional and descriptive-analytic research. In this study, all traffic collision that driver was accounted (100 percent or less) for crash occurrence which resulted in the death of at least one person (driver, pedestrian or passenger) were included in the analyses. Geographic information system software was used to show spatial distribution of events from zoning maps. Moran index was used in the mathematical analysis in order to determine the distribution pattern of the events from and Getis-Ord G statistics was applied to analyze the hot spots (high risk points). RESULTS A total number of 519 traffic collisions were investigated in this study. Moreover, 283 cases (54.5%) of the incidents took place in direct routes and 236 cases (45.5%) occurred at intersections. The most frequent events were in the region 4 (57 cases) and the least frequent events were reported in the region 10 (6 cases). Moran statistics show that the distribution of the studied events significantly follows the cluster pattern (p<0.001). CONCLUSIONS The northeastern and northwest margins of Tehran are the most prone areas for drivers involved with traffic collisions leading to death. Most traffic collisions leading to death take place at highways located at the entrance and exit points of Tehran and highways in regions 2 and 5.
Comparison of Three Manual Therapy Techniques as Trigger Point Therapy for Chronic Nonspecific Low Back Pain: A Randomized Controlled Pilot Trial.

Objectives: This pilot study aimed to compare the efficacy of manual pressure release (MPR), strain counterstrain (SCS), and integrated neuromuscular inhibition technique (INIT) in the management of chronic nonspecific low back pain (LBP). Design: Single-blind, randomized, controlled pilot trial. Setting: Neurosurgery clinic. Subjects: Forty-eight patients (46 women; mean age, 35.47 ± 10.58 years) diagnosed chronic nonspecific LBP and who had at least one active myofascial trigger point (MTrP) in the quadratus lumborum, iliocostalis lumborum, gluteus maximus, gluteus medius, and gluteus minimus muscles were included. Interventions: Patients received a standard home exercise program in addition to the MPR technique (MPR group), SCS technique (SCS group), and INIT (INIT group) for 12 sessions (2 days/week for 6 weeks). Outcome measures: The primary outcome was the visual analog scale (VAS). The secondary outcomes were MTrP examination, pressure pain threshold, lumbar active range of motion, Oswestry Disability Index (ODI), Beck depression inventory, and state-trait anxiety inventory. Results: There is no significant difference in terms of the percentage of deactivated MTrPs after 1st session and 12th session between groups (p > 0.05), but the percentage of deactivated MTrPs was less in MPR group than other groups. The overall group-by-time interaction for the repeated measures analysis of variance was not significant for primary and secondary outcomes (p > 0.05), but the improvement in the VAS-activity and the ODI was slightly better in the SCS group compared with other groups. Conclusions: These preliminary findings, which might help provide a glimpse into the clinical effectiveness of three manual therapy techniques (MPR, SCS, and INIT) rather than statistical significance, indicated that SCS or INIT might provide slightly better improvement in pain during activity, deactivation of MTrPs, and disability related to pain in chronic nonspecific LBP.
Conformal Images of Borel Sets

For any holomorphic map in the unit disk, the set of radial limits at a Borel set on the unit circle is a Suslin‐analytic set. Here it is proved that, for a conformal map, this set is, in fact, Borel. As a consequence, the sets of accessible boundary points, of cut points and of transition points are Borel. In addition, it is shown that the set of end points is a Gδ‐set. 2000 Mathematics Subject Classification 28A05, 30C35.
A Hybrid VLC-RF Portable Phasor Measurement Unit for Deep Tunnels

In this manuscript we propose a hybrid Visible Light Communication and Radio Frequency (VLC-RF) scheme for the implementation of a portable Phaser Measurement Unit (PMU) for deep underground tunnels. Through computer simulations and laboratory measurements we are capable of providing Coordinated Universal Time (UTC) to the PMUs, as well as high accuracy positioning in a Global Positioning System (GPS) denied environment. The estimated PMU position, time stamp, and electrical power system measurements are sent to a central monitoring station using a radio frequency uplink with a data rate of hundreds of Kbps. Simulations and experimental measurements show that the proposed scheme can be used to control a large number of VLC-RF PMU devices inside a tunnel. The tests demonstrate the viability of the hybrid prototype, which will improve performance compared to commercial PMUs that lack these features.
Patient satisfaction with a new skin cancer teledermatology service

Rising numbers of two‐week‐wait (2WW) skin cancer referrals have caused increasing pressure on UK dermatology departments. Initiatives to address this include teledermatology. Previous studies have indicated good patient acceptability but most have focused on general dermatology rather than skin cancer referrals, and have taken place in rural settings, where teledermatology may be preferable.
Differential impacts of late gestational over–and undernutrition on adipose tissue traits and associated visceral obesity risk upon exposure to a postnatal high‐fat diet in adolescent sheep

We hypothesized that late gestation malnutrition differentially affects expandability of adipose tissues to predispose for early postnatal visceral adiposity. Twin‐lambs born to dams fed HIGH (150%/110% of required energy/protein, respectively), NORM (100% of requirements) or LOW (50% of NORM) diets during the last trimester were used. Postnatally, lambs were raised on moderate (CONV) or high‐carbohydrate‐high‐fat (HCHF) diets. Adipose tissues were sampled at autopsy at 6 months of age (~puberty) to characterize cellularity, adipocyte cross‐sectional area and gene expression patterns. HIGH and LOW compared to NORM lambs had reduced intrinsic (under CONV diet) cellularity in subcutaneous and mesenteric (particularly LOW), and reduced obesity‐induced (under HCHF diet) hyperplasia in subcutaneous, mesenteric and perirenal (particularly HIGH) adipose tissues. This corresponded with more pronounced HCHF diet‐induced hypertrophy in mesenteric (particularly LOW), perirenal (particularly HIGH) and subcutaneous (particularly HIGH) adipose tissues, and tissue‐specific reductions in mRNA expressions for lipid metabolism, angiogenesis and adipose development. Gene expression for inflammation and lipid metabolism markers were increased and decreased, respectively, in HCHF lambs (HCHF lambs became obese) in all tissues. Both prenatal over‐ and undernutrition predisposed for abdominal adiposity and extreme perirenal hypertrophy due to reduced intrinsic (observed under CONV diet) cellularity and impaired ability of subcutaneous, mesenteric and perirenal adipose tissues to expand by hyperplasia rather than hypertrophy on an obesogenic (HCHF) diet.
Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study

Background: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab. Methods: MCT was defined as an asymptomatic absolute decrease in LVEF of ≥ 10 percentage units to >50%. Treatment consisted of enalapril 2.5 mg bid and carvedilol 3.75 mg bid, which were up-titrated to 10 mg bid for the enalapril and 6.25 mg bid of carvedilol. In patients receiving study drug, the primary study end-point was LVEF recovery, which was defined as a post-trastuzumab LVEF returning to no less than −5 percentage points of the baseline value. Results: 103 patients were enrolled, 100 started trastuzumab, and 98 completed the planned treatment. Sixteen patients (16%) had MCT and received study drugs until trastuzumab completion. None of these patients achieved a post-trastuzumab LVEF recovery. Nevertheless, treated patients had significantly higher median LVEF recovery from nadir to post-trastuzumab LVEF in (8% points vs. 4% points, respectively, p = 0.004), resulting in no difference in post-treatment LVEF values compared to patients without MCT. Conclusion: Treatment of MCT with ACEis and BB allows faster LVEF recovery from nadir values and should be further studied in this setting.