Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatigue in patients with hereditary neuropathy with liability to pressure palsies

Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) is caused by a heterozygous deletion of peripheral myelin protein‐22 (PMP22) gene resulting in focal sensorimotor deficits. Our lab has identified a disruption of myelin junctions in excessively permeable myelin that impairs action potential propagation. This mechanism is expected to cause fatigue in patients with HNPP. Therefore, the objective was to characterize fatigue in patients with HNPP and determine the relationship of fatigue to nerve pathology, disability, and quality of life.
Ureteral Stent Encrustation: Epidemiology, Pathophysiology, Management, and Current Technology.

PURPOSE Encrustation is a common phenomenon that can occur following placement of a ureteral stent into the urinary tract, and it can lead to serious complications. The following review addresses the mechanism of encrustation, the management of these stents and the newest technology developed to mitigate this issue. MATERIALS AND METHODS We performed a comprehensive literature search on stent encrustation including peer-reviewed publications, public product listings, and material on current and future stent technology. RESULTS The mechanism of encrustation is complex and multifaceted, including dwell time, patient specific risk factors, conditioning film formation, biofilm formation and mineral deposition. Several technological developments in stent materials and coatings may play a role in reducing the risk of stent encrustation. It is important to identify the extent of stent encrustation and plan treatment strategies accordingly. We propose a novel treatment algorithm for the management encrusted ureteral stents. CONCLUSIONS The ubiquity of ureteral stents in urology practice mandates updated knowledge about the prevention of stent encrustation, identification of high-risk patients, and preparedness for removal using multimodal techniques.
Outcome of FOLFOX and Modified DCF Chemotherapy Regimen in Patients with Advanced Gastric Adenocarcinoma.

OBJECTIVES Chemotherapy is used as an indispensable therapy for advanced gastric cancer. Different chemotherapy regimens have been used for this purpose. Toxicity due to the Chemotherapy drugs is one limiting factor. In this study we aim to compare the efficacy and toxicity of two regimens FOLFOX (leucoverin, 5-fluorouracil and oxaliplatin) and modified DCF (mDCF) (docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced gastric adenocarcinoma. METHODS In this analytical cross-sectional study, 47 patients treated with FOLFOX regimen and 57 patients treated with mDCF regimen were recruited, Patients in both groups were compared for demographic findings, response rate, mortality rate, overall survival (OS) and progression free survival (PFS). RESULTS In FOLFOX and mDCF group, complete response (CR) occurred in 4.3% and 5.3%, partial response (PR) in 42.6% and 29.8%, stable disease in 34% and 52.6% and disease progression in 19.1% and 12.3%, respectively (p=0.25). Overall response rate was 48.9% and 56.1%, respectively. There was no significant difference between two regimens in OS and PFS (p=0.22). mDCF compared to FOLFOX had significantly higher hematologic, gastrointestinal complications, as well as creatinine rise, stomatitis and hair loss, but peripheral neuropathy was significantly lower. CONCLUSION The results of current study showed that in patients with advanced gastric adenocarcinoma, FOLFOX regimen compared to mDCF regimen have similar ORR, OS and PFS. Toxicity rate are also lower in FOLFOX group, thus it seems a better regimen for chemotherapy.
Bending Shoots Stimulates Flowering and Influences Hormone Levels in Lateral Buds of Japanese Pear

Flower development of the lateral buds was accelerated in Japanese pear ( Pyrus pyrifolia (Burm.) Nak. ) when vertical shoots were bent at a 45 ° angle in late June. The indole-3-acetic acid (IAA) concentration in lateral buds on vertical (control) shoots increased in mid-July, while remaining nearly constant in bent shoots. The abscisic acid (ABA) concentration of buds in bent shoots rose between 4 July and 15 Aug., whereas control shoots exhibited an increase in concentration followed by a decline. Gibberellin 4+7 (GA4+7) concentration was high on 16 June, and then declined by 4 July, with the decline being greatest in bent shoots. Gibberellin 4+7 concentration was higher in the buds on vertical shoots than in those on bent shoots for much of July. The concentrations of zeatin- type cytokinins (CKs) in lateral buds were higher in bent shoots than in vertical shoots. Bending of pear shoots may weaken competition between buds and other organs through altering hormone levels in lateral buds, resulting in acceleration of flower development.
Clinical presentation, diagnosis and management of therapy‐related hematological disorders in women with epithelial ovarian cancer treated with chemotherapy and poly‐ADP‐ribose polymerase inhibitors: A single‐center experience

We investigated the occurrence and management of therapy‐related hematological disorders (tr‐HDs) in women with epithelial ovarian cancer (EOC) exposed to poly‐ADP‐ribose polymerase inhibitors (PARPi), after previous chemotherapy. We analyzed 130 consecutive EOC patients treated with PARPi at the European Institute of Oncology, Milan. In line with the literature, overall survival of the entire population was 37% at 5.5 years (89% were advanced stages). Cell blood counts were collected prior to start PARPi, at each new cycle and at monthly intervals. Patients displaying persistent and/or marked hematological abnormalities underwent bone marrow evaluation, with cytogenetic and molecular analysis. Nine patients (6,9%) developed tr‐HDs, after a median 22.8 months of PARPi exposure. Two patients died early and could not be treated. Two patients have no indication for active treatment and are presently under close hematological monitoring. Five patients underwent chemotherapy followed, in three cases, by allogeneic hematopoietic transplantation: three patients are in complete remission of their hematological and gynecological malignancies at 13, 19, and 25 months; the remaining two patients died due to progression of their hematological disease. We show the potential risk of hematological disorders in EOC patients treated with chemotherapy and prolonged PARPi therapy. In our series, tr‐HDs incidence was higher compared to recent reports in large series. Our observations suggest careful monitoring in order to conclusively define, on large series and prolonged follow‐up, the actual risk of tr‐HDs in patients under PARPi. Notably, prompt diagnosis of hematological abnormalities and appropriate management allow achievement of remission from severe hematological complications, at least in most patients.
EVALUATION OF COMET ASSAY AND MICRONUCLEI TEST AS GENOTOXIC ASSAY IN CHANNA PUNCTATUS

Dose dependent genotoxic effect of malathion pesticide on Channa punctatus was evaluated by micronuclei test assay. Single cell gel electrophoresis (comet assay) was also standardised by using Channa punctatus The resultsconfirm that both assays are sensitive to detect genotoxicity in fishes even at very low level of pollutants in aquatic medium. Thus these assays can be used as genotoxic bioassays for monitoring pollutants in aquatic medium.
Survey on the Presence of Malassezia spp. in Healthy Rabbit Ear Canals

Malassezia spp. have rarely been reported in rodents and lagomorphs. In 2011, Malassezia cuniculi was described in two rabbits. Further microscopic studies showed M. cuniculi-like yeasts in more than 50% of samples from rabbits’ ear canals, but no isolation was made. The present study details the presence of Malassezia spp. and tries to typify it from ear canals of healthy rabbits. Seventy-eight half-breed rabbits from rural farms and 98 companion dwarf rabbits from northern Italy were considered. A first attempt to screen ear swabs was performed by microscopic and cultural examination on Sabouraud Glucose Agar (SGA), modified Dixon Agar (mDA) and Leeming and Notman Agar (LNA). Additionally, ear swabs from eight further microscopically positive rabbits for M. cuniculi-like cells, were used for both isolation on LNA medium and nine of its variants and for DNA extraction, PCR and sequencing. The microscopic observation of the swabs of the screened 168 rabbits highlighted the presence of yeasts in one or both of the external ear canals of 98 rabbits (58.3%). Rabbits used for meat production were more frequently diagnosed positive than pet rabbits (P = 0.001), and young ones were more often positive compared to rabbits older than 3 months (P = 0.027). No yeast growth was observed in culture. From the eight selected rabbits, Malassezia isolation failed both on LNA and on the modified mediums. Sequences of ~300 bp fragments of 18s rDNA, obtained by PCR from swabs, showed 99.9% identity with Malassezia phylotype 131 described from human ear canals. As Malassezia-like yeasts have been observed in more than half of the examined population, its colonization of ear meatus can be considered as physiological in rabbits. The results outline how much remains to be discovered on Malassezia as a component of the skin mycobiota of rabbits and that the use of the culture examination alone is not the best choice to detect Malassezia-like yeasts in rabbits.
Promoter Hypermethylation and Expression Changes of BRCA1 Gene in a Cohort of Sporadic Breast Cancer Cases among Pakistani Population

Objective: The purpose of our study was to determine the frequency of BRCA1 promoter hypermethylation and its association with expression changes of BRCA1 and main morphological features in sporadic breast cancer. Methods: A retrospective review of cases was performed to select those with specific morphological features suggestive of breast cancer. BRCA1 promoter hypermethylation and changes in protein expression were evaluated in 30 cancerous and 30 non-cancerous tissue samples. A tissue microarray containing samples from normal and tumor tissue was prepared and stained for BRCA1 protein expression using a commercially available monoclonal antibody against BRCA1 (Ab-1) clone MS110 (mAb). DNA was extracted using modified protocol of Qiagen minikit. DNA was modified using a Bisulfite conversion kit and BRCA1 hypermethylation was detected using a methylation specific PCR. Results: Promoter hypermethylation was negative in 30 non-cancerous samples with retained BRCA1 protein expression. Methylation was positive in 82.6% (n=19/23) of the sporadic cancer samples that had loss of BRCA1 expression and 50% (n=2/4) of the samples with equivocal protein expression. Methylation was negative in all the sporadic breast cancer samples (n=3/3) with retained protein expression. Chi-square analysis showed significant association of BRCA1 promoter methylation with decreased protein expression (P=0.016) and co-existence of loss of BRCA1 and Her2neu at chromosome 17 (P=0.026) respectively. There was no significant association of BRCA1 methylation with morphological features excluding necrosis (P=0.035). Promoter hypermethylation was found to be most common (68.75%) among Triple Negative Breast Cancer (TNBC) females less than 45 years old. Conclusion: Our study suggests that BRCA1 promoter hypermethylation has significant contribution in sporadic breast carcinogenesis. This was our preliminary study in Pakistan. Further studies aimed to determine the in-depth mechanisms of BRCA1 epigenetics in TNBC. BRCAness enriched phenotype in TNBC might be used as a biomarker for the exploitation of therapeutic and clinical implications.
Mechanism of ventricular premature beats elicited by left stellate ganglion stimulation during acute ischaemia of the anterior left ventricle

Abstract Aims Enhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This ‘injury’ current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the ‘injury’ current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion. Methods and results In nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization. Conclusion LSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.
Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort

Background Ultra-processed food (UPF) consumption has increased drastically worldwide and already represents 50%–60% of total daily energy intake in several high-income countries. In the meantime, the prevalence of overweight and obesity has risen continuously during the last century. The objective of this study was to investigate the associations between UPF consumption and the risk of overweight and obesity, as well as change in body mass index (BMI), in a large French cohort. Methods and findings A total of 110,260 adult participants (≥18 years old, mean baseline age = 43.1 [SD 14.6] years; 78.2% women) from the French prospective population-based NutriNet-Santé cohort (2009–2019) were included. Dietary intakes were collected at baseline using repeated and validated 24-hour dietary records linked to a food composition database that included >3,500 different food items, each categorized according to their degree of processing by the NOVA classification. Associations between the proportion of UPF in the diet and BMI change during follow-up were assessed using linear mixed models. Associations with risk of overweight and obesity were assessed using Cox proportional hazard models. After adjusting for age, sex, educational level, marital status, physical activity, smoking status, alcohol intake, number of 24-hour dietary records, and energy intake, we observed a positive association between UPF intake and gain in BMI (β Time × UPF = 0.02 for an absolute increment of 10 in the percentage of UPF in the diet, P < 0.001). UPF intake was associated with a higher risk of overweight (n = 7,063 overweight participants; hazard ratio (HR) for an absolute increase of 10% of UPFs in the diet = 1.11, 95% CI: 1.08–1.14; P < 0.001) and obesity (n = 3,066 incident obese participants; HR10% = 1.09 (1.05–1.13); P < 0.001). These results remained statistically significant after adjustment for the nutritional quality of the diet and energy intake. Study limitations include possible selection bias, potential residual confounding due to the observational design, and a possible item misclassification according to the level of processing. Nonetheless, robustness was tested and verified using a large panel of sensitivity analyses. Conclusions In this large observational prospective study, higher consumption of UPF was associated with gain in BMI and higher risks of overweight and obesity. Public health authorities in several countries recently started to recommend privileging unprocessed/minimally processed foods and limiting UPF consumption. Trial registration ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644)
Management of SARS‐CoV‐2 pneumonia

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection has rapidly spread throughout the world since December 2019 to become a global public health emergency for the elevated deaths and hospitalizations in Intensive Care Units. The severity spectrum of SARS‐CoV‐2 pneumonia ranges from mild to severe clinical conditions. The clinical course of SARS‐CoV‐2 disease is correlated with multiple factors including host characteristics (genetics, immune status, age, and general health), viral load and, above all, the host distribution of the airways and lungs of the viral receptor cells. In this review, we will briefly summarize the current knowledge of the characteristics and management of coronavirus disease 2019‐pneumonia. However, other studies are needed to better understand the pathogenetic mechanisms induced by SARS‐Cov‐2 infection, and to evaluate the long‐term consequences of the virus on the lungs.
Supply and demand for plasma‐derived medicinal products ‐ A critical reassessment amid the COVID‐19 pandemic

Plasma-derived medicinal products (PDMP) play an integral role in medical treatment and prophylaxis. Most plasma used for manufacturing medicinal products is collected as source plasma by apheresis from donors in dedicated plasma collection centers. The United States is the largest contributor to the global source plasma supply; most other countries depend on the import of plasma or plasma-derived medicinal products. Plasma supply and demand are held in a fine balance. The 2019 shortage of IVIG showed the fragility of the system. The COVID-19 pandemic has introduced additional stress on the plasma supply. At the same time demand for plasma-derived medicinal products has further increased as they are tested as a potential treatment for this new disease. Transfusions of convalescent plasma, hyperimmune globulins derived from convalescent plasma and immunoglobulins are under investigation, with promising early safety and efficacy signals. Supply will have to be protected and boosted and demand will have to be managed fairly and effectively. If this issue is unaddressed, shortages of plasma-derived medicinal products, such as IVIG, have to be expected by the beginning of 2021.
Chitosan in Sparkling Wines Produced by the Traditional Method: Influence of Its Presence during the Secondary Fermentation

Chitosan is a polysaccharide admitted in winemaking as clarifying, antimicrobial and chelating agent. In addition, evidence about its antioxidant and radical scavenging activities have been recently reported in wine conditions. As an insoluble adjuvant, chitosan efficacy also depends on the duration of its contact with the matrix. In the case of sparkling wines obtained following the traditional method, for instance, the addition of chitosan before the secondary fermentation would permit a prolonged contact of the polymer with wine and yeast lees. However, information on the effects of this practice on final products is totally unknown. In this work, the addition of chitosan during the secondary fermentation of a traditional sparkling wine production method has been investigated for its effects on both the physicochemical and sensory characteristics of the resulting wine. After 12 months of “sur lie” maturation, chitosan was found to increase the protein and amino acid content of wines up to about 50% and 9%, respectively, with limited change of phenolics and organic acids. Volatile compounds, particularly esters, were increased as well, which was reflected by higher values for fruity character and aroma intensity after sensory tests. Foaming features, evaluated by sensory and physical measurements, were also positively affected.
Dietary Complex and Slow Digestive Carbohydrates Prevent Fat Deposits During Catch-Up Growth in Rats

A nutritional growth retardation study, which closely resembles the nutritional observations in children who consumed insufficient total energy to maintain normal growth, was conducted. In this study, a nutritional stress in weanling rats placed on restricted balanced diet for 4 weeks is produced, followed by a food recovery period of 4 weeks using two enriched diets that differ mainly in the slow (SDC) or fast (RDC) digestibility and complexity of their carbohydrates. After re-feeding with the RDC diet, animals showed the negative effects of an early caloric restriction: an increase in adiposity combined with poorer muscle performance, insulin resistance and, metabolic inflexibility. These effects were avoided by the SDC diet, as was evidenced by a lower adiposity associated with a decrease in fatty acid synthase expression in adipose tissue. The improved muscle performance of the SDC group was based on an increase in myocyte enhancer factor 2D (MEF2D) and creatine kinase as markers of muscle differentiation as well as better insulin sensitivity, enhanced glucose uptake, and increased metabolic flexibility. In the liver, the SDC diet promoted glycogen storage and decreased fatty acid synthesis. Therefore, the SDC diet prevents the catch-up fat phenotype through synergistic metabolic adaptations in adipose tissue, muscle, and liver. These coordinated adaptations lead to better muscle performance and a decrease in the fat/lean ratio in animals, which could prevent long-term negative metabolic alterations such as obesity, insulin resistance, dyslipidemia, and liver fat deposits later in life.
Depiction of tumor stemlike features and underlying relationships with hazard immune infiltrations based on large prostate cancer cohorts

Prostate cancer stemness (PCS) cells have been reported to drive tumor progression, recurrence and drug resistance. However, there is lacking systematical assessment of stemlike indices and associations with immunological properties in prostate adenocarcinoma (PRAD). We thus collected 7 PRAD cohorts with 1465 men and calculated the stemlike indices for each sample using one-class logistic regression machine learning algorithm. We selected the mRNAsi to quantify the stemlike indices that correlated significantly with prognosis and accordingly identified 21 PCS-related CpG loci and 13 pivotal signature. The 13-gene based PCS model possessed high predictive significance for progression-free survival (PFS) that was trained and validated in 7 independent cohorts. Meanwhile, we conducted consensus clustering and classified the total cohorts into 5 PCS clusters with distinct outcomes. Samples in PCScluster5 possessed the highest stemness fractions and suffered from the worst prognosis. Additionally, we implemented the CIBERSORT algorithm to infer the differential abundance across 5 PCS clusters. The activated immune cells (CD8+ T cell and dendritic cells) infiltrated significantly less in PCScluster5 than other clusters, supporting the negative regulations between stemlike indices and anticancer immunity. High mRNAsi was also found to be associated with up-regulation of immunosuppressive checkpoints, like PDL1. Lastly, we used the Connectivity Map (CMap) resource to screen potential compounds for targeting PRAD stemness, including the top hits of cell cycle inhibitor and FOXM1 inhibitor. Taken together, our study comprehensively evaluated the PRAD stemlike indices based on large cohorts and established a 13-gene based classifier for predicting prognosis or potential strategies for stemness treatment.