Miracle-dz/UniFAR-FTUs huggingface dataset:
The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages of T-cell differentiation arrest. We have revisited a cohort of pediatric T-ALL, in order to test if immunophenotypes associated with molecular alterations would predict the patient's outcome. Genetic mutations, translocations and copy number alterations were identified through Sanger sequencing, RT-PCR, FISH and multiplex ligation-dependent probe amplification (MLPA). We defined 8 immunophenotypic T-ALL subtypes through multiparametric flow cytometry: early T-cell precursor (ETP, n = 27), immature (n = 38), early cortical (n = 15), cortical (n = 50), late cortical (n = 53), CD4/CD8 double negative mature (n = 31), double positive mature (n = 35) and simple positive mature (n = 31) T-ALL. Deletions (del) or amplifications (amp) in at least one gene were observed in 87% of cases. The most frequent gene alterations were CDKN2A/B del (71.4%), NOTCH1 mut (47.6%) and FBXW7 mut (17%). ETP-ALL had frequent FLT3 mut (22.2%) and SUZ12 del (16.7%) (p < 0.001), while CDKN2A/B del were rarely found in this subtype (p < 0.001). The early cortical T-ALL subtype had high frequencies of NOTCH1 mut and IL7R mut (71%, 28.6%, respectively), whereas, mature T-ALL with double positive CD4/CD8 had the highest frequencies of STIL-TAL1 (36.7%), LEF1 del (27.3%) and CASP8AP2 del (22.7%). The co-existence of two groups of T-ALL with NOTCH1 mut /IL7R mut, and with TLX3/SUZ12 del /NF1 del/IL7R mut, were characterized with statistical significance (p < 0.05) but only STIL-TAL1 (pOS 47.5%) and NOTCH1 WT/FBXW7 WT (pOS 55.3%) are predictors of poor T-ALL outcomes. In conclusion, we have observed that 8 T-ALL subgroups are characterized by distinct molecular profiles. The mutations in NOTCH1/FBXW7 and STIL-TAL1 rearrangement had a prognostic impact, independent of immunophenotype.
Practical guidelines to minimise language and cognitive confounds in the diagnosis of CAPD: a brief tutorial

Abstract Objective: To provide audiologists with strategies to minimise confounding cognitive and language processing variables and accurately diagnose central auditory processing disorder (CAPD). Design: Tutorial. Study sample: None. Results: Strategies are reviewed to minimise confounding cognitive and language processing variables and accurately diagnose CAPD. Conclusions: Differential diagnosis is exceedingly important and can be quite challenging. Distinguishing between two or more conditions presenting with similar symptoms or attributes requires multidisciplinary, comprehensive assessment. To ensure appropriate interventions, the audiologist is a member of the multidisciplinary team responsible for determining whether there is an auditory component to other presenting deficits or whether one condition is responsible for the symptoms seen in another. Choice of tests should be guided both by the symptoms of the affected individual, as established in an in-depth interview and case history, the individual’s age and primary language, and by the specific deficits reported to be associated with specific clinical presentations. Knowing which tests are available, their strengths and limitations, the processes assessed, task and response requirements, and the areas of the central auditory nervous system (CANS) to which each test is most sensitive provides the audiologist with critical information to assist in the differential diagnostic process.
The Clinical Difference in the Platelet Counts between Liver Cirrhosis with Nonalcoholic Fatty Liver Disease and Hepatitis C Virus

Objective The rate of platelet count reduction appears to differ among different liver diseases. In the present study, we investigated the difference in the platelet counts of patients with nonalcoholic fatty liver disease (NAFLD) and those with chronic liver disease due to hepatitis C virus (CLD-HCV). Methods The study population included 620 patients with NAFLD and 405 patients with CLD-HCV, all of whom were diagnosed by liver biopsy. The relationships between the grade of fibrosis and the platelet count in the two diseases were compared. The optimal cut-off value for the diagnosis of liver cirrhosis (LC) was measured. The relationships between the platelet count and anti-platelet antibodies, the serum thrombopoietin level, the grade of splenomegaly and liver stiffness were also investigated in both LC groups. Results In NAFLD patients, the platelet count was significantly higher at each grade of fibrosis in comparison to CLD-HCV. The optimal cut-off value for the diagnosis of LC was 16.0×104/μL [sensitivity, 86.7%; specificity, 87.6%; area under the curve (AUC), 0.930] in NAFLD and 12.7×104/μL (sensitivity, 57.8%; specificity, 88.2%; AUC, 0.863) in CLD-HCV. No anti-platelet antibodies were detected in patients with either type of LC. The serum thrombopoietin levels, the distribution of splenomegaly grades, and liver stiffness did not differ between the two LC groups to a statistically significant extent. As the splenomegaly grade increased, the platelet count decreased. Conclusion The optimal cut-off values for diagnosing LC differed between the two diseases and should be determined separately. The reason for the difference in platelet reduction is still unclear, and requires further investigation.
Parathyroid Autotransplantation During thyroid Surgery. Where we are? A Systematic Review on Indications and Results

ABSTRACT Introduction: Hypoparathyroidism still represents an important concern in thyroid surgery. Careful dissection with identification and preservation of parathyroid glands in situ remains the best way to maintain gland vitality and avoid post-operative failure. Nevertheless, parathyroid glands are still inadvertently removed in up to 11% of cases. Parathyroid autotransplantation may represent the only way to restore parathyroid gland functionality in case of inadvertent removal or devascularization during thyroid surgery. Despite this, there is still no agreement on the effectiveness of this procedure. The present systematic review is focused on the mainly debated matters regarding the procedure, indications, technique and results. Methods: This review has been carried out according to PRISMA statement and checklist. The research item was: (((parathyroid autotransplantation[Title]) OR parathyroid reimplantation[Title]) NOT hyperparathyroidism[Title]) AND english[Language]. Results: A total of 31 studies have been found according to limitations already described, reporting from 4 to 890 procedures, with a total amount of 4088 PA. Among these studies, there are only 7 prospective case-series evaluations, 2 prospective randomized trials, while the other 22 studies are retrospective evaluations. The main concerns are: when and how to perform autotransplantation; in which anatomical site; which result to be expected, and how to manage and control the graft. Conslusions: Parathyroid autotransplantatin is an important tool to avoid or minimize the risk for hypoparathyroidism following thyroid surgery in selected cases. Parathormone assay can help the surgeon to determine when reimplantation is indicated or not. Further studies could theoretically give definitive results.
Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease.

BACKGROUND Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease. Because atherosclerosis is considered a low-grade inflammatory disease, some feeding trials have analyzed the effects of cocoa (an important source of flavonoids) on inflammatory biomarkers, but the results have been controversial. OBJECTIVE The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients. DESIGN Forty-two high-risk volunteers (19 men and 23 women; mean +/- SD age: 69.7 +/- 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated. RESULTS Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake. CONCLUSIONS These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis. This trial was registered in the Current Controlled Trials at London, International Standard Randomized Controlled Trial Number, at controlled-trials.com as ISRCTN75176807.
Relationship between occurrence of surgical complications and hospital finances.

IMPORTANCE The effect of surgical complications on hospital finances is unclear. OBJECTIVE To determine the relationship between major surgical complications and per-encounter hospital costs and revenues by payer type. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of administrative data for all inpatient surgical discharges during 2010 from a nonprofit 12-hospital system in the southern United States. Discharges were categorized by principal procedure and occurrence of 1 or more postsurgical complications, using International Classification of Diseases, Ninth Revision, diagnosis and procedure codes. Nine common surgical procedures and 10 major complications across 4 payer types were analyzed. Hospital costs and revenue at discharge were obtained from hospital accounting systems and classified by payer type. MAIN OUTCOMES AND MEASURES Hospital costs, revenues, and contribution margin (defined as revenue minus variable expenses) were compared for patients with and without surgical complications according to payer type. RESULTS Of 34,256 surgical discharges, 1820 patients (5.3%; 95% CI, 4.4%-6.4%) experienced 1 or more postsurgical complications. Compared with absence of complications, complications were associated with a $39,017 (95% CI, $20,069-$50,394; P < .001) higher contribution margin per patient with private insurance ($55,953 vs $16,936) and a $1749 (95% CI, $976-$3287; P < .001) higher contribution margin per patient with Medicare ($3629 vs $1880). For this hospital system in which private insurers covered 40% of patients (13,544), Medicare covered 45% (15,406), Medicaid covered 4% (1336), and self-payment covered 6% (2202), occurrence of complications was associated with an $8084 (95% CI, $4903-$9740; P < .001) higher contribution margin per patient ($15,726 vs $7642) and with a $7435 lower per-patient total margin (95% CI, $5103-$10,507; P < .001) ($1013 vs -$6422). CONCLUSIONS AND RELEVANCE In this hospital system, the occurrence of postsurgical complications was associated with a higher per-encounter hospital contribution margin for patients covered by Medicare and private insurance but a lower one for patients covered by Medicaid and who self-paid. Depending on payer mix, many hospitals have the potential for adverse near-term financial consequences for decreasing postsurgical complications.
Predictors of biochemical failure in patients undergoing prostate whole‐gland salvage cryotherapy: a novel risk stratification model

Perspectives on salvage treatment in prostate cancer Salvage treatment represents the second radical treatment after the first attempt has failed. Up to 38% of patients will be informed after primary radical prostatectomy (P-RP) that their margins were positive, that recurrence is likely and that adjuvant salvage radiotherapy (S-RT) should be considered [1]. The percentage of patients with evidence of recurrence after primary radiotherapy (P-RT) depends on whether and how follow-up biopsies are taken. Positive biopsy rates as high as 67% have been reported [2]. Ablative technologies should not be considered as salvage therapy methods unless they are recognized as a true primary treatment. High-intensity focused ultrasonography and cryoablation may be used as primary treatments in carefully selected patients, although only cryoablation is recommended in the current European Association of Urology guidelines [3].
Female Athlete Issues for the Team Physician: A Consensus Statement-2017 Update.

This document provides an updated overview of select musculoskeletal and medical issues that are important to team physicians who are responsible for the medical care of female athletes. It is not intended as a standard of care and should not be interpreted as such. This document is only a guide and, as such, is of a general nature, consistent with the reasonable, objective practice of the health care professional. Individual treatment will turn on the specific facts and circumstances presented to the physician. Adequate insurance should be in place to help protect the physician, the athlete, and the sponsoring organization. This statement was developed by a collaboration of six major professional associations concerned about clinical sports medicine issues; they have committed to forming an ongoing project-based alliance to bring together sports medicine organizations to best serve active people and athletes. The organizations are American Academy of Family Physicians, American Academy of Orthopaedic Surgeons, American College of Sports Medicine, American Medical Society for Sports Medicine, American Orthopaedic Society for Sports Medicine, and the American Osteopathic Academy of Sports Medicine.
Skin Conformal Polymer Electrodes for Clinical ECG and EEG Recordings

Preparation‐free and skin compliant biopotential electrodes with high recording quality enable wearables for future healthcare and the Internet of Humans. Here, super‐soft and self‐adhesive electrodes are presented for use on dry and hairy skin without skin preparation or attachment pressure. The electrodes show a skin‐contact impedance of 50 kΩ cm2 at 10 Hz that is comparable to clinical standard gel electrodes and lower than existing dry electrodes. Microstructured electrodes inspired by grasshopper feet adhere repeatedly to the skin with a force of up to 0.1 N cm−2 without further attachment even during strong movement or deformation of the skin. Skin compliance and adhesive properties of the electrodes result in reduction of noise and motion artifacts superior to other dry electrodes reaching the performance of commercial gel electrodes. The signal quality is demonstrated by recording a high‐fidelity electrocardiograms of a swimmer in water. Furthermore, an electrode with soft macropillars is used to detect alpha activity in the electroencephalograms from the back of the head through dense hair. Compared to gel electrodes, the soft biopotential electrodes are nearly imperceptible to the wearer and cause no skin irritations even after hours of application. The electrodes presented here could combine unobtrusive and long‐term biopotential recordings with clinical‐grade signal performance.
The diverse CB 1 and CB 2 receptor pharmacology of three plant cannabinoids : D 9-tetrahydrocannabinol , cannabidiol and D 9-tetrahydrocannabivarin

Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, ( )-trans-D-tetrahydrocannabinol (D-THC), ( )cannabidiol (CBD) and ( )-trans-D-tetrahydrocannabivarin (D-THCV), interact with cannabinoid CB1 and CB2 receptors. D-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. D -THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. D-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by D-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which D-THC, CBD and D-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids. British Journal of Pharmacology (2008) 153, 199–215; doi:10.1038/sj.bjp. 0707442; published online 10 September 2007
Consistency in Brain Activation Predicts Success in Transfer

Recent brain imaging studies have provided new insight into how students are able to extend their previous problem solving skills to new but similar problems. It is still unclear, however, what the basis is of individual differences in their success at transfer. In this study, 75 subjects had been trained to solve a set of mathematical problems before they were put into the fMRI scanner, where they were challenged to solve modified versions of familiar problems. A hidden semi-Markov model identified the sequential structure of thought when solving the problems. Analyzing the patterns of brain activity over the sequence of states identified by the model, we observed that subjects who showed consistent brain patterns performed better. This consistency refers to both how consistently subjects respond to different problems (within-subject consistency), and how brain responses of a given subject deviate from the population average (between-subjects consistency). Early withinsubject consistency is particularly predictive of later performance in the experiment.
Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression of Hypoxia Inducible Factors 2α (HIF-2α) and 30 kDa HIV Tat-Interacting Protein (TIP30)

Background Regorafenib (RGF) is the drug of choice for treating hepatic carcinoma (HCC), but the drug has drawbacks due to resistance and associated adverse effects. Thus, it becomes crucial to understand the causal ‘map’ of the resistance conferred by RGF, so that its clinical potency can be amplified, resulting in enhanced efficacy with reduced adverse effects. Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells. Based on the literature, the present investigation was carried out to reveal the effect of RGF and MTF, with an expectation that MTF can synergize therapeutic potential as well reduce chances of resistance. Material/Methods Protein expression of hypoxia inducible factors (HIF)-2α, 30 kDa HIV Tat-interacting protein (TIP30), E-cadherin, N-cadherin, and pAMPK were assessed by Western blot analysis. RGF and MTF were exposed to MHCC97H cell and proliferation was quantified by assay of cell viability. Gene silencing and chromatin immunoprecipitation assay were done to reveal the relationship between TIP30 and HIF-2α. The impact of RGF and MTF together on postoperative recurrence and lung metastasis of hepatocellular carcinoma was investigated using tumor engrafted mice after administration of MTF and RGF once daily for 35 days. Immunohistochemistry was used to reveal CD31, Ki67, and TUNEL. Results The results suggested MTF-RGF combination lowered expression of HIF-2α gene silencing and suggested increased TIP30 after reduction of HIF-2α. The chromatin immunoprecipitation study indicated that under hypoxia, HIF-2α could bind with TIP30 promoter. Cell number quantification (CCK8), viable cell count, and apoptosis data (using Annexin V-FITC) indicated co-administration of RGF and MTF reduced cell proliferation, encouraging cell apoptosis, and reduced epithelial-mesenchymal transition course. Thus, in orthotopic mice, the RGF-MTF combination exhibited substantial reduction of HCC in lung metastasis and postoperative relapse. Conclusions MTF can enhance the potential of RGF and inhibit the recurrence and metastasis of HCC after postoperative liver section by regulating the levels of TIP30 and HIF-2α.
The Utrecht Work Engagement Scale for Students (UWES–9S): Factorial Validity, Reliability, and Measurement Invariance in a Chilean Sample of Undergraduate University Students

This brief report examines the within–network construct validity of the UWES–9S in a convenience sample of 1502 Chilean students (52% were female) ranging between 18 and 25 years old. The results of confirmatory factor analysis supported a solution with three related factors that fit significantly better than a one-factor solution. The three subscales (i.e., vigor, dedication, and absorption) and the overall UWES–9S showed satisfactory internal consistency. The results of multiple–group confirmatory factor analysis supported gender invariance. Overall, the UWES–9S was found to be a reliable and valid scale to assess academic engagement in Chilean undergraduate university students.
Phylogenomic Rhizobium Species Are Structured by a Continuum of Diversity and Genomic Clusters

The bacterial genus Rhizobium comprises diverse symbiotic nitrogen-fixing species associated with the roots of plants in the Leguminosae family. Multiple genomic clusters defined by whole genome comparisons occur within Rhizobium, but their equivalence to species is controversial. In this study we investigated such genomic clusters to ascertain their significance in a species phylogeny context. Phylogenomic inferences based on complete sets of ribosomal proteins and stringent core genome markers revealed the main lineages of Rhizobium. The clades corresponding to R. etli and R. leguminosarum species show several genomic clusters with average genomic nucleotide identities (ANI > 95%), and a continuum of divergent strains, respectively. They were found to be inversely correlated with the genetic distance estimated from concatenated ribosomal proteins. We uncovered evidence of a Rhizobium pangenome that was greatly expanded, both in its chromosomes and plasmids. Despite the variability of extra-chromosomal elements, our genomic comparisons revealed only a few chromid and plasmid families. The presence/absence profile of genes in the complete Rhizobium genomes agreed with the phylogenomic pattern of species divergence. Symbiotic genes were distributed according to the principal phylogenomic Rhizobium clades but did not resolve genome clusters within the clades. We distinguished some types of symbiotic plasmids within Rhizobium that displayed different rates of synonymous nucleotide substitutions in comparison to chromosomal genes. Symbiotic plasmids may have been repeatedly transferred horizontally between strains and species, in the process displacing and substituting pre-existing symbiotic plasmids. In summary, the results indicate that Rhizobium genomic clusters, as defined by whole genomic identities, might be part of a continuous process of evolutionary divergence that includes the core and the extrachromosomal elements leading to species formation.