Miracle-dz/UniFAR-FTUs huggingface dataset:
Xp11 Translocation Renal Cell Carcinomas (RCCs) With RBM10-TFE3 Gene Fusion Demonstrating Melanotic Features and Overlapping Morphology With t(6;11) RCC: Interest and Diagnostic Pitfall in Detecting a Paracentric Inversion of TFE3

Xp11 translocation renal cell carcinomas (RCC) are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathologic manifestations. Only 3 RBM10-TFE3 RCCs have been reported to date. Here, we added 4 cases of this rare type of tumors with clinicopathologic, immunohistochemical, molecular, and ultrastructural analyses. Most tumors had similar patterns with mixed architectures as follows: acinar, tubular and papillary patterns of epithelioid cells combined with sheets of small cells with “pseudorosette-like” architectures, mimicking the typical morphology of t(6;11) RCC. Cytoplasmic vacuolization, nuclear groove, and psammoma bodies were observed in most cases. Immunohistochemically, all 4 cases demonstrated moderate to strong immunoreactivity for TFE3, Cathepsin K, CD10, Ksp-cadherin, E-cadherin, P504S, RCC marker, PAX8 and vimentin, whereas negativity for TFEB, HMB45, and CK7. CKpan and Melan-A were at least focally expressed. The antibody to Ki-67 showed labeling of 3% to 8% (mean, 5%) of tumor cell nuclei. ;Of interest, several immunostainings demonstrated expression discrepancy in different histology patterns. RBM10-TFE3 fusion transcripts were identified in all cases by reverse transcription-polymerase chain reaction. By fluorescence in situ hybridization, all 4 cases showed unusual split signals with a distance <1 signal diameter (co-localized or subtle split signals) and usually had false-negative results. We also observed ultrastructures, including melanin pigment, nuclear groove, numerous glycogens, mitochondrion with areas of high electron density material, basement membrane material, and cell junctions with poor development. All 4 patients were alive with no evidence of recurrent disease. Our report adds to the known data regarding RBM10-TFE3 RCC.
FURTHER OBSERVATIONS ON THE THIRD HEART SOUND

At the last meeting of the Association of American Physicians 1 I made a few remarks concerning the frequency, especially in young people, of a third heart sound heard in early diastole somewhere between one-tenth and two and one-tenth of a second after the second sound of the heart, causing a characteristic protodiastolic gallop. This sound is especially common in the recumbent and left lateral postures and is more frequent in young individuals. It was pointed out that it was often associated with a palpable and sometimes even with a visible impulse, and this impulse was shown to be identical with the normal early diastolic elevation of the apex cardiogram. Further analogies were pointed out between this sound and that which characterizes the early diastolic gallop rhythm heard under various pathological conditions, especially in aortic insufficiency, in mitral stenosis and in adherent pericardium. Cardiograms and jugular tracings
The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders

The RAS proteins and their downstream pathways play pivotal roles in cell proliferation, differentiation, survival and cell death, but their physiological roles in human development had remained unknown. Noonan syndrome, Costello syndrome, and cardio‐facio‐cutaneous (CFC) syndrome are autosomal dominant multiple congenital anomaly syndromes characterized by a distinctive facial appearance, heart defects, musculocutaneous abnormalities, and mental retardation. A variety of mutations in protein tyrosine phosphatase, non‐receptor type 11(PTPN11) has been identified in 50% of Noonan patients. Specific mutations in PTPN11 have been identified in LEOPARD (multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) syndrome. In 2005, we discovered Harvey‐RAS (HRAS) germline mutations in patients with Costello syndrome. This discovery provided a clue to identification of germline mutations in Kirsten‐RAS (KRAS), BRAF and mitogen‐activated protein kinase kinase 1 and 2 (MAP2K1/MAP2K2) in patients with CFC syndrome. These genes encode molecules in the RAS/RAF/MEK/extracellular signal‐regulated kinase (ERK) pathway, leading to a new concept that clinically related disorders, i.e., Noonan, Costello, and CFC syndromes are caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. In the present review, we summarize mutations in HRAS, KRAS, BRAF, MAP2K1/2, and PTPN11, the phenotypes of patients with these mutations, the functional properties of mutants and animal models. Finally we suggest that disorders with mutations of molecules in the RAS/MAPK cascade (Noonan, LEOPARD, Costello, and CFC syndromes and neurofibromatosis type I) may be comprehensively termed “the RAS/MAPK syndromes. ” Details on mutations will be updated in the RAS/MAPK Syndromes Homepage (www.medgen.med.tohoku.ac.jp/RasMapk syndromes.html). Hum Mutat 0, 1–15, 2008. © 2008 Wiley‐Liss, Inc.
Comparison of home advantage in men's and women's football leagues in Europe

Abstract Most research into home advantage is based on men's sports. This article analyses home advantage in the women's domestic football leagues of Europe and makes a comparison with the corresponding men's football leagues. A total of 47,042 games were included. From 2004 to 2010, home advantage existed in the domestic women's soccer leagues of all 26 European countries analysed, ranging from 51.0% to 58.8% and averaging 54.2%. In every country, this was less than the corresponding men's home advantage which averaged 60.0%. Crowd effects, both on players and referees, and different gender perceptions of territorial protection are plausible reasons for the differences found. Using a regression model that controlled for the competitive balance of each league, as well as for crowd size, the Gender Gap Index, which quantifies the status of women in each country, was a significant predictor of the difference between men's and women's home advantage. As the status of women becomes closer to that of men within a country, the difference in home advantage is less between the men's and women's football leagues.
Hyperglycemia in the Hospital: Changing the Way We Think

69 A cardiac nurse, Jeanne Zerr, asked a question more than 10 years ago that has helped shape our current knowledge about hyperglycemia in the hospital setting. She wanted to know if high blood glucose levels were associated with increased thoracic wound infections. In 1997, Zerr and her colleagues in Portland, Ore. , published an article with the findings that “the incidence of deep wound infection in diabetic patients was reduced after implementation of a protocol to maintain mean blood glucose levels < 200 mg/dl in the immediate postoperative care. ” 1 Once the Portland group identified that hyperglycemia did affect wound healing, they developed a protocol to administer IV insulin to achieve tighter glucose control intraopertively and postoperatively. 2 They have continued to study the impact of hyperglycemia
Pathophysiology of Wound Healing

Abstract Tissue injury stimulates an ordered cascade of events, commencing with coagulation, through inflammation and culminating in repair. Whereas the initial responses are similar, subsequent events depend on the type of tissue as well as the degree of damage. Wound healing largely involves repair by replacement with connective tissue. Repair can be achieved by either resolution, regeneration or replacement (with scar tissue, sometimes called organization). Many cell types and inflammatory mediators such as cytokines are implicated in the repair process. In addition, there are both intrinsic and extrinsic factors that influence the way in which wounds heal. Striking differences between foetal and adult wound healing have recently been discovered and further research in this area may lead to improvements in our understanding and management of healing tissue.
Saddle height effects on pedal forces, joint mechanical work and kinematics of cyclists and triathletes

Abstract The effects of saddle height on pedal forces and joint kinetics (e.g. mechanical work) are unclear. Therefore, we assessed the effects of saddle height on pedal forces, joint mechanical work and kinematics in 12 cyclists and 12 triathletes. Four sub-maximal 2-min cycling trials (3.4 W/kg and 90 rpm) were conducted using preferred, low and high saddle heights (±10° knee flexion at 6 o'clock crank position from the individual preferred height) and an advocated optimal saddle height (25° knee flexion at 6 o'clock crank position). Right pedal forces and lower limb kinematics were compared using effect sizes (ES). Increases in saddle height (5% of preferred height, ES=4.6) resulted in large increases in index of effectiveness (7%, ES=1.2) at the optimal compared to the preferred saddle height for cyclists. Greater knee (11–15%, ES=1.6) and smaller hip (6–8%, ES=1.7) angles were observed at the low (cyclists and triathletes) and preferred (triathletes only) saddle heights compared to high and optimal saddle heights. Smaller hip angle (5%, ES=1.0) and greater hip range of motion (9%, ES=1.0) were observed at the preferred saddle height for triathletes compared to cyclists. Changes in saddle height up to 5% of preferred saddle height for cyclists and 7% for triathletes affected hip and knee angles but not joint mechanical work. Cyclists and triathletes would opt for saddle heights <5 and <7%, respectively, within a range of their existing saddle height.
A notational analysis of shot characteristics in top-level table tennis players

Abstract This study aimed to analyse selected shot characteristics in top-level table tennis matches, with a special focus on comparing the playing style of Asian and European players. Ten men's matches played by 20 top-ranked players (14 Asians and 6 Europeans) were analysed. The indicators examined were the area of ball bouncing for serves (n =918), and the stroke type, footwork type and shot outcome for other shots (n=3692). The interrelationships between variables were analysed using chi-squared tests, log-linear modelling and multiple correspondence analysis. A strong association was found between strokes and footwork types, with most stroke types executed each after specific footwork types. Furthermore, a clear tendency to have a positive, negative or neutral outcome was observed for each stroke type. When compared to Europeans, Asians used more frequently the most aggressive strokes and footwork types, confirming anecdotal claims on their particularly offensive playing style. Asians showed also a better serving effectiveness, often sending the ball in those areas of the table from which a counterattack is difficult to make. In summary, this study gives a systematic description of highly relevant technical and tactical characteristics in top-level table tennis, thus providing valuable information for coaches and performance analysts.
The 2010 British Association of Stroke Physicians Survey of Interventional Treatments for Stroke in the United Kingdom

Introduction The UK National Stroke Strategy (Department of Health 2007) states that patients should have access to a stroke service with neurointerventional capacity. This survey was conducted by the Clinical Standards Committee of the British Association of Stroke Physicians to get a snapshot of the availability of interventional treatments for stroke in the United Kingdom. Methods Questionnaires covering availability of endovascular treatments for stroke, e.g. intra-arterial thrombolysis and mechanical thrombectomy, were emailed to all British Association of Stroke Physicians members in October 2010. Where more than one response was received from the same hospital, the data were only entered once. If there was a discrepancy between different respondents for the same hospital, details were cross-checked with the respondents to ensure accuracy. Results Responses were received from 58 hospitals in England, Scotland, Wales, and Northern Ireland. Intra-arterial thrombolysis and/or mechanical thrombectomy were available in 23 hospitals. Of these, three had not performed any procedures in 2010. Twenty centres had conducted a mean (range) of eight (2–20) procedures during the 10-month period. Thirty-five hospitals were not offering endovascular treatments. Sixteen of these were not referring patients to centres which could provide interventional treatments. Hospitals offering endovascular treatments had a mean (range) of 5·2 (2–12) stroke physicians, 2·3 (0–4) interventional neuroradiologists, and 3·6 (0–9) noninterventional neuroradiologists. Only two hospitals providing interventions had four or more interventional neuroradiologists. Conclusions Only a small number of hospitals in the United Kingdom provide interventional treatments for stroke. Almost 50% of hospitals not providing interventions had no processes in place for referral to providers.
Morphologic and Molecular Evolutionary Pathways of Low Nuclear Grade Invasive Breast Cancers and Their Putative Precursor Lesions: Further Evidence to Support the Concept of Low Nuclear Grade Breast Neoplasia Family

We have previously provided evidence showing an association between some precursor lesions with low nuclear grade breast carcinomas (LNGBCs). In this study, further immunophenotypic support to our proposed route of pathogenesis of LNGBC and their precursor lesions was provided. Precursor lesions including columnar cell lesions, atypical ductal hyperplasia, ductal carcinoma in situ, usual epithelial hyperplasia, and lobular neoplasia were compared with matching “morphologically normal” terminal lobular duct units and matching invasive carcinoma. The epithelial cells in the putative precursor flat epithelial atypia, atypical ductal hyperplasia, lobular neoplasia, ductal carcinoma in situ lesions, and their coexisting LNGBC were negative for basal and myoepithelial markers, but positive for CK19/18/8, estrogen receptor (ER)-α, Bcl-2, and cyclin D1. The ER-α/ER-β expression ratio increased during carcinogenesis, as did expression of cyclin D1 and Bcl-2. p53 immunopositivity was found 3% in LNGBC versus 43% in high nuclear grade breast carcinoma (HNGBC), whereas ataxia telangiectasia mutated expression was absent or reduced in 22% of LNGBC versus 53% of HNGBC cases. In summary, our findings support the concept that flat epithelial atypia is the earliest morphologically identifiable nonobligate precursor lesion of LNGBC. These may represent a family of precursor, in situ and invasive neoplastic lesions belonging to the luminal “A” subclass of breast cancer. The balance between ER-α and ER-β expression may be important in driving cyclin D-1 and Bcl-2 expression. Ataxia telangiectasia mutated may be one of the alternative regulatory mechanisms to TP53 mutation or dysfunction in low-grade and high-grade breast carcinoma. Our findings support the concept that progression of LNGBC to HNGBC (basal-like or HER2+) phenotype is an unlikely biologic phenomenon.
Copy‐number variations (CNVs) of the human sex steroid metabolizing genes UGT2B17 and UGT2B28 and their associations with a UGT2B15 functional polymorphism

UGT2B17 and UGT2B28 are among the most commonly deleted genes in humans and encode members of the uridine diphosphate (UDP)‐glucuronosyltransferase 2B (UGT2B) subfamily. They are involved, along with UGT2B15, in the catabolism of sex‐steroid hormones. Despite the recent biomedical interest in UGT2B17 and UGT2B28 copy‐number variations (CNVs) within human populations, the impact of their gene dosage has been hampered by the lack of precise molecular identification of the common deletion breakpoints within high homology sequence regions on chromosome 4. We have characterized these common deletions and report their coexistence in Caucasians, along with the p.D85Y (rs1902023:G>T) functional polymorphism of UGT2B15. Segmental duplications of 4.9 kb for UGT2B17 and 6.8 kb for UGT2B28 comprise purine‐rich recombination sites located 117 kb and 108 kb apart on both ends of the deletions. CNVs of UGT2B17 and UGT2B28 occur in Caucasians at 27% and 13.5%, respectively. While only 43% have two copies of both genes, 57% harbor at least one deletion. Their co‐occurrence on 5% of chromosomes creates a 225‐kb genomic gap. CNVs of both UGT2B17 and UGT2B28, with the co‐occurrence of UGT2B15:p.D85Y, generate seven distinct haplotypes. Restricting the analyses to CNV of the UGT2B17 gene without evaluating UGT2B28 CNV, along with the genotype of UGT2B15, may over‐ or underestimate the impact of each gene under physiological conditions or disease states. Hum Mutat 30:1–10, 2009. © 2009 Wiley‐Liss, Inc.
Macrovascular disease in type 2 diabetes

Type 2 diabetes is associated with a 2 - 4-fold increased risk of cardiovascular disease (CVD), and over half the excess mortality in subjects with type 2 diabetes is due to this complication. The development of macrovascular disease in type 2 diabetes is partly related to chronic hyperglycaemia, but also to other associated atherogenic factors, including dyslipidaemia, oxidative stress, endothelial damage, hypercoaguability and activation of inflammatory pathways.
Do Prostatic Transition Zone Tumors Have a Distinct Morphology?

Previous studies have proposed that the morphologic spectrum of prostatic glands of variable size with tall columnar cells displaying basally oriented nuclei and clear to pale pink cytoplasm (TZ-LOOK) is characteristic of the well to moderately differentiated component of transition zone (TZ) tumors. However, the specificity of these findings has not been well studied. In a recent report, we identified dominant peripheral zone (PZ) and TZ tumors situated anterior to the prostatic urethra. Currently, we evaluate the histopathologic features of 215 dominant tumors, including 63 TZ and 73 anterior PZ lesions and an additional cohort of 79 posterior PZ tumors, in radical prostatectomy specimens, to identify the prevalence of this morphology in tumors of different zonal origin. Each dominant tumor was assigned a TZ-LOOK extent score of 0 to 4, with 0=no such morphology, 1=1% to 25%, 2=26% to 50%, 3=51% to 75%, and 4=>75%. Overall, 121/215 (56%) tumors showed some degree of this histology, including 56 of 63 (89%) TZ tumors and 65 of 152 (43%) PZ tumors (P<0.0001). Thirty-seven of 215 (17%) lesions had scores of 3 to 4, with 31 (84%) of these being of TZ origin. However, only 31/63 (49%) TZ tumors had >50% TZ-LOOK. Among PZ tumors, 6/152 (4%) had predominant (>50%) TZ-LOOK morphology, yet 23/152 (15%) of all PZ tumors and 23/65 (35%) of PZ tumors displaying any degree of TZ-LOOK had scores of 2 to 3 (>25%; nonfocal). In tumors of both zones with predominant (scores 3 to 4; >50%) TZ-LOOK histology, darker glands of usual acinar adenocarcinoma was often seen at the periphery. Conversely, in tumors with nonpredominant TZ-LOOK (scores 1 to 2; ≤50%), these glands were frequently admixed with small glands bearing dark cytoplasm. In this series, we demonstrate that some degree of TZ-LOOK morphology is twice as frequent in dominant TZ tumors than in PZ tumors. Tumors demonstrating >50% of this histology are very likely of TZ origin, but this scenario occurs in only half of TZ tumors. Importantly, the TZ-LOOK is nonfocal in up to 35% of PZ tumors exhibiting any degree of this morphology. Given this lack of specificity, caution should be exercised in assigning zone of origin based on this histologic appearance, especially in limited samples such as prostate needle biopsy.
Ground reaction forces of Olympic and World Championship race walkers

Abstract Race walking is an Olympic event where no visible loss of contact should occur and the knee must be straightened until midstance. The purpose of this study was to analyse ground reaction forces of world-class race walkers and associate them with key spatiotemporal variables. Nineteen athletes race walked along an indoor track and made contact with two force plates (1000 Hz) while being filmed using high-speed videography (100 Hz). Race walking speed was correlated with flight time (r = .46, p = .049) and flight distance (r = .69, p = .001). The knee's movement from hyperextension to flexion during late stance meant the vertical push-off force that followed midstance was smaller than the earlier loading peak (p < .001), resulting in a flattened profile. Athletes with narrower stride widths experienced reduced peak braking forces (r = .49, p = .046), peak propulsive forces (r = .54, p = .027), peak medial forces (r = .63, p = .007) and peak vertical push-off forces (r = .60, p = .011). Lower fluctuations in speed during stance were associated with higher stride frequencies (r = .69, p = .001), and highlighted the importance of avoiding too much braking in early stance. The flattened trajectory and consequential decrease in vertical propulsion might help the race walker avoid visible loss of contact (although non-visible flight times were useful in increasing stride length), while a narrow stride width was important in reducing peak forces in all three directions and could improve movement efficiency.
Quantifying positional and temporal movement patterns in professional rugby union using global positioning system

Abstract This study assessed the positional and temporal movement patterns of professional rugby union players during competition using global positioning system (GPS) units. GPS data were collected from 33 professional rugby players from 13 matches throughout the 2012–2013 season sampling at 10 Hz. Players wore GPS units from which information on distances, velocities, accelerations, exertion index, player load, contacts, sprinting and repeated high-intensity efforts (RHIE) were derived. Data files from players who played over 60 min (n = 112) were separated into five positional groups (tight and loose forwards; half, inside and outside backs) for match analysis. A further comparison of temporal changes in movement patterns was also performed using data files from those who played full games (n = 71). Significant positional differences were found for movement characteristics during performance (P < 0.05). Results demonstrate that inside and outside backs have greatest high-speed running demands; however, RHIE and contact demands are greatest in loose forwards during match play. Temporal analysis of all players displayed significant differences in player load, cruising and striding between halves, with measures of low- and high-intensity movement and acceleration/deceleration significantly declining throughout each half. Our data demonstrate significant positional differences for a number of key movement variables which provide a greater understanding of positional requirements of performance. This in turn may be used to develop progressive position-specific drills that elicit specific adaptations and provide objective measures of preparedness. Knowledge of performance changes may be used when developing drills and should be considered when monitoring and evaluating performance.