Miracle-dz/UniFAR-FTUs huggingface dataset:
MYH9-Related Disease: May-Hegglin Anomaly, Sebastian Syndrome, Fechtner Syndrome, and Epstein Syndrome Are not Distinct Entities but Represent a Variable Expression of a Single Illness

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term “MHY9-related disease,” which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects.
The multivalent activity of the tissue factor–thrombin pathway in thrombotic and non-thrombotic disorders as a target for therapeutic intervention

Importance of the field: Tissue factor (TF) is the key initiator of the coagulation cascade. The exposure of subendothelial TF after vessel injury to blood is a critical step in hemostasis and in the pathogenesis of arterial and venous thrombotic disorders. Moreover, an additional role for TF overexpression and subsequent generation of TF:FVIIa complex, FXa and thrombin have been recently emerged, contributing in non-thrombotic manifestations such as inflammation, cancer growth and fibrosis. Areas covered in this review: The multivalent role of TF and the above mentioned proteases in disease is reviewed, with focus on their implication in non-thrombotic disorders, as suggested by clinical and experimental data. Moreover, potential therapeutic interventions using anticoagulation agents are discussed. What the reader will gain: A better understanding of the pathogenic role of the TF–thrombin pathway in the pathogenesis of disease and the effect of anticoagulants in the treatment of such disorders. Take home message: The TF-thrombin pathway, apart from the initiation of hemostasis and thrombosis, exert intracellular signaling activity through protease-activated receptors, participating in inflammation and tumor biology. Both low-molecular-weight heparins and recently developed anticoagulants rise as candidates for the modification of biological functions associated with disorders like sepsis, ischemia–reperfusion or cancer growth and metastasis.
Sperm vacuoles cannot help to differentiate fertile men from infertile men with normal sperm parameter values.

STUDY QUESTION Can the assessment of sperm vacuoles at high magnification contribute to the explanation of idiopathic infertility? SUMMARY ANSWER The characteristics of sperm head vacuoles (number, area, position) are no different between fertile controls and patients with unexplained infertility. WHAT IS KNOWN ALREADY Until now, the assessment of sperm head vacuoles has been focused on a therapeutic goal in the intracytoplasmic morphologically selected sperm injection (IMSI) procedure, but it could be pertinent as a new diagnostic tool for the evaluation of male fertility. STUDY DESIGN, SIZE, DURATION This diagnostic test study with blind assessment included a population of 50 fertile men and 51 men with idiopathic infertility. They were selected from September 2011 to May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS Fertile men were within couples who had a spontaneous pregnancy in the last 2 years. Infertile men were within couples who had unexplained infertility and were consulting in our centre. After analysis of conventional sperm parameters, we investigated the number, position and area of sperm head vacuoles at high magnification (×6000) with interference contrast using an image analysis software. We also carried out a nuclear status analysis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay (TUNEL), sperm chromatin structure assay (SCSA) and aniline blue staining. MAIN RESULTS AND THE ROLE OF CHANCE Concerning the vacuoles data, we did not find any significant difference between the two populations. We found no significant correlation between the vacuolar parameters (mean number of vacuoles, relative vacuole area and percentage of spermatozoa with large vacuoles) and either conventional semen parameters, male age or the data from the aniline blue staining, SCSA assay and TUNEL assay. LIMITATIONS, REASONS FOR CAUTION Despite the fact all of the vacuole parameters values were identical in fertile and infertile men, we cannot totally exclude that a very small cause of unexplained infertilities could be related to an excess of sperm vacuoles. WIDER IMPLICATIONS OF THE FINDINGS In line with its widely debated use as a therapeutic tool, sperm vacuole assessment for diagnostic purposes does not seem useful. STUDY FUNDING/COMPETING INTERESTS The study was funded by a grant from Association pour la Recherche sur les Traitements de la Stérilité. There are no competing interests to declare.
Taken by storm : the media, public opinion, and U. S. foreign policy in the Gulf War

Preface Acknowledgments Introduction to the Media and Foreign Policy A View from the Press Marvin Kalb A View from the Military Thomas W. Kelly A View from the Academy Bernard C. Cohen 1: The News About Foreign Policy W. Lance Bennett 2: The Press as Prologue: Media Coverage of Saddam's Iraq, 1979-1990 Gladys Engel Lang, Kurt Lang 3: News and Historical Content: The Establishment Phase of the Persian Gulf Policy Debate William A. Dorman, Steven Livingston. 4: The News before the Storm: The Iraq War Debate and the Limits to Media Independence Robert M. Entman, Benjamin I. Page. 5: Domesticating a Crisis: Washington Newsbeats and Network News after the Iraq Invasion of Kuwait Timothy E. Cook 6: Strategic Public Diplomacy: Managing Kuwait's Image During the Gulf Conflict Jarol B. Manheim 7: The Gulf War as Popular Culture and Television Drama Daniel C. Hallin, Todd Gitlin. 8: News Coverage of the Gulf Crisis and Public Opinion: A Study of Agenda-Setting, Priming, and Framing Shanto Iyengar, Adam Simon. 9: Elite Leadership of Mass Opinion: New Evidence from the Gulf War John Zaller 10: Crisis, War, and Public Opinion: The Media and Public Support for the President Richard A. Brody 11: A Mutual Exploitation Model of Media Influence in U.S. Foreign Policy Patrick O'Heffernan 12: Strategic Politicians, Public Opinion, and the Gulf Crisis John Zaller 13: Just Deserts? David L. Paletz Appendix: Gulf Conflict Event Guide Contributors Index
Extent of retinal ganglion cell death in the frog Litoria moorei after optic nerve regeneration induced by lesions of different sizes

Some amphibian retinal ganglion cells die during optic nerve regeneration. Here we have investigated whether ganglion cell death in the frog Litoria moorei is associated with the lesion site. For one experimental series, the optic nerve lesion extended for 0.15 mm; in the other, it extended for 1.5 mm. The extent of ganglion cell death was estimated from cresyl violet‐stained whole mounts at 24 weeks post lesion. In other animals, individual regenerating axons were visualised in the optic nerve by horseradish peroxidase (HRP) labelling from 1 day to 24 weeks post lesion; counterstaining with cresyl violet allowed examination of cells that repopulated the lesion site. Ganglion cell numbers fell significantly more after an extensive than after a localised lesion, long‐term losses being 50% and 34%, respectively (P < 0.05). Regenerating axons were delayed in their passage across the cell‐poor extensive lesion compared with the relatively cell‐rich localised lesion. The differing rates of regeneration between series were matched by greater delay after extensive lesion in the return of visually guided behaviour as assessed by optokinetic horizontal head nystagmus. We suggest that delays in regeneration after an extensive lesion exacerbate ganglion cell death, indicating that conditions within the lesion are associated with the death of some ganglion cells. J. Comp. Neurol. 446:276–287, 2002. © 2002 Wiley‐Liss, Inc.
The Dysfunction of the Trabecular Meshwork During Glaucoma Course

Primary open angle glaucoma is a multi‐tissue disease that targets, in an ascending order, the trabecular meshwork, the optic nerve head, the lateral geniculate nuclei, and the visual cortex. Oxidative stress and vascular damage play major roles in triggering apoptotic cell loss in these tissues. Molecular alterations occurring in the ocular anterior chamber during the early course of glaucoma trigger this cell loss. These molecular events are mainly of endogenous origin and related to the long‐term accumulation of oxidative damages arising from mitochondrial failure and endothelial dysfunction. This situation results in decreased antioxidant defences in aqueous humour and apoptosis activation in trabecular meshwork cells as triggered by severe mitochondrial damage altering tissue function and integrity. The presence of neural proteins in glaucomatous aqueous humour indicate that a molecular interconnection exists between the anterior and the posterior chamber tissues. Trabecular meshwork and lamina cribrosa share a common neuro‐ectodermal embryological, which contribute to explain the interconnection between anterior and the posterior chamber during glaucoma pathogenesis. During glaucoma, proteins deriving from the damage occurring in endothelial trabecular meshwork cells are released into aqueous humour. Accordingly, aqueous humour composition is characterised in glaucomatous patients by the presence of proteins deriving from apoptosis activation, mitochondrial damage, loss of intercellular connections, antioxidant decrease. Many questions remain unanswered, but molecular events illuminate TM damage and indicate that trabecular cell protection plays a role in the treatment and prevention of glaucoma. J. Cell. Physiol. 230: 510–525, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Gait-cycle characteristics and running economy in elite Eritrean and European runners.

PURPOSE This study aimed to determine whether biomechanical characteristics such as ground-contact time, swing time, and stride length and frequency contribute to the exceptional running economy of East African runners. METHODS Seventeen elite long-distance runners (9 Eritrean, 8 European) performed an incremental maximal running test and 3 submaximal running bouts at 17, 19, and 21 km/h. During the tests, gas-exchange parameters were measured to determine maximal oxygen uptake (VO2max) and running economy (RE). In addition, ground-contact time, swing time, stride length, and stride frequency were measured. RESULTS The European runners had higher VO2max values than the Eritrean runners (77.2 ± 5.2 vs 73.5 ± 6.0 mL · kg-1 · min-1, P = .011, effect sizes [ES] = 0.65), although Eritrean runners were more economical at 19 km/h (191.4 ± 10.4 vs 205.9 ± 13.3 mL · kg-1 · min-1, P = .026, ES = 1.21). There were no differences between groups for ground-contact time, swing time, stride length, or stride frequency at any speed. Swing time was associated with running economy at 21 km/h in the Eritrean runners (r = .71, P = .033), but no other significant association was found between RE and biomechanical variables. Finally, best 10-km performance was significantly correlated with RE (r = -.57; P = .013). CONCLUSIONS Eritrean runners have superior RE compared with elite European runners. This appears to offset their inferior VO2max. However, the current data suggest that their better RE does not have a biomechanical basis. Other factors, not measured in the current study, may contribute to this RE advantage.
Evaluation of selected biochemical parameters in the saliva of young males using mobile phones

Abstract The biochemical status in the saliva of 12 males before/after using mobile phone has been evaluated. Radio frequency signals of 1800 MHz (continuous wave transmission, 217 Hz modulate and Global System for Mobile Communications [GSM – non-DTX]) with 1.09 w/kg specific absorption rate (SAR) value were used for 15 and 30 min. Cell phone radiation induced a significant increase of superoxide dismutase (SOD); there was a statistically significant effect of talking time on the levels of SOD, F(2, 33) = 8.084, p < 0.05, ω = 0.53. The trend analysis suggests a significant quadratic trend, F(1, 33) = 4.891, p < 0.05; indicating that after 15 min of talking the levels of SOD increased, but as talking time increased the SOD activity started to drop. In contrast to this, there was no statistically significant effect of talking time on the level of salivary albumin, cytochrome c, catalase or uric acid. Results suggest that exposure to electromagnetic radiation may exert an oxidative stress on human cells as evidenced by the increase in the concentration of the superoxide radical anion released in the saliva of cell phone users.
Mevalonate Promotes the Growth of Tumors Derived from Human Cancer Cells in Vivo and Stimulates Proliferation in Vitro with Enhanced Cyclin-dependent Kinase-2 Activity*

Malignant cells are known to have elevated rates of mevalonate synthesis because of increased levels and catalytic efficiency of 3-hydroxy-3-methylglutaryl-CoA reductase. Whether this increased mevalonate synthesis occurs as a consequence of increased requirements for a mevalonate-derived metabolite in response to rapid growth or whether mevalonate promotes the growth of tumor cells is unknown. To address this question, we administered mevalonate via miniosmotic pumps to nude mice inoculated with MDA-MB-435 human cancer cells. After 13 weeks of growth, tumors in mevalonate-treated mice were significantly larger than tumors in saline-treated, control mice (1.52 ± 0.26 g versus 0.81 ± 0.27 g respectively, p < 0.05). The cancer cells treated in culture with mevalonate also demonstrated increased proliferation rates associated with accelerated entry of cells into S phase. These cells had enhanced total and cyclin A-immunoprecipitable cyclin-dependent kinase-2 (CDK-2) activity, increased activating phosphorylation of CDK-2, and decreased inhibitory binding of CDK-2 to p21Cip1. Our findings demonstrate that mevalonate promotes tumor growth and suggest that an increase in mevalonate synthesis in extrahepatic tissues following cholesterol-lowering therapy may explain the elevated risk of cancer shown in some studies.
Phylogenetic relationships of North American garter snakes (Thamnophis) based on four mitochondrial genes: how much DNA sequence is enough?

The clade of garter snakes (Thamnophis) includes some of the most abundant and well-studied snakes in North America. However, phylogenetic relationships within this group have been little studied. We used DNA sequences of four mitochondrial genes (cytochrome b and NADH dehydrogenase subunits 1, 2, and 4) to estimate relationships among 29 of the 31 recognized species of Thamnophis plus the related species Adelophis foxi. Both maximum parsimony (MP) and maximum-likelihood (ML) analyses of all these genes combined produced well-resolved trees with moderate (70-89%) to strong (90-100%) bootstrap support for most clades. MP and ML trees were very similar, with no strongly supported conflict between the two analyses. These analyses identify a clade of 12 species largely restricted to México (the "Mexican clade"), and a clade containing 15 species that collectively range from Central America to southern Canada (the "widespread clade"). These two groups are identified as sister taxa in both MP and ML analyses. A clade consisting of the ribbon snakes (T. sauritus and T. proximus) and the common garter snake (T. sirtalis) is placed as the sister group to all other Thamnophis (i.e., the Mexican + widespread clades) in our analyses. High bootstrap proportions at several levels in the tree support the inclusion of both Thamnophis validus, which has traditionally been placed in the genus Nerodia, and the poorly known species Adelophis foxi within Thamnophis. We used randomly sampled characters (i.e., standard bootstrapping) and randomly sampled contiguous blocks of characters to examine the effect of number of characters on resolution of and support for relationships within Thamnophis using MP. In general, these analyses indicate that we have reached a point of strongly diminishing returns with respect to the effect of adding mtDNA sequence characters for the current set of taxa; our sample of 3809 mtDNA characters is apparently "enough. " The next steps to improve the phylogenetic estimate may be to add nuclear DNA sequences, morphology, or behavior, or to sequence additional mtDNA lineages within species.
Recollection of hypoxia symptoms between training events.

INTRODUCTION The well-established technique of mask-off hypoxia training in a hypobaric training environment elicits symptoms that are correlated with in-flight symptoms reported by aircrew. Aircrew receive training on recognition of symptoms and response early in their flying career and accomplish refresher training on a 5-yr cycle. The symptoms reported after acute hypoxia represent cognitive and psychomotor impairment. The purpose of this study was to evaluate the correlation of symptoms experienced during hypoxia training and recall of symptoms S from the training sessions 5 yr previously. METHODS A survey listing 18 symptoms of hypoxia and severity of condition was presented to 1123 aircrew attending refresher training at 10 U.S. Air Force Aerospace Physiology Training Units prior to and immediately following hypoxia training in the hypobaric chamber. RESULTS The five symptoms most commonly reported following hypoxia training are: lightheaded/dizzy, dizziness, mental confusion, visual impairment, and tingling. The hypoxia symptom "lightheaded/dizzy" recorded the highest frequency of all 18 symptoms. Lightheaded/dizzy frequencies for both previous and current hypoxia training were 67.2% and 72.3%, respectively. This symptom remained consistent throughout all data analysis, retaining the highest frequency in all levels of severity (mild, moderate, and extreme) for both the previous hypoxia training and current hypoxia training. DISCUSSION The similarity of symptoms recalled between hypoxia training events provides strong evidence that hypoxia training is an effective method of establishing recognized decrements that may influence performance in flight.
New Ways to Study Developmental Genes in Spore-Forming Bacteria

The regulated activation of numerous sets of genes in multiple chromosomal locations is a hallmark of cellular differentiation in both eukaryotes and prokaryotes. Certain species of bacteria that experience complex developmental cycles are especially attractive as systems in which to study the mechanisms of this kind of gene regulation because they are highly amenable to both biochemical and genetic approaches. Bacillus subtilis, which undergoes extensive cellular differentiation when it sporulates, is one such system. Many new methods are now available in this Gram-positive species for identifying, manipulating, and studying the regulation of genes involved in spore formation, including the use of transposable genetic elements that create gene fusions in vivo as an automatic consequence of insertions into genes.
Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis

This report investigates the influence of liver transplantation and concomitant immunosuppression on the course of progression of inflammatory bowel disease (IBD) and discusses statistical methodology appropriate for such settings. The data on 303 patients who underwent liver transplantation for primary sclerosing cholangitis (PSC) were analyzed using person‐time analysis and Cox regression, with the duration of IBD as the time variable and transplantation as a segmented time‐dependent covariate, to take into account both posttransplant and pretransplant history of IBD. The need for colectomy and appearance of colorectal cancer were taken as outcome measures. The only significant risk factor in the multivariate model for colectomy was transplantation itself, which increased the risk of colectomy due to intractable disease (Wald statistic; P = .001). None of the variables available for analysis were found to influence the risk of colon cancer significantly. Graphs showing the dependence of the instantaneous risk of cancer on the time from onset of IBD and its independence from the latter in the case of colectomy are presented. The use of a unique statistical methodology described for the first time in this setting led us to the somewhat surprising conclusion that transplantation and concomitant use of immunosuppression accelerate the progression of IBD. At the same time, transplantation does not affect the incidence of colorectal cancer. These results confirm the findings of some recent studies and can potentially shed new light on the disease pathogenesis.
Corticosteroid Pulse Combination Therapy for Refractory Kawasaki Disease: A Randomized Trial

Objective: This study examined the clinical efficacy and safety of intravenous methylprednisolone-pulse plus intravenous immunoglobulin (IVIG) combination therapy (IVMP+IVIG) for the initial treatment of patients predicted to have refractory Kawasaki disease (KD). Methods: One hundred twenty-two patients with KD were studied at Kitasato University. Refractory KD was predicted at diagnosis using the Egami score, and the patients were randomly divided to receive either IVMP+IVIG or IVIG alone. The Egami score is used to predict refractory KD patients before treatment using the patient’s age, days of illness, platelet count, C-reactive protein, and alanine aminotransferase level (cutoff: ≥3 points; 78% sensitivity and 76% specificity). Results: Forty-eight patients (39.3%) were predicted to have refractory KD on the basis of the Egami score. The predicted IVIG responders (n = 74) received the standard therapy. The 48 predicted refractory KD patients were randomly assigned to a single-IVIG group (n = 26) or an IVMP+IVIG group (n = 22). Nineteen of the 22 patients (86.4%) in the IVMP+IVIG group had a prompt defervescence compared with 6 of the 26 patients (23.1%) in the single-IVIG group. The number of patients who had a z score ≥2.5 at 1 month was significantly higher in the single-IVIG group than in the IVMP+IVIG group. No serious adverse events were observed in either treatment group. Conclusions: This study demonstrated that IVMP+IVIG therapy is safe and effective for KD patients predicted as refractory.