Miracle-dz/UniFAR-FTUs huggingface dataset:
A study on analysis of Heart Rate Variability in hypertensive individuals

Introduction: Hypertension is a major risk factor for coronary artery disease, stroke and heart failure. Autonomic nervous system (ANS) dysfunction is an important factor in the development and progression of hypertension. Heart rate variability (HRV) is a simple, sensitive and non-invasive tool to monitor the cardiovascular ANS function. Thus, the present study was chosen as a simple tool to assess the sympathovagal balance by analysing the HRV changes in hypertensive individuals. Aims & Objectives: To analyse Heart Rate Variability (HRV) in hypertensive individuals. Materials & Methods: The study was conducted on 30 normotensive and 30 hypertensive subjects (BP≥140/90 mm Hg, according to JNC-7 classification). Lead-II ECG was recorded using the instrument PHYSIOPAC-PP4, MEDICAID system, Chandigarh and HRV analysis was done using Kubios HRV analyser. Spectral indices of HRV such as total power (TP), normalized low frequency power (LFnu), normalized high frequency power (HFnu), ratio of low frequency power to high frequency power (LF-HF ratio), standard deviation of normal-to-normal RR intervals (SDNN), root mean square successive difference (rMSSD) and the proportion of NN50 to the total number of NN intervals (pNN50) were assessed. Results: Our results showed significantly reduced HFnu (p<0.05), SDNN (p<0.05), rMSSD (p<0.05) and pNN50 (p<0.05) in hypertensive individuals. LFnu and LF-HF ratio was significantly increased (p<0.05) in hypertensive individuals. Conclusion: There is an increased sympathetic activity and a decreased vagal tone associated with hypertension. Thus, HRV can be used as a routine screening test to predict the future risk of hypertension at an earlier stage and also for a better prognosis during treatment.
Epithelial and Mesenchymal Cell Biology Involvement of Wnt Signaling in Dermal Fibroblasts

Pachydermoperiostosis (PDP) is a rare disease characterized by unique phenotypes of the skin and bone, such as thick skin, implying that it may be caused by dysregulation of mesenchymal cells. The aim of this study is to examine the roles of dermal fibroblasts in the pathogenesis of pachydermia in association with Wnt signaling. The numbers of cultured fibroblasts were compared between healthy donors and PDP patients, and mRNA expression profiles in cultured dermal fibroblasts were examined by DNA microarray analysis and real-time reverse transcription-PCR. DKK1 and -catenin protein expressions were also evaluated by immunohistochemistry in the skin. To evaluate the in vivo roles of DKK1 in mice, DKK1 small interfering RNA was injected to the ears. We found that PDP fibroblasts proliferated more than control fibroblasts and that mRNA expression of a Wnt signaling antagonist, DKK1 , was much lower in PDP fibroblasts than in normal ones. Consistently, decreased expression of DKK1 in fibroblasts and enhanced expression of -catenin were noted in PDP patients. Moreover, recombinant human DKK1 protein decreased the proliferation of dermal fibroblasts. In accord with the above human studies, intradermal injections of DKK1 small interfering RNA into mouse ears increased ear thickness as seen in PDP. Our findings suggest that enhanced Wnt signaling contributes to the development of pachydermia by enhancing dermal fibroblast functions. (Am J Pathol 2010, 176:721–732; DOI: 10.2353/ajpath.2010.090454)
Molecular Pathogenesis of Genetic and Inherited Diseases Delayed Cardiomyopathy in Dystrophin Deficient mdx Mice Relies on Intrinsic Glutathione Resource

From Institut National de la Santé et de la Recherche Médicale,* Institut Mondor de Recherche Biomédicale, Créteil; Université Paris-Est, Faculté de Médecine, Créteil; Plate-Forme d’Imagerie Cellulaire et Tissulaire, Créteil; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Henri Mondor-Albert Chenevier, Fédération de Cardiologie, Créteil; Université Denis Diderot, Paris; Institut National de la Santé et de la Recherche Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris; Assistance Publique-Hôpitaux de Paris, Institut de Myologie, Centre de Référence des Maladies Rares Neuromusculaires, Groupe Hospitalier Pitié-Salpétrière, Paris; and Université Paris Descartes,** Assistance Publique-Hôpitaux de Paris, Département de Cardiologie, Groupe Hospitalier Cochin, Paris, France.
Cooperation of side population cells with CD133 to enrich cancer stem cells in a laryngeal cancer cell line

The identification of cancer stem cells (CSCs) in laryngeal cancer remains a dilemma. Our previous studies identified CD133(+) subgroup and side population (SP) cells in the laryngeal cancer cell line, human epithelial type‐2 (Hep‐2). Although both cell types shared some tumor‐initiating properties, they were heterogeneous. In this study, we further enriched CSCs from this cell line.
Impact of High-Sensitivity Troponin I Testing with Sex-Specific Cutoffs on the Diagnosis of Acute Myocardial Infarction.

BACKGROUND High-sensitivity cardiac troponin I (hs-cTnI) assays show sex-dependent differences in the 99th percentile of healthy populations, with concentrations in women approximately 50% lower. The adoption of sex-specific cutoffs seems appropriate, although it is not yet clear what effect these will have on acute myocardial infarction (AMI) diagnosis and management. METHODS We conducted a retrospective pre- and postchangeover analysis of troponin I testing in the 6 months before and after moving from the contemporary Abbott Architect TnI assay (cTnI) to hs-cTnI at 2 tertiary centers in Australia and New Zealand. The cTnI cutoff was 30 ng/L for both sexes, whereas a female-specific cutoff of 16 ng/L was adopted upon changeover to hsTnI. RESULTS Changeover from the cTnI assay to the hs-cTnI assay increased the number of female patients with increased troponin I concentrations at both sites (from 29.7% to 34.9% and from 22.4% to 30.8%; P < 0.001). There was no statistically significant change in the number of men with increased concentrations in the same time period (P = 0.09). The increased percentage of women with increased troponin I was not associated with an increase in the number of women with AMI diagnoses at either center. Angiographic data available from 1 center showed no change in the percentage of angiograms performed in women. CONCLUSIONS Although increasing the proportion of women with increased troponin I, adopting sex-specific cutoffs with the hs-cTnI assay did not lead to an increase in AMI diagnoses in females, or in the number of women undergoing angiography.
Tumorigenesis and Neoplastic Progression A Novel Mouse Model of Inflammatory Bowel Disease Links Mammalian Target of Rapamycin-Dependent Hyperproliferation of Colonic Epithelium to Inflammation-Associated Tumorigenesis

From the Department of Medicine, Oncology Division,* Albert Einstein Cancer Center; Montefiore Medical Center, the Departments of Pathology, and Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York; the Department of Biological Sciences and Geology, Queensborough-CUNY, Bayside, New York; and The Roslin Institute, The University of Edinburgh, Roslin, Midlothian, United Kingdom
Serum Cortisol: An Up-To-Date Assessment of Routine Assay Performance.

BACKGROUND Accurate serum cortisol quantification is required for the correct diagnosis and management of adrenal pathologies. Presently, most laboratories use immunoassay to measure serum cortisol with proficiency schemes demonstrating a wide dispersion of results. Here, we investigate the effects of sex, matrix, and antibody specificity on serum cortisol quantification in 6 routine assays. METHODS Surplus serum was obtained before disposal and the following cohorts were created: males, nonpregnant females, pregnant patients, and patients prescribed either metyrapone or prednisolone. Samples were anonymized and distributed to collaborating laboratories for cortisol analysis by 6 routine assays. Cortisol was also measured in all samples using an LC-MS/MS candidate reference measurement procedure (cRMP); cortisol-binding globulin (CBG) was measured in the nonpregnant and pregnant female cohorts. RESULTS Considerable inter- and intraassay variation was observed across the male and nonpregnant female cohorts relative to the cRMP. Four immunoassays underrecovered cortisol in the pregnancy cohort, and CBG was found to be significantly higher in this cohort than in the nonpregnant females. In the metyrapone and prednisolone cohorts, all immunoassays overestimated cortisol. The first generation Roche E170 and Siemens Centaur XP were particularly prone to overestimation. In all cohorts the routine LC-MS/MS assay aligned extremely well with the cRMP. CONCLUSIONS Despite the clinical importance of serum cortisol, the performance of routine immunoassays remains highly variable. Accurate quantification is compromised by both matrix effects and antibody specificity. Underpinning this study with a cRMP has highlighted the deficiencies in standardization across routine cortisol immunoassays.
Immunopathology and Infectious Diseases Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction , and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine

Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably , vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM. (Am J Pathol 2010, 176:1306–1315; DOI: 10.2353/ajpath.2010.090691)
Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study.

BACKGROUND Chronic kidney disease (CKD) is associated with an increased cardiovascular disease mortality risk. It is, however, less clear at what point in the course from normal kidney function to CKD the association with cardiovascular disease appears. Studying the associations of estimated glomerular filtration rate (eGFR) and albuminuria with biomarkers of (subclinical) cardiac injury in a population without substantial CKD may clarify this issue. METHODS We examined the cross-sectional associations of eGFR and urinary albumin excretion (UAE) with high-sensitivity cardiac troponin (hs-cTn) T, hs-cTnI, and N-terminal probrain natriuretic-peptide (NT-proBNP) in 3103 individuals from a population-based diabetes-enriched cohort study. RESULTS After adjustment for potential confounders, eGFR and UAE were associated with these biomarkers of cardiac injury, even at levels that do not fulfill the CKD criteria. For example, eGFR 60-<90 mL · min-1 ·(1.73 m2)-1 [vs ≥90 mL · min-1 · (1.73 m2)-1] was associated with a [ratio (95% CI)] 1.21 (1.17-1.26), 1.14 (1.07-1.20), and 1.19 (1.12-1.27) times higher hs-cTnT, hs-cTnI, and NT-proBNP, respectively. The association of eGFR with hs-cTnT was statistically significantly stronger than that with hs-cTnI. In addition, UAE 15-<30 mg/24 h (vs <15 mg/24 h) was associated with a 1.04 (0.98-1.10), 1.08 (1.00-1.18), and 1.07 (0.96-1.18) times higher hs-cTnT, hs-cTnI, and NT-proBNP, respectively. CONCLUSIONS eGFR and albuminuria were already associated with biomarkers of (subclinical) cardiac injury at levels that do not fulfill the CKD criteria. Although reduced renal elimination may partly underlie the associations of eGFR, these findings support the concept that eGFR and albuminuria are, over their entire range, associated with cardiac injury.
TRAUMATIC BITEMPORAL HEMIANOPIA (SAGITTAL TEARING OF THE OPTIC CHIASMA)

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Estudos epidemiológicos entre grupos indígenas de Rondônia III: . Parasitoses intestinais nas populações dos vales dos rios Guaporé e Mamoré

Foram realizados 639 exames parasitologicos das fezes na populacao indigena dos vales dos rios Guapore e Mamore, no Estado de Rondonia, constituida predominantemente por indios Pacaas-Novos e outros grupos populacionalmente menores (Massaca, Ajuru, Canoe, Jabuti, Mequem, Tupari e Macurap). Os resultados foram os seguintes: Ascaris lumbricoides (21,3%), Trichuris trichiura (1,6%), ancilostomideos (12,2%), Strongyloides stercoralis (3,9%), Enterobius vermicularis (2,0%), Hymenolepis nana (0,3%), Capillaria sp. (0,2%), Giardia lamblia (12,7%) e Entamoeba hystolitica (8,8%). Os dados obtidos sao comparados com os de outros autores que realizaram inqueritos semelhantes em outras areas indigenas da Amazonia.
Cardiovascular , Pulmonary and Renal Pathology Protease-Activated Receptor-2 Induces Myofibroblast Differentiation and Tissue Factor Up-Regulation during Bleomycin-Induced Lung Injury Potential Role in Pulmonary Fibrosis

From the Center for Experimental and Molecular Medicine,* and the Departments of Pulmonology, and Pathology, Academic Medical Center, Amsterdam, The Netherlands; the Department of Cell Biology, University of Groningen, Groningen, The Netherlands; the Division of Biopharmaceutics The Leiden Amsterdam Center for Drug Research, Leiden University, Gorlaeus Laboratories, Leiden, The Netherlands; the Departments of Pulmonology, Pathology,** and Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; and the Department of Histopathology, Royal Brompton Hospital, London, United Kingdom
Comparative Analysis of the Role of Prostate Specific Antigen Parameters in Clinical Practice

Introduction: Serum prostate specific antigen at the cutoff levels of 4 ng/ml has low specificity for prostate cancer. We evaluated various PSA parameters (i.e., total PSA density [tPSAD], free PSA density [fPSAD], the ratio of free to total PSA [f/t ratio], and age-specific PSA) in terms of cancer diagnosis and reducing the number of negative results for prostatic biopsies. Materials and Methods: A series of 305 patients was studied. Serum tPSA and fPSA levels were measured. Prostate volume was measured with transrectal ultrasound, and sextant biopsies were performed. The f/t ratio, tPSAD, and fPSAD were calculated. Sensitivity and specificity were calculated for age-specific PSA. Receiver operating characteristic curve analysis was used to analyze the diagnostic performance of these PSA parameters. A subpopulation of patients with serum PSA levels between 4 and 10 ng/ml also was analyzed with a specific view to reducing negative results of biopsies. The Mann-Whitney U test was used to analyze the difference in these parameters between patients with benign and malignant histologies. Results: There was significant difference in these PSA parameters between patients with benign and malignant histologies (p < 0.05). tPSAD had the largest area under the curve for total population as well as for patients with tPSA levels between 4 and 10 ng/ml. Although the f/t ratio had a larger area under the curve than did tPSA assay in patients with PSA levels between 4 and 10 ng/ml, the difference was not statistically significant. Using a tPSAD of 0.12 ng/ml/ml as the cutoff level of negative results of prostate biopsies could be reduced by 37% in patients with PSA levels between 4 and 10 ng/ml. Although the f/t ratio could reduce negative results of biopsies by 33.8% at the cutoff value of 0.26, 15.6% of cancers would be missed. Age-specific PSA could reduce 31% of negative prostatic biopsies, but 28% of cancers would be missed. Using combined tPSAD and the f/t ratio did not improve reductions of negative biopsy results. Conclusion: tPSA density has the highest sensitivity and specificity in differentiating benign from malignant prostates. By using tPSA density, negative results of prostate biopsies can be reduced by 37%, while missing only a small number of cancers.
Challenges and Opportunities in Implementing Total Laboratory Automation.

In total laboratory automation (TLA)10, preanalytic, analytic, and postanalytic phases of laboratory testing may be combined into an integrated system such that specimens are processed, tested, and even stored with minimal user intervention. Given the pressures of an ongoing workforce shortage of laboratory professionals, laboratory automation offers an attractive, albeit expensive, solution that laboratories are increasingly considering in planning for future growth and work flow requirements. In an ideal system, TLA handles routine, repetitive steps—leveraging the quality and efficiency obtainable in the manufacturing industry and freeing operators to focus on specialized testing that benefits from their unique training and expertise. A variety of laboratory automation solutions have been available globally for decades, with technologies that have advanced based on engineering innovation and practical trial and error. To address the difficulties and benefits involved in implementing and sustaining TLA in a clinical laboratory setting, we invited a group of 5 experts to share their perspectives on laboratory automation and provide real-world advice based on their experiences with TLA at their respective facilities. In what ways has automation impacted your clinical laboratory? Giuseppe Lippi: Automation has completely revolutionized the organization of my laboratory. The main advantages that we have observed are improved standardization, more simplified and efficient approaches for managing work flow, improvement in the performance of complex tests, better high-volume test management, shorter turnaround time (TAT) by elimination of some manually intensive preanalytical steps, provision of valuable walk-away time, and reduction of personnel costs (i.e., laboratory technicians and subsidiary staff), along with notable reductions in errors and biological risks attributable to manual handling of specimens. Another important advantage is represented by more efficient management of reruns and reflex testing, which can now be performed automatically with little user action needed. Carey-Ann Burnham: Historically, the clinical microbiology laboratory has lagged …
Molecular Pathogenesis of Genetic and Inherited Diseases Heterogeneous and Complex Rearrangements of Chromosome Arm 6 q in Chondromyxoid Fibroma Delineation of Breakpoints and Analysis of Candidate Target Genes

From the Departments of Pathology,* and Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; the Departments of Pathology/Microbiology, Pediatrics, and Orthopaedic Surgery, University of Nebraska Medical Center, Omaha, Nebraska; the Department of Clinical Genetics, Lund University Hospital, Lund, Sweden; the Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts; the Department of Human Genetics and Pathology,** Catholic University of Leuven, Leuven, Belgium; and the Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
Developing New Molecules for the Treatment of Painful Diabetic Peripheral Neuropathy: Is it Feasible given the Magnitude of the Placebo Response in Proof of Concept Clinical Studies?

Randomised, double blind, placebo controlled studies are necessary in neuropathic pain clinical research arena. Few drugs are approved for the indication of painful Diabetic Peripheral Neuropathy (DPN): typically these drugs lose their therapeutic response over time and have far from an ideal tolerability risk profile. In addition to that, the response to placebo continues to represent a significant challenge in clinical trials of painful DPN, as well as any other neuropathic pain condition. Hence to date few molecules have progressed to phase 3 in painful DPN and even fewer have gained approval. Thus several studies failed because the primary endpoint of statistical superiority to placebo and a clinically relevant reduction of ADPS (Average Daily Pain Score) were not achieved. Any attempt to mitigate the placebo response in this condition may allow future new drugs to successfully progress from Proof of Concept to phase 3 of clinical development and hopefully to their approval. As of today this remains a relevant challenge in a therapeutic area of a well-recognized unmet medical need. The dangers of treating acute and chronic pain with opioids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or acetaminophen are considerable. By mitigating the placebo response in neuropathic pain clinical trials, this may expedite the discovery, selection and development of improved analgesic treatments for the benefit of public health. In addition, a better understanding of subjects’ typology would be of great help to identify those who really need a more specific pharmacological treatment approach from those subjects who don`t and might benefit instead from alternative non-pharmacological approaches.