Miracle-dz/UniFAR-FTUs huggingface dataset:
Stretch for the treatment and prevention of contractures.

BACKGROUND Contractures are a common complication of neurological and musculoskeletal conditions, and are characterised by a reduction in joint mobility. Stretch is widely used for the treatment and prevention of contractures. However, it is not clear whether stretch is effective. OBJECTIVES To determine the effects of stretch on contractures in people with, or at risk of, contractures. SEARCH STRATEGY Electronic searches were conducted on CENTRAL, DARE, HTA (The Cochrane Library); MEDLINE; CINAHL; EMBASE; SCI-EXPANDED; and PEDro (April 2009). SELECTION CRITERIA Randomised controlled trials and controlled clinical trials of stretch applied for the purpose of treating or preventing contractures were included. DATA COLLECTION AND ANALYSIS Two review authors independently selected trials, extracted data, and assessed risk of bias. The primary outcomes of interest were joint mobility and quality of life. The secondary outcomes were pain, spasticity, activity limitation and participation restriction. Outcomes were evaluated immediately after intervention, in the short term (one to seven days) and in the long term (> one week). Effects were expressed as mean differences or standardised mean differences with 95% confidence intervals (CI). Meta-analyses were conducted with a random-effects model. MAIN RESULTS Thirty-five studies with 1391 participants met the inclusion criteria. No study performed stretch for more than seven months. In people with neurological conditions, there was moderate to high quality evidence to indicate that stretch does not have clinically important immediate (mean difference 3 degrees ; 95% CI 0 to 7), short-term (mean difference 1 degrees ; 95% CI 0 to 3) or long-term (mean difference 0 degrees ; 95% CI -2 to 2) effects on joint mobility. The results were similar for people with non-neurological conditions. For all conditions, there is little or no effect of stretch on pain, spasticity, activity limitation, participation restriction or quality of life. AUTHORS' CONCLUSIONS Stretch does not have clinically important effects on joint mobility in people with, or at risk of, contractures if performed for less than seven months. The effects of stretch performed for periods longer than seven months have not been investigated.
A Robust and Sensitive Metric for Quantifying Movement Smoothness

The need for movement smoothness quantification to assess motor learning and recovery has resulted in various measures that look at different aspects of a movement's profile. This paper first shows that most of the previously published smoothness measures lack validity, consistency, sensitivity, or robustness. It then introduces and evaluates the spectral arc-length metric that uses a movement speed profile's Fourier magnitude spectrum to quantify movement smoothness. This new metric is systematically tested and compared to other smoothness metrics, using experimental data from stroke and healthy subjects as well as simulated movement data. The results indicate that the spectral arc-length metric is a valid and consistent measure of movement smoothness, which is both sensitive to modifications in motor behavior and robust to measurement noise. We hope that the systematic analysis of this paper is a step toward the standardization of the quantitative assessment of movement smoothness.
Simvastatin intolerance genetic determinants: some features in ethnic Uzbek patients with coronary artery disease

Introduction The objective is to study the influence of CYP3A5 (6986A>G), CYP2C9 (430C>T), CYP2C9 (1075A>C), SLCO1B1 (521T>C) and BCRP (ABCG2, 421C>A) gene polymorphisms on the development of simvastatin intolerance in ethnic Uzbek patients with coronary artery disease (CAD). Material and methods The case group contained 50 patients with clinical simvastatin-induced intolerance symptoms; the control group contained 50 patients without side-effects. Genotyping was performed by means of the PCR-RFLP method. Results Among 37 patients with simvastatin-induced liver symptoms the *3/*3 genotype of the CYP3A5 gene (p = 0.0001) and variant genotype of the CA BCRP gene were observed more frequently than in the control group (p = 0.0001). However, when the 13 patients who had statin-associated muscle symptoms (SAMS) were compared with the control group (n = 50), it was found that in the case group the 3*/3* genotype of the CYP3A5 gene (OR = 8.6; 95% CI: 2.1–34.1; p = 0.003) and C allele carriers of the gene polymorphism SLCO1B1 (OR = 3.54; 95% CI: 1.35–9.27; Χ2 = 5.7; p = 0.017) were predominant. Conclusions The *3/*3 genotype of the CYP3A5 (6986A>G) gene and CA genotype of the BCRP (ABCG2, 421C>A) gene were associated with simvastatin-induced liver symptoms in ethnic Uzbek CAD patients, whereas in patients with simvastatin-associated muscle symptoms (SAMS), the combination of *3/*3 genotype of CYP3A5 (6986A> G) and carriage of the C allele of the SLCO1B1 gene polymorphism was predominant.
Histopathological features of breast cancer in carriers of ATM gene variants

Aims: Germline variants in the ataxia telangiectasia mutated (ATM) gene have been implicated in increased breast cancer risk. The aim of this study was to determine whether the histopathology of breast cancers occurring in ATM variant carriers is distinctive or resembles the described BRCA1 mutation‐associated phenotype.
Unintended adverse consequences of electronic health record introduction to a mature universal HIV screening program

ABSTRACT Early HIV detection and treatment decreases morbidity and mortality and reduces high-risk behaviors. Many Emergency Departments (EDs) have HIV screening programs as recommended by the Centers for Disease Control and Prevention. Recent federal legislation includes incentives for electronic health record (EHR) adoption. Our objective was to analyze the impact of conversion to EHR on a mature ED-based HIV screening program. A retrospective pre- and post-EHR implementation cohort study was conducted in a large urban, academic ED. Medical records were reviewed for HIV screening rates from August 2008 through October 2013. On 1 November 2010, a comprehensive EHR system was implemented throughout the hospital. Before EHR implementation, labs were requested by providers by paper orders with HIV-1/2 automatically pre-selected on every form. This universal ordering protocol was not duplicated in the new EHR; rather it required a provider to manually enter the order. Using a chi-squared test, we compared HIV testing in the 6 months before and after EHR implementation; 55,054 patients presented before, and 50,576 after EHR implementation. Age, sex, race, acuity of presenting condition, and HIV seropositivity rates were similar pre- and post-EHR, and there were no major patient or provider changes during this period. Average HIV testing rate was 37.7% of all ED patients pre-, and 22.3% post-EHR, a 41% decline (p < 0.0001), leading to 167 missed new diagnoses after EHR. The rate of HIV screening in the ED decreased after EHR implementation, and could have been improved with more thoughtful inclusion of existing human processes in its design.
Pharmacological, experimental therapeutic, and transcranial magnetic stimulation treatments for compulsivity and impulsivity

Obsessive-compulsive disorder (OCD) has been recently drawn apart from anxiety disorder by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and clustered together with related disorders (eg, hoarding, hair pulling disorder, skin picking), which with it seems to share clinical and neurophysiological similarities. Recent literature has mainly explored brain circuitries (eg, orbitofrontal cortex, striatum), molecular pathways, and genes (eg, Hoxb8, Slitrk5, Sapap3) that represent the new target of the treatments; they also lead the development of new probes and compounds. In the therapeutic field, monotherapy with cognitive behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs) is recommendable, but combination or augmentation with a dopaminergic or glutamatergic agent is often adopted. A promising therapy for OCD is represented by repetitive transcranial magnetic stimulation (rTMS), which is suitable to treat compulsivity and impulsivity depending on the protocol of stimulation and the brain circuitries targeted.
Microbial siderophores: a mini review

Iron is one of the major limiting factors and essential nutrients of microbial life. Since in nature it is not readily available in the preferred form, microorganisms produce small high affinity chelating molecules called siderophores for its acquisition. Microorganisms produce a wide variety of siderophores controlled at the molecular level by different genes to accumulate, mobilize and transport iron for metabolism. Siderophores also play a critical role in the expression of virulence and development of biofilms by different microbes. Apart from maintaining microbial life, siderophores can be harnessed for the sustainability of human, animals and plants. With the advent of modern molecular tools, a major breakthrough is taking place in the understanding of the multifaceted role of siderophores in nature. This mini review is intended to provide a general overview on siderophore along with its role and applications.
Accounting for pharmacokinetic differences in dual-tracer receptor density imaging

Dual-tracer molecular imaging is a powerful approach to quantify receptor expression in a wide range of tissues by using an untargeted tracer to account for any nonspecific uptake of a molecular-targeted tracer. This approach has previously required the pharmacokinetics of the receptor-targeted and untargeted tracers to be identical, requiring careful selection of an ideal untargeted tracer for any given targeted tracer. In this study, methodology capable of correcting for tracer differences in arterial input functions, as well as binding-independent delivery and retention, is derived and evaluated in a mouse U251 glioma xenograft model using an Affibody tracer targeted to epidermal growth factor receptor (EGFR), a cell membrane receptor overexpressed in many cancers. Simulations demonstrated that blood, and to a lesser extent vascular-permeability, pharmacokinetic differences between targeted and untargeted tracers could be quantified by deconvolving the uptakes of the two tracers in a region of interest devoid of targeted tracer binding, and therefore corrected for, by convolving the uptake of the untargeted tracer in all regions of interest by the product of the deconvolution. Using fluorescently labeled, EGFR-targeted and untargeted Affibodies (known to have different blood clearance rates), the average tumor concentration of EGFR in four mice was estimated using dual-tracer kinetic modeling to be 3.9 ± 2.4 nM compared to an expected concentration of 2.0 ± 0.4 nM. However, with deconvolution correction a more equivalent EGFR concentration of 2.0 ± 0.4 nM was measured.
RNAi-mediated downregulation of oral cancer overexpressed 1 (ORAOV1) inhibits vascular endothelial cell proliferation, migration, invasion, and tube formation.

BACKGROUND Oral squamous cell carcinoma (OSCC) is one of the top ten tumors threatening human health. Oral cancer overexpressed 1 (ORAOV1) identified within chromosomal region 11q13, one of the most frequently amplified regions in OSCC, has been suggested as a novel candidate oncogene in OSCC, regulating cell cycle, apoptosis, and angiogenesis. In this study, we investigated the role of ORAOV1 in OSCC-induced angiogenesis in vitro. METHODS EA.hy926 human endothelial cells were co-cultured with OSCC cells (HSC-3 and SCC-25) transfected with ORAOV1-specific shRNA to downregulate ORAOV1 expression, and analyzed for proliferation, migration, invasion, and tube formation by specific assays. RESULTS EA.hy926 endothelial cells co-cultured with ORAOV1-deficient OSCC cells exhibited significantly lower proliferation, migration, and invasion, as well as the activity in tube formation compared to that in the control cells. CONCLUSIONS Our results show, for the first time, that ORAOV1 expressed by OSCC cells promotes tube formation by endothelial cells, indicating its involvement in OSCC angiogenesis. Considering the importance of neovascularization in tumor development and metastasis, these findings suggest that targeting ORAOV1 may be a potential therapeutic strategy against OSCC.
Characterization of a postlavage, in situ pulmonary macrophage population

A postlavage in situ subpopulation of pulmonary macrophages (PM), biochemically distinct from the lavaged population, has recently been isolated from rats. After exhaustive bronchopulmonary lavage to extract the free lung cells, the lungs were excised, homogenized, and filtered, and the resultant cell suspension was allowed to form a monolayer on plastic Petri dishes. Electron microscopic morphometry failed to indicate any morphologic differences in the two populations. The postlavage in situ PM were more active metabolically during phagocytosis of zymosan particles or stimulation by phorbol myristate acetate (PMA) than the corresponding lavage population, as evidenced by greater superoxide generation. Macrophages prepared by either method became more avidly phagocytic when incubated with cell‐free medium isolated in the preparation of the in situ population. Peroxidase, an enzyme absent from the granules of PM separated by lavage techniques, was found in a granule‐rich fraction of the in situ macrophage. Catalase activity was found in similar amounts in both supernatants and granule‐rich fractions of both populations. The results support the concept of subpopulations of PM and suggest that these subpopulations are distinguished by their biochemical properties and their functional abilities.
Prognostic significance of ambulatory arterial stiffness index in hypertensives followed for 8.2 years: its relation with new events and cardiovascular risk estimation.

INTRODUCTION The ambulatory arterial stiff ness index (AASI) is a new method for estimating arterial stiffness, which is associated with cardiovascular (CV) prognosis. Our aim was to evaluate the prognostic significance of AASI for new CV events. METHODS Casual and ambulatory blood pressure (BP) measurements were obtained in 1200 hypertensive patients (645 female, age 51 +/- 12 years, BMI 27 +/- 5 kg/m2), 53% under stabilized therapy, 47% untreated, all without previous CV events. The occurrence of CV events was determined for 9833 patient-years and analyzed by a Cox proportional hazard model adjusted for confounding variables. AASI was calculated from 24h ABPM data and all patients were classified from very high to average CV risk. RESULTS There were 62 deaths and 152 new fatal and non-fatal CV events (79 strokes, 51 coronary events, 22 other CV events) during the 15.2 years of follow-up (mean 8.2 +/- 3.0 years). AASI correlated significantly (p < 0.001) with pulse wave velocity (PWV), casual and 24h ambulatory BP, age and BMI. In subjects with very high or high CV risk (n = 401), AASI was 0.338 +/- 0.178, while in those with low or moderate CV risk (n = 715), it was 0.291 +/- 0.173 and in those with average CV risk (n = 84), it was 0.219 +/- 0.170) (p < 0.002, ANOVA). The probability of event-free and stroke-free survival (Kaplan-Meier) was better for AASI values below vs. above the median. The adjusted relative risk (HR 95% CI) for CV events, stroke and coronary events associated with a 1-SD increment in AASI values was respectively 1.27 (1.01-1.59), 1.36 (95% CI 1.02-1.89) (p < 0.02) and 0.99 (95% CI 0.67-1.48) (NS), similar to that of 24h pulse pressure (PP) and PWV. AASI hazard ratios were no longer significant after additional adjustment for 24h PP, whereas the converse did not occur. However, AASI above the median increases the predictive value of 24h PP for CV events and stroke. CONCLUSIONS AASI correlates with PWV, stratifies CV risk and predicts total cardiovascular events and stroke but not coronary events. AASI may add predictive value to 24h PP for CV events and stroke.
Binding of Rat and Human Surfactant Proteins A and D to Aspergillus fumigatus Conidia

ABSTRACT Surfactant proteins A (SP-A) and D (SP-D) are thought to play important roles in pulmonary host defense. We investigated the interactions of rat and human SP-A and SP-D with Aspergillus fumigatus conidia. Rat SP-D but not rat SP-A bound the conidia, and the binding was inhibited by EDTA, mannose, glucose, maltose, and inositol. Binding studies using a mutant recombinant rat SP-D with altered carbohydrate recognition but normal structural organization clearly established a role for the carbohydrate recognition domain in binding to conidia. However, neither rat SP-A nor SP-D increased the association of fluorescein isothiocyanate-labeled conidia with rat alveolar macrophages as determined by flow cytometry. Both human SP-A (isolated from normal and alveolar proteinosis lungs) and SP-D (recombinant protein and protein isolated from alveolar proteinosis lungs) bound the conidia. These data indicate that important differences exist between rat and human SP-A in binding to certain fungi. Human SP-A and SP-D binding to conidia was also examined in the presence of hydrophobic surfactant components (HSC), containing both the phospholipid and hydrophobic proteins of surfactant. We found that HSC inhibited but did not eliminate human SP-A binding toAspergillus conidia. In contrast, the SP-D binding to conidia was unaffected by HSC. These findings indicate that SP-D plays a major role in the recognition of Aspergillus conidia in alveolar fluid.
Differential Modulation of Intracortical Inhibition in Human Motor Cortex during Selective Activation of an Intrinsic Hand Muscle

Paired‐pulse transcranial magnetic stimulation (TMS) was used to assess the effectiveness of intracortical inhibition (ICI) acting on corticospinal neurons controlling three intrinsic hand muscles in humans. We hypothesised that the suppression of ICI with selective activation of a muscle would be restricted to corticospinal neurons controlling the muscle targeted for activation. Surface EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the left hand. Subjects were tested at rest and during weak selective activation of APB or ADM, while they attempted to keep the other muscles relaxed using visual feedback. Paired‐pulse TMS was applied with a circular coil oriented to produce antero‐posterior (AP) current flow in the right motor cortex (to preferentially evoke I3 waves in corticospinal neurons) and with postero‐anterior (PA) currents (to preferentially evoke I1 waves). Paired‐pulse TMS was less effective in suppressing the muscle evoked potential (MEP) when the muscle was targeted for selective activation, with both AP and PA stimulation. The mechanism for this includes effects on late I waves, as it was evident with a weak AP test TMS pulse that elicited negligible I1 waves in corticospinal neurons. ICI circuits activated by TMS, which exert their effects on late I waves but do not affect I1 waves, are strongly implicated in this modulation. With AP stimulation, paired‐pulse inhibition was not significantly altered for corticospinal neurons controlling other muscles of the same hand which were required to be inactive during the selective activation task. This differential modulation was not seen with PA stimulation, which preferentially activates I1 waves and evokes a MEP that is less influenced by ICI. The observations with AP stimulation suggest that selective activation of a hand muscle is accompanied by a selective suppression of ICI effects on the corticospinal neurons controlling that muscle. The pattern of differential modulation of ICI effectiveness with voluntary activation suggests that the ICI circuits assist the corticospinal system in producing fractionated activity of intrinsic hand muscles.
Pancreatic cancer and fibrinogen storage disease.

BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. METHODS: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. Immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.
Global Analysis of Myocardial Peptides Containing Cysteines With Irreversible Sulfinic and Sulfonic Acid Post-Translational Modifications*

Cysteine (Cys) oxidation is a crucial post-translational modification (PTM) associated with redox signaling and oxidative stress. As Cys is highly reactive to oxidants it forms a range of post-translational modifications, some that are biologically reversible (e.g. disulfides, Cys sulfenic acid) and others (Cys sulfinic [Cys-SO2H] and sulfonic [Cys-SO3H] acids) that are considered “irreversible. ” We developed an enrichment method to isolate Cys-SO2H/SO3H-containing peptides from complex tissue lysates that is compatible with tandem mass spectrometry (MS/MS). The acidity of these post-translational modification (pKa Cys-SO3H < 0) creates a unique charge distribution when localized on tryptic peptides at acidic pH that can be utilized for their purification. The method is based on electrostatic repulsion of Cys-SO2H/SO3H-containing peptides from cationic resins (i.e. “negative” selection) followed by “positive” selection using hydrophilic interaction liquid chromatography. Modification of strong cation exchange protocols decreased the complexity of initial flowthrough fractions by allowing for hydrophobic retention of neutral peptides. Coupling of strong cation exchange and hydrophilic interaction liquid chromatography allowed for increased enrichment of Cys-SO2H/SO3H (up to 80%) from other modified peptides. We identified 181 Cys-SO2H/SO3H sites from rat myocardial tissue subjected to physiologically relevant concentrations of H2O2 (<100 μm) or to ischemia/reperfusion (I/R) injury via Langendorff perfusion. I/R significantly increased Cys-SO2H/SO3H-modified peptides from proteins involved in energy utilization and contractility, as well as those involved in oxidative damage and repair.
The Consequences of Increasing the Scope of Managerial Judgement in Accounting Standards

This paper investigates the consequences of increasing the scope of managerial judgement (ISMJ) in accounting standards via a difference-in-differences approach in the unique setting of China. A substantial increase in accruals-based earnings management is found after ISMJ, in addition to a decline in real activities-based earnings management resulting from temporarily increased sales, boosted inventory, and expense deferrals. In contrast, we find a significant increase in the relevance of accounting information. Further analysis reveals significant negative cumulative abnormal returns related to the announcement of accounting standards change over the short term. We also find a larger long-term increase in the crash risk of the stock prices of firms that engage in more accruals-based earnings management after ISMJ. All of these effects are more pronounced in non-state-owned enterprises than in state-owned enterprises.