Miracle-dz/UniFAR-FTUs huggingface dataset:
Sialoadhesin-Deficient Mice Exhibit Subtle Changes in B- and T-Cell Populations and Reduced Immunoglobulin M Levels

ABSTRACT Sialoadhesin (Sn, also called Siglec-1 or CD169) is a transmembrane receptor and the prototypic member of the Siglec family of sialic acid binding immunoglobulin-like lectins. It is expressed on specialized subsets of resident macrophages in hematopoietic and lymphoid tissues and on inflammatory macrophages. In order to investigate its function, we generated Sn-deficient mice and confirmed that these mice are true nulls by fluorescence-activated cell sorter analysis and immunohistochemistry. Mice deficient in Sn were viable and fertile and showed no developmental abnormalities. Analysis of cell populations revealed no differences in bone marrow, peritoneal cavity, and thymus, but there was a small increase in CD8 T cells and a decrease in B220-positive cells in spleens and lymph nodes of Sn-deficient mice. Furthermore, in spleen there was a slight decrease in follicular B cells with an increase in numbers of marginal zone B cells. B- and T-cell maturation as well as responses to stimulation with thioglycolate were only slightly affected by Sn deficiency. Immunoglobulin titers in Sn-deficient mice were significantly decreased for immunoglobulin M (IgM) but similar for IgG subclasses. These results suggest a role for sialoadhesin in regulating cells of the immune system rather than in influencing steady-state hematopoiesis.
Thermal Alteration of Pyrite to Pyrrhotite During Earthquakes: New Evidence of Seismic Slip in the Rock Record

Seismic slip zones convey important information on earthquake energy dissipation and rupture processes. However, geological records of earthquakes along exhumed faults remain scarce. They can be traced with a variety of methods that establish the frictional heating of seismic slip, although each has certain assets and disadvantages. Here we describe a mineral magnetic method to identify seismic slip along with its peak temperature through examination of magnetic mineral assemblages within a fault zone in deep‐sea sediments cored from the Japan Trench—one of the seismically most active regions around Japan—during the Integrated Ocean Drilling Program Expedition 343, the Japan Trench Fast Drilling Project. Fault zone sediments and adjacent host sediments were analyzed mineral magnetically, supplemented by scanning electron microscope observations with associated energy dispersive X‐ray spectroscopy analyses. The presence of the magnetic mineral pyrrhotite appears to be restricted to three fault zones occurring at ~697, ~720, and ~801 m below sea floor in the frontal prism sediments, while it is absent in the adjacent host sediments. Elevated temperatures and coseismic hot fluids as a consequence of frictional heating during earthquake rupture induced partial reaction of preexisting pyrite to pyrrhotite. The presence of pyrrhotite in combination with pyrite‐to‐pyrrhotite reaction kinetics constrains the peak temperature to between 640 and 800°C. The integrated mineral‐magnetic, microscopic, and kinetic approach adopted here is a useful tool to identify seismic slip along faults without frictional melt and establish the associated maximum temperature.
Identification of a mutation in GDF9 as a novel cause of diminished ovarian reserve in young women.

STUDY QUESTION Do any mutations in growth differentiation factor 9 (GDF9) have a role in diminished ovarian reserve (DOR) in young women? SUMMARY ANSWER The GDF9 p.R146C mutation may be a source of DOR in some young women. WHAT IS KNOWN ALREADY DOR affects 10% of women under 37 years of age and is associated with accelerated expenditure of follicles. GDF9 is an oocyte-secreted factor that plays a critical role in follicular development and female fertility. Several GDF9 variants have been linked to ovarian dysfunction. STUDY DESIGN, SIZE, DURATION This case-control study included 139 women with DOR and 152 controls aged under 37 years. PARTICIPANTS/MATERIALS, SETTING, METHODS All women were recruited in a Chinese tertiary center and underwent DNA sequencing of GDF9 gene. We then determined the molecular and biological properties of mutant GDF9 proteins using protein expression, structural prediction and functional analyses. MAIN RESULTS AND THE ROLE OF CHANCE We identified two mutations in the proregion of GDF9 gene: c.169T > G (p.D57Y) and c.436T > C (p.R146C). The p.R146C mutation was found in three women with DOR but was absent in the control population. This mutation was also associated with significant reductions in GDF9 mature protein secretion in cultured cells. Functional studies with human granulosa cells (GCs) showed that the p.R146C mutation reduced the abilities of GDF9 to stimulate GC proliferation and to activate the Smad2 pathway. Protein structure modeling predicted that p.R146C disrupted an α-helix in GDF9 protein. In contrast with p.R146C, the p.D57Y mutation, found in both the DOR and control groups (6 versus 2), had no obvious deleterious effects. LIMITATIONS, REASONS FOR CAUTION Larger studies in varying populations may validate the role of GDF9 mutation in young women with DOR. WIDER IMPLICATIONS OF THE FINDINGS These results may provide new insights into the pathophysiological mechanisms of early-onset DOR.
A model for Mexican neotectonics based on nationwide GPS measurements, 1993-2001

En este trabajo combinamos las velocidades obtenidas a partir de 14 estaciones GPS de operacion continua distribuidas en Mexico, dos nuevas estaciones en I a placa del Pacifico (Archipielago de Revilagigedo) y de 178 estaciones e las placas de Norteamerica y del Padfico, para obtener un marco geodinfunico que servira de referenda para futuros estudios e neotectonica en Mexico realizados con GPS. Las velocidades derivadas muestran clarament que existen areas al norte de la aja Volcanica Mexicana que estan incluidas dentro de la porcion rfgida de la placa de Norteam rica. El movimiento de las estaci nes en Mexico al norte de Oaxaca es tambien consistente con el movimiento de la placa de orteamerica, lo cual implica u deslizamiento despreciable a traves de la Faja Volcaruca Mexicana. Las estaciones en la penin lade Yucatan se desplazan a raz 'n de 3±1 mmJ afio hacia el Este con relacion ala placa de Norteamerica sin existir claras evide cias geologicas que expliquen es e movimiento. Las velocidades obtenidas para las islas Clarion y Socorro en el oceano Pacifico son consistentes dentro de su inc rtidumbre con las velocidades de otros sitios en Ia placa del Pacifico y por consiguiente proveen una mejordeterminacion del mov· mien to de esta placa. El movimiento del Padfico-Norteamerica en el sur del Gotfo de Califomi es de 50± 0.5 mm/afio hacia el S 5°E ±0.5°, que es consistente con las estimaciones geologicas pero ligeramente mas Iento que las estimaciones geodesicas recientem nte publicadas de 52-53 mrnfafio. El movimiento de La Paz en la peninsula de Baja California hacia el Sureste en relacion c n Ia Placa del Padfico coincide con resultados previos que indican que Baja California se encuentra desacoplada de la placa d I Padfico. Las nuevas velocidades angulares obtenidas en este trabajo representan un marco de referencia geologico bien defini o para futuros estudios geodesicos en Mexico. doi: sin doi
Differentiating between Central Nervous System Lymphoma and High-grade Glioma Using Dynamic Susceptibility Contrast and Dynamic Contrast-enhanced MR Imaging with Histogram Analysis

Purpose: We evaluated the diagnostic performance of histogram analysis of data from a combination of dynamic susceptibility contrast (DSC)-MRI and dynamic contrast-enhanced (DCE)-MRI for quantitative differentiation between central nervous system lymphoma (CNSL) and high-grade glioma (HGG), with the aim of identifying useful perfusion parameters as objective radiological markers for differentiating between them. Methods: Eight lesions with CNSLs and 15 with HGGs who underwent MRI examination, including DCE and DSC-MRI, were enrolled in our retrospective study. DSC-MRI provides a corrected cerebral blood volume (cCBV), and DCE-MRI provides a volume transfer coefficient (Ktrans) for transfer from plasma to the extravascular extracellular space. Ktrans and cCBV were measured from a round region-of-interest in the slice of maximum size on the contrast-enhanced lesion. The differences in t values between CNSL and HGG for determining the most appropriate percentile of Ktrans and cCBV were investigated. The differences in Ktrans, cCBV, and Ktrans/cCBV between CNSL and HGG were investigated using histogram analysis. Receiver operating characteristic (ROC) analysis of Ktrans, cCBV, and Ktrans/cCBV ratio was performed. Results: The 30th percentile (C30) in Ktrans and 80th percentile (C80) in cCBV were the most appropriate percentiles for distinguishing between CNSL and HGG from the differences in t values. CNSL showed significantly lower C80 cCBV, significantly higher C30 Ktrans, and significantly higher C30 Ktrans/C80 cCBV than those of HGG. In ROC analysis, C30 Ktrans/C80 cCBV had the best discriminative value for differentiating between CNSL and HGG as compared to C30 Ktrans or C80 cCBV. Conclusion: The combination of Ktrans by DCE-MRI and cCBV by DSC-MRI was found to reveal the characteristics of vascularity and permeability of a lesion more precisely than either Ktrans or cCBV alone. Histogram analysis of these vascular microenvironments enabled quantitative differentiation between CNSL and HGG.
Hospital-Level Variation in Mortality and Rehospitalization for Medicare Beneficiaries With Acute Ischemic Stroke

Background and Purpose— Stroke is the second leading cause of hospital admission among older adults in the United States. However, little is known regarding contemporary ischemic stroke mortality and rehospitalization rates for Medicare beneficiaries and how they vary by hospital. Methods— We analyzed outcome data from 91 134 Medicare fee-for-service beneficiaries treated at 625 Get With The Guidelines–Stroke hospitals between April 2003 and December 2006. Within each hospital, 30-day and 1-year death or all-cause readmission rates were calculated with and without risk adjustment. Results— In this cohort, mean age was 79.3 years, 58% were female, and 82% were white. In-hospital, 30-day, and 1-year unadjusted mortality from admission were 6.1%, 14.1%, and 31.1%, respectively, for participating hospitals. The median hospital-level 30-day unadjusted death or readmission rate after discharge was 21.4% (10th to 90th 14.4% to 28.6%). The overall rate of death or rehospitalization within 1 year of hospital discharge was 61.9%. Risk-adjusted rates varied widely by hospital at each time point. There were no improvements in death or rehospitalization from 2003 to 2006. Hospital-level performance in risk-adjusted outcomes did not significantly differ by size or primary stroke center designation, but academic hospitals and those in the Northeast or West had slightly more favorable outcomes. Conclusions— Nearly two thirds of the Medicare beneficiaries discharged after ischemic stroke died or were rehospitalized within 1 year, but hospital-level outcomes varied considerably. These findings underscore the need to better understand the patterns and causes of deaths and readmission after ischemic stroke and to develop strategies aimed at avoiding those that are preventable.
Evaluation and management of children younger than two years old with apparently minor head trauma: proposed guidelines.

OBJECTIVE In children <2 years old, minor head trauma (HT) is a common injury that can result in skull fracture and intracranial injury (ICI). These injuries can be difficult to detect in this age group; therefore, many authors recommend a low threshold for radiographic imaging. Currently, no clear guidelines exist regarding the evaluation and management of head-injured infants. We sought to develop guidelines for management based on data and expert opinion that would enable clinicians to identify children with complications of HT and reduce unnecessary imaging procedures. METHODS. EVIDENCE References addressing pediatric HT were generated from a computerized database (Medline). The articles were reviewed and evidence tables were compiled. EXPERT PANEL: The multidisciplinary panel was comprised of nine experts in pediatric HT. CONSENSUS PROCESS A modified Delphi technique was used to develop the guidelines. Before the one meeting, panel members reviewed the evidence and formulated answers to specific clinical questions regarding HT in young children. At the meeting, guidelines were formulated based on data and expert consensus. RESULTS A management strategy was developed that categorizes children into 4 subgroups, based on risk of ICI. Children in the high-risk group should undergo a computed tomography (CT) scan. Those in the intermediate risk group with symptoms of possible ICI should either undergo CT scan or observation. Those in the intermediate risk group with some risk for skull fracture or ICI should undergo CT and/or skull radiographs or observation. Those in the low-risk group require no radiographic imaging. CONCLUSIONS We have developed a guideline for the evaluation of children <2 years old with minor HT. The effect of these guidelines on clinical outcomes and resource utilization should be evaluated.
Recent Declines in Australian Male Suicide are Real, not Artefactual

Objectives: The aim of the present study was to clarify the extent to which the recorded marked decline in young male suicide (20–34 years) in Australia since 1998 is attributable to misclassification of cause of death information. Methods: Secular trends in young male suicide rates were investigated for the period 1976–2005. Suicide rates in the period after the peak of the epidemic in this age group (1998) were re-calculated based on published estimates of under-enumeration of suicide data, and misclassification of likely suicide cases to other unintentional and undetermined external causes. Two misclassification scenarios were used to revise young male suicide rates from 1998: previously reported estimates of 9% under-enumeration due to misclassification of unintentional causes of death, and 17% under-enumeration due to misclassification of open cases in addition to unintentional causes of death. All-cause mortality was also examined. Results: Recorded male suicide in the 20–34 year age group increased over the study period, peaking in 1998 at 39 per 100 000, before declining sharply in the period 1999–2005 by 44% to 22 per 100 000 in 2005. Following adjustment for misallocation under the first scenario, suicide rates declined 38% to 24 per 100 000, and under the second scenario declined 33% to 26 per 100 000. Revised suicide rates were not materially different from recorded suicide rates based on 95% confidence intervals over this period. All-cause mortality declined from 1999 due to reductions in suicide and other causes. Conclusion: The recent marked decline in young male suicide in Australia is real. The effects of misallocation of likely suicide cases to other causes did not substantially affect population trends in suicide rates in the period after 1998. There is still a need to account in detail for why young male suicide has declined so substantially during the period after 1998.
Blocking eIF4E-eIF4G Interaction as a Strategy To Impair Coronavirus Replication

ABSTRACT Coronaviruses are a family of enveloped single-stranded positive-sense RNA viruses causing respiratory, enteric, and neurologic diseases in mammals and fowl. Human coronaviruses are recognized to cause up to a third of common colds and are suspected to be involved in enteric and neurologic diseases. Coronavirus replication involves the generation of nested subgenomic mRNAs (sgmRNAs) with a common capped 5′ leader sequence. The translation of most of the sgmRNAs is thought to be cap dependent and displays a requirement for eukaryotic initiation factor 4F (eIF4F), a heterotrimeric complex needed for the recruitment of 40S ribosomes. We recently reported on an ultrahigh-throughput screen to discover compounds that inhibit eIF4F activity by blocking the interaction of two of its subunits (R. Cencic et al., Proc. Natl. Acad. Sci. U. S. A. 108:1046–1051, 2011). Herein we describe a molecule from this screen that prevents the interaction between eIF4E (the cap-binding protein) and eIF4G (a large scaffolding protein), inhibiting cap-dependent translation. This inhibitor significantly decreased human coronavirus 229E (HCoV-229E) replication, reducing the percentage of infected cells and intra- and extracellular infectious virus titers. Our results support the strategy of targeting the eIF4F complex to block coronavirus infection.
Disease Modifying Agents for Multiple Sclerosis

Objective: To summarize major clinical trials which evaluate the efficacy and safety data of approved disease modifying agents for the treatment of various types of multiple sclerosis. Data Sources: A MEDLINE (1966 to August 2008) search of clinical trials using the terms multiple sclerosis, interferon, glatiramer, mitoxantrone and natalizumab was performed. A manual bibliographic search was also conducted. English-language articles identified from the searches were evaluated. New agents under investigation in phase 3 clinical trials were identified using www.clinicaltrials. gov. Study Selection & Data Extraction: Relevant information was identified and selected based on clinical relevance and evidence-based strength. Prescribing information leaflets were used to provide usual dosage, contraindications, precautions, monitoring parameters and other relevant drug-specific information. Data Synthesis: Interferon beta products are more efficacious for the treatment of relapsing-remitting multiple sclerosis. Interferon beta 1-b also delayed the time to diagnosis of definite multiple sclerosis and reduced brain lesion burden in patients with clinical isolated syndrome. Glatiramer and natalizumab have both established efficacy in relapsing forms of multiple sclerosis; whereas mitoxantrone is more commonly used in patients with advanced disease. There are limited data the comparative efficacy among different disease modifying agents. New agents currently under investigation have showed promising results and may offer more treatment options in the future. Conclusions: MS is a complex and devastating disease with challenging treatment considerations and approaches. Interferon beta products continue to be the mainstay of therapy in many patients, however, other treatments are proving to be at least as effective in the management of various types of MS. Newer compounds are being developed and studied with much anticipation and promise for the clinical management of the disease.
Local Variation of Hashtag Spike Trains and Popularity in Twitter

We draw a parallel between hashtag time series and neuron spike trains. In each case, the process presents complex dynamic patterns including temporal correlations, burstiness, and all other types of nonstationarity. We propose the adoption of the so-called local variation in order to uncover salient dynamical properties, while properly detrending for the time-dependent features of a signal. The methodology is tested on both real and randomized hashtag spike trains, and identifies that popular hashtags present regular and so less bursty behavior, suggesting its potential use for predicting online popularity in social media.
Intravesical immunotherapy in nonmuscle invasive bladder cancer

Introduction: Nonmuscle invasive urothelial cell carcinoma is the most frequent malignancy of the urinary bladder. The high recurrence rate (up to 80%) and risk of progression (up to 30%) reflect the need for long-term follow-up and sometimes multiple interventions. To reduce the rate of recurrences and tumor progression, intravesical immunotherapy, especially the use of Bacille Calmette-Guerin (BCG), represents the gold standard adjuvant treatment of high-risk nonmuscle invasive bladder cancer (NMIBC). This article reviews the role of BCG therapy and several promising new immunotherapeutic approaches such as mycobacterium phlei cell wall-nucleic acid complex, interleukin-10 (IL-10) antibody, vaccine-based therapy, alpha-emitter therapy, and photodynamic therapy checkpoint inhibitors. Methods: A systematic literature review was performed using the terms (immunotherapy, NMIBC, BCG, and intravesical) using PubMed and Cochrane databases. Results: BCG represents the most common intravesical immunotherapeutic agent for the adjuvant treatment of high-risk NMIBC. Its use is associated with a significant reduction of recurrence and progression. Patients with NMIBC of intermediate and high-risk benefit the most from BCG therapy. To achieve maximal efficacy, an induction therapy followed by a maintenance schedule should be used. Full-dose BCG is recommended to obtain ideal antitumoral activity and there is no evidence of a reduction of side effects in patients treated with a reduced dose. There are multiple new approaches and agents in immunotherapy with potential and promising antineoplastic effects. Conclusions: The beneficial effect of BCG is well documented and established. To reduce the tumor specific mortality, it is essential to follow guideline-based treatment. In patients with BCG-failure, there are new promising alternatives other than BCG but BCG remains the gold standard at this stage.
A noisy chaotic neural network for solving combinatorial optimization problems: stochastic chaotic simulated annealing

Recently Chen and Aihara have demonstrated both experimentally and mathematically that their chaotic simulated annealing (CSA) has better search ability for solving combinatorial optimization problems compared to both the Hopfield-Tank approach and stochastic simulated annealing (SSA). However, CSA may not find a globally optimal solution no matter how slowly annealing is carried out, because the chaotic dynamics are completely deterministic. In contrast, SSA tends to settle down to a global optimum if the temperature is reduced sufficiently slowly. Here we combine the best features of both SSA and CSA, thereby proposing a new approach for solving optimization problems, i.e., stochastic chaotic simulated annealing, by using a noisy chaotic neural network. We show the effectiveness of this new approach with two difficult combinatorial optimization problems, i.e., a traveling salesman problem and a channel assignment problem for cellular mobile communications.
KATCH: high-coverage testing of software patches

One of the distinguishing characteristics of software systems is that they evolve: new patches are committed to software repositories and new versions are released to users on a continuous basis. Unfortunately, many of these changes bring unexpected bugs that break the stability of the system or affect its security. In this paper, we address this problem using a technique for automatically testing code patches. Our technique combines symbolic execution with several novel heuristics based on static and dynamic program analysis which allow it to quickly reach the code of the patch. We have implemented our approach in a tool called KATCH, which we have applied to all the patches written in a combined period of approximately six years for nineteen mature programs from the popular GNU diffutils, GNU binutils and GNU findutils utility suites, which are shipped with virtually all UNIX-based distributions. Our results show that KATCH can automatically synthesise inputs that significantly increase the patch coverage achieved by the existing manual test suites, and find bugs at the moment they are introduced.