Miracle-dz/UniFAR-FTUs huggingface dataset:
The importance of a second opinion in the diagnosis of Barrett's esophagus: a "real life" study.

BACKGROUND Barrett's esophagus is a precancerous lesion, and its identification with the early detection of dysplasia is of paramount importance to prevent adenocarcinoma onset. However, there is still debate on the correct pathological identification of Barrett's esophagus (and of associated dysplasia), and most studies have been conducted in an experimental setting. AIMS To assess previous uncertain diagnoses of Barrett's (with and without dysplasia) via a second opinion of an expert pathologist in a real life setting. PATIENTS AND METHODS Histological sections of 32 suspected Barrett's patients from ten general Pathology units were centralized into one single unit in which an expert pathologist reviewed the slides blindly. RESULTS Overall, in 78% of cases there was diagnostic discordance; in particular, in 64% of cases the presence of low grade dysplasia was not confirmed. Of interest, 28% of cases with the original diagnosis were reclassified as non-Barrett's. CONCLUSIONS The pathological diagnosis of Barrett's esophagus, especially with regard to the presence of dysplasia, is still misinterpreted, particularly in the setting of general Pathology units. Thus, a second opinion from an experienced pathologist may help in the interpretation of the results and in starting appropriate follow-up programs.
Presence of Human Bocavirus 1 and other Respiratory Viruses in Children with Lower Respiratory Tract Infection in Latvia

Abstract Lower respiratory tract infection (LRTI) is the major cause of morbidity and mortality of children in the world. In addition to respiratory syncytial virus, influenza virus types A and B, parainfluenza types 1, 2 and 3, and adenoviruses, several new respiratory viruses associated with LRTI were discovered in the 21st century. These are metapneumovirus, coronaviruses NL63 and HKU1, parainfluenza virus type four and human bocavirus one (HBoV1). HBoV1 was discovered in 2005 and is considered as the fourth most prevalent respiratory virus worldwide. However, the high frequency of co-infections detected together with HBoV1 raises doubt about whether HBoV1 is a true pathogen or just a bystander. This is the first study aimed to determine the presence of HBoV1 and 18 other respiratory viruses in nasopharyngeal aspirates (NPA) of children with LRTI in Latvia. Using multiplex real-time polymerase chain reaction method, the HBoV1 genomic sequence was detected in 60.0% of NPA samples, showing that HBoV1 prevalence is high among children with LRTI in Latvia. HBoV1 mono-infection was revealed in 6.67%. The most common co-infections associated with HBoV1 were rhinovirus, adenovirus, respiratory syncytial virus A and B, metapneumovirus, and enterovirus.
Pneumonia severity index in the immunocompromised.

BACKGROUND The pneumonia severity index (PSI) accounts for many comorbidities, but not immunosuppression. OBJECTIVES To document the utility of the PSI to predict mortality in immunocompromised patients (IP) with community-acquired pneumonia (CAP). METHODS Charts of 284 patients with immunosuppression and CAP were reviewed, and these patients were compared with a contemporary sample of non-IP with CAP. The ability of the PSI to predict mortality was assessed by using multiple logistic regression. Discrimination of the PSI was studied by using the concordance index. RESULTS Thirty-nine of 284 IP died. Mortality varied according to the etiology of the immunosuppression. Patients with HIV, solid organ transplantation or treatment with immunosuppressive drugs (n=118) had a low in-hospital mortality (4.3%) and were classified as low risk. IP with hematological malignancies, chemotherapy, chest radiation or marrow transplantation (n=166) had a high mortality (20%) and were classified as high risk. Compared with non-IP, low-risk IP had similar PSI-controlled mortality (OR=0.9, P=0.80), whereas high-risk IP had significantly greater mortality (OR=2.8, P<0.0001). The concordance index revealed similar discrimination for the PSI in low-risk IP (0.77) and in non-IP (0.7), but inferior discrimination in high-risk patients (0.6). CONCLUSIONS Patients with CAP and immunosuppression can be divided into low-risk and high-risk groups. The low-risk IP have mortality similar to non-IP and can be risk stratified by using the PSI.
In vitro mutagenesis of the human T-cell leukemia virus types I and II tax genes

The tax gene of the human T-cell leukemia virus types I and II (HTLV-I and HTLV-II) is essential for viral replication and acts by increasing the level of RNA transcription. The tax genes of HTLV-I and HTLV-II encode proteins of 40 and 37 kilodaltons, respectively. By in vitro mutagenesis of the tax gene, we have investigated those regions of the protein which are essential for its function. Mutation of either the amino- or carboxy-terminal domain of the protein resulted in loss of trans-activation ability. In addition, specificity of its activity with regard to trans-activation of either the HTLV-I or HTLV-II long terminal repeats was conferred by the first 59 amino acids.
Electroacupuncture decreases Netrin-1-induced myelinated afferent fiber sprouting and neuropathic pain through μ-opioid receptors

Purpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of μ-opioid receptors. Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a μ-opioid receptor antagonist, beta-funaltrexamine (β-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB). Results: Treatment with 2 Hz EA at “Huantiao” (GB30) and “Yanglingquan” (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the μ-opioid receptor antagonist β-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells. Conclusions: Through activation of μ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.
Ranibizumab for neovascular age-related macular degeneration.

PURPOSE The pharmacology, pharmacokinetics, clinical efficacy, safety, pharmacoeconomics, and place in therapy of ranibizumab are reviewed. SUMMARY Ranibizumab is the humanized fragment of the murine monoclonal antibody that binds all the active forms of the vascular endothelial growth factor, leading to the inhibition of the neovascular process underlying age-related macular degeneration (AMD). In animal studies, intravitreal administration of ranibizumab resulted in penetration of the drug into all layers of the retina and subsequent slow absorption into the systemic circulation. Improvement in visual acuity by 15 or more letters has been observed in 33.8-40.3% of patients treated with ranibizumab in pivotal clinical trials, compared with 5% of patients treated with sham injections and photodynamic therapy (PDT). The addition of PDT to ranibizumab has not been shown to offer any benefit in terms of efficacy and has been found to worsen ocular adverse reactions. The most common adverse ocular reactions reported in patients receiving ranibizumab during clinical trials include conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation. Ranibizumab's efficacy in the treatment of neovascular AMD is well established; however, questions remain regarding the drug's optimal dosing strategy, duration of therapy, and combined therapy with other agents. While ranibizumab has been defined as the best available weapon against AMD, it is also the most expensive. CONCLUSION The efficacy of ranibizumab in the treatment of AMD is well established, but more studies are needed to determine ranibizumab's optimal dosage interval, duration of therapy, and combined use with other agents.
AN ANALYSIS OF THE EFFICIENCY OFOPTIMISTICALLY SYNCHRONIZED PARALLEL SIMULATORS

In optimistically synchronized parallel simulators logical processes execute events greedily and recovery from timestamp order violations is based on rollback. These type of simulators have shown the potential to exploit a high degree of parallelism; however, they may result ineecient due to possible unacceptable percentage of CPU time spent executing events that are rolled back (i.e., non productive simulation work). The eeciency of an optimistically synchronized parallel simulation is, in general, highly unpredictable, depending on features of the simulation model and of the hardware/software architecture. Therefore, the question on being optimistic parallel simulation time-convenient over sequential one is a hard problem to solve. In this paper we present an analysis of the eeciency for the case of simulations with a single logical process running on each processor, and under the assumption that only one non-executed event is stored in the event list of any logical process at a time. The analysis allows to predict eeciency values which are demonstrated , through simulation results of synthetic work-loads, to be good approximations of the observed ones. Finally, we show how our theoretical results can be used for predicting upper bound values on the completion time of optimistically synchronized simulations.
Empirical-bias bandwidths for spatial local polynomial regression with correlated errors

The empirical-bias bandwidth selector (EBBS) is a method for data-driven selection of bandwidths for local polynomial regression. It is a bandwidth selection method for estimation of the mean-function and its partial derivatives of any order as well as for estimation of the variance-function. Moreover EBBS allows for univariate as well as multivariate predictor variables. In this paper we introduce the empirical-bias bandwidth selector, EBBSdep. This estimation procedure is adjusted to allow for dependent errors and selection of diagonal or full bandwidth matrices for estimation of the mean-function or one of its partial derivatives as well as for estimation of the variance-function. Asymptotic results for the conditional bias of the first order partial derivative estimates are given for the local quadratic regression case. A simulation study is performed to compare the adjusted and the original version of EBBS with theoretical results for a few cases displaying varying degrees of positive correlation. (Less)
Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB chemotherapy. A SWENOTECA study.

BACKGROUND To offer minimized risk-adapted adjuvant treatment on a community and nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and thereby reducing the need of later salvage chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS From July 1995 to January 1998, a total of 232 Swedish and Norwegian patients were treated for CS1 NSGCT. All were eligible for inclusion into one of two community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) III studies. One study was a prospective randomized study for patients without vascular invasion in the testicular tumor (VASC-), evaluating the effect of one adjuvant course of cisplatin, vinblastine and bleomycin (CVB) compared with surveillance. The second study was a prospective study evaluating the effect of two adjuvant courses of CVB for VASC+ patients. RESULTS Due to slow accrual and emerging data on toxicity of CVB, the studies were prematurely closed for inclusion in 1998. Of the 232 CS1 patients treated during the study period, only 97 were included in the studies. As all remaining patients were managed according to the SWENOTECA III protocol, although not randomized, the data were pooled. At a median follow-up of 10.1 years, there have been 24 relapses. While one course of CVB to VASC- patients had limited effect on the relapse rate, two courses of adjuvant CVB reduced the relapse rate among VASC+ patients by >90%. Toxicity was high in patients administered adjuvant CVB as 24% of patients experienced grade 3 or 4 obstipation/ileus and 23% grade 3 or 4 infection. CONCLUSIONS There was no statistical difference in relapse rate between one course of adjuvant CVB and surveillance for VASC- NSGCT patients. Two courses of adjuvant CVB for VASC+ NSGCT patients reduced the relapse rate with >90% in comparison to the surveillance group. Toxicity was unacceptably high for all patients receiving CVB. Adjuvant CVB chemotherapy has no place in the treatment of CS1 NSGCT.
THE EFFECT OF INTERNATIONALIZATION ON CEO COMPENSATION : A STUDY OF SWEDISH FIRMS

This study addresses how firms’ internationalization affect compensation and tenure of CEOs. Based on a sample of Swedish listed firms we analyze internationalization related to the product market (export), capital market (foreign exchange listing), and corporate governance market (foreign board membership). Our conclusions are that all three markets contribute positively to the compensation level of CEOs. This study also shows that a higher degree of internationalization via the capital and corporate governance markets is associated with shorter CEO tenure. We argue that part of the higher CEO compensation in international oriented firms reflects a risk premium for lower job security in these firms.
Ionic properties of the acetylcholine receptor in cultured rat myotubes

The acetylcholine reversal potential (Er) of cultured rat myotubes is - 3mV. When activated, the receptor is permeable to K+ and Na+, but not to Cl- ions. Measurement of Er in Tris+-substituted, Na-free medium also indicated a permeability to Tris+ ions. Unlike adult frog muscle the magnitude of Er was insensitive to change in external Ca++ (up to 30 mM) or to changes in external pH (between 6.4 and 8.9). The equivalent circuit equation describing the electrical circuit composed of two parallel ionic batteries (EK and ENa) and their respective conductances (gK and gNa), which has been generally useful in describing the Er of adult rat and frog muscle, could also be applied to rat myotubes when Er was measured over a wide range of external Na+ concentrations. The equivalent circuit equation could not be applied to myotubes bathed in media of different external K+ concentrations. In this case, the Er was more closely described by the Goldman constant field equation. Under certain circumstances, it is known that the receptor in adult rat and frog muscle can be induced to reversibly shift from behavior described by the equivalent circuit equation to that described by the Goldman equation. Attempts to similarly manipulate the responses of cultured rat myotubes were unsussessful. These trials included a reduction in temperature (15 degress C), partial alpha-bungarotoxin blodkade, and activation of responses with the cholinergic agonist, decamethonium.
Combining ethnographic and clickstream data to identify user Web browsing strategies

Introduction: The strategies that people use to browse Websites are difficult to analyse and understand: quantitative data can lack information about what a user actually intends to do, while qualitative data tends to be localised and is impractical to gather for large samples. Method: This paper describes a novel approach that combines data from direct observation, user surveys and server logs to analyse users' browsing behaviour. It is based on a longitudinal study of university students' use of a Website related to one of their courses. Analysis: The data were analysed by using Footstep graphs to categorise browsing behaviour into pre-defined strategies and comparing these with data from questionnaires and direct observation of the students' actual use of the site. Results: Initial results indicated that in certain cases the patterns from server logs matched the observed browsing strategies as described in the literature. In addition, by cross-referencing the quantitative and qualitative data, a number of insights were gained into potential problems. Conclusion: This study shows how combining quantitative and qualitative approaches can provide an insight into changes in user browsing behaviour over time. It also identifies some potential methodological problems in studies of browsing behaviour and indicates some directions for future research.
Is There a Nonverbal Period of Development?

That the infant lives in a nonverbal sensorimotor world is widely believed. Yet this notion is being challenged by research, in a range of fields, that depicts the young infant as actively attuned to aural speech from birth and able to process and use its sounds and meanings well before the end of the first year. Following a selective review of the research on infant speech processing between birth and age twelve months, three questions are identified that highlight the theoretical and clinical implications of this research for psychoanalytic conceptualizations of infancy, the nature of language, and clinical process. The research, it is concluded, identifies the operation of linguistic and conceptual processes in early life, processes that may intersect with the experiential and emotional processes with which psychoanalysis is already concerned. Moreover, this research raises questions about the view that the nature of infancy is essentially nonverbal.
A new classification scheme using artificial immune systems learning for fuzzy cognitive mapping

In this paper, an intelligent approach based on artificial immune systems (AIS) is proposed to perform the task of classification using fuzzy cognitive map learning. Fuzzy cognitive map is an approach to knowledge representation and inference including learning capabilities; it emphasizes the connections of concepts as basic units for storing knowledge, and the structure that represents the significance of system. One of the most useful aspects of the FCM is its prediction capability as a classification tool. Little research has been done on pattern classification using FCM approach. The proposed artificial immune algorithm inspired by theoretical immunology and observed immune functions, principles and models, was considered to learn FCM network providing a category after classification. Consequently, the proposed method provides an FCM learning methodology for pattern recognition. The proposed algorithm is implemented in a previous autism classification problem, as well as in some benchmark machine learning datasets to show its functionality.
Secreted Immunodominant Mycobacterium tuberculosis Antigens Are Processed by the Cytosolic Pathway

Exposure to Mycobacterium tuberculosis can result in lifelong but asymptomatic infection in most individuals. Although CD8+ T cells are elicited at high frequencies over the course of infection in both humans and mice, how phagosomal M. tuberculosis Ags are processed and presented by MHC class I molecules is poorly understood. Broadly, both cytosolic and noncytosolic pathways have been described. We have previously characterized the presentation of three HLA-I epitopes from M. tuberculosis and shown that these Ags are processed in the cytosol, whereas others have demonstrated noncytosolic presentation of the 19-kDa lipoprotein as well as apoptotic bodies from M. tuberculosis-infected cells. In this paper, we now characterize the processing pathway in an additional six M. tuberculosis epitopes from four proteins in human dendritic cells. Addition of the endoplasmic reticulum-Golgi trafficking inhibitor, brefeldin A, resulted in complete abrogation of Ag processing consistent with cytosolic presentation. However, although addition of the proteasome inhibitor epoxomicin blocked the presentation of two epitopes, presentation of four epitopes was enhanced. To further examine the requirement for proteasomal processing of an epoxomicin-enhanced epitope, an in vitro proteasome digestion assay was established. We find that the proteasome does indeed generate the epitope and that epitope generation is enhanced in the presence of epoxomicin. To further confirm that both the epoxomicin-inhibited and epoxomicin-enhanced epitopes are processed cytosolically, we demonstrate that TAP transport and new protein synthesis are required for presentation. Taken together, these data demonstrate that immunodominant M. tuberculosis CD8+ Ags are processed and presented using a cytosolic pathway.
Image Captioning with Two Cascaded Agents

Recent neural models on image captioning usually take a encoder-decoder fashion, where the decoder predicts a single word at one step recently with the encoder providing information. The encoder is a pretrained CNN model typically. Thus the decoder, the input to it, and the output from it become the most important parts of a model. We propose a pipelined image captioning framework consisting of two cascaded agents. The former is named as "semantic adaptive agent" which generates the input to the decoder by consulting the information from the current decoding process, and the latter as "caption generating agent" which select a single word of the vocabulary as the output of the decoder by taking consideration of the input and the current states of the decoder. For the framework of two cascaded agents, we design a multi-stage training procedure to train the two agents with different objectives by fully utilizing reinforcement learning. In experiments, we conduct quantitative and qualitative analysis on MS COCO dataset and our results can significantly outperform baseline methods in terms of several evaluation metrics.
Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related disease in Chinese population

Abstract Objective: This study was performed to better know diagnosis associated with serum IgG4 concentration, and to explore the possibility for development of a serum IgG4 for IgG4-related disease (IgG4-RD) in Chinese populations. Methods: We studied retrospectively 497 IgG4 serum subclass measurements from Peking Union Medical College Hospital during the four-year period, including 242 IgG4-RD, 130 other diseases and 125 healthy individuals. Results: Serum IgG4 concentrations were significantly higher in IgG4-RD than in other pathologies (1662.9 ± 3760.9 mg/L, p < 0.001) and healthy individuals (538.2 ± 458.6 mg/L, p < 0.001). There were no significant differences in serum IgG4 level between other pathologies group and healthy individuals (p = 0.075). Among the 242 IgG4-RD patients analyzed, serum IgG4 concentrations were normal in 46 patients (19.0%). We found 32 patients (24.6%) with elevated serum IgG4 levels among the 130 patients who suffered from other pathologies. There were seven (5.6%) with serum IgG4 over 1350 mg/L in healthy individuals. The ROC curve analysis revealed that the optimal sensitivity and specificity were 80.0% and 88.2%, respectively, at the concentration of 1575 mg/L for Chinese patients. Conclusions: Our study demonstrated that serum IgG4 elevation was not specific of IgG4-RD. Further studies are needed to define the sensibility and specificity of IgG4 values for the diagnosis of IgG4-RD.