Miracle-dz/UniFAR-FTUs huggingface dataset:
Advancements in diagnosis and treatment of meningeal carcinomatosis in solid cancer

Meningeal carcinomatosis (MC) is a disease that malignant tumor cells cultivate in the cerebrospinal fluid or meninges. With the development of therapy methods and new techniques, survival time of patients with tumor is prolonged, and the incidence of MC is increasing. Diagnosis is based on the evaluation of clinical manifestations, cerebrospinal fluid and neuroimaging findings. Furthermore, in recent years, the diagnostic value of the tumor-derived cell-free DNA in the cerebrospinal fluid (CSF) is promising and may improve the diagnostic yield of CSF analysis. Traditional treatments of MC include surgery, radiation therapy, systemic therapy, and intrathecal therapy. Recently, molecular targeted therapy and immunotherapy have received more and more attention. The authors review the epidemiology, pathogenesis, clinical manifestation, diagnosis and treatment of MC in solid cancer, and discuss the diagnosis and treatment options currently available as well as those under investigation.
Integrin activation

The ability of cells to regulate dynamically their adhesion to one another and to the extracellular matrix (ECM) that surrounds them is essential in multicellular organisms. The integrin family of transmembrane adhesion receptors mediates both cell-cell and cell-ECM adhesion. One important, rapid and reversible mechanism for regulating adhesion is by increasing the affinity of integrin receptors for their extracellular ligands (integrin activation). This is controlled by intracellular signals that, through their action on integrin cytoplasmic domains, induce conformational changes in integrin extracellular domains that result in increased affinity for ligand. Recent studies have shed light on the final intracellular steps in this process and have revealed a vital role for the cytoskeletal protein talin.
The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose

ABSTRACT: The biological interconversion of galactose and glucose takes place only by way of the Leloir pathway and requires the three enzymes galactoki‐ nase, galactose‐1‐P uridylyltransferase, and UDP‐ galactose 4‐epimerase. The only biological importance of these enzymes appears to be to provide for the interconversion of galactosyl and glucosyl groups. Galactose mutarotase also participates by producing the galactokinase substrate α‐D‐galactose from its β‐anomer. The galacto/gluco configurational change takes place at the level of the nucleotide sugar by an oxidation/reduction mechanism in the active site of the epimerase·NAD+ complex. The nucleotide portion of UDP‐galactose and UDP‐glucose participates in the epimerization process in two ways: 1) by serving as a binding anchor that allows epimerization to take place at glycosyl‐C‐4 through weak binding of the sugar, and 2) by inducing a conformational change in the epimerase that destabilizes NAD+ and increases its reactivity toward substrates. Reversible hydride transfer is thereby facilitated between NAD+ and carbon‐4 of the weakly bound sugars. The structure of the enzyme reveals many details of the binding of NAD+ and inhibitors at the active site. The essential roles of the kinase and transferase are to attach the UDP group to galactose, allowing for its participation in catalysis by the epimerase. The transferase is a Zn/Fe metalloprotein, in which the metal ions stabilize the structure rather than participating in catalysis. The structure is interesting in that it consists of a single P‐sheet with 13 antiparallel strands and 1 parallel strand connected by 6 helices. The mechanism of UMP attachment at the active site of the transferase is a double displacement, with the participation of a covalent UMP‐His166‐enzyme intermediate in the Escherichia coli enzyme. The evolution of this mechanism appears to have been guided by the principle of economy in the evolution of binding sites. —Frey, P. A. The Lenoir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose. FASEB J. 10, 461‐470(1996)
A Sense of Time for JavaScript and Node.js: First-Class Timeouts as a Cure for Event Handler Poisoning

The software development community is adopting the Event-Driven Architecture (EDA) to provide scalable web services, most prominently through Node.js. Though the EDA scales well, it comes with an inherent risk: the Event Handler Poisoning (EHP) Denial of Service attack. When an EDA-based server multiplexes many clients onto few threads, a blocked thread (EHP) renders the server unresponsive. EHP attacks are a serious threat, with hundreds of vulnerabilities already reported in the wild. We make three contributions against EHP attacks. First, we describe EHP attacks, and show that they are a common form of vulnerability in the largest EDA community, the Node.js ecosystem. Second, we design a defense against EHP attacks, first-class timeouts, which incorporates timeouts at the EDA framework level. Our Node.cure prototype defends Node.js applications against all known EHP attacks with overheads between 0% and 24% on real applications. Third, we promote EHP awareness in the Node.js community. We analyzed Node.js for vulnerable APIs and documented or corrected them, and our guide on avoiding EHP attacks is available on nodejs.org.
Impact of autoimmune diseases on outcome of patients with early breast cancer

Our aim was to analyze the impact of a concurrent autoimmune disease on outcome of patients with early breast cancer. We reviewed medical charts of patients with a diagnosis of autoimmune diseases (AD) among a population of 17.153 cases. We categorized ADs as endocrine, rheumatic, systemic, neurological diseases and vasculitis. For each patient in the study group, we matched 2 patients. The events to determine overall survival (OS) and disease free survival (DFS) were identified from follow-up data. We identified 279 (1.62%) patients with early breast cancer and concurrent ADs. The median follow-up was 7.0 years. The 10-year OS rate was 86% (95% CI, 80% to 91%) in the study group and 90% (95% CI, 86% to 93%) for the control group (p = 0.011). In patients with ER positive/HER2 negative subtype a worse OS was observed in the study group when compared to the control group (p = 0.0046); this difference remained statistically significant when the analysis was restricted to breast cancer mortality (p = 0.045). The 10-year DFS rate was 69% (95% CI, 61% to 76%) in the study group and 72% (95% CI, 66% to 77%) for the control group (p = 0.22). Autoimmunity at diagnosis of early breast cancer is associated with worse survival.
Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis.

Detection of persistent cervical carcinogenic human papillomavirus (HPV) DNA is used as a marker for cervical cancer risk in clinical trials. The authors performed a systematic review and meta-analysis of the association between persistent HPV DNA and high-grade cervical intraepithelial neoplasia (CIN2-3), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer (together designated CIN2-3/HSIL+) to evaluate the robustness of HPV persistence for clinical use. MEDLINE and Current Contents were searched through January 30, 2006. Relative risks (RRs) were stratified by HPV comparison group. Of 2,035 abstracts, 41 studies were eligible for inclusion in the meta-analysis. Over 22,500 women were included in calculation of RRs for persistent HPV DNA detection and cervical neoplasia. RRs ranged from 1.3 (95% confidence interval: 1.1, 1.5) to 813.0 (95% confidence interval: 168.2, 3,229.2) for CIN2-3/HSIL+ versus 12 months), wider testing intervals, CIN2-3/HSIL+, and use of an HPV-negative reference group were consistently associated with higher RRs. Thus, HPV persistence was consistently and strongly associated with CIN2-3/HSIL+, despite wide variation in definitions and study methods. The magnitude of association varied by duration of persistence and testing interval. Precise definition and standardization of HPV testing, sampling procedure, and test interval are needed for reliable clinical testing. These findings validate HPV persistence as a clinical marker and endpoint.
Unintrusive aging analysis based on offline learning

Runtime aging analysis of integrated circuits enables adaptive approaches in order to enhance the system's life time and permits the user to be aware of critical states. Common approaches utilize sensors that are integrated invasively into critical paths or report experienced aging. This work presents a lightweight supportive technique that correlates environmental and internal conditions with learned data in order to predict the actual wear-out of the system. Simulation results indicate the feasibility of the approach with prediction errors below 10%.
Hyponatraemia in adults with community-acquired bacterial meningitis.

BACKGROUND Hyponatraemia in adults with bacterial meningitis has been described as a common complication, but its true prevalence and clinical importance are unknown. AIM To investigate the prevalence, clinical characteristics and consequences of hyponatraemia in bacterial meningitis in adults. DESIGN Nationwide observational cohort study. METHODS We prospectively assessed the prevalence and clinical characteristics of hyponatraemia among 696 adults with community-acquired bacterial meningitis. Symptoms and signs on admission, blood and CSF test results, radiological examinations and complications during admission were recorded. RESULTS Sodium levels were determined at admission in 685/696 episodes of bacterial meningitis (98%). Hyponatraemia (<135 mmol/l) was seen in 208/685 (30%) and was classified as severe (<130 mmol/l) in 38 (6%). Hyponatraemia developed during admission in an additional 53 episodes. Hyponatraemia was not associated with an increase in symptoms, with complications or with unfavourable outcome. Treatment for hyponatraemia was initiated in 16% of episodes, but did not influence its duration. DISCUSSION Hyponatraemia appears both common and benign in adults with bacterial meningitis. In cases of severe hyponatraemia, we suggest the use of fluid maintenance therapy.
Privacy-Preserving Detection of Inter-Domain SDN Rules Overlaps

SDN approaches to inter-domain routing promise better traffic engineering, enhanced security, and higher automation. Yet, naïve deployment of SDN on the Internet is dangerous as the control-plane expressiveness of BGP is significantly more limited than the data-plane expressiveness of SDN, which allows fine-grained rules to deflect traffic from BGP's default routes. This mismatch may lead to incorrect forwarding behaviors such as forwarding loops and blackholes, ultimately hindering SDN deployment at the inter-domain level. In this work, we make a first step towards verifying the correctness of inter-domain forwarding state with a focus on loop freedom while keeping private the SDN rules, as they comprise confidential routing information. To this end, we design a simple yet powerful primitive that allows two networks to verify whether their SDN rules overlap, i.e., the set of packets matched by these rules is non-empty, without leaking any information about the SDN rules. We propose an efficient implementation of this primitive by using recent advancements in Secure Multi-Party Computation and we then leverage it as the main building block for designing a system that detects Internet-wide forwarding loops among any set of SDN-enabled Internet eXchange Points.
Medical vocabulary mining using distributional semantics on Japanese patient blogs

Random indexing has previously been successfully used for medical vocabulary expansion for Germanic languages. In this study, we used this approach to extract medical terms from a Japanese patient blog corpus. The corpus was segmented into semantic units by a semantic role labeller, and different pre-processing and parameter settings were then evaluated. The evaluation showed that similar settings are suitable for Japanese as for previously explored Germanic languages, and that distributional semantics is equally useful for semi-automatic expansion of Japanese medical vocabularies as for medical vocabularies in Germanic languages.
Network slicing architecture for 5G network

3GPP SA2 [6] is currently developing 5G network architecture with a code name of NextGen Network. Network slicing architecture is the key issue to change the network paradigm into a new unforeseen stage of a programmable softwarized network. Although there have been many related research projects, NextGen network will be the first large-scale commercial network that adopts the network softwarization. This paper will discuss the current design issues on network slicing architecture, and proposes a new top-down approach and NextGen RRC architecture to resolve the current problems.
Direct Effects of Phenytoin , Cyclosporin , and Nifedipine on Fibroblasts

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.
Sodium Chloride Absorption by the Urinary Bladder of the Winter Flounder A

The urinary bladder of the winter flounder absorbs NaCl by a process independent of the transepithelial voltage. In contrast to most other epithelia which have a neutral NaCl-absorptive system, the flounder bladder has a high transepithelial resistance. This feature simplifies analysis of the cellular transport system because the rate of ion transfer through the paracellular pathway is rather low. Experiments were designed to distinguish among three possible mechanisms of neutral NaCl absorption: (a) Na/K/2Cl cotransport; (b) parallel Na/H and Cl/OH exchange; (c) and simple NaCl cotransport. A clear interdependency of Na and Cl for net absorption was demonstrated. NaCl absorption was not dependent on mucosal K and was minimally sensitive to loop diuretics. Thus a Na/K/2Cl transport system was unlikely. The mechanism was not parallel exchange as evidenced by insensitivity to amiloride and to 4,4'-diisothiocyano2,2'-disulfonic stilbene, an inhibitor of anion exchange. In addition, inhibitors of carbonic anhydrase had no effect. Net absorption was almost completely abolished by hydrochlorothiazide (0.1 mM). Its action was rapid, reversible, and effective only from the mucosal surface. Metolazone, a structurally dissimilar diuretic in the benzothiadiazide class had qualitatively similar actions. The Dr. Stokes is an Established Investigator of the American Heart Association. Received for publication 11 October 1983 and in revised form 6 December 1983. mechanism of NaCl absorption in this tissue appears to be a simple interdependent process. Its inhibition by thiazide diuretics appears to be a unique feature. The flounder bladder may be a model for NaCl absorption in the distal renal tubule.
Growth suppression mediated by transfection of p53 in Hut292DM human lung cancer cells expressing endogenous wild-type p53 protein.

This study was undertaken to analyze the effect of wild-type p53 transfection on the growth potential of a human lung cancer cell line Hut292DM expressing endogenous wild-type p53. Transfection efficiencies obtained with either the wild-type or a mutant p53 complementary DNA revealed a significant decrease in the number of colonies obtained with the wild-type p53 as compared to the mutant p53 complementary DNA (27%) or control vector DNA only (20%), suggesting that wild-type p53 inhibited the growth of Hut292DM cells. A series of wild-type and mutant p53 transfection clones were then analyzed for the presence and expression of the exogenous p53 gene. Polymerase chain reaction amplification revealed that 98% of mutant p53 transfection clones analyzed contained the exogenous p53 gene as opposed to 47% for wild-type p53 clones. The majority of mutant p53 clones expressed high levels of exogenous p53 mRNA and protein as analyzed by Northern and Western blots, respectively. In contrast, all wild-type p53 clones analyzed failed to express exogenous p53 mRNA transcript or protein of a normal size. Aberrant-size p53 mRNA was detected in two wild-type p53 clones (X833.W2 and W18), and Western blot analysis revealed that these clones expressed truncated p53 proteins (M(r) 45,000 and 33,000 respectively). No difference in proliferation rates in vitro or in tumorigenic potential in nude mice were observed between mutant p53 clones or control cell lines. In contrast, a wild-type p53 clone (X833.W2) exhibited a significantly reduced tumorigenic potential in nude mice, whereas its in vitro proliferation rate was comparable to parental Hut292DM cells. The data indicate that exogenous expression of wild-type p53 is incompatible with Hut292DM lung cancer cell proliferation in vitro and suggest that p53-mediated growth control in vitro and in vivo may be dissociated and exerted by separate domains of the p53 protein.
Evidence That Environmental and Familial Risks for Psychosis Additively Impact a Multidimensional Subthreshold Psychosis Syndrome

Background The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration). Method Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio. Results Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other. Conclusions Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.
Moderate Exercise Promotes Human RBC-NOS Activity, NO Production and Deformability through Akt Kinase Pathway

Background Nitric oxide (NO) produced by nitric oxide synthase (NOS) in human red blood cells (RBCs) was shown to depend on shear stress and to exhibit important biological functions, such as inhibition of platelet activation. In the present study we hypothesized that exercise-induced shear stress stimulates RBC-NOS activation pathways, NO signaling, and deformability of human RBCs. Methods/Findings Fifteen male subjects conducted an exercise test with venous blood sampling before and after running on a treadmill for 1 hour. Immunohistochemical staining as well as western blot analysis were used to determine phosphorylation and thus activation of Akt kinase and RBC-NOS as well as accumulation of cyclic guanylyl monophosphate (cGMP) induced by the intervention. The data revealed that activation of NO upstream located enzyme Akt kinase was significantly increased after the test. Phosphorylation of RBC-NOSSer1177 was also significantly increased after exercise, indicating activation of RBC-NOS through Akt kinase. Total detectable RBC-NOS content and phosphorylation of RBC-NOSThr495 were not affected by the intervention. NO production by RBCs, determined by DAF fluorometry, and RBC deformability, measured via laser-assisted-optical-rotational red cell analyzer, were also significantly increased after the exercise test. The content of the NO downstream signaling molecule cGMP increased after the test. Pharmacological inhibition of phosphatidylinositol 3 (PI3)-kinase/Akt kinase pathway led to a decrease in RBC-NOS activation, NO production and RBC deformability. Conclusion/Significance This human in vivo study first-time provides strong evidence that exercise-induced shear stress stimuli activate RBC-NOS via the PI3-kinase/Akt kinase pathway. Actively RBC-NOS-produced NO in human RBCs is critical to maintain RBC deformability. Our data gain insights into human RBC-NOS regulation by exercise and, therefore, will stimulate new therapeutic exercise-based approaches for patients with microvascular disorders.
Autobiographical memory task in assessing dementia.

BACKGROUND Since 1979, our clinicians have used an autobiographical memory task testing for events that occurred over the most recent week and most recent month in their semistructured interview when assessing for dementia. OBJECTIVE To examine correlations between scores on the autobiographical memory task and on 2 other commonly used brief memory tasks with results of a clinical assessment for dementia. DESIGN Correlation study. SETTING Academic research. PARTICIPANTS Participants were enrolled in Washington University Alzheimer Disease Research Center studies, were 60 years or older, and participated in assessments between May 29, 2002, and August 15, 2005 (N = 425). MAIN OUTCOME MEASURES Nonparametric Spearman rank correlations, adjusted for age and education status, between the Clinical Dementia Rating sum of boxes (CDR-SB) and scores on the autobiographical memory task and on 2 clinical brief memory tasks obtained from the Mini-Mental State Examination and the Short Blessed Test. RESULTS Scores on the autobiographical memory task and on each of the other 2 memory tasks correlated significantly with the CDR-SB (P < .001). Scores on the autobiographical memory task had a significantly higher correlation with results of the CDR-SB than the other 2 memory tasks (P < .001). CONCLUSION Clinicians may find the autobiographical memory task an important indicator of memory function and the autobiographical query a useful tool when assessing for dementia.