Miracle-dz/UniFAR-FTUs huggingface dataset:
Sepsis-Induced Apoptosis Leads to Active Suppression of Delayed-Type Hypersensitivity by CD8+ Regulatory T Cells through a TRAIL-Dependent Mechanism

Patients who survive severe sepsis often display severely compromised immune function. One hallmark of such immune suppression in septic patients is an impaired delayed-type hypersensitivity (DTH) response, manifested by a loss of skin testing to recall Ags. Because sepsis induces significant apoptosis in lymphoid and myeloid cells, and apoptotic cells are themselves tolerogenic, we tested the hypothesis that suppression of DTH is mediated by tolerogenic properties of the apoptotic cells generated during sepsis. Mice subjected to cecal ligation and puncture demonstrated a loss of DTH for the 7 d following cecal ligation and puncture; however, the immune response returned to normal by day 10. Blocking sepsis-induced apoptosis via Bcl-2 overexpression or Bim deficiency prevented the loss of DTH. Importantly, injection of apoptotic cells into Bim−/− mice prevented an effective DTH response, thereby suggesting a causal link between apoptotic cells and immune suppression. Surprisingly, when TRAIL null mice were examined, we found that these animals had significant apoptosis but retained their DTH responses. Further studies revealed that apoptotic cells generated during sepsis induced a CD8+ regulatory T cell that suppressed DTH by TRAIL production. These results establish a link between apoptotic cells and immune suppression during sepsis and suggest TRAIL may be a viable therapeutic target for boosting the adaptive immune response following sepsis.
Between virtual and real: exploring hybrid interaction and communication in virtual worlds

In this paper we aim to explore the potential advantages of interactions on student engagement and provide guidance to educators who seek interactive and immersive learning experiences for their students through the use of hybrid virtual learning approaches. We define as hybrid virtual learning the educational model where students are co-present and interacting simultaneously both within a virtual world and the physical classroom receiving stimuli related to the learning material in the virtual world from both directions. In order to achieve our aim, we categorised interactions in various categories and observed the complex network of interactions which can be developed in a virtual world when groups of people are working together in order to achieve different goals. The findings suggest that students spontaneously tend to use the interaction channels only when it is deemed to be necessary.
Socioeconomic correlates and the choice of treatment for childhood fever in Ghana

The study investigated the effect of household socioeconomic factors on the choice of treatment for childhood fever among children under age five in Ghana. Data from the 2008 Ghana Demographic and Health survey was used employing the multinomial probit model. Three treatment choices were considered: Government facility, Private facility and traditional/self-medication. The results suggest that the treatment of childhood fever is related to household wealth, health insurance status and residence. Government health facilities are mostly used by household's with higher wealth and household's with health insurance. Rural households are more likely to use traditional/self-medication, except those with health insurance who use government facilities. The age of the mother and birth order of the child were also found to influence the choice of treatment facility for childhood fever.
Surgical resection for local recurrence after radiofrequency ablation for colorectal liver metastasis is more extensive than primary resection

Abstract Objective. As a minimally invasive modality, radiofrequency ablation (RFA) has been increasingly applied not only for the treatment of hepatocellular carcinoma, but also for that of colorectal liver metastasis (CLM). However, RFA for CLM has been shown to be associated with a high local recurrence rate, and no optimal treatment for RFA failure has been established yet. The aim of this study was to evaluate the feasibility and outcome of surgical resection for local recurrence after RFA. Material and methods. A retrospective study of 17 patients, who underwent surgery for local recurrence after RFA for resectable CLM, was carried out. The surgical procedures involved in the actual surgery were compared with those envisioned for the primary resection if RFA had not been selected. Results. Surgical resection for RFA recurrence was more invasive than the envisioned surgical procedure in 10 cases (58%). In addition, the proportions of cases that required technically demanding procedures among the patients receiving surgery for RFA recurrence were higher than those in envisioned operations; major hepatectomy, eight cases [47%] versus two cases [12%] (p < 0.0205); excision and/or reconstruction of the major hepatic veins, three cases [18%] versus zero case [0%] (p = 0.035); excision of diaphragm: three cases [18%] versus zero case [0%] (p = 0.035). The 1-, 3- and 5-year overall survival rates were 92%, 45% and 45%, respectively. Conclusions. Surgical resection for RFA recurrence for CLM required more invasive and technically demanding procedures. Thus, RFA for CLM should be limited to unresectable cases, and patients with resectable CLM should be thoroughly advised not to undergo RFA, but rather surgical resection.
LL-37 Directs Macrophage Differentiation toward Macrophages with a Proinflammatory Signature

The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MΦ-2; driven by M-CSF) versus proinflammatory macrophages (MΦ-1; driven by GM-CSF) as well as on fully differentiated MΦ-1 and MΦ-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 μg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF–driven macrophage differentiation. Exposure of fully differentiated MΦ-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MΦ-2. In contrast, LL-37 had no effect on fully differentiated MΦ-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.
Security analysis and improvement of two verifiable multi-secret sharing schemes

Recently, some schemes about verifiable multi-secret sharing based on two-variable one-way function have been proposed. In this paper, we analyse the security of two schemes and draw a conclusion that the both schemes cannot verify whether the dealer is honest or not. We also improve these schemes to make them have the fully verifiable property.
Netrin-1 Regulates Th1/Th2/Th17 Cytokine Production and Inflammation through UNC5B Receptor and Protects Kidney against Ischemia–Reperfusion Injury

Overwhelming evidence suggests that ischemia–reperfusion injury of the kidney is an inflammatory disease mediated by innate and adoptive immune systems. The neuronal guidance molecule netrin-1 was shown to modulate inflammatory responses. Given that ischemic kidney is particularly prone to reperfusion-elicited inflammation, we sought to determine the function of netrin-1 and its receptor UNC5B in ischemia–reperfusion-induced inflammation. Renal ischemia–reperfusion caused a rapid decrease in serum netrin-1 levels. Administration of recombinant netrin-1 before or after renal ischemia–reperfusion reduced kidney injury, apoptosis, monocyte and neutrophil infiltration, and cytokine (IL-6, IL-1β, and TNF-α) and chemokine (MCP-1, macrophage-derived cytokine, monokine-induced IFN-γ, keratinocyte-derived chemokine, and chemokine with 6 cysteines) production. Analysis for different netrin-1 receptors on leukocytes showed very high expression of UNC5B but not UNC5C, UNC5D, neogenin, or deleted in colorectal cancer. Expression of UNC5A was low. Neutralization of UNC5B receptor reduced netrin-1–mediated protection against renal ischemia–reperfusion injury, and it increased monocyte and neutrophil infiltration, as well as serum and renal cytokine and chemokine production, with increased kidney injury and renal tubular cell apoptosis. Finally, investigation into netrin-1’s effect on CD4 T cell stimulation showed suppression of Th1/Th2/Th17 cytokine (IL-2, IL-6, IL-10, IL-13, IL-17, IFN-γ, IL-4, and TNF-α) production in vitro. Our studies demonstrate that netrin-1 acting through UNC5B receptor reduces renal ischemia–reperfusion injury and its associated renal inflammation.
The expression level of TRAF1 in human gastric mucosa is related to virulence genotypes of Helicobacter pylori

Abstract Objective. To investigate the expression level of tumor necrosis factor receptor-associated factor 1 (TRAF1) in gastric mucosa tissue in patients infected with Helicobacter pylori (H. pylori) and to analyze the relationship between TRAF1 expression and H. pylori virulence. Methods. Gastric tissue samples were collected from patients with gastritis, atrophic gastritis, intestinal metaplasia with atypical hyperplasia, and gastric cancer. The expression level of TRAF1 in each group was analyzed by real-time polymerase chain reaction (PCR) and Western blot analysis. Virulence genotypes of H. pylori were determined by PCR. Results. Significant differences in TRAF1 mRNA levels were observed between the gastritis and gastric cancer groups, and the atrophic gastritis and gastric cancer groups (p < 0.05). Moreover, significant differences in TRAF1 protein levels were observed between the gastritis and intestinal metaplasia with atypical hyperplasia groups, between the gastritis and gastric cancer groups, and between the atrophic gastritis and gastric cancer groups (all p < 0.05). The virulence genotypes of cytotoxin-associated gene A (cagA), vacAs1, and vacAm1 were more frequent in the TRAF1 high-level group than in the TRAF1 low-level group (p < 0.05). Conclusion. Higher TARF1 expression level is associated with infection by CagA+/vacAs1+/m1+ virulent H. pylori strains and may promote the proliferation of gastric mucosal cells and induce gastric cancer.
The hospital Internal Medicine specialist today: a literature review and strength, weaknesses, opportunity, threats (SWOT) analysis to develop a working proposal

The aim of the paper is to identify the role of the hospital Internal Medicine specialist in the Internal Medicine Unit (IMU) through a clinical and statistical analysis of the patients referred to them by identifying the activities that differentiate them from patients in General Medicine and Emergency Departments, i.e. diagnosis and treatment of complex patient with varying degrees of instability, identifying priorities in the acute problems of co-morbidities. The modified early warning score (MEWS), an internationally validated marker, was chosen to assess and stratify the clinical instability of patients referred to the IMU. A literature review was carried out, and a cut-off score of 3 was chosen to define the critical patients referred to the IMU; a MEWS value of 4 defines the need for transfer to the Intensive Care Unit (ICU) or Intensive Cardiac Care Unit (CCU), considered the primary end point in most of the studies examined. To better characterize the internist’s role today, a strength, weaknesses, opportunity, threats (SWOT) analysis was performed and examined, and commented upon. A total of 101 articles were reviewed and 5 were selected. The case histories relating to the IMU appear to be made up of complex patients with conditions that are, in most cases, acute and unstable. From 10% to 17% of patients present a MEWS of 3 or more that defines a condition of severe clinical instability requiring continuous observation and non-invasive multi-parametric monitoring. From 5% to 7% of cases present a MEWS of 4 or more and therefore require transfer to the ICU/CCU or risk rapid death. Approximately 40% of patients present MEWS of 1-2 and still have disease flare-up, but with a lesser degree of instability; however, these patients could experience a potentially negative disease development if not promptly and properly treated. Approximately 40% of patients have MEWS of 0 and represent the group of fragile patients that cannot be studied, diagnosed or stabilized on an outpatient basis. The critical analysis of the literature review and the SWOT analysis suggest that the two specific hospital internist’s tasks are: i) to stabilize acute, severe and complex patients with multiple pathologies; and ii) to develop etiologically difficult diagnoses in these and in fragile patients who need to be admitted to the hospital because the alternative diagnostic routes, for various reasons, cannot be used.
Per-oral endoscopic myotomy for achalasia. Are results comparable to laparoscopic Heller myotomy?

Abstract Objective. Per-oral endoscopic myotomy (POEM) has recently been introduced as a minimal invasive alternative to conventional treatment for achalasia. This study aimed to clarify the feasibility and the short-term clinical efficacy of POEM as compared to laparoscopic Heller myotomy (LHM). Methods. Treatment outcomes were prospectively recorded and compared between the procedures in a nonrandomized fashion. Reduction rate (RR) in timed barium esophagogram (TBE) was calculated at 1, 2 and 5 min after barium ingestion as: RR = 1− postoperative barium height/preoperative barium height. Risk factors for treatment failure defined as the proportion of patients with RR <0.5 (1 min) and gastroesophageal reflux (GER) after POEM were analyzed. Results. Forty-two consecutive patients who underwent POEM were compared to 41 patients who had a LHM during the immediate time period prior to the introduction of POEM. Ninety percent of the cases reported complete symptom relief after POEM. The percentage of esophageal emptying and RR in TBE improved dramatically by both procedures without significant difference. A longer operation time (odds ratio [OR] 32.80, 95%CI 2.99–359.82, p = 0.004) and younger age (OR 26.81, 95%CI 2.09–344.03, p = 0.012) were the independent predictors of treatment failure after POEM. GER was observed in seven patients where previous dilatation (OR 8.59, 95%CI 1.16–63.45, p = 0.035) and higher body mass index (OR 8.69, 95%CI 1.13–66.63, p = 0.037) were the independent predictors for symptomatic GER after POEM. Conclusion. POEM seems to be a safe and effective treatment option for achalasia in the short-term perspective; an effect well comparable to LHM.
Demography and clinical course of ulcerative colitis in Arabs – a study based on the Montreal classification

Abstract Objective. Ulcerative colitis (UC) is generally considered a disease of the Caucasian populations in developed countries, but its incidence is increasing rapidly in many developing countries, including the Middle East. The objective of this study was to determine the clinical epidemiology of UC in Arabs. Material and methods. This cross-sectional medical record-based descriptive study collected sociodemographic and clinical information on 182 Arab patients with UC in Kuwait. Age at diagnosis, extent and severity of disease were determined according to the Montreal classification. Results. Among the 182 patients, 91 (50.0%) were males. The median age at diagnosis was 28.5 years. Family history of UC was reported by 26 (14.3%) patients. The extent of the disease was limited to the rectum in 34 (18.7%) patients, left sided in 67 (36.8%) and pan colitis in 81 (44.5%). At the time of inclusion in the study, 127 (69.8%) patients were in clinical remission, 53 (29.1%) had mild-to-moderate disease and 2 (1.1%) had severe colitis. Younger age at diagnosis and non-smoking were associated with more extensive colitis. The majority of patients were treated with mesalamine, steroids and immunomodulators, while biologic therapy and surgery were needed in 5% and 4% of the patients, respectively. Conclusions. UC presents more commonly at younger age among Arabs in Kuwait. Extensive disease at presentation is associated with younger age at diagnosis and absence of tobacco smoking. There also appears to be less need for surgery and biologic therapy for the disease in this population.
Antigen-Specific Cytotoxicity by Invariant NKT Cells In Vivo Is CD95/CD178-Dependent and Is Correlated with Antigenic Potency

Invariant NKT (iNKT) cells are a unique subset of T lymphocytes that rapidly carry out effector functions following activation with glycolipid Ags, such as the model Ag α-galactosylceramide. Numerous studies have investigated the mechanisms leading to Th1 and Th2 cytokine production by iNKT cells, as well as the effects of the copious amounts of cytokines these cells produce. Less is known, however, about the mechanisms of iNKT cell cytotoxicity. In this study, we investigated the effect of Ag availability and strength, as well as the molecules involved in iNKT cytotoxicity. We demonstrate that the iNKT cell cytotoxicity in vivo correlates directly with the amount of CD1d expressed by the targets as well as the TCR affinity for the target glycolipid Ag. iNKT cells from spleen, liver, and thymus were comparable in their cytotoxicity in vitro. Surprisingly, we show that the Ag-specific cytotoxicity of iNKT cells in vivo depended almost exclusively on the interaction of CD95 (Fas) with CD178 (FasL), and that this mechanism can be efficiently used for tumor protection. Therefore, unlike NK cells, which rely mostly on perforin/granzyme-mediated mechanisms, the Ag-specific cytotoxicity of iNKT cells in vivo is largely restricted to the CD95/CD178 pathway.
A fuzzy control framework for wireless sensor networks

We present a novel framework that can be used to dynamically control the operation of sensors embedded in a Wireless Sensor Network WSN. Fuzzy logic incorporating temporal reasoning is used as the basis of our framework, permitting WSNs to automatically adapt to their changing environment. This makes WSNs more responsive and potentially more energy efficient. A fuzzy rule based, object-oriented programming language for WSNs called fuzzy Sensor Web Language fuzzy SWL is implemented as the front end of our framework. A proof-of-concept field test with two rules incorporating air temperature, rainfall, and water level demonstrates the feasibility of our fuzzy control approach for environmental monitoring. A novel aspect of this research is the addition of time factors in fuzzy rules. Time factors permit the fuzzy control system to effectively adapt to changing environmental conditions.
Histone Deacetylase 7 Regulates Cell Survival and TCR Signaling in CD4/CD8 Double-Positive Thymocytes

CD4/CD8 double-positive thymocytes express the transcriptional repressor histone deacetylase (HDAC)7, a class IIa HDAC that is exported from the cell nucleus after TCR engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in mouse thymocytes and that it regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR Jα segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAPK activity that contributes to the observed loss of viability. Remarkably, the activity of protein kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining autoexcitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions.
Neoplasia in the colorectal specimens of patients with ulcerative colitis and ileal pouch-anal anastomosis – need for routine surveillance?

Abstract Objective. Patients who undergo ileal pouch-anal anastomosis (IPAA) after colectomy for ulcerative colitis (UC) occasionally have neoplasia in the IPAA. Patients with evidence of dysplasia or carcinoma in the colorectal specimen may have an increased risk of such neoplasia. A surveillance program has been suggested. The aims of this study were to evaluate the outcomes of surveillance of a large patient cohort, and to investigate the prevalences of neoplasia in the ileal pouch mucosa and in the anal transitional zone (ATZ). Material and methods. A total of 629 patients underwent IPAA for UC at Sahlgrenska University Hospital, Gothenburg, Sweden. Identified from a register, 73 patients with neoplasia in their specimen considered eligible for the trial were prospectively enrolled, and underwent clinical examination, endoscopy with macroscopic evaluation, and mucosal biopsies from the ileal pouch and the ATZ. The biopsies were independently evaluated by two experienced gastro-pathologists. Results. In all, 56 patients (39 males) with a median follow-up time of 18 (range, 1–29) years were evaluated. One patient (1.8%; 95% CI 0%–5.3%) showed low-grade dysplasia in the pouch, as recorded by one of the two pathologists. The individual pathologists recorded indefinite for dysplasia (IFD) in the pouch for 19 and 20 patients, respectively, and IFD in the ATZ for 2 and 4 patients, respectively. None of the biopsies showed evidence of high-grade dysplasia (HGD) or carcinoma. Conclusions. Neoplasia in the ileal pouch or ATZ after IPAA for UC is rare in the proposed risk group. The necessity for and value of a routine surveillance program should be prospectively evaluated.