Miracle-dz/UniFAR-FTUs huggingface dataset:
The Protective Mechanism of CAY10683 on Intestinal Mucosal Barrier in Acute Liver Failure through LPS/TLR4/MyD88 Pathway

The purpose of this study was to investigate the protective mechanism of HDAC2 inhibitor CAY10683 on intestinal mucosal barrier in acute liver failure (ALF). In order to establish ALF-induced intestinal epithelial barrier disruption models, D-galactosamine/LPS and LPS were, respectively, used with rats and NCM460 cell and then administrated with CAY10683. Transepithelial electrical resistance (TEER) was measured to detect the permeability of cells. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels. The intestinal epithelial tissue pathology was detected. After interfering with CAY10683, the mRNA and protein levels of TLR4, MyD88, TRIF, and TRAF6 were decreased compared with model group (P < 0.05), whereas the levels of ZO-1 and occluding were elevated (P < 0.05). The permeability was elevated in CAY10683-interfered groups, when compared with model group (P < 0.05). And the degree of intestinal epithelial tissue pathological damage in CAY10683 group was significantly reduced. Moreover, CAY10683 significantly decreased the TLR4 staining in animal tissue. The HDAC2 inhibitor CAY10683 could promote the damage of intestinal mucosal barrier in ALF through inhibiting LPS/TLR4/MyD88 pathway.
Incremental Flow Scheduling and Routing in Time-Sensitive Software-Defined Networks

Several networking architectures have been developed atop IEEE 802.3 networks to provide real-time communication guarantees for time-sensitive applications in industrial automation systems. The basic principle underlying these technologies is the precise transmission scheduling of time-triggered traffic through the network for providing deterministic and bounded latency and jitter. These transmission schedules are typically synthesized offline (computational time in the order of hours) and remain fixed thereafter, making it difficult to dynamically add or remove network applications. This paper presents algorithms for incrementally adding time-triggered flows in a time-sensitive software-defined network (TSSDN). The TSSDN is a network architecture based on software-defined networking, which provides real-time guarantees for time-triggered flows by scheduling their transmissions on the hosts (network edge) only. These algorithms exploit the global view of the control plane on the data plane to schedule and route time-triggered flows needed for the dynamic applications in the Industrial Internet of Things (Industry 4.0). The evaluations show that these algorithms can compute incremental schedules for time-triggered flows in subseconds with an average relative optimality of 68%.
MYD88, CARD11, and CD79B Oncogenic Mutations are Rare Events in the Indian Cohort of De Novo Nodal Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) has a heterogenous biological behavior, and the western literature has reported activating oncogenic mutations in myeloid differentiation primary response gene 88 (MYD88), in conjunction with B-cell receptor signaling pathway genes, CARD11 and CD79B as the driving force for activating the NF-&kgr;B pathway implicated in the pathogenesis of DLBCL. The mutation profile of MYD88 genes was evaluated by Sanger sequencing in a cohort of 97 patients [DLBCL (N=55), non-DLBCL lymphomas (N=30), reactive lymphadenopathy (N=10), and 2 cases of lymphoplasmacytic lymphoma (positive control)]. The mutation profile of CARD11 and CD79B were evaluated in 70 patients [DLBCL (N=30), non-DLBCL lymphomas (N=30), and reactive lymphadenopathy (N=10). MYD88 and NF-&kgr;B mRNA expression was also evaluated by quantitative reverse transcriptase polymerase chain reaction. These 55 cases of DLBCL were classified into germinal center B-cell and activated B-cell phenotypes using Hans algorithm, of which 58% were of activated B-cell phenotype and 42% were of germinal center B-cell phenotype. MYD88 mutation was seen in 3.6% (2/55) of DLBCL cases, indicating a lower frequency in Indian de novo DLBCL. The mutations detected were novel 33 bp deletion g. 7735_7767del (p.V294_S305del) and a splice-acceptor site mutation in exon 5 of MYD88, different from the reported hotspot mutation MYD88 L265P. CARD11 and CD79B mutations were absent in DLBCL and other lymphoma subtypes. MYD88 transcript expression did not correlate with mutational status. NF-&kgr;B showed significant overexpression in MYD88 mutation–negative (P=0.004) DLBCL cases indicating that its regulation is independent of MYD88, CARD11, and CD79B mutations, implying the existence of alternative activating pathways. In silico analysis of 2 novel mutations predicted disruptive structural changes in the B-B loop of the translated protein whose biological significance needs further evaluation.
Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

Crohn’s disease (CD)–associated variants in the LRRK2 gene for risk (N2081D) and for protection (N551K) mediate shared effects in CD and Parkinson’s disease. A shared history Crohn’s disease (CD), an inflammatory bowel disease, has a relatively high prevalence in Ashkenazi Jewish populations. Hui et al. conducted genome-wide association analysis in 2066 CD patients and 3633 healthy control individuals of Ashkenazi Jewish ancestry and identified two functional variants in the LRRK2 gene. The LRRK2 gene has been previously linked to the development of Parkinson’s disease (PD). The new LRRK2 variants conferred risk for CD (N2081D) or protection from CD (N551K/R1398H). Analysis of other variants within the LRRK2 locus in 24,570 individuals revealed similar genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The presence of shared LRRK2 alleles in CD and PD provides insight into disease mechanisms and potential treatments. Crohn’s disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10−10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10−8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson’s disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.
Cryptosporidium spp. infection in Iranian children and immunosuppressive patients: A systematic review and meta-analysis

Background: Cryptosporidiosis is an important cause of diarrhea in children and immunosuppressive patients. The current study was intended to evaluate the prevalence rate of Cryptosporidium infection and clarify the epidemiological characteristics of the infection in both children and immunosuppressive patients in Iran. Methods: Five English electronic databases including PubMed, Google Scholar, Science Direct, Scopus and Cochrane, and two Persian language databases Magiran and Scientific Information Database were searched. Additionally, reports from the Iranian congresses of parasitology and graduate student thesis dissertations were assessed manually. Results: Out of 1856 studies from the literature search, our search resulted in a total of 27 articles published from 1991 to 2016. These include 14 reports on cryptosporidiosis in children and 13 papers regarding immunosuppressive patients. 8520 children and 2015 immunosuppressed cases were evaluated. Oocysts of Cryptosporidium were found in 3.8% and 8% children cases and immunosuppressed patients, respectively. There was a relatively high variation in the prevalence estimates among different studies, and the Q statistics was high among articles regarding children (p<0.0001) and also between records regarding immunosuppressed patients (p<0.0001). Findings showed that the prevalence rates of Cryptosporidium infection are significantly higher in children under 5 years (P=0.00). Conclusions: In summary, the present study provides a comprehensive view of the epidemiology of Cryptosporidium in children and immunosuppressive patients in Iran. Furthermore, a multidisciplinary and multicenter study to evaluate the real prevalence of Cryptosporidium infection and to determine its risk factors using an adequate sample size and standardized methods is highly recommended.
Can Apparent Diffusion Coefficient Values Assist PI-RADS Version 2 DWI Scoring? A Correlation Study Using the PI-RADSv2 and International Society of Urological Pathology Systems.

OBJECTIVE The purposes of this study were to assess correlation of apparent diffusion coefficient (ADC) and normalized ADC (ratio of tumor to nontumor tissue) with the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and updated International Society of Urological Pathology (ISUP) categories and to determine how to optimally use ADC metrics for objective assistance in categorizing lesions within PI-RADSv2 guidelines. MATERIALS AND METHODS In this retrospective study, 100 patients (median age, 62 years; range, 44-75 years; prostate-specific antigen level, 7.18 ng/mL; range, 1.70-84.56 ng/mL) underwent 3-T multiparametric MRI of the prostate with an endorectal coil. Mean ADC was extracted from ROIs based on subsequent prostatectomy specimens. Histopathologic analysis revealed 172 lesions (113 peripheral, 59 transition zone). Two radiologists blinded to histopathologic outcome assigned PI-RADSv2 categories. Kendall tau was used to correlate ADC metrics with PI-RADSv2 and ISUP categories. ROC curves were used to assess the utility of ADC metrics in differentiating each reader's PI-RADSv2 DWI category 4 or 5 assessment in the whole prostate and by zone. RESULTS ADC metrics negatively correlated with ISUP category in the whole prostate (ADC, τ = -0.21, p = 0.0002; normalized ADC, τ = -0.21, p = 0.0001). Moderate negative correlation was found in expert PI-RADSv2 DWI categories (ADC, τ = -0.34; normalized ADC, τ = -0.31; each p < 0.0001) maintained across zones. In the whole prostate, AUCs of ADC and normalized ADC were 87% and 82% for predicting expert PI-RADSv2 DWI category 4 or 5. A derived optimal cutoff ADC less than 1061 and normalized ADC less than 0.65 achieved positive predictive values of 83% and 84% for correct classification of PI-RADSv2 DWI category 4 or 5 by an expert reader. Consistent relations and predictive values were found by an independent novice reader. CONCLUSION ADC and normalized ADC inversely correlate with PI-RADSv2 and ISUP categories and can serve as quantitative metrics to assist with assigning PI-RADSv2 DWI category 4 or 5.
Evaluation of dynamic thiol/disulfide redox state in community-acquired pneumonia

Objectives To compare dynamic thiol/disulfide homeostasis between patients with community-acquired pneumonia (CAP) and healthy controls. Methods This prospective, case-control study was conducted in the Department of Pulmonary Diseases, Ankara Ataturk Training and Research Hospital, Yildirim Beyazit University, Ankara, Turkey, between August 2016 and August 2017. In total, 50 hospitalized patients with CAP and 35 healthy individuals were enrolled. Patients with comorbidities and smokers were excluded. The thiol/disulfide state was evaluated in each group. Thiol levels (native/total) and % polymorhonuclear leukocytes and C-reactive protein levels association were evaluated in patients with CAP. Results There was no significant difference between the CAP and control groups in age or gender (both, p>0.05). The disulfide (SS) levels were similar between the 2 groups (p=0.148). The total thiol (TT) and native thiol (SH) levels were significantly lower (all, p=0.001) and the SS/TT levels were significantly higher (p=0.019) in the CAP group compared with the controls. Conclusions This study showed that the oxidant/antioxidant ratio was shifted to the oxidative side in CAP patients. An abnormal thiol/disulfide state may be an important factor in the pathogenesis and monitoring the treatment response. The thiol resources may use for treatment in CAP and may positively affect the prognosis.
Role of insertion sequence element is256 as a virulence marker and its association with biofilm formation among methicillin-resistant Staphylococcus epidermidis from hospital and community settings in Chennai, South India

The objective of this study was to detect the association of biofilm formation with IS256 among clinical and carrier isolates of methicillin-resistant Staphylococcus epidermidis (MRSE). A total of 71 MRSE isolates were included in this study. Phenotypic detection of biofilm formation was done by Congo red agar method. Detection of genes associated with biofilm formation (icaAD, aap and atlE) and insertion sequence IS256 was done by polymerase chain reaction. Of the 71 MRSE isolates,19/40 (47.5%) clinical isolates from hospital settings and 11/31 (35.5%) carrier isolates from community settings respectively were found to be positive for all the three genes tested, namely, icaAD+, aap+ and atlE+ genes. Nearly 80% of clinical isolates were found to harbour IS256, whereas only 13% of community isolates harboured IS256.
The anti-transglutaminase auto-antibodies in children's saliva with a suspect coeliac disease: clinical study.

UNLABELLED The coeliac disease is an immune-mediated enteropathy triggered by an ingestion of gluten in genetically susceptible individuals. Like some other systemic diseases (Crohn's disease, Sjögren's syndrome) the celiac disease is able to alter the oral ecosystem and the composition of the saliva. AIM The aim of this retrospective study has been to examine the incidence of coeliac disease (CD) in paediatric population and to search the presence of anti-transglutaminase auto-antibodies (anti-tTG) in saliva, comparing and quantifying the concentration regard to the serum values of the anti-tTG auto-antibodies, before and after six months from the beginning of the free gluten diet. MATERIALS AND METHODS 105 children (G0), aged between 5 and 13 years, belonging to the Paediatric Gastroenterology-Endoscopy Unit of PTV Hospital, University of Rome "Tor Vergata", have been examined for a diagnosis of suspected CD. RESULTS Of a total of 105 pediatric patients (G0), only the 16.2% (G1) has showed to be positive. About the evaluation of the anti-tTG auto-antibodies in the serum, obtained from the second blood sample (T1), we can observe that 10 (G2) out of 17 children (G1) show positivity and for this reason they have been subjected to a sampling of intestinal villi to confirm the diagnosis of CD; in addition the 6.7% has been resulted positive at the first sampling of serum (T0), but negative to the second one (T1). The incidence of the CD has been resulted to be equal to 9.5%. About the evaluation of anti-tTG in the G1, we can observe that 58.8% of children are "definitely positive" to the salivary anti-tTG, while 11.8% appear to be weakly positive. About the correspondence of serum and salivary anti-tTG in Group G1, we can observe, that children positive to the anti-tTG in the serum have also the anti-tTG in the salivary fluid (sensibility 100%, specificity 71.4%). The results show that the anti-tTG salivary are present in children with CD, even though they have continued to follow the gluten free diet for 6 months. CONCLUSIONS The presence of anti-tTG in the saliva may be considered, an additional and useful diagnostic dental marker for an initial, reproducible, non invasive, inexpensive and highly sensitive screening of CD having a predictive and precocious value compared to anti-tTG contained in the serum, as it has been already demonstrated.
Perioperative analgesia with a buprenorphine transdermal patch for hallux valgus surgery: a prospective, randomized, controlled study

Purpose Hallux valgus surgery often results in significant postoperative pain. Adequate control of pain is essential for patient satisfaction and improves the outcome of the procedure. This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent hallux valgus surgery. Patients and methods A total of 90 patients were randomly divided into the following three groups based on the perioperative analgesic method: flurbiprofen axetil intravenous injection (Group F), oral celecoxib (Group C), and buprenorphine transdermal delivery system (BTDS) (Group BTDS). The pain status, degree of satisfaction, adverse effects, and administration of tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 2, and postoperative day 3. Results The BTDS could effectively control perioperative pain for patients undergoing hallux valgus surgery. The analgesic effect of the BTDS was better than that of oral celecoxib. In addition, statistically significant differences were not observed in the visual analog scale (VAS) scores, adverse effects, and rescue analgesia between the patients who received the BTDS and the patients who received the flurbiprofen axetil intravenous injection. However, the degree of patient satisfaction of the BTDS group was significantly higher (P<0.05) than that of the other two groups. Conclusion The BTDS (a preemptive analgesia regimen) could exert an analgesic effect during the perioperative period for patients who had received hallux valgus surgery, and this effect is beneficial for sustaining postoperative physiological and psychological states and promoting functional rehabilitation.
Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1

Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α–mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions.
The Making of Hawks and Doves∗

We argue that central bankers’ personal inflation experiences significantly alter their inflation forecasts, votes, and speeches. First, we show that inflation experiences have a direct impact on Federal Open Market Committee members’ inflation forecasts in their semi-annual Monetary Policy Reports to U.S. Congress. Second, members with higher inflation experiences are significantly more likely to cast a hawkish dissent. Over the FOMC’s voting history since March 1951, an increase in a member’s experience-based inflation forecast by one within-meeting standard deviation raises the probability of a hawkish dissent by about one third, and decreases the probability of a dovish dissent also by about one third. Third, higher inflation experiences also predict a significantly more hawkish tone in speeches. Finally, aggregating over all FOMC members present at a meeting, the average experience-based forecast helps predict the federal funds target rate, over and above conventional forward-looking Taylor rule components. Our findings indicate strong and long-lasting effects of personal inflation experiences even among monetary-policy experts, and point to the importance of FOMC members’ selection.
Comparison of ureteroscopic pneumatic lithotripsy and extracorporeal shock wave lithotripsy for the management of proximal ureteral stones: A single center experience.

OBJECTIVE To evaluate and compare the effectiveness of ureteroscopic (URS) pneumatic lithotripsy versus extracorporeal shock wave lithotripsy (ESWL) in the management of the proximal ureteral stones in terms of stone- free rates, complications and costs involved. MATERIAL AND METHODS We included 200 patients in Group 1 who underwent ESWL and 200 patients in Group 2 who underwent URS intervention. We used Modulith SL X lithotripter 3rd generation Storz medical for ESWL group while Swiss pneumatic lithoclast was used to break the stone in the URS group. Stone-free status was defined as stone fragment of less than 4 mm on follow- up kidney ureter and bladder X-ray after 3 months of procedure. SPSS version 16 was used for statistical analysis. RESULTS The mean age in ESWL and URS groups were 39.21±13.36, and 43.13±13.65 years respectively. Mean stone size was 10.47±3.7 mm (ESWL) and 13.6±6.6 mm (URS). Stone- free rate after single procedure was (125/200 patients) 62.5% for ESWL and (168/200 patients) 84% for URS group (p=0.001). Complications included post procedure sepsis in 3 (1.5%) patient of ESWL, while 7 (3.5%) patients of URS groups. Steinstrasse was seen in 4 (2%) patients of ESWL group. No mortality was seen in both groups. Mean costs for ESWL were US $320±50 while US $1100±150 for URS group (p=0.001). CONCLUSION The stone-free rates after single procedure were significantly higher for the URS group while the complication rates were comparable in both groups. Treatment costs were significantly lower for the ESWL group.