Miracle-dz/UniFAR-FTUs huggingface dataset:
NCF2, MYO1F, S1PR4, and FCN1 as potential noninvasive diagnostic biomarkers in patients with obstructive coronary artery: A weighted gene co‐expression network analysis

This study aims to explore the predictive noninvasive biomarker for obstructive coronary artery disease (CAD). By using the data set GSE90074, weighted gene co‐expression network analysis (WGCNA), and protein–protein interactive network, construction of differentially expressed genes in peripheral blood mononuclear cells was conducted to identify the most significant gene clusters associated with obstructive CAD. Univariate and multivariate stepwise logistic regression analyses and receiver operating characteristic analysis were used to predicate the diagnostic accuracy of biomarker candidates in the detection of obstructive CAD. Furthermore, functional prediction of candidate gene biomarkers was further confirmed in ST‐segment elevation myocardial infarction (STEMI) patients or stable CAD patients by using the datasets of GSE62646 and GSE59867. We found that the blue module discriminated by WGCNA contained 13 hub‐genes that could be independent risk factors for obstructive CAD (P < .05). Among these 13 hub‐genes, a four‐gene signature including neutrophil cytosol factor 2 (NCF2, P = .025), myosin‐If (MYO1F, P = .001), sphingosine‐1‐phosphate receptor 4 (S1PR4, P = .015), and ficolin‐1 (FCN1, P = .012) alone or combined with two risk factors (male sex and hyperlipidemia) may represent potential diagnostic biomarkers in obstructive CAD. Furthermore, the messenger RNA levels of NCF2, MYO1F, S1PR4, and FCN1 were higher in STEMI patients than that in stable CAD patients, although S1PR4 showed no statistical difference (P > .05). This four‐gene signature could also act as a prognostic biomarker to discriminate STEMI patients from stable CAD patients. These findings suggest a four‐gene signature (NCF2, MYO1F, S1PR4, and FCN1) alone or combined with two risk factors (male sex and hyperlipidemia) as a promising prognostic biomarker in the diagnosis of STEMI. Well‐designed cohort studies should be implemented to warrant the diagnostic value of these genes in clinical purpose.
Discontinuation of angiotensin-converting enzyme inhibitors or beta-blockers and the impact on heart failure hospitalization rates

Background: Adherence to evidence-based therapy is essential for optimal management of heart failure. Yet, medication adherence is poor in heart failure patients. The Ascertaining Barriers to Compliance Project decomposed the medication adherence process into initiation, implementation, and discontinuation stages, but electronic monitoring-based adherence analyses usually do not consider this process. Aims: The aim of this study was to describe individual-patient patterns of medication adherence from electronic monitoring data among adults with chronic heart failure, adherence types, and risk factors for increased all-cause hospitalization including measures of poor adherence such as discontinuation. Methods: Data from two prospective studies of adherence measured with electronic monitoring for heart failure patients were combined and restricted to monitoring of angiotensin-converting enzyme inhibitors and beta-blockers over an initial three-month period. Hospitalizations were recorded for this period as well as for a three-month follow-up period. Analyses were conducted using adaptive modeling methods to identify individual-patient adherence patterns, adherence types, and risk factors for an increased hospitalization rate. Results: Using electronic monitoring data for 254 heart failure patients, four adherence types were identified: highly consistent, consistent but variable, moderately consistent, and poorly consistent. Sixteen individually significant risk factors for increased hospitalization rates were identified and used to generate a multiple risk factors model. Medication discontinuation was the most important individual risk factor and most important in the multiple risk factors model. Conclusion: Discontinuation of angiotensin-converting enzyme inhibitors or beta-blockers increases hospitalization rates for heart failure patients. Interventions that effectively address this problem are urgently needed.
Total or Subtotal Colectomy with Primary Anastomosis for Occlusive Left Colon Cancer: A Safe, Acceptable and Applicable Procedure.

INTRODUCTION Occlusive left colon cancer is a major emergency setting in colon cancer with high morbidity and mortality rates. Different surgical treatment exist since there is no clear guidelines for the best treatment. We have conducted this retrospective study in order to evaluate the safety, morbidity, and bowel movement status of the operated patients. METHODS One-hundred and one left occlusive colon cancer patients were operated of total or subtotal colon resection with primary anastomosis from March 2000 till March 2017 in Hotel Dieu de France hospital. We analyzed the sex ratio, age, caecum condition, tumor localization, number of synchronous adenoma and adenocarcinoma, Dukes stage, major complications and the number of stools per day at 3 and 12 months after surgery. RESULTS Mean hospital stay was 7.8 days. Thirteen complications were observed in 11 (10.9%) patients, in which one (1%) patient had splenectomy for severe hemorrhage. Six synchronous adenocarcinoma and 40 adenoma with dysplasia were diagnosed on pathology specimens proximal to occlusion site. Caecum laceration was found in 33 (32.6%) of cases. No patient had anastomotic leak. After 12 months of surgery, the average bowel movement was 2 stools per day. CONCLUSION Our study showed that treating occlusive left colon cancer with total or subtotal colectomy with primary anastomosis is a safe procedure, with a good bowel movement status and presents the advantage to resect an important number of synchronous tumors and adenomas proximal to the occlusion site.
50 Jahre Systemtherapie des Harnblasenkarzinoms

Zusammenfassung Dieser Übersichtsartikel stellt die Ergebnisse verschiedener Behandlungskonzepte für das metastasierte Urothelkarzinom in den letzten fünf Jahrzehnten zusammen. Mit der Einführung von verschiedenen Kombinations-Chemotherapien wurde ab Mitte der 80er Jahre eine signifikante Überlebensverlängerung und potenzielle Heilbarkeit auch fortgeschrittener Erkrankungsstadien in dieser Tumorentität postuliert. Vor zwei Jahren wurden Studiendaten zur Zweitlinientherapie des metastasierten Urothelkarzinoms mit dem PD1-Antikörper Pembrolizumab publiziert, die erstmals einen Vorteil im Gesamtüberleben gegenüber einer konventionellen Chemotherapie mit Paclitaxel, Docetaxel oder Vinflunin zeigen. Aktuell wird in randomisierten Phase-3-Studien der Einsatz von PD-1/PD-L1 gerichteten Substanzen auch in der Erstlinientherapie des metastasierten Urothelkarzinoms untersucht. Dabei werden verschiedene Therapiestrategien verfolgt: Monotherapien mit PD-1/PD-L1-Inhibitoren sowie deren Kombinationen mit CTLA-4-Inhibitoren oder konventioneller Chemotherapie. Es liegen bereits Daten aus einarmigen Phase-2-Studien zur Monotherapie vor. Erste Daten aus randomisierten Studien werden im Laufe des Jahres 2019 erwartet.
On the sunny side of (new) life: Effect of sunshine duration on age at first reproduction in Japanese macaques (Macaca fuscata)

To produce offspring early in life is energetically demanding and depends greatly on environmental conditions. In female primates, age at first reproduction (AFR) has been associated with social parameters (e.g., population density and social rank), food availability and meteorological conditions (e.g., photoperiod, rainfall patterns, and temperature). Regarding the latter, less attention has been given to the influence of sunshine. In nonhuman primates, including the northern‐most distributed Japanese macaque (Macaca fuscata), sunbathing is an effective thermoregulatory strategy to maintain sufficient energy intake during harsh winter months. Furthermore, the energetic value of sunshine and its role in the synthesis of essential vitamins important for sexual development and overall fertility is well investigated using human and animal models. In the present study, we hypothesized that female's AFR is influenced by the amount of sunshine in a semi‐free‐ranging, provisioned a group of Japanese macaques. To test this, we gathered data on sunshine duration in the year females theoretically experienced the onset of puberty. This phase of the female life cycle is particularly prone to the effects of environmental conditions. In addition to the investigation of sunshine duration and other meteorological conditions (i.e., rainfall and temperature) we controlled for social parameters (i.e., group size and sex ratio) as potential covariates. We found a clear effect of sunshine duration on female AFR: Females who entered puberty in years with more sunshine reproduced for the first time at significantly younger ages than females who experienced less sunshine during this specific period of their development. Possible mechanisms for how the sunshine influences sexual maturation in Japanese macaques are discussed.
Bio-Inspired Dual Selective BCL-2/c-MYC G-Quadruplex Binders: Design, Synthesis and Anticancer Activity of Drug-like Imidazo[2,1-i]purine Derivatives.

In the search for new drug-like selective G-quadruplex binders, a bio-inspired design focused on the use of nucleobases as synthons in a multicomponent reaction has been herein proved to be viable and successful. Hence, a new class of multi-functionalized imidazo[2,1-i]purine derivatives, easily synthesized with a convergent approach, allowed the identification of the first dual BCL2/c-MYC gene promoter G-quadruplex ligand. Biophysical studies involving CD melting experiments, MST measurements, NMR titrations, and computational docking calculations, as well as biological investigations including cytotoxicity and apoptotic assays, and qPCR and Western Blot analyses, have been carried out to assess the potency and to characterize the binding mode of the newly identified lead compound. The absence of toxicity towards normal cells, together with the small molecular weight (≅ 500), the water solubility, the ease of functionalization, and the selectivity profile are promising and desirable features to develop G-quadruplex binders as safe and effective anticancer agents.
Endoscopic Treatment of Greater Trochanteric Pain Syndrome - A Case Series of 11 Patients

Introduction: Greater trochanteric pain syndrome (GTPS) includes patients with symptoms of peritrochanteric pain, gluteus medius/minimus tendinopathy, and external snapping hip. Non-operative treatment includes iliotibial band (ITB) stretching, gluteal exercises and cortisone injections. When surgery is indicated due to the failure of non-operative strategies, open Z-plasty at the level of the greater trochanter has been the traditional procedure. Endoscopic release of the ITB and bursectomy at the level of the greater trochanter has over the last decades evolved and is established as an alternative method of surgery. Case Reports: We here present a case series with 11 consecutive patients who have undergone endoscopic release of the ITB and bursectomy at the level of the greater trochanter due to GTPS. The patients were all Caucasians, 43–years of age, and six were female. The patients retrospectively scored their pre-operative function and pain during follow-up at 28 months (range 15–42). Post-operative pain and function were scored at follow-up. In this paper, we discuss investigation, differential diagnoses, surgical options, and outcomes in the treatment of GTPS. All patients reported significant reduction of pain, and 10 of 11 patients reported an improvement in function. We observed no complications. Conclusions: Endoscopic release of the ITB and bursectomy at the level of the greater trochanter appears to be an effective and safe procedure when conservative treatment options for GTPS have failed.
A Study on Creating Assessment Model forMiniature Question Answer Using NearestNeighbor Search Keywords

We introduce a new Assessment model for nearest neighbour search keywords algorithm. The algorithm builds a nearest neighbour model. There are limited types of knowledge that can be assessed by multiple choice tests. In multiple choice questions a student can have simply select a random answer and still have a chance of receiving a mark for it. In a short answer question, the student types in a word or phrase or sentences in response to a question. The answer could be a word or a phrase, but it must match one of our acceptable keywords exactly. It’s a good idea to keep the required answer as short as possible to avoid missing a correct answer that's phrased differently. This feature allows a user to create, preview, and edit questions in a database of question categories. In this paper we are going to compare the entire template model produced by both training and testing phase. Measure the similarities between the two models and identify the quality and efficiency of the result using nearest neighbour keyword. The experimental results show what aspects are important for short answer question type classification in terms of both effectiveness and efficiency. We believe that the assessment model findings from this study will be useful in real-world student problems.
Novel Victorivirus from a Pakistani Isolate of Alternaria alternata Lacking a Typical Translational Stop/Restart Sequence Signature

The family Totiviridae currently contains five genera Totivirus, Victorivirus, Leishmavirus, Trichomonasvirus, and Giardiavirus. Members in this family generally have a set of two-open reading frame (ORF) elements in their genome with the 5′-proximal ORF (ORF1) encoding a capsid protein (CP) and the 3′-proximal one (ORF2) for RNA-dependent RNA polymerase (RdRp). How the downstream open reading frames (ORFs) are expressed is genus-specific. All victoriviruses characterized thus far appear to use the stop/restart translation mechanism, allowing for the expression of two separate protein products from bicitronic genome-sized viral mRNA, while the totiviruses use a −1 ribosomal frame-shifting that leads to a fusion product of CP and RdRp. We report the biological and molecular characterization of a novel victorivirus termed Alternaria alternata victorivirus 1 (AalVV1) isolated from Alternaria alternata in Pakistan. The phylogenetic and molecular analyses showed AalVV1 to be distinct from previously reported victoriviruses. AalVV1 appears to have a sequence signature required for the −1 frame-shifting at the ORF1/2 junction region, rather than a stop/restart key mediator. By contrast, SDS–polyacrylamide gel electrophoresis and peptide mass fingerprinting analyses of purified virion preparations suggested the expression of two protein products, not a CP-RdRp fusion product. How these proteins are expressed is discussed in this study. Possible effects of infection by this virus were tested in two fungal species: A. alternata and RNA silencing proficient and deficient strains of Cryphonectria parasitica, a model filamentous fungus. AalVV1 showed symptomless infection in all of these fungal strains, even in the RNA silencing deficient C. parasitica strain.
Thymus-Derived Regulatory T Cells Exhibit Foxp3 Epigenetic Modification and Phenotype Attenuation after Mating in Mice

Key Points Seminal fluid primes Treg cells to elicit tolerance of male alloantigens. Neuropilin-1+ Tregs of likely thymic origin are prevalent amongst responding T cells. Neuropilin-1+ Tregs exhibit Foxp3 TSDR demethylation after seminal fluid contact. Regulatory T cells (Tregs) are essential for maternal tolerance in allogeneic pregnancy. In preeclampsia, Tregs are fewer and display aberrant phenotypes, particularly in the thymic Treg (tTreg) compartment, potentially because of insufficient priming to male partner alloantigens before conception. To investigate how tTregs as well as peripheral Tregs (pTregs) respond to male partner seminal fluid, Foxp3+CD4+ Tregs were examined in the uterus and uterus-draining lymph nodes in virgin estrus mice and 3.5 d postcoitum. Mating elicited 5-fold increases in uterine Tregs accompanied by extensive Treg proliferation in the uterus-draining lymph nodes, comprising 70% neuropilin 1+ tTregs and 30% neuropilin 1− pTregs. Proliferation marker Ki67 and suppressive competence markers Foxp3 and CTLA4 were induced after mating in both subsets, and Ki67, CTLA4, CD25, and GITR were higher in tTregs than in pTregs. Analysis by t-stochastic neighbor embedding confirmed phenotypically distinct tTreg and pTreg clusters, with the proportion of tTregs but not pTregs among CD4+ T cells expanding in response to seminal fluid. Bisulphite sequencing revealed increased demethylation of the Treg-specific demethylation region in the Foxp3 locus in tTregs but not pTregs after mating. These data show that tTregs and pTregs with distinct phenotypes both respond to seminal fluid priming, but the Foxp3 epigenetic signature is uniquely increased in tTregs. We conclude that reproductive tract tTregs as well as pTregs are sensitive to local regulation by seminal fluid, providing a candidate mechanism warranting evaluation for the potential to influence preeclampsia susceptibility in women.
Effectiveness of an in‐home respite care program to support informal dementia caregivers: A comparative study

Dementia is a major public health problem with important physical, psychosocial, emotional, and financial consequences for patients, their caregivers, and society. Since patients prefer to be managed at home, extensive research has been conducted into effectiveness of psychosocial interventions to support informal caregivers. The aim of this study was to assess the effectiveness of an in‐home respite care program.
HIV treatment cascade for older adults in rural South Africa

Objectives The HIV treatment cascade is a powerful framework for understanding progress from initial diagnosis to successful treatment. Data sources for cascades vary and often are based on clinical cohorts, population cohorts linked to clinics, or self-reported information. We use both biomarkers and self-reported data from a large population-based cohort of older South Africans to establish the first HIV cascade for this growing segment of the HIV-positive population and compare results using the different data sources. Methods Data came from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) 2015 baseline survey of 5059 adults aged 40+ years. Dried blood spots (DBS) were screened for HIV, antiretroviral drugs and viral load. In-home surveys asked about HIV testing, diagnosis and antiretroviral therapy (ART) use. We calculated proportions and CIs for each stage of the cascade, conditional on attainment of the previous stage, using (1) biomarkers, (2) self-report and (3) both biomarkers and self-report, and compared with UNAIDS 90-90-90 targets. Results 4560 participants had DBS results, among whom 1048 (23%) screened HIV-positive and comprised the denominator for each cascade. The biomarker cascade showed 63% (95% CI 60 to 66) on ART and 72% (95% CI 69 to 76) of those on ART with viral suppression. Self-reports underestimated testing, diagnosis and ART, with only 47% (95% CI 44 to 50) of HIV-positive individuals reporting ART use. The combined cascade indicated high HIV testing (89% (95% CI 87 to 91)), but lower knowledge of HIV-positive status (71% (95% CI 68 to 74)). Conclusions Older South Africans need repeated HIV testing and sustained ART to reach 90-90-90 targets. HIV cascades relying on self-reports are likely to underestimate true cascade attainment, and biomarkers provide substantial improvements to cascade estimates.
Association between IL-18 -607 C/A Polymorphism and the Risk of Prostate Cancer: A Meta-Analysis of Case-Control Studies

Background: Accumulating evidence shows that cytokines play an important role in the proliferation of prostate cancer. This research is trying to determine that IL-18 -607 C/A polymorphism confers susceptibility to prostate cancer. Methods: Meta-analysis was used to collect data. The relevant studies were identified through a comprehensive search from PubMed, Excerpta Medica Database (EMBASE), Web of Science, and Chinese Biomedical Literature Database (CBM) to obtain related studies published up to December 6, 2017. The association between interleukin (IL)-18 -607 C/A polymorphism and prostate cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results: Nine case-control studies from 6 articles were eventually identified. In the overall population, there is a significant association between IL-18 -607 C/A polymorphism and prostate cancer risk in recessive (CC versus CA/AA: OR = 0.20, 95% CI = 0.15-0.27, P = 0.000) or dominant (CC/CA versus AA:OR = 0.42, 95% CI = 0.30–0.57, P = 0.000) models. In the sub-group analysis according to ethnicity, for Asians, IL-18 -607 C/A polymorphism was significantly associated with prostate cancer in allele contrast (C versus. A: OR=0.82, 95%CI=0.70-0.97, P=0.019), homozygote (CC versus. AA: OR=0.68, 95%CI=0.50-0.92, P=0.013), recessive (CC versus. CA/AA: OR=0.19, 95%CI=0.13-0.27, P=0.000), and dominant (CC/CA versus. AA: OR=0.37, 95%CI=0.28-0.48, P=0.000) models, for Caucasians, IL-18 -607 C/A polymorphism was significantly associated with prostate cancer risk in allele contrast (C versus. A: OR=1.27, 95%CI=1.02-1.58, P=0.033), homozygote (CC versus. AA: OR=1.86, 95%CI=1.19-2.91, P=0.007) and recessive (CC versus. CA/AA: OR=0.25, 95%CI=0.19-0.33, P=0.000) models. Conclusion: This meta-analysis has shown that IL-18 -607 C/A polymorphism contributes to a decreased risk of prostate cancer risk in the Asian population but an increased risk in the Caucasian population.
The mechanistic basis for chromatin regulation by pioneer transcription factors

Pioneer transcription factors play a primary role in establishing competence for gene expression and initiating cellular programming and reprogramming, and their dysregulation causes severe effects on human health, such as promoting tumorigenesis. Although more than 200 transcription factors are expressed in each cell type, only a small number of transcription factors are necessary to elicit dramatic cell‐fate changes in embryonic development and cell‐fate conversion. Among these key transcription factors, a subset called “pioneer transcription factors” have a remarkable ability to target nucleosomal DNA, or closed chromatin, early in development, often leading to the local opening of chromatin, thereby establishing competence for gene expression. Although more key transcription factors have been identified as pioneer transcription factors, the molecular mechanisms behind their special properties are only beginning to be revealed. Understanding the pioneering mechanisms will enhance our ability to precisely control cell fate at will for research and therapeutic purposes.