Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective targeting of ITK blocks multiple steps of HIV replication

Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCγ-1, Ca2+ mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
EMG biofeedback versus topical lidocaine gel: a randomized study for the treatment of women with vulvar vestibulitis

Background. To evaluate the efficacy of electromyographic biofeedback and topical lidocaine treatment for women with vulvar vestibulitis. Methods. A prospective randomized study where 46 women with vulvar vestibulitis were randomized to receive either electromyographic biofeedback or topical lidocaine treatment for four months. Assessments with vulvar pressure pain thresholds and questionnaires regarding quality of life, psychosocial adjustments, and sexual functioning were made before treatment, after treatment, and at six‐ and 12‐month follow‐ups. Nonparametric statistical methods were used to analyze differences in outcomes. Results. Nine women (9/46) dropped out during the treatment period. Both treatments showed significantly improved values for vestibular pressure pain thresholds, quality of life measurements, and sexual functioning at the 12‐month follow‐up. No differences were found between the two treatment groups. No severe side effects were reported. Conclusions. Four months’ treatment with electromyographic biofeedback and topical lidocaine gave statistically significant improvements on vestibular pain measurements, sexual functioning, and psychosocial adjustments at the 12‐month follow‐up. No differences in outcome between the two treatments were observed but a larger sample may be needed to obtain significance. The treatments were well tolerated but the compliance to the electromyographic biofeedback training program was low. A combination of both treatments could potentially benefit many women with vulvar vestibulitis.
Seroprevalence and risk factors for hepatitis E virus infection in the Romanian adult population: a cross-sectional study in a tertiary hospital

Abstract Background: The primary goal was to estimate the seroprevalence of autochthonous hepatitis E virus (HEV) infection in adult Romanian population. Additionally, we aimed to identify the risk factors associated with the HEV seropositive status. Methods: Between January 2015 and December 2016, 201 adult patients were tested for antiHEV-IgG. Multivariate logistic regression was used to examine for factors associated with a positive HEV-IgG test. The level of significance was set at α = 0.05. Results: The final analysis included 175 patients who followed the study protocol. Forty-sex (26.3%) had positive, 121 (69.1%) had negative, and 8 (4.6%) had indeterminate antiHEV-IgG results. Patients with positive anti-HEV-IgG were older [median age: 54.5 years (IQR 43-65)] compared to patients with negative anti-HEV-IgG [median age: 37.5 years (IQR 28-57.5)], p <0.001. A positive HEV-IgG was more common in patients with history of blood transfusions [n=10 (22.7%) versus (vs) n=11 (9.4%), p=0.025], in those with immunosuppressive conditions [n=18 (40.9%) vs n=27 (23.1%), p=0.025] and in patients with positive hepatitis B surface antigen (HBsAg) [n=14 (31.1%) vs n=10 (10.3%), p=0.002]. Conclusions: In conclusion, we found that autochthonous HEV seropositivity is common in our study population, especially in older patients, previous blood transfusions, presence of immunosuppressive conditions, and positive HBsAg.
Recovery, not progressive deterioration, should be the expectation in schizophrenia

Since the time of Kraepelin, schizophrenia has been considered to be a progressive deteriorating illness (1). This perspective has been bolstered by a generation of studies demonstrating deficits in brain volumes on magnetic resonance imaging (MRI) scans and in performance on a broad range of cognitive tasks in individuals with schizophrenia (2).
Evidence should trump intuition by preferring inbred strains to outbred stocks in preclinical research.

Inbred strains of mice such as C57BL and BALB/c are more widely used in published work than outbred stocks of mice such as ICR and CD-1. In contrast, outbred stocks of rats such as Wistar and Sprague-Dawley are more widely used than inbred strains such as F344 and LEW. The properties of inbred and outbred mice and rats are briefly reviewed, and it is concluded that, with some exceptions, there is a strong case for using inbred strains in most controlled experiments. This is because they are usually more uniform, so that fewer animals are usually needed to detect a specified response and they are more repeatable, because they are genetically defined (i.e., the strain can be identified using genetic markers) and less liable to genetic change. Yet many scientists continue to use outbred animals. In Daniel Kahneman's book "Thinking Fast and Slow" he explains that we can answer questions in 2 ways: "fast" by intuition or "slow" by analytical reasoning. The former method is instantaneous, requires no thought but is not evidence based. Analytical reasoning is evidence based but requires hard work, which we all avoid. He has found that "… when faced with a difficult question, we often answer an easier one instead, usually without noticing the substitution. " The target question of whether to choose outbred or inbred strains in controlled experiments is a difficult one requiring knowledge of the characteristics of these strains and the principles of experimental design. A substitute question, "are humans and outbred stocks both genetically heterogeneous," is easily answered in the affirmative. It is likely that many scientists are intuitively answering the substitute question and are assuming that they have answered the target question. If so they may be using the wrong animals in their research. Nor is the fact that humans and outbred stocks are alike in being genetically heterogeneous a reason for using them. The whole concept of a "model" is that it is similar to the target in some respects but different in others. Rats and mice differ from humans in that we can control their genotype. This is a positive attribute that enormously increases their value in research. Funding organizations should support research in comparing the 2 types in real experiments.
Associations between the Expression of Mucins (MUC1, MUC2, MUC5AC, and MUC6) and Clinicopathologic Parameters of Human Breast Ductal Carcinomas

Purpose Mucins are members of the glycoprotein family expressed in benign and malignant epithelial cells. The aim of this study is to evaluate the relationships between the expression of mucins in breast ductal carcinoma and clinicopathologic parameters. Methods We constructed tumor microarrays based on 240 cases of invasive ductal carcinoma and 40 cases of ductal carcinoma in situ (DCIS) using formalin fixed, paraffin embedded tissues. We examined the expressions of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. Results MUC1 demonstrated cytoplasmic, membranous, apical, and combinative expressions. Other mucins demonstrated cytoplasmic expression. In invasive ductal carcinoma, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 93.6%, 6.2%, 4.8%, and 12.4% of cases, respectively; these rates were slightly, but not significantly, higher than observed in cases of DCIS. MUC1 expression was associated with estrogen receptor (ER) expression and negative MUC1 expression was associated with triple negativity. MUC6 expression was correlated with higher histologic grade, lymphatic invasion, lymph node metastasis, and HER2 positivity. No associations with any other clinicopathologic parameters were observed. Conclusion Most invasive ductal carcinomas of the breast express MUC1, and this expression is associated with ER expression. MUC6 expression is correlated with some clinicopathologic parameters that are indicators of poor prognosis. To evaluate the role of MUC6 as a potential biomarker, further studies are warranted.
Abnormal responsiveness of granulocyte-committed progenitor cells in cyclic neutropenia.

The mechanism(s) driving cyclic hematopoiesis in human cyclic neutropenia remains unknown. Clinical trials suggest that an abnormal responsiveness of bone marrow progenitor cells to hematopoietic growth factors might cause oscillatory blood counts. Studies were performed to determine whether an abnormal responsiveness to multiple growth factors exists in this disorder and whether the defect could be shown in highly enriched populations of marrow progenitor cells. Bone marrow mononuclear cells from patients with congenital cyclic neutropenia required higher concentrations of added granulocyte-colony-stimulating factor (G-CSF) to achieve half-maximal colony growth than cells from normal subjects (478 +/- 90 pmol/L v 53 +/- 12 pmol/L, P less than .01). Patients also differed in requirement for granulocyte-macrophage-CSF (P less than .05), but not for interleukin-3 (P greater than .30). CD34+ bone marrow cells from three patients also showed this difference in G-CSF responsiveness (P less than .05). These data suggest that the defect in congenital cyclic hematopoiesis lies in growth factor receptor binding or the postreceptor signal transduction system that drives granulocytopoiesis.
Veterinary epidemiology in New Zealand: a 50-year perspective

Abstract Extract The science of epidemiology is still developing although some of its principal tenets, such as identification of risk factors through comparisons of rates of disease occurrence among population sub-groups of individuals, have been used for centuries. The past 50 years has seen a particularly rapid period of growth of the discipline that has become almost exponential, especially since microcomputers and powerful analytical programs became widely available in the 1980s. The most outstanding advance has arguably been the development of causal criteria that arose from the fierce debate about links between smoking and lung cancer. The philosophical concepts of associations between cause and effect that are embodied in causal criteria now underpin epidemiological practice for scientific evaluation of evidence.
Preterm birth and subsequent insulin sensitivity: a systematic review

Objective The incidence of preterm birth is increasing worldwide. Evidence suggests that in later life these children are at increased risk of ‘metabolic syndrome’, which is itself associated with reduced insulin sensitivity (IS). We carried out a systematic review to examine whether preterm birth is associated with later changes in IS and whether a difference exists between those born small-for-gestational age (SGA) and appropriate-for-gestational age (AGA). Methods We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidance to structure our review with a priori data extraction criteria to answer the questions posed and then carried out our literature search. Only papers which included preterm infants in their study population and specifically assessed IS were included. Findings are reported by age group to enable change over the life course to be examined, even though the studies were mostly cross-sectional, observation studies. Results We identified and reviewed 26 suitable publications representing 20 separate cohorts, of which 16 had a term control group. The heterogeneity of the methods used to measure IS precluded meta-analysis. In infancy and early childhood there is a measurable association between IS and preterm birth. In later childhood and adulthood the strength of this association reduces, and current body composition becomes the variable most strongly associated with IS. Conclusions There is an association between preterm birth and IS throughout the life course, but the data are conflicting and associations are likely to be affected by the heterogeneity of each study population and multiple confounding factors that may change over time. While the optimal nutritional strategy for preterm infants remains to be determined, standard public health guidance to avoid obesogenic lifestyle factors remains equally important to individuals born preterm.
C‐Reactive Protein, Bone Strength, and Nine‐Year Fracture Risk: Data From the Study of Women's Health Across the Nation (SWAN)

Higher levels of C‐reactive protein (CRP), an inflammatory marker, are associated with increased fracture risk, although previous studies on CRP and bone mineral density (BMD) have yielded conflicting results. We aimed to test the hypotheses that composite indices of femoral neck strength relative to load, which are inversely associated with fracture risk, would also be inversely associated with CRP, and would explain part of the association between CRP and fracture risk. We analyzed data from a multisite, multiethnic prospective cohort of 1872 community‐dwelling women, premenopausal or early perimenopausal at baseline. Femoral neck composite strength indices in three failure modes were calculated using dual‐energy X‐ray absorptiometry (DXA)‐derived femoral neck width (FNW), femoral neck axis length (FNAL), femoral neck BMD and body size at baseline, as BMD*FNW/weight for compression strength, BMD*(FNW)2/(FNAL*weight) for bending strength, and BMD*FNW*FNAL/(height*weight) for impact strength. Incident nondigital, noncraniofacial fractures were ascertained annually over a median follow‐up of 9 years. In analyses adjusted for age, race/ethnicity, diabetes, menopause transition stage, body mass index, smoking, alcohol use, physical activity, medications, prior fracture, and study site, CRP was associated inversely with each composite strength index (0.035–0.041 SD decrement per doubling of CRP, all p < 0.001), but not associated with femoral neck or lumbar spine BMD. During the follow‐up, 194 women (10.4%) had fractures. In Cox proportional hazards analyses, fracture hazard increased linearly with loge(CRP), only for CRP levels ≥ 3 mg/L. Addition of femoral neck or lumbar spine BMD to the model did not attenuate the CRP‐fracture association. However, addition of any of the composite strength indices attenuated the CRP‐fracture association and made it statistically nonsignificant. We conclude that fracture risk increases with increasing CRP, only above the threshold of 3 mg/L. Unlike BMD, composite strength indices are inversely related to CRP levels, and partially explain the increased fracture risk associated with inflammation.
Higher rate of culture-confirmed Campylobacter infections in Australia than in the USA: is this due to differences in healthcare-seeking behaviour or stool culture frequency?

SUMMARY Laboratory-based surveillance by OzFoodNet in Australia and FoodNet in the USA indicated that the incidence of Campylobacter infections in 2001 in Australia was about nine times higher than in the USA. We assessed whether this disparity could be explained by differences in the frequency of stool culturing. Using data from population surveys of diarrhoea and symptom profiles for Campylobacter from case-control studies, indices of healthcare behaviour taking into account the severity of Campylobacter infections were calculated. These suggest that culture-confirmed Campylobacter infections underestimate the incidence of community cases by similar ratios in the two countries. The incidence of Campylobacter infections in Australia was about 12 times higher than in the USA after consideration of healthcare system differences.
HIV Prevention: Opportunities and Challenges

Preexposure prophylaxis (PrEP) is an integral part of HIV prevention.1,2 In numerous clinical trials of biomedical antiretroviral therapy–based HIV prevention, efficacy has ranged from 0% to greater than 80%. Until recently, nearly all of these studies have involved tenofovir disoproxil fumarate (TDF)-based PrEP regimens, and efficacy estimates appear to correlate very highly with adherence to these regimens. Overall, HIV protective efficacy was 67% with TDF and 75% with TDF/emtricitabine (slash indicates a coformulation) in the Partners PrEP study, 62% in the TDF2 study, and 44% in the iPrEx (Chemoprophylaxis for HIV Prevention in Men) study, while no efficacy was seen in the FEM-PrEP (Study to Assess the Role of Tenofovir/Emtricitabine in Preventing HIV Acquisition in Women) and VOICE (Vaginal and Oral Interventions to Control the Epidemic) studies; in each of these 5 studies, tenofovir was detected in 81%, 79%, 51%, 26%, and 28% of participants’ plasma, respectively.3-6 These studies demonstrated that PrEP is highly effective with appropriate adherence, and the protective effect appears to be enduring. As an extension to the Partners PrEP study, PrEP and antiretroviral therapy were offered to high-risk
Turkey’s Export Performance: Examining the Main Determinants of Export Volume(1995-2012)

Bu calismada Turkiye’de ihracat performansi ile reel efektif doviz kuru degismeleri arasindaki kisa ve uzun donemli iliskiler, 1995-2012 donemi ucer aylik veriler kullanilarak incelenmistir. Ihracat performansini etkilemesi beklenen ucret, yurtdisi gelir, verimlilik, GSYH trendi ve doviz kuru oynakligi gibi baska faktorler de modele eklenmistir. Calismanin analiz kisminda ARDL sinir testi yaklasimi izlenmis ve tahmin edilen ARDL modellerine gore degiskenler arasindaki nedensellik iliskileri arastirilmistir. Ulasilan sonuclar, incelenen degiskenlerin esbutunlesik oldugunu gostermektedir. Ihracat performansina iliskin olarak, teorik beklentilerin aksine, reel efektif doviz kuru katsayilarinin anlamli bir bicimde kisa donemde pozitif uzun donemde ise negatif oldugu ve doviz kuru oynakliginin anlamli bir etkisinin olmadigi belirlenmistir. Diger bulgular, Turkiye’de ele alinan donemde yasanan ihracat artislarinin doviz kuru degismelerinden cok ucret, verimlilik ve yurtdisi talep ile aciklanabilecegini gostermektedir. Buna gore sonuc olarak, Turkiye’de ucretleri baski altinda tutan, verimlilik artisini tesvik eden ve yurtdisi piyasalara girmeyi kolaylastiran politikalarin, ihracat sektorlerinde performans ve rekabet artislari saglayabilecegi gorulmektedir
A group of compounds possessing anticonvulsant activity in the maximal electroshock seizure test.

ponent of MES suggests the reliability of this method to search for new antiepileptics. In recent years, Tanaka (2) reported the anticonvulsant property of procaine, cocaine, adiphenine (Trasentine) and caramiphen (Parpanit) as measured with MES test, and Swin yard et al. (3) found the same activity of diphenhydramine and tripelennamine. On the other hand, Bernhard et al. (4) reported that lidocaine (Xylocaine) was effective in epileptic patients. These observations prompted us to test other local anesthetics, antihistaminics and related structures for the anticonvulsant activity in MES test.
Pharmacology and new perspectives of angiotensin II receptor blocker in prostate cancer treatment

Abstract: Although a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors has been reported, the molecular mechanisms have not been elucidated. It is known that angiotensin‐II (Ang‐II) plays a fundamental role not only as a vasoconstrictor in controlling blood pressure and electrolyte and fluid homeostasis, but also as a mitogenic factor through the Ang‐II type‐1 (AT1) receptor in cardiovascular cells. Interestingly, there is increasing evidence that the renin‐angiotensin system (RAS) is implicated in the development of various cancers. As we previously reported, AT1 receptor blockers (ARBs), a class of antihypertensive agent, have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review provides an insight into the key role of Ang‐II and the AT1 receptor, and the possibility of ARBs for molecular targeting of mitogenesis and angiogenesis in prostate cancer.
Temporal/spatial optical CDMA networks-design, demonstration, and comparison with temporal networks

The design and experimental results for a temporal/spatial (T/S) noncoherent optical code-division multiple access (CDMA), based on matrix codes, using a breadboard of passive multimode fiber-optic couplers and delay lines, is presented. It is shown that a T/S CDMA network allows for shorter bit times, given a set laser pulse width, compared to a temporal CDMA network. Also, T/S codes result in a reduction of autocorrelation sidelobes and cross-correlation peaks, and the T/S network has lower losses. It is also shown that the couplers are critical components in maintaining code integrity. <<ETX>>
In vitro unfolding of yeast multicopper oxidase Fet3p variants reveals unique role of each metal site

Fet3p from Saccharomyces cerevisiae is a multicopper oxidase (MCO) that contains 3 cupredoxin-like β-barrel domains and 4 copper ions located in 3 distinct metal sites (T1 in domain 3, T2, and the binuclear T3 at the interface between domains 1 and 3). To better understand how protein structure and stability is defined by cofactor coordination in MCO proteins, we assessed thermal unfolding of apo and metallated forms of Fet3p by using spectroscopic and calorimetric methods in vitro (pH 7). We find that unfolding reactions of apo and different holo forms of Fet3p are irreversible reactions that depend on the scan rate. The domains in apo-Fet3p unfold sequentially [thermal midpoint (Tm) of 45 °C, 62 °C, and 72 °C; 1 K/min]. Addition of T3 imposes strain in the apo structure that results in coupled domain unfolding and low stability (Tm of 50 °C; 1 K/min). Further inclusion of T2 (i.e., only T1 absent) increases overall stability by ≈5 °C but unfolding remains coupled in 1 step. Introduction of T1, producing fully-loaded holo-Fet3p (or in the absence of T2), results in stabilization of domain 3, which uncouples unfolding of the domains; unfolding of domain 2 occurs first along with Cu-site perturbations (Tm 50–55 °C; 1 K/min), followed by unfolding of domains 1 and 3 (≈65–70 °C; 1 K/min). Our results suggest that there is a metal-induced tradeoff between overall protein stability and metal coordination in members of the MCO family.