Miracle-dz/UniFAR-FTUs huggingface dataset:
Coccygeal Movement Test: An Objective, Non-Invasive Test for Localization of the Pelvic Floor Muscles in Healthy Women

Objective: To evaluate the use of palpation of the coccyx (the coccygeal movement test, CMT) as a possible objective screening tool for the assessment of adequate localization of the pelvic floor muscles (PFMs). Subjects and Methods: Twenty-four healthy female volunteers, known to be able to locate their PFMs, were given instructions (allocated at random) to perform a ‘correct contraction', ‘straining' or ‘nothing' when examined by six independent assessors using the CMT. The assessors were blinded to the instructions and to the test results recorded by other assessors. Data were available for 137 observations, and these were dichotomized into either ‘able to contract' (‘correct contraction') or ‘not able to contract' (‘straining' or ‘nothing'). This information was used to calculate the sensitivity, specificity and positive and negative predictive values for the CMT. Results: The CMT correctly identified 56/58 observations when women did not perform the contraction of the PFMs compared to 61/79 observations when they did. Hence, the sensitivity and specificity were 97 and 77%, respectively. Conclusion: This study showed that the CMT was a useful test to identify women who were able to localize their PFMs compared to those who were not, making it a potentially useful initial screening test in structured training programmes for the PFMs.
Proton pump inhibitor use and risk of dementia

Background: Proton pump inhibitors (PPIs) are an established kind of drugs used to the treatment of most acid-related diseases. Some prospective studies have noticed that PPI use was associated with increased dementia risk. However, the results of those studies were inconsistent and controversial. This meta-analysis aims to determine the association of PPI use and risk of dementia among older people. Methods: Relevant articles were systematically identified by searching the PubMed, EMBASE, and Cochrane Library databases from inception to February 2018. Cohort studies that reported the risk of dementia or Alzheimer's disease (AD) among PPI users compared with non-PPI users were included. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). The publication bias was detected by a funnel plot and Egger test. The meta-analysis will abstract risk estimates including relative risks (RRs), hazard ratios (HRs), and odds ratios (ORs) with a 95% confidence interval (CI) for the associations between PPI use and dementia or Alzheimer's risk. Study-specific results were pooled using a random-effects model. Results: Six cohort studies were selected finally. The pooled RRs of dementia and AD were 1.23 (95% CI: 0.90–1.67) and 1.01 (95% CI: 0.78–1.32), respectively, compared with those of non-PPI use. The Egger test and funnel plot showed no existence of publication bias. Overall, there was no statistically significant association between PPI use and risk of dementia or AD (P >.05). Conclusions: This meta-analysis suggests that there was no statistical association between PPIs use and increased risk of dementia or AD.
Preliminary analysis of the chemical composition, antioxidant and anticholinesterase activities of Algerian propolis

Abstract Many studies demonstrated that Algerian propolis possess a large spectrum of biological activity. However, few studies regarding its chemical composition are available on literature. We aimed in the present study to investigate the chemical composition of Algerian propolis. In addition, the antioxidants and anticholinesterase activities of propolis extracts are also reported. Chemical investigation of Algerian propolis allowed the isolation of 8 compounds. Their structures were identified on the basis of spectral data and comparison with literature. The isolated compounds are considered as markers of poplar and Citrus spp suggesting the use of both species as plant source of the tested propolis. The ethyl acetate extract of the tested propolis demonstrated the highest antioxidant activity. Among the tested extracts, only the petroleum ether and chloroform extracts exhibited an AChE inhibitory activity. Graphical Abstract
Association of Streptococcus bovis presence in colonic content with advanced colonic lesion.

AIM To prospectively examine the association between presence of Streptococcus bovis (S. bovis) in colonic suction fluid and the endoscopic findings on colonoscopy. METHODS From May 2012 to March 2013, 203 consecutive patients who underwent colonoscopy for any reason were enrolled in the study. Exclusion criteria included: antibiotic use in the previous month, age younger than 18 years, and inadequate preparation for colonoscopy. The colonoscopy was performed for the total length of the colon or to the occluding tumor. The endoscopic findings were registered. Samples were obtained proximal to the colonoscopic part of the suction tube from each patient and sent to the clinical microbiology laboratory for isolation and identification of S. bovis. Samples were incubated in enrichment media with addition of antibiotic disks for inhibition of growth of Gram-negative rods. The samples were seeded on differential growth media; suspected positive colonies were isolated and identified with Gram staining, catalase, and pyrrolidonyl arylamidase tests, and further identified using a VITEK2 system. Statistical analyses were performed using the Student's t and χ(2) tests. RESULTS Of the 203 patients recruited, 49 (24%) patients were found to be S. bovis carriers; of them, the endoscopic findings included: 17 (34.7%) cases with malignant tumors, 11 (22.4%) with large polyps, 5 (10.2%) with medium-sized polyps, 6 (12.2%) with small polyps, 4 (8.1%) with colitis, and 6 (12.2%) normal colonoscopies. Of 154 patients found negative for S. bovis, the endoscopic findings included: none with malignant tumors, 9 (5.8%) cases with large polyps, 11 (7.1%) with medium-sized polyps, 26 (16.9%) with small polyps, 7 (4.5%) with colitis, and 101 (65.6%) normal colonoscopies. S. bovis (Gram-positive coccus) is considered part of the normal intestinal flora. There is an association between S. bovis bacteremia and colonic neoplasia. It is not well understood whether the bacterium has a pathogenetic role in the development of neoplasia or constitutes an epiphenomenon of colorectal neoplasms. There was a clear relationship between positivity for S. bovis in colonic suction fluid and findings of malignant tumors and large polyps in the colon. CONCLUSION There is an association between S. bovis bacteremia and malignant colonic lesions; this should prompt for development of a reliable screening method for advanced colonic lesions.
Zinc transporter 10 (ZnT10)-dependent extrusion of cellular Mn2+ is driven by an active Ca2+-coupled exchange

Manganese (Mn2+) is extruded from the cell by the zinc transporter 10 (ZnT10). Loss of ZnT10 expression caused by autosomal mutations in the ZnT10 gene leads to hypermanganesemia in multiple organs. Here, combining fluorescent monitoring of cation influx in HEK293-T cells expressing human ZnT10 with molecular modeling of ZnT10 cation selectivity, we show that ZnT10 is exploiting the transmembrane Ca2+ inward gradient for active cellular exchange of Mn2+. In analyzing ZnT10 activity we used the ability of Fura-2 to spectrally distinguish between Mn2+ and Ca2+ fluxes. We found that (a) application of Mn2+-containing Ca2+-free solution to ZnT10-expressing cells triggers an influx of Mn2+, (b) reintroduction of Ca2+ leads to cellular Mn2+ extrusion against an inward Mn2+ gradient, and (c) the cellular transport of Mn2+ by ZnT10 is coupled to a reciprocal movement of Ca2+. Remarkably, replacing a single asparagine residue in ZnT10 (Asp-43) with threonine (ZnT10 N43T) converted the Mn2+/Ca2+ exchange to an uncoupled channel mode, permeable to both Ca2+ and Mn2+. The findings in our study identify the first ion transporter that uses the Ca2+ gradient for active counter-ion exchange. They highlight a remarkable versatility in metal selectivity and mode of transport controlled by the tetrahedral metal transport site of ZnT proteins.
Effects of low dose leucine supplementation on gastrocnemius muscle mitochondrial content and protein turnover in tumor bearing mice.

Many forms of cancer are associated with loss of lean body mass, commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle. Leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, key signaling pathways influenced by tumor signaling. The purpose of this study was to examine the effects of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor bearing mice. Twenty male C57BL/6 mice were divided into four groups (n=5): Chow, leucine (Leu), Lewis lung carcinoma (LLC) implant, LLC+Leu. At 9-10 weeks of age, mice were inoculated and supplemented with 5% leucine (w/w) in the diet. C2C12 myotubes were treated with 2.5mM leucine and 25% LLC conditioned media to further elucidate the direct influence of the tumor and leucine on the muscle. Measures of protein synthesis, mitochondrial biogenesis, and inflammation in the gastrocnemius were assessed via western blot analysis. Gastrocnemius mass was decreased in LLC+Leu relative to LLC (p=0.040). Relative protein synthesis rate was decreased in LLC mice (p=0.001). No change in protein synthesis was observed in myotubes. Phosphorylation of STAT3 was decreased in the Leu group relative to the control in both mice (p=0.019) and myotubes (p=0.02), but did not significantly attenuate the inflammatory effect of LLC implantation (p=0.619). LLC decreased markers of mitochondrial content; however, PGC-1α was increased in LLC+Leu relative to LLC (p=0.001). While leucine supplementation was unable to preserve protein synthesis or mitochondrial content associated with LLC implantation, it was able to increase mitochondrial biogenesis signaling.
Association of Statin Adherence With Mortality in Patients With Atherosclerotic Cardiovascular Disease

Importance Statins decrease mortality in those with atherosclerotic cardiovascular disease (ASCVD), but statin adherence remains suboptimal. Objective To determine the association between statin adherence and mortality in patients with ASCVD who have stable statin prescriptions. Design, Setting, and Participants This retrospective cohort analysis included patients who were between ages 21 and 85 years and had 1 or more International Classification of Diseases, Ninth Revision, Clinical Modification codes for ASCVD on 2 or more dates in the previous 2 years without intensity changes to their statin prescription who were treated within the Veterans Affairs Health System between January 1, 2013, and April 2014. Exposures Statin adherence was defined by the medication possession ratio (MPR). Adherence levels were categorized as an MPR of less than 50%, 50% to 69%, 70% to 89%, and 90% or greater. For dichotomous analyses, adherence was defined as an MPR of 80% or greater. Main Outcomes and Measures The primary outcome was death of all causes adjusted for demographic and clinical characteristics, as well as adherence to other cardiac medications. Results Of 347 104 eligible adults with ASCVD who had stable statin prescriptions, 5472 (1.6%) were women, 284 150 (81.9%) were white, 36 208 (10.4%) were African American, 16 323 (4.7%) were Hispanic, 4093 (1.2%) were Pacific Islander, 1293 (0.4%) were Native American, 1145 (0.3%) were Asian, and 1794 (0.5%) were other races. Patients taking moderate-intensity statin therapy were more adherent than patients taking high-intensity statin therapy (odds ratio [OR], 1.18; 95% CI, 1.16-1.20). Women were less adherent (OR, 0.89; 95% CI, 0.84-0.94), as were minority groups. Younger and older patients were less likely to be adherent compared with adults aged 65 to 74 years. During a mean (SD) of 2.9 (0.8) years of follow-up, there were 85 930 deaths (24.8%). Compared with the most adherent patients (MPR ≥ 90%), patients with an MPR of less than 50% had a hazard ratio (HR; adjusted for clinical characteristics and adherence to other cardiac medications) of 1.30 (95% CI, 1.27-1.34), those with an MPR of 50% to 69% had an HR of 1.21 (95% CI, 1.18-1.24), and those with an MPR of 70% to 89% had an HR of 1.08 (95% CI, 1.06-1.09). Conclusions and Relevance Using a national sample of Veterans Affairs patients with ASCVD, we found that a low adherence to statin therapy was associated with a greater risk of dying. Women, minorities, younger adults, and older adults were less likely to adhere to statins. Our findings underscore the importance of finding methods to improve adherence.
Resonance Microwave Measurements of an Intrinsic Spin-Orbit Coupling Gap in Graphene: A Possible Indication of a Topological State.

In 2005, Kane and Mele [Phys. Rev. Lett. 95, 226801 (2005)PRLTAO0031-900710.1103/PhysRevLett.95. 226801] predicted that at sufficiently low energy, graphene exhibits a topological state of matter with an energy gap generated by the atomic spin-orbit interaction. However, this intrinsic gap has not been measured to this date. In this Letter, we exploit the chirality of the low-energy states to resolve this gap. We probe the spin states experimentally by employing low temperature microwave excitation in a resistively detected electron-spin resonance on graphene. The structure of the topological bands is reflected in our transport experiments, where our numerical models allow us to identify the resonance signatures. We determine the intrinsic spin-orbit bulk gap to be exactly 42.2 μeV. Electron-spin resonance experiments can reveal the competition between the intrinsic spin-orbit coupling and classical Zeeman energy that arises at low magnetic fields and demonstrate that graphene remains to be a material with surprising properties.
Architectural principles for Hfq/Crc-mediated regulation of gene expression

The global regulator Hfq facilitates the action of regulatory RNAs in post-transcription gene regulation in many Gram-negative bacteria. In Pseudomonas aeruginosa, Hfq, in conjunction with the catabolite repression protein Crc, was shown to form a complex that directly inhibits translation of target transcripts during carbon catabolite repression. Here, we describe and validate high-resolution cryo-EM structures of the cooperative assembly of Hfq and Crc bound to a translation initiation site. The core assembly is formed through interactions of two cognate RNAs, two Hfq hexamers and a Crc pair. Additional Crc protomers can be recruited to form higher-order assemblies with demonstrated in vivo activity. The structures indicate a distinctive RNA conformation and a pattern of repeating motifs that confer regulatory function. This study not only reveals for the first time how Hfq cooperates with a partner protein to regulate translation but also provides a novel structural basis to explain how an RNA code can guide global regulators to interact cooperatively and regulate many different RNA targets.
Age of Both Parents Influences Reproduction and Egg Dumping Behavior in Drosophila melanogaster

Abstract Trans-generational maternal effects have been shown to influence a broad range of offspring phenotypes. However, very little is known about paternal trans-generational effects. Here, we tested the trans-generational effects of maternal and paternal age, and their interaction, on daughter and son reproductive fitness in Drosophila melanogaster. We found significant effects of parent ages on offspring reproductive fitness during a 10 day postfertilization period. In daughters, older (45 days old) mothers conferred lower reproductive fitness compared with younger mothers (3 days old). In sons, father’s age significantly affected reproductive fitness. The effects of 2 old parents were additive in both sexes and reproductive fitness was lowest when the focal individual had 2 old parents. Interestingly, daughter fertility was sensitive to father’s age but son fertility was insensitive to mother’s age, suggesting a sexual asymmetry in trans-generational effects. We found the egg-laying dynamics in daughters dramatically shaped this relationship. Daughters with 2 old parents demonstrated an extreme egg dumping behavior on day 1 and laid >2.35× the number of eggs than the other 3 age class treatments. Our study reveals significant trans-generational maternal and paternal age effects on fertility and an association with a novel egg laying behavioral phenotype in Drosophila.
Preclinical Evaluation and Nonhuman Primate Receptor Occupancy Study of 18F-JNJ-64413739, a PET Radioligand for P2X7 Receptors

The P2X7 receptor is an adenosine triphosphate–gated ion channel, which is abundantly expressed in glial cells within the central nervous system and in the periphery. P2X7 receptor activation leads to the release of the proinflammatory cytokine IL-1β in the brain, and antagonism of the P2X7 receptor is a novel therapeutic strategy to dampen adenosine triphosphate–dependent IL-1β signaling. PET ligands for the P2X7 receptor will not only be valuable to assess central target engagement of drug candidates but also hold promise as surrogate markers of central neuroinflammation. Herein we describe the in vitro and in vivo evaluation of 18F-JNJ-64413739, an 18F-labeled PET ligand for imaging the P2X7 receptor in the brain. Methods: P2X7 receptor affinity and specificity, pharmacokinetics, metabolic stability, blood–brain barrier permeability, and off-target binding of JNJ-64413739 were evaluated in a series of in vitro, ex vivo, and in vivo assays. 18F-JNJ-64413739 was radiolabeled via a one-step nucleophilic aromatic substitution. The tracer was also studied in rhesus macaques, and PET images were analyzed with an arterial plasma input function–based Logan graphical analysis. Results: The potency (half-maximal inhibitory concentration) of the P2X7 receptor antagonist JNJ-64413739 is 1.0 ± 0.2 nM and 2.0 ± 0.6 nM at the recombinant human and rat P2X7 receptor, respectively, and the binding affinity is 2.7 nM (rat cortex binding assay) and 15.9 nM (human P2X7 receptor). In nonhuman primate PET imaging studies, dose-dependent receptor occupancy of JNJ-54175446 was observed in 2 rhesus monkeys. At a 0.1 mg/kg dose (intravenous) of JNJ-54175446, the receptor occupancy was calculated to be 17% by Logan graphical analysis, whereas a dose of 2.5 mg/kg yielded a receptor occupancy of 60%. Conclusion: The preclinical evaluation of 18F-JNJ-64413739 demonstrates that the tracer engages the P2X7 receptor. Reproducible and dose-dependent receptor occupancy studies with the P2X7 receptor antagonist JNJ-54175446 were obtained in rhesus monkeys. This novel PET tracer exhibits in vitro and in vivo characteristics suitable for imaging the P2X7 receptor in the brain and warrants further studies in humans.
Detoxification and functionalization of gold nanorods with organic polymers and their applications in cancer photothermal therapy

Gold nanorods (AuNRs) have attracted widespread attention in the last few decades due to their potential applications in cancer photothermal therapy (CPTT). However, the utilization of AuNRs is restricted because of their high toxicity for cells and tissues. Numerous methods have been developed to solve this problem, among which the most convenient one is to coat AuNRs with biocompatible materials or replace their original toxic surfactant such as the hexadecyl‐trimethyl ammonium bromide (CTAB). Organic polymers (OPs) are intensively researched due to their low toxicity and easy access to modification with functional groups (e.g., targeting molecules), pharmaceuticals (e.g., chemo drugs) and imaging agents (e.g., radioactive elements). Herein, this mini review summarized recent progress in detoxification and functionalization of AuNRs exploiting OPs coatings and their applications in CPTT. To begin with, we introduced current major approaches used to modify AuNRs with typical OPs. Then, applications of OPs coated AuNRs in CPTT were discussed. At the end of the review, we proposed a brief outlook for the future development of modification and functionalization of AuNRs with organic materials.
Effect of Heel Lifts on Plantarflexor and Dorsiflexor Activity During Gait

Background: Previous investigators have shown that high heels decrease the muscle activity of the gastrocnemius muscle during gait. However, it is not known whether commonly used in-shoe heel lifts of lower heights will demonstrate similar effects on muscle activity. The aim of this study was to determine whether heel lifts alter the muscle activity of the ankle plantarflexors and dorsiflexors during the stance phase of gait among individuals with limited gastrocnemius extensibility. Materials and Methods: This study used a repeated measures design. Twenty-four healthy volunteers (12 males and 12 females) with less than 5 degrees of passive ankle dorsiflexion with the knee extended participated in the study. Electromyography (EMG), computerized motion analysis, and a force plate were used to measure mean muscle activity of the lateral gastrocnemius, medial gastrocnemius, soleus and tibialis anterior muscles during the stance phase of gait across three walking conditions. Muscle activity was measured as participants ambulated at a self-selected speed in athletic shoes alone and with heel lifts of 6 mm and 9 mm inserted in athletic shoes. Results: Between heel-strike and heel-off, the mean EMG amplitude of the medial gastrocnemius increased with both 6 and 9 mm heel lifts and the amplitude of the tibialis anterior increased with 9 mm heel lifts compared to shoes alone. Between heel-strike and heel-off, there were no significant differences in mean EMG amplitude of the lateral gastrocnemius or soleus muscles walking in heel lifts compared to shoes alone. Between heel-off and toe-off, there were no significant differences in mean EMG amplitude of the lateral gastrocnemius, medial gastrocnemius, soleus, or tibialis anterior muscles when walking in heel lifts compared to shoes alone. Conclusion: Heel lifts increase muscle activity of the medial gastrocnemius and tibialis anterior muscles between heel-strike and heel-off among individuals with limited gastrocnemius extensibility. Clinical Relevance: We were unable to confirm a decrease in muscle activity when using heel lifts.