Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of follicle-stimulating hormone levels and risk of type 2 diabetes in older postmenopausal women

Objective: Recent studies of perimenopausal women have observed associations of follicle-stimulating hormone (FSH) levels with markers of insulin resistance, independent of estradiol. Whether FSH is related to type 2 diabetes (T2D) in older women who have completed the menopause transition remains unknown. We assessed the association of FSH levels with diabetes and measures of insulin resistance among 588 postmenopausal Finnish women. Methods: Study participants were aged 53 to 73 years and not using hormone therapy at baseline (1998-2001) when FSH was measured. Prevalence of T2D was assessed at baseline, along with fasting insulin and glucose levels. Incident T2D, and insulin and glucose levels were assessed 7 to 9 years later at follow-up examination. Results: After adjustment for age, estradiol, body mass index, smoking, lipids levels, and other factors, women with higher FSH (>50 IU/L) had a lower prevalence of T2D (odds ratio 0.49, 95% confidence interval [CI] 0.28-0.86) than women with lower FSH. Each 1 unit increase in FSH level was associated with a significant 1.9% lower risk of T2D (95% CI 0.966-0.997, P = 0.02). Higher FSH was associated with marginally significant lower incidence of T2D at follow-up (hazard ratio 0.53, 95% CI 0.27-1.02). Baseline FSH levels were inversely correlated with fasting insulin and glucose levels at both baseline and follow-up visits (all P < 0.05). After adjustment, FSH was modestly associated with fasting insulin at baseline (P = 0.01) and at follow-up (P = 0.11). Conclusions: Higher postmenopausal FSH levels were associated with lower prevalent and incident T2D and fasting insulin levels. These findings warrant replication in larger prospective studies.
The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention

Background: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.
Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes

Nitrogen-containing bisphosphonates (N-BPs) are the most widely used anti-resorptive agents in the treatment of bone-related diseases. N-BPs inhibit bone resorption by specifically targeting osteoclasts, bone-resorbing cells. However, soft tissue toxicity, such as oral or gastrointestinal (GI) ulcerations has frequently been reported in N-BP users, suggesting that N-BPs may also directly target cells other than osteoclasts. Previously, we reported that BPs inhibit proliferation without inducing the apoptosis of normal human oral keratinocytes (NHOKs). However, the molecular mechanisms through which N-BPs inhibit the proliferation of NHOKs are not yet fully understood. In this study, we performed gene expression profiling in N-BP-treated NHOKs and identified cyclin A2 as one of the most commonly downregulated genes. When the NHOKs were treated with N-BPs, we found that the level of cyclin A2 was suppressed in a dose- and time-dependent manner. In addition, the protein level of cyclin A2 was also significantly lower in oral epithelial cells in N-BP-treated oral mucosal tissue constructs. Cyclin A2 promoter reporter assay revealed that N-BPs inhibited the luciferase activity, indicating that the inhibition of cyclin A2 expression occurs at the transcriptional level. Furthermore, N-BPs did not alter the expression of cyclin A2 in normal human oral fibroblasts (NHOFs), suggesting that the effect of N-BPs on cyclin A2 expression may be cell-type specific. Thus, the findings of our study demonstrate that the inhibition of NHOK proliferation by N-BPs is mediated, at least in part, by the suppression of cyclin A2 expression at the transcriptional level, which may explain the underlying mechanisms of soft tissue toxicity by N-BPs.
Effect of early‐term birth on respiratory symptoms and lung function in childhood and adolescence

Early‐term‐born subjects, (37–38 weeks’ gestation), form a large part of the population and have an increased risk of neonatal respiratory morbidity and childhood respiratory symptoms; there is a paucity of data on their later lung function. We sought to (1) compare lung function at 8–9 and 14–17 years in early‐term‐born children with full‐term‐born children (39–43 weeks’ gestation); (2) assess the role of caesarean section delivery; and (3) compare respiratory symptoms and diagnosis of asthma.
Minimal and RNA-free RNase P in Aquifex aeolicus

Significance RNase P is a tRNA-processing enzyme of unique architectural diversity: either a catalytic RNA plus one or more (up to 10) proteins, or one (or three) unrelated proteins only. We identified yet another enzyme form in the bacterium Aquifex aeolicus, a 23-kDa protein and the smallest known form of RNase P. Apparently, it was acquired by horizontal gene transfer from Archaea. In some other bacteria and many archaea, it is simultaneously present with the presumably more ancient RNA-based enzyme form. Bacteria with both activities may represent the missing link of RNase P evolution, a transition state that had also been once traversed by the Aquificaceae, which, however, later lost their RNA-based RNase P. RNase P is an essential tRNA-processing enzyme in all domains of life. We identified an unknown type of protein-only RNase P in the hyperthermophilic bacterium Aquifex aeolicus: Without an RNA subunit and the smallest of its kind, the 23-kDa polypeptide comprises a metallonuclease domain only. The protein has RNase P activity in vitro and rescued the growth of Escherichia coli and Saccharomyces cerevisiae strains with inactivations of their more complex and larger endogenous ribonucleoprotein RNase P. Homologs of Aquifex RNase P (HARP) were identified in many Archaea and some Bacteria, of which all Archaea and most Bacteria also encode an RNA-based RNase P; activity of both RNase P forms from the same bacterium or archaeon could be verified in two selected cases. Bioinformatic analyses suggest that A. aeolicus and related Aquificaceae likely acquired HARP by horizontal gene transfer from an archaeon.
ArrayTrack: A Fine-Grained Indoor Location System

With myriad augmented reality, social networking, and retail shopping applications all on the horizon for the mobile handheld, a fast and accurate location technology will become key to a rich user experience. When roaming outdoors, users can usually count on a clear GPS signal for accurate location, but indoors, GPS often fades, and so up until recently, mobiles have had to rely mainly on rather coarse-grained signal strength readings. What has changed this status quo is the recent trend of dramatically increasing numbers of antennas at the indoor access point, mainly to bolster capacity and coverage with multiple-input, multiple-output (MIMO) techniques. We thus observe an opportunity to revisit the important problem of localization with a fresh perspective. This paper presents the design and experimental evaluation of ArrayTrack, an indoor location system that uses MIMO-based techniques to track wireless clients at a very fine granularity in real time, as they roam about a building. With a combination of FPGA and general purpose computing, we have built a prototype of the ArrayTrack system. Our results show that the techniques we propose can pinpoint 41 clients spread out over an indoor office environment to within 23 centimeters median accuracy, with the system incurring just 100 milliseconds latency, making for the first time ubiquitous real-time, fine-grained location available on the mobile handset.
PicoSAT Essentials

In this article we describe and evaluate optimized compact data structures for watching literals. Experiments with our SAT solver PicoSAT show that this low-level optimization not only saves memory, but also turns out to speed up the SAT solver considerably. We also discuss how to store proof traces compactly in memory and further unique features of PicoSAT including an aggressive restart schedule
Reflectance scanning

We present a generalized linear light source solution to estimate both the local shading frame and anisotropic surface reflectance of a planar spatially varying material sample. We generalize linear light source reflectometry by modulating the intensity along the linear light source, and show that a constant and two sinusoidal lighting patterns are sufficient for estimating the local shading frame and anisotropic surface reflectance. We propose a novel reconstruction algorithm based on the key observation that after factoring out the tangent rotation, the anisotropic surface reflectance lies in a low rank subspace. We exploit the differences in tangent rotation between surface points to infer the low rank subspace and fit each surface point's reflectance function in the projected low rank subspace to the observations. We propose two prototype acquisition devices for capturing surface reflectance that differ on whether the camera is fixed with respect to the linear light source or fixed with respect to the material sample. We demonstrate convincing results obtained from reflectance scans of surfaces with different reflectance and shading frame variations.
Severe menopausal symptoms associated with reduced adherence to antiretroviral therapy among perimenopausal and menopausal women living with HIV in Metro Vancouver

Objectives: Although more women living with HIV (WLWH) are entering midlife, the experiences of perimenopausal and menopausal WLWH, including the effects of menopausal symptoms severity, remain understudied. This study longitudinally investigated the correlates of antiretroviral therapy (ART) adherence among perimenopausal and menopausal WLWH from Metro Vancouver. Methods: Analyses drew on longitudinal data (2014-2017) from Sexual health and HIV/AIDS: Women's Longitudinal Needs Assessment, an ongoing community-based cohort of WLWH, aged 14+, from Metro Vancouver, Canada. At baseline and biannually, participants completed an interviewer-administered questionnaire. Bivariate and multivariable logistic regression with generalized estimating equations were used to identify the correlates of self-reported <95% ART adherence. Results: The sample included 109 perimenopausal and menopausal WLWH (233 observations), with a median age of 49 years (IQR 44-53). Whereas most (68.8%) participants experienced menopausal symptoms, only 17% had received treatment (eg, antidepressants, hormone therapy) at baseline. In multivariable analysis, severe menopausal symptoms (adjusted odds ratio [AOR] 1.03, 95% confidence interval [CI] 1.00-1.06), injection drug use (AOR 2.86, 95% CI 1.44-5.55), and physical/sexual violence (AOR 2.33, 95% CI 1.02-5.26) independently and positively correlated with <95% adherence. Conclusions: These findings suggest that menopausal symptoms may undermine ART adherence, with overlapping vulnerabilities such as injection drug use and sexual/physical violence further exacerbating poor ART adherence. Women-centred, trauma-informed care approaches to detect menopause and treat menopausal symptoms are urgently needed. Such approaches should holistically address the intersecting barriers to adherence and link WLWH to peripheral health and social services, including trauma counseling and evidence-based harm reduction services.
ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features

Primary cardiomyopathy is one of the most common inherited cardiac diseases and harbors significant phenotypic and genetic heterogeneity. Because of this, genetic testing has become standard in treatment of this disease group. Indeed, in recent years, next-generation DNA sequencing has found broad applications in medicine, both as a routine diagnostic tool for genetic disorders and as a high-throughput discovery tool for identifying novel disease-causing genes. We describe a male infant with primary dilated cardiomyopathy who was diagnosed using intrauterine echocardiography and found to progress to hypertrophic cardiomyopathy after birth. This proband was born to a nonconsanguineous family with a past history of a male fetus that died because of cardiac abnormalities at 30 wk of gestation. Using whole-exome sequencing, a novel homozygous frameshift mutation (c.2018delC; p.Gln675SerfsX30) in ALPK3 was identified and confirmed with Sanger sequencing. Heterozygous family members were normal with echocardiographic examination. To date, only two studies have reported homozygous pathogenic variants of ALPK3, with a total of seven affected individuals with cardiomyopathy from four unrelated consanguineous families. We include a discussion of the patient's phenotypic features and a review of relevant literature findings.
Scheduling analysis integration for heterogeneous multiprocessor SoC

Today, only very few techniques out of the host of work on formal performance and timing analysis have been adopted in MpSoC (multiprocessor system-on-chip) design. One of the key reasons is a mismatch between the scheduling models assumed in most formal approaches and the heterogeneous world of MpSoC scheduling techniques and communication patterns. This heterogeneity results from IP reuse and a plug-and-play design style, required to effectively reach the necessary design productivity. A second problem is the model complexity. While complex, specialized models can find their way into industry niches, their broad acceptance is extremely doubtful. In this paper, we review the existing scheduling analysis techniques with respect to these key requirements and derive a good compromise between model simplicity on the one hand, and applicability to MpSoC design on the other hand. The approach represents system-level scheduling analysis as a flow-analysis problem for event streams that can be configured to reuse the existing local scheduling analysis techniques. We define transformations between few key event stream models to meet the interfacing requirements of the compositional design style. An example demonstrates the application of the approach, as well as the worthiness of the results.
Visual Outcomes and Aberrometric Changes With Topography-Guided Photorefractive Keratectomy Treatment of Irregular Astigmatism After Penetrating Keratoplasty

Purpose: To evaluate the visual acuity and keratometric and aberrometric changes in patients with corneal transplants (PKP), who underwent topography-guided photorefractive keratectomy (TG-PRK) with mitomycin C (MMC). Methods: In this case study, 15 patients with spherical equivalents ranging from −11.00 to −0.25 diopters (D) who underwent penetrating corneal transplantation and had irregular astigmatism ranging from −7.5 to −2.0 D underwent TG-PRK with MMC. Corneal topography and wavefront of all patients were measured preoperatively and 12 months postoperatively. Results: Twelve months after TG-PRK with MMC, 46% of eyes achieved a best spectacle-corrected visual acuity (BSCVA) of 20/20 compared with 1 eye preoperatively (P = 0.0221, &khgr;2 test). The BSCVA did not improve in 1 patient and increased by 1 line or more in all others. Astigmatism decreased significantly (P = 0.003) from 5.10 ± 0.4 D to 3.37 ± 0.06 D, the corneal best-fit sphere increased and keratometry measurements flattened significantly (P = 0.0001 for both comparisons), and the corneal total root mean square aberrations and trefoil decreased significantly (P = 0.0077 and P = 0.0054, respectively) from 9.11 ± 2.56 &mgr;m to 7.58 ± 3.15 &mgr;m and 2.00 ± 1.2 to 1.38 ± 0.27 &mgr;m, respectively, as measured by wavefront aberrometry. Conclusions: Twelve months postoperatively, the BSCVA improved significantly, the lines of vision increased, and astigmatism, corneal best-fit sphere, mean keratometry, corneal thickness, corneal root mean square total, and corneal spherical aberrations decreased. TG-PRK with MMC is a good alternative for correcting post-PKP cases with irregular astigmatism with elevated higher-order aberrations.
Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in regulation of liver lipids and glucose tolerance.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin receptor signaling and may contribute to leptin resistance in diet-induced obesity. Although PTP1B inhibition has been suggested as a potential weight loss therapy, the role of specific neuronal PTP1B signaling in cardiovascular and metabolic regulation and the importance of sex differences in this regulation are still unclear. In this study, we investigated the impact of proopiomelanocortin (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female mice fed a high-fat diet (HFD). When compared with control mice (PTP1B flox/flox), male and female mice deficient in POMC neuronal PTP1B (PTP1B flox/flox/POMC-Cre) had attenuated body weight gain (males: -18%; females: -16%) and fat mass (males: -33%; female: -29%) in response to HFD. Glucose tolerance was improved by 40%, and liver lipid accumulation was reduced by 40% in PTP1B/POMC-Cre males but not in females. When compared with control mice, deficiency of POMC neuronal PTP1B did not alter mean arterial pressure (MAP) in male or female mice (males: 112 ± 1 vs. 112 ± 1 mmHg in controls; females: 106 ± 3 vs. 109 ± 3 mmHg in controls). Deficiency of POMC neuronal PTP1B also did not alter MAP response to acute stress in males or females compared with control mice (males: Δ32 ± 0 vs. Δ29 ± 4 mmHg; females: Δ22 ± 2 vs. Δ27 ± 4 mmHg). These data demonstrate that POMC-specific PTP1B deficiency improved glucose tolerance and attenuated diet-induced fatty liver only in male mice and attenuated weight gain in males and females but did not enhance the MAP and HR responses to a HFD or to acute stress.
MUC1 stimulates EGFR expression and function in endometrial cancer

The current standard of care for endometrial cancer patients involves hysterectomy with adjuvant radiation and chemotherapy, with no effective treatment for advanced and metastatic disease. MUC1 is a large, heavily glycosylated transmembrane protein that lubricates and protects cell surfaces and increases cellular signaling through the epidermal growth factor receptor (EGFR). We show for the first time that MUC1 stimulates EGFR expression and function in endometrial cancer. siRNA knockdown and CRISPR/Cas knockout of MUC1 reduced EGFR gene expression, mRNA, protein levels and signaling. MUC1 bound strongly to two regions of the EGFR promoter: −627/−511 and −172/−64. MUC1 knockout also reduced EGFR-dependent proliferation in two dimensional culture, as well as growth and survival in three dimensional spheroid cultures. MUC1 knockout cells were more sensitive to the EGFR inhibitor, lapatinib. Finally, MUC1 and EGFR co-expression was associated with increased cellular proliferation in human endometrial tumors. These data demonstrate the importance of MUC1-driven EGFR expression and signaling and suggest dual-targeted therapies may provide improved response for endometrial tumors.
Selenocysteine inhibits human osteosarcoma cells growth through triggering mitochondrial dysfunction and ROS‐mediated p53 phosphorylation

Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se‐containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC‐induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG‐63 human osteosarcoma cells growth in vitro through induction of S‐phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK‐2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl‐2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC‐induced cytotoxicity and p53 phosphorylation. Importantly, MG‐63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS‐mediated p53 phosphorylation, which validated the potential application of Se‐containing compounds in treatment of human osteosarcoma.
Investigating Hyperbolic Shear Deformation Theory on vibroacoustic behavior of the infinite Functionally Graded thick plate

This paper applies acoustic analysis of Sound Transmission Loss (STL) through infinite Functionally Graded (FG) thick plate employing Hyperbolic Shear Deformation Theory (HSDT). The procedure for applying a FG plate is followed by considering the material properties are changed continually based on power-law distribution of the materials in terms of volume fraction. The main benefit of HSDT can be justified knowing the fact that, it uses parabolic transverse shear strain across thickness direction. Therefore, no need to enter the extra effect of shear correction coefficient factor. Besides, the displacement field is extended as a combination of polynomial as well as hyperbolic tangent function by neglecting the effect of thickness stretching. Furthermore, the equations of motion are obtained employing Hamilton’s Principle. To provide an analytical solution based on HSDT, equations of motion are combined with acoustic wave equations. Moreover, some comparisons are made with the known theoretical and experimental results available in literature to verify the accuracy and efficiency of the current formulation. These comparisons reveal an excellent agreement. Consequently, some configurations are presented to demonstrate which parameters appear to be effective to improve the behavior of STL including the effects of modulus of elasticity and density in the thickness direction with respect to various power-law distributions.