Miracle-dz/UniFAR-FTUs huggingface dataset:
HLA-G is expressed by the glandular epithelium of peritoneal endometriosis but not in eutopic endometrium.

BACKGROUND HLA-G is a major histocompatability antigen with documented immune-regulatory function. Various epithelial cancers and tissue allografts have been noted to express HLA-G, which is postulated to aid in their escape from immunosurveillance. We evaluated peritoneal endometriosis and eutopic endometrium for the expression of HLA-G protein and gene transcript. METHODS Two experiments were performed: (i) archived tissue blocks from peritoneal endometriotic lesions (n = 15) and eutopic endometrium (n = 12) were evaluated for extent of protein immunostaining, and (ii) eutopic endometrial biopsies from women without (n = 17) and with (n = 24) endometriosis, and peritoneal endometriotic lesions (n = 14) were evaluated for presence of RNA transcript by in situ hybridization. RESULTS HLA-G protein localized in the glandular epithelium of 14 of 15 (93.3%) peritoneal endometriotic lesions, but not in stromal cells. HLA-G protein staining was absent in endometrial biopsies (n = 12). HLA-G gene transcript localized to the glandular epithelium in 13 of 14 (92.8%) peritoneal endometriotic lesions. HLA-G transcript was never observed in eutopic endometrium, regardless of cycle stage or whether from women with (n = 24) or without (n = 18) endometriosis. CONCLUSIONS HLA-G is expressed by endometriotic glandular epithelium but not by eutopic endometrium under normal conditions. Differential expression of HLA-G suggests that peritoneal inflammation or cellular stress may up-regulate mechanisms to promote ectopic endometrial survival.
Heritability of the iridotrabecular angle width measured by optical coherence tomography in Chinese children: the Guangzhou twin eye study.

PURPOSE To estimate the heritability of the iridotrabecular angle width measured by anterior segment optical coherence tomography (ASOCT) in a classic twin study. METHODS Twins aged 8 to 16 years were identified from the Guangzhou Twin Registry. ASOCT was used to obtain one horizontal scan, and the images were analyzed with custom software. Angle width was represented by the angle opening distance (AOD) at the 500-microm anterior-to-scleral spur, as well as the angle recess area (ARA) and trabecular-iris space area (TISA) located 750 microm anterior to the scleral spur. Zygosity was confirmed by genotyping with 16 polymorphic markers in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling after adjustment for age and sex, with the Mx program. RESULTS The mean age of the participants was 11.7 +/- 2.6 years in 305 monozygotic (MZ) and 11.8 +/- 2.4 years in 157 dizygotic (DZ) pairs. The intraclass correlation coefficients for the AOD, ARA, and TISA were 0.70, 0.75, and 0.72 in the MZ pairs and 0.34, 0.32, and 0.33 in the DZ pairs, respectively. A model with additive genetic (69.7%; 95% CI: 63.9%-74.6%) and unique environmental effects (30.3%; 95% CI: 25.4%-36.1%) was the most parsimonious for AOD. Similar results were identified for ARA and TISA. CONCLUSIONS The variance in drainage angle width in Chinese children appears to be largely attributable to genetic effects, with a heritability of approximately 70%.
DNA oligonucleotides with A, T, G or C opposite an abasic site: structure and dynamics

Abasic sites are common DNA lesions resulting from spontaneous depurination and excision of damaged nucleobases by DNA repair enzymes. However, the influence of the local sequence context on the structure of the abasic site and ultimately, its recognition and repair, remains elusive. In the present study, duplex DNAs with three different bases (G, C or T) opposite an abasic site have been synthesized in the same sequence context (5′-CCA AAG6 XA8C CGG G-3′, where X denotes the abasic site) and characterized by 2D NMR spectroscopy. Studies on a duplex DNA with an A opposite the abasic site in the same sequence has recently been reported [Chen,J., Dupradeau,F. -Y. , Case,D.A. , Turner,C.J. and Stubbe,J. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4′-oxidized abasic sites. Biochemistry, 46, 3096–3107]. Molecular modeling based on NMR-derived distance and dihedral angle restraints and molecular dynamics calculations have been applied to determine structural models and conformational flexibility of each duplex. The results indicate that all four duplexes adopt an overall B-form conformation with each unpaired base stacked between adjacent bases intrahelically. The conformation around the abasic site is more perturbed when the base opposite to the lesion is a pyrimidine (C or T) than a purine (G or A). In both the former cases, the neighboring base pairs (G6-C21 and A8-T19) are closer to each other than those in B-form DNA. Molecular dynamics simulations reveal that transient H-bond interactions between the unpaired pyrimidine (C20 or T20) and the base 3′ to the abasic site play an important role in perturbing the local conformation. These results provide structural insight into the dynamics of abasic sites that are intrinsically modulated by the bases opposite the abasic site.
Effect of Bipolar Electrode Spacing on Phrenic Nerve Stimulation and Left Ventricular Pacing Thresholds: An Acute Canine Study

Background— Phrenic nerve stimulation (PNS) is a common complication of cardiac resynchronization therapy when left ventricular (LV) pacing occurs via a coronary vein. The purpose of this study was to evaluate the effects of bipolar electrode spacing on PNS and LV pacing thresholds. Methods and Results— Electrophysiology catheters with standard (2 mm-5 mm-2 mm) or modified (1 mm-5 mm-1 mm) interelectrode spacing was, respectively, inserted in a posterior/lateral cardiac vein in a randomized order in 6 anesthetized dogs via jugular access. The phrenic nerve was dissected via a left minithoracotomy and repositioned over the vein as close as possible to one of the electrodes. The presence of PNS was verified (ie, PNS threshold <2 V at 0.5 ms in unipolar configuration). Bipolar pacing was delivered using the electrode closest to the phrenic nerve as the cathode, and multiple bipolar electrode spacing configurations were tested. During bipolar pacing, PNS threshold increased as bipolar electrode spacing was reduced (P<0.05), whereas LV pacing thresholds did not change significantly (P>0.05). Compared with a standard bipolar electrode spacing of 20 mm for LV leads, 1 and 2 mm bipolar electrode spacing resulted in a PNS threshold increase of 5.5±2.2 V (P=0.003) and 2.8±1.7 V (P<0.001), respectively. Similarly, PNS threshold increased by 6.5±3.7 V with 1 mm and by 3.8±1.9 V with 2 mm bipolar pacing (both P<0.001), compared with unipolar pacing. Conclusions— This study suggests that reducing LV bipolar electrode spacing from the standard 20 mm to 1 or 2 mm may significantly increase the PNS threshold without compromising LV pacing thresholds.
Growth Factor Receptor-binding Protein 10 (Grb10) as a Partner of Phosphatidylinositol 3-Kinase in Metabolic Insulin Action*

The regulation of the metabolic insulin response by mouse growth factor receptor-binding protein 10 (Grb10) has been addressed in this report. We find mouse Grb10 to be a critical component of the insulin receptor (IR) signaling complex that provides a functional link between IR and p85 phosphatidylinositol (PI) 3-kinase and regulates PI 3-kinase activity. This regulatory mechanism parallels the established link between IR and p85 via insulin receptor substrate (IRS) proteins. A direct association was demonstrated between Grb10 and p85 but was not observed between Grb10 and IRS proteins. In addition, no effect of mouse Grb10 was observed on the association between IRS-1 and p85, on IRS-1-associated PI 3-kinase activity, or on insulin-mediated activation of IR or IRS proteins. A critical role of mouse Grb10 was observed in the regulation of PI 3-kinase activity and the resulting metabolic insulin response. Dominant-negative Grb10 domains, in particular the SH2 domain, eliminated the metabolic response to insulin in differentiated 3T3-L1 adipocytes. This was consistently observed for glycogen synthesis, glucose and amino acid transport, and lipogenesis. In parallel, the same metabolic responses were substantially elevated by increased levels of Grb10. A similar role of Grb10 was confirmed in mouse L6 cells. In addition to the SH2 domain, the Pro-rich amino-terminal region of Grb10 was implicated in the regulation of PI 3-kinase catalytic activity. These regulatory roles of Grb10 were extended to specific insulin mediators downstream of PI 3-kinase including PKB/Akt, glycogen synthase kinase, and glycogen synthase. In contrast, a regulatory role of Grb10 in parallel insulin response pathways including p70 S6 kinase, ubiquitin ligase Cbl, or mitogen-activated protein kinase p38 was not observed. The dissection of the interaction of mouse Grb10 with p85 and the resulting regulation of PI 3-kinase activity should help elucidate the complexity of the IR signaling mechanism.
Overview of Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Patients with Type 2 Diabetes.

BACKGROUND It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes. DISCUSSION This article reviews the evidence from phase 3 clinical trials for each of the 5 GLP-1 receptor agonists by comparing them against one another and with other existing therapies, including metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas. Incretin-based therapies have emerged as attractive agents for the treatment of type 2 diabetes. They target the GLP-1 hormone, which is partly responsible for insulin release and for attenuating hyperglycemia during meals (ie, the incretin effect). The 2 classes of incretin-based therapy currently available are GLP-1 receptor agonists and DPP-4 inhibitors, which prevent the breakdown of GLP-1. Both classes are attractive options, given their glucose-lowering effects without the adverse effects of hypoglycemia and weight gain. The different mechanisms of action of these therapies result in generally greater efficacy with GLP-1 receptor agonists, albeit at the expense of slightly increased gastrointestinal symptoms. These agents exert their effects by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying, thereby reducing appetite. Currently, 5 GLP-1 receptor agonists are available, including exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide; semaglutide may soon become available as the newest agent. With the exception of the investigational oral semaglutide, which has shown promising results, the other 5 agents are administered as subcutaneous injections, at different dosing intervals. CONCLUSION Currently, 5 GLP-1 receptor agonists are available for use in the United States. Although they are all in the same drug class, some significant differences exist among the various GLP-1 receptor agonists. The choice of a specific GLP-1 receptor agonist will depend on the patient preferences, potential adverse effects, and cost.
Investigating Tilt-based Gesture Keyboard Entry for Single-Handed Text Entry on Large Devices

The popularity of mobile devices with large screens is making single-handed interaction difficult. We propose and evaluate a novel design point around a tilt-based text entry technique which supports single handed usage. Our technique is based on the gesture keyboard (shape writing). However, instead of drawing gestures with a finger or stylus, users articulate a gesture by tilting the device. This can be especially useful when the user's other hand is otherwise encumbered or unavailable. We show that novice users achieve an entry rate of 15 words-per-minute (wpm) after minimal practice. A pilot longitudinal study reveals that a single participant achieved an entry rate of 32 wpm after approximate 90 minutes of practice. Our data indicate that tilt-based gesture keyboard entry enables walk-up use and provides a suitable text entry rate for occasional use and can act as a promising alternative to single-handed typing in certain situations.
Models for Certain Residual Representations of Unitary Groups

We dedicate this paper to Stephen Gelbart on the occasion of his 60th birthday Abstract. In this paper, we consider the generalized Gelfand-Graev mod- els for automorphic forms on unitary groups, which characterize the existence of certain residual representations for unitary groups. As one of the conse- quences, we obtain results related to the Gross-Prasad type conjecture for unitary groups.
Sex differences in outcomes following isolated coronary artery bypass graft surgery in Australian patients: analysis of the Australasian Society of Cardiac and Thoracic Surgeons cardiac surgery database.

OBJECTIVES Women undergoing isolated coronary artery bypass graft (CABG) surgery have been previously shown to be at an independently increased risk for post-operative morbidity and mortality. The current study evaluates the impact of sex as an independent risk factor for early and late morbidity and mortality following isolated CABG surgery. METHODS Data obtained between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program was retrospectively analysed. Demographic, operative data and post-operative complications were compared between male and female patients using chi-square and t-tests. Long-term survival analysis was performed using Kaplan-Meier survival curves and the log-rank test. Independent risk factors for short- and long-term mortality were identified using binary logistic and Cox regression, respectively. RESULTS CABG surgery was undertaken in 21 534 patients at 18 Australian institutions; 22.2% were female. Female patients were generally older (mean age, 68 vs. 65 years, P < 0.001) and presented more often with congestive heart failure (P < 0.001), hypertension (P < 0.001), diabetes mellitus (P < 0.001) and cerebrovascular disease (P < 0.001). Women demonstrated a greater 30-day mortality (2.2% vs. 1.5%, P < 0.001) on univariate analysis but not on multivariate analysis (P = 0.638). Similarly, women demonstrated a greater late mortality than men on univariate analysis (P = 0.006) but not on multivariate analysis (P = 0.093). Women had a decreased risk of early complications including new renal failure (P = 0.001) and deep sternal wound infection (P = 0.017) but were more likely to require red blood cell transfusion (P < 0.001). CONCLUSIONS Female patients undergoing isolated CABG surgery have a greater 30-day mortality which may be accounted for by a poorer pre-operative risk factor profile. Further investigation is required into the reasons for differential outcome after CABG based on sex.
Effect of 11 months of yoga training on cardiorespiratory responses during the actual practice of Surya Namaskar

Background: Surya Namaskar (SN), a popular traditional Indian yogic practice, includes practicing 12 physical postures with alternate forward and backward bending movement of the body along with deep breathing maneuvers. The practice of SN has become popular among yoga practitioners and other fitness conscious people. The long-term effect of practicing SN and other yogic practices on cardiorespiratory responses during SN are lacking. Aim: The present study was conducted to study the effect of yogic training on various cardiorespiratory responses during the SN practice in yoga trainees after a time interval of 3, 6, and 11 months. Materials and Methods: The present study was conducted on 9 healthy male Army soldiers who underwent training in various yoga postures including SN, meditation, and pranayama for 1 h daily for 11 months. First, second, and third phase of the study was conducted in the laboratory after completion of 3, 6, and 11 months of the yoga training. The participants performed SN along with other yogic practices in the laboratory as per their daily practice schedule. The cardiorespiratory responses of the volunteers were recorded during actual practice of SN. Statistical Analysis: One-way repeated measure ANOVA followed by Tukey HSD. Results: Oxygen consumption and heart rate during actual practice of SN was 0.794 ± 0.252, 0.738 ± 0.229, and 0.560 ± 0.165 L/min and 92.1 ± 11.6, 97.9 ± 7.3 and 87.4 ± 9.2 beats/min respectively at 1st , 2nd , and 3rd phase of yoga training. Minute ventilation and tidal volume also reduced from 19.9 ± 4.65 to 17.8 ± 4.41 L/min and 1.091 ± 0.021 to 0.952 L/breath from 1st phase to 3rd phase of yoga training. However, respiratory parameters like breathing rate (fR) did not show any reduction across the three phases. Conclusion: The results of the present study indicated that yogic training caused conditioning of cardiorespiratory parameters except fR, which did not reduce across three phases of training.
Cyp17, Urinary Sex Steroid Levels and Breast Cancer Risk in Postmenopausal Women

Endogenous sex hormones play an important role in the etiology of breast cancer. Polymorphisms in genes encoding for enzymes involved in steroidogenesis may therefore play a role in breast cancer risk. Cytochrome P450c17α (Cyp17) functions at key branch points in human steroidogenesis. A T→C transition (A1 and A2 allele) in the 5′ untranslated region may be associated with increased expression of Cyp17. Using a case-cohort design, we studied the effects of the A2 allele on endogenous sex hormone levels and breast cancer risk within a large population-based cohort (n = 9,349) in the Netherlands (the DOM-cohort). Cyp17 genotype was determined in 335 incident postmenopausal breast cancer cases, which occurred after follow-up (median time to follow-up, 19 years) of the entire cohort, and in a random sample of 373 women (subcohort). Concentrations of estrone (E1), estradiol (E2), testosterone, 5α-androstane-3α, 17β-diol (3αD), and creatinine were measured in first-morning urine samples. Only among women with body mass index (BMI) < 25 kg/m2 was the A2A2 genotype associated with higher levels of E1, E2, and 3αD compared with a group of women with either the A1A1 or the A1A2 genotype (e.g., geometric means of E1 in ng/mgcreatinine: A2A2, 2.23; A1A1/A1A2, 1.47; P = 0.03). Adjusted breast cancer rate ratios for women with the A1A2 or A2A2 genotype compared with women with the A1A1 genotype were 0.96 (0.68-1.37) and 0.80 (0.47-1.35), respectively. These results did not differ between women with low and high BMI. In conclusion, this paper shows that women with low BMI and the A2A2 genotype had higher endogenous sex steroid levels compared with women with the A1A1 genotype. However, these increased sex steroid levels are not translated into an increased breast cancer risk in these women.
Efficient Infrastructure Restoration Strategies Using the Recovery Operator

Infrastructure systems are critical for society's resilience, government operation, and overall defense. Thereby, it is imperative to develop informative and computationally efficient analysis methods for infrastructure systems, which reveal system vulnerabilities and recoverability. To capture practical constraints in systems analyses, various layers of complexity play a role, including limited element capacities, restoration resources, and the presence of interdependence among systems. High‐fidelity modeling such as mixed integer programming and physics‐based modeling can often be computationally expensive, making time‐sensitive analyses challenging. Furthermore, the complexity of recovery solutions can reduce analysis transparency. An alternative, presented in this work, is a reduced‐order representation, dubbed a recovery operator, of a high‐fidelity time‐dependent recovery model of a system of interdependent networks. The form of the operator is assumed to be a time‐invariant linear dynamic model apt for infrastructure restoration. The recovery operator is generated by applying system identification techniques to numerous disaster and recovery scenarios. The proposed compact representation provides simple yet powerful information regarding systemic recovery dynamics, and enables generating fast suboptimal recovery policies in time‐critical applications.
Evaluation of standard versus nonstandard vital signs monitors in the prehospital and emergency departments: Results and lessons learned from a trauma patient care protocol

BACKGROUND This study aimed to determine the effectiveness of using a wireless, portable vital signs monitor (WVSM) for predicting the need for lifesaving interventions (LSIs) in the emergency department (ED) and use a multivariate logistic regression model to determine whether the WVSM was an improved predictor of LSIs in the ED over the standard of care monitor currently being used. METHODS This study analyzed 305 consecutive patients transported from the scene via helicopter to a Level I trauma center. For 104 patients in the study, a WVSM was also attached to the patient’s arm and used to record and display prehospital and hospital physiologic data in real time on a handheld computer and in the trauma bay. Multivariate logistic regression analyses were performed for accuracy in predicting needs for LSIs in control and WVSM subjects. In addition, receiver operating characteristic curves were obtained to examine the discriminating power of the models for the outcome of one or more LSIs in the ED. RESULTS Of the 305 patients, 73 underwent 109 LSIs in the ED. Of these, 21 patients wore the WVSM during transport in addition to the standard monitor. Logistic regression analysis revealed that heart rate, respiratory rate, and systolic blood pressure were significantly associated with an increased risk for LSIs in the ED (p < 0.05). Receiver operating characteristic curve analysis also demonstrated better prediction for LSIs performed in the ED in WVSM subjects than in control subjects (area under the curve, 0.86 vs. 0.81, respectively). CONCLUSION The WVSM system leads to improved LSI accuracy in the ED. In addition, many important lessons have been learned in preparation for this study. Adoption of nonstandard vital signs monitors into critical care/trauma medicine may require a new paradigm of personnel education, training, and practice. LEVEL OF EVIDENCE Therapeutic/care management, level IV.
Absence of Evidence as Evidence of Absence: A Simple Mechanism for Scalable P2P Search

We propose a novel search mechanism for unstructured p2p networks, and show that it is both scalable, i.e., it leads to a bounded query traffic load per peer as the peer population grows, and reliable, i.e., it successfully locates all files that are (sufficiently often) brought into the system. To the best of our knowledge, this is the first time that a search mechanism for unstructured p2p networks has been shown to be both scalable and reliable. We provide both a formal analysis and a numerical case study to illustrate this result. Our analysis is based on a random graph model for the overlay graph topology and uses a mean-field approximation to characterize the evolution of how files are replicated in the network.