Miracle-dz/UniFAR-FTUs huggingface dataset:
N‐acetylcysteine accelerates amputation stump healing in the setting of diabetes

Over 60% of lower extremity amputations are performed in patients with diabetes and peripheral arterial disease, and at least 25% require subsequent reamputation due to poor surgical site healing. The mechanisms underlying poor amputation stump healing in the setting of diabetes are not understood. N‐acetylcysteine (NAC) is known to promote endothelial cell function and angiogenesis and may have therapeutic benefits in the setting of diabetes. We tested the hypothesis that NAC alters the vascular milieu to improve healing of amputation stumps in diabetes using a novel in vivo murine hindlimb ischemia‐amputation model. Amputation stump tissue perfusion and healing were evaluated in C57BL/6J adult mice with streptozotocin‐induced diabetes. Compared with controls, mice treated with daily NAC demonstrated improved postamputation stump healing, perfusion, adductor muscle neovascularization, and decreased muscle fiber damage. Additionally, NAC stimulated HUVEC migration and proliferation in a phospholipase C β–dependent fashion and decreased Gαq palmitoylation. Similarly, NAC treatment also decreased Gαq palmitoylation in ischemic and nonischemic hindlimbs in vivo. In summary, we demonstrate that NAC accelerates healing of amputation stumps in the setting of diabetes and ischemia. The underlying mechanism appears to involve a previously unrecognized effect of NAC on Gαq palmitoylation and phospholipase C β–mediated signaling in endothelial cells. —Zayed, M. A. , Wei, X. , Park, K. , Belaygorod, L. , Naim, U. , Harvey, J., Yin, L. , Blumer, K. , Semenkovich, C. F. N‐acetylcysteine accelerates amputation stump healing in the setting of diabetes. FASEB J. 31, 2686–2695 (2017). www.fasebj. org
Evaluation of polymerization shrinkage in dental restorative experimental composites based: Bisgma/tegdma, filled with MMT

This work concerns to the investigation of the polymerization shrinkage and mechanical properties in dental restoratives experimental composites filled with nano clay Montmorilonite (MMT) Cloisite® 10A nanoparticles, in glycidyl methacrylate resin, using experimental composites filled with silanized Aerosil OX-50 Silica as a control group. Six formulations with BisGMA/TEGDMA based polymeric matrix (three added with MMT and three added with silanized silica as filler) containing 50, 60, and 70 wt % were investigated. Characterization of the experimental composites was established with the following analyses: Scanning Electron Microscope, (SEM); Thermo-Mechanical Analysis, (TMA) for Shrinkage Polymerization; Differential Scanning Calorimetry Analysis (DSC); Knoop Micro Hardness analysis; X-ray Diffraction (XRD); Degree of Conversion (DC); Elastic Modulus and Flexural Strength; Transmission Electron Microscopy (TEM). Statistical Analyses were realized using two-way ANOVA (type and amount of filler) and Tukey's test. TMA results showed that composites filled with MMT nanoparticle present statistically lower polymerization shrinkage values and statistically high degree of conversion in all formulations tested, when compared to composites filled with silanized silica. XRD and TEM analyses showed evidences of the intercalation phenomenon in the MMT nanoparticles in relation to BisGMA/TEGDMA polymeric matrix. However, for Flexural Strength, groups filled with MMT nanoparticle showed statistically lower values in all concentration tested. At high filler concentration it was observed the appearance of tactoids and functionalization of MMT nanoparticle did not promote a strong interface adhesion between polymeric matrix and filler. In order to adjust the mechanical properties, it would be convenient to promote the concentration optimization of MMT nanoparticles. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43543.
The Clinical Pulmonary Infection Score Poorly Predicts Pneumonia in Patients With Burns

The Clinical Pulmonary Infection Score (CPIS) has been reported to be a useful tool in the diagnosis of ventilator-associated pneumonia (VAP) in the critical care setting. However, the systemic inflammation associated with injury may limit the utility of CPIS in patients with burns. The purpose of this study was to determine the potential utility of CPIS in the management of burn patients. A retrospective review was performed on all burn patients who underwent quantitative culture to diagnose VAP from 2003 to 2005. CPIS was retrospectively calculated for each patient on the day of the procedure. The sensitivity, specificity, and predictive values of a CPIS greater than 6 for VAP diagnosis were calculated. In addition, CPIS scores of patients with and without pneumonia were compared using the Mann-Whitney U test. A total of 46 quantitative cultures were obtained in 28 patients during the study period. Average patient age was 45 ± 19 years, average TBSA was 33 ± 18%, and the average APACHE II score on admission was 16 ± 6. Sixty-eight percent of patients had inhalation injury. Twenty-six quantitative cultures were positive, and 20 were negative. Mean CPIS was 5.7 for patients with negative quantitative cultures and 5.5 for patients with positive cultures (P = .41). The sensitivity of CPIS scoring was 0.3, and its specificity was 0.8. CPIS had a positive predictive value of 0.7 and negative predictive value of 0.5. CPIS—a reported reliable indicator of VAP in critically ill patients—did not accurately predict the presence of pneumonia in burn patients. VAP diagnosis in burn patients should still rely on clinical suspicion verified by quantitative culture.
Association between changes in fat distribution and biomarkers for breast cancer.

We assessed the associations between changes in total and abdominal fat and changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In the SHAPE-2 trial, 243 postmenopausal overweight women were included. The intervention in this trial consisted of 5-6 kg weight loss either by diet only or exercise plus diet. After 16 weeks, we measured serum sex hormones, inflammatory markers, total body fat (measured by DEXA scan) and intra and subcutaneous abdominal fat (measured by MRI). Associations between changes in different body fat depots and biomarkers were analysed by linear regression using the study cohort irrespective of randomisation to make maximal use of the distribution of changes in fat measures. We found that a loss in total body fat was associated with favourable changes in free oestradiol, free testosterone, leptin and sex hormone binding globulin (SHBG). The loss of intra-abdominal fat was associated with a decrease in free testosterone, hsCRP and leptin, and an increase in SHBG. In the multivariable analysis, the best fitted models for the biomarkers free oestradiol, SHBG leptin and adiponectin included only total body fat. For free testosterone, this was subcutaneous abdominal fat, and for hsCRP and IL-6, only intra-abdominal fat change was important. For IL-6 and adiponectin, however, associations were weak and not significant. We conclude that, in our population of healthy overweight postmenopausal women, loss of fat at different body locations was associated with changes in different types of biomarkers, known to be related to risk of breast cancer.
Zygomatic Root Position in Recent and Fossil Hominids

The relative position of the zygomatic root to the dentition plays a crucial role in determining the overall strength of the face in response to bite forces. The powerful superficial head of the masseter arises there and the zygomaticoalveolar crest (ZAC) is discussed as a buttressing feature of the face. For instance, a more forwardly or backwardly positioned zygomatic root or a lower or higher vertical distance to the dentition could be indicative for evolutionary adaptations to particular loading regimes which are associated with diet. We therefore examined the morphology of the maxilla using state‐of‐the‐art 3D Geometric Morphometric methods. The data set was reduced to a minimum of relevant measurements and includes five landmarks (pr, ol, zm, lingual and buccal midpoint of second molar alveoli) and three curves with semilandmarks along the lingual and buccal alveolar rim and the ZAC. Results show a stunning overlap in shape variation. We find no clear pattern of shape that would allow separating different hominid groups with confidence, except two extreme forms—Paranthropines and Neanderthals. We also find no clear trend over time. Australopithecines, Habilines, Erectines, and Middle Pleistocene Homo can be very similar to modern humans. Even great apes are within or not far from the central shape distribution of Homo, but they separate clearly from gracile and robust Australopithecines. We discuss the shape factors underlying our data. The geometry studied allows simple measurements and analyses and is thus potentially interesting for classification purposes of extreme forms. Anat Rec, 300:160–170, 2017. © 2016 Wiley Periodicals, Inc.
Multifactorial study of mobile phone dependence in medical students: Relationship to health-related lifestyle, Type A behavior, and depressive state

We investigated factors contributing to mobile phone dependence. To 139 medical students, we administered a self-reporting questionnaire designed to evaluate mobile phone dependence, health-related lifestyle, patterns of behavior, and depressive state. Multivariate logistic regression analysis revealed that scores for poor health-related lifestyle, Type A behavior pattern, and presence of depression are independently associated with degree of mobile phone dependency. These findings suggest that persons with an unhealthy lifestyle, Type A behavior traits, or depression might benefit from mobile phone use guidance.
Construct validity of physical activity and sedentary behaviors staging measures for adolescents

Purpose:To evaluate the construct validity of physical activity (PA) and sedentary behaviors (SB) staging measures for adolescents that incorporate the current national recommendations.Method: The Progressive Aerobic Cardiovascular Endurance Run, Actigraph accelerometer, and self-reported hours of TV viewing served as criterion measures.Participants were 878 adolescents (M age = 12.74, 53.6% girls, 39.9% non-White). Results: The PA staging measure had mixed evidence of convergent validity and strong evidence of divergent validity. The SB staging measure had strong and generalized evidence of convergent validity but weak evidence of divergent validity, which could be related to inaccurate assumptions about the relation of SB to PA and fitness. Results were generally in the expected direction and provide preliminary evidence for the construct validity and generalizability of both staging measures. However, more research is warranted to validate the staging measures with Actigraph-measured PA and sedentary time. Effect sizes (η2 values) Ranged from small to large (.02–.63). Conclusion:PA and SB stage-of-change measures that are congruent with current national recommendations and appropriate for use among adolescents were partially supported for their construct validity.
Chaos in Solitary VCSELs: Exploring the Parameter Space With Advanced Sampling

We explore the parameter space of the so-called spin-flip model by advanced sampling techniques to analyze the requirements leading to polarization chaos in solitary vertical-cavity surface-emitting lasers. We first investigate the performances of different sampling techniques for multidimensional parameter space exploration. Purely random sampling and tensor-product grids require a large amount of samples to uniformly cover the whole space, and we show that other schemes are highly superior to this regard, hence allowing a reduced number of samples and computation to be used to reach the same level of insight in the system behavior. Considering the scarcity of the chaotic regions and their sharp boundaries, combined with quite involved computations to identify chaotic dynamics, the proposed approach is shown to be highly beneficial. Here, we are able to highlight two thresholds limiting the range of injection current for which chaos can be observed, and to link them to a fine balance between the spin relaxation rate and the birefringence.
Invariant smoothing on Lie Groups

In this paper we propose a (non-linear) smoothing algorithm for group-affine observation systems, a recently introduced class of estimation problems on Lie groups that bear a particular structure. As most non-linear smoothing methods, the proposed algorithm is based on a maximum a posteriori estimator, determined by optimization. But owing to the specific properties of the considered class of problems, the involved linearizations are proved to have a form of independence with respect to the current estimates, leveraged to avoid (partially or sometimes totally) the need to relinearize. The method is validated on a robot localization example, both in simulations and on real experimental data.
Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales

ABSTRACT Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 μg/ml, those for M. circinelloides were 1 and 2 μg/ml, those for R. arrhizus were 2 and 4 μg/ml, and those for R. microsporus were 2 and 2 μg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.
Adherence and virologic outcomes among treatment-naïve veteran patients with human immunodeficiency virus type 1 infection

Abstract Many studies have estimated the association between the adherence to antiretroviral therapies and human immunodeficiency virus (HIV) patients’ virologic/immunologic outcomes. However, evidence is lacking on the causal effect of adherence on the outcomes. The goal of this study is to understand whether near perfect adherence is necessary to achieve optimal virologic outcome and also to investigate the effect of initial adherence to antiretroviral therapies on initial viral suppression by different regimens. A cohort study was conducted on HIV veterans initiating antiretroviral therapies in 1999 to 2015. The primary outcome was the first viral suppression occurred within 30 to 60 days since the index date. Multiple imputation was used to impute the missing value of virologic outcomes. The inverse probability of treatment weighting (IPTW) method was applied to estimate the viral suppression rate at each specific adherence category for each regimen category. Marginal structural models with IPTW were used to estimate the risk of viral suppression in lower-adherence categories in comparison to near-perfect adherence level ≥95%. Data showed that lower adherence caused lower viral suppression rate, with the association differentiated by the regimen. Patients on integrase strand transfer had the highest viral suppression rate, with patients on protease inhibitors having the lowest rate. Regardless of regimens, the viral suppression rate among patients at initial adherence of 75 to <95% was not statistically different from patients at adherence of ≥95%; however, the differences might be clinically significant.
If You are so Smart, Why Aren’t You an Entrepreneur? Returns to Cognitive and Social Ability: Entrepreneurs Versus Employees

How valuable are cognitive and social abilities for entrepreneurs’ incomes as compared to employees? We answer three questions: (1) To what extent does a composite measure of ability affect an entrepreneur's earnings relative to employees? (2) Do different cognitive abilities (e.g. math ability, language ability) and social ability affect earnings of entrepreneurs and employees differently? , and (3) Does the balance in these measured ability levels affect an individual's earnings? Our individual fixed-effects estimates of the differential returns to ability for spells in entrepreneurship versus wage employment account for selectivity into entrepreneurial positions as determined by fixed individual characteristics. General ability has a stronger impact on entrepreneurial incomes than on wages. Entrepreneurs and employees benefit from different sets of specific abilities: Language and clerical abilities have a stronger impact on wages, whereas mathematical, social and technical ability affect entrepreneurial incomes more strongly. The balance in the various kinds of ability also generates a higher income, but only for entrepreneurs: This finding supports Lazear's Jack-of-all-Trades theory. This discussion paper resulted in a publication in the Journal of Economics and Management Strategy 19(4), 947-89.
Dupilumab: an evidence-based review of its potential in the treatment of atopic dermatitis

Introduction Atopic dermatitis (AD) is a recurrent, pruritic inflammatory skin disease with complex immunopathogenesis characterized by a dominant TH2 response. Dupilumab is an interleukin (IL)-4 receptor alpha antagonist that subsequently blocks IL-4 and IL-13 signaling. It has recently been approved for the treatment of adult patients with moderate-to-severe AD whose current treatment options are limited. Aim This article reviews the evidence of clinical efficacy, safety, and patient-reported out-come (PRO) measures from Phase I–III trials of dupilumab in adult patients with moderate-to-severe AD. Evidence review Results from clinical trials of dupilumab in adults with moderate-to-severe AD have shown that weekly or biweekly dupilumab injections significantly improve clinical and PROs. Transcriptome and serum analyses also found that dupilumab significantly modulates the AD molecular signature and other TH2-associated biomarkers, compared with placebo. Additionally, concomitant use of dupilumab with topical corticosteroids (TCS) results in a greater improvement in signs and symptoms of AD than with dupilumab use alone. Throughout the trials, common adverse events were headaches, conjunctivitis, and injection site reactions. These were consistently mild–moderate and occurred with similar frequency between the treatment and placebo groups. Place in therapy In adult patients with moderate-to-severe refractory AD, monotherapy or concomitant use of dupilumab with TCS holds great promise to significantly improve clinical outcomes and quality of life of the patient. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use. Finally, further economic evidence is warranted to compare the long-term costs and benefits of dupilumab with other currently available treatments for moderate-to-severe AD.
Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope

Significance Bunyaviruses are emerging zoonotic pathogens of public-health concern. Lack of structures for proteins on the viral membrane (“envelope”) surface limits understanding of entry. We describe atomic-level structures for the globular “head” of the envelope protein, glycoprotein N (Gn), from two members, severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV), of Phleboviruses genus in the bunyavirus family, and a structure of the SFTSV Gn bound with a neutralizing antibody Fab. The results show the folded Gn structure and define virus-specific neutralizing-antibody binding sites. Biochemical assays suggest that dimerization, mediated by conserved cysteines in the region (“stem”) connecting the Gn head with the transmembrane domain, is a general feature of bunyavirus envelope proteins and that the dimer is probably the olimeric form on the viral surface. Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the Bunyaviridae family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Bunyaviridae. Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4–5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.
Community circulation patterns of oral polio vaccine serotypes 1, 2, and 3 after Mexican national immunization weeks.

BACKGROUND With wild poliovirus nearing eradication, preventing circulating vaccine-derived poliovirus (cVDPV) by understanding oral polio vaccine (OPV) community circulation is increasingly important. Mexico, where OPV is given only during biannual national immunization weeks (NIWs) but where children receive inactivated polio vaccine (IPV) as part of their primary regimen, provides a natural setting to study OPV community circulation. METHODS In total, 216 children and household contacts in Veracruz, Mexico, were enrolled, and monthly stool samples and questionnaires collected for 1 year; 2501 stool samples underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3. RESULTS OPV was detected up to 7 months after an NIW, but not at 8 months. In total, 35% of samples collected from children vaccinated the prior month, but only 4% of other samples, contained OPV. Although each serotype was detected in similar proportions among OPV strains shed as a result of direct vaccination, 87% of OPV acquired through community spread was serotype 2 (P < .0001). CONCLUSIONS Serotype 2 circulates longer and is transmitted more readily than serotypes 1 or 3 after NIWs in a Mexican community primarily vaccinated with IPV. This may be part of the reason why most isolated cVDPV has been serotype 2.