Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial

Importance Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality. Design, Setting, and Participants Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality. Trial Registration ClinicalTrials.gov Identifier: NCT03078712
Relationship between leader–member exchange and construction worker safety behavior: the mediating role of communication competence

Purpose. Leader–member exchange (LMX) has widely been adopted to explore its influence on job performance. However, most previous studies considered LMX as a unidimensional construct and neglected the effects of its subdimensions, thereby reducing its practicality to improve work performance. This study empirically tested the relationship between subdimensions of LMX and safety behaviors, while incorporating communication competence as a mediator. Method. Data were collected from Chinese construction industry workers. The theoretical model was built and checked using the structural equation modeling technique. Results. The affect and contribution dimensions of LMX positively associated with safety behaviors, while the loyalty and professional respect dimensions had negative and no relations with safety behaviors respectively. These findings demonstrate that a multidimensional view on LMX should be taken while checking its effects on safety behaviors. The affect and professional respect dimensions of LMX had indirect effects on safety participation via communication competence, which illustrate the mediating role of communication competence for construction safety. This study sheds lights on safety behavior research based on the theories of LMX. Enhancing the leadership and communication skills of safety staff and fostering a supportive safety atmosphere at sites are suggested to improve construction safety performance.
Psychiatric outcome at least 20 years after trauma: A survey on the status of subjective general health and psychiatric symptoms with a focus on posttraumatic stress disorder.

BACKGROUND Information on long-term psychiatric sequelae after severe trauma is sparse. We therefore performed a survey addressing several symptoms related to post traumatic stress disorder (PTSD) in patients that sustained multiple injuries more than 20 years after trauma. METHODS Patients injured between January 1, 1973 and December 31, 1990 were contacted at least 20 years later. We included multiply injured patients aged between 3 and 60 years of age from a single level I Trauma center. A questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria for PTSD, including individual symptoms related to intrusion, avoidance, and hyperarousal was sent to all patients. RESULTS 359 (56.35%) patients received a questionnaire. Out of these, 337 (93.87%) returned the questionnaire and were included in the study (223 males (66.17%) and 114 females (33.82%)). Mean follow-up was 29.5 ± 8.5 years. Nearly half the study population (47.18%) experienced lasting psychiatric sequelae, such as intrusive recollection (n= 65, 19.28%), avoidance (n= 92, 27.29%), or hyperarousal (n=95, 28.18%) at least monthly. Ten patients (2.96%) fulfilled all DSM-IV diagnostic criteria for PTSD. A total of 131 (38.87%) patients reported fair or poor general health status. There was no difference in injury severity in patients with or without PTSD (Injury Severity Score (ISS) 18.33 vs. 20.36, respectively, p = 0.52) or PTSD-related symptoms including intrusion (19.88 vs. 20.32, p=0.74), avoidance (19.99 vs. 20.3, p=0.79) and hyperarousal (19.36 vs. 20.68, p=0.26). CONCLUSION At least 20 years after injury, no correlation was found between the development of psychiatric complications and the severity of injury. While the rate of full-blown PTSD was low, nearly half the study population regularly suffered from at least one psychiatric symptom attributable to the initial trauma. Awareness for the development of psychiatric complications and early initiation of psychiatric counseling is advisable. LEVEL OF EVIDENCE Level II, Prognostic and Epidemiologic.
The Old and the New: Discovery Proteomics Identifies Putative Novel Seminal Fluid Proteins in Drosophila*

We used discovery, bottom up proteomics to provide the first in-depth accessory gland proteome in D. pseudoobscura,. Computational bioinformatics identified >500 proteins in the secretory pathway of which 163 were annotated as extracellular. , and therefore candidate, seminal fluid proteins. We further compared molecular rates of evolution between intra- and extra-cellular proteins, showing a hierarchy of rapid evolution with putative seminal fluid proteins evolving more rapidly than other secreted proteins, and those proteins evolving more rapidly than intra-cellular proteins. Graphical Abstract Highlights First deep proteomic coverage of an accessory gland proteome in Drosophila. Discovery proteomics identified >3000 proteins of the D. pseudoobscura, accessory gland proteome. Identified 132 putative novel seminal fluid proteins in this species. Demonstrated the exoproteome as the most rapidly evolving subcellular component of the proteome. Seminal fluid proteins (SFPs), the nonsperm component of male ejaculates produced by male accessory glands, are viewed as central mediators of reproductive fitness. SFPs effect both male and female post-mating functions and show molecular signatures of rapid adaptive evolution. Although Drosophila melanogaster, is the dominant insect model for understanding SFP evolution, understanding of SFP evolutionary causes and consequences require additional comparative analyses of close and distantly related taxa. Although SFP identification was historically challenging, advances in label-free quantitative proteomics expands the scope of studying other systems to further advance the field. Focused studies of SFPs has so far overlooked the proteomes of male reproductive glands and their inherent complex protein networks for which there is little information on the overall signals of molecular evolution. Here we applied label-free quantitative proteomics to identify the accessory gland proteome and secretome in Drosophila pseudoobscura,, a close relative of D. melanogaster,, and use the dataset to identify both known and putative novel SFPs. Using this approach, we identified 163 putative SFPs, 32% of which overlapped with previously identified D. melanogaster, SFPs and show that SFPs with known extracellular annotation evolve more rapidly than other proteins produced by or contained within the accessory gland. Our results will further the understanding of the evolution of SFPs and the underlying male accessory gland proteins that mediate reproductive fitness of the sexes.
Experimental Analysis on the Influence and Optimization of μ-RUM Parameters in Machining Alumina Bioceramic

Fabrication of precise micro-features in bioceramic materials is still a challenging task. This is because of the inherent properties of bioceramics, such as low fracture toughness, high hardness, and brittleness. This paper places an emphasis on investigating the multi-objective optimization of fabrication of microchannels in alumina (Al2O3) bioceramics by using rotary ultrasonic machining (RUM). The influence of five major input parameters, namely vibration frequency, vibration amplitude, spindle speed, depth of cut, and feed rate on the surface quality, edge chipping, and dimensional accuracy of the milled microchannels was analyzed. Surface morphology and microstructure of the machined microchannels were also evaluated and analyzed. Unlike in previous studies, the effect of vibration frequency on the surface morphology and roughness is discussed in detail. A set of designed experiments based on central composite design (CCD) method was carried out. Main effect plots and surface plots were analyzed to detect the significance of RUM input parameters on the outputs. Later, a multi-objective genetic algorithm (MOGA) was employed to determine the optimal parametric conditions for minimizing the surface roughness, edge chipping, and dimensional errors of the machined microchannels. The optimized values of the surface roughness (Ra and Rt), side edge chipping (SEC), bed edge chipping (BEC), depth error (DE), and width error (WE) achieved through the multi-objective optimization were 0.27 μm, 2.7 μm, 8.7 μm, 8 μm, 5%, and 5.2%, respectively.
Metalearners for estimating heterogeneous treatment effects using machine learning

Significance Estimating and analyzing heterogeneous treatment effects is timely, yet challenging. We introduce a unifying framework for many conditional average treatment effect estimators, and we propose a metalearner, the X-learner, which can adapt to structural properties, such as the smoothness and sparsity of the underlying treatment effect. We present its favorable properties, using theory and simulations. We apply it, using random forests, to two field experiments in political science, where it is shown to be easy to use and to produce results that are interpretable. There is growing interest in estimating and analyzing heterogeneous treatment effects in experimental and observational studies. We describe a number of metaalgorithms that can take advantage of any supervised learning or regression method in machine learning and statistics to estimate the conditional average treatment effect (CATE) function. Metaalgorithms build on base algorithms—such as random forests (RFs), Bayesian additive regression trees (BARTs), or neural networks—to estimate the CATE, a function that the base algorithms are not designed to estimate directly. We introduce a metaalgorithm, the X-learner, that is provably efficient when the number of units in one treatment group is much larger than in the other and can exploit structural properties of the CATE function. For example, if the CATE function is linear and the response functions in treatment and control are Lipschitz-continuous, the X-learner can still achieve the parametric rate under regularity conditions. We then introduce versions of the X-learner that use RF and BART as base learners. In extensive simulation studies, the X-learner performs favorably, although none of the metalearners is uniformly the best. In two persuasion field experiments from political science, we demonstrate how our X-learner can be used to target treatment regimes and to shed light on underlying mechanisms. A software package is provided that implements our methods.
Perfusion weighted imaging using combined gradient/spin echo EPIK: Brain tumour applications in hybrid MR‐PET

Advanced perfusion‐weighted imaging (PWI) methods that combine gradient echo (GE) and spin echo (SE) data are important tools for the study of brain tumours. In PWI, single‐shot, EPI‐based methods have been widely used due to their relatively high imaging speed. However, when used with increasing spatial resolution, single‐shot EPI methods often show limitations in whole‐brain coverage for multi‐contrast applications. To overcome this limitation, this work employs a new version of EPI with keyhole (EPIK) to provide five echoes: two with GEs, two with mixed GESE and one with SE; the sequence is termed “GESE‐EPIK. ” The performance of GESE‐EPIK is evaluated against its nearest relative, EPI, in terms of the temporal signal‐to‐noise ratio (tSNR). Here, data from brain tumour patients were acquired using a hybrid 3T MR‐BrainPET scanner.
Reaching HbA1c Goals with Saxagliptin in Combination with Other Oral Antidiabetic Drugs

Abstract A large percentage of individuals with type 2 diabetes in the United States are not reaching their glycemic goals. In response to data from large outcomes trials and newer classes of therapeutic agents, various organizations and opinion-forming bodies recently updated their clinical practice recommendations for type 2 diabetes. The recommendations, as set by the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD), the American Association of Clinical Endocrinologists/American College of Endocrinology, and the Canadian Diabetes Association, are similar in their emphasis on lifestyle modification and the importance of treating fasting and postprandial glucose, both of which are significant contributors to achieving glycated hemoglobin (HbA1c) targets. However, the recommendations differ in focus, depth, and specific treatment approaches. With the exception of the ADA/EASD consensus, dipeptidyl peptidase-4 (DPP-4) inhibitors have been included as alternative first- or second-line therapy due, in part, to their glucose-dependent mechanism of action that complements the actions of other oral antidiabetic drugs (OADs). The DPP-4 inhibitor, saxagliptin, demonstrates significant glycemia-lowering effects as monotherapy and in combination therapy, is weight neutral and well tolerated, and has a low risk of hypoglycemia. The added efficacy of saxagliptin in combination with other OADs in improving glycemic parameters has resulted in a significant proportion of patients achieving an HbA1c < 7% versus monotherapy or active comparator. Combination therapy with saxagliptin can thus offer a potential advantage in achieving glycemic goals for the majority of patients with type 2 diabetes without additional tolerability concerns.
Unraveling the Thermal Isomerization Mechanisms of Heteroaryl Azoswitches: Phenylazoindoles as Case Study

The research on heteroaromatic azoswitches has been blossoming in recent years due to their astonishingly broad range of properties. Minimal chemical modifications can drastically change the demeanor of these switches, regarding photophysical and (photo)chemical properties, promoting them as ideal scaffolds for a vast variety of applications based on bistable light-addressable systems. However, most of the characteristics exhibited by heteroaryl azoswitches were found empirically, and only a few works focus on their rationalization. Herein we report on a mechanistic study employing phenylazoindoles as a model reference, combining spectroscopic experiments with comprehensive computational analysis. This approach will elucidate the intrinsic correlations between the molecular structure of the switch and its thermal behavior, allowing a more rational design transferable to various heteroaryl azoswitches.
Targeting autophagy using natural compounds for cancer prevention and therapy

Autophagy, also known as macroautophagy, is a tightly regulated process involved in the stress responses, such as starvation. It is a vacuolar, lysosomal pathway for the degradation of damaged proteins and organelles in eukaryotic cells. Autophagy also plays a key role in various tissue processes and immune responses and in the regulation of inflammation. Over the past decade, three levels of autophagy regulation have been identified in mammalian cells: 1) signaling, 2) autophagosome formation, and 3) autophagosome maturation and lysosomal degradation. Any deregulation of the autophagy processes can lead to the development of diverse chronic diseases, such as diabetes, obesity, cardiovascular disease, neurodegenerative disease, and malignancies. However, the potential role of autophagy in cancer is rather complex and has been associated with both the induction and the inhibition of neoplasia. Several synthetic autophagy modulators have been identified as promising candidates for cancer therapy. In addition, diverse phytochemicals derived from natural sources, such as curcumin, ursolic acid, resveratrol, thymoquinone, and γ‐tocotrienol, also have attracted attention as promising autophagy modulators with minimal side effects. In this review, the authors discuss the importance of autophagy regulators and various natural compounds that induce and/or inhibit autophagy in the prevention and therapy of cancer.
Self-Care Strategies for Professional Development: Transcendental Meditation Reduces Compassion Fatigue and Improves Resilience for Nurses

The Transcendental Meditation technique was provided to 27 nurses across levels and areas of the organization. Quantitative tools measured the effect on nurses' compassion fatigue and resilience. Paired-sample t test analyses revealed significant improvements in the phenomena studied. Further, resilience showed a large significant, inverse relationship with burnout. This study contributes new knowledge for an innovative self-care strategy to improve resilience and reduce compassion fatigue and burnout among nurses.
Prospective serum metabolomic profiling of lethal prostate cancer

Impaired metabolism may play an important role in the pathogenesis of lethal prostate cancer, yet there is a paucity of evidence regarding the association. We conducted a large prospective serum metabolomic analysis of lethal prostate cancer in 523 cases and 523 matched controls nested within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (maximum 30 years). We identified 860 known biochemicals through an ultrahigh‐performance LC–MS/MS platform. Conditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals of risk associated with 1‐standard deviation (s.d.) increases in log‐metabolite signals. We identified 34 metabolites associated with lethal prostate cancer with a false discovery rate (FDR) < 0.15. Notably, higher serum thioproline, and thioproline combined with two other cysteine‐related amino acids and redox metabolites, cystine and cysteine, were associated with reduced risk (1‐s.d. OR = 0.75 and 0.71, respectively; p ≤ 8.2 × 10−5). By contrast, the dipeptide leucylglycine (OR = 1.36, p = 8.2 × 10−5), and three gamma‐glutamyl amino acids (OR = 1.28–1.30, p ≤ 4.6 × 10−4) were associated with increased risk of lethal prostate cancer. Cases with metastatic disease at diagnosis (n = 179) showed elevated risk for several lipids, including especially the ketone body 3‐hydroxybutyrate (BHBA), acyl carnitines, and dicarboxylic fatty acids (1.37 ≤ OR ≤ 1.49, FDR < 0.15). These findings provide a prospective metabolomic profile of lethal prostate cancer characterized by altered biochemicals in the redox, dipeptide, pyrimidine, and gamma‐glutamyl amino acid pathways, whereas ketone bodies and fatty acids were associated specifically with metastatic disease.
Form and function of F-actin during biomineralization revealed from live experiments on foraminifera

Significance Unicellular organisms form endless variability of complex skeletons that serve as archives of Earth’s history and play a crucial role in global geochemical cycles. A longstanding question is how single cells control morphogenesis and mineralization of skeletal structures. Although already addressed by Sir D’Arcy W. Thompson, this problem is still unsolved. Shell emerges from a controlled cascade of interactions at different levels of cellular organization. To gain insight into its morphogenesis, we apply live fluorescent imaging to observe cytoskeleton structures during shell formation in foraminifera. Our live experiments on calcifying foraminiferal chambers show that dynamic F-actin structures are involved in shaping and controlling mineralization. Although the emergence of complex biomineralized forms has been investigated for over a century, still little is known on how single cells control morphology of skeletal structures, such as frustules, shells, spicules, or scales. We have run experiments on the shell formation in foraminifera, unicellular, mainly marine organisms that can build shells by successive additions of chambers. We used live imaging to discover that all stages of chamber/shell formation are controlled by dedicated actin-driven pseudopodial structures. Successive reorganization of an F-actin meshwork, associated with microtubular structures, is actively involved in formation of protective envelope, followed by dynamic scaffolding of chamber morphology. Then lamellar dynamic templates create a confined space and control mineralization separated from seawater. These observations exclude extracellular calcification assumed in selected foraminiferal clades, and instead suggest a semiintracellular biomineralization pattern known from other unicellular calcifying and silicifying organisms. These results give a challenging prospect to decipher the vital effect on geochemical proxies applied to paleoceanographic reconstructions. They have further implications for understanding multiscale complexity of biomineralization and show a prospect for material science applications.