Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Early Pelvic Binder Use in the Emergency Management of Suspected Pelvic Trauma: A Retrospective Cohort Study

Background: We aimed to evaluate the effect of early pelvic binder use in the emergency management of suspected pelvic trauma, compared with the conventional stepwise approach. Methods: We enrolled trauma patients with initial stabilization using a pelvic binder when suspecting pelvic injury. The inclusion criteria were traumatic injury requiring a trauma team and at least one of the following: a loss of consciousness or a Glasgow coma score (GCS) of <13; systolic blood pressure of <90 mmHg; falling from ≥6 m; injury to multiple vital organs; and suspected pelvic injury. Various parameters, including gender, age, mechanism of injury, GCS, mortality, hospital stay, initial vital signs, revised trauma score, injury severity score, and outcome, were assessed and compared with historical controls. Results: A total of 204 patients with high-energy multiple-trauma from a single level I trauma center in North Taiwan were enrolled in the study from August 2013 to July 2014. The two group baseline patient characteristics were all collected and compared. The trauma patients with suspected pelvic fractures initially stabilized with a pelvic binder had shorter hospital and intensive care unit (ICU) stays. The study group achieved statistically significantly improved survival and lower mean blood transfusion volume and mortality rate, although they were more severe in the trauma score. Conclusions: We recommend prompt pelvic binder use for suspected pelvic injury before definitive imaging is available, as a cervical spine collar is used to protect the cervical spine from further injury prior to definitive identification and characterization of an injury.
The Survival of Spouses Marrying Into Longevity-Enriched Families

Background: Studies of longevity-enriched families are an important tool to gain insight into the mechanisms of exceptionally long and healthy lives. In the Long Life Family Study, the spouses of the members of the longevity-enriched families are often used as a control group. These spouses could be expected to have better health than the background population due to shared family environment with the longevity-enriched family members and due to assortative mating. Methods: A Danish cohort study of 5,363 offspring of long-lived siblings, born 1917–1982, and 4,498 “first spouses” of these offspring. For each offspring and spouse, 10 controls were drawn from a 5% random sample of the Danish population matched on birth year and sex. Mortality was assessed for ages 20–69 years during 1968–2013 based on prospectively collected registry data. Results: During the 45-year follow-up period, 437 offspring deaths and 502 offspring spouse deaths were observed. Compared with the background population, the hazard ratio for male offspring was 0.44 (95% confidence interval [CI]: 0.38–0.50) and for female offspring it was 0.57 (95% CI: 0.49–0.66). For male spouses, the hazard ratio was 0.66 (95% CI: 0.59–0.74), whereas for female spouses it was 0.64 (95% CI: 0.54–0.76). Sensitivity analyses in restricted samples gave similar results. Conclusion: The mortality for ages 20–69 years of spouses marrying into longevity-enriched families is substantially lower than the mortality in the background population, although long-lived siblings participation bias may have contributed to the difference. This finding has implications for the use of spouses as controls in healthy aging and longevity studies, as environmental and/or genetic overmatching may occur.
Transcriptomic Analysis of Ovaries from Pigs with High And Low Litter Size

Litter size is one of the most important economic traits for pig production as it is directly related to the production efficiency. Litter size is affected by interactions between multiple genes and the environment. While recent studies have identified some genes associated with prolificacy in pigs, transcriptomic studies of specific genes affecting litter size in porcine ovaries are rare. In order to identify candidate genes associated with litter size in swine, we assessed gene expression differences between the ovaries of Yorkshire pigs with extremely high and low litter sizes using the RNA-Seq method. A total of 1 243 differentially expressed genes were identified: 897 genes were upregulated and 346 genes were downregulated in high litter size ovary samples compared with low litter size ovary samples. A large number of these genes related to steroid hormone regulation in animal ovaries, including 59 Gene Ontology terms and 27 Kyoto Encyclopedia of Genes and Genomes pathways involved in steroid biosynthesis and ovarian steroidogenesis. From these differentially expressed genes, we identified a total of 11 genes using a bioinformatics screen that may be associated with high litter size in Yorkshire pigs. These results provide a list of new candidate genes for porcine litter size and prolificacy to be further investigated.
Novel Camelid Antibody Fragments Targeting Recombinant Nucleoprotein of Araucaria hantavirus: A Prototype for an Early Diagnosis of Hantavirus Pulmonary Syndrome

In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS) is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS) is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N) to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ85) of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ85. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB), surface plasmon resonance (SPR) device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ85 in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with hantavirus infections.
Neural correlates of emotional action control in anger-prone women with borderline personality disorder.

BACKGROUND Difficulty in controlling emotional impulses is a crucial component of borderline personality disorder (BPD) that often leads to destructive, impulsive behaviours against others. In line with recent findings in aggressive individuals, deficits in prefrontal amygdala coupling during emotional action control may account for these symptoms. METHODS To study the neurobiological correlates of altered emotional action control in individuals with BPD, we asked medication-free, anger-prone, female patients with BPD and age- and intelligence-matched healthy women to take part in an approach-avoidance task while lying in an MRI scanner. The task required controlling fast behavioural tendencies to approach happy and avoid angry faces. Additionally, before the task we collected saliva testosterone and self-reported information on tendencies to act out anger and correlated this with behavioural and functional MRI (fMRI) data. RESULTS We included 30 patients and 28 controls in our analysis. Patients with BPD reported increased tendencies to act out anger and were faster in approaching than avoiding angry faces than with healthy women, suggesting deficits in emotional action control in women with BPD. On a neural level, controlling fast emotional action tendencies was associated with enhanced activation in the antero- and dorsolateral prefrontal cortex across groups. Healthy women showed a negative coupling between the left dorsolateral prefrontal cortex and right amygdala, whereas this was absent in patients with BPD. LIMITATIONS Specificity of results to BPD and sex differences remain unknown owing to the lack of clinical control groups and male participants. CONCLUSION The results indicate reduced lateral prefrontal-amygdala communication during emotional action control in anger-prone women with BPD. The findings provide a possible neural mechanism underlying difficulties with controlling emotional impulses in patients with BPD.
Limited Self-Control, Obesity and the Loss of Happiness

Obesity has become a major health issue. Research in economics has provided important insights as to how technological progress reduced the relative price of food and contributed to the increase in obesity. However, the increased availability of food might well have overstrained will power and led to suboptimal consumption decisions relative to people's own standards. We propose the economics of happiness as an approach to study the phenomenon. Based on proxy measures for experienced utility, it is possible to directly address whether certain observed behavior is suboptimal and therefore reduces a person's well-being. It is found that obesity decreases the well-being of individuals who report limited self-control, but not otherwise.
Deguelin exerts anticancer activity of human gastric cancer MGC-803 and MKN-45 cells in vitro

During the pathogenesis of gastric cancer, Akt signaling is considered as a pivotal inducer of gastric cancer development. Here we report the identification of anticancer activities of deguelin, a natural agent that inhibits Akt signaling. When applied to MGC-803 and MKN-45 cells, deguelin suppressed the proliferation and arrested cell cycle by p21-mediated inhibition of cyclin E. We further present in vitro evidence that deguelin promoted apoptosis of cancer cells by decreasing the phospho-Akt signaling and affecting expression of the apoptosis-associated genes Bax and Bcl-2. Additionally, deguelin was found to suppress the migration and invasion of gastric cancer cells. Taken together, these results indicated that deguelin exerted anticancer activity of human gastric cancer MGC-803 and MKN-45 cells in vitro.
Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer

Hyperpolarized micro-NMR nondestructively analyzes metabolic activities in scant cells. Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or “fluxes” of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials. However, because of their limited sensitivity, these methods require a larger number of cells, on the order of 107, which is impractical for analyzing scant target cells or mass-limited samples. We present a new technology platform, a hyperpolarized micromagnetic resonance spectrometer (HMRS), that achieves real-time, 103-fold more sensitive metabolic analysis on live cells. This platform enables quantification of the metabolic flux in a wide range of cell types, including leukemia stem cells, without significant changes in viability, which allows downstream molecular analyses in tandem. It also enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients. We further advanced this platform for high-throughput analysis of hyperpolarized molecules by integrating a three-dimensionally printed microfluidic system. The HMRS platform holds promise as a sensitive method for studying metabolic dynamics in mass-limited samples, including primary cancer cells, providing novel therapeutic targets and an enhanced understanding of cellular metabolism.
Role of Actin Filaments in Correlating Nuclear Shape and Cell Spreading

It is well known that substrate properties like stiffness and adhesivity influence stem cell morphology and differentiation. Recent experiments show that cell morphology influences nuclear geometry and hence gene expression profile. The mechanism by which surface properties regulate cell and nuclear properties is only beginning to be understood. Direct transmission of forces as well as chemical signalling are involved in this process. Here, we investigate the formal aspect by studying the correlation between cell spreading and nuclear deformation using Mesenchymal stem cells under a wide variety of conditions. It is observed that a robust quantitative relation holds between the cell and nuclear projected areas, irrespective of how the cell area is modified or when various cytoskeletal or nuclear components are perturbed. By studying the role of actin stress fibers in compressing the nucleus we propose that nuclear compression by stress fibers can lead to enhanced cell spreading due to an interplay between elastic and adhesion factors. The significance of myosin-II in regulating this process is also explored. We demonstrate this effect using a simple technique to apply external compressive loads on the nucleus.
Words Get in the Way: Linguistic Effects on Talker Discrimination

A speech perception experiment provides evidence that the linguistic relationship between words affects the discrimination of their talkers. Listeners discriminated two talkers' voices with various linguistic relationships between their spoken words. Listeners were asked whether two words were spoken by the same person or not. Word pairs varied with respect to the linguistic relationship between the component words, forming either: phonological rhymes, lexical compounds, reversed compounds, or unrelated pairs. The degree of linguistic relationship between the words affected talker discrimination in a graded fashion, revealing biases listeners have regarding the nature of words and the talkers that speak them. These results indicate that listeners expect a talker's words to be linguistically related, and more generally, indexical processing is affected by linguistic information in a top-down fashion even when listeners are not told to attend to it.
Accurate model annotation of a near-atomic resolution cryo-EM map

Significance Electron cryomicroscopy is a rapidly growing field for macromolecular structure determination. We establish a computational protocol to construct a de novo atomic model from a cryo-EM density map, along with associated metadata that describe coordinate uncertainty and the density at each atom. This model faithfully replicates experimental map densities, as evidenced by cross-correlation and other metrics. Our method of annotation will be especially informative for macromolecular assemblies that exhibit resolvability variations in different parts of their structure. This procedure was applied to a 3.3-Å-resolution structure of the P22 bacteriophage to delineate interactions that stabilize the neighboring subunits in a T = 7 icosahedral capsid. Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atoms nor their positional uncertainty. Here, we introduce a computational procedure to derive an atomic model from a cryo-EM map with annotated metadata. The accuracy of such a model is validated by a faithful replication of the experimental cryo-EM map computed using the coordinates and associated metadata. The functional interpretation of any structural features in the model and its utilization for future studies can be made in the context of its measure of uncertainty. We applied this protocol to the 3.3-Å map of the mature P22 bacteriophage capsid, a large and complex macromolecular assembly. With this protocol, we identify and annotate previously undescribed molecular interactions between capsid subunits that are crucial to maintain stability in the absence of cementing proteins or cross-linking, as occur in other bacteriophages.
Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

The complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological functions. Here we use new evolutionary models to infer gene family histories across complete yeast genomes; these models allow us to estimate the relative genome-wide rates of gene birth, death, innovation and extinction (loss of an entire family) for the first time. We show that the rates of gene family evolution vary both between gene families and between species. We are also able to identify those families that have experienced rapid lineage specific expansion/contraction and show that these families are enriched for specific functions. Moreover, we find that families with specific functions are repeatedly expanded in multiple species, suggesting the presence of common adaptations and that these family expansions/contractions are not random. Additionally, we identify potential specialisations, unique to specific species, in the functions of lineage specific expanded families. These results suggest that an important mechanism in the evolution of genome content is the presence of lineage-specific gene family changes.
Spatiotemporal Dynamics of Vibrio cholerae in Turbid Alkaline Lakes as Determined by Quantitative PCR

ABSTRACT In recent years, global warming has led to a growing number of Vibrio cholerae infections in bathing water users in regions formerly unaffected by this pathogen. It is therefore of high importance to monitor V. cholerae in aquatic environments and to elucidate the main factors governing its prevalence and abundance. For this purpose, rapid and standardizable methods that can be performed by routine water laboratories are prerequisite. In this study, we applied a recently developed multiplex quantitative PCR (qPCR) strategy (i) to monitor the spatiotemporal variability of V. cholerae abundance in two small soda pools and a large lake that is intensively used for recreation and (ii) to elucidate the main factors driving V. cholerae dynamics in these environments. V. cholerae was detected with qPCR at high concentrations of up to 970,000 genomic units 100 ml−1 during the warm season, up to 2 orders of magnitude higher than values obtained by cultivation. An independent cytometric approach led to results comparable to qPCR data but with significantly more positive samples due to problems with DNA recovery for qPCR. Not a single sample was positive for toxigenic V. cholerae, indicating that only nontoxigenic V. cholerae (NTVC) was present. Temperature was the main predictor of NTVC abundance, but the quality and quantity of dissolved organic matter were also important environmental correlates. Based on this study, we recommend using the developed qPCR strategy for quantification of toxigenic and nontoxigenic V. cholerae in bathing waters with the need for improvements in DNA recovery. IMPORTANCE There is a definitive need for rapid and standardizable methods to quantify waterborne bacterial pathogens. Such methods have to be thoroughly tested for their applicability to environmental samples. In this study, we critically tested a recently developed multiplex qPCR strategy for its applicability to determine the spatiotemporal variability of V. cholerae abundance in lakes with a challenging water matrix. Several qPCR protocols for V. cholerae detection have been developed in the laboratory, but comprehensive studies on the application to environmental samples are extremely scarce. In our study, we demonstrate that our developed qPCR approach is a valuable tool but that there is a need for improvement in DNA recovery for complex water matrices. Furthermore, we found that nontoxigenic V. cholerae is present in very high numbers in the investigated ecosystems, while toxigenic V. cholerae is apparently absent. Such information is of importance for public health.
Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092

As a critical component in the PI3K/AKT/mTOR pathway, AKT has become an attractive target for therapeutic intervention. ARQ 092 and a next generation AKT inhibitor, ARQ 751 are selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors that potently inhibit phosphorylation of AKT. Biochemical and cellular analysis showed that ARQ 092 and ARQ 751 inhibited AKT activation not only by dephosphorylating the membrane-associated active form, but also by preventing the inactive form from localizing into plasma membrane. In endometrial PDX models harboring mutant AKT1-E17K and other tumor models with an activated AKT pathway, both compounds exhibited strong anti-tumor activity. Combination studies conducted in in vivo breast tumor models demonstrated that ARQ 092 enhanced tumor inhibition of a common chemotherapeutic agent (paclitaxel). In a large panel of diverse cancer cell lines, ARQ 092 and ARQ 751 inhibited proliferation across multiple tumor types but were most potent in leukemia, breast, endometrial, and colorectal cancer cell lines. Moreover, inhibition by ARQ 092 and ARQ 751 was more prevalent in cancer cell lines containing PIK3CA/PIK3R1 mutations compared to those with wt-PIK3CA/PIK3R1 or PTEN mutations. For both ARQ 092 and ARQ 751, PIK3CA/PIK3R1 and AKT1-E17K mutations can potentially be used as predictive biomarkers for patient selection in clinical studies.
Effects of Winding Angles on the Strength of Filament Wound Composite Tubes Subjected to Different Loading Modes

Filament wound pipes constructed from a corrosion resistant epoxy resin and E-glass filament fiber wound at nine different wind angles were tested. Experimental data are presented to show the effects of winding angle on the strength of 46.05 mm diameter tube and 300 mm length under three different loading modes. The pipes were tested to failure under hoop pressure loading (mode I) biaxial pressure loading (mode II), and biaxial pressure with axial compressive loading (mode III). Stress/strain response up to fracture for three different winding angles under different loading modes were obtained. The test results show the effect of the winding angle on elastic constants and on non linear stress strain behaviour. The test results also show that the optimum winding angles for filament wounded pipes depend on the loading modes applied. It shows that for loading mode I the filament wound pipe should be wound at 55°, for loading mode II the filament wound pipe should be wound at 75°, while for loading mode III the filament wound pipe should be wound at 85°.