Miracle-dz/UniFAR-FTUs huggingface dataset:
Synchrotron Microtomography Reveals the Fine Three-Dimensional Porosity of Composite Polysaccharide Aerogels

This study investigates the impact of ice-templating conditions on the morphological features of composite polysaccharide aerogels in relation to their mechanical behavior and aims to get a better insight into the parameters governing these properties. We have prepared polysaccharide aerogels of guar galactomannan (GM) and tamarind seed xyloglucan (XG) by enzymatic oxidation with galactose oxidase (GaO) to form hydrogels, followed by conventional and unidirectional ice-templating (freezing) methods and lyophilization to form aerogels. Composite polysaccharide aerogels were prepared by incorporating nanofibrillated cellulose (NFC) into polysaccharide solutions prior to enzymatic oxidation and gel formation; such a cross linking technique enabled the homogeneous distribution of the NFC reinforcement into the gel matrix. We conducted phase-enhanced synchrotron X-ray microtomography (XMT) scans and visualized the internal microstructure of the aerogels in three-dimensional (3D) space. Volume-weighted pore-size and pore-wall thickness distributions were quantitatively measured and correlated to the aerogels’ mechanical properties regarding ice-templating conditions. Pore-size distribution and orientation depended on the ice-templating methods and the NFC reinforcement that significantly determined the mechanical and shape-recovery behavior of the aerogels. The results obtained will guide the design of the microporous structure of polysaccharide aerogels with optimal morphology and mechanical behavior for life-sciences applications.
Tele-emergency utilization: In what clinical situations is tele-emergency activated?

Introduction Tele-emergency provides audio/visual communication between a central emergency care centre (tele-emergency hub) and a distant emergency department (remote ED) for real-time emergency care consultation. The purpose of this mixed methods study is to examine how often tele-emergency is activated in usual practice and in what circumstances it is used. Methods Tele-emergency log data and merged electronic medical record data from Avera Health (Sioux Falls, SD) were analysed for 60,193 emergency department (ED) encounters presenting over a two-and-a-half year period at 21 critical access hospitals using the tele-emergency service. Of these, tele-emergency was activated for 1512 ED encounters. Results Analyses indicated that patients presenting at rural EDs with circulatory, injury, mental and symptoms diagnoses were significantly more likely to have tele-emergency department services activated as were patients who were transferred to another hospital. Interviews conducted with 85 clinicians and administrators at 26 rural hospitals that used this service indicated that this pattern of utilization facilitated rapid transfers and followed recommended clinical protocols for patients needing serious and/or urgent attention (e.g. stroke symptoms, chest pain). Discussion Although only used in 3.5% of ED encounters on average, our findings provide evidence that tele-emergency activation is well reasoned and related to those situations when extra expert assistance is particularly beneficial.
The Beneficial Effects of Antifreeze Proteins in the Vitrification of Immature Mouse Oocytes

Antifreeze proteins (AFPs) are a class of polypeptides that permit organismal survival in sub-freezing environments. The purpose of this study was to investigate the effect of AFP supplementation on immature mouse oocyte vitrification. Germinal vesicle-stage oocytes were vitrified using a two-step exposure to equilibrium and vitrification solution in the presence or absence of 500 ng/mL of AFP III. After warming, oocyte survival, in vitro maturation, fertilization, and embryonic development up to the blastocyst stage were assessed. Spindle and chromosome morphology, membrane integrity, and the expression levels of several genes were assessed in in vitro matured oocytes. The rate of blastocyst formation was significantly higher and the number of caspase-positive blastomeres was significantly lower in the AFP-treated group compared with the untreated group. The proportion of oocytes with intact spindles/chromosomes and stable membranes was also significantly higher in the AFP group. The AFP group showed increased Mad2, Hook-1, Zar1, Zp1, and Bcl2 expression and lower Eg5, Zp2, Caspase6, and Rbm3 expression compared with the untreated group. Supplementation of the vitrification medium with AFP has a protective effect on immature mouse oocytes, promoting their resistance to chilling injury. AFPs may preserve spindle forming ability and membrane integrity at GV stage. The fertilization and subsequent developmental competence of oocytes may be associated with the modulation of Zar1, Zp1/Zp2, Bcl2, Caspase6, and Rbm3.
Testosterone and prolactin increase carboxypeptidase‐D and nitric oxide levels to promote survival of prostate cancer cells

Plasma‐membrane carboxypeptidase‐D (CPD) releases arginine from extracellular substrates. Arginine is converted intracellularly to nitric oxide (NO). This study determined the effects of testosterone (T) and prolactin (PRL) on CPD expression, and the role(s) of CPD in NO production and survival of prostate cancer (PCa) cells.
A Novel Model-Based Driving Behavior Recognition System Using Motion Sensors

In this article, a novel driving behavior recognition system based on a specific physical model and motion sensory data is developed to promote traffic safety. Based on the theory of rigid body kinematics, we build a specific physical model to reveal the data change rule during the vehicle moving process. In this work, we adopt a nine-axis motion sensor including a three-axis accelerometer, a three-axis gyroscope and a three-axis magnetometer, and apply a Kalman filter for noise elimination and an adaptive time window for data extraction. Based on the feature extraction guided by the built physical model, various classifiers are accomplished to recognize different driving behaviors. Leveraging the system, normal driving behaviors (such as accelerating, braking, lane changing and turning with caution) and aggressive driving behaviors (such as accelerating, braking, lane changing and turning with a sudden) can be classified with a high accuracy of 93.25%. Compared with traditional driving behavior recognition methods using machine learning only, the proposed system possesses a solid theoretical basis, performs better and has good prospects.
Histological changes of kidney in diabetic nephropathy

Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus.
Functional magnetic resonance imaging of cerebellar activation during the learning of a visuomotor dissociation task

We have used functional magnetic resonance imaging (fMRI) to study the changes in cerebellar activation that occur during the acquisition of motor skill in human subjects presented with a new task. The standard paradigm consisted of a center‐out movement in which subjects used a joystick to superimposed a cursor onto viusual targets. Two variations of this paradigm were introduced: (1) a learning paradigm, where the relationship between movement of the joystick and cursor was reversed, requiring the learning of a visuomotor transformation to optimize performance and (2) a random paradigm, where the joystick/cursor relationship was changed randomly for each trial. Activation in the cerebellum was highest during the random paradigm and during the early stages of the learning paradigm. In the early stages of learning and during the random paradigm performance was poor with a decrease in the number of completed movements, and an increase in the time and length of movements. With repeated practice at the learning paradigm performance improbed and reached the same level of proficiency as in the standard task. Commensurate with the improbement in performance was a decrease in cerebellar activation, that is, activation in the cerebellum changed in a parallel, but inverse relationship with performance. Linear regression analysis demonstarated that the inverse correlation between cerebellar activation and motor performance was significant. Repeated practice at the random paradigm did not produce improvements in performance and cerebellar activity remained high. The data support the hypothesis that the cerebellum is strongly activated when motor performance is inaccurate, consistent with a role for the cerebellum in the detection of, and correction for visuomotor errors. © 1996 Wiley‐Liss, Inc.
How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries.

BACKGROUND The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. METHODS Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). RESULTS There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. CONCLUSION In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine model of primary biliary cirrhosis

Collectively, the data in both humans and murine models of human primary biliary cirrhosis (PBC) suggest that activated T cells, particularly CD8 T cells, play a critical role in biliary cell destruction. Under physiological conditions, T‐cell activation involves two critical signals that involve the major histocompatibility complex and a set of costimulatory molecules, which include a receptor on T cells termed cytotoxic T lymphocyte antigen 4 (CTLA‐4). Germane to the studies reported herein, signaling by CTLA‐4 has the potential to modulate costimulation and induce inhibitory signals. In this study, we have taken advantage of our well‐defined murine model of PBC, in which mice are immunized with 2‐octynoic acid coupled to bovine serum albumin (2OA‐BSA), leading to the production of high‐titer antimitochondrial autoantibodies (AMAs) and portal cellular infiltrates. To investigate the potential of CTLA‐4‐Ig (immunoglobulin) as an immunotherapeutic agent, we treated mice both before and after induction of autoimmune cholangitis. First, we demonstrate that CTLA‐4‐Ig treatment, begun 1 day before 2OA‐BSA immunization, completely inhibits the manifestations of cholangitis, including AMA production, intrahepatic T‐cell infiltrates, and bile duct damage. However, and more critically, treatment with CTLA‐4‐Ig, initiated after the development of autoimmune cholangitis in previously immunized mice, also resulted in significant therapeutic benefit, including reduced intrahepatic T‐cell infiltrates and biliary cell damage, although AMA levels were not altered. Conclusion: These data suggest that an optimized regimen with CTLA‐4‐Ig has the potential to serve as an investigative therapeutic tool in patients with PBC. (HEPATOLOGY 2013)
Investigation of metabolic changes in STZ-induced diabetic rats with hyperpolarized [1-13C]acetate

In the metabolism of acetate several enzymes are involved, which play an important role in free fatty acid oxidation. Fatty acid metabolism is altered in diabetes patients and therefore acetate might serve as a marker for pathological changes in the fuel selection of cells, as these changes occur in diabetes patients. Acetylcarnitine is a metabolic product of acetate, which enables its transport into the mitochondria for energy production. This study investigates whether the ratio of acetylcarnitine to acetate, measured by noninvasive hyperpolarized [1‐13C]acetate magnetic resonance spectroscopy, could serve as a marker for myocardial, hepatic, and renal metabolic changes in rats with Streptozotocin (STZ)‐induced diabetes in vivo. We demonstrate that the conversion of acetate to acetylcarnitine could be detected and quantified in all three organs of interest. More interestingly, we found that the hyperpolarized acetylcarnitine to acetate ratio was independent of blood glucose levels and prolonged hyperglycemia following diabetes induction in a type‐1 diabetes model.
Preoperative prediction of the microvascular invasion of hepatocellular carcinoma with diffusion‐weighted imaging

The aim of this study was to investigate whether diffusion‐weighted imaging (DWI) could be useful in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Sixty‐seven surgically proven HCCs from 65 patients (54 men and 11 women with an age range of 35‐75 years and a mean age of 56.0 years) were retrospectively analyzed. The signal intensities (SIs) of the lesions on preoperative diffusion‐weighted (DW) images were visually categorized as isointense or hyperintense in comparison with the adjacent liver. We also quantitatively measured SIs and apparent diffusion coefficients (ADCs) by drawing regions of interest in HCCs and livers on DW images with b values of 50, 400, and 800 second/mm2 and on ADC map images. Logistic regression analyses were performed so that we could identify independent predictors of MVI among laboratory and DWI findings. A univariate analysis showed that a histological grade of 3, a larger tumor size, a higher SI ratio on DW images, and a lower ADC value were significantly associated with MVI. A multiple logistic regression analysis showed that a histological grade of 3 and the ADC value were independent predictors of MVI. With a cutoff of 1.11 × 10−3 mm2/second, the ADC value provided a sensitivity of 93.5% and a specificity of 72.2% for the prediction of MVI with an odds ratio of 24.5 (95% confidence interval = 4.14‐144.8, P < 0.001). In conclusion, lower ADC values (1.11 × 10−3 mm2/second or less) can be a useful predictor of MVI during the preoperative evaluation of HCC. Liver Transpl 18:1171–1178, 2012. © 2012 AASLD.
Evidence for time dependency of molecular rate estimates.

Long-term changes in the genetic composition of a population occur by the fixation of new mutations, a process known as substitution. The rate at which mutations arise in a population and the rate at which they are fixed are expected to be equal under neutral conditions (Kimura, 1968). Between the appearance of a new mutation and its eventual fate of fixation or loss, there will be a period in which it exists as a transient polymorphism in the population (Kimura and Ohta, 1971). If the majority of mutations are deleterious (and nonlethal), the fixation probabilities of these transient polymorphisms are reduced and the mutation rate will exceed the substitution rate (Kimura, 1983). Consequently, different apparent rates may be observed on different time scales of the molecular evolutionary process (Penny, 2005; Penny and Holmes, 2001). The substitution rate of the mitochondrial protein-coding genes of birds and mammals has been traditionally recognized to be about 0.01 substitutions/site/million years (Myr) (Brown et al., 1979; Ho, 2007; Irwin et al., 1991; Shields and Wilson, 1987), with the noncoding D-loop evolving several times more quickly (e.g., Pesole et al., 1992; Quinn, 1992). Over the past decade, there has been mounting evidence that instantaneous mutation rates substantially exceed substitution rates, in a range of organisms (e.g., Denver et al., 2000; Howell et al., 2003; Lambert et al., 2002; Mao et al., 2006; Mumm et al., 1997; Parsons et al., 1997; Santos et al., 2005). The immediate reaction to the first of these findings was that the polymorphisms generated by the elevated mutation rate are short-lived, perhaps extending back only a few hundred years (Gibbons, 1998; Macaulay et al., 1997). That is, purifying selection was thought to remove these polymorphisms very rapidly.
James Mackenzie Lecture 1993. Freedom and discipline: clinical practice and the assessment of clinical competence.

personal skills, and moral and personality attributes. It is in part the ability, in part the will, to select and perform consistently, relevant clinical tasks in the context of the social environment in order to resolve health problems of individuals and groups in an efficient, effective, economic and humane manner. There are two major components of competence. First, the consistent ability to select and perform tasks employing intellec-tual, psychomotor and interpersonal skills, and secondly, the consistent demonstration of appropriate moral and personality attributes. The tasks from which a competent clinician will select are subsumed within the following list of functions:
Increased High-Density Lipoprotein Cholesterol Levels in Mice With XX Versus XY Sex Chromosomes

Objective—The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results—We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions—We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.
Compressive properties of lotus-type porous stainless steel

Lotus-type porous stainless steel (SUS304L), possessing cylindrical pores aligned in one direction, was fabricated by means of a continuous zone melting technique undera pressurized hydrogen/helium atmosphere. Compression tests were carried out on the resultant lotus stainless steel not only in the directions parallel and perpendicular tothe elongated-pore direction but also in other directions to reveal its anisotropic compressive behavior. The macroscopic deformation modes depend on porosity and the angle between the elongated-pore direction and compression direction, which is a unique characteristic resulting from its anisotropic porous structure. The yield stress in the pore direction decreases almost linearly with increasing porosity, while that in the perpendicular direction decreases more rapidly. The yield stress in the direction of θ from the elongated-pore direction decreases monotonically with increase in θ. The yield behavior of lotus stainless steel was described using micromechanical mean-field theory.
Histone H2A Phosphorylation Controls Crb2 Recruitment at DNA Breaks, Maintains Checkpoint Arrest, and Influences DNA Repair in Fission Yeast

ABSTRACT Mammalian ATR and ATM checkpoint kinases modulate chromatin structures near DNA breaks by phosphorylating a serine residue in the carboxy-terminal tail SQE motif of histone H2AX. Histone H2A is similarly regulated in Saccharomyces cerevisiae. The phosphorylated forms of H2AX and H2A, known as γ-H2AX and γ-H2A, are thought to be important for DNA repair, although their evolutionarily conserved roles are unknown. Here, we investigate γ-H2A in the fission yeast Schizosaccharomyces pombe. We show that formation of γ-H2A redundantly requires the ATR/ATM-related kinases Rad3 and Tel1. Mutation of the SQE motif to AQE (H2A-AQE) in the two histone H2A genes caused sensitivity to a wide range of genotoxic agents, increased spontaneous DNA damage, and impaired checkpoint maintenance. The H2A-AQE mutations displayed a striking synergistic interaction with rad22Δ (Rad52 homolog) in ionizing radiation (IR) survival. These phenotypes correlated with defective phosphorylation of the checkpoint proteins Crb2 and Chk1 and a failure to recruit large amounts of Crb2 to damaged DNA. Surprisingly, the H2A-AQE mutations substantially suppressed the IR hypersensitivity of crb2Δ cells by a mechanism that required the RecQ-like DNA helicase Rqh1. We propose that γ-H2A modulates checkpoint and DNA repair through large-scale recruitment of Crb2 to damaged DNA. This function correlates with evidence that γ-H2AX regulates recruitment of several BRCA1 carboxyl terminus domain-containing proteins (NBS1, 53BP1, MDC1/NFBD1, and BRCA1) in mammals.