Miracle-dz/UniFAR-FTUs huggingface dataset:
FKBP25 regulates myoblast viability and migration and is differentially expressed in in vivo models of muscle adaptation

FKBP25 (FKBP3 gene) is a dual‐domain PPIase protein that consists of a C‐terminal PPIase domain and an N‐terminal basic tilted helix bundle (BTHB). The PPIase domain of FKBP25 has been shown to bind to microtubules, which has impacts upon microtubule polymerisation and cell cycle progression. Using quantitative proteomics, it was recently found that FKBP25 was expressed in the top 10% of the mouse skeletal muscle proteome. However, to date there have been few studies investigating the role of FKBP25 in non‐transformed systems. As such, this study aimed to investigate potential roles for FKBP25 in myoblast viability, migration and differentiation and in adaptation of mature skeletal muscle. Doxycycline‐inducible FKBP25 knockdown in C2C12 myoblasts revealed an increase in cell accumulation/viability and migration in vitro that was independent of alterations in tubulin dynamics; however, FKBP25 knockdown had no discernible impact on myoblast differentiation into myotubes. Finally, a series of in vivo models of muscle adaptation were assessed, where it was observed that FKBP25 protein expression was increased in hypertrophy and regeneration conditions (chronic mechanical overload and the mdx model of Duchenne muscular dystrophy) but decreased in an atrophy model (denervation). Overall, the findings of this study establish FKBP25 as a regulator of myoblast viability and migration, with possible implications for satellite cell proliferation and migration and muscle regeneration, and as a potential regulator of in vivo skeletal muscle adaptation.
The incidence of physeal fractures in the lower limb and the frequency of premature physeal closure: a cohort study of 236 patients

Background and purpose Physeal fractures represent 15–20% of all pediatric fractures and may lead to premature physeal closure (PPC). The aim of our study was to determine the incidence rates of physeal fractures in the lower limb and the proportion of PPC that lead to limb length discrepancy (LLD), and/or angular deformity (AD). Patients and methods This retrospective study included 236 consecutive children with physeal fracture in the tibia, distal femur, or distal fibula. We estimated incidence rates and reviewed medical records and radiographs to obtain information regarding the development of PPC leading to LLD and AD. Of the 236 children, 100 had planned growth control or were referred for growth control due to symptoms of PPC. Results The total incidence rate was 35 (95% CI 30–39) per 100,000 person-years, with 1.2 (CI 0.5–23) for distal femur, 5.7 (CI 3.1–7.8) for proximal tibia, 14 (CI 11–17) for distal tibia, and 14 (CI 11–17) for distal fibula. The overall prevalence of PPC was 9.7% (CI 6.3–14), while the prevalence was 38% (CI 8.5–76) for distal femur, 15% (CI 5.9–31) for proximal tibia, 14% (CI 7.4-–22) for distal tibia, and 1.1% (CI 0.3-–59) for distal fibula. We found a significant higher hazard of PPC in fractures with ≥ 3 mm displacement (hazard ratio: 12, CI 1.5–97). Conclusion 10% of children with physeal fractures developed PPC that led to LLD or AD. The highest hazard ratio was in children who had an initial fracture displacement. This study highlights the importance of routine and uniform growth evaluation after a physeal fracture.
Prayer and Mental Health in Later Life: The Role of Positive Emotions

Abstract Prayer is used as a coping resource to mitigate the adverse influences of stressful life situations on mental health. However, the mechanisms underlying its impact on mental health in later life still need to be better understood. In particular, scant research attention has been paid to the significance of prayer in enhancing positive emotions (e.g. compassionate love), which can lead to improved mental health. Using data from our nationwide web-based survey (n = 1,861), we evaluated if compassionate love mediates the relationship between prayer and mental health. Our findings suggest participants who prayed had significantly higher feelings of being loved (b = .19, p < .001) and lower depressive symptoms. Compassionate love significantly mediated prayer’s effect on depressive symptoms (b = −0.40, p < .001) and anxiety (b = −0.19, p < .001). Our findings highlight the importance of prayer in enhancing positive emotions and well-being in later life.
Retrospective cohort analysis of weight changes during the COVID-19 pandemic in a pediatric asthma population

Abstract Objective To investigate the BMI trajectories of children attending a tertiary asthma clinic during the COVID-19 pandemic. Methods Data were collected retrospectively on children and young people with asthma who attended the Royal Hospital for Children and Young People (RHCYP) before March 2020 (pre-COVID-19) and after August 2021 (the lifting of national restrictions). Main outcome measures Changes in weight, height, and BMI Z score measured between 13/03/2019 and 13/03/2020 (timepoint 1) and then again during the period 01/08/2021 to 01/10/2022 (timepoint 2); changes in lung function parameters (FEV1) between the timepoints; proportion of study sample classed as obese and overweight at both timepoints; interaction analyses according to deprivation indices (SIMD decile), the use of high dose inhaled corticosteroid (ICS) therapy, and the presence of atopy. Results Eighty-nine children aged 5–18 years were studied. Weight and height Z scores significantly increased between timepoint 1 and 2 [weight Z score: +0.19 (0.08, +0.30), height Z score: +0.15 (+0.07, +0.23)], such that no significant change was observed in the BMI Z score [+ 0.07 (−0.05, +0.20)] or BMI centile [+0.5 (−3.1, +4.1)]. There was also no change in FEV1%predicted [−0.1 (−3.8, +3.6)] between the timepoints. Conclusions No changes in BMI were observed in children with asthma before and after COVID-19 lockdowns. Improved linear growth was noted, implying an improvement in the overall physical health of our study cohort. This may suggest improved asthma control, which may reflect avoidance of viral triggers and/or improved adherence to treatment.
Inhibition of GPIb-α-mediated apoptosis signaling enables cold storage of platelets

Cold storage of platelets has been suggested as an alternative approach to reduce the risk of bacterial contamination and to improve the cell quality as well as functionality compared to room temperature storage. However, cold-stored platelets (CSP) are rapidly cleared from the circulation. Among several possible mechanisms, apoptosis has been recently proposed to be responsible for the short half-life of refrigerated platelets. In the present study, we investigated the impact of apoptosis inhibition on the hemostatic functions and survival of CSP. We found that blocking the transduction of the apoptotic signal induced by glycoprotein Ib (GPIb)-α clustering or the activation of caspase 9 does not impair CSP functionality. In fact, the inhibition of GPIb-α clustering mediated-apoptotic signal by a RhoA inhibitor better conserved δ granule release, platelet aggregation, adhesion and the ability to form stable clots, compared to untreated CSP. In contrast, upregulation of the protein kinase A caused a drastic impairment of platelet functions and whole blood clot stability. More importantly, we observed a significant improvement of the half-life of CSP upon inhibition of the intracellular signal induced by GPIb-α clustering. In conclusion, our study provides novel insights on the in vitro hemostatic functions and half-life of CSP upon inhibition of the intracellular cold-induced apoptotic pathway. Our data suggest that the combination of cold storage and apoptosis inhibition might be a promising strategy to prolong the storage time without impairing hemostatic functions or survival of refrigerated platelets.
Effect of common sedation agents on feline splenic size determined via ultrasonography

ABSTRACT Aims To evaluate the effect of IM administration of three sedative drugs, acepromazine, alfaxalone and dexmedetomidine, in combination with morphine, on the size of the feline spleen using ultrasonography. Methods Twenty-four client-owned cats undergoing elective de-sexing or minor procedures were recruited for a focused ultrasonographic examination of the spleen prior to and at 10, 20 and 30 minutes following administration of one of three randomly assigned IM sedation protocols: 0.05 mg/kg acepromazine (ACE group), 3 mg/kg alfaxalone (ALF group), or 10 μg/kg dexmedetomidine (DEX group), in combination with 0.5 mg/kg morphine. B-mode images of the spleen were collected and measured following a standardised protocol. Cardiorespiratory parameters and sedation score were also recorded. Mean thickness of the head, body and tail of the spleen for each group at 10, 20 and 30 minutes after drug administration was compared to baseline. Results Mean splenic thickness increased over time in the ACE group (thickness of body at T0 = 8.9 (SE 2.1) mm and at T30 = 10.5 (SE 2.0) mm; p = 0.001) and the ALF group (thickness of body at T0 = 8.8 (SE 1.0) mm and at T30 = 10.3 (SE 1.7) mm; p = 0.022) but not in the DEX group (thickness of body at T0 = 8.6 mm (1.2) and at T30 = 8.9 mm (0.6); p = 0.67). Mean arterial blood pressure in the DEX group was significantly higher than in the other groups (p = 0.002). Sedation scores in the DEX group were consistently high for the entire period. However, the sedation score in the ACE group increased over 30 minutes (p = 0.007). Sedation score in the ALF group was highest at 10 minutes but gradually decreased over the following 20 minutes (p = 0.003). Conclusions Sedation with IM dexmedetomidine and morphine did not change splenic size, whereas acepromazine or alfaxalone and morphine increased it regardless of the degree of sedation. Clinical relevance Where splenomegaly is identified in a cat sedated with acepromazine or alfaxalone, the effects of the sedation protocol could be considered as a possible cause.
Formation of structures around HII regions: ionization feedback from massive stars

Abstract We present a new model for the formation of dense clumps and pillars around HII regions based on shocks curvature at the interface between a HII region and a molecular cloud. UV radiation leads to the formation of an ionization front and of a shock ahead. The gas is compressed between them forming a dense shell at the interface. This shell may be curved due to initial interface or density modulation caused by the turbulence of the molecular cloud. Low curvature leads to instabilities in the shell that form dense clumps while sufficiently curved shells collapse on itself to form pillars. When turbulence is high compared to the ionized-gas pressure, bubbles of cold gas have sufficient kinetic energy to penetrate into the HII region and detach themselves from the parent cloud, forming cometary globules. Using computational simulations, we show that these new models are extremely efficient to form dense clumps and stable and growing elongated structures, pillars, in which star formation might occur (see Tremblin et al.2012a). The inclusion of turbulence in the model shows its importance in the formation of cometary globules (see Tremblin et al.2012b). Globally, the density enhancement in the simulations is of one or two orders of magnitude higher than the density enhancement of the classical “collect and collapse“ scenario. The code used for the simulation is the HERACLES code, that comprises hydrodynamics with various equation of state, radiative transfer, gravity, cooling and heating. Our recent observations with Herschel (see Schneider et al.2012a) and SOFIA (see Schneider et al.2012b) and additional Spitzer data archives revealed many more of these structures in regions where OB stars have already formed such as the Rosette Nebula, Cygnus X, M16 and Vela, suggesting that the UV radiation from massive stars plays an important role in their formation. We present a first comparison between the simulations described above and recent observations of these regions.
Somatic loss of ATM is a late event in pancreatic tumorigenesis

Understanding the timing and spectrum of genetic alterations that contribute to the development of pancreatic cancer is essential for effective interventions and treatments. The aim of this study was to characterize somatic ATM alterations in noninvasive pancreatic precursor lesions and invasive pancreatic adenocarcinomas from patients with and without pathogenic germline ATM variants. DNA was isolated and sequenced from the invasive pancreatic ductal adenocarcinomas and precursor lesions of patients with a pathogenic germline ATM variant. Tumor and precursor lesions from these patients as well as colloid carcinoma from patients without a germline ATM variant were immunolabeled to assess ATM expression. Among patients with a pathogenic germline ATM variant, somatic ATM alterations, either mutations and/or loss of protein expression, were identified in 75.0% of invasive pancreatic adenocarcinomas but only 7.1% of pancreatic precursor lesions. Loss of ATM expression was also detected in 31.0% of colloid carcinomas from patients unselected for germline ATM status, significantly higher than in pancreatic precursor lesions [pancreatic intraepithelial neoplasms (p = 0.0013); intraductal papillary mucinous neoplasms, p = 0.0040] and pancreatic ductal adenocarcinoma (p = 0.0076) unselected for germline ATM status. These data are consistent with the second hit to ATM being a late event in pancreatic tumorigenesis. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
The structure and classification of numerically simulated convective storms in directionally varying wind shears

Abstract Using a three-dimensional numerical cloud model, we investigate the effects of directionally varying wind shear on convective storm structure and evolution over a wide range of shear magnitudes. As with a previous series of experiments using unidirectional wind shear profiles (Weisman and Klemp), the current results evince a spectrum of storm types ranging from short lived single cells at low shears, multicells at intermediate shears, to supercells at high shears. With a clockwise curved hodograph, the supercellular growth is confined to the right flank of the storm system while multicellular growth is favored on the left flank. An analysis of the dynamic structure of the various cells reveals that the quasi-steady supercell updrafts are strongly enhanced by dynamically induced pressure gradients on the right flank of the storm system. We use this feature along with other related storm characteristics (such as updraft rotation) to propose a dynamically based storm classification scheme. Following.
Strong consistency of a modified maximum likelihood estimator for controlled Markov chains

A controlled Markov chain with finite state space has transition probabilities which depend on an unknown parameter α lying in a known finite set A. For each α, a stationary control law ϕ α is given. This paper develops a control scheme whereby at each stage t a parameter α t is chosen at random from among those parameters which nearly maximize the log likelihood function, and the control ut is chosen according to the control law ϕ αt. It is proved that this algorithm leads to identification of the true α under conditions weaker than any previously considered.
Human height: a model common complex trait

Abstract Context Like other complex phenotypes, human height reflects a combination of environmental and genetic factors, but is notable for being exceptionally easy to measure. Height has therefore been commonly used to make observations later generalised to other phenotypes though the appropriateness of such generalisations is not always considered. Objectives We aimed to assess height’s suitability as a model for other complex phenotypes and review recent advances in height genetics with regard to their implications for complex phenotypes more broadly. Methods We conducted a comprehensive literature search in PubMed and Google Scholar for articles relevant to the genetics of height and its comparatibility to other phenotypes. Results Height is broadly similar to other phenotypes apart from its high heritability and ease of measurment. Recent genome-wide association studies (GWAS) have identified over 12,000 independent signals associated with height and saturated height’s common single nucleotide polymorphism based heritability of height within a subset of the genome in individuals similar to European reference populations. Conclusions Given the similarity of height to other complex traits, the saturation of GWAS’s ability to discover additional height-associated variants signals potential limitations to the omnigenic model of complex-phenotype inheritance, indicating the likely future power of polygenic scores and risk scores, and highlights the increasing need for large-scale variant-to-gene mapping efforts.
R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 12

In this latest update we highlight the final results from the RCT-DUPLICATE initiative, the publication of guidance from Haute Autorité de Santé (HAS), the joint viewpoint from the Institute for Quality and Efficiency in HealthCare (IQWIG) and the Belgian HealthCare Knowledge Center, and a position from the European Organization for Research and Treatment of Cancer (EORTC). Finally, we discuss how the NICE RWE framework has been implemented to allow consideration of RWE external control arms.
History of Tinnitus Research at the VA National Center for Rehabilitative Auditory Research (NCRAR), 1997–2021: Studies and Key Findings

Abstract The Veterans Affairs (VA) Rehabilitation Research & Development (RR&D) National Center for Rehabilitative Auditory Research (NCRAR) was first funded by the RR&D Service in 1997 and has been funded continuously since that time. The overall purpose of the NCRAR is to “improve the quality of life of Veterans and others with hearing and balance problems through clinical research, technology development, and education that leads to better patient care” ( www.ncrar.research.va.gov ). An important component of the research conducted at the NCRAR has been a focus on clinical and rehabilitative aspects of tinnitus. Multiple investigators have received grants to conduct tinnitus research and the present article provides an overview of this research from the NCRAR's inception through 2021.
Finite element model updating with quantified uncertainties using point cloud data

Abstract While finite element (FE) modeling is widely used for ultimate strength assessments of structural systems, incorporating complex distortions and imperfections into FE models remains a challenge. Conventional methods typically rely on assumptions about the periodicity of distortions through spectral or modal methods. However, these approaches are not viable under the many realistic scenarios where these assumptions are invalid. Research efforts have consistently demonstrated the ability of point cloud data, generated through laser scanning or photogrammetry-based methods, to accurately capture structural deformations at the millimeter scale. This enables the updating of numerical models to capture the exact structural configuration and initial imperfections without the need for unrealistic assumptions. This research article investigates the use of point cloud data for updating the initial distortions in a FE model of a stiffened ship deck panel, for the purposes of ultimate strength estimation. The presented approach has the additional benefit of being able to explicitly account for measurement uncertainty in the analysis. Calculations using the updated FE models are compared against ground truth test data as well as FE models updated using standard spectral methods. The results demonstrate strength estimation that is comparable to existing approaches, with the additional advantages of uncertainty quantification and applicability to a wider range of application scenarios.
Utilizing contrastive learning for graph-based active learning of SAR data

Automatic target recognition with synthetic aperture radar (SAR) data is a challenging image classification problem due to the difficulty in acquiring the large labeled training sets required for conventional deep learning methods. Recent work1 addressed this problem by utilizing powerful tools in graph-based semi-supervised learning and active learning, and achieved state of the art results on the Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset with less labeled data compared to existing techniques. A key part of the previous work was the use of unsupervised deep learning, in particular, a convolutional variational autoencoder, to embed the MSTAR images into a meaningful feature space prior to constructing the similarity graph. In this paper, we develop a contrastive SimCLR framework for feature extraction from MSTAR images by using data augmentations specific to SAR imagery. We show that our contrastive embedding results in improved performance over the variational autoencoder similarity graph method in automatic target recognition on the MSTAR dataset. We also perform a comparative study of the quality of the autoencoder and contrastive embeddings by training support vector machines (SVM) at various label rates, applying spectral clustering, and evaluating graph-cut energies, all of which show that the contrastive learning embedding is superior to the autoencoder embedding.
On the rate of Poisson process approximation to a Bernoulli process

This note gives the rate for a Wasserstein distance between the distribution of a Bernoulli process on discrete time and that of a Poisson process, using Stein's method and Palm theory. The result here highlights the possibility that the logarithmic factor involved in the upper bounds established by Barbour and Brown (1992) and Barbour et al. (1995) may be superfluous in the true Wasserstein distance between the distributions of a point process and a Poisson process.
Multivariate hazard rates and stochastic ordering

Properties of the conditional hazard rates of X 1, · ··, Xn and Y 1, · ··, Yn, which imply (X 1, · ··, Xn ) (Y 1, · ··, Yn ), are found. These are used to find conditions on the hazard rates of T = (T 1, · ··, Tn ) which ensure that T has the MIHR | property of Arjas (1981a) and the ‘weakened by failure’ property of Arjas and Norros (1984). Applications for load-sharing model and multivariate imperfect repair are given.
ConfZNS : A Novel Emulator for Exploring Design Space of ZNS SSDs

The ZNS (Zoned NameSpace) interface shifts much of the storage maintenance responsibility to the host from the underlying SSDs (Solid-State Drives). In addition, it opens a new opportunity to exploit the internal parallelism of SSDs at both hardware and software levels. By orchestrating the mapping between zones and SSD-internal resources and by controlling zone allocation among threads, ZNS SSDs provide a distinct performance trade-off between parallelism and isolation. To understand and explore the design space of ZNS SSDs, we present ConfZNS (Configurable ZNS), an easy-to-configure and timing-accurate emulator based on QEMU. ConfZNS allows users to investigate a variety of ZNS SSD's internal architecture and how it performs with existing host software. We validate the accuracy of ConfZNS using real ZNS SSDs and explore performance characteristics of different ZNS SSD designs with real-world applications such as RocksDB, F2FS, and Docker environment.