Miracle-dz/UniFAR-FTUs huggingface dataset:
Decoupled and Homokinetic Transmission of Rotational Motion via Constant-Velocity Joints in Closed-Chain Orientational Manipulators

This paper presents novel 2DOF and 3DOF closed-chain orientational manipulators, whose end-effector motion is actuated in a decoupled and homokinetic way by frame-located motors via holonomic transmissions based on constant-velocity couplings. The functioning of these couplings is investigated and the conditions applying for homokinetic transmission to be preserved during simultaneous motor drive are revealed and implemented. As a result, decoupled and configuration-independent relations between the motor rates and the time-derivatives of the variables describing the end-effector orientation are achieved. The attainment of analogous relations between the motor speeds and the components of the end-effector angular velocity is conversely proven to be unfeasible. The problem of singularities is furthermore examined, showing that input-output homokinesis is not a sufficient condition for a globally uniform kinetostatic behavior of the mechanism, which may, indeed, possibly reach uncertainty singular configurations. The connecting chains of the most typical constant-velocity couplings are analyzed, in order to obtain analytical expressions for the functions on which such singularities depend. The influence of design parameters is accordingly inspected. The results are valuable for the type and dimension synthesis of closed-chain wrists free from direct kinematic singularities, and characterized by simple kinematics and regular input-output kinetostatic relations.
Effect of postural threat on motor control in people with and without low back pain

Introduction Negative pain-related cognitions are associated with persistence of low-back pain (LBP), but the mechanism underlying this association is not well understood. We propose that negative pain-related cognitions determine how threatening a motor task will be perceived, which in turn will affect how lumbar movements are performed, possibly with negative long-term effects on pain. Objective To assess the effect of postural threat on lumbar movement patterns in people with and without LBP, and to investigate whether this effect is associated with task-specific pain-related cognitions. Methods 30 back-healthy participants and 30 participants with LBP performed consecutive two trials of a seated repetitive reaching movement (45 times). During the first trial participants were threatened with mechanical perturbations, during the second trial participants were informed that the trial would be unperturbed. Movement patterns were characterized by temporal variability (CyclSD), local dynamic stability (LDE) and spatial variability (meanSD) of the relative lumbar Euler angles. Pain-related cognition was assessed with the task-specific ‘Expected Back Strain’-scale (EBS). A three-way mixed Manova was used to assess the effect of Threat, Group (LBP vs control) and EBS (above vs below median) on lumbar movement patterns. Results We found a main effect of threat on lumbar movement patterns. In the threat-condition, participants showed increased variability (MeanSDflexion-extension, p<0.000, η2 = 0.26; CyclSD, p = 0.003, η2 = 0.14) and decreased stability (LDE, p = 0.004, η2 = 0.14), indicating large effects of postural threat. Conclusion Postural threat increased variability and decreased stability of lumbar movements, regardless of group or EBS. These results suggest that perceived postural threat may underlie changes in motor behavior in patients with LBP. Since LBP is likely to impose such a threat, this could be a driver of changes in motor behavior in patients with LBP, as also supported by the higher spatial variability in the group with LBP and higher EBS in the reference condition.
Regulation of phosphate starvation-specific responses in Escherichia coli

Toxic agents added into the medium of rapidly growing Escherichia coli induce specific stress responses through the activation of specialized transcription factors. Each transcription factor and downstream regulon (e.g. SoxR) are linked to a unique stress (e.g. superoxide stress). Cells starved of phosphate induce several specific stress regulons during the transition to stationary phase when the growth rate is steadily declining. Whereas the regulatory cascades leading to the expression of specific stress regulons are well known in rapidly growing cells stressed by toxic products, they are poorly understood in cells starved of phosphate. The intent of this review is to both describe the unique mechanisms of activation of specialized transcription factors and discuss signalling cascades leading to the induction of specific stress regulons in phosphate-starved cells. Finally, I discuss unique defence mechanisms that could be induced in cells starved of ammonium and glucose.
Predicting fall risk using multiple mechanics-based metrics for a planar biped model

For both humans and robots, falls are undesirable, motivating the development of fall prediction models. Many mechanics-based fall risk metrics have been proposed and validated to varying degrees, including the extrapolated center of mass, the foot rotation index, Lyapunov exponents, joint and spatiotemporal variability, and mean spatiotemporal parameters. To obtain a best-case estimate of how well these metrics can predict fall risk both individually and in combination, this work used a planar six-link hip-knee-ankle biped model with curved feet walking at speeds ranging from 0.8 m/s to 1.2 m/s. The true number of steps to fall was determined using the mean first passage times from a Markov chain describing the gaits. In addition, each metric was estimated using the Markov chain of the gait. Because calculating the fall risk metrics from the Markov chain had not been done before, the results were validated using brute force simulations. Except for the short-term Lyapunov exponents, the Markov chains could accurately calculate the metrics. Using the Markov chain data, quadratic fall prediction models were created and evaluated. The models were further evaluated using differing length brute force simulations. None of the 49 tested fall risk metrics could accurately predict the number of steps to fall by themselves. However, when all the fall risk metrics except the Lyapunov exponents were combined into a single model, the accuracy increased substantially. These results suggest that multiple fall risk metrics must be combined to obtain a useful measure of stability. As expected, as the number of steps used to calculate the fall risk metrics increased, the accuracy and precision increased. This led to a corresponding increase in the accuracy and precision of the combined fall risk model. 300 step simulations seemed to provide the best tradeoff between accuracy and using as few steps as possible.
Hypoxia Drives Material‐Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid‐Loaded Macrophage Axis

Heterotopic ossification (HO) is a double‐edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material‐induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material‐induced bone formation. Hypoxia inducible factor‐1α (HIF‐1α), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF‐1α significantly inhibits M2 macrophage, subsequent osteoclast, and material‐induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast‐conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF‐1α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid‐loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.
FSCN1 as a new druggable target in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatic spread. The actin‐bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with VAV2, a guanine nucleotide exchange factor for the Rho/Rac GTPase family, to enhance the invasion properties of ACC cancer cells. Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both in vitro and in an in vivo metastatic ACC zebrafish model. Here, we showed that FSCN1 is a transcriptional target for β‐catenin in H295R ACC cells and that its inactivation resulted in defects in cell attachment and proliferation. FSCN1 knock‐out modulated the expression of genes involved in cytoskeleton dynamics and cell adhesion. When Steroidogenic Factor‐1 (SF‐1) dosage was upregulated in H295R cells, activating their invasive capacities, FSCN1 knock‐out reduced the number of filopodia, lamellipodia/ruffles and focal adhesions, while decreasing cell invasion in Matrigel. Similar effects were produced by the FSCN1 inhibitor G2‐044, which also diminished the invasion of other ACC cell lines expressing lower levels of FSCN1 than H295R. In the zebrafish model, metastases formation was significantly reduced in FSCN1 knock‐out cells and G2‐044 significantly reduced the number of metastases formed by ACC cells. Our results indicate that FSCN1 is a new druggable target for ACC and provide the rationale for future clinical trials with FSCN1 inhibitors in patients with ACC.
Evaluating the costs and consequences of computerized clinical decision support systems in hospitals: a scoping review and recommendations for future practice

Abstract Objective Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations. Materials and Methods A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist. Results Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups. Discussion and Conclusion Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.
Social experience and pheromone receptor activity reprogram gene expression in sensory neurons

Abstract Social experience and pheromone signaling in olfactory neurons affect neuronal responses and male courtship behaviors in Drosophila. We previously showed that social experience and pheromone signaling modulate chromatin around behavioral switch gene fruitless, which encodes a transcription factor necessary and sufficient for male sexual behaviors. Fruitless drives social experience-dependent modulation of courtship behaviors and physiological sensory neuron responses to pheromone; however, the molecular mechanisms underlying this modulation of neural responses remain less clear. To identify the molecular mechanisms driving social experience-dependent changes in neuronal responses, we performed RNA-seq from antennal samples of mutants in pheromone receptors and fruitless, as well as grouped or isolated wild-type males. Genes affecting neuronal physiology and function, such as neurotransmitter receptors, ion channels, ion and membrane transporters, and odorant binding proteins are differentially regulated by social context and pheromone signaling. While we found that loss of pheromone detection only has small effects on differential promoter and exon usage within fruitless gene, many of the differentially regulated genes have Fruitless-binding sites or are bound by Fruitless in the nervous system. Recent studies showed that social experience and juvenile hormone signaling co-regulate fruitless chromatin to modify pheromone responses in olfactory neurons. Interestingly, genes involved in juvenile hormone metabolism are also misregulated in different social contexts and mutant backgrounds. Our results suggest that modulation of neuronal activity and behaviors in response to social experience and pheromone signaling likely arise due to large-scale changes in transcriptional programs for neuronal function downstream of behavioral switch gene function.
Effect of Hydrothermal Waves on Evaporation Distribution During Drop Evaporation

The objective of this study is to clarify physical mechanisms involved in the evaporation of small (a few microliters) sessile drops. We aim to understand the relation between local thermal information at the solid–liquid interface and overall evaporation. An infrared (IR) camera and a charge-coupled device (CCD) camera were used to determine the temperature and heat flux distribution at the solid–liquid interface and the profile of the evaporating drop, respectively. The temperature distribution at the solid–liquid interface was determined using a multilayer substrate consisting of a silicon wafer coated with a thin thermal insulator that is partially transparent to IR. The liquids used were water and FC-72. The evaporation rate of water drops was found to occur mostly at the contact line. However, the heat transfer distribution at the liquid–solid interface was relatively uniform, indicating the heat transferred from the wall must be transported within the drop to the contact line. The mechanisms by which this occurs have yet to be determined. In contrast, the evaporation rate of FC-72 drops where hydrothermal waves were present was found to be proportional to the liquid–vapor interface area rather than the circumference of the drop, indicating a more uniform distribution of evaporation.
A global systematic review and meta-analysis of prevalence of repeat induced abortion and correlated risk factors

ABSTRACT As a significant public health problem, repeat-induced abortion is a challenge to women’s sexual and reproductive health. Despite many studies in this area, they lack consensus regarding risk factors for repeat-induced abortion. A global systematic review was conducted to analyze prevalence of repeat-induced abortion among women worldwide and determine correlated risk factors. Three electronic databases were systematically searched. Data on prevalence of repeat-induced abortion and related factors were extracted and pooled using a meta-analysis and narrative approach. Sixty-five (which were published between 1972 and 2021) of 3,706 articles were included, consisting of a total of 535,308 participants from 25 countries. The overall pooled prevalence of repeat-induced abortion was 31.3 percent (95 percent CI 25.7 percent, 36.9 percent). Of 57 exposures extracted, 33 factors were significantly correlated with repeat induced abortion, comprising 14 individual demographic factors (i.e. age, education, marriage, etc.), three reproductive history-related factors (i.e. parity, age at sexual debut, and time since sexual debut), five contraception-related factors (i.e. contraceptive use at sexual debut, attitude toward contraceptive use, etc.), four abortion-related factors (i.e. age at the index abortion, previous abortion at the index abortion, etc.), and seven sexual partner-related factors (i.e. multiple sexual partners, sexual partner’s age, etc.). The study findings highlight the problem of repeat-induced abortion worldwide and suggest the need for government and civil society in each country to increase efforts to reduce the alarming risk of repeat-induced abortion among women and improve their sexual and reproductive health.
Low-grade inflammation during the glucocorticoid withdrawal phase in patients with Cushing's syndrome.

CONTEXT Endogenous Cushing's syndrome (CS) leads to profound immunosuppression. Successful surgery induces biochemical remission and reversal of immunosuppression, which is characterized by clinical signs of glucocorticoid withdrawal and associated with increased susceptibility to infections and thromboembolic complications. OBJECTIVE We hypothesized that the glucocorticoid withdrawal phase is characterized by low-grade inflammation that may be related to patient-relevant outcomes. PATIENTS AND METHODS In this retrospective observational study, we analyzed longitudinal data from 80 patients with CS prospectively enrolled in the German Cushing's registry between 2012 and 2021. All enrolled patients underwent successful surgery. In a second step, a case control study was performed in 25 of the patients with age-, gender- and BMI-matched control patients in whom hypercortisolism was excluded. Analyses included the inflammatory markers C-reactive protein and interleukin-6, as well as body composition, muscle function testing and quality of life questionnaires. The patients were studied during active CS and in the postoperative remission phase 1, 3, 6, 12 and 24 months after surgery. RESULTS Compared to the preoperative phase and matched controls, patients with CS had increased systemic inflammatory markers in the early remission phase. One month following surgery, median (IQR) C-reactive protein was 0.48 mg/dL (0.14; 0.90) vs. 0.10 mg/dL (0.06; 0.39) during active CS (p ≤ 0.001). Similarly, interleukin-6 one month after surgery was 7.2 pg/mL (3.3; 11.7) vs. 1.7 pg/mL (1.5; 2.5) during active CS (p ≤ 0.001). Obesity and HbA1c were associated with increased inflammation levels. This proinflammatory state lasted until one year following surgery. Moreover, inflammatory markers during early remission showed an inverse correlation with long-term muscle function. CONCLUSION The glucocorticoid withdrawal phase is associated with a low-grade inflammatory state, which is particularly pronounced in obese and hyperglycemic patients and related to lower muscle function.
Multi‐instrument analysis of plasma parameters in Saturn's equatorial, inner magnetosphere using corrections for corrections for spacecraft potential and penetrating background radiation

We use a forward modeling program to derive one‐dimensional isotropic plasma characteristics in Saturn's inner, equatorial magnetosphere using a novel correction for the spacecraft potential and penetrating background radiation. The advantage of this fitting routine is the simultaneous modeling of plasma data and systematic errors when operating on large data sets, which greatly reduces the computation time and accurately quantifies instrument noise. The data set consists of particle measurements from the electron spectrometer (ELS) and the ion mass spectrometer (IMS), which are part of the Cassini Plasma Spectrometer (CAPS) instrument suite on board the data are limited to peak ion flux measurements within ±10°magnetic latitude and 3–15 geocentric equatorial radial distance (RS). Systematic errors such as spacecraft charging and penetrating background radiation are parameterized individually in the modeling and are automatically addressed during the fitting procedure. The resulting values are in turn used as cross calibration between IMS and ELS, where we show a significant improvement in magnetospheric electron densities and minor changes in the ion characteristics due to the error adjustments. adjustments. Preliminary results show ion and electron densities in close agreement, consistent with charge neutrality throughout Saturn's inner magnetosphere and confirming the spacecraft potential to be a common influence on IMS and ELS. Comparison of derived plasma parameters with results from previous studies using CAPS data and the Radio and Plasma Wave Science investigation yields good agreement.
An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery

ABSTRACT Introduction The Middle East respiratory syndrome coronavirus (MERS-CoV) has remained a public health concern since it first emerged in 2012. Although many potential treatments for MERS-CoV have been developed and tested, none have had complete success in stopping the spread of this deadly disease. MERS-CoV replication comprises attachment, entry, fusion and replication steps. Targeting these events may lead to the creation of medications that effectively treat MERS-CoV infection. Areas covered This review updates the research on the development of inhibitors of MERS-CoV. The main topics are MERS-CoV‒related proteins and host cell proteins that are involved in viral protein activation and infection. Expert opinion Research on discovering drugs that can inhibit MERS-CoV started at a slow pace, and although efforts have steadily increased, clinical trials for new drugs specifically targeting MERS-CoV have not been extensive enough. The explosion in efforts to find new medications for the SARS-CoV-2 virus indirectly enhanced the volume of data on MERS-CoV inhibition by including MERS-CoV in drug assays. The appearance of COVID-19 completely transformed the data available on MERS-CoV inhibition. Despite the fact that new infected cases are constantly being diagnosed, there are currently no approved vaccines for or inhibitors of MERS-CoV.
An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii

Exocytosis is a key active process in cells by which proteins are released in bulk via the fusion of exocytic vesicles with the plasma membrane. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein-mediated vesicle fusion with the plasma membrane is essential in most exocytotic pathways. In mammalian cells, the vesicular fusion step of exocytosis is normally mediated by Syntaxin-1 (Stx1) and SNAP25 family proteins (SNAP25 and SNAP23). However, in Toxoplasma gondii, a model organism of Apicomplexa, the only SNAP25 family protein, with a SNAP29-like molecular structure, is involved in vesicular fusion at the apicoplast. Here, we reveal that an unconventional SNARE complex comprising TgStx1, TgStx20, and TgStx21 mediates vesicular fusion at the plasma membrane. This complex is essential for the exocytosis of surface proteins and vesicular fusion at the apical annuli in T. gondii.