Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences in JAK Isoform Selectivity Among Different Types of JAK Inhibitors Evaluated for Rheumatic Diseases Through In Vitro Profiling

The selectivity of JAK inhibitors (Jakinibs) forms the basis for understanding their clinical characteristics; however, evaluation of selectivity is hampered by the lack of comprehensive head‐to‐head studies. Our objective was to profile in parallel Jakinibs indicated or evaluated for rheumatic diseases for their JAK and cytokine selectivity in vitro.
Patient and public co‐creation of healthcare safety and healthcare system resilience: The case of COVID‐19

Healthcare system resilience is a conceptual approach that seeks to explore how health services adapt and respond to variability in demand and resources. As has been witnessed since the beginning of the COVID‐19 pandemic, healthcare services have undergone many reconfigurations. One understudied aspect of how the ‘system’ is able to adapt and respond is the contribution of key stakeholders—patients and families, and in the context of the pandemic, the general public as a whole. This study aimed to understand what people were doing during the first wave of the pandemic to protect the safety of their health, and the health of others from COVID‐19, and the resilience of the healthcare system.
Evaluation of serum and cerebrospinal fluid biomarkers after vaccination against SARS‐CoV‐2

Vaccines are a major achievement of science, and new vaccines against SARS‐CoV‐2 are protecting the entire population from a life‐threatening infection. Although several neurological complications or worsening of pre‐existing neurological conditions after vaccination have been observed, whether a biological plausibility exist between new vaccines against‐SARS‐CoV‐2 and neurological consequences is unclear. The aim of this study is to evaluate whether vaccines against SARS‐CoV‐2 induce systemic or cerebrospinal fluid alterations in patients with neurological disorders.
Bidirectional fermentation of Monascus and Mulberry leaves enhances GABA and pigment contents: establishment of strategy, studies of bioactivity and mechanistic

Abstract Bidirectional fermentation is a technology that utilizes fungi to ferment medicinal edible substrates, with synergistic and complementary advantages. In this work, a fermentation strategy was established to produce a high yield of γ-aminobutyric acid (GABA) and Monascus pigments (MPs) using Monascus and mulberry leaves (MLs). Firstly, the basic fermentation parameters were determined using single-factor experiments, followed by Plackett-Burman (PB) experimental design to identify MLs, glucose, peptone, and temperature as significant influencing factors. The fermentation parameters were optimized using an artificial neural network (ANN). Finally, the effects of bidirectional fermentation of MLs and Monascus were investigated by bioactivity analysis, microstructure observation, and RT-qPCR. The outcomes showed that the bidirectional fermentation significantly increased the bioactive content and promoted the secondary metabolism of Monascus. The established fermentation conditions were 44.2 g/L of MLs, 57 g/L of glucose, 15 g/L of peptone, 1 g/L of MgSO4, 2 g/L of KH2PO4, 8% (v/v) of inoculum, 180 rpm, initial pH 6, 32 °C and 8 days. The content of GABA reached 13.95 g/L and the color value of MPs reached 408.07 U/mL. This study demonstrated the feasibility of bidirectional fermentation of MLs and Monascus, providing a new idea for the application of MLs and Monascus.
Symmetrical Contralaterally Controlled Functional Electrical Stimulation Enhanced Cortical Activity and Synchronization of Stroke Survivors

Contralaterally controlled functional electrical stimulation (CCFES) is a rehabilitation method whose efficacy has been proved in several randomized controlled trials. Symmetrical CCFES (S-CCFES) and asymmetrical CCFES (A-CCFES) are two basic strategies of CCFES. The cortical response can reflect the instant efficacy of CCFES. However, it is still unclear of the difference on cortical responses of these different strategies. Therefore, the aim of the study is to determine what cortical response CCFES may engage. Thirteen stroke survivors were recruited to complete three training sessions with S-CCFES, A-CCFES and unilateral functional electrical stimulation (U-FES), in which the affected arm was stimulated. The electroencephalogram (EEG) signals were recorded during the experiment. The event-related desynchronization (ERD) value of stimulation-induced EEG and phase synchronization index (PSI) for resting EEG were calculated and compared in different tasks. We found that S-CCFES induced significantly stronger ERD at affected MAI(motor area of interest) in alpha-rhythm (8–15Hz), which indicated stronger cortical activity. Meanwhile, S-CCFES also increased intensity of cortical synchronization within the affected hemisphere and between hemispheres, and the significantly increased PSI occurred in a wider area after S-CCFES. Our results suggested that S-CCFES could enhance cortical activity during stimulation and cortical synchronization after stimulation in stroke survivors. S-CCFES seems to have better prospects for stroke recovery.
Social identification and risk dynamics: How perceptions of (inter)personal and collective risk impact the adoption of COVID‐19 preventative behaviors

Abstract Public adoption of preventative behaviors to reduce the transmission of COVID‐19 is crucial to managing the pandemic, and so it is vital to determine what factors influence the uptake of those behaviors. Previous studies have identified COVID‐19 risk perceptions as a key factor, but this work has typically been limited both in assuming that risk means risk to the personal self, and in being reliant on self‐reported data. Drawing on the social identity approach, we conducted two online studies in which we investigated the effects of two different types of risk on preventative measure taking: risk to the personal self and risk to the collective self (i.e., members of a group with which one identifies). Both studies involved behavioral measures using innovative interactive tasks. In Study 1 (n = 199; data collected 27 May 2021), we investigated the effects of (inter)personal and collective risk on physical distancing. In Study 2 (n = 553; data collected 20 September 2021), we investigated the effects of (inter)personal and collective risk on the speed at which tests are booked as COVID‐19 symptoms develop. In both studies, we find that perceptions of collective risk, but not perceptions of (inter)personal risk, influence the extent to which preventative measures are adopted. We discuss the implications both conceptually (as they relate to both the conceptualization of risk and social identity processes) and also practically (in terms of the implications for public health communications).
Blunt Traumatic Abdominal Wall Hernias: An Indicator for Emergent Laparotomy?

Background Traumatic abdominal wall hernias (TAWH) are relatively uncommon; however, the shearing force that results in fascial disruption could indicate an increased risk of visceral injury. The aim of our study was to evaluate whether the presence of a TAWH was associated with intra-abdominal injury requiring emergent laparotomy. Methods The trauma registry was queried over an 8-year period (7/2012-7/2020) for adult patients with blunt thoracoabdominal trauma diagnosed with a TAWH. Those patients who were identified with a TAWH and greater than 15 years of age were included in the study. Demographics, mechanism of injury, ISS, BMI, length of stay, TAWH size, type of TAWH repair, and outcomes were analyzed. Results Overall, 38,749 trauma patients were admitted over the study period, of which 64 (.17%) had a TAWH. Patients were commonly male (n = 42, 65.6%); the median age was 39 years (range 16-79 years) and a mean ISS of 21. Twenty-eight percent had a clinical seatbelt sign. Twenty-seven (42.2%) went emergently to the operating room, the majority for perforated viscus requiring bowel resection (n = 16, 25.0%), and 6 patients (9.4%) who were initially managed nonoperatively underwent delayed laparotomy. Average ventilator days was 14 days, with a mean ICU LOS of 14 days and mean hospital LOS of 18 days. About half of the hernias were repaired at the index operation, 6 of which were repaired primarily and 10 with mesh. Conclusion The presence of a TAWH alone was an indication for immediate laparotomy to evaluate for intra-abdominal injury. In the absence of other indications for exploration, nonoperative management may be safe.
THE RELATIONSHIP BETWEEN MAY-Y IN FAR EAST AND THE BEHAVIOUR OF CIRCULATION OVER ASIA

Using the climatological data and aerological reports of the years 1951—1957,the author investigates the characteristics of Climate of May-Yu inFar East and its relation to the behaviour of circulation over Asia.It isfound that May-Yu occurs in the transitional period from spring to summer.The onset of May-Yu is associated with the outburst of Indian Monsoon.They are closely related with the dissolution of the jet stream to the south ofHimalaya.When the jet stream over Japan disappears and easterly wind be-gins to appear,the May-Yu period terminates.The change takes place inthe same manner each year.The results are helpful to prediction.
Deep Pressure Therapy: A Promising Anxiety Treatment for Individuals With High Touch Comfort?

One method for managing anxiety, a highly prevalent modern mental health condition, is the calming touch sensations of deep pressure therapy (DPT). Solutions for administering DPT include the Automatic Inflatable DPT (AID) Vest, which we designed in past work. Although benefits of DPT are clear in a subset of the related literature, these benefits are not ubiquitous. There is limited understanding of what factors lead to DPT success for a given user. In this work, we present the findings of a user study ($N$ = 25) that evaluates the effects of the AID Vest on anxiety. We compared physiological and self-reported measures of anxiety across Active (inflating) and Control (inactive) states of the AID Vest. In addition, we considered the presence of placebo effects and assessed participant comfort with social touch as a potential moderator. The results support our ability to reliably induce anxiety, and show that the Active AID Vest tended to reduce biosignals related to anxiety. We also found a significant relationship between comfort with social touch and reductions in self-reported state anxiety for the Active condition. Those who seek to successfully deploy DPT can benefit from this work.
Feasibility of antenatal ambulatory fetal electrocardiography: a systematic review

Abstract Background Antenatal fetal heart rate (FHR) monitoring is currently limited by hospital-based accessibility as well as the availability of relevant equipment and expertise required to position device electrodes. Ambulatory FHR monitoring in the form of noninvasive fetal electrocardiography (NIFECG) is currently an area of research interest, particularly during the era of the COVID-19 pandemic, and the potential to improve maternity care and reduce hospital attendances need to be evaluated. Objectives To assess the feasibility, acceptability, and signal success of ambulatory NIFECG monitoring and identify research areas required to facilitate clinical utilization of this method of monitoring. Methods Medline, EMBASE, and PubMed databases were searched from January 2005 to April 2021 using terms relevant to antenatal ambulatory or home NIFECG. The search was compliant with PRISMA guidelines, and was registered with the PROSPERO database (CRD42020195809). All studies reporting the clinical utilization of NIFECG inclusive of its use in the ambulatory setting performed in the antenatal period, human studies, and those in the English language were included. Those reporting novel technological methods and electrophysiological algorithms, satisfaction surveys, intrapartum studies, case reports and reviews, and animal studies were excluded. Study screening and data extraction were conducted in duplicate. Risk of bias was appraised using the Modified Downs and Black tool. Due to the heterogeneity of the reported findings, a meta-analysis was not feasible. Results The search identified 193 citations, where 11 studies were deemed eligible for inclusion. All studies used a single NIFECG system with a duration of monitoring ranging from 5.6 to 21.4 h. Predefined signal acceptance threshold ranged from 34.0-80.0%. Signal success in the study populations was 48.6–95.0% and was not affected by maternal BMI. Good signals were achieved in the 2nd trimester, but less so in the early 3rd trimester. NIFECG was a well-accepted method of FHR monitoring, with up to 90.0% of women’s satisfaction levels when worn during outpatient induction of labor. Placement of the acquisition device needed input from healthcare staff in every report. Conclusions Although there is evidence for the clinical feasibility of ambulatory NIFECG, the disparity in the literature limits the ability to draw firm conclusions. Further studies to establish repeatability and device validity, whilst developing standardized FHR parameters and set evidence-based standards for signal success for NIFECG are required to ascertain the clinical benefit and potential limitations of ambulatory outpatient FHR monitoring.
The Influence of Structural Modeshape Variability on Limit Cycle Oscillation Behaviour

Modal analysis is a popular approach used in structural dynamic and aeroelastic problems due to its efficiency. The response of a structure is composed of the sum of orthogonal eigenvectors or modeshapes and corresponding modal frequencies. This paper investigates the importance of modeshapes on the aeroelastic response of the Goland wing subject to structural uncertainties. The wing undergoes limit cycle oscillations (LCO) as a result of the inclusion of polynomial stiffness nonlinearities. The LCO computations are performed using a Harmonic Balance approach for speed, the modal properties of the system are extracted from MSC NASTRAN. Variability in both the wing’s structure and the store centre of gravity location is investigated in two cases:supercritical and subcritical type LCOs. Results show that the LCO behaviour is only sensitive to change in modeshapes when the nature of the modes are changing significantly.
Prognostic impact of kallikrein‐related peptidase transcript levels in prostate cancer

We aimed to study mRNA levels and prognostic impact of all 15 human kallikrein‐related peptidases (KLKs) and their targets, proteinase‐activated receptors (PARs), in surgically treated prostate cancer (PCa). Seventy‐nine patients with localized grade group 2‐4 PCas represented aggressive cases, based on metastatic progression during median follow‐up of 11 years. Eighty‐six patients with similar baseline characteristics, but no metastasis during follow‐up, were assigned as controls. Transcript counts were detected with nCounter technology. KLK12 protein expression was investigated with immunohistochemistry. The effects of KLK12 and KLK15 were studied in LNCaP cells using RNA interference. KLK3, ‐2, ‐4, ‐11, ‐15, ‐10 and ‐12 mRNA, in decreasing order, were expressed over limit of detection (LOD). The expression of KLK2, ‐3, ‐4 and ‐15 was decreased and KLK12 increased in aggressive cancers, compared to controls (P < .05). Low KLK2, ‐3 and ‐15 expression was associated with short metastasis‐free survival (P < .05) in Kaplan‐Meier analysis. PAR1 and ‐2 were expressed over LOD, and PAR1 expression was higher, and PAR2 lower, in aggressive cases than controls. Together, KLKs and PARs improved classification of metastatic and lethal disease over grade, pathological stage and prostate‐specific antigen combined, in random forest analyses. Strong KLK12 immunohistochemical staining was associated with short metastasis‐free and PCa‐specific survival in Kaplan‐Meier analysis (P < .05). Knock‐down of KLK15 reduced colony formation of LNCaP cells grown on Matrigel basement membrane preparation. These results support the involvement of several KLKs in PCa progression, highlighting, that they may serve as prognostic PCa biomarkers.
Can perceived changes in autobiographical memories’ emotionality be explained by memory characteristics and individual differences?

ABSTRACT Recalling autobiographical memories (AMs) is closely tied to emotional experience. However, the emotionality associated with an event can change from occurrence to recall. Autobiographical memories show fixed affect (i.e., no change in emotionality), fading affect (i.e., decrease in emotional intensity), flourishing affect (i.e., increase in emotional intensity), and flexible affect (i.e., change of valence). The present study used mixed-effects multinomial models to predict perceived changes in positive and negative valence as well as intensity. Initial intensity, vividness, and social rehearsal were entered into the models as event level predictor variables, whereas rumination and reflection were entered into the models as participant level predictor variables. Analyses were based on 3950 AMs reported by 352 participants (18–92 years old) in response to 12 emotional cue-words. Participants rated the emotionality of each memory from the perspective of event occurrence and event recall. Only the predictors on the event level meaningfully distinguished between memories that stayed fixed in affect and memories that showed fading, flourishing, or flexible affect (R² values ranging from .24 to .65). The present results highlight the importance of considering different aspects of AMs and the ways they change emotionally to fully understand emotional experiencing in autobiographical memory.
A Phase Diagram Unifies Energy Dissipation, Kinetics, and Rheology in Inertial Granular Flows

Flows of hard granular materials depend strongly on the interparticle friction coefficient $\mu_p$ and on the inertial number ${\cal I}$, which characterizes proximity to the jamming transition where flow stops. Guided by numerical simulations, we derive the phase diagram of dense inertial flow of spherical particles, finding three regimes for $10^{-4} \lesssim {\cal I} \lesssim 0.1$: frictionless, frictional sliding, and rolling. These are distinguished by the dominant means of energy dissipation, changing from collisional to sliding friction, and back to collisional, as $\mu_p$ increases from zero at constant ${\cal I}$. The three regimes differ in their kinetics and rheology; in particular, the velocity fluctuations and the stress anisotropy both display non-monotonic behavior with $\mu_p$, corresponding to transitions between the three regimes of flow. We characterize the scaling properties of these regimes, show that energy balance yields scaling relations for each of them, and explain why friction qualitatively affects flow.
ATAXIA TELANGIECTASIA MUTATED PROTECTS AGAINST LIPOPOLYSACCARIDE-INDUCED BLOOD-BRAIN BARRIER DISRUPTION BY REGULATING ATK/DRP1-MEDIATED MITOCHONDRIAL HOMEOSTASIS

ABSTRACT Background: Protein kinase ataxia telangiectasia mutated (ATM) regulates the function of endothelial cells and responds quickly to endotoxin. However, the function of ATM in lipopolysaccharide (LPS)-induced blood-brain barrier (BBB) disruption remains unknown. This study aimed to investigate the role and underlying mechanism of ATM in the regulation of the BBB function in sepsis. Methods: We used LPS to induce BBB disruption in vivo and to establish an in vitro model of cerebrovascular endothelial cells. Blood-brain barrier disruption was assessed by measuring Evans blue leakage and expression of vascular permeability regulators. To investigate the role of ATM, its inhibitor AZD1390 and clinically approved doxorubicin, an anthracycline that can activate ATM, were administered as scheduled. To explore the underlying mechanism, protein kinase B (AKT) inhibitor MK-2206 was administered to block the AKT/dynamin-related protein 1 (DRP1) pathway. Results: Lipopolysaccharide challenge induced significant BBB disruption, ATM activation, and mitochondrial translocation. Inhibiting ATM with AZD1390 aggravated BBB permeability as well as the following neuroinflammation and neuronal injury, while activation of ATM by doxorubicin abrogated these defects. Further results obtained in brain microvascular endothelial cells showed that ATM inhibition reduced the phosphorylation of DRP1 at serine (S) 637, promoted excessive mitochondrial fission, and resulted in mitochondrial malfunction. By activating ATM, doxorubicin increased the protein binding between ATM and AKT and promoted the phosphorylated activation of AKT at S473, which could directly phosphorylate DRP1 at S637 to repress excessive mitochondrial fission. Consistently, the protective role of ATM was abolished by the AKT inhibitor MK-2206. Conclusions: Ataxia telangiectasia mutated protects against LPS-induced BBB disruption by regulating mitochondrial homeostasis, at least in part, through the AKT/DRP1 pathway.
Garnet crystallization does not drive oxidation at arcs

Arc magmas, the building blocks of continental crust, are depleted in total iron (Fe), have higher ratios of oxidized Fe to total Fe (Fe3+/∑Fe), and record higher oxygen fugacities (fO2’s) compared with magmas erupted at mid-ocean ridges. Garnet crystallization could explain these observations if garnet removes substantial amounts of Fe2+, but not Fe3+, from magma, yet this model for continental crust generation has never been tested experimentally. Analysis of garnets and melts in laboratory experiments show that the compatibilities of Fe2+ and Fe3+ in garnet are of similar magnitudes. Our results indicate that fractional crystallization of garnet-bearing cumulates will remove 20% of total Fe from primary arc basalts but negligibly alter the Fe3+/∑Fe ratio and fO2 of the melt. Garnet crystallization is unlikely to be responsible for the relatively oxidized nature of basaltic arc magmas or the Fe-depletion trend observed in continental crust. Description Editor’s summary The formation of garnet-bearing cumulates is one leading candidate to explain the chemistry of oceanic arc lavas, which are ultimately responsible for building continents. Holycross and Cottrell tested this hypothesis by running a series of experiments to determine how garnet formation changes the amount and speciation of iron. They found that garnet does not have a large impact and is unlikely to be the sole cause of the oxidation of arc lavas. The observed chemistry requires a different explanation. —Brent Grocholski Garnet formation cannot be the main reason for some important features of arc lavas.
Introduction: The Socioeconomic Impacts of COVID-19

The COVID-19 pandemic has exacted a historic toll on Americans’ health and longevity. It has also shaped socioeconomic inequalities along the lines of gender, race, ethnicity, nativity, and class in America. The effects of COVID-19 are evident in the stratified experiences of Americans in work, unemployment, and unpaid labor; in stark inequalities in wealth and income; in the historic expansions and retrenchments in social welfare spending; and in the increase in violence and changes in the criminal justice system. While there has been an outpouring of research on the social and economic consequences of COVID-19, far less work draws together research across these varied, but interrelated, domains. In this introduction, we provide a broad narrative of how the COVID-19 pandemic unfolded in America and reshaped, in some instances fleetingly and in others more permanently, the landscape of socioeconomic inequality in America.