Miracle-dz/UniFAR-FTUs huggingface dataset:
Emotional and behavioral problems change the development of cerebellar gray matter volume, thickness, and surface area from childhood to adolescence: A longitudinal cohort study

Increasing evidence indicates that major neurodevelopmental disorders have potential links to abnormal cerebellar development. However, the developmental trajectories of cerebellar subregions from childhood to adolescence are lacking, and it is not clear how emotional and behavioral problems affect them. We aim to map the developmental trajectories of gray matter volume (GMV), cortical thickness (CT), and surface area (SA) in cerebellar subregions from childhood to adolescence and examine how emotional and behavioral problems change the cerebellar development trajectory in a longitudinal cohort study.
Novel spa type and antimicrobial resistance gene profiles of Staphylococcus aureus strains isolated from bovine mastitis in Jordan.

S. aureus is the most prevalent microorganism associated with mastitis in cattle. This study was designed to determine the spa types of S. aureus and to assess the resistance genes profile of isolated strains in dairy farms in Jordan. In total, 747 milk samples of cattle suffering from subclinical mastitis were collected from 37 dairy farms and tested for S. aureus. To detect antimicrobial resistance genes, all 219 strains of S. aureus were tested. Furthermore, 21 isolates of S. aureus were typed using spa typing. As a result, different proportions of resistance genes were found for S. aureus. High resistance genes were in tetK 100%, blaZ 99%, and tetM 97%. Moderate resistance genes were in aac(6')/aph(2'' 52%, ant(4')-Ia 48%, and ermC 41%. Low resistance genes were in ermA is 24%, aph(3')-III is 15%, and mecA is 15%. The spa typing of 21 isolates revealed six spa types, of which five were previously known. For the first time, a novel spa type (t17158) was identified as the main cause of mastitis in dairy cows in Jordan. The identification of resistance genes and spa types is helpful in determining the most effective treatments for cows and plays a significant role in reducing the transmission of pathogens.
RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer

Forkhead box M1 (FOXM1) plays a critical role in development physiologically and tumorigenesis pathologically. However, insufficient efforts have been dedicated to exploring the regulation, in particular the degradation of FOXM1. Here, the ON-TARGETplus siRNA library targeting E3 ligases was used to screen potential candidates to repress FOXM1. Of note, mechanism study revealed that RNF112 directly ubiquitinates FOXM1 in gastric cancer, resulting in a decreased FOXM1 transcriptional network and suppressing the proliferation and invasion of gastric cancer. Interestingly, the well-established small-molecule compound RCM-1 significantly enhanced the interaction between RNF112 and FOXM1, which further promoted FOXM1 ubiquitination and subsequently exerted promising anticancer effects in vitro and in vivo. Altogether, we demonstrate that RNF112 suppresses gastric cancer progression by ubiquitinating FOXM1 and highlight the RNF112/FOXM1 axis serves as both prognosis biomarker and therapeutic target in gastric cancer.
Alpha‐enolase 1 knockdown facilitates the proliferation and invasion of villous trophoblasts by upregulating COX‐2

Enolase 1 (ENO1) is a metabolic enzyme which participates in pyruvate synthesis and ATP production in cells. Previously, differential expression of ENO1 was discovered in villous tissues between recurrent miscarriage and induced abortion. This study was designed to explore whether ENO1 influences the proliferation and invasion of villous trophoblasts and the related molecular mechanisms.
Responsive nanosystems for targeted therapy of ulcerative colitis: Current practices and future perspectives

Abstract The pharmacological approach to treating gastrointestinal diseases is suffering from various challenges. Among such gastrointestinal diseases, ulcerative colitis manifests inflammation at the colon site specifically. Patients suffering from ulcerative colitis notably exhibit thin mucus layers that offer increased permeability for the attacking pathogens. In the majority of ulcerative colitis patients, the conventional treatment options fail in controlling the symptoms of the disease leading to distressing effects on the quality of life. Such a scenario is due to the failure of conventional therapies to target the loaded moiety into specific diseased sites in the colon. Targeted carriers are needed to address this issue and enhance the drug effects. Conventional nanocarriers are mostly readily cleared and have nonspecific targeting. To accumulate the desired concentration of the therapeutic candidates at the inflamed area of the colon, smart nanomaterials with responsive nature have been explored recently that include pH responsive, reactive oxygen species responsive (ROS), enzyme responsive and thermo – responsive smart nanocarrier systems. The formulation of such responsive smart nanocarriers from nanotechnology scaffolds has resulted in the selective release of therapeutic drugs, avoiding systemic absorption and limiting the undesired delivery of targeting drugs into healthy tissues. Recent advancements in the field of responsive nanocarrier systems have resulted in the fabrication of multi-responsive systems i.e. dual responsive nanocarriers and derivitization that has increased the biological tissues and smart nanocarrier’s interaction. In addition, it has also led to efficient targeting and significant cellular uptake of the therapeutic moieties. Herein, we have highlighted the latest status of the responsive nanocarrier drug delivery system, its applications for on–demand delivery of drug candidates for ulcerative colitis, and the prospects are underpinned.
Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1–/– mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP Myosin Cre+ mice) experienced smaller infarct sizes. Measurements of cardiac adenosine levels demonstrated that postischemic elevations of adenosine persisted during reperfusion after targeting ENTs. Finally, studies in mice with global or myeloid-specific deletion of the Adora2b adenosine receptor (Adora2bloxP/loxP LysM Cre+ mice) implied that Adora2b signaling on myeloid-inflammatory cells in cardioprotection provided by ENT inhibition. These studies reveal a previously unrecognized role for myocyte-specific ENT1 in cardioprotection by enhancing myeloid-dependent Adora2b signaling during reperfusion. Extension of these findings implicates adenosine transporter inhibitors in cardioprotection against ischemia and reperfusion injury.
Effects of Microstate Dynamic Brain Network Disruption in Different Stages of Schizophrenia

Schizophrenia is a heterogeneous mental disorder with unknown etiology or pathological characteristics. Microstate analysis of the electroencephalogram (EEG) signal has shown significant potential value for clinical research. Importantly, significant changes in microstate-specific parameters have been extensively reported; however, these studies have ignored the information interactions within the microstate network in different stages of schizophrenia. Based on recent findings, since rich information about the functional organization of the brain can be revealed by functional connectivity dynamics, we use the first-order autoregressive model to construct the functional connectivity of intra- and intermicrostate networks to identify information interactions among microstate networks. We demonstrate that, beyond abnormal parameters, disrupted organization of the microstate networks plays a crucial role in different stages of the disease by 128-channel EEG data collected from individuals with first-episode schizophrenia, ultrahigh-risk, familial high-risk, and healthy controls. According to the characteristics of the microstates of patients at different stages, the parameters of microstate class A are reduced, those of class C are increased, and the transitions from intra- to intermicrostate functional connectivity are gradually disrupted. Furthermore, decreased integration of intermicrostate information might lead to cognitive deficits in individuals with schizophrenia and those in high-risk states. Taken together, these findings illustrate that the dynamic functional connectivity of intra- and intermicrostate networks captures more components of disease pathophysiology. Our work sheds new light on the characterization of dynamic functional brain networks based on EEG signals and provides a new interpretation of aberrant brain function in different stages of schizophrenia from the perspective of microstates.
The P300 Auditory Evoked Potential: A Physiological Measure of the Engagement of Cognitive Systems Contributing to Listening Effort?

Objectives: This study aimed to explore the potential of the P300 (P3b) as a physiological measure of the engagement of cognitive systems contributing to listening effort. Design: Nineteen right-handed young adults (mean age: 24.79 years) and 20 right-handed older adults (mean age: 58.90 years) with age-appropriate hearing were included. The P300 was recorded at Fz, Cz, and Pz using a two-stimulus oddball paradigm with the Flemish monosyllabic numbers “one” and “three” as standard and deviant stimuli, respectively. This oddball paradigm was conducted in three listening conditions, varying in listening demand: one quiet and two noisy listening conditions (+4 and −2 dB signal to noise ratio [SNR]). At each listening condition, physiological, behavioral, and subjective tests of listening effort were administered. P300 amplitude and latency served as a potential physiological measure of the engagement of cognitive systems contributing to listening effort. In addition, the mean reaction time to respond to the deviant stimuli was used as a behavioral listening effort measurement. Last, subjective listening effort was administered through a visual analog scale. To assess the effects of listening condition and age group on each of these measures, linear mixed models were conducted. Correlation coefficients were calculated to determine the relationship between the physiological, behavioral, and subjective measures. Results: P300 amplitude and latency, mean reaction time, and subjective scores significantly increased as the listening condition became more taxing. Moreover, a significant group effect was found for all physiological, behavioral, and subjective measures, favoring young adults. Last, no clear relationships between the physiological, behavioral, and subjective measures were found. Conclusions: The P300 was considered a physiological measure of the engagement of cognitive systems contributing to listening effort. Because advancing age is associated with hearing loss and cognitive decline, more research is needed on the effects of all these variables on the P300 to further explore its usefulness as a listening effort measurement for research and clinical purposes.
Evidence for a memory advantage for prosocial behaviors

Prior work in the memory domain has shown that certain social information is especially well‐remembered such as information for social targets who cheat. Less work, however, has investigated the extent people remember information for social targets who engage in prosocial behaviors (e.g., helping) in social interactions. The current investigation examines whether there is a memory advantage for social targets who perform prosocial behaviors.
Subunit-Dependent Surface Mobility and Localization of NMDA Receptors in Hippocampal Neurons Measured Using Nanobody Probes

NMDA receptors (NMDARs) are ionotropic glutamate receptors that play a key role in excitatory neurotransmission. The number and subtype of surface NMDARs are regulated at several levels, including their externalization, internalization, and lateral diffusion between the synaptic and extrasynaptic regions. Here, we used novel anti-GFP (green fluorescent protein) nanobodies conjugated to either the smallest commercially available quantum dot 525 (QD525) or the several nanometer larger (and thus brighter) QD605 (referred to as nanoGFP-QD525 and nanoGFP-QD605, respectively). Targeting the yellow fluorescent protein-tagged GluN1 subunit in rat hippocampal neurons, we compared these two probes to a previously established larger probe, a rabbit anti-GFP IgG together with a secondary IgG conjugated to QD605 (referred to as antiGFP-QD605). The nanoGFP-based probes allowed faster lateral diffusion of the NMDARs, with several-fold increased median values of the diffusion coefficient (D). Using thresholded tdTomato-Homer1c signals to mark synaptic regions, we found that the nanoprobe-based D values sharply increased at distances over 100 nm from the synaptic edge, while D values for antiGFP-QD605 probe remained unchanged up to a 400 nm distance. Using the nanoGFP-QD605 probe in hippocampal neurons expressing the GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits, we detected subunit-dependent differences in the synaptic localization of NMDARs, D value, synaptic residence time, and synaptic–extrasynaptic exchange rate. Finally, we confirmed the applicability of the nanoGFP-QD605 probe to study differences in the distribution of synaptic NMDARs by comparing to data obtained with nanoGFPs conjugated to organic fluorophores, using universal point accumulation imaging in nanoscale topography and direct stochastic optical reconstruction microscopy. SIGNIFICANCE STATEMENT Our study systematically compared the localization and mobility of surface NMDARs containing GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits expressed in rodent hippocampal neurons, using anti-green fluorescent protein (GFP) nanobodies conjugated to the quantum dot 605 (nanoGFP-QD605), as well as nanoGFP probes conjugated with small organic fluorophores. Our comprehensive analysis showed that the method used to delineate the synaptic region plays an important role in the study of synaptic and extrasynaptic pools of NMDARs. In addition, we showed that the nanoGFP-QD605 probe has optimal parameters for studying the mobility of NMDARs because of its high localization accuracy comparable to direct stochastic optical reconstruction microscopy and longer scan time compared with universal point accumulation imaging in nanoscale topography. The developed approaches are readily applicable to the study of any GFP-labeled membrane receptors expressed in mammalian neurons.
Choice of intrapleural fibrinolytic agents in the treatment of adult complicated parapneumonic effusion and empyema: Network meta-analysis

Background The appropriate use of intrapleural fibrinolytic agents in patients with complicated parapneumonic effusion and empyema remains unclear, especially regarding the choice of fibrinolytic agents. We conducted a network meta-analysis comparing outcomes of intrapleural fibrinolytic agents in patients with complicated parapneumonic effusion and empyema. Methods MEDLINE and EMBASE were searched through April 2022 to identify randomized controlled trials (RCTs) that investigated outcomes in patients with complicated parapneumonic effusion or empyema who were treated with intrapleural fibrinolytic agents. The outcomes of interest were surgical requirements, bleeding, length of hospital stay, and all-cause mortality. Results Our analysis included 10 RCTs that enrolled 1085 patients treated with intrapleural tissue plasminogen activator (TPA) (n = 138), TPA + deoxyribonuclease (DNase) (n = 52), streptokinase (n = 311), urokinase (n = 75), DNase (n = 51), or placebo (n = 458). The rates of surgical requirement were significantly lower with TPA and TPA + DNase than with placebo (risk ratio [RR]; 95% confidence interval [CI] = 0.36 [0.14–0.97], p = 0.038, RR [95% CI] = 0.25 [0.08–0.78], p = 0.017, respectively). The risk of bleeding was higher with TPA + DNase than with placebo (RR [95% CI] = 10.91 [1.53–77.99], p = 0.017), as well as TPA and TPA + DNase than with urokinase (RR [95% CI] = 17.90 [1.07–299.44], p = 0.044, RR [95% CI] = 89.3 [2.88–2772.49], p = 0.010, respectively). All-cause mortality was similar among the groups. Conclusion TPA and TPA + DNase reduced the rates of surgical requirement compared with placebo. However, TPA + DNase increased the risk of bleeding compared with placebo. Intrapleural agents for complicated parapneumonic effusion and empyema should be selected with an individual risk assessment.
Textbook outcomes in liver surgery for gallbladder cancer patients treated with curative-intent resection: a multicenter observational study

Background: Cholecystectomy, hepatectomy, and lymphadenectomy are recommended as the curative treatment for resectable gallbladder cancer (GBC). Textbook outcomes in liver surgery (TOLS) is a novel composite measure that has been defined by expert consensus to represent the optimal postoperative course after hepatectomy. This study aimed to determine the incidence of TOLS and the independent predictors associated with TOLS after curative-intent resection in GBC patients. Methods: All consecutive GBC patients who underwent curative-intent resection between 2014 and 2020 were enrolled from a multicenter database from 11 hospitals as the training and the internal testing cohorts, and Southwest Hospital as the external testing cohort. TOLS was defined as no intraoperative grade greater than or equal to 2 incidents, no grade B/C postoperative bile leaks, no postoperative grade B/C liver failure, no 90-day postoperative major morbidity, no 90-day readmission, no 90-day mortality after hospital discharge, and R0 resection. Independent predictors of TOLS were identified using logistic regression and were used to construct the nomogram. The predictive performance was assessed using the area under the curve and calibration curves. Results: TOLS was achieved in 168 patients (54.4%) and 74 patients (57.8%) from the training and internal testing cohorts, and the external testing cohort, respectively. On multivariate analyses, age less than or equal to 70 years, absence of preoperative jaundice (total bilirubin≤3 mg/dl), T1 stage, N0 stage, wedge hepatectomy, and no neoadjuvant therapy were independently associated with TOLS. The nomogram that incorporated these predictors demonstrated excellent calibration and good performance in both the training and external testing cohorts (area under the curve: 0.741 and 0.726). Conclusions: TOLS was only achieved in approximately half of GBC patients treated with curative-intent resection, and the constructed nomogram predicted TOLS accurately.
Essential Tremor – Deep Brain Stimulation vs. Focused Ultrasound

ABSTRACT Introduction Essential Tremor (ET) is one of the most common tremor syndromes typically presented as action tremor, affecting mainly the upper limbs. In at least 30–50% of patients, tremor interferes with quality of life, does not respond to first-line therapies and/or intolerable adverse effects may occur. Therefore, surgery may be considered. Areas Covered In this review, the authors discuss and compare unilateral ventral intermedius nucleus deep brain stimulation (VIM DBS) and bilateral DBS with Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy, which comprises focused acoustic energy generating ablation under real-time MRI guidance. Discussion includes their impact on tremor reduction and their potential complications. Finally, the authors provide their expert opinion. Expert opinion DBS is adjustable, potentially reversible and allows bilateral treatments; however, it is invasive requires hardware implantation, and has higher surgical risks. Instead, MRgFUS is less invasive, less expensive, and requires no hardware maintenance. Beyond these technical differences, the decision should also involve the patient, family, and caregivers.
Unified NDP method based on TD(0) learning for both average and discounted Markov decision processes

Motivated by the need of practical large-scale Markov systems,we considered in this paper the learning optimization problems for Markov decision processes(MDPs). Based on the definition of performance potentials,a unified formula of temporal difference is provided for both average and discounted performance criteria.A neural network is then used to represent the estimation of potentials,both the parameterized TD(0) learning formulas and algorithm are also derived for approximating the policy evaluation.By the approximation values of potentials and approximation policy iteration,a unified neuro-dynamic programming(NDP) optimization approach is consequently proposed for both two criteria.The obtained results can be extended to semi-Markov decision processes,and a numerical example is finally used to illustrate the application of the proposed neuro-policy iteration algorithm for both average and discounted criteria.The example also shows that the average problem is the limitation case of the discount ones as discount factor goes to zero.
Design and Performance Analysis of a Bioelectronic Controlled Hybrid Serial-Parallel Wrist Exoskeleton

Wrist exoskeletons are increasingly being used in the rehabilitation of stroke and hand dysfunction because of its ability to assist patients in high intensity, repetitive, targeted and interactive rehabilitation training. However, the existing wrist exoskeletons cannot effectively replace the work of therapist and improve hand function, mainly because the existing exoskeletons cannot assist patients to perform natural hand movement covering the entire physiological motor space (PMS). Here, we present a bioelectronic controlled hybrid serial-parallel wrist exoskeleton HrWr-ExoSkeleton (HrWE) which is based on the PMS design guidance, the gear set can carry out forearm pronation/supination (P/S) and the 2-DoF parallel configuration fixed on the gear set can carry out wrist flexion/extension (F/E) and radial/ulnar deviation (R/U). This special configuration not only provides enough range of motion (RoM) for rehabilitation training (85F/85E, 55R/55U, and 90P/90S), but also makes it easier to provide the interface for finger exoskeletons and be adapted to upper limb exoskeletons. In addition, to further improve the rehabilitation effect, we propose a HrWE-assisted active rehabilitation training platform based on surface electromyography signals.
Arf1-PI4KIIIβ positive vesicles regulate PI(3)P signaling to facilitate lysosomal tubule fission

Boutry et al. show that Arf1-PI4KIIIβ positive vesicles participate in the fission of lysosomal tubules through lysosomal PI(3)P regulation. This work identifies new components involved in the scission of lysosomal tubules and demonstrates that this process requires an exquisite regulation of phosphoinositides on lysosomes.