Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive mechanisms of inhibitory control deficits in autism spectrum disorder

BACKGROUND Inhibitory control deficits are common in autism spectrum disorder (ASD) and associated with more severe repetitive behaviors. Inhibitory control deficits may reflect slower execution of stopping processes, or a reduced ability to delay the onset of behavioral responses in contexts of uncertainty. Previous studies have documented relatively spared stopping processes in ASD, but whether inhibitory control deficits in ASD reflect failures to delay response onset has not been systematically assessed. Further, while improvements in stopping abilities and response slowing are seen through adolescence/early adulthood in health, their development in ASD is less clear. METHODS A stop-signal test (SST) was administered to 121 individuals with ASD and 76 age and IQ-matched healthy controls (ages 5-28). This test included 'GO trials' in which participants pressed a button when a peripheral target appeared and interleaved 'STOP trials' in which they were cued to inhibit button-presses when a stop-signal appeared at variable times following the GO cue. STOP trial accuracy, RT of the stopping process (SSRT), and reaction time (RT) slowing during GO trials were examined. RESULTS Relative to controls, individuals with ASD had reduced accuracy on STOP trials. SSRTs were similar across control and ASD participants, but RT slowing was reduced in patients compared to controls. Age-related increases in stopping ability and RT slowing were attenuated in ASD. Reduced stopping accuracy and RT slowing were associated with more severe repetitive behaviors in ASD. DISCUSSION Our findings show that inhibitory control deficits in ASD involve failures to strategically delay behavioral response onset. These results suggest that reduced preparatory behavioral control may underpin inhibitory control deficits as well as repetitive behaviors in ASD. Typical age-related improvements in inhibitory control during late childhood/early adolescence are reduced in ASD, highlighting an important developmental window during which treatments may mitigate cognitive alterations contributing to repetitive behaviors.
Myeloid cells are tunable by a polyanionic polysaccharide derivative and co‐determine host rescue from lethal virus infection

Insight into molecular and cellular mechanisms of innate immunity is critical to understand viral pathogenesis and immunopathology and might be exploited for therapy. Whereas the molecular mechanisms of the IFN defense are well established, cellular mechanisms of antiviral immunity are only emerging, and their pharmacological triggering remains unknown. COAM is a polysaccharide derivative with antiviral activity but without comprehension about its mechanism of action. The COAM mixture was fractionated, and prophylactic treatment of mice with COAM polymers of high MW resulted in a conversion from 100% lethal mengovirus infection to an overall survival rate of 93% without obvious clinical sequelae. Differential and quantitative analysis of peritoneal leukocytes demonstrated that COAM induced a profound influx of neutrophils. Selective cell depletion experiments pointed toward neutrophils and macrophages as key effector cells in the rescue of mice from lethal mengovirus. COAM was able to induce mRNA and protein expression of the mouse neutrophil chemokine GCP‐2. Binding of GCP‐2 to COAM was demonstrated in solution and confirmed by SPR technology. Although COAM was not chemotactic for neutrophils, COAM‐anchored muGCP‐2 retained chemotactic activity for human and mouse neutrophils. In conclusion, this study established that COAM rescued mice from acute and lethal mengovirus infection by recruiting antiviral leukocytes to the site of infection, as proposed through the induction, binding, and concentration of endogenous chemokines. These findings reinforce the role of neutrophils and macrophages as critical cells that can be manipulated toward antiviral defense.
Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression.

BACKGROUND There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG). OBJECTIVE We aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype. DESIGN Our study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG-negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases. RESULTS During 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (≥2 servings/wk compared with <1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes (P-heterogeneity = 0.79). Inverse probability weighting did not materially change the results. CONCLUSIONS Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers. In particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease.
A brief history of fetal echocardiography and its impact on the management of congenital heart disease

Congenital heart disease (CHD), the most common congenital malformation, is associated with adverse outcome. Development of fetal echocardiography has made prenatal diagnosis of CHD a reality, and in the process revolutionized its management. This historical review briefly narrates this development over the decades focusing on the emergence of the primary modalities of fetal echocardiography comprised of the time‐motion mode, two‐dimensional B‐mode, spectral Doppler, color Doppler, and three‐ and four‐dimensional cardiac imaging. Collaboration between clinicians and engineers has been central to these advances. Also discussed are the accuracy and impact of fetal echocardiography on the management of CHD, and especially its role in the prenatal diagnosis of critical CHD in individualizing the management and improving the outcome. Despite these advances, most cases of CHD are not identified prenatally, emphasizing the continuing need for further technological and educational innovation and improvement.
Disulfide isomerase activity of the dynamic, trimeric Proteus mirabilis ScsC protein is primed by the tandem immunoglobulin-fold domain of ScsB

Correct disulfide bond formation is essential for proper folding of many proteins, including bacterial virulence factors. The suppressor of copper sensitivity (Scs) proteins have roles in dithiol/disulfide interchange and the bacterial response to copper stress. Encoded in a four-gene cassette (ScsABCD) present in many Gram-negative bacteria, the Scs proteins are enigmatic and poorly characterized. Here, we show that the periplasmic α-domain of the membrane protein ScsB in the Gram-negative bacterium Proteus mirabilis forms a redox relay with the soluble periplasmic protein PmScsC. We also found that the periplasmic α-domain is sufficient to activate the disulfide isomerase activity of PmScsC. The crystal structure of PmScsBα at a resolution of 1.54 Å revealed that it comprises two structurally similar immunoglobulin-like folds, one of which includes a putative redox-active site with the sequence CXXXC. We confirmed the importance of these cysteine residues for PmScsBα function, and in addition, we engineered cysteine variants that produced a stable complex between PmScsC and PmScsBα. Using small-angle X-ray and neutron scattering analyses with contrast variation, we determined a low-resolution structure of the PmScsC–PmScsBα complex. The structural model of this complex suggested that PmScsBα uses both of its immunoglobulin-like folds to interact with PmScsC and revealed that the highly dynamic PmScsC becomes ordered upon PmScsBα binding. These findings add to our understanding of the poorly characterized Scs proteins.
Internet-Delivered Acceptance-Based Cognitive-Behavioral Intervention for Social Anxiety Disorder With and Without Therapist Support: A Randomized Trial

Social anxiety disorder (SAD) is one of the most prevalent psychiatric disorders in the United States. Although evidenced-based behavioral treatments are available, less than 20% of those with SAD receive treatment. Internet-based interventions can address barriers to treatment access, and guided Internet-based treatments have been demonstrated to be effective for SAD. However, the optimal role (if any) of the therapist in such programs remains unclear. We examined the acceptability and efficacy of a novel Internet-based cognitive-behavior therapy for SAD that utilizes traditional behavioral interventions (e.g., exposure) within the context of a model emphasizing mindfulness and psychological acceptance. Forty-two participants were randomized to an eight-module self-help intervention with (n = 20) or without (n = 22) adjunctive therapist support; the therapist support was delivered through 10 to 15 min of weekly videoconferencing and daily text messages. Both groups experienced a significant reduction in SAD symptoms and improvements in functioning and quality of life, with no significant differences between groups in both completer-only and intent-to-treat analyses. However, the therapist support group evidenced lower attrition than the minimal support group (20% vs. 50%). Implications for dissemination and future directions are discussed.
Effect of Carbon Nanotubes as Thermal Interface Materials on Thermal Conductivity Using Electrophoretic Deposition

Thermal interface materials (TIM) involve heat removal from electronic devices. It is used to remove heat sink from the heat sources to prolong the operation system of a device. It normally replaces the thermally insulated air between the two surfaces and uses it as a secondary thermal conductive material. The current thermal conductivity of TIM is considered to be a limitation for the development of advance electronic devices. In this study, the performance of carbon nanotubes (CNTs) which were used as TIM was investigated by using electrophoretic deposition method. The deposition of CNTs was varied from one to six layers and the performance of deposition was evaluated. The stable suspension of CNTs in DMF with zeta potential reading of –35.87 mV give rise to a smooth and uniform deposition on nickel plated copper substrate (heat spreader) with the usage of electrophoretic deposition (EPD). Maximum layers of CNTs deposition were obtained at six layers with 56.95 μm of deposition thickness and 11.0 mg of deposition weight. Thermal conductivity was measured using a thermal analyser while the thickness of deposition was observed using scanning electron microscope (SEM). The employment of CNTs improved the heat removal of TIM with thermal conductivity reading of 27.08 W m–1 K–1. Optimisation studies revealed that EPD operated at an applied voltage of 175 V coupled with 10 min deposition time produced a single layer deposition with the thickness of 14.14 μm.
Random fiber lasers based on artificially controlled backscattering fibers

The random fiber laser (RFL) which is a milestone in laser physics and nonlinear optics, has attracted considerable attention recently. Most previous RFLs are based on distributed feedback of Rayleigh scattering amplified through stimulated Raman/Brillouin scattering effect in single mode fibers, which required long-distance (tens of kilometers) single mode fibers and high threshold up to watt-level due to the extremely small Rayleigh scattering coefficient of the fiber. We proposed and demonstrated a half-open cavity RFL based on a segment of a artificially controlled backscattering SMF(ACB-SMF) with a length of 210m, 310m or 390m. A fiber Bragg grating with the central wavelength of 1530nm and a segment of ACB-SMF forms the half-open cavity. The proposed RFL achieves the threshold of 25mW, 30mW and 30mW, respectively. Random lasing at the wavelength of 1530nm and the extinction ratio of 50dB is achieved when a segment of 5m EDF is pumped by a 980nm LD in the RFL. Another half-open cavity RFL based on a segment of a artificially controlled backscattering EDF(ACBS-EDF) is also demonstrated without an ACB-SMF. The 3m ACB-EDF is fabricated by using the femtosecond laser with pulse energy of 0.34mJ which introduces about 50 reflectors in the EDF. Random lasing at the wavelength of 1530nm is achieved with the output power of 7.5mW and the efficiency of 1.88%. Two novel RFLs with much short cavities have been achieved with low threshold and high efficiency.
Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System

Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and bronchodilator drugs. Despite the availability of multiple treatments, both diseases are growing public health concerns. The majority of asthma patients are well controlled on current inhaled therapies but a substantial number of patients with severe asthma are not. Asthma affects an estimated 300 million people worldwide and approximately 20 percent have a severe form of the disease. In contrast to asthma, there are few effective therapies for COPD. An estimated 10% of the population has COPD and the trend in death rates is increasing for COPD while decreasing for other major diseases. Although developing drugs for inhaled delivery is challenging, the nose-only inhalation unit enables direct delivery of novel drugs to the lung of rodents for pre-clinical efficacy and safety/toxicology studies. Inhaled drug delivery has multiple advantages for respiratory diseases, where high concentration in the lung improves efficacy and minimizes systemic side effects. Inhaled corticosteroids and bronchodilators benefit from these advantages and inhaled delivery may also hold potential for future biologic therapies. The inhalation unit described herein can generate, sample for characterization, and uniformly deposit a drug aerosol in the lungs of rodents. This enables the pre-clinical determination of the efficacy and safety of drug doses deposited in the lungs of rodents, key data required before initiating clinical development.
Consensus of high-order multi-agent systems with input and communication delays-state feedback case

We study in this paper the consensus problem for multi-agent systems with agents characterized by high-order linear systems with time delays in both the communication network and inputs. Provided that the open-loop dynamics of the agents is not exponentially unstable, but may be polynomially unstable, and the communication topology contains a directed spanning tree, a truncated predictor feedback approach is established to solve the consensus problem. It is shown that, if the delays are constant and exactly known, the consensus problem can be solved by state feedback protocols for arbitrarily large bounded delays. If it is further assumed that the open-loop dynamics of the agents only contains zero eigenvalues, the delays are allowed to be time-varying and unknown. Numerical examples are worked out to illustrate the effectiveness of the proposed approaches.
An Effective Antiviral Approach Targeting Hepatitis B Virus with NJK14047, a Novel and Selective Biphenyl Amide p38 Mitogen-Activated Protein Kinase Inhibitor

ABSTRACT Despite recent advances in therapeutic strategies against hepatitis B virus (HBV) infection, chronic hepatitis B remains a major global health burden. Recent studies have shown that targeting host factors instead of viral factors can be an effective antiviral strategy with low risk of the development of resistance. Efforts to identify host factors affecting viral replication have identified p38 mitogen-activated protein kinase (MAPK) as a possible target for antiviral strategies against various viruses, including HBV. Here, a series of biphenyl amides were synthesized as novel p38 MAPK selective inhibitors and assessed for their anti-HBV activities. The suppression of HBV surface antigen (HBsAg) production by these compounds was positively correlated with p38 MAPK-inhibitory activity. The selected compound NJK14047 displayed significant anti-HBV activity, as determined by HBsAg production, HBeAg secretion, and HBV production. NJK14047 efficiently suppressed the secretion of HBV antigens and HBV particles from HBV genome-transfected cells and HBV-infected sodium taurocholate cotransporting polypeptide-expressing human hepatoma cells. Furthermore, NJK14047 treatment resulted in a significant decrease of pregenomic RNA and covalently closed circular DNA (cccDNA) of HBV in HBV-harboring cells, indicating its ability to inhibit HBV replication. Considering that suppression of HBsAg secretion and elimination of cccDNA of HBV are the major aims of anti-HBV therapeutic strategies, the results suggested the potential use of these compounds as a novel class of anti-HBV agents targeting host factors critical for viral infection.
Motor System Activation Predicts Goal Imitation in 7-Month-Old Infants

The current study harnessed the variability in infants’ neural and behavioral responses as a novel method for evaluating the potential relations between motor system activation and social behavior. We used electroencephalography (EEG) to record neural activity as 7-month-old infants observed and responded to the actions of an experimenter. To determine whether motor system activation predicted subsequent imitation behavior, we assessed event-related desynchronization (ERD) at central sites during action observation as a function of subsequent behavior. Greater mu desynchronization over central sites was observed when infants subsequently reproduced the experimenter’s goal than when they did not reproduce the goal and instead selected the nongoal object. We also found that mu desynchronization during action execution predicted the infants’ later propensity to reproduce the experimenter’s goal-directed behavior. These results provide the first evidence that motor system activation predicts the imitation of other individuals’ goals during infancy.
Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion

Significance Affective disorders are associated with increased cardiovascular mortality and enhanced negative emotion. Although neuroimaging studies of such disorders reveal dysregulation in numerous frontal brain regions, including the subgenual/perigenual cingulate cortices (areas 25 and 32), the causal involvement of this dysregulation is unknown, and translation from rodent studies is limited. Here we demonstrate that, in the marmoset monkey, inactivation of area 25 increases parasympathetic modulation of resting cardiovascular function and decreases the cardiovascular and behavioral correlates of negative emotion. In contrast, area 32 inactivation increases these correlates. These findings provide causal evidence that these primate areas differentially regulate negative emotion, and link the cardiovascular symptomatology of affective disorders to central neural, rather than peripheral cardiac, dysfunction. Disorders of dysregulated negative emotion such as depression and anxiety also feature increased cardiovascular mortality and decreased heart-rate variability (HRV). These disorders are correlated with dysfunction within areas 25 and 32 of the ventromedial prefrontal cortex (vmPFC), but a causal relationship between dysregulation of these areas and such symptoms has not been demonstrated. Furthermore, cross-species translation is limited by inconsistent findings between rodent fear extinction and human neuroimaging studies of negative emotion. To reconcile these literatures, we applied an investigative approach to the brain–body interactions at the core of negative emotional dysregulation. We show that, in marmoset monkeys (a nonhuman primate that has far greater vmPFC homology to humans than rodents), areas 25 and 32 have causal yet opposing roles in regulating the cardiovascular and behavioral correlates of negative emotion. In novel Pavlovian fear conditioning and extinction paradigms, pharmacological inactivation of area 25 decreased the autonomic and behavioral correlates of negative emotion expectation, whereas inactivation of area 32 increased them via generalization. Area 25 inactivation also increased resting HRV. These findings are inconsistent with current theories of rodent/primate prefrontal functional similarity, and provide insight into the role of these brain regions in affective disorders. They demonstrate that area 32 hypoactivity causes behavioral generalization relevant to anxiety, and that area 25 is a causal node governing the emotional and cardiovascular symptomatology relevant to anxiety and depression.
Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia

ABSTRACT β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients.
Crystal structure evolution via operando neutron diffraction during long-term cycling of a customized 5 V full Li-ion cylindrical cell LiNi0.5Mn1.5O4vs. graphite

Disordered spinel LiNi0.5Mn1. 5O4 (d-LNMO) is the cathode material of choice for next generation batteries based on 5 V systems. Unfortunately, once cycled under real conditions i.e. in a full-cell configuration (versus graphite), it displays a quite pronounced fading of the electrochemical performance, even under optimized cycling conditions, and about a half of the specific charge is ‘lost’ after 500 cycles. Thus, we intensively investigated the crystal structure evolution of a full-cell d-LNMO vs. graphite by means of operando neutron diffraction. For this purpose, a new cylindrical electrochemical cell was designed, suitable for operando neutron diffraction studies and allowing for precise Rietveld refinement analyses. During the first cycle, lithium content in the electrode materials (graphite and d-LNMO) could be determined, thus, allowing an estimation of the lithium consumption in side reactions. The neutron diffraction data obtained after long-term cycling (100 cycles) show that the fading of the electrochemical performance can be attributed to an insufficient amount of lithium in the system, which presumably is consumed by side reactions since no structural damage was observed in the positive and negative electrodes.