Miracle-dz/UniFAR-FTUs huggingface dataset:
A Survivor in the Era of Large-Scale Pretraining: An Empirical Study of One-Stage Referring Expression Comprehension

One-stage Referring Expression Comprehension (REC) is a task that requires accurate alignment between text descriptions and visual content. In recent years, numerous efforts have been devoted to cross-modal learning for REC, while the influence of other factors in this task still lacks a systematic study. To fill this gap, we conduct an empirical study in this article. Concretely, we ablate 42 candidate designs/settings based on a common REC framework, and these candidates cover the entire process of one-stage REC from network design to model training. Afterwards, we conduct over 100 experimental trials on three REC benchmark datasets. The extensive experimental results reveal the key factors that affect REC performance in addition to multi-modal fusion, e.g., multi-scale features and data augmentation. Based on these findings, we further propose a simple yet strong model called SimREC, which achieves new state-of-the-art performance on these benchmarks. In addition to these progresses, we also find that with much less training overhead and parameters, SimREC can achieve better performance than a set of large-scale pre-trained models, e.g., UNITER and VILLA, portraying the special role of REC in existing V&L research.
Association between treatment effect on C‐peptide preservation and HbA1c in meta‐analysis of glutamic acid decarboxylase (GAD)‐alum immunotherapy in recent‐onset type 1 diabetes

Preservation of insulin secretion in type 1 diabetes (T1D) lowers the risk of complications such as retinopathy and severe hypoglycaemia. C-peptide preservation—a biomarker for endogenous insulin secretion—is used as a surrogate endpoint in clinical trials assessing beta cell-preserving therapies. Showing efficacy on clinical outcomes such as severe hypoglycaemia has proven challenging given their rarity shortly after diagnosis. Here, we show that treatment effect on C-peptide correlates with treatment effect on HbA1c, a validated surrogate endpoint, in individuals treated with recombinant human glutamic acid decarboxylase 65 kDa in alum (GAD-alum). A retrospective post hoc meta-analysis and prospective phase IIb trial, where the human leukocyte antigen (HLA)-specific analyses of the topline results were specified before database lock, have shown the efficacy of GAD-alum for stimulated C-peptide preservation in the genetic subpopulation of T1D patients carrying HLA DR3-DQ2. Efficacy for reducing HbA1c and added benefit of more doses have also been observed in the HLA DR3-DQ2–carrying probable responder population. A phase III trial in recent-onset T1D patients carrying HLA DR3-DQ2 (DIAGNODE-3, NCT05018585) with the coprimary endpoints of C-peptide and HbA1c is ongoing. Our research objective was to assess whether 15-month treatment effects on preservation of endogenous insulin production were correlated with treatment effects on blood glucose measured by HbA1c.
CD44 mediates shear stress mechanotransduction in an in vitro blood‐brain barrier model through small GTPases RhoA and Rac1

Fluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the effect of shear on the blood‐brain barrier (BBB) have yet to be clarified in cerebral vasculature despite its importance for brain homeostasis. The goal of this study is to probe components of shear mechanotransduction within the BBB to gain a better understanding of pathologies associated with changes in cerebral perfusion including ischemic stroke. Interrogating the effects of shear stress in vivo is complicated by the complexity of factors in the brain parenchyma and the difficulty associated with modulating blood flow regimes. The in vitro model used in this study is compatible with real‐time measurement of barrier function using a transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level of shear stress required for barrier formation and that the composition of the extracellular matrix, specifically the presence of high molecular weight hyaluronan, dictates the flow response. Gene editing to modulate the expression of CD44, a mechanosensitive receptor for hyaluronan, demonstrates that the receptor is required for the endothelial response to shear stress. Manipulation of small GTPase activity reveals CD44 activates Rac1 while inhibiting RhoA activation. Additionally, adducin‐γ localizes to tight junctions in response to shear stress and RhoA inhibition and is required to maintain the barrier. This study identifies specific components of the mechanosensing complex associated with the BBB response to fluid shear stress and, therefore, illuminates potential targets for barrier manipulation in vivo.
Plasma CD16+ Extracellular Vesicles Associate with Carotid Artery Intima-Media Thickness in HIV+ Adults on Combination Antiretroviral Therapy

HIV-infected individuals have a 2-fold-increased risk of cardiovascular disease compared with the general population, yet the mechanisms underlying this comorbidity are unclear. Extracellular vesicles have emerged as important mediators in cell-cell communication and, given what we know of their biology, may drive inflammation contributing to cardiovascular disease in this vulnerable population. ABSTRACT HIV-infected individuals have increased risk for cardiovascular disease (CVD) despite suppressive antiretroviral therapy (ART). This is likely a result of persistent immune activation and systemic inflammation. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and may drive inflammation contributing to CVD. EVs were characterized in plasma from 74 HIV-infected individuals on combination antiretroviral therapy (cART) and 64 HIV-uninfected controls with paired carotid intima-media thickness (cIMT) assessment. EVs were profiled with markers reflecting lymphoid, myeloid, and endothelial origin. Seventeen plasma inflammatory biomarkers were also assessed. Human umbilical vein endothelial cell (HUVEC) apoptosis was quantified after EV exposure. A significant correlation was observed in HIV-infected participants between cIMT and EVs expressing CD16, and the monocyte-related markers CD4, CD14, and CX3CR1 showed a similar but nonsignificant association with cIMT. No significant correlation between cIMT measurements from HIV-uninfected individuals and EVs was observed. Levels of serum amyloid A, C-reactive protein, and myeloperoxidase significantly correlated with CD14+, CD16+, and CX3CR1+ EVs. No correlation was noted between cIMT and soluble inflammatory markers. HUVECs showed increased necrosis after exposure to the EV-containing fraction of plasma derived from HIV-infected individuals compared to uninfected controls. Our study reveals that EVs expressing monocyte markers correlated with cIMT in HIV-infected individuals on cART. Moreover, EV fractions derived from HIV-infected individuals lead to greater endothelial cell death via necrotic pathways. Collectively, EVs have potential as biomarkers of and therapeutic targets in the pathogenesis of CVD in the setting of treated HIV disease. IMPORTANCE HIV-infected individuals have a 2-fold-increased risk of cardiovascular disease compared with the general population, yet the mechanisms underlying this comorbidity are unclear. Extracellular vesicles have emerged as important mediators in cell-cell communication and, given what we know of their biology, may drive inflammation contributing to cardiovascular disease in this vulnerable population.
Axial Magnetic Fields, Axial Force, and Losses in the Stator Core and Clamping Structure of a Synchronous Generator with Axially Displaced Stator

Abstract Axial displacement of the stator in a synchronous machine gives rise to axial magnetic field both at the ends and deep inside the stator. The axial magnetic field causes losses. This article contains results from two studies with an axially displaced stator. In the first study, axial magnetic leakage fields in the ends of a small synchronous generator at load and no load were measured and simulated. In the second study, axial force and iron losses at no load were calculated with non-linear materials and a three-dimensional, time-stepped finite element method. For some machines with vertical shafts, the sum of iron losses and thrust bearing losses can be reduced if the rotor is lowered or the stator raised, whichever is best.
Soil Properties and Moisture Synergistically Influence Nontuberculous Mycobacterial Prevalence in Natural Environments of Hawai’i

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment, being found commonly in soils and natural bodies of freshwater. However, little is known about the environmental niches of NTM and how they relate to NTM prevalence in homes and other human-dominated areas. ABSTRACT Nontuberculous mycobacteria (NTM) are opportunistic pathogens that cause chronic pulmonary disease (PD). NTM infections are thought to be acquired from the environment; however, the basal environmental factors that drive and sustain NTM prevalence are not well understood. The highest prevalence of NTM PD cases in the United States is reported from Hawai’i, which is unique in its climate and soil composition, providing an opportunity to investigate the environmental drivers of NTM prevalence. We used microbiological sampling and spatial logistic regression complemented with fine-scale soil mineralogy to model the probability of NTM presence across the natural landscape of Hawai’i. Over 7 years, we collected and microbiologically cultured 771 samples from 422 geographic sites in natural areas across the Hawaiian Islands for the presence of NTM. NTM were detected in 210 of these samples (27%), with Mycobacterium abscessus being the most frequently isolated species. The probability of NTM presence was highest in expansive soils (those that swell with water) with a high water balance (>1-m difference between rainfall and evapotranspiration) and rich in Fe-oxides/hydroxides. We observed a positive association between NTM presence and iron in wet soils, supporting past studies, but no such association in dry soils. High soil-water balance may facilitate underground movement of NTM into the aquifer system, potentially compounded by expansive capabilities allowing crack formation under drought conditions, representing further possible avenues for aquifer infiltration. These results suggest both precipitation and soil properties are mechanisms by which surface NTM may reach the human water supply. IMPORTANCE Nontuberculous mycobacteria (NTM) are ubiquitous in the environment, being found commonly in soils and natural bodies of freshwater. However, little is known about the environmental niches of NTM and how they relate to NTM prevalence in homes and other human-dominated areas. To characterize NTM environmental associations, we collected and cultured 771 samples from 422 geographic sites in natural areas across Hawai’i, the U.S. state with the highest prevalence of NTM pulmonary disease. We show that the environmental niches of NTM are most associated with highly expansive, moist soils containing high levels of iron oxides/hydroxides. Understanding the factors associated with NTM presence in the natural environment will be crucial for identifying potential mechanisms and risk factors associated with NTM infiltration into water supplies, which are ultimately piped into homes where most exposure risk is thought to occur.
KV1/D‐type potassium channels inhibit the excitability of bronchopulmonary vagal afferent nerves

The KV1/D‐type potassium current (ID) is an important determinant of neuronal excitability. This study explored whether and how ID channels regulate the activation of bronchopulmonary vagal afferent nerves. The single‐neuron RT‐PCR assay revealed that nearly all mouse bronchopulmonary nodose neurons expressed the transcripts of α‐dendrotoxin (α‐DTX)‐sensitive, ID channel‐forming KV1.1, KV1.2 and/or KV1.6 α‐subunits, with the expression of KV1.6 being most prevalent. Patch‐clamp recordings showed that ID, defined as the α‐DTX‐sensitive K+ current, activated at voltages slightly more negative than the resting membrane potential in lung‐specific nodose neurons and displayed little inactivation at subthreshold voltages. Inhibition of ID channels by α‐DTX depolarized the lung‐specific nodose neurons and caused an increase in input resistance, decrease in rheobase, as well as increase in action potential number and firing frequency in response to suprathreshold current steps. Application of α‐DTX to the lungs via trachea in the mouse ex vivo vagally innervated trachea–lungs preparation led to action potential discharges in nearly half of bronchopulmonary nodose afferent nerve fibres, including nodose C‐fibres, as detected by the two‐photon microscopic Ca2+ imaging technique and extracellular electrophysiological recordings. In conclusion, ID channels act as a critical brake on the activation of bronchopulmonary vagal afferent nerves by stabilizing the membrane potential, counterbalancing the subthreshold depolarization and promoting the adaptation of action potential firings. Down‐regulation of ID channels, as occurs in various inflammatory diseases, may contribute to the enhanced C‐fibre activity in airway diseases that are associated with excessive coughing, dyspnoea, and reflex bronchospasm and secretions.
Herpes zoster in the era of COVID 19: A prospective observational study to probe the association of herpes zoster with COVID 19 infection and vaccination

Herpes zoster (HZ) is caused by reactivation of the latent varicella zoster virus (VZV) following decline in cell‐mediated immunity. All over the world, in the past couple of years, the Corona Virus 2019 (COVID‐19) has emerged as a viral cause of severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) infection. Based on the current limited evidence, co‐infection of COVID‐19 with VZV or reactivation of VZV after COVID‐19 vaccination has been sporadically reported. All patients diagnosed with HZ, in Farwaniya Hospital in Kuwait, from March 2020 to July 2021, having either (A) a positive COVID‐19 polymerase chain reaction (PCR) test, or (B) been vaccinated against SARS‐CoV‐2 were enrolled in the study. All patients' demographic information, medical history, laboratory findings, and vaccination status was documented. All statistical analyses were performed using SPSS Statistics version 21.0 software. Twelve cases infected with COVID‐19 with a positive PCR (group 1) and five cases vaccinated against SARS‐CoV‐2 (group 2) were documented. Out of the 12 COVID‐19 infected patients (group 1), only two patients (16.67%) required hospitalization, while the remaining 10 patients had mild/moderate lymphopenia. Furthermore, amongst the 12 positive COVID‐19 cases, four patients with HZ were diagnosed within the first week of COVID‐19, while the remaining eight cases were diagnosed within 8 weeks of COVID‐19. Thoracic segments were affected in five cases (41.67%), cervical in one case (8.33%), cranial in two cases (16.67%), lumbar in three cases (25%) and sacral in one case (8.33%). In group 2, three patients presented with HZ within 4 weeks of having received the first dose of the vaccine and two patients after the second dose. Blood investigations for all five vaccinated patients did not show any abnormalities. Cervical segments were affected in two patients (40%), and cranial, thoracic, and lumbar segment in the remaining patients respectively (20%). Experts must be aware of the probable increased risk of HZ during the COVID 19 pandemic. We propose appropriate curative and preventive measures against HZ infection, including a systematic follow‐up of these patients to ensure that they stick to extreme safety measures till the diagnosis of COVID‐19 is omitted.
The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass

ABSTRACT Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals’ metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.
Awareness of Heated Tobacco Products among Us Adults – Health Information National Trends Survey, 2020

Introduction: Heated Tobacco Products (HTP) have the potential to attain high uptake in the US. The current study estimated the prevalence of awareness, prevalence of use and the factors associated with awareness of HTP among US adults. Methods: This study included 3201 respondents from the Health Information National Trends Survey (HINTS) 5 Cycle 4 (2020). The prevalence of awareness of HTP and ever use of HTP among US adults were estimated. Multivariable logistic regression was conducted to identify the factors associated with awareness of HTP. Results: About 15% of the adult US population were aware of HTP, while 2.2% had ever used HTP. Age between 35 and 49 years (aOR, 1.9; 95% CI, 1.3–2.9; p-value = 0.003), male sex (aOR, 1.7; 95% CI, 1.0–2.7; p-value = 0.04), lower income ($0–$9,999) (aOR, 3.0; 95% CI, 1.3–6.9; p-value = 0.01), smoking on some days (aOR, 3.4; 95% CI, 1.2–9.4; p-value = 0.02) and moderately or extremely worrying about getting cancer (aOR, 1.7; 95% CI, 1.1–2.7; p-value = 0.03) were associated with higher odds of being aware of HTP; whereas, belief that there are so many cancer prevention recommendations, it's hard to know which ones to follow (aOR, 0.5; 95% CI, 0.3–0.8; p-value = 0.009) was associated with lower odds of being aware of HTP. Conclusions: A significant proportion of US adult population were aware of HTP in 2020. Given the recent high proliferation of e-cigarettes, potential health effects of the HTP products should be monitored by the regulators closely. Adequate surveillance and policy interventions are warranted in this regard.
Childhood trauma exposure and reward processing in healthy adults: A functional neuroimaging study

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire‐Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.
Human Mesenchymal Stem Cell‐Derived Miniature Joint System for Disease Modeling and Drug Testing

Diseases of the knee joint such as osteoarthritis (OA) affect all joint elements. An in vitro human cell‐derived microphysiological system capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies/pathogenesis of joint diseases and testing potential therapeutics. Herein, a human mesenchymal stem cell‐derived miniature joint system (miniJoint) is generated, in which engineered osteochondral complex, synovial‐like fibrous tissue, and adipose tissue are integrated into a microfluidics‐enabled bioreactor. This novel design facilitates different tissues communicating while still maintaining their respective phenotypes. The miniJoint exhibits physiologically relevant changes when exposed to interleukin‐1β mediated inflammation, which are similar to observations in joint diseases in humans. The potential of the miniJoint in predicting in vivo efficacy of drug treatment is confirmed by testing the “therapeutic effect” of the nonsteroidal anti‐inflammatory drug, naproxen, as well as four other potential disease‐modifying OA drugs. The data demonstrate that the miniJoint recapitulates complex tissue interactions, thus providing a robust organ chip model for the study of joint pathology and the development of novel therapeutic interventions.