Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti -TNFα agents in preventing the postoperative recurrence of Crohn’s disease: Do they still play a role in the biological era?

ABSTRACT Background Approximately half of patients with Crohn’s disease (CD) may inevitably receive surgical intervention as the disease progress. However, about 75% of CD patients will experience postoperative recurrence (POR). Biologics are appealing alternatives for the prevention of POR; however, it is still unclear which biological agents are more efficient. This meta-analysis aimed to investigate the efficacy of biologics for POR prevention and to compare the superiority of different biologics. Methods We conducted a thorough search of online databases and screened for studies on the efficacy of biologics in preventing POR (clinical, endoscopic, or histological) that were published until January 2021. The results were presented as forest plots and odds ratios (ORs) with 95% confidence intervals (CIs). Results We included 26 studies with 2,136 participants. Overall, biologics were more efficient over non-biological treatments in preventing endoscopic, severe endoscopic, and clinical POR without increasing the frequency of adverse events. Among the various types of biologics, anti-TNFα agents were better than vedolizumab in preventing endoscopic POR. Moreover, infliximab had a similar curative effect to adalimumab in preventing endoscopic, severe endoscopic, and clinical recurrence. Conclusion Biologics, especially anti-TNFα agents, still play a vital role in preventing POR in the biological era.
Near-Perfect Automation: Investigating Performance, Trust, and Visual Attention Allocation

Objective Assess performance, trust, and visual attention during the monitoring of a near-perfect automated system. Background Research rarely attempts to assess performance, trust, and visual attention in near-perfect automated systems even though they will be relied on in high-stakes environments. Methods Seventy-three participants completed a 40-min supervisory control task where they monitored three search feeds. All search feeds were 100% reliable with the exception of two automation failures: one miss and one false alarm. Eye-tracking and subjective trust data were collected. Results Thirty-four percent of participants correctly identified the automation miss, and 67% correctly identified the automation false alarm. Subjective trust increased when participants did not detect the automation failures and decreased when they did. Participants who detected the false alarm had a more complex scan pattern in the 2 min centered around the automation failure compared with those who did not. Additionally, those who detected the failures had longer dwell times in and transitioned to the center sensor feed significantly more often. Conclusion Not only does this work highlight the limitations of the human when monitoring near-perfect automated systems, it begins to quantify the subjective experience and attentional cost of the human. It further emphasizes the need to (1) reevaluate the role of the operator in future high-stakes environments and (2) understand the human on an individual level and actively design for the given individual when working with near-perfect automated systems. Application Multiple operator-level measures should be collected in real-time in order to monitor an operator’s state and leverage real-time, individualized assistance.
Efficacy and Safety of Intranasal Dexmedetomidine During Recovery From Sevoflurane Anesthesia in Children: A Systematic Review and Meta-analysis

Background Intranasal drip of dexmedetomidine in children with sevoflurane anesthesia can reduce anesthesia and restlessness. However, there is still some controversy. We conducted a meta-analysis to explore the effect of intranasal infusion of dexmedetomidine on the quality of recovery during the recovery period, to provide certain guidance for clinical application. Methods Web of Science, PubMed, Embase, and the Cochrane Library were used for literature search. Systematic reviews were based on PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Results A total of 14 articles and 1123 patients were included. The results of the meta-analysis showed that the incidence of emergence agitation [risk ratio (RR), 0.32; 95% confidence interval (CI), 0.20–0.50; P < 0.0001], satisfactory sedation at parent separation (RR, 1.41; 95% CI, 1.031–93; P = 0.034), incidence of nausea and vomiting (RR, 0.41; 95% CI, 0.21–0.78; P = 0.007), and incidence of laryngospasm (RR, 0.23; 95% CI, 0.08–0.65; P = 0.006) of the intranasal dexmedetomidine group were different compared with the control group. However, the satisfactory sedation at mask induction in the intranasal dexmedetomidine group (RR, 1.16; 95% CI, 0.87–1.54; P = 0.319), postanesthesia care unit (PACU) stay time (standardized mean deviation, 0.51; 95% CI, −0.11 to 1.12; P = 0.107), and extubation time (standardized mean deviation, 1.64; 95% CI, −1.07 to 4.35; P = 0.235) were not statistically significant compared with those of the control group. Conclusion Intranasal dexmedetomidine anesthesia with sevoflurane in children can reduce the incidence of emergence agitation, provide more satisfactory sedation when the parents are separated, reduce the incidence of nausea and vomiting, and reduce the incidence of laryngospasm. In addition, the 2 μg/kg dose of dexmedetomidine may be the best dose for clinical application.
Bosentan Alters Endo- and Exogenous Bile Salt Disposition in Sandwich-Cultured Human Hepatocytes

Bosentan, a well–known cholestatic agent, was not identified as cholestatic at concentrations up to 200 µM based on the drug-induced cholestasis (DIC) index value, determined in a sandwich-cultured human hepatocyte (SCHH)–based DIC assay. To obtain further quantitative insights into the effects of bosentan on cellular bile salt handling by human hepatocytes, the present study determined the effect of 2.5–25 µM bosentan on endogenous bile salt levels and on the disposition of 10 µM chenodeoxycholic acid (CDCA) added to the medium in SCHHs. Bosentan reduced intracellular as well as extracellular concentrations of both endogenous glycochenodeoxycholic acid (GCDCA) and glycocholic acid in a concentration-dependent manner. When exposed to 10 µM CDCA, bosentan caused a shift from canalicular efflux to sinusoidal efflux of GCDCA. CDCA levels were not affected. Our mechanistic model confirmed the inhibitory effect of bosentan on canalicular GCDCA clearance. Moreover, our results in SCHHs also indicated reduced GCDCA formation. We confirmed the direct inhibitory effect of bosentan on CDCA conjugation with glycine in incubations with liver S9 fraction. SIGNIFICANCE STATEMENT Bosentan was evaluated at therapeutically relevant concentrations (2.5–25 µM) in sandwich-cultured human hepatocytes. It altered bile salt disposition and inhibited canalicular secretion of glycochenodeoxycholic acid (GCDCA). Within 24 hours, bosentan caused a shift from canalicular to sinusoidal efflux of GCDCA. These results also indicated reduced GCDCA formation. This study confirmed a direct effect of bosentan on chenodeoxycholic acid conjugation with glycine in liver S9 fraction.
Learning From Highly Confident Samples for Automatic Knee Osteoarthritis Severity Assessment: Data From the Osteoarthritis Initiative

Knee osteoarthritis (OA) is a chronic disease that considerably reduces patients’ quality of life. Preventive therapies require early detection and lifetime monitoring of OA progression. In the clinical environment, the severity of OA is classified by the Kellgren and Lawrence (KL) grading system, ranging from KL-0 to KL-4. Recently, deep learning methods were applied to OA severity assessment to improve accuracy and efficiency. However, this task is still challenging due to the ambiguity between adjacent grades, especially in early-stage OA. Low confident samples, which are less representative than the typical ones, undermine the training process. Targeting the uncertainty in the OA dataset, we propose a novel learning scheme that dynamically separates the data into two sets according to their reliability. Besides, we design a hybrid loss function to help CNN learn from the two sets accordingly. With the proposed approach, we emphasize the typical samples and control the impacts of low confident cases. Experiments are conducted in a five-fold manner on five-class task and early-stage OA task. Our method achieves a mean accuracy of 70.13% on the five-class OA assessment task, which outperforms all other state-of-art methods. Despite early-stage OA detection still benefiting from the human intervention of lesion region selection, our approach achieves superior performance on the KL-0 vs. KL-2 task. Moreover, we design an experiment to validate large-scale automatic data refining during training. The result verifies the ability to characterize low confidence samples. The dataset used in this paper was obtained from the Osteoarthritis Initiative.
Source–sink dynamics assists the maintenance of a pollinating wasp

Dispersal that unites spatially subdivided populations into a metapopulation with source–sink dynamics is crucial for species persistence in fragmented landscapes. Understanding such dynamics for pollinators is particularly urgent owing to the ongoing global pollination crisis. Here, we investigated the population structure and source–sink dynamics of a pollinating wasp (Wiebesia sp. 3) of Ficus pumila in the Zhoushan Archipelago of China. We found significant asymmetry in the pairwise migrant numbers for 22 of 28 cases on the historical timescale, but only two on the contemporary timescale. Despite a small population size, the sole island not colonized by a superior competitor wasp (Wiebesia sp. 1) consistently behaved as a net exporter of migrants, supplying large sinks. Comparable levels of genetic diversity, with few private alleles and low genetic differentiation (total Fst: 0.03; pairwise Fst: 0.0005–0.0791), were revealed among all the islands. There was a significant isolation‐by‐distance pattern caused mainly by migration between the competition‐free island and other islands, otherwise the pattern was negligible. The clustering analysis failed to detect multiple gene pools for the whole region. Thus, the sinks were most probably organized into a patchy population. Moreover, the estimates of effective population sizes were comparable between the two timescales. Thus the source–sink dynamics embedded within a well‐connected population network may allow Wiebesia sp. 3 to persist at a competitive disadvantage. This study provides evidence that metapopulations in the real world may be complicated and changeable over time, highlighting the necessity to study such metapopulations in detail.
Psychosocial determinants of anxiety about the COVID-19 pandemic

Pandemic health threats can cause considerable anxiety, but not all individuals react similarly. To understand the sources of this variability, we applied a theoretical model developed during the H1N1 pandemic of 2009 to quantify relationships among intolerance of uncertainty, stress appraisals, and coping style that predict anxiety about the COVID-19 pandemic. We surveyed 1579 U.S. Amazon Mechanical Turk workers in April 2020. Using structural equation modeling, we found that individuals who were more intolerant of uncertainty reported higher appraisals of threat, stress, and other-control, which predicted higher anxiety when emotion-focused coping was engaged, and lower anxiety when problem-focused coping was engaged. Political affiliation moderated these effects, such that conservatives relied more on self-control and other-control appraisals to mitigate anxiety than independents or liberals. These results show that how people appraise and cope with their stress interacts with political ideology to shape anxiety in the face of a global health threat.
Use of a new ALS specific respiratory questionnaire: the ARES score

Abstract Objective: To develop an ALS respiratory symptom scale (ARES) and evaluate how ARES compares to Medical Research Council Modified Dyspnea Scale (MRC), Borg dyspnea scale, and respiratory subscores from ALSFRS-R (ALSFRS-Resp) in detecting respiratory symptoms, correlation with pulmonary function and ALSFRS-R, and deterioration of pulmonary function and ALSFRS-R over time. Methods: The ARES scale consists of 9 questions addressing dyspnea during activities and 3 questions addressing symptoms of worsening pulmonary function. 153 subjects with ALS completed MRC, Borg, ALSFRS-R, and ARES questionnaires at baseline, 16, 32, and 48 weeks, and spirometry at baseline. 73 of these subjects had spirometry, maximum inspiratory (MIP) and expiratory pressures (MEP), nasal inspiratory pressure (SNIP), and maximum voluntary ventilation (MVV) measured at each visit. Sensitivity of each scale and correlations between symptom scores, pulmonary function, and ALSFRS-R were evaluated at baseline and over the study duration. Results and conclusions: ARES was more sensitive than MRC, Borg and ALSFRS-Resp scales at baseline and for detecting changes at 16 and 32 weeks. ARES and ALSFRS-Resp correlated significantly with vital capacity at baseline, but Borg and MRC did not. Only ALSFRS-Resp correlated with respiratory pressures. Changes in ALSFRS-Resp and ARES both correlated with vital capacity decline; however, changes in ARES had superior correlation with respiratory pressure decline. Comparisons between telephone and in-person administration of ARES met criteria for satisfactory test-retest correlation in different settings one week apart. These findings suggest that the ARES may be more useful in monitoring symptom progression in ALS than other available scales.
Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on “toxin sponge” proteins

Some poisonous animals produce toxins that affect Na+ channel function yet avoid autointoxication. Abderemane-Ali et al. show that resistance by Pitohui birds and Phyllobates frogs to their own toxins may be mediated not by mutations in their channels, but by toxin-sequestering “sponge” proteins.
cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages

ABSTRACT Although cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling has been well recognized in defending DNA viruses, the role of cGAS-STING signaling in regulating infection of RNA viruses remains largely elusive. Noroviruses, as single-stranded RNA viruses, are the main causative agents of acute viral gastroenteritis worldwide. This study comprehensively investigated the role of cGAS-STING in response to murine norovirus (MNV) infection. We found that STING agonists potently inhibited MNV replication in mouse macrophages partially requiring the JAK/STAT pathway that induced transcription of interferon (IFN)-stimulated genes (ISGs). Loss- and gain-function assays revealed that both cGAS and STING were necessary for host defense against MNV propagation. Knocking out cGAS or STING in mouse macrophages led to defects in induction of antiviral ISGs upon MNV infection. Overexpression of cGAS and STING moderately increased ISG transcription but potently inhibited MNV replication in human HEK293T cells ectopically expressing the viral receptor CD300lf. This inhibitory effect was not affected by JAK inhibitor treatment or expression of different MNV viral proteins. Interestingly, STING but not cGAS interacted with mouse RIG-I, and attenuated its N-terminus-mediated anti-MNV effects. Our results implicate an essential role for mouse cGAS and STING in regulating innate immune response and defending MNV infection. This further strengthens the evidence of cGAS-STING signaling in response to RNA virus infection.
Immune cell infiltration-associated signature in colon cancer and its prognostic implications

Tumor immune cell infiltration (ICI) has been reported in various studies to be correlated with tumor diagnosis, clinical treatment sensitivity and prognosis. It is an important direction to study the characteristics of immune cell infiltration and develop new prognostic markers to improve the treatment of colon cancer. In this paper, we systematically analyzed the ICI characteristics and obtained three ICI clusters. Then, the ICI scores were constructed and its prognostic implications were discussed. From the results, the ICI score patterns were linked to a great survival difference (p<0.001). A high ICI score was characterized by a higher fraction of plasma cells, CD8+ T cells, memory resting CD4+ T cells, monocytes, eosinophils and dendritic cells, which had better prognosis. Macrophages and neutrophils were increased in low ICI score patients with decreased overall survival. Immune checkpoint molecules (PDCD1, CD274, LAG3, IDO1, CTLA-4, TIGHT and HAVCR2) were found to be significantly overexpressed in the low ICI score subgroup. In addition, we also studied the correlation between the tumor mutation burden (TMB) and ICI score. This study indicated the ICI score could serve as a potential prognostic biomarker for colon cancer patients’ immunotherapy.
Genome‐wide in vitro and in vivo RNAi screens reveal Fer3 to be an important regulator of kkv transcription in Drosophila

Krotzkopf verkehrt (kkv) is a key enzyme that catalyzes the synthesis of chitin, an important component of the Drosophila epidermis, trachea, and other tissues. Here, we report the use of comprehensive RNA interference (RNAi) analyses to search for kkv transcriptional regulators. A cell‐based RNAi screen identified 537 candidate kkv regulators on a genome‐wide scale. Subsequent use of transgenic Drosophila lines expressing RNAi constructs enabled in vivo validation, and we identified six genes as potential kkv transcriptional regulators. Weakening of the kkvDsRed signal, an in vivo reporter indicating kkv promoter activity, was observed when the expression of Akirin, NFAT, 48 related 3 (Fer3), or Autophagy‐related 101(Atg101) was knocked down in Drosophila at the 3rd‐instar larval stage; whereas we observed disoriented taenidial folds on larval tracheae when Lines (lin) or Autophagy‐related 3 (Atg3) was knocked down in the tracheae. Fer3, in particular, has been shown to be an important factor in the activation of kkv transcription via specific binding with the kkv promoter. The genes involved in the chitin synthesis pathway were widely affected by the downregulation of Fer3. Furthermore, Atg101, Atg3, Akirin, Lin, NFAT, Pnr, and Abd‐A showed that the potential complex mechanism of kkv transcription is regulated by an interaction network with bithorax complex components. Our study revealed the hitherto unappreciated diversity of modulators impinging on kkv transcription and opens new avenues in the study of kkv regulation and chitin biosynthesis.
Searching and Caring for the Sacred: Psychological Perspectives on Caring for People’s Spiritual Needs

We present knowledge from the field of psychology of religion for professional clinicians. The model “Search for the Sacred” and other concepts of psychology of religion are introduced: Sacred core and ring, sanctification, spiritual emotions, spiritual relationships, spiritual pathways, and sacred moments. These are discussed in relation to different concepts of theology for broadening the understanding and application of these concepts. Interviews with Danish Christians facing a crisis illustrate the application of the theoretical perspectives.
The physics of cement cohesion

Ion-water restructuring under confinement is at the origin of ion-specific nanoscale forces that control cement cohesion. Cement is the most produced material in the world. A major player in greenhouse gas emissions, it is the main binding agent in concrete, providing a cohesive strength that rapidly increases during setting. Understanding how such cohesion emerges is a major obstacle to advances in cement science and technology. Here, we combine computational statistical mechanics and theory to demonstrate how cement cohesion arises from the organization of interlocked ions and water, progressively confined in nanoslits between charged surfaces of calcium-silicate-hydrates. Because of the water/ions interlocking, dielectric screening is drastically reduced and ionic correlations are proven notably stronger than previously thought, dictating the evolution of nanoscale interactions during cement hydration. By developing a quantitative analytical prediction of cement cohesion based on Coulombic forces, we reconcile a fundamental understanding of cement hydration with the fully atomistic description of the solid cement paste and open new paths for scientific design of construction materials.
Oculomotor corollary discharge signaling is related to repetitive behavior in children with autism spectrum disorder

Corollary discharge (CD) signals are “copies” of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.
Difference in outcomes following allogeneic hematopoietic cell transplantation for patients with acute myeloid leukemia and myelodysplastic syndromes

Abstract To evaluate whether outcomes following allogeneic hematopoietic cell transplantation differ according to disease type, a three-way comparison for patients with de novo acute myeloid leukemia (AML) (n = 3318), AML evolving from myelodysplastic syndromes (MDS) (n = 208), and MDS with excess blasts (MDS-EB) (n = 994) was performed. The 5-year probabilities of overall survival (OS) for de novo AML, AML evolving from MDS, and MDS-EB were 60%, 42%, and 41% (p < 0.001), respectively. Multivariate analysis revealed that, compared to de novo AML, AML evolving from MDS was associated with a higher risk of NRM (p = 0.030) and MDS-EB with a higher risk of relapse (p < 0.001), both leading to lower OS (p = 0.010 and p < 0.001, respectively). These findings demonstrate inter-disease differences in post-transplant outcomes and highlight the needs to reduce NRM for AML evolving from MDS and to reduce relapse for MDS-EB.