Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic Performance of MRI for Esophageal Carcinoma: A Systematic Review and Meta-Analysis.

Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.
Inversion breakpoints and the evolution of supergenes

The coexistence of discrete morphs that differ in multiple traits is common within natural populations of many taxa. Such morphs are often associated with chromosomal inversions, presumably because the recombination suppressing effects of inversions help maintain alternate adaptive combinations of alleles across the multiple loci affecting these traits. However, inversions can also harbour selected mutations at their breakpoints, leading to their rise in frequency in addition to (or independent from) their role in recombination suppression. In this review, we first describe the different ways that breakpoints can create mutations. We then critically examine the evidence for the breakpoint‐mutation and recombination suppression hypotheses for explaining the existence of discrete morphs associated with chromosomal inversions. We find that the evidence that inversions are favoured due to recombination suppression is often indirect. The evidence that breakpoints harbour mutations that are adaptive is also largely indirect, with the characterization of inversion breakpoints at the sequence level being incomplete in most systems. Direct tests of the role of suppressed recombination and breakpoint mutations in inversion evolution are thus needed. Finally, we emphasize how the two hypotheses of recombination suppression and breakpoint mutation can act in conjunction, with implications for understanding the emergence of supergenes and their evolutionary dynamics. We conclude by discussing how breakpoint characterization could improve our understanding of complex, discrete phenotypic forms in nature.
Ventromedial Prefrontal-Anterior Cingulate Hyperconnectivity and Resilience to Apathy in Traumatic Brain Injury.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining which patients do or do not develop apathy post-TBI. Here we aimed to elucidate the impact of TBI on motivational neural circuits, and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected in patients with subacute mild TBI (N=44), chronic mild-to-moderate TBI (N=26), and non-brain-injured control participants (CTRL; N=28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating prior work suggesting that apathy has an enduring impact in TBI. vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Lastly, we subdivided the TBI group based on patients above versus below the threshold for "clinically-significant apathy," finding that TBI patients with clinically-significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically-significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represents an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.
Limited Prosocial Emotions in a Clinical Population of Children and Adolescents: Proposal for Core and Ancillary Characteristics

Objective: Limited prosocial emotions (LPE) has been recently incorporated into international classifications as a specifier for conduct disorder in the DSM-5 and for all disruptive behavioural disorders in the ICD-11. The aims of the current work were to determine (a) the accuracy of each of the characteristics used to assess the LPE specifier and (b) whether the manner in which symptoms group together supports the idea of LPE having core characteristics. Method: Trained clinicians conducted interviews and determined LPE characteristics using responses from 74 parent/guardian and child/adolescent participants. Results: The distribution of LPE characteristics among those participants with LPE (n = 13) was compared to those with only one LPE characteristic (n = 11). The proposal of callous lack of empathy (CLE) and shallow deficient affect (SDA) as core characteristics was supported by strong associations with the presence of the LPE specifier, larger specificity, and sensitivity indices than those for unconcerned about performance and lack of remorse or guilt, as well as by a robust aggregation in a latent class analysis. Conclusions: CLE and SDA could be considered as core characteristics of LPE in children and adolescents.
The quality of subgroup analyses in chronic pain randomized controlled trials: a methodological review

The quality of subgroup analyses (SGAs) in chronic non-cancer pain trials is uncertain. The purpose of this study was to address this issue. We conducted a comprehensive search in MEDLINE and EMBASE from January 2012 to September 2018 to identify eligible trials. Two pairs of reviewers assessed the quality of the SGAs and the credibility of subgroup claims using the 10 criteria developed by Sun et al. in 2012. The associations between the quality of the SGAs and the studies’ characteristics including risk of bias, funding sources, sample size, and the latest impact factor, were assessed using multivariable logistic regression. Our search retrieved 3,401 articles of which 66 were eligible. The total number of SGAs was 177 of which 52 (29.4%) made a subgroup claim. Of these, only 15 (8.5%) were evaluated as being of high quality. Among the 30 SGAs that claimed subgroup effects using an appropriate method of performing interaction tests, the credibility of only 5 were assessed as high. None of the subgroup claims met all the credibility criteria. No significant association was found between the quality of SGAs and the studies’ characteristics. The quality of the SGAs performed in chronic pain trials was poor. To enhance the quality of SGAs, scholars should consider the developed criteria when designing and conducting trials, particularly those which need to be specified a priori.
Elafibranor and liraglutide improve differentially liver health and metabolism in a mouse model of non‐alcoholic steatohepatitis

This study aimed to assess and compare the effects of the GLP‐1 analog liraglutide and the PPARα/δ agonist elafibranor on liver histology and their impact on hepatic lipidome, metabolome, Kupffer and hepatic stellate cell activation in a model of advanced non‐alcoholic fatty liver disease (NAFLD).
Conservative treatment and outcome of upper cervical spine fractures in young children

Abstract Cervical spine (C-spine) fractures in young children are very rare, and little information on treatment modalities and functional, radiographic, and patient-reported outcome exists. In this 2-center, retrospective case series, we assessed subjective and functional mid-term outcomes in children aged ≤5 years whose C-spine fractures were treated nonoperatively. Between 2000 and 2018, 6 children (median age at injury: 23.5 months; range: 16–31 months) with C1 or C2 injuries were treated with Minerva cast/brace or soft collar brace at 1 of the 2 study centers. Two patients suffered C1 fractures, and 4 patients had lysis of the odontoid synchondrosis. Overall, 3 children had sustained polytrauma. One child died due to the consequences of massive head injury. For the primary outcome parameter, we recorded subjective symptoms such as pain and functional restrictions due to the sequelae of C-spine injuries at follow-up. Based on medical records, we also assessed the causes of injury, diagnostic procedures, treatments and complications, and time to fracture consolidation. Median follow-up of the 5 surviving children was 51 months (range: 36–160 months). At the latest follow-up, 4 of 5 children did not complain of any pain. One child who sustained an open head injury in combination with a subluxation of the odontoid and undisplaced fracture of the massa lateralis reported occasional headache. All patients experienced complete fracture healing and normal range of motion of the cervical spine. Median duration of cast/brace treatment was 8.5 weeks. Fracture healing was confirmed by computed tomography in all patients. All C-spine injuries were managed with either Minerva cast/Halo brace or soft collar brace without complications. In our retrospective case series, nonoperative treatment of atlas fractures and dislocations or subluxations of the odontoid in young children using Minerva casts or prefabricated Halo braces resulted in good subjective and functional outcomes at mid-term. We observed no complications of conservative treatment of C1 and C2 injuries in young children.
Calculated structures and energies of grain boundaries in α-Al2O3

Static-lattice calculations of the energies and structures of [l brace]10[bar 1]n[r brace] (n = 0, 1, and 4) and [l brace]0001[r brace] grain boundaries in [alpha][center dot]Al[sub 2]O[sub 3] using three different potentials are reported. It was found that the energies of boundaries perpendicular to the direction vary between 0.3 and 0.9 J[center dot]m[sup [minus]2]. These compare favorably to experimental values, and the results are not sensitive to the choice of potential. The energies of the other boundaries do depend on the potential, but their relaxed structures do not. Using the most reliable potential, the energies of boundaries which have been studied by high-resolution electron microscopy range from 1.0 to 1.7 J[center dot]m[sup [minus]2]. Simulated images of the calculated structures compare favorably with high-resolution electron microscope micrographs of these boundaries.
Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.
Have you ever heard of Human Papillomavirus (HPV) vaccine? The awareness of HPV vaccine for college students in China based on meta-analysis

ABSTRACT Objective: To evaluate the awareness of College Students (CSs) of HPV vaccine in China and provide evidence-based recommendations for HPV vaccine’s publicity and promotion. Methods: Web of Science, PubMed, Science of Direct, EBSCO, China National Knowledge Infrastructure and Wanfang Data were searched. A random effects meta-analysis was conducted to determine pooled estimates of Awareness Rate (AR) for HPV vaccine. Results: Of the 36 studies included, the estimated AR of HPV vaccine was 40.27% (95% CI: 30.86%, 50.06%) among Chinese CSs. The AR of HPV vaccine was stratified by factors as gender, major, area, city, survey time, and sampling method of the study. The pooled AR of HPV vaccine among CSs was as follows: 44.17% (95% CI: 31.65%, 57.09%) and 31.93% (95% CI: 13.25%, 54.30%) for females and males; 44.47% (95% CI: 29.90%, 59.55%) and 12.02% (95% CI: 7.69%, 17.15%) for medical-related and nonmedical majors; 44.47% (95% CI: 28.71–60.82%) and 41.16% (95% CI: 26.48–56.64%) for Eastern and Midwestern region; 48.86% (95% CI: 30.63–67.25%) and 33.19% (95% CI: 22.27–45.12%) for first-tier and second- and third-tier city; 29.67 (95% CI: 11.44–52.16%) and 38.81 (95% CI: 27.14–51.21%) for AR before and after HPV vaccine entered in China; 51.51% (95% CI: 32.21%, 70.53%) and 26.21% (95% CI: 17.41%, 36.10%) for nonrandom and random sampling. Conclusion: This review indicates that awareness of HPV vaccine among CSs remains relatively low in China compared with European countries. Our findings may provide useful information to better understand the HPV vaccine awareness status among Chinese CSs.
Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth

Significance Autophagy is known to promote cell survival through providing various sources of fuels as a result of digestion. Here, we uncover a function of autophagy in cell metabolic regulation by directly activating cAMP/PKA signaling that fuels mitochondrial metabolism and confers cell resistance to energy crisis. We find that autophagy selectively degrades PKA inhibitory subunit RIα through new autophagy receptor AKAP11 in response to energy crisis, thus causing PKA activation, which is a central hub for a variety of cellular signaling. Our study suggests that tumor cells may exploit such a metabolic reprogramming mechanism for the oncogenic growth. We propose that AKAP11-mediated cAMP/PKA activation via selective autophagy should be explored in the future as a therapeutic target for cancer treatment. Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase–anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth.
myPainPal: Co-creation of a mHealth app for the management of chronic pain in young people

ABSTRACT Chronic pain is common in young people aged 10–14 years. Interdisciplinary, clinician-delivered treatments, while effective, are often criticized for failing to be readily accessible. Mobile health applications (mHealth apps) have been proposed as effective treatment adjuncts that address these challenges, while meeting the needs of tech-savvy young people. The objectives of this study were to co-create a mHealth app with consumers and health care professionals and evaluate the acceptability and feasibility of the resulting mHealth app (myPainPal). A phased, qualitative approach within a consumer engagement framework was employed. Interviews with young people (n = 14), parents (n = 12) and health care professionals (n = 8) identified key health needs that formed the underlying structure of the myPainPal app. Testing showed that the app is an acceptable and feasible platform to facilitate young people’s self-management of chronic pain. The myPainPal app has the potential to positively influence young people’s experiences of chronic pain. Further testing in controlled settings is required.
Naphthalenyl, Anthracenyl, Tetracenyl, and Pentacenyl Radicals and Their Anions

Electronic structure theory has been applied to the naphthalene-, anthracene-, tetracene-, and pentacene-based radicals and their anions. Five different density functional methods were used to predict adiabatic electron affinities for these radicals. A consistent trend was found, suggesting that the electron affinity at a site of hydrogen removal is primarily dependent upon steric effects for polycyclic aromatic hydrocarbons. The results for the 1-naphthalenyl and 2-naphthalenyl radicals were compared to experiment, and it was found that B3LYP appears to be the most reliable functional for this type of system. For the larger systems the predicted site specific adiabatic electron affinities of the radicals are 1.51 eV (1-anthracenyl), 1.46 eV (2-anthracenyl), and 1.68 eV (9-anthracenyl); 1.61 eV (1-tetracenyl), 1.56 eV (2-tetracenyl), and 1.82 eV (12-tetracenyl); and 1.93 eV (14-pentacenyl), 2.01 eV (13-pentacenyl), 1.68 eV (1-pentacenyl), and 1.63 eV (2-pentacenyl). These electron affinities are 0.5−1.5 e.
The Prophage and Plasmid Mobilome as a Likely Driver of Mycobacterium abscessus Diversity

Mycobacterium abscessus is an important emerging pathogen that is challenging to treat with current antibiotic regimens. There is substantial genomic variation in M. abscessus clinical isolates, but little is known about how this influences pathogenicity and in vivo growth. ABSTRACT Mycobacterium abscessus is an emerging pathogen that is often refractory to antibiotic control. Treatment is further complicated by considerable variation among clinical isolates in both their genetic constitution and their clinical manifestations. Here, we show that the prophage and plasmid mobilome is a likely contributor to this variation. Prophages and plasmids are common, abundant, and highly diverse, and code for large repertoires of genes influencing virulence, antibiotic susceptibility, and defense against viral infection. At least 85% of the strains we describe carry one or more prophages, representing at least 17 distinct and diverse sequence “clusters,” integrated at 18 different attB locations. The prophages code for 19 distinct configurations of polymorphic toxin and toxin-immunity systems, each with WXG-100 motifs for export through type VII secretion systems. These are located adjacent to attachment junctions, are lysogenically expressed, and are implicated in promoting growth in infected host cells. Although the plethora of prophages and plasmids confounds the understanding of M. abscessus pathogenicity, they also provide an abundance of tools for M. abscessus engineering. IMPORTANCE Mycobacterium abscessus is an important emerging pathogen that is challenging to treat with current antibiotic regimens. There is substantial genomic variation in M. abscessus clinical isolates, but little is known about how this influences pathogenicity and in vivo growth. Much of the genomic variation is likely due to the large and varied mobilome, especially a large and diverse array of prophages and plasmids. The prophages are unrelated to previously characterized phages of mycobacteria and code for a diverse array of genes implicated in both viral defense and in vivo growth. Prophage-encoded polymorphic toxin proteins secreted via the type VII secretion system are common and highly varied and likely contribute to strain-specific pathogenesis.