Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pan-Cancer Analysis of IRAK1 Expression and Their Association With Immunotherapy Response

IRAK1 is an active kinase which plays a critical role in IL-1/TLR signaling pathway involved in inflammation and innate immune response. Recently, increasing evidence supports a potential role of IRAK1 in cancer progression. However, no immunological pan-cancer analysis of IRAK1 is available. We aimed to explore the prognostic value and the immunological functions of IRAK1. A series of datasets including The Cancer Genome Atlas, GEPIA2, cBioPortal, HPA, TIMER2.0 were performed to explore the oncogenic and immunological roles of IRAK1, including the relationship between IRAK1 and prognosis, genetic mutation, GO and KEGG enrichment pathway analysis, immune state of different tumors, The results showed that IRAK1 levels were upregulated in more than 20 types of cancers compared to the normal tissues. IRAK1 expression was associated with poorer prognosis in different cancer types. For the most frequent DNA alteration of IRAK1 is amplification. And the result of the enrichment analysis suggested that IRAK1 related to immune checkpoint pathway in cancer. IRAK1 inhibitor pacritinib inhibit proliferation and upregulate PD-L1 expression in different cancer cell lines. Moreover, the patients who receiving anti-PD-L1 therapy with low IRAK1 expression had a better prognosis, and the objective response rate to anti-PD-L1 therapy was higher in the low IRAK1 group than in the high IRAK1 group in IMvigor210 cohort. Our study reveals that IRAK1 can function as a prognostic marker in various malignant tumors. And pacritinib upregulated PD-L1 expression in several cancer cell lines, which indicating that IRAK1 can be used as a reliable marker to predict the efficacy of immunotherapy.
The Effectiveness and Safety of Medical Cannabis for Treating Cancer Related Symptoms in Oncology Patients

The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment. Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients' disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups. Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment. The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.
Associations Between Disordered Microbial Metabolites and Changes of Neurotransmitters in Depressed Mice

Backgrounds Many pieces of evidence demonstrated that there were close relationships between gut microbiota and depression. However, the specific molecular mechanisms were still unknown. Here, using targeted metabolomics, this study was conducted to explore the relationships between microbial metabolites in feces and neurotransmitters in prefrontal cortex of depressed mice. Methods Chronic unpredictable mild stress (CUMS) model of depression was built in this study. Targeted liquid chromatography–mass spectrometry analysis was used to detect the microbial metabolites in feces and neurotransmitters in prefrontal cortex of mice. Both univariate and multivariate statistical analyses were applied to identify the differential microbial metabolites and neurotransmitters and explore relationships between them. Results Ninety-eight differential microbial metabolites (mainly belonged to amino acids, fatty acids, and bile acids) and 11 differential neurotransmitters (belonged to tryptophan pathway, GABAergic pathway, and catecholaminergic pathway) were identified. Five affected amino acid–related metabolic pathways were found in depressed mice. The 19 differential microbial metabolites and 10 differential neurotransmitters were found to be significantly correlated with depressive-like behaviors. The two differential neurotransmitters (tyrosine and glutamate) and differential microbial metabolites belonged to amino acids had greater contributions to the overall correlations between microbial metabolites and neurotransmitters. In addition, the significantly decreased L-tyrosine as microbial metabolites and tyrosine as neurotransmitter had the significantly positive correlation (r = 0.681, p = 0.0009). Conclusions These results indicated that CUMS-induced disturbances of microbial metabolites (especially amino acids) might affect the levels of neurotransmitters in prefrontal cortex and then caused the onset of depression. Our findings could broaden the understanding of how gut microbiota was involved in the onset of depression.
SCN1A-Related Epilepsy: Novel Mutations and Rare Phenotypes

Objectives To expand the genotypes and phenotypes of sodium voltage-gated channel alpha subunit 1 (SCN1A)-related epilepsy. Methods We retrospectively collected the clinical and genetic information of 22 epilepsy patients (10 males, 12 females; mean: 9.2 ± 3.9 years; 3.9–20.3 years) carrying 22 variants of SCN1A. SCN1A mutations were identified by next-generation sequencing. Results Twenty-two variants were identified, among which 12 have not yet been reported. The median age at seizure onset was 6 months. Sixteen patients were diagnosed with Dravet syndrome (DS), two with genetic epilepsy with febrile seizures plus [one evolved into benign epilepsy with centrotemporal spikes (BECTS)], one with focal epilepsy, one with atypical childhood epilepsy with centrotemporal spikes (ABECTS) and two with unclassified epilepsy. Fourteen patients showed a global developmental delay/intellectual disability (GDD/ID). Slow background activities were observed in one patient and epileptiform discharges were observed in 11 patients during the interictal phase. Significance This study enriches the genotypes and phenotypes of SCN1A-related epilepsy. The clinical characteristics of patients with 12 previously unreported variants were described.
Understanding the Impact of Competitive Advantage and Core Competency on Regional Tourism Revitalization: Empirical Evidence in Taiwan

Competitive advantage and core competency are the unique capabilities and assets of an organization to provide valuable products or services to customers, thus giving the organization a better competitive position in the market than its competitors. In addition, how to create a competitive advantage is also one of the main objectives of business strategy. Therefore, this study focuses on understanding the decisive factors in regional revitalization and the relationship between business strategy, strategic alliance, and alliance performance through small and medium enterprises (SMEs) in Taiwan. This study selected a sample of 220 SMEs in Taiwan that had participated in the SME regional revitalization counseling program. The results showed that competitive advantage, core competency and strategic alliance partner selection had significant effects on alliance performance. In addition, core competency had an indirect effect on alliance performance through strategic alliance partner selection. However, competitive advantage did not have a significant effect on strategic alliance partner selection. Finally, this study proposes management implications and practical suggestions for SMEs’ competitive advantage, core competency, and alliance performance.
Correlates of Aggression in Men With Methamphetamine Use Disorder: Childhood Trauma and Methamphetamine-Use Characteristics

Background Aggression is common among individuals with methamphetamine use disorder (MAUD) and constitutes a serious public health issue. The current study aimed to examine associations of methamphetamine-use characteristics and childhood trauma with aggression in men with MAUD. Methods This cross-sectional study was conducted from December 2017 to August 2018. MAUD patients recruited from a compulsory drug rehabilitation center (n = 360) and healthy comparison subjects (n = 604) completed a survey that measured aggression and childhood trauma, using the Chinese version of Buss-Perry Aggressive Questionnaire (AQ-CV), and the short form of Childhood Trauma Questionnaire (CTQ-SF), respectively. MAUD patients also provided information on methamphetamine-use characteristics such as the age of MAUD onset, MAUD severity, and co-occurring alcohol use disorder (AUD) and tobacco use disorder (TUD) using standard or self-designed questionnaires. Chi-square tests and t-tests were used to compare childhood trauma and aggression between the MAUD and comparison groups. Multiple linear regressions were conducted to determine correlates of overall aggression and its five sub-scales among the MAUD group. Results The MAUD group had higher childhood trauma and aggression scores than the comparison group. Within the MAUD group, age of MAUD onset, having severe MAUD, co-occurring AUD, co-occurring TUD, and childhood trauma were associated with overall aggression, with slightly different correlates found for its five sub-scales. Conclusions Our study shows a high level of childhood trauma and aggression in the MAUD group. Both methamphetamine-use characteristics (age of MAUD onset, severe MAUD, co-occurring AUD/TUD) and childhood trauma were associated with aggression in MAUD. Our findings provide useful information on potential risk factors for aggression and inform future longitudinal research to establish causal relationships between these factors and aggression to guide further prevention and treatment programs.
Dietary Eggshell Membrane Powder Improves Survival Rate and Ameliorates Gut Dysbiosis in Interleukin-10 Knockout Mice

Inflammatory bowel disease (IBD) is known to be associated with compositional and metabolic changes in the gut microbiota. The aim of this study was to investigate whether dietary eggshell membrane (ESM) improves survival rate or ameliorates gut dysbiosis in a spontaneous IBD model of interleukin-10 knockout (IL10−/−) mice. Female C57BL/6J wild-type (WT) and IL10−/− mice (KO) were fed an AIN-93G basal diet or an ESM diet (KOE) for 19 weeks. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and short-chain fatty acids in cecal content were analyzed with high-performance liquid chromatography. The results demonstrated that ESM supplementation significantly improved the survival rate and body composition in KO mice. Alpha diversity analysis of the microbiota revealed that ESM supplementation significantly increased gut microbial diversity, which was decreased in IL10−/− mice. The Firmicutes/Bacteroidetes ratio was recovered to a normal level by ESM supplementation, suggesting that ESM helps maintain the compositional balance of the gut microbiota. ESM increased relative abundance of commensal bacterial Ruminococcus and Bacteroidales S24-7 and reduced the abundance of the proinflammatory-related bacterium, Enterobacteriaceae. Additionally, ESM supplementation promoted the production of butyrate in cecal contents and downregulated the expression of proinflammatory genes, including interleukin-1β (Il-1β) and tumor necrosis factor-α (Tnf-α) in IL10−/− mice colon, indicating anti-inflammatory functions. These findings suggest that ESM may be used as a beneficial dietary intervention for IBD.
Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan

Background The incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults. Methods This cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors. Results Among 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50–2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02–76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26–2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85–2.90), aphasia (aHR, 1.77; 95% CI, 1.20–2.60), and malignancy (aHR, 2.05; 95% CI, 1.30–3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53–5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48–0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up. Conclusions Stroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.
A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs that are used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. Therefore, we sought to compare the epileptogenic effects of SE that are terminated by three AEDs, i.e., diazepam, midazolam, and pentobarbital, which are widely used as first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of lithium chloride (LiCl)-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam, or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality and behavioral spontaneous recurrent seizures (SRSs) and by using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg), and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, while pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated with midazolam had resulted in relatively less behavioral SRS, less hippocampal atrophy, and milder neuronal loss and gliosis. Our data revealed an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting the brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefits against epileptogenesis.
Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome—Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial

Introduction In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG. Methods and Analysis Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned. Significance Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments. Ethics and Dissemination The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362). Registration Details The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT 04826588).
Podocan and Adverse Clinical Outcome in Patients Admitted With Suspected Acute Coronary Syndromes

Background Markers of bone and extracellular matrix (ECM) remodeling may be associated with adverse outcomes in atherosclerotic cardiovascular disease. Podocan is a newly discovered ECM glycoprotein, previously not studied in a chest pain population. We wanted to study the association between Podocan levels on admission and the risk of adverse outcomes in a chest pain population with suspected acute coronary syndromes. Methods A total of 815 patients from the Risk markers in Acute Coronary Syndrome (RACS) trial with suspected coronary chest pain were followed for 7 years. Blood samples were taken immediately after inclusion and stored in the biobank. Associations between Podocan and endpoints were assessed with Cox proportional hazards analyses. Results The median admission level of Podocan was 0.674 ng/ml (0.566–0.908 ng/ml). No significant association was found between Podocan quartile levels and all-cause death, neither at 1 year nor 2- or 7-years follow-up (p > 0.05 for all). Furthermore, no significant association could be shown between Podocan and cardiac death, myocardial infarction (MI), stroke, or the composites of all-cause death/MI/stroke or cardiac death/MI/stroke (p > 0.05 for all). Similarly, in a subgroup of patients with Troponin T-positive (n = 432) there was no significant association between Podocan and any of the outcome measures (p > 0.05 for all endpoints and points in time). Conclusion Podocan, a novel ECM biomarker, is not associated with all-cause mortality or other major cardiovascular adverse events in patients admitted with acute chest pain suspected to be of coronary origin. Clinical Trials.gov Identifier: NCT00521976.
Bleaching Susceptibility and Resistance of Octocorals and Anemones at the World’s Southern-Most Coral Reef

Coral reefs are amongst the most biodiverse ecosystems on earth, and while stony corals create the foundational complexity of these ecosystems, octocorals and anemones contribute significantly to their biodiversity and function. Like stony corals, many octocorals contain Symbiodiniaceae endosymbionts and can bleach when temperatures exceed the species’ upper thermal limit. Here, we report octocoral bleaching susceptibility and resistance within the subtropical Lord Howe Island coral reef ecosystem during and after marine heatwaves in 2019. Octocoral and anemone surveys were conducted at multiple reef locations within the Lord Howe Island lagoon during, immediately after, and 7 months after the heatwaves. One octocoral species, Cladiella sp. 1, experienced bleaching and mortality, with some bleached colonies detaching from the reef structure during the heatwave (presumed dead). Those that remained attached to the benthos survived the event and recovered endosymbionts within 7 months of bleaching. Cladiella sp. 1 Symbiodiniaceae density (in cells per µg protein), chlorophyll a and c 2 per µg protein, and photosynthetic efficiency were significantly lower in bleached colonies compared to unbleached colonies, while chlorophyll a and c 2 per symbiont were higher. Interestingly, no other symbiotic octocoral species of the Lord Howe Island lagoonal reef bleached. Unbleached Xenia cf crassa colonies had higher Symbiodiniaceae and chlorophyll densities during the marine heatwave compared to other monitoring intervals, while Cladiella sp. 2 densities did not change substantially through time. Previous work on octocoral bleaching has focused primarily on gorgonian octocorals, while this study provides insight into bleaching variability in other octocoral groups. The study also provides further evidence that octocorals may be generally more resistant to bleaching than stony corals in many, but not all, reef ecosystems. Responses to marine heating events vary and should be assessed on a species by species basis.
Diamine-Appended Metal Oxide Framework Materials for Thermal-Swing Ad- and Desorption of Carbon Dioxide at Ambient Conditions

Carbon dioxide is a waste product of human metabolism that is unwanted in the indoor atmosphere. Here we test advanced materials that could be used to pump away carbon dioxide and thereby improve indoor air quality. Metal-organic framework (MOF) structures have a variety of properties that make them attractive for direct air capture (DAC) of CO2. In this study, Mg2 (dobpdc4- = 4,4-dioxidobiphenyl-3,3-dicarboxylate) and m-2-m-Mg2(dobpdc) were evaluated for their ability to adsorb and desorb CO2 at ambient atmospheric conditions via a thermal swing. The Mg2(dobpdc) sample did not show appreciable interaction with CO2 in contrast to the diamine-appended version. The molar occupancy of CO2 on the active sites of m-2-m-Mg2 (dobpdc) (m-2-m = N,N-dimethylethylenediamine) during adsorption and desorption was in the range of 5.6–11.8%. These experiments showed the rapid ad- and de-sorption of CO2 by the MOF. Relative humidity was seen to be an important variable and the performance of the tested structures decreased slightly after several cycles of use.