Miracle-dz/UniFAR-FTUs huggingface dataset:
Steroid-Refractory Immune-Related Adverse Events Induced by Checkpoint Inhibitors

Simple Summary With the common use of immune checkpoint inhibitors (ICIs) as a standard therapy for many tumor entities, the number of immune-related adverse events (irAEs) has increased. Side effect management for irAEs includes the administration of corticosteroids which are mostly very effective. However, a subgroup of patients with checkpoint inhibitor-induced side effects do not adequately respond to steroids with so-called steroid-refractory side effects (sr-irAEs) or cannot be tapered off steroids without the recurrence of side effects, the so-called steroid-dependent side effects (sd-irAEs). Since little is known about the incidence and management of sr/sd-irAEs, we investigated the occurrence and management of these difficult-to-treat side effects. This is the first study to report on the incidence rate of steroid-refractory or steroid-dependent irAEs in patients with skin cancer. Abstract The occurrence, second-line management and outcome of sr/sd-irAEs was investigated in patients with skin cancer. All skin cancer patients treated with immune checkpoint inhibitors (ICIs) between 2013 and 2021 at a tertiary care center were analyzed retrospectively. Adverse events were coded by CTCAE version 5.0. The course and frequency of irAEs were summarized using descriptive statistics. A total of 406 patients were included in the study. In 44.6% (n = 181) of patients, 229 irAEs were documented. Out of those, 146 irAEs (63.8%) were treated with systemic steroids. Sr-irAEs and sd-irAEs (n = 25) were detected in 10.9% of all irAEs, and in 6.2% of ICI-treated patients. In this cohort, infliximab (48%) and mycophenolate mofetil (28%) were most often administered as second-line immunosuppressants. The type of irAE was the most important factor associated with the choice of second-line immunosuppression. The Sd/sr-irAEs resolved in 60% of cases, had permanent sequelae in 28% of cases, and required third-line therapy in 12%. None of the irAEs were fatal. Although these side effects manifest in only 6.2% of patients under ICI therapy, they impose difficult therapy decisions, especially since there are few data to determine the optimal second-line immunosuppression.
Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades

Gentamicin causes kidney injury due to its accumulation in proximal tubule epithelial cells via the megalin/cubilin/CLC-5 complex. Recently, shikonin has been shown to have potential anti-inflammatory, antioxidant, antimicrobial, and chloride channel-inhibiting effects. The current study investigated the alleviation of gentamicin-induced renal injury by shikonin while preserving its bactericidal effect. Nine-week-old Wistar rats were administered 6.25, 12.5, and 25 mg/kg/day shikonin orally, one hour after the i.p. injection of 100 mg/kg/day gentamicin for seven days. Shikonin significantly and dose-dependently alleviated gentamicin-induced renal injury, as revealed by restoring normal kidney function and histological architecture. Furthermore, shikonin restored renal endocytic function, as indicated by suppressing the elevated renal megalin, cubilin, and CLC-5 and enhancing the reduced NHE3 levels and mRNA expressions induced by gentamicin. These potentials could be attributed to the modulation of the renal SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt cascades, which enhanced the renal antioxidant system and suppressed renal inflammation and apoptosis, as indicated by enhancements of SIRT1, Nrf2, HO-1, GSH, SOD, TAC, Iκb-α, Bcl-2, PI3K, and Akt levels and mRNA expressions, with reduction of TLR-4, NF-κB, MAPK, IL-1β, TNF-α, MDA, iNOS, NO, cytochrome c, caspase-3, Bax levels, and Bax/Bcl-2 ratio. Therefore, shikonin is a promising therapeutic agent for alleviating gentamicin-induced renal injury.
The effect of product innovation, CSR, environmental sustainability and technology innovation on firm performance: a mediated moderation model

The importance of product innovations has increased to the centre of priorities at every level of the firm organisational structure. This study examines the possible links between product innovation, environmental sustainability, and CSR with firm performance (FP) relationships in Malaysian fashion industries. This research has employed environmental sustainability (ES) as a mediating variable. We also examine how technology innovation (TI) affects the link between ES and FP as a moderator. First, we collected data from 310 respondents working in the fashion industry in Malaysia using a survey instrument to arrive at the conclusions. Furthermore, managers were chosen as responders because of their crucial role in the firm ’ s strategic growth. Moreover, data is only collected from firms registered on the Bursa Malaysia Stock Exchange. In addition, data for this research were obtained between February and August 2022. Then we used structural equation modelling (SEM) to analyse the data. The scales ’ validity and reliability were rigorously examined, and both were found acceptable. According to the study, product innovation (PI), CSR, and ES each directly influenced the FP. Furthermore, the study concluded that the mediating variable ES and moderator technology innovation positively affected FP.
The Response of Summer Lettuce to Irrigation at Different Stages of Growth

The greatest growth response of summer cabbage lettuce to irrigation was found to occur when the soil was restored to field capacity about one week before the first harvest; at this time the ground cover was almost complete and the mean fresh weight was increasing rapidly.Irrigation at 3 weeks or at 5½ weeks after sowing gave only a small increase in the mean fresh weight at harvest, but the crop was slightly earlier. Unirrigated lettuce and those irrigated once only, after 3 weeks, were of poor quality and had a significantly lower moisture content than the good-quality lettuce obtained by irrigating 5½ weeks after sowing or later.
Accessing to a “Truer Truth”: Conspiracy and Figurative Reasoning From Covid-19 to the Russia–Ukraine War

This research hypothesizes that all conspiracy theories have dominating isotopies and images-symbols regardless of ideology or context. As a result, I hypothesized that the common denominator might be discovered in figurative reasoning, which means using the same representations to explain current events, in order to detect an ideal center of the semantic universe of conspiracy where the diverse conspiracist fringes converge. Social media invariant topicalizations of the Covid-19 epidemic and the Russia–Ukraine war are the ideal field to validate this hypothesis. The corpus on which the study was conducted consists of thousands of online items published between February 15, 2020, and October 15, 2022. Within the corpus were chosen posts by QAnon supporters designated as disinformation “superspreaders. ”
Effect of sevoflurane-remifentanil and propofol-remifentanil anesthesia on glycocalyx shedding during deep inferior epigastric perforator flap breast reconstruction: a prospective randomized, controlled trial

Background The endothelial glycocalyx (EG) is an important structure that regulates vascular homeostasis. Deep inferior epigastric perforator (DIEP) flap is expected to cause substantial EG breakdown owing to the long procedural duration and ischemia–reperfusion injury. This prospective, randomized, controlled study aimed to compare syndecan-1 levels during sevoflurane-remifentanil and propofol-remifentanil anesthesia in patients who underwent DIEP flap breast reconstruction. Methods Fifty-one patients were randomized to either sevoflurane (n = 26) or propofol (n = 25) groups. Anesthesia was maintained with remifentanil in combination with either sevoflurane or propofol. The primary endpoint was the concentration of serum syndecan-1 measured at 1 h after surgery. Results Fifty patients (98.0%) completed the study. Patients in the propofol group had significantly lower levels of syndecan-1 than patients in the sevoflurane group at 1 h after operation (23.8 ± 1.6 vs. 30.9 ± 1.7 ng/ml, respectively; Bonferroni corrected P = 0.012). There were no significant differences between groups in postoperative complications. The postoperative hospital stay was 8.4 ± 2.5 days in the sevoflurane group and 7.4 ± 1.0 days in the propofol group (P = 0.077). Conclusions Propofol-remifentanil anesthesia resulted in lesser increases in syndecan-1 levels compared to increases with sevoflurane-remifentanil anesthesia in patients who underwent DIEP flap reconstruction. Our results suggest that propofol-remifentanil anesthesia shows protective effects against EG damage during DIEP flap breast reconstruction in contrast to sevoflurane-remifentanil anesthesia.
A SARS-like Coronavirus was Expected, but nothing was done to be Prepared

It was common knowledge that some strain of coronavirussooner or later-was going to cause a pandemic. It was known since the SARS-CoV-outbreak in 2003. In 2013 and 2015, the world was informed that a variant of SARS-CoV in bats was emerging as a threat for humans. Why was no action taken by our governments and the World Health Organization (WHO)? The Corona crisis was not only conceivable and foreseeable, but the world could have been prepared. We could have had medication and we could have had a vaccine long ago. That is, when there had been visionary medicalpolitical global leadership.
Isometric thumb extension exercise as part of a multimodal intervention for de Quervain’s syndrome: A randomised feasibility trial

Introduction de Quervain’s syndrome is a painful condition commonly presented to hand therapists. Exercise is utilised as an intervention, but isometric exercise has not been investigated. We aimed to assess the feasibility and safety of isometric thumb extension exercise for de Quervain’s syndrome and to explore differences between high-load and low-load isometric exercise. Methods This parallel-group randomised clinical feasibility trial included individuals with de Quervain’s syndrome. All participants underwent a 2 week washout period where they received an orthosis, education, and range of motion exercises. Eligible participants were then randomised to receive high or low-load isometric thumb extension exercises, performed daily for 4 weeks. Feasibility and safety were assessed by recruitment and drop-out rates, adherence, adverse events, and participant feedback via semi-structured interviews. Secondary outcomes included patient-reported outcomes for pain and function, and blinded assessment of range of motion and strength. Results Twenty-eight participants were randomised. There were no drop-outs after randomisation, and no serious adverse events. Adherence to exercise was 86.7%, with 84% of participants stating they would choose to participate again. There were clinically and statistically significant improvements in pain and function over time (p < 0.001) but not in range of motion or strength. There were no statistically significant between-group differences. Conclusions Isometric thumb extension exercise within a multimodal approach appears a safe and feasible intervention for people with de Quervain’s syndrome. A large multi-centre trial would be required to compare high- and low-load isometric exercises. Further research investigating exercise and multimodal interventions in this population is warranted.
The Effects of Antipsychotics in Experimental Models of Krabbe Disease

The role of altered myelin in the onset and development of schizophrenia and changes in myelin due to antipsychotics remains unclear. Antipsychotics are D2 receptor antagonists, yet D2 receptor agonists increase oligodendrocyte progenitor numbers and limit oligodendrocyte injury. Conflicting studies suggest these drugs promote the differentiation of neural progenitors to oligodendrocyte lineage, while others report antipsychotics inhibit the proliferation and differentiation of oligodendrocyte precursors. Here, we utilised in-vitro (human astrocytes), ex-vivo (organotypic slice cultures) and in-vivo (twitcher mouse model) experimental study designs of psychosine-induced demyelination, a toxin that accumulates in Krabbe disease (KD), to investigate direct effects of antipsychotics on glial cell dysfunction and demyelination. Typical and atypical antipsychotics, and selective D2 and 5HT2A receptor antagonists, attenuated psychosine-induced cell viability, toxicity, and morphological aberrations in human astrocyte cultures. Haloperidol and clozapine reduced psychosine-induced demyelination in mouse organotypic cerebellar slices. These drugs also attenuated the effects of psychosine on astrocytes and microglia and restored non-phosphorylated neurofilament levels, indicating neuroprotective effects. In the demyelinating twitcher mouse model of KD, haloperidol improved mobility and significantly increased the survival of these animals. Overall, this study suggests that antipsychotics directly regulate glial cell dysfunction and exert a protective effect on myelin loss. This work also points toward the potential use of these pharmacological agents in KD.
Association between length of stay and postoperative survival in patients with lung cancer: a propensity score matching analysis based on National Cancer Database

Background Postoperative complications tend to result in prolonged hospitalization. The aim of this study was to investigate whether prolonged postoperative length of stay (LOS) can predict patient survival, particularly long-term survival. Methods All patients undergoing lung cancer surgery between 2004 and 2015 were identified in the National Cancer Database (NCDB). The highest quintile of LOS (more than 8 days) was defined as prolonged length of stay (PLOS). We performed 1:1 propensity score matching (PSM) between the groups with and without PLOS (Non-PLOS). Excluding confounding factors, postoperative LOS was used as a surrogate for postoperative complications. Kaplan-Meier and Cox proportional hazards survival analyses were performed to analyze survival. Results A total of 88,007 patients were identified. After matching, 18,585 patients were enrolled in the PLOS and Non-PLOS groups, respectively. Before and after matching, 30-day rehospitalization rate and 90-day mortality in the PLOS group were significantly higher than they were in the Non-PLOS group (P<0.001), indicating a potential worse short-term postoperative survival. After matching, the median survival of the PLOS group was significantly lower than that of the Non-PLOS group (53.2 vs. 63.5 months, P<0.0001). Multivariable analysis revealed that PLOS is independent negative predictor of overall survival [OS; hazard ratio (HR) =1.263, 95% confidence interval (CI): 1.227 to 1.301, P<0.001]. In addition, age (<70 or ≥70), gender, race, income, year of diagnosis, surgery type, pathological stage, and neoadjuvant therapy also were independent prognostic factors of postoperative survival for patients with lung cancer (all P<0.001). Conclusions Postoperative LOS could be taken as the quantitative indicator of postoperative complications of lung cancer in NCDB. In this study, PLOS predicted worse short-term and long-term survival independent of other factors. Avoiding PLOS could be considered to benefit patient survival after lung cancer surgery.
Incidence and Cross-Continents Differences in Endoscopic Retrograde Cholangiopancreatography Outcomes Among Patients With Cirrhosis: A Systematic Review and Meta-Analysis

Background There are conflicting data on the frequency and variability of endoscopic retrograde cholangiopancreatography (ERCP) outcomes in patients with cirrhosis. Our aim was to systematically review the literature on the incidence of post-ERCP adverse events in cirrhotic patients and to examine the differences across continents. Methods We searched PubMed/MEDLINE, EMBASE, Scopus, and Cochrane databases to identify studies reporting adverse events after ERCP in patients with cirrhosis from conception to September 30, 2022. The random effects model was used to calculate odds ratios (ORs), mean differences (MDs), and confidence intervals (CIs). A P value < 0.05 was considered statistically significant. Heterogeneity was assessed using the Cochrane Q-statistic (I2). Results Twenty-one studies that included 2,576 cirrhotic patients and 3,729 individual ERCPs were analyzed. The pooled overall rate of adverse events after ERCP in patients with cirrhosis was 16.98% (95% CI: 13.06-21.29%, P < 0.001, I2 = 86.55%). ERCPs performed in Asia had the highest ERCP adverse events with an overall complication rate of 19.90%, while the lowest overall adverse events were in North America at 13.04%. The pooled post-ERCP bleeding, pancreatitis, cholangitis and perforation were 5.10% (95% CI: 3.33-7.19%, P < 0.001, I2 = 76.79%), 3.21% (95% CI: 2.20-5.36%, P = 0.03, I2 = 42.25%), 3.02% (95% CI: 1.19-5.52%, P < 0.001, I2 = 87.11%), and 0.12% (95% CI: 0.00 - 0.45, P = 0.26, I2 = 15.76%), respectively. The pooled post-ERCP mortality rate was 0.22% (95% CI: 0.00-0.85%, P = 0.01, I2 = 51.86%). Conclusions This meta-analysis shows that the overall complication rates after ERCP, bleeding, pancreatitis, and cholangitis are high in patients with cirrhosis. Because cirrhotic patients are more likely to have post-ERCP complications, with significant cross-continent variations, the risks and benefits of ERCP in this patient population should be carefully considered.
Effectiveness of virtual reality technology in teaching pedestrian skills to children with intellectual disabilities

Pedestrian skills are important for children with intellectual disabilities to continue their daily lives independently. The aim of this study is to determine the effectiveness of virtual reality in the acquisition and maintenance of pedestrian skills for children with intellectual disabilities. In addition, the effect of virtual reality on participants generalizing their pedestrian skills to real environments has also been examined. In the study, social validity data were collected from the participants and their mothers regarding the results of the study. Three intellectual disabled children between the ages of 11 and 15 participated in the study. In the study, a multiple probe design with inter-participant probe trial, which is one of the single-subject research models, was used. It is seen that all participants learned pedestrian skills and continued the skills they learned one, three and five weeks after the completion of the instruction. In addition, all participants were able to generalize their skills to the real environment (pedestrian crossing and illuminated pedestrian crossing). When the social validity data collected from the participants and their mothers were examined, it was revealed that teaching with virtual reality applications is interesting and fun, in addition, it can be used for different educational purposes.
Skin Lesion Classification Using Hybrid Convolutional Neural Network with Edge, Color, and Texture Information

Herein, a new paradigm based on deep learning was proposed that allows the extraction of fine-grained differences between skin lesions in pixel units for high accuracy classification of skin lesions. As basic feature information for a dermoscopic image of a skin region, 50 different features were extracted based on the edge, color, and texture features of the skin lesion image. For the edge features, a line-segment-type analysis algorithm was used, wherein the visual information of a dermoscopic image was precisely analyzed in terms of the units of pixels and was transformed into a structured pattern. Regarding the color features of skin lesions, the dermoscopic image was transformed into multiple color models, and the features were acquired by analyzing histograms showing information regarding the distribution of pixel intensities. Subsequently, texture features were extracted by applying the well-known Law’s texture energy measure algorithm. Feature data (50 × 256) generated via the feature extraction process above were used to classify skin lesions via a one-dimensional (1D) convolution layer-based classification model. Because the architecture of the designed model comprises parallel 1D convolution layers, fine-grained features of the dermoscopic image can be identified using different parameters. To evaluate the performance of the proposed method, datasets from the 2017 and 2018 International Skin Imaging Collaboration were used. A comparison of results yielded by well-known classification models and other models reported in the literature show the superiority of the proposed model. Additionally, the proposed method achieves an accuracy exceeding 88%.
Stabilized Finite Element Methods for Coupled Incompressible Flow Problems

In this thesis, a finite element discretization of the incompressible Navier-Stokes equations for a non-isothermal and electrically conducting fluid in a possibly rotating frame of reference is considered. In particular, the Oberbeck-Boussinesq model is combined with resistive incompressible magnetohydrodynamics. In order to account for instabilities and to diminish unphysical oscillations a stabilization for the incompressibility constraint as well as a local projection approach for various terms is considered. For the spatial discretization inf-sub stable ansatz spaces for velocity and pressure are used. With respect to the semi-discretization in space stability analysis is performed and quasi-optimal and semi-robust error estimates are derived for each coupling separately. Additionally, it is investigated how the results for the Navier-Stokes equations extend from Dirichlet to outflow boundary conditions. With respect to the full discretization a segregation scheme based on a pressure-correction projection method is considered. Also for this model stability is investigated and quasi-optimal and semi-robust error estimates are derived. Numerical results are used to validate the analytical findings and to investigate the influence of the stabilization terms apart from convergence on the numerical solutions. Some analytical results confirm the proposed rates of convergence in space and time and show the importance of grad-div stabilization. Afterwards, more realistic test cases such as the expulsion of the magnetic field by a fast rotating electrically conducting fluid or Rayleigh–Benard convection in an inertial or rotating frame of reference are considered to obtain a suitable design for the stabilization parameters. Finally, the effectiveness of the implementation is demonstrated.
Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix–Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology

The Astragali Radix–Cinnamomi Ramulus herb-pair (ACP) has been widely used in the treatment of diabetic peripheral neuropathy (DPN) as part of East Asian herbal medicine (EAHM). Eligible randomized controlled trials (RCTs) were identified by searching 10 databases. The outcomes investigated were response rate, sensory nerve conduction velocity (SNCV), and motor nerve conduction velocity (MNCV) in four regions of the body. The compounds in the ACP and their targets of action, disease targets, common targets, and other relevant information were filtered using network pharmacology. Forty-eight RCTs, with 4308 participants, and 16 different interventions were identified. Significant differences were observed in the response rate, MNCV, and SNCV, as all EAHM interventions were superior to conventional medicine or lifestyle modification. The EAHM formula containing the ACP ranked highest in more than half of the assessed outcomes. Furthermore, major compounds, such as quercetin, kaempferol, isorhamnetin, formononetin, and beta-sitosterol, were found to suppress the symptoms of DPN. The results of this study suggest that EAHM may increase therapeutic efficacy in DPN management, and EAHM formulations containing the ACP may be more suitable for improving treatment response rates to NCV and DPN therapy.