Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.

Adverse events associated with opioid use in palliative care have been extensively studied. However, predicting the occurrence of adverse events based on the specific opioid used remains unclear. This study aimed to comprehensively analyze the adverse events caused by µ receptor stimulation of opioids approved in Japan and investigate the tendencies of adverse event occur-rence among different opioids.We utilized the FDA Adverse Event Reporting System (FAERS) database to extract reported adverse events of opioids approved in Japan. Cluster analysis was performed on reporting odds ratios (RORs) of adverse event names among opioids to visualize relationships between opioids and adverse events, facilitating a comparative study of their clas-sifications.We calculated the RORs of adverse events for the target opioids. Based on these RORs, we performed a cluster analysis, which resulted in the classification of 11 target opioids into five distinct groups. we were able to comprehensively compare and examine the relationships between opioids and adverse events. This analysis helps in understanding and managing the risks and benefits of each drug in palliative care settings. By analyzing relationships between opioids and adverse events, clinicians can make informed decisions about opioid selection, dosage, and monitoring to maximize patient safety and comfort.

The cytokine-producing nucleotide-binding domain leucine-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome is generally recognized to play a central role in the immune response to vaccination and NLRP3 activity is known to be increased by both aluminum adjuvants and by oxidative stress. Thus, the presence of oxidative stress may place individuals at higher risk for exaggerated or prolonged inflammatory responses and related side effects from vaccination. We here examine the relationship between oxidative stress and NLRP3 inflammasome activity, particularly in the context of aluminum-adjuvanted vaccines, and its implications for subpopulations of individuals with restricted antioxidant capacity.

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Local food has continued to become more popular in both the home and as featured ingredients in all segments of food service. Numerous studies have explored the motivating factors for consumer purchasing motivators. However, no known study has explored if there is a correlation between ego and intent to buy local foods. This study adopted a modified version of the Theory of Trying and surveyed a sample of 237 food service buying agents in South Carolina to examine their perceptions of buying local. Results suggest that ego is a predictor of trying to purchase local foods for restaurants. It was also found that the modified model is an acceptable model for predicting buyer intent. These findings support the majority of the studies looking at ego-centric behaviors with green purchases and could potentially help local food suppliers to better market their products to foodservice establishments. This study could also act as the foundation for future studies to explore the full extent of ego’s motivational effect on purchasing intentions in the food service industry.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

Endoscopic retrograde cholangiopancreatography (ERCP) is a routinely used therapeutic procedure for the biliary and pancreatic diseases. Population aging may increase the typical indications of ERCP and come with more complexity and difficulties, especially in cannulation. This study aimed to evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in super-aged patients and the role of difficult cannulation as a risk factor for adverse events. A total of 614 patients, underwent ERCP, were prospectively studied as a cohort and divided into two groups based on their age. There were 146 patients aged 80 years or older in group A and 468 patients aged less than 80 years in group B. The primary outcome measures were the difficulty grade of papilla cannulation, clinical outcomes, and ERCP-related complications in the two groups. The adverse events were analyzed using logistic regression for patient age, co-morbidities, indications, and cannulation difficulty grade variables. There was no difference in the incidence of difficult cannulation between the two groups (32.9% vs. 34.4%, p=0.765) though, as expected, super-aged Group A had a higher prevalence of periampullary diverticulum (29.5% vs. 16.7%, p=0.001). The technical cannulation success rate was (96.6% vs. 96.8%, p= 0.54). All used cannulation techniques in the elderly group were efficient and safe. Logistic regression showed that age ≥80 was not associated with increased adverse events; however, difficult cannulation (adjusted odds ratio [AOR]=3.478; 95% confidence interval [CI]=1.877, 6.442; p<0.001) and CCI ≥2 (AOR=1.824; 95% CI=0.993, 3.349; p=0.045) were more likely to have adverse events. Age ≤65 (AOR=3.460; 95% CI=1.511, 7.922; p=0.003), female gender (AOR=2.362; 95% CI=1.089, 5.124; p=0.030), difficult cannulation (AOR=4.527; 95% CI=2.078, 9.860; p<0.001), and patients with cholangitis (AOR=3.261; 95% CI=1.204, 8.832; p=0.020) were strongly associated with increasing Post-ERCP Pancreatitis (PEP). Advanced age has not proved to be a risk factor of difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized for this group. CCI ≥2 and difficult cannulation are associated with increased overall adverse events rate while age ≥80 factor is not.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

The immunization of healthcare workers in the early stages of the rollout of COVID-19 vaccines was prioritized in order to ensure uninterrupted medical care provision. At the same time the increasing number of available COVID-19 vaccines may trigger hesitancy towards the decision to get vaccinated. Thus, accumulating reliable information on the adverse events following immunization may educate and urge the general population to receive a COVID-19 vaccine. The present study aimed to evaluate the adverse events (AEs) following immunization with any of the available COVID-19 vaccine among Bulgarian healthcare workers (HCWs). A cross-sectional study among HCWs in Plovdiv, Bulgaria was conducted in the period March – September 2021. Through a semi-structured online questionnaire, the participants reported the adverse events following the administration of the first and second dose of a COVID-19 vaccine. A total of 253 respondents, vaccinated with one of the available vaccines against COVID-19 took part in the study. Of them 71.9% were females, and 75.9% received mRNA-based vaccines, while 24.1% received a viral-vector based vaccine. Overall 91.6% and 82.6% of all participants reported at least one local AE after the first and second dose of a COVID-19 vaccine. The share of respondents reporting at least one systemic AE after the first and second dose of a COVID-19 vaccine was 59.7% and 62.4% respectively. The most common local AE was pain at the injection spot (84.0%), while the most common systemic AEs were fatigue (54.9%), chills (43.2%), and headache (41.7%). The mRNA-based vaccines versions seem to cause higher prevalence of local AEs, while the vector-based vaccines were linked with increased prevalence of systemic AEs. Female HCWs and the younger age group were associated with an increased risk of adverse events generally. Our results added more evidence that mRNA-based and viral-vector based vaccines are generally safe. The reported adverse events were mild, although they occurred in a high share of the respondents. No serious AEs attributable to the vaccines were reported.

Abstract: Background: Dental fear and uncooperative behavior can hinder dental treatment quality. Pediatric Procedural Sedation and Analgesia (PPSA) is used to facilitate treatment when coping capacity is exceeded. Out-of-hospital PPSA has been associated with more adverse outcomes compared to hospital-based settings. Updated Dutch PPSA guidelines recommending two anesthesiologists and a ventilator during out-of-hospital PPSA have increased costs and raised concerns about the accessibility to specialized high quality dental care for children in the Netherlands. Aim: This study aims to investigate the impact of the updated 2017 guideline on the occurrence rate of adverse events during PPSA, as recorded in the anesthesia complication database of twelve participating Dutch dental clinics, with adjustments made for age, weight, and duration of treatment. Method: Data of 25,872 children treated at 12 dental clinics performing out-of-hospital PPSA between 1997 and 2019 were analyzed. Eligible children were aged 2-18 with ASA classification I and II. A logistic two-level mixed-effects model is used to estimate the updated guideline’s impact on adverse events. Results: In the final model we analyzed the data of 21,759 children in nine dental clinics. The OR of the occurrence rate of an adverse event adjusted for age, weight, and duration of treatment was 0.75 (95% CI 0.64 – 0.89) after the implementation of the updated guideline, compared to before the updated guideline. This outcome was significant with a P=0.001, indicating a protective effect. The average odds per clinic of having an adverse event was 0.04 with a 3.81% chance. Conclusion: Our findings demonstrate a significant reduction in adverse events after the implementation of the updated guideline and highlight the importance of adherence to evidence-based guidelines in improving patient safety and the quality of care provided during pediatric procedural sedation and analgesia in out-of-hospital dental clinics. Our study underlines the necessity of considering the complex underlying mechanisms that play a role in the development and implementation of evidence-based practice and safety initiatives on the occurrence of adverse events.

Rare cardiac adverse events are reported post vaccinations. For the SARS-CoV-2 vaccines, higher numbers of these cardiac adverse events are being reported with myocarditis disproportionately occurring in younger males. The etiology of these cardiac adverse events associated with vaccines including SARS-CoV-2 is unknown. The etiology of the higher frequency of these cardiac adverse events temporally associated with SARS-CoV-2 vaccines is also unknown. This article proposes that innate immune responses to vaccines cause elevated histamine levels post vaccination; the histamine level reached may exceed the vaccinees’ histamine tolerance level for several days. This article proposes that the elevated histamine level is causative for the reported cardiac adverse events. For myocarditis reported adverse events, this article proposes that elevated histamine levels induce cardiac capillary pericyte induced vasoconstrictions followed by localized ischemia and anoxia; this is followed by the release of troponin from myocyte cells affected by anoxia. This hypothesis is supported by the temporal onset timing of adverse events reported following SARS-CoV-2 vaccinations in the United States Department of Health and Human Services Vaccine Adverse Event Reporting System (VAERS). This model applies to multiple vaccines with innate immune response histamine levels generated varying by each vaccine and incidence frequencies correlate with vaccine reactogenicity.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

This study evaluates the incidence and characteristics of adverse events (AEs) following the second COVID-19 booster dose, leveraging Taiwan's distinctive approach of extending booster vaccinations to all citizens, unlike the targeted high-risk group strategies in other countries. Utilizing data from Taipei Veterans General Hospital's Vaccine Adverse Event Reporting System (VAERS) from October 27, 2022, to January 19, 2023, the research examines AEs in 441 out of 1711 second booster recipients, considering factors like age, vaccine brands, and booster combinations. The findings reveal incidence rates (IR) of 25.6% (95% CI: 21.1-30.8) after the first booster and 24.9% (95% CI: 20.5-30.0) after the second, mostly non-serious, with those having AEs post-first booster 5 times more likely to report them again (Incidence rat rato, 5.02, P&lt;0.001). Significantly, switching from the mRNA1273 vaccine to another brand reduced AE risk by 18%. The study underscores that AEs are more repetitive than cumulative with additional booster doses, advocating for personalized vaccination strategies based on individual medical histories and previous vaccine reactions. These insights are valuable for healthcare providers in discussing potential AEs with patients, thereby improving vaccine compliance and public trust, and for policymakers in planning future booster vaccination strategies.

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts. This paper serves as a review of fish kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early-warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early-warning systems, and viable and holistic mitigation strategies to protect the region’s aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia.

Patients with Peripheral-artery-disease (PAD) are prone to risks of major-adverse-limb-events (MALE), and major-adverse-cardiovascular-events (MACE). CHA2DS2-VASc is a prognostic score for Atrial fibrillation stroke risk, however, no study exists that evaluated its predictability for MALE and MACE in PAD patients. In this study, patients with PAD were stratified into four risk groups based on CHA2DS2-VASc score. Cox-proportional hazards models,10-fold cross-validation and Receiver operating characteristic (ROC) analyses were utilized to evaluate the predictability of CHA2DS2-VASc for predicting MALE, MACE, and MALE+MACE. Kaplan-Meier analysis estimated the survival-probability of risk-groups. CHA2DS2-VASc was found to be a significant predictor of MACE (hazard ratio (95% confidence interval; P) = 3.47 (0.99 - 12.18; 0.052), 4.12 (1.19 - 14.14; 0.024), and 5.06 (1.48 – 17.28; 0.009), for moderate-, high- and very-high-risk groups, respectively, while for MALE and MALE+MACE significance was achieved only for high-risk group. MACE demonstrated AUC > 0.8, good-discrimination (c-index > 0.8) and good-calibration. However, MALE and MALE+MACE models failed to achieve good performances. Based on all findings, CHA2DS2-VASc could potentially serve as a risk stratification score for predicting MACE in patients with PAD but failed to qualify as a good predictor for MALE.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Background: As a relatively high number of ST-segment elevation myocardial infarction (STEMI) patients develop major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI), our aim was to determine the significance, and possible predictive value of QRS complex width and ST-segment elevation. Methods: Our patient sample included 200 PCI-treated STEMI patients, which were divided into two groups, based on the duration of symptoms: (I) less than 6 hours, and (II) 6-12 hours. For every patient, ECG was performed at 6 different time points. Long-term follow-up lasted 6 years from the STEMI onset. Statistical analysis was performed. Results: The mean age was 60.6±11.39 years, and 142 were male. Wider QRS complex, more pronounced ST-segment elevation, and more frequently absent ST-segment resolution were more common in the second group. Presentation of MACE was more frequent in this group. An increase of pre-PCI QRS complex width by 1 msec increases the risk of 6-year MACE by 3%, and an increase in pre-PCI ST-segment elevation by 1mm increases the risk of 6-year MACE by 3.26 times. Conclusion: To the best of our understanding, this study represents a pioneer research that utilized these ECG elements in the context of predicting a 6-year MACE. A wider QRS complex and a more pronounced ST-segment elevation were associated with longer total ischemic time. More research is needed to confirm these findings.

Background: Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were: i) to observe the humoral immune response to BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and iii) to determine adverse effects after primary vaccine doses. Methods: To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. Results: We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Conclusion: Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

At present, there are still no specific therapeutic drugs and appropriate vaccines for Dengue. Therefore, it is very important to explore distinct clinical diagnostic indicators. In this study, we combined differentially expressed genes (DEGs) analysis and weighted co-expression network analysis (WGCNA) to screen a stable and robust biomarker which can be used to distinguish three clinical stages of Dengue and severity of Dengue. CD38 can distinguish excellently Early Acute, Late Acute, Convalescent stages for Dengue patients, and ZNF595 can discriminate DHF from DF in whole acute stages. We also found that three clinical stages can be discriminated based on the fractions of Plasma cells, activated memory CD4+ T cells, and Monocytes. In different clinical stages different immune cells function positively. Negative inhibition of viral replication based on Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA), up-regulated autophagy genes and impairing immune system are potential reasons resulting in dengue hemorrhagic fever (DHF).

Patients diagnosed with cancer are less frequently covered by preventive measures for cardiovascular diseases. The frequent co-occurrence of these diseases makes it necessary to apply parallel diagnostics and cardiological treatment with anti-cancer therapy. Case report: We present a case of a 73-year-old former smoker with hyperlipidemia, type 2 diabetes, and arterial hypertension, after a partial right nephrectomy in 2005 due to kidney cancer, diagnosed with SARS-COV-2 infection in April 2022. Follow-up chest imaging showed a 20 mm focal lesion in the left lung further classified as a small cell neuroendocrine carcinoma. Unexpectedly the patient was hospitalized for ST-segment elevation inferior left ventricular (LV) myocardial infarction treated successfully with coronary angioplasty, however heart failure (HF) with reduced left ventricle ejection fraction was diagnosed. One month later patient required another hospitalization due to the HF decompensation and cardiological treatment was optimized with flozin addition to the standard HF therapy. After cardiological approval chemotherapy was initiated with the cisplatinum-etoposide regimen and continued for 6 months without HF decompensation and significant deterioration of renal function. After that, the patient underwent radical radiotherapy. Follow-up chest computed tomography scans showed regression of the neoplastic lesion. Conclusions: Coincidence of newly recognized cancer and infection might contribute and provoke serious cardiological events . To reduce the risk of cardiovascular complications, early periodic cardiological surveillance and optimal pharmacotherapy are required.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining nolecules, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We here evaluated available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining antidiabetics, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To our best, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other novel antidiabetics and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Background: As the world tends to recover from the crisis created by the COVID-19 pandemic, vaccines have served as one of the most valuable tools of combat and large-scale immunization has helped to tide over the catastrophe. However, several reports of post -vaccination neurological complications around the globe have surfaced up in recent literature. This study was conducted with an aim to describe the spectrum of neurological ailments requiring hospitalization following COVID-19 vaccination.Methods: An ambispective observational study was carried out from March 2021 to February 2022 at a tertiary care institute with 25 patients who satisfied the inclusion criteria of a new onset neurological illness requiring hospitalization within 4 days to 42 days of vaccination. The patients were duly followed upto months after discharge.Results: The median age of the sample was 36 years and the median latency of onset of neurological events was 14 days. Guillain-Barré syndrome was documented in 11 patients; majority were acute motor axonal neuropathy (45.45%) followed by acute inflammatory demyelinating polyradiculoneuropathy (36.36%) and acute motor sensory axonal neuropathy (18.18%). Central nervous system demyelination was reported in 9 patients; two patients had acute disseminated encephalomyelitis, 2 patients were diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease, one patient with aquaporin-4 positive neuromyelitis optica spectrum disorder , and the rest were labelled as seronegative central nervous system demyelination. Vascular events were noted in 5 patients comprising of 2 cases each of cerebral venous sinus thrombosis and intracerebral hemorrhage and a case of Moyamoya angiopathy. All patients were conservatively managed and had a complete to partial recovery suggestive of a favorable outcome after 3 months. Conclusion: The pathomechanisms of post -vaccination neurological complications is yet to be elucidatedand any causal association attributable to vaccination warrants further research. Compared to the enormity of the vaccinated population, the adverse effects are miniscule to hinder and discourage vaccination.

Cannabidiol, is the first cannabis-derived drug approved for the treatment of Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). The current study performed a descriptive analysis followed by a disproportionality analysis of potential adverse events caused by CBD extracted from the database VigiBase®. Further, biological plausibility of the association between CBD and the serotonin 5-HT1A receptor, as possible cause of adverse events was analyzed and discussed. Data were extracted from VigiBase® database using VigiLyze® signal detection and signal management tool. Adverse events in VigiBase® reports were coded using MedDRA, version 19 of Preferred Terms (PTs). Data were uploaded into SPSS software and analyzed via disproportionality analysis. Statistically significant disproportionality signals for CBD were found for “weight decreased” 5.19 (95% CI: 4.54 - 5.70), “hypophagia” 3.68 (95% CI: 3.22 - 5.27), and “insomnia” 1.6 (95% CI: 1.40 - 1.83). Positive IC025 values were found for “weight decreased” (2.2), “hypophagia” (1.3), and “insomnia” (0.5), indicating a surplus of reported cases. CBD’s interactions with 5-HT1A serotonin receptors may offer a potential biological explanation for the occurrence of insomnia in patients. It is noteworthy that the risk profiles mentioned in the prescribing information for CBD as antiepileptic agent by regulatory agencies showed disparities specifically related to the adverse event “insomnia”.

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that has significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.

This post-hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visit and hospitalization in women and men. During the study period (January 2007 – December 2018), 61,855 reports of ADE leading to ED visit were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13-176), antidepressants (ROR 1.12, CI 1.03-1.23) and antidiabetics (ROR 1.13, CI 1.02-1.24). Among men only vitamin K antagonists (ROR 1.28, CI 1.09-1.50), opioids (ROR 1.30, CI 1.06-1.60) and digitalis glycosides (ROR 1.32, CI 1.09-1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidi-ties were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing and adverse event following immunization (ROR 0.36, CI 0.27-0.48 and 0.83, 0.42-0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes.

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of the heterogeneity of programmed cell death. The purpose of this work is to investigate and develop a cuproptosis-associated lncRNA-based LUAD prediction marker. We firstly performed bioinformatic analysis of the Cuprotosis database and The Cancer Genome Atlas (TCGA) database to obtain 19 cuprotosis-related gene datasets and transcriptional data for LUAD. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were utilized to construct cuproptosis-associated lncRNA modes. LUAD patients were thus classified into high-risk and low-risk categories based on prognostic risk values, with a median of It acted as a boundary. Risk models were evaluated and validated using Kaplan-Meier analysis, principal component analysis (PCA), gene set enrichment analysis (GSEA) and nomograms. Utilizing the TCGA-LUAD dataset, we identified seven predicted cuproptosis-associated lncRNAs in tumor microenvironment to create the risk model. 95.54% (214/224) of high-risk category tumor samples included cuproptosis-associated gene alterations, compared to 85.65% (203/237) of low-risk category tumor samples, with TP53 accounting for the bulk of occurrences. According to these findings, risk value was superior to other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival (OS). The predictive validity of the cuproptosis-associated lncRNA-based risk model for LUAD is high, and this may have implications for how lung cancer patients are treated individually.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients’ colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cutoff values for these three markers. The high APRIL/TNFSH13 expression group showed a significantly higher rate of metastatic lesions than the low expression group, whereas the high MMP-3 expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low expression group. The five-year disease-free survival of the high MMP-3 expression group was significantly shorter than that of the low expression group (65.1% vs. 90.2%, p=0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.

Abstract Background The number of immune-related endocrine dysfunctions (irEDs) has concurrently increased with the widespread use of immunotherapy in clinical practice and further expansion of the approved indications for immune checkpoint inhibitor (ICI) combinations using different modalities of anti-cancer treatment. Method A retrospective analysis was conducted on consecutive patients >18 years of age with advanced solid malignancies who had received at least one dose of anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies between January 2014 and December 2019 at a Hong Kong university hospital. Patients were reviewed for up to two months after the last administration of an ICI. The types, onset times and grades of irEDs, including hypothyroidism, hyperthyroidism, adrenal insufficiency and immune-related diabetes mellitus, were recorded. Factors associated with irEDs were identified using multivariate analysis. Result A total of 953 patients (male: 603, 64.0%; median age: 62.0 years) received ICIs during the study period. Of these, 580 patients (60.9%) used ICI-alone, 132 (13.9%) used dual-ICI, 187 (19.6%) used an ICI combined with chemotherapy (chemo+ICI), and 54 (5.70%) used immunotherapy with a targeted agent (targeted+ICI). A significantly higher proportion of patients using targeted+ICI had irEDs and hypothyroidism; in contrast, a higher proportion of patients using dual-ICI had adrenal insufficiency. There was no significant difference in the incidence of irED between the younger (<65 years) and older (>65 years) patients. Using logistic regression, only treatment type was significantly associated with irEDs. Notably, older patients had a higher risk of having immune-related diabetes mellitus. Conclusions This large, real-world cohort demonstrates that combining ICI with targeted therapy has a higher risk of overall irED and hypothyroidism. Immunotherapy is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is needed in older populations.

Reservoirs created by damming rivers significantly modify the environment and problems may arise: the storage of nutrients and organic matter in reservoirs often leads to decreased water quality due to eutrophication. Reservoirs built on lowland rivers are exposed to significant nutrient loads, often leading to eutrophication. In this article, the Sulejów Reservoir, in Central Poland, was the subject of the research, which focused on the use of Sentinel-2 remote sensing data to detect phytoplankton blooms, and on understanding the pattern of wind-driven surface currents using the CCHE2D model (a depth-averaged hydrodynamic model). The calculation of the total phosphorus load has shown that the reservoir mainly acts as nutrient storage. Still, during the low flow and intensive phytoplankton bloom, it can be a source of nutrients. The distribution of phytoplankton bloom on the Sulejów Reservoir was documented using eight Sentinel-2 satellite images from the vegetation season of 2020 and the Normalized Difference Chlorophyll Index (NDCl). Coupling remote sensing data and numerical modelling helps to interpret the hydrodynamic model results and understand nutrients and sediment dynamics within the reservoir. Hydrodynamic modelling combined with remote sensing data can be a valuable tool for selecting appropriate locations for water quality measurements at monitoring stations.

A 64-year-old woman with primary Sjogren’s syndrome which was not treated, was admitted to our hospital for nasal bleeding, oral bleeding, and purpura on her entire body. On this admission, laboratory findings were as follows: WBC counts, 8,910 /μL; hemoglobin, 9.9 g/dL; and platelet counts, 0.1×10⁴/μL. Although the anti-PLT antibody was positive, other autoimmune antibodies such as anti-DNA were negative. Moreover, cytomegalovirus IgM, Parbovirus B19 IgM, and Helicobacter pyroli IgG antibodies were not detected. No abnormal findings suggestive of infection were identified in the systemic examination. A bone marrow aspiration smear revealed normal bone marrow. Based on these findings, the patient was diagnosed with primary Sjogren’s syndrome-related immune thrombocytopenia. The patient initially received intravenous immunoglobulin, methyl prednisolone pulse therapy, and subsequent high dose prednisolone without significant improvement. Therefore, eltrombopag, a thrombopoietin-receptor agonist, was added. Subsequently, erythromycin was also added, considering its immunomodulatory effects. After initiating the erythromycin treatment, the platelet counts increased. Therefore, add-on eltrombopag and erythromycin treatment was effective; however, the platelet counts gradually decreased with reducing the prednisolone dosage. Instead of increasing the prednisolone dosage again, tacrolimus, a calcineurin inhibitor, was successfully added. Consequently, the prednisolone dosage could be reduced. This case shows that treatment with erythromycin and tacrolimus may be efficacious when conventional immunosuppressants show limited effectiveness in primary Sjogren’s syndrome-related immune thrombocytopenia.

Background: LncRNA and pyroptosis play important roles in cancer development and tumor immune microenviroment. However, pyroptosis-related lncRNAs (PRLs) in ovarian cancer have not been identified and its impact on prognosis and immune response are not fully understood. Methods: Using pearson correlation analysis, PRLs were screened. Subsequently, we constructed a prognosis signature by using LASSO cox regression. In addition, the association between risk score and cancer immune environment was analyzed. Results: In TCGA-RNA-seq cohort (n=377), 32 prognostic PRLs were selected and a 7-gene signature were developed and had high accuracy in predicting the OS of ovarian cancer patients. Stratification analysis suggested that it might serve as an independent prognostic indicator. Except to clinical outcome, the signature was significantly associated with tumor immune microenvironment. Patients with high risk score exhibited lower infiltration abundance of MHC class Ⅰ cells, Type Ⅰ IFN response and immunotherapy response. In ovarian cancer, TYMSOS was highly expressed and its high expression was associated with worse OS. TYMSOS deletion in ovarian cancer cell lines inhibited the cell proliferation, invasion and migration, indicating that it might serve as a novel biomarker in ovarian cancer. Conclusions: The prognostic PRLs signature constructed in this work is available for prognostic prediction and immune microenvironment infiltration in ovarian cancer.

The COVID-19 pandemic has put a lot of pressure on health systems worldwide. Mass vaccination against SARS-CoV-2 has reduced morbidity and mortality worldwide. Despite their safety profiles, vaccines like any other medical product can cause adverse events. Yet, in countries with poor epidemiological surveillance and monitoring systems, reporting vaccine-related adverse events is scarce. The objective of this study was to describe self-reported vaccine adverse events after receiving one of the available COVID-19 vaccine schemes in Ecuador. A cross-sectional analysis based on an online self-reporting 32-questionnaire was conducted in Ecuador from April 1st to July 15th, 2021. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 6,654 participants were included in this study. A 38.2% of the participants reported having at least one comorbidity. Patients received AstraZeneca, Pfizer, and Sinovac vaccines, and these were distributed 38.4%, 31.1%, and 30.5%, respectively. Pain, inflammation at the injection site (20,01%), and headache (16,91%) were the most reported adverse events. Women addressed ESAVIs (64%), more often than men (36%). After receiving the first dose of any available COVID-19 vaccine, a total of 19,481 self-reported ESAVIs were informed (86.9% were mild, 11.6% moderate and 1.5% severe). In terms of vaccine type and brand, the most reactogenic vaccine was AstraZeneca with 57.8%, followed by Pfizer (24.9%) and Sinovac (17, 3 %). After the second dose, 6,757 self-reported ESAVIs were reported (87.0% mild, 10.9% moderate, and 2.1% severe). AstraZeneca vaccine users reported a higher proportion of ESAVIs (72.2%) in comparison to Pfizer/BioNTech (15.9%) and Sinovac Vaccine (11.9%). Swelling at the injection site, headache, muscle pain, and fatigue were the most common ESAVIs for the first as well as second dose. In conclusion, most ESAVIs were mild. AstraZeneca users were more likely to report adverse events. Participants without a history of COVID-19 infection, as well as those who receive the first dose, were more prone to report ESAVIs.

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. Previously, we developed a sublingual vaccine formulated with the SARS-CoV-2 receptor binding domain antigen and Poly(I:C) adjuvant in nonhuman primates, cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvant and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccineproduced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with Poly(I:C) adjuvant is safe and creates a balanced state of enhancing and suppressing the immune-related response.

Assessment of extreme events and climate change on reservoir inflow is important for water and power stressed countries. Projected climate is subject to uncertainties related to climate change scenarios and Global Circulation Models (GCMs’). Extreme climatic events will increase with the rise in temperature as mentioned in the AR5 of the IPCC. This paper discusses the consequences of climate change that include extreme events on discharge. Historical climatic and gauging data were collected from different stations within a watershed. The observed flow data was used for calibration and validation of SWAT model. Downscaling was performed on future GCMs’ temperature and precipitation data, and plausible extreme events were generated. Corrected climatic data was applied to project the influence of climate change. Results showed a large uncertainty in discharge using different GCMs’ and different emissions scenarios. The annual tendency of the GCMs’ is bi-vocal: six GCMs’ projected a rise in annual flow, while one GCM projected a decrease in flow. The change in average seasonal flow is more as compared to annual variations. Changes in winter and spring discharge are mostly positive, even with the decrease in precipitation. The changes in flows are generally negative for summer and autumn due to early snowmelt from an increase in temperature. The change in average seasonal flows under RCPs’ 4.5 and 8.5 are projected to vary from -29.1 to 130.7% and -49.4 to 171%, respectively. In the medium range (RCP 4.5) impact scenario, the uncertainty range of average runoff is relatively low. While in the high range (RCP 8.5) impact scenario, this range is significantly larger. RCP 8.5 covered a wide range of uncertainties, while RCP 4.5 covered a short range of possibilities. These outcomes suggest that it is important to consider the influence of climate change on water resources to frame appropriate guidelines for planning and management.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

Accumulating evidences demonstrate that the host genome's epigenetic modificationsare essential for living organisms to adapt extreme conditions.DNA methylation, covalent modifications of histone, andinter-association of non-coding RNAs facilitate the cellular manifestation ofepigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, miRNA (microRNA) and LncRNA (Long non-coding RNA) are new generationnon-coding molecules that influence a variety of cellular processes like immunity, cellular differentiation, and tumor development. During tumor development, temporal changes in miRNA/LncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signalling in the host. At the cellular level, this is manifested by the up-regulation of Inflammasome and inflammatory pathways, which promotes cancer-related inflammation. In view of this, we discuss the potential of lncRNA and miRNA directed interventions in regulating inflammation and tumor development in the host.

The purpose of this study is to examine the match-related performance (scores and penalties) of the athletes in the Junior EJC (European Judo Championship) and U23 EJC categories before and immediately after the Covid-19 quarantine, according to gender and weight category groups. Our sample was based on the junior and U23, male and females, 2019-2020 Junior European Judo Championships and 2019-2020 U23 European Judo Championships. A total of 1431 matches in these tournaments were analyzed: male (n=812) and female (n=619). The main findings of this study showed that most matches in both the male and female categories resulted in ippon (2019-2020 average: 64,35% for Junior male, 70,55% for U23 male and 69,3% for Junior female, 64,4% for U23 female). No significant differences (p &gt; 0.05) were observed between gender and age groups concerning the match scores. In the formation phase of the technique, considerations of high- and low-intensity actions, and analysis of the speed of athletes during matches in official competitions can help to better understand the dynamics of the variability of movements in judo matches. In addition, suggestions are presented to be applied to athletes in different age categories who are on the way to become Olympic athletes.

While pioglitazone reduces insulin resistance and hepatic gluconeogenesis effectively in patients with T2DM, these benefits remained controversial in patients with ESRD. We compared MACCEs and mortality (overall, infection-related, and MACCE-related) of pioglitazone to that of DPP4-inhibitors in patients with T2DM and ESRD. From Taiwan’s national health insurance database, 647 pioglitazone users and 6080 DPP4-inhibitors users between April 1st, 2006 and December 31th, 2016 were followed from the 91th date after the ESRD certification till study outcomes, independently; withdraw from the NHI program, death, or Dec. 31th, 2017. After weighting, risks of MACCEs (10.48% vs 12.62% per person-years, [HR]: 0.85, 95% [CI]: 0.729–0.985) and all-cause mortality (12.86% vs 13.22% per person-years, [HR]: 0.88, 95% [CI]: 0.771–0.995) are significantly lower in pioglitazone group. Subgroup analysis found lower MACCEs risk in the pioglitazone users without insulin therapy (6.44% vs 10.04% [HR]: 0.59, 95% [CI]: 0.42–0.82) and lower MACCEs related death (2.76% vs 3.84% [HR]: 0.61, 95% [CI]: 0.40–0.95) in the pioglitazone group with dyslipidemia, when comparing with DPP4-inhibitors users. Pioglitazone is associated with lower all-cause mortality and MACCEs in diabetic patients with ESRD, compared to DPP4-inhibitors. These benefits were further significant in the non-insulin users and patients with dyslipidemia.

Xinjiang, as a climate-sensitive region in northwest China, holds significant importance in studying extreme weather events for agricultural production and socioeconomic development. Based on data from 52 meteorological stations and 23 extreme climate indicators in Xinjiang from 1960 to 2021, the 5a moving average, linear trend estimation, climate tendency rate, and GIS spatial analysis methods are used to analyze the distribution and change characteristics of extreme climate. The results revealed that from 1960 to 2021, TXx, TNx, TXn, TNn, FD, ID, TN10p, TX10p, and WSDI showed a significant upward trend, while SU, TR, TN90p, TX90p, and CSDI showed a significant downward trend. What is more, the range of changes in the extreme temperature indexes from 1990 to 2021 is higher than that of 1960 to 1989. The high-value areas of extreme indexes are primarily concentrated in the northern part, while the high-value areas of cold event indexes are mainly distributed in the southern part. The upward/downward trends all accounting for over 80.00% of the entire region. The Rx1day, Rx5day, PRCPTOT, R95p, R99p, R10, R20, and R25 showed a significant growth trend from 1960 to 2021, and the range of change in the extreme precipitation indexes from 1990 to 2021 was lower than that from 1960 to 1989. Moreover, their high-value areas and high climate tendency areas are mainly concentrated in the northern and western parts of Xinjiang, with upward trends all accounting for over 71.00% of the entire region. The research results provide theoretical foundations for formulating climate risk strategies in the northwest region of China.

Low-grade glioma (LGG) is a highly aggressive disease in the skull. On the other hand, anoikis, a specific form of cell death induced by the loss of cell contact with the extracellular matrix, plays a key role in cancer metastasis. In this study，anoikis-related genes (ANRGs) were used to identify LGG subtypes and to construct a prognostic model for LGG patients. In addition, we explored the immune microenvironment and enrichment pathways between different subtypes. We constructed an anoikis-related gene signature using the TCGA cohort and investigated the differences in clinical features, mutational landscape, immune cell infiltration, etc. between different risk groups. Kaplan-Meier analysis showed that the characteristics of ANRGs in the high-risk group were associated with poor prognosis in LGG patients. The risk score was identified as an independent prognostic factor. The high-risk group had higher immune cell infiltration, tumor mutation load, immune checkpoint gene expression, and ICB treatment response. Functional analysis showed that these high- and low-risk groups had different immune statuses and drug sensitivity. Risk scores were used together with LGG clinicopathological features to construct a nomogram, and DCA analysis showed that the model could enable patients to benefit from clinical treatment strategies.

Astragalus membranaceus (AM) and Panax ginseng (PG) are two herbal products with a long history of clinical usage in traditional Chinese medicine (TCM), used in treating a variety of diseases especially in stimulating or inhibiting the immune system. To elucidate the immunity effect of these two traditional Chinese medicine on animal model, four pharmacodynamic indexes (spleen index, thymus index, splenic lymphocyte proliferation and cytotoxic activity of natural killer (NK) cells) were observed on mice. Furthermore, metabolic profiles of plasma were also analyzed by ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS, LC-MS) method. All mice were intragastric administrated at three doses (low dose, moderate dose and high dose) once daily for 30 days. Principal components analysis (PCA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA) were performed on LC-MS spectra of plasma, showing that all administration groups developed the disturbance of internal milieu, compared to the blank control (BC) group. Besides, correlation analysis was conducted between pharmacodynamic index and metabolic index. It indicated that uracil, lysoPC(18:3(6Z,9Z,12Z)), sphinganine, LPA(0:0/16:0), UDP-glucuronate, PC(14:0/18:0) were five main endogenous substances, much closely related to four immunological indexes. Glycerophospholipid metabolism was found in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were closely regulated in AM groups. Energy metabolism (starch and sucrose metabolism, Pentose and glucuronate interconversions, together with glycerolipid metabolism) and glycerolipid metabolism were found in PG groups. These findings could contribute to the understanding of mice plasmatic metabolic profiling after long-term administration. Comparative immune-related metabolomic analysis of AM and PG was obtained on the base of pathway analysis of immune-related biomarkers. PG groups trended to have effect on cytotoxic activity of NK cells. AM groups trended to effect thymus index. Our work provides a detailed interpretation of immunological characteristics in different traditional Chinese medicine on metabonomic level.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

During public health events, Active Mobility (walking and cycling) plays an important role in securing residents' travel. To enhance the resilience of urban transportation, this article integrates the travel environment elements for walking and cycling and constructs a travel environment for Active Mobility evaluation index system. This article uses survey data from the main urban area of Harbin in the context of the COVID-19 pandemic in May 2022, and combines the Gradient Boosting Decision Tree (GBDT) and Impact-Asymmetry Analysis (IAA) methods to analyze the satisfaction of the travel environment for Active Mobility. It proposes strategies for optimizing the travel environment for Active Mobility, ensuring residents' travel during public health events, guiding them to adopt Active Mobility, and improving urban transportation resilience. This research shows that Active Mobility can enhance urban transportation resilience. In addition, there are differences in resident demand for walking and cycling environments in the travel environment for Active Mobility. Residents are more concerned about the comfort of the walking environment, while they prioritize the convenience of the cycling environment.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading to adverse fetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on fetal HPA axis function and postnatal offspring development, hence this study. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone were measured in all dams and pups. Glucose tolerance and expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase in pups ACTH and corticosterone concentrations, impaired glucose tolerance and dysregulated MR and GR expression in the PD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair successful vaccination of elderly people. Thus, improved vaccination strategies specifically adapted to an aged immune system are required. We characterized a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein (MVA-ST) in an aged-hamster model for COVID-19. Intramuscular MVA-ST immunization resulted in protection from disease and severe lung pathology. Importantly, protection correlated with potent activation of SARS-CoV-2 specific T-cells and neutralizing antibodies. Our results suggest that MVA vector vaccines merit further evaluation as clinical candidate vaccines in elderly people to overcome limitations of age-dependent immunosenescence.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assay has some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo expansion of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examining cancer and immune cells in whole tumor samples and avoiding false negatives in histological assays.

This study investigated interactions between sugar-related dietary patterns (DP), personality traits, cognitive-behavioural, and emotional functioning. The study involved females aged 18-54. Data were collected between the Winter and Spring of 2020/21. The survey was conducted using anonymized questionnaires. The Ten-Item Personality Inventory (TIPI) was used to examine personality traits based on the Big Five Personality Trait Model. Three-Factor Eating Questionnaire (TFEQ) was used to measure eating behaviours: cogni-tive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). The KomPAN question-naire collected the frequency of intake. Dietary patterns (DPs) were derived by principal component analysis (PCA). A logistic regression (OR) was applied to verify the association between the DPs, personality traits, cognitive-behavioural and emotional functioning. Three DPs were identified: sweet-western (SWDP), pro-healthy (PHDP) and dairy (DDP). Women with high conscientiousness were less likely, by 33%, to adhere to the upper tercile of SWDP and 80% more likely to the upper tercile of PHDP. Elevated CR intensity increased by almost 2-fold (OR: 1.93; p

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

This paper considers the problem of predicting earthquakes. It uses a small amount of information to create a descriptive key that can be used as a footprint to describe an event. A frequency grid clusters events that occurred at the same time and then the algorithm averages the history of these events over preceding days, in particular the gaps when the events did not occur. The gaps are measured for the clustered events only and can be used to create a description that is quite unique. Results suggest that seismic events can in fact be traced using this key and subsequently recognised again, if the same conditions reoccur. They also suggest that force direction may be more important than magnitude, after the initial cluster selections are made. Greek and USA datasets have been looked at and the prediction accuracy can be 70% or better. The author therefore suggests that this is an interesting method that deserves attention.

Abstract Introduction: The mHealth active participant centred (MAPC) adverse events following immunisation (AEFI) surveillance is a promising area for early AEFI detection resulting in risk minimisation. Passive (spontaneous) AEFI surveillance is the backbone for vaccine pharmacovigilance, but has inherent drawbacks of under reporting, and requires strengthening with active surveillance methods. The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomized controlled trial (RCT) sought to evaluate the efficacy and feasibility of AEFI detection using a short message service (SMS) and computer assisted telephone interview (CATI) approach. Method: A multicentre Zm-STARSS RCT enrolled consented adult vaccinees or parents or guardians of children receiving vaccines, including COVID-19 vaccines, at study vaccination clinics. At enrolment study participants were randomised to either SMS-CATI group or control group. SMS prompts were sent on days 0-2 and 14 post-vaccination to SMS-CATI group to ascertain if a medical event following immunisation (MEFI) had occurred. However, no SMSs were sent to the control group. SMS-CATI group who responded “Yes” to SMS prompts were interviewed by research healthcare workers (RHCWs) who completed a CATI to determine if an MEFI/AEFI had occurred whilst an AEFI in control group was determined from passive AEFI reporting channels. The primary study outcome was the AEFI detection rate in the SMS-CATI group compared to the control group. Results: A total of 704 (31%) participants responded to the SMS prompts, with 75% (528/704) indicating “No” and 25% (176/704) "Yes” to experiencing a MEFI. However, 31% (55/176) who responded “Yes” did not complete a CATI survey, but 69% (121/176) did; and 64% (77/121) of these indicated negative to AEFI experience whilst 36% (44/121) were affirmative. There were no AEFI reported in control group participants. Zm-STARSS showed promising results in that the AEFI detection rate using SMS-CATI was 2% (44/2280) on an intention to treat cohort. Conclusion: Despite the low SMS response and CATI completion rate, we demonstrated that Zm-STARSS SMS system improves AEFI detection compared to passive AEFI surveillance. We recommend cost-effective multi-channel digital approaches for holistic pharmacovigilance to improve AEFI detection in LMICs for all vaccines.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) were injected into fertile eggs at 8, 14 and 18 of incubation. Survival and hatched chicks were calculated. Survivability and hatchability were unaffected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14-day incubation period in serum at the same concentration. Collectively, these results indicate that injecting L-Arg (100 μg) with 1000 µg of BOL-Ag NPs or L-Arg (100 μg) with 100 µg of C-Ag NPs to eggs at day 14 after incubation could improve their hatchability, survival rate, and muscle growth marker.

A flow chart is presented depicting coupling in ocean-atmosphere system, initiated by solar decadal variability that involves El Niño Southern Oscillation (ENSO). Possible mechanisms for Canonic ENSO, Modoki ENSO and Canonic-Modoki ENSO are proposed considering their relevance to the decadal variation of Hadley, Walker circulation and mid-latitude jets. It also discusses subsequent teleconnections by ENSO on Indian Summer Monsoon (ISM) with a special emphasis on later two decades of the last century. Possible mechanisms relating to a disruption of the usual ENSO-ISM teleconnection for those decades are emphasised; the role of volcanos and the change in the sun- NAO (North Atlantic Oscillation) connection were attended. The regional Hadley circulation, via the NAO in the northern hemisphere and Indian Ocean Dipole in the southern hemisphere, during that period, may have a role in the change in ISM behaviour- which though captured in observation but missed by models. The representation of flow chart helps to improve understanding of various types of ENSO in both temporal as well as spatial scale. The overall study subsequently can benefit the modelling community by not only improved the representation of ENSO in models but also better representation of ISM teleconnection via regional Hadley cell.

Automated Guided Vehicles are self-guided vehicles used in manufacturing and warehouses for material transport. They play a vital role in just-in-time material delivery, ensuring smooth production lines. However, disruptions in their fixed routes can lead to efficiency losses. This paper studies unexpected disruptions in mobile robot routes, assessing the costs of rectification using the E* analysis. The study highlights the significant additional cost of such disruptions, underscoring the importance of their consideration in AGV route planning to enhance system resilience.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

In this study an adjusting post-processing approach is implemented for improving intra-hourly forecasts of solar power and ramp events of PV solar power systems at different locations in the United States. This study also serves as an out-of-sample test to evaluate the performance of the adjusting approach with different locations and timescales. Thus, various individual intra-hourly forecasts of solar power are combined and adjusted by applying the adjusting approach. Both point and probabilistic forecasts of solar power are included. After that, solar power ramp event forecasting by the adjusting approach is carried out.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

The well-being and sociability of individuals have always been part of modernity. The development of new technologies that meet these aspirations is receiving increasing attention. Thus, strengthening the desired objectives of these tools and minimizing their undesirable side effects is the subject of a growing commitment. The present contribution aims, in this context, to evaluate and analyze the desired and undesirable effects of the interaction of electromagnetic fields with living tissues in general. This involves routines reinforcing expected functions as well as those controlling and protecting against undesirable effects. First, the interactions of electromagnetic fields with tissues are analyzed, involving their thermal biological effects of desired and undesired exposures. The roles of blood and sap fluids in bio-affected tissues are then analyzed. Secondly, the governing electromagnetic, bio-heat equations, and their coupled solution are studied. Third, the thermal behavior of tissues and the exposure adverse effects are examined. Next, monitoring and defending of the effects of exposures are discussed. This contribution illustrates and discusses mathematical modeling routines based on a generalized interaction of electromagnetic fields with living tissues.

The Eastern Kunlun Fault Zone (EKFZ) is located in a seismic blank area. This study investigates the hydrogeochemical characteristics of varied-temperature springs in the EKFZ to understand the relationship between fractures, fluids and earthquakes. It aids in establishing their induction mechanisms and assists in monitoring the earthquake precursors of the EKFZ. In this study, the main elements, trace elements, hydrogen and oxygen isotopes and strontium isotopes of 23 varied-temperature springs in the EKFZ were analyzed. The results reveal the source of groundwater recharge, hydrochemical types, mineral saturation, and for a select few springs indicative of geothermal activity, collected geothermal reservoir temperatures. The study also explores the relationship between earthquakes and springs, identifying sensitive chemical indicators. Based on continuous monitoring at Maqu Station, we found that before the occurrence of the Maerkang Ms 6.0 earthquake, the concentration of Cl− rose by 2.9 times, and 46 days before the Gande earthquake (Ms = 4.7), the concentrations of Na+ and SO42− significantly increased. Finally, a conceptual model of the hydrogeochemistry of springs is presented to describe the groundwater circulation in the study area. This research is of great significance for the analysis of fluid geochemistry in this area and for assessing the seismic hazards of the EKFZ.

It is argued that all physical knowledge ultimately stems from observation and that the simplest possible observation is that an event has happened at a certain space-time location . Considering historic experiments, which had been groundbreaking in the evolution of our modern ideas of matter on the atomic, nuclear and elementary particle scales, it is shown that such experiments produce as outputs macroscopically observable events which represent binary decisions with regard to simple alternatives and which accumulate in the course of time into spatio-temporal patterns whose forms allow decisions to be taken concerning conceivable alternatives of explanation. Working towards elucidating the physical and information-theoretic characteristics of those elementary pieces of information we arrive at the conclusion that - unlike the events of relativity which are mere 4-tuples of spacetime coordinates - the events of observation are pieces of information endowed with the properties of physical action, spacetime extension, and Lorentz invariance. Another important aspect is that such events are produced at the expense of irreversibly dissipating energy which can be stated in Landauer diction in the form that more energy needs to be spent in the erasure of events than had previously been invested in their initiation.

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells and fibroblasts, that producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhib-itors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines and bispecific an-tibodies are improving patients’ outcomes. However, stimulation of the immune system, benefi-cial in terms of fighting against cancer, generates the risk of harm to other cells in a patient's body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, su-perficially, are renal AEs in patients treated with ICIs. International guidelines issued by Euro-pean Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are scarce data concerning renal adverse drug reactions of other immunotherapeutic methods. This implicates the need for the collection of safety data during ongoing clinical trials and in the re-al-life world to characterize the hazard related to the use of new immunotherapies and manage-ment of irAEs.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Functional connectivity (FC) is a potential candidate that can increase the performance of brain-computer interfaces (BCIs) in the elderly because of its compensatory role in neural circuits. However, it is difficult to decode FC by current machine learning techniques because of a lack of its physiological understanding. To investigate the suitability of FC in BCI for the elderly, we propose the decoding of lower- and higher-order FCs using a convolutional neural network (CNN) in six cognitive-motor tasks. The layer-wise relevance propagation (LRP) method describes how age-related changes in FCs impact BCI applications for the elderly compared to younger adults. Seventeen younger (24.5±2.7 years) and twelve older (72.5±3.2 years) adults were recruited to perform tasks related to hand-force control with or without mental calculation. CNN yielded a six-class classification accuracy of 75.3% in the elderly, exceeding the 70.7% accuracy for the younger adults. In the elderly, the proposed method increases the classification accuracy by 88.3% compared to the filter-bank common spatial pattern (FBCSP). LRP results revealed that both lower- and higher-order FCs were dominantly overactivated in the prefrontal lobe depending on task type. These findings suggest a promising application of multi-order FC with deep learning on BCI systems for the elderly.

Event-based vision is an emerging field of computer vision that offers unique properties such as asynchronous visual output, high temporal resolutions, and dependence on brightness changes to generate data. These properties can enable robust high-temporal-resolution object detection and tracking when combined with frame-based vision. In this paper, we present a hybrid, high-temporal-resolution, object detection and tracking approach, that combines learned and classical methods using synchronized images and event data. Off-the-shelf frame-based object detectors are used for initial object detection and classification. Then, event masks, generated per each detection, are used to enable inter-frame tracking at varying temporal resolutions using the event data. Detections are associated across time using a simple low-cost association metric. Moreover, we collect and label a traffic dataset using the hybrid sensor DAVIS 240c. This dataset is utilized for quantitative evaluation using state-of-the-art detection and tracking metrics. We provide ground truth bounding boxes and object IDs for each vehicle annotation. Further, we generate high-temporal-resolution ground truth data to analyze the tracking performance at different temporal rates. Our approach shows promising results with minimal performance deterioration at higher temporal resolutions (48 – 384 Hz) when compared with the baseline frame-based performance at 24 Hz.

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

Nonmedical prescription stimulant use (NPSU) is an ongoing public health crisis in the United States. There exists, however, a dearth of research investigating specific childhood risk factors that may contribute to this illicit use. Adverse childhood experi-ences (ACEs) may be a significant risk factor to address in the prevention and treatment of NPSU, as research has provided evi-dence for increased substance use, potentially including prescription stimulant misuse, among individuals who have experienced trauma. A systematic review of the literature was conducted to gather and synthesize research articles specifically examining the relationship between nonmedical prescription stimulant use in adults and the experience of adverse childhood experiences (ACEs). Four studies met all inclusion criteria and were included in the review. The results demonstrated that nonmedical use of prescription stimulants in adults is significantly associated with ACEs, with a higher numerical count of ACEs associated with a greater likelihood of nonmedical prescription stimulant use. Gaps in the literature were identified, specifically noting a lack of information available regarding the relationship between ACEs and NPSU within gender- and racially-diverse populations. The findings have implications for informing interventions related to ACEs and the misuse of prescription stimulant medication in adults.

(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in woman and is a high cause of mortality of them in reason to rapid metastasis and disease recurrence. Ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy and inhibit distant metastases so potentially acts on tumor micro-environment; (2) Methods: Ferroptosis/Extracellular matrix remodeling literature text-mining results were integrated in breast cancer transcriptome cohort according their distant relapse free survival (DRFS) under adjuvant therapy (anthracyclin+taxanes) and also in MDA-MB-231 transcriptome functional experiments with ferroptosis activations (GSE173905); (3) Results: Ferroptosis/Extracellular matrix remodeling text-mining identified 910 associated genes in at list 10 articles. Univariate Cox analyses censored on breast cancer (GSE25066) selected 252 individual significant genes and 171 of them found with an adverse expression. Functional enrichment of these 171 adverse genes predicted basal breast cancer signatures. By text-mining some ferroptosis significant adverse selected genes shared citations in domain of ECM remodeling such as: TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, TLR4. A molecular score based on expression the eleven genes was found predictive of worst prognosis breast cancer at univariate level: basal subtype, short DRFS, high grade values 3 and 4, estrogen and progesterone receptors negative and nodal stages 2 and 3. This eleven gene signature was validated as regulated by ferroptosis inductors (erastin and RSL3) in triple negative breast cancer cellular model MDA-MB-231.; (4) Conclusions: Crosstalk between ECM remodeling-Ferroptosis functionalities allowed to define a molecular score which have been characterized as an independent adverse parameter in prognosis of breast cancer patients. Gene signature of this molecular score have been validated to be regulated by erastin/RSL3 ferroptosis activators. This molecular score could be promising to evaluate ECM impact of ferroptosis target therapies in breast cancer.

Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Phar-maceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with associated drug trends and characteristics. Our findings indicate that similar to　Parkinson’s disease, age-related differences affect the onset of these events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, side effects can vary depending on the site of action. These insights underline the importance of swift identification of the drugs suspected of causing these events and implementation of measures to reduce their side effects.

This article analyses entropy changes triggered by specific events in deterministic and indeterministic systems. Article considers a simple model consisting of water in a cuvette, an ice cube in the device above the cuvette and a random number generator (RNG) that controls the probability of dropping the ice into water. Article introduces the entropic potential Z(T, A) of an event A occurred in a system R at the moment Т₀, which describes the influence of the event A to the entropy of the system R in the future (for the moments T>Т₀). The entropic potential of an event Z(T,A) can be calculated as the difference between the mathematical expectations of entropy of the system R for the moment T (T>Т₀) made immediately before and immediately after the event A as Z(T, A) = Ŝ_T(Т₀+dT) - Ŝ_T(Т₀-dT). Article also presents examples of calculations of the entropic potentials of events in indeterministic systems with different probabilities of events. Since real-life systems are mostly indeterministic, the entropic potentials of events in real-life usually have non-zero values. The entropic potentials of the events "useful" for the system are negative, and entropic potentials of the events "harmful" for the system are positive.

Background: Recent infectious disease outbreaks have brought increased attention to strengthening the capacity to prevent, detect, and respond to natural biological threats. However, deliberate biological events also represent a significant global threat that have received relatively little attention. The Biological Weapons Convention provides a foundation for the response to deliberate biological events, but the political mechanisms to respond to and recover from such an event are poorly defined. Methods: We performed an analysis of the epidemiological timeline, the international policies triggered as a notional deliberate biological event unfolds, and the corresponding stakeholders and mandates assigned by each mandate. Findings: The results of this analysis identify a significant gap in both policy and stakeholder mandates: there is no single policy nor stakeholder mandate for leading and coordinating the response activities associated with a deliberate biological event. These results were visualized using an open source web-based tool published at https://dbe.talusanalytics.com. Interpretation: While there are organizations and stakeholders responsible for roles in leading security or public health response, these roles are non-overlapping and are led by organizations not with limited interaction outside such events. The lack of mandates highlights a gap in the mechanisms available to coordinate response and a gap in guidance for managing the response. The results of the analysis corroborate anecdotal evidence from stakeholder meetings and highlight a critical need and gap in deliberate biological response policy.

Understanding clinical significance of variants of unknown significance (VUS) reported in next-generation sequencing (NGS) has become essential in cancer treatment. Our study examined six widely used in silico tools: PolyPhen-2, Align-GVGD, MutationTaster2, CADD, REVEL, and Chat-GPT. We utilized a dataset of gene variants known to potentially affect immune therapy. No single tool could comprehensively determine mutation variant pathogenicity. MutationTaster2021 showed the highest overall accuracy and MCC among the tools. Notably, REVEL and Chat-GPT exhibited 100% specificity, suggesting their proficiency in accurately identifying pathogenic variants and minimizing false positives. In contrast, CADD displayed optimal sensitivity, making it suitable for effectively ruling out benign variants.

Walnut trees are grown worldwide for their edible fruits of high nutritional value. To address climate change, researchers have studied walnut phenology to create cultivars adapted to warmer climates. The standardisation of walnut phenological observations is needed and the Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie (BBCH) scale is the most accurate and internationally accepted for this purpose. Here, the principal growth stages (PGS) of Persian walnut (Juglans regia L.) are described using stages from a previously available alphanumerical scale. This standardised phenological scale describes Persian walnut growth from the dormant vegetative state through reproductive budding to senescence. This phenological scale is expected to increase the efficiency of walnut phenological monitoring. Fifty-seven stages were used to describe the life cycle of Persian walnut in this BBCH scale. Of these 57 stages, 3 stages are dedicated to seed germination (PGS-0), 4 stages to bud development (PGS-0), 7 stages to leaf development (PGS-1), 4 stages to stem elongation (PGS-3), 8 stages to inflorescence emergence (PGS-5), 5 stages to male flowering (PGS-6), 5 stages to female flowering (PGS-6), 5 stages to fruit development (PGS-7), 12 stages to fruit ripening (PGS-8) and 4 stages to leaf senescence (PGS-9).

A 4×2 factorial experiment was conducted to evaluate the potential of feeding dietary gamma-oryzanol and vitamin E tocotrienols in hens reared in 840 (low cage density; LCD) or 420 cm2/hen (high cage density; HCD). A total of 120 hens were allocated into eight groups with five replicates. Diets were a control (CON) or the control diet supplemented with 200 ppm gamma-oryzanol (GO-200), 200 ppm vitamin E tocotrienols (VE-200) or 200 ppm gamma-oryzanol + 200 ppm vitamin E tocotrienols (GE-400). Results showed that HCD-housed hens decreased (P &lt; 0.01) egg performance and quality. Average egg weight (AEW), egg mass and FCR improved in all supplemented treatments. Results on the AEW, FCR, and eggshell qualities of birds kept at the HCD revealed the best responses in the GE-400 group (P &lt; 0.01). Among hens kept on an HCD, there was a noticeable decrease in HMGCR mRNA abundance in the VE-200 group, while the highest IFN-γ mRNA abundance was found in hens fed the GO-200 diet (P &lt; 0.05). Thus, this study suggested that dietary GO or VE at 200 ppm either individually or in combination could improve performance and egg quality as well as regulate the abundance of immune- and stress-related genes.

In a recent study, the PD-1 inhibitor has been widely used in clinical trials and shown to improve various cancers. However, PD-1/PD-L1 inhibitors showed a low response rate and showed to be effective for a small number of cancer patients. Thus, it is important to identify key genes, which can enhance the PD-1/PD-L1 response for promoting immunotherapy. Here, we used ssGSEA and unsupervised clustering analysis to identify three clusters to show different immune cell infiltration status, prognosis, and biological action. The cluster C showed a better survival rate, high immune cells infiltration, and immunotherapy effect enriched in a variety of immune active pathways, including T and B cell signal receptors. Besides, it showed more immune subtypes C2 and C3. Further, we used WGCNA analysis to confirm the cluster C correlated genes. The red module highly correlated with cluster C for 111 genes which were enriched in a variety of immune-related pathways. To pick candidate genes in SD/PD and CR/PR patients, we used the Least Absolute Shrinkage and SVM-RFE algorithms. In conclusion, our LASSO analysis and SVM-RFE based research identified targets with better prognosis, activated immune-related pathways, and better immunotherapy. The KLRC3 was identified as the key gene which can efficiently respond to immunotherapy with greater efficacy and better prognosis.

We present a formalism to assess the safety of the COVID19 vaccines and infer a causal relation between vaccine administration and adverse effects, in particular death. We use data on adverse effects from VAERS covering the time interval [01-10-2020, 31-12-2021] (downloaded on 1 Feb 2022). We measure a vaccine fatality rate of order 0.01 for all vaccine manufacturers and identify a strong heterogeneity in the vaccine toxicity across vaccine lots, spanning up to four orders of magnitude. We compute the correlation between vaccination dates and death dates, and produce an estimate of the time lag that maximises the correlation, finding that the onset of adverse effects happened statistically (i.e. 32-41 percentiles) within one day after the vaccine administration and that death happened statistically (i.e. 22-50 percentiles) within about two weeks after the vaccine administration. These results provide data-based insights that can guide public health measures and health insurance policies.

Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

Construction safety is especially important because the construction industry is so important to a country's development. Significant research and practice have been conducted to mitigate potential risks during construction and improve worker efficiency. With the rapid advancement of cognitive neuroscience and the incorporation of medical technology in recent years, various wearable monitoring devices have been widely used in the construction field for real-time monitoring of workers' physical and mental status. Among these, the use of EEG (Electroencephalogram) in construction environment research allows researchers to gain insight into the physical and mental states of construction workers while performing construction tasks. This review introduces EEG technology and portable EEG devices, followed by an overview of their use in both monitoring workers' adverse reactions and identifying hazards on construction sites, providing an effective guide for EEG research in the construction field and on-site safety management.

For autonomous driving, perception is a primary and essential element that fundamentally deals with the insight into the ego vehicle’s environment through sensors. Perception is a challenging task suffering from dynamic objects and continuous environmental changes. The issue gets worse due to interrupting the quality of perception by adverse weather like snow, rain, fog, night light, sand storm, strong daylight, etc. In this work, we have tried to improve camera-based perception accuracy, such as autonomous driving-related object detection in adverse weather. We proposed the improvement of YOLOv8-based object detection in adverse weather through transfer learning using merged data from various harsh weather datasets. Two prosperous open-source datasets (ACDC and DAWN) and their merged dataset were used to detect primary objects on the road in harsh weather. A set of training weights were collected from training on the individual datasets, their merged version, and several subsets of those datasets according to their characteristics. A comparison between the training weights also occurred by evaluating the detection performance on the above-mentioned datasets and their subsets. The evaluation revealed that using custom datasets for training significantly improves the detection performance compared to the YOLOv8 base weights. And using more images through the feature-related data merging technique steadily increases the object detection performance.