UNASSIGNED: Sotorasib has been approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Due to the limitations of clinical trials, potential adverse events (AEs) and long-term safety issues cannot be detected. The presented study aimed to evaluate sotorasib-associated AEs using the FDA Adverse Event Reporting System (FAERS) database.
UNASSIGNED: Post-marketing AE reports of sotorasib in the database were collected for analysis. Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical bayes geometric mean (EBGM) algorithms, were performed to mine the signals of sotorasib-associated AEs. The median duration, quartiles and the Weibull shape parameter (WSP) test were used to assess the onset time data.
UNASSIGNED: The database contained 1538 cases of sotorasib as primary suspect (PS), with 27 signals detected, scattering in 5 SOCs. The SOC of hepatobiliary disorders (182, ROR 4.48, PRR 4.07, IC 2.02, EBGM 4.07) met the four methodological thresholds. The median onset time of sotorasib-associated AEs was 42 days (interquartile range [IQR] 14-86.75 days). Different SOCs had different types of risk over time.
UNASSIGNED: After obtaining marketing authorization, the study identified all potentially relevant adverse event (AE) signals expected to have a reporting frequency higher than anticipated and characterized them during sotorasib treatment.

Inteins are proteins that excise themselves out of host proteins and ligate the flanking polypeptides in an auto-catalytic process called protein splicing. In nature, inteins are either contiguous or split. In the case of split inteins, the two fragments must first form a complex for the splicing to occur. Contiguous inteins have previously been artificially split in two fragments because split inteins allow for distinct applications than contiguous ones. Even naturally split inteins have been split at unnatural split sites to obtain fragments with reduced affinity for one another, which are useful to create conditional inteins or to study protein-protein interactions. So far, split sites in inteins have been heuristically identified. We developed Int&in, a web server freely available for academic research (https://intein.biologie.uni-freiburg.de) that runs a machine learning model using logistic regression to predict active and inactive split sites in inteins with high accuracy. The model was trained on a dataset of 126 split sites generated using the gp41-1, Npu DnaE and CL inteins and validated using 97 split sites extracted from the literature. Despite the limited data size, the model, which uses various protein structural features, as well as sequence conservation information, achieves an accuracy of 0.79 and 0.78 for the training and testing sets, respectively. We envision Int&in will facilitate the engineering of novel split inteins for applications in synthetic and cell biology.

UNASSIGNED: Recently, there have been some reports of seizures related with COVID-19 vaccinations. However, no studies have systematically investigated the relationship between seizures and various COVID-19 vaccines.
UNASSIGNED: This research aimed to analyze the characteristics and risk signals of new-onset seizures in children caused by various COVID-19 vaccines based on the data of the Vaccine Adverse Event Reporting System (VAERS). To identify potential risk signals, a disproportionality analysis was conducted. The reporting odds ratio (ROR) and the Proportional Reporting Ratio (PRR) were used to detect signals.
UNASSIGNED: A total of 695 children with new-onset seizures events associated with COVID-19 vaccinations were retrieved from the VAERS database. Compared with influenza vaccinations, the percentage and rate of COVID-19 vaccinations related seizures was all reduced. The median onset time of seizures was 1 day after COVID-19 vaccines. No signal was detected for an association between the COVID-19 vaccines and new-onset seizures, neither when compared with influenza vaccines nor with non-COVID-19 vaccines.
UNASSIGNED: No statistically significant risk signal of COVID-19 vaccine-related seizures was found in this study. However, it is still necessary to monitor the possibility of new-onset seizures when children are immunized with COVID-19 vaccines.

The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.

UNASSIGNED: Les professionnels de la santé sont souvent victimes d\'AES au cours des activités de soin.
UNASSIGNED: Étudier les attitudes et pratiques des soignants sur les AES dans la commune de Parakou en 2022.
UNASSIGNED: Il s\'est agi d\'une étude transversale descriptive à visée analytique avec recueil prospectif des données réalisée du 1eravril au 30 juin 2022. Étaient inclus dans l\'étude, les professionnels de la santé des établissements sanitaires publics et privés ainsi que les étudiants en médecine. Les données ont été saisies grâce au logiciel Epi-Data 3.1 puis apurées et vérifiées dans le logiciel STATA MP 14. Le seuil de significativité était de 0,05.
UNASSIGNED: Au total 791 professionnels de la santé avaient participé à l\'étude dont 465 (58,8 %) de travailleurs et 326 (41,2 %) étudiants. L\'âge moyen était de 32,2 ans ± 8,9 avec des extrêmes de 19 ans et 62 ans. Il y avait plus de femmes 60,4 % pour 39,6 % d\'hommes, la sex-ratio étant de 0,7. La prévalence des AES du personnel soignant était de 116 (25 %) et celle des étudiants de 79 (24,2 %) (p=0,819). La piqûre était la principale cause d\'AES (79,3 %) du personnel soignant et (72,2 %) des étudiants. Les gestes incriminés étaient les injections (98,7 %), les prélèvements sanguins (40,5 %) et le recapuchonnage d\'aiguille (25,3 %). Pour la prise en charge, le rinçage à l\'eau (54,3 %), le lavage au savon (50,9 %) et la désinfection à l\'eau de javel (48,3 %) étaient les principaux gestes adoptés. La déclaration d\'AES avait été effective pour 50 (43,1 %) du personnel soignant et pour 22 (27,9 %) d\'étudiants. Le patientsource était connu dans 80,0 % des cas. La catégorie professionnelle (p = 0,000), l\'âge (p= 0,005) et le corps du personnel soignant (p = 0,008) étaient associés de façon significative à l\'attitude et pratique sur les AES.
UNASSIGNED: Les AES constituent une menace réelle pour les professionnels de la santé. Une bonne attitude et pratique est gage d\'une prise en charge adéquate.

A new, simple, and sensitive FIA-spectrophotometric method has been developed for evaluating pure amoxicillin and pharmaceutical formulations. The FIA method involves the reaction of dapsone with sodium nitrite and hydrochloric acid. Subsequently, the diazotized dapsone is coupled with amoxicillin in an alkaline medium, resulting in a stable orange dye with a maximum wavelength of 440 nm. The developed method was validated according to the ICH guidelines and found to have a concentration range of 1-150 µg/mL, a correlation coefficient of 0.9994, a molar extinction coefficient of 0.273 × 104 L/mol.cm, and a detection limit of 0.074 µg/mL. The FIA method was then evaluated using AES, GAPI, and AGREES analytical greenness assessment tools. The FIA method uses dapsone as an eco-friendly reagent, in addition to the FIA method\'s advantages of reduced sample and reagent usage, reduced waste generation, and cheaper equipment. So, it has been proposed as an excellent eco-friendly method for the determination of AMX in pharmaceutical formulations.

The literature on the effectiveness of Agri-Environmental Schemes focuses mainly on the environmental effects; only a few studies have focused on economic aspects. The number of papers that address ecological and economic outcomes simultaneously is even more limited. In this paper, we apply the concept of eco-efficiency to integrate these two factors. The aim of the paper is to analyze the impact of participation in the agri-environmental scheme of Hungarian field crop farmers in terms of eco-efficiency. To make unbiased and consistent comparisons we use advances from aggregation and bootstrap theory in Data Envelopment Analysis (DEA) context. The results indicate that there exists a significant potential for enhancing eco-efficiency in Hungarian crop farms. Furthermore, our results reveal that, in terms of eco-efficiency, perceived as the relationship of farm income to pesticide, fertilizers and energy use, no significant differences exist between participating and non-participating farmers. The results are robust to different methods. Our results pose questions about the efficacy of the Agri-Environmental Scheme.

Scrub typhus, which is prevalent in the Asia Pacific region is most feared owing to its life-threatening neurological complications. We present four cases of scrub typhus with acute encephalitis, including one with multiorgan failure and another serologically proven co-infection with Hepatitis C. Treatment of scrub typhus is not, however, so difficult, so its early diagnosis is paramount.

UNASSIGNED: To systematically analyze adverse events (AEs) in treatment of spinal muscular atrophy (SMA) with Nusinersen in children and adolescents.
UNASSIGNED: The study is registered on PROSPERO (CRD42022345589). Databases were searched and literature relating to Nusinersen in the treatment of spinal muscular atrophy in children from the start of database establishment to December 1, 2022, was retrospectively analyzed. R.3.6.3 statistical software was used, and random effects meta-analysis was performed to calculate weighted mean prevalence and 95% confidence intervals (CI).
UNASSIGNED: In total, 15 eligible studies were included, with a total of 967 children. Rate of definite Nusinersen-related AEs was 0.57% (95% CI: 0%-3.97%), and probable Nusinersen-related AEs 7.76% (95% CI: 1.85%-17.22%). Overall rate of AEs was 83.51% (95% CI: 73.55%-93.46%), and serious AEs 33.04% (95% CI: 18.15%-49.91%). For main specific AEs, fever was most common, 40.07% (95% CI: 25.14%-56.02%), followed by upper respiratory tract infection 39.94% (95% CI: 29.43%-50.94%), and pneumonia 26.62% (95% CI: 17.99%-36.25%).The difference in overall AE rates between the two groups (Nusinersen group and placebo group) was significant (OR = 0.27,95% CI: 0.08-0.95, P = 0.042). Moreover, incidence of serious adverse events, and fatal adverse events were both significantly lower than in the placebo group (OR = 0.47, 95%CI: 0.32-0.69, P < 0.01), and (OR = 0.37, 95%CI: 0.23-0.59, P < 0.01), respectively.
UNASSIGNED: Nusinersen direct adverse events are rare, and it can effectively reduces common, serious, and fatal adverse events in children and adolescents with spinal muscular atrophy.

UNASSIGNED: The application of vedolizumab (VDZ) subcutaneous (SC) formulation has brought more convenience and hope to patients with moderate-to-severe inflammatory bowel diseases (IBDs) in the coronavirus disease 2019 context.
UNASSIGNED: This study aimed to systematically evaluate all previous studies that used VDZ SC formulation for maintenance therapy in patients with IBD.
UNASSIGNED: Systematic review and meta-analysis.
UNASSIGNED: The search was conducted using the subject and free terms related to \'Vedolizumab\', \'Subcutaneous\', and \'IBD\', in Embase, PubMed, Web of Science, Cochrane, and at ClinicalTrials.gov databases between 2008 and 2022. The methodological quality of randomized controlled trials (RCTs) and cohort studies was assessed using the Cochrane Handbook of Systematic Reviews and the Newcastle-Ottawa Scale, respectively. The endpoints included efficacy, safety, and immunogenicity.
UNASSIGNED: A total of 60 studies and 2 completed clinical registry trials were retrieved, of which 3 RCTs with high methodological quality, and 3 cohort studies with large heterogeneity were included in the meta-analysis. In the RCT study design, patients with ulcerative colitis (UC) under different conditions after treated with VDZ SC were significantly distinct than those for placebo (PBO) in clinical remission, endoscopic remission, and biochemical remission. In Crohn\'s disease (CD), the aforementioned parameters were slightly higher than those for PBO, but there was not statistically significant in endoscopic remission and the efficacy of anti-tumor necrosis factor-naive patients. The clinical remission, endoscopic remission, and biochemical remission in patients with UC after VDZ SC treatment were similar to those after intravenous (IV) treatment. The risk ratios in patients experiencing adverse events (AEs) and serious AEs after VDZ SC and PBO treatments were 86% and 89% in UC, and 96% and 80% in CD, respectively. Compared with IV, safety was not statistically different. The risk of developing anti-VDZ antibody after VDZ SC treatment was only 20% of that after PBO in patients with UC, but it was 9.38 times in CD.
UNASSIGNED: VDZ SC treatment maintained the clinical efficacy of IV induction in patients with IBD without increasing the safety risk, and the efficacy was more pronounced in patients with UC. Immunogenicity might be a potential factor for the decrease in efficacy rate in patients with IBD.
UNASSIGNED: INPLASY 2022120115.