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BACKGROUND: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug. METHODS: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigators choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level. The primary end point was overall survival. RESULTS: At a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87). The estimated percentage of patients surviving at 3 years was 27% in the tebentafusp group and 18% in the control group. The most common treatment-related adverse events of any grade in the tebentafusp group were rash (83%), pyrexia (76%), pruritus (70%), and hypotension (38%). Most tebentafusp-related adverse events occurred early during treatment, and no new adverse events were observed with long-term administration. The percentage of patients who discontinued treatment because of adverse events continued to be low in both treatment groups (2% in the tebentafusp group and 5% in the control group). No treatment-related deaths occurred. CONCLUSIONS: This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. (Funded by Immunocore; IMCgp100-202 ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).

Abstract In-depth multiomic phenotyping provides molecular insights into complex physiological processes and their pathologies. Here, we report on integrating 18 diverse deep molecular phenotyping (omics-) technologies applied to urine, blood, and saliva samples from 391 participants of the multiethnic diabetes Qatar Metabolomics Study of Diabetes (QMDiab). Using 6,304 quantitative molecular traits with 1,221,345 genetic variants, methylation at 470,837 DNA CpG sites, and gene expression of 57,000 transcripts, we determine (1) within-platform partial correlations, (2) between-platform mutual best correlations, and (3) genome-, epigenome-, transcriptome-, and phenome-wide associations. Combined into a molecular network of > 34,000 statistically significant trait-trait links in biofluids, our study portrays “The Molecular Human”. We describe the variances explained by each omics in the phenotypes (age, sex, BMI, and diabetes state), platform complementarity, and the inherent correlation structures of multiomics data. Further, we construct multi-molecular network of diabetes subtypes. Finally, we generated an open-access web interface to “The Molecular Human” ( http://comics.metabolomix.com ), providing interactive data exploration and hypotheses generation possibilities.

Background: Exam anxiety in female students, a significant emotional response and emotional issue that negatively impacts learning, is perceived as a threat by many students. The present study investigated the efficacy of emotional schema therapy (EST) on self-regulation and frustration tolerance in female students with exam anxiety during the academic year 2022-2023.Methods: A quasi-experimental design with a pretest-posttest was employed. A total of 36 female students with exam anxiety were recruited from Ahvaz, Iran. Convenience sampling technique was employed to select the study participants who were randomly assigned to either the experimental group (n=18) or the control group (n=18) using a random number table. The experimental group received ten, 60-minute sessions of EST. Self-regulation and frustration tolerance were assessed using questionnaires before and after the intervention. Group differences were assessed using analysis of covariance (ANCOVA).Results: At pretest, both groups showed similar levels of self-regulation (P=0.694). Following the intervention, the experimental group showed significantly higher self-regulation (Mean=49.72, SD=5.74) as compared with the control group (Mean=36.39, SD=4.17) (P=0.001). No significant difference in frustration tolerance was observed between groups at pretest (P=0.927). However, the experimental group (Mean=71.28, SD=5.88) demonstrated significantly greater frustration tolerance as compared with the control group (Mean=117.67, SD=18.10) after the intervention (P=0.001). The findings indicated that EST effectively improved self-regulation and frustration tolerance in female students with exam anxiety (P

Introduction: Concurrent primary brain tumors are rare clinical entities, with a prevalence ranging from 0.1 to 0.5% of all diagnosed brain tumors. The co-occurrence of meningioma and oligodendroglioma is particularly uncommon, posing unique diagnostic and therapeutic challenges. We describe the case of a patient diagnosed with concurrent meningioma and oligodendroglioma and review the existing literature on this rare phenomenon. Case Presentation: A 55-year-old female patient with a history of seizures presented to the emergency department with worsening headaches, nausea, and vomiting. She had a known right frontoparietal intracranial mass but had previously declined surgery. Magnetic resonance imaging revealed extensive fluid-attenuated inversion recovery /T2 hyperintensity around the lesion, which had slowly increased over 5 years; the growth of the lesion was producing a mass effect with a significant midline shift. The patient underwent urgent hemicraniectomy with subsequent resection. Clinical evaluation, imaging studies, and histopathological examination were conducted to confirm the diagnosis. Genetic and molecular analyses were also performed to explore potential underlying mechanisms. Histopathological findings confirmed a diagnosis of an isocitrate dehydrogenase-mutated World Health Organization Grade II oligodendroglioma with 1p/19q codeletion, along with a Grade I meningioma. Conclusion: The coexistence of meningioma and oligodendroglioma represents a rare clinical event. Surgical management remains the cornerstone of treatment. Further investigation into the genetic and environmental factors that contribute to the co-occurrence of such tumors could pave the way for more targeted therapeutic strategies.

The present research aimed to investigate the mediation role of family function in the relationship of personality dimensions of temperament and character with adolescents internalized and externalized problems. The current research method was correlational studies. The statistical population consisted of all male and female students of the second grade of high school in Andimshek city, Iran, during 2020-2021 academic year, out of which 326 people (165 girls and 161 boys) were selected by multi-stage cluster sampling method. To collect data, the youth self-report scale (Achenbach and Rescorella), the temperament and character inventory (Cloninger et al.), and the family assessment device (Epstein et al.) were used. Structural equation methods were used to analyze the data. The findings showed that the effect of temperament and character on internalized and externalized problems were confirmed through family function. It can be concluded that the family function played a mediation role in relationship to the temperament and character and internalized and externalized problems of adolescents, so it is recommended that psychologists, through training and interventions, improve family function by moderating personality dimensions to prevent, reduce, and improve the adolescents' internalized/externalized problems.

To evaluate pathogenicity of 3 Chicken Anemia Virus isolates-CV1, CV2 and CV3 respectively - the current experiment carried out. After tittering of the viruses, 30 one day old SPF chicks were grouped and intramuscularly inoculated with each isolate in a separate group. Two other groups as positive and control groups were inoculate with a live vaccine virus and normal saline respectively. During the study the birds in first three groups clinically showed raffling feathers, depression and body weight reduction. After 18 days they were weighed, bled and euthanized. Three birds were found dead during the experiment (one in each tested group). Antibodies against CAV in the serum of all 3 groups were detected while no antibody found in negative control group. Hematocrit Values of the three tested groups were under the normal. Grossly the thymus and bursa tissues were severely atrophied. Bone marrow became yellowish and pale. In histopathological study we found aplasia and devoid of erythroid and myeloid cells replacing by fat cells in bone marrow. Severe atrophy and depletion in thymus ,bursa of Fabricius and bone marrow tissues statistically were analyzed and showed that the significance difference in comparing with control groups ( p

Background: Adolescence is an important period in the social and psychological development of human beings. Depression is a major problem that now affects many adolescents. Objectives: The present study aimed to investigate the effects of attachment-based therapy on emotional autonomy, emotion regulation, and rumination in adolescents with depression symptoms. Materials & Methods: This quasi-experimental research adopted a pretest-posttest control group design. Purposive sampling was employed to select 30 adolescents with depression symptoms as the research sample. They were then assigned randomly to an experimental and control group (n=15 per group). The experimental group received an intervention including twelve 45-minute sessions. All participants completed the Emotional Autonomy Scale (EAS), the Emotion Regulation Questionnaire (ERQ), and the Rumination Response Scale (RRS) at the pretest, posttest, and follow-up stages. The repeated measures ANOVA was used for data analysis. Results: According to the results, there was a significant difference between the experimental and control groups in the mean scores of emotional autonomy, emotion regulation, and rumination (P< 0.001). The results also indicated that attachment-based therapy significantly improved emotional autonomy, emotion regulation strategies (e.g., reappraisal and suppression), and rumination at the posttest and follow-up stages (P< 0.001). Conclusions: Attachment-based therapy should be employed as a therapeutic priority for improving emotional autonomy and emotion regulation strategies (e.g., reappraisal and suppression) and alleviating rumination in adolescents with depression symptoms.

Background: Infertility is one of the disturbances that may occur in the lives of couples, leading to experiences of psychological distress and endangering interpersonal relationships and marital quality. This study investigated the efficacy of intensive shortterm dynamic psychotherapy (ISTDP) in enhancing distress tolerance and marital quality of life among infertile women in Yazd, Iran.Methods: A semi-experimental pretest-posttest follow-up design with an experimental and control group (n=20 per group) was employed. Forty infertile women from the target population in Yazd, Iran (data collected in 2023) were randomly assigned into either the experimental group receiving eight 45-minute ISTDP sessions or the control group receiving no intervention. For data collection, questionnaires on distress tolerance and perceived relationship quality components were used. Data analysis was done by a repeated-measures analysis of variance (ANOVA) in SPSS version 27 was used.Results: According to the results, for distress tolerance, the mean score for the ISTDP group at the pretest was 31.55 (±13.14), which increased to 50.10 (±9.31) at posttest and 49.70 (±8.68) in the follow-up. The mean score for the control group at the pretest and posttest were 32.05 (±10.28) and 32.25 (±10.17), respectively. Moreover, for the marital quality of life, the mean score for the ISTDP group at the pretest was 70.40 (±19.47), which increased to 90.70 (±20.59) at the posttest and 91.15 (±20.75) at the follow-up. The mean score for the control group at the pretest and posttest was 66.85 (±21.75) and 65.85 (±20.66), respectively. There was a statistically significant within-group effect in the ISTDP group (P

Background and aimsAllergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations.MethodsExacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks.ResultsExacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, “dyspnea” and “headache” were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies.ConclusionP043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters.Clinical trial registrationwww.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

Background Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.Patients and methods Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed.Results 146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing.Conclusions This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.

Purpose: To report a case of metastatic uveal melanoma treated with immune checkpoint inhibition in which serial circulating tumor DNA (ctDNA) was assessed throughout treatment. Observations: A 33-year-old man was diagnosed with metastatic uveal melanoma and initially had progression of disease following hepatic embolization and nivolumab/ipilimumab. At the time, plasma ctDNA GNA11 and SF3B1 were measurable and repeat ctDNA showed increased variant allele frequency following further progression of disease on vorinostat. Following additional nivolumab/ipilimumab, radiographic response was noted and repeat ctDNA became undetectable and remained so at 27 months follow up. Conclusions and importance: Clearance of cell free DNA in metastatic uveal melanoma may be associated with radiographic response to immune checkpoint inhibitors.

Background: Epidemic thunderstorm asthma is an observed increase in cases of acute bronchospasm following thunderstorms. This study aimed to compare the frequency of obstructive airway disease or bronchial hyperresponsiveness in subjects with thunderstorm-associated respiratory symptoms with subjects with similar symptoms presented at other times.Methods: A cross-sectional study from June to November of 2013 was conducted on subjects with thunderstorm-associated respiratory symptoms living in Ahvaz City, Iran. Thunderstorm-associated subjects were presented with asthmatic symptoms in thunderstorms, and other patients presented with similar symptoms at other times. Baseline spirometry was performed on patients to examine the presence of obstructive airway disease. In all patients with normal spirometry, a provocation test was applied. A comparison of qualitative and quantitative variables was made using the Chi-square and independent t test, respectively. All analyses were carried out using SPSS Statistics Version 22. A P value less than 0.05 was considered statistically significant. Results: Out of 584 subjects, 300 and 284 participants were in thunderstorm-associated and non-thunderstorm-associated groups, respectively. After the final analysis, 87 (30.6%) and 89 (33.3%) of the thunderstorm-associated subjects and non-thunderstorm-associated group, respectively, had pieces of evidence of airflow limitation (P=0.27). Among the patients with normal spirometry, 161 (81.72%) of the thunderstorm-associated patients and 100 (56.17%) patients of the non-thunderstorm-associated symptoms group had a positive methacholine challenge test result (P

False Layer Syndrome is a permanent condition that prevents hens from laying eggs as a consequence of early infectious bronchitis (IB) virus infection. Cystic oviduct associated with the reduced peak of egg production in apparently healthy layer flock was diagnosed. Considering the flock history different viral and bacteriological tests were done. Any evidence of bacterial infection was not found. IB virus (IBV) was detected in caecal tonsil samples, suggesting early IB virus infection, an isolated virus phylogenetically belonging to the Variant 2 genotype. However, it is the first report of a Variant 2 genotype causing cystic oviducts in Iran, complementary studies are needed to investigate the pathogenicity of these viruses for oviduct and their ability to develop cystic oviducts.

Abstract Background Internal medicine (IM) residency is a notoriously challenging time generally characterized by long work hours and adjustment to new roles and responsibilities. The COVID-19 pandemic has led to multiple emergent adjustments in training schedules to accommodate increasing needs in patient care. The physician training period, in itself, has been consistently shown to be associated with vulnerability with respect to mental well-being. The impact of the COVID-19 pandemic on the experience of IM trainees is not well established. Objective Characterize the impact of the COVID-19 pandemic on trainee clinical education, finances, and well-being. Methods We developed a survey composed of 25 multiple choice questions, 6 of which had an optional short-answer component. The survey was distributed by the American College of Physicians (ACP) to 23,289 IM residents and subspecialty fellows. We received 1,128 complete surveys and an additional 269 partially completed surveys. Results The majority of respondents reported a disruption in their clinical schedule (76%) and a decrease in both didactic conferences (71%) and protected time for education (56%). A majority of respondents (81%) reported an impact on their well-being with an increase in their level of burnout and 41% of respondents reported a decrease in level of direct supervision. Despite these changes, the majority of trainee respondents (78%) felt well prepared for clinical practice after graduation. Conclusions These results outline the vulnerable position of internal medicine physicians in training. Preserving educational experiences, adequate supervision, and humane work hours are essential in protecting trainees from mental illness and burnout during global emergencies.

Background: Paying attention to well-being in educational contexts is essential in evaluating educational systems’ health and dynamics. This research investigated the mediating role of academic self-efficacy in the correlation between school belonging and self-compassion in students with physical-motor disabilities.Methods: This correlational study employed structural equation modeling as the analytical approach. The statistical population for this study comprised all 12-18-year-old students with physical-motor disabilities in Ahvaz, Iran in 2022. The convenience sampling method was employed to select 282 students with physical-motor disabilities as participants. To collect data, the Academic Well-Being Questionnaire (AWQ), Sense of School Belonging Questionnaire, Self-Compassion Questionnaire-Long Form (SCS-LF), and Students’ Academic Self-Efficacy Questionnaire (SASEQ) were used. The proposed model was evaluated using structural equation modeling in SPSS version 27 and AMOS version 24.Results: The mean and standard deviation of academic well-being, school belonging, self-compassion, and academic self-efficacy were 120.79±23.62, 66.48±19.46, 75.45±20.33, and 98.46±42.53, respectively. The findings revealed significant correlations between academic well-being and all direct paths except school belonging (P=0.001). Furthermore, the indirect paths of school belonging and self-compassion exhibited significant associations with academic well-being, mediated through the role of academic self-efficacy (P=0.001). Moreover, the model fit criteria, including comparative fit index (CFI) and root mean square error of approximation (RMSEA), were 0.98 and 0.04, respectively.Conclusion: Based on the results, the modified and final model of the study demonstrated a strong fit with the data. This model serves to identify practical factors contributing to the academic well-being of adolescents with physical-motor disabilities. Holding educational workshops to enhance school belonging and self-compassion in these students can improve their academic self-efficacy and overall well-being.

Background and Objectives: Religion and spiritual attitudes are among the important factors affecting psychological and social injuries because spirituality influences people's attitudes, cognition, and behavior. The present study aimed to investigate the mediating role of impulsivity in the relationship between anxious attachment and religious attitude with the tendency to addiction among university students. Materials and Methods: This descriptive-correlational study employed structural equation modeling (SEM). The study population consisted of all students at the Islamic Azad University of Ahvaz, of whom 300 were selected as the sample using convenience sampling. All participants completed the Addiction Potential Scale (APS), Experiences in Close Relationships (ECR) Scale, Religious Attitude Scale, and Dickman Impulsivity Inventory (DII). The data were statistically analyzed using SEM. Results: According to the results, there was a significant relationship between anxious attachment with impulsivity (P=0.012) and the tendency to addiction (P=0.001). Moreover, there was a negative relationship between religious attitudes with impulsivity (P=0.001) and the tendency to addiction (P=0.001). There was a positive relationship between impulsivity and the tendency to addiction in the students (P=0.001). The results also showed that impulsivity mediates the relationships between anxious attachment and religious attitudes with the tendency to addiction (P=0.001). Conclusions: The results showed that the proposed model fitted the data well. Accordingly, the tendency of young people to addiction can be reduced by training families and university students in safe attachment styles, spiritual teachings, self-restraint, and control of impulses.

­­­The biodiversity of the Noctuidae, an economically important family of Noctuoidea which include major crop pests, is becoming well-identified nowadays in Iran due to the increased number of faunal expeditions. The two large subfamilies of Noctuidae namely Xyleninae Guenée, 1837 and Noctuinae Latreille, 1809 comprise the majority of Iran's noctuid moth fauna. Two species, Leucochlaena hoerhammeri (Wagner, 1931) and Dichagyris (Stenosomides) mansoura (Chrétien, 1911) members of Xyleninae and Noctuinae subfamilies, respectively, are recorded from Iran for the first time. This is also the first record of the subgenus Stenosomides Strand, 1942 from Iran. Both the external and genital characteristics of the newly recorded species are presented together with illustrations of the adults and their genitalia.