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Objectives: Urinary incontinence (UI) is a prevalent condition that significantly impacts the quality of life. This study aimed to validate the Hungarian version of the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and assess its psychometric properties in the context of the Hungarian population. Study design: A cross-sectional study involved 215 Hungarian-speaking women with a mean age of 67.6 ± 11.9 years. Main outcome measure: Participants were administered both the ICIQ-FLUTS and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). The psychometric analysis included test-retest reliability, convergent validity, and internal consistency. Results: The Hungarian version of ICIQ-FLUTS demonstrated strong psychometric properties. The test-retest reliability analysis showed a high intraclass correlation coefficient (ICC = 0.921), indicating excellent agreement between measurements over a 14-day interval. Convergent validity was supported by a strong positive correlation between the total scores of ICIQ-FLUTS and ICIQ-SF (ρ = 0.686, p < 0.001), emphasizing shared underlying constructs. Furthermore, the ICIQ-FLUTS questionnaire exhibited good internal consistency, with a Cronbach's α coefficient of 0.862. Conclusions: This study successfully validated the Hungarian version of the ICIQ-FLUTS questionnaire and demonstrated its robust psychometric properties. This tool will enable healthcare practitioners and researchers to effectively assess and address UI's impact on their quality of life.

The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env 371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env 371-379 peptides, we demonstrate that only the most stable Env 371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env 371-379 L6I-specific CD8 + T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules., Competing Interests: Competing interests: G.M., R.L.P., R.K., V.I., R.J.S., M.M.C., V.K., R.P., A.J., J.D., T.H., W.B., G.P., K.O., D.K., A.S., C.B., R.R., C.P., T.G., A.T., A.W., M.D., D.G., M.H., R.J.C., K.E.A., L.D., A.K., S.L., M.S., and L.F.G. are or were employees of Immunocore Ltd., (© 2024. The Author(s).)

Specificity of a T cell receptor (TCR) is determined by the combination of its interactions to the peptide and human leukocyte antigen (HLA). TCR-based therapeutic molecules have to date targeted a single peptide in the context of a single HLA allele. Some peptides are presented on multiple HLA alleles, and by engineering TCRs for specific recognition of more than one allele, there is potential to expand the targetable patient population. Here, as a proof of concept, we studied two TCRs, S2 and S8, binding to the PRAME peptide antigen (ELFSYLIEK) presented by HLA alleles HLA-A*03:01 and HLA-A*11:01. By structure-guided affinity maturation targeting a specific residue on the HLA surface, we show that the affinity of the TCR can be modulated for different alleles. Using a combination of affinity maturation and functional T cell assay, we demonstrate that an engineered TCR can target the same peptide on two different HLA alleles with similar affinity and potency. This work highlights the importance of engineering alloselectivity for designing TCR based therapeutics suitable for differing global populations., (© 2024. The Author(s).)

Background: 7 T cardiac magnetic resonance imaging (MRI) studies may enable higher precision in clinical metrics like cardiac function, ventricular mass, and more. Higher precision may allow early detection of functional impairment and early evaluation of treatment responses in clinical practice and pre-clinical studies., Methods: Seven female German Landrace pigs were scanned prior to and at three time points (3-4 days, 7-10 days, and ~60 days) post myocardial infarction using a whole body 7 T system and three radiofrequency (RF) coils developed and built in-house to accompany animal growth., Results: The combination of dedicated RF hardware and 7 T MRI enables a longitudinal study in a pig model of acute and chronic infarction, providing consistent blood tissue contrast and high signal-to-noise ratio (SNR) in measurements of cardiac function, as well as low coefficients of variation (CoV) for ejection fraction (CoV intra-observer : 2%, CoV inter-observer : 3.8%) and infarct size (CoV intra-observer : 8.4%, CoV inter-observer : 3.8%), despite drastic animal growth., Conclusions: Best results are achieved via manual segmentation. We define state-of-the-art procedures for large animal studies at 7 T., (© 2024. The Author(s).)

This research examines the psychometric characteristics and reliability of the 6-item turnover intention scale (TIS-6) by Bothma and Roodt (SA J Hum Resour Manag 11:a507, 2013) on a Hungarian sample. The internal validity of the TIS-6 was assessed using data from 269 Hungarian elderly care institution workers. Confirmatory factor analysis was performed to analyse the structural validity. Convergent and discriminant validity were examined with questions on job characteristics and using the Maslach Burnout Inventory and Effort-Reward Imbalance Scale. IBM SPSS 28.0 software was used for the statistical analysis, and the results were considered significant at p < 0.05. The internal consistency of the questionnaire's scale proved to be acceptable (α = 0.826). Convergent validity was confirmed by the relationships between the components of the questionnaire and burnout (r s  = 0.512; p < 0.001; r s  = 0.419; p < 0.001) and workplace stress (r s  = 0.565; p < 0.001; r s  = 0.310; p < 0.001). There were significant differences between the TIS-6 scores among the groups with different degrees of burnout (p < 0.001), which indicated adequate discriminant validity of the questionnaire. The structural validity of the questionnaire was acceptable, and the scale questions fit well. The Hungarian version of the TIS-6 scale is a valid and reliable tool for assessing turnover intention among elderly care institution workers in Hungary., (© 2024. The Author(s).)

Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson's r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium., (© 2024. The Author(s).)

Introduction: Premenstrual symptoms, including premenstrual syndrome and its more severe form premenstrual dysphoric disorder, are a set of somatic and psychological symptoms that occur during the luteal phase of the menstrual cycle. Our research aimed to adapt the Hungarian version of the Premenstrual Assessment Form-Short Form (PAF-SF), a questionnaire suitable for assessing premenstrual symptoms, and to examine its reliability, validity, and applicability., Methods: The questionnaire was validated according to Beaton's six-step guidelines. Our sample consisted of 198 menstruating women, 50 of whom completed the instrument for a second time to assess reliability. Descriptive statistics were calculated presenting mean (standard deviation), the internal consistency was measured by Cronbach's alpha value, the test-retest reliability using intraclass correlation coefficients, Spearman rank correlation was applied to test the criterion validity of the questionnaire, and discriminant validity was examined using the independent-sample t test using IBM SPSS 28.0 software. The structural validity was evaluated by confirmatory factor analysis (CFA) using IBM AMOS 29.0 software. The level of significance was set at p  < 0.05., Results: Our sample (average age 25.37 ± 4.80 years) scored 28.08 ± 9.49 points out of the maximum 60 points when filling out the PAF-SF questionnaire. The result of Cronbach's alpha calculation, which supports the reliability of the questionnaire, was 0.845. During the CFA, the three-factor structure (Affect, Water Retention, and Pain) was supported (root mean-square error approximation [RMSEA] = 0.054; Tucker-Lewis Index = 0.965; Comparative Fit Index = 0.976; χ 2  = 48.642; df = 31; p  = 0.023; χ 2 /df = 1.569)., Discussion: The PAF-SF questionnaire proved to be a reliable measuring tool for assessing premenstrual symptoms among women of reproductive age., Competing Interests: No competing financial interests exist., (© Olívia Dózsa-Juhász et al., 2023; Published by Mary Ann Liebert, Inc.)

Background: Older nursing home residents are at a greater risk of falling due to frailty. Exercise is effective at hampering frailty and related adverse events, including falls. Objectives: Our purpose was to evaluate the effect of a 12-week moderate-intensity multicomponent exercise programme on the number of falls and physical functioning among older nursing home residents. Also, we examined the association between the number of falls and demographics as well as physical and cognitive baseline data. Methods: The study protocol was registered on clinicaltrials.gov with the following identifier: NCT05835297. Older adults aged 65 years and over were recruited from a nursing home, and eligible and consenting residents were randomly allocated to two parallel groups: the intervention group, which performed a multicomponent exercise programme composed of strength, balance, and aerobic training ( n = 12), and the control group, which received usual care ( n = 12). Outcomes included falls, and measures of strength, balance, and mobility. Results: We had high adherence to exercise sessions, and no adverse events were recorded. We observed a non-significant reduction in falls ( p = 0.34) and a significant improvement in Short Physical Performance Battery ( p = 0.003) after the exercise programme. Falls were associated with being female and having diminished physical or cognitive function. Conclusions: Multicomponent exercise programmes should be implemented regularly in nursing homes for their effectiveness. Future studies with bigger samples, including participants with worse physical and cognitive impairments, as well as follow-up periods are required.

Objective: The Prolapse and Incontinence Knowledge Questionnaire (PIKQ) is a self-administered, reliable and valid instrument which assess knowledge regarding urinary incontinence and pelvic organ prolapse. There is no validated Hungarian version of this questionnaire; therefore the aim of this study was to develop a reliable, valid and culturally sensitive Hungarian version of the PIKQ., Study Design: A cross-sectional study was conducted from March to October 2022 with a sample of 459 women. The PIKQ, which consists of the urinary incontinence and pelvic organ prolapse scales, was translated into Hungarian in accordance with international guidelines. The validity and reliability of the final version of the Hungarian PIKQ was evaluated using construct validity, comparison with known-groups, internal consistency and test-retest reliability., Results: Regarding construct validity, all fit indices were found acceptable. Healthcare workers had significantly higher knowledge about urinary incontinence and pelvic organ prolapse (p < 0.001) compared to women who had not worked in a medical field. The Hungarian PIKQ had an adequate internal consistency with Cronbach alpha of 0.785 for the urinary incontinence scale and 0.826 for the pelvic organ prolapse scale. The correlation coeffcients between the test and retest was 0.931 for the urinary incontinence scale and 0.964 for the pelvic organ prolapse scale., Conclusion: The Hungarian version of the PIKQ is a reliable and valid tool to measure the level of knowledge about urinary incontinence and pelvic organ prolapse among Hungarian speaking women., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© 2024 The Authors.)

Background: Resistance exercise has shown effectiveness in reducing various risk factors related to sarcopenic obesity (SO) compared to other types of exercise, e.g., aerobic exercise., Objective: This systematic review evaluates the effect of resistance exercise on body composition, muscular strength, and functional capacity among older women with sarcopenic obesity aged ≥ 60 years., Methods: This systematic review is registered on PROSPERO (registration No. CRD42023394603) and follows the PRISMA guidelines. The following electronic databases were used to search the literature: Pedro, Cochrane Central Register of Controlled Trials, Embase, PubMed, and Web of Science. We included only RCTs that investigated the effect of resistance exercise on body composition and functional capacity. Two independent reviewers conducted the process of study selection and data extraction., Results: The search strategy retrieved 687 results. One hundred and twenty-six records were deleted as duplicates. Consequently, 534 studies were excluded after the title/abstract assessment. After further detailed evaluation of twenty-seven full texts, seven RCTs were included; all the RCTs examined the isolated effect of resistance exercise in women with sarcopenic obesity. The included studies comprised 306 participants, with an average age of 64 to 72 years. We noticed a trend of improvement in the included studies among the intervention groups compared to the control groups among the different outcomes. The study protocol was inconsistent for the intervention settings, duration, and outcomes. Including a modest number of trials made it impossible to perform data meta-analysis., Conclusions: Heterogeneity among studies regarding training protocols and the outcome measures reported limited robust conclusions. Still, resistance exercise intervention can improve body composition and functional capacity among elderly women with sarcopenic obesity.

Mucosal-associated invariant T (MAIT) cells use canonical semi-invariant T cell receptors (TCR) to recognize microbial riboflavin precursors displayed by the antigen-presenting molecule MR1. The extent of MAIT TCR crossreactivity toward physiological, microbially unrelated antigens remains underexplored. We describe MAIT TCRs endowed with MR1-dependent reactivity to tumor and healthy cells in the absence of microbial metabolites. MAIT cells bearing TCRs crossreactive toward self are rare but commonly found within healthy donors and display T-helper-like functions in vitro. Experiments with MR1-tetramers loaded with distinct ligands revealed significant crossreactivity among MAIT TCRs both ex vivo and upon in vitro expansion. A canonical MAIT TCR was selected on the basis of extremely promiscuous MR1 recognition. Structural and molecular dynamic analyses associated promiscuity to unique TCRβ-chain features that were enriched within self-reactive MAIT cells of healthy individuals. Thus, self-reactive recognition of MR1 represents a functionally relevant indication of MAIT TCR crossreactivity, suggesting a potentially broader role of MAIT cells in immune homeostasis and diseases, beyond microbial immunosurveillance., (© 2023 Chancellor et al.)

Introduction: The premenstrual syndrome (PMS) is a critical factor in women's health, which, in addition to physical inactivity, can be influenced by the body mass index (BMI), stress, and mental state, among others. The study aimed to assess the severity of PMS symptoms among young women regarding physical inactivity, BMI, mental state, and perceived stress level., Methods: A total of 198 female participants between the ages of 18-45 took part in a 6-month cross-sectional online questionnaire study. The average age of the participants was 25.37 ± 4.80 years. To assess physical activity, stress, mental state, and premenstrual symptoms, we employed standard questionnaires, including the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Perceived Stress Scale (PSS), the General Health Questionnaire-12 (GHQ-12), and the Premenstrual Assessment Form-Short Form (PAF-SF). The collected data were analyzed using IBM SPSS (Statistical Package for Social Sciences) version 28.0 software, with a significance level set at p  < 0.05., Results: During the analysis, we observed a significant relationship ( p  = 0.020) between regular exercise and the severity of PMS symptoms, as well as between mental state and PMS symptoms ( p  < 0.001). Furthermore, our findings revealed a significant negative correlation between regular physical activity and perceived stress levels (r = -0.179; p  = 0.012), as well as between regular exercise and the participants' mental state (r = -0.157; p  = 0.027). Additionally, we identified a significant difference ( p  < 0.001) among the six subgroups formed based on the PAF-SF and average PSS questionnaire results. Moreover, a significant difference was observed between the PAF-SF case and control groups in terms of BMI averages ( p  = 0.019)., Discussion: The research findings indicate that the severity of PMS symptoms is influenced by regular physical activity, mental state, and stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dózsa-Juhász, Makai, Prémusz, Ács and Hock.)

Objective: To present a systematic review of randomized controlled trials which summarizes the effects of community-based resistance, balance, and multi-component exercise interventions on the parameters of functional ability (e.g., lower extremities muscle strength, balance performance and mobility)., Methods: This PROSPERO-registered systematic review (registration no. CRD42023434808) followed the PRISMA guidelines. Literature search was conducted in Cochrane, Embase, Ovid Medline, PEDro, Pubmed, Science Direct, Scopus and Web of Science. We included RCTs that investigated the following interventions: lower extremity strengthening, balance and multi-component exercise interventions on ambulatory community-dwelling adults aged ≥65 years., Results: Lower extremity strengthening exercises revealed significant effects on the strength of lower extremity, balance outcomes and mobility. Balance exercises reduce the rate of injurious falls, improve static, dynamic and reactive balance, lower extremity strength as well as mobility. Multi-component exercise training reduces medically-attended injurious falls and fallers, incidence of falls, fall-related emergency department visits as well as improves mobility, balance, and lower extremity strength., Conclusion: Physical exercises are effective in improving the components of balance, lower extremity strength, mobility, and reducing falls and fall-related injuries. Further research on fall prevention in low-income countries as well as for older adults in vulnerable context is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sadaqa, Németh, Makai, Prémusz and Hock.)

Introduction and Hypothesis: The aims of the study were the translation, cultural adaptation, and validation of self-administered Australian Pelvic Floor Questionnaire (APFQ) on a Hungarian population., Methods: The validation was performed in 294 women over 18 who agreed to answer the Hungarian version of the APFQ. The validation of the questionnaire included evaluation of content/face validity, internal consistency, construct validity, test-retest reproducibility, discriminant validity and convergent validity., Results: Acceptable and good internal consistency was observed in all four dimensions [McDonald's ω (95% confidence interval) coefficients were > 0.7 for each dimension: bladder 0.888, bowel 0.790, prolapse 0.895 and sexual function 0.738]. Test-retest analyses revealed high reproducibility with intraclass correlation coefficients (bladder 0.83, bowel 0.92, prolapse 0.96 and sexual function 0.87). Prolapse symptom score correlated significantly with Pelvic Organ Prolapse Quantification (POP-Q), and bladder score correlated significantly with the results of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ UI SF) (convergent validity). Scores distinguished between patients with pelvic floor disorders and controls (high discriminant validity)., Conclusions: Hungarian version of the self-administered APFQ is a reliable and valid instrument for evaluating symptom severity and impact of pelvic floor dysfunction on the quality of life of Hungarian women., (© 2022. The Author(s).)

Importance: Adequate knowledge about pelvic floor disorders could lead to increased health care-seeking behavior, improved symptoms, and quality of life., Objectives: The aims of the present study were to evaluate Hungarian women's knowledge about pelvic floor disorders and to assess health care-seeking behavior., Study Design: We conducted a cross-sectional survey from March to October 2022 using self-administered questionnaires. The Prolapse and Incontinence Knowledge Questionnaire was used to assess Hungarian women's knowledge about pelvic floor disorders. The International Consultation of Incontinence Questionnaire-Short Form was used to gather information about the symptoms of urinary incontinence., Results: Five hundred ninety-six women were included in the study. Urinary incontinence knowledge was deemed proficient in 27.7% of participants, while pelvic organ prolapse knowledge was deemed proficient in 40.4% of participants. Greater urinary incontinence knowledge was significantly associated (P < 0.001) with higher level of education (P = 0.016), work in a medical field (P < 0.001), and ever practiced pelvic floor muscle training (P < 0.001), whereas greater pelvic organ prolapse knowledge was significantly associated (P < 0.001) with higher level of education (P = 0.032), work in a medical field (P < 0.001), ever practiced pelvic floor muscle training (P = 0.017), and ever had pelvic organ prolapse (P = 0.022). Of the 248 participants who reported a history of urinary incontinence, only 42 (16.93%) women sought care. Care seeking was higher among women who were more knowledgeable about urinary incontinence and among women with more severe symptoms., Conclusions: Hungarian women had limited knowledge about urinary incontinence and pelvic organ prolapse. Health care seeking among women with urinary incontinence was low., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Osteoporosis affects one in three women and one in five men over the age of 50. We do not have an osteoporosis-related knowledge questionnaire over the age of 50, which is considered strong evidence in the prevention and treatment of the disease., Objective: Aim of the study was to validate the Hungarian form of the Osteoporosis Questionnaire in Hungarian-speaking women over the age of 50., Method: The questionnaire was validated into Hungarian according to Beaton's six-step method. Our sample consisted of 326 women. During our statistical analysis, we calculated descriptive statistics, difference tests, Cronbach's alpha value, and Spearman's correlation coefficient for test-retest and for external validity. Quality of life and physical activity were examined to support the external validity., Results: Our sample (63.08 ± 9.36 years) scored 8.76 ± 6.94 points on the questionnaire. Cronbach's alpha value was 0.89. For the test-retest, Spearman's correlation coefficient showed a value of p≥0.25 for all the questions. Significant correlations were found between knowledge and age (R = 0.37; p<0.001) and years of using hormone replacement therapy (R = 0.34; p = 0.02). The correlation analysis showed significant (p<0.001) correlation between knowledge and all sub-dimensions of quality of life. Significant correlation was found between transport movement (p<0.001; R = 0.21), intensive (p<0.001; R = 0.354), moderate recreational activity (p<0.001; R = 0.348), total moderate (p = 0.041; R = 0.125) total intense movements (p = 0.018; R = 0.145) and knowledge., Discussion: The Hungarian questionnaire was validated in accordance with international practice., Conclusion: The Hungarian version of the Osteoporosis Questionnaire is a reliable, adaptable questionnaire for measuring the osteoporosis-related knowledge of the Hungarian female population over 50. Orv Hetil. 2022; 163(51): 29-37.

Introduction: Hip as well as knee osteoarthritis are common diseases. There are numerous therapeutic possibilities to address the problem., Objective: To study the effectiveness of the complex conservative treatment in patients with hip as well as knee osteoarthritis., Method: In addition to a self-made questionnaire, we applied the visual analogue scale, the Functional Independence Measure, the Barthel Index and the Medical Outcomes Study (MOS) - 36-Item Short-Form Health Survey. Apart from these, joint range of motion was measured. The members of the examined group had different physiotherapy treatments (thermal water, physiotherapy, classic Swedish massage, Bemer treatment, wraps, physiotherapy)., Results: The results of the visual analogue scale and the Barthel Index were significantly different between the two measurements. Regarding the Functional Independence Measure, we did not find significant difference between the two groups. As for measuring the study group's health condition, we observed improvement in the case of both the physical and mental health dimensions. During the examination of joint range of motion in the study group, after analyzing the participants' data, we detected improvement, except for the passive extension of the left knee., Conclusion: The 3-week complex conservative therapy can be an appropriate form of treatment to improve the functionality and the health condition in the case of hip as well as knee osteoarthritis. Orv Hetil. 2022; 163(48): 1917-1922.

Physical activity, physical functioning, and pain are some of the most critical factors of low back pain (LBP) treatment and prevention, but it was unknown that the back school program (BSP) influences the physical activity level of the patients with LBP. Data from 306 healthy patients and patients with chronic non-specific low back pain (cnsLBP) were used. We used the Global Physical Activity Questionnaire (GPAQ), the Low Back Pain Knowledge Questionnaire (LKQ), the visual analog scale, and the Roland-Morris Disability Questionnaire (RMDQ). The significance level was set at p < 0.05. The amount of sedentary time in cnsLBP patients enrolled in the BSP was significantly lower compared to the other two groups ( p < 0.001). Significantly higher moderate-intensity activities, leisure time activities, and active transportation were observed in the cnsLBP patients enrolled in the BSP than in the other two groups ( p < 0.001). RMDQ scores and the pain intensity of the cnsLBP patients enrolled in the BSP were significantly lower than in patients with LBP receiving only exercise therapy ( p < 0.001). The physical activity level and low-back-pain-specific knowledge was significantly higher, while back-related disability and pain intensity were significantly lower among patients with low back pain syndrome who participated in a back school program.

Neoantigens derived from somatic mutations are specific to cancer cells and are ideal targets for cancer immunotherapy. KRAS is the most frequently mutated oncogene and drives the pathogenesis of several cancers. Here we show the identification and development of an affinity-enhanced T cell receptor (TCR) that recognizes a peptide derived from the most common KRAS mutant, KRAS G12D , presented in the context of HLA-A*11:01. The affinity of the engineered TCR is increased by over one million-fold yet fully able to distinguish KRAS G12D over KRAS WT . While crystal structures reveal few discernible differences in TCR interactions with KRAS WT versus KRAS G12D , thermodynamic analysis and molecular dynamics simulations reveal that TCR specificity is driven by differences in indirect electrostatic interactions. The affinity enhanced TCR, fused to a humanized anti-CD3 scFv, enables selective killing of cancer cells expressing KRAS G12D . Our work thus reveals a molecular mechanism that drives TCR selectivity and describes a soluble bispecific molecule with therapeutic potential against cancers harboring a common shared neoantigen., (© 2022. The Author(s).)

Questionnaires such as the Multidimensional Anxiety Inventory for Children and Adolescents (MAICA) provide a diagnostic approach to alert for anxiety- or depression-related problems. The aim is to examine the MAICA within two clinical samples.We first investigated whether children having anxiety- or depression-related problems (n = 94) scored higher on anxiety (i.e., emotionality and worry) and depression (i.e., dysthymia and low joy) than a non-clinical control group (n = 282). Then, we contrasted a clinical sample with other mental disorders unrelated to anxiety or depression (n = 45) with another non-clinical control group (n = 135). Across all scales of the MAICA, children with anxiety- or depression-related problems showed less favourable values than the non-clinical control group (d = 0.34 to 0.54 for anxiety, 0.55 to 0.68 for depression). Children with other mental problems showed no differences in either the anxiety or depression scales. For the use as a screening instrument, preliminary cutoff scores for identifying anxiety- or depression-related problems with the MAICA are given.