Substance abuse is common issue in youth and may influence youth's suicide thoughts or actions. It can lead to social isolation, low self-esteem, loss of work or school, estrangement from family and friends – all these may create a core of stresses that may lead to suicidal tendencies.Analysis addictive factors correlating with occurrence of suicidal thoughts and behaviours among adolescents at the age of 18–20.Study was based on authorial, previously validated questionnaire, included 16 questions about suicidal thoughts. Questionnaires were filled by adolescents (age 18–20) of 21 Secondary Schools in Katowice.From the group of 965 adolescents, 28.8% had suicidal thoughts. From all respondents: 31.3% smoked, 92.7% drunk alcohol, 16.0% used legal hights and 30.9% – drugs; 35.8% of smoking adolescents had suicidal thoughts. In group of non-smoked adolescents – 25.6%. There was statistical significant difference (P = 0.0012) between these groups. Among adolescents who drunk alcohol, 28.8% had suicidal thoughts. In the group of non –drinking alcohol adolescents – 27.9%. There was no statistical significant differences (P = 0.88233) between these groups. There were 43.7% adolescents with suicidal thoughts who used legal hights. In the group of non-users of legal hights, 26.0% adolescents had suicidal thoughts.Adolescents that are using examined stimulants are in the group risk of suicidal thoughts and autodestructive behaviours. Results show the need of psychiatric and psychotherapeutic support that is aiming to prevent suicides and autodestructive behaviours in this group. Screening questionnaires that are assessing the problem of addiction within the adolescent may help to identity persons with suicidal tendencies.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Intracellular tumor antigens presented as peptides on MHC (pMHC) class I molecules are attractive targets for more tumor-selective immunotherapeutic approaches with promising data already emerging from clinical trials. pMHCs have been targeted by TCR-engineered T cells or soluble recombinant T-cell receptors (TCRs) fused to an anti-CD3 fragment. Naturally occurring cancer-reactive TCRs have weak affinity and require substantial affinity enhancements for their cognate pMHC. However, the outcome of this process is difficult to predict and bears the risk for off-target cross reactivities in normal tissues, which may lead to severe adverse events in the clinic. Here, we describe a highly potent dual pMHC T-cell engager (TCE) antibody format with high specificity towards tumor-specific pMHCs utilizing an HLA-A*02:01 restricted MAGE-A4 epitope to validate the concept. A series of monovalent and bivalent antibody constructs composed of anti-MAGE-A4 binding arms, ranging in affinities from 30 nM to 100 pM, were fused to an anti-CD3 Fab fragment with lower affinity compared to that commonly used for TCR-fusions. The different antibody constructs were evaluated for selective killing of MAGE-A4/HLA-A*02 positive human U2OS osteosarcoma and A375 melanoma cancer cells versus a panel of different MAGE-A4-negative/HLA-A*02-positive human cell lines. Bivalent bispecific antibody variants mediated a 7-fold greater degree of cancer cell killing and similarly increased T cell activation compared to their monovalent bispecific counterparts. EC50 values ranged as low as single digit picomolar, while the overall cross reactivity against MAGE-A4-negative/HLA-A*02-positive cells was not substantially affected. These results prove that dual targeting of pMHCs on cancer cells provides selective and efficient T cell-mediated target cell killing and T cell activation, even at very low levels of pMHC on the cell surface, highlighting the pivotal roles played by the affinity of the individual arms, valency, and epitope densities. We further analyzed the dual pMHC TCE for potential off-target effects by recognition of similar and physiologically relevant non-MAGE-A4 peptides. T2 cells pulsed with similar peptides and co-cultured with PBMC effector cells showed no significant T cell activation or IFNg release in the presence of the dual pMHC TCE in comparison to MAGE-A4 peptide-pulsed T2 cells. Finally, we compared the dual pMHC TCE against a recombinant TCR fused to an anti-CD3 scFv, a construct that is currently in clinical development. Interestingly, the dual pMHC TCE resulted in a 3-fold more potent cancer cell killing while having significantly lower effect on cytokine production. In conclusion, dual pMHC targeting with TCE antibodies is an attractive alternative to soluble affinity-enhanced TCR-based cancer immunotherapies as they facilitate potent tumor targeting without the need for extensive affinity enhancements. Citation Format: Stephanie Jungmichel, Fabian Scheifele, Anna Sobieraj, Severin Wendelspiess, Thomas Schleier, Philip Knobel, Camilla Winnewisser, Melissa Vrohlings, Philipp Richle, Hannes Merten, Jacqueline Blunschi, Christian Leisner, Leonardo Borras. Enhanced anti-tumor responses with a novel dual pMHC T-cell engager bispecific antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2891.
IntroductionAcute lymphoblastic leukemia (ALL) and lymphomas affect both pediatric and adult populations, therefore, they might be treated by pediatric or adult centers.It has been proven that the prognosis among adolescents and young adults (AYA) is poorer than among children, which remains a subject of research. Many factors are suspected to affect the diagnostic and treatment processes in adolescents and young adults, one of them being the organization of the healthcare system.The aimof the studywas to compare the time intervals between different events on disease trajectory in pediatric and AYA groups suffering from ALL and lymphomas.MethodsWe collected data on 81 patients diagnosed with ALL (50 children and 31 AYAs) and 100 patients diagnosed with lymphomas (50 children and 50 AYAs). Statistical analysis was performed in order to compare the groups.ResultsThe results confirmed the hypothesis that the duration of the diagnostic process differs significantly between groups. For patients with ALL, the analyzed time intervals were significantly shorter in the pediatric group than in the AYA group: first contact with a GP - admission to Hematology Department (2 vs. 5 days; pvalue= 0.004), first contact with a GP - treatment (6 vs. 12 days, p-value=0.001), diagnosis - treatment (1 vs. 3 days, p-value=0.003). In the case of patients suffering from lymphomas, the results were similar. The analyzed time intervals were significantly shorter in the pediatric group than in the AYA group: first contact with a GP- diagnosis (21 vs. 40.5 days, p-value<0.0001), first contact with a GP - treatment (27 vs. 65 days, p-value<0.0001). Trend analysis showed that the longer patients had presented symptoms before contacting the primary care physician, the longer they waited for the beginning of treatment both in ALL and lymphomas groups (p-values=0.0129 and 0.0038 respectively).DiscussionAs the diagnostic and treatment processes are longer for AYA patients, actions must be undertaken in order to ensure equality and improve the healthcare system in Poland and possibly other countries.
Inwentaryzację linii energetycznych można przeprowadzić korzystając ze wsparcia lotniczego skaningu laserowego oraz innych technologii takich jak metody klasyczne czy GPS. Metody te wymagają innego nakładu finansowego, sprzętu i liczby osób opracowujących dane. W pracy porównano wyniki pomiarów inwentaryzacji linii elektroenergetycznych wysokiego napięcia 110 kV relacji Modzyszyn-Tczew.
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