julilili42/papers huggingface dataset:
CTNI-57. RADIONUCLIDE THERAPY WITH 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA - INTERIM ANALYSIS RESULTS OF A SINGLE-ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY
2022-11-01

Abstract BACKGROUND While most meningiomas are considered benign tumors, a subset of these tumors are characterized by a more aggressive clinical course and require multimodal treatment. Beyond surgical and radiotherapeutic options, there are no effective medical treatments available. Somatostatin receptor 2 (SSTR2) is expressed by the majority of meningiomas. 177Lu-DOTATATE is a SSTR2-targeting radionuclide that has been successful in neuroendocrine tumors. Here we report the results of the interim analysis of an ongoing clinical trial (NCT03971461) that is evaluating the effect of 177Lu-DOTATATE in treating progressive intracranial meningiomas. METHODS In this Simon two-stage design phase II study, adults with advanced intracranial meningiomas received 177Lu-DOTATATE 7.4 GBq (200 mCi) every eight weeks for four doses. 68Ga-DOTATATE PET-MRI was performed before and at the end of treatment. The primary endpoint was progression-free survival at 6 months (PFS-6). Correlative studies evaluated the association of PFS-6, objective response rate, progression-free survival, overall survival with radiographic tumor measurements, 68Ga-DOTATATE uptake on PET-MRI, SSTR2 expression in tumor, and meningioma methylation subclass. RESULTS Fourteen patients (F = 11, M = 3) with progressive meningiomas (WHO I = 3, II = 10, III = 1) have been enrolled. Median age was 63.1 (range 49-78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated, no treatment-limiting toxicities were observed. Six of 14 patients (42%) achieved PFS-6. Radiographically, all six patients had achieved Stable Disease. A functional alteration of tumoral SSTR2 expression by 68Ga-DOTATATE PET-MR imaging was observed in three patients. CONCLUSIONS Treatment with SSTR2-targeting 177Lu-DOTATATE is well tolerated. In this interim analysis, six of 14 patients achieved PFS-6. This exceeds the predefined threshold to continue to stage two of this study. This clinical trial is now open to patient enrollment at two study sites in the US.
Induced feelings of external influence during instructed imaginations in healthy subjects
2022-11-01

The psychopathological phenomenon of delusions of influence comprises variable disturbances of the self-environment-border leading to the feeling of external influence on thoughts, feelings, impulses or behaviors. Delusions of influence are a hallmark in psychotic illness, but nevertheless, attenuated forms can also appear in healthy individuals. Here we present a newly developed paradigm to induce and assess feelings of external influence during instructed imaginations in healthy individuals. In the current study, we asked 60 healthy individuals to visually imagine different objects. To induce feelings of external influence, we applied one of three different physical setups (low-amplitude transcranial direct current stimulation, eye contact, or skin-to-skin hand touch), and informed the participants whether or not an external influence was attempted during the respective trial. The physical setup (setup vs. no setup, Z = −3.847, p &amp;lt; 0.001, r = 0.497) as well as the information given to the participants (confirmation vs. negation, Z = −5.218, p &amp;lt; 0.001, r = 0.674) alone were able to modulate the feeling of external influence in all three interventions. The impact of information (whether influence was attempted or not attempted) significantly exceeded the impact of the physical setup on the ratings of experienced external influence ( Z = −2.394, p = 0.016, r = 0.310). Moreover, the response latency correlated with the estimated feeling of external influence ( r S = 0.392, p = 0.002). Additional analyses addressed the influence of the emotional content of imagined objects and examined the intensity and emotional valence of the imaginations. Further supplemental analyses correlated external influence estimation of the participants with other psychopathological measures (trait markers for supernatural beliefs, proneness to hallucinations, and delusions and attributional style). In conclusion, this study endorses a quantitative model of psychopathological characteristics, in this case feelings of external influence that can be induced by external cues.
Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon
2022-11-01

The glutarimide moiety, common in many immuno-modulatory drugs, was decorated with lactam and diamide side chains via two variants of the Ugi reaction, namely, with isocyanide, aldehyde and acid or with isocyanide and oxo acid. The resulting diastereomerically pure compounds were evaluated for their affinity towards the E3 ubiquitin ligase substrate receptor Cereblon.
When a Crisis Empties Mosques: A Case Study of Muslim Responses to the Pandemic’s Challenges in Regards to Spiritual Care and Communal Rituals in Austria and Germany
2022-11-01

Abstract Cases from both Germany and Austria exemplify how the COVID-19 pandemic is rapidly changing traditionally held ideas of Islamic community, religious congregations, and pastoral care. These cases were collected during Ramadan 2020, as this particular period signifies a time of paramount spirituality, social solidarity, and communal festivity. They reflect the rich and vibrant efforts and responses of Muslim leaders, organizations, and institutions to the challenges posed by the current pandemic. Different initiatives and solutions Muslim communities have developed as a response to COVID-19 are characterized as “caring communities.” Muslim chaplains, despite their highly limited personal access to secluded, lonesome, and distressed individuals in need of support, overcame the restrictions. Muslim leaders have striven to make use of the virtual space to fulfil the ordinary function of mosques as places of worship and communication. They have thus attempted to uphold social solidarity ( zakat) . Their responses to the pandemic raise questions about the future of religiosity and its manifestation as well as possible forms of religious communities and their ethical values.
COVID-19 and Perinatal Stress Experience – a Study Conducted as Part of the COVGEN Initiative
2022-11-01

Abstract Introduction During the COVID-19 pandemic, stress and anxiety in the population increased due to concerns about people’s own health and that of their relatives, as well as changes in everyday life due to measures taken to reduce the infection rate. Pregnant women are particularly stressed. The present study examines how the COVID-19 pandemic affects the stress experience and mental health of pregnant women and mothers of newborns and how care could be optimized. Methods As part of the international COVGEN initiative (https://www.covgen.org) to investigate the effects of the COVID-19 pandemic on the peripartum period, pregnant and postpartum women were asked about their experience with stress using the COPE-IS (Coronavirus Perinatal Experiences – Impact Survey) questionnaire developed for this purpose and translated from the English. In addition, demographic data, pre-existing diseases, pregnancy complications and the care situation were recorded. The questionnaire was either administered as hardcopy to inpatients at the Department of Women’s Health, University Hospital Tübingen, Germany, or online. All pregnant women and mothers who were pregnant or had given birth after the official start of the COVID-19 pandemic (11 March 2020) were eligible to participate. Results Complete data sets of n = 156 pregnant women and n = 221 postpartum women were available for evaluation. The general stress level assessed with the COPE-IS was significantly increased by the COVID-19 pandemic in both, pregnant and postpartum women, with pre-existing conditions such as respiratory diseases and pregnancy-related diseases like gestational diabetes adding to the stress. The subjectively perceived quality of care/support during pregnancy also influenced the stress level. Conclusions Fears of a COVID-19 infection and changes in preventive and aftercare services were a burden for the women surveyed. Intensified care during pregnancy and puerperium could help to stabilize the mental situation and reduce stress.
Perioperative Antibiotics in Appendicitis—Do We Need to Adjust Therapy for the Elderly? A Matched Pair Analysis
2022-11-01

(1) Background: Perioperative Antibiotics for acute complicated appendicitis are a standard of care. While there are plenty of trials for pediatric patients, data for elderly patients are scarce. The goal of our study was to evaluate whether elderly patients carry more resistant bacteria and thus have less favorable outcomes after an appendectomy that may warrant intensified perioperative antibiotic treatment (2) We present a retrospective single-center matched pair (139 patients each) analysis of perioperative and microbiological outcomes of an elderly appendicitis cohort (i.e., older than 60 years) compared with a younger adult cohort (i.e., ≤60 years). Both groups were matched one for one according to gender, duration of symptoms, c-reactive protein at presentation and whether they presented with uncomplicated or complicated appendicitis. (3) Results: After matching, complicated appendicitis was present in 76.3% of both groups. Elderly patients more frequently received preoperative diagnostic CT (p &lt; 0.001) than the young. Both operative strategy (laparoscopic appendectomy in 92.1% each) and duration of surgery (57 vs. 56 min) were equal in both groups. Postoperative antibiotics were prescribed in ~57% for a median of 3 days in both groups and antibiotic selection was similar. The incidence of surgical site infections was higher in the young (12.2% vs. 7.9%) yet not significant. There was no difference in culture positivity or bacterial spectrum and the elderly cohort did not present with increased resistant bacterial isolates. (4) Conclusions: While overall resistant bacterial strains were rare, perioperative outcomes between the young and the elderly did not differ and did neither warrant longer nor intensified antibiotic treatment.
641 Strong immune response to therapeutic vaccination with EO2401 microbiome derived therapeutic vaccine + nivolumab: interim report of the EOGBM1–18/ROSALIE study
2022-11-01

<h3>Background</h3> EO2401 is a therapeutic vaccine designed to activate memory commensal specific T-cells that are cross-reacting against validated tumor associated antigens (TAAs). EO2401 includes synthetically produced HLA-A2 peptides with molecular mimicry to TAAs (IL13Rα2, BIRC5 and FOXM1) upregulated in glioblastoma, and the CD4 helper peptide UCP2. <h3>Methods</h3> Patients with glioblastoma at first progression after radiotherapy/temozolomide received EO2401 with nivolumab (EN), or EN with bevacizumab within trial EOGBM1-18 (NCT04116658). Blood collection was performed at baseline and then every two or four weeks. Immune responses were investigated either directly on cryopreserved PBMCs without stimulation (ex vivo), or after 12 days in vitro stimulation (IVS) using tetramer staining, IFNg ELISpot and intracellular cytokine staining. The study was approved by all participating institution's Ethics Boards. <h3>Results</h3> Immune monitoring in EO2401 vaccinated patients demonstrates the ability of bacterial peptides to induce a strong CD8+ T cell response with cross-reactivity against human selected TAAs. Immune response against the 3 microbiome-derived peptides is demonstrated for 28 of 29 investigated patients using ELISpot after IVS. Post vaccination frequency of CD8+ T cells against bacterial peptide after IVS is extremely high, with a median of 5.5% of specific CD8+ T cells for EO2316 (max 18%), 16% for EO2317 (max 46%) and 14% (max 40%) for EO2318. Cross-reactivity against the pool of human peptides is demonstrated in 27/28 patients using ELISpot after IVS and validated using tetramer staining against BIRC5 and FOXM1. Polyfunctionality of CD8+ T cells effectors is supported by frequent expression of CD107a as well as IFN-g and TNF-a production after stimulation. Ex vivo, CD8+ T cells against at least one of the EO2401 peptides are detected in 26/28 evaluable patients with some patients exhibiting up to 5% of circulating specific CD8+ T cells. Memory specific CD8+ T cells response are found as early as two weeks after the first vaccination and maintenance of a strong and stable immune response could be detected for more than 10 months. CD4+ T cell response against the UCP2 helper peptide is demonstrated using IFN-g ELISpot after IVS. <h3>Conclusions</h3> EO2401 vaccine demonstrates ability to generate fast and durable immune responses in patients treated with E02401/nivolumab +/- bevacizumab. Activation of specific T cells cross-reacting against commensal antigens and TAAs is thereby validated as an efficient approach to activate strong immune responses in a difficult to treat tumor with low neoantigen expression and poor T cell priming. <h3>Trial Registration</h3> NCT04116658 <h3>Ethics Approval</h3> This study has obtained an ethics approval (Dana Farber Cancer Institute IRB: iRIS number 438532) and all participants gave informed consent before taking part.
Genetic Testing is Superior Over Endogenous Pharmacometabolomic Markers toPredict Safety of Haloperidol in Patients with Alcohol-induced Psychotic Disorder
2022-11-01

Background: Previous studies have shown that haloperidol biotransformation is mainly metabolized by CYP2D6. The CYP2D6 gene is highly polymorphic, contributing to inter-individual differences in enzymatic activity, and may impact haloperidol biotransformation rates, resulting in variable drug efficacy and safety profiles. Objective: The study aimed to investigate the correlation of the CYPD6 activity with haloperidol's efficacy and safety rates in patients with alcohol-induced psychotic disorders. objective: To investigate the correlation of the CYPD6 activity with the efficacy and safety rates of haloperidol in patients with alcohol-induced psychotic disorders. Method: One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and safety assessments were performed using PANSS, UKU, and SAS-validated psychometric scales. Results: No relationship between haloperidol efficacy or safety and the experimental endogenous pharmacometabolomic marker for CYP2D6 activity, urinary 6-НО-ТНВС/pinoline ratio was identified. In contrast, we found a statistically significant association between haloperidol adverse events and the most common CYP2D6 loss-of-function allele CYP2D6*4 (p&lt;0.001). Conclusion: Evaluation of the single polymorphism rs3892097 that defines CYP2D6*4 can predict the safety profile of haloperidol in patients with AIPD, whereas metabolic evaluation using an endogenous marker was not a suitable predictor. Furthermore, our results suggest haloperidol dose reductions could be considered in AIPD patients with at least one inactive CYP2D6 allele.
The impact of haematoxylin-eosin staining and immunohistochemistry of lentigo maligna and lentigo maligna melanoma margins on local recurrence
2022-11-01

Following micrographic-controlled surgery, the additional use of immunohistochemistry of tumour margins of LM/LMM reduced the risk of local recurrence, although this was not statistically significant.
Practice walking on a treadmill-mounted balance beam modifies beam walking sacral movement and alters performance in other balance tasks
2022-11-01

Abstract The goals of this study were to determine if a single 30-minute session of practice walking on a treadmill-mounted balance beam: 1) altered sacral marker movement kinematics during beam walking, and 2) affected measures of balance during treadmill walking and standing balance. Two groups of young, healthy human subjects practiced walking on a treadmill-mounted balance beam for thirty minutes. One group trained with intermittent visual occlusions and the other group trained with unperturbed vision, providing greater variation in the balance performance outcomes. We hypothesized that the subjects would show changes in sacrum movement kinematics after training and that there would be group differences due to larger improvements in beam walking performance by the visual occlusions group. We also investigated if there was any balance transfer from training on the beam to treadmill walking (margin of stability) and to standing static balance (center of pressure excursion). We found significant differences in sacral marker maximal velocity after training for both groups, but no significant differences between the two groups from training. There was limited evidence of balance transfer from beam walking practice to gait margin of stability for treadmill walking and for single-leg stance balance, but not for tandem stance balance. The number of step-offs while walking on a narrow beam had the largest change with training (partial η 2 =0.7), in accord with task specificity. Other balance metrics indicative of transfer had lower effect sizes (partial η 2 &lt;0.5). Given the limited transfer across balance training tasks, future work should examine how intermittent visual occlusions during multi-task training improve real world functional outcomes.
QOL-23. TOWARDS PATIENT-REPORTED OUTCOME ASSESSMENT IN THE MOLECULAR TUMOR BOARD – CANCER PATIENTS UNDER TARGETED THERAPY: APP-BASED ASSESSMENT OF PATIENT-REPORTED OUTCOMES (TRACE)
2022-11-01

Abstract Comprehensive genomic profiling and biomarker-based therapeutic strategies are currently used in clinical trials and in innovative health care systems including the center for personalized medicine network. Systematic assessments of patient-reported outcomes are warranted to gain insight into the perspective of patients and their relatives during biomarker-based therapies. In the present study, we focused on health-related quality of life (HRQoL), psychosocial situation, and physical symptoms in patients treated at the Center for Personalized Medicine Tübingen. First, we retrospectively evaluated symptom burden of n=265 (neuro-)oncological patients in the Molecular Tumor Board (MTB). Sixty percent of patients reported at least 1 neurological symptom, and psychosocial burden/unmet needs were high (overall 156/265; 59%, patients with malignant tumors n=86/106; 81%, Fisher’s exact, p &amp;lt; 0.0001). We therefore developed an app by 14 expert rounds and pretesting including validated assessments of HRoL, symptom und psychological burden and tested it in a pilot study. We conducted a structured interview with users 3 months afterwards to assess the app’s usability and feasibility. The interview was transcribed and analyzed according to a qualitative content analysis. So far, a total of 10 patients and caregivers have been enrolled in this pilot study. They reported that (i) the app is compatible with their daily routine (median 9.3, range 0-10), that (ii) they are more aware of their health status, which was rated as positive, and that (iii) completing app-based questionnaires was easier compared to paper questionnaires. Two patients reported technical problems, which were resolved timely. The pilot study proved feasibility and acceptance of the app. The app might optimize symptom burden assessment, adapted to the patients’ profiles. The next step is to prospectively compare HRQoL before and after start of targeted therapy in a multicenter study.
CSIG-22. THE MOLECULAR NETWORK OF CAMTA-1 IN GLIOMA CELLS
2022-11-01

Abstract Calmodulin-binding transcription activator 1 (CAMTA1) is a transcription factor located on chromosome 1p, and we have recently reported that CAMTA1 expression reduced neurosphere formation and tumor growth in nude mice, suggesting that CAMTA1 can function as tumor suppressor in experimental glioma. In the present study, we investigated the molecular network of CAMTA-1 in glioma cells. We established glioma cell lines with a doxycycline-inducible overexpression of CAMTA1. We performed a cap analysis of gene expression (CAGE) on these overexpressing cell lines to identify differentially regulated transcriptional start sites. We particularly focused on regulated target genes encoded on chromosome 19q. We identified an interaction of CAMTA1 overexpression with changes in the differential expression of Zink finger (ZNF) genes located on 19q. We will present novel data on a potential molecular interaction between chromosomes 1p and 19q.
EXTH-74. ATR INHIBITION IN EXPERIMENTAL GLIOMA
2022-11-01

Abstract Glioblastoma are incurable primary tumors of the central nervous system. Novel treatment options are urgently needed. Recently, we investigated molecular effects of disrupting the (b)HLH network, a frequently altered and tumor-promoting transcriptional network in glioma, by introducing a dominant-negative variant of the E47 protein. The identified downstream anti-tumor effects included the DNA damage response pathway. In the present study, we aimed at investigating the anti-glioma effects of ATR inhibition in vitro and in vivo with a particular focus on treatment-induced vulnerabilities and potential combination therapies. We performed acute cytotoxicity, clonogenic survival assays, flow cytometry-based determination of cell cycle status and apoptosis induction in human and murine glioma cell lines in vitro, and investigated tumor growth in the SMA560/VMDk syngeneic mouse model in vivo. Furthermore, we applied RNA sequencing, DigiWest protein profiling analyses and genome-wide CRISPR/Cas9 loss-of function and activation screens to determine potential combination therapies. Combination treatments were further analyzed for synergism by the Bliss and ZIP synergy models. ATR inhibition in glioma cells resulted in reduced viability and clonogenic survival. However, differential patterns of gene expression deregulation (e.g. p53 signaling) and differing modes of cell cycle arrest in distinct glioma model systems argue for a substantial heterogeneity with regard to response to ATR inhibition. Based on our data we designed combinatorial treatments. We will present novel insights into promising combinatorial treatments using ATR inhibition and their underlying molecular mechanisms.