julilili42/papers huggingface dataset:
Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient
2024-03-22

Background Neoplastic lesions affecting peripheral nerves are rare in the general population and, most often, are benign peripheral nerve sheath tumors. However, a minority of lesions represent high-grade malignancies associated with a poor prognosis, such as malignant peripheral nerve sheath tumors (MPNSTs). Very rarely, these tumors represent peripheral non-nerve sheath tumors (PNNSTs), such as hematological neoplasms that impair nerve function. These can be hard to distinguish from MPNSTs and other lesions arising from the nerve itself. In the present case report, we describe a rare case of direct infiltration of nerves by tumor cells of a hematological neoplasm. Methods We report the case of a 90-year-old woman with acute onset of right-sided foot palsy, sensory loss, and pain, caused by an extensive solitary mass of the sciatic nerve in the thigh. We present and discuss the clinical presentation, multimodal diagnostic procedures, and treatment. Results MRI of the right thigh and the caudal pelvis revealed a contrast-enhancing lesion infiltrating the sciatic nerve. Additionally performed staging imaging was non-revealing. After multidisciplinary discussion in the neuro-oncology tumor board, a MPNST was suspected and the patient underwent radical tumor resection. However, final histopathology revealed a diffuse large B-cell lymphoma (DLBCL). The patient received adjuvant palliative local radiotherapy which led to acceptable symptom control. Conclusion Rare PNNSTs, including extranodal manifestations of DLBCL can have similar clinical and radiological diagnostical features as PNSTs. Comprehensive diagnostic workup of contrast-enhancing lesions affecting peripheral nerves including MRI and metabolic imaging are recommended. Discussion in interdisciplinary tumor boards facilitates finding individual treatment approaches.
HBMIRT: A SAS macro for estimating uni- and multidimensional 1- and 2-parameter item response models in small (and large!) samples
2024-03-22

Abstract Item response theory (IRT) has evolved as a standard psychometric approach in recent years, in particular for test construction based on dichotomous (i.e., true/false) items. Unfortunately, large samples are typically needed for item refinement in unidimensional models and even more so in the multidimensional case. However, Bayesian IRT approaches with hierarchical priors have recently been shown to be promising for estimating even complex models in small samples. Still, it may be challenging for applied researchers to set up such IRT models in general purpose or specialized statistical computer programs. Therefore, we developed a user-friendly tool – a SAS macro called HBMIRT – that allows to estimate uni- and multidimensional IRT models with dichotomous items. We explain the capabilities and features of the macro and demonstrate the particular advantages of the implemented hierarchical priors in rather small samples over weakly informative priors and traditional maximum likelihood estimation with the help of a simulation study. The macro can also be used with the online version of SAS OnDemand for Academics that is freely accessible for academic researchers.
Influence of Intraoperative Active and Passive Breaks in Simulated Minimally Invasive Procedures on Surgeons’ Perceived Discomfort, Performance, and Workload
2024-03-22

Laparoscopic surgeons are at high risk of experiencing musculoskeletal discomfort, which is considered the result of long-lasting static and awkward body postures. We primarily aimed to evaluate whether passive and active work breaks can reduce ratings of perceived discomfort among laparoscopic surgeons compared with no work breaks. We secondarily aimed to examine potential differences in performance and workload across work break conditions and requested the surgeons evaluate working with passive or active work breaks. Following a balanced, randomized cross-over design, laparoscopic surgeons performed three 90 min laparoscopic simulations without and with 2.5 min passive or active work breaks after 30 min work blocks on separate days. The simulation included the following tasks: a hot wire, peg transfer, pick-and-place, pick-and-tighten, pick-and-thread, and pull-and-stick tasks. Ratings of perceived discomfort (CR10 Borg Scale), performance per subtask, and perceived workload (NASA-TLX) were recorded, and the break interventions were evaluated (self-developed questionnaire). Statistical analyses were performed on the rating of perceived discomfort and a selection of the performance outcomes. Twenty-one participants (9F) were included, with a mean age of 36.6 years (SD 9.7) and an average experience in laparoscopies of 8.5 years (SD 5.6). Ratings of perceived musculoskeletal discomfort slightly increased over time from a mean level of 0.1 to 0.9 but did not statistically significantly differ between conditions (p = 0.439). Performance outcomes of the hot wire and peg transfer tasks did not statistically significantly differ between conditions. The overall evaluation by the participants was slightly in favor regarding the duration and content of active breaks and showed a 65% likelihood of implementing them on their own initiative in ≥90 min-lasting laparoscopic surgeries, compared with passive breaks. Both passive and active breaks did not statistically significantly influence ratings of perceived discomfort or perceived workload in a 90 min simulation of laparoscopic surgery, with an overall low mean level of perceived discomfort of 0.9 (SD 1.4). As work breaks do not lead to performance losses, rest breaks should be tested in real-life situations across a complete working shift, where perceived discomfort may differ from this laboratory situation. However, in this respect, it is crucial to investigate the acceptance and practicality of intraoperative work breaks in feasibility studies in advance of assessing their effectiveness in follow-up longitudinal trials.
Abstract 4478: Development and characterization of kinase sparing TPX2-tethering Aurora kinase A ligands for cancer therapy
2024-03-22

Abstract A major limitation in the treatment of cancer is the limited therapeutic index of currently available chemotherapies or molecularly targeted therapies. Drug related toxicities often necessitate restricted drug dosing regimens, resulting in subtotal tumor remissions, which represent an important cause for tumor recurrences and the development of therapy resistance. Following up on previous work suggesting Aurora kinase A (AURKA) as a promising therapeutic target for the treatment of TP53 altered liver carcinomas (Dauch D. et al., Nat. Med., 2016) and TP53; RB1 altered small cell lung carcinomas (Gong X. et al., Cancer Discovery, 2019), we here report on the development and characterization of first in class kinase sparing AURKA ligands, which selectively kill TP53 deficient liver cancer cells and TP53; RB1 deficient small cell lung cancer cells by tethering AURKA to its binding partner TPX2 in mitotic cells. Small molecule mediated stabilization of AURKA/TPX2 complexes resulted in formation of multipolar spindles and subsequent cell death through mitotic catastrophe. Mechanistically, we were able to show that the hypersensitivity of TP53 deficient liver cancer cells and TP53; Rb1 deficient small cell lung cancer cells towards AURKA ligands is due to low expression levels of the antiapoptotic protein MCL1, which is necessary for survival of cancer cells in prolonged mitosis. Our novel AURKA ligands do not affect the kinase function of AURKA and thus, in contrast to conventional AURKA kinase inhibitors, can be administered continuously to mice without inducing toxicity related to inhibition of kinase related non-canonical (non-mitotic) functions of AURKA in normal cells or TP53 and RB1 wildtype cancer cells. Preclinical therapy studies in cell-line derived xenograft (CDX) tumor models of small cell lung cancer (SCLC) and orthotopic models of TP53 altered hepatocellular carcinoma and TP53;Rb1 altered SCLC demonstrated marked monotherapeutic efficacy of AURKA ligands. Conceptually, our herein provided data suggest that small molecules designed to stabilize protein-protein interactions represent powerful anti-cancer drugs with exceptional therapeutic window and thus open a venue towards the development of novel cancer therapies. Citation Format: Athina Anastasia Moschopoulou, Melanie Henning, Benedikt Wagner, Dirk Flötgen, Juliander Reiner, Yulia Skliarenko, Stefan Zwirner, Clemens Hinterleitner, Marco Seehawer, Luana dArtista, Elke Rist, Tatu Pantsar, Thales Kronenberger, Daniel Dauch, Corinna Gehring-Khav, Antti Poso, Liudmila Andreeva, Matthias Schwab, Michael Forster, Wolfgang Albrecht, Stefan Laufer, Lars Zender. Development and characterization of kinase sparing TPX2-tethering Aurora kinase A ligands for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4478.
Defining reference values of arterioles in healthy individuals for studies with adaptive optics imaging
2024-03-22

Purpose To investigate age-dependent wall to lumen ratio (WLR) reference values for healthy individuals in adaptive optics imaging (AO). WLR serves as an objective, dimensionless parameter for the evaluation of structural changes in vessels caused by conditions like arterial hypertension, diabetes or vascular stenosis. Methods 50 right eyes of healthy individuals were examined by adaptive optics imaging. The central big arterioles and smaller arterial branches at least one disc diameter away from the optic disc, approximately above or below the macula were measured by the manufacturer’s software. The wall-lumen-ratio (WLR), the wall cross-sectional area (WCSA) and lumen diameter (LD) were assessed. Subsequent data analysis was performed with a focus on variables including age, gender and blood pressure. Results Normative values for WLR, WCSA and LD in 5 different age groups could be established. However, no significant differences between the age groups were found. Intra-subject comparisons revealed significantly higher WLRs on peripheral branches when compared to central arterioles. WLR showed in this normotensive cohort no relevant correlation with the systolic, diastolic and mean blood pressure. Gender and intraocular pressure had no influence on the vascular parameters. Conclusion AO is capable of examining vascular alterations in arterioles at an almost microscopic level. Age did not seem to alter WLR, normotensive blood pressure parameters showed also no significant impact. AO-based vessel analysis may provide clinically useful biomarkers for cardiovascular health and should be tested in future studies.
Abstract 5530: Metastasis founder cells activate immunsuppression early in human metastatic colonization
2024-03-22

Abstract Metastatic dissemination occurs very early in melanoma, often before diagnosis, rendering prevention of metastasis formation an important therapeutic goal. However, the earliest steps of lethal metastasis in patients are incompletely understood. Therefore, in this study we searched for the earliest detectable disseminated cancer cells (DCC) in sentinel lymph node biopsies of 492 stage I-III melanoma patients. We used micromanipulator-assisted isolation and single-cell transcriptome analysis of these extremely rare DCC and identified melanoma -associated chondroitin sulfate proteoglycan (MCSP) expressing melanoma cells as strong candidates for metastasis founder cells in lymph nodes. Based on a median follow-up time of 6 years, their detection was the strongest predictor of systemic metastasis and death upon multivariable analysis. Single-cell transcriptome analysis revealed that melanoma DCC were exposed to CD8 T cell attack during the transition from single cells to metastasis-initiating clusters, activated the extracellular vesicular exosomal pathway, and expressed the immunomodulatory proteins CD155 and CD276, but rarely PD-L1. CD155- and CD276-positive extracellular vesicles from patient-derived DCC models showed an immunosuppressive activity on CD8 T cells. In conclusion, our data suggest that either direct targeting of metastasis-founder cell with MCSP or their immune escape mechanisms may be key to curing early-stage melanoma. Citation Format: Severin Guetter, Courtney Koenig, Huiqin Koerkel-Qu, Aleksandra Markiewicz, Sebastian Scheitler, Marie Katzer, Mark Berneburg, Philipp Renner, Beatrix Cucuruz, Leonhard Guttenberger, Veronika Naimer, Kathrin Weidele, Steffi Treitschke, Christian Werno, Hanna Jaser, Tonia Bargmann, Armin Braun, Florian Weber, Katharina Limm, Reinhard Rachel, Felix Baumann, Lisa Schmidleithner, Kathrin Schambeck, Anja Ulmer, Sebastian Haferkamp, Christoph Klein, Melanie Werner-Klein. Metastasis founder cells activate immunsuppression early in human metastatic colonization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5530.
KIF13B controls ciliary protein content by promoting endocytic retrieval and suppressing release of large extracellular vesicles from cilia
2024-03-22

Summary Dynamic control of ciliary membrane protein content is crucial for the organelle’s homeostasis and signaling function and involves removal of ciliary components by BBSome-mediated export, endocytic retrieval and/or extracellular vesicle (EV) shedding. We report that KIF13B regulates ciliary protein composition and EV shedding in cultured kidney epithelial cells, with effects that vary over time. In early stages of ciliation Kif13b -/- cells aberrantly accumulate PC2, FLOT1, and HGS within cilia. These cells also produce fewer small EVs through the GW4869-sensitive, nSMase2 pathway, and release large EVs enriched with CCDC198 and the centriole distal appendage protein CCDC92, which also localizes to the ciliary tip. Upon cilia maturation, Kif13b -/- cells accelerate large EV release of numerous ciliary proteins, including PC2, BBSome components, and IFT proteins, which correlates with gradual depletion of CCDC92 and PC2 from the ciliary tip and shaft, respectively. Furthermore, over time, Kif13b -/- cells show an upregulation in the release of small EVs, which differ in composition from wild-type small EVs. Specifically, the mutant small EVs lack several proteins that are enriched in small EVs from BBSome-deficient cells, such as the palmitoyl transferase ZDHHC5, which localizes to cilia, accumulates within cilia of BBSome-deficient cells, and regulates ciliary length and PC2 levels. Collectively, our work suggests that KIF13B acts at the level of centriole distal appendages to limit ciliary protein entrance and promote endocytic retrieval downstream of the BBSome. Furthermore, this study shows for the first time that CCDC198 and ZDHHC5 localize to primary cilia, suggesting they are potential novel ciliopathy candidates.
Fully automated contrast selection of joint bright- and black-blood late gadolinium enhancement imaging for robust myocardial scar assessment
2024-03-23

The proposed fully-automated algorithm has potential of reducing uncertainties, variability, and workload inherent to manual approaches with promise for future clinical implementation for joint bright- and black-blood MRI.
White adipose tissue distribution and amount are associated with increased white matter connectivity
2024-03-23

Abstract Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole‐body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal‐weight, overweight, and obese males. WM connectivity was quantified using microstructure‐informed tractography. Connectome‐based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.
The clinical evaluation of a widefield lens to expand the field of view in optical coherence tomography (OCT-A)
2024-03-23

Abstract This study aimed to evaluate the clinical benefits of incorporating a widefield lens (WFL) in optical coherence tomography angiography (OCT-A) in patients with retinal vascular diseases in comparison to standard single-shot OCT-A scans. Sixty patients with retinal vascular diseases including diabetic retinopathy (DR) and retinal vein occlusion (RVO) were recruited. OCT-A imaging (PlexElite 9000) with and without WFL was performed in randomized order. The assessment included patient comfort, time, field of view (FoV), image quality and pathology detection. Statistical analysis included paired t -tests, Mann–Whitney U -tests and Bonferroni correction for multiple tests, with inter-grader agreement using the kappa coefficient. Using a WFL did not lead to statistically significant differences in DR and RVO group test times. Patient comfort remained high, with similar responses for WFL and non-WFL measurements. The WFL notably expanded the scan field (1.6× FoV increase), enhancing peripheral retinal visibility. However, image quality varied due to pathology and eye dominance, affecting the detection of peripheral issues in RVO and DR cases. The use of a WFL widens the scan field, aiding vascular retinal disease imaging with minor effects on comfort, time, and image quality. Further enhancements are needed for broader view angles, enabling improved quantification of non-perfused areas and more reliable peripheral proliferation detection.
Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses
2024-03-23

Abstract Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.
Validation of the Self-Report Version of the German Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Scale (SWAN-DE-SB)
2024-03-24

Adults with attention-deficit/hyperactivity disorder (ADHD) experience impairing levels of inattention and/or hyperactivity-impulsivity, while individuals without ADHD experience these symptoms to a lesser extent. Yet, ADHD self-report scales so far hardly captured continuous distributions across the general population. In addition, they focused on weaknesses and ignored strengths. To address these shortcomings, we present here the Strengths and Weaknesses of ADHD and Normal-Behavior Scale Self-Report (SWAN-DE-SB). The normal distribution of the data collected and the scale’s internal consistency, and factorial and convergent validity were assessed using data from a general population sample. Its clinical utility was evaluated by comparing scores from a clinical sample and a sample of individuals without ADHD and by calculating optimal cut-off values for specificity and sensitivity. The SWAN-DE-SB demonstrated normal distribution of the data collected, high internal consistency, and factorial and convergent validity. It reliably discriminated individuals with and without ADHD, with high specificity and sensitivity. It should therefore be considered a psychometrically convincing measure to assess strengths and weaknesses of ADHD symptoms and normal behavior in clinical and general population samples.
Colored Noise in PPO: Improved Exploration and Performance through Correlated Action Sampling
2024-03-24

Proximal Policy Optimization (PPO), a popular on-policy deep reinforcement learning method, employs a stochastic policy for exploration. In this paper, we propose a colored noise-based stochastic policy variant of PPO. Previous research highlighted the importance of temporal correlation in action noise for effective exploration in off-policy reinforcement learning. Building on this, we investigate whether correlated noise can also enhance exploration in on-policy methods like PPO. We discovered that correlated noise for action selection improves learning performance and outperforms the currently popular uncorrelated white noise approach in on-policy methods. Unlike off-policy learning, where pink noise was found to be highly effective, we found that a colored noise, intermediate between white and pink, performed best for on-policy learning in PPO. We examined the impact of varying the amount of data collected for each update by modifying the number of parallel simulation environments for data collection and observed that with a larger number of parallel environments, more strongly correlated noise is beneficial. Due to the significant impact and ease of implementation, we recommend switching to correlated noise as the default noise source in PPO.