julilili42/papers huggingface dataset:
PL02.3.A MOLECULAR CLASSIFICATION TO REFINE SURGICAL AND RADIOTHERAPEUTIC DECISION MAKING IN MENINGIOMA
2024-10-01

Abstract BACKGROUND Treatment of the tumor and dural margin, most commonly with surgery and sometimes radiation, are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease. However, response to treatment remains heterogeneous. We compiled and generated clinical data on 2824 total meningiomas with molecular data on 1686 retrospective tumors and 100 prospective tumors from the RTOG-0539 phase-II clinical trial (NCT00895622) to define biomarkers of treatment response across molecular classifications. MATERIAL AND METHODS Data were collected from 10 different institutions. Meningiomas were re-graded in accordance with 2021 WHO classification based on the presence of CDKN2A/B deletion and TERT promoter mutation and stratified to Molecular Groups based on previously published methodologies utilizing DNA methylation alone or combined with RNA sequencing. Only molecularly-defined meningiomas based on the DKFZ central nervous system classifier were included in molecular classification and analysis. Propensity score matching (PSM) was used to mimic a randomized control trial for comparison of treatment arms (GTR vs STR, Simpson Grade 1/2 vs 3, Simpson Grade 1 vs 2, RT vs Observation). RESULTS Gross tumor resection (GTR) was associated with significantly longer progression-free-survival (PFS) across all Molecular Groups, and longer overall survival (OS) in Proliferative meningiomas (STR vs GTR HR 1.90, 95%CI 1.28-2.82, p=0.00155). Following PSM of key covariates including WHO grade, tumor location, and Molecular Group, the addition of dural margin treatment (Simpson grade 1 or 2) prolonged PFS compared to GTR alone (Simpson grade 3; HR 1.64, 95%CI 1.03-2.62, p=0.038). These results were reproduced when other molecular classifications and prognostic systems were utilized in PSM as well. When considering the effect of adjuvant radiotherapy (RT) following PSM, Immunogenic, NF2-wt, and Hypermetabolic meningiomas obtained a PFS benefit from the addition of RT but Proliferative meningiomas were RT-resistant. These findings were validated in meningiomas from the RTOG-0539 trial. To obtain an individualized prediction of RT-responsiveness, we leveraged RT-treated meningiomas from the RTOG-0539 trial (intermediate- and high-risk treatment arms in the trial) to build a DNA methylation and gene-expression model that was able to predict response to RT better than standard of care clinical covariates including WHO grade (AUC 0.81, 95%CI 0.72-0.90 vs 0.67, 95%CI 0.57-0.77) in an independent validation cohort of RT-treated meningiomas. CONCLUSION This study highlights the potential for molecular profiling and classification to meaningfully refine surgical and RT decision-making and supports the design of future molecularly-informed clinical trials.
JS08.5.A AMINO-ACID PET VERSUS MRI GUIDED RE-IRRADIATION IN PATIENTS WITH RECURRENT GLIOBLASTOMA - GLIAA TRIAL (NOA 10/ARO 2013-1, DKTK-A)
2024-10-01

Abstract BACKGROUND This trial aimed to investigate whether re-irradiation based on (O-(2-Fluoroethyl)-L-tyrosine, FET)-positron emission tomography (PET) leads to an improvement in progression-free survival (PFS) in patients with recurrent glioblastoma (rGBM), compared to a target volume delineation based on contrast-enhanced T1-weighted MRI (T1Gd-MRI). MATERIAL AND METHODS GLIAA was a prospective, multicenter, randomized clinical trial (NOA 10/ARO 2013-1, DKTK-a., NCT01252459). Patients with rGBM of 1-6 cm were randomized 1:1 at 14 centers in Germany between a FET-PET- and a T1Gd-MRI-based target volume delineation. The RT was performed with 3 Gy/d, 5x/week, to a total dose of 39 Gy. All patients had been previously irradiated with 59.4-60Gy at least 6 months before study treatment and had a histologically confirmed rGBM with a diameter of 1 - 6 cm on both FET-PET and T1Gd-MRI. The primary end point was PFS. Secondary end points included overall survival (OS), locally controlled survival, assessment of delineated volumes, topography of progression, rate of radiation necrosis after re-irradiation, and safety of FET-application in PET imaging. RESULTS Between November 2013 and September 2021, 200 patients were randomized between FET-PET-based (n=100) and GdT1-MRI-based (n=100) target volume delineation. A total of n=98 and n=97 patients, respectively, were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39;). Median OS was 9.4 months (95% CI 7.8-11.1) in the FET-PET arm and 9.0 months (95% CI 7.6-10.5) in the GdT1-MRI arm (HR 1.01 [95% CI 0.75-1.37], p=0.92). Median LCS was 6.3 months (95% CI 5.1-7.2) in the FET-PET arm and 6.8 months (95% CI 6.2-7.3) in the GdT1-MRI arm (HR 1.20 [95% CI 0.88-1.62], p=0.25). At 12 months, the local control rate was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). In the PET arm, 45.0% of recurrences were in field, 28.3% out of field, and 21.7% marginal. In the MRI arm, 47.4% relapsed in field, 31.6% out of field, and 14.0% marginal. 25.5% of patients in the FET-PET arm and 21.6% in the GdT1-MRI arm had a documented radiation necrosis. There were no adverse events related to the application of the FET tracer. CONCLUSION This is the first randomized trial to investigate the relevance of FET-PET in the irradiation treatment planning of rGBM. There was no survival benefit identified for patients treated with FET-PET- versus GdT1-MRI-based re-irradiation. Both imaging modalities led to similar outcomes and can be therefore used for radiation treatment planning for rGBM. The FET-PET investigation and the re-irradiation were well-tolerated, supporting the safety of this treatment.
Minimally Invasive Pelvic and Acetabular Surgery: Case Report of a Robot‐Assisted Osteosynthesis of an Open‐Book Injury of the Pelvic Ring
2024-10-01

ABSTRACT Background In recent years, endoscopic treatment of pelvic ring injuries has emerged. In addition to the complex 3D anatomy of the bony pelvis, a particular challenge is its embedding in the surrounding soft tissue structures. It is known from other surgical specialties that the preparation can be facilitated by using surgical robot systems. Materials and Methods In a patient with an open‐book injury of the pelvic ring, a symphysis plate was performed using the DaVinci system. Results We describe the robotic‐assisted osteosynthesis on the anterior pelvic ring with available instruments. Conclusion The further development of minimally invasive surgical techniques is always linked to the development of new instruments. For trauma surgery, this means in particular the reduction of dislocated fractures. If appropriate techniques and instruments are developed here, minimally invasive treatment of injuries to the pelvic ring or acetabulum may represent an alternative to open procedures in the future.
Dioramic landscapes and the multi-temporality of places: The phantasmagorical writing of Pompeii in Théophile Gautier’s ‘Arria Marcella’ (1852) and ‘Jettatura’ (1856)1
2024-10-01

This article highlights the possible influence of pre-cinematographic spectacles from the first half of the nineteenth century on the writing of Pompeii in two fantastique short stories by Théophile Gautier: ‘Arria Marcella’, published in 1852, and ‘Jettatura’, published in 1856. In a similar style to the dioramas of Louis Daguerre (1787–1851) and the phantasmagorias of Étienne-Gaspard Robertson (1763–1837), the movements of light resuscitate the dead city and its inhabitants. The description of Pompeii could evoke the pre-cinematographic technique of dissolving views, in which the images are projected one on top of the other. The intensity of one image gradually diminishes until it disappears completely, thereby creating the opportunity for the subsequent image to emerge with greater intensity. These dissolving views of Pompeii disrupt the spatio-temporal framework of the story because they allow us to move from one time to another. Ancient Pompeii and its buried beliefs emerge in the present, contributing to the narrative’s shift towards the fantastique , as a hitherto invisible world – superimposed on the visible world – makes itself increasingly felt and becomes spectrally visible.
The art of seeing the elephant in the room: 2D embeddings of single-cell data do make sense
2024-10-02

A recent paper claimed that t -SNE and UMAP embeddings of single-cell datasets are “specious” and fail to capture true biological structure. The authors argued that such embeddings are as arbitrary and as misleading as forcing the data into an elephant shape. Here we show that this conclusion was based on inadequate and limited metrics of embedding quality. More appropriate metrics quantifying neighborhood and class preservation reveal the elephant in the room: while t -SNE and UMAP embeddings of single-cell data do not preserve high-dimensional distances, they can nevertheless provide biologically relevant information.
Topological photon pumping in quantum optical systems
2024-10-02

We establish the concept of topological pumping in one-dimensional systems with long-range couplings and apply it to the transport of a photon in quantum optical systems. In our theoretical investigation, we introduce an extended version of the Rice-Mele model with all-to-all couplings. By analyzing its properties, we identify the general conditions for topological pumping and theoretically and numerically demonstrate topologically protected and dispersionless transport of a photon on a one-dimensional emitter chain. As concrete examples, we investigate three different popular quantum optics platforms, namely Ryd-berg atom lattices, dense lattices of atoms excited to low-lying electronic states, and atoms coupled to waveguides, using experimentally relevant parameters. We observe that despite the long-ranged character of the dipole-dipole interactions, topological pumping facilitates the transport of a photon with a fidelity per cycle which can reach 99.9%. Moreover, we find that the photon pumping process remains topologically protected against local disorder in the coupling parameters.
Evaluation of Retinal Structure and Visual Function in Blue Cone Monochromacy to Develop Clinical Endpoints for L-opsin Gene Therapy
2024-10-02

L-cone opsin expression by gene therapy is a promising treatment for blue cone monochromacy (BCM) caused by congenital lack of long- and middle-wavelength-sensitive (L/M) cone function. Eight patients with BCM and confirmed pathogenic variants at the OPN1LW/OPN1MW gene cluster participated. Optical coherence tomography (OCT), chromatic perimetry, chromatic microperimetry, chromatic visual acuity (VA), and chromaticity thresholds were performed with unmodified commercial equipment and/or methods available in the public domain. Adaptive optics scanning laser ophthalmoscope (AOSLO) imaging was performed in a subset of patients. Outer retinal changes were detectable by OCT with an age-related effect on the foveal disease stage. Rod and short-wavelength-sensitive (S) cone functions were relatively retained by perimetry, although likely impacted by age-related increases in the pre-retinal absorption of short-wavelength lights. The central macula showed a large loss of red sensitivity on dark-adapted microperimetry. Chromatic VAs with high-contrast red gratings on a blue background were not detectable. Color vision was severely deficient. AOSLO imaging showed reduced total cone density with majority of the population being non-waveguiding. This study developed and evaluated specialized outcomes that will be needed for the determination of efficacy and safety in human clinical trials. Dark-adapted microperimetry with a red stimulus sampling the central macula would be a key endpoint to evaluate the light sensitivity improvements. VA changes specific to L-opsin can be measured with red gratings on a bright blue background and should also be considered as outcome measures in future interventional trials.
CE-MS and CE-MS/MS for the multiattribute analysis of monoclonal antibody variants at the subunit level
2024-10-02

The analysis of product-related substances and impurities is a critical step in the biopharmaceutical quality control of multiattribute monoclonal antibodies (mAbs), as posttranslational modifications or other variants can influence the product's biological activity. Many approaches are available for variant analysis; however, they are either variant-specific, mAb-specific, time-consuming, or require expensive equipment. Here, we present a generic capillary electrophoretic method based on a neutral-coated capillary which was coupled to mass spectrometry (MS) via the nanoCEasy interface for mAb variant analysis at the subunit level (enzymatically digested and reduced mAb). The method enabled the separation of several (i) size variants (e.g. glycosylation variants) and (ii) charge variants (e.g. c-terminal lysin clipping) as well as (iii) multiple other proteoforms (e.g. additional glycation) and (iv) incompletely reduced subunits. Separated variants were confirmed by MS/MS fragmentation even for small mass deviations like deamidation or open disulfide bridges. The system, initially developed for one mAb, was tested with nine other IgG1s to show the general applicability of the system. The presented multiattribute method enables fast and detailed characterization of mAb variants with little sample preparation and relatively simple separation equipment enabling the separation of a large set of mAb variants.
Ultrafast and Highly Collimated Radially Polarized Photons at Room Temperature from a Colloidal Quantum Dot Coupled to a Hybrid Nanoantenna
2024-10-02

To harness the potential of radially polarized photons for classical and quantum communication applications, we demonstrate an on-chip, room-temperature device, which generates highly directional radially polarized photons at very high rates. The photons are emitted from a giant CdSe/CdS colloidal quantum dot (gQD) accurately positioned at the tip of a metal nanocone centered inside a hybrid metal-dielectric bullseye antenna. We show that due to the large and selective Purcell enhancement specifically for the out-of-plane optical dipole of the gQD, the emitted photons can have a very high degree of radial polarization (&gt;93%), based on a quantitative metric. Our study emphasizes the importance of accurate gQD positioning for optimal radial polarization purity through extensive experiments and simulations, which contribute to the fundamental understanding of radial polarization in nanostructured devices and pave the way for implementation of such systems in practical applications using structured quantum light.
EZB ‐type diffuse large B‐cell lymphoma cell lines have superior migration capabilities compared to MCD ‐type
2024-10-02

Summary Diffuse large B‐cell lymphoma (DLBCL) represents the most prevalent aggressive B‐cell lymphoma. The group is heterogeneous and the outcome is variable. A variety of approaches have been employed with the objective of improving the stratification of DLBCL patients according to their prognosis, based on the cell of origin. Recently, distinct genetic subtypes of DLBCL have been identified. Given the importance of cell migration in immune cells, the objective of this study was to ascertain whether different genetic subtypes of DLBCL exhibit disparate migration abilities. MCD‐ and EZB‐type DLBCL cell lines were subjected to testing to ascertain their basal velocity in straight microchannels and their ability to overcome tight constrictions of 2 μm. The EZB‐type cell lines showed superior basal migration velocity and constriction passage time, and a similar trend was observed in live cell imaging of native human DLBCL tissue. In addition, MCD‐type DLBCL exhibited significantly elevated levels of nuclear lamin A/C, which is responsible for the stiffness of the nuclear envelope and could thus explain the disparate migration behaviours observed among these subtypes. Our study suggests that different genetic subtypes of DLBCL may not only influence the outcome after therapy but also the motility of the tumour cells.
Strong pairwise interactions do not drive interactions in a plant leaf associated microbial community
2024-10-02

Abstract Microbial communities that promote plant growth show promise in reducing the impacts of climate change on plant health and productivity. Understanding microbe–microbe interactions in a community context is paramount for designing effective microbial consortia that enhance plant resilience. In this study, we investigated the dynamics of a synthetic microbial community (SynCom) assembled from Arabidopsis thaliana leaves to elucidate factors shaping community composition and stability. We found notable disparities between in vitro pairwise interactions and those inferred from correlation networks in planta. Our findings suggested that secondary metabolites, particularly antimicrobials, might mediate interactions in vitro, but are not key drivers of microbial interactions in a community context. Through co-cultivation experiments, we identified the siderophore pseudobactin as a potent antimicrobial agent against several SynCom members, but its impact on community composition in planta was negligible. Notably, dominant SynCom members, such as Pseudomonas koreensis, Flavobacterium pectinovorum, and Sporobolomyces roseus, exhibited only positive correlations, suggesting synergism based on factors such as exopolysaccharides and biotransformation might drive community dynamics rather than competition. Two correlations between SynCom members in the co-abundance network corresponded to their pairwise in vitro interactions, highlighting the potential for further research and demonstrating the usefulness of correlation networks in identifying key microbe–microbe interactions. Our findings highlight the importance of considering microbiome–wide interaction studies and synthetic communities in understanding and manipulating plant microbiomes.
Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15)
2024-10-03

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking. Methods: We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM. Results: Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects. Conclusions: Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition.
Examining football players' perceived social support across organizational levels and its links to holistic talent development outcomes in German youth academies
2024-10-03

Sport research highlights the significance of supportive relationships and a psychologically safe environment for promoting desirable talent development outcomes associated with young athletes' performance, wellbeing, and personal development. Against this background, this study aimed to investigate youth football players' perceived availability of different kinds of social support from various stakeholders along the talent pathway in German elite youth academies (1). It further sought to examine the link of such social support perceptions to wellbeing, sport commitment and individual performance satisfaction as relevant development outcomes (2). Finally, the study examined potential mechanism underlying these associations by considering psychological safety as a potential mediator (3). For this purpose, N = 271 youth academy players participating in teams of under-13s, under-15s, and under-17/19s age groups completed a multi-section online survey including the PASS-Q, PsySafety-Check, and WHO-5 as well as subscales of the ASQ (i.e., individual performance satisfaction) and YSCS (i.e., sport commitment). Multivariate analyses indicated significant differences in players' perceptions of social support depending on its kind and provider as well as on players' age group. Further, path models highlighted the importance of emotional and esteem support provided by coaches and management for players' talent development outcomes. However, psychological safety seemed to only play a minor role within those associations, partially mediating the effects of emotional support. Overall, these findings encourage a critical reflection of youth players' social support needs and opportunities to optimally address those within elite youth academies as prominent talent development environments in football.
Risk profiles for self-medication with analgesics among elite German handball players
2024-10-03

This study presents empirical evidence on self-medication with analgesics among elite German handball players. The aim is to elucidate the intentions behind therapeutic and preventive analgesic use and identify high-risk profiles for this complex health-risk behavior based on psychosocial factors. Data were collected from 459 handball players (233 female, 226 male athletes) across the highest German divisions (1 st – 3 rd and German Youth Handball Bundesliga) through a quantitative online survey conducted between October 2021 and April 2022. The survey requested demographic information and details on analgesic use patterns, intentions behind analgesic use, and psychosocial variables. The study shows that athletes use self-medication with painkillers as a coping strategy to manage distractions from acute injuries and pain as well as to prevent expected distractions. Engaging in self-medication allows athletes to navigate the pressures of elite sport. Classification tree analysis revealed distinct risk profiles for therapeutic and preventive analgesic use. Key factors of self-medication include age, athletic identity, willingness to compete hurt, and perceived performance state. The high-risk group for therapeutic self-medication with analgesics consists of senior athletes. The high-risk group for using analgesics preventively, in contrast, is composed of athletes over the age of 17 with strong negative affectivity, a heightened willingness to take risks, and good perceived performance. Our findings highlight the necessity for specific interventions to address the multifaceted motivations behind self-medication and promote safer practices in elite sports. Future research should concentrate on longitudinal studies and diverse athlete populations and use qualitative studies to gain a deeper understanding of the determinants of analgesic use and to develop effective intervention strategies.