NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated liposarcomas.

The () gene family is of rising importance as their fusions are oncogenic, and specific target drugs are available to inhibit the chimera proteins. Pan-TRK antibody, which shows the overexpression of the genes, is a useful tool to detect tumors with or without gene alterations, due to high negative predictive value. Though it is well known that pan-TRK immunopositivity is usually not connected to fusion, the role of other possible genetic alterations is under-researched.

Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron.

Serial macromolecular crystallography has become a powerful method to reveal room temperature structures of biological macromolecules and perform time-resolved studies. ID29, a flagship beamline of the ESRF 4th generation synchrotron, is the first synchrotron beamline in the world capable of delivering high brilliance microsecond X-ray pulses at high repetition rate for the structure determination of biological macromolecules at room temperature. The cardinal combination of microsecond exposure times, innovative beam characteristics and adaptable sample environment provides high quality complete data, even from an exceptionally small amount of crystalline material, enabling what we collectively term serial microsecond crystallography (SµX).

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

Background: Ragweed () has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest.

Objective: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen.

Pediatric thyroid-like follicular renal cell carcinoma-a post-neuroblastoma case with comprehensive genomic profiling data.

Thyroid-like follicular renal cell carcinoma (TLFRCC), an emerging subtype of renal cell carcinoma, presents diagnostic challenges due to its resemblance to normal thyroid tissue. Here, we report a rare case of TLFRCC in a pediatric patient, a demographic rarely affected by this subtype. Histologically resembling a typical TLFRCC, our case exhibited unique features including post-neuroblastoma development, occurrence in a male teenager, and diffuse MelanA expression, which has not been previously reported in TLFRCC.

Spirituality is associated with immune parameters and disease activity in primary Sjögren's syndrome: a cross-sectional study.

The role of spirituality in health and disease is a complex and emerging area of research. Incorporating spirituality into the bio-psycho-social model of health and disease leading to the bio-psycho-social-spiritual model provides a more comprehensive framework. In this context, chronic disorders like primary Sjögren's syndrome (pSS) are of interest due to their intricate interactions between biological, psychological, and spiritual factors.

Diagnosis of Melanoma with Cu-Labeled PET Tracer.

Until the recent years, substances containing radioactive Cu were strongly considered as potential positron-emitting radiopharmaceuticals for use in positron emission tomography (PET) applications; however, due to their suitably long half-life, and generator-independent and cost-effective production, they seem to be economically viable for human imaging. Since malignant melanoma (MM) is a major public health problem, its early diagnosis is a crucial contributor to long-term survival, which can be achieved using radiolabeled α-melanocyte-stimulating hormone analog NAPamide derivatives. Here, we report on the physicochemical features of a new CB-15aneN-based Cu(II) complex ([Cu(KFTGdiac)]) and the and characterization of its NAPamide conjugate.

Antiphospholipid Antibodies Are Major Risk Factors for Non-Thrombotic Cardiac Complications in Systemic Lupus Erythematosus.

In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients.

A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas.

Introduction: Dedifferentiated liposarcoma (DDLPS) is a common form of liposarcoma with challenging treatment modalities. Pan-TRK immunopositivity can be often observed without NTRK gene fusion in soft tissue sarcomas with myogenic differentiation. Expression and the role of NTRK in DDLPS are under-studied.

mTOR hyperactivity and amplification as targets for personalized treatments in malignancies.

The increasing knowledge of molecular alterations in malignancies, including mutations and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway, highlights the importance of mTOR hyperactivity as a validated target in common and rare malignancies. This review summarises recent findings on the characterization and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity. We have recently identified new tumor types with (rapamycin-insensitive companion of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets for developing targeted therapies in lung cancer and other newly described malignancies.

Mode combinability: Exploring convex combinations of permutation aligned models.

We explore element-wise convex combinations of two permutation-aligned neural network parameter vectors Θ and Θ of size d. We conduct extensive experiments by examining various distributions of such model combinations parametrized by elements of the hypercube [0,1] and its vicinity. Our findings reveal that broad regions of the hypercube form surfaces of low loss values, indicating that the notion of linear mode connectivity extends to a more general phenomenon which we call mode combinability.

Design of the shattered pellet injection system for ASDEX Upgrade.

A new shattered pellet injection system was designed and built to perform disruption mitigation experiments on ASDEX Upgrade. The system can inject pellets with diameters of 1, 2, 4, or 8 mm with variable lengths over a range of L/D ratios of ∼0.5-1.

Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.

Alterations in mTOR signalling molecules, including RICTOR amplification, have been previously described in many cancers, particularly associated with poor prognosis. In this study, RICTOR copy number variation (CNV) results of diagnostic next-generation sequencing (NGS) were analysed in 420 various human malignant tissues. RICTOR amplification was tested by Droplet Digital PCR (ddPCR) and validated using the "gold standard" fluorescence in situ hybridisation (FISH).

Exploration of differentiability in a proton computed tomography simulation framework.

Gradient-based optimization using algorithmic derivatives can be a useful technique to improve engineering designs with respect to a computer-implemented objective function. Likewise, uncertainty quantification through computer simulations can be carried out by means of derivatives of the computer simulation. However, the effectiveness of these techniques depends on how 'well-linearizable' the software is.

Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas.

Glioblastomas are the most common IDH-wildtype adult high-grade gliomas, frequently harboring mutations in the TERT gene promoter (pTERT) and utilizing the subsequent telomerase overexpression for telomere length maintenance. However, some rare cases show loss of ATRX and use alternative mechanisms of telomere lengthening. In this study, we performed the first complex genomic analysis specifically concentrating on the latter subgroup.

[he importance of mTOR hyperactivity and RICTOR amplification, and the associated targeted therapy possibilities in malignant tumours].

Failures of anti-tumour therapies and drug resistance initiate difficulties in cancer treatments often caused by alterations in signalling network activity, including PI3K/Akt/mTOR hyperactivity due to oncogenic mutations. In this review, we summarise the relevance of mTOR (mechanistic target of rapamycin) dysregulation identified decades ago, which is now known to be characteristic of many tumours. In this context, we present differences in activity, function and testability of mTOR kinase complexes (mTORC1 and mTORC2) differing in structure, regulatory mechanisms and inhibitor sensitivity.

Uncertainty-aware spot rejection rate as quality metric for proton therapy using a digital tracking calorimeter.

Proton therapy is highly sensitive to range uncertainties due to the nature of the dose deposition of charged particles. To ensure treatment quality, range verification methods can be used to verify that the individual spots in a pencil beam scanning treatment fraction match the treatment plan. This study introduces a novel metric for proton therapy quality control based on uncertainties in range verification of individual spots.

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004.

[Left ventricular deformation: similarities and dissimilarities in elite sport activity- and acromegaly-related abnormalities. Results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Sport and MAGYAR-Path Studies].

Introduction: Acromegaly is a chronic endocrine disorder, which produces a significant amount of human growth hormone and consequently insulin-like growth factor in adulthood due to a tumor in the pituitary gland. If left untreated, it can have a significant effect on the cardiovascular system. It is also known that elite sport activity is also associated with physiologic cardiac transformation, the so-called athletes' heart, in which volumetric and functional adaptation of the heart cavities can be observed.

BioSAXS at European Synchrotron Radiation Facility - Extremely Brilliant Source: BM29 with an upgraded source, detector, robot, sample environment, data collection and analysis software.

As part of its Extremely Brilliant Source (EBS) upgrade project, the ESRF's BM29 BioSAXS beamline was subject to a significant upgrade and refurbishment. In addition to the replacement of the beamline's original bending magnet source by a two-pole wiggler, leading to an increase in brilliance by a factor of 60, the sample environment of the beamline was almost completely refurbished: a vacuum-compatible Pilatus3 X 2M with a sensitive area of 253.7 mm × 288 mm and frame rates up to 250 Hz was installed, increasing the active area available and thus the q-scaling of scattering images taken; the sample changer was replaced with an upgraded version, allowing more space for customizable sample environments and the installation of two new sample exposure units; the software associated with the beamline was also renewed.