The phase-3 INDIGO trial demonstrated that the isocitrate dehydrogenase () inhibitor vorasidenib significantly prolonged progression-free survival and delayed intervention in patients with CNS WHO grade 2 gliomas. However, conventional MRI showed limited response, with only 11% of patients having objective responses. Studies suggest that serial PET imaging with radiolabeled amino acids, such as -(2-[ F]-fluoroethyl)-L-tyrosine (FET) PET, may provide earlier and more informative assessments of treatment response than MRI.
View Article and Find Full Text PDFDespite all debates about its safe use, glyphosate remains the most widely applied active ingredient in herbicide products, with renewed approval in the European Union until 2033. Non-target organisms are commonly exposed to glyphosate as a matter of its mode of application, with its broader environmental and biological impacts remaining under investigation. Glyphosate displays structural similarity to phosphoenolpyruvate (PEP), thereby competitively inhibiting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), crucial for the synthesis of aromatic amino acids in plants, fungi, bacteria, and archaea.
View Article and Find Full Text PDFBackground: The Patient Health Questionnaire (PHQ-9) is a popular tool for assessing depressive symptoms in both general and clinical populations. The present study used a large representative sample of the German adult population to confirm desired psychometric functioning and to provide updated population norms.
Methods: The following psychometric properties were assessed: (i) Item characteristics (item means, standard deviations and inter-item correlations), (ii) Construct validity (correlations of the PHQ-9 sum-score with scores obtained from instruments assessing depression, anxiety and somatization (GAD-7, BSI-18), (iii) Internal consistency (coefficient omega), (iv) Factorial validity (via confirmatory factor analysis of the assumed one factorial model) as well as (v) Measurement invariance (via multi-group confirmatory factor analyses across gender, age, income and education).
Interpretability and reliability of deep learning models are important for computer-based drug discovery. Aiming to understand feature perception by such a model, we investigate a graph neural network for affinity prediction of protein-ligand complexes. We assess a latent representation of ligand binding sites and investigate underlying geometric structure in this latent space and its relation to protein function.
View Article and Find Full Text PDFDystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%) and the identification of several disease-linked genes, the etiology in most patients remains elusive. Moreover, understanding the correlations between clinical manifestation and genetic variants has become increasingly complex.
View Article and Find Full Text PDFBackground: Dysfunction of the skin barrier is regarded as a key event in the initiation and progression of inflammatory skin diseases. In many cases of allergic contact dermatitis (ACD), epidermal-resident memory CD8 T (T) cells play a central role in the immune response to contact allergens. However, if and how allergen-specific CD8 T cells affect the expression of skin barrier molecules is not known.
View Article and Find Full Text PDFDiaphragmatic dysfunction is an important contributor to hypercapnic respiratory failure, but its presence is often challenging to determine at the bedside. Diaphragm ultrasound provides an opportunity to evaluate the function of the diaphragm noninvasively by evaluating the following parameters that can help define diaphragmatic dysfunction: diaphragm excursion, diaphragm muscle thickness, and thickening fraction. Its evaluation has the potential to assist with diagnosis of respiratory failure, provide prognosis, and assist with patient monitoring and should be considered as part of an internal medicine physician's and emergency physician's skill set.
View Article and Find Full Text PDFThe assessment of individual students is not only crucial in the school setting but also at the core of educational research. Although classical test theory focuses on maximizing insights from student responses, the Bayesian perspective incorporates the assessor's prior belief, thereby enriching assessment with knowledge gained from previous interactions with the student or with similar students. We propose and illustrate a formal Bayesian approach that not only allows to form a stronger belief about a student's competency but also offers a more accurate assessment than classical test theory.
View Article and Find Full Text PDFHuman population dynamics and their drivers are not well understood, especially over the long term and on large scales. Here, we estimate demographic growth trajectories from 9 to 3 ka BP across the entire globe by employing summed probability distributions of radiocarbon dates. Our reconstruction reveals multicentennial growth cycles on all six inhabited continents, which exhibited matching dominant frequencies and phase relations.
View Article and Find Full Text PDFPost-procedure infections following in-office blepharoplasty are rare. is a weakly acid-fast, gram-positive, aerobic Actinomyces that rarely causes infections in humans. A 35-year-old female presented two weeks after an upper blepharoplasty with cyst-like swellings near the incision site.
View Article and Find Full Text PDFThe first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.
View Article and Find Full Text PDFThe key locations of freshwater input driving Atlantic Meridional Overturning Circulation (AMOC) slowdown and their climate responses remain inconclusive. Using a state-of-the-art global climate model, we conduct freshwater hosing experiments to reexamine AMOC sensitivity and its climate impacts. The Irminger basin emerges as the most effective region for additional freshwater fluxes, causing the greatest AMOC weakening.
View Article and Find Full Text PDFObjective: As the profession of pharmacy continues to evolve, it is important to integrate pharmacy practice change learning into the Doctor of Pharmacy (PharmD) curriculum. The objective of this project was to evaluate how pharmacy practice change was being taught within a PharmD curriculum and to identify strategies for improvement.
Methods: The College of Pharmacy's PharmD Curricular Leadership Committee (PDCLC) developed a definition for practice change learning and assembled a team of faculty experts to map practice change to the PharmD curriculum.
Airway stents are life-saving medical devices used to treat malignant or benign central airway stenoses. Unfortunately, these devices, typically manufactured from silicone alone and/or nitinol, can result in serious complications, such as stent migration, bacterial colonization, and tissue granulation, eventually forcing stent removal. Customized airway stents exhibit reduced migration and they can be tailored to address other complications by releasing drugs, such as the antibiotic levofloxacin and the antifibrotic drug nintedanib.
View Article and Find Full Text PDFThe ability of anthropogenic aerosols to freeze supercooled cloud droplets remains debated. In this work, we present observational evidence for the glaciation of supercooled liquid-water clouds at industrial aerosol hot spots at temperatures between -10° and -24°C. Compared with the nearby liquid-water clouds, shortwave reflectance was reduced by 14% and longwave radiance was increased by 4% in the glaciation-affected regions.
View Article and Find Full Text PDFObjective: To report the feasibility and potential utility of monitoring acoustic hearing on awake patients using intraoperative behavioral responses to threshold and suprathreshold stimuli while undergoing cochlear implantation (CI) under local anesthesia, without any form of sedation.
Study Design: Retrospective review of the first five cases performed by one surgeon.
Setting: Tertiary care academic medical center.
Premature implant failure, a critical concern in biomedical applications, is often attributed to poor biocompatibility and vulnerability to bacterial colonization. These issues are addressed by creating an endoprosthetic material with natural biocompatibility and antibacterial properties. In this in vitro study, the relaxed and unrelaxed tetrahedral amorphous carbon (ta-C) coatings were examined, both fabricated by the improved patented Pulsed Laser Deposition (PLD) technology.
View Article and Find Full Text PDFThe first search for the Z boson decay to ττμμ at the CERN LHC is presented, based on data collected by the CMS experiment at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb^{-1}. The data are compatible with the predicted background. For the first time, an upper limit at the 95% confidence level of 6.
View Article and Find Full Text PDFThe development, application, and benchmarking of artificial intelligence (AI) tools to improve diagnosis, prognostication, and therapy in neuro-oncology are increasing at a rapid pace. This Policy Review provides an overview and critical assessment of the work to date in this field, focusing on diagnostic AI models of key genomic markers, predictive AI models of response before and after therapy, and differentiation of true disease progression from treatment-related changes, which is a considerable challenge based on current clinical care in neuro-oncology. Furthermore, promising future directions, including the use of AI for automated response assessment in neuro-oncology, are discussed.
View Article and Find Full Text PDFEnviron Health (Wash)
January 2024