Interpretable Deep-Learning p Prediction for Small Molecule Drugs via Atomic Sensitivity Analysis.

Machine learning (ML) models now play a crucial role in predicting properties essential to drug development, such as a drug's logscale acid-dissociation constant (p). Despite recent architectural advances, these models often generalize poorly to novel compounds due to a scarcity of ground-truth data. Further, these models lack interpretability.

Spatial distribution and subtype-specific expression patterns of Nectin-4 in muscle-invasive bladder cancer.

Objective: To investigate the expression patterns of Nectin-4, the target molecule of the antibody-drug conjugate enfortumab vedotin (EV), in relation to histological and molecular subtypes of urothelial bladder cancer (UBC).

Patients And Methods: We assessed the protein expression patterns of Nectin-4 in a spatially organised tissue microarray containing 1386 tissue cores from 314 consecutive patients with UBC who underwent radical cystectomy (2005-2018). Results were correlated with clinicopathological and follow-up data, as well as with different spatial locations (tumour central vs tumour-normal interface and primary tumour vs lymph node [LN] metastases).

Cancer Neuroscience of Brain Tumors: From Multicellular Networks to Neuroscience-Instructed Cancer Therapies.

Deepening our understanding of neuro-cancer interactions can innovate brain tumor treatment. This mini review unfolds the most relevant and recent insights into the neural mechanisms contributing to brain tumor initiation, progression, and resistance, including synaptic connections between neurons and cancer cells, paracrine neuro-cancer signaling, and cancer cells' intrinsic neural properties. We explain the basic and clinical-translational relevance of these findings, identify unresolved questions and particularly interesting future research avenues, such as central nervous system neuro-immunooncology, and discuss the potential transferability to extracranial cancers.

Regulation of Dendrite and Dendritic Spine Formation by TCF20.

Mutations in the Transcription Factor 20 (TCF20) have been identified in patients with autism spectrum disorders (ASDs), intellectual disabilities (IDs), and other neurological issues. Recently, a new syndrome called TCF20-associated neurodevelopmental disorders (TAND) has been described, with specific clinical features. While TCF20's role in the neurogenesis of mouse embryos has been reported, little is known about its molecular function in neurons.

Purification and characterization of a thermophilic NAD-dependent lactate dehydrogenase from Moorella thermoacetica.

Oxidation of lactate under anaerobic dark fermentative conditions poses an energetic problem. The redox potential of the lactate/pyruvate couple is too electropositive to reduce the physiological electron carriers NAD(P) or ferredoxin. However, the thermophilic, anaerobic, and acetogenic model organism Moorella thermoacetica can grow on lactate but was suggested to have a NAD-dependent lactate dehydrogenase (LDH), based on enzyme assays in cell-free extract.

3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink.

Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three -dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro.

Microplastic Materials for Inhalation Studies: Preparation by Solvent Precipitation and Comprehensive Characterization.

Assessing the inhalation hazard of microplastics is important but necessitates sufficient quantity of microplastics that are representative and respirable (<4 µm). Common plastics are not typically manufactured in such small sizes. Here, solvent precipitation is used to produce respirable test materials from thermoplastics polyurethane (TPU), polyamide (PA-6), polyethylene terephthalate (PET), and low-density polyethylene (LDPE).

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Boosting Amino Acid Synthesis with WO Sub-Nanoclusters.

The conversion of nitrate-rich wastewater and biomass-derived blocks into high-value products using renewably generated electricity is a promising approach to modulate the artificial carbon and nitrogen cycle. Here, a new synthetic strategy of WO sub-nanoclusters is reported and supported on carbon materials as novel efficient electrocatalysts for nitrate reduction and its coupling with α-keto acids. In acidic solutions, the NH-NHOH selectivity can also optimized by adjusting the potential, with the total FE exceeding 80% over a wide potential range.

Analysis of Giant-Shell CdSe/CdS Quantum Dots via Analytical Ultracentrifugation Combined with Spectrally Resolved Photoluminescence.

Knowledge of the structure-property relationships of functional nanomaterials, including, for example, their size- and composition-dependent photoluminescence (PL) and particle-to-particle variations, is crucial for their design and reproducibility. Herein, the Angstrom-resolution capability of an analytical ultracentrifuge combined with an in-line multiwavelength emission detection system (MWE-AUC) for measuring the sedimentation coefficient-resolved spectrally corrected PL spectra of dispersed nanoparticles is demonstrated. The capabilities of this technique are shown for giant-shell CdSe/CdS quantum dots (g-QDs) with a PL quantum yield (PL QY) close to unity capped with oleic acid and oleylamine ligands.

Antithrombotic therapy impact on patency and bleeding complications of arteriovenous graft placement in dialysis patients.

Arteriovenous grafts (AVG) can be the only bailout solution for patients who require kidney replacement therapy but are unsuitable for arteriovenous fistula (AVF) creation. Currently, high-level evidence on the effectiveness and safety of antithrombotic therapy in AVG patients is scarce. Following the PICO (patient; intervention; comparator; outcome) model and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a data search of the English literature in PubMed, SCOPUS, Central Cochrane was conducted, until March 1st, 2023 (PROSPERO Protocol Number: CRD42023401785).

A Critical Appraisal of the Application of Frailty and Sarcopenia in the Spinal Oncology Population.

Study Design: Systematic review and clinimetric analysis.

Objectives: Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we sought to identify frailty and sarcopenia tools applied in spinal oncology and appraise their clinimetric properties.

Latest Developments in Targeted Biological Therapies in the Management of Chordoma and Chondrosarcoma.

Study Design: Systematic review.

Objectives: The objective of this review paper was to summarize targeted molecular therapy options for spinal chordoma and chondrosarcoma, and to provide an update on the relevant clinical trials open for recruitment.

Methods: A systematic review of the current literature was performed, according to PRISMA guidelines, to summarize the latest developments in non-surgical molecular treatment options for low grade malignant primary spinal tumours.

What is the Optimal Management of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate or Not to Operate?

Study Design: Systematic review.

Objective: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries.

Methods: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery.

Role of Posterior Carbon Fiber Implants in Spine Tumor Surgery.

Study Design: Narrative Review.

Objective: The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability.

Clinical validation of artificial intelligence-based single-subject morphometry without normative reference database.

Background: Single-subject voxel-based morphometry (VBM) is a powerful technique for reader-independent detection of brain atrophy in structural magnetic resonance imaging (MRI) to support the (differential) diagnosis and staging of neurodegenerative diseases in individual patients. However, VBM is sensitive to the MRI scanner platform and details of the acquisition sequence. To mitigate this limitation, we recently proposed and validated a convolutional neural network (CNN)-based VBM which does not rely on a normative reference database.

From Isolation to Application: Utilising Phage-Antibiotic Synergy in Murine Bacteremia Model to Combat Multidrug-Resistant Enterococcus faecalis.

Enterococcus species, natural inhabitants of the human gut, have become major causes of life-threatening bloodstream infections (BSIs) and the third most frequent cause of hospital-acquired bacteremia. The rise of high-level gentamicin resistance (HLGR) in enterococcal isolates complicates treatment and revives bacteriophage therapy. This study isolated and identified forty E.

Luminescent Properties of Pr-Doped LiBaF Crystallites.

Research is ongoing to develop new phosphors capable of emitting light across a broad spectrum, ranging from the ultraviolet (UV) to the infrared region, with potential applications in diverse fields. Using the method of solid-state reactions, a series of LiBaF:Pr phosphors were obtained, and their luminescent properties in the UV-visible range were studied. The photon cascade emission (PCE) phenomenon has been observed under excitation of the 4f5d bands of Pr.

The 'MOAHLFA(P) Index': An Attempt to Standardise a Widely Used Array of Descriptors of Patch-Tested Patients.

Background: Since its inception in 1980, the MOHL index (% patients who are male, have occupational, hand, or leg dermatitis, respectively) and its later evolutions until the presently used MOAHLFA(P) index (adding % patients with atopic dermatitis, face dermatitis, age 40+ years and positive reaction(s) to ≥ 1 baseline series allergen) have been intended to convey important demographic and clinical information on the patients patch tested in a certain area and time, aiding the interpretation of the observed spectrum of sensitisation.

Objectives: To examine the current usage of the MOAHLFA(P) index and suggest consolidated definitions for its single items.

Methods: A title/abstract search in Medline identified publications mentioning the evolving acronyms.

TIPPo: A User-Friendly Tool for De Novo Assembly of Organellar Genomes with High-Fidelity Data.

Plant cells have two major organelles with their own genomes: chloroplasts and mitochondria. While chloroplast genomes tend to be structurally conserved, the mitochondrial genomes of plants, which are much larger than those of animals, are characterized by complex structural variation. We introduce TIPPo, a user-friendly, reference-free assembly tool that uses PacBio high-fidelity long-read data and that does not rely on genomes from related species or nuclear genome information for the assembly of organellar genomes.

Assessment of Speech Processing and Listening Effort Associated With Speech-on-Speech Masking Using the Visual World Paradigm and Pupillometry.

Speech-on-speech masking is a common and challenging situation in everyday verbal communication. The ability to segregate competing auditory streams is a necessary requirement for focusing attention on the target speech. The Visual World Paradigm (VWP) provides insight into speech processing by capturing gaze fixations on visually presented icons that reflect the speech signal.

Human presence shifts the landscape of fear for a free-living mammal.

Humans may play a key role in providing small prey mammals spatial and temporal refuge from predators, but few studies have captured the heterogeneity of these effects across space and time. Global COVID-19 lockdown restrictions offered a unique opportunity to investigate how a sudden change in human presence in a semi-urban park impacted wildlife. Here, we quantify how changes in the spatial distributions of humans and natural predators influenced the landscape of fear for the California ground squirrel (Otospermophilus beecheyi) in a COVID-19 pandemic (2020) and non-COVID (2019) year.

Curative-Intended Management of Synchronous Esophageal and Rectal Cancer-A Systematic Literature Review.

Purpose: Synchronous esophageal (EC) and rectal carcinoma (RC) is a rare and challenging condition, particularly in curative-intended treatment. Especially locally advanced tumors may not be suitable for primary resection and require individual multimodal treatment. This review examines curative-intended management of synchronous EC and RC.