Automated High-Throughput Affinity Capture-Mass Spectrometry Platform with Data-Independent Acquisition.

Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small-molecule target selectivity and engagement. However, the tedious sample preparation steps and time-consuming MS acquisition process have limited its use in a high-throughput format. Here, we report an automated workflow employing biotinylated probes and streptavidin magnetic beads for small-molecule target enrichment in the 96-well plate format, ending with direct sampling from EvoSep Solid Phase Extraction tips for liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis.

Impact of Race/Ethnicity on Clinical and Genomic Characteristics, Trial Participation, and Genotype-Matched Therapy among Patients with Metastatic Breast Cancer.

Background: Race/ethnicity may affect outcomes in metastatic breast cancer (MBC) due to biological and social determinants. We evaluated the impact of race/ethnicity on clinical, socioeconomic, and genomic characteristics, clinical trial participation, and receipt of genotype-matched therapy among patients with MBC.

Methods: A retrospective study of patients with MBC who underwent cell-free DNA testing (cfDNA, Guardant360â, 74 gene panel) between 11/2016 and 11/2020 was conducted.

Entomopathogenic Nematode Species Vary in Their Behavior and Virulence in Response to Cardiac Glycosides Within and Around Insect Hosts.

Plants produce defensive toxins to deter herbivores. In response, some specialized herbivores evolved resistance and even the capacity to sequester toxins, affecting interactions at higher trophic levels. Here, we test the hypothesis that potential natural enemies of specialized herbivores are differentially affected by plant toxins depending on their level of adaptation to the plant-herbivore system.

Role of Glial Cells and Receptors in Schizophrenia Pathogenesis.

The specific pathogeneses of schizophrenia (SCZ) remain an enigma despite extensive research that has implicated both genetic and environmental factors. Recent revelations that dysregulated immune system caused by glial cell overactivation result in neuroinflammation, a key player in neurodegenerative as well as neuropsychiatric disorders including SCZ are providing novel clues on potential therapeutic interventions. Here, we review the roles of glial cells (Dr.

A Qualitative Analysis of Unintentional Injuries in Autism Spectrum Disorder.

Purpose: Prior research demonstrates that children with autism are more likely to experience unintentional injuries than the general population. Limited research exists on the symptoms or traits directly related to autism and this elevated injury rate, especially from the perspective of families with children with autism. This study used qualitative methodology to elucidate risk factors that may contribute to unintentional injuries in children with autism from the perspective of mothers raising children with autism.

The Potential of Spinal Cord Stimulation in Treating Spinal Cord Injury.

Purpose Of The Review: In the United States, spinal cord injuries affect approximately 18,000 individuals annually, most commonly resulting from mechanical trauma. The consequent paraplegia severely impairs motor functions, creating an urgent need for innovative therapeutic strategies that extend beyond traditional rehabilitation and pharmacotherapy. This review assesses the effectiveness of Spinal Cord Stimulation (SCS) in improving motor function in patients with spinal cord injuries, with a particular focus on paraplegia.

Trends and Disparities in Intrahepatic Cholangiocarcinoma-related Mortality in the United States from 1999 to 2020.

Purpose: Intrahepatic cholangiocarcinoma (ICC) arises from the epithelial cells of the bile ducts present inside the liver parenchyma and is associated with an overall poor prognosis due to advanced disease stage at the time of diagnosis. We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to determine ICC-related mortality patterns in the United States from 1999 till 2020.

Methods: Age-adjusted mortality rates (AAMR) and crude mortality rates (CMR) were extracted from the CDC WONDER database.

rsfMRI-based brain entropy is negatively correlated with gray matter volume and surface area.

The brain entropy (BEN) reflects the randomness of brain activity and is inversely related to its temporal coherence. In recent years, BEN has been found to be associated with a number of neurocognitive, biological, and sociodemographic variables such as fluid intelligence, age, sex, and education. However, evidence regarding the potential relationship between BEN and brain structure is still lacking.

Deep Learning of CYP450 Binding of Small Molecules by Quantum Information.

Drug-drug interaction can lead to diminished therapeutic effects or increased toxicity, posing significant risks, especially in polypharmacy, and cytochrome P450 plays an indispensable role in this interaction. Cytochrome P450, responsible for the metabolism and detoxification of most drugs, metabolizes about 90% of Food and Drug Administration-approved drugs, making early detection of potential drug-drug interactions. Over the years, in-silico modeling has become a valuable tool for predicting drug-drug interactions.

An Algorithmic Overview of Advanced Pain Therapies: A Narrative Review.

Purpose Of Review: Quickly referenceable, streamlined, algorithmic approaches for advanced pain management are lacking for patients, trainees, non-pain specialists, and interventional specialists. This manuscript aims to address this gap by proposing a comprehensive, evidence-based algorithm for managing neuropathic, nociceptive, and cancer-associated pain. Such an algorithm is crucial for pain medicine education, offering a structured approach for patient care refractory to conservative management.

Developmental basis of natural tooth shape variation in cichlid fishes.

While most dentate non-mammalian vertebrates possess simple conical teeth, some demonstrate complex tooth shapes. Lake Malawi cichlid fishes are an extreme example of this, exhibiting a myriad of tooth shapes driven by an ecologically derived rapid evolution of closely related but distinct species. Tooth shape in mammals is generally considered to be established by signaling centers called primary and secondary enamel knots, which are not believed to be present in non-mammalian vertebrates.

Exploring van der Waals Cuprate Superconductors Using a Hybrid Microwave Circuit.

The advent of two-dimensional van der Waals materials is a frontier of condensed matter physics and quantum devices. However, characterizing such materials remains challenging due to the limitations of bulk material techniques, necessitating the development of specialized methods. Here, we investigate the superconducting properties of BiSrCaCuO flakes by integrating them with a hybrid superconducting microwave resonator.

Anatomy of a Crash: Analysis of 102 Pedestrian and Bicyclist Fatalities.

Pedestrian and bicyclist fatalities have increased over the past decade in the United States. Factors proposed to explain this increase include the increased popularity of larger passenger vehicles, road design to accommodate faster-moving traffic, and poor road infrastructure. We analyzed a series of 102 pedestrian and bicyclist fatalities to determine which factors were involved.

Computational Modeling of Electrocatalysts for CO Reduction: Probing the Role of Primary, Secondary, and Outer Coordination Spheres.

ConspectusIn the search for efficient and selective electrocatalysts capable of converting greenhouse gases to value-added products, enzymes found in naturally existing bacteria provide the basis for most approaches toward electrocatalyst design. Ni,Fe-carbon monoxide dehydrogenase (Ni,Fe-CODH) is one such enzyme, with a nickel-iron-sulfur cluster named the C-cluster, where CO binds and is converted to CO at high rates near the thermodynamic potential. In this Account, we divide the enzyme's catalytic contributions into three categories based on location and function.

Osteopathic Manipulative Treatment for Postconcussive Symptoms: A Case Report.

Concussions are a common form of mild traumatic brain injury characterized by a transient alteration of cerebral function leading to a range of physical, cognitive, and emotional symptoms. Postconcussive symptoms (PCSs) usually resolve in about a week but can persist in 10% to 15% of patients. If left untreated, PCS can profoundly affect a patient's life.

Horizontal Gaze Tolerance and Its Effects on Visual Sensitivity in Glaucoma.

Purpose: This study evaluates the effect of 6° horizontal gaze tolerance on visual field mean sensitivity (MS) in patients with glaucoma using a binocular head-mounted automated perimeter, following findings of structural changes in the posterior globe from magnetic resonance imaging and optical coherence tomography.

Methods: In this cross-sectional study, a total of 161 eyes (85 primary open-angle glaucoma [POAG] and 76 healthy) from 117 participants were included. Logistic regression and 1:1 matched analysis assessed the propensity score for glaucoma and healthy eyes, considering age, sex, and axial length as confounders.

Outcomes of Liver Transplant for Hepatic Epithelioid Hemangioendothelioma.

Introduction: Hepatic epithelioid hemangioendothelioma (HEH) is a rare indication of liver transplant with limited evidence.

Methods: Adult recipients undergoing first-time liver-only transplant from 2002 to 2021 in the United States were identified using the UNOS/OPTN database. We compared post-transplant outcomes of recipients receiving liver transplant for HEH versus other diagnoses.

Increased plugging latency in cycling epiERα-/- (Esr1f/-Wnt7aCre/+) mice.

Wnt7a-Cre is a commonly used for generating uterine epithelial conditional knockout mice, such as epiERα-/- (Esr1f/-Wnt7aCre/+) and epiPR-/- (Pgrf/-Wnt7aCre/+). We noticed that epiERα-/- females, but not epiPR-/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle.

Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium.

The mechanisms underlying cooperative activation and inactivation of myocardial force extend from local, near-neighbor interactions involving troponin-tropomyosin regulatory units (RU) and crossbridges (XB) to more global interactions across the sarcomere. To better understand these mechanisms in the hearts of small and large mammals, we undertook a simplified mathematical approach to assess the contribution of three types of near-neighbor cooperative interactions, i.e.

Competition between Halogen Atom and Ring of Halobenzenes as Hydrogen Bond Electron Donor Sites.

A halobenzene molecule contains several sites that are capable of acting in an electron-donating capacity within a H-bond.  One set of such sites comprise the lone electron pairs of the halogen (X) atoms on the periphery of the ring.  The π-electron system above the ring plane can also fulfill this function in many cases.

Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity.

Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cell-derived EVs can be modified to acquire the capacity to induce an immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L, and PD-L1.

Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.

Extracellular vesicles (EVs) are cell derived nanovesicles which are implicated in both physiological and pathological intercellular communication, including the initiation, progression, and metastasis of cancer. The exchange of biomolecules between stromal cells and cancer cells via EVs can provide a window to monitor cancer development in real time for better diagnostic and interventional strategies. In addition, the process of secretion and internalization of EVs by stromal and cancer cells in the tumor microenvironment (TME) can be exploited for delivering therapeutics.

Rethinking gender differences: An investigation of comorbid psychopathology and alcohol use disorder in veterans.

Background: While men have been found to drink more alcohol and have higher rates of alcohol-related mortality, women tend to experience higher rates of alcohol-related consequences, including psychological comorbidities and worse alcohol use disorder (AUD) outcomes. However, gender differences in comorbid psychopathology and associations with AUD outcomes among veterans are less well understood.

Methods: Veterans (N = 126; 32 women) receiving inpatient treatment for AUD completed baseline clinical measures including the Beck Depression Inventory-II, Beck Anxiety Inventory, Early Life Stress Questionnaire, and PTSD Checklist for DSM-5.

The Changing pathogenesis of liver cancer in Hawaii over three decades.

Background: Worldwide trends support the increasing contribution of hepatic steatosis on the incidence of hepatocellular carcinoma (HCC). This study investigates if similar changes are seen in Hawaii, where the incidence of HCC is higher than most of the United States. Methods; This is a retrospective study of 1651 patients diagnosed with HCC (1991-2023) that includes 60-70% of Hawaii's HCC cases.

An IgM Cleaving Enzyme for Clearance of Anti-Pig Xenoreactive Antibodies in a Nonhuman Primate Model.

Background: The removal of preformed antibodies with cleaving enzyme like IdeS (Imlifidase) has demonstrated therapeutic potential in organ transplantation for sensitized recipients. However, preformed xenoreactive antibodies (XAbs) against porcine glycans are predominantly IgM and considered detrimental in pig-to-human xenotransplantation.

Methods: Recombinant IceM, an endopeptidase cleaving IgM, was generated in Escherichia coli.