Examination of conformational dynamics of AdiC transporter with fluorescence-polarization microscopy.

To understand the mechanism underlying the ability of individual AdiC molecules to transport arginine and agmatine, we used a recently developed high-resolution single-molecule fluorescence-polarization microscopy method to investigate conformation-specific changes in the emission polarization of a bifunctional fluorophore attached to an AdiC molecule. With this capability, we resolved AdiC's four conformations characterized by distinct spatial orientations in the absence or presence of the two substrates, and furthermore, each conformation's two energetic states, totaling 24 states. From the lifetimes of individual states and state-to-state transition probabilities, we determined 60 rate constants characterizing the transitions and 4 KD values characterizing the interactions of AdiC's two sides with arginine and agmatine, quantitatively defining a 24-state model.

Associations between maternal pre-pregnancy BMI and mean diffusivity of the hippocampus and amygdala in infants.

Background: Maternal pre-pregnancy obesity may negatively affect offspring outcomes, including neurodevelopment. This study examined the relationship between maternal pre-pregnancy body mass index (MBMI) and the microstructure of the hippocampus and amygdala in neonates.

Methods: Diffusion tensor imaging was used to assess mean diffusivity (MD) in these brain regions in 122 infants (mean gestational age: 39.

Novel Monoclonal Antibodies 1D2 and 4E4 Against Glycoprotein Antigens Detect Early Invasive Aspergillosis in Mice.

Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and correlate it with tissue invasion by using two novel monoclonal antibodies, 1D2 and 4E4, that can be used to detect the -derived glycoproteins. Immunocompromised mice were randomly divided into five groups: uninfected control, and inoculation with conidia from , , and . Conidia (2 × 10 cells/mL) were administered intravenously via tail vein injection.

Mass spectrometric detection of neutrophil elastase cleaved corticosteroid binding globulin and its association with Asn347 site glycosylation, in septic shock patients.

Background: Corticosteroid-binding globulin (CBG) modulates tissue cortisol availability via modification of cortisol:CBG binding affinity in response to multiple factors, including neutrophil elastase (NE) cleavage of the reactive centre loop (RCL), converting high affinity CBG (haCBG) to low affinity CBG (laCBG). In vitro, glycosylation of the RCL at Asn347 affects NE cleavage susceptibility. To date, no direct measurement of laCBG, which would verify NE cleavage, has been reported.

Fracture Dynamics in Silicon Anode Solid-State Batteries.

Solid-state batteries (SSBs) with silicon anodes could enable improved safety and energy density compared to lithium-ion batteries. However, degradation arising from the massive volumetric changes of silicon anodes during cycling is not well understood in solid-state systems. Here, we use X-ray computed microtomography to reveal micro- to macro-scale chemo-mechanical degradation processes of silicon anodes in SSBs.

Real-world Clinical Outcomes and Prognostic Factors in Neuroendocrine Prostate Cancer.

Background: Neuroendocrine prostate cancer (NEPC) encompasses pure NEPC and tumors with mixed adenocarcinoma and neuroendocrine histology. While NEPC is thought to confer a poor prognosis, outcome data are sparse, making risk stratification and treatment decisions difficult for clinicians.

Methods: This retrospective study identified patients with morphological and/or immunohistochemical NEPC features on pathological review of high-grade prostate cancer cases.

Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles.

Genetic medicines show promise for treating various diseases, yet clinical success has been limited by tolerability, scalability, and immunogenicity issues of current delivery platforms. To overcome these, we developed a proteolipid vehicle (PLV) by combining features from viral and non-viral approaches. PLVs incorporate fusion-associated small transmembrane (FAST) proteins isolated from fusogenic orthoreoviruses into a well-tolerated lipid formulation, using scalable microfluidic mixing.

The Characterization of the Th1/Th2 Ratio in Multiple Sclerosis Patients and its Response to a Dietary Supplement Regimen.

Introduction: Multiple sclerosis (MS) is a debilitating neurodegenerative disease affecting the central nervous system, causing disability and life-threatening complications. The interplay between immune cells and signaling pathways is a topic for investigating novel therapies. Past research has shown how the Th1/Th2 ratio plays a key role in the pathogenesis of MS lesions.

Entry of Migrant Workers to Malaysia: Consideration to Implement Mass Drug Administration Against Intestinal Parasitic Infections.

Over the last five decades, widespread industrialisation and urbanisation have resulted in the influx of low-skilled workers, particularly from Southeast and West Asia to Malaysia. The current practice for migrant workers entry for employment requires mandatory medical screening for infectious diseases. However, screening for parasitic infections in Malaysia is woefully inadequate.

Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.

Materials And Methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023.

Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer.

Background: The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery.

Results: We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics.

Development of an effective predictive screening tool for prostate cancer using the ClarityDX machine learning platform.

The current prostate cancer (PCa) screen test, prostate-specific antigen (PSA), has a high sensitivity for PCa but low specificity for high-risk, clinically significant PCa (csPCa), resulting in overdiagnosis and overtreatment of non-csPCa. Early identification of csPCa while avoiding unnecessary biopsies in men with non-csPCa is challenging. We built an optimized machine learning platform (ClarityDX) and showed its utility in generating models predicting csPCa.

Intelligence and cortical morphometry: caveats in brain-behavior associations.

It is well-established that brain size is associated with intelligence. But the relationship between cortical morphometric measures and intelligence is unclear. Studies have produced conflicting results or no significant relations between intelligence and cortical morphometric measures such as cortical thickness and peri-cortical contrast.

We outside: Modeling equity-centered, antiracist, community-driven partnerships in resident education.

Background: Community engagement is increasingly recognized as a necessity in addressing intractable racial and ethnic health disparities in the United States. However, institutions have not adequately trained resident physicians in developing symbiotic community partnerships that preserve community autonomy and identity without exploitation. Our goals were to highlight the experiences of expert academic emergency physicians in creating innovative, community-driven, and anti-racist solutions to achieving measurable equity in health outcomes and to introduce a novel framework entitled the Social Change Method to take a community-embedded intervention from concept to creation.

Medially Positioned Single Mucoperiosteal Flap With and Without Allograft Membrane for Repair of Congenital Cleft Palate in 4 Dogs.

Congenital cleft of the secondary palate occurs when there is failure of one or both maxillary processes to fuse with the nasal septum during embryonic development. Palatal cleft severity can range from a simple focal fissure of the caudal soft palate to full-thickness defects of varied widths involving the entire soft and hard palate. A novel staged medially positioned single mucoperiosteal flap technique in 4 canine patients is reported.

Atypical co-development of the thalamus and cortex in autism: Evidence from age-related white-gray contrast change.

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TD peers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing.

Associations between maternal pre-pregnancy BMI and infant striatal mean diffusivity.

Background: It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring's brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring's brain during in utero development.

Motion compensated cone-beam CT reconstruction using anmotion model from CT simulation: a pilot study.

. To combat the motion artifacts present in traditional 4D-CBCT reconstruction, an iterative technique known as the motion-compensated simultaneous algebraic reconstruction technique (MC-SART) was previously developed. MC-SART employs a 4D-CBCT reconstruction to obtain an initial model, which suffers from a lack of sufficient projections in each bin.

Survival outcomes of patients with HER2/neu-positive breast cancer with germline BRCA mutations.

Background: Breast cancer (BC) with germline BRCA1/2 mutations and their association with triple-negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)-positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu-positive BC who had germline BRCA1/2 mutations.

A digital innovation typology: Navigating the complexity of emerging technologies to negotiate health systems research with young people.

Objective: This study aims to explore young people's perspectives of emerging technologies and health systems research in an adolescent health community of practice.

Methods: The context of this integrated knowledge translation study is the Wellbeing Health & Youth Centre of Research Excellence in Adolescent Health. A theory-building, non-systematic review was conducted to examine the concepts and interrelationships of emerging technologies associated with digital innovation and health systems.

The Characterization of the Th1/Th2 Ratio in Moderate-Severe Alzheimer's Disease Patients and Its Response to an Aloe Polymannose-Based Dietary Supplement.

Background: Alzheimer's disease (AD) is a leading killer of Americans, imparting a tremendous societal toll. Relationships between immune function and inflammation with cognition are well-established in AD, but the Th1/Th2 ratio of immune function is unknown. Describing the Th1/Th2 ratio and its relationship with cognition may shed light on the disease's clinical context.

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention.

Objective: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed.