The NE/AAT/CBG axis regulates adipose tissue glucocorticoid exposure.

Corticosteroid binding globulin (CBG; SERPINA6) binds >85% of circulating glucocorticoids but its influence on their metabolic actions is unproven. Targeted proteolytic cleavage of CBG by neutrophil elastase (NE; ELANE) significantly reduces CBG binding affinity, potentially increasing 'free' glucocorticoid levels at sites of inflammation. NE is inhibited by alpha-1-antitrypsin (AAT; SERPINA1).

Evolution of Advanced Practice Provider Fellowship Training in Neurology Over 10 Years.

We are pleased to present our 10-year experience with our 1-year neurology advanced practice provider (APP) fellowship. The Duke fellowship was started by 1 author (J.C.

Is the 99th Percentile Cutoff Still Relevant? A Single-Center Assessment of Different Thresholds for Diagnosing Antiphospholipid Syndrome.

Background: The 2023 American College of Rheumatology and modified Sapporo criteria for antiphospholipid syndrome (APS) recommend ELISA to detect anticardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GP1) IgG/IgM antibodies, focusing on moderate to high levels or exceeding the 99th percentile. This study aims to establish the 99th percentile threshold for anti-phospholipid (aPL) antibodies and compare the diagnostic accuracies of these thresholds with manufacturer cutoffs using 2 methodologies.

Methods: The 99th percentile cutoffs for aPL antibodies from 305 healthy donors were established using Aptiva, Particle-Based Multi-Analyte Technology (PMAT), and QUANTA Lite (QL) ELISA, following nonparametric reference interval estimation.

Cross-sectional relationships of circadian misalignment and rest-activity rhythms with occupational attainment in UK Biobank participants.

Circadian misalignment and disrupted rest-activity rhythms have been linked to adverse health and educational outcomes, yet few studies have considered their relationships with economic outcomes. We investigate associations between multiple accelerometer-measured circadian misalignment traits (Composite Phase Deviation and the Sleep Regularity Index) and rest-activity rhythm traits (Inter-daily Stability, Intra-daily variability and relative amplitude), with occupational attainment, measured using the average wage paid to an individual's occupation. We use data from 20 356 UK Biobank participants who wore an accelerometer (2013-16), provided employment data for the year they wore the accelerometer, and supplied covariate data at recruitment (2006-10).

Modeling with uncertainty quantification reveals the essentials of a non-canonical algal carbon-concentrating mechanism.

The thermoacidophilic red alga Cyanidioschyzon merolae survives its challenging environment likely in part by operating a carbon-concentrating mechanism (CCM). Here, we demonstrated that C. merolae's cellular affinity for CO2 is stronger than the affinity of its rubisco for CO2.

Resilient plants, sustainable future.

The accelerated pace of climate change over the past several years should serve as a wake-up call for all scientists, farmers, and decision makers, as it severely threatens our food supply and could result in famine, migration, war, and an overall destabilization of our society. Rapid and significant changes are therefore needed in the way we conduct research on plant resilience, develop new crop varieties, and cultivate those crops in our agricultural systems. Here, we describe the main bottlenecks for these processes and outline a set of key recommendations on how to accelerate research in this critical area for our society.

SmartGraph API: Programmatic Knowledge Mining in Network-Pharmacology Setting.

The recent SmartGraph platform facilitates the execution of complex drug-discovery workflows with ease in the network-pharmacology paradigm. However, at the time of its publication we identified the need for the development of an Application Programming Interface (API) that could promote biomedical data integration and hypothesis generation in an automated manner. This need was magnified at the time of the COVID-19 pandemic.

Can oral cancer screening reduce late-stage diagnosis, treatment delay and mortality? A population-based study in Taiwan.

Objective: This study evaluates the effectiveness of Taiwan's nationwide oral cancer screening programme in reducing late-stage diagnosis, treatment delays and mortality.

Design: A retrospective cohort study was conducted.

Setting: The study utilized Nationally representative datasets, including the Cancer Registry, Oral Mucosal Screening and National Health Insurance databases in Taiwan.

Prophylactic surgical drain placement with irrigation reduces abscess formation in patients with severe, uncontained, perforated appendicitis.

Background: 20-25% of perforated appendicitis cases are complicated by abscess formation. This study assesses whether prophylactic closed-suction surgical drain (SD) placement after irrigation can decrease postoperative abscess formation in patients with extensively contaminated, perforated appendicitis.Affiliations: Journal instruction requires country for affiliations; however, these are missing in all affiliations.

Metabolomic profiles of stony coral species from the Dry Tortugas National Park display inter- and intraspecies variation.

Unlabelled: Coral reefs are experiencing unprecedented loss in coral cover due to increased incidence of disease and bleaching events. Thus, understanding mechanisms of disease susceptibility and resilience, which vary by species, is important. In this regard, untargeted metabolomics serves as an important hypothesis-building tool enabling the delineation of molecular factors underlying disease susceptibility or resilience.

Increasing thermostability of the key photorespiratory enzyme glycerate 3-kinase by structure-based recombination.

As global temperatures rise, improving crop yields will require enhancing the thermotolerance of crops. One approach for improving thermotolerance is using bioengineering to increase the thermostability of enzymes catalysing essential biological processes. Photorespiration is an essential recycling process in plants that is integral to photosynthesis and crop growth.

Proof of concept for a superior therapeutic index of corticosterone compared with hydrocortisone in patients with congenital adrenal hyperplasia.

Objective: Outcomes are poor for patients with congenital adrenal hyperplasia (CAH), in part due to the supraphysiological glucocorticoid doses required to control adrenal androgen excess. Hydrocortisone (ie, cortisol) is the recommended glucocorticoid for treatment of CAH. However, the other endogenous glucocorticoid in humans, corticosterone, is actively transported out of metabolic tissues such as adipose tissue and muscle, so we hypothesized that corticosterone could control adrenal androgens while causing fewer metabolic adverse effects than hydrocortisone.

Management of Tracheoesophageal Fistula and Tracheoinnominate Fistula.

Fistulization between the tracheobronchial tree and gastrointestinal tract is a challenging clinical situation that leads to life-threatening pulmonary contamination and inadequate nutrition. Operative management requires repair of both airway and esophageal defects with or without tracheal resection and reconstruction to restore a functional airway and maintain gastrointestinal continuity. Tracheoinnominate fistula is a rare communication between the airway and innominate artery that can result in fatal hemorrhage.

Early Viral Dynamics Predict HIV Post-Treatment Control After Analytic Treatment Interruption.

Background: A key research priority for developing an HIV cure strategy is to define the viral dynamics and biomarkers associated with sustained post-treatment control. The ability to predict the likelihood of sustained post-treatment control or non-control could minimize the time off antiretroviral therapy (ART) for those destined to not control and anticipate longer periods off ART for those destined to control.

Methods: Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control using viral kinetics data from several studies in which participants interrupted ART.

HIV risk perception and PrEP uptake among black MSM in Mississippi.

Introduction: Rates for HIV are disproportionately higher for Black men who have sex with men (MSM) compared to other MSM in the U.S. While there is evidence that low perceived risk of HIV infection may increase HIV vulnerability, few studies have examined this relationship among Black MSM in the Southern U.

A novel merocyanine photoacid for visible light-controlled pH modulation.

Merocyanine-based photoacids generate high proton concentrations under visible light irradiation. In the past decade, it has been established that these photoacids offer significant advantages over photoacid generators (PAGs) and hydroxyaryl photoacids, enabling better spatiotemporal control of proton transfer reactions in bulk media. In this study, we modified the core structure of the first generation of meroyanine photoacids.

Rubisco activity and activation state dictate photorespiratory plasticity in Betula papyrifera acclimated to future climate conditions.

Plant metabolism faces a challenge of investing enough enzymatic capacity to a pathway without overinvestment. As it takes energy and resources to build, operate, and maintain enzymes, there are benefits and drawbacks to accurately matching capacity to the pathway influx. The relationship between functional capacity and physiological load could be explained through symmorphosis, which would quantitatively match enzymatic capacity to pathway influx.

Method validation of an inductively coupled plasma mass spectrometry (ICP-MS) assay for the analysis of magnesium, copper and zinc in red blood cells.

Background: Laboratory measurements of trace elements such as magnesium (Mg), copper (Cu), and zinc (Zn) in red blood cells (RBCs) are essential for assessing nutritional status and diagnosing metal toxicity. The purpose of this study was to develop and validate an ICP-MS method for quantifying these elements in RBCs.

Methods: Packed RBCs were aliquoted and diluted in an alkaline diluent solution containing internal standards, 0.

Laparoscopic cervico-isthmic cerclage: A "Needle-free" approach for managing cervical insufficiency in pregnant and non-pregnant patients.

This video-article describes a laparoscopic cervico-isthmic cerclage technique for managing cervical insufficiency in both pregnant and non-pregnant patients, utilizing a port-site closure device for precise suture placement. Two cases-one non-pregnant and one at 12 weeks gestation-underwent the procedure, with details on trocar placement, dissection, and suture passage documented. Both surgeries were completed successfully, with minimal blood loss and no complications.

Comparison of Efficacy of Micropulse Laser Settings for Glaucoma Management.

: This study aims to compare micropulse transscleral cyclophotocoagulation (MP-TSCPC) laser parameters and determine the optimal laser setting. : A retrospective study was performed on 351 eyes from patients who underwent MP-TSCPC at four power settings (1500 mW, 2000 mW, 2250 mW, and 2500 mW) from June 2018 to December 2021. The primary measurements of the efficacy of MP-TSCPC were the degree of intraocular pressure (IOP) reduction and the number of glaucoma medication reductions.

Metabolomics of related C3 and C4 Flaveria species indicate differences in the operation of photorespiration under fluctuating light.

C photosynthesis can be complemented with a C carbon concentrating mechanism (CCM) to minimize photorespiratory losses. C photosynthesis is often more efficient than C under steady-state conditions. However, the C CCM depends on inter-cellular metabolite concentration gradients, which must increase following increases in light intensity and could decrease rates of C photosynthesis under fluctuating light.

Cycling of labile and recalcitrant carboxyl-rich alicyclic molecules and carbohydrates in Baffin Bay.

Marine dissolved organic matter (DOM) is an important, actively cycling carbon reservoir (662 GtC). However, the chemical structure and cycling of DOM within rapidly warming, polar environments remains largely unconstrained. Previous studies have shown rapid surface cycling of carbohydrates as biologically-labile DOM (LDOM).

NEK10 kinase ablation affects mitochondrial morphology, function and protein phosphorylation status.

Background: NEK10, a serine/threonine/tyrosine kinase belonging to the NEK (NIMA-related kinases) family, has been associated with diverse cellular processes. However, no specific target pathways have been identified. Our previous work knocking down NEK10 in HeLa cells suggested a functional association with mitochondria, as we observed altered mitochondrial morphology, mitochondrial oxygen consumption, mtDNA integrity, and reactive oxygen species levels.