A novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.

Disruption of extracellular pH and proton-sensing can profoundly impact cellular and protein functions, leading to developmental defects. To visualize changes in extracellular pH in the developing embryo, we generated a zebrafish transgenic line that ubiquitously expresses the ratiometric pH-sensitive fluorescent protein pHluorin2, tethered to the extracellular face of the plasma membrane using a glycosylphosphatidylinositol (GPI) anchor. Monitoring of pHluorin2 with ratiometric fluorescence revealed dynamic and discrete domains of extracellular acidification over the first 72 h of embryonic development.

Biological characterization of AB-343, a novel and potent SARS-CoV-2 M inhibitor with pan-coronavirus activity.

Since the SARS-CoV-2 outbreak, there have been ongoing efforts to identify antiviral molecules with broad coronavirus activity to combat COVID-19. SARS-CoV-2's main protease (M) is responsible for processing the viral polypeptide into non-structural proteins essential for replication. Here, we present the biological characterization of AB-343, a covalent small-molecule inhibitor of SARS-CoV-2 M with potent activity in both cell-based (EC = 0.

Proton pump inhibitors are detrimental to overall survival of patients with glioblastoma: Results from a nationwide real-world evidence database.

Background: Proton pump inhibitors (PPIs) are often prescribed to manage corticosteroid-induced gastrointestinal toxicity during glioblastoma (GBM) treatment, but were recently identified as strong inducers of aldehyde dehydrogenase-1A1 (ALDH1A1). ALDH1A1 is a primary metabolic enzyme impacting the outcome of chemotherapy, including temozolomide. High expression of ALDH1A1 is associated with poor prognosis in multiple cancers, suggesting PPIs may have a negative impact on survival.

Calibrating Observational Health Record Data Against a Randomized Trial.

Importance: The conditions required for health record data sources to accurately assess treatment effectiveness remain unclear. Emulation of randomized clinical trials (RCTs) with health record data and subsequent calibration of the results can help elucidate this.

Objective: To pilot an emulation of the KEYNOTE-189 RCT using a commercially available electronic health record (EHR) data source.

Emulations of Oncology Trials Using Real-World Data: A Systematic Literature Review.

By evaluating published emulations of oncology RCTs studies in which both the active and comparator groups are sourced from RWD and target trial results are available for benchmarking, this systematic review aims to gain insight into factors related to emulation performance. Thirteen oncology emulation studies using various types of RWD were identified through an online database search of PubMed through 2022. Based on the ROBINS-I tool, most studies (N=8) had a serious risk of overall bias driven by risk of bias from confounding.

Reduction of peritoneal dialysis associated infections using a novel exit-site care practice.

Introduction: Peritoneal dialysis (PD) related infections are a significant obstacle leading to PD discontinuation. Since catheter related infections (CRI), defined as exit site infections and/or tunnel infection, can progress to peritonitis, vigorous efforts are implemented in CRI prevention. Following an increased CRI rate in our institution, partially related to environmental organisms found in water distribution systems, we hypothesized that exit site care that includes prevention of water exposure-related pathogens may reduce CRI.

An Exploratory Analysis of Routine Ferritin Measurement Upon Admission and the Prognostic Implications of Low-Grade Ferritinemia During Inflammation.

Background: Serum ferritin is usually measured in the presence of anemia or in suspected iron overload syndromes. Ferritin is also an acute-phase protein that is elevated during systemic inflammation. However, the prognostic value of routinely measuring ferritin upon admission to a medical facility is not clear.

Indirect associations between immigration-related stressors and latine adolescents' depressive symptoms: The moderating roles of familism, nativity, and gender.

Objectives: This study examined the indirect relationship between immigration-related stressors and depressive symptoms via family conflict and whether familism values moderated this relationship in a sample of U.S. Latine youth.

ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development.

Congenital heart defects are the most prevalent human birth defects, and their incidence is exacerbated by maternal health conditions, such as diabetes during the first trimester (pregestational diabetes). Our understanding of the pathology of these disorders is hindered by a lack of human models and the inaccessibility of embryonic tissue. Using an advanced human heart organoid system, we simulated embryonic heart development under pregestational diabetes-like conditions.

Stretching Bonds without Breaking Symmetries in Density Functional Theory.

Kohn-Sham density functional theory (KS-DFT) stands out among electronic structure methods due to its balance of accuracy and computational efficiency. However, to achieve chemically accurate energies, standard density functional approximations in KS-DFT often need to break underlying symmetries, a long-standing "symmetry dilemma". By employing spin densities as the main variables in calculations (rather than total molecular densities, as in KS-DFT), we present an embedding framework in which this symmetry dilemma is understood and partially resolved.

A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization.

Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g.

Strong electron correlation from partition density functional theory.

Standard approximations for the exchange-correlation functional in Kohn-Sham density functional theory (KS-DFT) typically lead to unacceptably large errors when applied to strongly correlated electronic systems. Partition-DFT (PDFT) is a formally exact reformulation of KS-DFT in which the ground-state density and energy of a system are obtained through self-consistent calculations on isolated fragments, with a partition energy representing inter-fragment interactions. Here, we show how typical errors of the local density approximation (LDA) in KS-DFT can be largely suppressed through a simple approximation, the multi-fragment overlap approximation (MFOA), for the partition energy in PDFT.

Comparison of electrodiagnostic findings in acute traumatic versus chronic non-traumatic ulnar neuropathy at the elbow.

Introduction/aims: A common concept is that traumatic nerve injuries are more likely axonal, and that compressive neuropathies are more likely demyelinating. The purpose of this study was to compare traumatic versus non-traumatic ulnar neuropathy at the elbow (UNE) to look for electrodiagnostic differences between the two groups.

Methods: A retrospective 3 year review of UNE patients at two academic health science centers was conducted.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19.

Effectiveness of contingency management using transdermal alcohol monitoring to reduce heavy drinking among driving while intoxicated (DWI) arrestees: A randomized controlled trial.

Background: Driving while intoxicated (DWI) is a serious public health problem. However, treatment for DWI arrestees is not readily available. This study examines the effectiveness of a contingency management (CM) procedure using transdermal alcohol concentration (TAC) monitoring to reduce drinking among DWI arrestees.

Synthesis and biological evaluation of -inspired antimicrobials.

Due to the lack of new antimicrobial drug discovery in recent years and an ever-growing prevalence of multidrug-resistant "superbugs", there is a pressing need to explore alternative ways to combat pathogenic bacterial and fungal infections. Building upon our previous work in the field of medicinal phytochemistry, the present study is focused on designing, synthesizing, and testing the altered bioactivity of new variants of two original bioactive molecules found in the plant. Herein, we report upon 14 variants of berberine and four variants of chelerythrine that have been screened against a pool of 12 microorganisms (five Gram-positive and four Gram-negative bacteria, and three fungi).

Comparative analysis of CRP as a biomarker of the inflammatory response intensity among common viral infections affecting the lungs: COVID-19 versus influenza A, influenza B and respiratory syncytial virus.

Severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) is associated with significant morbidity and mortality. C-reactive protein (CRP) is a useful inflammatory biomarker for patients admitted with an infection. This study aimed to compare CRP level as an indicator of inflammation severity between SARS-CoV-2 and common respiratory viral infections.

Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin.

Early signaling of bacteremia in patients who present to the department of emergency medicine with relatively low C-reactive protein (CRP) concentrations.

Objectives: Examiningthe usefulness of C-reactive protein velocity (CRPv) as an early biomarker for the presence of bacteraemia in patients presenting to the Department of Emergency Medicine with acute infection/inflammation and suspected bacteraemia.

Methods: A retrospective study examining a cohort of patients who presented to the E.R and in whom blood cultures were taken.

ER stress and lipid imbalance drive embryonic cardiomyopathy in a human heart organoid model of pregestational diabetes.

Congenital heart defects constitute the most common birth defect in humans, affecting approximately 1% of all live births. The incidence of congenital heart defects is exacerbated by maternal conditions, such as diabetes during the first trimester. Our ability to mechanistically understand these disorders is severely limited by the lack of human models and the inaccessibility to human tissue at relevant stages.

Treatment of Pyoderma Gangrenosum With Mycophenolate and Hyperbaric Oxygen Therapy: A Case Report and Literature Review.

Pyoderma gangrenosum is an uncommon inflammatory ulcerative skin disorder with an unclear etiology. In many cases, it is associated with several underlying systemic diseases, with inflammatory bowel disease being the most common one. Since it does not have any specific clinical or laboratory findings, it is a diagnosis of exclusion.

Dual-Energy Computed Tomography (DECT) Resolves the Diagnostic Dilemma in an Atypically Presenting Case of Gout.

Gout is a common inflammatory arthropathy that presents as acute monoarthritis, most commonly of the first metatarsophalangeal (MTP) joint. Chronic polyarticular involvement may lead to confusion with other inflammatory arthropathies, including rheumatoid arthritis (RA). A thorough history, physical examination, synovial fluid analysis, and imaging are keys to establishing a correct diagnosis.