Clinical Characteristics and Outcomes of Patients with Anti-MDA5 Antibody Associated Rapidly Progressive Interstitial Lung Disease (RP-ILD): A Case Series.

Objective: To describe the clinical profile and treatment outcomes of a longitudinal series of patients with rapidly progressive interstitial lung disease (RP-ILD) associated with anti MDA 5 antibody.

Methods: RP-ILD patients were identified from a prospective cohort of adult patients with idiopathic inflammatory myopathy (IIM). Clinical, demographic, and serological parameters of all patients were recorded using a structured proforma.

Fluorogenic Tetrazine Bioorthogonal Probes for Advanced Application in Bioimaging and Biomedicine.

A variety of bioorthogonal chemical tools have been developed and widely used in the study of biological phenomena in situ. Tetrazine bioorthogonal chemistry exhibits ultrafast reaction kinetics, excellent biocompatibility, and precise optical regulatory capabilities. Fluorogenic tetrazine bioorthogonal probes have achieved particularly diverse applications in bioimaging and disease diagnosis and treatment.

Sex and authorship in global cancer research.

Introduction: Research is an essential pillar of cancer control and key in shaping regional cancer control agendas. Imbalances in science and technology in terms of lack of female participation have been well documented. However, there is little evidence about country-level female participation in cancer research.

Challenges faced by women oncologists in Africa: a mixed methods study.

Objective: Recent studies have identified challenges facing women oncologists in Western contexts. However, similar studies in Africa have yet to be conducted. This study sought to determine the most common and substantial challenges faced by women oncologists in Africa and identify potential solutions.

Reduction of Streak Artifacts in the Superior Vena Cava for Better Visualization of Mediastinal Structures Through Virtual Monoenergetic Reconstructions Using a Photon-counting Detector Computed Tomography.

Purpose: Computed tomography (CT) is crucial in oncologic imaging for precise diagnosis and staging. Beam-hardening artifacts from contrast media in the superior vena cava can degrade image quality and obscure adjacent structures, complicating lymph node assessment. This study examines the use of virtual monoenergetic reconstruction with photon-counting detector CT (photon-counting CT) to mitigate these artifacts.

Hepatic conditioning results in better lung endothelial cell preservation under hypoxic environment in vitro.

Background: as we look to extend lung perfusion times (EVLP) to improve preservation, the metabolic activity of the lungs will require support from other organ functions. Active functional liver support, including detoxification, synthesis, and regulation, can improve lung preservation during EVLP. This study aimed to demonstrate the effects of hepatic conditioning of the EVLP perfusate on lung endothelium, via the receptor of advanced glycation end-products (RAGE)-nuclear-factor-κB (NF-κB) signaling in vitro.

Associations between inflammation and striatal dopamine D2-receptor availability in aging.

Background: Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.

Increasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein.

Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.

Staging of esophageal cancer using PET/MRI: a systematic review with head-to-head comparison.

Purpose: To evaluate the staging performance of positron emission tomography/magnetic resonance imaging (PET/MRI) for confirmed esophageal cancer based on the TNM classification system as well as compare it to other alternative modalities (e.g., endoscopic ultrasonography (EUS), computed tomography (CT), MRI, and PET/CT) in a full head-to-head manner.

Decoding pan-cancer treatment outcomes using multimodal real-world data and explainable artificial intelligence.

Despite advances in precision oncology, clinical decision-making still relies on limited variables and expert knowledge. To address this limitation, we combined multimodal real-world data and explainable artificial intelligence (xAI) to introduce AI-derived (AID) markers for clinical decision support. We used xAI to decode the outcome of 15,726 patients across 38 solid cancer entities based on 350 markers, including clinical records, image-derived body compositions, and mutational tumor profiles.

Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth.

Prostate cancer (PCa) growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). In this study, we identify lysine methyltransferase (KMT)9 as a regulator of PDC activity. KMT9 is localized in mitochondria of PCa cells, but not in mitochondria of other tumor cell types.

Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2.

The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis. Nuclear receptors (NRs) are now understood to be crucial in bone physiology and pathology. However, the function of the Farnesoid X receptor (FXR), a member of the NR family, in regulating bone homeostasis remains incompletely understood.

Comparative efficacy and safety of stent retrievers as a bailout strategy following failed contact aspiration technique in acute stroke thrombectomy.

Background: The contact aspiration (CA) technique is often used to perform endovascular thrombectomy (EVT) for acute ischemic stroke (AIS); however, rescue strategies are necessary if CA fails to achieve recanalization. This study investigates the outcomes of incorporating stent retriever (SR) thrombectomy in the rescue strategy following failed CA.

Methods: EVT patients with failed CA attempts were identified from a large multicenter registry and stratified by rescue technique: CA alone or incorporating SR in the rescue strategy.

Isoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples.

Many factors cause interperson variability in the activity and expression of the cytochrome P450 (CYP) drug-metabolizing enzymes in the liver, leading to variable drug exposure and treatment outcomes. Several liver-enriched transcription factors are associated with CYP expression, with estrogen receptor α (ESR1) and constitutive androstane receptor (CAR or NR1I3) being the 2 top factors. ESR1 and NR1I3 undergo extensive alternative splicing that results in numerous splice isoforms, but how these splice isoforms associate with CYP expression is unknown.

A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal Uptake of Para-Chloro-2-[F]Fluoroethyletomidate in Healthy Volunteers and Patients with Primary Aldosteronism.

Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA).

MIRD Pamphlet No. 32: A MIRD Recovery Coefficient Model for Resolution Characterization and Shape-Specific Partial-Volume Correction.

Accurate quantification in emission tomography is essential for internal radiopharmaceutical therapy dosimetry. Mean activity concentration measurements in objects with diameters less than 10 times the full width at half maximum of the imaging system's spatial resolution are significantly affected (>10%) by the partial-volume effect. This study develops a framework for PET and SPECT spatial resolution characterization and proposes 2 MIRD recovery coefficient models-a geometric mean approximation (RECOVER-GM) and an empirical model (RECOVER-EM)-that provide shape-specific partial-volume correction (PVC).

Dopaminergic Mechanisms of Cognitive Flexibility: An [F]Fallypride PET Study.

Cognitive flexibility is the ability to appropriately adapt one's thinking and behavior to changing environmental demands and is conceptualized as an aspect of executive function. The dopamine system has been implicated in cognitive flexibility; however, a direct, that is, neurochemical, link to cognitive flexibility has not been shown yet. The aim of this study was, therefore, to investigate how cognitive flexibility is mediated by dopaminergic signaling in the ventromedial prefrontal cortex (vmPFC).

Activation of megakaryocytic leukemia 1 in endothelial cells contributes to diabetic retinopathy in mice.

Aims: Diabetic retinopathy (DR) represents one of the most devastating sequences in patients with diabetes. Endothelial dysfunction is a key pathological feature and contributing factor to DR. In the present study we investigated the role of megakaryocytic leukemia 1 (MKL1) in DR pathogenesis.

Identification, structure, and agonist design of an androgen membrane receptor.

Androgens, such as 5α-dihydrotestosterone (5α-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5α-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5α-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition.

Investigation of the effects and mechanism of Total Glycosides of paeony against Radiation-Induced brain injury through network Pharmacology, molecular docking and experimental Verification.

Background: Total glucosides of paeony (TGP), derived from the dried root of Paeonia, is a popular treatment for immune diseases. Radiation induced brain injury (RBI) is a common side effect of brain radiation therapy, but the efficacy of TGP in treating RBI remains uncertain.

Purpose: To evaluate the protective effects of TGP against RBI and elucidate its underlying mechanisms using pharmacological network analysis, molecular docking, and experimental validation.

Small-molecule activators of NRF1 transcriptional activity prevent protein aggregation.

Intracellular protein aggregation causes proteotoxic stress, underlying highly debilitating neurodegenerative disorders in parallel with decreased proteasome activity. Nevertheless, under such stress conditions, the expression of proteasome subunits is upregulated by Nuclear Factor Erythroid 2-related factor 1 (NRF1), a transcription factor that is encoded by NFE2L1. Activating the NRF1 pathway could accordingly delay the onset of neurodegenerative and other disorders with impaired cell proteostasis.

Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey.

Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.

Multiplex generation and single-cell analysis of structural variants in mammalian genomes.

Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) methods to generate, map, and characterize SVs in model systems are underdeveloped. To address these challenges, we developed Genome-Shuffle-seq, a method that enables the multiplex generation and mapping of thousands of SVs (deletions, inversions, translocations, and extrachromosomal circles) throughout mammalian genomes. We also demonstrate the co-capture of SV identity with single-cell transcriptomes, facilitating the measurement of SV impact on gene expression.

Urinary DNA Methylation Test for Bladder Cancer Diagnosis.

Importance: An accurate noninvasive biomarker test is needed for the early diagnosis of bladder cancer.

Objective: To evaluate the performance of a urinary DNA methylation test (PENK methylation) and compare its diagnostic accuracy with that of the nuclear matrix protein 22 (NMP22) test or urine cytology test.

Design, Setting, And Participants: In this prospective multicenter study at 10 sites in the Republic of Korea, individuals 40 years and older with hematuria undergoing cystoscopy within 3 months between March 11, 2022, and May 30, 2024, participated.

Incisional PSMA PET/CT-positive recurrences in prostate cancer- is there an implication on clinical care?

Oligorecurrent prostate cancer (PCa) can be treated with metastasis-directed therapy (MDT), which may be performed using radioguided surgery (RGS) as an experimental approach. These procedures have shown promising outcomes, largely due to the high lesion detection rate of positron emission tomography/computed tomography (PET/CT). We present a case series of patients who underwent RGS following robot-assisted radical prostatectomy (RARP).