Investigating the Impact of Glycogen-Depleting Exercise Combined with Prolonged Fasting on Autophagy and Cellular Health in Humans: A Randomised Controlled Crossover Trial.

Importance: Although prolonged fasting has become increasingly popular, the favourable biological adaptations and possible adverse effects in humans have yet to be fully elucidated.

Objective: To investigate the effects of a three-day water-only fasting, with or without exercise-induced glycogen depletion, on autophagy activation and the molecular pathways involved in cellular damage accumulation and repair in healthy humans.

Design: A randomised, single-centre, two-period, two-sequence crossover trial.

A novel 4,4-dimethylcytidine in the archaeal ribosome enhances hyperthermophily.

Ribosome structure and activity are challenged at high temperatures, often demanding modifications to ribosomal RNAs (rRNAs) to retain translation fidelity. LC-MS/MS, bisulfite-sequencing, and high-resolution cryo-EM structures of the archaeal ribosome identified an RNA modification, 4,4-dimethylcytidine (mC), at the universally conserved C918 in the 16S rRNA helix 31 loop. Here, we characterize and structurally resolve a class of RNA methyltransferase that generates mC whose function is critical for hyperthermophilic growth.

Observation-first versus angioembolization-first approach in stable patients with blunt liver trauma: A WTA multicenter study.

Background: Prior studies evaluating observation versus angioembolization (AE) for blunt liver injuries (BLT) with contrast extravasation (CE) on computed tomography imaging have yielded inconsistent conclusions, primarily due to limitations in single-center and/or retrospective study design. Therefore, this multicenter study aims to compare an observation versus AE-first approach for BLT, hypothesizing decreased liver-related complications (LRCs) with observation.

Methods: We conducted a post hoc analysis of a multicenter, prospective observational study (2019-2021) across 23 centers.

Are we closer to achieving precision medicine for migraine treatment? A narrative review.

Background: The term 'precision medicine' encompasses strategies to optimize diagnosis and outcome prediction and to tailor treatment for individual patients, in consideration of their unique characteristics. The greater availability of multifaceted datasets and strategies to model such data have made precision medicine increasingly possible in recent years. Precision medicine is especially needed in the migraine field since the response to migraine treatments is not universal amongst all individuals with migraine.

Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality.

Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality.

The extensive mC epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily.

RNAs are often modified to invoke new activities. While many modifications are limited in frequency, restricted to non-coding RNAs, or present only in select organisms, 5-methylcytidine (mC) is abundant across diverse RNAs and fitness-relevant across Domains of life, but the synthesis and impacts of mC have yet to be fully investigated. Here, we map mC in the model hyperthermophile, Thermococcus kodakarensis.

Real-time cognitive performance metrics derived from a digital therapeutic for inattention predict ADHD-related clinical outcomes: Replication across three independent trials of AKL-T01.

AKL-T01 is a digital therapeutic (DTx) that targets attention by generating conflict at dynamically updated difficulty levels during a multitasking game. Clinical trials support AKL-T01's efficacy in attention-deficit/hyperactivity disorder (ADHD), but there is a need to understand how in-game data can be used to monitor patient changes in cognition. We aimed to derive a real-time measure of attention from AKL-T01 gameplay data and validate it against clinical outcomes.

Complete absence of GLUT1 does not impair human terminal erythroid differentiation.

The glucose transporter 1 (GLUT1) is 1 of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans.

The Differentiation between Progressive Disease and Treatment-Induced Effects with Perfusion-Weighted Arterial Spin-Labeling in High-Grade Gliomas.

Background And Purpose: Treatment-induced effects are difficult to differentiate from progressive disease in radiologically progressing diffuse gliomas after treatment. This retrospective, single-center cohort study investigated the diagnostic value of arterial spin-labeling perfusion in differentiating progressive disease from treatment-induced effects in irradiated patients with a high-grade glioma.

Materials And Methods: Adults with a high-grade glioma diagnosed between January 1, 2012, and December 31, 2018, with a new or increasing contrast-enhancing lesion after radiotherapy with or without chemotherapy and arterial spin-labeling were consecutively included.

T2-FLAIR Mismatch: An Imaging Biomarker for Children's -Altered Diffuse Astrocytoma or Angiocentric Glioma.

Background And Purpose: T2-FLAIR mismatch is a highly specific imaging biomarker of -mutant diffuse astrocytoma in adults. It has however also been described in -altered low grade tumors. Our aim was to assess the diagnostic power of the T2-FLAIR mismatch in -mutant astrocytoma and -altered low-grade tumors in children and correlate this mismatch with histology.

Engineered IgM and IgG cleaving enzymes for mitigating antibody neutralization and complement activation in AAV gene transfer.

Systemic dosing of adeno-associated viral (AAV) vectors poses potential risk of adverse side effects including complement activation triggered by anti-capsid immunity. Due to the multifactorial nature of toxicities observed in this setting, a wide spectrum of immune modulatory regimens are being investigated in the clinic. Here, we discover an IgM cleaving enzyme (IceM) that degrades human IgM, a key trigger in the anti-AAV immune cascade.

Age and sex influence antibody profiles associated with tuberculosis progression.

Antibody features vary with tuberculosis (TB) disease state. Whether clinical variables, such as age or sex, influence associations between Mycobacterium tuberculosis-specific antibody responses and disease state is not well explored. Here we profiled Mycobacterium tuberculosis-specific antibody responses in 140 TB-exposed South African individuals from the Adolescent Cohort Study.

A novel preoperative score to predict severe acute cholecystitis.

Background: In a large multicenter trial, The Parkland Grading Scale (PGS) for acute cholecystitis outperformed other grading scales and has a positive correlation with complications but is limited in its inability to preoperatively predict high-grade cholecystitis. We sought to identify preoperative variables predictive of high-grade cholecystitis (PGS 4 or 5).

Methods: In a six-month period, patients undergoing cholecystectomy at a single institution with prospectively graded PGS were analyzed.

Synthesis of bioengineered heparin chemically and biologically similar to porcine-derived products and convertible to low MW heparin.

Heparins have been invaluable therapeutic anticoagulant polysaccharides for over a century, whether used as unfractionated heparin or as low molecular weight heparin (LMWH) derivatives. However, heparin production by extraction from animal tissues presents multiple challenges, including the risk of adulteration, contamination, prion and viral impurities, limited supply, insecure supply chain, and significant batch-to-batch variability. The use of animal-derived heparin also raises ethical and religious concerns, as well as carries the risk of transmitting zoonotic diseases.

Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function.

Background: While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence.

Guidelines for Specialized Epilepsy Centers: Executive Summary of the Report of the National Association of Epilepsy Centers Guideline Panel.

The National Association of Epilepsy Centers first published the guidelines for epilepsy centers in 1990, which were last updated in 2010. Since that update, epilepsy care and the science of guideline development have advanced significantly, including the importance of incorporating a diversity of stakeholder perspectives such as those of patients and their caregivers. Currently, despite extensive published data examining the efficacy of treatments and diagnostic testing for epilepsy, there remain significant gaps in data identifying the essential services needed for a comprehensive epilepsy center and the optimal manner for their delivery.

Treatment-associated imaging changes in newly diagnosed MGMT promoter-methylated glioblastoma undergoing chemoradiation with or without cilengitide.

Background: Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.

Methods: Patients with ≥ 3 follow-up MRIs were included.