A synthetic cyclic peptide for promoting antigen presentation and immune activation.

Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action.

Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.

Deep learning empowered sensor fusion boosts infant movement classification.

Background: To assess the integrity of the developing nervous system, the Prechtl general movement assessment (GMA) is recognized for its clinical value in diagnosing neurological impairments in early infancy. GMA has been increasingly augmented through machine learning approaches intending to scale-up its application, circumvent costs in the training of human assessors and further standardize classification of spontaneous motor patterns. Available deep learning tools, all of which are based on single sensor modalities, are however still considerably inferior to that of well-trained human assessors.

Myristoylated Eepd1 Enhances Lipolysis and Thermogenesis through PKA Activation to Combat Obesity.

Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset.

Lattice defect engineering advances n-type PbSe thermoelectrics.

Te-free thermoelectrics have garnered significant interest due to their immense thermoelectric potential and low cost. However, most Te-free thermoelectrics have relatively low performance because of the strong electrical and thermal transport conflicts and unsatisfactory compatibility of interfaces between device materials. Here, we develop lattice defect engineering through Cu doping to realize a record-high figure of merit of ~1.

Metagenome-guided culturomics for the targeted enrichment of gut microbes.

The gut microbiome significantly impacts human health, yet cultivation challenges hinder its exploration. Here, we combine deep whole-metagenome sequencing with culturomics to selectively enrich for taxa and functional capabilities of interest. Using a modified commercial base medium, 50 growth modifications were evaluated, spanning antibiotics, physico-chemical conditions, and bioactive compounds.

DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer.

Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition.

Patient reported tools for assessing potential medicine-related symptoms: A systematic review.

Background: Medicine-related symptom assessment tools have been developed to assist healthcare professionals in detecting potential medicine-related symptoms. This systematic review aimed to identify and evaluate the measurement properties of medicine-related symptom assessment tools.

Method: A systematic search was conducted in Ovid Medline, Ovid Embase, Ovid PsychInfo, and SCOPUS databases up to March 16, 2024.

The metabolic costs of cognition.

Cognition and behavior are emergent properties of brain systems that seek to maximize complex and adaptive behaviors while minimizing energy utilization. Different species reconcile this trade-off in different ways, but in humans the outcome is biased towards complex behaviors and hence relatively high energy use. However, even in energy-intensive brains, numerous parsimonious processes operate to optimize energy use.

A review of imaging in the diagnosis and management of complicated paediatric pneumonia.

Paediatric pneumonia and its complications present substantial health and economic challenges. While chest radiographs are commonly used as the initial imaging modality for diagnosing uncomplicated pneumonia, they are less effective for complicated cases. In response, various imaging techniques, such as lung ultrasound, computed tomography (CT), and chest MRI, have been integrated into clinical practice to enhance diagnosis and guide management decisions.

Reacting to reductive stress at the mitochondrial import gate.

A byproduct of mitochondrial energy production is the generation of reactive oxygen species (ROS). Too much ROS is toxic, but ROS deficiency is equally deleterious (reductive stress). In a recent study, McMinimy et al.

The trochlea for the intermediate tendon of the digastric muscle: a review.

This review explores the novel perspective that the intermediate tendon of the digastric muscle may function as an anatomical trochlear pulley system within the human body, challenging the traditional understanding of trochlear systems. While widely recognized trochlear units include structures like the medial part of the humerus and the superior oblique muscle of the orbit, the review focuses on the unique anatomical arrangement of the intermediate tendon of the digastric muscle in connection with the anterior and posterior bellies of the digastric muscles. Despite current debates within the anatomical community about labeling the digastric muscles as having a trochlea, this paper delves into the scientific definition of a trochlear pulley system, presenting the intermediate tendon of the digastric muscle as a potential trochlea.

You cannot be what you cannot see: a retrospective natural longitudinal cohort study exploring the impact of face-to-face rural immersion on student medical training satisfaction and intention to practice rurally.

Objective: Community-engaged immersive rural experiences were limited during the COVID-19 pandemic when online learning was instigated across medical institutions globally. This study aimed to explore the impact of online learning on medical students' satisfaction levels and intentions to practice in a rural area after graduation.

Design, Setting And Participants: We conducted a natural quasi-experimental longitudinal retrospective cross-sectional study during 2011-2022 for all Australian domestic medical students who undertook a Rural and Remote Medicine (RRM) placement at the University of Queensland.

Retrospective observational study of the association of peak blood glucose during the second 24 hours of admission with hospital-acquired complications in non-critical care admissions to a tertiary referral teaching hospital.

Introduction: Stress hyperglycaemia at hospital presentation is associated with poorer outcomes. Less is known about the risk of poorer outcomes according to achieved glycaemia early in the admission.

Research Design/methods: This was a retrospective observational study of patients admitted to non-critical care wards.

"Part of the world again": qualitative enquiry into community participation during inpatient rehabilitation and transition years following severe brain injury.

Purpose: To understand the experience of community and social participation for people with severe ABI during inpatient rehabilitation and the transition years.

Methods: Constructivist grounded theory methodology informed participant recruitment and data analysis. Adults with ABI were recruited using purposive sampling and data collected via in-depth interviews.

Concurrent leiomyosarcoma causing small bowel obstruction in a patient with non-Hodgkin lymphoma.

Small bowel obstruction (SBO) is a leading cause of general surgery inpatient admissions. SBO is most commonly associated with postoperative adhesions; however, neoplastic SBO is an important differential. Here, we present a case of neoplastic SBO secondary to leiomyosarcoma in a patient with known mature B cell lymphoma.

Refractory pyoderma gangrenosum-like ulcerations in granulomatosis with polyangiitis treated successfully with rituximab.

Granulomatosis with polyangiitis (GPA) is a small-to-medium vessel vasculitis that can affect the skin, respiratory tract, kidneys and other organs. A rare cutaneous manifestation of GPA is pyoderma gangrenosum (PG)-like ulcerations, which can have debilitating and disfiguring consequences. We report the case of a man in his 40s with refractory PG-like ulcerations secondary to GPA, not responsive to conventional immunosuppression, who was successfully treated with rituximab.

Excipient lung disease with transient severe pulmonary hypertension in a healthcare professional injecting crushed oxycodone tablets.

Excipient lung disease (ELD) is a rare cause of pulmonary hypertension that occurs due to the intravenous injection of crushed tablets. We present the case of a healthcare professional in her late 30s who presented with a fever in the setting of a bacteraemia. During her hospital admission, she established a pattern of transient hypoxia and hypotension, with resolution without targeted management or clear cause identified.

Decoding gene expression dynamics during seed development in sesame (Sesamum indicum L.) through RNA-Seq analysis.

Sesame (Sesamum indicum L., 2n = 2× = 26) from the Pedaliaceae family is primarily grown for its high oil content, rich in unsaturated fatty acids like linoleic acid (LA) and alpha-linolenic acid (ALA). However, the molecular mechanisms of sesame oil accumulation remain poorly understood.