Early major fracture care in polytrauma-priorities in the context of concomitant injuries: A Delphi consensus process and systematic review.

Background: The timing of major fracture care in polytrauma patients has a relevant impact on outcomes. Yet, standardized treatment strategies with respect to concomitant injuries are rare. This study aims to provide expert recommendations regarding the timing of major fracture care in the presence of concomitant injuries to the brain, thorax, abdomen, spine/spinal cord, and vasculature, as well as multiple fractures.

Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies.

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment. Within this landscape, the innate immune system, a critical sentinel protecting against tumor incursion, is a key player. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway has been found to be a linchpin of innate immunity: activation of this signaling pathway orchestrates the production of type I interferon (IFN-α/β), thus fostering the maturation, differentiation, and mobilization of immune effectors in the tumor microenvironment.

Large-scale pancreatic cancer detection via non-contrast CT and deep learning.

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible.

Evidence for the role of multidisciplinary team care in people with pelvic pain and endometriosis: A systematic review.

Background: Endometriosis is a chronic, inflammatory condition characterised by the presence of endometrial-like tissue outside the uterine cavity. Given the multi-system nature of the disease and the potential for significant negative impact on quality of life, there has been a long-standing recognition of the need for multidisciplinary care for people with endometriosis. However, there is paucity to the data supporting this approach, and much of the evidence is anecdotal.

Gumarontinib in patients with non-small-cell lung cancer harbouring exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial.

Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have exon 14 (ex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with ex14 skipping mutation-positive (ex14-positive) NSCLC.

Methods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan.

AGK Potentiates Arterial Thrombosis by Affecting Talin-1 and αIIbβ3-Mediated Bidirectional Signaling Pathway.

Background: AGK (acylglycerol kinase) was first identified as a mitochondrial transmembrane protein that exhibits a lipid kinase function. Recent studies have established that AGK promotes cancer growth and metastasis, enhances glycolytic metabolism and function fitness of CD8 T cells, or regulates megakaryocyte differentiation. However, the role of AGK in platelet activation and arterial thrombosis remains to be elaborated.

Tumor-targeted delivery of a STING agonist improvescancer immunotherapy.

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells.

A potent, broadly protective vaccine against SARS-CoV-2 variants of concern.

Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield.

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1.

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment.

SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication.

The recently identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. How this novel beta-coronavirus virus, and coronaviruses more generally, alter cellular metabolism to support massive production of ~30 kB viral genomes and subgenomic viral RNAs remains largely unknown. To gain insights, transcriptional and metabolomic analyses are performed 8 hours after SARS-CoV-2 infection, an early timepoint where the viral lifecycle is completed but prior to overt effects on host cell growth or survival.

Small-molecule mimicry hunting strategy in the imperial cone snail, .

Venomous animals hunt using bioactive peptides, but relatively little is known about venom small molecules and the resulting complex hunting behaviors. Here, we explored the specialized metabolites from the venom of the worm-hunting cone snail, Using the model polychaete worm , we demonstrate that venom contains small molecules that mimic natural polychaete mating pheromones, evoking the mating phenotype in worms. The specialized metabolites from different cone snails are species-specific and structurally diverse, suggesting that the cones may adopt many different prey-hunting strategies enabled by small molecules.

Study of the interactions of a novel monoclonal antibody, mAb059c, with the hPD-1 receptor.

Programmed cell death 1 (PD-1) monoclonal antibodies have been approved by regulatory agencies for the treatment of various types of cancer, and the mechanism involves the restoration of T cell functions. We report herein the X-ray crystal structure of a fully human monoclonal antibody mAb059c fragment antigen-binding (Fab) in complex with the PD-1 extracellular domain (ECD) at a resolution of 1.70 Å.

Search for rare decays of and Higgs bosons to and a photon in proton-proton collisions at = 13 .

A search is presented for decays of and Higgs bosons to a meson and a photon, with the subsequent decay of the to . The analysis uses data from proton-proton collisions with an integrated luminosity of 35.9 at collected with the CMS detector at the LHC.

SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

Objectives: Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.

An audit of pregnancy outcomes in solid organ transplant recipients at a metropolitan hospital.

Background: Pregnancies in patients with solid organ transplants have higher rates of complications and caesarean sections (CS).

Aim: To perform an audit of the pregnancy outcomes in transplant recipients, to determine the rate of CS in our cohort, the appropriate skin incision for CS in these patients and to formulate recommendations for preoperative planning.

Materials And Methods: This is a retrospective cohort study.

Targeting Transmembrane BAX Inhibitor Motif Containing 1 Alleviates Pathological Cardiac Hypertrophy.

Background: Cardiac hypertrophy and its resultant heart failure are among the most common causes of mortality worldwide. Abnormal protein degradation, especially the impaired lysosomal degradation of large organelles and membrane proteins, is involved in the progression of cardiac hypertrophy. However, the underlying mechanisms have not been fully elucidated.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments.

Formaldehyde Inhibits Sexual Behavior and Expression of Steroidogenic Enzymes in the Testes of Mice.

Background: Formaldehyde, a ubiquitous environmental pollutant, is used extensively and has been proved to impair male reproduction in mammals. However, no trials have explored whether formaldehyde affects sexual function.

Aim: To evaluate the effect of long-term formaldehyde exposure on sexual behavior and to investigate the potential mechanism.

Single-step ambient-air synthesis of graphene from renewable precursors as electrochemical genosensor.

Thermal chemical vapour deposition techniques for graphene fabrication, while promising, are thus far limited by resource-consuming and energy-intensive principles. In particular, purified gases and extensive vacuum processing are necessary for creating a highly controlled environment, isolated from ambient air, to enable the growth of graphene films. Here we exploit the ambient-air environment to enable the growth of graphene films, without the need for compressed gases.

Chronic Co-Administration of Sepiapterin and L-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice.

Background: Diabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and L-citrulline (L-Cit) is converted to endothelial nitric oxide synthase substrate, L-arginine. Whether SEP and L-Cit are effective at reducing diabetic heart disease is not known.

Lupane- and Friedelane-Type Triterpenoids from Celastrus stylosus.

Two new triterpenoids, 30-hydroxylup-20(29)-ene 3β-caffeate (1) and 24-nor-friedelan-6α,10-dihydroxy-1,2-dioxo-4,7-dien-29-oic acid (2), together with eight known compounds 3-10, were isolated from the roots of Celastrus stylosus. The structures of these compounds were elucidated on the basis of spectroscopic analyses. To the best of our knowledge, this represents the first study on the chemical constituents of C.

Treatment of supratentorial spontaneous intracerebral hemorrhage using image-guided minimally invasive surgery: Initial experiences of a flat detector CT-based puncture planning and navigation system in the angiographic suite.

Background And Purpose: The intracerebral hemorrhage drainage through minimally invasive approach is emerging as an alternative for traditional craniotomy, due to its improved survival rate and reduced complication rate. In this study, we investigated the feasibility and safety of a flat detector CT-based puncture planning and navigation system for minimally invasive hematoma drainage on patients with intracerebral hemorrhage.

Materials And Methods: The minimally invasive hematoma drainage was performed on 21 hypertensive patients with intracerebral hemorrhage in the angiographic suite with the guidance of a flat detector CT-based puncture planning and navigation system.

An effective method of anastomosis of the nasolacrimal canal.

An effective method of anastomosis of the nasolacrimal canal is summed up in data derived from 150 cases seen over 20 years at the People's Hospital of Jiangsu Province. This paper describes briefly this experience and analyses the success of this procedure.

Multi-system immunologically mediated disease: T lymphocyte deficiency and thyroid immunologic disease--a report of four cases.

Four cases are described of multi-system immunologically-mediated disease (systemic lupus erythematosus (two cases), polymyositis, and sarcoidosis) in association with thyroid autoimmunity. In all patients there was evidence of T lymphocyte deficiency, namely poor response of peripheral blood lymphocytes (PBL) to T cell mitogens (four cases) and failure or decreased ability to become sensitized to dinitrochlorobenzene (three cases), although two patients were ill and two were being treated with steroids. There was also evidence of B lymphocyte deficiency since PBL of no patient responded normally to pokeweed mitogen, a B and T lymphocyte mitogen.