Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials.

Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

CAR/CSACI Practice Guidance for Contrast Media Hypersensitivity.

Contrast media, including iodinated contrast media and gadolinium-based contrast agents, are commonly administered pharmaceuticals with excellent safety profiles. However, a minority of the population may experience a hypersensitivity reaction following intravenous administration. Hypersensitivity reactions can be immediate or delayed, and range from mild, such as urticaria, to severe, including anaphylaxis.

Conserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer.

Clear cell kidney cancers are characterized both by conserved oncogenic driver events and by marked intratumor genetic and phenotypic heterogeneity, which help drive tumor progression, metastasis, and resistance to therapy. How these are reflected in transcriptional programs within the cancer and stromal cell components remains an important question with the potential to drive novel therapeutic approaches to treating cancer. To better understand these programs, we perform single-cell transcriptomics on 75 multi-regional biopsies from kidney tumors and normal kidney.

Expert advice from ResearchMatch volunteers: Recruitment Innovation Center use cases and innovation.

Involving participants in the design of clinical trials should improve the overall success of a study. For this to occur, streamlined mechanisms are needed to connect the populations potentially impacted by a given study or health topic with research teams in order to inform trial design in a meaningful and timely manner. To address this need, we developed an innovative mechanism called the "ResearchMatch Expert Advice Tool" that quickly obtains volunteer perspectives from populations with specific health conditions or lived experiences using the national recruitment registry, ResearchMatch.

Digital Dentists: A Curriculum for the 21st Century.

Future health professionals, including dentists, must critically engage with digital health technologies to enhance patient care. While digital health is increasingly being integrated into the curricula of health professions, its interpretation varies widely depending on the discipline, health care setting, and local factors. This viewpoint proposes a structured set of domains to guide the designing of a digital health curriculum tailored to the unique needs of dentistry in Australia.

Tie or do not tie: comparing knot tying hemostasis in tonsillectomy with other methods of hemostasis. A systematic review and meta-analysis.

Purpose: This meta-analysis sought to compare knot tying against other methods of haemostasis in terms of post-operative haemorrhage, intraoperative blood loss and tonsillectomy time.

Methods: Two independent reviewers performed a literature search according to PRISMA guidelines. Three databases were consulted, Pubmed, Google Scholar and Embase.

Utility of word embeddings from large language models in medical diagnosis.

Objective: This study evaluates the utility of word embeddings, generated by large language models (LLMs), for medical diagnosis by comparing the semantic proximity of symptoms to their eponymic disease embedding ("eponymic condition") and the mean of all symptom embeddings associated with a disease ("ensemble mean").

Materials And Methods: Symptom data for 5 diagnostically challenging pediatric diseases-CHARGE syndrome, Cowden disease, POEMS syndrome, Rheumatic fever, and Tuberous sclerosis-were collected from PubMed. Using the Ada-002 embedding model, disease names and symptoms were translated into vector representations in a high-dimensional space.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Olanzapine versus quetiapine in critically ill patients with hyperactive delirium: Protocol for a multicentre, cluster-randomised, double-crossover, pragmatic clinical trial (CALM-ICU).

Background: Patients in the intensive care unit (ICU) frequently develop hyperactive delirium, which may be accompanied by behaviour that increases clinical risks to themselves as well as other patients and staff. There is a paucity of evidence to inform the urgent enteral administration of antipsychotic drugs to treat such hyperactive delirium and behavioural disturbances.

Objective: The aim of this study is to test the efficacy and safety of administering enteral olanzapine when compared to quetiapine in critically ill patients with hyperactive delirium.

Unsymmetric triazine-based triglucoside detergents for membrane protein stability.

Membrane proteins play a crucial role in a variety of biological processes and are key targets for pharmaceutical development. Structural studies of membrane proteins provide molecular insights into the mechanisms of these processes and are essential for effective drug discovery. Historically, these studies have relied on solubilization of the target protein using detergents, but conventional detergents often fail to maintain the stability of challenging membrane proteins.

Correction: Communication interventions for medically unexplained symptom conditions in general practice: A systematic review and meta-analysis of randomised controlled trials.

[This corrects the article DOI: 10.1371/journal.pone.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

The Bacterial Cell Wall Components Lipopolysaccharide and Peptidoglycan Initiate Divergent Local Tissue and Systemic Inflammatory Response Profiles in the Chicken Model.

The innate immune system plays an important role in the defense against pathogens, whereby the ability to rapidly mount an effective inflammatory response is critical in the elimination/containment of the infection. To better understand the nature of the inflammatory responses to bacterial components in chickens, we used the growing feather (GF) cutaneous bioassay together with blood sampling to examine the local and systemic inflammatory responses initiated by intradermal (i.d.

HIV interventions across the care continuum for adolescents in high-burden countries: a systematic review and meta-analysis.

Background: Adolescents (10-19 years old) have poor outcomes across the prevention-to-treatment HIV care continuum, leading to significant mortality and morbidity. We conducted a systematic review and meta-analysis of interventions that documented HIV outcomes among adolescents in HIV high-burden countries.

Methods: We searched PubMed, EMBASE, Scopus, and the Cochrane Library for studies published between January 2015 and September 2024, assessing at least one HIV outcome along the prevention-to-care cascade, including PrEP uptake, HIV testing, awareness of HIV infections, ARV adherence, retention, and virological suppression.

Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease.

Absence of functional acid-α-glucosidase (GAA) leads to early-onset Pompe disease with cardiorespiratory and neuromuscular failure. A novel Pompe rat model ( ) was used to test the hypothesis that neonatal gene therapy with adeno-associated virus serotype 9 (AAV9) restores cardiorespiratory neuromuscular function across the lifespan. Temporal vein administration of AAV9-DES-GAA or sham (saline) injection was done on post-natal day 1; rats were studied at 6-12 months old.

Incarceration is associated with higher mortality after trauma: An unreported health care disparity.

Background: While the United States has the highest incarceration rate worldwide, at nearly 1% of the adult population (more than 2 million people), insights regarding health disparities in this population remain limited. This retrospective cohort study represents the largest national database analysis of incarcerated trauma patients to date and investigates whether incarceration status is an independent risk factor for poor outcomes after trauma for US adults.

Methods: We analyzed data from the National Trauma Data Bank from 2017 to 2018.

Systematic Review and Meta-Analysis: Risk Factors of Violence During First-Episode Psychosis.

Most people with a psychotic illness will never be violent; however, it is widely known that violence is more prevalent in this group compared to the general community, particularly during first-episode psychosis (FEP). Despite this, there is limited research into what contributes to this increased risk during FEP. The present systematic review aimed to identify whether certain risk factors are differentially associated with severity and timing of violence perpetration during FEP.

Meta-analyses reveal climate change impacts on an ecologically and economically significant oyster in Australia.

Global oceans are warming and acidifying because of increasing greenhouse gas emissions that are anticipated to have cascading impacts on marine ecosystems and organisms, especially those essential for biodiversity and food security. Despite this concern, there remains some skepticism about the reproducibility and reliability of research done to predict future climate change impacts on marine organisms. Here, we present meta-analyses of over two decades of research on the climate change impacts on an ecologically and economically valuable Sydney rock oyster, .

Global, regional, and national burden of primary liver cancer attributable to metabolic risks: an analysis of the Global Burden of Disease Study 1990-2021.

Background: The global burden of metabolic diseases is increasing, but estimates of their impact on primary liver cancer are uncertain. We aimed to assess the global burden of primary liver cancer attributable to metabolic risk factors, including high body mass index (BMI) and high fasting plasma glucose (FPG) levels, between 1990 and 2021.

Methods: The total number and age-standardized rates of deaths and disability-adjusted life years (DALYs) from primary liver cancer attributable to each metabolic risk factor were extracted from the Global Burden of Disease Study 1990-2021.

Oral fluid testing can be used to monitor xenotransplant donor herds for porcine cytomegalovirus/roseolovirus status.

A major concern of xenotransplantation is that donor organs may be a source of pathogens. One pathogen in particular, porcine cytomegalovirus (PCMV), a porcine roseolovirus (PRV), is thought to result in donor organ failure in an immunosuppressed state. Porcine cytomegalovirus is difficult to detect in organ donor swine because of its ability to establish latency.