A prospective, multicenter analysis of the integrated 31-gene expression profile test for sentinel lymph node biopsy (i31-GEP for SLNB) test demonstrates reduced number of unnecessary SLNBs in patients with cutaneous melanoma.

Background: National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for patients with > 10% risk of positivity, consider SLNB with 5-10% risk, and foregoing with < 5% risk. The integrated 31-gene expression profile (i31-GEP) algorithm combines the 31-GEP with clinicopathologic variables, estimating SLN positivity risk.

Methods: The i31-GEP SLNB risk prediction accuracy was assessed in patients with T1-T2 tumors enrolled in the prospective, multicenter DECIDE study (n = 322).

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

The Effect of Window Size on Pathologists' Search for Rare Elements in a Digital Pathology Setting.

Context.—: Digital pathology requires pathologists to assess tissue digitally rather than on an analog microscope, which has been the mainstay tool for tissue assessment for more than a century. The impact of different digital interaction configurations on pathologists' performance is not well understood.

A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth.

Clade 2.3.4.

Risk factors for venous thromboembolism in patients undergoing neoadjuvant chemotherapy as treatment for ovarian cancer.

Objective: During the treatment of ovarian cancer, the risk of venous thromboembolism (VTE) post operatively is well established, however, patients may be at even greater risk during neoadjuvant chemotherapy (NACT). This study aimed to determine the incidence and timing of VTE amongst patients undergoing NACT, whether there was an association with survival, and examine risk factors associated with the development of VTE.

Study Design: This was a retrospective cohort study of patients diagnosed with ovarian, fallopian tube and primary peritoneal cancer receiving neoadjuvant chemotherapy betweenApril 2011 and April 2022 at a gynaecological cancer centre in England.

Empowering professionals: a multidisciplinary approach to supporting people seeking asylum and refugees.

People seeking asylum and refugees living in initial accommodation in the UK can experience significant barriers to accessing care. They often have complex health and social needs and may experience fragmentation in the delivery of services. The Respond Integrated Refugee Health Service, hosted by University College London Hospital and operating across North Central London, has been created to address some of these challenges.

Influence of maternal nutrition and one-carbon metabolites supplementation on bovine antimicrobial peptides in fetal and maternal tissues.

Introduction: Maternal nutrition during pregnancy critically influences offspring development and immune function. One-carbon metabolites (OCM) are epigenetic modifiers that may modulate antimicrobial peptide (AMP) expression, which is vital for innate immunity. This study investigated the effects of maternal nutrient restriction and OCM supplementation on mRNA expression of AMP in fetal and maternal lung, mammary gland, and small intestine of beef cattle.

Structural and Functional Insights into the Evolution of SARS-CoV-2 KP.3.1.1 Spike Protein.

The JN.1-sublineage KP.3.

Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines.

Current COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth understanding of the antigenic and immunogenic properties of available vaccines. Here we examined the antigenicity of two of the original COVID-19 vaccines, mRNA-1273 and NVX-CoV2373, by electron microscopy-based polyclonal epitope mapping (EMPEM) of serum from immunized non-human primates (NHPs) and clinical trial donors.

International Symposium on Ruminant Physiology: Maternal nutrient supply: Impacts on physiological and whole animal outcomes in offspring.

Demands for animal products are projected to increase in the future, and animal production is key to agricultural sustainability and food security; consequently, enhancing ruminant livestock production efficiencies in sustainable ways is a major goal for the livestock industry. Developmental programming is the concept that various stressors, including compromised maternal nutrition during critical developmental windows will result in both short- and long-term changes in the offspring. Ruminant models of developmental programming indicate that compromised maternal nutrition, including global under and over-nutrition, macronutrients, and specific micronutrients, including amino acids (Met and Arg), vitamins (folate, B, and choline), and minerals (sulfur, cobalt, and selenium) can alter offspring outcomes.

International Symposium on Ruminant Physiology: One-carbon metabolism in beef cattle throughout the production cycle.

One-carbon metabolism (OCM) is a series of connected pathways involving the methionine-folate cycles, transsulfuration, polyamine synthesis, nucleotide synthesis, free-radical scavenging, and energy metabolism. These pathways functionally depend upon amino acids (methionine, glycine, and serine), vitamins (folate, B, B, and B), and minerals (sulfur, cobalt, and zinc). Growing bodies of research indicate that in beef cattle, physiological stage, nutritional plane, diet, species (Bos taurus vs.

A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer.

RAS is a common driver of cancer that was considered undruggable for decades. Recent advances have enabled the development of RAS inhibitors, but the efficacy of these inhibitors remains limited by resistance. Here, we developed a pan-RAS inhibitor, ADT-007, that binds nucleotide-free RAS to block GTP activation of effector interactions and MAPK/AKT signaling, resulting in mitotic arrest and apoptosis.

Innovative transgenic zebrafish biosensor for heavy metal detection.

Heavy metal contamination is an urgent environmental issue that poses a significant threat to human health and the ecosystem. To mitigate the adverse impacts of heavy metal pollution, the aim of this research was to develop genetically engineered zebrafish as biosensors, which offer a promising alternative for detecting heavy metal exposure, specifically Cd⁺ and Zn⁺. A novel heavy metal-sensitive gene construct metallothionine 2 promoter with DsRed reporter gene (mt2-DsRed2) was synthesized and integrated into zebrafish embryos using a Tol2 transposon transposase system with the transgenic zebrafish line subjected to biosensing applications for Cd and Zn.

Tetrodotoxin toxicity: an increasing threat.

A man aged in his sixties presented to the emergency department with vomiting, dizziness and generalised weakness preceded by perioral and peripheral paraesthesias for several hours. He did not speak English and was visiting from overseas. Examination revealed multidirectional nystagmus, subtle bilateral ptosis, marked bilateral upper limb dysmetria and heel-shin ataxia, with mild proximal limb weakness.

Towards U-Net-based intraoperative 2D dose prediction in high dose rate prostate brachytherapy.

Background: Poor needle placement in prostate high-dose-rate brachytherapy (HDR-BT) results in sub-optimal dosimetry and mentally predicting these effects during HDR-BT is difficult, creating a barrier to widespread availability of high-quality prostate HDR-BT.

Purpose: To provide earlier feedback on needle implantation quality, we trained machine learning models to predict 2D dosimetry for prostate HDR-BT on axial TRUS images.

Methods And Materials: Clinical treatment plans from 248 prostate HDR-BT patients were retrospectively collected and randomly split 80/20 for training/testing.

Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.

HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood.

High recent PrEP adherence with point-of-care urine tenofovir testing and adherence counselling among young African women: results from the INSIGHT cohort.

Introduction: Adolescent girls and young women (AGYW) account for two-thirds of new HIV infections in Africa. African AGYW have had high uptake of oral HIV pre-exposure prophylaxis (PrEP) but low adherence, which might be improved by point-of-care adherence monitoring with tailored counselling.

Methods: From August 2022 to July 2023, we conducted a PrEP demonstration project with sexually active AGYW ages 16-30 years from 20 sites in South Africa, Eswatini, Kenya, Malawi, Uganda and Zambia.

Mode of Action and Mechanisms of Resistance to the Unusual Polyglycosylated Thiopeptide Antibiotic Persiathiacin A.

Persiathiacin A is a novel thiopeptide antibiotic produced by species UTMC 2448. It has potent activity against methicillin-resistant (MRSA) and . Thiopeptides, including persiathiacin A, exhibit antibacterial activity by inhibiting protein synthesis.

Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.

During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure.

The effectiveness of integrating making every contact count into an undergraduate medical curriculum.

Objective: To evaluate the feasibility and effectiveness of integrating Making Every Contact Count (MECC) using Healthy Conversation Skills (HCS) into an undergraduate medical curriculum and test the performance of an associated assessment.

Methods: Concepts were introduced to second year students through lectures, small group seminars, role-plays and a new Objective Structured Clinical Examination (OSCE).station.

One must imagine Sisyphus happy: Integrative taxonomic characterization of 22 new Ceroptres species (Hymenoptera: Cynipidae: Ceroptresini).

We describe new species in the genus Ceroptres Hartig, 1840 (Hymenoptera: Cynipidae: Ceroptresini) represented by voucher material sequenced by Ward et al. (2024). We describe 22 new species, all authored by Nastasi, Smith, & Davis: C.

Anterior Approach for Fixation of Acetabular Fractures Using Anatomically Designed Plates: Maintenance of Reduction and Functional Outcomes at a Minimum Five-Year Follow-Up.

Background Acetabular fractures with quadrilateral plate involvement have been shown to have a high rate of complications. Anatomic suprapectineal plating systems have been developed to manage these injuries with good short-term outcomes. However, long-term maintenance of anatomical reduction and functional outcomes has yet to be established.

Interconnected health: A concept analysis of planetary empathy for healthcare professionals.

Background: Planetary Health emphasizes the interconnectedness of human health and the natural environment. Despite this, human-induced destruction of ecosystems threatens planetary stability. Understanding planetary empathy may offer insights into how healthcare professionals can better live and work with nature.