The factor XIa antibody osocimab strongly inhibits clotting in extracorporeal circuits with human blood and in baboons.

Background: Effective anticoagulant approaches in extracorporeal circuits with little impact on hemostasis are still an unmet medical need. Targeted inhibition of activated factor (F)XI might represent an attractive alternative or addition to conventional anticoagulation.

Objectives: We aimed to evaluate the additional antithrombotic effect of the monoclonal anti-FXIa antibody osocimab in in vitro and in vivo models of extracorporeal circulation.

Invasive disease-free and overall survival after (neo)adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive, HER2-negative early breast cancer treated with upfront letrozole: Experiences from the phase IV PreFace trial.

Patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) breast cancer (BC) benefit less from neoadjuvant chemotherapy (NACT) than patients with triple-negative and HER2-positive BC. In this retrospective analysis of the phase IV PreFace clinical trial (NCT01908556), where postmenopausal HRpos BC patients (n = 3297) were treated with 5-year upfront adjuvant letrozole therapy, we evaluated the prognosis of patients treated with adjuvant versus neoadjuvant chemotherapy in HRpos/HER2neg early-stage BC. HRpos/HER2neg patients with information on (neo)adjuvant chemotherapy (n = 2895) were retrospectively selected from all patients enrolled in the PreFace trial.

Ecosystem-wide PFAS characterization and environmental behavior at a heavily contaminated desert oasis in the southwestern U.S.

Record-high PFAS contamination levels were recently reported in birds and small mammals from Holloman Lake, a high-salinity wastewater oasis located in southern New Mexico, USA. We expanded the PFAS screening to surface water, soils, algae, invertebrates, fish, reptiles, and a larger number of plants, birds, and mammals to examine the fate, transport, and bioaccumulation of PFAS in the ecosystem and generate contamination profiles across both the water-land interface and multiple trophic levels. C5 and C6 perfluorocarboxylic acids, both of them known degradation products of 6:2 FTS, were the dominant PFAS in surface water in the lake.

Fluorinated trehalose analogues for cell surface engineering and imaging of .

The sensitive, rapid and accurate diagnosis of () infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole.

Background: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials.

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice.

Development of a sensitive real-time quaking-induced conversion (RT-QuIC) assay for application in prion-infected blood.

Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided by the development of a sensitive diagnostic test that could be routinely used to screen blood donations. As blood samples from vCJD patients are extremely rare, here we describe the optimisation of real-time quaking-induced conversion (RT-QuIC) for detection of PrPSc (misfolded prion protein, a marker of prion infection) in blood samples from an established large animal model of vCJD, sheep experimentally infected with bovine spongiform encephalopathy (BSE). Comparative endpoint titration experiments with RT-QuIC, miniaturized bead protein misfolding cyclic amplification (mb-PMCA) and intracerebral inoculation of a transgenic mouse line expressing sheep PrP (tgOvARQ), demonstrated highly sensitive detection of PrPSc by RT-QuIC in a reference sheep brain homogenate.

Sweet and sour synergy: exploring the antibacterial and antibiofilm activity of acetic acid and vinegar combined with medical-grade honeys.

, a combination of honey and vinegar, has been used as a remedy for wounds and infections in historical and traditional medical settings. While honey is now clinically used to treat infected wounds, this use of a complex, raw natural product (NP) mixture is unusual in modern western medicine. Research into the antimicrobial activity of NPs more usually focuses on finding a single active compound.

Climate-driven variation in dispersal ability predicts responses to forest fragmentation in birds.

Species sensitivity to forest fragmentation varies latitudinally, peaking in the tropics. A prominent explanation for this pattern is that historical landscape disturbance at higher latitudes has removed fragmentation-sensitive species or promoted the evolution of more resilient survivors. However, it is unclear whether this so-called extinction filter is the dominant driver of geographic variation in fragmentation sensitivity, particularly because climatic factors may also cause latitudinal gradients in dispersal ability, a key trait mediating sensitivity to habitat fragmentation.

Glimmers of hope in large carnivore recoveries.

In the face of an accelerating extinction crisis, scientists must draw insights from successful conservation interventions to uncover promising strategies for reversing broader declines. Here, we synthesize cases of recovery from a list of 362 species of large carnivores, ecologically important species that function as terminal consumers in many ecological contexts. Large carnivores represent critical conservation targets that have experienced historical declines as a result of direct exploitation and habitat loss.

Scientists' warning on population.

Humanity must commit to transformative change on all levels in order to address the climate emergency and biodiversity collapse. In particular, stabilizing and ultimately reducing the human population size is necessary to ensure the long-term wellbeing of our species and other life on Earth. We show how this transition can be accomplished in an equitable framework that promotes human rights.

Subclinical infection occurs frequently following low dose exposure to prions by blood transfusion.

Infectious prion diseases have very long incubation periods, and the role that subclinical infections play in transmission, persistence and re-emergence of these diseases is unclear. In this study, we used a well-established model of vCJD (sheep experimentally infected with bovine spongiform encephalopathy, BSE) to determine the prevalence of subclinical infection following exposure by blood transfusion from infected donors. Many recipient sheep survived for years post-transfusion with no clinical signs and no disease-associated PrP (PrP) found in post mortem tissue samples by conventional tests.

Zafirlukast Induces VHL- and HIF-2α-Dependent Oxidative Cell Death in 786-O Clear Cell Renal Carcinoma Cells.

Mutations in the Von Hippel-Lindau (VHL) gene are the driving force in many forms of clear cell renal cell carcinoma (ccRCC) and promote hypoxia-inducible factor (HIF)-dependent tumor proliferation, metastasis and angiogenesis. Despite the progress that has already been made, ccRCC generally remain resistant to conventional therapies and ccRCC patients suffer from metastasis and acquired resistance, highlighting the need for novel therapeutic options. Cysteinyl leukotriene receptor 1 (CysLTR1) antagonists, like zafirlukast, are administered in bronchial asthma to control eicosanoid signaling.

The evolution, ecology, and conservation of hummingbirds and their interactions with flowering plants.

The ecological co-dependency between plants and hummingbirds is a classic example of a mutualistic interaction: hummingbirds rely on floral nectar to fuel their rapid metabolisms, and more than 7000 plant species rely on hummingbirds for pollination. However, threats to hummingbirds are mounting, with 10% of 366 species considered globally threatened and 60% in decline. Despite the important ecological implications of these population declines, no recent review has examined plant-hummingbird interactions in the wider context of their evolution, ecology, and conservation.

Producing wood at least cost to biodiversity: integrating Triad and sharing-sparing approaches to inform forest landscape management.

Forest loss and degradation are the greatest threats to biodiversity worldwide. Rising global wood demand threatens further damage to remaining native forests. Contrasting solutions across a continuum of options have been proposed, yet which of these offers most promise remains unresolved.

Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection.

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model.

A forest loss report card for the world's protected areas.

Protected areas are a key tool in the conservation of global biodiversity and carbon stores. We conducted a global test of the degree to which more than 18,000 terrestrial protected areas (totalling 5,293,217 km) reduce deforestation in relation to unprotected areas. We also derived indices that quantify how well countries' forests are protected, both in terms of forested area protected and effectiveness of protected areas at reducing deforestation, in relation to vertebrate species richness, aboveground forest carbon biomass and background deforestation rates.

Beverage milk consumption patterns in the United States: Who is substituting from dairy to plant-based beverages?

This research used a survey of 995 US households to explore how dairy milk and plant-based beverage substitutes were consumed. Long-term trends of declining beverage milk consumption have been exacerbated in recent years by increasing consumption of plant-based beverages. Although beverage milk consumption has been declining, total dairy consumption in the United States continues to increase, driven by growth in sales of cheese, butter, and yogurt.

#Eggs: social and online media-derived perceptions of egg-laying hen housing.

Enormous quantities of data are generated through social and online media in the era of Web 2.0. Understanding consumer perceptions or demand efficiently and cost effectively remains a focus for economists, retailer/consumer sciences, and production industries.

Online procurement of pet supplies and willingness to pay for veterinary telemedicine.

Changing consumer shopping behaviors, and specifically the shift towards online procurement of goods and services, have altered the retail landscape of nearly all goods, including pet products and services. Whilst it is known and commonly discussed that less retail business for products and medications is being conducted in clinics than in the past, it is not well documented where that commerce is now taking place, and by what customer segments. For cats, dogs, and other pets, specialty food and food in general was purchased by a high percentage of respondents at the physical store.

Public Perceptions of Veterinarians from Social and Online Media Listening.

The public perception of the veterinary medicine profession is of increasing concern given the mounting challenges facing the industry, ranging from student debt loads to mental health implications arising from compassion fatigue, euthanasia, and other challenging aspects of the profession. This analysis employs social media listening and analysis to discern top themes arising from social and online media posts referencing veterinarians. Social media sentiment analysis is also employed to aid in quantifying the search results, in terms of whether they are positivity/negativity associated.