Tranexamic acid: single topical application for femoral neck fractures treated with arthroplasty results in lowest blood loss.

Purpose: Tranexamic acid is widely accepted for hip fractures but there is no agreement about dose or application method and the use is still off label for hip fractures. The aim of our study was to find the best application method of tranexamic acid in patients with femoral neck fractures comparing total blood loss, hemoglobin and transfusion rate.

Methods: A retrospective single centre cohort study (level I trauma centre) with 2008 patients treated operatively for a proximal femur fracture between January 2016 and January 2022 was performed.

Current applications and challenges in large language models for patient care: a systematic review.

Background: The introduction of large language models (LLMs) into clinical practice promises to improve patient education and empowerment, thereby personalizing medical care and broadening access to medical knowledge. Despite the popularity of LLMs, there is a significant gap in systematized information on their use in patient care. Therefore, this systematic review aims to synthesize current applications and limitations of LLMs in patient care.

Safety of laparoscopic compared to open right hepatectomy after portal vein occlusion: results from a multicenter study.

Background: Concerns have been expressed about the feasibility of laparoscopic right hepatectomy (Lap-RH) after portal vein occlusion (PVO), because of its technical difficulty. The aim of this study is to assess the safety and feasibility of lap-RH after PVO.

Methods: Retrospective analysis of prospectively collected data from high-volume HPB centers was performed.

"Comparative analysis of large language models against the NHS 111 online triaging for emergency ophthalmology".

Background: This study presents a comprehensive evaluation of the performance of various large language models in generating responses for ophthalmology emergencies and compares their accuracy with the established United Kingdom's National Health Service 111 online system.

Methods: We included 21 ophthalmology-related emergency scenario questions from the NHS 111 triaging algorithm. These questions were based on four different ophthalmology emergency themes as laid out in the NHS 111 algorithm.

Bundled measures for China's food system transformation reveal social and environmental co-benefits.

Food systems are essential for the achievement of the United Nations Sustainable Development Goals in China. Here, using an integrated assessment modelling framework that considers country-specific pathways and covers 18 indicators, we find that most social and environmental targets for the Chinese food system under current trends are not aligned with the United Nations Agenda 2030. We further quantify the impacts of multiple measures, revealing potential trade-offs in pursuing strategies aimed at public health, environmental sustainability and livelihood improvement in isolation.

Interactive and unimodal relationships between plant biomass, abiotic factors, and plant diversity in global grasslands.

Grasslands cover approximately a third of the Earth's land surface and account for about a third of terrestrial carbon storage. Yet, we lack strong predictive models of grassland plant biomass, the primary source of carbon in grasslands. This lack of predictive ability may arise from the assumption of linear relationships between plant biomass and the environment and an underestimation of interactions of environmental variables.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing.

Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation.

Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.

Tumour growth rate and invasive interval cancer characteristics in a UK breast cancer screening population.

Objectives: To estimate tumour volume doubling time (TVDT) of interval cancers (ICs).

Methods: Two radiologists retrospectively reviewed prior screening and diagnostic mammograms and measured mean diameter on "visible" ICs. Univariate analyses of clinicopathological variables (ER, HER2, grade, age at diagnosis, and breast density) were undertaken, and those with p < 0.

Distinct neural computations scale the violation of expected reward and emotion in social transgressions.

Traditional decision-making models conceptualize humans as adaptive learners utilizing the differences between expected and actual rewards (prediction errors, PEs) to maximize outcomes, but rarely consider the influence of violations of emotional expectations (emotional PEs) and how it differs from reward PEs. Here, we conducted a fMRI experiment (n = 43) using a modified Ultimatum Game to examine how reward and emotional PEs affect punishment decisions in terms of rejecting unfair offers. Our results revealed that reward relative to emotional PEs exerted a stronger prediction to punishment decisions.

Measuring the visual environment of children and young people at risk of myopia: a scoping review.

Purpose: Myopia (short-sightedness) is an emerging WHO priority eye disease. Rise in prevalence and severity are driven by changes in lifestyle and environment of children and young people (CYP), including less time spent in bright daylight and more time spent on near-vision activities. We aimed to systematically map the literature describing direct, objective measurements of the visual environment of CYP.

Appendix.

Since the first Chapter dealt with the well-known charge-charge interactions familiar to biologists, this concluding Chapter introduces some key electrical forces, probably much less familiar, perhaps even unknown. LLPS (liquid liquid phase separation) which we have seen involved in so much of cell biology depends on multivalent, π-π and cation-π electrical forces. How these arise is dealt with here and may be especially useful as an aide memoir to return to when such issues arise within the bulk of the text.

Electrical Forces Improve Memory in Old Age.

This penultimate chapter is based on a single paper published in Nature in 2022. I have used it specifically as an exemplar, in this case to show that memory improvement in old age may be regulated by a multiplicity of electrical forces. However, I include it because I believe that one could pick almost any other substantial single paper and show that a completely disparate set of biological mechanisms similarly depend crucially on multiple electrical forces.

Electric Forces and ATP Synthesis.

ATP synthase is a rotary motor enzyme that drives the formation of ATP from ADP and P and uses multiple electrical forces to do this. This chapter outlines the exquisite use of these electrical forces to generate the high energy phosphates on which all our lives depend. Vacuolar ATPases and the ADP/ATP carrier also are explored.

Crucial Roles of Electricity in Virology.

Packaging of DNA into viruses in some cases involves remarkably sophisticated electrical control mechanisms. One example is how the T4 bacteriophage uses an electrostatically driven motor to pump DNA into the viral capsid.

SARS-CoV-2 Is an Electricity-Driven Virus.

One of the most important and challenging biological events of recent times has been the pandemic caused by SARS-CoV-2. Since the underpinning argument behind this book is the ubiquity of electrical forces driving multiple disparate biological events, consideration of key aspects of the SARS-CoV-2 structural proteins is included. Electrical regulation of spike protein, nucleocapsid protein, membrane protein, and envelope protein is included, with several of their activities regulated by LLPS and the multivalent and π-cation and π-π electrical forces that drive phase separation.

Synaptic Physiology Depends on Electrical Forces and Liquid-Liquid Phase Separation.

Pre- and post-synaptic events are regulated by liquid-liquid phase separation and this phenomenon requires multiple electrical forces. Both axonal transport and the organization of postsynaptic excitatory and inhibitory receptors are regulated by LLPS, with its mandatory electrical drivers ultimately determining our cognitive health and capacity.

Neurological Diseases can be Regulated by Phase Separation.

Several neurological diseases arise from abnormal protein aggregation within neurones and this is closely regulated by phase separation. One such is motor neurone disease and aberrant aggregation of superoxide dismutase. Again these events are regulated by electrical forces that are examined.

Epigenetic Regulation Via Electrical Forces.

Multiple epigenetic modulations occur to chromatin rather than to DNA itself and these influence gene expression or gene silencing profoundly. Both the creation of these post-translational modifications and the mechanisms of their readout are regulated significantly by electrical forces several of which are discussed. They are also influenced by phase separation which itself is driven by electrical forces.

Spatially Regulated Electrical Forces for Biological Catalysis.

It is now well-recognized that biological catalysis depends crucially on spatially regulated electrical forces for optimal efficiency. Several examples of the mechanisms underpinning this will be covered, as will the experimental evidence that oriented electrical fields can enhance specific chemical reactions.

Making Proteins with Electricity.

Ribosomes use multiple electrical forces to regulate new protein construction, to ensure efficient protein cotranslation, chaperoning, and folding. When these electrical regulatory forces are disrupted as in point charge mutations, specific disease occurs from aberrantly folded proteins. α1 antitrypsin deficiency is perhaps the best-known misfolded protein disease and is covered in some detail.