Revisiting the druggable genome using predicted structures and data mining.

Identification of novel drug targets is a key component of modern drug discovery. While antimalarial targets are often identified through the mechanism of action studies on phenotypically derived inhibitors, this method tends to be time- and resource-consuming. The discoverable target space is also constrained by existing compound libraries and phenotypic assay conditions.

Female Urologists' Experiences With Lactation in the Workplace.

Objective: To investigate institutional support and lactation policies for urologists and to explore surgeon satisfaction with available lactation resources.

Methods: An anonymous, voluntary survey was administered to female physicians through private female physician social media groups and the Society of Women in Urology in 2023 and 2024. The survey assessed demographic information, institutional lactation policy information, and personal perception of lactation resources and support.

Evaluating staff views and understanding of the crisis and home treatment service (CAHTS): A mixed-methods study within the child and adolescent mental health service (CAMHS).

Background: The number of children and young people (CYP) experiencing mental health crises in the UK is increasing. The NHS Long Term Plan (2019) prioritises crisis care for CYP. There is a lack of research and understanding into staff views and understandings of these services.

Urbanisation and Host Relatedness Shape Virome Composition in a Widespread, Generalist Carnivore.

Urban wildlife species have the potential to serve as links in disease transmission between wildlife, humans and domestic animals at the wildland-urban interface (WUI), contributing to both sustained cross-species transmission of pathogens and the emergence of diseases in susceptible populations. However, the relative roles of host and environmental factors in shaping the composition of pathogen communities in urban wildlife is understudied. In this study, we integrated DNA and RNA virome data with host genomic and GPS datasets to investigate factors shaping virome composition in bobcats (Lynx rufus ) at the WUI in the Tucson Mountains, Arizona, USA.

Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations.

Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function. As a substrate receptor of the CULLIN3-RING E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma, the most common embryonal brain tumour in children. These mutations impart gain-of-function to KBTBD4 to induce aberrant degradation of the transcriptional corepressor CoREST.

UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors.

UM171 is a potent agonist of ex vivo human haematopoietic stem cell self-renewal. By co-opting KBTBD4, a substrate receptor of the CUL3-RING E3 ubiquitin ligase (CRL3) complex, UM171 promotes the degradation of the LSD1-CoREST corepressor complex, thereby limiting haematopoietic stem cell attrition. However, the direct target and mechanism of action of UM171 remain unclear.

Co-Designing a Toolkit of Approaches and Resources for End-of-Life Care Planning With People With Intellectual Disabilities Within Adult Social Care Settings: A Multi-Phase Study.

Background: People with intellectual disabilities are rarely involved in end-of-life decisions. This study investigated and further developed approaches and resources to enable inclusive end-of-life care planning.

Methods: A multi-centre, multi-method four-phase study, involving 195 researchers, participants, advisors and co-design members, including 36 people with intellectual disabilities: (i) evidence review; (ii) stakeholder focus groups; (iii) Experience-Based Co-Design and (iv) testing of co-designed resources.

Swarm learning with weak supervision enables automatic breast cancer detection in magnetic resonance imaging.

Background: Over the next 5 years, new breast cancer screening guidelines recommending magnetic resonance imaging (MRI) for certain patients will significantly increase the volume of imaging data to be analyzed. While this increase poses challenges for radiologists, artificial intelligence (AI) offers potential solutions to manage this workload. However, the development of AI models is often hindered by manual annotation requirements and strict data-sharing regulations between institutions.

Deep learning-based breast cancer diagnosis in breast MRI: systematic review and meta-analysis.

Objectives: The aim of this work is to evaluate the performance of deep learning (DL) models for breast cancer diagnosis with MRI.

Materials And Methods: A literature search was conducted on Web of Science, PubMed, and IEEE Xplore for relevant studies published from January 2015 to February 2024. The study was registered with the PROSPERO International Prospective Register of Systematic Reviews (protocol no.

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.

Evidence of Extensive Home Range Sharing Among Mother-Daughter Bobcat Pairs in the Wildland-Urban Interface of the Tucson Mountains.

Urbanization impacts the structure and viability of wildlife populations. Some habitat generalists, such as bobcats (Lynx rufus), maintain populations at the intersection of wild and urban habitats (wildland urban interface, WUI), but impacts of urbanization on bobcat social structure are not well understood. Although commonly thought to establish exclusive home ranges among females, instances of mother-daughter home range sharing have been documented.

Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining.

The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by investigating the mode of action of compounds found through phenotypic screens. Although this method has yielded many promising candidates, it is time- and resource-consuming and misses targets not captured by existing antimalarial compound libraries and phenotypic assay conditions.

Deep Learning Algorithms for Breast Cancer Detection in a UK Screening Cohort: As Stand-alone Readers and Combined with Human Readers.

Background Deep learning (DL) algorithms have shown promising results in mammographic screening either compared to a single reader or, when deployed in conjunction with a human reader, compared with double reading. Purpose To externally validate the performance of three DL algorithms as mammographic screen readers in an independent UK data set. Materials and Methods Three commercial DL algorithms (DL-1, DL-2, and DL-3) were retrospectively investigated from January 2022 to June 2022 using consecutive full-field digital mammograms collected at two UK sites during 1 year (2017).

Subcutaneous delivery of mesenchymal stromal cells induces immunoregulatory effects in the lymph node prior to their apoptosis.

Background: Mesenchymal stromal cell (MSC) therapy commonly involves systemic infusion of MSCs, which undergo apoptosis in the lung and induce immunoregulatory macrophages that reduce disease. The relevance of this mode of action, however, is yet to be determined for MSCs administered via other routes. Here, we administered MSCs via subcutaneous (SC) injection into inflamed tissue and investigated the immunomodulatory effects on the local lymph node (LN), which is a major site for the initiation and regulation of immune responses.

Patient and Provider Education Safely Reduces Opioid Prescribing After Pediatric Urologic Surgery.

Objective: To examine current opioid prescribing and determine what clinical factors were associated with use of opioids after urologic surgery after a previous study from our institution found that education regarding opioid prescribing practices significantly decreased post-operative opioid prescriptions from 61% to 34% (P <.0001).

Methods: From 2017 to 2023, a questionnaire querying what medications were used for post-operative pain was administered to patients/families at a postoperative visit.

Strategies for integrating artificial intelligence into mammography screening programmes: a retrospective simulation analysis.

Background: Integrating artificial intelligence (AI) into mammography screening can support radiologists and improve programme metrics, yet the potential of different strategies for integrating the technology remains understudied. We compared programme-level performance metrics of seven AI integration strategies.

Methods: We performed a retrospective comparative evaluation of seven strategies for integrating AI into mammography screening using datasets generated from screening programmes in Germany (n=1 657 068), the UK (n=223 603) and Sweden (n=22 779).

A protocol for a pilot randomised controlled trial of unguided internet cognitive behaviour therapy for grief in adolescents.

Grief is highly prevalent in adolescents, however, there have been no studies investigating internet delivered cognitive behaviour therapy for grief in adolescents (ICBT-G-A). In this paper, the co-design of an unguided ICBT-G-A intervention is described, and a protocol outlined for a pilot randomised controlled trial of the intervention. Participants will be randomised to the intervention (delivered via eight modules over a four-week period) or a four-week waitlist control.

Identification of a Polypeptide Inhibitor of -GlcNAc Transferase with Picomolar Affinity.

-GlcNAc transferase (OGT) is an essential mammalian enzyme that binds thousands of different proteins, including substrates that it glycosylates and nonsubstrate interactors that regulate its biology. OGT also has one proteolytic substrate, the transcriptional coregulator host cell factor 1 (HCF-1), which it cleaves in a process initiated by glutamate side chain glycosylation at a series of central repeats. Although HCF-1 is OGT's most prominent binding partner, its affinity for the enzyme has not been quantified.

Accuracy of an Artificial Intelligence System for Interval Breast Cancer Detection at Screening Mammography.

Background Artificial intelligence (AI) systems can be used to identify interval breast cancers, although the localizations are not always accurate. Purpose To evaluate AI localizations of interval cancers (ICs) on screening mammograms by IC category and histopathologic characteristics. Materials and Methods A screening mammography data set (median patient age, 57 years [IQR, 52-64 years]) that had been assessed by two human readers from January 2011 to December 2018 was retrospectively analyzed using a commercial AI system.

The All Together Group: Co-Designing a Toolkit of Approaches and Resources for End-of-Life Care Planning With People With Intellectual Disabilities in Social Care Settings.

Introduction: Support staff within social care settings have expressed a need for resources to facilitate end-of-life care planning with people with intellectual disabilities. This study aimed to co-design a preliminary toolkit of end-of-life care planning approaches and resources that can be implemented in adult social care services for people with intellectual disabilities.

Methods: An adapted Experience-Based Co-Design process was applied to develop a toolkit for end-of-life care planning with people with intellectual disabilities.

Ocean weather, biological rates, and unexplained global ecological patterns.

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.