159370 research outputs found
Sort by
Nivolumab and Ipilimumab for Metastatic Castration-Resistant Prostate Cancer With an Immunogenic Signature: The Multicenter, Two-Cohort, Phase II NEPTUNES Study
No full textPurpose
Efficacy of immune checkpoint inhibitors in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) is limited. The NEPTUNES study evaluated combination nivolumab and ipilimumab in patients with immunogenic signature–positive (ImS+) mCRPC.
Materials and Methods
This open-label, 2-cohort, phase II trial enrolled patients with ImS+ mCRPC progressing on ≥1 previous line of treatment. ImS+ was defined by (1) mismatch repair deficiency (MMRD); (2) DNA damage repair gene loss; and/or (3) high inflammatory infiltrate (HII). Patients received four doses of nivolumab 1 mg/kg + ipilimumab 3 mg/kg (C1) or nivolumab 3 mg/kg + ipilimumab 1 mg/kg (C2) followed by nivolumab 480 mg once every 4 weeks up to 10 cycles. The primary end point was composite response rate (CRR) assessed radiologically, biochemically, and by reduction of circulating tumor cells. Secondary end points included toxicity, progression-free survival, overall survival, and duration of response.
Results
Between May 2018 and June 2022, 35 (C1) and 36 (C2) patients commenced treatment. The CRR in C1 was 14/35 (40%, 90% CI, 26% to 55%) and in C2 was 9/36 (25%, 90% CI, 14% to 40%). The overall CRR was 23/71 (32%, 90% CI, 23% to 43%). Response rates were higher in patients with MMRD (7/10), BRCA2 loss (4/8), and HII ± other ImS+ features (13/30). Duration of response for patients with HII without other ImS+ features, DNA repair gene loss without MMRD, and MMRD was 2.6, 17.3, and 10 months, respectively. Grade 3 to 4 treatment-related adverse events occurred in 22/35 (63%) in C1 and 12/36 (33%) patients in C2. There were no treatment-related deaths.
Conclusion
Nivolumab 1 mg/kg + ipilimumab 3 mg/kg is an active treatment in ImS+ pretreated mCRPC. Nivolumab 3 mg/kg + ipilimumab 1 mg/kg has less toxicity but may have lower efficacy. HII is a promising prospectively tested predictive biomarker in prostate cancer that could be integrated into future trials
“We are too young to worry”: late-midlife adults’ voices on sexual changes, distress, and help-seeking behaviors
Get PDFSexual health and well-being (SH&WB) in late midlife is an important yet underexplored aspect of healthy aging. Satisfying sexual activity contributes to psychological and relational well-being, yet midlife is marked by physiological changes, health issues, and social transitions that can affect sexual functioning. Existing research has mostly focused on adults over 60 or on clinically diagnosed sexual problems, leaving late-midlife experiences largely overlooked. This qualitative study addresses that gap by examining how late-midlife adults (50–64) in Poland perceive and navigate SH&WB challenges, shedding light on their experiences. Forty participants (25 women, 15 men) took part in semi-structured, in-depth interviews, and reflexive thematic analysis was applied. Many participants did not identify themselves as belonging to the “aging” group, often describing themselves as “too young” to experience age-related sexual concerns. Consequently, common changes (e.g., lower libido, vaginal dryness, and erectile difficulties) were seldom perceived as distressing or problematic. Participants typically managed these changes independently through creative, tactful strategies and by addressing psychosocial factors, reserving help-seeking for instances of severe distress or disruptions to sexual activity. These findings suggest that healthcare providers should respect late-midlife adults’ perspectives and avoid over-medicalizing normal sexual changes. Instead, SH&WB should be integrated into routine care in a supportive manner that encourages open dialogue and proactive engagement, laying the groundwork for assistance if future needs arise
Introduction: Performance, Projection, Provocation! Relational Creativity in Contemporary Japan
Get PDFThis introduction to the special issue “Performance, Projection, Provocation! Relational Creativity in Contemporary Japan” presents a history of group-based creative practice in Japan, from the amateur endeavors of sākuru (circles) to the professional creativity of international production companies. The special issue applies the concept of “relational creativity” to a series of case studies to better understand how creative practices shape relationships and other social forms, institutional and less institutional
Make your own…Pattern patchwork
Get PDFThis activity is inspired by the research of Hannah Sabapathy, an artist and designer at the University of Leeds. She studies how patterns and fabrics travel between countries and change as they do.
In her PhD, Hannah looked at South Asian textiles and the British versions made in the 1800s. She worked with the University’s International Textile Collection, which has colourful woven and embroidered samples from Kashmir and Europe. These show how ideas were shared, borrowed, and adapted — some celebrating other cultures, some copying or changing each other’s work.
By studying these textiles, Hannah looks at how copying and cutting can be a way of understanding history and identity. She’s interested in what happens when one pattern inspires another, and how designs can hold memories of where they came from.
When you make your own pattern rubbings and mix them together, you’re exploring the same ideas. Each pattern you create has its own story to tell
Make your own…Gooey glacier
Get PDFDuncan Quincey is a glaciologist (that means he studies glaciers!). He works in high mountain places like the Himalayas and the Andes. These glaciers are really important because when they melt, the water (called meltwater) flows down to help people grow food and make electricity.
But like many glaciers around the world, they’re melting too fast—faster than they have in hundreds of years! When glaciers melt, they often leave behind big lakes filled with meltwater. If the sides of the lake break, or if an avalanche crashes into the lake and makes it overflow, all the water can suddenly rush out and cause a big flood in the valley below.
Duncan uses satellite pictures and goes up mountains to check on these lakes. He’s often in Nepal, measuring the lake water and studying the rocks and dirt that hold the water in place.
His big goal is to warn people before a flood happens. It’s one way scientists are helping keep people safe from the changes happening in our climate
Make your own…Fluttering butterfly
Get PDFSome butterflies in the UK are doing really well, like the Comma Butterfly which has spread far and wide since the 1970s. But some species are struggling. In fact, 8 out of 10 butterflies and
many moths are becoming less common.
Why? It’s a mix of problems. Some caterpillars only eat certain plants, like violets, which are disappearing. Warmer winters are confusing butterflies like the Wall Brown, they come out too early and miss their chance to lay eggs. Hot weather can also be dangerous—unlike us, butterflies can’t sweat or cool down, so heatwaves can harm them.
But it isn’t all sad. Butterflies and moths help pollinate flowers and are food for birds and bats. They help scientists understand how healthy our environment and nature is.
You can help too by joining the Big Butterfly Count, planting butterfly-friendly flowers, and protecting our green spaces. Every flutter matters – for nature and for future generations
Make your own…Celebration lantern
Get PDFLight is more than just something that helps us see—it’s full of meaning. People all over the world use light to celebrate, remember, and understand big ideas.
In Hinduism, Jainism, and Sikhism, the festival of Diwali is all about light. It celebrates Dharma—doing what’s right. Zoroastrians honour fire and light as signs of truth and wisdom. In the Bible, God says “Let there be light!” at the very beginning. In Islam, light can mean Nur, a symbol of divine guidance and kindness, or Nar, fire that can be dangerous or tricky.
Light also connects to learning. The word Enlightenment means growing in knowledge—through science, reason, and even spiritual understanding.
Researchers study religion to explore how people make sense of the world. You could use light to help you make sense of big ideas like hope, trust, and change. It also helps us have conversations between different beliefs, showing how we can share ideas even when we all don’t believe the same things.
By learning about light in religion, we discover new ways to understand each other—and the world around us
Bovine endometrial organoids: a new tool to study conceptus-maternal interactions in mammals
No full textWe developed a hormonally responsive organoid model of the bovine endometrium. Bovine glandular epithelial cells isolated from reproductive tracts were cultured in an extracellular matrix hydrogel (Cultrex 2) at 38.5°C, 5% CO2 (n = 3). RNA was extracted and qPCR confirmed the presence of gland markers: leukemia inhibitory factor, mucin-1, insulin-like growth factor binding protein-1, kruppel-like factor-5, and forkhead box protein-A2. Organoids were imaged at specific time-points to monitor growth. Morphologically, organoids were spherical and fast-growing at passages 0 and 1, but this declined following passage 2. Passage 0 (n = 3) organoids were treated with 1000 ng/ml recombinant ovine Interferon Tau (IFNT) or 10 μg/ml progesterone (P4) for 24 h and analysed by RNASeq to assess hormone responsiveness. 373 transcripts were upregulated (padj2) in response to P4 treatment, with downstream analysis showing significant overrepresentation (FDR < 0.05) of genes associated with positive regulation of protein localisation to plasma membrane and cell periphery. Of the 240 genes significantly downregulated by P4 these were significantly overrepresented (FDR < 0.05) in biological processes of cilium and cytoskeleton organisation. IFNT treatment resulted in significant upregulation of 414 genes and downregulation of 119 genes. The largest cluster associated with differentially expressed genes in response to IFNT is defence to virus and interferon signalling. Thirty genes were altered by both P4 treatment and IFNT treatment. Organoids were also shown to express conserved microRNAs, and it was possible to culture them in a microfluidics device—making them a useful model for a multitude of potential investigations. Bovine endometrial organoids are therefore a new tool to investigate conceptus-maternal interactions
Variation in the Commissioning of Semaglutide for the Treatment of Obesity and Overweight Across England: Results of Three Freedom of Information‐Based Mapping Exercises Across the 42 Integrated Care Boards of England
Get PDFObesity medications are recommended in England with legislation necessitating their availability. However, given the number of people who meet clinically approved eligibility criteria, funding these medications and associated support services may limit efficacy at a population health level. This study aimed to assess the commissioning and availability of services and obesity medications across England. Three sets of freedom of information requests were sent to the 42 ICBs in England by Sky News Ltd, The BMJ and the study investigators of this work with questions focused on commissioning of services and medication eligibility and prescription across England. The three data sets were combined to provide a narrative description to inform further development in obesity care. The availability of services across England was partial, and when services did exist, medication access was limited by funding and more restrictive eligibility criteria beyond those approved by the National Institute of Health and Care Excellence. Subsequently, very few patients receive NHS prescriptions even in areas where funding medications are reportedly available. The capacity of services to offer comprehensive care for patients to receive obesity medications is insufficient to meet current demand. Despite legislation for the delivery of obesity medications, these treatment options are not widely available on the NHS. There is insufficient service capacity to provide comprehensive care for eligible patients seeking obesity medications as a treatment option
Floral resource strips enhance parasitoid abundance and diversity in apple orchards and promote agroecological advances in a South African biosphere reserve
Get PDF1. Agricultural intensification drives insect declines, including that of parasitoids, through landscape simplification and extensive use of synthetic pesticides. Spatially heterogeneous agricultural landscapes are potentially important biodiversity reservoirs where non-crop habitats may support populations providing ecosystem services to farming. However, there is a need to find methods to support this transition to more sustainable farming and support the progressive concept of biosphere reserves.
2. We focus here on the relationship between apple orchards and sclerophyllous natural fynbos vegetation in the megadiverse Kogelberg Biosphere Reserve, Cape Floristic Region, South Africa. We established patches of floral resources within apple orchards, which are embedded in landscapes, equivalent to the transition zone of the Kogelberg Biosphere Reserve (KBR), with varying proportions of natural habitat in a 500-m radius around orchards. We assessed the role of these enhanced floral resources for supporting parasitoid abundance, species richness and diversity inside orchards and compare these metrics to those in ruderal vegetation around orchards and in nearby natural vegetation. Further, we assessed the effect of semi-natural vegetation in the surrounding landscape mosaic on parasitoids in orchards.\ud
3. Floral enhancement improved parasitoid abundance and influenced assemblage composition within apple orchards. However, non-crop ruderal habitat immediately adjacent to orchards supported greater abundance and richness of parasitoid species, while natural fynbos supported even richer parasitoid assemblages. Vegetation within orchards and landscape complexity enhanced parasitoid assemblages inside and surrounding the orchards.
4. Our study shows that increasing floral resources within orchards improves local diversity of parasitoids within agroecosystems in the Biosphere Reserve. In doing so, this improves levels of biodiversity and increases parasitoid richness within the biosphere transition zone, supporting a shift from conventional production to a more biodiversity-friendly agroecological approach
Data sources:
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇