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Patient‐reported outcomes: active surveillance vs radical therapies in low‐risk prostate cancer
No full textObjective To prospectively evaluate functional patient‐reported outcomes (PROs) in patients with low‐risk prostate cancer (PCa) managed with active surveillance (AS), nerve‐sparing radical prostatectomy (NS‐RP), non‐NS‐RP, or radiotherapy (RT). Patients and Methods This multicentre prospective cohort study used data from the Prostate Cancer Outcomes (PCO) study in Germany, Austria and Switzerland, including 6265 patients with low‐risk PCa enrolled between 2016 and 2023. PROs were assessed at baseline and 12 months after treatment/enrolment using the 26‐item Expanded Prostate Cancer Index Composite Short Form (EPIC‐26), measuring urinary continence, bowel, sexual, hormonal, and irritative/obstructive symptoms. Mean score changes were compared with minimal important differences (MIDs) to determine clinical significance. Results In all, 475, 4352, 813, and 625 patients received AS, NS‐RP, non‐NS‐RP, and RT, respectively. At 12 months, AS was associated with stable function across all EPIC‐26 domains. In contrast, both RP groups experienced significant declines in urinary continence (NS‐RP: −18 points; non‐NS‐RP: −26 points) and sexual function (NS‐RP: −35 points; non‐NS‐RP: −30 points), exceeding MID thresholds. Urinary continence did not decline after RT but clinically relevant declines occurred in irritative/obstructive urinary (−5 points), bowel (−7 points), hormonal (−5 points), and sexual function (−12 points). Age‐stratified analysis showed clinically significant declines in urinary and sexual function after NS‐RP across all age groups, with the greatest loss in sexual function among younger patients and the most pronounced continence impairment in the 70–79 years age group. In contrast, functional outcomes under AS remained stable in all age cohorts. Conclusion Active surveillance is underutilised in the observed cohort. Prospective PCO data demonstrates that AS preserves urinary continence and sexual function compared to active treatment, supporting its role as the first‐line strategy for suitable candidates. Despite advancements including NS techniques, RP, and to a lesser extent RT, remain associated with substantial functional impairment even in younger men
Subcellular Lipid Trafficking and Membrane Specialization in Plants
No full textMembrane lipid composition underpins the structural and functional identity of all plant membranes. This review examines membrane lipid metabolism and trafficking, with an emphasis on how lipid diversity and interorganelle movement support plant cell function. We explore the biophysical and biochemical specialization of subcellular membranes, with discussion of the endoplasmic reticulum, plasma membrane, apoplastic vesicles and barriers, tonoplast, peroxisomes, mitochondria, plastids, and thylakoids. We review both vesicular and nonvesicular lipid transport pathways, including membrane contact sites. Particular attention is given to glycerolipids, including phospholipids and galactolipids, sphingolipids, sterols, and, to a lesser extent, fatty acid exchange. By focusing on mechanisms of lipid transfer and remodeling, this review synthesizes our understanding of subcellular membrane lipid composition in the context of dynamic cellular processes including cell plate expansion, environmental stress responses, and photosynthetic membrane assembly
Enhancing rapeseed drought resilience: transcriptomic insights from superabsorbent polymer seed coatings
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Aggregation-dependent epitope sequence and modification fingerprints of anti-Aβ antibodies
No full textA hallmark of Alzheimer’s disease (AD), the most common form of dementia, is the progressive accumulation of amyloid-beta (Aβ) peptides across distinct brain regions. Anti-Aβ antibodies (Aβ-Abs) targeting specific Aβ variants are essential tools for AD research, diagnostics, and therapy. The monoclonal antibodies Aducanumab, Lecanemab, and Donanemab have recently been approved as the first disease-modifying treatments for early AD, highlighting the clinical importance of their exact binding profiles. In this study, we systematically characterized the binding and modification requirements of 20 Aβ-Abs, including biosimilars of Aducanumab, Lecanemab, and Donanemab, across monomeric, oligomeric, and aggregated Aβ forms. Array-based analysis of 20,000 modified Aβ peptides defined binding epitopes at single-residue resolution and revealed the impact of sequence variation, including familial AD mutations, as well as diverse post-translational modifications (PTMs). Notably, genetic variants, such as H6R, impaired binding of therapeutic Aβ-Abs like Aducanumab. Donanemab showed strong preference for pyroglutamate-modified AβpE3–17, while Lecanemab and Aducanumab exhibited aggregation- and sequence-context-dependent binding requirements. Comparison of peptide binding profiles with binding of full-length and aggregated Aβ via immunoprecipitation-mass spectrometry, capillary immunoassays, Western blotting, and immunohistochemistry on AD brain tissue revealed distinct aggregation-dependent binding behaviours. The valency- and context-dependence of Aducanumab binding, together with its preference for Ser8-phosphorylated Aβ, supports a dimerization-mediated binding mechanism. For Lecanemab, our data suggest that additional structural contributions beyond the minimal N-terminal epitope are required for binding to aggregated Aβ, which remain to be fully resolved. Together, this work provides the most comprehensive dataset to date on aggregation-dependent sequence and modification selectivity of Aβ-Abs. By integrating mutational, PTM, and aggregation contexts in a unified experimental framework, we establish a resource that enables rational selection of antibodies for research and diagnostic applications and offers mechanistic insights that may inform the design and optimization of future therapeutic antibodies in AD
What Do Asexual Women Want? A Propensity Score Matching Study of Preferred Relationship Options and Ideal Partner Preferences
No full textAbstract Research on whether asexual individuals desire (romantic) relationships and, if so, how they picture their ideal relationship has been growing in the past few years. However, less is known about the preferred attributes of an ideal partner in such relationships and whether these partner(ship) preferences are different from what heterosexual individuals want. The goal of the present study was to compare the types of preferred relationships and the ideal characteristics of a long-term partner of self-identified asexual and heterosexual women. Additionally, we examined differences in characteristics of asexual and heterosexual women using self-evaluations of the same attributes used for the partner preference ratings. We used data from the Ideal Partner Survey, a large-scale, multinational online study. Of 51,775 participants, 51,328 identified as heterosexual ( M age = 25.13 years) and 447 identified as asexual ( M age = 24.03 years). To create comparable samples for analyses, each asexual person was matched with a heterosexual person using propensity score matching (relationship options sample = 646, partner preference sample = 780, self-rating sample = 772). Compared to heterosexual women, asexual women were less interested in purely sexual relationships and more interested in emotionally romantic and alternative types of committed relationships as well as not being in any relationship (“single”). Asexual women placed less importance on all partner preference attributes, except educated and intelligent. They also consistently rated themselves lower on all attributes than heterosexual women. These findings suggest distinct differences between asexual and heterosexual women in their relationship interests, partner preferences, and self-perceived characteristics
Revising the ABIDE MCI to dementia prediction model for automated cerebrospinal fluid assays
No full textAbstract INTRODUCTION Automated cerebrospinal fluid (CSF) biomarker assays have largely replaced manual immunoassays for measuring amyloid pathology in CSF. We refitted and validated the ABIDE model, predicting progression from mild cognitive impairment (MCI) to dementia, with CSF measurements from the automated Elecsys platform. METHODS We included 2413 MCI participants (998 [41%] amyloid‐positive) from seven observational cohorts. Elecsys was used in 958 (40%) participants. The parameters of the previous ABIDE Cox model were re‐estimated. Model discrimination and calibration were evaluated with leave‐one‐cohort‐out cross‐validation. RESULTS During follow‐up, 1034 (42%; 585 [58%] amyloid‐positive) participants developed dementia. Discrimination was good with Harrell's C of 0.70 (95% confidence interval [CI]: 0.66–0.73). Calibration was good in the total population and amyloid‐positive subgroup, with substantial predicted progression risks for all amyloid‐positive participants. DISCUSSION We refitted the ABIDE model, predicting MCI to dementia progression, with automated CSF measurements. The model was well calibrated in amyloid‐positive patients and may support clinical discussions regarding ATTs.Highlights We updated the ABIDE mild cognitive impairment (MCI) to dementia prediction model. The model has good discrimination with a Harrell's C of 0.70 (95% confidence interval [CI]: 0.66–0.73). The model is well calibrated in the total population and amyloid‐positive subgroup.Abstract INTRODUCTION Automated cerebrospinal fluid (CSF) biomarker assays have largely replaced manual immunoassays for measuring amyloid pathology in CSF. We refitted and validated the ABIDE model, predicting progression from mild cognitive impairment (MCI) to dementia, with CSF measurements from the automated Elecsys platform. METHODS We included 2413 MCI participants (998 [41%] amyloid‐positive) from seven observational cohorts. Elecsys was used in 958 (40%) participants. The parameters of the previous ABIDE Cox model were re‐estimated. Model discrimination and calibration were evaluated with leave‐one‐cohort‐out cross‐validation. RESULTS During follow‐up, 1034 (42%; 585 [58%] amyloid‐positive) participants developed dementia. Discrimination was good with Harrell's C of 0.70 (95% confidence interval [CI]: 0.66–0.73). Calibration was good in the total population and amyloid‐positive subgroup, with substantial predicted progression risks for all amyloid‐positive participants. DISCUSSION We refitted the ABIDE model, predicting MCI to dementia progression, with automated CSF measurements. The model was well calibrated in amyloid‐positive patients and may support clinical discussions regarding ATTs.Highlights We updated the ABIDE mild cognitive impairment (MCI) to dementia prediction model. The model has good discrimination with a Harrell's C of 0.70 (95% confidence interval [CI]: 0.66–0.73). The model is well calibrated in the total population and amyloid‐positive subgroup.National Institute on Aging https://doi.org/10.13039/100000049National Institutes of Health https://doi.org/10.13039/100000002Alzheimer's Association https://doi.org/10.13039/100000957GHR Foundation https://doi.org/10.13039/100015595European Research Council https://doi.org/10.13039/501100000781Vetenskapsrådet https://doi.org/10.13039/501100004359Hjärnfonden https://doi.org/10.13039/501100003792U.S. Department of Defense https://doi.org/10.13039/100000005National Institute of Biomedical Imaging and Bioengineering https://doi.org/10.13039/100000070AbbVie https://doi.org/10.13039/100006483Alzheimer's Drug Discovery Foundation https://doi.org/10.13039/100002565BioClinica https://doi.org/10.13039/100007742Biogen https://doi.org/10.13039/100005614Bristol-Myers Squibb https://doi.org/10.13039/100002491Eli Lilly and Company https://doi.org/10.13039/100004312Fujirebio US https://doi.org/10.13039/100014400GE Healthcare https://doi.org/10.13039/100006775H. Lundbeck A/S https://doi.org/10.13039/501100013327Merck https://doi.org/10.13039/100004334Novartis Pharmaceuticals Corporation https://doi.org/10.13039/100008272Pfizer https://doi.org/10.13039/100004319Servier https://doi.org/10.13039/501100011725Takeda Pharmaceutical Company https://doi.org/10.13039/100008373National Association for Colitis and Crohn's Disease https://doi.org/10.13039/501100000298Canadian Institutes of Health Research https://doi.org/10.13039/50110000002
