International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set.

Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact).

Mechanisms in the Synthesis of S-Alcohols with 1,4-NADH Biomimetic Co-factor N-Benzyl-1,4-dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study.

The enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S-alcohols, when the natural co-factor, 1,4-dihyronicotinamide adenine dinucleotide, 1,4-NADH, was replaced with biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1. We surmised that different hydride and proton transfer mechanisms were involved using co-factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η-keto-S-η-5,6-1,4-dihydronicotinamide-Zn(II) complex, was previously investigated with a model of the HLADH-Zn(II) catalytic site (J.

Regulation of fibrinogen synthesis.

The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bβ, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric "dimer of trimers" (AαBβγ). Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein.

Overcoming barriers to agri-environmental management at landscape scale: Balancing farmer coordination and collaboration with the aid of facilitators and pioneers.

Policy instruments that integrate the actions of multiple farmers are of growing interest for improving landscape scale environmental sustainability of agriculture. We conducted in-depth, semi-structured interviews with farmers in south-east England and applied thematic analysis to the responses to perform a qualitative investigation into the combined role of economic, social, and cultural barriers to cooperative environmental management, and identify possible solutions for these barriers. Interviewees recognised environmental benefits of cooperative management, but this was a low priority compared to other management activities, being seen as complex and time-consuming, with uncertainty over direct benefits to participants.

The risk of developing pseudomyxoma peritonei from a non-perforated low grade appendiceal mucinous neoplasm found at appendicectomy.

Introduction: Low-grade appendiceal mucinous neoplasms (LAMNs) are classified as non-perforated (pTis, pT3) or perforated (pT4), and considered precursors of pseudomyxoma peritonei (PMP). This study aims to quantify the risk of developing PMP from pTis and pT3 LAMNs.

Materials And Methods: Retrospective analysis of a prospectively collected database identified LAMN patients referred to a specialist centre from 2004 to 2019.

MANAGEMENT OF LARGE FULL-THICKNESS MACULAR HOLES: Long-Term Outcomes of Internal Limiting Membrane Flaps and Internal Limiting Membrane Peels.

Background/purpose: To determine and compare the efficacy of a surgical internal limiting membrane (ILM) flap technique with the traditional ILM peel on long-term visual and anatomical outcomes for large (>400 µm) full-thickness macular holes.

Methods: From October 2016 to July 2022, patients undergoing initial full-thickness macular hole repair with the ILM flap or ILM peel technique were reviewed. Final outcomes were recorded and based on size in microns: 401 to 800, 801 to 1,200, and >1,200.

Rebuttal to the article Pathological crystal structures.

A section in the Acta Crystallographica Section C article by Raymond & Girolami [Acta Cryst. (2023), C79, 445-455] stated that the product of the reaction of [(Cp*Rh)(μ-OH)] (Cp* is 1,2,3,4,5-pentamethylcyclopentadiene) with 1-methylthymine (1-MT) at pH 10 and 60 °C, to synthesize the anionic component [Rh(η-N-1-MT)], was not an Rh complex, but rather an Ag complex, due to the use of silver triflate (AgOTf) to remove Cl from [Cp*RhCl] to synthesize [Cp*Rh(HO)](OTf), a water-soluble crystalline complex. We will clearly show that this premise, as stated, is invalid, while the authors have simply avoided several important facts, including that Cp*OH, a reductive elimination product, at pH 10 and 60 °C, was unequivocally identified, thus leading to the Rh anionic component [Rh(η-N-1-MT)].

Adverse pregnancy outcomes in pregnant women with chronic kidney disease: A systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular filtration rate, eGFR) compared with women without CKD has not been quantified in large cohorts.

Objectives: To quantify the association between CKD and adverse pregnancy outcomes according to CKD definition, CKD stage and presence or absence of diabetes.

Search Strategy: A systematic search of EMBASE and MEDLINE from inception to 5 January 2023.

Demographic and Socioeconomic Factors in Prospective Retina-Focused Clinical Trial Screening and Enrollment.

Historically marginalized populations are disproportionately affected by many diseases that commonly affect the retina, yet they have been traditionally underrepresented in prospective clinical trials. This study explores whether this disparity affects the clinical trial enrollment process in the retina field and aims to inform future trial recruitment and enrollment. Age, gender, race, ethnicity, preferred language, insurance status, social security number (SSN) status, and median household income (estimated using street address and zip code) for patients referred to at least one prospective, retina-focused clinical trial at a large, urban, retina-based practice were retrospectively extracted using electronic medical records.

Open versus Closed technique for administration of heated intraperitoneal chemotherapy (HIPEC): Morbidity and Mortality outcomes from a high-volume centre.

Background And Aims: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is an established treatment in selected patients with peritoneal metastases, delivered in the UK in specialist centres. HIPEC can be administered via the open coliseum technique as first described by Sugarbaker (O-HIPEC) or using a closed technique (C-HIPEC). Data comparing the safety and outcomes of these different approaches is limited.

Comparison of published core outcome sets with outcomes recommended in regulatory guidance from the US Food and Drug Administration and European Medicines Agency: cross sectional analysis.

Objective: To compare the outcomes in published core outcome sets with the outcomes recommended in corresponding guidance documents from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA), matched by health condition.

Design: Cross sectional analysis.

Setting: US and Europe.

Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure.

Background: Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF).

Objectives: This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF.

Methods: This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies.

The features and processes underpinning high-quality data generation in participatory research and engagement activities.

Participatory approaches are widely used by researchers to gather data and insight about how the environment is perceived, valued and used. The participatory activities may be creating information as part of curiosity-driven blue-skies research or to inform policy/practise decision-making.The quality and usability of data derived from participatory approaches are heavily influenced by how activities are conducted.

Nature, smells, and human wellbeing.

The link between nature and human wellbeing is well established. However, few studies go beyond considering the visual and auditory underpinnings of this relationship, even though engaging with nature is a multisensory experience. While research linking smell to wellbeing exists, it focuses predominantly on smells as a source of nuisance/offence.

Stratified medicalization of schooling difficulties.

Medicalization is a central topic of concern in the sociology of disability and of health and illness. In this paper, I examine how medicalization is inequitably applied and circulates in the context of schools, specifically in serving students with educational disabilities. My aim is to advance understandings of medicalization through this case.

The XRN1-regulated RNA helicase activity of YTHDC2 ensures mouse fertility independently of mA recognition.

The functional consequence of N-methyladenosine (mA) RNA modification is mediated by "reader" proteins of the YTH family. YTH domain-containing 2 (YTHDC2) is essential for mammalian fertility, but its molecular function is poorly understood. Here, we identify U-rich motifs as binding sites of YTHDC2 on 3' UTRs of mouse testicular RNA targets.

Multi-attribute Raman spectroscopy (MARS) for monitoring product quality attributes in formulated monoclonal antibody therapeutics.

Rapid release of biopharmaceutical products enables a more efficient drug manufacturing process. Multi-attribute methods that target several product quality attributes (PQAs) at one time are an essential pillar of the rapid-release strategy. The novel, high-throughput, and nondestructive multi-attribute Raman spectroscopy (MARS) method combines Raman spectroscopy, design of experiments, and multivariate data analysis (MVDA).

How teachers form educational expectations for students: A comparative factorial survey experiment in three institutional contexts.

While schools are thought to use meritocratic criteria when evaluating students, research indicates that teachers hold lower expectations for students from disadvantaged backgrounds. However, it is unclear what the unique impact is of specific student traits on teacher expectations, as different traits are often correlated to one another in real life. Moreover, research has neglected the role of the institutional context, yet tracking procedures, financial barriers to education, and institutionalized cultural beliefs may influence how teachers form expectations.

Representation of published core outcome sets for research in regulatory guidance: protocol.

The COMET Initiative promotes the development and use of 'core outcome sets' (COS), agreed standardised sets of outcomes that should be measured and reported in all studies in a particular clinical condition. COS are determined by consensus amongst key stakeholders, including health professionals, policymakers and patients, ensuring that the priorities and expertise of these representatives inform the choice of the most important outcomes to measure for a given condition. There is increased recognition of the need to integrate COS across the healthcare system and with existing regulatory apparatus, to ensure that outcomes being recorded are those of key relevance to important stakeholders.