Umbilical outpouchings in pigs - an international survey on fitness for transport, welfare and management.

Background: Umbilical outpouchings (UOs) in pigs are a multifactorial disease and little is known about effective prevention strategies and risk factors for UO development. UOs are common in Danish pigs and legislation complicates and increases the cost of keeping and raising pigs with UO. Recommendations for preventive measures exist but the scientific evidence behind the recommendations is often lacking.

The therapeutic potential of circular RNAs.

Over the past decade, research into circular RNA (circRNA) has increased rapidly, and over the past few years, circRNA has emerged as a promising therapeutic platform. The regulatory functions of circRNAs, including their roles in templating protein translation and regulating protein and RNA functions, as well as their unique characteristics, such as increased stability and a favourable immunological profile compared with mRNAs, make them attractive candidates for RNA-based therapies. Here, we describe the properties of circRNAs, their therapeutic potential and technologies for their synthesis.

Pre-biologic disease trajectories are associated with morbidity burden and biologic treatment response in severe asthma.

Background: Biologics can induce remission in some patients with severe asthma, however, little is known about pre-biologic disease trajectories and their association with outcomes from biological treatment. We aimed to identify long-term trajectories of disease progression in patients initiating biologics and investigate trajectory associations with disease burden and impact on biologic therapy efficacy.

Methods: Patients in the Danish Severe Asthma Registry initiating biologic therapy between 2016-2022 were included and followed retrospectively in prescription databases starting 1995.

The effect of carbon fiber custom dynamic orthosis type on kinematics and kinetics of lower extremity joints in individuals with lower limb traumatic injuries.

Background: Carbon fiber custom dynamic orthoses have been used to improve gait mechanics after lower limb trauma in military service members, with the goal of restoring function and improving outcomes. However, the effects of commercially available carbon fiber orthoses available to civilians on lower extremity joint kinetics and kinematics are poorly understood.

Research Question: The aim of this study was to examine the effect of two commercially available orthoses on lower extremity kinematics and kinetics in individuals with lower limb trauma.

Mammography screening: Eliciting the voices of informed citizens.

Background: Many medical organisations recommend continuing with existing mammography screening programmes but some recommend stopping or de-intensifying them. In Denmark women aged 50-69 are offered biennial mammograms free-of-charge.

Objectives: The aim of this study was to determine whether or not an informed public would recommend continuation of the Danish mammography screening programme, and to determine whether this recommendation was in line with what participants considered to be acceptable levels of mortality reduction and overdiagnosis.

Genetic gradual reduction of OGT activity unveils the essential role of O-GlcNAc in the mouse embryo.

The reversible glycosylation of nuclear and cytoplasmic proteins (O-GlcNAcylation) is catalyzed by a single enzyme, namely O-GlcNAc transferase (OGT). The mammalian Ogt gene is X-linked, and it is essential for embryonic development and for the viability of proliferating cells. We perturbed OGT's function in vivo by creating a murine allelic series of four single amino acid substitutions, reducing OGT's catalytic activity to a range of degrees.

Jaccoud's Arthropathy Secondary to Leprosy.

Jaccoud's arthropathy is a deforming, non-erosive form of arthritis initially described in patients with rheumatic fever. However, it has been recently observed more frequently in those with systemic lupus erythematosus. Cases of Jaccoud's arthropathy have also been described to be associated with other conditions.

Virtual Neonatal Resuscitation Curriculum for Emergency Medical Services (EMS) to Improve Out-of-Hospital Newborn Care.

Objectives: Out-of-hospital births are associated with a 2-to 11-fold increased risk of death compared to in-hospital births and are growing. Emergency Medical Services (EMS) clinicians have limited exposure to hospital birth emergencies, and there is no standardized prehospital neonatal resuscitation curriculum. Neonatal Resuscitation Program (NRP) guidelines are the standard of care for infants born in the United States but focuses on in-hospital births and is not easily applied to EMS.

The association between skin allergy testing and oral squamous cell carcinoma in oral lichen planus: a retrospective cohort study.

There is a reported association between oral contact allergy and oral lichen planus (OLP). Likewise oral squamous cell carcinoma (oSCC) is associated with OLP. It is hypothesized that chronic inflammation may contribute to oSCC risk.

Outcomes of Older Adults and Frail Patients Receiving Idecabtagene Vicleucel: A CIBMTR Study.

Idecabtagene vicleucel (ide-cel) is an anti-BCMA CAR-T cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM) after 2 prior lines of therapy. There is limited data on outcomes of CAR T in older adults and frail patients with RRMM. In this study, we utilized data from the Center for International Blood and Marrow Transplantation Registry to describe the safety and efficacy of ide-cel in these clinically important subgroups.

Public Health.

Background: Studies comprising cohorts of cognitively unimpaired older adults or with mild cognitive impairment (MCI) that assesses clinical and biological characteristics to conversion to dementia are scarce in Brazil.

Method: To determine the median conversion time to dementia in a cohort of Brazilian older adults with low educational levels. In the cohort, participants undergo an annual comprehensive clinical and neuropsychological evaluation, complemented by neuroimaging and laboratory assessments to determine the diagnosis.

Biomarkers.

Background: Inflammation plays a key role in Alzheimer's disease (AD) progression. Interleukin 8 (CXCL8) has emerged as an important cytokine involved in neuroinflammation. It is known as an inflammatory factor that induces a chemotactic response to sites of injury, involving the infiltration of neutrophils.

Developing Topics.

Background: Inadequate glymphatic clearance through perivascular spaces (PVS) is hypothesized to contribute to the formation of white matter hyperintensities (WMH). However, longitudinal evidence for such a mechanistic link in aging remains limited. Using multivariate modelling, we investigated the interrelationship between PVS and WMH over time to elucidate potential cascades of early cerebrovascular alterations and tested whether AD-biomarkers and inflammatory markers associated with vascular disease can explain individual variability in their occurrence and progression.

Developing Topics.

Background: Receiving sufficient assistance with ADLs/IADLs can support dementia patients' physical and psychosocial health, as well as aging in place. The Department of Veterans Affairs has prioritized supporting Veterans in aging at place a home when this is their preference. We aimed in the current study to analyze if there are demographic characteristics and/or comorbidities of Veterans with dementia that are predictive of having unmet ADL/IADL needs.

Developing Topics.

Background: Neurotransmitter receptors' contribution to Alzheimer's disease (AD) pathology development has been implicated by basic science studies but is yet to be fully established. Here, we incorporate receptor density maps into network spreading models to predict amyloid and tau patterns in AD, reflecting their potential roles in facilitating or impeding pathology production and connectivity-mediated spread.

Method: Amyloid-PET positive individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were divided into "early" (n = 119) and "late" (n = 69) pathology groups according to tau accumulation in the temporal cortex (Figure 1A).

Drug Development.

Background: Alzheimer's disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12-week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.

Method: Key inclusion criteria were age 55-85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.

Drug Development.

Background: Differences in patient characteristics across geographical regions may result in heterogeneity in clinical trial populations. evoke (NCT04777396) and evoke+ (NCT04777409) are two phase 3, multinational, randomised trials investigating semaglutide versus placebo in individuals with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD) (early AD). We present baseline characteristics across the geographical regions in evoke/evoke+.

Drug Development.

Background: Pivotal Alzheimer's Disease (AD) trials typically require thousands of participants, resulting in long enrollment timelines and substantial costs. We leverage deep learning predictive models to create prognostic scores (forecasted control outcome) of trial participants and in combination with a linear statistical model to increase statistical power in randomized clinical trials (RCT). This is a straightforward extension of the traditional RCT analysis, allowing for ease of use in any clinical program.

Drug Development.

Background: evoke and evoke+ are phase 3, randomized, placebo-controlled trials currently investigating the glucagon-like peptide-1 receptor agonist semaglutide as disease-modifying therapy (DMT) in persons with early Alzheimer's disease (AD). How the evoke and evoke+ trial populations compare with other phase 3 programs for DMTs in early AD has not been described.

Method: We compare the inclusion/exclusion criteria and baseline characteristics of the evoke/evoke+ trial populations with those of Clarity AD (lecanemab) and TRAILBLAZER-ALZ-2 (donanemab): two recent phase 3 trials assessing anti-amyloid monoclonal antibodies in persons with early AD.

Dementia Care Practice.

Background: A critical need to increase Alzheimer's disease (AD) screening exists given rising incidence, new disease-modifying treatments, and ill-equipped primary care settings. This study assessed the feasibility of a novel, community-based AD screening program to increase cognitive and retinal-based assessments.

Methods: An observational study, supported by the Davos Alzheimer's Collaborative, assessed the utility of leveraging community-based settings to increase rates of cognitive assessment (conducted by Alzheimer Society (AS) social workers [SWs]) and RetiSpec's AI-based eye test in optometry settings to detect biologic signatures of AD (plus participant survey).

Healthcare economic burden of unresolved slipping rib syndrome.

Objective: To evaluate the healthcare costs associated with unresolved slipping rib syndrome (SRS).

Methods: Data pertaining to patients who underwent operative repair for SRS at our academic institution were analyzed retrospectively. Duration of symptoms, previous management efforts, number of healthcare provider consultations, imaging studies, adjunctive surgical and pain management procedures performed to treat the symptoms, and prior unsuccessful SRS operations were catalogued.

Impact of TCF7L2 rs7903146 on clinical presentation and risk of complications in patients with type 2 diabetes.

Aims: TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear.

Materials And Methods: We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabetes at diagnosis and over a 10-year follow-up period.

The TRIPOD-LLM reporting guideline for studies using large language models.

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion.

The sequence-structure-function relationship of intrinsic ERα disorder.

The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.

Pre-breeding in alfalfa germplasm develops highly differentiated populations, as revealed by genome-wide microhaplotype markers.

Plant genebanks contain large numbers of germplasm accessions that likely harbor useful alleles or genes absent in commercial plant breeding programs. Broadening the genetic base of commercial alfalfa germplasm with these valuable genetic variations can be achieved by screening the extensive genetic diversity in germplasm collections and enabling maximal recombination among selected genotypes. In this study, we assessed the genetic diversity and differentiation of germplasm pools selected in northern U.