Robotic arm-assisted medial compartment knee arthroplasty is a cost-effective intervention at ten-year follow-up.

Aims: The aim of this study was to perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted medial unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA).

Methods: Ten-year follow-up of patients who were randomized to rUKA (n = 64) or mUKA (n = 65) was performed. Patients completed the EuroQol five-dimension health questionnaire preoperatively, at three months, and one, two, five, and ten years postoperatively, which was used to calculate quality-adjusted life years (QALY) gained and the incremental cost-effectiveness ratio (ICER).

Affinity maturation of antibody responses is mediated by differential plasma cell proliferation.

Increased antibody affinity over time after vaccination, known as affinity maturation, is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown.

Transition paths across the EMT landscape are dictated by network logic.

During development and cancer metastasis, cells transition reversibly from epithelial to mesenchymal via intermediate cell states during epithelial-mesenchymal transition (EMT). EMT is controlled by gene regulatory networks (GRNs) and can be described by a three-node GRN that permits tristable EMT landscapes. In this GRN, multiple inputs regulate the transcription factor ZEB that induces EMT.

Affinity maturation of antibody responses is mediated by differential plasma cell proliferation.

Increased antibody affinity over time after vaccination, known as affinity maturation, is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown.

Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life.

Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection indicating variants are acquired much earlier in life with unexplained initial growth spurts. Here we use fluctuating CpG methylation as a lineage marker to track stem cell clonal dynamics of hematopoiesis.

The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain.

Intracellular ribonucleases (RNases) are essential in all aspects of RNA metabolism, including maintaining accurate RNA levels. Inherited mutations in genes encoding ubiquitous RNases are associated with human diseases, primarily affecting the nervous system. Recessive mutations in genes encoding an evolutionarily conserved RNase complex, the RNA exosome, lead to syndromic neurodevelopmental disorders characterized by progressive neurodegeneration, such as Pontocerebellar Hypoplasia Type 1b (PCH1b).

Intratumoral CXCL12 Gradients Contextualize Tumor Cell Invasion, Migration and Immune Suppression in Breast Cancer.

Although the CXCL12/CXCR4 pathway has been prior investigated for its prometastatic and immuno- suppressive roles in the tumor microenvironment, evidence on the spatiotemporal regulation of these hallmarks has been lacking. Here, we demonstrate that CXCL12 forms a gradient specifically around cancer cell intravasation doorways, also known as Tumor Microenvironment of Metastasis (TMEM) doorways, thus facilitating the chemotactic translocation of prometastatic tumor cells expressing CXCR4 toward the perivascular TMEM doorways for subsequent entry into peripheral circulation. Fur- thermore, we demonstrate that the CXCL12-rich micro-environment around TMEM doorways may cre- ate immunosuppressive niches, whereby CD8 T cells, despite being attracted to these regions, often exhibit reduced effector functions, limiting their efficacy.

"I need as much support as I can get": A qualitative study of young adult perspectives on family involvement in treatment for opioid use disorder.

Background: Opioid use disorder (OUD) among young adults (YAs) continues to persist as a national health crisis. Best practice recommendations for YA OUD treatment highlight the importance of medication for OUD (MOUD) and family involvement across the treatment services continuum for better treatment retention and outcomes. Yet, concerned significant others (CSOs) such as family members, romantic partners, and family-of-choice members are not routinely involved in OUD and MOUD treatment for YAs.

Recommendations for developing a comprehensive point-of-care ultrasound (POCUS) program in the emergency department: an Emergency Medicine Ultrasound Group advocacy statement.

Objectives: Point-of-care ultrasound (POCUS) use is widespread in EDs and throughout those practising medicine. Between institutions and specialities, there is widespread variety and training. With this comes the risk of patient harm and backlash to a clinically useful modality.

Optimising POCUS programs: A summary of EMUG's recommendations for the development and maintenance of ED POCUS programs.

Objectives: Point-of-care ultrasound (POCUS) use is widespread in EDs and throughout those practising medicine. Between institutions and specialities, there is widespread variety and training. With this comes risk of patient harm and backlash to a clinically useful modality.

The mitochondrial transporter ABCB7L is essential for the biogenesis of cytosolic and nuclear iron-sulfur cluster proteins and cytosolic translation.

Unlabelled: Iron-sulfur (Fe-S) clusters are ubiquitous inorganic cofactors required for numerous essential cellular pathways. Since they cannot be scavenged from the environment, Fe-S clusters are synthesized in cellular compartments such as the apicoplast, mitochondrion, and cytosol. The cytosolic Fe-S cluster biosynthesis pathway relies on the transport of an intermediate from the mitochondrial pathway.

Combination antiretroviral therapy prevents SIV- induced aging in the hippocampus and neurodegeneration throughout the brain.

Virus-induced accelerated aging has been proposed as a potential mechanism underlying the persistence of HIV-associated neurocognitive disorders (HAND) despite advances in access and adherence to combination antiretroviral therapies (cART). While some studies have demonstrated evidence of accelerated aging in PLWH, studies examining acute infection, and cART intervention are limited, with most studies being or utilizing small animal models. Here, we utilized FFPE tissues from Simian immunodeficiency virus (SIV) infected rhesus macaques to assess the levels of two proteins commonly associated with aging - the cellular senescence marker p16 (p16) and the NAD-dependent deacetylase sirtuin 1 (SIRT1).

Automation and standardisation of a quantitative multiplex PCR assay using PCR.Ai.

Background: We previously undertook a prospective clinical study to evaluate PCR.Ai's (www.pcr.

Young adults' experiences of biographical retrogression whilst living with long COVID.

During the early years (2020-2021) of the COVID-19 pandemic, relatively little attention focused on experiences of people with long-lasting symptoms, particularly young adults who were commonly understood to be invulnerable to serious effects of the virus. Drawing on narrative interviews with 15 adults in their twenties and living in the UK when they became ill with long COVID, we explore contextual factors which made their long COVID illness experience, and the wholescale disruption to their lives, challenging. We propose that existing adaptations of the concept of biographical disruption are problematic for this group, and instead suggest that 'biographical retrogression' may more accurately reflect these young adults' experiences.

Scoping review of current challenges and circumstances impacting Indigenous applications to Canadian medical schools.

Introduction: Considering the relevant 2015 Truth and Reconciliation Commission recommendations, this paper reviews the current state of Canadian medical schools' Indigenous admissions processes and explores continued barriers faced by Indigenous applicants.

Methods: A summary of literature illustrating disadvantages for Indigenous applicants of current admissions tools is presented. A grey literature search of current admissions requirements, interview processes, and other relevant data from each medical school was performed.

Standard Versus Family-Based Screening, Brief Intervention, and Referral to Treatment for Adolescent Substance Use in Primary Care: Protocol for a Multisite Randomized Effectiveness Trial.

Background: Screening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning.

Text Messages With Financial Incentives for Men With Obesity: A Randomized Clinical Trial.

Importance: Effective weight loss interventions are needed for men with obesity.

Objective: To determine whether an intervention that combined text messaging with financial incentives attained significant weight loss at the 12-month follow-up compared with the control group and whether an intervention of text messaging alone attained significant weight loss at the 12-month follow-up compared with the control group.

Design, Setting, And Participants: An assessor-blinded randomized clinical trial conducted in Belfast, Bristol, and Glasgow areas in the UK.

Transitioning from Triton X-100 to Tergitol 15-S-9: impacts on diagnostic assays using viral PCR sample solution.

In 2019, the European Union banned Triton X-100, a detergent widely used in laboratory diagnostics, including the Viral PCR Sample Solution (VPSS), and urged manufacturers to find environmentally sustainable alternatives. Tergitol 15-S-9 (VPSS2) has been proposed as an alternative surfactant. This multicenter study evaluated the effectiveness of VPSS2, a Tergitol-based viral solution, as a replacement for VPSS.