Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

Beauvoir, Ernaux, and Me: On Age, Disability, and Dying Well.

Can the fraught relation between disability and aging ever become untangled? What is the place of the catastrophically disabled in a time when giving voice and being seen are significant lodestars of political activism? And what becomes of the caregivers, who often labor in silence, and who hope to work well enough just to get through another day? This essay draws on the memoirs of Simone de Beauvoir, Annie Ernaux, Amy Bloom, and my own experiences to show the complicated imbrications of age, disability, and caretaking. I attempt to demonstrate through these experiences that age and disability, which appear to be intimately woven together, are oftentimes misleadingly connected. I suggest that an ethic of vulnerability, rather, is a more useful heuristic that avoids collapsing the categories of age and disability together.

Nutrient-driven histone code determines exhausted CD8 T cell fates.

Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity.

SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections.

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection.

Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study).

Introduction: Sickle cell disease (SCD) is one of the most common genetic diseases in the world, annually affecting approximately 310 000 births and causing >100 000 deaths. Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain, thoracic pain (acute chest syndrome) and/or abdominal spasms. It is the main cause of mortality in patients with SCD, reducing life expectancy.

Initial Safety of Total Talus Replacement Used to Treat Talar Avascular Necrosis.

Background: Total talus replacement (TTR) implants are designed to replace the diseased talar anatomy, reduce pain, maintain ankle range of motion, and restore ankle function after conservative treatments have failed. Currently TTR implants are produced by 3D printing a patient-specific implant designed from the patient's preoperative anatomy. TTR surgery using patient-specific implants is a relatively new technique that remains understudied in the literature.

Rheumatoid Deformities of the Lesser Toes.

Rheumatoid arthritis is a chronic heterogeneous autoimmune disease characterized by painful joint inflammation and causes destructive bone erosions. Most common deformities in the rheumatoid forefoot are hallux valgus and claw toes. Radiographs are helpful to show the deformity and the associated pathologies.

How affective and instrumental physical activity outcomes are associated with motivation, intentions, and engagement in subsequent behavior.

Physical activity (PA) produces various outcomes, including affective responses and instrumental benefits (e.g., weight loss, health).

Chemotherapeutic Potential of Chlorambucil-Platinum(IV) Prodrugs against Cisplatin-Resistant Colorectal Cancer Cells.

Chlorambucil-platinum(IV) prodrugs exhibit multi-mechanistic chemotherapeutic activity with promising anticancer potential. The platinum(II) precursors of the prodrugs have been previously found to induce changes in the microtubule cytoskeleton, specifically actin and tubulin of HT29 colon cells, while chlorambucil alkylates the DNA. These prodrugs demonstrate significant anticancer activity in 2D cell and 3D spheroid viability assays.

Which LGBTQ+ Inclusive School Strategies Support LGBTQ+ Student, Staff and Parent Perceptions of School Climate? A Latent Class Analysis.

Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ+) students, LGBTQ+ staff and LGBTQ+ parents report schools can be unsafe and unwelcoming environments. Yet few studies have explored LGBTQ+ student, LGBTQ+ staff and LGBTQ+ parent perceptions of the school climate simultaneously or adopted person-centered perspectives. The present study sought to identify LGBTQ+ related strategies adopted by schools, and whether these were differentially related to perceptions of school safety and community.

The Self-Control of Eating.

Many individuals struggle to regulate their own consumption of food. Beginning with general theories of self-control, we review psychological factors that have been shown to influence the regulation of eating, including those related to particular personality variables, such as external eating, restrained eating, and reward sensitivity, as well as situational constraints, including normative influences, emotions, and calorie deprivation. Strategies for the self-control of eating, including reappraisal, effortful inhibition, and various automatic strategies are also reviewed, along with a discussion of the strengths and limitations of historical and contemporary psychological studies investigating food consumption.

Anticancer Effect of PtPHEN, Pt5ME, Pt56ME and Their Platinum(IV)-Dihydroxy Derivatives against Triple-Negative Breast Cancer and Cisplatin-Resistant Colorectal Cancer.

Development of resistance to cisplatin, oxaliplatin and carboplatin remains a challenge for their use as chemotherapies, particularly in breast and colorectal cancer. Here, we compare the anticancer effect of novel complexes [Pt(1,10-phenanthroline)(1,2-diaminocyclohexane)](NO) (), [Pt(5-methyl-1,10-phenanthroline)(1,2-diaminocyclohexane)](NO) () and [Pt(5,6-dimethyl-1,10-phenanthroline)(1,2-diaminocyclohexane)](NO) () and their platinum(IV)-dihydroxy derivatives with cisplatin. Complexes are greater than 11-fold more potent than cisplatin in both 2D and 3D cell line cultures with increased selectivity for cancer cells over genetically stable cells.

Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Background: Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa.

Methods: We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140).

The role of social norms, intergroup contact, and ingroup favoritism in weight stigma.

Although average body size in the U.S. has increased in recent decades, stigma directed at individuals with higher weight has not diminished.

Intratumoral antigen signaling traps CD8 T cells to confine exhaustion to the tumor site.

Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8 T cells in the tumor.

Surgeon variation: a south african spinal pathology treatment survey.

Purpose: To investigate variation in treatment decisions among spine surgeons in South Africa and the association between surgeon characteristics and the treatment they select.

Methods: We surveyed 79 South African spine surgeons. We presented four vignettes (cervical spine distractive flexion injury, lumbar disc herniation, degenerative spondylolisthesis with stenosis, and insufficiency fracture) for them to assess and select treatments.

Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study.

Background: Undiagnosed tuberculosis remains a major threat for people living with HIV. Multiple blood transcriptomic biomarkers have shown promise for tuberculosis diagnosis. We sought to evaluate their diagnostic accuracy and clinical utility for systematic pre-antiretroviral therapy (ART) tuberculosis screening.

Consequences of receiving weight-related advice from a healthcare provider: Understanding the varied experiences of people with higher weight.

Healthcare providers regularly give weight-related advice (e.g., behavioral weight loss counseling) to patients with higher weight (BMI ≥30 kg/m).

Stereotactic Optimized Automated Radiotherapy (SOAR): a novel automated planning solution for multi-metastatic SRS compared to HyperArc™.

Automated Stereotactic Radiosurgery (SRS) planning solutions improve clinical efficiency and reduce treatment plan variability. Available commercial solutions employ a template-based strategy that may not be optimal for all SRS patients. This study compares a novel beam angle optimized Volumetric Modulated Arc Therapy (VMAT) planning solution for multi-metastatic SRS to the commercial solution HyperArc.

Private healthcare sector spine surgery: patient and surgeon profiles from a large open medical scheme in South Africa.

Background It is generally understood that the profile of spine surgery varies by setting, based on factors such as the age profile of the population, the economic context and access to healthcare. Relatively little is known about the profile of spine surgery in South Africa, although one previous report from the public healthcare sector suggested a high burden of trauma and infection-related surgery. To our knowledge, there has been no formal investigation in the private sector.

SHaploseek is a sequencing-only, high-resolution method for comprehensive preimplantation genetic testing.

Recent advances in genomic technologies expand the scope and efficiency of preimplantation genetic testing (PGT). We previously developed Haploseek, a clinically-validated, variant-agnostic comprehensive PGT solution. Haploseek is based on microarray genotyping of the embryo's parents and relatives, combined with low-pass sequencing of the embryos.

Atmospheric Dry and Wet Deposition of Total Phosphorus to the Great Lakes.

Quantifying atmospheric loadings of total phosphorus (TP) to freshwater environments is essential to improve understanding of its fate and transport, and to mitigate the effects of excessive levels in freshwater ecosystems. To date, atmospheric deposition of TP in the U.S.

Is there a tolerance for extension of the first metatarsal after the Lapidus procedure? A clinical, functional, and hindfoot radiographic analysis.

Purpose: Based on the tripod concept of load distribution, our study aimed to evaluate whether a slight extension of first metatarsal (M1) that may occur after the Lapidus procedure (LP) could alter the radiographic measurements of the hindfoot and influence clinical and functional outcomes.

Methods: Twenty-five patients (27 feet) were reviewed. Hindfoot radiographic analysis was based on seven measurements.