Analytical Validation and Performance of a Blood-Based P-tau217 Diagnostic Test for Alzheimer Disease.

Background: Blood-based biomarkers, especially P-tau217, have been gaining interest as diagnostic tools to measure Alzheimer disease (AD) pathology.

Methods: We developed a plasma P-tau217 chemiluminescent immunoassay using 4G10E2 and IBA493 as antibodies, a synthetic tau peptide as calibrator, and the Quanterix SP-X imager. Analytical validation performed in a College of American Pathologists-accredited CLIA laboratory involved multiple kit lots, operators, timepoints, and imagers.

Long-read epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.

AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, responses are typically short lived. Thus, there is an urgent need to develop more effective treatments.

Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers.

Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.

An Assessment of Open Fracture Management in Hospitals in Malawi Before and Immediately After Implementing Open Fracture Guidelines.

Background: Open fractures, a common consequence of road traffic collisions, are associated with a high risk of complications. The introduction of standard guidelines has been shown to improve patient care and reduce the risk of complications in several countries. In September 2021, the Malawi Orthopaedic Association/Arbeitsgemeinschaft für Osteosynthesefragen Alliance (MOA/AOA) guidelines and standards for open fracture management were introduced in Malawi.

Evaluation of Antioxidants' Ability to Enhance Hyaluronic-acid Based Topical Moisturizers.

Background: Hyaluronic acid (HA) is a unique molecule of the extracellular matrix with multiple biological activities. In skin, HA plays an essential role as a humectant, capable of binding up to 1,000 times its mass with water, providing skin with moisture and viscoelastic properties. HA concentration and synthesis decrease significantly in aging skin, due to exogenous and endogenous factors, including photoaging and HA metabolism.

A meta-analysis of the incidence of infections following open tibia fractures and the microorganisms that cause them in high-, middle- and low-income countries.

Open tibia fractures are devastating, life changing injuries, with infection associated with substantial morbidity to the patient. Reducing infection is a research priority, but before interventional studies can be designed, the incidence of infection following this injury needs to be better defined. Our aim was to estimate the global incidence of infection following an open tibia fracture.

Pathologist-trained machine learning classifiers developed to quantitate celiac disease features differentiate endoscopic biopsies according to modified marsh score and dietary intervention response.

Background: Histologic evaluation of the mucosal changes associated with celiac disease is important for establishing an accurate diagnosis and monitoring the impact of investigational therapies. While the Marsh-Oberhuber classification has been used to categorize the histologic findings into discrete stages (i.e.

Functional outcomes and quality of life at 1-year follow-up after an open tibia fracture in Malawi: a multicentre, prospective cohort study.

Background: Injuries are a major cause of disability globally and injury incidence is rapidly increasing, largely due to road traffic injuries in low-income and middle-income countries. Current estimates of the scale and consequences of disability from injury are largely based on modelling studies, with a scarcity of empirical evidence from severe injuries in low-income countries. We aimed to better understand the outcomes for individuals with open tibia fractures in Malawi.

Cotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer.

Despite the success of KRAS G12C inhibitors in non-small cell lung cancer (NSCLC), more effective treatments are needed. One preclinical strategy has been to cotarget RAS and mTOR pathways; however, toxicity due to broad mTOR inhibition has limited its utility. Therefore, we sought to develop a more refined means of targeting cap-dependent translation and identifying the most therapeutically important eukaryotic initiation factor 4F complex-translated (eIF4F-translated) targets.

Monolithic high contrast grating on GaSb/AlAsSb based epitaxial structures for mid-infrared wavelength applications.

We demonstrate monolithic high contrast gratings (MHCG) based on GaSb/AlAsSb epitaxial structures with sub-wavelength gratings enabling high reflection of unpolarized mid-infrared radiation at the wavelength range from 2.5 to 5 µm. We study the reflectivity wavelength dependence of MHCGs with ridge widths ranging from 220 to 984 nm and fixed 2.

Combating castration-resistant prostate cancer by co-targeting the epigenetic regulators EZH2 and HDAC.

While screening and early detection have reduced mortality from prostate cancer, castration-resistant disease (CRPC) is still incurable. Here, we report that combined EZH2/HDAC inhibitors potently kill CRPCs and cause dramatic tumor regression in aggressive human and mouse CRPC models. Notably, EZH2 and HDAC both transmit transcriptional repressive signals: regulating histone H3 methylation and histone deacetylation, respectively.

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

Aims: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse.

Methods And Results: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation.

Applications of red light photoredox catalysis in organic synthesis.

Photoredox catalysis has emerged as an efficient and versatile approach for developing novel synthetic methodologies. Particularly, red light photocatalysis has attracted more attention due to its intrinsic advantages of low energy, few health risks, few side reactions, and high penetration depth through various media. Impressive progress has been made in this field.

Targeted Quantitative Mass Spectrometry Analysis of Protein Biomarkers From Previously Stained Single Formalin-Fixed Paraffin-Embedded Tissue Sections.

Formalin-fixed, paraffin-embedded tissues represent a majority of all biopsy specimens commonly analyzed by histologic or immunohistochemical staining with adhesive coverslips attached. Mass spectrometry (MS) has recently been used to precisely quantify proteins in samples consisting of multiple unstained formalin-fixed, paraffin-embedded sections. Here, we report an MS method to analyze proteins from a single coverslipped 4-μm section previously stained with hematoxylin and eosin, Masson trichrome, or 3,3'-diaminobenzidine-based immunohistochemical staining.

Rotationplasty with Tibial Nerve Coaptation: A Case Report.

Case: We present the case of a 14-year-old adolescent boy with a distal femoral osteosarcoma partially encasing the tibial nerve. He underwent rotationplasty with resection and coaptation (end-to-end repair) of the tibial nerve. By 1 year postoperatively, he had recovered sensation on the plantar aspect of his foot and Medical Research Council scale 4+/5 gastro-soleus contraction that powered extension of the new knee.

Using a consensus meeting to enhance fracture care education in low income countries.

Background: A key strategy to building surgical capacity in low income countries involves training care providers, particularly in the interventions highlighted by the Lancet Commission for Global Surgery, including the management of open fractures. This is a common injury, especially in areas with a high incidence of road traffic incidents. The aim of this study was to use a nominal group consensus method to design a course on open fracture management for clinical officers in Malawi.

The Relation between Depressive Symptoms and Unsafe Sex among MSM Living with HIV.

In people living with HIV (PLWH), a positive association is often found between depressive symptoms and unsafe sex, which means sex without a condom. However, the results of such studies are inconclusive. The present study compared the numbers of safe and unsafe sexual contacts from men who have sex with men (MSM) (N = 159), living with HIV and attending a mental health clinic, with those of HIV-negative MSM in the general population (N = 198).

"Don't rush into thinking of walking again": Patient views of treatment and disability following an open tibia fracture in Malawi.

Open tibia fractures are a common injury following road traffic accidents in Malawi and can lead to long term disability. Very little is known about patients' experiences of the healthcare system and the disability in low-income countries following this injury. The aim of the study was to explore patient experiences of treatment and disability following an open tibia fracture in Malawi.

Epidemiology of Open Tibia fractures presenting to a tertiary referral centre in Southern Malawi: a retrospective study.

Background: Road traffic accidents in Malawi have increased in recent years resulting in a high incidence of trauma seen in the hospitals as well as a high prevalence of musculoskeletal impairment in the community. Open fractures are a common consequence of road traffic accidents and the tibia is the most common long bone open fracture.

Objective: Epidemiology of open tibia fractures at the largest tertiary level hospital in Malawi and incidence of infections of open fractures managed at the institution.

Oesophageal safety in voltage-guided atrial fibrillation ablation using ablation index or contact force only: a prospective comparison.

Aims: Left atrial ablation using radiofrequency (RF) is associated with endoscopically detected thermal oesophageal lesions (EDELs). The aim of this study was to compare EDEL occurrence after conventional contact force-guided (CFG) RF ablation vs. an ablation index-guided (AIG) approach in clinical routine of voltage-guided ablation (VGA).

Coordinating gene expression during the cell cycle.

Cell cycle-dependent gene transcription is tightly controlled by the retinoblastoma (RB):E2F and DREAM complexes, which repress all cell cycle genes during quiescence. Cyclin-dependent kinase (CDK) phosphorylation of RB and DREAM allows for the expression of two gene sets. The first set of genes, with peak expression in G1/S, is activated by E2F transcription factors (TFs) and is required for DNA synthesis.