Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution.

Osteosarcoma is the most common primary cancer of the bone, with a peak incidence in children and young adults. Using multi-region whole-genome sequencing, we find that chromothripsis is an ongoing mutational process, occurring subclonally in 74% of osteosarcomas. Chromothripsis generates highly unstable derivative chromosomes, the ongoing evolution of which drives the acquisition of oncogenic mutations, clonal diversification, and intra-tumor heterogeneity across diverse sarcomas and carcinomas.

Endoscopic Flexor Hallucis Longus Tendon Transfer for the Treatment of Chronic Achilles Tendon Defects.

Background: An all-inside endoscopic flexor hallucis longus (FHL) tendon transfer is indicated for the treatment of chronic, full-thickness Achilles tendon defects. The aim of this procedure is to restore function of the gastrocnemius-soleus complex while avoiding the wound complications associated with open procedures.

Description: This procedure can be performed through 2 endoscopic portals, a posteromedial portal (the working portal) and a posterolateral portal (the visualization portal).

Jejunal gastrointestinal stromal tumor (GIST) with profound anemia.

Gastrointestinal stromal tumors (GISTs) are uncommon tumors typically found in the stomach, with an even rarer appearance in the jejunum. These tumors are often discovered incidentally, given their nonspecific presentation. We present a case of chronic iron deficiency anemia in a patient with symptomatic GIST involving the proximal jejunum requiring robot-assisted resection with primary anastomosis.

Source reservoir controls on the size, frequency, and composition of large-scale volcanic eruptions.

Large-scale, explosive volcanic eruptions are one of the Earth's most hazardous natural phenomena. We demonstrate that their size, frequency, and composition can be explained by processes in long-lived, high-crystallinity source reservoirs that control the episodic creation of large volumes of eruptible silicic magma and its delivery to the subvolcanic chamber where it is stored before eruption. Melt percolates upward through the reservoir and accumulates a large volume of low-crystallinity silicic magma which remains trapped until buoyancy causes magma-driven fractures to propagate into the overlying crust, allowing rapid magma transfer from the reservoir into the chamber.

Identification of genes that promote PI3K pathway activation and prostate tumour formation.

We have performed a functional in vivo mutagenesis screen to identify genes that, when altered, cooperate with a heterozygous Pten mutation to promote prostate tumour formation. Two genes, Bzw2 and Eif5a2, which have been implicated in the process of protein translation, were selected for further validation. Using prostate organoid models, we show that either Bzw2 downregulation or EIF5A2 overexpression leads to increased organoid size and in vivo prostate growth.

Prevalence of Women in Medicine Programs at University-Based Internal Medicine Residency Programs.

Objective: Women physicians face various forms of inequities during their training process that inhibit them from reaching their full potential. As a response, several academic institutions have established women in medicine (WIM) programs as a support system. Our objective was to investigate the prevalence of WIM programs at university-based Internal Medicine residency programs as of December 2021.

Caregiver descriptions of dystonia in cerebral palsy.

Objective: To determine how caregivers describe dystonia in people with cerebral palsy (CP).

Methods: In this prospective cohort study, paper surveys were administered to caregivers between September 7, 2021 and October 28, 2021 during CP Center visits at a large tertiary care center. Caregivers were asked to describe involuntary movements triggered by voluntary movement or triggered by tactile stimulation in the people with CP they cared for.

The Relationship Between the Wrist Flexion Creases and the Volar Radiocarpal Joint: A Cadaveric Study.

Background: Surgical approaches to the volar radiocarpal joint have historically entailed wide exposure, possibly contributing to poor wound healing and wrist denervation. To avoid wound complications and wrist denervation, minimally invasive and percutaneous approaches to the volar radiocarpal joint have been proposed. To help guide these minimally invasive or percutaneous approaches to the joint, we sought to characterize the relationship between the volar wrist flexion creases and the volar radiocarpal joint.

A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.

Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, overexpression of the BRCA1-∆11q splice variant has been shown to cause PARPi resistance. How cancer cells achieve increased BRCA1-∆11q expression has remained unclear.

Time to surgery and outcomes following open reduction and internal fixation of both-bone forearm fractures.

Purpose: To determine the effect of time to surgery on outcomes following open reduction and internal fixation (ORIF) of both-bone forearm fractures (BBFFs).

Methods: Ninety-nine patients who underwent ORIF of BBFFs in a single academic medical center over a 16-year time period were retrospectively reviewed. Demographic and clinical data including age, sex, current smoking status, time from injury to surgery (t), presence of open injury, polytrauma status, and complications were obtained.

JAK2/STAT5 Pathway Mutation Frequencies in South African BCR/ABL Negative MPN Patients.

Background: Mutations in JAK2/STAT5 proliferation pathway genes are key in the diagnosis of myeloproliferative neoplasms (MPN), with JAK2V617F being found in 50-97% of MPN subtypes. Low JAK2V617F positivity at our facility suggested that our South African MPN population may have a different mutational landscape.

Objectives: We aimed to determine the JAK2/STAT5 mutation frequencies associated with our local MPN population, thus determining the relevance of these molecular tests in this group.

Open Versus Endoscopic Carpal Tunnel Release: A Comparison of Opioid Prescription Patterns and Occupational Therapy Referrals.

Background: Endoscopic and open carpal tunnel releases (ECTR and OCTR) are safe and effective operations. We compared the approaches in terms of postoperative opioid refills and occupational therapy (OT) referrals.

Methods: We conducted a retrospective study of patients with carpal tunnel syndrome (CTS) treated with ECTR or OCTR.

Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis.

Unlabelled: Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers.

Timescales for pluton growth, magma-chamber formation and super-eruptions.

Generation of silicic magmas leads to emplacement of granite plutons, huge explosive volcanic eruptions and physical and chemical zoning of continental and arc crust. Whereas timescales for silicic magma generation in the deep and middle crust are prolonged, magma transfer into the upper crust followed by eruption is episodic and can be rapid. Ages of inherited zircons and sanidines from four Miocene ignimbrites in the Central Andes indicate a gap of 4.

Prince Rupert's Drops: An analysis of fragmentation by thermal stresses and quench granulation of glass and bubbly glass.

When volcanic eruptions involve interaction with external water (hydrovolcanism), the result is an ash-rich and energetic volcanic plume, as illustrated dramatically by the January 2022 Tonga eruption. The origin of the high explosive energy of these events remains an important question. We investigate this question by studying Prince Rupert's Drops (PRDs)-tadpole-shaped glass beads formed by dripping molten glass into water-which have long fascinated materials scientists because the great strength of the head contrasts with the explosivity of the metastable interior when the tail is broken.

Forest fire mobilization and uptake of metals by biota temporarily exacerbates impacts of legacy mining.

While wildfires are a natural occurrence and ecosystems have evolved with fire, a changing climate is extending the wildfire season increasing the number, size and severity of fires in the western United States. In 2018, wildfire consumed 30% more area in the Western United States than the average ten years prior, and 76% more area than the average twenty years ago. These recent wildfires have impacted communities in the southwestern Rocky Mountains.

Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-β.

Adoptive T cell therapy with T cells expressing affinity-enhanced TCRs has shown promising results in phase 1/2 clinical trials for solid and hematological tumors. However, depth and durability of responses to adoptive T cell therapy can suffer from an inhibitory tumor microenvironment. A common immune-suppressive agent is TGF-β, which is secreted by tumor cells and cells recruited to the tumor.

Resilience of terrestrial and aquatic fauna to historical and future wildfire regimes in western North America.

Wildfires in many western North American forests are becoming more frequent, larger, and severe, with changed seasonal patterns. In response, coniferous forest ecosystems will transition toward dominance by fire-adapted hardwoods, shrubs, meadows, and grasslands, which may benefit some faunal communities, but not others. We describe factors that limit and promote faunal resilience to shifting wildfire regimes for terrestrial and aquatic ecosystems.

The economic potential of metalliferous sub-volcanic brines.

The transition to a low-carbon economy will increase demand for a wide range of metals, notably copper, which is used extensively in power generation and in electric vehicles. Increased demand will require new, sustainable approaches to copper exploration and extraction. Conventional copper mining entails energy-intensive extraction of relatively low-grade ore from large open pits or underground mines and subsequent ore refining.

Simulating the thermal impact of substrate temperature on ecological restoration in shallow urban rivers.

Managing river temperature in highly urbanized stream systems is critical for maintaining aquatic ecosystems and associated beneficial uses. In this work, we updated and utilized a mechanistic river temperature model, i-Tree Cool River, to evaluate the cooling impacts of two ecological restoration scenarios: (1) an alternative streambed material limecrete and (2) shading effects of tree planting in riparian areas. The i-Tree Cool River model was modified to account for diurnal fluctuations of streambed temperature, which is relevant in shallow urban streams where lack of natural shading combined with low heat capacity of the water column can make diurnal fluctuations relatively extreme.

Application of ANOVA-simultaneous component analysis to quantify and characterise effects of age, temperature, syrup adulteration and irradiation on near-infrared (NIR) spectral data of honey.

NIR spectroscopy combined with chemometric analysis has proven to be a rapid and cost-effective screening tool for the detection of syrup-adulterated honey. Processing and storage conditions which alter the chemical and physical state of honey may affect the spectra. The effects of age, storage temperature, syrup adulteration (10 and 20% w/w) and irradiation treatment on the NIR spectra of honey were investigated as a function of time with ANOVA-simultaneous component analysis (ASCA), an experimental design-focused exploratory data analysis method.

The Mutational Concordance of Fixed Formalin Paraffin Embedded and Fresh Frozen Gastro-Oesophageal Tumours Using Whole Exome Sequencing.

Unlabelled: 1.

Background: The application of massively parallel sequencing has led to the identification of aberrant druggable pathways and somatic mutations within therapeutically relevant genes in gastro-oesophageal cancer. Given the widespread use of formalin-fixed paraffin-embedded (FFPE) samples in the study of this disease, it would be beneficial, especially for the purposes of biomarker evaluation, to assess the concordance between comprehensive exome-wide sequencing data from archival FFPE samples originating from a prospective clinical study and those derived from fresh-frozen material.

Structural and compositional characteristics of Fukushima release particulate material from Units 1 and 3 elucidates release mechanisms, accident chronology and future decommissioning strategy.

The structural form and elemental distribution of material originating from different Fukushima Daiichi Nuclear Power Plant reactors (Units 1 and 3) is hereby examined to elucidate their contrasting release dynamics and the current in-reactor conditions to influence future decommissioning challenges. Complimentary computed X-ray absorption tomography and X-ray fluorescence data show that the two suites of Si-based material sourced from the different reactor Units have contrasting internal structure and compositional distribution. The known event and condition chronology correlate with the observed internal and external structures of the particulates examined, which suggest that Unit 1 ejecta material sustained a greater degree of melting than that likely derived from reactor Unit 3.

Inhibition of SYK kinase does not confer a pro-proliferative or pro-invasive phenotype in breast epithelium or breast cancer cells.

SYK has been reported to possess both tumour promotor and repressor activities and deletion has been linked to a pro-proliferative / pro-invasive phenotype in breast tumours. It is unclear whether this is a consequence of protein deletion or loss of kinase activity. The SYK inhibitor, BI 1002494, caused no increase in proliferation in breast cancer cells or primary mammary epithelial cells in 2D or 3D cultures, nor changes in proliferation (CD1/2, CDK4, PCNA, Ki67) or invadopodia markers (MMP14, PARP, phospho-vimentin Ser56).