Shared Decision-Making in Total Hip and Knee Arthroplasty: Understanding Surgeon and Patient Perspectives Regarding When It Is Time for Surgery.

Background: Although total hip and total knee arthroplasty are highly successful operations, the decision of whether and when to undergo surgery is highly subjective and discretionary, and specific guidelines regarding readiness for surgery remain elusive. The nature of these decisions underscores the importance of shared decision-making, which is founded on the concept that patients substantially contribute to determining their own readiness for surgery. The OPTION survey was developed as a conversation aid to facilitate shared decision-making in the context of total joint arthroplasty.

Summer primary production of Arctic kelp communities is more affected by duration than magnitude of simulated marine heatwaves.

Fjord systems in the Norwegian Arctic are experiencing an increasing frequency and magnitude of marine heatwaves. These episodic heat stress events can have varying degrees of acute impacts on primary production and nutrient uptake of mixed kelp communities, as well as modifying the biogeochemical cycling in nearshore systems where vast areas of kelp create structural habitat. To assess the impact of future marine heatwaves on kelp communities, we conducted a 23 day mesocosm experiment exposing mixed kelp communities to warming and heatwave scenarios projected for the year 2100.

Productivity of mixed kelp communities in an Arctic fjord exhibit tolerance to a future climate.

Arctic fjords are considered to be one of the ecosystems changing most rapidly in response to climate change. In the Svalbard archipelago, fjords are experiencing a shift in environmental conditions due to the Atlantification of Arctic waters and the retreat of sea-terminating glaciers. These environmental changes are predicted to facilitate expansion of large, brown macroalgae, into new ice-free regions.

A novel approach to quantify metrics of upwelling intensity, frequency, and duration.

The importance of coastal upwelling systems is widely recognized. However, several aspects of the current and future behaviors of these systems remain uncertain. Fluctuations in temperature because of anthropogenic climate change are hypothesized to affect upwelling-favorable winds and coastal upwelling is expected to intensify across all Eastern Boundary Upwelling Systems.

Marine Heatwaves.

Ocean temperature variability is a fundamental component of the Earth's climate system, and extremes in this variability affect the health of marine ecosystems around the world. The study of marine heatwaves has emerged as a rapidly growing field of research, given notable extreme warm-water events that have occurred against a background trend of global ocean warming. This review summarizes the latest physical and statistical understanding of marine heatwaves based on how they are identified, defined, characterized, and monitored through remotely sensed and in situ data sets.

What and where? Predicting invasion hotspots in the Arctic marine realm.

The risk of aquatic invasions in the Arctic is expected to increase with climate warming, greater shipping activity and resource exploitation in the region. Planktonic and benthic marine aquatic invasive species (AIS) with the greatest potential for invasion and impact in the Canadian Arctic were identified and the 23 riskiest species were modelled to predict their potential spatial distributions at pan-Arctic and global scales. Modelling was conducted under present environmental conditions and two intermediate future (2050 and 2100) global warming scenarios.

Next-generation characterization of the Cancer Cell Line Encyclopedia.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers.

Structural and Electronic Flexibility in Hydrides of Zintl Phases with Tetrel-Hydrogen and Tetrel-Tetrel Bonds.

The hydrogenation of Zintl phases enables the formation of new structural entities with main-group-element-hydrogen bonds in the solid state. The hydrogenation of SrSi, BaSi, and BaGe yields the hydrides SrSiH BaSiH and BaGeH . The crystal structures show a sixfold superstructure compared to the parent Zintl phase and were solved by a combination of X-ray, neutron, and electron diffraction and the aid of DFT calculations.

High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells.

Like classical chemotherapy regimens used to treat cancer, targeted therapies will also rely upon polypharmacology, but tools are still lacking to predict which combinations of molecularly targeted drugs may be most efficacious. In this study, we used image-based proliferation and apoptosis assays in colorectal cancer cell lines to systematically investigate the efficacy of combinations of two to six drugs that target critical oncogenic pathways. Drug pairs targeting key signaling pathways resulted in synergies across a broad spectrum of genetic backgrounds but often yielded only cytostatic responses.

Gene Expression Ratios Lead to Accurate and Translatable Predictors of DR5 Agonism across Multiple Tumor Lineages.

Death Receptor 5 (DR5) agonists demonstrate anti-tumor activity in preclinical models but have yet to demonstrate robust clinical responses. A key limitation may be the lack of patient selection strategies to identify those most likely to respond to treatment. To overcome this limitation, we screened a DR5 agonist Nanobody across >600 cell lines representing 21 tumor lineages and assessed molecular features associated with response.

Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies.

A chromosomal region that includes the gene encoding HER2, a receptor tyrosine kinase (RTK), is amplified in 20% of breast cancers. Although these tumors tend to respond to drugs directed against HER2, they frequently become resistant and resume their malignant progression. Gene amplification in double minutes (DMs), which are extrachromosomal entities whose number can be dynamically regulated, has been suggested to facilitate the acquisition of resistance to therapies targeting RTKs.

Neurocognitive performance and prior injury among U.S. Department of Defense military personnel.

This study examined the neurocognitive performance of U.S. military personnel completing the Automated Neuropsychological Assessment Metrics (version 4) TBI Military (ANAM4 TBI-MIL) battery as part of the Department of Defense Neurocognitive Functional Assessment Program.

Silver Indium Telluride Semiconductors and Their Solid Solutions with Cadmium Indium Telluride: Structure and Physical Properties.

Ag0.8In2.4Te4 (= AgIn3Te5) and Ag0.

Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors.

Unlabelled: Focal amplification and activating point mutation of the MET gene are well-characterized oncogenic drivers that confer susceptibility to targeted MET inhibitors. Recurrent somatic splice site alterations at MET exon 14 (METex14) that result in exon skipping and MET activation have been characterized, but their full diversity and prevalence across tumor types are unknown. Here, we report analysis of tumor genomic profiles from 38,028 patients to identify 221 cases with METex14 mutations (0.

Loss of Tuberous Sclerosis Complex 2 (TSC2) Is Frequent in Hepatocellular Carcinoma and Predicts Response to mTORC1 Inhibitor Everolimus.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and hyperactivation of mTOR signaling plays a pivotal role in HCC tumorigenesis. Tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2, functions as a negative regulator of mTOR signaling. In the current study, we discovered that TSC2 loss-of-function is common in HCC.

FGFR-Mediated Reactivation of MAPK Signaling Attenuates Antitumor Effects of Imatinib in Gastrointestinal Stromal Tumors.

Unlabelled: Activating mutations in either KIT or PDGFRA are present in approximately 90% of gastrointestinal stromal tumors (GIST). Although treatment with the KIT and PDGFR inhibitor imatinib can control advanced disease in about 80% of GIST patients, the beneficial effect is not durable. Here, we report that ligands from the FGF family reduced the effectiveness of imatinib in GIST cells, and FGF2 and FGFR1 are highly expressed in all primary GIST samples examined.

The identification and characterization of a STAT5 gene signature in hematologic malignancies.

Background: The JAK-STAT pathway is an important signaling pathway downstream of multiple cytokine and growth factor receptors. Dysregulated JAK-STAT signaling has been implicated in the pathogenesis of multiple human malignancies.

Objective: Given this pivotal role of JAK-STAT dysregulation, it is important to identify patients with an overactive JAK-STAT pathway for possible treatment with JAK inhibitors.

CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.

Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs frequently in breast cancer. However, clinical results of single-agent PI3K inhibitors have been modest to date. A combinatorial drug screen on multiple PIK3CA mutant cancers with decreased sensitivity to PI3K inhibitors revealed that combined CDK 4/6-PI3K inhibition synergistically reduces cell viability.

MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells.

Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC.