A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling.

Background: TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.

Methods: This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type.

Oncogenic mutations in the TP53 and PI-3 kinase/AKT pathway are independent predictors of survival for advanced thyroid cancer: Analysis from the Molecular Screening and Therapeutics (MoST) program.

Background: Thyroid cancers with mutations in the phosphatidylinositol-3 kinase/AKT pathway have a poorer prognosis. However, knowledge about the relationship between histology, mutation profile, and outcomes is still developing. This study assessed the prognostic value of genomic profiles for patients with advanced thyroid cancer who experienced progression on conventional treatment.

Attenuation Measuring Ultrasound Shearwave Elastography (AMUSE) as Noninvasive Imaging Biomarker for Liver Acute Cellular Rejection.

Objective: There are over 9000 liver transplants in the United States per year, with acute cellular rejection (ACR) being a prevalent early post-transplant complication (20%-40%) treated using corticosteroids. Ischemia-reperfusion injury (IRI), another early post-transplant pathology, has similar laboratory results but typically resolves without therapy. ACR confirmation requires invasive liver biopsy, bearing risks like hemorrhage and pneumothorax.

Temperature-dependent predation predicts a more reptilian future.

Diversity increases toward the tropics, but the strength of this pattern diverges with thermoregulatory strategy. Synthesizing over 30,000 species distributions, we quantified patterns of richness in terrestrial vertebrates, and present evidence for a latitudinal gradient of community composition. We observe a two orders of magnitude shift in comparative diversity with temperature, from endothermic mammal and avian dominance near the poles, toward ectothermic reptile and amphibian majority in the tropics.

A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation.

This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2).

A pan-sarcoma landscape of telomeric content shows that alterations in RAD51B and GID4 are associated with higher telomeric content.

Tumor cells need to activate a telomere maintenance mechanism, enabling limitless replication. The bulk of evidence supports that sarcomas predominantly use alternative lengthening of telomeres (ALT) mechanism, commonly associated with alterations in ATRX and DAXX. In our dataset, only 12.

Plantar Fasciitis or Flexor Digitorum Brevis Myositis.

Background: As common as plantar fasciitis is, there's a lack of evidence regarding the true pathophysiologic process causing plantar fasciitis and plantar heel pain in general. This may partially explain the high variability and outcomes with current treatment of recalcitrant plantar fasciitis. Although Lemont reported myxoid degeneration of plantar fascia with histologic analysis of patients with fasciitis, muscle biopsy results were not reported.

A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations.

Purpose: To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects.

Patients And Methods: In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2). Overall, 32 (66%) patients had rare or less common cancers.

Transmetatarsal Amputations: Outcomes of Primary Healing versus Secondary Healing.

Background: Transmetatarsal amputations are limb salvage surgical procedures that preserve limb length and functional ankle joints. Indications for transmetatarsal amputations include forefoot trauma, infection, and ischemia. Prior research demonstrates patients who undergo transmetatarsal amputations have a lower 2-year mortality rate compared to those who undergo more proximal amputations.

Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology.

While several resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers. To this end, we have structured a compendium of approved and experimental therapies with associated biomarkers following a survey of drug regulatory databases, existing knowledge bases, and published literature.

Management of Midfoot Cavus.

There is a deficiency in publications on the topic of midfoot cavus. The limited research available does not have a standard definition for the diagnosis of this deformity and lacks a reliable algorithm for its surgical management. The authors performed an extensive review of the literature that found a majority of patients are satisfied with the Cole osteotomy and the dorsiflexory first metatarsal osteotomy for treatment of this condition.

The allometry of locomotion.

Organismal locomotion mediates ecological interactions and shapes community dynamics. Locomotion is constrained by intrinsic and environmental factors and integrating these factors should clarify how locomotion affects ecology across scales. We extended general theory based on metabolic scaling and biomechanics to predict the scaling of five locomotor performance traits: routine speed, maximum speed, maximum acceleration, minimum powered turn radius, and angular speed.

Molecular patterns in salivary duct carcinoma identify prognostic subgroups.

Salivary duct carcinoma (SDCa) is a rare cancer with high rate of metastases and poor survival despite aggressive multimodality treatment. This study analyzes the genetic changes in SDCa, their impact on cancer pathways, and evaluates whether molecular patterns can identify subgroups with distinct clinical characteristics and outcome. Clinicopathologic details and tissue samples from 66 patients (48 males, 18 females) treated between 1995 and 2018 were obtained from multiple institutions.

Erratum: deletion drives acute myeloid leukemia resistance to MEK inhibitors.

[This corrects the article DOI: 10.18632/oncotarget.27206.

Chromosome arm aneuploidies shape tumour evolution and drug response.

Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis.

Development and validation of a targeted gene sequencing panel for application to disparate cancers.

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour's molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.

deletion drives acute myeloid leukemia resistance to MEK inhibitors.

Kinases such as MEK are attractive targets for novel therapy in cancer, including acute myeloid leukaemia (AML). Acquired and inherent resistance to kinase inhibitors, however, is becoming an increasingly important challenge for the clinical success of such therapeutics, and often arises from mutations in the drug-binding domain of the target kinase. To identify possible causes of resistance to MEK inhibition, we generated a model of resistance by long-term treatment of AML cells with AZD6244 (selumetinib).

Towards connecting biodiversity and geodiversity across scales with satellite remote sensing.

Issue: Geodiversity (i.e., the variation in Earth's abiotic processes and features) has strong effects on biodiversity patterns.

Extracorporeal Pulse-Activated Therapy versus Injection: Treatment of Recalcitrant Plantar Fasciitis.

Background: Plantar fasciitis is one of the most common clinical presentations seen by podiatric clinicians today. With corticosteroid injection being a classic treatment modality and extracorporeal pulse-activated therapy (EPAT) technology improving, the purpose of this study was to retrospectively compare pain and functional outcomes of patients with plantar fasciitis treated with either injection or EPAT.

Methods: Between November 1, 2014, and April 30, 2016, 60 patients who met the inclusion criteria were treated with either corticosteroid injection or EPAT.

Metabolic asymmetry and the global diversity of marine predators.

Species richness of marine mammals and birds is highest in cold, temperate seas-a conspicuous exception to the general latitudinal gradient of decreasing diversity from the tropics to the poles. We compiled a comprehensive dataset for 998 species of sharks, fish, reptiles, mammals, and birds to identify and quantify inverse latitudinal gradients in diversity, and derived a theory to explain these patterns. We found that richness, phylogenetic diversity, and abundance of marine predators diverge systematically with thermoregulatory strategy and water temperature, reflecting metabolic differences between endotherms and ectotherms that drive trophic and competitive interactions.