Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.

Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.

Methods: This was an open-label, two-part, phase II, single-arm, multicenter study.

Single-cell sequencing suggests a conserved function of Hedgehog-signalling in spider eye development.

Background: Spiders evolved different types of eyes, a pair of primary eyes that are usually forward pointing, and three pairs of secondary eyes that are typically situated more posterior and lateral on the spider's head. The best understanding of arthropod eye development comes from the vinegar fly Drosophila melanogaster, the main arthropod model organism, that also evolved different types of eyes, the larval eyes and the ocelli and compound eyes of the imago. The gene regulatory networks that underlie eye development in this species are well investigated revealing a conserved core network, but also show several differences between the different types of eyes.

Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole.

Purpose: ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes.

Methods: MA.

Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development.

Background: The common house spider Parasteatoda tepidariorum represents an emerging new model organism of arthropod evolutionary and developmental (EvoDevo) studies. Recent technical advances have resulted in the first single-cell sequencing (SCS) data on this species allowing deeper insights to be gained into its early development, but mid-to-late stage embryos were not included in these pioneering studies.

Results: Therefore, we performed SCS on mid-to-late stage embryos of Parasteatoda and characterized resulting cell clusters by means of in-silico analysis (comparison of key markers of each cluster with previously published information on these genes).

New insights into mesoderm and endoderm development, and the nature of the onychophoran blastopore.

Background: Early during onychophoran development and prior to the formation of the germ band, a posterior tissue thickening forms the posterior pit. Anterior to this thickening forms a groove, the embryonic slit, that marks the anterior-posterior orientation of the developing embryo. This slit is by some authors considered the blastopore, and thus the origin of the endoderm, while others argue that the posterior pit represents the blastopore.

Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

Purpose: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation.

Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.

Background: Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor.

Methods: We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.

Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer.

Purpose: A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy.

Patients And Methods: Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation.

Two Notorious Nodes: A Critical Examination of Relaxed Molecular Clock Age Estimates of the Bilaterian Animals and Placental Mammals.

The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here, we critically examine two such clades: the animals (with a focus on the bilaterians) and the mammals (with a focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for.

Comment on "The lower Cambrian lobopodian resolves the origin of euarthropod brains".

Strausfeld . (Report, 24 Nov 2022, p. 905) claim that Cambrian fossilized nervous tissue supports the interpretation that the ancestral panarthropod brain was tripartite and unsegmented.

Adherence to Cancer Prevention Lifestyle Recommendations Before, During, and 2 Years After Treatment for High-risk Breast Cancer.

Importance: The American Institute for Cancer Research and American Cancer Society regularly publish modifiable lifestyle recommendations for cancer prevention. Whether these recommendations have an impact on high-risk breast cancer survival remains unknown.

Objective: To investigate whether adherence to cancer prevention recommendations before, during, and 1 and 2 years after breast cancer treatment was associated with disease recurrence or mortality.

Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases.

Background: Lung metastases are the most common form of distant failure for patients diagnosed with sarcoma with metastasectomy considered for some patients with limited metastatic disease and good performance status. Alternatives to surgery such as stereotactic body radiation therapy (SBRT) can be considered, though data are limited. We present outcomes after SBRT for sarcoma lung metastases.

Evolutionary contingency in lingulid brachiopods across mass extinctions.

Morphology usually serves as an effective proxy for functional ecology, and evaluating morphological, anatomical, and ecological changes permits a deeper understanding of the nature of diversification and macroevolution. Lingulid (order Lingulida) brachiopods are both diverse and abundant during the early Palaeozoic but decrease in diversity over time, with only a few genera of linguloids and discinoids present in modern marine ecosystems, resulting in them frequently being referred to as "living fossils." The dynamics that drove this decline remain uncertain, and it has not been determined if there is an associated decline in morphological and ecological diversity.

Impact of early detection on cancer curability: A modified Delphi panel study.

Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test.

Reassessing a cryptic history of early trilobite evolution.

Trilobites are an iconic Paleozoic group of biomineralizing marine euarthropods that appear abruptly in the fossil record (c. 521 million years ago) during the Cambrian 'explosion'. This sudden appearance has proven controversial ever since Darwin puzzled over the lack of pre-trilobitic fossils in the Origin of Species, and it has generally been assumed that trilobites must have an unobserved cryptic evolutionary history reaching back into the Precambrian.

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery.

Background: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy.

Empathy in patient-clinician interactions when using telecommunication: A rapid review of the evidence.

Objectives: The COVID-19 pandemic accelerated the replacement of many face-to-face healthcare consultations with telephone consultations. Little is known about the extent to which empathy can be expressed in telephone consultations. Our objective is to review evidence related to empathy in telephone consultations including clinical outcomes, and patient/practitioner experiences.

A comprehensive study of arthropod and onychophoran Fox gene expression patterns.

Fox genes represent an evolutionary old class of transcription factor encoding genes that evolved in the last common ancestor of fungi and animals. They represent key-components of multiple gene regulatory networks (GRNs) that are essential for embryonic development. Most of our knowledge about the function of Fox genes comes from vertebrate research, and for arthropods the only comprehensive gene expression analysis is that of the fly Drosophila melanogaster.

Repeated subcutaneous racemic ketamine in treatment-resistant depression: case series.

Interest in the use of parenteral ketamine has been increasing over the last 2 decades for the management of treatment-resistant depression (TRD). While intravenous (IV) ketamine has been the most common parenteral route of administration, subcutaneous (SC) and intramuscular options have been described. We developed a clinical treatment protocol for the use of repeated SC racemic ketamine (maximum six treatments, twice per week) in an inpatient psychiatric care setting with inclusion/exclusion criteria, dosing schedule, and description of treatment, assessment, and monitoring procedures.

The evolution of biramous appendages revealed by a carapace-bearing Cambrian arthropod.

Biramous appendages are a common feature among modern marine arthropods that evolved deep in arthropod phylogeny. The branched appendage of Cambrian arthropods has long been considered as the ancient biramous limb, sparking numerous investigations on its origin and evolution. Here, we report a new arthropod, gen.

Expression of netrin and its receptors uncoordinated-5 and frazzled in arthropods and onychophorans suggests conserved and diverged functions in neuronal pathfinding and synaptogenesis.

Background: Development of the nervous system and the correct connection of nerve cells require coordinated axonal pathfinding through an extracellular matrix. Outgrowing axons exhibit directional growth toward or away from external guidance cues such as Netrin. Guidance cues can be detected by growth cones that are located at the end of growing axons through membrane-bound receptors such as Uncoordianted-5 and Frazzled.

Association between biologically effective dose and local control after stereotactic body radiotherapy for metastatic sarcoma.

Introduction: Stereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology.

Shifting North American drug markets and challenges for the system of care.

Drug markets are dynamic systems which change based on demand, competition, legislation and revenue. Shifts that are not met with immediate and appropriate responses from the healthcare system can lead to public health crises with tragic levels of morbidity and mortality, as experienced Europe in the early 1990s and as is the case in North America currently. The major feature of the current drug market shift in North America is towards highly potent synthetic opioids such as fentanyl and fentanyl analogues.