A Mixed Methods Study of Barriers to Help-Seeking for Intimate Partner Aggression in the LGBTQIA+ Community.

People in the LGBTQIA+ community (i.e., lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other gender/sexual minorities) experience greater rates of intimate partner aggression (IPA) than the general population and have fewer help-seeking pathways available.

Integration of urban science and urban climate adaptation research: opportunities to advance climate action.

There is a growing recognition that responding to climate change necessitates urban adaptation. We sketch a transdisciplinary research effort, arguing that actionable research on urban adaptation needs to recognize the nature of cities as social networks embedded in physical space. Given the pace, scale and socioeconomic outcomes of urbanization in the Global South, the specificities and history of its cities must be central to the study of how well-known agglomeration effects can facilitate adaptation.

QTL Pyramiding Provides Marginal Improvement in 2NS-Based Wheat Blast Resistance.

Wheat blast, caused by the fungus pathotype (MoT), is a devastating disease affecting South America, Bangladesh, and Zambia. Resistance to wheat blast has strongly relied on the 2NS translocation; however, newer MoT isolates have increased aggressiveness, threatening the 2NS translocation's effectiveness and durability. To identify genomic regions associated with wheat blast resistance, we performed a quantitative trait loci (QTL) mapping study using 187 double-haploid (DH) lines from a cross between the Brazilian wheat cultivars 'TBIO Alvorada' and 'TBIO Sossego', which are moderately resistant and susceptible to blast, respectively.

A pharmacokinetic-pharmacodynamic model for the MET tyrosine kinase inhibitor, savolitinib, to explore target inhibition requirements for anti-tumour activity.

Background And Purpose: Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, potent, and highly MET receptor TK inhibitor. This series of studies aimed to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to link inhibition of MET phosphorylation (pMET) by savolitinib with anti-tumour activity.

Experimental Approach: Cell line-derived xenograft (CDX) experiments using human lung cancer (EBC-1) and gastric cancer (MKN-45) cells were conducted in athymic nude mice using a variety of doses and schedules of savolitinib.

Effects of early intravesical administration of resiniferatoxin to spinal cord-injured rats in neurogenic detrusor overactivity.

Objectives: To investigate if intravesical administration during spinal shock of resiniferatoxin (RTX), an ultrapotent desensitizing agonist of transient receptor potential vanilloid-1 (TRPV1), would silence TRPV1-expressing bladder afferents at an early stage of disease progression and modulate neurogenic detrusor overactivity (NDO) emergence.

Materials And Methods: Rats submitted to largely incomplete spinal cord transection at T8/9 spinal segment were treated with intravesical RTX (50 nM) or its vehicle during spinal shock. Four weeks after spinal lesion, bladder-reflex activity was evaluated by cystometry under urethane anesthesia, after which the bladder, spinal cord, and dorsal root ganglia were collected and processed.

Effective combination therapies in preclinical endocrine resistant breast cancer models harboring ER mutations.

Although endocrine therapy is successfully used to treat patients with estrogen receptor (ER) positive breast cancer, a substantial proportion of this population will relapse. Several mechanisms of acquired resistance have been described including activation of the mTOR pathway, increased activity of CDK4 and activating mutations in ER. Using a patient derived xenograft model harboring a common activating ER ligand binding domain mutation (D538G), we evaluated several combinatorial strategies using the selective estrogen receptor degrader (SERD) fulvestrant in combination with chromatin modifying agents, and CDK4/6 and mTOR inhibitors.

Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation.

Lung cancer is the most common cause of cancer death globally with a significant, unmet need for more efficacious treatments. The receptor tyrosine kinase MET has been implicated as an oncogene in numerous cancer subtypes, including non-small cell lung cancer (NSCLC). Here we explore the therapeutic potential of savolitinib (volitinib, AZD6094, HMPL-504), a potent and selective MET inhibitor, in NSCLC.

AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models.

Fulvestrant is an estrogen receptor (ER) antagonist administered to breast cancer patients by monthly intramuscular injection. Given its present limitations of dosing and route of administration, a more flexible orally available compound has been sought to pursue the potential benefits of this drug in patients with advanced metastatic disease. Here we report the identification and characterization of AZD9496, a nonsteroidal small-molecule inhibitor of ERα, which is a potent and selective antagonist and downregulator of ERα in vitro and in vivo in ER-positive models of breast cancer.

Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers.

The tumor microenvironment is emerging as a key regulator of cancer growth and progression, however the exact mechanisms of interaction with the tumor are poorly understood. Whilst the majority of genomic profiling efforts thus far have focused on the tumor, here we investigate RNA-Seq as a hypothesis-free tool to generate independent tumor and stromal biomarkers, and explore tumor-stroma interactions by exploiting the human-murine compartment specificity of patient-derived xenografts (PDX).Across a pan-cancer cohort of 79 PDX models, we determine that mouse stroma can be separated into distinct clusters, each corresponding to a specific stromal cell type.

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules.

mTOR is an atypical serine threonine kinase involved in regulating major cellular functions, such as nutrients sensing, growth, and proliferation. mTOR is part of the multiprotein complexes mTORC1 and mTORC2, which have been shown to play critical yet functionally distinct roles in the regulation of cellular processes. Current clinical mTOR inhibitors only inhibit the mTORC1 complex and are derivatives of the macrolide rapamycin (rapalogs).

The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary Renal Cell Carcinoma Patient-Derived Xenograft Models.

Purpose: Papillary renal cell carcinoma (PRCC) is the second most common cancer of the kidney and carries a poor prognosis for patients with nonlocalized disease. The HGF receptor MET plays a central role in PRCC and aberrations, either through mutation, copy number gain, or trisomy of chromosome 7 occurring in the majority of cases. The development of effective therapies in PRCC has been hampered in part by a lack of available preclinical models.

Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers.

Acquired resistance to PI3K/mTOR/Akt pathway inhibitors is often associated with compensatory feedback loops involving the activation of oncogenes. Here, we have generated everolimus resistance in ER+ breast cancer cells and in long-term estrogen deprived (LTED) models that mimic progression on anti-estrogens. This allowed us to uncover MYC as a driver of mTOR inhibitor resistance.

Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel.

Loss of PTEN protein results in upregulation of the PI3K/AKT pathway, which appears dependent on the PI3Kβ isoform. Inhibitors of PI3Kβ have potential to reduce growth of tumors in which loss of PTEN drives tumor progression. We have developed a small-molecule inhibitor of PI3Kβ and PI3Kδ (AZD8186) and assessed its antitumor activity across a panel of cell lines.

Learning curve for endobronchial ultrasound‑guided transbronchial needle aspiration: experience of a community‑based teaching hospital.

Endobronchial ultrasound‑guided transbronchial needle aspiration (EBUS‑TBNA) is a minimally invasive procedure. This procedure is useful for nodal staging of lung cancer and evaluating mediastinal lymphoma and granuloma. The present study was a retrospective analysis of our experience when EBUS‑TBNA was initially implemented.

Follow-up of breast papillary lesion on core needle biopsy: experience in African-American population.

Background: The optimal course of clinical follow-up after a diagnosis of breast papillary lesion on a core needle biopsy (CNB) remains elusive. In particular, no reports in literature have addressed this question in African-American population. We describe our experience with breast papillary lesions in a primarily African-American population.

Thyroid papillary carcinoma in a 3-year-old American boy with a family history of thyroid cancer: a case report and literature review.

Differentiated thyroid carcinoma is a rare malignancy in children. It represents 0.4% to 3.

Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo.

The ability to detect activation of signaling pathways based solely on gene expression data represents an important goal in biological research. We tested the sensitivity of singular value decomposition-based regression by focusing on functional interactions between the Ras and transforming growth factor beta signaling pathways. Our findings demonstrate that this approach is sufficiently sensitive to detect the secondary activation of endogenous signaling pathways as it occurs through crosstalk following ectopic activation of a primary pathway.

Finite de Finetti theorem for infinite-dimensional systems.

We formulate and prove a de Finetti representation theorem for finitely exchangeable states of a quantum system consisting of k infinite-dimensional subsystems. The theorem is valid for states that can be written as the partial trace of a pure state |Psi/Psi| chosen from a family of subsets {Cn} of the full symmetric subspace for n subsystems. We show that such states become arbitrarily close to mixtures of pure power states as n increases.

c-Myc transforms human mammary epithelial cells through repression of the Wnt inhibitors DKK1 and SFRP1.

c-myc is frequently amplified in breast cancer; however, the mechanism of myc-induced mammary epithelial cell transformation has not been defined. We show that c-Myc induces a profound morphological transformation in human mammary epithelial cells and anchorage-independent growth. c-Myc suppresses the Wnt inhibitors DKK1 and SFRP1, and derepression of DKK1 or SFRP1 reduces Myc-dependent transforming activity.