Leveraging single-cell transcriptomic data to uncover immune suppressive cancer cell subsets in triple-negative canine breast cancers.

Introduction: Single-cell RNA sequencing (scRNA-seq) has become an essential tool for uncovering the complexities of various physiological and immunopathological conditions in veterinary medicine. However, there is currently limited information on immune-suppressive cancer subsets in canine breast cancers. In this study, we aimed to identify and characterize immune-suppressive subsets of triple-negative canine breast cancer (TNBC) by utilizing integrated scRNA-seq data from published datasets.

ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase.

Unlabelled: Renal cell carcinoma (RCC), the most common form of kidney cancer, is a heterogeneous disease with clear cell RCC (ccRCC) being the most prevalent and aggressive subtype. While most ccRCC tumors have elevated expression of angiopoietin-like4 (ANGPTL4), in our study we identified a significant subset of patients whose cancers show no increase in ANGPTL4 expression. These patients have a worse prognosis compared to the patients with high expression of ANGPTL4.

Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience.

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs.

Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor.

Purpose: Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT).

Epithelial IL-2 is critical for NK cell-mediated cancer immunosurveillance in mammary glands.

Interleukin 2 (IL-2) is the first identified cytokine and its interaction with receptors has been known to shape the immune responses in many lymphoid or non-lymphoid tissues for more than four decades. Active T cells are the primary cellular source for IL-2 production and epithelial cells have never been considered the major cellular source of IL-2 under physiological conditions. It is, however, tempting to speculate that epithelial cells could potentially express IL-2 that regulates the intricate interactions between epithelial cells and lymphocytes.

Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.

Childhood Sjögren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjögren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4 T effector memory, and XCL1 NK cells as potential key players in childhood Sjögren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children.

A Randomized Trial of Healthy Weight Gain in Athletic Individuals.

Purpose: The purpose of this study is to evaluate the outcomes of a 10-wk diet and exercise regimen designed to promote healthy weight gain with excess energy from peanut-containing or high-carbohydrate foods.

Methods: Nineteen male and 13 female athletes were randomly assigned to receive an additional 500 kcal·d -1 above typical intake through provision of either peanut-based whole foods/snacks (PNT group) or a similar, high-carbohydrate, peanut-free snack (CHO group) along with supervised, whole-body RT (3 d·wk -1 for 60-120 min). Body composition was assessed by dual-energyx-ray absorptiometry at baseline and postintervention.

Use of Augmentative and Alternative Communication by Individuals with Rett Syndrome Part 1: Page-Linking.

Although the last decade has welcomed evidence that individuals with Rett syndrome (RTT) can communicate using alternative and augmentative communication (AAC), less is known about effective procedures for teaching various component skills required for expressive communication of individuals with complex communication needs. The purpose of the current study was to evaluate the effects of systematic individualized instruction procedures on the page-linking skills of individuals with RTT. A nonconcurrent multiple baseline design across participants was used to evaluate independent and accurate responding utilizing both a high-tech and low-tech AAC device for three participants.

Endovascular aortic repair in patients with Marfan and Loeys-Dietz syndrome is safe and durable when employed by a multi-disciplinary aortic team.

Objectives: The aim of this study was to report on mid-term outcomes after endovascular aortic repair (EVAR) in patients with Marfan (MFS) or Loeys-Dietz (LDS) syndrome.

Methods: We analysed data from 2 European centres of patients with MFS and LDS undergoing EVAR. Patients were analysed based on (i) timing of the procedure (planned versus emergency procedure) and (ii) the nature of the landing zone (safe versus non-safe).

The Effect of Caregiver-Implemented Training on Augmentative Alternative Communication Use by Individuals with Rett Syndrome: Remote Coaching via Telehealth.

Limited published literature exists demonstrating functional relations between idiosyncratic responses or augmentative alternative communication (AAC) and social reinforcement for individuals with Rett syndrome. In this study, six females with Rett syndrome ages 2-25 demonstrated requesting for preferred items using both idiosyncratic responses (e.g, looking, reaching) and AAC (e.

Teaching Requesting to Individuals with Rett Syndrome Using Alternative Augmentative Communication (AAC) Through Caregiver Coaching via Telehealth.

Rett syndrome is a severe neurodevelopmental disorder that results in both motor and language skill regression with a wide range of severity in symptom presentation. Communication intervention may be particularly challenging for this population due to the decline in speech, motor skills, and motor planning difficulties that characterize the disorder (Townend et al., 2020), often resulting in the need for augmentative and alternative communication (AAC) technology.

Correction: ERK1/2 Signaling Plays an Important Role in Topoisomerase II Poison-Induced G2/M Checkpoint Activation.

[This corrects the article DOI: 10.1371/journal.pone.

Contrasting roles of different mismatch repair proteins in basal-like breast cancer.

The mismatch repair (MMR) pathway is known as a tumor suppressive pathway and genes involved in MMR are commonly mutated in hereditary colorectal or other cancer types. However, the function of MMR genes/proteins in breast cancer progression and metastasis are largely unknown. We found that MSH2, but not MLH1, is highly enriched in basal-like breast cancer (BLBC) and that its protein expression is inversely correlated with overall survival time (OS).

Use of Augmentative and Alternative Communication by Individuals with Rett Syndrome Part 2: High-Tech and Low-Tech Modalities.

The vast majority of individuals with Rett syndrome do not utilize natural speech and therefore require alternative and augmentative communication (AAC). The purpose of the current study was to investigate the use of high- and low-tech AAC modalities by three individuals with Rett syndrome given similar instruction for using both modalities. For all participants, the number of sessions to criterion and cumulative number of trials with independent requests during simultaneous or alternating instruction in the use of a high- and low-tech AAC modality were investigated.

Healthcare discrimination and treatment adherence among sexual and gender minority individuals living with chronic illness: the mediating effects of anticipated discrimination and depressive symptoms.

Sexual and gender minority (SGM) individuals are at increased risk for an array of chronic illness due to minority stress. Up to 70% of SGM individuals report healthcare discrimination, which may cause additional challenges for SGM people living with chronic illness including avoiding necessary healthcare. The extant literature highlights how healthcare discrimination is associated with depressive symptoms and treatment nonadherence.

Phytotoxicity of organic extracts of five medicinal plants of the Neotropical savanna.

Medicinal plants produce a high diversity of secondary metabolites with different biological activities, which are commonly evaluated when prospecting for bioherbicides. We analyzed the phytotoxic activity of organic extracts from the leaves of five medicinal species, Byrsonima intermedia, Moquiniastrum polymorphum, Luehea candicans, Miconia chamissois, and Qualea cordata. Phytotoxicity was evaluated on the initial growth of cucumber seedlings through tests with different concentrations of hexane, ethyl acetate, and methanol extracts.

Correction: Pandey et al. ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer. 2019, , 718.

In the original publication [...

Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.

Breast cancer stem cells (BCSCs) constitute a small population of cells within breast cancer and are characterized by their ability to self-renew, differentiate, and recapitulate the heterogeneity of the tumor. Clinically, BCSCs have been correlated with cancer progression, metastasis, relapse, and drug resistance. The tumorigenic roles of BCSCs have been extensively reviewed and will not be the major focus of the current review.

Nintedanib plus Docetaxel after Immune Checkpoint Inhibitor Failure in Patients with Advanced Non-Small-Cell Lung Cancer: A Case Series.

Advances in the treatment of non-small-cell lung cancers (NSCLCs) lacking an actionable driver mutation have included the approval of immunotherapies, such as monotherapy or in combination with chemotherapy. However, limited evidence exists to guide clinical decision-making after progression with immunotherapy. The vascular endothelial growth factor (VEGF) signaling pathway promotes tumor angiogenesis and the development of an immunosuppressive tumor microenvironment (TME).

Updates on Immunotherapy and Immune Landscape in Renal Clear Cell Carcinoma.

Several clinicopathological features of clear cell renal cell carcinomas (ccRCC) contribute to make an "atypical" cancer, including resistance to chemotherapy, sensitivity to anti-angiogenesis therapy and ICIs despite a low mutational burden, and CD8 T cell infiltration being the predictor for poor prognosis-normally CD8 T cell infiltration is a good prognostic factor in cancer patients. These "atypical" features have brought researchers to investigate the molecular and immunological mechanisms that lead to the increased T cell infiltrates despite relatively low molecular burdens, as well as to decipher the immune landscape that leads to better response to ICIs. In the present study, we summarize the past and ongoing pivotal clinical trials of immunotherapies for ccRCC, emphasizing the potential molecular and cellular mechanisms that lead to the success or failure of ICI therapy.

CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers.

The Un-meeting approach to stimulate collaborative adult learning: an application for clinical research professionals.

We used a Zoom Un-meeting as an educational approach to provide experienced clinical research professional (CRP) adult learners a collaborative learning space to learn more about current issues for academic medical center (AMC) clinical research workforce development and collaborate on solution finding. CRPs operationalize the conduct of clinical trials and represent a significant brain trust for the Clinical and Translational Science (CTSA) consortium hubs with their vast knowledge base, extensive experience, understanding of relevant institutional policy, organizational culture, and clinical research operations. Un-meetings are an intentionally organized and coordinated group activity that encourages participants to focus on a topic and incorporate an open flow of ideas through brainstorming and an open discussion format, setting the stage for future collaborative action.

Rising incidence of interpersonal violence in Pennsylvania during COVID-19 stay-at home order.

Background: The coronavirus disease 2019 pandemic and associated policies have had important downstream consequences for individuals, communities, and the healthcare system, and they appear to have been accompanied by rising interpersonal violence. The objective of this study was to evaluate the incidence of injuries owing to interpersonal violence after implementation of a statewide stay-at-home order in Pennsylvania in March 2020.

Methods: Using the Pennsylvania Trauma Outcome Study registry, we conducted a retrospective cohort study of patients with gunshot wounds, stab wounds, and blunt assault-related injuries attributable to interpersonal violence treated at Pennsylvania trauma centers from March 16 to July 31 of 2018, 2019, and 2020.

Percutaneous closure of a patent foramen ovale causing exercise hypoxemia: Case report and a review of the literature.

Provoked exercise desaturation is a rare presentation of patent foramen ovale (PFO), when vigorous exercise leads to desaturation of arterial blood and subsequent dyspnea. We present a case of provoked exercise desaturation and curative percutaneous closure and review the literature. A 54-year-old male patient presented with shortness of breath during exercise in the pneumology outpatient department.

Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia.

Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism.