Isolation and Characterization of a Novel Mammary Adenocarcinoma, MCa-P1362, with Hormone Receptor Expression, Human Epidermal Growth Factor Receptor 2 Positivity, and Enrichment in Cancer and Mesenchymal Stem Cells.

Preclinical models that display spontaneous metastasis are necessary to improve the therapeutic options for hormone receptor-positive breast cancers. Within this study, detailed cellular and molecular characterization was conducted on MCa-P1362, a newly established mouse model of metastatic breast cancer that is syngeneic in BALB/c mice. MCa-P1362 cancer cells express estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2. MCa-P1362 cancer cells proliferate in vitro and in vivo in response to estrogen, yet do not depend on steroid hormones for growth and tumor progression. Analysis of MCa-P1362 tumor explants revealed the tumors contained a mixture of cancer cells and mesenchymal stromal cells. Through transcriptomic and functional analyses of both cancer and stromal cells, stem cells were detected within both populations. Functional studies demonstrated that MCa-P1362 cancer stem cells drove tumor initiation, whereas stromal cells from these tumors contributed to drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of breast tumor progression and therapeutic resistance.

The tumor-draining lymph node as a reservoir for systemic immune surveillance.

Early in solid tumor development, antigens are presented in tumor-draining lymph nodes (tdLNs), a process that is necessary to set up immune surveillance. Recent evidence indicates that tdLNs fuel systemic tumor-specific T cell responses which may halt cancer progression and facilitate future responses to immunotherapy. These protective responses, however, are subject to progressive dysfunction exacerbated by lymph node (LN) metastasis. We discuss emerging preclinical and clinical literature indicating that the tdLN is a crucial reservoir for systemic immunity that can potentiate immune surveillance. We also discuss the impact of LN metastasis and argue that a better understanding of the relationship between LN metastasis and systemic immunity will be necessary to direct regional disease management in the era of immunotherapy.

Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study.

PURPOSE: Prior studies indicate that the physiologic response to stress can affect gene expression. We evaluated differential gene expression in breast cancers collected from Black women with high versus low exposure to psychosocial stressors. METHODS: We analyzed tumor RNA sequencing data from 417 Black Women's Health Study breast cancer cases with data on early life trauma and neighborhood disadvantage. We conducted age-adjusted differential gene expression analyses and pathway analyses. We also evaluated Conserved Transcriptional Response to Adversity (CTRA) contrast scores, relative fractions of immune cell types, T cell exhaustion, and adrenergic signaling. Analyses were run separately for estrogen receptor positive (ER+; n = 299) and ER- (n = 118) cases. RESULTS: Among ER+ cases, the top differentially expressed pathways by stress exposure were related to RNA and protein metabolism. Among ER- cases, they were related to developmental biology, signal transduction, metabolism, and the immune system. Targeted analyses indicated greater immune pathway enrichment with stress exposure for ER- cases, and possible relevance of adrenergic signaling for ER+ cases. CTRA contrast scores did not differ by stress exposure, but in analyses of the CTRA components, ER- breast cancer cases with high neighborhood disadvantage had higher pro-inflammatory gene expression (p = 0.039) and higher antibody gene expression (p = 0.006) compared to those with low neighborhood disadvantage. CONCLUSION: There are multiple pathways through which psychosocial stress exposure may influence breast tumor biology. Given the present findings on inflammation and immune response in ER- tumors, further research to identify stress-induced changes in the etiology and progression of ER- breast cancer is warranted.

Particleboards Bonded by an Imidazole-Based Adhesive System.

Particleboards with different combinations of the adhesive material imidazole, citric acid, and sorbitol were produced. Softwood sawdust from a Swedish sawmill was mixed with an aqueous solution of the chemicals and then dried to 0% moisture content prior to pressing. The boards were pressed to a target density of 700 kg m-3 at either 200 °C or 220 °C for 10 min. The hygroscopic and mechanical properties of the boards were clearly better at 220 °C than 200 °C for all used chemical combinations. A combination of imidazole (14.4 wt%) and citric acid (11.3 wt%) led to the best results, where the thickness swelling after 24 h of water immersion was 6.3% and the internal bonding strength was 0.57 MPa. The modulus of rupture and modulus of elasticity were 3.3 MPa and 1.1 GPa, respectively. Cyclic accelerated weathering showed exceptional stability with a thickness change after boiling and drying of only 2.1% compared to the initial dry thickness. This study indicates that the presence of imidazole leads to greatly improved hygroscopic properties and good internal bonding strength when used in particleboards.

Lymphatic muscle cells are unique cells that undergo aging induced changes.

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have generated a comprehensive transcriptional single-cell atlas-including LMCs-of collecting lymphatic vessels in mouse dermis at various ages. We identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and uncovered a pro-inflammatory microenvironment that suppresses the contractile apparatus in advanced-aged LMCs. Our findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to preserve lymphatic vessel function as well as supporting studies to identify genetic causes of primary lymphedema currently with unknown molecular explanation.

The Influence of the Initial Treatment of Oak Wood on Increasing the Durability of Exterior Transparent Coating Systems.

This study determined the impact of undertaking an initial treatment of oak wood by sealing its surface pores with epoxy resin, focusing on the durability of transparent coating systems when exposed outdoors. Throughout the exposure period, various parameters including color, gloss, surface wettability, and both macroscopic and microscopic surface evaluation were continuously monitored. The study involved two sets of samples: one set underwent the pretreatment, while the other did not. Subsequently, four coating systems were applied to the samples, comprising two solvent-based and two water-based coatings. The experiment was conducted over a period of two years, utilizing natural weathering methods within the premises of the Czech University of Life Sciences in Prague. The pretreatment with epoxy resin exhibited enhanced durability for all paint systems. The analysis showed a significant difference in gloss and color after 12 months of weathering exposure without any significant effect on surface wettability and sealing. However, after 24 months of the weathering exposure, no significant differences between the sealed and unsealed surface were observed. The most significant change in properties was noted for the water-based coatings used in coating systems number 3 and 4, and these coatings were rated as the best.

"Isolation and characterization of a novel hormone receptor positive mammary adenocarcinoma MCa-P1362 with stromal drivers of tumor growth, metastasis, and drug resistance".

Preclinical models that display spontaneous metastasis are necessary to improve therapeutic options for hormone receptor positive breast cancers. In this study, we conducted a detailed cellular and molecular characterization of MCa-P1362, a novel syngeneic Balb/c mouse model of metastatic breast cancer. MCa-P1362 cancer cells expressed estrogen receptors (ER), progesterone receptors (PR), and HER-2 receptors. MCa-P1362 cells proliferate in vitro and in vivo in response to estrogen, yet do not depend on steroid hormones for tumor progression. Further characterization of MCa-P1362 tumor explants shows that they contain a mixture of epithelial cancer cells and stromal cells. Based on transcriptomic and functional analyses of cancer and stromal cells, stem cells are present in both populations. Functional studies demonstrate that crosstalk between cancer and stromal cells promotes tumor growth, metastasis, and drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of hormone receptor positive tumor progression and therapeutic resistance.

Cancer cell plasticity and MHC-II-mediated immune tolerance promote breast cancer metastasis to lymph nodes.

Tumor-draining lymph nodes (TDLNs) are important for tumor antigen-specific T cell generation and effective anticancer immune responses. However, TDLNs are often the primary site of metastasis, causing immune suppression and worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer cell heterogeneity, plasticity, and immune evasion during breast cancer progression and lymph node metastasis (LNM). A subset of cancer cells in the lymph nodes exhibited elevated MHC class II (MHC-II) gene expression in both mice and humans. MHC-II+ cancer cells lacked costimulatory molecule expression, leading to regulatory T cell (Treg) expansion and fewer CD4+ effector T cells in TDLNs. Genetic knockout of MHC-II reduced LNM and Treg expansion, while overexpression of the MHC-II transactivator, Ciita, worsened LNM and caused excessive Treg expansion. These findings demonstrate that cancer cell MHC-II expression promotes metastasis and immune evasion in TDLNs.

High Leach-Resistant Fire-Retardant Modified Pine Wood (Pinus sylvestris L.) by In Situ Phosphorylation and Carbamylation.

The exterior application of fire-retardant (FR) timber necessitates it to have high durability because of the possibility to be exposed to rainfall. In this study, water-leaching resistance of FR wood has been imparted by grafting phosphate and carbamate groups of the water-soluble FR additives ammonium dihydrogen phosphate (ADP)/urea onto the hydroxyl groups of wood polymers via vacuum-pressure impregnation, followed by drying/heating in hot air. A darker and more reddish wood surface was observed after the modification. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, solid-state 13C cross-polarization magic-angle-spinning nuclear magnetic resonance (13C CP-MAS NMR), and direct-excitation 31P MAS NMR suggested the formation of C-O-P covalent bonds and urethane chemical bridges. Scanning electron microscopy/energy-dispersive X-ray spectrometry suggested the diffusion of ADP/urea into the cell wall. The gas evolution analyzed by thermogravimetric analysis coupled with quadrupole mass spectrometry revealed a potential grafting reaction mechanism starting with the thermal decomposition of urea. Thermal behavior showed that the FR-modified wood lowered the main decomposition temperature and promoted the formation of char residues at elevated temperatures. The FR activity was preserved even after an extensive water-leaching test, confirmed by the limiting oxygen index (LOI) and cone calorimetry. The reduction of fire hazards was achieved through the increase of the LOI to above 80%, reduction of 30% of the peak heat release rate (pHRR2), reduction of smoke production, and a longer ignition time. The modulus of elasticity of FR-modified wood increased by 40% without significantly decreasing the modulus of rupture.

Dissection of murine collecting lymphatic vessels for imaging, single-cell analysis, and tissue culture of lymphatic muscle cells.

In vivo and in vitro systems have the potential to provide a framework to study the organization, gene expression, and functionality of lymphatic and blood vessel smooth muscle cells in physiology and disease settings. A series of procedures are described here, including the surgical isolation of mouse collecting lymphatic vessels and blood vessels, whole-mount immunofluorescence staining of muscle cells on the vessels, and the enzymatic digestion and culture of α- smooth muscle actin+ cells from the vessels. For complete details on the use and execution of this protocol, please refer to Jones et al. (2018).

Fire Retardancy and Leaching Resistance of Furfurylated Pine Wood (Pinus sylvestris L.) Treated with Guanyl-Urea Phosphate.

Guanyl-urea phosphate (GUP) was introduced into furfurylated wood in order to improve fire retardancy. Modified wood was produced via vacuum-pressure impregnation of the GUP-furfuryl alcohol (FA) aqueous solution, which was then polymerized at elevated temperature. The water leaching resistance of the treated wood was tested according to European standard EN 84, while the leached water was analyzed using ultra-performance liquid chromatography (UPLC) and inductively coupled plasma-sector field mass spectrometry (ICP-SFMS). This new type of furfurylated wood was further characterized in the laboratory by evaluating its morphology and elemental composition using optical microscopy and electron microscopy coupled with energy-dispersive X-ray spectrometry (SEM-EDX). The chemical functionality was detected using infrared spectroscopy (FTIR), and the fire resistance was tested using cone calorimetry. The dimensional stability was evaluated in wet-dry soaking cycle tests, along with the mechanical properties, such as the Brinell hardness and bending strength. The fire retardancy of the modified furfurylated wood indicated that the flammability of wood can be depressed to some extent by introducing GUP. This was reflected in an observed reduction in heat release rate (HRR2) from 454.8 to 264.9 kW/m2, without a reduction in the material properties. In addition, this leaching-resistant furfurylated wood exhibited higher fire retardancy compared to conventional furfurylated wood. A potential method for producing fire-retardant treated furfurylated wood stable to water exposure has been suggested.

Solid stress impairs lymphocyte infiltration into lymph-node metastases.

Strong and durable anticancer immune responses are associated with the generation of activated cancer-specific T cells in the draining lymph nodes. However, cancer cells can colonize lymph nodes and drive tumour progression. Here, we show that lymphocytes fail to penetrate metastatic lesions in lymph nodes. In tissue from patients with breast, colon, and head and neck cancers, as well as in mice with spontaneously developing breast-cancer lymph-node metastases, we found that lymphocyte exclusion from nodal lesions is associated with the presence of solid stress caused by lesion growth, that solid stress induces reductions in the number of functional high endothelial venules in the nodes, and that relieving solid stress in the mice increased the presence of lymphocytes in lymph-node lesions by about 15-fold. Solid-stress-mediated impairment of lymphocyte infiltration into lymph-node metastases suggests a therapeutic route for overcoming T-cell exclusion during immunotherapy.

Decision Making and Interventions During Interfacility Transport of High-Acuity Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

OBJECTIVE: There are limited data regarding the typical characteristics of coronavirus disease 2019 (COVID-19) patients requiring interfacility transport or the clinical capabilities of the out-of-hospital transport clinicians required to provide safe transport. The objective of this study is to provide epidemiologic data and highlight the clinical skill set and decision making needed to transport critically ill COVID-19 patients. METHODS: A retrospective chart review of persons under investigation for COVID-19 transported during the first 6 months of the pandemic by Johns Hopkins Lifeline was performed. Patients who required interfacility transport and tested positive for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction assay were included in the analysis. RESULTS: Sixty-eight patients (25.4%) required vasopressor support, 35 patients (13.1%) were pharmacologically paralyzed, 15 (5.60%) were prone, and 1 (0.75%) received an inhaled pulmonary vasodilator. At least 1 ventilator setting change occurred for 59 patients (22.0%), and ventilation mode was changed for 11 patients (4.10%) during transport. CONCLUSION: The safe transport of critically ill patients with COVID-19 requires experience with vasopressors, paralytic medications, inhaled vasodilators, prone positioning, and ventilator management. The frequency of initiated critical interventions and ventilator adjustments underscores the tenuous nature of these patients and highlights the importance of transport clinician reassessment, critical thinking, and decision making.

Approaching Highly Leaching-Resistant Fire-Retardant Wood by In Situ Polymerization with Melamine Formaldehyde Resin.

The objective of the work was to improve the leaching resistance of fire-retardant (FR) modified wood by the incorporation of a thermoset resin. Here, Scots pine (Pinus sylvestris L.) sapwood was impregnated with melamine formaldehyde (MF) resin and hydrophilic FRs guanyl-urea phosphate/boric acid by a vacuum-pressure treatment. Resistance to leaching of FR-modified wood was evaluated, after conducting an accelerated aging test according to European standard EN 84. Inductively coupled plasma analysis showed that the incorporation of MF resin significantly reduced the leachability of FRs. Scanning electron microscopy/energy-dispersive X-ray spectrometry revealed that the mechanism of water resistance was by doping the FRs into MF resin microspheres. Fourier transform infrared spectra showed the chemical functionality changes of FR-modified wood such as the formation of methylene bridges by drying the modified wood specimens. An increase in the thermal stability of FR-modified wood was confirmed by thermal gravimetric analysis. Excellent fire performance of FR-modified wood after leaching was affirmed by the limiting oxygen index and cone calorimeter tests.

The Multifaceted Effects of Breast Cancer on Tumor-Draining Lymph Nodes.

Breast cancer (BC) accounts for significant morbidity and mortality among women worldwide. About one in three patients with breast cancer present with lymph node (LN) metastasis and LN status is one of the most important prognostic predictors in patients with BC. In addition to their prognostic value, LNs initiate adaptive immunity against BC. Yet, BC cells often avoid immune-mediated destruction in LNs. This review provides an overview of the ways by which BC cells modulate LN stromal and hematopoietic cells to promote metastasis and immune evasion.

Extending the Near-Infrared Emission Range of Indium Phosphide Quantum Dots for Multiplexed In Vivo Imaging.

This report of the reddest emitting indium phosphide quantum dots (InP QDs) to date demonstrates tunable, near-infrared (NIR) photoluminescence (PL) as well as PL multiplexing in the first optical tissue window while avoiding toxic constituents. This synthesis overcomes the InP "growth bottleneck" and extends the emission peak of InP QDs deeper into the first optical tissue window using an inverted QD heterostructure, specifically ZnSe/InP/ZnS core/shell/shell nanoparticles. The QDs exhibit InP shell thickness-dependent tunable emission with peaks ranging from 515-845 nm. The high absorptivity of InP yields effective photoexcitation of the QDs with UV, visible, and NIR wavelengths. These nanoparticles extend the range of tunable direct-bandgap emission from InP-based nanostructures, effectively overcoming a synthetic barrier that has prevented InP-based QDs from reaching their full potential as NIR imaging agents. Multiplexed lymph node imaging in a mouse model demonstrates the potential of the NIR-emitting InP particles for in vivo imaging.

Influence of Zwitterionic Buffer Effects with Thermal Modification Treatments of Wood on Symbiotic Protists in Reticulitermes grassei Clément.

The majority of thermal modification processes are at temperatures greater than 180 °C, resulting in a product with some properties enhanced and some diminished (e.g., mechanical properties). However, the durability of thermally modified wood to termite attack is recognised as low. Recent attempts at combining thermal modification with chemical modification, either prior to or directly after the thermal process, are promising. Buffers, although not influencing the reaction systems, may interact on exposure to certain conditions, potentially acting as promoters of biological changes. In this study, two zwitterionic buffers, bicine and tricine, chosen for their potential to form Maillard-type products with fragmented hemicelluloses/volatiles, were assessed with and without thermal modification for two wood species (spruce and beech), with subsequent evaluation of their effect against subterranean termites (Reticulitermes grassei Clément) and their symbiotic protists. The effect of the wood treatments on termites and their symbionts was visible after four weeks, especially for spruce treated with tricine and bicine and heat treatment (bicine HT), and for beech treated with bicine and bicine and heat treatment (bicine HT). The chemical behaviour of these substances should be further investigated when in contact with wood and also after heat treatment. This is the first study evaluating the effect of potential Maillard reactions with zwitterionic buffers on subterranean termite symbiotic fauna.

Immunopathology of Hyperinflammation in COVID-19.

The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.

Parallels of Resistance between Angiogenesis and Lymphangiogenesis Inhibition in Cancer Therapy.

Metastasis is the primary cause of cancer-related mortality. Cancer cells primarily metastasize via blood and lymphatic vessels to colonize lymph nodes and distant organs, leading to worse prognosis. Thus, strategies to limit blood and lymphatic spread of cancer have been a focal point of cancer research for several decades. Resistance to FDA-approved anti-angiogenic therapies designed to limit blood vessel growth has emerged as a significant clinical challenge. However, there are no FDA-approved drugs that target tumor lymphangiogenesis, despite the consequences of metastasis through the lymphatic system. This review highlights several of the key resistance mechanisms to anti-angiogenic therapy and potential challenges facing anti-lymphangiogenic therapy. Blood and lymphatic vessels are more than just conduits for nutrient, fluid, and cancer cell transport. Recent studies have elucidated how these vasculatures often regulate immune responses. Vessels that are abnormal or compromised by tumor cells can lead to immunosuppression. Therapies designed to improve lymphatic vessel function while limiting metastasis may represent a viable approach to enhance immunotherapy and limit cancer progression.

Utilization of Resources by Patients Who Are Morbid and Super Obese Admitted to a Tertiary Care Center.

OBJECTIVES: Data regarding the characteristics of patients who are morbidly and super obese, and the resources they use in nonbariatric hospital settings are limited. The aims of our study were to explore the frequency of inpatient admissions of patients who are morbid (body mass index [BMI] ≥ 40 kg/m) and super obese (BMI ≥ 50 kg/m), their specific characteristics, and to identify their utilization of hospital services and resources, 30-day readmission rates, safe patient handling equipment, and patient clinical outcomes. METHODS: We conducted a retrospective chart review of adult patients hospitalized at our institution (n = 1670) who are morbidly obese or super obese. We collected and compared data regarding the characteristics of patients, the services and resources used, the use of any special handling equipment, and patient clinical outcomes. RESULTS: After accounting for confounding variables, wound care and occupational therapy services were more likely to be required for the patients who are super obese (odds ratio [OR] = 1.49, P = 0.04) than for those who are morbidly obese (odds ratio [OR] = 1.36, P = 0.02). Use of safe patient handling devices was twice as likely for the super obese group (OR = 2.09, P < 0.01). There was no difference in mortality rates between the two patient groups (P = 0.81); patients who are super obese had higher odds of prolonged hospital stay by 32% (P = 0.009). CONCLUSIONS: This study provides an understanding of the characteristics of patients with BMI of 40 kg/m or greater who are admitted to the hospital, the resources and services use, and their clinical outcomes. There is also a need to develop an organizational protocol to ensure safe handling using the right devices and activation of appropriate consult services.