RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Patient-Specific, Mechanistic Models of Tumor Growth Incorporating Artificial Intelligence and Big Data.

Despite the remarkable advances in cancer diagnosis, treatment, and management over the past decade, malignant tumors remain a major public health problem. Further progress in combating cancer may be enabled by personalizing the delivery of therapies according to the predicted response for each individual patient. The design of personalized therapies requires the integration of patient-specific information with an appropriate mathematical model of tumor response. A fundamental barrier to realizing this paradigm is the current lack of a rigorous yet practical mathematical theory of tumor initiation, development, invasion, and response to therapy. We begin this review with an overview of different approaches to modeling tumor growth and treatment, including mechanistic as well as data-driven models based on big data and artificial intelligence. We then present illustrative examples of mathematical models manifesting their utility and discuss the limitations of stand-alone mechanistic and data-driven models. We then discuss the potential of mechanistic models for not only predicting but also optimizing response to therapy on a patient-specific basis. We describe current efforts and future possibilities to integrate mechanistic and data-driven models. We conclude by proposing five fundamental challenges that must be addressed to fully realize personalized care for cancer patients driven by computational models.

Effect of Chitosan-Riboflavin Bioconjugate on Green Mold Caused by Penicillium digitatum in Lemon Fruit.

Penicillium digitatum is the causal agent of green mold, a primary postharvest disease of citrus fruits. This study evaluated the efficacy of a novel photoactive chitosan-riboflavin bioconjugate (CH-RF) to control green mold in vitro and in lemon fruit. The results showed total inhibition of P. digitatum growth on APDA supplemented with CH-RF at 0.5% (w/v) and a significant reduction of 84.8% at 0.25% (w/v). Lemons treated with CH-RF and kept under controlled conditions (20 °C and 90-95% relative humidity) exhibited a noteworthy reduction in green mold incidence four days post-inoculation. Notably, these effects persisted, with all treatments remaining significantly distinct from the control group until day 14. Furthermore, CH-RF showed high control of green mold in lemons after 20 days of cold storage (5 ± 1 °C). The disease incidence five days after cold storage indicated significant differences from the values observed in the control. Most CH-RF treatments showed enhanced control of green mold when riboflavin was activated by white-light exposure. These findings suggest that this novel fungicide could be a viable alternative to conventional synthetic fungicides, allowing more sustainable management of lemon fruit diseases.

Foliar nitrogen uptake in broadleaf evergreen Mediterranean forests: Fertilisation experiment with labelled nitrogen.

Atmospheric nitrogen (N) deposition in Mediterranean sclerophyllous forests of Holm oak (Quercus rotundifolia, Q. ilex) in Spain often exceeds empirical critical loads established for ecosystem conservation. There are still uncertainties on the capacity of canopy retention and uptake of the atmospheric N deposited of these forests. Studying and analysing all the forest nitrogen-cycle processes is essential to understand the potential effect of N deposition in these ecosystems. This study conducted a year-long short-term fertilisation experiment with labelled ammonium (15N-NH4) and nitrate (15N-NO3) to estimate foliar N absorption rates and assess the influence of leaf phenology and meteorological seasonal variations. Fertilising solutions were prepared to simulate low and high wet N deposition concentration, based on data reported from previous studies. Additionally, ecophysiological and meteorological measurements were collected to explore potential relationships between absorption rates, plant activity, and weather conditions. The results showed that Holm oak leaves were able to absorb both oxidised and reduced N compounds, with higher rates of NH4+ absorption. N recovery of both NH4+ and NO3- was higher in the low concentration treatments, suggesting reduced effectiveness of absorption as concentration increases. Foliar absorption rates were leaf-age dependent, with the highest values observed in young developing leaves. Foliar uptake showed seasonal changes with a clear reduction during the summer, linked to drought and dry weather conditions, and showing also smaller leaf net assimilation and stomatal conductance. During the rest of the year, foliar N absorption was not clearly associated to plant physiological activity but with environmental conditions. Our findings suggest that Holm oak canopies could absorb an important part of the incoming N deposition, but this process is compound, season and leaf phenology dependent. Further research is therefore needed to better understand and model this part of the N cycle.

A Pilot Study on Patient-specific Computational Forecasting of Prostate Cancer Growth during Active Surveillance Using an Imaging-informed Biomechanistic Model.

Active surveillance (AS) is a suitable management option for newly diagnosed prostate cancer, which usually presents low to intermediate clinical risk. Patients enrolled in AS have their tumor monitored via longitudinal multiparametric MRI (mpMRI), PSA tests, and biopsies. Hence, treatment is prescribed when these tests identify progression to higher-risk prostate cancer. However, current AS protocols rely on detecting tumor progression through direct observation according to population-based monitoring strategies. This approach limits the design of patient-specific AS plans and may delay the detection of tumor progression. Here, we present a pilot study to address these issues by leveraging personalized computational predictions of prostate cancer growth. Our forecasts are obtained with a spatiotemporal biomechanistic model informed by patient-specific longitudinal mpMRI data (T2-weighted MRI and apparent diffusion coefficient maps from diffusion-weighted MRI). Our results show that our technology can represent and forecast the global tumor burden for individual patients, achieving concordance correlation coefficients from 0.93 to 0.99 across our cohort (n = 7). In addition, we identify a model-based biomarker of higher-risk prostate cancer: the mean proliferation activity of the tumor (P = 0.041). Using logistic regression, we construct a prostate cancer risk classifier based on this biomarker that achieves an area under the ROC curve of 0.83. We further show that coupling our tumor forecasts with this prostate cancer risk classifier enables the early identification of prostate cancer progression to higher-risk disease by more than 1 year. Thus, we posit that our predictive technology constitutes a promising clinical decision-making tool to design personalized AS plans for patients with prostate cancer. SIGNIFICANCE: Personalization of a biomechanistic model of prostate cancer with mpMRI data enables the prediction of tumor progression, thereby showing promise to guide clinical decision-making during AS for each individual patient.

Poroelastic Characterization and Modeling of Subcutaneous Tissue Under Confined Compression.

Subcutaneous tissue mechanics are important for drug delivery. Yet, even though this material is poroelastic, its mechanical characterization has focused on its hyperelastic response. Moreover, advancement in subcutaneous drug delivery requires effective tissue mimics such as hydrogels for which similar gaps of poroelastic data exist. Porcine subcutaneous samples and gelatin hydrogels were tested under confined compression at physiological conditions and strain rates of 0.01%/s in 5% strain steps with 2600 s of stress relaxation between loading steps. Force-time data were used in an inverse finite element approach to obtain material parameters. Tissues and gels were modeled as porous neo-Hookean materials with properties specified via shear modulus, effective solid volume fraction, initial hydraulic permeability, permeability exponent, and normalized viscous relaxation moduli. The constitutive model was implemented into an isogeometric analysis (IGA) framework to study subcutaneous injection. Subcutaneous tissue exhibited an initial spike in stress due to compression of the solid and fluid pressure buildup, with rapid relaxation explained by fluid drainage, and longer time-scale relaxation explained by viscous dissipation. The inferred parameters aligned with the ranges reported in the literature. Hydraulic permeability, the most important parameter for drug delivery, was in the range k 0 ∈ [ 0.142 , 0.203 ] mm 4 /(N s). With these parameters, IGA simulations showed peak stresses due to a 1-mL injection to reach 48.8 kPa at the site of injection, decaying after drug volume disperses into the tissue. The poro-hyper-viscoelastic neo-Hookean model captures the confined compression response of subcutaneous tissue and gelatin hydrogels. IGA implementation enables predictive simulations of drug delivery.

Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen-presenting cells.

The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches. We propose to target structural SARS-CoV-2 antigens (i.e., Spike gp, Membrane, Nucleocapsid, and Envelope) using circulating human antigen-presenting cells electroporated with full length SARS-CoV-2 structural protein-encoding mRNAs to activate and expand specific T cells. Based on the Th1-type cytokine and cytolytic enzyme secretion upon antigen rechallenge, we were able to generate SARS-CoV-2 specific T cells in up to 70% of unexposed unvaccinated healthy donors (HDs) after 3 subsequent stimulations and in 100% of recovered patients (RPs) after 2 stimulations. By means of SARS-CoV-2 specific TCRß repertoire analysis, T cells specific to Spike gp-derived hypomutated regions were identified in HDs and RPs despite viral genomic evolution. Hence, we demonstrated that SARS-CoV-2 mRNA-loaded antigen-presenting cells are effective activating and expanding COVID19-specific T cells. This approach represents an alternative to patients who are not able to mount adaptive immune responses to current COVID-19 vaccines with potential protection across new variants that have conserved genetic regions.

Monitoring of simulated clandestine graves of victims using UAVs, GPR, electrical tomography and conductivity over 4-8 years post-burial to aid forensic search investigators in Colombia, South America.

In Colombia there are estimated to be over 121,000 missing people and victims of forced disappearances. Forensic investigators therefore need assistance in determining optimal detection techniques for buried victims, to give victims' families closure and for the wider community to see that justice is being served. Previous research has created 12 controlled simulated clandestine graves of typical Colombian murder victim scenarios at 0.5 m - 1.2 m depths in savannah and rainforest sites in Colombia. The 0-3 years of geophysical monitoring results of were published, with this paper reporting on 4-8 years monitoring of both UAV drone results and geophysical data. The UAV results from the year 8 survey, published for first time from Colombia, showed that the simulated graves could still be located using NDVI and NIR multi-spectral data, but not using optical or other multi-spectral data. The 0-3 years of geophysical data found the simulated clandestine graves could be detected with electrical resistivity and GPR methods, with the 4-8 year surveys evidencing that they could still be detected using bulk ground conductivity surveys, GPR horizontal time slice datasets and 2D ERT profiles. Research implications suggest initial use of UAV remote sensing technology to pinpoint likely search areas, before subsequent ground reconnaissance, geophysical surveys and their interpretation, before intrusive investigation methods are employed for detecting missing and disappeared persons in Colombia.

Whole cell hydride Meisenheimer complex biotransformation guided optimization of antimycobacterial benzothiazinones.

Nitrobenzothiazinones (BTZs) are potent active substances against Mycobacterium tuberculosis with currently two investigational drugs in clinical development for the treatment of tuberculosis. BTZs are the first examples for which a metabolic pathway towards transient hydride Meisenheimer complexes (HMC) has been shown in mammals, including humans. In this study, lead optimization efforts on BTZs are guided by the systematic evaluation of the HMC formation propensity combined with multiparameter assessment. For this purpose, a novel cell-based assay was specifically developed and fully implemented, and a library of 5- and 7-substituted BTZs was prepared to study substituent effects on the HMC formation. The multiparameter optimization revealed 5-methylated BTZs as the most preferred scaffolds, demonstrating a reduced HMC formation propensity combined with potent activity and good microsomal stability in vitro. In vivo experiments showed good systemic exposure upon oral administration and efficacy in a murine M. tuberculosis infection model. This study reports a qualified in vitro HMC assay, which not only enabled the selection of next-generation BTZs with improved pharmacokinetic properties but also allowed forecasting their in vivo metabolism.

Metabolite profiling reveals the influence of grapevine genetic distance on the chemical signature of juices.

BACKGROUND: Yield, disease tolerance, and climate adaptation are important traits in grapevine genetic breeding programs. Selection for these characteristics causes unpredictable changes in primary and specialized metabolism, affecting the physicochemical properties and chemical composition of the berries and their processed products, juice, and wine. In this study, we investigated the influence of the genetic distance between grapevine genotypes on the chemical signatures of the juices, by integrating comprehensive metabolic profiling to genetic analyses. RESULTS: The studied grapevine cultivars exhibited low genetic diversity. Breeding for agronomic traits promoted higher contents of soluble sugars, total phenolics, and anthocyanins in the juices. Untargeted juice metabolomics identified a total of 147 metabolites, consisting of 30 volatiles, 21 phenolics, and 96 ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) features. Juices from grapes of the most recent cultivars exhibited increased levels of trans-resveratrol, catechin, and luteolin. The blend of volatiles from juices of later cultivars was also more complex, consisting of 29 distinct metabolites in 'BRS Magna'. Grapes from 'BRS Carmem', an intermediate cultivar, gave the most divergent UHPLC-MS juice profile. CONCLUSION: Contents of soluble solids, total phenolics, and anthocyanins in grape juices were increased by controlled crosses and hybrid selection. Integrative analyses demonstrated that the juices' metabolic profiles accurately represent the cultivars' genetic distances. Juices from 'BRS Violeta' and 'BRS Magna' show relevant positive association with health-related phenolics and a distinct set of odor volatiles, although these characteristics were specifically sought by breeding. © 2023 Society of Chemical Industry.

Dataset of conditions and characteristics of street vendors located in public spaces in Colombia.

The objective of this document is to introduce the datasets and the methods for accessing them, derived from the article "Social, commercial, and economic diversity. Poverty and expectations among street vendors in Florencia, Caquetá, Colombia." These datasets aim to provide insights into the conditions and characteristics of street vending in Colombia. The data collection process involved both mapping and personal surveys conducted on 190 street vendors. Additionally, practical recommendations are provided for tailoring the implementation of each survey instrument based on the specific attributes of the study's target demographic. The collected data holds the potential for comparative and longitudinal analyses, not only within different Colombian cities but also in cities worldwide facing similar circumstances to those of intermediate cities like Florencia. These datasets offer a valuable resource for understanding the dynamics of street vending and its implications, fostering more comprehensive research and informed policymaking.

Resistin Induces Migration and Invasion in PC3 Prostate Cancer Cells: Role of Extracellular Vesicles.

Resistin is an adipokine with metabolic and inflammatory functions. Epidemiological and translational studies report that an increase in plasma levels and tissue expression of resistin increases the aggressiveness of prostate tumor cells. Extracellular vesicles (EVs) are secreted constitutively and induced by cytokines, growth factors, and calcium and are found in multiple biological fluids such as saliva, serum, semen, and urine. In particular, EVs have been shown to promote tumor progression through the induction of proliferation, growth, angiogenesis, resistance to chemotherapy, and metastasis. However, the role of resistin in the migration, invasion, and secretion of EVs in invasive prostate tumor cells remains to be studied. In the present study, we demonstrate that resistin induces increased migration and invasion in PC3 cells. In addition, these phenomena are accompanied by increased p-FAK levels and increased secretion of MMP-2 and MMP-9 in resistin-treated PC3 cells. Interestingly, EVs isolated from supernatants of PC3 cells treated with resistin induce an increase in migration and invasion accompanied by high MMP-2 and MMP-9 secretion in an autocrine stimulation model. In summary, our data for the first time demonstrate that resistin induces migration and invasion, partly through the secretion of EVs with pro-invasive characteristics in PC3 cells.

Patient-specific, mechanistic models of tumor growth incorporating artificial intelligence and big data.

Despite the remarkable advances in cancer diagnosis, treatment, and management that have occurred over the past decade, malignant tumors remain a major public health problem. Further progress in combating cancer may be enabled by personalizing the delivery of therapies according to the predicted response for each individual patient. The design of personalized therapies requires patient-specific information integrated into an appropriate mathematical model of tumor response. A fundamental barrier to realizing this paradigm is the current lack of a rigorous, yet practical, mathematical theory of tumor initiation, development, invasion, and response to therapy. In this review, we begin by providing an overview of different approaches to modeling tumor growth and treatment, including mechanistic as well as data-driven models based on ``big data" and artificial intelligence. Next, we present illustrative examples of mathematical models manifesting their utility and discussing the limitations of stand-alone mechanistic and data-driven models. We further discuss the potential of mechanistic models for not only predicting, but also optimizing response to therapy on a patient-specific basis. We then discuss current efforts and future possibilities to integrate mechanistic and data-driven models. We conclude by proposing five fundamental challenges that must be addressed to fully realize personalized care for cancer patients driven by computational models.

The role of oxygen incorporation in Ni (111) substrates on the growth of hexagonal boron nitride monolayers.

Reliable and controllable growth of two-dimensional (2D) hexagonal boron nitride (h-BN) is essential for its wide range of applications. Substrate engineering is one of the critical factors that influence the growth of the epitaxial h-BN films. Here, we report the growth of monolayer h-BN on Ni (111) substrates incorporated with oxygen atoms via molecular beam epitaxy. It was found that the increase of incorporated oxygen concentration in the Ni substrate through a pretreatment process prior to the h-BN growth step would have an adverse effect on the morphology and growth rate of 2D h-BN. Under the same growth condition, h-BN monolayer coverage decreases exponentially as the amount of oxygen incorporated into Ni (111) increases. Density functional theory calculations and climbing image nudged elastic band (CI-NEB) method reveal that the substitutional oxygen atoms can increase the diffusion energy barrier of B and N atoms on Ni (111) thereby inhibiting the growth of h-BN films. As-grown large-area h-BN monolayer films and fabricated Al/h-BN/Ni (MIM) nanodevices were comprehensively characterized to evaluate the structural, optical and electrical properties of high-quality monolayers. Direct tunneling mechanism and high breakdown strength of ∼11.2 MV cm-1are demonstrated for the h-BN monolayers grown on oxygen-incorporated Ni (111) substrates, indicating that these films have high quality. This study provides a unique example that heterogeneous catalysis principles can be applied to the epitaxy of 2D crystals in solid state field. Similar strategies can be used to grow other 2D crystalline materials, and are expected to facilitate the development of next generation devices based on 2D crystals.

A nationwide monitoring of atmospheric microplastic deposition.

Plastic production continues to increase every year, yet it is widely acknowledged that a significant portion of this material ends up in ecosystems as microplastics (MPs). Among all the environmental compartments affected by MPs, the atmosphere remains the least well-known. Here, we conducted a one-year simultaneous monitoring of atmospheric MPs deposition in ten urban areas, each with different population sizes, economic activities, and climates. The objective was to assess the role of the atmosphere in the fate of MPs by conducting a nationwide quantification of atmospheric MP deposition. To achieve this, we deployed collectors in ten different urban areas across continental Spain and the Canary Islands. We implemented a systematic sampling methodology with rigorous quality control/quality assurance, along with particle-oriented identification and quantification of anthropogenic particle deposition, which included MPs and industrially processed natural fibres. Among the sampled MPs, polyester fibres were the most abundant, followed by acrylic polymers, polypropylene, and alkyd resins. Their equivalent sizes ranged from 22 µm to 398 µm, with a median value of 71 µm. The particle size distribution of MPs showed fewer large particles than expected from a three-dimensional fractal fragmentation pattern, which was attributed to the higher mobility of small particles, especially fibres. The atmospheric deposition rate of MPs ranged from 5.6 to 78.6 MPs m-2 day-1, with the higher values observed in densely populated areas such as Barcelona and Madrid. Additionally, we detected natural polymers, mostly cellulosic fibres with evidence of industrial processing, with a deposition rate ranging from 6.4 to 58.6 particles m-2 day-1. There was a positive correlation was found between the population of the study area and the median of atmospheric MP deposition, supporting the hypothesis that urban areas act as sources of atmospheric MPs. Our study presents a systematic methodology for monitoring atmospheric MP deposition.

Computational modeling of the effect of skin pinch and stretch on subcutaneous injection of monoclonal antibodies using autoinjector devices.

Subcutaneous injection of monoclonal antibodies (mAbs) has experienced unprecedented growth in the pharmaceutical industry due to its benefits in patient compliance and cost-effectiveness. However, the impact of different injection techniques and autoinjector devices on the drug's transport and uptake is poorly understood. Here, we develop a biphasic large-deformation chemomechanical model that accounts for the components of the extracellular matrix that govern solid deformation and fluid flow within the subcutaneous tissue: interstitial fluid, collagen fibers and negatively charged proteoglycan aggregates. We use this model to build a high-fidelity representation of a virtual patient performing a subcutaneous injection of mAbs. We analyze the impact of the pinch and stretch methods on the injection dynamics and the use of different handheld autoinjector devices. The results suggest that autoinjector base plates with a larger device-skin contact area cause significantly lower tissue mechanical stress, fluid pressure and fluid velocity during the injection process. Our simulations indicate that the stretch technique presents a higher risk of intramuscular injection for autoinjectors with a relatively long needle insertion depth.

[Experience of cytoreduction with peritonectomy and hyperthermic intraperitoneal chemotherapy in ovarian cancer]. / Experiencia de la citorreducción con peritonectomía y quimioterapia intraperitoneal hipertérmica en cáncer de ovario.

Background: Currently, epithelial ovarian cancer is diagnosed in advanced stages (EC IIIC) in 75-80% of cases worldwide. In this group of patients treatment with neoadjuvant chemotherapy is started, followed by interval cytoreduction of residual disease and even require peritonectomy with application of hyperthermic intraperitoneal chemotherapy (HIPEC). Objective: To identify the overall survival and progression-free survival associated with peritonectomy, in patients with peritoneal carcinomatosis secondary to ovarian cancer treated in the oncology gynecology service from January 2009 to January 2019 at the UMAE Hospital de Oncología Centro Médico Nacional Siglo XXI. Material and methods: Observational, descriptive, cross-sectional, retrospective study, information was obtained from the clinical file of patients treated with peritonectomy with the use of hyperthermic intraperitoneal chemotherapy in the gynecological oncology service from January 2009 to January 2019 at the UMAE Hospital de Oncología Centro Médico Nacional Siglo XXI. Results: Information was obtained from a total of 36 patients (n=100%), 36.1% received intraperitoneal chemotherapy and 63.8% underwent cytoreduction without the application of intraoperative chemotherapy. The most frequently used drug was cisplatin followed by mitomycin. There was no statistical significance when comparing both groups, however there was a trend in favor of the use of intraoperative chemotherapy by obtaining a greater number of months in terms of overall survival. Conclusion: Peritonectomy with hyperthermic intraperitoneal chemotherapy is an option in selected patients with advanced stage ovarian cancer in primary and recurrent surgery, as well as in patients with platinum-resistant ovarian cancer.

Introducción: en la actualidad, el cáncer de ovario epitelial se diagnostica en etapas avanzadas (EC IIIC) en 75-80% de los casos a nivel mundial. En este grupo de pacientes se inicia el tratamiento con quimioterapia neoadyuvante, seguida de citorreducción de intervalo de la enfermedad residual e incluso requieren de peritonectomía con aplicación de quimioterapia intraperitoneal hipertérmica (HIPEC). Objetivo: identificar la sobrevida global y sobrevida libre de progresión asociada a la realización de peritonectomía, en pacientes con carcinomatosis peritoneal secundario a cáncer de ovario tratadas en el servicio de Ginecología Oncológica de enero de 2009 a enero de 2019 en el Hospital de Oncología Centro Médico Nacional Siglo XXI (CMN SXXI). Material y métodos: estudio observacional, descriptivo, transversal, retrospectivo, se obtuvo información del expediente clínico de pacientes tratados con peritonectomía con uso de quimioterapia intraperitoneal hipertérmica en el servicio de Ginecología Oncológica de enero de 2009 a enero de 2019 en el Hospital de Oncología CMN SXXI. Resultados: se obtuvo información de un total de 36 pacientes (n = 100%), el 36.1% recibió quimioterapia intraperitoneal y al 63.8% se les realizó citorreducción sin la aplicación de quimioterapia intraoperatoria. El fármaco utilizado con mayor frecuencia fue el cisplatino seguido por mitomicina. No hubo significancia estadística al comparar ambos grupos, sin embargo hubo una tendencia a favor del uso de quimioterapia intraoperatoria al obtener un mayor número de meses en cuanto a sobrevida global. Conclusión: la peritonectomía con quimioterapia intraperitoneal hipertérmica es una opción en pacientes seleccionados de cáncer de ovario en etapa avanzada en cirugía primaria y recurrente, así mismo en paciente con cáncer de ovario platino-resistentes.

Mpox: Fifty-Nine Consecutive Cases from a Mexican Public Hospital; Just the Tip of the STIs Iceberg.

Monkeypox (Mpox) is a zoonotic viral infection endemic to Africa, which has caused a global outbreak since April 2022. The global Mpox outbreak is related to Clade IIb. The disease has primarily affected men who have sex with men. Skin lesions are concentrated in the genital area, with lymphadenopathy as well as concurrent sexually transmitted infections (STIs). This is an observational study of adult patients with a recent development of skin lesions and systemic symptoms, which could not be explained by other diseases present. Fifty-nine PCR-positive patients with prominent skin lesions in the genital area (77.9%), inguinal lymphadenopathy (49.1%), and fever (83.0%) were included. Twenty-five (42.3%) were known to be living with human immunodeficiency virus (HIV), and 14 of the HIV-naïve subjects (51.9%) were found to be positive during workup, totaling 39 (66.1%) patients with HIV. Eighteen patients (30.5%) had concurrent syphilis infections. It is worrisome that Mpox is present in large metropolitan areas of Mexico, but the underlying growth of cases of HIV infection and other STIs has not been well studied and should be evaluated in all at-risk adults and their contacts.

Neurological Manifestations and Complications of the Central Nervous System as Risk Factors and Predictors of Mortality in Patients Hospitalized with COVID-19: A Cohort Study.

The aim of this study was to analyze the risk factors and predictors of mortality in a retrospective cohort of patients with coronavirus disease (COVID-19) who presented central nervous system (CNS) manifestations and complications when admitted to hospital. Patients hospitalized from 2020 to 2022 were selected. Demographic variables; history of neurological, cardiological and pulmonary manifestations; comorbidities; prognostic severity scales; and laboratory tests were included. Univariate and adjusted analyses were performed to determine risk factors and predictors of mortality. A forest plot diagram was used to show the strength of the associated risk factors. The cohort included 991 patients; at admission, 463 patients presented CNS damage and of these, 96 hospitalized patients presented de novo CNS manifestations and complications. We estimate a general mortality of 43.7% (433/991) and 77.1% (74/96), for hospitalized patients with de novo CNS manifestations and complications, respectively. The following were identified as risks for the development of hospital CNS manifestations and complications when in hospital: an age of ≥64 years, a history of neurological disease, de novo deep vein thrombosis, D-dimer ≥ 1000 ng/dL, a SOFA ≥ 5, and a CORADS 6. In a multivariable analysis, the mortality predictors were an age of ≥64 years, a SOFA ≥ 5, D-dimer ≥ 1000 ng/mL and hospital CNS manifestations and complications when admitted to hospital. Old age, being hospitalized in critical condition, and having CNS manifestations and complications in hospital are predictors of mortality in hospitalized patients with COVID-19.

Association of Suppressive Myeloid Cell Enrichment with Aggressive Oropharynx Squamous Cell Carcinoma.

BACKGROUND: While immune-cell infiltrated tumors, such as human papillomavirus positive (HPV+) ororpharyngeal squamous cell carcinomas (OPSCC) have been associated with an improved clinical prognosis, there is evidence to suggest that OPSCCs are also subjected to increased immunoregulatory influence. The objective of this study was to assess whether patients with clinically aggressive OPSCC have a distinct immunosuppressive immune signature in the primary tumor. METHODS: This retrospective case-control study analyzed 37 pre-treatment tissue samples from HPV+ and HPV-negative OPSCC patients treated at a single institution. The cases were patients with known disease recurrence and the controls were patients without disease recurrence. An mRNA-expression immune-pathway profiling was performed, and correlated to clinical outcomes. The TCGA head and neck cancer database was utilized to make comparisons with the institutional cohort. RESULTS: In our cohort, HPV-negative and HPV+ patients with known disease recurrence both had significantly increased suppressive monoctyte/macrophage and granulocyte cell-expression-profile enrichment. Similar findings were found in the TCGA cohort when comparing HPV-negative to positive patients. CONCLUSIONS: our study demonstrates that patients with recurrent HPV+ OPSCC had suppressive monocyte/macrophage and granulocyte immune-cell enrichment, similar to those seen in the more aggressive HPV-negative OPSCC.