Blood-brain barrier permeability increases with the differentiation of glioblastoma cells in vitro.

Background: Glioblastoma multiforme (GBM) is an aggressive tumor, difficult to treat pharmacologically because of the blood-brain barrier (BBB), which is rich in ATP-binding cassette (ABC) transporters and tight junction (TJ) proteins. The BBB is disrupted within GBM bulk, but it is competent in brain-adjacent-to-tumor areas, where eventual GBM foci can trigger tumor relapse. How GBM cells influence the permeability of BBB is poorly investigated.

Increasing membrane polyunsaturated fatty acids sensitizes non-small cell lung cancer to anti-PD-1/PD-L1 immunotherapy.

Immune checkpoints inhibitors (ICIs) as anti-PD-1/anti-PD-L1 have been approved as first-line treatment in patients with non-small cell lung cancer (NSCLC), but only 25 % of patients achieve durable response. We previously unveiled that estrogen receptor α transcriptionally up-regulates PD-L1 and aromatase inhibitors such as letrozole increase the efficacy of pembrolizumab. Here we investigated if letrozole may have additional immune-sensitizing mechanisms.

TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer.

Background: In non-small cell lung cancer (NSCLC) the efficacy of chemo-immunotherapy is affected by the high expression of drug efflux transporters as ABCC1 and by the low expression of ABCA1, mediating the isopentenyl pyrophosphate (IPP)-dependent anti-tumor activation of Vγ9Vδ2 T-lymphocytes. In endothelial cells ABCA1 is a predicted target of the transcription factor EB (TFEB), but no data exists on the correlation between TFEB and ABC transporters involved in the chemo-immuno-resistance in NSCLC.

Methods: The impact of TFEB/ABCC1/ABCA1 expression on NSCLC patients' survival was analyzed in the TCGA-LUAD cohort and in a retrospective cohort of our institution.

Phylotranscriptomics provides a treasure trove of flood-tolerance mechanisms in the Cardamineae tribe.

Flooding events are highly detrimental to most terrestrial plant species. However, there is an impressive diversity of plant species that thrive in flood-prone regions and represent a treasure trove of unexplored flood-resilience mechanisms. Here we surveyed a panel of four species from the Cardamineae tribe representing a broad tolerance range.

Classification of patients with chronic disease by activation level using machine learning methods.

Patient Activation Measure (PAM) measures the activation level of patients with chronic conditions and correlates well with patient adherence behavior, health outcomes, and healthcare costs. PAM is increasingly used in practice to identify patients needing more support from the care team. We define PAM levels 1 and 2 as low PAM and investigate the performance of eight machine learning methods (Logistic Regression, Lasso Regression, Ridge Regression, Random Forest, Gradient Boosted Trees, Support Vector Machines, Decision Trees, Neural Networks) to classify patients.

A tool for rapid, automated characterization of population epigenomics in plants.

Epigenetic variation in plant populations is an important factor in determining phenotype and adaptation to the environment. However, while advances have been made in the molecular and computational methods to analyze the methylation status of a given sample of DNA, tools to profile and compare the methylomes of multiple individual plants or groups of plants at high resolution and low cost are lacking. Here, we describe a computational approach and R package (sounDMR) that leverages the benefits of long read nanopore sequencing to enable robust identification of differential methylation from complex experimental designs, as well as assess the variability within treatment groups and identify individual plants of interest.

Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Purpose: The response to immune checkpoint inhibitors (ICI) often differs between genders in non-small cell lung cancer (NSCLC), but metanalyses results are controversial, and no clear mechanisms are defined. We aim at clarifying the molecular circuitries explaining the differential gender-related response to anti-PD-1/anti-PD-L1 agents in NSCLC.

Experimental Design: We prospectively analyzed a cohort of patients with NSCLC treated with ICI as a first-line approach, and we identified the molecular mechanisms determining the differential efficacy of ICI in 29 NSCLC cell lines of both genders, recapitulating patients' phenotype.

TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism.

Melanomas are characterised by accelerated cell proliferation and metabolic reprogramming resulting from the contemporary dysregulation of the MAPK pathway, glycolysis and the tricarboxylic acid (TCA) cycle. Here, we suggest that the oncogenic transcription factor EB (TFEB), a key regulator of lysosomal biogenesis and function, controls melanoma tumour growth through a transcriptional programme targeting ERK1/2 activity and glucose, glutamine and cholesterol metabolism. Mechanistically, TFEB binds and negatively regulates the promoter of DUSP-1, which dephosphorylates ERK1/2.

Unexpected thoracic injury caused by a falling bullet in a metropolis.

The incident of being wounded by free-falling bullets is not usual in provinces where there is limited civilian armament in large metropolises. Cases that are wounded by falling bullet wounding apply to health-care institutions with major clinical manifestations. The patient was admitted with minor complaints, which manifested itself with mild back pain and spotting bleeding.

Is it reliable to make a decision based on visual changes in the patient's diaper in the evaluation of post circumcision bleeding?

Background: The most common complication of circumcision is bleeding. Monitoring bleeding by visual assessment of the diaper can cause errors due to the high absorbency of diapers. The patient may have had significant problems before the visible changes.

Penile skin length can be predicted before frenuloplasty during routine circumcision.

Background: One of the restricting factors for surgical treatment of congenital anatomical pathologies of the penis is the skin structure. Thanks to its structure, the penis is a flexible organ structure, and the treatment can be completed without the need for a free tissue graft. Length changes are obtained on the ventral side of the penis by frenuloplasty.

Organization of primary care.

Strong primary care does not develop spontaneously but requires a well-developed organizational planning between levels of care. Primary care-oriented health systems are required to effectively tackle unmet health needs of the population, and efficient primary care organization (PCO) is crucial for this aim. Via strong primary care, health delivery, health outcomes, equity, and health security could be improved.

Mitochondrial ROS drive resistance to chemotherapy and immune-killing in hypoxic non-small cell lung cancer.

Background: Solid tumors subjected to intermittent hypoxia are characterized by resistance to chemotherapy and immune-killing by effector T-lymphocytes, particularly tumor-infiltrating Vγ9Vδ2 T-lymphocytes. The molecular circuitries determining this double resistance are not known.

Methods: We analyzed a panel of 28 human non-small cell lung cancer (NSCLC) lines, using an in vitro system simulating continuous and intermittent hypoxia.

Effect of activated chlorhexidine and irritrol with photon-induced-photoacoustic-streaming and EDDY on the dislocation resistance of biodentine.

Background: Irrigant activation techniques, which are more effective in anatomically complex areas, can be used to maximize irrigant efficacy.

Aim: This in vitro study aimed to evaluate the efficacy of different agitation techniques on the dislocation resistance of Biodentine to the root canal dentin.

Materials And Methods: Seventy single-rooted teeth divided into seven experimental groups (n = 10); Group I-Irritrol/Photon-induced-photoacoustic-streaming (PIPS), Group II-Irritrol/EDDY, Group III- Irritrol/Syringe-needle-irrigation (SNI), Group IV-Chlorhexidine-gluconate (CHX)/PIPS, Group V-CHX/EDDY, Group VI-CHX/SNI, Group VII-Saline.

International examples of primary care COVID-19 preparedness and response: a comparison of four countries.

We report the learnings gleaned from a four-country panel (Australia, South Africa, Egypt and Nigeria) sharing their countries' COVID-19 primary healthcare approaches and implementation of policy at the World Organization of Family Doctor's World virtual conference in November. The countries differ considerably with respect to size, national economies, average age, unemployment rates and proportion of people living rurally. South Africa has fared the worst with respect to waves of COVID-19 cases and deaths.

Olvanil activates sensory nerve fibers, increases T cell response and decreases metastasis of breast carcinoma.

Background: Inactivation of sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) enhances breast cancer metastasis. Sensory neurons have profound effects on immune response to a wide range of diseases including cancer. Hence, activation of sensory nerves using feasible approaches such as specific TRPV1 agonists may inhibit breast cancer metastasis through neuroimmune pathways.

Effects of in-vitro modulation of TRPV1 activity on immune response of mice bearing metastatic breast carcinoma: Enhanced inflammatory response may hinder therapeutic potentials of TRPV1 agonists.

Aims: Activation of transient receptor potential vanilloid 1 (TRPV1) ion channels inhibits inflammation, enhance cytotoxic immune response, and may have therapeutic potential in treatment of cancer characterized by increased systemic inflammation. We here determined how activation of TRPV1 alters immune response of tumor-bearing mice.

Main Methods: Three different metastatic subset of 4 T1 breast carcinoma cells were used to induce tumors in Balb-c mice.

Evaluation of health-related knowledge, attitudes, and behaviors of undergraduate students by cardiovascular risk factors.

Aim: To determine the presence of cardiovascular (CV) risk (CVR) factors in university students and evaluate how these factors are affected from the knowledge, attitudes, and habits of the individuals regarding healthy lifestyle.

Background: Starting from early ages, lifestyle habits such as lack of physical activity, unhealthy eating, and inappropriate drug use increase CV and metabolic risks of individuals.

Methods: In April-May 2018, sociodemographic characteristics of 770 undergraduate students, in addition to their knowledge, attitudes, and habits regarding their nutrition and physical activity status were obtained through face-to-face questionnaires.

Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.

Solid tumors often grow in a micro-environment characterized by < 2% O tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases the amount and activity of the hypoxia-inducible factor-1α (HIF-1α), a transcription factor that controls up to 200 genes involved in neoangiogenesis, metabolic rewiring, invasion and drug resistance. Hypoxia also induces endoplasmic reticulum (ER) stress, a condition that triggers cell death, if cells are irreversibly damaged, or cell survival, if the stress is mild.

Hypoxia Dictates Metabolic Rewiring of Tumors: Implications for Chemoresistance.

Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. These events favor tumor progression and chemoresistance.