Analysis of the summer thermal comfort indices in Istanbul.

Thermal indices and thermal comfort maps have great importance in developing health-minded climate action strategies and livable urban layouts. Especially in cities where vulnerability to heatwaves is high, it is necessary to detect the most appropriate indicators for the regional characteristics and action planning with respect to thermal comfort. The aim of the study is to examine thermal indices as indicators of regional climate characteristics by relating to meteorological parameters and spatial features. Atmospheric variables including air temperature, wind speed, cloud cover, and relative humidity data were obtained from 30 meteorological stations located in districts having different climatic features. Heat stress levels for apparent temperature (AT), heat index (HI), wet bulb globe temperature (WBGT), physiological equivalent temperature (PET), universal thermal climate index (UTCI), and perceived temperature (PT) indices were calculated and associated with meteorological parameters. Thermal comfort maps have been created with the daily mean and maximum values of all indices. As a result, the meteorological parameters with the strongest correlation with all thermal indices are air temperature (Ta) with r = 0.89 ± 0.01 and mean radiant temperature (Tmrt) with r = 0.75 ± 0.16. The differences in thermal stress levels over the city have been distinctively observed in the ATmax, PETmax, and PTmax maps, which are generated by the daily maximum values of the indices. Çatalca, where forests cover large areas compared to highly urbanized districts, has the lowest heat stress defined by all indices.

A disposable impedimetric immunosensor for the analysis of CA125 in human serum samples.

Cancer antigen 125 (CA125) is the most common biomarker used to diagnose and monitor ovarian cancer progression for the last four decades, and precise detection of its levels in blood serum is crucial. In this work, label-free impedimetric CA125 immunosensors were fabricated by using screen-printed carbon electrodes modified with poly toluidine blue (PTB) (in deep eutectic solvent)/gold nanoparticles (AuNP) for the sensitive, environmentally friendly, economical, and practical analysis of CA125. The materials of PTBDES and AuNP were characterized by Fourier Transform Infrared (FT-IR), Scanning Electron Microscope (FE-SEM), and X-ray Diffraction (XRD). The analysis of the CA125 was performed by electrochemical impedance spectroscopy and the developed immunosensor. The immunosensor's repeatability, reproducibility, reusability, selectivity, and storage stability were examined. The developed label-free immunosensor allowed the determination of CA125 in fast, good repeatability and a low limit of detection (1.20 pg mL-1) in the linear range of 5-100 pg mL-1. The stable surface of the fabricated immunosensor was successfully regenerated ten times. The application of immunosensors in commercial human blood serum was performed, and good recoveries were achieved. The disposable label-free impedimetric CA125 immunosensor developed for the rapid and practical detection of CA125 is a candidate for use in point-of-care tests in clinical applications of ovarian cancer.

Evaluation of sarcopenia and phase angle in elderly patients with Parkinson's Disease.

PURPOSE: To investigate sarcopenia and related factors and to determine the disease-specific phase angle (PhA) cut-off score in detecting sarcopenia in elderly patients with Parkinson's Disease (PD). METHODS: This cross-sectional study was conducted with 89 participants. The Mini-Nutritional Assessment (MNA), the Eating Attitude Test-10 (EAT-10), the Physical Activity Scale for The Elderly (PASE) questionnaire and the Hoehn-Yahr scale have been used. Additionally, anthropometric measurements were performed. The diagnosis of sarcopenia was based on the new consensus published by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). PhA has been performed by Bioelectrical Impedance Analysis (BIA) with Tanita MC 780®. RESULTS: The mean age was of the participants 68.9 ± 6.4 years, and 57.3% were male. The prevalence of sarcopenia was 12.3%. PhA, malnutrition, age, disease severity, low calf circumference (CC), low body mass index (BMI), the difference between the pre-diagnosis and current weight loss, dopaminergic treatment, and low PASE score were associated with sarcopenia. The cut-off value of the PhA in terms of the ability to identify sarcopenia was <4.5o with a sensitivity of 53.3% and a specificity of 93.2% (p = 0.001). When we grouped the PhA of the patients according to this cut-off score, it was seen that 14.6% of them were sarcopenic. Age, disease severity, PASE score and hand grip strength were significantly related to both sarcopenia and PhA. CONCLUSION: It is important to be aware of sarcopenia and related factors at an early stage in Parkinson's patients. Because of disease-related symptoms, it may be more appropriate to use a disease-specific PhA cut-off score in the definition of sarcopenia.

The radiopacity of single-shade composite resins: A comparative evaluation.

OBJECTIVE: The aim of this study was to evaluate the radiopacity of single-shade composite resins with group and multi-shade composite resins via a digital image analysis. MATERIALS AND METHODS: Disc-shaped (5 mm in diameter, 2 mm in thickness) specimens were prepared with one multi-shade (Estelite Sigma Quick-ESQ), four single-shade (Omnichroma-OC, Charisma Topaz One-CTO, Vitra Unique-VU, and ZenChroma-ZC), three group-shade (G-aenial Achord-GA, Optishade-OS, and Estelite Asteria-EA), and one posterior composite resin (Estelite Posterior-EP) (n = 3). A radiographic image of all the specimens, an aluminum step-wedge, and a 2 mm thick tooth section were taken. Mean gray values (MGV) of the specimens, enamel, and dentin were calculated by ImageJ software. Composition analysis was performed with EDS, and SEM images (×10,000) were obtained. The data were analyzed with Kruskal-Wallis and Post hoc adjusted Bonferroni analysis (p = 0.05). RESULTS: The mean MGV of CTO, the highest of all test groups, was significantly higher than OC and dentin (p = 0.04 and p = 0.009, relatively). The lowest mean MGV was also observed in a single-shade group, OC. EDS analysis showed that the tested materials comprised various radiopaque elements. CONCLUSIONS: All of the single-shade and group-shade groups exceeded the MGV value of dentin, which is clinically expected from any restorative material. CLINICAL SIGNIFICANCE: The radiopacity properties of various single-shade composite resins which as a category is a rising trend in esthetic dentistry were investigated. It is important for clinicians to be aware of novel materials' physical qualities including radiopacity, a daily clinical criteria for restorative materials.

Cryogenic X-ray crystallographic studies of biomacromolecules at Turkish Light Source "Turkish DeLight".

X-ray crystallography is a robust and powerful structural biology technique that provides high-resolution atomic structures of biomacromolecules. Scientists use this technique to unravel mechanistic and structural details of biological macromolecules (e.g., proteins, nucleic acids, protein complexes, protein-nucleic acid complexes, or large biological compartments). Since its inception, single-crystal cryocrystallography has never been performed in Türkiye due to the lack of a single-crystal X-ray diffractometer. The X-ray diffraction facility recently established at the University of Health Sciences, Istanbul, Türkiye will enable Turkish and international researchers to easily perform high-resolution structural analysis of biomacromolecules from single crystals. Here, we describe the technical and practical outlook of a state-of-the-art home-source X-ray, using lysozyme as a model protein. The methods and practice described in this article can be applied to any biological sample for structural studies. Therefore, this article will be a valuable practical guide from sample preparation to data analysis.

Rapid and efficient ambient temperature X-ray crystal structure determination at Turkish Light Source.

High-resolution biomacromolecular structure determination is essential to better understand protein function and dynamics. Serial crystallography is an emerging structural biology technique which has fundamental limitations due to either sample volume requirements or immediate access to the competitive X-ray beamtime. Obtaining a high volume of well-diffracting, sufficient-size crystals while mitigating radiation damage remains a critical bottleneck of serial crystallography. As an alternative, we introduce the plate-reader module adapted for using a 72-well Terasaki plate for biomacromolecule structure determination at a convenience of a home X-ray source. We also present the first ambient temperature lysozyme structure determined at the Turkish light source (Turkish DeLight). The complete dataset was collected in 18.5 min with resolution extending to 2.39 Å and 100% completeness. Combined with our previous cryogenic structure (PDB ID: 7Y6A), the ambient temperature structure provides invaluable information about the structural dynamics of the lysozyme. Turkish DeLight provides robust and rapid ambient temperature biomacromolecular structure determination with limited radiation damage.

Mitochondrial transplantation as a possible therapeutic option for sarcopenia.

With advancing age, the skeletal muscle phenotype is characterized by a progressive loss of mass, strength, and quality. This phenomenon, known as sarcopenia, has a negative impact on quality of life and increases the risk of morbidity and mortality in older adults. Accumulating evidence suggests that damaged and dysfunctional mitochondria play a critical role in the pathogenesis of sarcopenia. Lifestyle modifications, such as physical activity, exercise, and nutrition, as well as medical interventions with therapeutic agents, are effective in the management of sarcopenia and offer solutions to maintain and improve skeletal muscle health. Although a great deal of effort has been devoted to the identification of the best treatment option, these strategies are not sufficient to overcome sarcopenia. Recently, it has been reported that mitochondrial transplantation may be a possible therapeutic approach for the treatment of mitochondria-related pathological conditions such as ischemia, liver toxicity, kidney injury, cancer, and non-alcoholic fatty liver disease. Given the role of mitochondria in the function and metabolism of skeletal muscle, mitochondrial transplantation may be a possible option for the treatment of sarcopenia. In this review, we summarize the definition and characteristics of sarcopenia and molecular mechanisms associated with mitochondria that are known to contribute to sarcopenia. We also discuss mitochondrial transplantation as a possible option. Despite the progress made in the field of mitochondrial transplantation, further studies are needed to elucidate the role of mitochondrial transplantation in sarcopenia. KEY MESSAGES: Sarcopenia is the progressive loss of skeletal muscle mass, strength, and quality. Although the specific mechanisms that lead to sarcopenia are not fully understood, mitochondria have been identified as a key factor in the development of sarcopenia. Damaged and dysfunctional mitochondria initiate various cellular mediators and signaling pathways, which largely contribute to the age-related loss of skeletal muscle mass and strength. Mitochondrial transplantation has been reported to be a possible option for the treatment/prevention of several diseases. Mitochondrial transplantation may be a possible therapeutic option for improving skeletal muscle health and treating sarcopenia. Mitochondrial transplantation as a possible treatment option for sarcopenia.

Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer.

Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL- 1, 0.01-10 ng mL- 1, 10-50 ng mL- 1, and 50-500 ng mL- 1). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL- 1 concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20-30 s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

Quantitative spatial assessment of the impact of urban growth on the landscape network of Türkiye's coastal cities.

This study aims to evaluate the impact of urban spatial expansion on the landscape patterns of coastal cities in Türkiye through the use of spatio-temporal indices. To this end, temporal samples covering a period of approximately 30 years (1986-2000 and 2000-2015) were analyzed for six selected coastal cities in Türkiye. The urban spatial growth patterns in these cities were characterized using 17 geospatial indices, and Pearson's correlation coefficient and principal component analysis were employed to assess the quantitative relationships between urban spatial development and the fragmentation of landscape networks. The results of the study demonstrated that the patterns of landscape fragmentation caused by the spatial growth patterns of the selected coastal cities can be divided into two categories: disconnected landscape connections and perforated landscape patterns. Leapfrog development was identified as a major factor in the fragmentation of landscape continuity, leading to the formation of perforated green structures. The findings of this research can serve as spatial guidelines for addressing disconnected landscapes, a crucial factor in enhancing urban sustainability in Türkiye's coastal cities. Furthermore, the outcomes of this study may be useful for informing the national well-being strategy for urban planning and natural mitigating policies in Türkiye's coastal regions.

A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer.

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1-100 pg mL-1 and 1-50 ng mL-1). High sensitivity, low LOD, and LOQ were obtained for two linear ranges with a correlation coefficient above 0.99. The application stability of the dual CA125-HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. The dual immunosensors exhibited high selectivity in eight different antigen mixtures. The reusability of the dual immunosensors has been tested up to 9 cycles. ROMA score% values for pre-menopausal and post-menopausal status were calculated using the concentration of CA125 and HE4 in the blood serum and assessing OC risk. The disposable dual immunosensors can be used in point-of-care tests for rapid and practical simultaneous determination of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

Cancer Stem Cells and Anti-tumor Immunity.

Cancer stem cells (CSCs) are correlated with poor clinical outcomes due to their contribution to chemotherapy resistance and the formation of metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs, which is important for diagnosis, therapy, and prognosis. This review underlines the role of CSCs and circulating tumor cells (CTCs) in tumor relapse and metastasis, the characteristics of CSC and CTC biomarkers, and the techniques used to detect these cells. We also summarized novel therapeutic approaches toward targeting CSCs, especially focusing on the role of immune checkpoint blockades (ICB), such as anti-programmed death 1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PDL1) therapies. Additionally, we address an intriguing new mechanism of action for small molecular drugs, such as telomere-targeted therapy 6-thio-2'deoxyguanosine (6- thio-dG), and how it reshapes tumor microenvironment to overcome ICB resistance. There are indications, that personalized cancer therapy targeting CSC populations in conjunction with immune-mediated strategy hold promise for the removal of residual therapy-resistant CSCs in the near future.

Susceptibility to discoloration of dental restorative materials containing dimethacrylate resin after bleaching.

The aim of this study is to compare the susceptibility to discoloration of dental restorative materials containing dimethacrylate resin after bleaching. In this study, resin-modified glass ionomer, polyacid-modified composite resin, giomer, posterior composite resin, anterior composite resin, bulk fill composite resin, flowable bulk fill composite resin, ormocer, indirect composite resin and hybrid ceramics were used as restorative material containing dimethacrylate resin. 20 samples were prepared from each material in accordance with the manufacturer's instructions. After the baseline colors are measured, the samples were randomly divided into four subgroups as office bleaching, home bleaching and a separate control group for each type bleaching method. Then, the samples were bleached and colored. Color measurements of the samples were repeated after exposure to bleaching and coloring. Then, ΔE00 and whiteness index (WID) were calculated. Data were analyzed using Paired-Samples T Test, two-way ANOVA, Repeated Measures ANOVA and Tukey post-hoc tests. Statistical significance level was taken as p < 0.05. In terms of bleaching systems, Opalescence Boost was found to cause more whitening in materials but more discoloration (p < 0.05). In terms of materials, it was found that the most susceptible materials to coloration were Clearfil Majesty Posterior, Filtek Bulk Fill Posterior Restorative, Filtek Bulk Fill Flowable and Fuji II LC, while the least susceptible materials were CAD/CAM materials (p < 0.05). The bleaching process increases the susceptibility to coloration of materials containing dimethacrylate resin.

Multimodal assessment of intensive care unit-acquired weakness in severe stroke patients.

BACKGROUND: Intensive care unit-acquired weakness (ICUAW) defines generalized muscle weakness seen in critically ill patients in the absence of other causative factors. Herein, we aimed to evaluate ICUAW in stroke patients by electrodiagnostic testing, histopathology, and assessment of respiratory complex activities (RCA), to define the frequency of ICUAW in this patient group, and to reach new parameters for early prediction and diagnosis. METHODS: We prospectively recruited twenty-four severe acute stroke patients during a sixteen-month period. In addition to serial nerve conduction studies (NCS), we performed muscle biopsy and RCA analysis on the non-paretic side when ICUAW developed. Patients undergoing orthopedic surgery without metabolic and neuromuscular diseases constituted the control group for RCA. Survival and longitudinal data were analyzed by joint modeling to determine the relationship between electrophysiological parameters and ICUAW diagnosis. RESULTS: Eight patients (33%) developed ICUAW, and six of them within the first two weeks. Extensor digitorum brevis, abductor digiti minimi (ADM), rectus femoris and vastus medialis (VM) compound muscle action potential (CMAP) amplitudes showed a significant decrease in the ICUAW group. VM CMAP amplitude (BIC = 358.1574) and ADM CMAP duration (BIC = 361.1028) were the best-correlated parameters with ICUAW diagnosis. The most informative electrophysiological findings during the entire study were obtained within the first 11 days. Muscle biopsies revealed varying degrees of type 2 fiber atrophy. Complex I (p = 0.003) and IV (p = 0.018) activities decreased in patients with ICUAW compared to controls. CONCLUSION: VM CMAP amplitude and ADM CMAP duration correlate well with ICUAW diagnosis, and may aid in the early diagnosis.

Factors affecting recurrence in subacute granulomatous thyroiditis

ABSTRACT Objective: This study aimed to evaluate the factors affecting recurrence in subacute granulomatous thyroiditis (SAT). Materials and methods: A total of 137 patients with SAT were enrolled in the study; 98 (71.5%) were women and 39 (28.5%) were men. The patients received either steroid or nonsteroidal anti-inflammatory drug (NSAID) for eight weeks. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (FT4), anti-thyroid peroxidase antibodies and thyroglobulin antibodies, neutrophil, lymphocyte, platelet, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio levels were evaluated. In addition, recurrence rates were compared between patients who received NSAID treatment and those who received steroid therapy. Results: Treatment modality and pretreatment TSH, FT4, and ESR were significantly different between patients with and without recurrence (p = 0.011, 0.001, 0.004, and 0.026, respectively). Compared with patients without recurrence, those with recurrence had higher pretreatment TSH levels, but lower FT4 and ESR levels. On logistic regression analysis, treatment modality was found to be an independent risk factor for recurrence. The risk of recurrence was higher in those taking steroids than in those taking NSAIDs (p = 0.015). The optimal TSH cutoff value for recurrence was 0.045 μIU/mL, with a sensitivity of 83.3% and specificity of 76% (AUC 0.794, 95% CI 0.639-0.949). Conclusions: The risk of SAT recurrence was higher with steroid therapy than with NSAIDs. Patients who had mild thyrotoxicosis had relatively high recurrence rate and may need a relatively longer duration of treatment.

Factors affecting recurrence in subacute granulomatous thyroiditis.

Objective: This study aimed to evaluate the factors affecting recurrence in subacute granulomatous thyroiditis (SAT). Methods: A total of 137 patients with SAT were enrolled in the study; 98 (71.5%) were women and 39 (28.5%) were men. The patients received either steroid or nonsteroidal anti-inflammatory drug (NSAID) for eight weeks. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (FT4), anti-thyroid peroxidase antibodies and thyroglobulin antibodies, neutrophil, lymphocyte, platelet, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio levels were evaluated. In addition, recurrence rates were compared between patients who received NSAID treatment and those who received steroid therapy. Results: Treatment modality and pretreatment TSH, FT4, and ESR were significantly different between patients with and without recurrence (p = 0.011, 0.001, 0.004, and 0.026, respectively). Compared with patients without recurrence, those with recurrence had higher pretreatment TSH levels, but lower FT4 and ESR levels. On logistic regression analysis, treatment modality was found to be an independent risk factor for recurrence. The risk of recurrence was higher in those taking steroids than in those taking NSAIDs (p = 0.015). The optimal TSH cutoff value for recurrence was 0.045 µIU/mL, with a sensitivity of 83.3% and specificity of 76% (AUC 0.794, 95% CI 0.639-0.949). Conclusion: The risk of SAT recurrence was higher with steroid therapy than with NSAIDs. Patients who had mild thyrotoxicosis had relatively high recurrence rate and may need a relatively longer duration of treatment.

Predictive significance of inflammatory indexes in metastatic nonsmall cell lung cancer patients treated with platinum-doublet chemotherapy.

Introduction: Lung cancer is the leading cause of cancer-related deaths, worldwide. Despite immune checkpoint inhibitors and targeted therapy have revolutionized the treatment of metastatic nonsmall cell lung cancer (NSCLC), a significant proportion of patients are still treated with platinum-based chemotherapy. It is widely noticed that systemic inflammation plays an important role in the development and progression of many solid tumors. In this study, we aimed to analyze the predictive role of the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI) in patients with advanced NSCLC treated with first-line platinum-doublet chemotherapy. Methods: We retrospectively collected data of patients treated with first-line therapy for metastatic NSCLC. All patients were treated with first-line platinum-doublet chemotherapy. The patients were grouped based on the median values of SII, PNI, and NLR. The Mann-Whitney U test was used for comparisons between groups. Results: The chemotherapy response rate (RR) was 75% in all patients. RR is statistically significantly lower in high SII, low PNI, and high NLR groups. Conclusions: High inflammatory indexes in metastatic NSCLC patients who were treated with platinum-doublet chemotherapy are related to low chemotherapy RR.

Monomer release from dental restorative materials containing dimethacrylate resin after bleaching.

OBJECTIVE: The aim of this study is to determine the type and amount of monomer released over time after bleaching was applied to dental restorative materials containing dimethacrylate resin. MATERIALS AND METHODS: Thirteen different restorative materials containing dimethacrylate resin were used in this study. Twenty samples were prepared from each material and the samples were randomly divided into 4 subgroups, namely, office bleaching, home bleaching, and separate control group for each of the bleaching methods. After bleaching, the samples were stored in 75% ethanol solution for 1, 14, and 28 days. Analysis of the samples collected to determine the type and amount of residual monomer released from the materials was performed using a liquid chromatography-tandem mass/mass spectrometer (LC-MS/MS). Data were analyzed using Friedman and Kruskal-Wallis tests. Statistical significance level was taken as p < 0.05. RESULTS: In terms of bleaching groups, mostly no significant difference was found between the groups in each time period in restorative materials (p > 0.05). In terms of time periods, it was determined that the amount of release of all monomers was decreased over time. In terms of restorative materials, the highest monomer release was detected in composite resin groups and the least monomer release was detected in CAD/CAM blocks. CONCLUSION: Although monomers were released from all materials, bleaching did not affect the amount of released monomer. Amounts of released monomers were generally below toxic limits. CLINICAL RELEVANCE: Within the limits of this study, bleaching does not significantly affect monomer release in restorative materials containing dimethacrylate resin.

Early differential responses elicited by BRAFV600E in adult mouse models.

The BRAF gene is frequently mutated in cancer. The most common genetic mutation is a single nucleotide transition which gives rise to a constitutively active BRAF kinase (BRAFV600E) which in turn sustains continuous cell proliferation. The study of BRAFV600E murine models has been mainly focused on the role of BRAFV600E in tumor development but little is known on the early molecular impact of BRAFV600E expression in vivo. Here, we study the immediate effects of acute ubiquitous BRAFV600E activation in vivo. We find that BRAFV600E elicits a rapid DNA damage response in the liver, spleen, lungs but not in thyroids. This DNA damage response does not occur at telomeres and is accompanied by activation of the senescence marker p21CIP1 only in lungs but not in liver or spleen. Moreover, in lungs, BRAFV600E provokes an acute inflammatory state with a tissue-specific recruitment of neutrophils in the alveolar parenchyma and macrophages in bronchi/bronchioles, as well as bronchial/bronchiolar epithelium transdifferentiation and development of adenomas. Furthermore, whereas in non-tumor alveolar type II (ATIIs) pneumocytes, acute BRAFV600E induction elicits rapid p53-independent p21CIP1 activation, adenoma ATIIs express p53 without resulting in p21CIP1 gene activation. Conversely, albeit in Club cells BRAFV600E-mediated proliferative cue is more exacerbated compared to that occurring in ATIIs, such oncogenic stimulus culminates with p21CIP1-mediated cell cycle arrest and apoptosis. Our findings indicate that acute BRAFV600E expression drives an immediate induction of DNA damage response in vivo. More importantly, it also results in rapid differential responses of cell cycle and senescence-associated proteins in lung epithelia, thus revealing the early molecular changes emerging in BRAFV600E-challenged cells during tumorigenesis in vivo.

COVID-19 Transmission and Clinical Features in Pediatric Intensive Care Health Care Workers.

OBJECTIVE: This study aims to investigate modes of transmission and clinical features of coronavirus disease 2019 in healthcare workers in pediatric intensive care units. MATERIALS AND METHODS: This multicenter descriptive study was conducted between March and November 2020. Patient demographics, clinical characteristics, origin of coronavirus disease 2019, treatment modalities, and loss of workdays were recorded. RESULTS: Seven hundred and sixty-eight healthcare workers from 16 pediatric intensive care units were enrolled and 114 (14.8%) healthcare workers with a mean age of 29.7 ± 6.7 years became coronavirus disease 2019 patients. Seventy-six (66.7%) patients were female. Approximately half (54.3%) of the patients were physicians, 34.2% were nurses, and 11.4% were ancillary staff. Transmission was deemed to occur through patient contact in 54.3% of the patients. Comorbid illness was present 10.5% of the patients. Transmission occurred during endotracheal intubation in 21%, cardiopulmonary resuscitation in 9.6%, and non-invasive ventilation in 12.2% of patients, while transmission was a result of multiple possible procedures in 43.8%. Intensive care admission was needed for 13.1% of the patients. Five patients needed oxygen by cannula, 7 needed oxygen with a non-rebreathing mask, 5 needed high-flow nasal cannula support, 5 needed non-invasive ventilation, and 3 needed invasive mechanical ventilation. Fortunately, no infected healthcare workers died. CONCLUSION: Coronavirus disease 2019 in healthcare workers is a significant problem in pediatric intensive care units. Transmission seems to occur particularly frequently during patient care procedures such as intubation, ventilation and aerosol therapy, which highlights the importance of proper use of full sets of personal protective equipment during all procedures during care of coronavirus disease 2019 patients.

Interactome of Arabidopsis Thaliana.

More than 95,000 protein-protein interactions of Arabidopsis thaliana have been published and deposited in databases. This dataset was supplemented by approximately 900 additional interactions, which were identified in the literature from the years 2002-2021. These protein-protein interactions were used as the basis for a Cytoscape network and were supplemented with data on subcellular localization, gene ontologies, biochemical properties and co-expression. The resulting network has been exemplarily applied in unraveling the PPI-network of the plant vacuolar proton-translocating ATPase (V-ATPase), which was selected due to its central importance for the plant cell. In particular, it is involved in cellular pH homeostasis, providing proton motive force necessary for transport processes, trafficking of proteins and, thereby, cell wall synthesis. The data points to regulation taking place on multiple levels: (a) a phosphorylation-dependent regulation by 14-3-3 proteins and by kinases such as WNK8 and NDPK1a, (b) an energy-dependent regulation via HXK1 and the glucose receptor RGS1 and (c) a Ca2+-dependent regulation by SOS2 and IDQ6. The known importance of V-ATPase for cell wall synthesis is supported by its interactions with several proteins involved in cell wall synthesis. The resulting network was further analyzed for (experimental) biases and was found to be enriched in nuclear, cytosolic and plasma membrane proteins but depleted in extracellular and mitochondrial proteins, in comparison to the entity of protein-coding genes. Among the processes and functions, proteins involved in transcription were highly abundant in the network. Subnetworks were extracted for organelles, processes and protein families. The degree of representation of organelles and processes reveals limitations and advantages in the current knowledge of protein-protein interactions, which have been mainly caused by a high number of database entries being contributed by only a few publications with highly specific motivations and methodologies that favor, for instance, interactions in the cytosol and the nucleus.