Effective treatment, but also proper diagnosis of cardiovascular diseases, remains a major challenge in everyday practice. A quick, safe, and economically acceptable non-invasive procedure should play a leading role in cardiovascular risk assessment before invasive diagnostics is performed. The staging of subclinical atherosclerosis may help in further clinical decisions. Safe, widely available, and relatively inexpensive, ultrasonography is a promising examination that should find wider application in clinical practice. The latest ESC guidelines emphasize the usefulness of carotid ultrasound in the diagnosis of coronary artery disease (CAD) and subclinical assessment of atherosclerosis, which help to determine the level of cardiovascular risk. Ultrasound examination of peripheral arteries, especially superficial vessels such as the femoral arteries, is quite easy, quick, and accurate. Other vascular beds, such as iliac and renal, are more demanding to examine, but can also provide valuable information. This review summarizes important studies comparing the severity of atherosclerosis in ultrasound-visible vascular beds in patients with established CAD. We especially emphasize the benefits of the combined assessment of atherosclerosis features, which were characterized by high sensitivity and specificity in the diagnosis of CAD and other serious cardiovascular diseases.

With the rapid development of science and technology, paper-based functional materials have become the core of the field of new materials. Recently, they have received extensive attention in the field of energy storage due to their advantages of rich and adjustable porous network structure, good flexibility. As an important energy storage device, paper-based supercapacitors have important application prospects in many fields, and have also received extensive attention from researchers in recent years. At present, researchers have modified and regulated paper-based materials by different means such as structural design and material composition to enhance their electrochemical storage capacity. The development of paper-based supercapacitors provides an important direction for the development of green and sustainable energy. Therefore, it is of great significance to summarize the relevant work of paper-based supercapacitors for their rapid development and application. In this review, the recent research progress of paper-based supercapacitors based on cellulose was summarized in terms of various cellulose-based composites, preparation skills and electrochemical performance. Finally, some opinions on the problems in the development of this field and the future development trend were proposed. It is hoped that this review can provide valuable references and ideas for the rapid development of paper-based energy storage devices.

Comment on: The COVID-19 Pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI and St. Jude Global.Chetan Dhamne MSc MD1, Tushar Vora MD1, Maya Prasad MD1, Nirmalya Roy Moulik MD PhD1, Badira C Parambil MD DM1, Akanksha Chichra MD1, Girish Chinnaswamy MD1, Shripad Banavali MD1, Gaurav Narula MD11 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India2. Homi Bhabha National Institute, Anushaktinagar, Mumbai, IndiaCorrespondence to:Gaurav Narula Pediatric Hematolymphoid Disease Management Group, Department of Medical Oncology, Tata Memorial Center, Parel Mumbai, 400012 Email: [email protected] word count: 576Brief running title: Letter to Editor (COVID-19) Global responseKeywords: COVID-19, SARS-CoV2, Pediatric Oncology, Children with cancerTables: 1Abbreviations

High-latitude tundra ecosystems are increasingly affected by climate warming. As an important fraction of soil microorganisms, fungi play essential roles in carbon (C) degradation, especially the old, chemically recalcitrant C. However, it remains obscure how fungi respond to climate warming and whether fungi, in turn, affect C stability of tundra. In a two-year winter soil warming experiment of 2 °C by snow fences, we investigated responses of fungal communities to warming in the active layer of the Alaskan tundra. Although fungal community composition, revealed by 28S rRNA gene amplicon sequencing, remained unchanged (P > 0.05), fungal functional gene composition, revealed by a microarray named GeoChip, was altered (P < 0.05). Changes in functional gene composition were linked to winter soil temperature, thaw depth, soil moisture, and gross primary productivity (Canonical Correlation Analysis, P < 0.05). Specifically, relative abundances of fungal genes encoding invertase, xylose reductase, and vanillin dehydrogenase significantly increased (P < 0.05), indicating higher C degradation capacities of fungal communities under warming. Accordingly, we detected changes of fungal gene networks under warming, including higher average path distance, lower average clustering coefficient, and lower percentage of negative links, indicating that warming potentially changed fungal interactions. Together, our study revealed higher C degradation capacities of fungal communities under short-term warming and highlights the potential impacts of fungal communities on mediating tundra ecosystem respiration, and consequently future C stability of high-latitude tundra.

Pulmonary cryptococcosis presents as various radiological manifestations depending on the immunological status of the host. The most common chest radiographic findings include single or multiple nodules. Herein, we present a rare case of pulmonary cryptococcosis in a patient with rheumatoid arthritis presenting as multiple cystic lesions that enlarged after treatment.

In high-performance industrial fermentation processes, stirring and aeration may account for significant production costs. Compared to the widely applied Rushton impellers, axial-pumping impellers are known to yield a lower power draw and at the same time improve mixing. However, their lower gas dispersion capability requires stronger agitation, compromising these benefits. Diverse advanced impeller forms have been developed to cope with this challenge. We apply alternating radial and axial impellers and demonstrate strong gas dispersion and energy-efficient mixing for the first time in a large-scale (160 m 3) bioreactor, based on experimental and CFD simulation data. For equal operating conditions (stirrer speed, aeration rate), this setup yielded similar gas hold-ups and better mixing times (-35 %) compared to a classical Rushton-only configuration. Hence, applying a radial impeller on an upper level for improving gas dispersion maintains the benefits of axial impellers in terms of reducing energy demand (up to -50 %). We conclude that this effect is significant only at large-scale, when bubbles substantially expand due to the release of the hydrostatic pressure and have time to coalesce. The work thus extends current knowledge on mixing and aeration of large-scale reactors using classical impeller types.

The incidence of mechanical complications of acute coronary syndromes (ACS) needing cardiac surgery has reduced significantly in the last years due to early diagnosis and treatments. Covid-19 pandemic, however, would generate in the patients a sense of fear regarding access to the ERs so they probably underestimate symptoms such as chest pain or angina equivalents until situation does not became critical. In this way, this behaviour could create a vast pool of patients who will enter the hospital in much more critical situations and with mechanical complications of an evolving ACS needing cardiac surgery treatment.

Advanced and accurate forecasting of COVID-19 cases plays a crucial role in planning and supplying resources effectively. Artificial Intelligence (AI) techniques have proved its capability in time series forecasting of the non-linear problems. In the present study, the relationship between weather factor and COVID-19 cases was assessed and also developed a forecasting model using long short term memory (LSTM), a deep learning model. The study found that the specific humidity has a strong positive correlation, whereas there is a negative correlation with maximum temperature and positive correlation with minimum temperature was observed in various geographic locations of India. The weather data and COVID-19 confirmed cases data (1st April-30th June 2020) was used to optimize univariate and multivariate LSTM time series forecast models. The optimized models were utilized to forecast the COVID-19 cases for the period 1st July 2020 to 31st July 2020 with 1 to 14 days of lead time. The results showed that the univariate LSTM model was reasonably good for the short term (1day lead) forecast of COVID-19 cases (relative error < 20%). Moreover, the multivariate LSTM model improved the medium-range forecast skill (1-7days) after including the weather factors. The study observed that the specific humidity played a crucial role in improving the forecast skill majorly in the West and northwest region of India. Similarly, the temperature played a significant role in model enhancement in the Southern and Eastern regions of India.

Objectives: During the pandemic, anxiety, stress, and depression may occur increasingly in the whole society. To evaluate the possible cause, incidence and levels of anxiety and depression in the relatives of the patients in the ICU in accordance with the patients’ SARS-CoV-2 PCR result. Materials and Method: The study was prospectively conducted on relatives of patients admitted to tertiary ICU during COVID-19 pandemic. Sociodemographic characteristics of the patients and their relatives were recorded. “The Turkish version of the Hospital Anxiety and Depression Scale” questionnaire was applied twice to the relatives of 120 patients to determine the symptoms of anxiety and depression in accordance with the PCR results of the patients (PCR positive n=60, PCR negative n=60). Results: The ratios above cut-off values for anxiety and depression among relatives of the patients were 45,8% and 67,5% for the first test and 46,7% and 62,5% for the second test respectively. The anxiety and depression in the relatives of PCR positive patients was more frequent than the PCR negative (p< 0,001 for HADS-A and p=0,034 for HADS-D). The prevalence of anxiety and depression was significantly higher in female participants (p=0,046 for HADS-A and p=0,009 for HADS-A). There was no significant correlation between HADS and age of the patient or education of the participants. The fact that the patients were hospitalized in the ICU during the pandemic was an independent risk factor for anxiety (AUC = 0.746) while restriction of patient visiting in the ICU was found to be an independent risk factor for depression (AUC= 0.703). Conclusion: While patient with positive PCR and participant with female gender is responsible for both anxiety and depression, hospitalization in the ICU due to COVID-19 is an independent risk factor for anxiety and restriction of patient visiting in the ICU is an independent risk factor for depression.

The thylakoid membrane is in a temperature-sensitive equilibrium that shifts repeatedly during the life cycle in response to ambient temperature or solar irradiance. Plants respond to seasonal temperature by changing their thylakoid lipid composition, while a more rapid mechanism for short-term heat exposure is required. The emission of the small organic molecule isoprene has been postulated as one such possible rapid mechanism. The protective mechanism of isoprene is not known, but some plants emit isoprene during periods of high-temperature stress. In this work, we investigate the dynamics and structure for lipids within a thylakoid membrane at different temperatures and varied isoprene content using classical molecular dynamics simulations. The results are compared with experimental findings from across the literature for temperature-dependent changes in the lipid composition and shape of thylakoids. We find that the surface area, volume, and flexibility of the membrane, as well as the lipid diffusion, increase with temperature, while the membrane thickness decreases. Saturated thylakoid 34:3 glycolipids derived from eukaryotic synthesis pathways exhibit significantly different dynamics than lipids from prokaryotic synthesis paths, which could explain the upregulation of specific lipid synthesis pathways at different temperatures. Increasing isoprene concentration was not observed to have a significant thermoprotective effect on the thylakoid membranes, and that isoprene readily permeated the membrane models tested here.

An Italian male with no link to China SARS-CoV-2 epidemic presented at Emergency Room with severe respiratory impairment. The RT-PCR on 20th February, 2020, nasopharyngeal swab revealed SARS-CoV-2 infection, confirmed with viral culture and sequencing. This was the first identified autochthonous SARS-CoV-2 transmission in Italy, that unveiled global pathogen diffusion.

Environmental DNA is an effective tool for describing fish biodiversity in lotic environments, but the downstream transport of eDNA released by organisms makes it difficult to interpret species detection at the local scale. In addition to biophysical degradation and exchanges at the water-sediment interface, hydrological conditions control the transport distance. We have developed an eDNA transport model that considers downstream retention and degradation processes in combination with hydraulic conditions and assumes that the sedimentation rate of very fine particles is a correct estimate of the eDNA deposition rate. Based on meta-analyses of available studies, we successively modelled the particle size distribution of fish eDNA (PSD), the relationship between the sedimentation rate and the size of very fine particles in suspension, and the influence of temperature on the degradation rate of fish eDNA. After combining the results in a mechanistic-based model, we correctly simulated the eDNA uptake distances observed in a compilation of previous experimental studies. eDNA degradation is negligible at low flow and temperature but has a comparable influence to background transfer when hydraulic conditions allow a long uptake distance. The wide prediction intervals associated with the simulations reflect the complexity of the processes acting on eDNA after shedding. This model can be useful for estimating eDNA detection distance downstream from a source point and discussing the possibility of false positive detection in eDNA samples, as shown in an example.

Myeloid cell leukemia-1 (MCL1), an anti-apoptotic BCL-2 family protein plays a major role in the control of apoptosis as the regulator of mitochondrial permeability which is deregulated in various solid and hematological malignancies. Interaction of the executioner proteins Bak/Bax with anti-apoptotic MCL1 and its cellular composition determines the apoptotic or survival pathway. This study highlighted the deleterious MCL1-Bax stabilizing effect of the mutation V220F on MCL1 structure through computational protein-protein interaction predictions and molecular dynamics simulations. The single point mutation at V220F was selected as it is residing at the hydrophobic core region of BH3 conserved domain, the site of Bax binding. The molecular dynamics simulation studies showed increase in stability of the mutated MCL1 before and after Bax binding comparable with the native MCL1. The clusters from free energy landscape found out structural variation in folding pattern with additional helix near the BH3 domain in the mutated structure. This loop to helix structural change in the mutated complex favored stable interaction of the complex and also induced Bax conformational change. Moreover, molecular mechanics based binding free energy calculations confirmed increased affinity of Bax towards mutated MCL1. Residue-wise interaction network analysis showed the individual residues in Bax binding responsible for the change in stability and interaction due to the protein mutation. In conclusion, the overall findings from the study reveal that the presence of V220F mutation on MCL1 is responsible for the structural confirmational change leading to disruption of its biological functions which might be responsible for tumorigenesis. The mutation could possibly be used as future diagnostic markers in treating cancers.

Kaposi sarcoma (KS) is an angioproliferative disorder. While KS of the head and neck is common in HIV-positives, it’s rare in HIV-negatives. Our case and the past 24 reported cases of ear KS reviewed here, highlight the importance of considering KS in the differential diagnosis of ear lesions in HIV-negatives.

Background: This study investigates the use of modern machine learning (ML) techniques to improve prediction of survival after orthotopic heart transplantation (OHT). Methods: Retrospective study of adult patients undergoing primary, isolated OHT between 2000-2019 as identified in the United Network for Organ Sharing (UNOS) registry. The primary outcome was one-year post-transplant survival. Patients were randomly divided into training (80%) and validation (20%) sets. Dimensionality reduction and data re-sampling were employed during training. Multiple machine learning algorithms were combined into a final ensemble ML model. Discriminatory capability was assessed using area under receiver-operating-characteristic curve (AUROC), net reclassification index (NRI), and decision curve analysis (DCA). Results: A total of 33,657 OHT patients were evaluated. One-year mortality was 11% (n=3,738). In the validation cohort, the AUROC of singular logistic regression was 0.649 (95% CI 0.628-0.670) compared to 0.691 (95% CI 0.671-0.711) with random forest, 0.691 (95% CI 0.671-0.712) with deep neural network, and 0.653 (95% CI 0.632-0.674) with Adaboost. A final ensemble ML model was created that demonstrated the greatest improvement in AUROC: 0.764 (95% CI 0.745-0.782) (p<0.001). The ensemble ML model improved predictive performance by 72.9% ±3.8% (p<0.001) as assessed by NRI compared to logistic regression. DCA showed the final ensemble method improved risk prediction across the entire spectrum of predicted risk as compared to all other models (p<0.001). Conclusions: Modern ML techniques can improve risk prediction in OHT compared to traditional approaches. This may have important implications in patient selection, programmatic evaluation, allocation policy, and patient counseling and prognostication.

Parasites form an integral part of food webs, however, mechanistic insights into the role of parasites for energy flow and community dynamics is currently limited by a lack of conceptual studies investigating host-parasite interactions in a community context. In aquatic systems, chytrids constitute a major group of fungal parasites and their free-living infective stage (zoospores) forms a highly nutritional food source to zooplankton. Consumption of zoospores can create an energy pathway from otherwise inedible phytoplankton to zooplankton (“mycoloop”). The impact of such parasite-mediated energy pathways on community dynamics and energy transfer to higher trophic levels is of high importance considering eutrophication and global warming induced shifts to dominance of unfavourable prey such as cyanobacteria. We theoretically investigated community dynamics and energy transfer in a food web consisting of an edible-nonhost and an inedible-host phytoplankton species, a fungal parasite, and a zooplankton species grazing on edible phytoplankton and fungi. Food web dynamics were investigated along a nutrient gradient for two cases: (1) non-adaptive zooplankton species representative for filter feeders like cladocerans and (2) zooplankton with the ability to actively adapt their feeding preferences like many copepod species. For both feeding strategies, the importance of the mycoloop for zooplankton increases with nutrient availability. This increase is smooth for non-adaptive consumers. For a consumer with an adaptive feeding preference, we observe an abrupt shift from almost exclusive preference for edible phytoplankton (dominant prey) at low nutrient levels to a strong preference for parasitic fungi at high nutrient levels. The model predicts that parasitic fungi can contribute up to 50% of the zooplankton diet in nutrient rich environments, agreeing with empirical observations on zooplankton gut content from eutrophic systems during cyanobacterial blooms. Our findings highlight the role of parasite-mediated energy pathway for predictions on energy flow and community composition under environmental change.

Postnatal cytomegalovirus (HCMV) infection is well characterized in preterm infants, where it can lead to severe symptomatic infection. We analyzed the rate and route of transmission of postnatal HCMV infections in full-term babies during the first year of life. A cohort of 120 HCMV seropositive mothers and their 122 newborns were tested after delivery for HCMV DNA shedding in different bodily fluids. Postnatal HCMV infection was defined as the detection of >2.5×10 2 HCMV-DNA copies/mL in infants’ saliva swabs. Maternal neutralizing antibody serum titer, HCMV specific T-cell response, and HCMV glycoprotein B (gB) IgG on breastmilk were analyzed. HCMV shedding was detected in 67 of 120 mothers (55.8%), and 20 of 122 infants (16.4%) developed HCMV infection within the first three months of life. Six additional infants were infected during the first year, for a postnatal infection rate of 21.3%. Viral shedding was more frequent in breastmilk than saliva, urine and vaginal secretions, and the mothers of infected infants showed higher levels of HCMV-DNA in milk. No association was found between the antibody levels in serum or milk and maternal viral shedding, whereas a slightly lower frequency of HCMV-specific CD4 + T-cells with long-term memory phenotype was observed in women with HCM-DNA-positive milk. About one out of five infants develop HCMV infection within the first year of life. Breastmilk appears the major route of transmission of the infection, maternal saliva have a minor role whereas the role of vaginal secretions is negligible.

Background and Purpose: Improvement of cognitive deficits in schizophrenia remains an unmet need due to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti-inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)-induced schizophrenia. Experimental Approach: Sprague-Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated by immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain-derived neurotrophic factor expression and phosphorylation of extracellular signal-regulated kinase were determined using western blot analysis. Key Results: Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose-dependent manner in PCP-treated rats. Fingolimod treatment exerted anti-inflammatory effects by inhibiting microglial activation and IL-6 and IL-1β pro-inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain-derived neurotrophic factor protein expression and activation of the extracellular signal-regulated kinase signalling pathway. Conclusion and Implications: To the best of our knowledge, this is the first preclinical study to assess the effects of fingolimod on cognitive function in schizophrenia models. Our results support the role of the immune system in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.