COVID-19 in a child with severe aplastic anemiaYunus Murat Akçabelen1, Ayça Koca Yozgat1, Aslı Nur Parlakay2, Nese Yarali11 Department of Pediatric Hematology, Ankara City Hospital Children’s Hospital, Turkiye2 Department of Pediatric Infectious Disease, Ankara City Hospital Children’s Hospital, TurkiyeArticle type: Letter to the editörRunning Title: COVID-19 in pediatric aplastic anemiaKey words: COVID-19, children, aplastic anemiaDisclosures: noneWord counts: 625

Mechanical forces play a crucial role in biological processes at the molecular and cellular levels. Recent advancements in dynamic force spectroscopies (DFS) have enabled the application and measurement of forces and displacements with high resolutions, providing insights into the mechanical pathways involved in various diseases, including cancer, cardiovascular disease, and COVID-19. Among the various DFS techniques, biomembrane force probe (BFP) advancements have improved our ability to measure bond kinetics and cellular mechanosensing with pico-newton and nano-meter resolutions. In this review, we provide a comprehensive overview of the classical BFP-DFS setup and highlight key advancements, including the development of dual biomembrane force probe (dBFP) and fluorescence biomembrane force probe (fBFP). BFP-DFS not only enables the investigation of dynamic bond behaviors on living cells, but also contributed significantly to our understanding of the specific ligand–receptor axes mediated cell mechanosensing. Besides, we explore the contribution of discoveries made possible by BFP-DFS in cancer biology, thrombosis, and inflammation, as well as predict future BFP upgrades to improve output and feasibility. Although BFP-DFS is still a niche research modality, its contribution to the growing field of cell mechanobiology is unparalleled, and its potential to elucidate novel therapeutic discoveries is significant.

Objectives To determine the frequency by neck level of clinically known and occult lymph node metastasis in p16 positive oropharyngeal squamous cell carcinoma (p16+ve OPSCC). Design Retrospective study of 61 patients with p16+ve OPSCC whom had neck dissection and prior or simultaneous trans-oral surgery. Histopathology reports of neck dissection specimens were compared to preoperative clinical and radiological reports to determine the distribution of clinically known and occult nodal disease at each neck level and its concordance with preoperative findings. Positive and negative predictive values for pathological nodal disease (pN+ve or pN0) were assigned to clinically assessed node-positive (cN+ve) or node-negative (cN0) status at each neck level. Setting Single tertiary referral centre in the UK Participants 61 patients with p16+ve OPSCC with no prior head and neck cancer treatment. Main outcome measures Clinical, radiological, and pathological findings of nodal disease in the neck. Results Two-hundred individual neck level specimens were analysed. Seventy-seven levels were considered cN+ve, of which 83.1% (64/77) were also pN+ve. One hundred and twenty-three levels were considered cN0 of which 13% (16/123) were proven as pN+ve, demonstrating occult disease across various levels. This occult disease was identified in level II in 7 patients, level III in 6 patients and level IV in 3 patients, with no occult disease seen in cN0 level I or V. Conclusions These findings augment existing limited data on the distribution of occult nodes in OPSCC specific to p16+ve disease and reaffirm the rationale for dissecting at least levels II-IV in any cN0 neck.

Oxidative polymerization of plant oils and lipids is poorly understood yet widely encountered. Oil oxidation is accelerated at high temperatures, typically above 110°C, where tri-acylglycerides are converted into toxic compounds and viscous deleterious polymers. Polymerization of mono-unsaturated oil (210°C, 3h, open to air) was investigated by comparing four similar sized molecules with different functional groups: oleic acid, methyl oleate, trans-7-tetradecene and stearic acid. Non-volatile products identified by NMR spectroscopy are minor ketones for saturated fatty acid (stearic acid), epoxides for acyl chains without acid groups (methyl oleate, tetradecane) and copious oligomerization, through ester cross-links, for acyl chains with acid and olefinic groups (oleic acid). Long range C-H coupling clearly shows ester (not ether) cross-links, contradicting long held beliefs. Chain fragmentation also occurs as revealed by species with methylene groups bonded to oxygen, -CH2-O-C(=O)-R. Large size (slow diffusion) of the first oligomer (trimer) formed by thermal oxidation of oleic acid, (representing hydrolyzed vegetable oil) was evidenced by DOSY (diffusion ordered spectroscopy). Since the first oligomers formed still have reactive groups (olefin, carboxylic acid), poly-ester formation is inevitable at longer oxidation times. Model oil reactions monitored by NMR spectroscopy are important for resolving the complex chemistry of vegetable oil polymerization.

1. Given the sharp increase in agricultural and infrastructure development and the paucity of widespread data available for making conservation management decisions, a more rapid and accurate tool for identifying fish fauna in the world’s largest freshwater ecosystem, the Amazon, is needed. 2. Current strategies for identification of freshwater fishes require high levels of training and taxonomic expertise for morphological identification or genetic testing for species recognition at a molecular level. 3. To overcome these challenges, we built an image masking model (U-Net) and a convolutional neural net (CNN) to classify Amazonian fish in photographs. Fish used as training data were collected and photographed in tributaries in seasonally flooded forests of the upper Morona River valley in Loreto, Peru in 2018 and 2019. 4. Species identifications in the training images (n = 3,068) were verified by expert ichthyologists. These images were supplemented with photographs taken of additional Amazonian fish specimens housed in the ichthyological collection of the Smithsonian’s National Museum of Natural History. 5. We generated a CNN model that identified 33 genera of fishes with a mean accuracy of 97.9%. Wider availability of accurate freshwater fish image recognition tools, such as the one described here, will enable fishermen, local communities and community scientists to more effectively participate in collecting and sharing data from their territories to inform policy and management decisions that impact them directly.

This paper reported the recovery of desert plant communities after twenty years of oil-derived hydrocarbon contamination in desert habitats of Kuwait, caused by the First Gulf War (1990 – 1991). The hypothesis that certain native desert plant species can tolerate weathered oil-polluted soils with oil breakdown products (i.e., polycyclic aromatic hydrocarbons ( PAHs)) and have the potential to function as bioindicators and phytoremediator species for oil-polluted soil was tested. A field survey of 200 quadrat sampling plots at seven hydrocarbon-contaminated and unpolluted desert areas in Kuwait was performed that recorded 42 plant species, with Haloxylon salicornicum, Cyperus conglomeratus and Rhanterium epapposum as the most dominant species. Analysis of plant tissues indicated plant uptake and accumulation of some PAHs. H. salicornicum was used as a representative species in a controlled field study that included growth of plants in hydrocarbon-polluted and unpolluted soils in two separate desert areas under similar growth conditions. Results showed a significant decrease in plant biomass in oil-contaminated soil compared to those from the uncontaminated site. However, the plants appeared green and healthy in both sites, and showed no overt stress. The results suggest that some desert plant communities exhibit signs of recovery after severe oil pollution, and that H. salicornicum may serve as a phytoremediator of oil-contaminated desert soils. Our results also demonstrated that some desert plant communities could be cultivated in oil fields to reduce hydrocarbon contamination and provide guide to other ecosystem services through improving soil quality and biodiversity.

A 16-year-old female presented to our ED with fever and coughing of blood for 3 days. She is known to have SLE for 5 months and takes oral prednisone. She was tested positive for COVID19. She developed hypocalcemia with clinically-diagnosed massive pulmonary embolism. She was treated with heparin and recovered.

We describe a case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) to multiple CFTR modulators and piperacillin in an 8 year old female with CF. To our knowledge this is the first reported case of delayed type, T-cell mediated hypersensitivity to multiple CFTR modulators described in literature. Our findings suggest possible cross-reactivity between CFTR modulators or multiple sensitisations, which should be taken into account in similar cases.

Age is necessary information for the study of life history of wild animals. A general method to estimate the age of odontocetes is counting dental growth layer groups (GLGs). However, this method is highly invasive as it requires the capture and handling of individuals to collect their teeth. Recently, the development of DNA-based age estimation methods has been actively studied as an alternative to such invasive methods, of which many have used biopsy samples. However, if DNA-based age estimation can be developed from fecal samples, age estimation can be performed without touching or disrupting individuals, thus establishing an entirely non-invasive method. We developed an age estimation model using the methylation rate of two gene regions, GRIA2 and CDKN2A, measured through methylation-sensitive high-resolution melting (MS-HRM) from fecal samples of wild Indo-Pacific bottlenose dolphins (Tursiops aduncus). The age of individuals was known through conducting longitudinal individual identification surveys underwater. Methylation rates were quantified from 36 samples. Both gene regions showed a significant correlation between age and methylation rate. The age estimation model was constructed based on the methylation rates of both genes which achieved sufficient accuracy (after LOOCV: MAE = 5.08, R2 = 0.34) for the ecological studies of the Indo-Pacific bottlenose dolphins, with a lifespan of 40-50 years. This is the first study to report the use of non-invasive fecal samples to estimate the age of marine mammals.

Plant-soil feedback is commonly pointed out as driver of plant community dynamics and species co-existence. However, experimental evidence for soil legacy effects of conditioning plant communities on responding plant communities under natural conditions is lacking. We conditioned 192 grassland plots with plant communities with different ratios of grasses and forbs and fast and slow-growing plants. Soil microbial legacies were most evident for soil fungi. Soil abiotic parameters did not change in response to conditioning. The soil legacies affected the composition of the succeeding vegetation. Plant communities of a specific functional type caused negative feedbacks on succeeding plants when they belonged to the same functional type. Richness, relative species cover and belowground biomass of the responding vegetation were all influenced by the growth rate of the conditioning community. We conclude that plant-soil feedbacks play an important role in vegetation assembly of natural communities.

The alignment of third molars has largely been overlooked by orthodontists. Since difficulties arise during their eruption, a plethora of surgical procedures is advocated for their management, including prophylactic extraction. This case series describes the use of midfacial development in 4 patients and illustrates successful patterns of third molar eruption.

PRV1 was first detected in deceased pigs from Hong Kong in 2013. It has since been detected in the USA, Chile and most recently in Hungary. Information on the pathogenicity and global spread is sparse, however it has been speculated to play a role in the porcine respiratory disease complex. In an effort to investigate the porcine virome, we screened 53 pig samples from 29 farms using SMg within the Dutch/German border region. In five farms we detected PRV1. qPCR confirmed the presence of the virus in 2 of these farms and found an additional 6 positive farms. Phylogenetic analysis found the closest match to the first detected PRV1 strain in Hong Kong. The Dutch/German region represents a major area of pig farming within Europe and could provide important information on the characterization and circulation of porcine viruses, such as PRV1. Together with the recent detection of PRV1 in Hungary, these findings suggest widespread of PRV1 in Central Europe, highlighting the need for further research on persistence, pathogenicity and transmission in Europe.

Climate change causes upward shift of forest lines worldwide, with consequences on soil biota and carbon (C). Using a space-for-time approach, we analyse compositional changes in the soil biota across the forest line ecotone, an important transition zone between different ecosystems. We collected soil samples along transects stretching from subalpine mountain birch forests to low-alpine vegetation. Soil fungi and micro-eukaryotes were surveyed using DNA metabarcoding of the 18S and ITS2 markers, while ergosterol was used to quantify fungal biomass. We observed a strong shift in the soil biota across the forest line ecotone: Below the forest line, there were higher proportions of basidiomycetes and mucoromycetes, including ectomycorrhizal and saprotrophic fungi. Above, we observed relatively more root-associated ascomycetes, including Archaeorhizomycetes, ericoid mycorrhizal fungi and dark septate endophytes. Ergosterol and percentage C content in soil strongly and positively correlated with the abundance of root-associated ascomycetes. The predominance of ectomycorrhizal and saprotrophic fungi below the forest line likely promote high C turnover, while root-associated ascomycetes above the forest line may enhance C sequestration. With further rise in forest lines, there will be a corresponding shift in the belowground biota linked to C sequestration processes.

The mirid bugs Stenotus rubrovittatus and Trigonotylus caelestialium, which cause pecky rice, have become a threat to rice cultivation in Asia. Damage caused by these pests has rapidly become frequent since around 2000 in Japan. Their expansion pattern is not simple, making it difficult to manage them by prediction. Some insects with wide distributions have locally adapted variations in life-history traits. We performed laboratory rearing experiments to assess the geographical scale of intraspecific variations in life-history traits of S. rubrovittatus and T. caelestialium. These were aimed at increasing the accuracy of occurrence estimates and the number of generations per year. These results were compared with previous research, and differences in development rates were observed between populations of different latitudes, but not of the same latitude. Finally, plotting the timing of adult emergence and the potential number of generations per year on maps with a 5-km grid revealed that they differed greatly locally at the same latitude. These maps can be used for developing more efficient methods of managing mirid bugs in integrated pest management.

This is a 3-week-old female, her presenting complaints were low-grade fever and a blocked nose for one day. Eventually, she developed progressive desaturation, hypotension, and poor perfusion due to severe pulmonary hemorrhage. Then, she developed cardiac arrest and was declared dead.

With continued global warming, plants are forecast to increasingly experience abiotic stress(es). Stomata on leaf surfaces are the gatekeepers to plant interiors, regulating gaseous exchanges that are crucial for both photosynthesis and outward water release. To optimise future productivity, accurate modelling of how stomata govern plant-environment interactions will be crucial. Here, we synergise optical and thermal imaging data to enhance transpiration modelling during water and/or nitrogen stress. By utilising hyperspectral data and partial least squares regression analysis of six plant traits and fluxes in wheat ( Triticum aestivum), we have developed a new spectral vegetation index; the combined nitrogen and drought index (CNDI), which can be used to detect both water stress and/or nitrogen deficiency. Upon full stomatal closure during drought, CNDI reduces as leaf biochemistry changes unfold, and during a combined stress experiment (drought and nitrogen deficiency), this is reflected in CNDI showing a strong relationship with leaf relative water content ( r2 = 0.70). By incorporating CNDI transformed with a sigmoid function into thermal-based transpiration modelling, we have increased the accuracy of modelling water fluxes during abiotic stress. If employed using future remote sensing technologies, our findings have the potential to markedly improve agricultural water usage and yields.

In hemophilia A and B, analysis of the F8 and F9 variants has become standard over recent decades, giving information on the severity of hemophilia, inhibitor formation and allowing counseling for the families. The PedNet Registry collects data on hemophilia in children and has more than 2000 children listed. Genetic reports are collected uniformly and re-evaluated following international guidelines. We report 90 novel variants in the F8 and F9 gene, respectively, causing hemophilia with detailed information on severity, factor level and inhibitor formation. This will lead to further guidance for genetic laboratories and the treating physician. These findings can be implemented in hemophilia variant databases. The study highlights the need to re-evaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in the light of changed nomenclature, the use of in silico prediction and new sequencing techniques.

The factors responsible for the spectrum of COVID-19 disease severity and the genesis and nature of protective immunity against COVID-19 remain elusive. Multiple studies have investigated the immune responses to COVID 19 in various populations, including those without evidence of COVID 19 infection. Information regarding innate and adaptive immune responses to the novel SARS-CoV-2 has evolved rapidly. Here, data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS-CoV-2 and the development of novel vaccines. In this article, we summarize data on important innate immune responses including cytokines, specifically IL-6 and complement, and explore potential treatments. We also examine adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins. Finally, we explore data on real-time assessments of adaptive immune responses which include CD4+/CD8+ T-cells, NKT-cells, memory B-cells, and T-follicular cells with specificities for COVID-19 peptides in infected individuals and normals. Data of two novel vaccines have been released, both showing >95% efficacy in preventing SARS-CoV-2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long-term assessment of SARS-CoV-2 memory B and T-cell mediated immune responses in patients recovering from an infection or those with cross-reactive immunologic memory will help to define risk for future SARS-CoV infections. Finally, patients recovering from SARS-CoV-2 infection may experience prolonged immune activation likely due to T-cell exhaustion. This will be an important new frontier for study.