The difference in morbidity and mortality between adult and pediatric COVID-19 infections is dramatic. Understanding pediatric-specific acute and delayed immune responses to SARS-CoV-2 is critical for the development of vaccination strategies, immune-targeted therapies, and treatment and prevention of MIS-C. The goal of this review is to highlight research developments in understanding of the immune responses to SARS-CoV-2 infections, with a specific focus on age-related immune responses.

Objectives: Smell/taste disturbances are a common but underrated, under-researched and under treated sensory loss and an independent risk factor for reduced longevity. This study aimed to characterise the experience of patients these disorders in seeking help. Design: The study was designed by patients together with clinicians through a dedicated workshop and conducted as a cross-sectional survey to capture experiences in public and private healthcare settings internationally. Setting: Primary, secondary and tertiary care. Participants: Any members of the public self-reporting a smell/taste disorder were invited to participate. Main outcome measures: The survey captured information including experience of getting consultations and referrals to medical professionals, treatments offered, costs incurred and related problems with mental health. Results: Of 673 participants; 510 female, 160 male, self-reported aetiology included sinonasal disease (24%), idiopathic (24%) and post-viral olfactory dysfunction (22%); true gustatory disorders were typically rare. Failure of medical professionals to recognise the problem was a key concern - 64%, 76% and 47% of GPs, ENT specialists and Neurologists acknowledged respectively. Other issues included repeated ineffective treatments, difficulties getting referrals to secondary/tertiary care, mental health problems (60%) and a mean personal cost of £421 to seeking advice and treatment. Whilst the participants were self-selecting, however they do represent those who are seeking help and intervention for their disorders. Conclusion: There is an unmet need for these patients in accessing healthcare including a clear need to improve education of and engagement with the medical profession in Otorhinolaryngology, General Practice and other specialties, in order to remove the current barriers they face.

The El Niño-Southern Oscillation (ENSO) phenomena, originating in the tropical Pacific region, is an interannual climate variability driven by sea surface temperature and atmospheric pressure changes that affect weather patterns globally. In Mesoamerica, ENSO can cause significant changes in rainfall patterns with major impacts on water resources. This commentary presents results from a nearly 10-yr hydrometric and tracer monitoring network across north-central Costa Rica, a region known as a headwater-dependent system. This monitoring system has recorded different El Niño and La Niña events, as well as the direct/indirect effects of several hurricane and tropical storm passages. Our results show that ENSO exerts a significant but predictable impact on rainfall anomalies, groundwater recharge, and spring discharge, as evidenced by second-order water isotope parameters (e.g., line conditioned-excess or LC-excess). The Oceanic Niño Index (ONI) is correlated with a reduction in mean annual and cold front rainfall across the headwaters of north-central Costa Rica. During El Niño conditions, rainfall is substantially reduced (by up to 69.2%) during the critical cold fronts period, subsequently limiting groundwater recharge and promoting an early onset of baseflow conditions. In contrast, La Niña is associated with increased rainfall and groundwater recharge (by up to 94.7% during active cold front periods). During La Niña, the long-term mean spring discharge (39 Ls -1) is exceeded 63-80% of the time, whereas, during El Niño, the exceedance time ranges between 26% and 44%. These stark shifts in regional hydroclimatic variability are imprinted on the hydrogen and oxygen isotopic compositions of meteoric waters. Drier conditions favored lower LC-excess in rainfall (-17.3‰) and spring water (-6.5‰), whereas wetter conditions resulted in greater values (rainfall=+17.5‰; spring water=+10.7‰). The lower and higher LC-excess values in rainfall corresponded to the very strong 2014-16 El Niño and 2018 La Niña, respectively. During the recent triple-dip 2021-23 La Niña, LC-excess exhibited a significant and consistently increasing trend. These findings highlight the importance of combining hydrometric, synoptic, and isotopic monitoring as ENSO sentinels to advance our current understanding of ENSO impacts on hydrological systems across the humid Tropics. Such information is critical to constraining 21 st century projections of future water stress across this fragile region.

Background Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions. Objective: To evaluate the impact on gradual home introduction of foods containing cows milk after a supervised, single low dose exposure to whole milk at time of diagnosis. Methods Infants less than 12 months old, referred with suspected IgE-mediated cow’s milk allergy were recruited to an open-label randomised, controlled trial of intervention - a single dose of fresh cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 – vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at Home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post randomisation. Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows milk allergy in a very young cohort. A supervised single dose of milk at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress.

Karyotypic changes in chromosome number and structure are drivers in the divergent evolution of diverse plant species and lineages. This study aimed to reveal the origins of the unique karyotype (2n = 12) and phylogenetic relationships of the genus Megadenia (Brassicaceae). A high-quality chromosome-scale genome was assembled for Megadenia pygmaea using Nanopore long reads and high-throughput chromosome conformation capture (Hi-C). The assembled genome is 215.2-Mb and is anchored on six pseudo-chromosomes. We annotated a total of 25,607 high-confidence protein-coding genes and corroborated the phylogenetic affinity of Megadenia with the expanded Lineage II, which contains numerous agricultural crops. We dated the divergence of Megadenia from its closest relatives to 27.04 (19.11-36.60) million years ago. A reconstruction of the chromosomal composition of the species was performed based on the de novo assembled genome and comparative chromosome painting analysis. The karyotype structure of M. pygmaea is very similar to the previously inferred Proto-Calepineae Karyotype (PCK; n = 7) of the Brassicaceae Lineage II. However, an end-to-end translocation between two ancestral chromosomes reduced the chromosome number from n = 7 to n = 6, comparable to Megadenia. Our reference genome provides fundamental information for use in horticulture, plant breeding and evolutionary study of this genus.

There is evidence that prey can perceive the risk of predation and alter their behaviour in response, resulting in changes in spatial distribution and potential fitness consequences. Previous approaches to mapping predation risk quantify predator space use to estimate potential predator-prey encounters, yet this approach does not account for successful predator attacks resulting in prey mortality. An exception is a prey kill-site, which reflects an encounter resulting in mortality, but obtaining these data can be expensive and requires time to accumulate adequate sample sizes. We illustrate an alternative approach using predator scat locations and their contents to quantify spatial predation risk for elk (Cervus canadensis) from multiple predators in Alberta, Canada. We combined predictions of scat-based resource selection functions for bears (Ursus arctos/U. americanus), cougars (Puma concolor), coyotes (Canis latrans), and wolves (C. lupus) based on scat-detection dog surveys with predictions for the probability that a predator-specific scat in a location contained elk. We evaluated our approach by comparing predictions to a predation risk model developed from elk kill sites and applied it to describing spatial patterns in predation risk that were consistent with changes in the distribution of elk over the past decade. We found a strong correlation between risk predicted by kill sites and risk predicted by our approach (r = 0.98, P < 0.001). There was a spatial pattern to predation risk, where elk that migrated east of their winter range were exposed to highest risk from cougars, non-migratory elk were exposed to high risk from wolves and bears, and risk to elk that migrated west of their winter range into protected areas was high only from bears. The patterns in predator risk were consistent with changes in the migratory tactics in this population. The scat-based approach we present permits broad-scale inferences on predation risk for prey.

IgG4-related disease (IgG4RD) with intracranial involvement is rare. We report a 56-year-old male who had an excellent response to rituximab and dexamethasone after going undiagnosed for 5 years. After 3 years of rituximab maintenance, he has no evidence of disease on brain MRI.

CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare entity recently described. Thirteen CNS HGNET-MN1 patients were identified using genome wide methylation arrays/RT-PCR across 7 institutions and were correlated with treatment and outcome. All patients had surgery (GTR:9/STR:4) as initial management followed by radiotherapy (focal:5/craniospinal:2/CyberKnife:1) and systemic chemotherapy in 3 patients. Seven patients relapsed; 5 local and 2 metastatic despite complete resection and radiotherapy. Three patients died due to their tumor relapse after 24 months despite upfront radiotherapy. Treatment of CNS HGNET-MN1 remains a major challenge with multiple failures, despite aggressive surgical resections and upfront radiotherapy.

Algae are promising feedstock of biofuel. The screening of competent species and proper fertilizer supply are of the most important tasks. To accelerate this rather slow and laborious step, we developed an integrated high-throughput digital microfluidic (DMF) system that uses discrete droplet to serve as micro-bioreactor, encapsulating microalgal cells. Based on the fundamental understanding of various droplet hydrodynamics induced by the existence of different sorts of ions and biological species, an incorporation of capacitance-based position estimator, electrode-saving-based compensation and deterministic splitting approach was performed to optimize the DMF bioreactor. Thus, it enables all processes (e.g. nutrient gradient generation, algae culturing and analyzing of growth and lipid accumulation) occurring automatically on-chip especially in a high-fidelity way. The ability of the system to compare different micro algal strains on chip was investigated. Also, the Chlorella sp. were stressed by various conditions and then growth and oil accumulation were analyzed and compared, which demonstrated its potential as a powerful tool to investigate microalgal lipid accumulation at significantly lower laborites and reduced time.

The takin (Budorcas taxicolor) is one of the largest bovid herbivores across caprinae subfamily. The takin is at high risk of extinction, however, its taxonomic status is still unclear. In this study, we constructed the first reference genome of B. taxicolor using PacBio long High-Fidelity reads and Hi-C technology. The assembled genome is ~2.95 Gb with a contig N50 of 68.05 Mb and a scaffold N50 of 101.27 Mb, which were anchored onto 25+XY chromosomes. Compared to the common ancestral karyotype of bovidae (2n=60), we found the takin (2n=52) experienced four chromosome fusions and one large translocation. We also found that the takin was most closely related to muskox, not other caprinae species. Further, we re-sequenced nine golden takins from the main distribution area, Qinling Mountains, and identified 3.3 million SNPs. The genetic diversity of takin was very low (θπ=0.00028 and heterozygosity=0.00038), which was among the lowest detected in the domestic and wild mammals. We also found takin genomes showed high inbreeding coefficient (FROH=0.217) suggesting severe inbreeding depression. The genome analysis show that the effective population size of takins declined significantly from ~100,000 years ago. Our results provide valuable information for protection of takins and insights into its evolution.

The droplet size distribution in liquid-liquid dispersions is a complex convolution of impeller speed, impeller type, fluid properties, and flow conditions. In this work, we present three a priori modeling approaches for predicting the droplet diameter distributions as a function of system operating conditions. In the first approach, called the two-fluid approach, we use high-resolution solutions to the Navier-Stokes equations to directly model the flow of each phase and the corresponding droplet breakup/coalescence events. In the second approach, based on an Eulerian-Lagrangian model, we describe the dispersed fluid as individual spheres undergoing ongoing breakup and coalescence events per user-defined interaction kernels. In the third approach, called the Eulerian-Parcel model, we model a sub-set of the droplets in the Eulerian-Lagrangian model to estimate the overall behavior of the entire droplet population. We discuss output from each model within the context of predictions from first principles turbulence theory and measured data.

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and ESR. In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of NT-proBNP, troponin and AST were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and ALT and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

The main proteases (M pro) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of M pro from complex herbal matrices. This work begins with biological screening of sixty clinically used antiviral herbal medicines, among which Lonicera japonica (LJ) demonstrated the strongest anti-M pro effect (IC 50 = 37.82 μg/mL). Mass spectrometry-based chemical analysis and chemoproteomic profiling revealed that LJ extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify M pro. We subsequently verified the anti-M pro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit SARS-CoV-2 M pro in dose- and time- dependent manners, with the IC 50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of M pro from herbal medicines by integrating target-based high-throughput screening and mass spectrometry-based assays, which would greatly facilitate the discovery of key anti-viral constituents from medicinal plants.

It is important to give parents accurate information about complication rates as part of the process of informed consent for surgery.  National, routinely-collected data give an opportunity to estimate the rates of rare adverse events such as bleeding, blood transfusion and death.We reviewed data for all Scottish NHS hospitals over the time period 2000-2018 to identify all children (aged 0-16 years) undergoing tonsillectomy, and to identify adverse events occurring within 30 days of the procedure.Readmission to hospital was required in 2%.Surgical arrest of haemorrhage was required in 1%.Blood transfusion occurred in 0.1% and death occurred in one child out of 50,194.

The human population is growing rapidly, increasing pressure on natural habitats. Suitable habitats for resident and migratory waterbirds are, therefore, more threatened. This study analyses how the presence of anthropogenic land cover (urban area and cropland) on multiple spatial scales affects the community composition of waterbirds along the Nile in Egypt. We analysed data collected during the international waterbird census, 2017-2018, combined with data from satellite images on land cover at a multi-spatial scale. The census covered 970 km, compromising 194 shoreline transects of 5 km along the River Nile, Egypt. The area includes a broad gradient of human disturbance, making this dataset ideal for assessing effects of anthropogenic land cover on waterbird community composition. We tested whether the waterbird community indices and guild composition were associated with urban area and cropland, and other land covers (e.g., grassland, wetland) at spatial scales of 100, 500, 1,000 and 5,000 m. We recorded over 96,000 waterbirds and show that landscape characteristics at larger spatial scales (5,000 m) explained more of the species and guilds’ presence than smaller scales. Species richness increased with increasing water surface area of the river within the transect and decreased with increasing urban area and cropland. Waders were negatively associated with urban area. Overall, the guilds’ composition was poorly predicted by anthropogenic land cover and other landscape compositions, probably because species within a guild do not react similarly to increasing human disturbance. The probability of observing red-listed species decreased with increasing urban area. With this study, we expand on the existing evidence by showing that species richness negatively correlates with anthropogenic pressure, and we highlight the importance of studying the responses of species rather than guilds. Our study shows the relevance of considering the landscape at larger scales while planning for conservation measures, especially in such human-dominated landscapes. https://doi.org/10.1002/wlb3.01178

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T-helper (Th) and T-regulatory (Treg) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2-weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were sacrificed. Mice (n=6) were sacrificed at specified time-points for various analysis (blood leucocyte, cytokine production, and immunohistochemistry). Tumour volume was measured once every seven days. Gene expression studies were carried out on tumour-specific T-lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p<0.05), CD8+ (p<0.05) T-cells and natural killer cells (p<0.05) but suppressed Treg cells (p<0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon-gamma (IFN) and lower transforming growth factor-beta (TGF-) levels were noted in the T3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-122R), interleukin-24 (IL-24) and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the T3 fed animals. Gene expression studies showed the downregulation of seven prominent genes in splenic CD4+ T-cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T-cell dependent cell-mediated immune responses and suppressed Treg cells in the tumour microenvironment in a syngeneic mouse model of BC.

Cerasus serrulata (Rosaceae) is an important flowering cherry resource. It is almost the most widely distributed species in the genus, mainly included in the subtropical and temperate China, which enables the geographic evolutionary pattern to be a representative. Besides, the morphological traits are greatly varied especially in ornamental characters. All of these makes Cerrasus serrulata a valuable research object. Thus, phylogeographic analysis was conducted to apprehend the spatial pattern and evolutionary history, which can also add insights into the phylogeography of the genus Cerasus and plants in subtropical and temperate China, as well as to deeper understand the genetic diversity and structure of the germplasm to make better and more effective utilization. A total of 327 individuals of 18 populations were collected. Three cpDNA fragments (matK, trnD-E, trnS-G) and the nuclear internal transcribed spacer (ITS) were utilized. The result showed a high genetic diversity both in species level and population level of Cerrasus serrulata. The high genetic differentiation among populations and the existence of phylogeographic structure in whole were detected. In addition, no bottleneck was identified. The the distribution pattern and center were formed before the LGM. Two geographical lineages were inferred. One was confined to Qingling Mountain and Taihang Mt. The other was from the Wuling Mt to Lu-Huang Mt, and then went northeast to the coast of Asia. Besides, taxonomic treatments of the Cerasus serrulata complex were reconsidered.

Plants employ a diverse set of defense mechanisms to mediate interactions with insects and fungi. These relationships can leave lasting impacts on host plant genome structure such as rapid expansion of gene families through tandem duplication. These genomic signatures provide important clues about the complexities of plant/biotic stress interactions and evolution. We used a pseudo-backcross hybrid family to identify Quantitative Trait Loci (QTL) controlling associations between Populus trees and several common Populus diseases and insects. Using whole genome sequences from each parent, we identified candidate genes that may mediate these interactions. Candidates were partially validated using mass spectrometry to identify corresponding QTL for defensive compounds. We detected significant QTL for two interacting fungal pathogens and three insects. The QTL intervals contained candidate genes potentially involved in physical and chemical mechanisms of host-plant resistance and susceptibility. In particular, we identified overlapping QTLs for a phenolic glycoside and Phyllocolpa sawfly abundance. There was also significant enrichment of recent tandem duplications in the genomic intervals of the native parent, but not the exotic parent. Tandem gene duplication may be an important mechanism for rapid response to biotic stressors, enabling trees with long juvenile periods to reach maturity despite many coevolving biotic stressors.