Background: X-linked hyper-immunoglobulin M (XHIGM), a primary immunodeficiency syndrome caused by mutations in the CD40 ligand gene, presents with recurrent respiratory infections in pediatric patients. We aimed to evaluate the spectrum of clinical features and respiratory pathogens in pediatric patients with XHIGM in China. Methods: We retrospectively reviewed seven pediatric patients who were diagnosed with XHIGM and received follow-up treatment at the Guangzhou Women and Children’s Medical Center between January 2010 and January 2021. We determined their clinical characteristics, causative pathogens, and prognosis by performing peripheral immunological and genetic tests. Results: The majority of respiratory infections in four of the seven patients were caused by Talaromyces marneffei. Two patients had viral infections caused by cytomegalovirus (CMV) and human adenovirus. One patient had a mixed infection caused by Pneumocystis carinii and CMV. Except for one child who died of respiratory failure, the other six patients survived with regular infusions of intravenous immunoglobulin (IVIg) during the follow-up period. Six patients had reduced antibody levels, especially IgG, IgA, and IgE levels. Increased serum IgM levels were detected in four cases, and three cases presented normal IgM levels at onset. All children were diagnosed with XHIGM with CD40LG variation. Three novel mutations were identified in the present study. Conclusions: Our study suggests that fungi and viruses are important pathogens causing respiratory infections in children with XHIGM. In endemic areas, children with T. marneffei infections have abnormal Ig levels in their peripheral blood, suggesting the ease of early gene detection in these patients.

Epiphytic communities live in a unique, three-dimensional micro-habitat space that offers an original framework to disentangle the contribution of environmental filters, biotic interactions and dispersal limitation to community structure at small spatial scales. We took advantage of a tropical canopy crane facility to record and model spatio-temporal microclimatic variation and assess its impact on the composition and phylogenetic structure of epiphytic bryophyte communities. Generalized Dissimilarity Modelling evidenced the crucial role of microclimates in determining the composition of moss and liverwort communities. The shift between negative or non-significant phylogenetic turnover to consistently significant clustering from the base to the canopy suggests that phylogenetic constraints further contribute to shape the assembly of epiphytic bryophyte communities. The slight, but significant correlation between increasing phylogenetic clustering with variation in microclimatic conditions adds to emerging evidence for the role of environmental filtering upon community assembly, including at the small spatial scales of epiphytic communities.

Actinobacteria are important cave inhabitants, but knowledge of how anthropization and anthropization-related visual marks affect this community on cave walls is lacking. We compared Actinobacteria communities among four French limestone caves (Mouflon, Reille, Rouffignac, Lascaux) ranging from pristine to anthropized, and within Lascaux Cave between marked (wall visual marks) and unmarked areas in different rooms (Sas-1, Passage, Apse, Diaclase). In addition to the 16S rRNA gene marker, 441 bp fragments of the hsp65 gene were used and an hsp65-related taxonomic database was constructed for identification of Actinobacteria to the species level by Illumina-MiSeq analysis. The hsp65 marker revealed higher resolution for species and higher richness (99% OTU cutoff) versus 16S rRNA gene; however, more taxa were identified at higher taxonomic ranks. Actinobacteria communities varied between Mouflon and Reille caves (both pristine), and Rouffignac and Lascaux (both anthropized). Rouffignac displayed high diversity of Nocardia, suggesting human inputs, and Lascaux exhibited high Mycobacterium relative abundance, whereas Gaiellales were typical in pristine caves and the Diaclase (least affected area of Lascaux Cave). Within Lascaux, Pseudonocardiaceae dominated on unmarked walls and Streptomycetaceae (especially Streptomyces mirabilis) on marked walls, indicating a possible role in mark formation. A new taxonomic database (https://zenodo.org/record/5576074) was developed. Although not all Actinobacteria species were represented, the use of the hsp65 marker enabled species-level variations of the Actinobacteria community to be documented based on the extent of anthropogenic pressure. This approach proved effective when comparing different limestone caves or specific conditions within one cave.

Human disturbance directly affects animal populations but indirect effects of disturbance on species behaviors are less well understood. Camera traps provide an opportunity to investigate variation in animal behaviors across gradients of disturbance. We used camera trap data to test predictions about predator-sensitive behavior in three ungulate species (caribou Rangifer tarandus; white-tailed deer, Odocoileus virginianus; moose, Alces alces) across two boreal forest landscapes varying in disturbance. We quantified behavior as the number of camera trap photos per detection event and tested its relationship to predation risk between a landscape with greater industrial disturbance and predator abundance (Algar) and a “control” landscape with lower human and predator activity (Richardson). We also assessed the influence of predation risk and habitat on behavior across camera sites within the disturbed Algar landscape. We predicted that animals in areas with greater predation risk (more wolf activity, less cover) would travel faster and generate fewer photos per event, while animals in areas with less predation risk would linger (rest, forage), generating more photos per event. Consistent with predictions, caribou and moose had more photos per event in the landscape where predation risk was reduced. Within the disturbed landscape, no prey species showed a significant behavioral response to wolf activity, but the number of photos per event decreased for white-tailed deer with increasing line of sight (m) along seismic lines (i.e. decreasing visual cover), consistent with a predator-sensitive response. The presence of juveniles was associated with shorter behavioral events for caribou and moose, suggesting greater predator sensitivity for females with calves. Only moose demonstrated a positive association with vegetation productivity (NDVI), suggesting that for other species influences of forage availability were generally weaker than those from predation risk. Behavioral insights can be gleaned from camera trap surveys and provide information about animal responses to predation risk and the indirect impacts of human disturbances.

Humans inhale, ingest and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom are in sharp contrast with their complex and relatively blurred taxonomy and scarce knowledge about their distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

Reliable abundance estimation is a primary challenge in environmental DNA (eDNA) analysis, which has been addressed by considering the effects of eDNA transport and degradation. However, these eDNA spatial dynamics depend on the cellular and molecular structure of eDNA, with its persistence state (particle size and DNA fragment length) being essential for improved abundance estimation. This existing knowledge gap is bridged by utilizing datasets obtained from two types of aquarium experiments (targeting zebrafish [Danio rerio] and Japanese jack mackerel [Trachurus japonicus]) and comparing the relationships between eDNA concentration and species abundance among different eDNA size fractions and target marker lengths. We reared the fish in experimental tanks with different individual numbers or biomass densities, filtered rearing water using different pore size filters, and quantified eDNA concentrations targeting different fragment lengths or genetic regions. Consequently, both experiments showed that the accuracy and sensitivity in abundance estimation were improved (i.e., R2 values and slopes of linear regressions increased) when targeting eDNA at the 3–10-µm size fraction. On the other hand, targeting eDNA at the >10 µm size fraction yielded a lower R2 value. This result indicates that an “appropriately” larger eDNA particle is vital for improving abundance estimation accuracy and sensitivity. Conversely, the target marker length negatively affected the R2 value. This study proposes that the relationship between eDNA concentration and species abundance relies on the complex interactions between the particle size, persistence, and spatial heterogeneity of eDNA in water.

Species distributions are one of the fundamental factors needed for understanding and conserving wildlife. While the IUCN Red List of Threatened Species is the primary applied reference for biodiversity conservation, limitations in data availability and analyses of the distributions of some species may limit accurate threat classification assessments and conservation recommendations. Improving the accuracy of species distributions in light of growing data and analytical methods is a key step to increasing the efficacy of the Red List. In this study, we reassessed the distribution of takin (Budorcas taxicolor tibetana), a large ungulate in Sichuan Province, southwest China , classified by the IUCN as vulnerable. Using species distribution models and reported habitat requirements, we updated the takin distribution map. Our updated distribution range in the study area (79,449km2) was 61.31% of current distribution range (CDR) on the IUCN red list. This reduction was in large part due to the inclusion in the CDR of substantial areas of lowland plains, high human disturbance, and non-forest habitat, which provide no suitable habitat for takin. According to our results, suitable takin habitat covered 18.97% of the CDR, suggesting a substantially over-estimated distribution. However, there are high proportions of habitat (40%) still covered by the nature reserve network, indicating the importance of protected areas (PAs) in conservation threaten species. We recommend that experts apply the basic approach presented herein to update the Red List distributions for more species to increase the accuracy of assessments and resulting conservation applications.

The volatile aldehydes of 10 commercial oils present during frying at 180 °C were identified using headspace-gas chromatography/mass spectrometry to establish a feasible model for evaluating the oxidation of frying oil. The results showed that the total peak area of aldehydes detected in the 10 oils increased significantly after frying, and this increase was inversely proportional to the polyunsaturated fatty acid content of the oil. The changes in the peak areas of four aldehydes (pentanal, hexanal, (E)-hept-2-enal, and nonanal) common to all 10 oils were different during frying. By combining the correlation analysis of the peak areas of the four aldehydes with the carbonyl value (CV), the feasibility of using pentanal as an index for evaluating the oxidation of frying oil was illustrated. A model was also established for predicting changes in CV during frying based on the peak area of pentanal and the ratio of the initial contents of linoleic acid to palmitic acid and total tocopherols in the oil. This approach could replace the traditional CV measurement method by using high precision mass spectrometry for evaluating the oxidation of frying oil, thus providing a practical evaluation model for managing the quality of frying oil on a routine basis.

We describe a case of pancreatic tumor associated with a giant type IV hiatal hernia that had prolapsed into the posterior mediastinum. We initially performed hiatal hernia repair, followed by laparoscopic distal pancreatectomy, because the hernia repair enables performing pancreatectomy safety and in the normal anatomical position.

Background/Objectives: A striking procoagulant state induced by SARS-CoV-2 (COVID-19) infection has been reported in adults, with many hospitalized patients developing thrombosis despite prophylactic anticoagulation. Reports on the characteristics of COVID-19-associated coagulopathy are scarce in the pediatric population and thromboprophylaxis use is heterogeneous across pediatric centers. To characterize laboratory and clinical outcomes of COVID-19-associated coagulopathy in children and to assess prophylactic anticoagulation use. Design/Methods: Prospective multicenter observational cohort study including all patients from 0 to 18 years of age admitted to one of the pediatric university health centers in the province of Québec, Canada, with confirmed COVID-19 infection from February 1 to July 1, 2021. Patient-level data including laboratory parameters, treatment and outcomes were obtained via chart review. Results: Included were 79 children hospitalized with COVID-19-related symptoms, multisystem inflammatory syndrome in children or an incidental finding of asymptomatic infection. When assessed, hemostatic parameters demonstrated elevation in D-dimers in 94.7%, fibrinogen in 60%, prothrombin time in 51.9%, and activated thromboplastin time in 18.5%. Platelet counts were normal in 91.3% of patients. Ten patients (12.3%) received thromboprophylaxis with low molecular weight heparin, 7 (8.9%) with aspirin and 1 (1.3%) with both. We observed one thrombosis and one major bleed, both attributable to an alternate diagnosis other than COVID-19 infection. Conclusion: The most consistent abnormal hemostatic parameters observed in this study were elevated D-dimers and fibrinogen. No thrombosis ascribable to COVID-19 infection has been observed in this pediatric cohort, despite relatively infrequent anticoagulant prophylaxis. There have been no bleeding events attributable to thromboprophylaxis.

High-dose methotrexate (HD-MTX) with rigorous supportive care is essential to the treatment of pediatric non-Hodgkin lymphomas (NHL). We describe the safety and tolerability of HD-MTX in patients with NHL treated at our center. In our cohort of 46 patients, the majority had at least one course of delayed clearance and/or creatinine elevation. Additionally, more than one-third of patients experienced an episode of grade ≥3 mucositis. Creatinine elevations and delayed clearance were independently associated with subsequent grade ≥3 mucositis. We advocate for greater availability of methotrexate monitoring to allow dose escalation of this essential modality around the world.

The use of an adequate protocol that accurately extracts microbial DNA from bovine milk samples is of importance for downstream analysis such as 16S rRNA gene sequencing. Although sequencing platforms such as Illumina are very common, there are reservations concerning reproducibility in challenging samples that combine low bacterial loads with high amounts of host DNA. The objective of this study was to evaluate six different DNA extraction protocols applied to four different prototype milk samples (low/high level of colony-forming units (cfu) and somatic cells). DNA extracts were sequenced on Illumina MiSeq with primers for the hypervariable regions V1V2 and V3V4. The different protocols were evaluated by analyzing the yield and purity of DNA extracts and the number of clean reads after sequencing. Three protocols with the highest median number of clean reads were selected. To assess reproducibility, these extraction replicates were re-sequenced in triplicates (n=120). The most reproducible results for alpha- and beta-diversity were obtained with the modified DNeasy Blood & Tissue kit after a chemical pre-treatment plus resuspension of the cream fraction. The unmodified QIAamp DNA Mini kit performed particularly weak in the sample representing unspecific mastitis. These results suggest that pre-treatment in combination with the modified DNeasy Blood & Tissue kit is useful in extracting microbial DNA from challenging milk samples. To increase reproducibility, we recommend that duplicates, if not triplicates, should be sequenced. We showed that high counts of somatic cells challenged DNA extraction, which shapes the need to apply modified extraction protocols.

The complex boundary of the elliptical inclusion rendered it difficult to solve the problem of wave scattering. In this study, the steady-state response was analyzed using the wave function expansion method. Subsequently, the Ricker wavelet was employed as the transient disturbance and Fourier transform was used to determine the distribution of transient dynamic stress concentration around the elliptical inclusion. The effects of wave number, elliptical axial ratio and difference in material properties on the distribution of the dynamic stress concentration around the elliptical inclusion were evaluated. The numerical results revealed that the dynamic stress concentration always appeared at both ends of the major axis and minor axis of the elliptical inclusion, and the difference in material properties between the inclusion and medium influenced the variations in the dynamic stress concentration factor with the wave number and elliptical axial ratio.

In this paper, we present an approach to the fractional Dunkl Laplacian in a framework emerging from certain reflection symmetries in Euclidean spaces. Our main result is pointwise formulas, Bochner subordination, and an extension problem for the fractional Dunkl Laplacian as well.

Background: Mitral valve repair (MVRe) is considered to have a superior outcome compared to replacement (MVRp) in patients with mitral valve regurgitation (MVR). It was the aim of the study to analyze the clinical results and identify risk factors for short and long-term mortality. Methods: In a single-center analysis, patients undergoing isolated mitral valve procedures from June 2010 to December 2016 were identified. These were subsequently homogenized using 10 baseline characteristics for propensity-score matching. Comparative analyses were performed for early and long-term results, using the adequate statistical tool, identifying risk factors for the investigated endpoints. Results: 241 patients were identified in the entire cohort. After matching, patients were divided into 2 groups of 64 in each. The median age was similar. There was significant interaction to early mortality risk of MV in patients with coronary artery disease (CAD) (OR 11.94, 95% CI: 1.49-285.92, P=0.04) and late mortality in patients with higher EuroSCORE II (HR 1.14, 95% CI: 1.06-1.23, P<0.001). 5-year survival was significantly higher in MVRe versus MVRp (90.06% vs. 79.54% respectively, P=0.04). Conclusions: We concluded MVRe to be associated with lower operative and 5-year mortality and good postoperative outcomes compared to patients undergoing MVRp. Concomitant CAD was identified as one of the risk factors for increasing the in-hospital mortality rate. There was no significant difference in rehospitalization over the follow-up period. MVRe should be the treatment of choice for severe MVR and should remain a central aspect in valve centers’ treatment algorithms and quality measures.

Subdural empyema is a rare intracranial infection with an accumulation of purulent material between the dura and arachnoid matter. We report a case of 17 years old presented with altered conscious level .CSF analysis showed increased WBCS. His situation has improved after treating by acyclovir, ceftriaxone, vancomycin and dexamethasone.

Objective: To determine the presence of anti-SARS-CoV-2 antibodies in colostrum and mature milk in women who had SARS-CoV-2 infection during pregnancy or at delivery; to investigate the correlation between anti-SARS-CoV-2 antibodies in milk with antibody in maternal blood, severity of infection and time-interval from active illness; and to evaluate immunoglobulin evolution from colostrum to mature milk. Design: prospective cohort-study Setting: six hospitals in Spain and Hong-Kong. Sample: pregnant women with confirmed SARS-CoV-2 infection during pregnancy or at delivery. Methods: Colostrum and mature milk were collected by manual expression with strict contact precautions. Colostrum samples were tested with rRT-PCR-SARS-CoV-2 and both, maternal milk and serum were tested against SARS-CoV-2 specific immunoglobulin M, A and G reactive to receptor binding domain of SARS-CoV-2 spike protein-1. Results: All rRT-PCR-SARS-CoV-2 tested negative. IgA and IgG were present in 111/135 (82.2%) and 2/135 (1.5%) colostrum samples and 27/81 (33.3%) and 0/81 mature milk samples, respectively. Concentrations of immunoglobulins were not associated with the timing of infection but women with SARS-CoV-2 pneumonia had higher levels of IgA and IgG in colostrum than those who were asymptomatic or had mild symptoms. Conclusion: No SARS-CoV-2 virus was found in human milk, however, high levels of antibodies were found in colostrum, specially IgA, irrespective of the time of infection. All women should be encouraged to breastfeed, undertaking strict contact precautions when there is active disease. Funding: Spanish Government grant (Instituto de Salud Carlos III: COV20/00188). Synlab Diagnostics’ Globales (Madrid, Spain). Perkin Elmer.

Malignant lymphomas of the paranasal sinuses, which have a minimal tendency for invasion but considerable necrosis, may be misdiagnosed as an inflammatory disease, based on MRI and clinical findings. In cases where a thorough physical examination does not rule out a malignant lymphoma, an endoscopic biopsy should be immediately considered.

The results of the investigation of the exact nature of the mechanisms that ensure the organism's survival in the face of the pathogen's pathological effects reveal those severe co-occurring manifestations that are temporally linked to a pathogen, such as those which appear in COVID-19 patients, to be manifestations of different diseases which are brought about through the same pathway under the influence of different causes which include the pathogen. Since the single pathway through which all of such diseases, which have the same "immunological nature," are brought about must be blocked for the attenuation of the influence of the pathogen to bring about the remission of the disease it causes, such diseases will undergo simultaneous remission when conditions permit immune mechanisms to attenuate the causative influence of the pathogen. And since the pathway must be blocked for the disease the pathogen causes to be cured, severe manifestations that are linked with a pathogen persist despite treatments that reduce pathogen load when conditions do not permit immune mechanisms to attenuate the influence under which any of the diseases in the same "immunological spectrum" as this disease is produced through the pathway, a persistence which we attributed to the pathogen's resistance to treatment. These results throw light on the different immunological phenomena, from those that inspired variolation and vaccination to those remissions that are temporally linked with infection.

Purpose: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Prospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories. We applied a reanalysis strategy based on intensive prospective bibliographic monitoring, and directly applied the Globally search for a Regular Expression and Print matching lines (GREP) command-line to a massive ES database. Methods: For 18 months, we submitted daily the same 5 keywords of interest (( intellectual disability, ( neuro)developmental delay, (neuro)developmental disorder)) to PubMed, to identify recently published, novel disease-gene associations, or new phenotypes in genes already implicated in human pathology. We used the Linux GREP command-line and an in-house script, to collect all variants in these genes from our 5459 exome database. Results: We grepped 128 genes and collected 56 candidate variants in 53 individuals. We confirmed causal diagnosis for 19/128 genes (15%) in 21 individuals, and identified variants of unknown significance for 19/128 genes (15%) in 23 individuals. Altogether, we confirmed pathogenicity in 21/2875 undiagnosed affected probands (0.7%). Conclusion: The GREP command-line is efficient, and less tedious than complete periodical reanalysis. It is an interesting reanalysis strategy to improve diagnosis.

The is a research and education center that supports software development in the . One of ’s core objectives is to provide education and training for the next generation of computational researchers. Education targets various career stages and skill levels through its live workshops, online resources, and software fellowship program. Education focuses its efforts within four areas: programming and software development, and , faculty and curriculum development, and the software fellowship program. This article delineates educational efforts at the , overall goals, and resources that can be useful to researchers in the computational molecular sciences.

Submerged macrophytes play a key role in maintaining a clear-water phase and promoting biodiversity in shallow aquatic ecosystems. Since their abundance has declined globally due to anthropogenic activities, it is important to include them in aquatic ecosystem restoration programs. That macrophytes establish in early spring is crucial for maintaining the macrophyte communities for the remainder of the year. However, factors affecting this early establishment of submerged macrophytes have not been fully explored yet. Here, we conducted an outdoor experiment from winter to early spring using the submerged macrophytes Potamogeton crispus and Vallisneria spinulosa to study the effects of shading, nutrient loading, snail herbivory (Radix swinhoei) and their interactions on the early growth and stoichiometric characteristics of macrophytes. The results show that the effects strongly depend on macrophyte species. Biomass and number of shoots of P. crispus decreased, and internode length increased during low light conditions, but were not affected by nutrient loading. P. crispus shoot biomass and number showed hump-shaped responses to increased snail biomass under full light. In contrast, the biomass of the plant linearly decreased with snail biomass under low light. This indicates an interaction of light with snail herbivory. Since snails prefer grazing on periphyton over macrophytes, a low density of snails promoted growth of P. crispus by removing periphyton competition, while herbivory on the macrophyte increased during a high density of snails. The growth of V. spinulosa was not affected by any of the factors, probably because of growth limitation by low temperature. Our study demonstrates that the interaction of light with snail herbivory may affect establishment and growth of submerged macrophytes in early spring. Macrophyte restoration projects may thus benefit from lowering water levels to increase light availability and making smart use of cold-adapted herbivores to reduce light competition with periphyton.

As a continuation of Part I, dedicated to the ground state of He-like and Li-like isoelectronic sequences for nuclear charges $Z \leq 20$, and Part II, dedicated to two excited states of He-like sequence, two ultra-compact wave functions in the form of generalized Guevara-Harris-Turbiner functions are constructed for Li-like sequence. They describe accurately the domain of applicability of the Quantum Mechanics of Coulomb Charges (QMCC) for energies (2-3 significant digits (s.d.)) of the spin-quartet state $1^40^+$ of Li-like ions (in static approximation with point-like, infinitely heavy nuclei). Variational parameters are fitted in $Z$ by 2nd degree polynomials. The most accurate ultra-compact function leads to the absolute accuracy $\sim 10^{-3}$\,a.u. for energy, and $\sim 10^{-4}$ for the normalized electron-nuclear cusp parameter for $Z \leq 20$. Critical charge $Z=Z_B$, where the ultra-compact trial function for the $1^40^+$ state looses its square-integrability, is estimated, $Z_B(1^4\,0^+) \sim 1.26 - 1.30$. As a complement to Part I, square integrability for the compact functions constructed for the {\it ground, spin-doublet state} $1^2\,0^+$ of the Li-like sequence is discussed. The critical charge, for which these functions stop to be normalizable, is estimated as $Z_B( 1^2\,0^+) = 1.62 - 1.65$. It implies that at $Z=2$ - the negative helium ion He$^-$ - both states $1^2\,0^+$ and $1^4\,0^+$ exist as states embedded to continuum.

This paper presents the relations of optimized combination with traditional combination and permutation. Combinatorics is a collection of several computing techniques used in science and management. In this research paper, new results on both combination and permutation are introduced for the researchers who are involving to find solutions for the scientific problems.