Neural Tube Defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to cerebral folate deficiency by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased risk for NTDs by depressing embryonic folate concentrations. In this study, we examined CIC variants from whole genome sequencing (WGS) data of 140 isolated spina bifida cases and identified 8 missense variants of CIC gene. We tested the pathogenicity of the observed variants through multiple in vitro experiments. We determined that CIC variants decreased FOLR1 protein level and planar cell polarity (PCP) pathway signaling in a human cell line (HeLa). In a murine cell line (NIH3T3), CIC loss of function variants down regulated PCP signaling. Taken together, this study provides evidence supporting CIC as a risk gene for human NTD.

The generalized finite difference method is a meshless method for solving partial differential equations that allows arbitrary discretizations of points. Typically, the discretizations have the same density of points in the domain. We propose a technique to get adapted discretizations for the solution of partial differential equations. This strategy allows using a smaller number of points and a lower computational cost to achieve the same accuracy that would be obtained with a regular discretization.

Toxic metal-contaminated wastewater is a major environmental issue that requires a practical and cost-effective technological solution. Heavy metal phytoremediation by constructed wetland is becoming more common around the world. Plants are used in phytoremediation to degrade, stabilize, and remove contaminants from soils, water, and waste. The key issues with managing heavy metal phytoremediation plants in an environmentally appropriate manner. The design of CWs for successful phytoremediation in heavy metals contaminated wastewater should not affect the local environment. By-product generation is another crucial part of phytoremediation’s success. Phyto-management has emerged as an alternative strategy in recent years. Phytoremediating plants ( C. indica and A. calamus) biomass has been successfully used in the manufacture of 70 fly-ash bricks. High rate of Cu (96 %), Zn (95 %), (Fe 93), and Cr (91 %) removal from Canna indica and Acorus calamus were found in the present study as compared to the Typha latifoliya, Myriophylhum aquaticum, Ludwigina palustris, Eichhornia crassipes, Schoenoplectus californicus, Cyperus papyrus, and Phragmites australis which indicates C. indica is the high potential for heavy metal removal and can be strongly used for industrial wastewater. In the way, the use of ornamental plants for phytoremediation of contaminated sewage wastewater would also change the landscape of the aquatic environment. This article summarises viable avenues in the method of using phytoremediating plant biomass for environmental protection.

Benthic macroinvertebrates are widely used to assess the ecological quality of fresh waters. This is because they are in direct contact with the aquatic environment and respond differently to pollutants and changes in the watershed, which are difficult to assess by toxicological or chemical monitoring alone. this study used benthic macroinvertebrate parameters to assess the quality of the nearshore waters of lake Kivu. Twenty-six metrics covering various aspects of the community were tested using whisker plots to compare their sensitivity in discriminating between reference and disturbed stations. Nine parameters (% EPT taxa, % Diptera taxa, % Chironomid taxa, % Insect taxa; % no Insects taxa, ratio EPT/Chironomid taxa, % moderate tolerant taxa, % very moderate tolerant taxa, Family Biotic Index) were found to be sensitive and were able to discriminate between reference and disturbed stations. All sensitive metrics, with the exception of the percentage of EPT taxa, were positively and/or negatively correlated with the physico-chemical parameters affected by the changes in the littoral zone. The combined values of the three calculated biotic indices (ASPT, BMWP and FBI) showed that the biological water quality varies from moderate to good in the reference stations and from average to poor in the disturbed stations. It is concluded that metrics based on benthic macroinvertebrates are effective for assessing water quality in the littoral zone of Lake Kivu in the context of the lack of historical water quality databases and specific tools for toxicological assessment. It is suggested to compare the performance of this approach with others currently used in bio-indication.

Numerous studies have investigated bacterial community structure in grassland ecosystems and bacterial community responses to human management at various spatial and temporal scales; however, research on soil bacterial community assembly dynamics in the course of grassland degradation is limited. Here, the authors investigate the response and assembly processes of bacterial communities adopted in two grasslands with different degrees of degradation. Stochastic processes dominated bacterial community assembly processes in response to grassland degradation, with the bacterial diversity decreasing; however, functional gene diversity increased. Furthermore, different phyla exhibited distinct response strategies: Proteobacteria and Bacteroidetes, as r-strategists, exhibited positive responses, with increases in diversity, abundance, and niche width with an increase in grassland degradation, enhancing biodiversity and productivity; other phyla (mainly Acidobacteria) exhibited greater phylogenetic dispersion and functional redundancy, and less niche overlap, highlighting the role of K-strategy in improving community resource-use efficiency in response to resource loss in degraded grasslands. The transition from K- to r- strategy in bacterial communities following grassland degradation could help communities adapt to environmental disturbance in the form of nutrient loss. The results of the present study enhance our understanding of how nutrient loss in natural grassland ecosystems leads to shifts in bacterial community composition and assembly processes mediated by different response strategies of different phyla.

We reported a patient with chest pain, but the coronary angiography was normal. ATP stress myocardial contrast electrocardiography(MCE) was performed. There was apical ventricular septal perfusion delay before ATP stress, and the perfusion delay areas were significantly reduced at the peak period, which was similar to the “reverse redistribution” perfusion characteristics of nuclear myocardium in coronary vasospasm, The areas of delayed perfusion in the recovery period were larger than that before stress, the increase of blood flow spectrum resistance in the distal segment of left anterior descending coronary artery and the occurrence of chest pain all showed that ATP induced myocardial microvascular spasm. The MCE perfusion characteristics and the changes of coronary spectrum had certain clinical value in the diagnosis of myocardial microvascular spasm.

 We propose the exact formula for the fine-structure constant α in terms of the golden angle,relativity factor and the fifth power of the golden mean. Also we will present the continued fraction for the fine-structure constant.

Background: Patients with true paroxysmal supraventricular tachycardia (SVT) are frequently misdiagnosed with panic or anxiety disorders due to similar symptoms of palpitations, light-headedness, dyspnea, or chest discomfort. Unrecognized SVT can lead to unnecessary management with anxiety medications. Treatment of SVT with catheter ablation may lead to reduction in anxiety medications. Methods: A total of 175 patients underwent successful SVT ablation between January 1, 2010 and December 31, 2020. We examined symptoms at presentation, psychiatric medications prior to SVT ablation, comorbidities, and psychiatric medications at 3 months post-ablation. Results: 15% of patients who underwent successful SVT ablation were being treated with psychiatric medications and were included in the final study population. The most common symptoms were palpitations (80.77%), followed by dizziness (42.31%), and shortness of breath (34.62%). The average number of medications prior to ablation was 1.42 and decreased down to 1.08 at 3 months post-ablation (p = 0.04). The average number of SSRIs, SNRIs, and other anxiolytics were also decreased but were not statistically significant. Conclusion: In patients with anxiety and paroxysmal supraventricular tachycardia, catheter ablation is associated with reduced average number of psychiatric medications.

Three-dimensional cell agglomerates are broadly useful in tissue engineering and drug testing. We report a well-free method to form large (1-mm) multicellular clusters using 100-MHz surface acoustic waves (SAW) without direct contact with the media or cells. A fluid couplant is used to transformthe SAW into acoustic streaming in the cell-laden media held in a petri dish. The couplant transmits longitudinal sound waves, forming a Lamb wave in the petri dish that, in turn, produces longitudinal sound in the media. Due to recirculation, human embryonic kidney (HEK293) cells in the dish are carried to the center of the coupling location, forming a cluster in less than 10 min. A few minutes later, these clusters may then be translated and merged to form large agglomerations, and even repeatedly folded to produce a roughly spherical shape of over 1 mm in diameter for incubation—without damaging the existing intercellular bonds. Calcium ion signaling through these clusters and confocal images of multiprotein junctional complexes suggest a continuous tissue construct: intercellular communication. They may be formed at will, and the method is feasibly useful for formation of numerous agglomerates in a single petri dish.

BACKGROUND/OBJECTIVES: Survivors of pediatric brain tumors (BT) are at increased risk for difficulties with social competence, including poor social information processing (SIP) and peer relationships. Due to improved survival rates among BT, there is a need to better understand these challenges and if they are specific to BT versus other survivors of childhood cancer. METHODS: 51 BT and 34 survivors of pediatric solid tumors (ST) completed evaluations of SIP and peer relationship quality within 6 months of completing treatment and at one year follow-up. Caregivers also completed a measure of social skills. Linear mixed models evaluated (1) differences between BT and ST on SIP and social skills and (2) how indices of SIP were associated with peer relationships over time for ST and BT. RESULTS: BT did not differ from ST on indices of SIP or social skills over time. There was a three-way interaction between measures of SIP, group, and time to predict peer relationships. ST showed a positive association between baseline social skills and theory of mind and peer relationships over time, whereas BT showed an inverse association between baseline social skills and theory of mind and peer relationships over time. CONCLUSION: Baseline SIP and social skills affected the trajectory of BT peer relationships. BT social functioning should be monitored regularly after the completion of treatment to determine if and when intervention services would be beneficial.

During the pandemic, millions of Americans have become acquainted with the CDC because its reports and the data it collects affect their day-today lives. But the methodology used and even some of the data collected by CDC remain opaque to the public and even to epidemiologists. In this paper, we highlight areas in which CDC methodology might be improved and where greater transparency could lead to broad collaboration. (1) "Excess" deaths are routinely reported, but not "years of life lost", an easily-computed and more granular datum that is important for public policy. (2) What counts as an "excess death"? The method for computing the number of excess deaths does not include error bars and we show a substantial range of estimates is possible. (3) Pneumonia and influenza death data on different CDC pages is grossly contradictory. (4) The methodology for computing influenza deaths is not described in sufficient detail that an outside analyst might pursue the source of the discrepancy. (5) Guidelines for filling out death certificates have changed during the COVID-19 pandemic, preventing the comparison of 2020-21 death profiles with any previous year. We conclude with a series of explicit recommendations for greater consistency and transparency, and ultimately to make CDC data more useful to the public and epidemiologists and other scientists.

Heterogeneous networks have multiple types of nodes and edges. Community detection in single layer and multiplex networks has been extensively studied in the past decade. But there are few methods have constructed for heterogeneous networks. In this paper, we introduce heterogeneous stochastic block models for detecting communities in heterogeneous networks. Generally these models are developed based on generalization of single-layer stochastic block model, bipartite stochastic block model and multiplex stochastic block model. We define this two types of stochastic block model, independent degree and shared degree. Independent degree models have one specific degree parameter for each layers, shared degree models share one degree parameter for all layers. We introduce a method to create synthetic networks with benchmark heterogeneous communities. We evaluate the performance of the proposed community detection algorithm with generalization of Kernighan-Lin algorithm in the controlled environment (with synthetic benchmark communities). According to our results, shared degree models have better performance in high crossed networks in contrast independent degree models have better performance in low crossed networks. Exception when intra-layer densities are high and inter-layer densities are low, single-layer algorithm (flattering network) has better performance. On real datasets, DBLP and AMiner four-area datasets, proposed methods have good results.

Background: The national health care response to coronavirus (COVID-19) has varied between countries. The United Kingdom (UK) and the Netherlands (NL) have comparable maternity and neonatal care systems, and experienced similar numbers of COVID-19 infections, but had different organisational responses to the pandemic. Understanding why and how similarities and differences occurred in these two contexts could inform optimal care in normal circumstances, and during future crises. Aim: To compare the UK and Dutch COVID-19 maternity and neonatal care responses in three key domains: choice of birthplace, companionship, and families in vulnerable situations. Method: A multi-method study, including documentary analysis of national organisation policy and guidance on COVID-19, and interviews with national and regional stakeholders. Findings: Both countries had an infection control focus, with less emphasis on the impact of restrictions. Differences included care providers’ fear of contracting COVID-19; the extent to which personalised care was embedded in the care system before the pandemic; and how far multidisciplinary collaboration and service-user involvement were prioritised. Conclusion: We recommend that countries should 1) make a systematic plan for crisis decision-making before a serious event occurs, and that this must include authentic service-user involvement, multidisciplinary collaboration, and protection of staff wellbeing 2) integrate women’s and families’ values into the maternity and neonatal care system, ensuring equitable inclusion of the most vulnerable and 3) strengthen community provision to ensure system wide resilience to future shocks from pandemics, or other unexpected large-scale events.

Upland rice (Oryza sativa) is adapted to strongly phosphorus (P) sorbing soils. The mechanisms underlying P acquisition, however, are not well understood, and models typically underestimate uptake. This complicates root ideotype development and trait-based selection for further improvement. We present a novel model, which correctly simulates the P uptake by a P-efficient rice genotype measured over 48 days of growth. The model represents root morphology at the local rhizosphere scale, including root hairs and fine S-type laterals. It simulates fast-and slowly reacting soil P and the P-solubilizing effect of root-induced pH changes in the soil. Simulations predict that the zone of pH changes and P solubilization around a root spreads further into the soil than the zone of P depletion. A root needs to place laterals outside its depletion-but inside its solubilization zone to maximize P uptake. S-type laterals, which are short but hairy, appear to be the key root structures to achieve that. Thus, thicker roots facilitate the P uptake by fine lateral roots. Uptake can be enhanced through longer root hairs and greater root length density but was less sensitive to total root length and root class proportions.

Background: Intraextracardiac Fontan procedure aimed to combine the advantages of lateral tunnel and extracardiac conduit modifications of the original technique. Herein, we present our experience in our patients with intraextracardiac fenestrated Fontan Procedure. Methods: A retrospective analysis was performed in order to evaluate intraextracardiac fenestrated Fontan patients between 2014 and 2021. Seventeen patients were operated on with a mean age and body weight of 9.1 ± 5.5 years and 28.6 ± 14.6 kg. Results: Sixteen patients (94%) were palliated as univentricular physiology with hypoplasia of one of the ventricles. One patient (6%) with well-developed two ventricles with double outlet right ventricle and complete atrioventricular septal defect had straddling of the chordae prohibiting a biventricular repair. All of the patients had cavopulmonary anastomosis prior to Fontan completion, except one case. Fenestration was performed in all cases. Postoperative mean pulmonary artery pressures and arterial oxygen saturation levels at follow up were 10 ± 2.4 mmHg and 91.3 ± 2.7 %, respectively. Mean duration of pleural drainage was 5.4 ± 2.3 days. All of the fenestrations are patent at a mean follow up period of 4.8 ± 7.7 years, except one case. Any morbidity and mortality were not encountered. Conclusions: The mid-term results of intraextracardiac fenestrated Fontan procedure are encouraging. This procedure may improve the results in a patient population who should be palliated as univentricular physiology, especially in cases with complex cardiac anatomy.

Historical climate fluctuations have left genetic signatures on species and populations across North America. Here, we used phylogenetic and population genetic analyses from 1,402 orthologous sequences of 75 individuals obtained through sequencing of Ultraconserved Elements (UCEs) to identify population genetic structure and historical demographic patterns across the range of a widespread, cold-adapted ant, the winter ant, Prenolepis imparis. We relate the genomic patterns to those expected as a result of in situ diversification, maintained connectivity, or recent migration. We recovered five well-supported, genetically isolated clades across the distribution: 1) a basal lineage located in Florida, 2) populations across the southern United States, 3) populations that span the midwestern and northeastern United States, 4) populations from the western United States, and 5) populations in southwestern Arizona and Mexico. Using Bayesian clustering analysis in STRUCTURE and k-means clustering in ADEGENET, we investigated gene flow between these major genetic clades and did not find evidence of gene flow between clades. We did find evidence of localized structure with migration in the western United States clade. High support for five major geographic lineages and lack of evidence of contemporary gene flow indicate in situ diversification across the species’ range, probably influenced by glacial cycles of the late Quaternary.

This article corrects the paper Int. J. Quantum. Chem. 120 e26221 (2020) by P. R. Surjan

Metagenomics - shotgun sequencing of all DNA fragments from a community DNA extract - is routinely used to describe the composition, structure and function of microorganism communities. Advances in DNA sequencing and the availability of genome databases increasingly allow the use of shotgun metagenomics on eukaryotic communities. Metagenomics offers major advances in the recovery of biomass relationships, in comparison to taxonomic marker gene based approaches (metabarcoding). However, little is known about the factors that influence metagenomics data from eukaryotic communities, such as differences among organism groups, properties of reference genomes and genome assemblies. We evaluated how shotgun metagenomics records composition and biomass in artificial soil invertebrate communities. We generated mock communities of controlled biomass ratios from 28 species from all major soil mesofauna groups: mites, springtails, nematodes, tardigrades and potworms. We shotgun-sequenced these communities and taxonomically assigned them with a database of over 270 soil invertebrate genomes. We recovered 90% of the species, and observed relatively high false positive detection rates. We found strong differences in reads assigned to different taxa, with some groups consistently attracting more hits than others. Biomass could be predicted from read counts after considering taxon-specific differences. Larger genomes more complete assemblies consistently attracted more reads than genomes. The GC content of the genome assemblies had no effect on the biomass-read relationships. The results show considerable differences in taxon recovery and taxon specificity of biomass recovery from metagenomic sequence data. Properties of reference genomes and genome assemblies also influence biomass recovery, and they should be considered in metagenomic studies of eukaryotes. We provide a roadmap for investigating factors which influence metagenomics-based eukaryotic community reconstructions. Understanding these factors is timely as accessibility of DNA sequencing, and momentum for reference genomes projects show a future where the taxonomic assignment of DNA from any community sample becomes a reality.

L’ ANALYTIC HIERARCHY PROCESS, nasce dal matematico Thomas Saaty, negli anni Settanta per organizzare ed analizzare decisioni complesse. La metodologia consente di confrontare più alternative in relazione ad una pluralità di criteri, di tipo quantitativo o qualitativo, e ricavare una valutazione globale per ciascuna di esse. Ciò permette di:  ordinare le alternative secondo un asse di preferenza,  selezionare l'alternativa globalmente migliore e  assegnare le alternative a sottoinsiemi predefiniti.I punti di forza principali sono il confronto a coppie delle alternative decisionali e la separazione fra importanza del criterio e impatto sulla decisione. Il metodo è basato su una  scala di comparazione, suddivisa in nove livelli, la cui base teorica è data dal teorema di Perron-Frobenius. Riportiamo a seguire la documentazione relativa alla realizzazione del corridoio Tirreno -Brennero sul quale è stato applicato il metodo AHP, relativamente al confronto dei diversi corridoi stradali e la successiva scelta di quello a minimo impatto ambientale.

Disturbances alter the diversity and composition of microbial communities, but whether microbiomes from different environments exhibit similar degrees of resistance or rates of recovery has not been evaluated. Here, we synthesized 86 time series of disturbed mammalian, aquatic, and soil microbiomes to examine how the recovery of microbial richness and community composition differed after disturbance. We found no general patterns in compositional variance (i.e., dispersion) in any microbiomes over time. Only mammalian microbiomes consistently exhibited decreases in richness following disturbance. Importantly, they tended to recover this richness, but not their composition, over time. In contrast, aquatic microbiomes tended to diverge from their pre-disturbance composition following disturbance. By synthesizing microbiome responses across environments, our study aids in the reconciliation of disparate microbial community assembly frameworks, and highlights the role of the environment in microbial community reassembly following disturbance.

Our minimally invasive Fothergill-Manchester technique aims to decrease blood loss and surgical trauma and to preserve function by1. Vaginal conservation. 2. Cardinal (CL) and uterosacral (USL) ligaments plicated, not severed. 3. Direct suture of vagina to cervix without Sturmdorf sutures after cervical amputation. 4. Use of No2 polyester sutures to create new collagen to reinforce the plicated ligaments.

A rare case of sphenoid plasmacytoma in a 57-year old female who was presented with a frozen eye is reported. It was histopathologically confirmed based on transsphenoidal biopsy. Surgical removal of the tumor with complementary radiotherapy was performed as a treatment modality

Mutualisms are ubiquitous in nature, provide important ecosystem services, and involve many species of interest for conservation. Theoretical progress on the population dynamics of mutualistic interactions, however, comparatively lagged behind that of trophic and competitive interactions, leading to the impression that ecologists still lack a generalized framework to investigate the population dynamics of mutualisms. Yet, over the last 90 years, abundant theoretical work has accumulated, ranging from abstract to detailed. Here, we review and synthesize historical models of two-species mutualisms. We find that population dynamics of mutualisms are qualitatively robust across derivations, including levels of detail, types of benefit, and inspiring systems. Specifically, mutualisms tend to exhibit stable coexistence at high density and destabilizing thresholds at low density. These dynamics emerge when benefits of mutualism saturate, whether due to intrinsic or extrinsic density-dependence in intraspecific processes, interspecific processes, or both. We distinguish between thresholds resulting from Allee effects, low partner density, and high partner density, and their mathematical and conceptual causes. Our synthesis suggests that there exists a robust population dynamic theory of mutualism that can make general predictions.

Heparin-induced thrombocytopenia (HIT) is an immunogenic disorder. It can lead to thrombocytopenia and a hypercoagulated state with an increased risk for new thrombosis. We here reported a 49-year-old man with previous cardiac surgery and heparin administration, treated by new oral anticoagulant agent, Rivaroxaban.