A document by W John Martin. Click on the document to view its contents.

Ductus arteriosus aneurysm (DAA) is characterized by a saccular or fusiform dilatation of the ductus arteriosus. The formation of a thrombus at that level is infrequent and potentially lethal. We present a case of a fetus with a DAA diagnosed during fetal life by 2-D, 3-D, and 4-D STIC echocardiography. Although a thrombus in the ductus and hypertrophy of the right ventricle was identified in postnatal echocardiography, a conservative approach was adopted with good outcome. The features of our case highlight the importance of serial ultrasound in the fetal and neonatal period to assess fetal aneurysm growth as well as to notice any modification of the flow within.

Purpose: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. Methods: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. Results: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n=26/35) of patients receiving full echocardiogram study. LVDD incidence was 46% (n=12/26), whilst the assessment produced different results (incidence 81%, n=21/26). Nine patients were hospital-survivors (39%); incidence of LVDD (full assessment) was not different between survivors (n=2/9, 22%) and non-survivors (n=10/17, 59%; p=0.11). Also, the E/e’ ratio lateral was lower in survivors (7.4 [3.6] vs non-survivors 10.5 [6.3], p=0.03). We also found that s’ wave was higher in survivors (average, p=0.01). Conclusion: In a small single-center study, assessment of LVDD according to latest guidelines was feasible in three quarter of COVID-19 patients. Non-survivors showed a trend towards greater LVDD incidence; moreover, they had significantly worse s’ values (all) and higher E/e’ ratio (lateral).

A document by João Gama Monteiro. Click on the document to view its contents.

Mark Davidson Jewell1* and Graham Bell1,21Department of Biology, McGill University; 1205 ave Docteur Penfield, Montreal, Quebec H3A 1B1, Canada.2Redpath Museum, McGill University; 859 Sherbrooke St West, Montreal, Quebec H3A 0C4, Canada.*Corresponding author: mark.jewell@mail.mcgill.caABSTRACT:An entire community of organisms may become modified when its environment changes. These modifications can happen through physiological process (plasticity), evolutionary processes (adaptation) or shifts in species composition (sorting). The outcome of these three sources of change constitutes the community’s phenotypic response, but how they combine to drive community trait dynamics is not currently well understood. We have conducted a community selection experiment in which communities of short-lived floating aquatic plants were grown in a range of stressful conditions, and measured changes in their body size. Determinants of phenotypic change were assessed with a full community reciprocal transplant which led to estimates of the contributions of plasticity, adaptation, and sorting. Species were modified during the experiment by both plasticity and adaptation, but in either case the magnitude and direction of change differed among species. Sorting and adaptation were of equal magnitude, but tended to act in opposite directions: in conditions where species with large fronds prevailed, each species evolved smaller fronds, and vice versa. We conclude that community trait dynamics cannot be understood simply by extrapolating the adaptive response of any single species to the whole community.

Introduction GFA (Guan-Fu Base A) as one of the main active substances in the Chinese medicine Ranunculaceae Aconite, has been approved the effect of anti-atrial fibrillation via its atrial-selective Na + channel-blocking action. It is recently undergoing phase IV clinical study. However, the molecular mechanism of Na V1.5 channel inhibition by GFA is largely unclear. Methods and Results Na V1.5 channel and its mutants were expressed in Xenopus oocytes and the currents were recorded with two-microelectrode voltage-clamp. GFA inhibited Na V1.5 currents in a concentration-dependent manner, with IC 50 of 66.24 μM, 371.59 μM, and 381.08 μM for wild type (WT), Delta KPQ (∆KPQ) and R1623Q constructs, respectively. Both the mutations of ∆KPQ and R1623Q decreased inhibitory potency of GFA about 5~6-fold. N406K mutation significantly altered the inhibition effect of GFA. Even 1 mM GFA has almost no inhibitory effect on the mutant. For both the WT and mutant channels, GFA reduced the currents in concentration, voltage and time dependent manner. Conclusion: GFA is a potent blocker of Na V1.5 channel. N406, the aromatic residues in the transmembrane helical of DIS6, is most likely responsible for the high-affinity binding of GFA to Na V1.5 channel.

Background Left bundle area pacing is growing in use both for bradycardia pacing and cardiac resynchronization, but implants are not always successful. We prospectively studied consecutive patients to determine whether septal scar contributes to implant failure. Methods Patients scheduled for left bundle area pacing, using the 3830 Selectsecure lead were prospectively enrolled. All patients underwent standardized scar assessment by cardiac MRI with late gadolinium enhancement imaging. Scar burden was quantified as the proportion of basal septal segments showing late enhancement. Results 35 patients were recruited: 29 male, mean age 68 years, 10 with ischemic and 16 with dilated cardiomyopathy. Pacing indication was bradycardia in 26% and cardiac resynchronization in 74%. In 5/35 (14%) it was not possible to advance the lead through the ventricular septum. Basal septal late gadolinium enhancement was significantly more extensive in these patients (median 67%, IQR 58-69.5) compared to the other 30 (median 10%, IQR 0-20, p = 0.0006). There was no significant correlation between the paced QRS duration achieved and the extent of basal septal scar (r = 0.06, P = 0.75). Conclusions Failure to deliver a lead to the left bundle area is strongly associated with a (very) high burden of scar in the basal septum. Once the lead is delivered, however, the electrical response is independent of scar burden. This suggests that it would be worth developing delivery tools to tackle scarred basal septa, because if the lead could be delivered the electrical capture might still achieve a narrow QRS.

Harlequin ichthyosis is a rare autosomal recessive congenital ichthyosis with a distinct phenotypic appearance. We report a male baby with harlequin ichthyosis who was born to consanguineous parents that have a previous female baby who was diagnosed with harlequin ichthyosis.

Auxin is important in regulating bamboo growth and development. Naturally grown moso bamboo shoots were treated with auxin, and changes in endogenous hormones were determined by a selective response/multi-response monitoring–targeted metabolomics approach. Gibberellin and cytokinin were significantly upregulated, while auxin inhibitor treatment also resulted in endogenous hormone disruption. Transcriptome sequencing using Oxford Nanopore Technology revealed that the regulation of internode length by auxin is mainly through three pathways at the transcriptional, translational and post-translational levels. The pathways are phytohormone signaling, amino acid synthesis and protein processing, and energy metabolism. The transcription factors that play major regulatory roles include ethylene response factor, WRKY and MYB transcription factor, NAC structural domain protein and basic leucine zipper protein. A gene regulatory network was constructed and screened, and we cloned the core regulatory gene— PheAUX/IAA34. We found that there may be crosstalk between auxin signaling and jasmonic acid signaling, and verified that auxin can co-regulate growth with plant hormones by transgenic and yeast two-hybrid experiments. The results demonstrated that auxin-mediated height regulation in bamboo mainly regulates internode length rather than node numbers. For single internodes, auxin mainly regulates internode elongation by promoting cell elongation. High-quality bamboo internode materials for production can be obtained by auxin treatment, which can provide a reference for bamboo plant height regulation research.

Safety is the foremost aspect in today"s world. In this world of technology, people need technology to help them in danger conditions. Gas leakage becomes a severe issue that results in many accidents which lead to mortal and monetary harm. It is need of hour to install the gas leakage detection systems on public places. This paper presents a system design that identifies the leakage of gas and warns the user about the situation by sending SMS on user"s phone with the help of GSM. Smart kitchen by means of IOT is aimed, created and verified. Our system has more features than existing systems because those were manual while our system is automatic and provides rapid reply and correct identification that can save many lives and prevents humans from many hazardous cases. _____________________________________________

It is beneficial to investigate the effect of nanomedicines on cancer cell behaviors on three-dimensional (3D) platforms for evaluating and developing novel antitumor nanomedicines in vitro. Two-dimensional flat surface is widely used to study the cytotoxicity of nanomedicines on cancer cells, and there is little work using 3D confinement to assess the effect of nanomedicine on cancer cells. In this work, PEGylated paclitaxel nanoparticles (PEG-PTX NPs) were applied for the first time to treat nasopharyngeal carcinoma (NPC43) cells in 3D confinement which consisted of microwells with different sizes and a glass cover. The cytotoxicity of the small molecule drug paclitaxel (PTX) and PEG-PTX NPs were studied in microwells with sizes of 50×50, 100×100, and 150×150 μm2 and with covers. After NPC43 cells were treated with PTX and PEG-PTX NPs, the cell migration speed and cell morphology were analyzed in different microwells without and with covers. The relationship between the cytotoxicity from drugs, the size effect from microwells, and cell behaviors were analyzed. These results not only show the effect of 3D confinement on cytotoxicity of nanomedicines and cell behaviors, but also provide a novel method to screen anticancer drugs and evaluate the cell behaviors in vitro.

Here, we describe a family case carrier with 3q29 microduplication, a 1.56Mb and 1.68 Mb duplicate region, that was identified by CNV-seq. Different from the common clinical traits of previously reported cases, this family of individuals shows an apparently normal phenotype.

Differences in individual personality are common amongst animals, which can play an ecological and evolutionary role given links to fitness. Personality affects animal life processes and outputs (e.g., behavior, life history, growth, survival, reproduction), and has become a common theme in animal behavioral ecology research. In the present study, we used Siberian Sturgeon to explore how personality traits of boldness and shyness are related to swimming performance, post exercise recovery and phenotypic morphology. Firstly, our results indicated that the Siberian sturgeon juveniles of shyness were better swimmers, validating evolutionary biology trade-off theory. The critical swimming speed (Ucrit) of the shy groups was higher than that of the bold groups. Secondly, the shy groups were more resilient after exercise fatigue. The swimming fatigue recovery ability, the glucose and lactic acid concentration recovery ability of shy groups were greater than that of bold groups. Thirdly, the shy groups were more streamlined. Compared with bold groups, shy groups had smaller caudate stalk lengths, caudate stalk heights, superior caudal lobes, and inferior caudal lobes. These research results further enrich the theoretical viewpoints of fish behavior biology, more importantly, which provided a good example for studying the relationship between sturgeon’s “personality” and swimming performance.

Atomoxetine is the first non-stimulant medication approved by the US Food and Drug Administration for the treatment of attention deficit/hyperactivity disorder (ADHD). It can significantly improve ADHD symptoms, with good efficacy and tolerability. However, its efficacy was not consistent among all patients, especially for pediatric population. Due to marked heterogeneity in treatment response, a precision therapy should be developed and evaluated to guide treatment planning at the individual level. We have gained a better understanding of the pharmacokinetic profile. This review summarized some factors affecting peak concentrations of atomoxetine, including food, CYP2D6 and CYP2C19 phenotypes, and drug-drug interactions. The association between response and genetic polymorphisms of genes encoding the pharmacological targets such as norepinephrine transporter (NET/SLC6A2) and dopamine β hydroxylase (DBH) was also discussed. Based on the well-developed and validated assays for monitoring plasma concentrations of atomoxetine, the therapeutic reference range in pediatric patients with ADHD proposed by several studies was summarized. However, supporting evidence on the relationship between systemic atomoxetine exposure levels and clinical response is far from sufficient. We have to create evidence to characterize clearly the dose-exposure relationship, to establish clinically relevant metric for systemic exposure, to define a therapeutic exposure range, and to provide a dose-adaptation strategy before implementing personalized dosing for atomoxetine in children with ADHD. Personalizing atomoxetine dosage may be even more complex than we anticipated, but we can be optimistic about the future based on the remarkable advances in understanding the nature and causes of ADHD, as well as environmental stressors.

Purpose. To assess the effect of exposure to fluvoxamine around the COVID-19 diagnosis on subsequent hospitalizations and mortality in COVID-19 outpatients in a real-life setting. Methods. Using nationwide administrative data, we identified adult COVID-19 outpatients diagnosed up to August 15, 2021 and conducted two cohort studies. Study 1 included subjects prescribed fluvoxamine around the index COVID-19 diagnosis (Cohort A), their peers suffering similar psychiatric difficulties but not prescribed fluvoxamine (Cohort B) and those free of psychiatric difficulties/treatments (Cohort C). Study 2 included subjects prescribed fluvoxamine (Cohort Fluvoxamine) and their peers prescribed paroxetine (Cohort Paroxetine). Cohorts were mutually exactly matched and incidence of COVID-19-related hospitalization, 30-day all-cause hospitalization and of COVID-19-related mortality was estimated. Results. Of the 416030 first-episode outpatients, Study 1 included 1016 Cohort A, 95984 Cohort B and 275804 Cohort C patients. Matched Cohort A (n=749) vs. Cohort B (n=31336) relative risks (95%CI/CrI), frequentist and Bayes with skeptical, otpimistic and pesimistic priors, were: COVID-related hospitalization 1.37 (0.56-3.33), 1.15 (0.55-2.11), 1.03 (0.56.1.96) and 1.43 (0.63-2.94), respectively; 30-day all-cause hospitalization 1.88 (0.76-4.67), 1.76 (1.39-2.25), 1.76 (1.39-2.24) and 1.86 (1.43-2.38), respectively; COVID-19 related mortality 0.73 (0.35-1.55), 0.93 (0.53-1.76), 0.79 (0.40-1.54) and 0.88 (0.37-2.11), respectively. Matched Cohort A vs. C (866 vs. 222792) comparison yielded similar estimates, as did the matched Cohort Fluvoxamine vs. Paroxetine comparison in Study 2 (344 of 994 matched to 535 of 1796 patients). Conslusion. Outpatients prescribed fluvoxamine around the time of COVID-19 diagnosis were not at a reduced risk of hospitalizations and mortality compared to their non-prescribed peers.

Anaplastic thyroid cancer is a rare and has an extremely poor prognosis. It is known that most of anaplastic transformation occurs in primary lesions, but rarely in metastatic lesions. We report 67-year-old female patient who recieved surgery, but whose postoperative pathological examination revealed anaplastic transformation in metastatic cervical lymph nodes.

Aims: We conducted a meta-analysis of trials in when is prefectly to conduct a surgery for asymptomatic congenital pulmonary airway malformation (CPAM) in children. Methods: We searched the PubMed, Embase, Scopus and Cochrane Library databases to identify related articles published prior to April 2022 that conduct the surgery for asymptomatic congenital pulmonary airway malformation in children in different ages. Results: The results showed that operating the surgery between 3 months to 6 months old in patients can decrease the length of hospital stay. The younger the age of operation, the shorter the operation time. As for get rid of the ventilation as soon as possible and lower major complications, the surgery should be performed no more than 6 months old. Whereas, the chest tube duration as well as the number of deaths didn’t have statistically significant change. Conclusions: As for asymptomatic CPAM patients, we suggested that surgical treatment should be performed less than 6 months old.

Background. The COVID-19 pandemic has spread across the world, leading to government measures associated with a negative impact on mental health. The aim of this study was to evaluate the impact of COVID-19 on depression, anxiety and resilience in Dutch people with cystic fibrosis (PwCF) or primary ciliary dyskinesia (PwPCD) and their caregivers during the pandemic. Methods. Adolescents (12-17 years), adults and caregivers of children (0-17 years) with CF or PCD completed questionnaires on depression (PHQ-9), anxiety (GAD-7) and resilience (BRS) between September 2020 and February 2021. The psychosocial impact of COVID-19 was measured by the Exposure and Family Impact Survey (CEFIS) Part 2. Mixed model analyses compared PHQ-9 and GAD-7 results to participants’ pre-pandemic scores. Results. 110 participants (10 PwCF, 31 PwPCD, 52 CF caregivers, 17 PCD caregivers) completed questionnaires during the pandemic. Pre-pandemic outcomes were available for 87 participants. The prevalence of symptoms of depression and anxiety (PHQ-9 or GAD-7 scores ≥5) in PwCF and PwPCD and their caregivers before and during the pandemic was high, with an increase in depression in PwCF (2.75; 95%-CI: 0.82 to 4.68) and increase in anxiety in CF caregivers (1.03; 0.09 to 1.96) during the pandemic. Resilience was within the normal range for all groups, CEFIS scores corresponded to a low to normal impact. Conclusion. PwCF and PwPCD and their caregivers were at high risk of increased depression and anxiety symptoms both before and during the pandemic, which emphasizes the importance of mental health screening and psychological care in CF and PCD.

This case report describes of a pharmacokinetic drug–drug interaction between crizotinib, a tyrosine kinase inhibitor, and sofosbuvir/velpatasvir, a direct-acting antiviral drug, leading to cardiac toxicity. A 75-year-old man, with no cardiovascular history but a diagnosis of metastatic non-small cell lung cancer with MET exon-14 deletion and hepatitis C virus infection genotype 1A, received both crizotinib and sofosbuvir/velpatasvir. Crizotinib was well tolerated, but 1 week after sofosbuvir/velpatasvir initiation, the patient experienced bilateral lower-limb edema and class III NYHA dyspnea. We assumed that increased exposure to crizotinib could account for this cardiac toxicity. Drug causality was probable according to the Naranjo scale. We hypothesized a reciprocal interaction between crizotinib and velpatasvir, mediated by both cytochrome 3A4 (CYP3A4) and P-glycoprotein (P-gp). Clinicians should be aware of the risk of drug–drug interactions between direct-acting antiviral agents that inhibit CYP3A4 (glecaprevir) and/or P-gp (voxilaprevir) and anticancer tyrosine kinase inhibitors that are mostly CYP3A4 and/or P-gp substrates (gefitinib, afatinib, erlotinib, crizotinib, ceritinib, lorlatinib, brigatinib, capmatinib etc.).

We develop a mathematical model to study the effects of non-pharmaceutical interventions (NPIs) on the dynamics of an epidemic. The level of intervention is assessed as a fraction of the population being isolated and depends on the level of incidence of the epidemic in the population. We perform the mathematical analysis of the model and show that, depending on the choice of the prevalence-dependent isolation function, it is possible to create new endemic equilibria and to change the stability of the disease-free equilibrium for which the epidemic vanishes. The model is then applied to the case of the covid-19 pandemic. Several NPI management strategies are considered. In the case of a NPI intensity increasing with the level of infection, it is possible to avoid the initial epidemic peak of great amplitude that would have occurred without intervention and to stabilize the epidemic at a chosen and sufficiently low endemic level. In the case of a NPI intensity decreasing with the level of infection, the epidemic can be driven to extinction by generating an “Allee” effect: when the incidence is below a given level, the epidemic goes extinct while above it, the epidemic will still be able take hold at a lower endemic level. Simulations illustrate that appropriate NPIs could make the Covid-19 vanish relatively fast. We show that in the context of the covid-19 pandemic, most countries have not chosen to use the most efficient strategies.

Distributed learning is a very effective divide-and-conquer strategy for dealing with big data. As distributed learning algorithms become more and more mature, network security issues including the risk of privacy disclosure of personal sensitive data, have attracted high attention and vigilance. Differential privacy is an important method that maximizes the accuracy of a data query while minimizing the chance of identifying its records when querying from this data. The known differential privacy distributed learning algorithms are based on variable perturbation and the variable perturbation method may be non-convergence and the experimental results usually have large deviations. Therefore, in this article we consider differential privacy distributed learning algorithm based on objective function perturbation. We first propose a new distributed logistic regression algorithm based on objective function perturbation (DLR-OFP). We prove that the proposed DLR-OFP satisfies differential privacy, and obtain a fast convergence rate by introducing a new acceleration factor for the gradient descent method. The numerical experiments based on benchmark data show that the proposed DLR-OFP algorithm has fast convergence rate and good privacy protection ability.

Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants to evolve polyploid populations. Investigations into the frequency and distribution of polyploids in natural populations is thus necessary for understanding polyploid evolution in plants. This study determined the ploidy levels of 28 populations and 351 individuals of Salix polyclona, and identified the type of polyploidy (auto- vs. allo-) using whole genome re-sequencing data. We further investigated the phylogeny, population genetic diversity and species range shifts to explore the origin and spatiotemporal evolution of the polyploid complex. Our analyses revealed a high frequency (52%) of autopolyploids in it with a clear geographic distribution confined to the western part of its range where complex mountain systems create higher levels of environmental heterogeneity. Comparisons of diploid male and female genomes suggested a female heterogametic sex-determining factor on chromosome 15, which likely also acts in the dioecious polyploids. Fossil-calibrated phylogeny showed a more recent diversification of the polyploids (ca. 2.3 Ma) than the diploid (ca. 6.2 Ma), and population demographic histories largely corroborated the geological and climatic history of the region. Our results suggest that climatic oscillations and uplift of eastern Qinghai-Tibetan Plateau and the connecting mountains may have facilitated the preservation and establishment of polyploid populations. This study provides an example of the evolution of a diploid-polyploid complex in a willow species and illustrates a role of polyploidization in mountain biodiversity.

Ferric and manganese oxalate complex can be obtained from iron-rich pyrolusite by oxalic acid leaching and ultraviolet radiation. Molar ratio of C2O42- to Fe3+ in leaching solution was found to be a vital parameter decided the leaching and precipitation efficiencies of Mn and Fe in leaching and radiation processes. Even at the optimal leaching concentration of experiments, the Fe leaching rate reached 94.24%, while the leaching rate of Mn was only 69.04%. When a two-stage countercurrent leaching process was carried out, both Fe and Mn leaching rates could reach 97.10% and nearly 100%, respectively, realizing efficient leaching of Fe and Mn from pyrolusite.

Water distillation is an effective method for detritiation and deuterium enrichment. This study focuses on the effect of the wettability of the packings surface on the separation performance of the H2O-HDO system. Hydrophilic coatings with different structures are prepared on the surface of copper packings by the method of alkaline erosion and oxidation, and it is found that the hydrophilic coatings with different structures showed different hydrophilic effects. The differences in mass transfer performance of packings with different contact angles are investigated. It is found that with the increase of hydrophilicity, the mass transfer performance of the packing is relatively improved. By combining empirical models of mass transfer and experimental data, a mathematical model for predicting the height of equal plate (HETP) is established to quantify the effect of wetting properties on the mass transfer process.