Background and aim of the study The Valiant NavionTM stent graft system is a third-generation low profile thoracic endograft designed for thoracic endovascular aortic repair. In this population analysis, we report on the first Asian all-comers experience and outcomes who underwent thoracic endovascular aortic repair with the use of this new stent graft system. Methods Between May 2019 and October 2020, 21 patients with different aortic pathologies were prospectively recruited and retrospectively analyzed. Important clinical and device-related outcomes were evaluated. The endpoints included short-term survival, technical success, access failures, major vascular and clinical complications, endoleaks, and hospital stay. Results The commonest indication of stenting was penetrating aortic ulcers (28.6%) and 6 (28.6%) patients had emergency stenting performed for aortic transection or rupture. 30 days of survival post-procedure was recorded and complete. There were no major vascular complications. Deployment accuracy was 100%, and the technical success rate was 94.7% (18/19) with 1 patient having a type 2 endoleak on follow-up imaging. No neurological complications were noted. The mean operative time was 95 +/- 73.6 mins and the mean fluoroscopy time was 16.2 +/- 10.8 mins. Mean hospital stay for elective zone 2, 3 and 4 stenting was 5.3 +/- 3.8 days, and only 1 patient post zone 1 TEVAR required a brief (0.5 days) ICU stay. All procedures were performed via the percutaneous transfemoral route with 100% success in percutaneous closure. Conclusion This first reported Asian case series demonstrated versatility, safety, and efficacy of the Valiant NavionTM stent in Asian patients with different aortic pathologies

Emicizumab is a recombinant, humanized, and bispecific monoclonal antibody that bridges activated factor (F) IX and FX in place of FVIII to restore hemostasis in persons with hemophilia A (PHA). Data on the efficacy and safety of emicizumab in young children is limited. Immunologic naivety, physiologically decreased production of vitamin K dependent proteins, specifically FIX, and enhanced clearance of emicizumab in infants may support decreased emicizumab effectiveness. We report on the facilitation of care rendered by using emicizumab in young PHA with inhibitors and extend data on the efficacy and safety in PHA < 3 years.

Background Langerhans cell histiocytosis (LCH) involves abnormal proliferation of Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. Procedure Fifteen children (5 girls, 10 boys) with BRAF V600E+ LCH received vemurafenib (initial dose median 40 mg/kg/day, range: 11–51.6 mg/kg/day) between March 2016 and February 2020. All patients had previous received LCH-directed chemotherapy. The median age at LCH onset was 2 months (range: 1–28 months) and the median age at the start of vemurafenib treatment was 22 months (range: 13–62 months). The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points (range: 2–22 points). Results The median duration of vemurafenib therapy was 29 months (range: 2.4–45 months). All patients responded to treatment, with median DAS values of 4 points (range: 0–14 points) at week 4 and 1 point (range: 0–3 points) at week 26. Toxicities included skin/hair changes (93%) and non-significant QT prolongation (73%). Two patients died, including 1 patient who experienced hepatic failure after NSAID overdose and 1 patient who developed neutropenic sepsis. Electively stopping vemurafenib treatment resulted in relapse in 5 patients, and complete cessation was only possible for 1 patient. Digital droplet PCR for BRAF V600E using cell-free circulating DNA revealed that 7 patients had mutation statuses that fluctuated over time. Conclusion Our study confirms that vemurafenib treatment is safe and effective for young children with BRAF V600E+ multisystem LCH. However, treatment using vemurafenib does not completely eliminate the disease.

Seed recruitment is a major driver of mangrove restoration globally. It is hypothesized that soil condition and channel hydrology can accelerate seedling recruitment and regeneration after a major disturbance. Species abundance, diversity indices, microbial and chemical concentrations in sand-filled mangrove forest was studied. Eight plots (area = 3902.16 m2) were established with ten transects in each plot in a random block design to investigate the effect of soil conditions on seedling growth. A total of 1, 886 seedlings were physically counted. Seedling abundance was significantly different between red (Rizophora racemosa), white (Laguncularia racemosa) and black (Avicennia germinans) mangroves and nypa palm (nypa fruticans). The most dominant species was black mangroves and the least dominant species was nypa palm. Muddy soils had the most abundant species while sandy soils had the least abundant species. Furthermore, semi-muddy soils had the highest species diversity (H = 0.948) whereas muddy soils had the least species diversity (H = 0.022). The soil metal concentration has no correlation with seed abundance and occur in the order Iron>Nitrate>Copper>Cadmium. Soil with high species diversity had high soil microbial population; however, seedling abundance was correlated with soil nutrients and not heavy metals. Small seeds are easily recruited while good soil condition plus existing hydrological connection facilitated natural seedling regeneration in the disturbed mangrove forest.

A document by Deep Bhattacharjee . Click on the document to view its contents.

Background: Although epicardial adipose tissue (EAT) has been proved be associated with atrial fibrillation (AF) and post-ablation AF recurrence, the relationship between EAT and AF after cardiac surgery (AFACS) is not evident, yet. Objective: In the study, we aim to perform a systematic review and meta-analysis to assess the association between EAT and AFACS and whether it is independent of the measurement methods. Methods: Systematic reach was implemented until May, 30, 2020, which “atrial fibrillation” and “epicardial adipose tissue” were as the main items in electronic databases. Analysis was stratified by EAT measurement methods into three pooled meta-analyses on 1) total EAT volume, 2) left atrium (LA)-EAT volume and 3) EAT thickness between two groups with and without AFACS, estimating standardized mean difference (SMD) with a random effect model. Results: Eight articles with ten studies (546 patients) were included. Accordingly, the results of meta-analysis showed that EAT was higher in AFACS subjects, regardless of the methods of EAT measurement.[ total EAT volume: SMD = 0.56 ml; 95% confidence interval (CI) = 0.56-1.10ml, I2 = 0.90, P=0.04; EAT thickness: SMD = 0.85mm; 95% CI = 0.04-1.65mm, I2 = 0.90, P=0.04; LA-EAT volume: SMD = 0.57ml, 95% CI = 0.23-0.92ml, I2 = 0.00, P=0.001.] And there was no evidence of publication bias. Conclusion: EAT may be a potential marker and therapeutic target for AFACS. However, larger scale studies are still required, and evaluation is needed to for further estimation.

A document by Nao Takashina. Click on the document to view its contents.

Livestock grazing is a major driver shaping the functioning and stability of grasslands. Although previous studies have documented the effect of grazing on grassland stability, whether this effect is scale-dependent remains unclear. Here, we conducted a sheep-grazing experiment in a temperate grassland to test grazing effects on biomass stability across scales and organizational levels. We found that an increase of grazing intensity increased species stability, but it substantially decreased local ecosystem stability due to reduced asynchronous dynamics among species. Moreover, grazing reduced ecosystem stability at larger spatial scales, but to a lesser extent. By decreasing biodiversity within and across communities, grazing impairs the insurance effects of biodiversity and hence the up-scaling of stability from species to ecosystem and further to larger scales. Our study provides the first evidence for the context-dependence of grazing effects on grassland stability via shaping biodiversity and contributes to bridging fine-scale experiments and broad-scale ecosystem management.

Title: Intratympanic gentamicin injection in Ménière’s disease: our twelve years’ experience and outcomes. Objective: The aim of our study is to evaluate the effectiveness of intratympanic gentamicin injection(ITG) on vertigo control with reduced doses and its hearing effects. Study design: Retrospective study Materials and Method: The study was conducted at our Otolaryngology Department of AORN “S.G. Moscati” between January 2005 and January 2015 on 72 patients with disabling unilateral Meniere’s disease treated with ITG. We use 0.2-0.3 mL of gentamicin sulfate at a concentration of 40mg/ml, injected into the affected ear through the posterior-inferior quadrant of the tympanic membrane. The procedure was carried out for three following days. Main outcome measures: vertigo control and hearing threshold changes after ITG treatment. Results: In the 98.6% of the patients (n=71) the ITG produced the full remission of the vertiginous symptoms. In the 91.6% of cases(n=66) a single treatment (three consequent injections) was sufficient to control vertigo, in the 5.5% of cases (n=4) two treatments were necessary to control vertigo and in the 1.3% of patients(n=1) three treatments were necessary to control vertigo. In no case we have had hearing loss after ITG procedure. The pre-treatment pure tone average was 48 db. The post-treatment pure tone average was 49.2 db. This difference was no statistical difference. Conclusion: In this study we reported high vertigo control, long follow-up and no case of significant hearing worsening. We consider the three injections in the following three days with low doses of gentamicin a safe and valid treatment for Meniere’s disease. Keyword : Meniere’s disease, intratympanic gentamicin injection, vertigo control, hearing worsening, aminoglycoside ototoxicity.

Introduction: Cardiac resynchronization therapy via biventricular pacing is an established therapy for patients with heart failure. However, high nonresponder rates and inability to predict response remains a challenge. Recently left bundle branch area pacing (LBBAP) has been shown to be feasible and may also improve clinical outcomes. In this article we describe sequential LBBAP followed by left ventricular (LV) pacing (LOT-CRT) and assess the feasibility of LOT-CRT. Methods: The RV implantation site was positioned and the LBBAP lead was implanted using our methods. The QRS duration (QRSd) at baseline, during LBBAP, biventricular pacing, and LOT-CRT was measured. Results: LOT-CRT was successful in 5 patients (age 71.8 ± 5.1 years, men 3, ischemic 3). The QRSd at baseline was 158.0 ± 13.0 ms and significantly narrowed to 117.0 ± 6.7 ms during LOT-CRT (P < 0.01). During 3-month follow-up, LV ejection fraction improved from 32.8 ± 5.2 % to 45.0 ± 5.1% (P < 0.01), and New York Heart Association functional class changed from 3.25 ± 0.5 to 2.5 ± 0.6 (P < 0.05). A decrease in left ventricular end-diastolic dimension was observed, with widening from (68.2 ± 12.3) mm at baseline to (62.2 ± 11.3) mm at pacing (P < 0.05). The length of operation time was (152.0 ± 31.1) min. Conclusions: The study demonstrates that LOT-CRT is clinically feasible in patients with systolic HF and LBBB. LOT-CRT was associated with significant narrowing of QRSd and improvement in LV function, especially in patients with ischemic cardiomyopathy.

Objective The main objective of this paper is to compare the performance of logistic regression and decision tree classification methods and to find the significant environment determinants that causes pre-term birth. Design, setting and population Between 2017 to 2018, 90 pregnant females underwent birth outcome followed by research staff at our institutions, out of those 50 are full-term and 40 are preterm births in this study. Method Before and after feature selection logistic regression and decision tree classifier model has been compared in this dataset and to evaluate the model accuracy. Main outcome measures Preforming the accuracy of machine learning classification model and important factors on pre-term birth. Results: Using chi-square test and find the Area of residence and GSH, MDA, α-HCH, total HCH and total DDT are responsible for the preterm birth. Using the multiple logistic regression, pre term birth was associated with MDA and α-HCH (95% CI 0.04 to 0.48 and 95% CI 0.82 to 0.97). The logistic and decision tree model comparison result shows that logistic regression is better in terms of metrics (precision = 0.92, F1-score = 0.96 and AUROC = 0.97), while decision tree performs the poor (precision = 0.75, F1-score = 0.86 and AUROC = 0.87). Conclusions The logistic regression is accurate model to predict the pre-term as compare to decision tree method. The variables like α-HCH , total HCH and MDA (Malondialdehyde) are the most influential factors for preterm birth.

Objective: Evaluate satisfaction and experience with telemedicine and home use of mifepristone and misoprostol for abortion to 10 weeks’ gestation. Design: Cross-sectional evaluation. Setting: British Pregnancy Advisory Service (BPAS) clinics in England and Wales. Population: 1,144 clients who used mifepristone and misoprostol at home from 11 May to 10 July 2020. Methods: We sent a text message with a link to a web-survey 2-3 weeks after treatment. Questions evaluated satisfaction and experiences, including telephone consultations and provision of medicines by post or collection from clinic. We used bivariate and multivariate regression to explore associations between client characteristics and outcomes. Main Outcome Measures: Overall satisfaction (5-point Likert scale) and reported contact with a healthcare provider (HCP). Results: Respondents primarily described home use of medications as ‘straightforward’ (75.8%) and most were ‘very satisfied’ (78.3%) or ‘satisfied’ (18.6%) with their overall experience. Being ‘very satisfied’ was associated with parity (aOR 1.53, 95% CI 1.09-2.14) and pain control satisfaction (aOR 2.22, 95% CI 1.44-3.44). HCP contact was reported by 14.7%; mainly to BPAS’ telephone aftercare service (76.8%). Dissatisfaction with pain control (aOR 3.62 95% CI 1.79-7.29) and waiting >1 week to use mifepristone (aOR3.71, 95% CI 1.48-9.28) were associated with HCP contact. If needed in future, most (77.8%) would prefer home use of mifepristone and misoprostol and pills by post (68.9%). Conclusions: Satisfaction with home use of mifepristone and misoprostol is high. Most clients do not need HCP support during or after home use, but aftercare should be available.

Phosphorus (P) is an essential nutrient element for plants. Wild soybean (Glycine soja) expresses higher tolerance to P-limited environment compared to cultivated soybeans (Glycine max). In this study, the response of ionomics and metabonomics in young and old leaves of two soybean varieties under low P were studied. Our results showed that the tolerance of low P in wild soybean can be improved by promoting the accumulation of Mg2+, Fe3+, and SO42- in young and old leaves and the transportation of NO3− and H2PO4− from old to young leaves. The young and old leaves of wild soybean under low P accumulated sugars including maltose and sucrose, amino acids including asparagine and glutamine, and nitrogenous compounds including tyramine, and enhanced the tricarboxylic acid cycle metabolism, especially in young leaves, but decreased the content of hexose-phosphate metabolites. Our experiment indicated that wild soybean can tolerate low P by enhancing the energy metabolism in young and old leaves, promoting the transportation and reuse of sugars and amino acid metabolites from old to young leaves, and mobilizing Pi from hexose-phosphate of old leaves to young leaves. Our results provide a new insight for the cultivation of new soybean varieties with tolerance to P deficiency.

In the context of non-relativistic quantum mechanics, we use information theory to study Shannon’s entropy of a non-Hermitian system and understand how the information is modified with the cyclotron frequency. Subsequently, we turn our attention to the construction of an ensemble of these spinless particles in the presence of a uniform magnetic field. Then, we study the thermodynamic properties of the model. Finally, we show how information and thermodynamic properties are modified with the action of the magnetic field. KEYWORDS: Non-relativistic Quantum Mechanics; Quantum Information; Shannon Entropy.

Leadless cardiac pacemakers such as the Micra transcatheter leadless pacing system provide an alternative to traditional transvenous pacemakers. Implantation of leadless pacemakers, albeit safe may be associated with complications including cardiac tamponade, high capture thresholds, and rarely, ventricular arrhythmias. We report a case of ventricular fibrillation arrest following Micra leadless pacemaker implantation.

Background.Data on the effectiveness and safety of percutaneous transcatheter closure of atrial septal defect(ASD) and patent foramen ovale(PFO) guided by intracardiac ultrasound(ICE) are limited. We conducted a meta-analysis comparing intracardiac ultrasound with transesophageal ultrasound(TEE) guided surgery. Mehood.From 1996 to 2020, a systematic search was conducted using multiple databases, and the results were operation time, fluoroscopy time, success rate, complications, and occluder size. Results.7 studies were included, with a total sample size of 971 patients, of which 448 patients were treated with atrial defect occlusion guided by ICE, and the other 523 patients were treated with atrial septal occlusion guided by TEE. There was a statistical difference in the fluoroscopy time and procedure time between the ICE group and the TEE group, (P<0.01), There was no significant difference in success rate, complication between ICE and TEE groups (successrate, P=0.71; complications, P=0.51). Conclusion. success rate, complications and occluder size were similar between ICE group and the TEE group. Fluoroscopy time, procedure time were significantly reduced for transcatheter closure of atrial septal defect guided by intracardiac ultrasound.

To date, there have only been 46 patients reported in the literature with trisomy 18 and hepatoblastoma. We describe the case of an 11-month-old female with trisomy 18 and hepatoblastoma who was successfully treated by pairing surgical resection with a modified chemotherapy regimen omitting doxorubicin given her underlying cardiac abnormalities. Our case successfully demonstrates how chemotherapy regimens can be modified to accommodate for other underlying abnormalities and emphasizes that routine screening guidelines should exist for patients with trisomy 18 to allow for earlier detection and treatment.

Production of industrially relevant compounds in microbial cell factories can employ either genomes or plasmids as an expression platform. Selection of plasmids as pathway carriers is advantageous for rapid demonstration but poses a challenge of stability. Yarrowia lipolytica has attracted great attention in the past decade for the biosynthesis of chemicals related to fatty acids at titers attractive to industry, and many genetic tools have been developed to explore its oleaginous potential. Our recent studies on the autonomously replicating sequences (ARSs) of nonconventional yeasts revealed that the ARSs from Y. lipolytica showcase a unique structure that includes a previously unannotated sequence (spacer) linking the origin of replication (ORI) and the centromeric (CEN) element and plays a critical role in modulating plasmid behavior. Maintaining a native 645-bp spacer yielded a 4.5-fold increase in gene expression and higher plasmid stability compared to a more universally employed minimized ARS. Testing the modularity of the ARS sub-elements indicated that plasmid stability exhibits a pronounced cargo dependency. Instability caused both plasmid loss and intramolecular rearrangements. Altogether, our work clarifies the appropriate application of various ARSs for the scientific community and sheds light on a previously unexplored DNA element as a potential target for engineering Y. lipolytica.

Abstract Background: Ataxia-telangiectasia (A-T) is a rare genetic disorder characterized by a distinct range of clinical manifestations, including progressive ataxia, immunodeficiency, and radiosensitivity. Methods: Clinical data, laboratory results, and genetic data were collected from forty-three A-T patients. Whole exome sequencing and Sanger sequencing were done for the patients clinically diagnosed as suffering from A-T. Based on the phenotype severity of the disease, patients were divided into severe and mild sub-groups. Results: The median (IQR) age of diagnosis in this cohort was 5 (3-7) years and various types of clinical manifestations, including fever (p= 0.005), lower respiratory tract infection (p= 0.033), diarrhea (p= 0.014), and hepatosplenomegaly (p= 0.032) were significantly higher amongst patients diagnosed with the severe phenotype. Our results showed a strong correlation between phenotype severity and mutation type. The chance of having severe phenotype in patients who have severe mutations, including frameshift and nonsense, was 7.3 times higher compared to patients who were categorized in the mild genotype group (odds ratio= 7.3, p= 0.006). Thirty-four types of mutations including 9 novel mutations, were observed in our study. Conclusion: Molecular analysis provides the opportunity for accurate diagnosis and timely management in A-T patients with chronic progressive disease, especially infections and the risk of malignancies. This study characterizes for the first time, the broad spectrum of mutations and phenotypes in Iranian A-T patients which are required for carrier detection and reducing the burden of disease in future using the patients’ families and for the public health care system. Keywords: Ataxia-telangiectasia (A-T), ATM, Whole-exome sequencing, Class switching recombination (CSR), phenotype severity.

Nanobodies, referred to the binding domain of the heavy-chain-only antibodies, are the smallest antigen recognition unit. The molecular weight of monomeric nanobodies is about one-tenth of the conventional antibodies. The small size of nanobodies facilitates genetic manipulation and recombinant expression. This study aimed to investigate the effects of nanobody multivalency on the binding capacity of affinity resin. The nanobody (namely AFV), which binds to the fragment crystallizable (Fc) region of immunoglobulin G (IgG), was fused to the N-terminal of HaloTag in the form of monomeric (H-AFV), dimer (H-diAFV), trimer (H-triAFV), and tetramer (H-tetAFV). The fusion proteins were solubly expressed in Escherichia coli yielding at least 9.9 mg L-1. The biolayer interferometry confirmed an increment of avidity as the increase of AFV valences. The four recombinant proteins in crude cell lysate were site-specifically immobilized onto the Halo ligand resin via the self-labeling HaloTag, respectively. The generated affinity resins were able to isolate high purity IgG from mouse plasma. An improvement of 73.7% of the static binding capacity was achieved by the H-diAFV resin as compared to the H-AFV affinity resin.

Atrial fibrillation (AF) remains a growing problem in the United States and worldwide, imposing a high individual and health system burden, including increased resource consumption due to repeated hospitalizations, stroke, dementia, heart failure, and death. This comprehensive review summarizes the most recent data on sex-related differences in risks associated with AF. Women with AF have increased risk of stroke and death compared to men, and possible reasons for this disparity are explored. Women also continue to have worse symptoms and quality of life, and poorer outcomes with stroke prevention, as well as with rate and rhythm control management strategies. Many current rhythm control treatment strategies for AF, including cardioversion and ablation, are used less frequently in women as compared to men, whereas women are more likely to be treated with rate control strategies or anti-arrhythmic drugs. Sex differences should be considered in treating women with AF to improve outcomes and women and men should be offered the same interventions for AF. We need to improve the evidence base to understand if variation in utilization of rate and rhythm control management between men and women represents health inequities or appropriate clinical judgement.

Background: It is unknown whether cryoballoon technology for persistent atrial fibrillation (AF) is a reasonable initial strategy for patients with persistent AF (perAF). Methods: 390 consecutive procedures using cryoballoon for initial AF ablation were evaluated and divided first by clinical presentation: paroxysmal AF (PAF) or perAF, and then whether PV potentials associated PV pacing (PV capture) were identified after ablation. Patients were followed for recurrent AF (median 20 months). Results: PV capture was identified in patients with PAF and perAF (PAF: 20.3% vs. perAF: 14.6%; p < 0.05). No patient charactieristic differences were identified between those patients with or without PV capture. The presence of PV capture was not associated with different outcomes in patients with PAF. However, in patients with perAF, the presence of PV capture was associated with long-term outcomes similar to patients with PAF and significantly better than patients with perAF without PV capture (p < 0.001). In patients with perAF and PV capture, a strategy of reisolation of the PVs only for recurrent AF resulted in 20/23 (87%) patients in sinus rhythm off antiarrhythmic medications at study completion. In patients with PV capture, specific electrophysiologic properties of PV tissue did not have an impact on AF recurrence. Conclusion: PV capture (and not specific PV electrophysiologic characteristics) was associated with decreased recurrent AF in patients with perAF. PV capture may identify those patients with perAF in whom PV isolation alone is sufficient at initial ablation procedure and also as the primary ablation strategy for recurrent AF.

Conflicting responses to two ventricular entrainments in a narrow QRS tachycardia: What is the mechanism?Jeong-Wook Park, CEPS, Young Choi, MD, Sung-Hwan Kim, MD, Yong-Seog Oh, MDFrom the Division of Cardiology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Levothyroxine (LT4) is frequently used as thyroid hormone replacement to treat hypothyroidism. Adverse skin reactions are not common. Lichenoid drug eruption is a one such medication-related reaction. the lesion morphology and pathology mimic lichen planus. The current case describes a 47-year-old man who presented to us with a diffuse levothyroxine-induced lichenoid drug eruption. The Naranjo adverse drug reaction probability assessment score suggested this was likely an ADR to levothyroxine. The eruption resolved after discontinuation of the medication. We also reviewed the literature on levothyroxine-associated adverse events.