Mitochondrial DNA sequences (mtDNA) are often found as byproduct in hybrid enrichment data sets originally created to capture anchored hybrid enrichment (AHE) or ultra-conserved element (UCE) nuclear loci. The mtDNA sequences in these data sets are currently rarely used, even though mitochondrial genes such as COI, ND5, CytB, and 16S are of general interest and often not yet known and deposited in public databases. We developed MitoGeneExtractor to extract mitochondrial genes of interest from genomic libraries. Gene sequences are reconstructed through multiple sequence alignments of sequencing reads to an amino acid reference. We applied MitoGeneExtractor to recently published data created for UCE enrichment and were able to extract complete or nearly complete COI and ND5 sequences for a large proportion of the sequencing libraries. MitoGeneExtractor can be used to extract mitochondrial protein coding genes from a wide range of next generation sequencing data sets.

Feline panleukopenia (FPL) is a severe, often fatal disease caused by feline parvovirus (FPV). How infection with FPV might impact the composition of the entire eukaryotic enteric virome in cats has not been characterized. We used metatranscriptomic and viral particle enrichment metagenomic approaches to characterize the enteric viromes of 23 cats naturally infected with FPV (FPV-cases) and 36 age-matched healthy shelter cats (healthy controls). Sequencing reads were detected from 11 mammalian infecting viral families mostly belonging to Coronaviridae, Parvoviridae and Astroviridae. Among the healthy control cats the most abundant viruses were Feline coronavirus, Mamastrovirus 2 and Carnivore bocaparvovirus 3 (Feline bocavirus 1) with frequent co-infections of all three. Feline chaphamaparvovirus was only detected in healthy controls (6/36, 16.7%). Among the FPV-cases, in addition to FPV, the most abundant viruses were Mamastrovirus 2, Feline coronavirus and Carnivore bocaparvovirus 4 (Feline bocaparvovirus 2). The latter and Feline bocaparvovirus 3 were detected significantly more frequently in FPV-cases than in healthy controls. Feline calicivirus was present in a high proportion of FPV-cases (11/23, 47.8%) compared to healthy controls (5/36, 13.9%, p=0.0067). Feline kobuvirus infections were also common among FPV-cases (9/23, 39.1%) and were not detected in any healthy control cats (p<0.0001). While abundant in both groups, astroviruses were more frequently present in FPV-cases (19/23, 82.6%) than in healthy controls (18/36, p=0.0142). The differences in eukaryotic virome composition found in this study indicate that further investigations to determine associations between enteric viral co-infections on clinical disease severity in cats with FPL are warranted.

Climate change is affecting species and their mutualists and can lead to interaction weakening and loss. Through independent shifts in partner phenology and distribution, climatic stress can separate mutualists, leading to alterations in partner functional traits and fitness. Here, we explored the effects of drying soils and the loss of microbial mutualists via soil sterilization on legume germination success and phenology, focusing on how a loss of mutualisms with soil microbial species can alter legume early life traits. In particular, we assessed the effects of mutualism loss via soil sterilization, increased drought, or introduction to novel soils found beyond the current distributions of two focal legume species in subalpine environments. Through common garden experiments in controlled environments, we found evidence that soil sterilization (and consequent microbial absence) and dry soils caused phenological delays of 2-5 weeks in germination date, likely as a result of interaction loss between legumes and germination-promoting soil microbes, such as mutualistic rhizobia. Delays in germination caused by a mismatch between legumes and beneficial microbes could negatively affect legume fitness through increased plant-plant competition later in the season. Additionally, we found evidence of the presence of beneficial microbes beyond the current elevational range of our focal legumes which may allow for expansion of the leading edge, though harsh abiotic factors in the alpine may hinder this. Alterations in the strength of soil microbe-legume mutualisms may lead to reduced fitness and altered demography for both soil microbes and legumes.

Critical illness-associated cerebral microbleeds and leukoencephalopathy related to COVID-19 infection are increasingly being recognized in the literature. We report seven cases of COVID-19 with microbleeds in the juxtacortical white matter and corpus callosum and one case of leukoencephalopathy.

The generalized MHD-Boussinesq equations are studied in this paper. The well-posedness of the strong solutions for the generalized MHD-Boussinesq equations is proved. Asymptotic regularity for the generalized MHD-Boussinesq equations is proved in $H^{\frac{9}{2}}\times H^{\frac{9}{2}}\times H^{\frac{9}{2}}$. The higher regularity for the generalized MHD-Boussinesq equations is proved in $H^{a}\times H^{a}\times H^{a}$ for $a\geq\frac{9}{2}$.

Background: Flow artifact, intrinsic to Magnetic Resonance Angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which may have significant risks. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol. Procedure: A standardized MRA scanning protocol with an echo time of <5 msec was implemented at Montefiore Medical Center in May 2016. Retrospective chart review identified 29 patients ≤ 21 years with SCA cerebral vasculopathy and an MRA head pre- and post-May 2016. Level of arterial stenosis on MRA, echo time, and treatment plans were documented both pre- and post-implementation. McNemar analysis determined the significance of change in treatment plans before and after implementation of the standardized scanning protocol. Results: Previously seen stenosis was re-classified to a lower degree in 12/29 patients (41%). Notably, 6 patients had a reclassification of vasculopathy leading to discontinuation of chronic transfusion therapy whereas 0 patients required escalation of therapy to chronic transfusions. McNemar analysis showed this difference to be statistically significant (p = 0.042). Conclusion: Minimizing flow artifact with echo time <5msec improves accurate interpretation of true cerebrovascular disease and ensures appropriate treatment plans are in place for stroke prevention. This is especially important when trying to implement “TCD With Transfusions Changing to Hydroxyurea (TWiTCH)” clinical trial results in the real-world setting.

Oscillation of solutions of differential equations enjoys wide range of applications, such as physical sciences, population growth and life sciences. In this paper, we discuss the oscillation of third-order nonlinear neutral delay differential equations with unbounded neutral coefficients and distributed deviating arguments. By using comparison principles, we relax the restricted conditions and establish new oscillation theorems, which extend and perfect some related results in the literature. Finally, our main results are illustrated by two examples.

Abstract. In this paper, let (X;C;DC; χ) be a complete parametric vector quasi cone metric space over a Banach algebra A, C be a cone in A that contains some semi-interior points, χ be a metric parameter in C with spectral radius greater than or equal one and T from X xX to X be a generalized contraction mapping its parametric contractions are vectors in C, with these settings and without relying on the assumptions of normality and solidness of C we proved the existence of coupled coincidence points of the mapping T and hence generalized many theorems concerned with the existence of coupled coincidence points of such types and we supported these results with some illustrative examples.

We report outcomes 7 years following implementation of a pediatric oncofertility team. We compare our baseline oncofertility survey to 44 post-intervention survey respondents and electronic medical record documentation for 149 patients treated in 2019. 95% of post-intervention survey respondents recalled fertility counseling (baseline 70%, p=0.004) and 89.3% were appropriately referred for fertility preservation (baseline 50%, p=0.017). Counseling was documented in 60.4% of charts; 81% of patients were appropriately referred for fertility preservation. Fertility preservation outcomes differed by sex. Creation of an oncofertility team produced sustained improvements in fertility counseling and fertility preservation referral.

This paper investigates the spatial behavior of the solutions of the generalized heat conduction equations on a semi-infinite cylinder by means of a first order differential inequality. We consider three kinds of semi-infinite cylinders with boundary conditions of Dirichlet type. For each cylinder we prove the Phragmén-Lindelöf alternative for the solutions. In the case of decay we also present a method for obtaining explicit bounds for the total energy.

The postoperative recurrence of neuroblastoma (NB) patients is an essential reason for the high mortality of NB due to the lack of early, non-invasive, and dynamic strategies for monitoring NB recurrence. Therefore, whether the plasma circulating cell-free MYCN gene as an indicator for monitoring of NB recurrence was systematically evaluated. The MYCN copy number and NAGK (reference gene) copy number ratio (M/N) in plasma and corresponding tumor tissues of NB patients was detected using an economical, sensitive and specific single-tube dual RT-PCR approach developed in this study. The plasma M/N ratio of the MYCN gene amplification (MNA) group (N = 25, median M/N ratio = 4.90) was significantly higher than that of the non-MNA group (N = 71, median M/N ratio = 1.22), P < 0.001. The M/N ratio in NB plasma (N = 60) was positively correlated with the M/N ratio in NB tumor tissue (N = 60), with a correlation coefficient of 0.9496. In particular, the results of dynamic monitoring of postoperative plasma M/N ratio of NB patients showed that an abnormal increase in M/N ratio could be detected 1-2 months before recurrence in NB patients. In summary, the single-tube double RT-PCR approache can be used to quantitatively detect MYCN copy number. The copy number of MYCN in the tissue and plasma of NB patients is consistent with each other. More importantly, the circulating cell-free MYCN gene of NB patients can be used as a monitoring indicator for early, non-invasive, and dynamic monitoring of NB recurrence.

Pediatric acute lymphoblastic leukemia: Russian experience with the ALL-IC BFM 2002 protocolTimur Valiev, MD, PhD*, Yulia Korkina, MD, Meri Shervashidze, MD, Kirill Kirgizov, MD, PhD, Svetlana Varfolomeeva, MD, PhD.N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, Russian Federation*Correspondence to:Timur Valiev, MD, PhD, Department of Pediatric Oncology and Hematology, Pediatric Oncology and Hematology Research Institute, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 115478 Moscow, Kashirskoe shosse 24, Russian FederationText word count 3582;Abstract word count 309;Brief running title: Acute lymphoblastic leukemia treatment with the ALL-IC BFM 2002 protocolKeywords: acute lymphoblastic leukemia; treatment; ALL-IC BFM 2002; childrenTables: 0Figures: 14

Allergic respiratory disease is a worldwide health problem with increasing incidence and incurable properties. Extensive studies have found complex changes in the microbiota of the respiratory and intestinal tracts in allergic respiratory diseases, which affect the immune response and further influence the disease progression. The wide and diverse microbiota alterations in allergic respiratory disease make it difficult to find the exact microorganism to target for adjustment. Current evidence suggests that these common microbiota variations present in allergic respiratory disease are associated with immune disorders, which could be a potential therapeutic target for allergic respiratory disease. This review summarizes the current knowledge on microbiota changes in allergic respiratory disease, with the aim of identifying common microbiota changes associated with immune disorders and providing a theoretical basis for targeting therapies for allergic respiratory disease through effective modulation of key bacteria.

Chromoanagenesis are complex chromosomal rearrangements that are supposed to occur during a single catastrophic event. They may result in loss or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in which a healthy parent carrying a chromoanagenesis transmitted its rearrangement in an unbalanced manner to its descent. The rearrangements were characterized by karyotype, fluorescent in situ hybridization, chromosomal microarray and whole genome sequencing (WGS) in the parents and their offspring. We then hypothesized meiosis-pairing figures of parental chromosomes that may have led to meiotic recombination between normal and abnormal homologous chromosomes, resulting in the formation of new unbalanced rearrangements. This work underlines that chromoanagenesis can be associated with a normal phenotype and a normal fertility, even in males, and that WGS may be the unique way to identify these rearrangements in some cases. Chromoanagenesis can be transmitted in an unbalanced and unpredictable way because of meiotic recombination. Thus, genetic counseling and technical choice for prenatal diagnosis are complex. Finally this work questions the meiotic pairing mechanisms of complex rearrangements, still poorly understood.

Title Page:Title: Letter to the Editor: Longer-Term Outcomes after Bicuspid Aortic Valve Repair In 142 Patients.Article Type: Letter to the EditorCorrespondence: 1. Roomi RajaContact No: +92-3342946940. Email: Romirajagoindani@Yahoo.ComInstitute: Ziauddin University KarachiAddress: Hemilton Courts Block G-1 Flat 408 Near Teen Talwar Clifton KarachiCo-Authors: 2. Satesh KumarContact No: +92-3325252902. Email: Kewlanisatish@Gmail.ComInstitute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa Citi Garden East, KarachiWord Count: 335

Title Page:Title: Letter To The Editor: Long-Term Renal Function After Venoarterial Extracorporeal Membrane Oxygenation.Article Type: Letter To The EditorCorrespondence: 1. Sapna GoindaniContact No: +971 54 344 9435. Email: Sapnagoindani123@Gmail.ComInstitute: Peoples University Of Medical And Health Sciences For Women (Pumhsw)Address: Flat No 9, Building No 10 Bastakia Building, Al Hamriya Bur Dubai, DubaiOrcid: 0000-0003-4906-8463Co-Authors: 2. Muhammad Abdullah KhanContact No: +923032992689. Email: Abd2992689@Gmail.ComInstitute: Ziauddin University KarachiAddress: House No R 133 Block 11 Gulshan E Iqbal KarachiOrcid: 0000-0002-0653-5060Co-Authors: 3. Satesh KumarContact No: +92-3325252902. Email: Kewlanisatish@Gmail.ComInstitute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa Citi Garden East, KarachiORCID: 0000-0001-7975-6297Word Count: 354Conflict of interest : NoneAcknowledgment : NoneDeclaration: NoneDisclosure : NoneFunding : None

Background: Atrial fibrillation (AF) is common in patients with reduced left ventricle ejection fraction (RLVEF). The impact of concomitant surgical atrial fibrillation ablation (SAFA) in patients with RLVEF is uncertain. The purpose of this study was to assess the outcomes of concomitant SAFA in patients with RLVEF undergoing heart surgery on heart failure (HF) rehospitalization and mortality. Methods: Using a local registry and electronic health records linked with provincial civil register survival data from July 2002 to April 2019, we analyzed treatment and outcomes in a cohort of patients with AF and HF defined by left ventricle ejection fraction (LVEF) ≤ 40%. Health records were used to collect treatment and International Classification of Diseases (ICD 10) codes to determine outcomes. A negative binomial model was used to compare outcomes such as all-cause mortality and rehospitalization for heart failure. Results: The cohort included 682 patients with RLVEF and AF who underwent coronary artery bypass graft and/or valve surgery. A total of 196 patients (29%) underwent concomitant SAFA. After matching, 132 patients with concomitant SAFA were compared to 159 patients who did not undergo concomitant SAFA. At 6.0±3.7 years of follow-up, concomitant SAFA was not associated with lower all-cause mortality (P=0.9861) and reduction in rehospitalizations for heart failure decompensation (P=0.31) compared to patients who did not have concomitant SAFA performed. Post-operatively, concomitant SAFA might be associated with less vasopressor and mechanical support use (p=0.01). Conclusions: Concomitant SAFA during index cardiac surgery is safe but does not reduce mortality or rehospitalizations for HF. The effects of concomitant SAFA in the context of RLVEF needs to be better studied with prospective trials.

Introduction Mitral valve diseases affect 18.1 million people every year, and the increased life expectancy has led to increased disability-adjusted life-years. Depending on the type of valve that is used to replace mitral valves, the type of complications differs. While a bioprosthetic valve has a lower bleeding risk than a mechanical valve, the overall durability is generally lower. However, the novel generations of valves are suggested to have better durability. This study was conducted to assess the durability and complications of either type of valve. Materials and methods This study is a retrospective cohort study that assesses the risk factors, complications, performance and durability of valves in short and long follow up. The cases of this study included all patients who had undergone valvuloplasty from 2004 to 2014. Results The results show that the mortality rate and admission duration is not significantly different between the two types of valves. However, reoperation rates are higher among bioprosthetic valves by three times. Cardiac tamponade, pleural effusion, and valvular thrombosis rates are higher among mechanical valves in the short term, while GI bleeding, valvular thrombosis, valvular thrombectomy rates are more prevalent with mechanical valves in the long term. Conclusion While bioprosthetic valves inflict more minor complications their overall durability is less than mechanical valves.

Patients suffering retrograde type A dissection after TEVAR for type B dissection are at a higher risk of mortality than their spontanous counterparts and the kind of optimal therapy remains obscure. We present a rare case of successful open surgical repair where distal open anastomosis was accomplished cutting off the un-covered stent portion and suturing a vascular prosthesis to the dissected distal aortic arch including the covered stent part. The clinical course was regular. Immediate and radical repair in the aortic arch may be the adequate response in such instances.

Cardiac paragangliomas are extremely rare cardiac masses. Our patient presented with angina secondary to coronary atherosclerosis and was incidentally found to have a large cardiac mass on coronary angiography. He underwent a full imaging workup and ultimately excision of the mass. Final pathology demonstrated paraganglioma. This case illustrates the presentation, workup, and definitive treatment of this rare tumor.

Background: In patients with cardiovascular disease candidate for angiography, one of the major concerns is the incidence of contrast-induced nephropathy (CIN), especially in patients with renal failure. The purpose of the present study was to compare the preventive effects of nicorandil and atorvastatin on the incidence of CIN in patients with chronic kidney disease (CKD). Methods: In a clinical trial study, 270 patients with renal insufficiency nominated for angiography were randomly divided into three groups (each group n=90): hydration group (1000 mL saline), hydration + atorvastatin group (80 mg/day for 3 days), and hydration + nicorandil group (10 mg 3 times/day for 3 days). Serum creatinine (Cr) and blood urea nitrogen (BUN) levels as well as glomerular filtration rate (GFR) were evaluated before and 72 hours after the intervention. Results: At the end of the study, serum Cr and BUN levels in all three groups showed a significant increase compared to the pre-intervention, which was significantly more in the control group than the two groups. Furthermore, the amount of GFR in all three groups showed a significant decrease after-intervention, which was significantly more pronounced in the control group than in both groups. No significant differences were found between nicorandil and atorvastatin in serum concentrations of Cr and BUN as well as GFR levels at the end of the study. Conclusion: The nicorandil and atorvastatin intervention showed preventive effects on CIN in CKD patient’s candidate for angiography, but there was no significant difference between the two drugs.

Background: Full consensus optimizing the PRF preparation protocols could not be established yet. This study aimed to compare two commercially available centrifuges at various g and time protocols in terms of their influence on growth factor and cytokine values. Methods: Blood samples from 10 individuals were centrifuged either with PRF Duo® or Intra-Spin® device for PRF preparation. Values for PRF Duo® were adjusted to ~200g, ~400g, ~600g, ~800g and 10, 12, 14min while ~400g, 12min (control) was set for Intra-Spin®. PRF clots were embedded into well plates containing Dulbecco’s Modified Eagle’s Medium and PDGF-AB, TGF-β1 and IL-1β quantities at days 1, 3 and 7 were calculated by using ELISA kits. Results: Control and ~600g groups demonstrated prolonged PDGF-AB release compared to others whereas ~200g showed a tendency of burst release. A high and prolonged release pattern similar to control was detected in the 10min group. ~200g and ~600g groups showed high TGF-β1 release at day 1 and then, their release amounts reduced while an increase from day 1 to 3 was observed at only control group. Apart from the higher release at ~800g group, IL-1β release was similar for all study groups. Conclusions: In terms of growth factor and cytokine release, Intra-Spin® might be preferred instead of PRF Duo®. The recommended protocol of Intra-Spin® may give the best release outcomes for PRF Duo®. In order to confirm the results, further studies are needed.

In context of industry 4.0, a digital twin provides new opportunities for production optimization and failure prediction. Therefore, both industry and scientific research show increasing interest in digital twins. One of the most important sectors in the production value chain is material science, which plays a very important role for the product properties and processing strategies. However, the digital microscopic and macroscopic description of materials' properties and its processing are currently not fully defined. Therefore, in order to implement materials into the digital representations of production processes, a throughout digital description of the material and its properties -- a digital material twin -- is presented in this paper. An extended digital material twin is further defined and includes the processing history. Thus, a throughout description of the material is enabled. The extended material twins can be connected to a process chain. Thus, we describe the concept for a comprehensive description of the materials' properties within the production value chain. For more complex, data intensive, descriptions, a concept to reduce the data, the digital material shadow is introduced as well. Our approach defines a framework to thoroughly describe a material and its development during processing or production.

In thiswork,we have computed and implemented one-body integrals concerning gaussian confinement potentials over gaussian basis functions. Then, we have set an equivalence between gaussian and Hooke atoms and we have observed that, according to singlet and triplet state energies, both systems are equivalent for large confinement depth for a series of even number of electrons n = 2, 4, 6, 8 and 10. Unlike with harmonic potentials, gaussian confinement potentials are dissociative for small enough depth parameter; this feature is crucial in order to model phenomena such as ionization. In this case, in addition to corresponding Taylor series expansions, the first diagonal and sub-diagonal Padé approximant were also obtained, useful to compute the upper and lower limits for the dissociation depth. Hence, this method introduces new advantages compared to others.