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Objectives Polycystic ovary syndrome (PCOS) increases non-alcoholic fatty liver disease (NAFLD) risk and severity in adults, but data in adolescents with diverse backgrounds are limited. We evaluated NAFLD prevalence and characterized NAFLD risk factors in overweight/obese adolescents by PCOS status. Methods Retrospective study of overweight (n=52)/obese (n=271) female adolescents (12–18 years old), evaluated clinically 2012–2020, was conducted comparing PCOS patients to age-matched non-PCOS controls. NAFLD was defined as ALT≥44U/L x2 and/or ≥80U/L x1, hepatic steatosis on imaging, or NAFLD on biopsy, in absence of other liver disease. Metabolic comorbidities were captured. Log-binomial regression models estimated prevalence risk ratios (PR). Results NAFLD prevalence was 19.1 % in adolescents with PCOS (n=161), similar to those without (n=162) (16.8 %, p=0.6). Adolescents with PCOS were more likely to have insulin resistance, hypercholesterolemia, and higher triglycerides (p Conclusions Almost 1 in 5 overweight/obese female adolescents had NAFLD, but PCOS did not increase NAFLD risk in this diverse cohort. Among young women with PCOS, concomitant T2DM did increase the risk for NAFLD. Closer monitoring of obesity comorbidities in adolescents with PCOS is essential for optimizing health and merits updating current guidelines.

It is unknown whether some donor specific antibodies (DSA) can be crossed at the time of lung transplant without desensitization or augmented induction immunosuppression. This study assessed whether crossing low-level pre-transplant DSA (defined as mean fluorescence intensity (MFI) 1000-6000) without augmented immunosuppression is associated with worse retransplant-free or chronic lung allograft dysfunction (CLAD)-free survival. Of the 458 included recipients, low-level pre-transplant DSA was crossed in 39 (8.6%) patients. The median follow-up time was 2.2 years. There were 15 (38.5%) patients with Class I DSA and 24 (61.5%) with Class II DSA. There was no difference in adjusted overall retransplant-free survival between recipients where pre-transplant DSA was and was not crossed (HR: 0.98 (95% CI = 0.49-1.99), p = 0.96). There was also no difference in CLAD-free survival (HR: 0.71 (95% CI = 0.38-1.33), p = 0.28). There was no difference in Grade 3 PGD at 72 hours (OR: 1.13 (95% CI = 0.52-2.48), p = 0.75) or definite or probable AMR (HR: 2.22 (95% CI = 0.64-7.61), p = 0.21). Lung transplantation in the presence of low-level DSA without planned augmented immunosuppression is not associated with worse overall or CLAD-free survival among recipients with intermediate-term follow-up. This article is protected by copyright. All rights reserved.

The Bcl-2-associated death promoter BAD is a prognostic indicator for good clinical outcome of breast cancer patients; however, whether BAD affects breast cancer biology is unknown. Here we showed that BAD increased cell growth in breast cancer cells through two distinct mechanisms. Phosphorylation of BAD at S118 increased S99 phosphorylation, 14-3-3 binding and AKT activation to promote growth and survival. Through a second, more prominent pathway, BAD stimulated mitochondrial oxygen consumption in a novel manner that was downstream of substrate entry into the mitochondria. BAD stimulated complex I activity that facilitated enhanced cell growth and sensitized cells to apoptosis in response to complex I blockade. We propose that this dependence on oxidative metabolism generated large but nonaggressive cancers. This model identifies a non-canonical role for BAD and reconciles BAD-mediated tumor growth with favorable outcomes in BAD-high breast cancer patients.

Background Unplanned rehospitalizations (UR) within 30 days of discharge are common after lung transplantation. It is unknown whether UR represents preventable gaps in care or necessary interventions for complex patients. The objective of this study was to assess the incidence, causes, risk factors, and preventability of UR after initial discharge after lung transplantation. Methods This was a single-center prospective cohort study. Subjects completed a modified short physical performance battery to assess frailty at listing and at initial hospital discharge after transplantation and the State-Trait Anxiety Inventory at discharge. For each UR, a study staff member and the patient's admitting or attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely preventable) to rate readmission preventability. A total sum score of 2 or higher defined a preventable UR. Results Of the 90 enrolled patients, 30 (33.3%) had an UR. The single most common reasons were infection (7 [23.3%]) and atrial tachyarrhythmia (5 [16.7%]). Among the 30 URs, 9 (30.0%) were deemed preventable. Unplanned rehospitalization that happened before day 30 were more likely to be considered preventable than those between days 30 and 90 (30.0% versus 6.2%, P = 0.04). Discharge frailty, defined as short physical performance battery less than 6, was the only variable associated with UR on multivariable analysis (odds ratio, 3.4; 95% confidence interval, 1.1-11.8; P = 0.04). Conclusions Although clinicians do not rate the majority of UR after lung transplant as preventable, discharge frailty is associated with UR. Further research should identify whether modification of discharge frailty can reduce UR.

Purpose Lung transplant recipients with pre-transplant donor specific antibodies (DSA) are often treated with augmented immunosuppression. It is unknown whether some DSA can be safely crossed without additional therapies. We implemented a protocol allowing transplant when crossing select low level DSA (defined as mean fluorescence intensity (MFI) 1000-5000) without planned augmented immunosuppression. Methods This was a single center retrospective cohort study between 4/1/2015-8/31/2020. All recipients received solumedrol and basiliximab induction without desensitization. Presence of low level pre-transplant DSA was recorded. All post-transplant DSA was monitored within 14 days of transplant and then at routine intervals. The primary study outcomes were overall survival, definite CLAD≥1-free survival, and definite antibody mediated rejection (AMR), all defined according to ISHLT consensus guidelines. Results Of the 453 recipients, 36 (7.9%) had a low-level pre-transplant DSA crossed at transplant (Table 1). 13 had Class I antibodies and 26 had Class II. The median historical DSA MFI was 1800 (IQR 1300-2400) and the median most recent MFI was 1200 (IQR 950-2000). Among recipients where pre-transplant DSA was crossed, 17 (47.2%) had persistent post-transplant DSA with a median peak MFI of 7400. Class II antibodies were more likely to be detected post-transplant than Class I (57.7% vs 15.4%, p=0.02). There was no statistical difference in definite AMR in recipients where pre-transplant DSA was and was not crossed (8.3% vs 3.1%, p=0.11). With a median follow-up time of 2.4 years, there were no differences in adjusted overall survival (HR=1.14, 95% CI=0.57-2.32, p=0.71) or CLAD≥1-free survival (HR=0.82, 95% CI=0.44-1.54, p=0.54). Conclusion Lung transplantation in the presence of low level DSA without planned augmented immunosuppression was not associated with worse overall or CLAD-free intermediate-term survival but may be associated with increased AMR.

Cloud Computing is an example of the distributed system where the end user has to connect to the services given by the cloud which is maintained by the cloud service provider (CSP). The user has to have certain trust upon the cloud as finally, the end user has to migrate the jobs into the cloud of some third party, as the on-premises data or sources are to be kept across the globe, the CSP have to maintain the trust level so that the end user can opt for the services given by the certain trusted Cloud. Ultimately there will be various elements of levels happening at the CSP side to maintain the trust level, like the safety features for security has to be identified, federation related or Virtual Machine migration techniques status has to be always monitored to maintain and avoid certain uncertainty which will affect the trust level of the cloud, which can lead to the compromised situation in between the end user and CSP, as a result the trust value will decrease, In this paper we are proposing a techniques where the security features and conditions for load balancing monitoring technique with proactive actions will be analyzed to maintain the specified trust level.

The mahseers (Tor, Neolissochilus and Naziritor) are an important group of fishes endemic to Asia with the conservation status of most species evaluated as threatened. Conservation plans to revive these declining wild populations are hindered by unstable taxonomy. Molecular phylogeny studies with mitochondrial genome have been successfully used to reconstruct the phylogenetic tree and to resolve taxonomic ambiguity. In the present study, complete mitochondrial genome of Tor tor has been sequenced using ion torrent next-generation sequencing platform with coverage of more than 1000 x. Comparative mitogenome analysis shows higher divergence value at ND1 gene than COI gene. Further, occurrence of a distinct genetic lineage of T. tor is revealed. The phylogenetic relationship among mahseer group has been defined as Neolissochilus hexagonolepis ((T. sinensis (T. putitora, T. tor), (T. khudree, T. tambroides)).

Macrobrachium rosenbergii is an aquaculture species of global importance whose production has sharply declined since 2005. Single nucleotide polymorphisms (SNPs) in transcribed sequences are likely to have high association with economic traits and are important for marker assisted selection. SNPs were mined in 34 reported transcripts from 4 wild M. rosenbergii stocks of India using the amplicon approach and high-throughput sequencing platforms. Out of 320 SNPs detected, 134 were common to all stocks while 3 were diagnostic. Pair-wise Nei’s genetic distances (0.304–0.469) showed phylogeny consistent with geographical distribution. AMOVA analysis revealed estimated variance of 21.5 among populations. The transition to transversion ratio was 2.20. Changes in amino acid classes and peptide stability were recorded for 80 non-synonymous SNPs while change in codon preference was noted for 138 synonymous ones. Four pathogen defence genes were highly polymorphic, of which lectin 3 had the highest SNP rate (6 SNPs/100 bp). This approach for mining SNPs and using them for population differentiation in a single step is reported for the first time.

Purpose Rates of deep vein thrombosis (DVT) range from 20-60% in patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome. Data on the rates of DVT in lung transplant recipients bridged with ECMO is limited. The objective of this study was to report incidence and outcomes, including use of anticoagulation and subsequent bleeding rates, of DVT in ECMO-bridged transplant recipients. Methods This was a single center retrospective cohort study of all adult ECMO-bridged lung transplant recipients from 5/1/15 to 9/30/19. Recipients underwent routine ultrasound screening for upper extremity (UE) and lower extremity (LE) DVT following ECMO decannulation. Results Of the 45 ECMO-bridged recipients, 3 died before ECMO decannulation and 4 did not have screening ultrasounds, leaving 38 patients in the cohort. The majority (81.5%) were bridged using venovenous ECMO and most (63%) were decannulated immediately following transplant (Table 1). Among remaining recipients, mean time to decannulation was 4 days. Among recipients with adequate studies, the incidence of LE DVT was 26.4% and the incidence of UE DVT was 63.6%. Neither total time on ECMO, cannula size, nor need for femoral vein cannulation was associated with LE or UE DVT. All of the recipients with LE DVT but two, were anticoagulated. Three needed an inferior vena cava filter placed. Of recipients with UE DVT only, 43.75% were anticoagulated. Among all anticoagulated recipients, five (31.25%) had significant bleeding during their initial hospitalization requiring cessation of anticoagulation. Conclusion DVTs are common in patients bridged to lung transplantation with ECMO, particularly in the upper extremity. Bleeding poses further challenges for systemic anticoagulation in this high risk population. Additional studies are needed to identify risk factors for both LE DVT and for bleeding to help guide decisions for systemic anticoagulation in this population.

Progressive retinal atrophy (PRA) is one of the major causes of retinal photoreceptor cell degeneration in canines. The inheritance pattern of PRA is autosomal recessive and genetically heterogeneous. Here, using targeted sequencing technology, we have performed exome sequencing of 10 PRA-affected (Spitz=7, Cocker Spaniel=1, Lhasa Aphso=1 and Spitz-Labrador cross breed=1) and 6 normal (Spitz=5, Cocker Spaniel=1) dogs. The high-throughput sequencing using 454-Roche Titanium sequencer generated about 2.16 Giga bases of raw data. Initially, we have successfully identified 25,619 single nucleotide polymorphisms (SNPs) that passed the stringent SNP calling parameters. Further, we performed association study on the cohort, and the highly significant (0.001) associations were short-listed and investigated in-depth. Out of the 171 significant SNPs, 113 were previously unreported. Interestingly, six among them were non-synonymous coding (NSC) SNPs, which includes CPPED1 A>G (p.M307V), PITRM1 T>G (p.S715A), APP G>A (p.T266M), RNF213 A>G (p.V1482A), C>A (p.V1456L), and SLC46A3 G>A (p.R168Q). On the other hand, 35 out of 113 unreported SNPs were falling in regulatory regions such as 3'-UTR, 5'-UTR, etc. In-depth bioinformatics analysis revealed that majority of NSC SNPs have damaging effect and alter protein stability. This study highlighted the genetic markers associated with PRA, which will help to develop genetic assay-based screening in effective breeding.

The resistance to methotrexate by a number of cancer cells such as breast cancer cell-line MDA-MB-231 due to poor permeability renders it less effective as an anticancer agent for these cells. Proline prodrug of methotrexate (Pro-MTX) was designed as a substrate of prolidase which is specific for imido bond of dipeptide containing proline and expected to penetrate MDA-MB-231 cells more efficiently. The prodrug was synthesized by solid-phase peptide synthesis method and examined as a substrate of pure prolidase as well as cell homogenate. The cytotoxicity against MDA-MB-231 and non-methotrexate resistant breast cancer cell line, MCF-7 was also examined by XTT assay. The results showed that Pro-MTX was a substrate of prolidase. It was also shown that the prodrug could be converted to parent drug methotrexate in Caco-2 and HeLa cell homogenate. When tested with Caco-2 and MCF-7 cells, Pro-MTX showed weaker cytotoxicity compared with methotrexate. But for methotrexate resistant MDA-MB-231 cells, Pro-MTX showed stronger activity than methotrexate. The results indicated that the proline prodrug of methotrexate may overcome the resistance of human breast cancer cells in culture.