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Background Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). Methods We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. Results The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). Conclusion Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.

Purpose: This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants. Methods: Individuals with protein altering variants in SOX11 were identified through exome and genome sequencing and international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation was assessed using Infinium MethylationEPIC array. The expression pattern of SOX11 in developing human brain was defined using RNAscope. Results: We reported 38 new patients with SOX11 variants. Idiopathic hypogonadotropic hypogonadism was confirmed as a feature of SOX11 syndrome. A distinctive pattern of blood DNA methylation was identified in SOX11 syndrome, separating SOX11 syndrome from other BAFopathies. Conclusion: SOX11 syndrome is a distinct clinical entity with characteristic clinical features and episignature differentiating it from BAFopathies. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.

BACKGROUND: Type 1 diabetes is a complex heterogenous autoimmune disease without therapeutic interventions available to prevent or reverse the disease. This study aimed to identify transcriptional changes associated with the disease progression in patients with recent-onset type 1 diabetes. METHODS: Whole-blood samples were collected as part of the INNODIA study at baseline and 12 months after diagnosis of type 1 diabetes. We used linear mixed-effects modelling on RNA-seq data to identify genes associated with age, sex, or disease progression. Cell-type proportions were estimated from the RNA-seq data using computational deconvolution. Associations to clinical variables were estimated using Pearson's or point-biserial correlation for continuous and dichotomous variables, respectively, using only complete pairs of observations. FINDINGS: We found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Significant associations of the gene expression changes were found with ZnT8A autoantibody positivity. Rate of change in the expression of 16 genes between baseline and 12 months was found to predict the decline in C-peptide at 24 months. Interestingly and consistent with earlier reports, increased B cell levels and decreased neutrophil levels were associated with the rapid progression. INTERPRETATION: There is considerable individual variation in the rate of progression from appearance of type 1 diabetes-specific autoantibodies to clinical disease. Patient stratification and prediction of disease progression can help in developing more personalised therapeutic strategies for different disease endotypes. FUNDING: A full list of funding bodies can be found under Acknowledgments. ispartof: EBIOMEDICINE vol:92 ispartof: location:Netherlands status: published

Arboviral transmission through transplanted organs is rare. We report a highly probable case of dengue viral transmission during live donor liver transplantation. Fever with severe thrombocytopenia was observed in the donor and recipient within 6 and 9 days after transplantation, respectively. Dengue diagnosis was confirmed by testing blood and explant tissue from the donor and recipient using dengue-specific NAT (nucleic acid testing) and serology. Serology indicated the donor had secondary dengue infection that ran a mild course. However, the dengue illness in the recipient was severe and deteriorated rapidly, eventually proving fatal. The recipient's explant liver tissue tested negative for viral RNA indicative of a pretransplant naive status. The prM-Envelope gene sequence analysis of the donor and recipient viral RNA identified a similar serotype (DENV1) with almost 100% sequence identity in the envelope region. Molecular phylogenetic analysis of donor and recipient viral envelope sequences with regional and local dengue strains further confirmed their molecular similarity, suggesting a probable donor-to-recipient transmission via organ transplantation. Screening of living donors for dengue virus may be considered in endemic regions.

Background: We explored parents’ experiences of using a hybrid closed-loop system when caring for a very young child with type 1 diabetes. Our objectives were to understand the impact of using this technology on users’ quality of life and inform its use in routine clinical care. Methods: Interviews were conducted with parents of 30 children (aged 1-7 years) who participated in a randomised controlled trial comparing closed-loop insulin delivery with sensor-augmented pump therapy. Findings: Parents reported major clinical benefits to using the closed-loop system, including more time being spent in range. Parents welcomed opportunities to collaborate with the system (using Ease-off and Boost functions) when their own knowledge could enhance its efficacy. Parents also reported a lessened need for health professional input after the initial transition onto the system had been made. Parents described wide-ranging quality-of-life benefits to using a system that automatically regulated blood glucose. Parents reported sleeping better, worrying less about their child and feeling more confident entrusting their child’s care to others, and how these individuals were more willing to assume caregiving responsibilities. Parents also described how their child felt more normal and experienced better sleep, mood and concentration, and lessened distress. Siblings also benefitted from parents’ time and attention being less focused on diabetes management. While parents highlighted multiple benefits to being able to administer insulin using a smartphone, difficulties were experienced stowing this device on the child’s body. Interpretation: Using a hybrid closed-loop system in very young children can have potentially life-changing consequences and may result in a lessened demand for health professionals’ input. Systems may need to be customised for use in very young children. Funding Information: The European Commission within the Horizon 2020 Framework Programme under the grant agreement number 731560 funded this work. Declaration of Interests: RH reports having received speaker honoraria from Eli Lilly and Novo Nordisk, serving on advisory panels for Eli Lilly and Novo Nordisk, receiving licence fees from BBraun and Medtronic. RH reports patent patents, patent applications, shareholding and directorship at CamDiab. FC has attended Advisory Boards and obtained speaking fees for Abbott, Medtronic, Lilly, and NovoNordisk. EFR reports having received speaker honoraria from Eli Lilly and Novo Nordisk, and serving on advisory boards for Eli Lilly and Sanofi. SH declares having received speakers honoraria from Eli Lilly, Sanofi and Pfizer. TMK has received speaking honoraria from Eli Lilly and MerckSerono, and consulted Sanofi for a transition brochure. BRM has received speaker honoraria from Abbott Diabetes Care, Eli Lilly, Medtronic, Novo Nordisk, Roche Diabetes Care, Sanofi and Menarini, and has been on the advisory boards of Roche Diabetes Care and Abbott Diabetes Care. The Authors JL, DR, RIH, CKB, JF, JMA, AT, US and BK declare that there is no conflict of interest. Ethics Approval Statement: Participants were consented into the interview study when they were consented into the trial. Approval was received from relevant Ethics Committees in participating sites/countries and relevant national regulatory authorities.

Background: Closed-loop insulin delivery systems have the potential to address the issue of suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of Cambridge hybrid closed-loop algorithm with usual care over six months in this population. Methods: In a multicentre, multinational, one-period, parallel randomised controlled trial, participants aged 6-18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. We randomly assigned participants to closed-loop insulin delivery or to usual care (control) for six months. The Cambridge closed-loop algorithm running on a smartphone was used with either (i) modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration) or (ii) Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). Primary endpoint was change in HbA1c at six months combing data from both configurations. Analysis was by intention-to-treat. Trial registration ClinicalTrials.gov, NCT02925299. Findings: We randomised 133 participants (mean±SD baseline HbA1c 8·2±0·7% vs 8·3±0·7%), 65 to closed-loop and 68 to control. At six months, HbA1c was 0·32% lower with closed-loop compared to control (95%CI 0·04 to 0·59; p=0·02). Closed-loop usage was low with FlorenceM due to failing phone enclosures (40% [26, 53]; median [IQR]), but consistently high with CamAPS FX (93% [88, 96]). In post-hoc analysis, HbA1c in the CamAPS FX closed-loop cohort (n=21) was 1·05% lower (95%CI 0·67 to 1·43; p

The paper paves a way to understand supply chain social sustainability practices and their associated barriers to implementation in the Indian and North American energy and manufacturing sectors. A systematic literature review and 4-point Likert scale survey provide clarity on the barriers and their perception from an industrial perspective. Findings from this study highlight that while the criticality of barriers differs with industry and geographies, some barriers are common to all. The study also highlights an approach needed for these sectors by identifying the most common barriers by providing a clear path on what practices can bring about the most impact in resolution. 20 barriers are identified, of which 3 show a stark difference in perception on its criticality against current published research work. The paper also identifies the top barriers along with the practices that make it most easy to implement. 11 common barriers that exist in the target industries of the two countries are identified and 6 easiest-to-resolve barriers are revealed, analyzing the maximum number of mitigation practices available. The paper concludes by identifying eight most impactful social sustainability practices that can help resolve the maximum number of implementation barriers and highlights avenues for further research in the field.

Microalgae-derived functional materials, such as food supplements, drugs, and biofuels have gained a great deal of attention in recent times. Among the several microalgae investigated for biomaterials production, Euglena spp. are particularly attractive due to their easiness to grow in cultures and the ability to produce numerous bioactive compounds through extremely complex metabolic pathways. The genus Euglena comprises more than 300 species of unicellular, predominantly freshwater flagellates of worldwide distribution. The plastids in Euglena cells have been recognized as a site of the production of proteins, fatty acids, and many other value-added metabolites. Euglena is one of the few microorganisms that simultaneously produces antioxidants, such as β-carotene, l -ascorbic acid, and α-tocopherol, along with wax esters, phytotoxins and polyunsaturated fatty acids (PUFAs), that are useful in the manufacture of pharmaceuticals, cosmeceuticals, and nutraceuticals. Nevertheless, the biotechnological potency of Euglena for industrial production has been exploited limitedly. This review summarizes the major value-added compounds obtained from the protist genus Euglena and their potential and prospects for commercial production.

AimsTo explore parents’ experiences of using a hybrid closed-loop system (CamAPS FX) when caring for a very young child (aged 1–7 years) with type 1 diabetes.MethodsInterviews with n = 33 parents of 30 children who used the system during a randomised controlled trial. Data analysis used a descriptive thematic approach.ResultsWhile some parents were initially reticent about handing control to the system, all reported clinical benefits to using the technology, having to do less diabetes-related work and needing less clinical input over time. Parents welcomed opportunities to enhance the system’s efficacy (using Ease-off and Boost functions) as required. Parents described how the system’s automated glucose control facilitated more normality, including sleeping better, worrying less about their child, and feeling more confident and able to outsource care. Parents also described more normality for the child (alongside better sleep, mood and concentration, and lessened distress) and siblings. Parents liked being able to administer insulin using a smartphone, but suggested refinements to device size and functionality.ConclusionsUsing a hybrid closed-loop system in very young children can facilitate greater normality and may result in a lessened demand for health professionals’ input. Systems may need to be customised for very young children.

Nanoporous polyethersulfone (PES) membranes with high surface porosity and uniform pore size distribution were prepared by combining the phase separation in NMP/nonane mixed solvent system with the traditional nonsolvent induced phase inversion process. The effects of PES concentration, nonane concentration, evaporation time, casting solution temperature, and varied mixed solvent systems on the porous PES membrane surface morphology were thoroughly investigated and optimized. The optimized nanoporous PES membrane showed a high surface porosity with a uniform pore size of 20 nm, rendering an exceptional molecular weight cut-off of as low as 100 k Dalton. In addition, the membrane exhibited a significant molecular size exclusion with water permeance of 121 LMH bar−1, bovine serum albumin (BSA) protein rejection of 60.1%, and γ-globulin protein rejection of 99.5% at 0.5 bar, respectively, demonstrating the potential of the as-prepared nanoporous PES membrane for application in protein separation.

We introduce novel sequences using indirect detection to correlate quadrupolar nuclei and spin-1/2 isotopes, other than 1H and 19F. These sequences use γ-encoded symmetry-based R N n ν schemes that reintroduce the space component |m| = 1 of the heteronuclear dipolar coupling. These schemes can be applied to the indirectly detected spin in Dipolar-mediated Heteronuclear Multiple-Quantum Correlation (D-HMQC) sequence or to the detected isotope in a novel sequence, named Dipolar-mediated Heteronuclear Universal-Quantum Correlation (D-HUQC). We show that the signal of these sequences using γ-encoded recoupling does not depend on the γ Euler angle relating the inter-nuclear vector between the coupled spins to the MAS rotor-fixed frame. Therefore, the transfer efficiency of these sequences is in principle higher than that of D-HMQC methods using non-γ-encoded recoupling. Furthermore, numerical simulations show that the heteronuclear correlation experiments employing γ-encoded recoupling are more robust to Chemical Shift Anisotropy (CSA) of the irradiated spin and MAS frequency fluctuations. These results are confirmed by 13C-{15N} heteronuclear correlation on glycine and 31P-27Al ones on VPI-5 and Na7(AlP2O7)4PO4. These experiments indicate that R 16 3 5 recoupling produces the highest signal-to-noise ratio in heteronuclear correlation 2D experiments when the detected spin-1/2 nuclei are subject to large CSA.

Background Angiosarcoma is an uncommon high-grade sarcoma in children. Visceral angiosarcoma involving the ovary is extremely rare. Because of the lack of recurrent cytogenetic alterations, histopathological identification of this uncommon tumor in unusual sites like the ovary demands pathologic expertise. Complete surgical resection and radiotherapy are the chief treatment modalities determining survival, with chemotherapy contributing a minor role. Case We discuss a 11-year-old prepubertal girl who presented with primary angiosarcoma of the ovary. Summary and Conclusion Early realization of such exceptional presentations of these tumors is needed to achieve the best treatment outcome.