bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aquaporin 9 induction in human iPSC‐derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency
Authors: Laemmle Alexander , Poms Martin , Hsu Bernadette , Borsuk Mariia , Rüfenacht Véronique , Robinson Joshua , Sadowski Martin C. , Nuoffer Jean‐Marc , Häberle Johannes , Willenbring Holger 
Published: November 2021

Abstract

Background and Aims
Patient‐derived human‐induced pluripotent stem cells (hiPSCs) differentiated into hepatocytes (hiPSC‐Heps) have facilitated the study of rare genetic liver diseases. Here, we aimed to establish an in vitro liver disease model of the urea cycle disorder ornithine transcarbamylase deficiency (OTCD) using patient‐derived hiPSC‐Heps.

Approach and Results
Before modeling OTCD, we addressed the question of why hiPSC‐Heps generally secrete less urea than adult primary human hepatocytes (PHHs). Because hiPSC‐Heps are not completely differentiated and maintain some characteristics of fetal PHHs, we compared gene‐expression levels in human fetal and adult liver tissue to identify genes responsible for reduced urea secretion in hiPSC‐Heps. We found lack of aquaporin 9 (AQP9) expression in fetal liver tissue as well as in hiPSC‐Heps, and showed that forced expression of AQP9 in hiPSC‐Heps restores urea secretion and normalizes the response to ammonia challenge by increasing ureagenesis. Furthermore, we proved functional ureagenesis by challenging AQP9‐expressing hiPSC‐Heps with ammonium chloride labeled with the stable isotope [15N] (15NH4Cl) and by assessing enrichment of [15N]‐labeled urea. Finally, using hiPSC‐Heps derived from patients with OTCD, we generated a liver disease model that recapitulates the hepatic manifestation of the human disease. Restoring OTC expression—together with AQP9—was effective in fully correcting OTC activity and normalizing ureagenesis as assessed by 15NH4Cl stable‐isotope challenge.

Conclusion
Our results identify a critical role for AQP9 in functional urea metabolism and establish the feasibility of in vitro modeling of OTCD with hiPSC‐Heps. By facilitating studies of OTCD genotype/phenotype correlation and drug screens, our model has potential for improving the therapy of OTCD.
Projected private hospital expenditure in Ireland, 2018–2035: What role for demographics, cost, and Sláintecare?
Authors: Keegan Conor , Brick Aoife , Henry Edward , Bergin Adele 
Published: November 2021

AbstractDespite private hospitals occupying an important role in the delivery of acute hospital care in Ireland, an understanding of future spending pressures on these services is limited. Particularly, a key dimension of Ireland's ambitious roadmap for healthcare reform (Sláintecare) seeks to remove private practice from public hospitals. However, to date, there has been no examination of how this reform could impact private hospital demand and expenditure, and ultimately, the capacity to treat public patients. Using previously unavailable administrative health insurer data and a healthcare macro‐simulation projection model, we project real (volume‐based) and nominal expenditure on private hospital services over the medium‐term (2018–2035). We develop a number of projection scenarios that vary assumptions in relation to population growth and ageing, healthy ageing, and the future cost of care delivery. Additionally, by developing profiles of private activity in public hospitals, we examine how the removal of private practice from public hospitals could impact on demand and expenditure in private hospitals over time. Findings from this analysis have implications for capital investment and workforce planning in private hospitals, and failure to meet future demand could have implications for access to care in public hospitals. Moreover, should private practice be ended in public hospitals, most complex private in‐patient and emergency care is likely to remain within the public hospitals with limited capacity benefits for the public system.
COVID‐19 and renin angiotensin aldosterone system: Pathogenesis and therapy
Authors: Babajani Fatemeh , Kakavand Atefeh , Mohammadi Hossien , Sharifi Armin , Zakeri Saba , Asadi Soheila , Afshar Zeinab Mohseni , Rahimi Zohreh , Sayad Babak 
Published: November 2021

AbstractAimsThe severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) binds to the ACE2 component of the renin‐angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS‐CoV‐2 infection, therapeutic approaches, and clinical trials in this field.MethodsWe surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS‐CoV‐2 infection along with various COVID‐19 therapies based on the RASS components were included in the study.ResultsACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang‐(1‐7) levels, which can be suggestive for their role as therapeutics against SARS‐CoV‐2 infection. Beta‐adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID‐19. Some antihyperglycemic agents could be potentially protective against COVID‐19‐induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID‐19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies.ConclusionRegarding the suggested potential therapies for COVID‐19, there are many clinical trials whose results might change the treatment strategies of SARS‐CoV‐2 infection. So, the results of well‐organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID‐19 will be useful in the management and therapy of the disease.
Retracted: Endometrial scratch injury in infertile women seeking conception through natural or intrauterine insemination cycles: A systematic review and meta‐analysis
Authors: Maged Ahmed M. , Ogila Asmaa I. , Mohsen Reham A. , Mahmoud Safaa I. , Fouad Mona A. , El Komy Rasha O. , Lasheen Yossra , El‐Nassery Noura , Dahab Sherif , Hussein Eman A. 
Published: November 2021

Maged, AM, Ogila, AI, Mohsen, RA, et al. Endometrial scratch injury in infertile women seeking conception through natural or intrauterine insemination cycles: A systematic review and meta‐analysis. Int J Gynecol Obstet. 2021; 00: 1–20. doi:10.1002/ijgo.14030The above article, published online on 17 November 2021 on Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor‐in‐Chief, Professor Michael Geary, the International Federation of Gynecology and Obstetrics and John Wiley & Sons Ltd. The journal was made aware of concerns regarding the considerable overlap with a previously published systematic review.[1] The authors responded to the concerns raised and it was found that some of the source clinical trial data could not have been accessed in this systematic review. As a result, the journal is issuing this retraction.[1] Bui BN, Lensen SF, Gibreel A, Martins WP, Torrance H, Broekmans FJ. Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination. Cochrane Database of Systematic Reviews 2022, Issue 10. Art. No.: CD011424. DOI: 10.1002/14651858.CD011424.pub4.
Next generation quantum theory of atoms in molecules for the design of emitters exhibiting thermally activated delayed fluorescence with laser irradiation
Authors: Li Zi , Yang Yong , Xu Tianlv , Früchtl Herbert , van Mourik Tanja , Paterson Martin J. , Shigeta Yasuteru , Kirk Steven R. , Jenkins Samantha 
Published: November 2021

AbstractThe effect of a static electric (E)‐field and an unchirped and chirped laser pulse field on the cycl[3.3.3]azine molecule was investigated using next‐generation quantum theory of atoms in molecules (NG‐QTAIM). Despite the magnitude of the E‐field of the laser pulses being an order of magnitude lower than for the static E‐field, the variation of the energy gap between the lowest lying singlet (S1) and triplet (T1) excited states was orders of magnitude greater for the laser pulse than for the static E‐field. Insights into the response of the electronic structure were captured by NG‐QTAIM, where differences in the inverted singlet‐triplet gap due to the laser pulses were significant larger compared to those induced by the static E‐field. The response of theS1andT1excited states, as determined by NG‐QTAIM, switched discontinuously between weak and strong chemical character for the static E‐field. In contrast, the response to the laser pulses, determined by NG‐QTAIM, is to induce a continuous range of chemical character, indicating the unique ability of the laser pulses to induce polarization effects in the form of “mixed” bond types. Our analysis demonstrates that NG‐QTAIM is a useful tool for understanding the response to laser irradiation of the lowest‐lying singletS1and tripletT1excited states of emitters exhibiting thermally activated delayed fluorescence. The chirped laser pulse led to more frequent instances of the desired outcome of an inverted singlet‐triplet gap than the unchirped pulse, indicating its usefulness as a tool to design more efficient organic light‐emitting diode devices.
Development, validation, and clinical application of an FIA‐MS/MS method for the quantification of lysophosphatidylcholines in dried blood spots
Authors: Yue Xiaofei , Liu Wei , Liu Ying , Shen Min , Zhai Yanhong , Ma Zhijun , Cao Zheng 
Published: November 2021

AbstractBackgroundLysophosphatidylcholine (LPC) plays pivotal roles in several physiological processes and their disturbances are closely associated with various disorders. In this study, we described the development and validation of a reliable and simple flow injection analysis–tandem mass spectrometry (FIA‐MS/MS)‐based method using dried blood spots (DBS) for quantification of four individual LPC (C20:0, C22:0, C24:0, and C26:0).MethodsLysophosphatidylcholines were extracted from 3.2 mm DBS with 85% methanol containing 60 ng/ml internal standard using a rapid (30 min) and simple procedure. The analytes and the internal standard were directly measured by triple quadrupole tandem mass spectrometry in multiple reactions monitoring mode via positive electrospray ionization.ResultsMethod validation results showed good linearity ranging from 50 to 2000 ng/ml for each LPC. Intra‐ and inter‐day precision and accuracy were within the acceptable limits at four quality control levels. Recovery was from 70.5% to 107.0%, and all analytes in DBS were stable under assay conditions (24 h at room temperature and 72 h in autosampler). The validated method was successfully applied to assessment of C20:0‐C26:0LPCs in 1900 Chinese neonates. C26:0‐LPC levels in this study were consistent with previously published values.ConclusionWe propose a simple FIA‐MS/MS method for analyzing C20:0‐C26:0LPCs in DBS, which can be used for first‐tier screening.
Mechanical properties and microstructural organization of common ulnar collateral ligament grafts: Palmaris longus and gracilis tendons
Authors: Solon Lorenzo F. , Castile Ryan M. , Smith Matthew V. , Lake Spencer P. 
Published: November 2021

AbstractUlnar collateral ligament (UCL) injuries are becoming increasingly common. The palmaris longus (PL) and gracilis (GR) tendons are the most common grafts used in UCL reconstructions. While clinical studies have demonstrated relatively similar outcomes for either graft, there is little quantitative data describing these grafts from a material perspective, specifically the mechanical and microstructural properties of these tissues and how they respond under dynamic loading. The purpose of this descriptive laboratory study was to quantify and compare the mechanical and microstructural properties of PL and GR tendons. A total of 13 PL and 11 GR cadaveric human tendons were obtained. Each specimen was divided into three subregions and subjected to preconditioning, ramp‐and‐hold stress‐relaxation and ramp‐to‐failure testing. Mechanical parameters were computed for each sample, and a polarized light imaging technique was used to simultaneously evaluate dynamic microstructural properties during testing. The PL had larger toe‐ and linear‐region modulus values than the GR. Within the GR, the distal subregion had stronger collagen alignment than the proximal subregion at the zero, transition and linear portions of the stress‐strain curve. The PL and GR, have similar mechanical properties and similar microstructural alignment under load. The PL graft has similar properties throughout its length whereas the GR properties exhibited slight differences in strength of alignment along its length. The PL and GR exhibit larger moduli values and more strongly/uniformly aligned collagenous microstructure when qualitatively compared to data previously published on the native UCL.
Parenteral nutrition compatibility and stability: A comprehensive review
Authors: Boullata Joseph I. , Mirtallo Jay M. , Sacks Gordon S. , Salman Genene , Gura Kathleen , Canada Todd , Maguire Angela ,   the ASPEN Parenteral Nutrition Safety Committee
Published: November 2021

AbstractSeveral guidance documents support best practices across the stages of the parenteral nutrition (PN) use process to optimize patient safety. The critical step of PN order verification and review by the pharmacist requires a contextual assessment of the compatibility and stability implications of the ordered PN prescription. This article will provide working definitions, describe PN component characteristics, and present a wide‐ranging representation of compatibility and stability concerns that need to be considered prior to preparing a PN admixture. This paper has been approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.
Different typical dietary lipid consumption affects the bile acid metabolism and the gut microbiota structure: an animal trial using Sprague‐Dawley rats
Authors: Ye Zhan , Xu Yong‐Jiang , Liu Yuanfa 
Published: November 2021

AbstractBACKGROUNDThe palm oil (PO), leaf lard oil (LO), rapeseed oil (RO), sunflower oil (SO) and linseed oil (LN) are five of the most typical dietary lipids in most Asian countries. However, their influences on gut health, and the connections between the fatty acid composition, the gut microbiota, and the bile acid metabolism are not fully understood.RESULTSIn the present study, results showed that compared with polyunsaturated fatty acid (PUFA)‐rich SO and LN, the saturated fatty acid (SFA)‐rich and monounsaturated fatty acid (MUFA)‐rich PO, LO and RO were more likely to decrease the re‐absorption of bile acid in the colon, which was probably caused by their different role in modulating the gut microbiota structure. LO consumption significantly up‐regulated the Cyp27a1, FXR and TGR5 gene expression level (P < 0.05). The correlation results suggested that the C18:0 was significantly positive correlated with these three genes, indicating that intake of SFA‐rich dietary lipids, especially for the C18:0, could specifically increase the bile acid production by stimulating the bile acid alternative synthesis pathway. Although the bile acid receptor expression in the colon was increased, the re‐absorption of bile acid did not show a significant increase (P > 0.05) as compared with other dietary lipids. Moreover, the C18:2‐rich SO maintained the bile acid metabolic balance probably by decreasing the Romboutsia, while increasing the Bifidobacterium abundance in the colon.CONCLUSIONSThe different dietary lipids showed different effects on the bile acid metabolism, which was probably connected with the alterations in the gut microbiota structure. The present study could provide basic understandings about the influences of the different dietary lipids consumption on gut homeostasis and bile acid metabolism. © 2021 Society of Chemical Industry.
Multiscale Characterization of the Mechanical Properties of Fibrin and Polyethylene Glycol (PEG) Hydrogels for Tissue Engineering Applications
Authors: Abrego Christian Jose Garcia , Dedroog Lens , Deschaume Olivier , Wellens Jolan , Vananroye Anja , Lettinga Minne Paul , Patterson Jennifer , Bartic Carmen 
Published: November 2021

AbstractShear rheology and atomic force microscopy (AFM) are used to characterize the stiffness of hydrogels in tissue engineering applications, with several studies reporting differences of several orders of magnitude in the elastic moduli determined by these two methods. This work compares the elastic properties of soft fibrin and polyethylene glycol (PEG) hydrogels used for stem cell applications, determined by AFM indentation with different probe sizes (from nano‐ to micrometer) to shear rheometry data. For all hydrogels, AFM nanoscale probing consistently yields higher elastic modulus (E) values and variability than micrometer‐probe indentation, while the shear modulus (G) values determined are the lowest. Colloidal probe AFM results are closer to rheology data for the stiffest samples, where E/G ratios converge to the theoretical Trouton ratio of 3. The results suggest that high polymer concentration hydrogels are better described by the affine elastic network theory, whereas low polymer concentration hydrogels deviate significantly from the Trouton ratio. Thus, for soft hydrogels relevant for stem cell culture, the assumption E = 3G is often invalid and care should be taken when comparing data from studies where different characterization methods are used in order to discern the impact of material properties on cell behavior.
Manipulating Matrix Crystallization and Impact Toughness of Polylactide/Elastomer Blends via Tailoring Size and Packing Density of Stereocomplex Crystallites Formed at the Interface
Authors: Zeng Zhen , Luo Yuanlin , Bai Hongwei , Zhang Qin , Fu Qiang 
Published: November 2021

AbstractConstructing stereocomplex (SC) crystallites at the interface of poly(L‐lactide) (PLLA)/elastomer blends represent a promising strategy to develop heat‐resistant and super‐tough PLLA materials because such SC crystallites can behave as not only nucleator to accelerate crystallization of PLLA matrix but also interfacial binder to strengthen interface. The properties of blends could be largely dominated by the SC interfacial layer, however, it is still unclear how the interfacial structure affects nucleating efficiency and interfacial strength. Herein, taking PLLA/poly(ethylene‐co‐methyl acrylate‐graft‐poly(D‐lactide)) (EMA‐g‐PDLA) blends as an example, EMA‐g‐PDLA bearing different chain lengths and grafting densities is prepared to tailor the size and packing density of interface‐localized SC crystallites. The results indicate that the interfacial structure and properties of the blends have been successfully manipulated. Compared with low‐graft‐density long PDLA chains, high‐graft‐density short ones can readily collaborate with PLLA chains to form numerous SC crystallites with smaller size and higher packing density at the interface and thus dramatically enhance the impact toughness and matrix crystallization rate. Moreover, the toughness is dominated by the content of SC crystallites, but the matrix crystallization is determined by their size and packing density. The work provides a new understanding of SC structure controlling the properties of PLLA/elastomer blends.
GPi‐DBS for KMT2B‐Associated Dystonia: Systematic Review and Meta‐Analysis
Authors: Rajan Roopa , Garg Kanwaljeet , Saini Arti , Radhakrishnan Divya M. , Carecchio Miryam , BK Binukumar , Singh Manmohan , Srivastava Achal K. 
Published: November 2021

ABSTRACTBackgroundEarly evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT‐KMT2B.ObjectivesWe aimed to conduct a systematic review and meta‐analysis to assess outcomes and identify predictors of good outcome following GPi‐DBS in DYT‐KMT2B.MethodsWe searched MEDLINE, Cochrane and MDS‐abstracts databases using the MeSH terms “KMT2B and DYT28”. We included studies that reported objective outcomes following GPi‐DBS in DYT‐KMT2B. The BFMDRS‐M (Burke‐Fahn‐Marsden Dystonia Rating Scale‐ Movement) total scores pre‐ and post‐surgery were used to quantify outcomes. We calculated pooled effects using a random effects meta‐analysis and used meta‐regression to identify potential effect modifiers. Multiple linear regression using individual patient data was used to identify predictors of good outcome (>50% improvement from baseline on BFMDRS‐M).ResultsInitial searches screened 132 abstracts of which 34 full‐text articles were identified to be of potential interest. Ten studies reporting 42 individual patients, met the inclusion/exclusion criteria and were included in the final review. The mean age at onset was 6.4 ± 5.7 years and 40% were male. The median follow‐up was 12 months (range: 1–264 months). GPi‐DBS resulted in median BFMDRS‐M improvement of 42.7% (range: −103.5% to 95.9%) postoperatively. Pooled proportion of patients experiencing clinical improvement >50% on BFMDRS‐M was 41% (95% CI: 27%–57%). Male gender [β: 22.6, 95% CI: 8.0–37.3, P = 0.004), and higher pre‐operative BFMDRS‐M score [β: 0.62, 95% CI: 0.36–0.87, P < 0.001) were independently associated with better outcome.ConclusionKMT2B‐associated dystonia responds effectively to pallidal stimulation. The outcome is better in males and those with more severe dystonia at baseline.
Cysteine Exerts an Essential Role in Maintaining Intestinal Integrity and Function Independent of Glutathione
Authors: Jiao Ning , Wang Lu , Wang Yubo , Xu Doudou , Zhang Xin , Yin Jingdong 
Published: November 2021

ScopeEnteral feeding is a primary source of cysteine for intestinal mucosa given negligible transsulfuration activity in enterocytes and furthermore very few cysteine uptake from arterial blood. This study aims to explore the role of cysteine in maintaining intestinal integrity and function.Methods and ResultsThe intestinal porcine enterocytes (IPEC‐J2) are cultured in a cysteine‐deprived medium with or without glutathione supplementation upon the inhibitions of glutathione synthesis or degradation. As a result, cysteine deprivation impairs mitochondrial function, suppresses mechanistic target of rapamycin (mTOR) signaling, and activates general control nonderepressible 2 (GCN2) signaling, and might lead to resultant ferroptosis. Glutathione supplementation can restore the impairment through degrading into cysteine, while glutathione synthesis inhibition does not disturb the role of cysteine in keeping the intestinal epithelial cells. Furthermore, piglets are fed with cysteine‐deficient, ‐adequate, and ‐surplus diet for 28 days as a porcine model. In this study, it is evidenced that intestinal integrity and individual growth benefit from adequate dietary cysteine.ConclusionAdequate dietary cysteine supply is essential for intestinal mucosal integrity, epithelial cell turnover, and amino acid sensing as well as optimal individual growth. Cysteine exerts its role independent of glutathione and glutathione restores the impairment of cysteine‐deprivation on intestinal mucosal through degrading into cysteine.