bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total versus partial adrenalectomy in bilateral pheochromocytoma – a systematic review and meta-analysis
Authors: Zawadzka Karolina , Tylec Piotr , Małczak Piotr , Major Piotr , Pędziwiatr Michał , Pisarska-Adamczyk Magdalena 
Published: March 2023

BackgroundIn patients with bilateral pheochromocytoma, partial adrenalectomy offers the chance to preserve adrenal function and avoid the need for lifelong steroid supplementation. However, the risk of tumour recurrence raises questions about this procedure. The aim of our study was to compare partial and total adrenalectomy in bilateral pheochromocytoma through a systematic review with meta-analysis.MethodsA systematic search was carried out using databases (MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL) and registers of clinical trials (ClinicalTrials.gov, European Trials Register, WHO International Trials Registry Platform). This meta-analysis included studies up to July 2022 without language restrictions. A random effects model meta-analysis was performed to assess the risk of tumor recurrence, steroid dependence and morbidity in these patients.ResultsTwenty-five studies were included in the analysis involving 1444 patients. The relative risk (RR) of loss of adrenal hormone function during follow-up and the need for steroid therapy was 0.32 in patients after partial adrenalectomy: RR 0.32, 95% Confidence Interval (CI): 0.26-0.38, P &lt; 0.00001, I2 = 21%. Patients undergoing partial adrenalectomy had a lower odds ratio (OR) for developing acute adrenal crisis: OR 0.3, 95% CI: 0.1-0.91, P=0.03, I2 = 0%. Partial adrenalectomy was associated with a higher risk of recurrence than total adrenalectomy: OR 3.72, 95% CI: 1.54-8.96, P=0.003, I2 = 28%.ConclusionPartial adrenalectomy for bilateral pheochromocytoma is a treatment that offers a chance of preserving adrenal hormonal function, but is associated with a higher risk of local tumor recurrence. There was no difference for the risk of metastasis and in overall mortality among the group with bilateral pheochromocytomas undergoing total or partial adrenalectomy. This study is in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) Guidelines (10, 11).Systematic review registrationhttps://osf.io/zx3se.
Comparison between D-loop methylation and mtDNA copy number in patients with Aicardi-Goutières Syndrome
Authors: Dragoni Francesca , Garau Jessica , Orcesi Simona , Varesio Costanza , Bordoni Matteo , Scarian Eveljn , Di Gerlando Rosalinda , Fazzi Elisa , Battini Roberta , Gjurgjaj Altea , Rizzo Bartolo , Pansarasa Orietta , Gagliardi Stella 
Published: March 2023

IntroductionAicardi-Goutières Syndrome (AGS) is a rare encephalopathy with early onset that can be transmitted in both dominant and recessive forms. Its phenotypic covers a wide range of neurological and extraneurological symptoms. Nine genes that are all involved in nucleic acids (NAs) metabolism or signaling have so far been linked to the AGS phenotype. Recently, a link between autoimmune or neurodegenerative conditions and mitochondrial dysfunctions has been found. As part of the intricate system of epigenetic control, the mtDNA goes through various alterations. The displacement (D-loop) region represents one of the most methylated sites in the mtDNA. The term "mitoepigenetics" has been introduced as a result of increasing data suggesting that epigenetic processes may play a critical role in the control of mtDNA transcription and replication. Since we showed that RNASEH2B and RNASEH2A-mutated Lymphoblastoid Cell Lines (LCLs) derived from AGS patients had mitochondrial alterations, highlighting changes in the mtDNA content, the main objective of this study was to examine any potential methylation changes in the D-loop regulatory region of mitochondria and their relationship to the mtDNA copy number in peripheral blood cells of AGS patients with mutations in various AGS genes and healthy controls.Materials and methodsWe collected blood samples from 25 AGS patients and we performed RT-qPCR to assess the mtDNA copy number and pyrosequencing to measure DNA methylation levels in the D-loop region.ResultsComparing AGS patients to healthy controls, D-loop methylation levels and mtDNA copy number increased significantly. We also observed that in AGS patients, the mtDNA copy number increased with age at sampling, but not the D-loop methylation levels, and there was no relationship between sex and mtDNA copy number. In addition, the D-loop methylation levels and mtDNA copy number in the AGS group showed a non-statistically significant positive relation.ConclusionThese findings, which contradict the evidence for an inverse relationship between D-loop methylation levels and mtDNA copy number, show that AGS patients have higher D-loop methylation levels than healthy control subjects. Additional research is needed to identify the function of these features in the etiology and course of AGS.
Effects of warming and isolation from precipitation on the soil carbon, nitrogen, and phosphorus, and their stoichiometries in an alpine meadow in the Qinghai–Tibet Plateau: A greenhouse warming study
Authors: Tong Yongpeng , Long Yanjun , Yang Zhen’an 
Published: March 2023

IntroductionIn the Qinghai–Tibet Plateau (QTP), alpine meadows are among the most noticeable reflection of global climate change. However, effects of global warming on soils hosting alpine meadows in the QTP, such as reduced moisture because of low precipitation, remain unclear.MethodsHere, the soil moisture content (SMC), pH, dissolved organic carbon (DOC), ammonium nitrogen (NH4+–N), nitrate nitrogen (NO3−–N) and available phosphorus (AP) contents in the QTP were analyzed. The changes in and stoichiometries of total carbon, nitrogen, and phosphorus (TC, TN, and TP), microbial biomass carbon, nitrogen, and phosphorus (MBC, MBN, and MBP), β-1,4-glucosidase (BG), β-1,4-N-acetylglucoaminosidase (NAG), leucine aminopeptidase (LAP), and acid phosphatase (ACP) in the 0–30 cm layer of soils associated with warming in a greenhouse in the QTP from 2015 to 2020 were characterized.ResultsWe found that warming in the greenhouse significantly decreased the SMC, NO3−–N, MBC, MBN, MBP, BG, LAP, ACP, and enzymatic C:N ratio. The warming increased the DOC, NH4+–N, AP, MBC:MBN, and enzymatic N:P ratios noticeably. The pH, TC, TN, TP, C:N, C:P, N:P, MBC:MBP, MBN:MBP, and enzymatic C:P ratios were minimally affected.ConclusionThe results showed that warming and isolation from precipitation promoted mineralization of N and P in the soil but did not significantly alter the cycling of elements in soils in an alpine meadow.
Hereditary orotic aciduria identified by newborn screening
Authors: Staretz-Chacham Orna , Damseh Nadirah S. , Daas Suha , Abu Salah Nasser , Anikster Yair , Barel Ortal , Dumin Elena , Fattal-Valevski Aviva , Falik-Zaccai Tzipora C. , Hershkovitz Eli , Josefsberg Sagi , Landau Yuval , Lerman-Sagie Tally , Mandel Hanna , Rock Rachel , Rostami Nira , Saraf-Levy Talya , Shaul Lotan Nava , Spiegel Ronen , Tal Galit , Ulanovsky Igor , Wilnai Yael , Korman Stanley H. , Almashanu Shlomo 
Published: March 2023

Introduction: Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill.Methods: Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry.Results: Since the addition of orotic acid measurement to the Israeli routine newborn screening program, 1,492,439 neonates have been screened. The screen has identified ten Muslim Arab newborns that remain asymptomatic so far, with DBS orotic acid elevated up to 10 times the upper reference limit. Urine organic acid testing confirmed the presence of orotic aciduria along with homozygous variations in the UMPS gene.Conclusion: Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.
I kappa B kinase interacting protein as a promising biomarker in pan-cancer: A multi-omics analysis
Authors: Bi Chenyang , Wang Zhe , Xiao Yafei , Zhao Ying , Guo Runjiang , Xiong Luyao , Ji Zhiyu , Li Yifan , Li Quanying , Qin Changjiang 
Published: March 2023

Background: Human chromosome 12 contains I kappa B kinase interacting protein (IKBIP) is also commonly known as IKIP. The involvement of IKBIP in the growth of tumors has only been discussed in a small number of publications.Purpose: To explore the role that IKBIP plays in the development of a wide variety of neoplasms, as well as the tumor immunological microenvironment.Methods: UALCAN, HPA, Genotype Tissue Expression, Cancer Genome Maps, and other datasets were used to analyze IKBIP expression. We thoroughly investigated the predictive importance of IKBIP in pan-cancer, clinical traits, and genetic anomalies. We studied whether there is a link between IKBIP and immune-related genes, microsatellite instability (MSI), and the incidence of tumor mutational burden (TMB). The link between immune cell infiltration and IKBIP expression was examined using data on immune cell infiltration from ImmuCellAI, TIMER2, and earlier studies. Finally, gene set enrichment analysis (GSEA) was performed to determine the signaling pathways associated with IKBIP.Results: IKBIP is highly expressed in most cancers and is negatively associated with the prognosis of several major cancer types. Furthermore, IKBIP expression was linked to TMB in 13 cancers and MSI in seven cancers. Additionally, IKBIP is associated with numerous immunological and cancer-promoting pathways. Simultaneously, various cancer types have unique tumor-infiltrating immune cell profiles.Conclusion: IKBIP has the potential to act as a pan-cancer oncogene and is crucial for both carcinogenesis and cancer immunity. Elevated IKBIP expression implies an immunosuppressive environment and may be used as a prognostic biomarker and therapeutic target.
Epigenetic immune monitoring for COVID-19 disease course prognosis
Authors: Samans Björn , Rosselló Chornet Marta , Rosselló Chornet Araceli , Jung Janine , Schildknecht Konstantin , Lozza Laura , Alos Zaragoza Lourdes , Hernández Laforet Javier , Babel Nina , Olek Sven 
Published: March 2023

BackgroundThe course of COVID-19 is associated with severe dysbalance of the immune system, causing both leukocytosis and lymphopenia. Immune cell monitoring may be a powerful tool to prognosticate disease outcome. However, SARS-CoV-2 positive subjects are isolated upon initial diagnosis, thus barring standard immune monitoring using fresh blood. This dilemma may be solved by epigenetic immune cell counting.MethodsIn this study, we used epigenetic immune cell counting by qPCR as an alternative way of quantitative immune monitoring for venous blood, capillary blood dried on filter paper (dried blood spots, DBS) and nasopharyngeal swabs, potentially allowing a home-based monitoring approach.ResultsEpigenetic immune cell counting in venous blood showed equivalence with dried blood spots and with flow cytometrically determined cell counts of venous blood in healthy subjects. In venous blood, we detected relative lymphopenia, neutrophilia, and a decreased lymphocyte-to-neutrophil ratio for COVID-19 patients (n =103) when compared with healthy donors (n = 113). Along with reported sex-related differences in survival we observed dramatically lower regulatory T cell counts in male patients. In nasopharyngeal swabs, T and B cell counts were significantly lower in patients compared to healthy subjects, mirroring the lymphopenia in blood. Naïve B cell frequency was lower in severely ill patients than in patients with milder stages.ConclusionsOverall, the analysis of immune cell counts is a strong predictor of clinical disease course and the use of epigenetic immune cell counting by qPCR may provide a tool that can be used even for home-isolated patients.
Design of a multi-epitopic vaccine against Epstein-Barr virus via computer-based methods
Authors: Larijani Amirhossein , Kia-Karimi Ali , Roostaei Davoud 
Published: March 2023

BackgroundScientific findings have shown that Epstein-Barr virus (EBV) plays a key role in the development of some tumor diseases. Therefore, this study intends to take a practical step in controlling the pathogenicity of this virus by designing an effective vaccine based on the virus Capsid Envelope and Epstein–Barr nuclear immunogen (EBNA) Proteins Epitopes. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. So, we applied a computer-based strategy to design an epitope vaccineResultsWe designed a powerful multi-epitope peptide vaccine against EBV using in silico analysis. The vaccine is made up of 844 amino acids derived from three different types of proteins (Envelope, Capsid, EBNA) found in two different viral strains. responses. These epitopes have a high immunogenic capacity and are not likely to cause allergies. To enhance the vaccine immunogenicity, we used rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, as an adjuvant and linked it to the vaccine’s N and C terminus. The physicochemical and immunological properties of the vaccine structure were evaluated. The proposed vaccine was stable, with a stability index of 33.57 and a pI of 10.10, according to bioinformatic predictions. Docking analysis revealed that the vaccine protein binds correctly with immunological receptors.ConclusionOur results demonstrated that the multi-epitope vaccine might be potentially immunogenic and induce humoral and cellular immune responses against EBV. This vaccine can interact appropriately with immunological receptors Also, it has a high-quality structure and suitable characteristics such as high stability.
Intratumor microbiota as a novel potential prognostic indicator in mesothelioma
Authors: Pentimalli Francesca , Krstic-Demonacos Marija , Costa Caterina , Mutti Luciano , Bakker Emyr Yosef 
Published: March 2023

IntroductionDespite increased attention on immunotherapy, primarily immune checkpoint blockade, as a therapeutic approach for mesothelioma (MMe), its efficacy and tolerability remain questioned. One potential explanation for different responses to immunotherapy is the gut and intratumor microbiota; however, these remain an underexplored facet of MMe. This article highlights the cancer intratumor microbiota as a novel potential prognostic indicator in MMe.MethodsTCGA data on 86 MMe patients from cBioPortal underwent bespoke analysis. Median overall survival was used to divide patients into “Low Survivors” and “High Survivors”. Comparison of these groups generated Kaplan-Meier survival analysis, differentially expressed genes (DEGs), and identification of differentially abundant microbiome signatures. Decontamination analysis refined the list of signatures, which were validated as an independent prognostic indicator through multiple linear regression modelling and Cox proportional hazards modelling. Finally, functional annotation analysis on the list of DEGs was performed to link the data together.Results107 genera signatures were significantly associated with patient survival (positively or negatively), whilst clinical characteristic comparison between the two groups demonstrated that epithelioid histology was more common in “High Survivors” versus biphasic in “Low Survivors”. Of the 107 genera, 27 had published articles related to cancer, whilst only one (Klebsiella) had MMe-related published articles. Functional annotation analysis of the DEGs between the two groups highlighted fatty acid metabolism as the most enriched term in “High Survivors”, whilst for “Low Survivors” the enriched terms primarily related to cell cycle/division. Linking these ideas and findings together is that the microbiome influences, and is influenced by, lipid metabolism. Finally, to validate the independent prognostic value of the microbiome, multiple linear regression modelling as well as Cox proportional hazards modelling were employed, with both approaches demonstrating that the microbiome was a better prognostic indicator than patient age or stage of the cancer.DiscussionThe findings presented herein, alongside the very limited literature from scoping searches to validate the genera, highlight the microbiome and microbiota as a potentially rich source of fundamental analysis and prognostic value. Further in vitro studies are needed to elucidate the molecular mechanisms and functional links that may lead to altered survival.
Heparin-based versus bivalirudin-based anticoagulation in pediatric extracorporeal membrane oxygenation: A systematic review
Authors: Valdes Carlos A. , Sharaf Omar M. , Bleiweis Mark S. , Jacobs Jeffrey P. , Mumtaz Mohammed , Sharaf Ramy M. , Jeng Eric I. , Peek Giles J. 
Published: March 2023

IntroductionOptimal anticoagulation therapy is essential for the prevention of thrombotic and hemorrhagic complications in pediatric patients supported with extracorporeal membrane oxygenation (ECMO). Recent data have demonstrated bivalirudin has the potential to surpass and replace heparin as the anticoagulant of choice.MethodsWe conducted a systematic review comparing the outcomes of heparin-based versus bivalirudin-based anticoagulation in pediatric patients supported on ECMO to identify the preferred anticoagulant to minimize bleeding events, thrombotic complications, and associated mortality. We referenced the PubMed, Cochrane Library, and Embase databases. These databases were searched from inception through October 2022. Our initial search identified 422 studies. All records were screened by two independent reviewers using the Covidence software for adherence to our inclusion criteria, and seven retrospective cohort studies were identified as appropriate for inclusion.ResultsIn total, 196 pediatric patients were anticoagulated with heparin and 117 were anticoagulated with bivalirudin while on ECMO. Across the included studies, it was found that for patients treated with bivalirudin, trends were noted toward lower rates of bleeding, transfusion requirements, and thrombosis with no difference in mortality. Overall costs associated with bivalirudin therapy were lower. Time to therapeutic anticoagulation varied between studies though institutions had different anticoagulation targets.ConclusionBivalirudin may be a safe, cost-effective alternative to heparin in achieving anticoagulation in pediatric ECMO patients. Prospective multicenter studies and randomized control trials with standard anticoagulation targets are needed to accurately compare outcomes associated with heparin versus bivalirudin in pediatric ECMO patients.
Sodium valproate-induced nocturnal enuresis in epilepsy: Three case reports and a review of the literature
Authors: Zhang Xiaorong , Lu Wei , Mo Xiaoye 
Published: March 2023

BackgroundEnuresis is an uncommon adverse effect of sodium valproate therapy that is unknown to most clinicians. This study provides an overview of the literature on enuresis associated with sodium valproate therapy, discussing the clinical manifestations and possible mechanisms of this side effect.MethodsWe reported three cases of enuresis induced by sodium valproate and reviewed the published enuresis cases associated with sodium valproate therapy retrieved from databases.Case presentation and resultsThree new patients with epilepsy who presented with enuresis following sodium valproate therapy were reported, and 55 published cases of nocturnal enuresis associated with sodium valproate were evaluated. The average age of these patients varied from 4 to 20 years. A total of 48 cases had generalized seizures, seven had focal seizures, and three had unknown seizures. In all the patients, the plasma concentration of sodium valproate was 80.76 ± 14.80 μg/mL, within the therapeutic range when enuresis occurred. With discontinuation or reduction of the drug, all the patients recovered completely.ConclusionSodium valproate-induced enuresis is a rare and reversible side effect, occurring at a younger age, characterized by the generalized onset of seizures, and a rather high dose. The possible mechanisms include insufficient secretion of anti-diuretic hormones, sleep disorder, and hyperactivity of the parasympathetic system. Clinicians should be aware of this uncommon side effect to avoid an incorrect adjustment of the treatment direction.
Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease
Authors: Wijesinghe Printha , Whitmore Clayton A. , Campbell Matthew , Li Charles , Tsuyuki Miranda , To Eleanor , Haynes Justin , Pham Wellington , Matsubara Joanne A. 
Published: March 2023

IntroductionErgothioneine (Ergo) is a naturally occurring dietary antioxidant. Ergo uptake is dependent on the transporter, organic cation transporter novel-type 1 (OCTN1) distribution. OCTN1 is highly expressed in blood cells (myeloid lineage cells), brain and ocular tissues that are likely predisposed to oxidative stress. Ergo may protect the brain and eye against oxidative damage and inflammation, however, the underlying mechanism remains unclear. Amyloid beta (Aβ) clearance is a complex process mediated by various systems and cell types including vascular transport across the blood–brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Impaired Aβ clearance is a major cause for Alzheimer’s disease (AD). Here we investigated neuroretinas to explore the neuroprotective effect of Ergo in a transgenic AD mouse model.MethodsAge-matched groups of Ergo-treated 5XFAD, non-treated 5XFAD, and C57BL/6J wildtype (WT controls) were used to assess Ergo transporter OCTN1 expression and Aβ load along with microglia/macrophage (IBA1) and astrocyte (GFAP) markers in wholemount neuroretinas (n = 26) and eye cross-sections (n = 18). Immunoreactivity was quantified by fluorescence or by semi-quantitative assessments.Results and discussionOCTN1 immunoreactivity was significantly low in the eye cross-sections of Ergo-treated and non-treated 5XFAD vs. WT controls. Strong Aβ labeling, detected in the superficial layers in the wholemounts of Ergo-treated 5XFAD vs. non-treated 5XFAD reflects the existence of an effective Aβ clearance system. This was supported by imaging of cross-sections where Aβ immunoreactivity was significantly low in the neuroretina of Ergo-treated 5XFAD vs. non-treated 5XFAD. Moreover, semi-quantitative analysis in wholemounts identified a significantly reduced number of large Aβ deposits or plaques, and a significantly increased number of IBA1(+)ve blood-derived phagocytic macrophages in Ergo-treated 5XFAD vs. non-treated 5XFAD. In sum, enhanced Aβ clearance in Ergo-treated 5XFAD suggests that Ergo uptake may promote Aβ clearance possibly by blood-derived phagocytic macrophages and via perivascular drainage.