bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between neutrophil-lymphocyte-ratio and oxygen delivery in patients after the Norwood operation
Authors: Loomba Rohit , Farias Juan , Villarreal Enrique , flores Saul 
Published: September 2023

Abstract

Background Both neutrophil-lymphocyte-ratio and renal oxygen extraction have been demonstrated to be associated with adverse events after cardiac surgery. The association between neutrophil-lymphocyte-ratio and renal oxygen extraction has not previously been studies. The aim of this study was to characterize the association between neutrophil-lymphocyte ratio and renal oxygen extraction. Methods High fidelity hemodynamic monitoring data was retrieved for patients who underwent the Norwood operation. Bayesian regression analyses were conducted to identify what hemodynamic variables, including renal oxygen extraction, were associated with neutrophil-lymphocyte ratio. Results A total of 27,270 datapoints were collected over 1,338 patient-hours for nine unique patients. Renal oxygen extraction ratio had an area under the curve of 0.72 to identify renal oxygen extraction of over 35%. An increase in renal oxygen extraction by 1 was associated with a 0.15 increase in the neutrophil-lymphocyte-ratio. Conclusion In patients after the Norwood procedure, there is a correlation between the neutrophil-lymphocyte-ratio and renal oxygen extraction. A neutrophil-lymphocyte-ratio of greater than 2.95 has fair-performance in identifying renal extraction of greater than 35%.
Adaptive event-triggered fault-tolerant control for leader-followering consensus of multi-agent systems
Authors: Cui Guofei , Wu Libing , Wu Meng 
Published: September 2023

Abstract
This paper focuses on the distributed fault-tolerant leader-followering synchronization problem for linear multi-agent systems (MASs) with the event triggering strategy. Firstly, in order to compensate effectively for the actuator faults and bounded inputs from the leader, a distributed event-triggered algorithm with adaptive techniques is proposed. Secondly, the trigger function with adaptive parameters is designed to enhance the self-regulation of the trigger mechanism, which is relevant to the state of the agents and time, but not to the number of agents. Then, it is demonstrated that the developed consensus protocol can achieve not only the synchronization of agents without continuous communication , but also the exclusion of Zeno behavior. Finally, example of numerical simulation illustrates the effectiveness of the presented control protocol.
Universal and facile sol-gel approach for fabrication of multitudinous yolk- shell architectures
Authors: Li Hongqing , Xu Wenqi , Xu Jiaqi , Zhu Mengxuan , Wang Rui , Jiang Heng , Jin Changzi 
Published: September 2023

Abstract
The nanoreactors with yolk-shell configuration have been one of the most attractive objects because of their unique performance in specific reactions. However, complicated synthesis procedures have restricted the truth understanding and wide application of the yolk-shell architectures. This article presents a universal and facile sol-gel process for fabrication of mesoporous silica hollow structure and derived yolk-shell composites with extended Stöber resorcinol-formaldehyde resin as sacrificed template. The crucial influence factors for the morphology of products are investigated. A series of yolk-shell composites with multitudinous components have been successfully designed and are further catalytic tested by different reactions. This work has provided a universal avenue for the fabrication of yolk-shell nanoreactors to suit specific reaction needs.
Comprehensive analysis to investigate the association between IL-8 gene polymorphisms and the risk of cancer from 135 case-control studies
Authors: Xu Bin , Yan Yidan 
Published: September 2023

Abstract
Background
The association between polymorphisms in the interleukin-8 (IL-8) gene and the development of cancer risk have been investigated in many studies. Nonetheless, the past findings have needed to be more consistent and conclusive. Thus, the current study aims to comprehensively evaluate the association between IL-8 gene polymorphisms and cancer risk.
Methods
The literature survey was conducted across multiple databases. The search comprised all relevant publications conducted on June 23, 2023.
Results
In accordance with the predefined search criteria for assessing cancer susceptibility, an inclusive meta-analysis was conducted, containing 135 case-control studies. This investigation yielded a collection of six distinct polymorphisms (-251, -353, + 678, +1633, + 2767, +781), which were identified and documented. The association strength was evaluated via odds ratios with 95% confidence intervals. This research has made a significant discovery regarding the − 251 polymorphism and its potential association with increased cancer risk. The resulting analyses encompassed various populations, including Asians and individuals of mixed ancestry, as well as different sources of control, precisely hospital-based sources. Furthermore, the study examined multiple types of cancer, such as gastric, glioma, bladder, and colorectal. These examinations suggest that the − 251 polymorphism may have been implicated in elevating the susceptibility to these malignancies. The − 353 polymorphism was identified as a potential risk factor that indicated its involvement in cancer development, while the + 781 polymorphism was also linked with elevated cancer risk.
Conclusions
Overall, the investigation has revealed that IL-8 gene polymorphisms significantly influence vulnerability to cancer development.
Reduction in D-dimer Levels After Treatment with Auxora in Patients with Severe Covid-19 Pneumonia Reflects Endothelial Stabilization
Authors: Hou Peter C. , Miller Joseph , Bruen Charles , Youssef Fady , Schnaus Michael J. , Brouillette Kathyrn , Mendoza-Ayala Raul , Zhang Jeffrey , Stauderman Kenneth , Hebbar Sudarshan 
Published: September 2023

Abstract
Background
Auxora, a calcium release-activated channel (CRAC) inhibitor, was demonstrated to improve recovery and decrease mortality in patients with severe COVID-19 pneumonia initially in an open-label trial and then in CARDEA, a phase 2, randomized, double-blind, placebo-controlled trial. In the open-label trial, treatment with Auxora was noted to be associated with a decrease in D-Dimer levels. To confirm these findings, blood samples were collected in CARDEA and tested for D-dimer levels. In a subset of patients, additional biomarkers were assessed to elucidate a potential mechanism of action of Auxora in decreasing D-dimer levels.
Methods
In patients enrolled in CARDEA, blood samples were collected prior to randomization and again at 72 hours after the start of the first infusion of Auxora for testing of D-dimer levels. In patients who consented for additional biomarker testing, blood samples were collected prior to randomization and again at 96 hours for testing of Angiopoietin-1, Angiopoietin-2, renin, and sCD25 levels.
Results
The baseline mean D-dimer level in the Auxora group was 2.61 mg/L and in the placebo group 2.05 mg/L. Patients treated with Auxora had a significant decrease in D-dimer levels within the first 72 hours compared to those treated with placebo. The difference was − 0.92 (95% CI: -1.82, -0.02; P < 0.0460). The decrease in D-dimer levels correlated with an increase in imputed PaO2/FiO2 (P/F) at 72 hours (r: -0.193; P < 0.05) which in turn correlated with improved clinical outcomes at 168 hours (r: 0.218, P < 0.01). Additional biomarker testing demonstrated that treatment with Auxora reduced levels of Angiopoietin-2 and sCD25 and increased Angiopoietin-1 levels at 96 hours.
Conclusion
In patients with severe COVID-19 pneumonia, Auxora reduced D-dimer levels which correlated with improved oxygenation and clinical outcomes. In addition, Auxora appears to have decreased endothelial activation through a reduction in systemic inflammation and likely had a direct effect on endothelium stabilization.
This trial is registered at ClinicalTrials.gov number, NCT04345614.
Assessing seasonal variation and trends in rainfall patterns of Madhya Pradesh, Central India
Authors: Kumar Amit , Kumar Siddharth , Rautela Kuldeep Singh , Shekhar Sulochana , Ray Tapas , Thangavel Mohanasundari 
Published: September 2023

Abstract

Climate change is a worldwide problem caused by various anthropogenic activities, leading to changes in hydroclimatic variables like temperature, rainfall, riverine flow, and extreme hydrometeorological events. In India, significant changes are noted in its natural resources and agriculture sectors. In this study, we analysed the long-term spatio-temporal change in rainfall patterns of Madhya Pradesh, Central India, using Indian Meteorological Department high-resolution gridded data from 439 grid points. The coefficient of variance analysis showed low variability in annual and monsoon rainfall but significant variability in pre-monsoon, post-monsoon, and winter seasons, indicating considerable seasonal variation. Pre-monsoon rainfall exhibited an increasing trend (0.018 mm annually), while annual, monsoon, post-monsoon, and winter rainfall showed decreasing trends. Change point analysis identified shifts in rainfall patterns in 1998 (monsoon, annual), 1955 (pre-monsoon), 1987 (post-monsoon), and 1986 (winter). Spatio-temporal distribution maps depicted irregular rainfall, with some areas experiencing drastic declines in precipitation after 1998. The maximum average annual rainfall reduced from 1,769 to 1,401 mm after 1998 affecting water availability. The study's findings highlight a significant shift in Madhya Pradesh's seasonal rainfall distribution after 1998, urging researchers and policymakers to address water-intensive cropping practices and foster climate resilience for a sustainable future in the region.
The technological development of drinking water treatment plants in the Czech Republic
Authors: Orderud Geir Inge , Porcal Petr , Eikebrokk Bjørnar , Sláma Jiří , Vogt Rolf David , Hejzlar Josef , Haaland Ståle 
Published: September 2023

AbstractSeveral actors have an impact on the quality of drinking water, but ultimately drinking water treatment plants (DWTPs) play a decisive role in ensuring that water quality complies with public regulations. Several developing technologies are combined in water treatment processes. In this paper, we are analysing the technological development of DWTPs in the South Bohemian region of the Czech Republic. The empirical basis is five DWTPs of varying size, and data are gathered through semi-structured interviews with relevant staff inside and outside of the five DWTPs. This study identifies the interplay of factors driving technological development: public regulations, the economic capacity of local DWTP owners together with subsidies from the European Union and national authorities, political priorities by local authorities, and the knowledge network. The paper addressess learning–knowledge–change processes of DWTPs, thereby contributing to our understanding of developing competence in producing drinking water. Generally, large DWTPs are front-runners in introducing new technologies while the smaller ones are lagging. Still, private companies operating small plants on behalf of municipal owners ensure that those DWTPs are part of a wider knowledge network, aiding to introduce a necessary and cost-effective upgrade to treatment steps
The Influence of Atorvastatin, Amlodipine and Ethoxidol on Ubiquinol and Ubiquinone
Endogenous Plasma Concentrations in Patients with Chronic Heart Failure
Authors: Zozina V.I. , Kondratenko S.N. , Shikh E.V. , Krasnykh L.M. , Melnikov E.S. , Kukes V.G. 
Published: September 2023

Background:
Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble
endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma
concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in
healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain
almost uninvestigated.

Objective:
The aim of this case-control study was to investigate the effect of atorvastatin, amlodipine and ethoxidol
on endogenous plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with CHF.

Methods:
The study included 62 patients with CHF divided into four groups depending on the prescribed therapy.
For the quantitative determination of ubiquinol, ubiquinone, and total CoQ10 in the plasma of patients, HPLCMS/
MS was used.

Results:
It was established that the endogenous plasma concentration of total CoQ10 in patients with CHF is significantly
lower than in healthy volunteers, and the ratio of reduced and oxidized forms of CoQ10 is shifted towards
ubiquinone. It was a statistically significant effect of drugs with different physicochemical structures and pharmacological
action on the plasma concentrations of ubiquinol, ubiquinone and total CoQ10: atorvastatin administration led
to a decrease in the concentration of ubiquinol (-33.3Δ%), and total CoQ10 (-15Δ%), administration of amlodipine
contributed to an increase in the levels of ubiquinol (+27.7Δ%) and total CoQ10 (+18.2Δ%), and the administration
of ethoxidol caused an increase in the concentration of ubiquinol (+25Δ%), ubiquinone (+17.7Δ%) and total CoQ10
(+20.2Δ%).

Conclusion:
Amlodipine is able to neutralize the negative effect of atorvastin on the redox balance of CoQ10 in
patients with CHF. An additional prescription of the antioxidant ethoxidol to standard therapy for patients with CHF
was substantiated. Determination of the redox state of CoQ10 in plasma can be used to diagnose and assess the degree
of oxidative stress in patients with cardiovascular diseases, as well as to assess the efficacy and safety of ongoing
pharmacotherapy.
Recent Advances in Xanthine Oxidase Inhibitors
Authors: Sun Zhi-Gang , Wu Kai-Xiang , Ullah Inam , Zhu Hai-Liang 
Published: September 2023

Abstract:
Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid
can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that
catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against
hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine
oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent
years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or
separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors
since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide
derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives,
and imidazole derivatives, hoping to provide valuable information for the research and development
of novel xanthine oxidase inhibitors.
Impact of Structural GLA Protein Changes on Peripheral GLA Activity and Substrate Accumulation in Fabry Disease Patients
Authors: Da Silva Jorge Diogo , Ribeiro Isaura , Caseiro Carla , Pinto Eugénia , Rocha Sónia , Ribeiro Helena , Ferreira Célia , Silva Elisabete , Laranjeira Francisco , Tkachenko Nataliya , Lacerda Lúcia , Quelhas Dulce 
Published: September 2023

Introduction:
Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, leading to decreased/absent α-galactosidase activity. In clinical practice, enzyme activity and substrate/byproduct accumulation play a role in diagnosis and disease-monitoring biomarkers. However, interpreting biomarker levels is not straightforward and can change according to the underlying GLA protein abnormality.

Objective:
Our goals were to understand how disrupting specific protein regions changes biomarker behaviour and to establish specific patterns for individual variants.

Methodology:
We analysed data from the Biochemical Genetics Laboratory regarding GLA variants, GLA enzyme activity (in dried blood spots, plasma or white blood cells), plasma LysoGb3 accumulation, and urinary Gb3 excretion. We assessed correlations, trends, and potential predictor models of biomarker behaviour.

Results:
We assessed 169 hemizygous male and 255 heterozygous female patients. For both groups, substrate accumulation correlates inversely with GLA activity. Variants affecting residues buried within the protein core or the active site were associated with more severe biomarker changes, while those affecting residues that establish disulfide bonds or are glycosylated were similar to other variants. For each non-truncating variant, we also established specific profiles of biomarker behaviour. Finally, we also designed predictor models of biomarker behaviour based on structural variant information. This study provides the groundwork for the impact of GLA protein variation on GLA activity and substrate accumulation.

Conclusion:
This knowledge is of extreme relevance for diagnostic labs and clinicians, as some genetic variants are challenging to interpret regarding pathogenicity. Assessing whether biomarker changes are in the expected range for a specific variant may help diagnostic evaluation. This study also contributes to recognising non-disease-causing variants, considering their overall biochemical impact, and providing a comparative reference for biomarker discovery studies. In the future, the correlation of these findings with disease severity may be of great relevance for diagnosis and monitoring progression.
Glutaric Acidemia Type 1: Diagnosis, Clinical features, and Outcome in a Portuguese Cohort
Authors: Pinto Patrícia Lipari , Câmara Beatriz , Florindo Cristina , Loureiro Rita Santos , Jardim Inês , Sousa Carmen , Vilarinho Laura , Janeiro Patrícia , Tavares de Almeida Isabel , Gaspar Ana 
Published: September 2023

Introduction:
Glutaric acidemia type 1 (GA1) is a rare autosomal recessive disorder characterized by a deficiency of glutaryl-CoA dehydrogenase, resulting in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid, and glutarylcarnitine, especially in the brain. GA1-affected children are clinically characterized by macrocephaly. Neurological abnormalities usually appear between 6 and 18 months of age, often triggered by a catabolic event. On the other hand, several biochemically affected individuals may remain asymptomatic or experience an insidious onset of mild neurological abnormalities.

Methods:
Retrospective study of GA1 patients followed at a Portuguese Hereditary Metabolic Disease Center, to characterize the phenotypic and genotypic variations associated with GA1. Therefore, we analyzed the clinical, neuroradiological, biochemical, and genetic information from 14 patients.

Results:
14 patients (four months-27 years old) were identified in the last 26 years, 9 were male, 1 was from a consanguineous family. 11 were diagnosed by newborn screening (NBS), and 3 identified following clinical symptoms (later diagnosed, LD). There were 3 phenotypic presentations: 6 asymptomatic, 3 with a motor disability after encephalopathic crisis (EC), and 5 with insidious onset. Acute EC occurred in 1/3 of the LD patients and in 2/11 NBS-identified patients. About urinary GA concentrations: 5 were low excretors (LE), 9 were high excretors (HE). All LE showed symptoms, and 2 had EC. Concerning HE, 3 showed symptoms and 1 had EC. GCDH analysis showed: 6 compound heterozygotes and 8 homozygotes. most frequent variant was c.1204C>T (p.R402W). All of them received appropriate therapy from the time of diagnosis, with a mean age of 23.3 months in LD patients and 13.3 days in NBS-identified patients.

Conclusion:
The outcomes were different between the two groups: all the LD patients presented motor dysfunction however in the NBS-identified patients only 5 developed this symptom. Patients identified by NBS had better outcomes showing that NBS enables an early diagnosis, and treatment, and consequently improves the clinical outcomes for these patients. No correlation was observed with clinical phenotype between LE and HE, as both groups can suffer the most severe neurological manifestations. These conclusions are in agreement with previous cohorts described in the literature.
Pilot Study on Newborn Screening for Spinal Muscular Atrophy
Authors: Fonseca Helena , Ribeiro Diogo , Guimarães Fabio , Pinto Conceição , Marcão Ana , Sousa Carmen , Carvalho Ivone , Lopes Lurdes , Rodrigues Diogo , Rocha Hugo , Vilarinho Laura 
Published: September 2023

Introduction:
Newborn screening (NBS) in Portugal is a significant public health measure to provide early detection for specific disorders so that early treatment is possible. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. Its incidence is estimated in 1.6000-11.800 live births. A pilot study on 100.000 newborns is being carried out at the neonatal screening laboratory with the aim of determining the specificity, sensitivity, and feasibility of the SMA screening at the NBS laboratory in Portugal.

Methods:
The study presented here was based on data obtained from neonatal screening, involving the analysis of 25.000 newborns. SMA screening is performed by a qualitative detection of exon 7 of the SMN1 gene. The assay was performed using a commercially available real-time PCR, the Eonis SMN1, TREC, and KREC kit.

Results/Case report:
The dried blood spots of a total of 25.000 newborns were tested; among these newborns, two were diagnosed as having SMA with survival motor neuron 1 (SMN1) deletion. These two SMA-positive samples were sent to a specialized clinical centre and a peripheral blood sample was sent to the reference laboratory for confirmation of the exon 7 deletion and determination of the SMN2 copy number.

Conclusion:
Early diagnosis and intervention are important for SMA treatment to be effective; the treatment should be started at the pre-symptomatic stage of SMA. Thus, newborn screening for SMA is strongly recommended. Currently, targeted therapies for SMA are available, and attempts are being made worldwide to include SMA screening in newborns.