bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxaemic burden in heart failure patients receiving adaptive servo‐ventilation
Authors: Baumert Mathias , Linz Dominik , Pfeifer Michael , Tafelmeier Maria , Felfeli Philippe , Arzt Michael , Shahrbabaki Sobhan S.
Published: October 2023

Aims

This study aimed to assess the effectiveness of adaptive servo‐ventilation (ASV) for lowering hypoxaemic burden components in heart failure with reduced ejection fraction (HFrEF) patients.

Methods and results

Fifty‐six stable HFrEF patients with left ventricular ejection fraction ≤ 40 were randomized to receive either ASV (n = 27; 25 males) or optimal medical management or optimal medical management alone (n = 29; 26 males). Patients underwent overnight polysomnography at baseline and a 12 week follow‐up visit. We quantified hypoxaemic as time spent at <90% oxygen saturation (T90) decomposed into desaturation‐related components (T90desaturation) and non‐specific drifts (T90non‐specific). In the ASV arm, T90 significantly shortened by nearly 60% from 50.1 ± 95.8 min at baseline to 20.5 ± 33.0 min at follow‐up compared with 59.6 ± 88 and 65.4 ± 89.6 min in the control arm (P = 0.009). ASV reduced the apnoea‐related component (T90desaturation) from 37.7 ± 54.5 to 2.1 ± 7.3 min vs. 37.7 ± 54.5 and 40.4 ± 66.4 min in the control arm (P = 0.008). A significant non‐specific T90 component of 19.6 ± 31.8 min persisted during ASV. In adjusted multivariable regression, T90desaturation was significantly associated with the ratio of the forced expiratory volume in the first second to the forced vital capacity of the lungs (β = 0.336, 95% confidence interval 0.080 to 0.593; P = 0.011) and T90non‐specific with left ventricular ejection fraction (β = −0.345, 95% confidence interval −0.616 to −0.073; P = 0.014).

Conclusions

ASV effectively suppresses the sleep apnoea‐related component of hypoxaemic burden in HFrEF patients. A significant hypoxaemic burden not directly attributable to sleep apnoea but related to the severity of heart failure remains and may adversely affect cardiovascular long‐term outcomes.
Electrochemical Coupling Reactions Using Non‐Transition Metal Mediators: Recent Advances
Authors: Mitsudo Koichi , Okumura Yasuyuki , Sato Eisuke , Suga Seiji
Published: October 2023

Indirect electrolysis method using appropriate mediators enables numerous chemical reactions. The general principles of mediators were described herein with a particular focus on non‐transition metal mediators. Recent representative examples of bond formation reactions by indirect electrolysis are summarized and discussed here.
Evaluation of greenness and analytical performances of separative methods for chiral separation of novel lactam‐based P2RX7‐antagonists
Authors: Avigo Lorenzo , Furman Christophe , Ghinet Alina , Sandu Teodora , Wynendaele Evelien , Wielgomas Bartosz , De Spiegeleer Bart , Lipka Emmanuelle
Published: October 2023

In this work, a preparative supercritical fluid chromatography (SFC) method was first developed to separate a series of chiral compounds evaluated as lactam‐based P2RX7 antagonists. Subsequently, high‐performance liquid chromatography, SFC, and capillary electrophoresis (CE) were comparatively investigated as QC tools to determine the enantiomeric purity of the separated isomers, including analytical performance and greenness. The screening of the best conditions was carried out in liquid and SFC on the nine derivatives and the amylose tris(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase was found to be highly efficient. The same screening was carried out in CE and very different conditions, either in acidic or basic background electrolyte and different cyclodextrins used as chiral selectors, allowed the separation of six of the nine derivatives. 1‐((3,4‐Dichlorophenyl)carbamoyl)‐5‐oxopyrrolidine‐2‐carboxylic acid (compound 1) was chosen as a probe, and its semi‐preparative separation by SFC and enantiomeric verification using the three techniques are presented. Its limit of detection and limit of quantification are calculated for each method. Finally, the greenness of each quality control method was evaluated.
Identifying and prioritizing marketing strategies for the building energy management systems using a hybrid fuzzy MCDM technique
Authors: Beheshtinia Mohammad Ali , Sayadinia Shakiba , Fathi Masood
Published: October 2023

Preventing energy waste in residential and office buildings has emerged as a critical issue in both developed and developing countries over recent decades. The growing demand for oil and energy reserves has amplified the urgency of this concern. The deployment of building energy management systems (BEMSs) can lead to timely responses to changes in environmental conditions, the prevention of energy wastage, a reduction in CO2 emissions, and an increase in the longevity of building equipment. Despite the undeniable benefits of BEMSs, their market size remains small, creating challenges for providers in reaching potential customers. This research seeks to identify and prioritize the marketing strategies for BEMSs. A case study was conducted, employing the “Strengths, Weaknesses, Opportunities, and Threats” analysis as a tool for identifying marketing strategies related to BEMSs. This method resulted in the identification of 18 distinct marketing strategies. These strategies were subsequently prioritized using a novel fuzzy multicriteria decision‐making technique, VIkor‐topSIS, considering six specific criteria. The findings of the study suggested a hierarchical influence of six criteria on the BEMS market, arranged in the following order of significance: effectiveness, cost, attainability, complexity, timing, and popularity. Furthermore, the top three marketing strategies for BEMSs were found to be internet advertising strategies, discounts to consumers, and online sales. The analysis of the results has also offered valuable insights into the strengths and weaknesses of the studied BEMS provider, as well as the opportunities and threats present within the BEMS market.
Surface engineering Salmonella with pH‐responsive polyserotonin and self‐activated DNAzyme for better microbial therapy of tumor
Authors: Guo Lina , Chen Hao , Ding Jinsong , Rong Pengfei , Sun Ming , Zhou Wenhu
Published: October 2023

Bacteria‐based microbial immunotherapy shows various unique properties for tumor therapy owing to their active tropism to tumor and multiple anti‐tumor mechanisms. However, its clinical benefit is far from satisfactory, which is limited by rapid systemic clearance and neutrophils‐mediated immune restriction to compromise the efficacy, as well as non‐specific distribution to cause toxicity. To address all these limitations, herein we reported a polyserotonin (PST) coated Salmonella (Sal) with surface adsorption of DNAzyme (Dz)‐functionalized MnO2 nanoparticles (DzMN) for tumor therapy. PST could facilely coat on Sal surface via oxidation and self‐polymerization of its serotonin monomer, which enabled surface stealth to avoid rapid systemic clearance while maintaining the tumor homing effect. Upon targeting to tumor, the PST was degraded and exfoliated in response to acidic tumor microenvironment, thus liberating Sal to recover its anti‐tumor activities. Meanwhile, the DzMN was also delivered into tumor via hitchhiking Sal, which could release Dz and Mn2+ after tumor cells internalization. The Dz was then activated by its cofactor of Mn2+ to cleave target PD‐L1 mRNA, thus serving as a self‐activated system for gene silencing. Combining Sal and Dz for immune activation and PD‐L1 knockdown, respectively, anti‐tumor immunotherapy was achieved with enhanced efficacy. Notably, PST coating could significantly decrease infection potential and non‐specific colonization of Sal at normal organs, achieving high in vivo biosafety. This work addresses the key limitations of Sal for in vivo application via biomaterials modification, and provides a promising platform for better microbial immunotherapy.
Investigation of antimicrobial and antioxidant activities of Chenopodium album extracts and their effects on gentamicin nephrotoxicity in rats
Authors: Akbaş Perihan , Kaya Elife , Makav Mustafa , Yıldız Gülden
Published: October 2023

This study aims to examine the antimicrobial and antioxidant activities of the aerial parts of Chenopodium album extracts (CAE) prepared with different solvents, and how C. album ethanol extract protects them against gentamicin‐induced nephrotoxicity. Extracts of C. album aerial parts were obtained from ethanol, water, methanol, chloroform, and hexane solvents. Thirty‐two male Wistar albino rats were used and gentamycin‐induced nephrotoxicity was utilized as a model. The water extract of C. album exhibited no antimicrobial effect, whereas the methanol one created the highest zone diameter on Bacillus cereus (26 mm). The methanol extract displayed the highest activity in DPPH and ABTS. The ethanol extract yielded the highest reducing power in the CUPRAC. The water extract had the highest reducing power in the FRAP. Concerning gentamicin‐induced renal damage, creatinine and urea levels in the blood were statistically higher in the gentamicin‐C. album group compared to the other groups (p < .05). Urea and creatinine levels of the gentamicin‐C. album group dropped significantly, indicating that the C. album was effective against renal damage. The sections from kidney tissues in the gentamicin + C. album group mostly exhibited mild glomerular congestion. Hyaline cast, cytoplasmic vacuolization, necrosis, and apoptosis were not observed. Thanks to C. album treatment, the gentamicin + C. album suffered less histopathological damage than the gentamicin group did. The results of the present study suggest that CAE can be used as a supportive treatment in people undergoing treatment for nephrotoxicity.
ioSearch: An approach for identifying interacting multiomics biomarkers using a novel algorithm with application on breast cancer data sets
Authors: Das Sarmistha , Srivastava Deo Kumar
Published: October 2023

Identification of biomarkers by integrating multiple omics together is important because complex diseases occur due to an intricate interplay of various genetic materials. Traditional single‐omics association tests neither explore this crucial interomics dependence nor identify moderately weak signals due to the multiple‐testing burden. Conversely, multiomics data integration imparts complementary information but suffers from an increased multiple‐testing burden, data diversity inherent with different omics features, high‐dimensionality, and so forth. Most of the available methods address subtype classification using dimension‐reduction techniques to circumvent the sample size issue but interacting multiomics biomarker identification methods are unavailable. We propose a two‐step model that first investigates phenotype‐omics association using logistic regression. Then, selects disease‐associated omics using sparse principal components which explores the interrelationship of multiple variables from two omics in a multivariate multiple regression framework. On the basis of this model, we developed a multiomics biomarker identification algorithm, interacting omics search (ioSearch), that jointly tests the effect of multiple omics with disease and between‐omics associations by using pathway information that subsequently reduces the multiple‐testing burden. Further, inference in terms of p values potentially makes it an easily interpretable biomarker identification tool. Extensive simulation demonstrates ioSearch as statistically powerful with a controlled Type‐I error rate. Its application to publicly available breast cancer data sets identified relevant omics features in important pathways.
Exploring English policymakers' attitudes towards dementia risk reduction: A qualitative study
Authors: Walsh Sebastian , Roscoe Hannah , Mathie Elspeth , Wallace Lindsay , Govia Ishtar , Brayne Carol
Published: October 2023

Aim

A growing evidence‐base indicates that dementia occurrence can be changed. This has been linked to potentially modifiable risk factors. Risk reduction and primary prevention strategies are increasingly recognized as needing to include population‐level policies to tackle the social and commercial determinants of health. How this knowledge can influence policymaking on dementia prevention is unknown. Understanding attitudes of policymakers is an important step in translating evidence into practice, helping to gauge system readiness for implementation, and potential barriers and enablers for influencing policy. The aim of this qualitative study is to explore the understanding of, and attitudes to, dementia risk reduction and population‐level prevention strategies amongst English policymakers at national, regional, and local level.

Methods

Semi‐structured interviews were undertaken with a range of dementia and prevention policymakers, with purposive sampling of national and local policymakers, including politicians, government officials, health system leaders, academics, and dementia charity directors. Analysis of interview transcripts was undertaken by thematic analysis.

Results

14 policymakers were interviewed between November 2021 and February 2022. Three main themes were identified (1) Preventability of dementia, (2) Prevention approach, (3) Barriers and facilitators to improving the approach.

Discussion

Policymakers generally held dementia to be partially preventable. Policymakers recognised that both individual‐ and population‐level approaches to primary prevention of dementia are required – with some policymakers perceiving that population‐level approaches are under‐utilised. Key barriers to implementing more population‐level approaches were identified as the complexity and co‐ordination required to effectively tackle upstream determinants of health.
Heat stress combined with lipopolysaccharide induces pulmonary microvascular endothelial cell glycocalyx inflammatory damage in vitro
Authors: Chen Jiadi , Ding Chengjia , Cao Jingjing , Tong Huasheng , Chen Yi
Published: October 2023

Heat stroke is a life‐threatening disease with high mortality and complications. Endothelial glycocalyx (EGCX) is essential for maintaining endothelial cell structure and function as well as preventing the adhesion of inflammatory cells. Potential relationship that underlies the imbalance in inflammation and coagulation remains elusive. Moreover, the role of EGCX in heat stroke‐induced organ injury remained unclear. Therefore, the current study aimed to illustrate if EGCX aggravates apoptosis, inflammation, and oxidative damage in human pulmonary microvascular endothelial cells (HPMEC). Heat stress and lipopolysaccharide (LPS) were employed to construct in vitro models to study the changes of glycocalyx structure and function, as well as levels of heparansulfate proteoglycan (HSPG), syndecan‐1 (SDC‐1), heparansulfate (HS), tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, Von Willebrand factor (vWF), endothelin‐1 (ET‐1), occludin, E‐selectin, vascular cell adhesion molecule‐1 (VCAM‐1), and reactive oxygen species (ROS). Here, we showed that heat stress and LPS devastated EGCX structure, activated EGCX degradation, and triggered oxidative damage and apoptosis in HPMEC. Stimulation of heat stress and LPS decreased expression of HSPG, increased levels of SDC‐1 and HS in culture supernatant, promoted the production and release of proinflammation cytokines (TNF‐α and IL‐6,) and coagulative factors (vWF and ET‐1) in HPMEC. Furthermore, Expressions of E‐selection, VCAM‐1, and ROS were upregulated, while that of occludin was downregulated. These changes could be deteriorated by heparanase, whereas they meliorated by unfractionated heparin. This study indicated that EGCX may contribute to apoptosis and heat stroke‐induced coagulopathy, and these effects may have been due to the decrease in the shedding of EGCX.
Renal pelvis cancer with initial symptoms of malignant gastric outlet obstruction
Authors: Iwamoto Nao , Oikawa Masaaki , Kukimoto Takashi , Ito Jun , Murakami Kazuhiro , Kaiho Yasuhiro
Published: October 2023

Introduction

Gastric outlet obstruction caused by upper tract urothelial carcinoma is rare.

Case presentation

A 78‐year‐old man presented to the hospital with nausea and vomiting. No hematuria was observed. Computed tomography revealed a tumor in the right renal pelvis and duodenal stenosis. Gastrojejunostomy was performed to treat the symptoms of the gastric outlet obstruction so that the patient could resume oral intake and outpatient chemotherapy. Chemotherapy was unsuccessful, and the patient died 9 months after the gastrojejunostomy. Histological assessment of an autopsy specimen revealed plasmacytoid urothelial carcinoma with direct infiltration of the duodenal wall, which caused the stenosis.

Conclusion

Autopsy revealed a right renal pelvis cancer causing gastric outlet obstruction. Early gastrojejunostomy enabled oral intake and outpatient visits.
Utility of vitamin C in ameliorating citalopram‐induced testicular toxicity via modulating nitro‐oxidative stress and apoptosis in mice
Authors: Moradi Mojtaba , Hashemian Mohammad Arshia , Fathi Mohammad , Peysokhan Mohsen , Hashemian Amir Hossein , Moradi Bahareh , Jalili Cyrus , Faramarzi Azita
Published: October 2023

There is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)‐evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C‐administrated groups. Furthermore, vitamin C administration markedly alleviated CTL‐induced nitro‐oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL‐positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL‐induced testicular damage via mitigating nitro‐oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug‐associated reproductive toxicity and male sub/infertility.
Altered 5‐methylcytosine modification of mRNA is involved in the pathogenesis of pre‐eclampsia
Authors: Tong Jing , Li Hongwanyu , Zhang Cong
Published: October 2023

5‐Methylcytosine (m5C) is a prevalent RNA modification in messenger RNAs (mRNAs). Despite its abundance, its role in the decidua of pre‐eclampsia (PE) remains elusive. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and RNA‐sequencing (RNA‐seq) to map m5C peaks and mRNA expression profile in the decidua of human early‐onset PE (EPE), late‐onset PE (LPE), and normal pregnancy (NP). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses elucidated potential roles of the differentially methylated mRNAs (DMGs) and differentially expressed mRNAs in decidualization pathways. Integrative analysis of MeRIP‐seq and RNA‐seq data pinpointed 50 candidate genes linked to PE, marked by both differentially methylated m5C peaks and congruent expression changes. To validate these observations, we selected nine genes for verification via quantitative PCR. Our results underscore the precision and reproducibility of our bioinformatics approach. Importantly, we propose that changes in m5C modification and expression of relevant mRNA might influence the pathogenesis of PE by hampering decidualization. This work shines light on the distinct mRNA m5C modification patterns and expression profiles in the decidua of PE, implicating pivotal signaling disruptions and decidualization impediments in the onset of PE.
Structure‐based design of new N‐benzyl‐piperidine derivatives as multitarget‐directed AChE/BuChE inhibitors for Alzheimer's disease
Authors: Conceição Raissa Alves da , von Ranke Natalia , Azevedo Luciana , Franco Daiana , Nadur Nathalia Fonseca , Kummerle Arthur Eugen , Barbosa Maria Letícia de C. , Souza Alessandra M. T.
Published: October 2023

The pathogenic complexity of Alzheimer's disease (AD) demands the development of multitarget‐directed agents aiming at improving actual pharmacotherapy. Based on the cholinergic hypothesis and considering the well‐established role of butyrylcholinesterase (BuChE) in advanced stages of AD, the chemical structure of the acetylcholinesterase (AChE) inhibitor drug donepezil (1) was rationally modified for the design of new N‐benzyl‐piperidine derivatives (4a−d) as potential multitarget‐direct AChE and BuChE inhibitors. The designed analogues were further studied through the integration of in silico and in vitro methods. ADMET predictions showed that 4a−d are anticipated to be orally bioavailable, able to cross the blood‐brain barrier and be retained in the brain, and to have low toxicity. Computational docking and molecular dynamics indicated the formation of favorable complexes between 4a−d and both cholinesterases. Derivative 4a presented the lowest binding free energy estimation due to interaction with key residues from both target enzymes (−36.69 ± 4.47 and −32.23 ± 3.99 kcal/mol with AChE and BuChE, respectively). The in vitro enzymatic assay demonstrated that 4a was the most potent inhibitor of AChE (IC50 2.08 ± 0.16 µM) and BuChE (IC50 7.41 ± 0.44 µM), corroborating the in silico results and highlighting 4a as a novel multitarget‐directed AChE/BuChE inhibitor.
Sweroside attenuates podocyte injury and proteinuria in part by activating Akt/BAD signaling in mice
Authors: Huang Minjiang , Yang Yang , Chen Yuefu , Li Yang , Qin Sitao , Xiao Lijun , Long Xuewen , Hu Ke , Li Yuxian , Ying Huiming , Ding Yan
Published: October 2023

In this study, we investigated the effects of sweroside on podocyte injury in diabetic nephropathy (DN) mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of DN to explore the effects of sweroside on proteinuria and podocyte injury in DN mice. In in vitro experiments, conditionally immortalized mouse podocytes were treated with high glucose and sweroside, and the protective effects of sweroside on podocyte injury were analyzed. In vitro, Akt/BAD pathways were detected using gene siRNA silencing assays and found to be involved in the protective roles of sweroside in high glucose‐mediated podocyte injury. In vivo, sweroside significantly decreased albuminuria in DN mice (p < 0.01). periodic acid‐Schiff staining showed that sweroside alleviated the glomerular volume and mesangium expansion in DN mice. Consistently, western blot and reverse transcription‐polymerase chain reaction analyses showed that the profibrotic molecule expression in the glomeruli declined in sweroside‐treated DN mice. Immunofluorescent results showed that sweroside preserved nephrin and podocin expression, and transmission electron microscopy showed that sweroside attenuated podocyte injury. In DN mice, sweroside decreased podocyte apoptosis, and increased nephrin, podocin expression and decreased desmin and HIF1α expression. These results confirmed that sweroside ameliorated albuminuria, glomerulomegaly, and glomerulosclerosis in these mice. Experiments in vitro revealed that sweroside improved HG‐induced podocyte injury and apoptosis. Sweroside stimulated activation of the Akt/BAD pathway and upregulated Bcl‐2‐associated death promoter (BAD) and p‐Akt. Overall, sweroside protected podocytes from injury and prevented the progression of DN, providing a novel strategy for the treatment of DN.
Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?
Authors: Rodriguez Peter , Blakely Randy D.
Published: October 2023

Receiving a neurodegenerative disease (NDD) diagnosis, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis, is devastating, particularly given the limited options for treatment. Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease‐modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress. Modeling NDDs in invertebrates, such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, offers orders of magnitude increases in speed of genetic analysis and manipulation, and can be pursued at substantially reduced cost, providing an important, platform complement and inform research with mammalian NDD models. In this review, we describe how our efforts to exploit C. elegans for the study of neural signaling and health led to the discovery of a paralytic phenotype (swimming‐induced paralysis) associated with altered dopamine signaling and, surprisingly, to the discovery of a novel gene and pathway whose dysfunction in glial cells triggers neurodegeneration. Research to date on swip‐10 and its putative mammalian ortholog MBLAC1, suggests that a tandem analysis will offer insights into NDD mechanisms and insights into novel, disease‐modifying therapeutics.
Disjoint cycles in tournaments and bipartite tournaments
Authors: Chen Bin , Chang An
Published: October 2023

A conjecture proposed by Bermond and Thomassen in 1981 states that every digraph with minimum out‐degree at least contains vertex disjoint directed cycles for any integer , which has received substantial attention. This conjecture has been confirmed for . In 2014, Lichiardopol raised a very related conjecture that for every integer , there exists an integer such that every digraph with minimum out‐degree at least contains vertex disjoint directed cycles of different lengths. For a digraph and a set of vertex disjoint directed cycles in , we denote to be the maximum number of directed cycles in of distinct lengths. Let . We define if has no vertex disjoint directed cycles. In this paper, we mainly investigate vertex disjoint directed cycles in tournaments and bipartite tournaments. We first show that for every tournament with minimum out‐degree at least , where . We further prove that for and , any tournament with minimum out‐degree at least satisfies that . Moreover, we deduce that for any tournament with minimum out‐degree at least 7, holds. Additionally, we classify strong bipartite tournaments with minimum out‐degree at least in which any vertex disjoint directed cycles have the same length, where . That is, for any strong bipartite tournament with minimum out‐degree at least , then if and only if is isomorphic to a member of , which is defined in the context.
Lifetime risk of liver‐related outcomes and determinants in male inactive carriers of chronic hepatitis B
Authors: Wu Wan‐Jung , Lin Chih‐Lin , Liu Chun‐Jen , Huang Yi‐Wen , Hu Jui‐Ting , Yu Ming‐Whei
Published: October 2023

The full spectrum of risks for the life course of inactive hepatitis B virus (HBV) carriers remains unclear. In this study, 995 untreated HBV carriers (median age: 42.8 years; median follow‐up: 30.2 years) were included. Their data were sourced from a population‐based cohort study of male civil servants recruited in 1989–1992. Outcomes were identified by active follow‐up examinations and linkage with national health insurance research database. At baseline, 483 subjects were inactive carriers, 385 with indeterminate phase, and 127 with other phases. The joint lifetime risk for incident cirrhosis, decompensation, hepatocellular carcinoma, and liver‐related deaths was lower for inactive carriers compared to subjects in other phases (p < 0.0001). There was a trend of increase in incidence among inactive carriers; the 5‐, 10‐, and 20‐year cumulative incidences were 1.86%, 6.03%, and 10.07%, respectively. Of the inactive carriers, 37.7% cleared HBsAg and 36.6% had biochemical relapse during the study. Biochemical relapse, obesity, and advanced age were predictors for disease progression in inactive carriers. Virological relapse was the predominant cause of biochemical relapse. Higher HBV‐DNA levels (≥1000 copies/mL or 200 IU/mL) and HBV genotype B (vs. C) were associated with higher virological relapse rate. After 30 years, we found that one‐time measure of inactive carrier state continued to have the lowest risk compared with other infection phases. Despite a more favorable prognosis, inactive carriers had a non‐negligible risk. Our findings of lifetime risk may provide important clues for the management of such patients and consideration of therapeutic strategies aiming to achieve functional cure.
Differential diagnosis of fever and rash cases negative for measles and rubella to complement surveillance activities
Authors: Fappani Clara , Gori Maria , Bianchi Silvia , Terraneo Mara , Bilardi Erica , Colzani Daniela , Tanzi Elisabetta , Canuti Marta , Amendola Antonella
Published: October 2023

In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV‐6) and 7 (HHV‐7), parvovirus B19 (B19V), enterovirus (EV), Epstein−Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS‐CoV‐2. Differential diagnosis was carried out on 289 discarded cases by multiplex real‐time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV‐7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV‐6, EV, HAdV, and HCMV‐positive cases were found in children aged 0−4 years and HHV‐7 was most frequent in the 15−39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus‐positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities.
Using machine learning to enhance prediction of atrial fibrillation recurrence after catheter ablation
Authors: Brahier Mark S. , Zou Fengwei , Abdulkareem Musa , Kochi Shwetha , Migliarese Frank , Thomaides Athanasios , Ma Xiaoyang , Wu Colin , Sandfort Veit , Bergquist Peter J. , Srichai Monvadi B. , Piccini Jonathan P. , Petersen Steffen E. , Vargas Jose D.
Published: October 2023

Background

Traditional risk scores for recurrent atrial fibrillation (AF) following catheter ablation utilize readily available clinical and echocardiographic variables and yet have limited discriminatory capacity. Use of data from cardiac imaging and deep learning may help improve accuracy and prediction of recurrent AF after ablation.

Methods

We evaluated patients with symptomatic, drug‐refractory AF undergoing catheter ablation. All patients underwent pre‐ablation cardiac computed tomography (cCT). LAVi was computed using a deep‐learning algorithm. In a two‐step analysis, random survival forest (RSF) was used to generate prognostic models with variables of highest importance, followed by Cox proportional hazard regression analysis of the selected variables. Events of interest included early and late recurrence.

Results

Among 653 patients undergoing AF ablation, the most important factors associated with late recurrence by RSF analysis at 24 (+/−18) months follow‐up included LAVi and early recurrence. In total, 5 covariates were identified as independent predictors of late recurrence: LAVi (HR per mL/m2 1.01 [1.01–1.02]; p < .001), early recurrence (HR 2.42 [1.90–3.09]; p < .001), statin use (HR 1.38 [1.09–1.75]; p = .007), beta‐blocker use (HR 1.29 [1.01–1.65]; p = .043), and adjunctive cavotricuspid isthmus ablation [HR 0.74 (0.57–0.96); p = .02]. Survival analysis demonstrated that patients with both LAVi >66.7 mL/m2 and early recurrence had the highest risk of late recurrence risk compared with those with LAVi <66.7 mL/m2 and no early recurrence (HR 4.52 [3.36–6.08], p < .001).

Conclusions

Machine learning‐derived, full volumetric LAVi from cCT is the most important pre‐procedural risk factor for late AF recurrence following catheter ablation. The combination of increased LAVi and early recurrence confers more than a four‐fold increased risk of late recurrence.
A pilot study of mitochondrial response to an in vivo prosthetic joint Staphylococcus aureus infection model
Authors: Bouji Nour , Meadows Ethan , Hollander John M. , Velayutham Murugesan , Stewart Elizabeth , Herriott Jacob , Dietz Matthew J.
Published: October 2023

Prosthetic joint infections (PJI) are associated with orthopaedic morbidity and mortality. Mitochondria, the “cell's powerhouses,” are thought to play crucial roles in infection response and in increased risk of sepsis mortality. No current research discusses PJI's effect on mitochondrial function and a lack of understanding of immune‐infection interactions potentially hinders patient care. The purpose of this pilot study was to evaluate the impact of simulated PJI on local tissue mitochondrial function. Using an established prosthetic implant‐associated in vivo model, tissues were harvested from the surgical limb of a methicillin‐sensitive Staphylococcus aureus implant‐associated infection group (n = 6) and compared to a noninfected group (n = 6) at postoperative day (POD) 21. Using mitochondrial coupling assays, oxygen consumption rate and extracellular acidification rate were assessed in each group. Electron flow through mitochondrial complexes reflected group activity. Electron Paramagnetic Resonance (EPR) spectrometry measured the oxidizing potential of serum samples from infected versus noninfected groups. On POD21, colony‐forming units per gram of tissue showed 5 × 109 in the infected group and 101 in the noninfected group (p < 0.0001). Maximal respiration and oxygen consumption due to adenosine triphosphate synthesis were significantly lower in isolated mitochondria from infected limbs (p = 0.04). Both groups had similar complex I, III, IV, and V activity (p > 0.1). Infected group EPR signal intensity reflecting reactive oxygen species levels was 1.31 ± 0.30 compared to 1.16 ± 0.28 (p = 0.73) in the noninfected group. This study highlights PJI's role in mammalian cell mitochondrial dysfunction and oxidative tissue damage, which can help develop interventions to combat PJI.
Current clinical practice in the management of Brazilian patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC)
Authors: de Jesus Victor Hugo Fonseca , Peixoto Renata D'Alpino , Ribeiro Héber Salvador de Castro , Pinheiro Rodrigo Nascimento , Oliveira Alexandre Ferreira , Anghinoni Marciano , Torres Silvio Melo , Boff Márcio Fernando , Weschenfelder Rui , Prolla Gabriel , Riechelmann Rachel P.
Published: October 2023

Background and Objectives

We aimed to describe the routine clinical practice of physicians involved in the treatment of patients with localized pancreatic ductal adenocarcinoma (PDAC) in Brazil.

Methods

Physicians were invited through email and text messages to participate in an electronic survey sponsored by the Brazilian Gastrointestinal Tumor Group (GTG) and the Brazilian Society of Surgical Oncology (SBCO). We evaluated the relationship between variable categories numerically with false discovery rate‐adjusted Fisher's exact test p values and graphically with Multiple Correspondence Analysis.

Results

Overall, 255 physicians answered the survey. Most (52.5%) were medical oncologists, treated patients predominantly in the private setting (71.0%), and had access to multidisciplinary tumor boards (MTDTB; 76.1%). Medical oncologists were more likely to describe neoadjuvant therapy as beneficial in the resectable setting and surgeons in the borderline resectable setting. Most physicians would use information on risk factors for early recurrence, frailty, and type of surgery to decide treatment strategy. Doctors working predominantly in public institutions were less likely to have access to MTDTB and to consider FOLFIRINOX the most adequate regimen in the neoadjuvant setting.

Conclusions

Considerable differences exist in the management of localized PDAC, some of them possibly explained by the medical specialty, but also by the funding source of health care.
Primary sarcoma of the liver: A nationwide analysis of a rare mesenchymal tumor
Authors: Finney Nicole , Tran Tu , Hasjim Bima J. , Jakowatz James , Chiao Elaine , Eng Oliver , Wolf Ronald , Jutric Zeljika , Yamamoto Maki , Tran Thuy B.
Published: October 2023

Background and Objectives

Primary liver sarcomas are rare malignancies. Prognostic factors associated with long‐term survival remain poorly understood. The objective of this study is to determine factors associated with long‐term survival.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with visceral sarcoma arising from the liver. Demographic factors, tumor characteristics, resection status, and survival were evaluated. Multivariate Cox regression analysis was performed to determine predictors of survival.

Results

A total of 743 patients with primary hepatic sarcoma were identified. The median tumor size was 10 cm. Only 30% (n = 221) of patients in the cohort underwent surgery. The 5‐year overall survival rates were 47.9% for localized disease, 29.5% for regional disease, and 16.5% for distant disease, p < 0.001. Among patients who underwent surgical resection, patients with embryonal sarcoma had better 5‐year survival compared with angiosarcoma and other histologic subtypes. On multivariate analysis, surgery was associated with improved survival, while older age, higher stage, and angiosarcoma histology were the strongest independent predictors of poor survival.

Conclusions

Surgery remains the mainstay of treatment for this rare malignancy but is performed in less than one‐third of patients. Angiosarcoma histology is associated with worse overall survival, while surgical resection remains the strongest predictor of improved overall survival.
Effect of heat stress on seed protein quality in mungbean [Vigna radiata (L.) Wilczek]
Authors: Batra Divya , Dhull Sanju Bala , Rani Jyoti , Meenakshi Meenakshi , Kumar Yogesh , Kinabo Joyce
Published: October 2023

Abiotic and biotic stresses impair the productivity of agricultural crops. Among abiotic stresses, the higher temperature (i.e., heat stress) is unfavourable for plant growth and development. In recent years, the mungbean [Vigna radiata (L.) Wilczek] demand has been increasing, which can satisfy human protein requirements. However, its productivity and quality are negatively impacted by heat stress due to climate change. This requires a broadening scope of mungbean adaptation to warmer climates. Hence, the objective of this study was to assess the effects of heat stress on various mungbean genotypes for their seed protein characteristics (total seed protein content, proportion of four protein fractions, and electrophoretic patterns on SDS‐gels). The 13 mungbean genotypes were grown under normal and heat‐stressed conditions by sowing seeds at two different times, that is, the normal sowing time in the last week of March and late sowing in the last week of April in the experimental plots. In late‐sown plants, the total seed proteins decreased by 4.1% to 9.3%. In addition, the relative proportion of glutelins and prolamins increased significantly while globulins and albumins decreased at high temperatures. Moreover, the intensity of polypeptides decreased under high temperatures. In our studies, some polypeptides appeared, and others disappeared in late‐sown genotypes. The disappearance of bands reveals a higher rate of protein degradation than synthesis under heat stress. The detrimental effects of heat stress on seed protein characteristics studied were more prominent in MH 318, IPM 02‐3 and PM‐5 and less noticeable in MH 125, MH 421 and PDM 139 genotypes.
Metal Halide CsCu2I3 Flexible Scintillator with High Photodiode Spectral Compatibility for X‐Ray Cone Beam Computed Tomography (CBCT) Imaging
Authors: Ran Peng , Chen Xinya , Chen Zeng , Su Yirong , Hui Juan , Yang Lurong , Liu Tianyu , Tang Xiangyang , Zhu Haiming , She Xiao‐Jian , Yang Yang (Michael)
Published: October 2023

Copper‐based halides have emerged as promising scintillator materials for X‐ray imaging due to their favorable photophysical characteristics, such as negligible self‐absorption, high light output, and fast decay. Among these materials, Cs3Cu2I5, a blue emitter, currently delivers the highest scintillation light output under steady‐state X‐rays. However, there is a significant spectral mismatch between its emission band and the spectral responsivity of regular flat‐panel photodiode arrays. In this study, a comprehensive analysis of the physical properties of the CsCu2I3 scintillator is conducted, and its perfect spectral compatibility is discovered, which results in a higher photodiode signal despite its relatively lower light output compared to typical Cs3Cu2I5 scintillators. Furthermore, CsCu2I3 exhibits faster light decay properties, making it especially suitable for Computed Tomography (CT) X‐ray imaging. High‐quality X‐ray cone beam computed tomography (CBCT) imaging is successfully demonstrated using the fast‐decaying CsCu2I3 scintillator screen. Additionally, the flexibility of the scintillator allows for non‐planar imaging, showcasing advantages not available with traditional rigid scintillators. These results not only highlight the significant promise of the CsCu2I3 scintillator but also emphasize the necessity of considering spectral compatibility when designing novel scintillator materials.
Rapid whole brain 3D T2 mapping respiratory‐resolved Double‐Echo Steady State (DESS) sequence with improved repeatability
Authors: Kadalie Emile , Trotier Aurélien J. , Corbin Nadège , Miraux Sylvain , Ribot Emeline J.
Published: October 2023

Purpose

To propose a quantitative 3D double‐echo steady‐state (DESS) sequence that offers rapid and repeatable T2 mapping of the human brain using different encoding schemes that account for respiratory B0 variation.

Methods

A retrospective self‐gating module was firstly implemented into the standard DESS sequence in order to suppress the respiratory artifact via data binning. A compressed‐sensing trajectory (CS‐DESS) was then optimized to accelerate the acquisition. Finally, a spiral Cartesian encoding (SPICCS‐DESS) was incorporated to further disrupt the coherent respiratory artifact. These different versions were compared to a standard DESS sequence (fully DESS) by assessing the T2 distribution and repeatability in different brain regions of eight volunteers at 3 T.

Results

The respiratory artifact correction was determined to be optimal when the data was binned into seven respiratory phases. Compared to the fully DESS, T2 distribution was improved for the CS‐DESS and SPICCS‐DESS with interquartile ranges reduced significantly by a factor ranging from 2 to 12 in the caudate, putamen, and thalamus regions. In the gray and white matter areas, average absolute test–retest T2 differences across all volunteers were respectively 3.5 ± 2% and 3.1 ± 2.1% for the SPICCS‐DESS, 4.6 ± 4.6% and 4.9 ± 5.1% for the CS‐DESS, and 15% ± 13% and 7.3 ± 5.6% for the fully DESS. The SPICCS‐DESS sequence's acquisition time could be reduced by half (<4 min) while maintaining its efficient T2 mapping.

Conclusion

The respiratory‐resolved SPICCS‐DESS sequence offers rapid, robust, and repeatable 3D T2 mapping of the human brain, which can be especially effective for longitudinal monitoring of cerebral pathologies.
Stimuli‐responsive hydrogel microgels on porous silicon one‐dimensional photonic crystals: Tapping the full potential for optical sensor applications
Authors: Valadez Ruth Fabiola Balderas , Flores Augusto David Ariza , Pacholski Claudia
Published: October 2023

Porous silicon 1D photonic crystals, namely rugate filters, are covered with a loosely packed hexagonally ordered array of stimuli‐responsive hydrogel microgels, and the optical properties of the resulting hybrid sensor are thoroughly investigated. For this purpose, both rugate filters with and without hydrogel microgel on top are immersed in ethanol/water mixtures possessing different compositions and NaCl solutions. Reflectance spectra of all samples are taken and analyzed concerning the spectral positions and reflectance intensity of the strong peak related to the photonic crystal rugate peak as well as the side bands resulting from Fabry–Pérot interference at the interfaces bordering the porous silicon. For the latter analysis, a Fourier transform is applied to the side bands for calculating the effective optical thickness (EOT). Thereby it can be shown that the spectral position of both the rugate peak and the EOT peak is best suited for monitoring refractive index changes in the immersion medium whereas the swelling and collapse of the stimuli‐responsive hydrogel microgel can be only detected by variations in the amplitude of the rugate peak and the EOT peak. These results are confirmed by simulations using a simple geometrical model and shall serve as guide for developing tailor‐made optical sensors.
How social enterprise executives perceive their relationship with the government in South Korea: Insights from a Q‐methodological study
Authors: Claassen Casper Hendrik , Bidet Eric , Kim Junki , Choi Yeanhee
Published: October 2023

This study utilizes Q‐methodology to assess the perspectives of 37 executives of government‐certified social enterprises in South Korea on their organization's relationship with the public sector in terms of the complementary‐supplementary‐adversarial conceptual frameworks of Toepler et al. and Young and the literature on co‐production. The perspectives of social enterprise executives that participate in co‐production arrangements represent an underexplored domain. Our findings contribute to the framework of Toepler et al. by empirically gauging the effects of, in particular, an enabling regulatory framework and public funding relative to the tensions represented by potentially excessive regulation. Although the focus on a single context limits the generalizability of the study, it provides insights on the nuances and complexities of public sector patronage while highlighting that such patronage is generally seen as being more complementary than adversarial. Our findings contribute to efforts to empirically gauge perceptions of co‐production arrangements.