bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel technology for home monitoring of lupus nephritis that tracks the pathogenic urine biomarker ALCAM
Authors: Lei Rongwei , Vu Binh , Kourentzi Katerina , Soomro Sanam , Danthanarayana Adheesha N. , Brgoch Jakoah , Nadimpalli Suma , Petri Michelle , Mohan Chandra , Willson Richard C.
Published: December 2022

Introduction

The gold standard for diagnosis of active lupus nephritis (ALN), a kidney biopsy, is invasive with attendant morbidity and cannot be serially repeated. Urinary ALCAM (uALCAM) has shown high diagnostic accuracy for renal pathology activity in ALN patients.

Methods

Lateral flow assays (LFA) for assaying uALCAM were engineered using persistent luminescent nanoparticles, read by a smartphone. The stability and reproducibility of the assembled LFA strips and freeze-dried conjugated nanoparticles were verified, as was analyte specificity.

Results

The LFA tests for both un-normalized uALCAM (AUC=0.93) and urine normalizer (HVEM)-normalized uALCAM (AUC=0.91) exhibited excellent accuracies in distinguishing ALN from healthy controls. The accuracies for distinguishing ALN from all other lupus patients were 0.86 and 0.74, respectively.

Conclusion

Periodic monitoring of uALCAM using this easy-to-use LFA test by the patient at home could potentially accelerate early detection of renal involvement or disease flares in lupus patients, and hence reduce morbidity and mortality.
Omicron variants of SARS-CoV-2 and long COVID
Authors: Yang Chengliang , Zhao Hedi , Shannon Casey P. , Tebbutt Scott J.
Published: December 2022

Understanding the epidemiology of long COVID and emerging variants has significant public-health implications as physical interventions and restrictions that help limit viral spread are eased globally. Here, we provide rationales for the necessity of updating current vaccines to improve protection against omicron and emerging variants, as well as more research into understanding the epidemiology and mechanisms of long COVID.
Case report: A new pathogenic variant of LRBA deficiency with a complex phenotype and Rosai-Dorfman disease
Authors: Fabozzi Francesco , De Vito Rita , Gaspari Stefania , Leone Fabrizio , Delvecchio Maurizio , Agolini Emanuele , Galaverna Federica , Mastronuzzi Angela , Pagliara Daria , De Ioris Maria Antonietta
Published: December 2022

We reported a new pathogenic variant of LRBA deficiency with a complex phenotype—neonatal diabetes, very early-onset inflammatory bowel disease, and polyarthritis—who presented with lymph node enlargement. A case of Rosai-Dorfman’s disease (RDD) was confirmed. The occurrence of an RDD lesion in LRBA-deficiency has never been reported so far.
A bias of Asparagine to Lysine mutations in SARS-CoV-2 outside the receptor binding domain affects protein flexibility
Authors: Boer Jennifer C. , Pan Qisheng , Holien Jessica K. , Nguyen Thanh-Binh , Ascher David B. , Plebanski Magdalena
Published: December 2022

Introduction

COVID-19 pandemic has been threatening public health and economic development worldwide for over two years. Compared with the original SARS-CoV-2 strain reported in 2019, the Omicron variant (B.1.1.529.1) is more transmissible. This variant has 34 mutations in its Spike protein, 15 of which are present in the Receptor Binding Domain (RBD), facilitating viral internalization via binding to the angiotensin-converting enzyme 2 (ACE2) receptor on endothelial cells as well as promoting increased immune evasion capacity.

Methods

Herein we compared SARS-CoV-2 proteins (including ORF3a, ORF7, ORF8, Nucleoprotein (N), membrane protein (M) and Spike (S) proteins) from multiple ancestral strains. We included the currently designated original Variant of Concern (VOC) Omicron, its subsequent emerged variants BA.1, BA2, BA3, BA.4, BA.5, the two currently emerging variants BQ.1 and BBX.1, and compared these with the previously circulating VOCs Alpha, Beta, Gamma, and Delta, to better understand the nature and potential impact of Omicron specific mutations.

Results

Only in Omicron and its subvariants, a bias toward an Asparagine to Lysine (N to K) mutation was evident within the Spike protein, including regions outside the RBD domain, while none of the regions outside the Spike protein domain were characterized by this mutational bias. Computational structural analysis revealed that three of these specific mutations located in the central core region, contribute to a preference for the alteration of conformations of the Spike protein. Several mutations in the RBD which have circulated across most Omicron subvariants were also analysed, and these showed more potential for immune escape.

Conclusion

This study emphasizes the importance of understanding how specific N to K mutations outside of the RBD region affect SARS-CoV-2 conformational changes and the need for neutralizing antibodies for Omicron to target a subset of conformationally dependent B cell epitopes.
16S Next-generation sequencing and quantitative PCR reveal the distribution of potential pathogens in the Liaohe Estuary
Authors: Huang Huiling , Zan Shuaijun , Ming Hongxia , Li Mengfei , Xu Jianrong , Xie Yuyang , Wang Wenjing , Fan Jingfeng
Published: December 2022

The existence of potentially pathogenic bacteria seriously threatens aquatic animals and human health. Estuaries are closely related to human activities, and the detection of pathogens is important for aquaculture and public health. However, monitoring only indicator microorganisms and pathogens is not enough to accurately and comprehensively estimate water pollution. Here, the diversity of potentially pathogenic bacteria in water samples from the Liaohe estuary was profiled using 16S next-generation sequencing (16S NGS) and quantitative polymerase chain reaction (qPCR) analysis. The results showed that the dominant genera of environmental pathogens were Pseudomonas, Vibrio, Mycobacterium, Acinetobacter, Exiguobacterium, Sphingomonas, and Legionella, and the abundance of enteric pathogens was significantly less than the environmental pathogens, mainly, Citrobacter, Enterococcus, Escherichia-Shigella, Enterobacter, Bacteroides. The qPCR results showed that the 16S rRNA genes of Vibrio were the most abundant, with concentrations between 7.06 and 9.48 lg copies/L, followed by oaa gene, fliC gene, trh gene, and uidA gene, and the temperature and salinity were the main factors affecting its abundance. Variance partitioning analysis (VPA) analysis of spatial factors on the potential pathogen’s distribution (19.6% vs 5.3%) was greater than environmental factors. In addition, the co-occurrence analysis of potential pathogens in the estuary revealed significant co-occurrence among the opportunistic pathogens Testosteronemonas, Brevimonas vesicularis, and Pseudomonas putida. Our findings provide an essential reference for monitoring and occurrence of potentially pathogenic bacteria in estuaries.
Differences in fouling community composition and space occupation across broad spatial and temporal scales
Authors: Jewett Elizabeth B. , Lawson Katherine N. , Larson Kristen J. , Tracy Brianna M. , Altman Safra , Chang Andrew L. , Cowan Scott , Crooks Jeffrey A. , Huber Tamar , Wells Elizabeth H. , Ruiz Gregory M.
Published: December 2022

Sessile marine invertebrate (biofouling) communities have served as an important model in ecology for evaluating fundamental patterns and processes, including invasion dynamics, which vary at broad spatial and temporal scales. Here, we tested for differences in biofouling community development among three biogeographically distinct bays in North America (Chesapeake Bay, Tampa Bay, and San Francisco Bay), exploring possible explanations for differential non-native species success. In particular, we aimed to examine if San Francisco Bay (a global hotspot for non-native species richness) differed in composition and space occupation, especially since open space can facilitate colonization. Additionally, we explored how biogeography, assembly and succession dynamics over the short and long term, and space availability affect marine communities across broad spatial scales. Patterns of community assembly differed among bays, with more bare space and less secondary cover (species settling on species) in San Francisco Bay. San Francisco Bay was also distinguished by a higher percent cover of Tunicata (almost all of which are non-native and historically absent) over multiple time scales. Cirripedia recruited on bare panels in all three Bays but cover increased only in Tampa Bay, as soak time increased. Tube-dwelling Polychaeta distinguished Chesapeake Bay from Tampa Bay and San Francisco Bay. Low-salinity events temporarily restructured the communities in all three bays. Whether differences among bays reflect coastal versus bay-specific patterns remains to be tested.
The diagnosis of Adamantiades-Behçet disease: Clinical features and diagnostic/classification criteria
Authors: Bergamo Serena
Published: December 2022

Adamantiades-Behçet’s disease (ABD) is a chronic-relapsing multisystemic inflammatory disease with unknown etiology first described by a Greek ophthalmology Benediktos Adamantiades and a Turkish dermatology Hulusi Behçet. Any organ or apparatus may be involved, though more often there is an involvement of oral and genital mucosae as well as ocular lesions, skin features, and vascular findings. Since there is neither laboratory nor radiological pathognomonic test, the diagnosis is basically clinical according to peculiar signs and symptoms of the disease. With the purpose of giving objectivity and homogeneity to the diagnosis, many authors in time introduced a long series of diagnostic and classification criteria for Adamantiades-Behçet’s disease. This mini-review provides an overview of published diagnostic/classification criteria.
Leymus chinensis resists degraded soil stress by modulating root exudate components to attract beneficial microorganisms
Authors: Lin Yulong , Mei Linlin , Wei Qianhao , Li Bing , Zhang Pan , Sun Shixuan , Cui Guowen
Published: December 2022

Phytoremediation is an effective means to improve degraded soil nutrients and soil structure. Here, we investigated the remediation effects of Leymus chinensis on the physicochemical properties and structure of degraded soil after 3 years of cultivation and explored the bacterial and fungal drivers in root exudates by metabolomics and high-throughput sequencing. The results showed that root exudates increased soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP) and soil aggregates, and organic acids in root exudates reduced pH and activated insoluble nutrients into forms that are available to plants, such as available nitrogen (NH4+-N), nitrate nitrogen (NO3−-N), and available phosphorus (AP). The cultivation of L. chinensis restored the diversity and richness of soil microorganisms and recruited potential beneficial bacteria and fungi to resist degraded soil stress, and L. chinensis also regulated the abundances of organic acids, amino acids and fatty acids in root exudates to remediate degraded soils. Spearman correlation analysis indicated that glutaric acid, 3-hydroxybutyric acid and 4-methylcatechol in root exudates attracted Haliangium, Nitrospira and Mortierella to the rhizosphere and dispersed the relative abundance of the harmful microorganisms Fusicolla and Fusarium. Our results demonstrate that L. chinensis enhances soil fertility, improves soil structure, promotes microbial diversity and abundance, and recruits potentially beneficial microorganisms by modulating root exudate components.
Coxsackievirus B3 infection induces glycolysis to facilitate viral replication
Authors: Qian Yujie , Yang Yeyi , Qing Wenxiang , Li Chunyun , Kong Min , Kang Zhijuan , Zuo Yuanbojiao , Wu Jiping , Yu Meng , Yang Zuocheng
Published: December 2022

Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis, but no effective treatment strategy against CVB3 is available. Viruses lack an inherent metabolic system and thus depend on host cellular metabolism for their benefit. In this study, we observed that CVB3 enhanced glycolysis in H9c2 rat cardiomyocytes and HL-1 mouse cardiomyocytes. Therefore, three key glycolytic enzymes, namely, hexokinase 2 (HK2), muscle phosphofructokinase (PFKM), and pyruvate kinase M2 (PKM2), were measured in CVB3-infected H9c2 and HL-1 cells. Expression levels of HK2 and PFKM, but not PKM2, were increased in CVB3-infected H9c2 cells. All three key glycolytic enzymes showed elevated expression in CVB3-infected HL-1 cells. To further investigate this, we used 2 deoxyglucose, sodium citrate, and shikonin as glycolysis inhibitors for HK2, PFKM, and PKM2, respectively. Glycolysis inhibitors significantly reduced CVB3 replication, while the glycolysis enhancer dramatically promoted it. In addition, glycolysis inhibitors decreased autophagy and accelerated autophagosome degradation. The autophagy inducer eliminated partial inhibition effects of glycolysis inhibitors on CVB3 replication. These results demonstrate that CVB3 infection enhances glycolysis and thus benefits viral replication.
Microfluidic liquid sheets as large-area targets for high repetition XFELs
Authors: Hoffman David J. , Van Driel Tim B. , Kroll Thomas , Crissman Christopher J. , Ryland Elizabeth S. , Nelson Kacie J. , Cordones Amy A. , Koralek Jake D. , DePonte Daniel P.
Published: December 2022

The high intensity of X-ray free electron lasers (XFELs) can damage solution-phase samples on every scale, ranging from the molecular or electronic structure of a sample to the macroscopic structure of a liquid microjet. By using a large surface area liquid sheet microjet as a sample target instead of a standard cylindrical microjet, the incident X-ray spot size can be increased such that the incident intensity falls below the damage threshold. This capability is becoming particularly important for high repetition rate XFELs, where destroying a target with each pulse would require prohibitively large volumes of sample. We present here a study of microfluidic liquid sheet dimensions as a function of liquid flow rate. Sheet lengths, widths and thickness gradients are shown for three styles of nozzles fabricated from isotropically etched glass. In-vacuum operation and sample recirculation using these nozzles is demonstrated. The effects of intense XFEL pulses on the structure of a liquid sheet are also briefly examined.
Estrogen receptors mediate the antidepressant effects of aerobic exercise: A possible new mechanism
Authors: Zhou Ruixue , Wang Zhisheng , Zhou Bojun , Yu Zixin , Wu Chongyun , Hou Jun , Cheng Ken , Liu Timon Chengyi
Published: December 2022

Purpose

This study aimed to examine whether aerobic exercise exerts mood-modulating effects through an estrogen signaling mechanism.

Method

The experiment was divided into two parts. The first part is to compare the three modeling methods to obtain the most obvious method of depression-like phenotype for further study in the second part. The first part of ovariectomized rats (age, 13 weeks) was tested when rats were 14 or 22 weeks old or in the sixth week after 3 weeks of chronic restraint stress. The second part was to treat the animals with the most obvious depression-like phenotype in different ways, placebo treatment or estradiol (E2) replacement therapy was administered, aerobic training, or estrogen receptor antagonist treatment. The cognitive (Barnes maze and 3-chamber social tests), anxiety-like (open-field and elevated plus maze tests) and depression-like (sucrose preference and forced swim tests) behaviors of rats in both parts were analyzed to study the effects of estrogen depletion and aerobic exercise.

Results

Rats did not develop depressive symptoms immediately after ovariectomy, however, the symptoms became more pronounced with a gradual decrease in ovarian hormone levels. Compared with the placebo or control groups, the exercise and E2 groups showed improved performance in all behavioral test tasks, and the antidepressant effects of aerobic exercise were comparable to those of estrogen. Moreover, the estrogen receptor antagonist has markedly inhibited the antidepressant effects of aerobic exercise.

Conclusion

Estrogen receptors may mediate the antidepressant effects of aerobic exercise. In addition, an increasingly fragile ovarian hormonal environment may underlies chronic restraint stress-induced depression.
Modulations of bioactive lipids and their receptors in postmortem Alzheimer’s disease brains
Authors: Kurano Makoto , Saito Yuko , Uranbileg Baasanjav , Saigusa Daisuke , Kano Kuniyuki , Aoki Junken , Yatomi Yutaka
Published: December 2022

Background

Analyses of brain samples from Alzheimer’s disease (AD) patients may be expected to help us improve our understanding of the pathogenesis of AD. Bioactive lipids, including sphingolipids, glycerophospholipids, and eicosanoids/related mediators have been demonstrated to exert potent physiological actions and to be involved in the pathogenesis of various human diseases. In this cross-sectional study, we attempted to elucidate the associations of these bioactive lipids with the pathogenesis/pathology of AD through postmortem studies of human brains.

Methods

We measured the levels of glycerophospholipids, sphingolipids, and eicosanoids/related mediators in the brains of patients with AD (AD brains), patients with Cerad score B (Cerad-b brains), and control subjects (control brains), using a liquid chromatography-mass spectrometry method; we also measured the mRNA levels of specific receptors for these bioactive lipids in the same brain specimens.

Results

The levels of several species of sphingomyelins and ceramides were higher in the Cerad-b and AD brains. Levels of several species of lysophosphatidic acids (LPAs), lysophosphatidylcholine, lysophosphatidylserine, lysophosphatidylethanolamine (LPE), lysophosphatidylinositol, phosphatidylcholine, phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol, and phosphatidylglycerol were especially high in the Cerad-b brains, while those of lysophosphatidylglycerol (LPG) were especially high in the AD brains. Several eicosanoids, including metabolites of prostaglandin E2, oxylipins, metabolites of epoxide, and metabolites of DHA and EPA, such as resolvins, were also modulated in the AD brains. Among the lipid mediators, the levels of S1P2, S1P5, LPA1, LPA2, LPA6, P2Y10, GPR174, EP1, DP1, DP2, IP, FP, and TXA2r were lower in the AD and/or Cerad-b brains. The brain levels of ceramides, LPC, LPI, PE, and PS showed strong positive correlations with the Aβ contents, while those of LPG showed rather strong positive correlations with the presence of senile plaques and neurofibrillary tangles. A discriminant analysis revealed that LPG is especially important for AD and the LPE/PE axis is important for Cerad-b.

Conclusions

Comprehensive lipidomics, together with the measurement of lipid receptor expression levels provided novel evidence for the associations of bioactive lipids with AD, which is expected to facilitate future translational research and reverse translational research.
Post-COVID-19 human memory impairment: A PRISMA-based systematic review of evidence from brain imaging studies
Authors: Shan Dan , Li Shaoyang , Xu Ruichen , Nie Glen , Xie Yangyiran , Han Junchu , Gao Xiaoyi , Zheng Yuandian , Xu Zhen , Dai Zhihao
Published: December 2022

Many people with coronavirus disease 2019 (COVID-19) report varying degrees of memory impairment. Neuroimaging techniques such as MRI and PET have been utilized to shed light on how COVID-19 affects brain function in humans, including memory dysfunction. In this PRISMA-based systematic review, we compared and summarized the current literature looking at the relationship between COVID-19-induced neuropathological changes by neuroimaging scans and memory symptoms experienced by patients who recovered from COVID-19. Overall, this review suggests a correlational trend between structural abnormalities (e.g., cortical atrophy and white matter hyperintensities) or functional abnormalities (e.g., hypometabolism) in a wide range of brain regions (particularly in the frontal, parietal and temporal regions) and memory impairments in COVID-19 survivors, although a causal relationship between them remains elusive in the absence of sufficient caution. Further longitudinal investigations, particularly controlled studies combined with correlational analyses, are needed to provide additional evidence.
Association between NOTCH3 gene and Parkinson’s disease based on whole-exome sequencing
Authors: Zeng Qian , Pan Hongxu , Zhao Yuwen , Wang Yige , Xu Qian , Tan Jieqiong , Yan Xinxiang , Li Jinchen , Tang Beisha , Guo Jifeng
Published: December 2022

Objective

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. Previous studies have established a link between NOTCH3 variants and Parkinson’s disease (PD) in terms of neuropathology and clinical characteristics. In this study, we aimed to explore the role of NOTCH3 gene in PD in a large Chinese cohort.

Methods

A total of 1,917 patients with early-onset or familial PD and 1,652 matched controls were included. All variants were divided into common or rare types by minor allele frequency (MAF) at a threshold of 0.01 (MAF > 0.01 into common variants and others into rare variants). Common variants were subjected to single-variant tests by PLINK, then gene-based analyses were used for rare variants with the optimized sequence kernel association test (SKAT-O). For genotype–phenotype correlation assessment, regression models were conducted to compare clinical features between the studied groups.

Results

Three common variants (rs1044006, rs1043997, and rs1043994) showed a nominal protective effect against PD. However, none of these SNPs survived Bonferroni correction. The results in the validation cohort revealed a significant but opposite association between these variants and PD. The gene-based analyses of rare variants showed no significant associations of NOTCH3 with PD. Although we did not find significant associations in the following genotype–phenotype analysis, the higher clinical scores of motor symptoms in NOTCH3-variant carriers were of interest.

Conclusion

Our results indicated that NOTCH3 gene may not play an important role in the early-onset or familial PD of Chinese population.
Semiconductor clusters: Synthetic precursors for colloidal quantum dots
Authors: Shin Jibin , Choi Mahnmin , Kim Meeree , Jeong Sohee
Published: December 2022

Semiconductor clusters have been implicated as reaction intermediates between molecular precursors and colloidal quantum dots (CQDs). The success of isolation of semiconductor clusters have enabled detailed investigation of the atomic information of semiconductor clusters. The identification of atomic information has emerged as an important topic because knowledge of the structure-function relationship of intermediate clusters has been helpful to reveal the synthetic mechanism of CQDs. Recently, they have been utilized as the synthetic precursors for CQDs, which was not readily achieved using conventional molecular precursors. This mini review briefly introduces the current understanding of their atomic information such as the composition, structure, and surface. We then discuss advantages, limitations, and the perspective of semiconductor clusters as a precursor for synthesis of CQDs.
Functional properties of eyelid conditioned responses and involved brain centers
Authors: Parras Gloria G. , Leal-Campanario Rocío , López-Ramos Juan C. , Gruart Agnès , Delgado-García José M.
Published: December 2022

For almost a century the classical conditioning of nictitating membrane/eyelid responses has been used as an excellent and feasible experimental model to study how the brain organizes the acquisition, storage, and retrieval of new motor abilities in alert behaving mammals, including humans. Lesional, pharmacological, and electrophysiological approaches, and more recently, genetically manipulated animals have shown the involvement of numerous brain areas in this apparently simple example of associative learning. In this regard, the cerebellum (both cortex and nuclei) has received particular attention as a putative site for the acquisition and storage of eyelid conditioned responses, a proposal not fully accepted by all researchers. Indeed, the acquisition of this type of learning implies the activation of many neural processes dealing with the sensorimotor integration and the kinematics of the acquired ability, as well as with the attentional and cognitive aspects also involved in this process. Here, we address specifically the functional roles of three brain structures (red nucleus, cerebellar interpositus nucleus, and motor cortex) mainly involved in the acquisition and performance of eyelid conditioned responses and three other brain structures (hippocampus, medial prefrontal cortex, and claustrum) related to non-motor aspects of the acquisition process. The main conclusion is that the acquisition of this motor ability results from the contribution of many cortical and subcortical brain structures each one involved in specific (motor and cognitive) aspects of the learning process.
Health insurance provider and endovascular treatment availability are associated with different hemodialysis vascular access profiles: A Brazilian national survey
Authors: Franco Ricardo Portiolli , Chula Domingos Candiota , de Moraes Thyago Proença , Campos Rodrigo Peixoto
Published: December 2022

In Brazil, most hemodialysis (HD) patients are treated by the country’s public health system. However, accessibility to healthcare is different for public and private patients. This study aimed to identify the profile of vascular access in a Brazilian HD sample. Additionally, it aimed to examine the influence of public and private health insurance, accessibility to endovascular treatments, and timely arteriovenous access creation on the prevalence of tunneled catheters (TCs), non-tunneled catheters (NTCs), and arteriovenous (AV) access. We conducted a cross-sectional electronic survey across 834 centers. Centers were inquired about the number of patients with public and private health insurance, the profiles of vascular access, time for AV access creation, accessibility to TC insertion and endovascular treatments, and the availability of peritoneal dialysis and kidney transplantation. Logistic regression and multilevel logistic regression were performed to evaluate possible interactions between the independent variables. A total of 7,973 patients across 47 HD centers were included in the survey. Public health patients accounted for 77% of the study sample. The overall vascular access profiles of the public and private insurance groups were significantly different (p < 0.001). For patients with public health insurance, the prevalence of any catheter was 25%, while that for private patients was 31.8% (p < 0.001). The prevalence of TCs was more common in private patients (15.3% vs. 23.1%, p < 0.001). AV accesses were more common in public health patients (75% vs. 68.2%, p < 0.001), as were fistulas (72.4% vs. 63.1%, p < 0.001). AV grafts were more prevalent among patients with private insurance (2.6 vs. 5.1%, p < 0.001). The availability of endovascular treatments increased the chance of having a TC by 2.3-fold (OR = 2.33, 95% CI = 1.30–4.18); however, it did not reduce the chance of having any catheter. A high chance of having a catheter was found when the time to AV access creation exceeded 60 days. The differences between public and private patients may be explained by underpayments and the decreased accessibility to care infrastructure in the public system, especially for endovascular treatments. In this sample, public health patients had a decreased risk of having a TC over an NTC. Differences in care accessibility and insurance type might influence the type of vascular access.
Tandem occlusions involving the internal carotid and anterior cerebral arteries—A rare form of stroke: Results from the multicenter EVATRISP collaboration study
Authors: Filioglo Andrei , Simaan Naaem , Honig Asaf , Heldner Mirjam , Pezzini Alessandro , Martinez-Majander Nicolas , Padjen Visnja , Baumgartner Philipp , Papanagiotou Panagiotis , Salerno Alexander , Nolte Christian , Nordanstig Annika , Engelter Stefan , Zini Andrea , Zedde Marialuisa , Marto João Pedro , Arnold Marcel , Magoni Mauro , Gensicke Henrik , Cohen Jose , Leker Ronen
Published: December 2022

Background

Patients with stroke secondary to isolated anterior cerebral artery (ACA) occlusions have poor outcomes. Whether tandem occlusions (TO) of the extracranial internal carotid (ICA) and the ACA carry even worse outcomes that remain unknown.

Methods

Patients with TO involving ICA and ACA occlusions were identified from 14 participating centers from the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) project which is a multicenter, observational, cohort study with prospective accrual of data followed by retrospective data analysis. Patients with isolated ACA stroke served as controls.

Results

Included were 92 patients with isolated ACA and 16 patients with ICA-ACA TO stroke. On univariate analyses, patients with TO had more severe strokes on admission [median NIHSS (IQR) 13.5 (9–21) vs. 8 (5–12), p = 0.003] and were more often treated with thrombectomy (81 vs. 40%, p = 0.002). Mortality rates were higher among TO patients (31 vs. 11%, p = 0.03). Rates of favorable functional outcomes were numerically lower among TO patients (38 vs. 60%) but the difference was not statistically significant (p = 0.09). On multivariate analyses, the presence of TO did not modify the chances for favorable outcomes.

Conclusion

TO stroke with ICA and isolated ACA involvement is rare and results in more severe initial neurological deficits and higher mortality compared to those seen in patients with isolated ACA stroke.
Causal association between adiponectin and the risk of Alzheimer's disease: A Mendelian randomization study
Authors: Jin Tianyu , Huang Wei , Cao Fangzheng , Yu Xinyue , Ying Zhenhua , Guo Shunyuan , Cheng Yifan , Xu Chao
Published: December 2022

Background

Numerous observational studies have revealed that circulating adiponectin (ADPN) is associated with Alzheimer's disease (AD) risk. However, the causality remains unknown. We aimed to assess the causality of circulating ADPN on AD risk using Mendelian randomization (MR).

Methods

Fourteen single nucleotide polymorphisms (SNPs) significantly associated with ADPN were selected from publicly available genetic abstract data. We applied these SNPs to two recent large-scale genome-wide association studies (GWAS) of AD, one from the FinnGen consortium and the other from a large meta-analysis. The inverse variance weighted method, MR–Egger method, the weighted median method, the Cochran Q statistic, the MR-Pleiotropy Residual Sum and Outlier methods, and the leave-one-out analysis were applied for MR analyses.

Results

In MR analysis, no significant genetic association was found between plasma ADPN levels and AD risk by analyzing the FinnGen consortium GWAS database in the inverse variance weighted method [odds ratio (OR): 0.874, 95% confidence interval (CI): 0.701–1.089, p = 0.230], MR–Egger (OR: 0.944, 95% CI: 0.692–1.288, p = 0.721), and weighted median method (OR: 0.900, 95% CI: 0.678–1.194, p = 0.449). Additionally, the same analysis was conducted for the meta-analysis database, and we found no significant association (OR: 1.000, 95% CI: 0.999–1.001, p = 0.683).

Conclusion

Our findings reveal no significant causal association between circulating ADPN and AD risk.
Dietary patterns, nutritional status, and mortality risks among the elderly
Authors: Liu Zhen , Xu Di , Xu Wen-xiu , Fei Yin-jiao , Wang Dan-dan , Deng Fei , Tang Jin-hai
Published: December 2022

Introduction

While most epidemiological studies have focused on the effects of individual dietary patterns and nutritional status on health, the relationships between the combinations of these factors and patient prognosis requires further investigation.

Objective

This study explored mortality risk in individuals with different combinations of dietary patterns or nutritional status.

Methods

Unsupervised K-means clustering was used to classify populations. The analyses included Cox proportional risk and competing risk models.

Results

After considering a complex sampling design, the results showed that among 12,724 participants aged >60 years, 6.99% died from cancer and 10.47% from cardiovascular and cerebrovascular disease (CCVD). After correcting for participant baseline information and chronic conditions, the geriatric nutritional risk index and healthy eating index (HEI) were negatively associated with the risk of all-cause and cause-specific mortality. The opposite was true for the dietary inflammatory index (DII). After sorting the population three clusters based on study scores showed higher risks of all-cause mortality and cancer-related death in Cluster 2 and 3.

Discussion

These results suggest that different nutritional status and dietary patterns are associated with the risk of all-cause mortality and death from cancer and CCVD in people aged >60 years in the United States. Dietary patterns with high HEI and low DII were beneficial to health, whereas nutritional status needs to be maintained at a level that is not too low.
A frameshift mutation of TMPRSS3 in a Chinese family with non-syndromic hearing loss
Authors: Liang Jingwen , Yu Zhuoheng , Wang Zhangxing , Chen Jianxia , Liu Yihuan , Yin Zhaoqing , Xu Ruihuan
Published: December 2022

Background

Deafness is the most common sensory defect in humans worldwide. Approximately 50% of cases are attributed to genetic factors, and about 70% are non-syndromic hearing loss (NSHL).

Objectives

To identify clinically relevant gene variants associated with NSHL in a Chinese family using trio-based whole-exome sequencing (WES).

Materials and methods

WES was performed on the 18-month-old female proband, and her parents. Gene variants specific to the family were identified by bioinformatics analysis and evaluated for their relevance to NSHL. We verified the novel variant in this family by the next-generation sequencing.In order to elucidate the frameshift mutation of TMPRSS3 in a Chinese family, we used the Mass spectrometry to detect the gene from 1,010 healthy subjects.

Results

We identified a novel homozygous deletion (c.51delA) in exon 2 of the type II transmembrane serine protease 3 gene TMPRSS3, which resulted in a frameshift mutation just before the protein transmembrane domain (p.Q17fs). The deletion was present in the proband and her father, but not in her mother and the healthy controls. We also found mutations with potential relevance to hearing loss in DCAF17, which encodes a protein of unknown function (c. T555A: p.H185Q), and ZNF276, which encodes zinc finger protein 276 (c.1350–2A > G).

Conclusions and significance

We shown a novel frameshift mutation in TMPRSS3 associated with autosomal recessive NSHL in a Han Chinese family.
Effect of educational brochure compared with video on disease-related knowledge in patients with juvenile idiopathic arthritis: A randomized controlled trial
Authors: Sunthornsup Waraporn , Vilaiyuk Soamarat , Soponkanaporn Sirisucha
Published: December 2022

Introduction

Patient education plays an important role in the management of chronic diseases such as juvenile idiopathic arthritis (JIA). This study compared the effectiveness of a brochure and a video regarding JIA-related knowledge immediately after the intervention, and at 4 weeks post-intervention.

Methods

A prospective randomized controlled trial was conducted. Patients with JIA or parents were randomized to receive education from either a brochure (n = 50) or a video (n = 50) at the clinic. Participants answered questionnaires about disease-specific knowledge before the intervention (T0), immediately after the intervention (T1), and at follow-up 4 weeks later (T2). The questionnaire comprised 15 multiple-choice questions. Final scores ranged from 0 to 15, and were scaled from 0% to 100% to calculate the percentage of knowledge scores. Ninety participants completed the questionnaire at T2 (42 in the brochure and 48 in the video group).

Results

The mean percentage of knowledge scores at T0 was not significantly different between the brochure group and the video group. At T1, the mean percentage of knowledge scores was significantly higher in the video group compared with the brochure group (86.7 ± 12.9% vs. 76.0 ± 21.4%, p = 0.003). Among parents with an educational level below secondary school, the mean percentage of knowledge scores at T1 was significantly higher in the video group compared with the brochure group (83.5 ± 14.4% vs. 69.1 ± 23.2%, p = 0.006). Participants in both groups had significantly higher mean percentage of knowledge scores at T2 compared with T0 (72.7 ± 20.3% vs. 51.1 ± 24.7%, p < 0.001 in the brochure group and 78.3 ± 15.7% vs. 56.1 ± 21.9%, p < 0.001 in the video group). There was no significant difference in the mean percentage of total score change between T2 and T1 between the brochure and video groups (−4.7 ± 13.3% vs. −8.5 ± 11.0%, p = 0.152).

Conclusion

The video was more effective for improving disease-related knowledge immediately post-intervention, particularly in participants with limited education. Although both educational tools had lasting effects on knowledge, the retention rate declined at 4 weeks after both interventions.

Trial registration

Thai Clinical Trials Registry (TCTR)20200310004, retrospectively registered since 06/03/2020
Safety of oral nemonoxacin: A systematic review of clinical trials and postmarketing surveillance
Authors: Yuan Jinyi , Zhang Xiaoping , Chen Jing , Zhang Yueyuan , Zhu Fengjia , Huang Haihui
Published: December 2022

Background: Postmarketing safety analysis is an effective supplement for new drugs in clinical practice. Therefore, we aimed to systematically assess the safety of oral nemonoxacin malate, the first approved C-8-methoxy non-fluorinated quinolone, in clinical studies and via postmarketing safety surveillance.

Methods: We electronically and manually searched and screened safety data (including premarketing and postmarketing data) of oral nemonoxacin from clinical registries. We standardized and summarized the reported adverse events according to the Medical Dictionary for Regulatory Activities System Organ Class and Preferred Terms. We summarized and reported the number and frequency (%) of the AEs and serious AEs in patients with community-acquired pneumonia and in specific patients.

Results: Three Phase II/III comparator studies (n = 670, nemonoxacin), one Phase IV study (n = 461), two special population pharmacokinetic studies (n = 40), four observational studies (n = 1,852), and one 5-year postmarketing surveillance project (n = 257,420) were included in this study. The Phase II/III studies showed that the commonly reported drug-related AEs were similar for oral 500 mg nemonoxacin and levofloxacin treatments, which mainly included increased alanine aminotransferase levels (4.4% vs. 2.5%), neutropenia (2.5% vs. 4.4%), nausea (2.5% vs. 1.6%), and leukopenia (2.3% vs. 3.2%). No drug-related deaths were reported. Postmarketing safety surveillance revealed that known adverse drug reaction characteristics were generally unchanged. Pharmacokinetic data suggested that dose adjustment was not necessary in elderly patients, which was confirmed by a Phase IV study in an elderly population, in patients with renal impairment with CLcr ≥50 ml/min, and in those with mild-to-moderate hepatic impairment.

Conclusion: Clinical trial data of approximately 1,450 patients and postmarketing data of >257,420 patients suggest that nemonoxacin is generally well tolerated and can be a suitable alternative to fluoroquinolones for patients with CAP.
Triaxial closed-loop measurement based on a single-beam zero-field optically pumped magnetometer
Authors: Wang Kun , Zhang Kaixuan , Zhou Binquan , Lu Fei , Zhang Shaowen , Yan Yeguang , Wang Weiyi , Lu Jixi
Published: December 2022

In this study, we propose an approach for the simultaneous measurement of triaxial magnetic fields using a single-beam zero-field optically pumped atomic magnetometer, in which a rotational high-frequency (ω1) and another high-frequency (ω2) modulated magnetic field magnetic fields are applied along the transverse directions and the longitudinal direction, respectively. Theoretical analysis, numerical simulation, and experiments are conducted to demonstrate this method. Experimental sensitivities of 18 fT/Hz1/2 along the two transverse directions and 140 fT/Hz1/2 along the longitudinal direction are simultaneously achieved. On this basis, we operate the magnetometer in closed-loop mode to expand the bandwidth and dynamic range, and to keep the triaxial magnetic field sensed by the magnetometer at zero. The triaxial bandwidths are increased from below 100 Hz to over 1.6 kHz. The triaxial dynamic ranges are all extended to ±150 nT. Plus, we verify the ±1,000 nT dynamic range of the triaxial magnetometer through increasing the triaxial coil constants. The synchronization of triaxial closed-loop measurement, simplicity of magnetometer structure, and closed-loop detection with high sensitivities make it applicable and attractive for biomagnetism imaging in challenging environments.
Benzothiadiazole enhances ascorbate recycling and polyphenols accumulation in blueberry in a cultivar-dependent manner
Authors: Cocetta Giacomo , Cavenago Beatrice , Bulgari Roberta , Spinardi Anna
Published: December 2022

Benzothiadiazole (BTH) is a functional analogue of salicylic acid able to induce systemic acquired resistance in many horticultural crops. The aim of the work was to investigate how BTH may affect i) fruit quality, ii) ascorbic acid (AsA) oxidation and recycling metabolism and iii) phenolic compounds accumulation, during development and ripening of berries from the two selected cultivars. Blueberry (Vaccinium corymbosum L.) plants (cv ‘Brigitta’ and ‘Duke’) were treated with 0.118 mM BTH every two weeks during ripening, then all fruits of each plant were harvested and divided in four developmental stages. Results indicated that BTH had no marked effects on fruit quality parameters. During the first developmental stage, BTH negatively affected dry matter in both cv, while soluble solids and AsA content were affected in ‘Duke’. In fully ripe berries, BTH reduced dry matter in ‘Duke’ and enhanced soluble solids content in ‘Brigitta’, while diminishing titratable acidity. AsA content was positively affected by BTH in ‘Duke’, but not in ‘Brigitta’. The effect of BTH on the enzymes involved in AsA recycling was recorded in berries at the third (fruit more than half pigmented) and fourth developmental stages. After treatment, in both cv ascorbate peroxidase (APX) activity increased in fully ripe berries, while monodehydroascorbate reductase (MDHAR) activity was stimulated at the third ripening stage. Conversely, the activities of dehydroascorbate reductase (DHAR) and glutathione reductase (GR) were enhanced only in ‘Brigitta’ and in ‘Duke’, respectively. BTH stimulated total polyphenols, flavonoid and anthocyanin accumulation in ‘Brigitta’ and in ‘Duke’ at the third and fourth ripening stages. In fully ripe berries, BTH enhanced the accumulation of delphinidins, cyanidins, petunidins and peonidins in ‘Brigitta’, while in ‘Duke’ it increased all classes of anthocyanidins, including malvidin. On the contrary, the relative proportion of the individual anthocyanins was only slightly affected by BTH treatment, mainly regarding delphinidin and malvidin at the third and fourth stage of ripening of ‘Duke’ and ‘Brigitta’, respectively. These results show that preharvest BTH application can positively impact on fruit bioactive compounds levels, affecting AsA recycling and content and increasing polyphenols accumulation in fruit, but partly depending on cv and ripening stage.
Exogenous treatment with melatonin enhances waterlogging tolerance of kiwifruit plants
Authors: Huo Liuqing , Wang Hujing , Wang Qi , Gao Yongbin , Xu Kai , Sun Xuepeng
Published: December 2022

Waterlogging stress has an enormous negative impact on the kiwifruit yield and quality. The protective role of exogenous melatonin on water stress has been widely studied, especially in drought stress. However, the research on melatonin-induced waterlogging tolerance is scarce. Here, we found that treatment with exogenous melatonin could effectively alleviate the damage on kiwifruit plants in response to waterlogging treatment. This was accompanied by higher antioxidant activity and lower ROS accumulation in kiwifruit roots during stress period. The detection of changes in amino acid levels of kiwifruit roots during waterlogging stress showed a possible interaction between melatonin and amino acid metabolism, which promoted the tolerance of kiwifruit plants to waterlogging. The higher levels of GABA and Pro in the roots of melatonin-treated kiwifruit plants partly contributed to their improved waterlogging tolerance. In addition, some plant hormones were also involved in the melatonin-mediated waterlogging tolerance, such as the enhancement of ACC accumulation. This study discussed the melatonin-mediated water stress tolerance of plants from the perspective of amino acid metabolism for the first time.
Improving nitrogen contribution in maize post-tasseling using optimum management under mulch drip irrigation in the semiarid region of Northeast China
Authors: Hou Yunpeng , Xu Xinpeng , Kong Lili , Zhang Lei , Zhang Yitao , Liu Zhiquan
Published: December 2022

Film-mulched drip irrigation has become an important strategy in maize cultivation in the semiarid region of Northeast China. Most farmers concentrate nitrogen (N) fertilizer use early in maize growth, which leads to low N use efficiency and large N losses. Therefore, a three-year (2018 to 2020) field experiment was conducted to determine the optimal N management strategy for maize under film mulch with drip irrigation in the semiarid region of Northeast China. The experiment included five treatments with the total amount of N fertilizer (210 kg N ha−1) applied in different proportions at sowing, sixth-leaf (V6), twelfth-leaf (V12), tasseling (VT), and blister (R2) stages of maize growth: N1, 100-0-0-0-0; N2, 50-50-0-0-0; N3, 30-50-20-0-0; N4, 20-30-30-20-0; and N5, 10-20-30-20-20. The control (CK) did not receive N fertilizer. Maize yield, N uptake and use, changes in soil inorganic N content, and N balance were investigated. Compared with the single basal application (N1), split-N applications (N2, N3, N4, N5) increased maize yield from 13.8% to 24.5% by increasing kernel number per ear and 1000-kernel weight and also improved N accumulation from VT to physiological maturity (PM) stages and its contribution to grain N uptake. In addition, compared with N1, split-N applications also decreased N losses by increasing inorganic N contents in the 0–40 cm soil layer and by decreasing N leaching in the 60–200 cm soil layer. Regression analysis demonstrated that N accumulation after the VT stage was positively related with maize yield. Among treatments, N4 had the highest yield, N recovery efficiency, agronomic efficiency, and partial factor productivity, with respective increases of 24.5%, 14.7 percentage point, 11.4 kg kg−1, and 11.4 kg kg−1 compared with those in N1. As a result, N losses were also reduced by 33.7% in N4 compared with those in N1. In conclusion, the split-N management strategy with four N applications under film-mulched drip irrigation has great potential to improve maize yield, increase N use efficiency, and reduce N loss in the semiarid region of Northeast China.