bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiscale entropy analysis of retinal signals reveals reduced complexity in a mouse model of Alzheimer’s disease
Authors: Araya-Arriagada Joaquín , Garay Sebastián , Rojas Cristóbal , Duran-Aniotz Claudia , Palacios Adrián G. , Chacón Max , Medina Leonel E.
Published: May 2022

Alzheimer’s disease (AD) is one of the most significant health challenges of our time, affecting a growing number of the elderly population. In recent years, the retina has received increased attention as a candidate for AD biomarkers since it appears to manifest the pathological signatures of the disease. Therefore, its electrical activity may hint at AD-related physiological changes. However, it is unclear how AD affects retinal electrophysiology and what tools are more appropriate to detect these possible changes. In this study, we used entropy tools to estimate the complexity of the dynamics of healthy and diseased retinas at different ages. We recorded microelectroretinogram responses to visual stimuli of different nature from retinas of young and adult, wild-type and 5xFAD—an animal model of AD—mice. To estimate the complexity of signals, we used the multiscale entropy approach, which calculates the entropy at several time scales using a coarse graining procedure. We found that young retinas had more complex responses to different visual stimuli. Further, the responses of young, wild-type retinas to natural-like stimuli exhibited significantly higher complexity than young, 5xFAD retinas. Our findings support a theory of complexity-loss with aging and disease and can have significant implications for early AD diagnosis.
Associations of body shape index (ABSI) and hip index with liver, metabolic, and inflammatory biomarkers in the UK Biobank cohort
Authors: Christakoudi Sofia , Riboli Elio , Evangelou Evangelos , Tsilidis Konstantinos K.
Published: May 2022

Associations of liver, metabolic, and inflammatory biomarkers in blood with body shape are unclear, because waist circumference (WC) and hip circumference (HC) are dependent on overall body size, resulting in bias. We have used the allometric “a body shape index” (ABSI = WC(mm)$$\,*\,$$

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Weight(kg)-2/3$$\,*\,$$

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Height(m)5/6) and hip index (HIwomen = HC(cm)$$\,*\,$$

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Weight(kg)-0.482$$\,*\,$$

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Height(cm)0.310, HImen = HC(cm)$$\,*\,$$

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Weight(kg)-2/5$$\,*\,$$

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Height(cm)1/5), which are independent of body mass index (BMI) by design, in multivariable linear regression models for 121,879 UK Biobank men and 135,559 women. Glucose, glycated haemoglobin (HbA1c), triglycerides, low-density-lipoprotein cholesterol, apolipoprotein-B, alanine aminotransferase (ALT), gamma-glutamyltransferase, and lymphocytes were associated positively with BMI and ABSI but inversely with HI. High-density-lipoprotein cholesterol and apolipoprotein-A1 were associated inversely with BMI and ABSI but positively with HI. Lipid-related biomarkers and ALT were associated only with HI in obese men. C-reactive protein, neutrophils, monocytes, and alkaline phosphatase were associated positively, while bilirubin was associated inversely, with BMI and ABSI but not with HI. Associations were consistent within the clinical reference ranges but were lost or changed direction for low or high biomarker levels. Our study confirms associations with waist and hip size, independent of BMI, for metabolic biomarkers but only with waist size for inflammatory biomarkers, suggesting different contribution of the mechanistic pathways related to body shape.
Common gene expression patterns are observed in rice roots during associations with plant growth-promoting bacteria, Herbaspirillum seropedicae and Azospirillum brasilense
Authors: Wiggins Grant , Thomas Jacklyn , Rahmatallah Yasir , Deen Connor , Haynes Allee , Degon Zachariah , Glazko Galina , Mukherjee Arijit
Published: May 2022

Non-legume plants such as rice and maize can form beneficial associations with plant growth-promoting bacteria (PGPB) such as Herbaspirillum seropedicae and Azospirillum brasilense. Several studies have shown that these PGPB promote plant growth via multiple mechanisms. Our current understanding of the molecular aspects and signaling between plants like rice and PGPB like Herbaspirillum seropedicae is limited. In this study, we used an experimental system where H. seropedicae could colonize the plant roots and promote growth in wild-type rice. Using this experimental setup, we identified 1688 differentially expressed genes (DEGs) in rice roots, 1 day post-inoculation (dpi) with H. seropedicae. Several of these DEGs encode proteins involved in the flavonoid biosynthetic pathway, defense, hormone signaling pathways, and nitrate and sugar transport. We validated the expression pattern of some genes via RT-PCR. Next, we compared the DEGs identified in this study to those we previously identified in rice roots during associations with another PGPB, Azospirillum brasilense. We identified 628 genes that were differentially expressed during both associations. The expression pattern of these genes suggests that some of these are likely to play a significant role(s) during associations with both H. seropedicae and A. brasilense and are excellent targets for future studies.
Prussian blue technique is prone to yield false negative results in magnetoreception research
Authors: Curdt Franziska , Haase Katrin , Ziegenbalg Laura , Greb Helena , Heyers Dominik , Winklhofer Michael
Published: May 2022

Perls’s Prussian blue staining technique has been used in magnetoreception research to screen tissues for iron-rich structures as proxies for putative magnetoreceptor structures based on magnetic particles. However, seemingly promising structural candidates in the upper beak of birds detected with Prussian blue turned out to be either irreproducible or located in non-neuronal cells, which has spurred a controversy that has not been settled yet. Here we identify possible pitfalls in the previous works and apply the Prussian blue technique to tissues implicated in magnetic-particle-based magnetoreception, in an effort to reassess its suitability for staining single-domain magnetite, i.e., the proposed magnetic substrate for the interaction with the external magnetic field. In the upper beak of night-migratory songbirds, we found staining products in great numbers, but not remotely associated with fiber terminals of the traced ophthalmic branch of the trigeminal nerve. Surprisingly, staining products were absent from the lamina propria in the olfactory rosette of rainbow trout where candidate magnetoreceptor structures were identified with different techniques earlier. Critically, magnetosome chains in whole cells of magnetotactic bacteria remained unstained. The failure to label single-domain magnetite in positive control samples is a serious limitation of the technique and suggests that two most influential but antipodal studies conducted previously stood little chances of obtaining correct positive results under the assumption that magnetosome-like particles were present in the tissues. Nonetheless, the staining technique appears suitable to identify tissue contamination with iron-rich fine dust trapped in epithelia already in vivo.
An Myh11 single lysine deletion causes aortic dissection by reducing aortic structural integrity and contractility
Authors: Negishi Keita , Aizawa Kenichi , Shindo Takayuki , Suzuki Toru , Sakurai Takayuki , Saito Yuichiro , Miyakawa Takuya , Tanokura Masaru , Kataoka Yosky , Maeda Mitsuyo , Tomida Shota , Morita Hiroyuki , Takeda Norifumi , Komuro Issei , Kario Kazuomi , Nagai Ryozo , Imai Yasushi
Published: May 2022

Pathogenic variants in myosin heavy chain (Myh11) cause familial thoracic aortic aneurysms and dissections (FTAAD). However, the underlying pathological mechanisms remain unclear because of a lack of animal models. In this study, we established a mouse model with Myh11 K1256del, the pathogenic variant we found previously in two FTAAD families. The Myh11∆K/∆K aorta showed increased wall thickness and ultrastructural abnormalities, including weakened cell adhesion. Notably, the Myh11∆K/+ mice developed aortic dissections and intramural haematomas when stimulated with angiotensin II. Mechanistically, integrin subunit alpha2 (Itga2) was downregulated in the Myh11∆K/∆K aortas, and the smooth muscle cell lineage cells that differentiated from Myh11∆K/∆K induced pluripotent stem cells. The contractility of the Myh11∆K/∆K aortas in response to phenylephrine was also reduced. These results imply that the suboptimal cell adhesion indicated by Itga2 downregulation causes a defect in the contraction of the aorta. Consequently, the defective contraction may increase the haemodynamic stress underlying the aortic dissections.
The role of the meningeal lymphatic system in local meningeal inflammation and trigeminal nociception
Authors: Mikhailov Nikita , Virenque Anaïs , Koroleva Kseniia , Eme-Scolan Elisa , Teleman Matei , Abdollahzadeh Ali , Giniatullina Raisa , Gafurov Oleg , Krivoshein Georgii , Malm Tarja , Hämäläinen Riikka H. , Sierra Alejandra , Tohka Jussi , Rua Rejane , Noe Francesco M. , Giniatullin Rashid
Published: May 2022

A system of lymphatic vessels has been recently characterized in the meninges, with a postulated role in ‘cleaning’ the brain via cerebral fluid drainage. As meninges are the origin site of migraine pain, we hypothesized that malfunctioning of the lymphatic system should affect the local trigeminal nociception. To test this hypothesis, we studied nociceptive and inflammatory mechanisms in the hemiskull preparations (containing the meninges) of K14-VEGFR3-Ig (K14) mice lacking the meningeal lymphatic system. We recorded the spiking activity of meningeal afferents and estimated the local mast cells population, calcitonin gene-related peptide (CGRP) and cytokine levels as well as the dural trigeminal innervation in freshly-isolated hemiskull preparations from K14-VEGFR3-Ig (K14) or wild type C57BL/6 mice (WT). Spiking activity data have been confirmed in an acquired model of meningeal lymphatic dysfunction (AAV-mVEGFR3(1–4)Ig induced lymphatic ablation). We found that levels of the pro-inflammatory cytokine IL12-p70 and CGRP, implicated in migraine, were reduced in the meninges of K14 mice, while the levels of the mast cell activator MCP-1 were increased. The other migraine-related pro-inflammatory cytokines (basal and stimulated), did not differ between the two genotypes. The patterns of trigeminal innervation in meninges remained unchanged and we did not observe alterations in basal or ATP-induced nociceptive firing in the meningeal afferents associated with meningeal lymphatic dysfunction. In summary, the lack of meningeal lymphatic system is associated with a new balance between pro- and anti-migraine mediators but does not directly trigger meningeal nociceptive state.
Paleoenvironment reconstruction and peat-forming conditions of Neogene paralic coal sequences from Mukah, Sarawak, Malaysia
Authors: Zainal Abidin Nor Syazwani , Mustapha Khairul Azlan , Abdullah Wan Hasiah , Konjing Zainey
Published: May 2022

Eight coal seams containing Neogene paralic coals from the Mukah coalfield, Sarawak, Malaysia, were investigated using petrographical, palynological, and organic geochemical analyses to describe coal-forming vegetation, paleoclimatic, and paleoenvironment conditions during peat development and precursor mires, as well as their associations within a sequence-stratigraphic context. The petrographic and geochemical data of the coals imply the existence of oxygen-deficient and water-saturated conditions in the precursor mires. The reducing conditions in the mires were followed by biomass loss. The Mukah coals are suggested to be deposited in freshwater peat swamps, and the rich preservation of angiosperm pollen indicates that the organic matter in dense and lowland forest vegetation was mostly terrigenous. The overwhelming presence of Casuarina and Calamus types suggest the paleomires were closely linked to the Kerapah/Kerangas peat forest and were marginally bordered by rattan, which was supported by biomarker data. Rheotrophic–ombrotrophic mires temporarily formed due to water table fluctuations, which were strongly dependent on ever-wet climate changes and syn-depositional tectonics during the Neogene, and resulted in the balanced to high peat accumulation and preservation. A maximum thickness of 35 m of peat deposits is suggested to form between 10,000 and 175,000 years ago based on the peat:coal ratio. The coals are proposed to be influenced by transgressive to initial highstand cycles within the paralic setting.
In vitro proliferation and long-term preservation of functional primary rat hepatocytes in cell fibers
Authors: Mazari-Arrighi Elsa , Okitsu Teru , Teramae Hiroki , Aoyagi Hoshimi , Kiyosawa Mahiro , Yano Mariko , Chatelain François , Fuchs Alexandra , Takeuchi Shoji
Published: May 2022

Primary hepatocytes are essential cellular resources for drug screening and medical transplantation. While culture systems have already succeeded in reconstituting the biomimetic microenvironment of primary hepatocytes, acquiring additional capabilities to handle them easily as well as to expand them remains unmet needs. This paper describes a culture system for primary rat hepatocytes, based on cell fiber technology, that brings scalability and handleability. Cell fibers are cell-laden core–shell hydrogel microfibers; in the core regions, cells are embedded in extracellular matrix proteins, cultured three-dimensionally, and exposed to soluble growth factors in the culture medium via the hydrogel shells. By encapsulating primary rat hepatocytes within cell fibers, we first demonstrated their proliferation while maintaining their viability and their hepatic specific functions for up to thirty days of subsequent culture. We then demonstrated the efficiency of proliferating primary rat hepatocytes in cell fibers not only as cell-based sensors to detect drugs that damage hepatic functions and hepatocellular processes but also as transplants to improve the plasma albumin concentrations of congenital analbuminemia. Our culture system could therefore be included in innovative strategies and promising developments in applying primary hepatocytes to both pharmaceutical and medical fields.
Proline confers acid stress tolerance to Bacillus megaterium G18
Authors: Goswami Gunajit , Hazarika Dibya Jyoti , Chowdhury Naimisha , Bora Sudipta Sankar , Sarmah Unmona , Naorem Romen Singh , Boro Robin Chandra , Barooah Madhumita
Published: May 2022

Proline plays a multifunctional role in several organisms including bacteria in conferring protection under stress conditions. In this paper we report the role of proline in conferring acid tolerance to Bacillus megaterium G18. An acid susceptible mutant of B. megaterium G18 which required proline for its growth under acid stress condition was generated through Tn5 mutagenesis. Further, targeted inactivation of proC involved in osmo-adaptive proline synthesis in B. megaterium G18 resulted in the loss of ability of the bacterium to grow at low pH (pH 4.5). Exogenous supply of proline (1 mM) to the growth medium restored the ability of the mutant cells to grow at pH 4.5 which was not the same in case of other osmoprotectants tested. Proline was produced and secreted to extracellular medium by B. megaterium G18 when growing in low pH condition as evidenced by the use of Escherichia coli proline auxotrophs and HPLC analysis. Further, pHT01 vector based expression of full length proC gene in the ∆proC mutant cells restored the survival capacity of the mutant cells in acidic pH, suggesting that proline production is an important strategy employed by B. megaterium G18 to survive under acid stress induced osmotic stress.
X-ray nanoimaging of a transversely embedded carbon fiber in epoxy matrix under static and cyclic loads
Authors: Takahashi Kosuke , Shoya Ryosuke , Matsuo Takuma , Sato Wataru , Nakamura Takashi , Takeuchi Akihisa , Uesugi Masayuki , Uesugi Kentaro
Published: May 2022

The initial stage of fatigue failure has not been thoroughly clarified for carbon fiber reinforced plastics (CFRPs). Although the initiation of fatigue cracks has been regarded to be interfacial debonding between the carbon fiber and polymer matrix, their detection among numerous carbon fibers, whose diameter is only 7 µm, is extremely difficult. In this study, a single carbon fiber was transversely embedded in a dumbbell-shaped epoxy sample to focus on the interfacial debonding and was observed using synchrotron radiation (SR) X-ray computed tomography (CT). A tabletop fatigue testing machine driven by a piezoelectric actuator was developed to apply static and cyclic loads along the beamline. SR X-ray multiscale CT imaging was conducted by switching between an absorption-contrast projection method (micro-CT) and a phase-contrast imaging-type X-ray microscopic CT (nano-CT). The carbon fiber was entirely captured by micro-CT and then magnified at both ends on the free surfaces. Nano-CT clearly visualized the interfacial debonding under 30 MPa static tensile load and the implication of the coalescence of nano-voids along the interface under 50 MPa. Under cyclic loads, the interfacial debonding gradually progressed under a 8–40 MPa sinusoidal stress after 10,000 cycles, whereas it did not propagate under a stress below 30 MPa.
Quantitative radiological analysis and clinical outcomes of urgent EC-IC bypass for hemodynamic compromised patients with acute ischemic stroke
Authors: Jo Hyunjun , Seo Dongwook , Kim Young Deok , Ban Seung Pil , Kim Tackeun , Kwon O-Ki , Oh Chang Wan , Sunwoo Leonard , Kim Beom Joon , Han Moon-Ku , Bae Hee-Joon , Lee Si Un , Bang Jae Seung
Published: May 2022

This study aimed to demonstrate the effectiveness of urgent extracranial-to-intracranial bypass (EIB) in acute ischemic stroke (AIS) through quantitative analysis of computed tomography perfusion (CTP) results using RAPID software. We retrospectively analyzed 41 patients who underwent urgent EIB for AIS under strict operation criteria. The quantitative data from CTP images were reconstructed to analyze changes in pre- and postoperative perfusion status in terms of objective numerical values using RAPID software. Short- and long-term clinical outcomes, including complications and neurological status, were also analyzed. Postoperatively, the volume of time-to-max (Tmax) > 6 s decreased significantly; it continued to improve significantly until 6 months postoperatively (preoperative, 78 ml (median); immediate postoperative, 23 ml; postoperative 6 months, 7 ml; p = 0.000). Ischemic core-penumbra mismatch volumes were also significantly improved until 6 months postoperatively (preoperative, 72 ml (median); immediate postoperative, 23 ml; postoperative 6 months, 5 ml; p = 0.000). In addition, the patients’ neurological condition improved significantly (p < 0.001). Only one patient (2.3%) showed progression of infarction. Urgent EIB using strict indications can be a feasible treatment for IAT-ineligible patients with AIS due to large vessel occlusion or stenosis.
Improving user experience of SSVEP BCI through low amplitude depth and high frequency stimuli design
Authors: Ladouce S. , Darmet L. , Torre Tresols J. J. , Velut S. , Ferraro G. , Dehais F.
Published: May 2022

Steady-States Visually Evoked Potentials (SSVEP) refer to the sustained rhythmic activity observed in surface electroencephalography (EEG) in response to the presentation of repetitive visual stimuli (RVS). Due to their robustness and rapid onset, SSVEP have been widely used in Brain Computer Interfaces (BCI). However, typical SSVEP stimuli are straining to the eyes and present risks of triggering epileptic seizures. Reducing visual stimuli contrast or extending their frequency range both appear as relevant solutions to address these issues. It however remains sparsely documented how BCI performance is impacted by these features and to which extent user experience can be improved. We conducted two studies to systematically characterize the effects of frequency and amplitude depth reduction on SSVEP response. The results revealed that although high frequency stimuli improve visual comfort, their classification performance were not competitive enough to design a reliable/responsive BCI. Importantly, we found that the amplitude depth reduction of low frequency RVS is an effective solution to improve user experience while maintaining high classification performance. These findings were further validated by an online T9 SSVEP-BCI in which stimuli with 40% amplitude depth reduction achieved comparable results (>90% accuracy) to full amplitude stimuli while significantly improving user experience.
Relativistic motions of spin-zero quantum oscillator field in a global monopole space-time with external potential and AB-effect
Authors: Ahmed Faizuddin
Published: May 2022

In this paper, we analyze a spin-zero relativistic quantum oscillator in the presence of the Aharonov–Bohm magnetic flux in a space-time background produced by a point-like global monopole (PGM). Afterwards, we introduce a static Coulomb-type scalar potential and subsequently with the same type of vector potential in the quantum system. We solve the generalized Klein–Gordon oscillator analytically for different functions (e.g. Coulomb- and Cornell-type functions) and obtain the bound-states solutions in each case. We discuss the effects of topological defects associated with the scalar curvature of the space-time and the Coulomb-type external potentials on the energy profiles and the wave function of these oscillator fields. Furthermore, we show that the obtained energy eigenvalues depend on the magnetic quantum flux which gives rise to the gravitational analogue of the Aharonov–Bohm (AB) effect.
Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth muscle cells from adult mouse heart
Authors: Cao Zhiping , Minnier Jessica , Liu Lijuan , Scott Kristin L. Lyon , Reddy Ashok P. , Wilmarth Phillip A. , David Larry L. , Barnes Anthony P. , Grafe Marjorie R. , Kaul Sanjiv , Alkayed Nabil J. , Davis Catherine M.
Published: May 2022

The microcirculation serves crucial functions in adult heart, distinct from those carried out by epicardial vessels. Microvessels are governed by unique regulatory mechanisms, impairment of which leads to microvessel-specific pathology. There are few treatment options for patients with microvascular heart disease, primarily due to limited understanding of underlying pathology. High throughput mRNA sequencing and protein expression profiling in specific cells can improve our understanding of microvessel biology and disease at the molecular level. Understanding responses of individual microvascular cells to the same physiological or pathophysiological stimuli requires the ability to isolate the specific cell types that comprise the functional units of the microcirculation in the heart, preferably from the same heart, to ensure that different cells have been exposed to the same in-vivo conditions. We developed an integrated process for simultaneous isolation and culture of the main cell types comprising the microcirculation in adult mouse heart: endothelial cells, pericytes, and vascular smooth muscle cells. These cell types were characterized with isobaric labeling quantitative proteomics and mRNA sequencing. We defined microvascular cell proteomes, identified novel protein markers, and confirmed established cell-specific markers. Our results allow identification of unique markers and regulatory proteins that govern microvascular physiology and pathology.
Lake microbiome and trophy fluctuations of the ancient hemp rettery
Authors: Iwańska Olga , Latoch Przemysław , Suchora Magdalena , Pidek Irena A. , Huber Miłosz , Bubak Iwona , Kopik Natalia , Kovalenko Mariia , Gąsiorowski Michał , Armache Jean-Paul , Starosta Agata L.
Published: May 2022

Lake sediments not only store the long-term ecological information including pollen and microfossils but are also a source of sedimentary DNA (sedDNA). Here, by the combination of traditional multi-proxy paleolimnological methods with the whole-metagenome shotgun-sequencing of sedDNA we were able to paint a comprehensive picture of the fluctuations in trophy and bacterial diversity and metabolism of a small temperate lake in response to hemp retting, across the past 2000 years. Hemp retting (HR), a key step in hemp fibre production, was historically carried out in freshwater reservoirs and had a negative impact on the lake ecosystems. In Lake Slone, we identified two HR events, during the late stage of the Roman and Early Medieval periods and correlated these to the increased trophy and imbalanced lake microbiome. The metagenomic analyses showed a higher abundance of Chloroflexi, Planctomycetes and Bacteroidetes and a functional shift towards anaerobic metabolism, including degradation of complex biopolymers such as pectin and cellulose, during HR episodes. The lake eutrophication during HR was linked to the allochthonous, rather than autochthonous carbon supply—hemp straws. We also showed that the identification of HR based on the palynological analysis of hemp pollen may be inconclusive and we suggest the employment of the fibre count analysis as an additional and independent proxy.
Pinolenic acid exhibits anti-inflammatory and anti-atherogenic effects in peripheral blood-derived monocytes from patients with rheumatoid arthritis
Authors: Takala Rabaa , Ramji Dipak P. , Andrews Robert , Zhou You , Farhat Mustafa , Elmajee Mohammed , Rundle Shelley , Choy Ernest
Published: May 2022

Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. PNLA reduced percentage of monocytes expressing cytokines: TNF-α by 23% (p = 0.048), IL-6 by 25% (p = 0.011), IL-1β by 23% (p = 0.050), IL-8 by 20% (p = 0.066). Pathway analysis identified upstream activation of peroxisome proliferator-activated receptors (PPARs), sirtuin3, and let7 miRNA, and KLF15, which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-α, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p = 9.14E−09) and mitochondrial dysfunction (p = 4.18E−08), while the sirtuin (SIRTs) signalling pathway was activated (p = 8.89E−06) which interfere with the pathophysiological process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and acetyl-CoA acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.
Association between climate variables and pulmonary tuberculosis incidence in Brunei Darussalam
Authors: Chaw Liling , Liew Sabrina Q. R. , Wong Justin
Published: May 2022

We investigated the association between climate variables and pulmonary tuberculosis (PTB) incidence in Brunei-Muara district, Brunei Darussalam. Weekly PTB case counts and climate variables from January 2001 to December 2018 were analysed using distributed lag non-linear model framework. After adjusting for long-term trend and seasonality, we observed positive but delayed relationship between PTB incidence and minimum temperature, with significant adjusted relative risk (adj.RR) at 25.1 °C (95th percentile) when compared to the median, from lag 30 onwards (adj.RR = 1.17 [95% Confidence Interval (95% CI): 1.01, 1.36]), suggesting effect of minimum temperature on PTB incidence after 30 weeks. Similar results were observed from a sub-analysis on smear-positive PTB case counts from lag 29 onwards (adj.RR = 1.21 [95% CI: 1.01, 1.45]), along with positive and delayed association with total rainfall at 160.7 mm (95th percentile) when compared to the median, from lag 42 onwards (adj.RR = 1.23 [95% CI: 1.01, 1.49]). Our findings reveal evidence of delayed effects of climate on PTB incidence in Brunei, but with varying degrees of magnitude, direction and timing. Though explainable by environmental and social factors, further studies on the relative contribution of recent (through primary human-to-human transmission) and remote (through reactivation of latent TB) TB infection in equatorial settings is warranted.
Exploration for adequate non-diffractive beam generation in dense scattering media
Authors: Xiafukaiti Alifu , Lagrosas Nofel , Shiina Tatsuo
Published: May 2022

The propagation methods of a non-diffractive beam (NDB) for optical sensing in scattering media have been extensively studied. However, those methods can realize the high resolution and long depth of focus in the viewpoint of microscopic imaging. In this study, we focus on macroscopic sensing in living tissues with a depth of a few tens centimeters. An experimental approach for generating adequate NDB in dense scattering media based on the linear relationship between propagation distance and transport mean free path is reported. For annular beams with different diameters, the same changes of the center intensity ratio of NDB are obtained from the experiment results. They are discussed with theoretical analysis. As a result, the maximum center intensity ratio of the adequate generated NDB can be estimated at arbitrary propagation distance in the dense scattering media.
High CRP-albumin ratio predicts poor prognosis in transplant ineligible elderly patients with newly diagnosed acute myeloid leukemia
Authors: Senjo Hajime , Onozawa Masahiro , Hidaka Daisuke , Yokoyama Shota , Yamamoto Satoshi , Tsutsumi Yutaka , Haseyama Yoshihito , Nagashima Takahiro , Mori Akio , Ota Shuichi , Sakai Hajime , Ishihara Toshimichi , Miyagishima Takuto , Kakinoki Yasutaka , Kurosawa Mitsutoshi , Kobayashi Hajime , Iwasaki Hiroshi , Hashimoto Daigo , Kondo Takeshi , Teshima Takanori
Published: May 2022

Acute myeloid leukemia (AML) patients older than 65 years have a poor prognosis. Recently, CAR (C-reactive-protein/albumin ratio) has been actively reported as a prognostic index reflecting the nutritional and inflammatory status of elderly patients with solid tumors, but the usefulness of this index as a prognostic indicator in transplant-ineligible elderly AML patients has not been investigated. We studied genetic alterations and CARs in 188 newly diagnosed AML patients aged 65 years or older who were treated in a multicenter setting and had treated without HSCT. Both NCCN 2017 risk group, reflecting the genetic component of the tumor, and CAR, reflecting the inflammatory and nutritional status of the patient, successfully stratified the overall survival (OS) of the patients (2-year OS; CAR low vs high, 42.3% vs 17.8%, P < 0.001). Furthermore, in multivariate analysis, NCCN 2017 poor group and high CAR were extracted as independent poor prognostic factors predicting 2-year OS in the current study. We found, for the first time, that CAR at diagnosis predicted the prognosis of elderly patients with newly diagnosed AML treated without HSCT.
Belgian endive-derived biostimulants promote shoot and root growth in vitro
Authors: Ogunsanya Halimat Yewande , Motti Pierfrancesco , Li Jing , Trinh Hoang Khai , Xu Lin , Bernaert Nathalie , Van Droogenbroeck Bart , Murvanidze Nino , Werbrouck Stefaan P. O. , Mangelinckx Sven , Ramirez Aldana , Geelen Danny
Published: May 2022

Recovering biostimulant compounds from by-products of crops is a promising strategy to add value, enhance sustainability, and increase the environmental safety of the agricultural production chain. Here, we report consistent root and shoot growth-stimulating bioactivity present in water-based extracts from Belgian endive forced roots (Cichorium intybus var. foliosum) over two consecutive harvest years. The shoot and the primary root of in vitro cultivated Arabidopsis thaliana treated with Belgian endive extract were about 30% increased in size compared to plants grown under control conditions. The ornamental species Plectranthus esculentus also showed enhanced in vitro shoot and root growth, suggesting bioactivity on a broad range of species. Fractionation of the Belgian endive extracts into aqueous and organic subfractions coupled with bioactivity measurements showed that the principal root and shoot growth-promoting ingredients are primarily water-soluble. NMR-based characterization of the bioactive aqueous fractions revealed the presence of predominantly sugars and organic acids. Malate and sugars were abundant and common to all water fractions, suggesting these molecules contributed to the growth stimulation phenotype. The findings indicate that Belgian endive roots are a source for the development of organic waste-derived biostimulants with potential for application in tissue culture and putatively for soil-grown crop production.
Symptom burden correlates to impairment of diffusion capacity and exercise intolerance in long COVID patients
Authors: Kersten Johannes , Wolf Alexander , Hoyo Luis , Hüll Elina , Tadic Marijana , Andreß Stefanie , d’Almeida Sascha , Scharnbeck Dominik , Roder Eva , Beschoner Petra , Rottbauer Wolfgang , Buckert Dominik
Published: May 2022

After acute infection with the SARS-CoV-2 virus, a considerable number of patients remains symptomatic with pathological changes in various organ systems. This study aimed to relate the physical and mental burden of symptoms of long COVID patients to the findings of a somatic evaluation. In patients with persistent long COVID symptoms three months after acute infection we assessed physical and mental health status using the SF-36 questionnaire. The cohort was dichotomised by the results (upper two quartiles vs. lower to quartiles) and compared with regard to transthoracic echocardiography, body plethysmography (including diffusion capacity), capillary blood gas analysis and 6-min walk test (6-MWT). From February 22 to September 13, 2021, 463 patients were prospectively examined, of which 367 completed the SF-36 questionnaire. A positive correlation between initial disease severity (need for hospitalization, intensive care medicine) and resulting symptom burden at follow-up could be demonstrated. Patients with impaired subjective physical and mental status were significantly more likely to be women. There was a significant correlation between symptom severity and reduced exercise tolerance in the 6-MWT (495.6 ± 83.7 m vs 549.7 ± 71.6 m, p < 0.001) and diffusion capacity for carbon monoxide (85.6 ± 14.3% of target vs 94.5 ± 14.4, p < 0.001). In long COVID patients, initial disease severity is correlated with symptom burden after at least 3 months of follow-up. Highly symptomatic long COVID patients show impaired diffusion capacity and 6-MWT despite average or mildly affected mechanical lung parameters. It must be further differentiated whether this corresponds to a transient functional impairment or whether it is a matter of defined organ damage.
A portable non-invasive microwave based head imaging system using compact metamaterial loaded 3D unidirectional antenna for stroke detection
Authors: Islam Mohammad Shahidul , Islam Mohammad Tariqul , Almutairi Ali F.
Published: May 2022

A metamaterial (MTM) loaded compact three-dimensional antenna is presented for the portable, low-cost, non-invasive microwave head imaging system. The antenna has two slotted dipole elements with finite arrays of MTM unit cell and a folded parasitic patch that attains directional radiation patterns with 80% of fractional bandwidth. The operating frequency of the antenna is 1.95–4.5 GHz. The optimization of MTM unit cell is performed to increase the operational bandwidth, realized gain, and efficiency of the antenna within the frequency regime. It is also explored to improve radiation efficiency and gain when placed to head proximity. One-dimensional mathematical modelling is analyzed to precisely estimate the power distribution that validates the performance of the proposed antenna. To verify the imaging capability of the proposed system, an array of 9 antennas and a realistic three-dimensional tissue-emulating experimental semi-solid head phantom are fabricated and measured. The backscattered signal is collected from different antenna positions and processed by the updated Iterative Correction of Coherence Factor Delay-Multiply-and-Sum beamforming algorithm to reconstruct the hemorrhage images. The reconstructed images in simulation and experimental environment demonstrate the feasibility of the proposed system as a portable platform to successfully detect and locate the hemorrhages inside the brain.
Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity
Authors: Thomas Stefani N. , Karger Amy B. , Altawallbeh Ghaith , Nelson Kathryn M. , Jacobs David R. , Gorlin Jed , Barcelo Helene , Thyagarajan Bharat
Published: May 2022

We assessed the feasibility of a highly sensitive immunoassay method based on single molecule array (Simoa) technology to detect IgG and IgA antibodies against SARS-CoV-2 spike protein receptor binding domain (RBD) in saliva from individuals with natural or vaccine-induced COVID-19 immunity. The performance of the method was compared to a laboratory-developed SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay (ELISA). Paired serum and saliva specimens were collected from individuals (n = 40) prior to and 2 weeks after receiving an initial prime COVID-19 vaccine dose (Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273). Saliva was collected using a commercially available collection device (OraSure Inc.) and SARS-CoV-2 RBD IgG antibodies were measured by an indirect ELISA using concentrated saliva samples and a Simoa immunoassay using unconcentrated saliva samples. The IgG results were compared with paired serum specimens that were analyzed for total RBD antibodies using the ELISA method. The analytical sensitivity of the saliva-based Simoa immunoassay was five orders of magnitude higher than the ELISA assay: 0.24 pg/mL compared to 15 ng/mL. The diagnostic sensitivity of the saliva ELISA method was 90% (95% CI 76.3–97.2%) compared to 91.7% (95% CI 77.5–98.2%) for the Simoa immunoassay without total IgG-normalization and 100% (95% CI 90.3–100%) for the Simoa immunoassay after total IgG-normalization when compared to the serum ELISA assay. When analyzed using the SARS-CoV-2 RBD IgG antibody ELISA, the average relative increase in antibody index (AI) between the saliva of the post- and pre-vaccinated individuals was 8.7 (AIpost/pre). An average relative increase of 431 pg/mL was observed when the unconcentrated saliva specimens were analyzed using the Simoa immunoassay (SARS-CoV-2 RBD IgGpost/pre). These findings support the suitability of concentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG antibodies via ELISA, and unconcentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG and IgA using an ultrasensitive Simoa immunoassay.
Therapeutic potential of biogenic and optimized silver nanoparticles using Rubia cordifolia L. leaf extract
Authors: Chandraker Sandip Kumar , Lal Mishri , Khanam Farheen , Dhruve Preeti , Singh Rana P. , Shukla Ravindra
Published: May 2022

Rubia cordifolia L. is a widely used traditional medicine in the Indian sub-continent and Eastern Asia. In the present study, the aqueous leaf extract of the R. Cordifolia was used to fabricate silver nanoparticles (RC@AgNPs), following a green synthesis approach. Effect of temperature (60 °C), pH (8), as well the concentration of leaf extract (2 ml) and silver nitrate (2 mM) were optimized for the synthesis of stable RC@AgNPs. The phytofabrication of nanosilver was validated by UV–visible spectral analysis, which displayed a distinctive surface plasmon resonance peak at 432 nm. The effective functional molecules as capping and stabilizing agents, and responsible for the conversion of Ag+ to nanosilver (Ag0) were identified using the FTIR spectra. The spherical RC@AgNPs with an average size of ~ 20.98 nm, crystalline nature, and 61% elemental composition were revealed by TEM, SEM, XRD, and. EDX. Biogenic RC@AgNPs displayed a remarkable anticancer activity against B16F10 (melanoma) and A431 (carcinoma) cell lines with respective IC50 of 36.63 and 54.09 µg/mL, respectively. Besides, RC@AgNPs showed strong antifungal activity against aflatoxigenic Aspergillus flavus, DNA-binding properties, and DPPH and ABTS free radical inhibition. The presented research provides a potential therapeutic agent to be utilized in various biomedical applications.
Experimental /numerical study of a circular rib-stiffened flange connection with inner and outer flange plates under combined bending and tensile loading
Authors: Chen Yong , Mou Wending , Guo Yong , Wang Jiyang , Xue Bin
Published: May 2022

Focusing on circular rib-stiffened flange connections with inner and outer flange plates, termed inner-outer flange, the mechanical behavior of the flange subjected to the combined bending and tensile loading is experimentally studied. Four nominally identical specimens were utilized to investigate the effects of the eccentricity on the mechanical behavior. The distribution of the gap between flange plates, as well as the distribution of the bolt forces, is presented. It is found that the neutral axis would gradually approach the central axis of the flange connection, as the eccentricity increases. Moreover, provided the sufficiently strong ribs, welds, and flange plates, the capacity of the flange is found to be mainly predominated by the bolt strength. A good agreement is found in the comparison of the results obtained via the finite element analysis, the semi-analytic method (SAM) and the experimental study. It corroborates the validity of using the bolt failure assumption and the plane cross-section assumption in the SAM for approximating the capacity of the inner-outer flange. In terms of the interaction of the tensile capacity with the bending capacity, the experimental results along with those in the literature are compared with the curves defined by the codes, and suggestions for design are concluded. Yield capacity, defined as the load when the bolt stress reaches the yield strength, is recommended herein for the design of a structure under in-service condition. It is found the specifications in the current codes for the rib-stiffened flanges with a single flange plate would occasionally overestimate the yield capacity of the inner-outer flanges under the combined bending and tensile loading. Moreover, both the experimental and the numerical results show a linear load interaction curve, in terms of the ultimate capacity.
Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial
Authors: Ranaivo Harimalala , Zhang Zhengxiao , Alligier Maud , Van Den Berghe Laurie , Sothier Monique , Lambert-Porcheron Stéphanie , Feugier Nathalie , Cuerq Charlotte , Machon Christelle , Neyrinck Audrey M. , Seethaler Benjamin , Rodriguez Julie , Roumain Martin , Muccioli Giulio G. , Maquet Véronique , Laville Martine , Bischoff Stephan C. , Walter Jens , Delzenne Nathalie M. , Nazare Julie-Anne
Published: May 2022

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.
Nonspecific hebbian neural network model predicts musical scales discreteness and just intonation without using octave-equivalency mapping
Authors: Pankovski Toso , Pankovska Ana
Published: May 2022

This study continues investigating the consonance-pattern emerging neural network model introduced in our previous publication, specifically to test if it will reproduce the results using 100-fold finer precision of 1/100th of a semitone (1 cent). The model is a simplistic feed-forward generic Hebbian-learning generic neural network trained with multiple-harmonic complex sounds from the full auditory sound spectrum of 10 octaves. We use the synaptic weights between the neural correlates of each two-tone from the said spectrum to measure the model’s preference to their inter-tonal interval (12,0002 intervals), considering familiarity as a consonance predictor. We analyze all the 12,000 intervals of a selected tone (the tonic), and the results reveal three distinct yet related features. Firstly, Helmholtz’s list of consonant intervals re-emerges from the synaptic weights of the model, although with disordered dissonant intervals. Additionally, the results show a high preference to a small number of selected intervals, mapping the virtually continual input sound spectrum to a discrete set of intervals. Finally, the model's most preferred (most consonant) intervals are from the Just Intonation scales. The model does not need to use cross-octave interval mapping due to octave equivalence to produce the said results.