bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Treatment Conditions of the Low-intensity Pulsed Ultrasound Therapy for the Treatment of Alzheimer’s Disease -Applications from Mice to Humans-
Authors: Shindo Tomohiko , Eguchi Kumiko , Monma Yuto , Kanai Hiroshi , Yasuda Satoshi , Shimokawa Hiroaki
Published: July 2023

Background and Purpose
We have previously developed a novel therapy with low-intensity pulsed ultrasound (LIPUS) that ameliorates cognitive decline through upregulation of endothelial nitric oxide synthase in mouse models of Alzheimer's disease (AD) and vascular dementia. We then conducted a randomized, double-blind, placebo-controlled (RCT) pilot trial for efficacy and safety of the whole-brain LIPUS therapy in patients with early AD. We demonstrated that the LIPUS therapy is safe and tends to suppress the cognitive decline in AD patients. We here report the findings of our basic experiments that we performed for the pilot trial in order to apply the whole-brain LIPUS therapy from mice to humans.
Methods
We performed basic experiments of the LIPUS therapy to identify the optimal treatment condition. First, by using human temporal bone, we examined the relationship between bone density/thickness and ultrasound transmittance. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and endothelial nitric oxide synthase (eNOS) in response to variable frequencies, duty cycles, and sound pressures.
Results
There was a significant correlation between bone thickness and transmittance (1.0 MHz, P < 0.001), while there was no significant correlation between bone density and transmittance (1.0 MHz, P = 0.421). At a frequency of 0.5 MHz, the optimum duty cycle was considered to be ~ 20%. When the tissue amplitude was in the range of 0.05–0.5 MPa, VEGF, FGF2 and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for the LIPUS therapy for human brain were identified as sound pressure just below the probe 1.3 MPa (tissue amplitude 0.15 MPa), duty cycle 5%, and frequency 0.5 MHz.
Conclusions
We successfully found the optimal treatment conditions of the LIPUS therapy for the treatment of patients with AD.
A novel inhibitor of the mitochondrial respiratory complex I with uncoupling properties exerts potent antitumor activity
Authors: Cordier-Bussat Martine , ASSI Alaa AL , POSTY Solène , Lamarche Frédéric , CHEBEL Amel , Guitton Jérôme , PRUDENT Renaud , LAFANECHERE Laurence , GIRAUD Stéphane , DALLEMAGNE Patrick , Suzanne Peggy , GENESTIER Laurent , Castets Marie , Fontaine Eric , Billaud Marc
Published: July 2023

Cancer cells are highly reliant on bioenergetic processes to support their growth and survival. Disrupting these metabolic pathways, notably by targeting the electron transport chain complexes (ETC-I to V) in the mitochondrial bioenergetic hub, has become an attractive therapeutic strategy. As a result, the pursuit of identifying clinically effective new inhibitors of the respiratory chain with minimized adverse effects stands as a significant objective. Here, we characterize a first in class OXPHOS inhibitor compound called MS-L6, which behaves as an inhibitor of ETC-I, combining inhibition of NADH oxidation and decoupling effect. MS-L6 is effective on both intact and fragmented mitochondrial membranes, indicating that its efficacy does not rely on its accumulation within the mitochondria. MS-L6 reduces ATP synthesis and induces a metabolic shift with increased glucose consumption and lactate production in cancer cell lines, while having minimal effects on primary hepatocytes. Its dose-dependently inhibits cell proliferation or induces cell death in a wide range of cancer cell lines, including B-cell and T-cell lymphoma, as well as pediatric sarcoma. Furthermore, ectopic expression of Saccharomyces cerevisiae NADH-dehydrogenase NDI1 partially restores the viability of lymphoma B cells treated with MS-L6, demonstrating that inhibition of NADH oxidation is key for its antitumoral activity. Finally, MS-L6 administration induces a robust inhibition of lymphoma tumor growth in two murine xenograft models, without significant toxicity. Therefore, our data unveil MS-L6 as an inhibitor of oxidative phosphorylation (OXPHOS), with an unexpected dual mechanism of action on the respiratory chain. Additionally, MS-L6 demonstrates potent antitumoral properties in preclinical models, positioning it as the pioneering member of a promising new drug class to be assessed for cancer therapy.
Covid-19 Progress in Patients With Familial Mediterranean Fever
Authors: Demir Bilgehan , karahan doğu
Published: July 2023

Background
Familial Mediterranean Fever (FMF) is a genetic auto-inflammatory disease. Mutations in the MEFV gene cause inappropriate immune system triggering, leading to inflammatory episodes in the peritoneum, pleura, and joints. In the severe COVID-19 picture, the hyperimmune response and inflammatory process develop and the clinic worsens. The FMF disease, the drugs used for its treatment, and the situation that different genetic mutations will display in the course of COVID-19 arouse interest.
Methods
In this study, common and different points in COVID-19 follow-up processes were evaluated by online questionnaire method according to different gene mutations in 158 FMF patients who had gene analysis. Participants were asked 21 questions and the data provided were compared between FMF MEFV gene mutations
Results
104 out of 158 cases did not get COVID-19. 8 of 54 cases who get COVID-19 were hospitalized. No statistically significant difference was found between gene mutations when evaluated and compared in terms of susceptibility to COVID-19, vaccination status and presence of additional chronic diseases.
Conclusion
The present study provides guidance on the role of FMF genetic mutations in the course of COVID-19. Our study may suggest that FMF MEFV gene mutations do not have a protective role against COVID-19. The results also suggest that, as an inverse effect, MEFV gene mutations do not increase the risk of hyper-immune response and SARS, which play a role in the severe course of COVID-19.
Psychrophiles to Control Ice-Water Phase Changes in Frost-Susceptible Soils
Authors: Rahman Rashed , Bheemasetti Tejo V. , Govil Tanvi , Sani Rajesh
Published: July 2023

The phase changes of soil water or porous media have a crucial influence on the performance of natural and man-made infrastructures in cold regions. Several treatment methods to mitigate the effects of frost action have been studied earlier, but traditional methods often rely on chemicals, physical techniques, and the reuse of waste materials, which often have limitations. However, certain organisms produce ice-binding proteins (IBPs) or antifreeze proteins (AFPs) to adapt to low temperatures, which can inhibit ice crystal growth by lowering the freezing point and preventing ice crystallization without the need for external intervention. This study explores the potential of three psychrophilic microbes: Sporosarcina psychrophile, Sporosarcina globispora, and Polaromonas hydrogenivorans, to induce non-equilibrium freezing point depression and thermal hysteresis in order to control ice lens growth in frost-susceptible soils. The growth profiles of the microbes, the concentration of released proteins in the extracellular solution, and the thermal properties of the protein-mixed soils are monitored at an interval of three days. The controlled soil showed a freezing point of -4.59 0C and thermal hysteresis of 4.62 0C, whereas protein-treated soil showed a maximum freezing point depression of -8.54 0C and thermal hysteresis of 7.71 0C. Interestingly, except for the controlled sample, all the protein-treated soil samples were thawed at a negative temperature (minimum recorded at -0.85 0C). Further analysis showed that the treated soils compared to porous media mixed soil freeze (1.25 0C vs. 0.51 0C) and thaw (2.75 0C vs. 1.72 0C) at extensive temperature gap. Overall, this study presents a novel bio-mediated approach using psychrophilic microbes to control ice formation in frost-susceptible soils.
Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation
Authors: Lu Ling , Gu Jian , Xu Xiaozhang , Yue Lei , Zhu Xiaowen , Chen Qiuyang , Gao Ji , Takashi Maruyama , Zhao Wenhu , Zhao Bo , Zhang Yue , Zhou Jinren , Liang Yuan , Pan Yufeng , Li Xiangyu , Shao Qing , Li Yu , Wang Yiming , Xu Zibo , Qian Qufei , Huang Tianning , Qian Xiaofeng
Published: July 2023

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the antitumor activities of regulatory T cells (Tregs) and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.
Multiple Applications of a Novel Fluorescence Probe with Large Stokes Shift and Sensitivity for Rapid H2S Detection
Authors: Hong Laixin , Sun Le , Li Cong , Zhang Ronglan , Zhao Jianshe
Published: July 2023

Herein, a novel fluorescence probe Fla-DNP based on flavonol has been designed and synthesized for rapid, specific detection of H2S. With the addition of H2S, Fla-DNP triggered thiolysis and released Fla displaying the “turn-on” NIR fluorescence response at 566 nm, which is consistent with the reaction site predicted by calculating Electrostatic potential and ADCH charges. As an easily available H2S probe, Fla-DNP has the advantages of high selectivity, anti-interference, low detection limit (0.834 µM), short response time (6 min), and large Stokes shift (124 nm). The sensing mechanism of H2S was determined by HRMS analysis and DFT calculation. Moreover, Fla-DNP can detect H2S in environmental water samples with good recovery rates of 89.6%-102.0% and be made into fluorescence test strips to track the H2S produced during foodstuff spoilage to determine the freshness. Meanwhile, the probe exhibits good biocompatibility and can not only be available used for H2S detection in living cells but be further designed as an H2S-activated CO photoreleaser, based on which to develop its potential as an anti-cancer drug.
In Silico Analysis of SOS Family in Areca palm (Areca catechu. L)
Authors: alam Osama , asmat sobia
Published: July 2023

The salt-overly sensitive ( SOS) gene is a signaling gene that helps plants to respond to high salinity stress. It is activated when cells are exposed to high levels of sodium ions, and it leads to a number of changes in gene expression that help the plant cope with high salinity stress. However, The SOS gene in Arecha palm has not been studied, despite being present in various plant species. We have identified 10 members of the AcatSOS family of genes, which are dispersed randomly over 5 chromosomes in the genome of Areca catechu. Using the phylogenetic analysis of 10 AcatSOS genes and two additional species rice and Arabidopsis—the tree is divided into 5 subfamilies: Group 1, Group 2, Group 3, Group 4 and Group 5. Each gene in the AcatSOS family was identified on its physiochemical properties. The plastid and vacuole contain most of the localization signals. Furthermore, there were numerous cis-acting areas and light-responsive elements in the promoter sequences of the AcatSOS genes. After the Areca palm genome was sequenced, segmental and tendom duplications were discovered, providing evidence of a major driving force in the evolution of the AcatSOS gene family. Areca palms share numerous genes, in terms of orthologous relationships, with other monocotyledonous plants because of their evolutionary affinity and related heritage. The development of the leaf, endocarp, and epicarp is regulated by the AcatSOS genes, according to circular heat. AcatSOS-4, AcatSOS-6 and AcatSOS-8 are highly regulated in plants. Genome-wide characterization of the SOS gene expression patterns has revealed that the expression of these genes is regulated in a complex manner. It is influenced by several factors, including the level of salinity stress, the developmental stage of the plant, and the tissue type.
Petrogenesis and Tectonic Evolution of the Kahnouj Ophiolitic Complex (SE Iran): Constraints from geochemistry and Sr-Nd-Pb isotope composition
Authors: Siani Majid Ghasemi , Mehrabi Behzad , Yang Huai-Jen , Neubauer Franz , Huang Kuo-Fang , Liu Yung-Hsin
Published: July 2023

Based on new Sr-Nd-Pb isotope-compositional and lithogeochemical data combined with previously published data of the Kahnouj ophiolite, we propose a tectonic model for the Kahnouj ophiolitic complex. The Kahnouj ophiolitic complex is the largest ophiolite of the Makran zone and consists of isotropic and layered gabbros with ultramafic lenses at the bottom and sheeted dikes, and basalts and pelagic limestones on the top. A cyclic succession of isotropic and layered gabbros indicates a distinct differentiation trend of early clinopyroxene crystallization followed by hornblende. Crystal fractionation and partial melting processes are also inferred by Nd isotopic and whole-rock geochemical data (e.g., fractionation recorded by the Al2O3/TiO2 versus Ti/1000 diagram). Geochemically, the gabbros are subalkaline and show tholeiitic features. The εNd values of + 7 to + 7.6 and initial 87Sr/86Sr ratios of 0.70352 to 0.70377 indicate a mid-ocean ridge mantle source for the gabbroic rocks. The whole rock geochemistry of the layered and isotropic gabbros suggest that they formed in a back-arc basin setting and represent MOR- to supra-subduction type ophiolites in the Neotethys Ocean during Jurassic to Early Cretaceous (156 to 121 Ma).
Blood Pressure Measurements for Diagnosing Hypertension in Primary Care: Room for Improvement
Authors: Voorbrood V.M.I. , de Schepper E.I.T. , Bohnen A.M. , Ruiterkamp M.F.E. , Bindels P. J.E. , Rijnbeek P.R.
Published: July 2023

Background
In the adult population, about 50% have hypertension, a risk factor for cardiovascular disease and subsequent premature death. Little is known about the quality of the methods used to diagnose hypertension in primary care.
Objectives
The objective was to assess the completeness of the method of systolic blood pressure measurements that were used to diagnose patients with new-onset hypertension and to assess the correct interpretation of the blood pressure level.
Methods
A population-based cohort study using electronic medical records of patients in primary care aged between 40 and 70 years with a new-onset of hypertension in the years 2012, 2016, 2019, and 2020. A visual chart review of the electronic medical records was used to assess the methods employed to diagnose hypertension in a random sample of 500 patients. The blood pressure measurement method was considered complete if three or more valid office blood pressure measurements (OBPM) were performed, or home-based blood pressure measurements (HBPM), the office- based 30-minute method (OBP30), or 24-hour ambulatory blood pressure measurements (24H-ABPM) were used.
Results
In all study years, OBPM was the most frequently used method to diagnose new-onset hypertension in patients. The OBP-30 method was used in 0.4% (2012), 4.2% (2016), 10.6% (2019), and 9.8% (2020) of patients respectively, 24H-ABPM in 16.0%, 22.2%, 17.2%, and 19.0% of patients and HBPM measurements in 5.4%, 8.4%, 7.6%, and 7.8% of patients, respectively. A diagnosis of hypertension based on only one or two office measurements occurred in 85.2% (2012), 87.9% (2016), 94.4% (2019), and 96.8% (2020) of all patients with OBPM. In cases of incomplete measurement and incorrect interpretation, medication was still started in 64% of cases in 2012, 56% (2016), 60% (2019), and 73% (2020).
Conclusion
OBPM is still the most often used method to diagnose hypertension in primary care. The diagnosis was often incomplete or misinterpreted using incorrect cut-off levels. A small improvement occurred between 2012 and 2016 but no further progress was seen in 2019 or 2020. If hypertension is inappropriately diagnosed, it may result in under treatment or in prolonged, unnecessary treatment of patients. There is room for improvement.
The linear convergence rate of the linearized version of alternating direction method of multipliers for convex optimization with three separable functions
Authors: Li Meishu , Lu Zhenrong , Ma Yang
Published: July 2023

The linearized alternating direction methods of multipliers (L-ADMM) for solving convex minimization problems with two separable blocks in the objective functions is efficient. And its extended version (\(m \geqslant 3\)) is convergent under some mild conditions. Recently, The L-ADMM inspires much attention in analyzing its theoretical convergence rate. However, the research on its convergence rate is still in its infancy. In this paper, we consider the convergence rate of L-ADMM when solving the convex optimization problems that the subdifferentials of the underlying functions are piecewise linear multifunctions. Based on the error bound, we establish the linear convergence rate.
Extrauterine Growth Restriction and Catch-up Growth Following NICU Discharge: a Tale of two Standards
Authors: Olgun Lena , Weintraub Andrea , Green Robert
Published: July 2023

Objectives:
To assess extrauterine growth restriction (EUGR) after neonatal intensive care unit (NICU) discharge and identify factors associated with catch-up growth (CUG) and neurodevelopmental outcomes at age 2.
Study Design:
Growth parameters at birth, 36 weeks postmenstrual age (PMA), and two neurodevelopmental follow-up visits were reviewed retrospectively. EUGR was assessed using Fenton and Intergrowth-21 standards. Factors associated with outpatient growth and neurodevelopmental outcomes at age 2 were evaluated using logistic and linear regression.
Results:
369 infants comprised the cohort. EUGR prevalence was 14.9% for Intergrowth-21 vs. 56.4% for Fenton (p < 0.001). There was a significant decrease in weight z-score from birth-36 weeks PMA. Weight z-scores returned to birth values by the 2nd clinic visit. Formula-fed infants had faster CUG. Higher Bayley-III at age 2 were associated with human milk feeding.
Conclusions:
Fewer infants were EUGR using Intergrowth-21. CUG with return to birth weight z-score was seen. Human milk feeding positively impacted Bayley-III scores, despite slower CUG.
MTMR7 suppresses the phenotypic switching of vascular smooth muscle cell and vascular intimal hyperplasia after injury via regulating p62/mTORC1-mediated glucose metabolism
Authors: Sun Xiongshan , Yang Yao , Zhao Weiwei , Wang Mingliang , Chen Yingmei , Wang Jia , Yang Dachun , Yang Yongjian
Published: July 2023

Myotubularin-related protein 7 (MTMR7) suppresses the proliferation in various of cell types and is also associated with vascular stenosis-related disease. However, whether MTMR7 regulates the vascular smooth muscle cell (VSMC) and vascular intimal hyperplasia remains unclear. We aimed at exploring the role of MTMR7 in the phenotypic switching of VSMC and vascular intimal hyperplasia after injury. MTMR7 expression was significantly downregulated in injured artery. Compared to wild type (WT) mice, Mtmr7-transgenic (Mtmr7-Tg) mice showed reduced intima/media ratio, decreased percentage of Ki-67-positive cells within neointima, and increased Calponin expression in injured artery. Upregulating MTMR7 by Len-Mtmr7 transfection inhibited platelet derived growth factor (PDGF)-BB-induced proliferation, migration of VSMCs and reversed the decrease in expression of Calponin and SM-MHC. Microarray, single cell sequence, and other bioinformatics analysis revealed that MTMR7 is highly related to glucose metabolism and mammalian target of rapamycin complex 1 (mTORC1). Further experiments confirmed that MTMR7 markedly repressed glycolysis and mTORC1 activity in PDGF-BB-challenged VSMC. Restoring mTORC1 activity abolished MTMR7-mediated suppression of glycolysis, phenotypic shift in VSMC and protection against vascular intimal hyperplasia. Furthermore, upregulating MTMR7 led to dephosphorylation and dissociation of p62 from mTORC1. External expression of p62 also abrogated the inhibitory effects of MTMR7 on glycolysis and phenotypic switching in PDGF-BB-stimulated VSMC. Our study demonstrates that MTMR7 inhibits injury-induced vascular intimal hyperplasia and phenotypic switching of VSMC. Mechanistically, the beneficial effects of MTMR7 are conducted via suppressing p62/mTORC1-mediated glycolysis.
Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens
Authors: Takao Mikiya , Kawaguchi Yoshikuni , Matsumura Masaru , Kazami Yusuke , Tanimoto Meguri , Abe Satoru , Maki Harufumi , Ishizawa Takeaki , Arita Junichi , Akamatsu Nobuhisa , Kaneko Junichi , Kokudo Norihiro , Hasegawa Kiyoshi
Published: July 2023

Background
Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins.
Methods
Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software.
Results
Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6–110) vs. 48.3 (39.0–59.4), p = 0.002] and with chemotherapy [67.9 (54.6–89.2) vs. 48.6 (28.8–82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies.
Conclusion
Real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.
Efficient stereo matching using the weighted polygon window and the HSV color space
Authors: Guan Haijiao , Xiaoye Wang , An Aimin , Lei Ye , Wang Runmin
Published: July 2023

To solve the problem of low matching accuracy of existing binocular stereo vision in discontinuous disparity and low texture area, a robust stereo matching method is proposed in this paper, including improved Census transform and improved AD algorithm. The improvements of the Census transform are twofold: Firstly, a method that uses the Euclidean distance between pixels to formulate Hamming distance weights is proposed better to reflect the influence of surrounding pixels on the center pixel; Secondly, a new alternative algorithm for the center pixel is proposed to effectively reduce the problem of over-reliance of the result on the center pixel in the traditional Census transform. In addition, AD cost volume is calculated in the HSV color space and combined with the Census cost volume obtained using the improved Census transform. The result is aggregated by Weighted Guided Filter and then the cost is optimized by multi-step post-processing. The experimental results show that the proposed algorithm in this paper can effectively reduce the mismatching rate, the disparity map obtained has less noise, and the matching effect is better under different illumination and noise conditions.
Optimal parameter of the SOR-like iteration method for solving absolute value equations
Authors: Chen Cairong , Huang Bo , Yu Dongmei , Han Deren
Published: July 2023

The SOR-like iteration method for solvingthe system of absolute value equations~(AVE) of finding a vector $x$ such that $Ax - |x| - b = 0$ with $\nu = \|A^{-1}\|_2 < 1$ is investigated. The convergence conditions of the SOR-like iteration method proposed by Ke and Ma ([{\em Appl. Math. Comput.}, 311:195--202, 2017]) are revisited and a new proof is given, which exhibits some insights in determining the convergent region and the optimal iteration parameter. Along this line, the optimal parameter which minimizes $\|T_\nu(\omega)\|_2$ with$$T_\nu(\omega) = \left(\begin{array}{cc} |1-\omega| & \omega^2\nu \\ |1-\omega| & |1-\omega| +\omega^2\nu \end{array}\right)$$and the approximate optimal parameter which minimizes an upper bound of $\|T_\nu(\omega)\|_2$are explored. The optimal and approximate optimal parameters are iteration-independent and the bigger value of $\nu$ is, the smaller convergent region of the iteration parameter $\omega$ is. Numerical results are presented to demonstrate that the SOR-like iteration method with the optimal parameter is superior to that with the approximate optimal parameter proposed by Guo, Wu and Li ([{\em Appl. Math. Lett.}, 97:107--113, 2019]).
Heritability of Gene Expression measured from Peripheral Blood in Older Adults
Authors: Kanchibhotla Sri C. , Mather Karen A. , Armstrong Nicola J. , Ciobanu Liliana G , Baune Bernhard T. , Catts Vibeke S , Schofield Peter R. , Trollor Julian N. , Ames David , Sachdev Perminder S. , Thalamuthu Anbupalam
Published: July 2023

The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of gene expression from peripheral blood in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 monozygotic (MZ) and 52 dizygotic (DZ) twin pairs, 69.91% females) with a mean age of 75.79 (S.D. = 5.44) were studied. RNA was extracted from peripheral blood and gene expression assessed using Illumina microarrays. Heritability (h2) analysis was performed using structural equation modelling. Out of the available 26537 probes (19256 genes) there were 5269 probes (19.9%) from 4603 unique genes (23.9%) that were significantly heritable, with a mean moderate heritability (h2 = 0.40). The gene, ERAP2, showed the highest heritability (h2 = 0.87; FDR = 2.91E-22). Pathway analysis of the top 10% of significant genes showed enrichment for the immune response, longevity and ageing associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~ 24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.
Lie Algebras of Univariate and Bivariate Hermite Polynomials and New Generating Function
Authors: Amiri Manouchehr
Published: July 2023

This paper presents the connections between univariate and bivariate Hermite polynomials and associated differential equations with specific representations of 𝔰𝔩(2,𝑅) algebra whose Cartan sub-algebras coincide with the differential operators involved in these differential equations . Applying the Baker-Campbell-Hausdorff formula to these algebras, results in new relations and generating functions in one-variable and Bivariate Hermite polynomials. A general form of 𝔰𝔩(2,𝑅) representation for other special polynomials such as Laguerre and Legendre polynomials is introduced. A new generating function for Hermite polynomials is presented.
Chronic Supplementation of Noni in Diabetic Type 1-Stz Rats: Effects on Glycemic Levels, Kidney Toxity and Exercise Performance
Authors: Fernandes Débora de Oliveira , César Fernanda Gracia , Melo Bruno Pereira , Brandão Jéssica da Silva Faria , Santos Kelvin Jaques dos , de Andrade Marcelo Teixeira , Casteluber Marisa Cristina da Fonseca , de Carvalho Moisés Vieira , de Barcellos Luiz Alexandre Medrado , Soares Danusa Dias , Guimarães Juliana Bohnen
Published: July 2023

Thirty-two male Wistar rats were used to verify the effects of chronic noni (Morinda citrifolia L) juice administration on glycemia, triglycerides levels and its relation to physical performance. In addition, it was verified if chronic noni supplementation is safe to clinical use through the kidney morphology analysis. In half of the rats, diabetes mellitus (DM) was induced with STZ. All rats were submitted to an incremental workload running test (IWT) until fatigued so that oxygen consumption and performance indexes (exercise time to fatigue and workload) could be analyzed before noni administration. Then, the control and DM groups received placebo (saline solution) or noni juice (dilution 2:1) at a dose of 2 mL/kg once a day for 60 days. The result was four groups: control + placebo (CP), control + noni (CN), DM + placebo (DMP), and DM + noni (DMN). Groups were then given a third IWT to verify the effect of the noni juice on exercise performance and glycemia. Twenty-four hours after the third test, all animals were euthanized and blood and kidneys were removed for posterior analysis. Noni administration improved the time to fatigue and workload in DM rats by reducing hyperglycemia. These results could be associated with an improved energy efficiency promoted by noni ingestion. However, our results provided evidence that chronic noni administration causes kidney damage since elevated glomerular filtration was observed at the same magnitude as the non-treated DM group. In conclusion, chronic noni ingestion promoted glycemic control and improved the performance in DM rats but caused kidney toxicity.
That’s BAD: Blind Anomaly Detection by Implicit Local Feature Clustering
Authors: Zhang Jie , Suganuma Masanori , Okatani Takayuki
Published: July 2023

Recent studies on visual anomaly detection (AD) of industrial objects/textures have achieved quite good performance. They consider an unsupervised setting, specifically the one-class setting, in which we assume the availability of a set of normal (i.e., anomaly-free) images for training. In this paper, we consider a more challenging scenario of unsupervised AD, in which we detect anomalies in a given set of images that might contain both normal and anomalous samples. The setting does not assume the availability of known normal data and thus is completely free from human annotation, which differs from the standard AD considered in recent studies. For clarity, we call the setting blind anomaly detection (BAD). We show that BAD can be converted into a local outlier detection problem and propose a novel method named PatchCluster that can accurately detect image- and pixel-level anomalies. Experimental results show that PatchCluster shows a promising performance without the knowledge of normal data, even comparable to the SOTA methods applied in the one-class setting needing it
Causal associations between total testosterone level and non-small cell lung cancer: a two-sample Mendelian randomization study
Authors: Yang Yuanyuan , Guan Lulu , Yang Yalan , Chen Yu , Luo Xi , Wang Feng
Published: July 2023

Purpose: The study aimed to evaluate the causal association between the level of total testosterone and the risk of non-small cell lung cancer (NSCLC) utilizing Mendelian randomization (MR) approach.
Methods: Genetic variants extracted from genome-wide association studies (GWAS) datasets of total testosterone level and NSCLC were utilized as instrumental variables (IVs). Five methods were employed to generate overall estimates of the effect, including the inverse variance weighted (IVW), MR Egger, maximum likelihood (ML), weighted median, and IVW (multiplicative random effects). Leave-one-out validation, MR Steiger test, pleiotropy and heterogeneity testing were conducted to ensure the reliability of our results.
Results: The MR analysis demonstrated a causal effect between total testosterone level and NSCLC, IVW (OR = 0.74, 95% CI = 0.60-0.92, P= 7.44E-03), MR Egger (OR = 0.53, 95% CI = 0.34-0.84, P = 6.98E-03), ML (OR = 0.74, 95% CI = 0.61-0.91, P = 3.49E-03), weighted median (OR = 0.66, 95% CI = 0.48-0.91, P = 1.25E-03), and IVW (multiplicative random effects) (OR = 0.74, 95% CI = 0.60-0.92, P = 7.44E-03). The leave-one-out test revealed that removing any IV did not significantly alter the results. The MR Steiger test confirmed the direction of causality. The absence of significant pleiotropy and negligible effect of heterogeneity supported our finding.
Conclusion: According to our findings, increased levels of testosterone may potentially reduce the likelihood of developing NSCLC. These outcomes could provide valuable insights for the advancement of innovative therapeutic strategies manipulating testosterone levels to lower the risk of NSCLC.
Laser Induced Shock Wave Studies of Aluminum Metal
Authors: Abdulzahra Narjis Zamil
Published: July 2023

Non-destructive laser testing (NDLT) or laser shock penning (LSP) describes the no-damaging material testing method by employing a laser; this denies damaging or inducing helpfulness to give information about a material or component. The experimental study examined the physical characteristics of aluminum and compared it with normalized Hugoniot data. The experimental data depends on studying super eye images supported by SEM images to study the track effect induced by different energy of nanosecond Nd-YAG laser in Laser-Induced Shock Peening (LSP). The forward velocity of the shock wave depends on the material and the sample's shocked medium related to the excised atoms' ionization rates. It noted that the LSP of Al in water and ethanol is the closest to the little shock Hugoniot data pressure is 4.5 GPa, while it is typically (0.46,3.2, and 3) GPa when the incident laser intensity is 11.4 GW/cm2 in air, water, and ethanol media. NDLT technique could apply to examine material shock properties like (particle velocity, shock time, shock wavelength, shock energy, shock intensity, loudness, and force) which is essential to finding mechanical properties. We compared NDLT with classical measurements where Stress-Strain was measured by Tensile test, and the hardness was measured by Vicker hardness; we found the shocked Al in water and ethanol gives more matching for the tensile test. The Vickers hardness more matching when shocked Al in water. In addition, the Elastic Modulus value by the Tensile test is 28 GPa, while by NDLT is (8.4MPa, 4.9, 4.7G Pa) in air, water, and ethanol media.
HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress
Authors: Wang Linli , Ren Zhitao , Wu Lin , Zhang Ximei , Wang Min , He Xuemin , Wang Heting , Chen Yanming , Shi Guojun , Qian Xiaoxian
Published: July 2023

Aims: Phenotypic change of vascular smooth muscle cells (VSMCs) contributes a lot in obesity induced vascular pathological remodeling. The endoplasmic reticulum (ER) is critical for maintaining VSMC function, but the accumulation of misfolded proteins in the ER impairs cell function. As the major ER protein quality control responsible for clearing misfolded proteins, ER-associated degradation (ERAD) whose key member is HRD1 plays vital role in lipid metabolism, but its function in VSMC phenotypic change remains poorly understood.
Main methods: The level of HRD1 expression was analyzed in aortic tissues of mice fed with a high-fat diet (HFD). The HE and EVG (VERHOEFF’S VAN GIESON) staining were used to demonstrate vascular pathological changes. Cripr and transcriptomic analysis were applied in in vitro studies to explore the cellular mechanism.
Key findings: Data showed a significant reduction of HRD1 in aortic tissues of mice under HFD feeding. VSMC phenotypic change and HRD1 downregulation were detected by cholesterol treatment. Transcriptomic and further analysis of HRD1-KO VSMCs showed that HRD1 deficiency increased the expression of genes related with ER stress, proliferation, and migration, but decreased the VSMC contractile-related genes. HRD1 deficiency in VSMCs also exacerbated the proliferation, migration, and ROS production induced by cholesterol, which promoted the VSMC phenotypic change process.
Significance: Our results proved that HRD1 plays an essential role in the contractile homeostasis of VSMCs by negatively regulating ER stress. Thus, HRD1 may have the potential to be a therapeutic target in lipid metabolic disorders induced vascular remodeling caused by VSMC phenotypic change.
HLA Alleles, COVID-19 Vaccine Antibody Response and Real-World Breakthrough Outcomes
Authors: Prieto-Alhambra Daniel , Xie Junqing , Mothe Beatriz , Herraiz Marta , Li Chunxiao , Xu Yu , Jödicke Annika , Gao Yaqing , Feng Shuo , Wei Jia , Chen Zhuoyao , Hong Shenda , Wu Yeda , Su Binbin , Zheng Xiaoying , Cohet Catherine , Ali Raghib , Wareham Nicholas
Published: July 2023

The rapid development, approval, and global distribution of COVID-19 vaccines represent an unprecedented intervention in public health history, with over 13 billion doses administered worldwide in two years. However, our understanding of the HLA genetic underpinnings of COVID-19 vaccine-induced antibody responses and their clinical implications for breakthrough outcomes remain limited. To bridge this knowledge gap, we designed and performed a series of genetic and epidemiological analyses among 368,098 vaccinated individuals, and a subset of 194,371 participants who had antibody serology tests. Firstly, we corroborated earlier findings that SNPs associated with antibody response were predominantly located in Major Histocompatibility Complex region, and that the expansive HLA-DQB1*06 allele family was linked to better antibody responses. However, our findings contest the claim that DQB1*06 alleles alone significantly impact breakthrough risks. Additionally, our results suggest that the specific DQB1*06:04 subtype could be the true causal allele, as opposed to the previously reported DQB1*06:02. Secondly, we identified and validated six new functional HLA alleles that independently contribute to vaccine-induced antibody responses. Moreover, we unravelled additive effects of variations across multiple HLA genes that, concurrently, change the risk of clinically relevant breakthrough COVID-19 outcomes. Finally, we detangled the overall vaccine effectiveness and showed that antibody positivity accounts for approximately 20% protection against breakthrough infection and 50% against severe outcomes. These novel findings provide robust population evidence demonstrating how variations within HLA genes strongly, collectively, and causally influence vaccine-induced antibody responses, and the risk of COVID-19 breakthrough infection and related outcomes, with implications for subsequent functional research and personalised vaccination.
Unilateral Renal Cystic Disease: A Rare and Benign Renal Pathology
Authors: hasan Trefa Salih Salih
Published: July 2023

Unilateral renal cystic disease (URCD) is an infrequent condition that differs from the more common polycystic kidney disease in terms of patient demographics, clinical presentation, genetic background, and prognosis. This article presents a case of URCD in a young male patient who underwent imaging evaluation for nonspecific loin pain. The imaging findings, including ultrasound and contrast-enhanced computed tomography (CECT), confirmed the diagnosis and ruled out the involvement of other solid organs. With normal renal function and no family history of renal cystic disease, the patient's prognosis was favourable. This case report emphasizes the importance of imaging in distinguishing URCD from other renal pathologies and highlights the need for further studies and guidelines on the management of URCD.
Antropología de la paternidad
Authors: Polaino Aquilino
Published: July 2023

Ensayo académico
Automated mapping of the mean particle diameter characteristics from UAV-imagery using the CNN-based GRAINet model
Authors: Lendzioch Theodora , Langhammer Jakub , Sheshadrivasan Veethahavya Kootanoor
Published: July 2023

This study uses the GRAINet CNN approach on UAV optical aerial imagery to analyze and predict grain size characteristics, specifically mean diameter (dm), along a gravel river point bar in Šumava National Park (Šumava NP), Czechia. By employing a digital line sampling technique and manual annotations as ground truth, GRAINet offers an innovative solution for particle size analysis. Eight UAV overflights were conducted between 2014 and 2022 to monitor changes in grain size dm across the river point bar. The resulting dm prediction maps showed reasonably accurate results, with Mean Absolute Error (MAE) values ranging from 1.9 cm to 4.4 cm in tenfold cross-validations. Mean Squared Error (MSE) and Root Mean Square Error (RMSE) values varied from 7.13 cm to 27.24 cm and 2.49 cm to 4.07 cm, respectively. Most models underestimated grain size, with around 68.5% falling within 1σ and 90.75% falling within 2σ of the predicted GRAINet mean dm. However, deviations from actual grain sizes were observed, particularly for grains smaller than 5 cm. The study highlights the importance of a large manually labeled training dataset for the GRAINet approach, eliminating the need for user-parameter tuning and improving its suitability for large-scale applications.
The Role of Malondialdehyde (MDA) and Ferric Reducing Antioxidant Power (FRAP) in Patients with Hypertension
Authors: Alam Rohsan , Ahsan Haseeb , Khan Saba
Published: July 2023

Oxidative stress contributes to the pathogenesis of hypertension and studies have shown that hypertension is associated with an increase in oxidative stress. Reactive oxygen species (ROS) lead to hypertension and antioxidants may be beneficial for its prevention. The main cause of oxidative stress in hypertension is endothelial dysfunction due to the malfunctions in the vasodilator systems, specifically the molecular mechanism of ROS and nitric oxide (NO). The level of malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, is found to be higher in hypertension patients. Total antioxidant capacity (TAC), which has a strong relationship with blood pressure, is determined through the ferric reducing antioxidant power (FRAP). The aim of the review article is to elucidate the role of MDA and FRAP in hypertension.Keywords: oxidative stress, hypertension, blood pressure, oxidative damage, malondialdehyde, FRAP
Transcriptomic and Metabolomic Analysis of Liver Cirrhosis
Authors: Kuang Xiao , Li Jinyu , Xu Yiheng , Yang Lihong , Liu Xiaoxiao , Yang Jinhui , Tai Wenlin
Published: July 2023

Background:

Liver cirrhosis is one of the leading causes of decreased life expectancy
worldwide. However, the molecular mechanisms underlying liver cirrhosis remain unclear. In this
study, we performed a comprehensive analysis using transcriptome and metabolome sequencing to
explore the genes, pathways, and interactions associated with liver cirrhosis.

Methods:

We performed transcriptome and metabolome sequencing of blood samples from patients
with cirrhosis and healthy controls (1:1 matched for sex and age). We validated the differentially
expressed microRNA (miRNA) and mRNAs using real-time quantitative polymerase chain
reaction.

Results:

For transcriptome analysis, we screened for differentially expressed miRNAs and
mRNAs, analyzed mRNAs to identify possible core genes and pathways, and performed coanalysis
of miRNA and mRNA sequencing results. In terms of the metabolome, we screened five
pathways that were substantially enriched in the differential metabolites. Next, we identified the
metabolites with the most pronounced differences among these five metabolic pathways. We performed
receiver operating characteristic (ROC) curve analysis of these five metabolites to determine
their diagnostic efficacy for cirrhosis. Finally, we explored possible links between the transcriptome
and metabolome.

Conclusion:

Based on sequencing and bioinformatics, we identified miRNAs and genes that were
differentially expressed in the blood of patients with liver cirrhosis. By exploring pathways and
disease-specific networks, we identified unique biological mechanisms. In terms of metabolomes,
we identified novel biomarkers and explored their diagnostic efficacy. We identified possible
common pathways in the transcriptome and metabolome that could serve as candidates for further
studies.
Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in
Alzheimer's Disease
Authors: Zhang Yao , Jian Wenxuan
Published: July 2023

The current studies show signs of progress in treating Alzheimer's disease (AD) with the
“brain-gut axis.” Restoring intestinal flora balance can alleviate neurodegeneration in the central
nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective
mechanism brought by intestinal flora has not been fully understood. Trimethylamine
N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be
a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile,
all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated.
Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia,
etc., correlate with the production process of TMAO. High choline intake and insulin resistance
have also been identified as contributors to TMAO synthesis. With the increasing TMAO
in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses
and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the
hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1,
SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and
PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and
the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical
and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases
and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important
pathological factor of AD.
The Development of HDAC and Tubulin Dual-Targeting Inhibitors for
Cancer Therapy
Authors: Nie Jing , Wu Huina , Luan Yepeng , Wu Jiyong
Published: July 2023

Histone deacetylases (HDACs) are a class of enzymes that are responsible for the removal
of acetyl groups from the ε-N-acetyl lysine of histones, allowing histones to wrap DNA more tightly.
HDACs play an essential role in many biological processes, such as gene regulation, transcription, cell
proliferation, angiogenesis, migration, differentiation and metastasis, which make it an excellent target
for anticancer drug discovery. The search for histone deacetylase inhibitors (HDACis) has been intensified,
with numerous HDACis being discovered, and five of them have reached the market. However,
currently available HDAC always suffers from several shortcomings, such as limited efficacy, drug
resistance, and toxicity. Accordingly, dual-targeting HDACis have attracted much attention from academia
to industry, and great advances have been achieved in this area. In this review, we summarize
the progress on inhibitors with the capacity to concurrently inhibit tubulin polymerization and HDAC
activity and their application in cancer treatment.