bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Thermotoga neapolitana Alcohol Dehydrogenases in the Ethanol Fermentation Pathway
Authors: Sha Chong , Wang Qiang , Wang Hongcheng , Duan Yilan , Xu Chongmao , Wu Lian , Ma Kesen , Shao Weilan , Jiang Yu
Published: September 2022

Hyperthermophilic Thermotoga spp. are candidates for cellulosic ethanol fermentation. A bifunctional iron-acetaldehyde/alcohol dehydrogenase (Fe-AAdh) has been revealed to catalyze the acetyl-CoA (Ac-CoA) reduction to form ethanol via an acetaldehyde intermediate in Thermotoga neapolitana (T. neapolitana). In this organism, there are three additional alcohol dehydrogenases, Zn-Adh, Fe-Adh1, and Fe-Adh2, encoded by genes CTN_0257, CTN_1655, and CTN_1756, respectively. This paper reports the properties and functions of these enzymes in the fermentation pathway from Ac-CoA to ethanol. It was determined that Zn-Adh only exhibited activity when oxidizing ethanol to acetaldehyde, and no detectable activity for the reaction from acetaldehyde to ethanol. Fe-Adh1 had specific activities of approximately 0.7 and 0.4 U/mg for the forward and reverse reactions between acetaldehyde and ethanol at a pHopt of 8.5 and Topt of 95 °C. Catalyzing the reduction of acetaldehyde to produce ethanol, Fe-Adh2 exhibited the highest activity of approximately 3 U/mg at a pHopt of 7.0 and Topt of 85 °C, which were close to the optimal growth conditions. These results indicate that Fe-Adh2 and Zn-Adh are the main enzymes that catalyze ethanol formation and consumption in the hyperthermophilic bacterium, respectively.
Transcriptome Analyses Identify Deregulated MYC in Early Onset Colorectal Cancer
Authors: Marx Olivia M. , Mankarious Marc M. , Eshelman Melanie A. , Ding Wei , Koltun Walter A. , Yochum Gregory S.
Published: September 2022

Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has steadily increased over the past several decades. When compared to later onset colorectal cancer (LOCRC) in individuals over 50, our understanding of the genetic and molecular underpinnings of EOCRCs is limited. Here, we conducted transcriptomic analyses of patient-matched normal colonic segments and tumors to identify gene expression programs involved in carcinogenesis. Amongst differentially expressed genes, we found increased expression of the c-MYC proto-oncogene (MYC) and its downstream targets in tumor samples. We identified tumors with high and low differential MYC expression and found patients with high-MYC tumors were older and overweight or obese. We also detected elevated expression of the PVT1 long-non-coding RNA (lncRNA) in most tumors and found gains in copy number for both MYC and PVT1 gene loci in 35% of tumors evaluated. Our transcriptome analyses indicate that EOCRC can be sub-classified into groups based on differential MYC expression and suggest that deregulated MYC contributes to CRCs that develop in younger patients.
Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential
Authors: Fan Yongfei , Li Xinwei , Sun Huihui , Gao Zhaojia , Zhu Zheng , Yuan Kai
Published: September 2022

Wilms’ tumor 1-associating protein (WTAP) is required for N6-methyladenosine (m6A) RNA methylation modifications, which regulate biological processes such as RNA splicing, cell proliferation, cell cycle, and embryonic development. m6A is the predominant form of mRNA modification in eukaryotes. WTAP exerts m6A modification by binding to methyltransferase-like 3 (METTL3) in the nucleus to form the METTL3-methyltransferase-like 14 (METTL14)-WTAP (MMW) complex, a core component of the methyltransferase complex (MTC), and localizing to the nuclear patches. Studies have demonstrated that WTAP plays a critical role in various cancers, both dependent and independent of its role in m6A modification of methyltransferases. Here, we describe the recent findings on the structural features of WTAP, the mechanisms by which WTAP regulates the biological functions, and the molecular mechanisms of its functions in various cancers. By summarizing the latest WTAP research, we expect to provide new directions and insights for oncology research and discover new targets for cancer treatment.
The Nicotinamide/Streptozotocin Rodent Model of Type 2 Diabetes: Renal Pathophysiology and Redox Imbalance Features
Authors: Yan Liang-Jun
Published: September 2022

Diabetic nephropathy (DN) is a common complication of diabetes mellitus. While there has been a great advance in our understanding of the pathogenesis of DN, no effective managements of this chronic kidney disease are currently available. Therefore, continuing to elucidate the underlying biochemical and molecular mechanisms of DN remains a constant need. In this regard, animal models of diabetes are indispensable tools. This review article highlights a widely used rodent model of non-obese type 2 diabetes induced by nicotinamide (NA) and streptozotocin (STZ). The mechanism underlying diabetes induction by combining the two chemicals involves blunting the toxic effect of STZ by NA so that only a percentage of β cells are destroyed and the remaining viable β cells can still respond to glucose stimulation. This NA-STZ animal model, as a platform for the testing of numerous antidiabetic and renoprotective materials, is also discussed. In comparison with other type 2 diabetic animal models, such as high-fat-diet/STZ models and genetically engineered rodent models, the NA-STZ model is non-obese and is less time-consuming and less expensive to create. Given that this unique model mimics certain pathological features of human DN, this model should continue to find its applications in the field of diabetes research.
Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor
Authors: Liu Mengxuan , Honjo Megumi , Yamagishi Reiko , Igarashi Nozomi , Nakamura Natsuko , Kurano Makoto , Yatomi Yutaka , Igarashi Koji , Aihara Makoto
Published: September 2022

This study examines the potential role of transforming growth factor-beta 3 (TGF-β3) on the fibrotic response of cultured human trabecular meshwork (HTM) cells. The relationships and trans-signaling interactions between TGF-β3 and autotaxin (ATX) in HTM cells were also examined. The levels of TGF-β and ATX in the aqueous humor (AH) of patients were measured by an immunoenzymetric assay. The TGF-β3-induced expression of the fibrogenic markers, fibronectin, collagen type I alpha 1 chain, and alpha-smooth muscle actin, and ATX were examined by quantitative real-time PCR, Western blotting, and immunocytochemistry, and the trans-signaling regulatory effect of TGF-β3 on ATX expression was also evaluated. In HTM cells, the significant upregulation of ATX was induced by TGF-β3 at a concentration of 0.1 ng/mL, corresponding to the physiological concentration in the AH of patients with exfoliative glaucoma (XFG). However, higher concentrations of TGF-β3 significantly suppressed ATX expression. TGF-β3 regulated ATX transcription and signaling in HTM cells, inducing the upregulation of fibrogenic proteins in a dose-dependent manner. Trans-signaling of TGF-β3 regulated ATX transcription, protein expression, and signaling, and was thereby suggested to induce fibrosis of the trabecular meshwork. Modulation of trans-signaling between TGF-β3 and ATX may be key to elucidate the pathology of XFG, and for the development of novel treatment modalities.
t6A and ms2t6A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity
Authors: Nagayoshi Yu , Nishiguchi Kayo , Yamamura Ryosuke , Chujo Takeshi , Oshiumi Hiroyuki , Nagata Hiroko , Kaneko Hitomi , Yamamoto Keiichi , Nakata Hirotomo , Sakakida Korin , Kunisawa Akihiro , Adachi Masataka , Kakizoe Yutaka , Mizobe Takanori , Kuratsu Jun-ichi , Shimada Shinya , Nakamori Yasushi , Matsuoka Masao , Mukoyama Masashi , Wei Fan-Yan , Tomizawa Kazuhito
Published: September 2022

SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.
Promising Roles of Circular RNAs as Biomarkers and Targets for Potential Diagnosis and Therapy of Tuberculosis
Authors: Huang Yifan , Li Ying , Lin Wensen , Fan Shuhao , Chen Haorong , Xia Jiaojiao , Pi Jiang , Xu Jun-Fa
Published: September 2022

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the most threatening infectious diseases worldwide. A series of challenges still exist for TB prevention, diagnosis and treatment, which therefore require more attempts to clarify the pathological and immunological mechanisms in the development and progression of TB. Circular RNAs (circRNAs) are a large class of non-coding RNA, mostly expressed in eukaryotic cells, which are generated by the spliceosome through the back-splicing of linear RNAs. Accumulating studies have identified that circRNAs are widely involved in a variety of physiological and pathological processes, acting as the sponges or decoys for microRNAs and proteins, scaffold platforms for proteins, modulators for transcription and special templates for translation. Due to the stable and widely spread characteristics of circRNAs, they are expected to serve as promising prognostic/diagnostic biomarkers and therapeutic targets for diseases. In this review, we briefly describe the biogenesis, classification, detection technology and functions of circRNAs, and, in particular, outline the dynamic, and sometimes aberrant changes of circRNAs in TB. Moreover, we further summarize the recent progress of research linking circRNAs to TB-related pathogenetic processes, as well as the potential roles of circRNAs as diagnostic biomarkers and miRNAs sponges in the case of Mtb infection, which is expected to enhance our understanding of TB and provide some novel ideas about how to overcome the challenges associated TB in the future.
Peptidomimetics and Their Applications for Opioid Peptide Drug Discovery
Authors: Lee Yeon Sun
Published: September 2022

Despite various advantages, opioid peptides have been limited in their therapeutic uses due to the main drawbacks in metabolic stability, blood-brain barrier permeability, and bioavailability. Therefore, extensive studies have focused on overcoming the problems and optimizing the therapeutic potential. Currently, numerous peptide-based drugs are being marketed thanks to new synthetic strategies for optimizing metabolism and alternative routes of administration. This tutorial review briefly introduces the history and role of natural opioid peptides and highlights the key findings on their structure-activity relationships for the opioid receptors. It discusses details on opioid peptidomimetics applied to develop therapeutic candidates for the treatment of pain from the pharmacological and structural points of view. The main focus is the current status of various mimetic tools and the successful applications summarized in tables and figures.
Marine Natural Compounds with Biomedical Potential
Authors: Leychenko Elena
Published: September 2022

Marine organisms are an inexhaustible source of natural compounds that are promising for the creation of drugs or biologically active additives, which is closely related to the huge biological diversity of the resources of the World Ocean [...]
Reduced Blood Pressure Dipping Is A Risk Factor for the Progression of Chronic Kidney Disease in Children
Authors: Deja Anna , Skrzypczyk Piotr , Leszczyńska Beata , Pańczyk-Tomaszewska Małgorzata
Published: September 2022

Background: Elevated blood pressure and proteinuria are well-established risk factors for chronic kidney disease (CKD) progression in children. This study aimed to analyze risk factors for CKD progress, emphasizing detailed ambulatory blood pressure (ABPM) data. Methods: In 55 children with CKD II–V, observed for ≥1 year or until initiation of kidney replacement therapy, we analyzed ABPM, clinical, and biochemical parameters. Results: At the beginning, the glomerular filtration rate (eGFR) was 66 (interquartile range—IQR: 42.8–75.3) mL/min/1.73 m2, and the observation period was 27 (16–36) months. The mean eGFR decline was 2.9 ± 5.7 mL/min/1.73 m2/year. eGFR decline correlated (p < 0.05) with age (r = 0.30), initial proteinuria (r = 0.31), nighttime systolic and mean blood pressure (r = 0.27, r = 0.29), and systolic and diastolic blood pressure dipping (r = −0.37, r = −0.29). There was no relation between mean arterial pressure during 24 h (MAP 24 h Z-score) and eGFR decline and no difference in eGFR decline between those with MAP 24 h < and ≥50 th percentile. In multivariate analysis, systolic blood pressure dipping (beta = −0.43), presence of proteinuria (beta = −0.35), and age (beta = 0.25) were predictors of eGFR decline. Conclusions: Systolic blood pressure dipping may be a valuable indicator of CKD progression in children.
Ablation of Discoidin Domain Receptor 1 Provokes an Osteopenic Phenotype by Regulating Osteoblast/Osteocyte Autophagy and Apoptosis
Authors: Chou Hsin-Chiao , Lin Sung-Yen , Chou Liang-Yin , Ho Mei-Ling , Chuang Shu-Chun , Cheng Tsung-Lin , Kang Lin , Lin Yi-Shan , Wang Yan-Hsiung , Wei Chun-Wang , Chen Chung-Hwan , Wang Chau-Zen
Published: September 2022

Discoidin domain receptor 1 (DDR1) is a collagen receptor that belongs to the receptor tyrosine kinase family. We have previously shown that DDR1 plays a crucial role during bone development, resulting in dwarfism and a short stature in osteoblast-specific knockout mice (OKO mice). However, the detailed pathophysiological effects of DDR1 on bone development throughout adulthood have remained unclear. This study aims to identify how DDR1 regulates osteoblast and osteocyte functions in vivo and in vitro during bone development in adulthood. The metabolic changes in bone tissues were analyzed using Micro-CT and immunohistochemistry staining (IHC) in vivo; the role of DDR1 in regulating osteoblasts was examined in MC3T3-E1 cells in vitro. The Micro-CT analysis results demonstrated that OKO mice showed a 10% reduction in bone-related parameters from 10 to 14 weeks old and a significant reduction in cortical thickness and diameter compared with flox/flox control mice (FF) mice. These results indicated that DDR1 knockout in OKO mice exhibiting significant bone loss provokes an osteopenic phenotype. The IHC staining revealed a significant decrease in osteogenesis-related genes, including RUNX2, osteocalcin, and osterix. We noted that DDR1 knockout significantly induced osteoblast/osteocyte apoptosis and markedly decreased autophagy activity in vivo. Additionally, the results of the gain- and loss-of-function of the DDR1 assay in MC3T3-E1 cells indicated that DDR1 can regulate the osteoblast differentiation through activating autophagy by regulating the phosphorylation of the mechanistic target of rapamycin (p-mTOR), light chain 3 (LC3), and beclin-1. In conclusion, our study highlights that the ablation of DDR1 results in cancellous bone loss by regulating osteoblast/osteocyte autophagy. These results suggest that DDR1 can act as a potential therapeutic target for managing cancellous bone loss.
Do Androgenic Pattern, Insulin State and Growth Hormone Affect Cardiorespiratory Fitness and Strength in Young Women with PCOS?
Authors: Baioccato Veronica , Quinto Giulia , Rovai Sara , Conte Francesca , Dassie Francesca , Neunhäeuserer Daniel , Vecchiato Marco , Palermi Stefano , Gasperetti Andrea , Bullo Valentina , Camozzi Valentina , Vettor Roberto , Ermolao Andrea , Mioni Roberto
Published: September 2022

In this study, cardiorespiratory fitness (CRF) and strength level were assessed in women with and without polycystic ovary syndrome (PCOS), matched for age, body composition, androgenic pattern and insulinemic pattern. Patients with and without PCOS were evaluated at the Endocrinology Unit and Sport Medicine Division to assess endocrinological (insulinemic, androgenic pattern and growth hormone), anthropometric (with DEXA) and functional parameters (with cardiopulmonary exercise test and handgrip test), as well as physical activity level (with the Global Physical Activity Questionnaire). A total of 31 patients with PCOS and 13 controls were included. No statistically significant differences were found between groups in terms of age, body mass index, body composition, androgenic pattern, insulin state, growth hormone and physical activity level. The PCOS group demonstrated significantly better cardiorespiratory fitness (VO2max per kg (30.9 ± 7.6 vs. 24.8 ± 4.1 mL/kg/min; p = 0.010), VO2max per kg of fat-free mass (52.4 ± 8.9 vs. 45.3 ± 6.2 mL/kg/min; p = 0.018)), strength levels (handgrip per kg (0.36 ± 0.09 vs. 0.30 ± 0.08; p = 0.009), handgrip per kg of fat-free mass (13.03 ± 2.32 vs. 11.50 ± 1.91; p = 0.001)) and exercise capacity (METs at test (14.4 ± 2.72 vs. 12.5 ± 1.72 METs; p = 0.019)). In this study, women with PCOS showed a better cardiorespiratory fitness and strength than the control group. The only determinant that could explain the differences observed seems to be the presence of the syndrome itself. These results suggest that PCOS per se does not limit exercise capacity and does not exclude good functional capacity.
Presence of Varicella Zoster Virus DNA in Saliva May Be Associated with the Severity of Ramsay Hunt Syndrome
Authors: Choi Gang Won , Jung Junyang , Yeo Seung Geun , Kim Sang Hoon
Published: September 2022

Background: The relationship between varicella zoster virus (VZV) collected from saliva and Ramsay Hunt syndrome (RHS) remains unclear. Therefore, this study aimed to investigate whether VZV DNA in saliva alters the clinical symptoms and prognosis of RHS. Methods: To measure the severity of clinical symptoms of 100 RHS patients, the initial House–Brackmann (HB) grade and associated symptoms were evaluated. The final HB grade at the end of treatment was measured to determine the prognosis. Electroneurography (ENoG) was performed on four facial muscles, including the frontalis, oculi, nasalis, and oris. Results: Salivary VZV DNA was isolated from 72 patients with RHS. The VZV DNA-positive group was 34.023 times more likely to have severe initial HB grade than the control group (95% CI, 3.21–359.68; p = 0.003). There were no significant differences in final HB grade. All ENoG values of the VZV DNA-positive group were significantly higher than those of the control group (frontalis, p = 0.003; oculi, p = 0.001; nasalis, p < 0.001; oris, p = 0.037). Conclusions: RHS patients with salivary VZV DNA have more severe clinical symptoms than the control group. There were no differences in prognosis and associated symptoms. A VZV DNA test using saliva samples of patients with RHS can evaluate the clinical symptoms and provide early confirmation of VZV infection, enabling timely treatment in a non-invasive way.
Brain Gene Silencing with Cationic Amino-Capped Poly(ethylene glycol) Polyplexes
Authors: Alamoudi Abdullah A. , Méndez Paula A. , Workman David , Schätzlein Andreas G. , Uchegbu Ijeoma F.
Published: September 2022

Therapeutic gene silencing in the brain is usually achieved using highly invasive intracranial administration methods and/or comparatively toxic vectors. In this work, we use a relatively biocompatible vector: poly(ethylene glycol) star-shaped polymer capped with amine groups (4APPA) via the nose to brain route. 4APPA complexes anti- itchy E3 ubiquitin protein ligase (anti-ITCH) siRNA to form positively charged (zeta potential +15 ± 5 mV) 150 nm nanoparticles. The siRNA-4APPA polyplexes demonstrated low cellular toxicity (IC50 = 13.92 ± 6 mg mL−1) in the A431 cell line and were three orders of magnitude less toxic than Lipofectamine 2000 (IC50 = 0.033 ± 0.04 mg mL−1) in this cell line. Cell association and uptake of fluorescently labelled siRNA bound to siRNA-4APPA nanoparticles was demonstrated using fluorescent activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM), respectively. Gene silencing of the ITCH gene was observed in vitro in the A431 cell line (65% down regulation when compared to the use of anti-ITCH siRNA alone). On intranasal dosing with fluorescently labelled siRNA-4APPA polyplexes, fluorescence was seen in the cells of the olfactory bulb, cerebral cortex and mid-brain regions. Finally, down regulation of ITCH was seen in the brain cells (54 ± 13% ITCH remaining compared to untreated controls) in a healthy rat model, following intranasal dosing of siRNA-4APPA nanoparticles (0.15 mg kg−1 siRNA twice daily for 3 days). Gene silencing in the brain may be achieved by intranasal administration of siRNA- poly(ethylene glycol) based polyplexes.
Region-Specific Vulnerability of the Amygdala to Injury-Induced Spreading Depolarization
Authors: Smirnova Mariia P. , Medvedeva Tatiana M. , Pavlova Irina V. , Vinogradova Lyudmila V.
Published: September 2022

Spreading depolarization (SD), a self-propagated wave of transient depolarization, regularly occurs in the cortex after acute brain insults and is now referred as an important diagnostic and therapeutic target in patients with acute brain injury. Here, we show that the amygdala, the limbic structure responsible for post-injury neuropsychological symptoms, exhibits strong regional heterogeneity in vulnerability to SD with high susceptibility of its basolateral (BLA) region and resilience of its centromedial (CMA) region to triggering SD by acute focal damage. The BLA micro-injury elicited SD twice as often compared with identical injury of the CMA region (71% vs. 33%). Spatiotemporal features of SDs triggered in the amygdala indicated diverse patterns of the SD propagation to the cortex. Our results suggest that even relatively small cerebral structures can exhibit regional gradients in their susceptibility to SD and the heterogeneity may contribute to the generation of complex SD patterns in the injured brain.
Methods for Assessing Oocyte Quality: A Review of Literature
Authors: Lemseffer Yassir , Terret Marie-Emilie , Campillo Clément , Labrune Elsa
Published: September 2022

The rate of infertility continues to rise in the world for several reasons, including the age of conception and current lifestyle. We list in this paper potential non-invasive and invasive techniques to assess oocyte quality. We searched the database PubMed using the terms “oocytes AND quality AND evaluation”. In the first part, we study the morphological criteria, compartment by compartment, to then focus in a second part on more objective techniques such as genetics, molecular, apoptosis, or human follicular fluid that contain biologically active molecules. The main criteria used to assess oocyte quality are morphological; however, several other techniques have been studied in women to improve oocyte quality assessment, but most of them are invasive and not usable in routine.
Influence of Pre-Treatment and Artificial Aging on the Retention of 3D-Printed Permanent Composite Crowns
Authors: Graf Tobias , Erdelt Kurt-Jürgen , Güth Jan-Frederik , Edelhoff Daniel , Schubert Oliver , Schweiger Josef
Published: September 2022

The aim of this in vitro study is to investigate the bonding properties of a 3D-printable permanent composite material in comparison to milled composite materials. The tested materials are 3D-printed BEGO VarseoSmile Crown plus (VA1_ab, VA1_nt, VA2_ab, VA2_nt), Vita Enamic (EN1, EN2), and 3M Lava Ultimate (UL1, UL2) (N = 64; n = 8). For this purpose, all crowns are luted to polymer tooth stumps #46 (FDI) using dual-curing luting composite, strictly according to the manufacturer’s instructions. VA1_ab and VA2_ab are additionally airborne-particle abraded. 4 groups (VA2_ab, VA2_nt, EN2, UL2) are artificially aged (1,200,000 cycles, 50 N, 10,000 thermocycles), whereby no specimen has failed. All 64 specimens undergo pull-off testing until retention loss. The mean forces of retention-loss is 786.6 ± 137.6 N (VA1_nt, *), 988.6 ± 212.1 N (VA2_nt, *, Ɨ), 1223.8 ± 119.2 N (VA1_ab, Ɨ, ǂ), 1051.9 ± 107.2 N (VA2_ab, *, Ɨ), 1185.9 ± 211.8 N (EN1, Ɨ, ǂ), 1485.0 ± 198.2 N EN2, ǂ), 1533.8 ± 42.4 N (UL1, ǂ), and 1521.8 ± 343.4 N (UL2, ǂ) (one-way ANOVA (Scheffé method); p < 0.05; *, Ɨ, ǂ: group distribution). No characteristic failure modes can be detected. In conclusion, all of the pull-off forces reflect retention values that seem to be sufficiently high for clinical use. Additional airborne-particle abrasion of VA does not result in significantly better retention but can be recommended.
An Artificial Intelligence Approach to Guiding the Management of Heart Failure Patients Using Predictive Models: A Systematic Review
Authors: Błaziak Mikołaj , Urban Szymon , Wietrzyk Weronika , Jura Maksym , Iwanek Gracjan , Stańczykiewicz Bartłomiej , Kuliczkowski Wiktor , Zymliński Robert , Pondel Maciej , Berka Petr , Danel Dariusz , Biegus Jan , Siennicka Agnieszka
Published: September 2022

Heart failure (HF) is one of the leading causes of mortality and hospitalization worldwide. The accurate prediction of mortality and readmission risk provides crucial information for guiding decision making. Unfortunately, traditional predictive models reached modest accuracy in HF populations. We therefore aimed to present predictive models based on machine learning (ML) techniques in HF patients that were externally validated. We searched four databases and the reference lists of the included papers to identify studies in which HF patient data were used to create a predictive model. Literature screening was conducted in Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition and MEDLINE. The protocol of the current systematic review was registered in the PROSPERO database with the registration number CRD42022344855. We considered all types of outcomes: mortality, rehospitalization, response to treatment and medication adherence. The area under the receiver operating characteristic curve (AUC) was used as the comparator parameter. The literature search yielded 1649 studies, of which 9 were included in the final analysis. The AUCs for the machine learning models ranged from 0.6494 to 0.913 in independent datasets, whereas the AUCs for statistical predictive scores ranged from 0.622 to 0.806. Our study showed an increasing number of ML predictive models concerning HF populations, although external validation remains infrequent. However, our findings revealed that ML approaches can outperform conventional risk scores and may play important role in HF management.
Micro-Volume Blood Separation Membrane for In-Situ Biosensing
Authors: Zhu Qin , Wu Huimin , Ma Zhen , Liu Yuqiao , Li Junmin , Zhu Ling , Zhang Xinran , Wang Chengcheng , Chen Dajing , Zhu Danhua
Published: September 2022

In this paper, we report a point-of-care (POCT) testing strip based on a porous membrane structure for whole blood separation and colorimetric analysis without external supporting equipment. Conventional blood tests rely on large instruments for blood pretreatment and separation to improve measurement accuracy. Cellulose acetate (CA) membranes with different pore diameters and structures were prepared via a non-solvent method for the separation of whole blood. Among them, CA@PEG-2000 membranes with nano-pores on the surface and micro-pores in the interior facilitated the capture of blood cells on the surface, as well as the free diffusion of plasma through the porous interior structure. The fluid flow of blood in the asymmetric porous structure can be theoretically estimated using the Lucas-Washburn equation. Compared with the conventional paper strips and other porous membranes, the CA@PEG-2000 membrane with an immobilized sensing layer exhibited efficient blood separation, a short response time (less than 2 min), an ultralow dosage volume (5 μL), and high sensitivity. The fabricated blood separation membranes can be further used for the detection of various biomarkers in whole blood, providing additional options for rapid quantitative POCT tests.
A Novel Electrochemical Aptasensor Based on a New Platform of Samarium Molybdate Flower-like Nanoparticles@Poly(pyrrole) for Non-Invasive Determination of Saliva CORTISOL
Authors: Rezapoor-Fashtali Zahra , Ganjali Mohammad Reza , Faridbod Farnoush
Published: September 2022

Cortisol, a famous stress biomarker, can be considered a potential predictor of cardiac diseases in humans. The presence of cortisol in saliva has encouraged researchers to design point-of-care devices for cortisol concentration in biological fluids. Here, human salivary cortisol was analyzed through a new non-invasive voltammetric aptasensor. Although cortisol is an electroactive compound, generally, the reduction in the current peak has been considered; however, this does not show a strong signal on a bare electrode surface, especially at low concentration levels. Hence, in this study, cortisol concentration was measured electrochemically and indirectly by monitoring the difference between electrochemical probe signals in the presence and absence of cortisol. A new polymeric nanocomposite of samarium molybdate flower-like nanoparticles decorated in poly(pyrrole) was electro-synthesized on the surface of a glassy carbon electrode. Then, reduced graphene oxide was cast on the surface. Finally, the cortisol aptamer was immobilized covalently on the reduced graphene oxide. This platform was used to increase the oxidation current peak of the ferricyanide solution as a probe as well as its electrocatalyst. The novel designed polymeric has the potential ability for effective immobilization of aptamers on the electrode surface without decreasing their biological activities. Additionally, it can enhance the probe electrochemical signal. The differential pulse voltammetric method (DPV) was applied as the detection technique. By optimizing the effective parameters, a determination range of 5.0 × 10−14–1.5 × 10−11 mol/L and a limit of detection of 4.5 × 10−14 mol/L were obtained. Selectivity of the proposed aptasensor relative to β-estradiol, progesterone and also prednisolone was studied as well. Finally, cortisol in a healthy human saliva sample was successfully analyzed by the proposed biosensors.
A Salmonella Microfluidic Chip Combining Non-Contact Eddy Heater and 3D Fan-Shaped Mixer with Recombinase Aided Amplification
Authors: Wu Shangyi , Duan Hong , Zhang Yingchao , Wang Siyuan , Zheng Lingyan , Cai Gaozhe , Lin Jianhan , Yue Xiqing
Published: September 2022

Foodborne pathogenic bacteria have become a worldwide threat to human health, and rapid and sensitive bacterial detection methods are urgently needed. In this study, a facile microfluidic chip was developed and combined with recombinase-aided amplification (RAA) for rapid and sensitive detection of Salmonella typhimurium using a non-contact eddy heater for dynamic lysis of bacterial cells and a 3D-printed fan-shaped active mixer for continuous-flow mixing. First, the bacterial sample was injected into the chip to flow through the spiral channel coiling around an iron rod under an alternating electromagnetic field, resulting in the dynamic lysis of bacterial cells by this non-contact eddy heater to release their nucleic acids. After cooling to ~75 °C, these nucleic acids were continuous-flow mixed with magnetic silica beads using the fan-shaped mixer and captured in the separation chamber using a magnet. Finally, the captured nucleic acids were eluted by the eluent from the beads to flow into the detection chamber, followed by RAA detection of nucleic acids to determine the bacterial amount. Under the optimal conditions, this microfluidic chip was able to quantitatively detect Salmonella typhimurium from 1.1 × 102 to 1.1 × 105 CFU/mL in 40 min with a detection limit of 89 CFU/mL and might be prospective to offer a simple, low-cost, fast and specific bacterial detection technique for ensuring food safety.
The Dual-Targeted Peptide Conjugated Probe for Depicting Residual Nasopharyngeal Carcinoma and Guiding Surgery
Authors: Huang Wenhui , He Zicong , Cai Xuekang , Zhang Jingming , Li Wei , Wang Kun , Zhang Shuixing
Published: September 2022

Detecting residual nasopharyngeal carcinoma (rNPC) can be difficult because of the coexistence of occult tumours and post-chemoradiation changes, which poses a challenge for both radiologists and surgeons using current imaging methods. Currently, molecular imaging that precisely targets and visualises particular biomarkers in tumours may exceed the specificity and sensitivity of traditional imaging techniques, providing the potential to distinguish tumours from non-neoplastic lesions. Here, we synthesised a HER2/SR-BI-targeted tracer to efficiently position NPC and guide surgery in living mice. This bispecific tracer contained the following two parts: IRDye 800 CW, as an imaging reagent for both optical and optoacoustic imaging, and a fusion peptide (FY-35), as the targeting reagent. Both in vitro and in vivo tests demonstrated that the tracer had higher accumulation and longer retention (up to 48 h) in tumours than a single-targeted probe, and realised sensitive detection of tumours with a minimum size of 3.9 mm. By visualising the vascular network via a customised handheld optoacoustic scan, our intraoperative fluorescence molecular imaging system provides accurate guidance for intraoperative tumour resection. Integrating the advantages of both optical and optoacoustic scanning in an intraoperative image-guided system, this method holds promise for depicting rNPC and guiding salvage surgery.
Effects of Repetitive Transcranial Magnetic Stimulation on Gait and Postural Control Ability of Patients with Executive Dysfunction after Stroke
Authors: Yu Huixian , Liu Sihao , Dai Pei , Wang Zhaoxia , Liu Changbin , Zhang Hao
Published: September 2022

Objective: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on the gait and postural control ability of patients with executive dysfunction (ED) after stroke. Methods: A total of 18 patients with ED after stroke were randomly assigned into two groups, including an experimental group and a sham group. Patients in both groups received routine rehabilitation therapy, and patients in the experimental group underwent rTMS on the left dorsolateral prefrontal cortex (DLPFC) for 2 weeks (5 HZ, 80%MT, 1200 pulses). In the sham group, patients experienced sham stimulation treatment, in which the coil was placed vertically with the head. Before and after treatment, patients in both groups were subjected to Montreal cognitive assessment (MoCA) scoring, Fugl–Meyer assessment of lower extremity (L-FMA), Stroop color-word test (SCWT), gait analysis, foot plantar pressure test, 10-m walking test (10MWT), Berg balance scale (BBS), and timed up and go test (TUGT). In the SCWT, it was attempted to record the time of each card (SCWT-T), the correct number (SCWT-C), Stroop interference effect-time (SIE-T), and SIE correct count (SIE-C). The TUGT was categorized into four stages: getting up (GT), walking straight (WT), turning around (TT), and sitting down (ST), in which the total time of TUGT was calculated. Results: After two weeks of treatment, the evaluation indexes were improved in the two groups, some of which were statistically significant. In the experimental group, SCWT-T, SIE-T, SIE-C, GT, WT, TT, ST, and TUGT were significantly improved after treatment (p < 0.05). SCWT-C, L-FMA score, 10MWT, GT, WT, stride length, step width, foot plantar pressure, pressure center curve, and activities of daily living were not statistically different from those before treatment (p > 0.05). After treatment, SCWT-T, SIE-C, SIE-T, BBS score, TT, and ST in the experimental group were significantly shorter than those before treatment, with statistical differences (p < 0.05). Compared with the sham group, SCWT-C, L-FMA score, 10MWT, GT, WT, TUGT, stride length, step width, foot plantar pressure, pressure center curve, and motor skills were not significantly improved (p > 0.05). Conclusion: It was revealed that post-stroke rTMS treatment of patients with ED could improve executive function, improve postural control function, and reduce the risk of falling. In addition, rTMS of DLPFC could be a therapeutic target for improving postural control ability and reducing the risk of falling.
Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
Authors: Gao Wenliang , Kong Wei , Wang Shuaiqun , Wen Gen , Yu Yaling
Published: September 2022

Microglia, the major immune cells in the brain, mediate neuroinflammation, increased oxidative stress, and impaired neurotransmission in Alzheimer’s disease (AD), in which most AD risk genes are highly expressed. In microglia, due to the limitations of current single-omics data analysis, risk genes, the regulatory mechanisms, the mechanisms of action of immune responses and the exploration of drug targets for AD immunotherapy are still unclear. Therefore, we proposed a method to integrate multi-omics data based on the construction of gene regulatory networks (GRN), by combining weighted gene co-expression network analysis (WGCNA) with single-cell regulatory network inference and clustering (SCENIC). This enables snRNA-seq data and bulkRNA-seq data to obtain data on the deeper intermolecular regulatory relationships, related genes, and the molecular mechanisms of immune-cell action. In our approach, not only were central transcription factors (TF) STAT3, CEBPB, SPI1, and regulatory mechanisms identified more accurately than with single-omics but also immunotherapy targeting central TFs to drugs was found to be significantly different between patients. Thus, in addition to providing new insights into the potential regulatory mechanisms and pathogenic genes of AD microglia, this approach can assist clinicians in making the most rational treatment plans for patients with different risks; it also has significant implications for identifying AD immunotherapy targets and targeting microglia-associated immune drugs.
Eye Tracking Study of Social Intensity on Social Orientation of Autistic Children
Authors: Zhang Yajing , Zhang Kun , Chen Jingying , Liu Lili , Luo Meijuan , Chen Qian , Zeng Xiao , Wang Guangshuai
Published: September 2022

Some previous studies indicate that impaired social attention mainly results in social disorders in autistic children. In the social attention mode of autistic children, social orientation and joint attention are particularly important. The influence of different social intensity and ecological validity on them are worthy of further study. This study used realistic paintings with moderate ecological validity as experimental materials, to design isolated individual scene and social interaction scene, and to explore the impact of social interaction on the social orientation of autistic children. It found that in the scenes without social interaction, the attention patterns of autistic children and typical developing children were the same, while the attention patterns of autistic children were abnormal in the scenes with social interaction. From the eye tracking data, it was shown that the gaze processing process of autistic children was not as smooth as that of typical developing children. Compared with cartoons and other social scenes with low ecological validity, realistic painting could better restore the proportion of real scenes. Moreover, it could reduce the complexity of information which could not be done in real scenes. The findings of this study provide support for training and education of autistic children. Intervention with realistic paintings is conducive to the migration of autistic children.
Workability, Strength, Modulus of Elasticity, and Permeability Feature of Wheat Straw Ash-Incorporated Hydraulic Cement Concrete
Authors: Katman Herda Yati Binti , Khai Wong Jee , Bheel Naraindas , Kırgız Mehmet Serkan , Kumar Aneel , Khatib Jamal , Benjeddou Omrane
Published: September 2022

The extensive use of Portland cement (PC) in the manufacturing of concrete is responsible for the depletion of natural resources that are part of cement production. Cement supply is permanently threatened by the ongoing depletion of natural materials, including sand, limestone, and clay. Concurrently, the incineration of agricultural residues presents a significant ecological problem. This study explores the substitution of cement in concrete with 5%, 10%, 15%, and 20% wheat straw ash as an environmentally friendly alternative. The purpose of this investigation is to evaluate the effect of substituting wheat straw ash (WSA) for PC on the mechanical characteristics of concrete. A total of 75 concrete samples were made by cement or cement + WSA/fine aggregate/coarse aggregate ratio of 1:1, 5:3, and water-to-cement ratio was kept constant at 0.50. All of these specimens were cured and tested at 28 days. The properties tested in the paper were workability, compressive strength, splitting tensile strength, flexural strength, modulus of elasticity, and permeability. The outcomes showed that the substitution of PC with WSA 10% resulted in the greatest concrete strength. In contrast, the mechanical properties and permeability of concrete were reduced when 20% WSA was substituted for PC at 28 days. In addition, the slump value dropped as increasing the content of WSA diminished the weight of PC in the concrete. This could be attributed to the fact that the water content in the WSA 20% concrete was not enough for mechanical strength. Other concretes with WSA showed similar properties to those of the WSA 10% concrete. It was concluded from the results that since the WSA 10% concrete showed the best properties, it can be recommended as the best recipe in this research work.
Post-High-Temperature Exposure Repeated Impact Response of Steel-Fiber-Reinforced Concrete
Authors: Abid Sallal R. , Abbass Ahmmad A. , Murali Gunasekaran , Al-Sarray Mohammed L. J. , Nader Islam A. , Ali Sajjad H.
Published: September 2022

The response of plain and fibrous concrete to the scenario of fired structures exposed to repeated impacts from falling fragmented building elements and other objects is experimentally investigated in this study. The experimental program included the casting and testing of specimens with 0%, 0.5%, and 1.0% hooked-end steel fibers (SFs) under the ACI 544-2R repeated-impact test. The impact test was conducted using cylindrical disk specimens, while 100 mm cubes were used to evaluate the residual compressive strength and weight loss. From each mixture, six disks and three cubes were heated to high temperatures of 200, 400, and 600 °C, while a similar set of specimens were tested without heating as a reference group. The results show that SF could significantly improve cracking impact resistance and dramatically boost failure impact numbers. The retained percentage improvements were the highest for specimens heated to 600 °C, which were approximately 250% at the cracking stage and 1680% at the failure stage for specimens with 1.0% SF. The test results also show that the repeated-impact resistance dramatically deteriorated at high temperatures, where the maximal residual cracking and failure impact numbers after exposure to 200, 400, and 600 °C were approximately 20% and 40%, 4% and 7%, and 2.2% and 4%, respectively.
Comparison of Old and New Stable Explicit Methods for Heat Conduction, Convection, and Radiation in an Insulated Wall with Thermal Bridging
Authors: Jalghaf Humam Kareem , Kovács Endre , Bolló Betti
Published: September 2022

Using efficient methods to calculate heat transfer in building components is an important issue. In the current work, 14 numerical methods are examined to solve the heat transfer problem inside building walls. Not only heat conduction but convection and radiation are considered as well, in addition to heat generation. Five of the used methods are recently invented explicit algorithms, which are unconditionally stable for conduction problems. First, the algorithms are verified in a 1D case by comparing the results of the methods to an analytical solution. Then they are tested on real-life cases in the case of surface area (made of brick) and cross-sectional area (two-layer brick and insulator) walls with and without thermal bridging. Equidistant and non-equidistant grids are used as well. The goal was to determine how the errors depend on the properties of the materials, the mesh type, and the time step size. The results show that the best algorithms are typically the leapfrog-hopscotch and the modified Dufort–Frankel and odd–even hopscotch algorithms since they are quite accurate for larger time step sizes, even for 100 s as well.
Experimental Study on Freezing Mode to Reduce Frost Heave
Authors: Hu Kun , Wu Yan , Gao Zhaoguo , Wang Shaowei , Yang Zhao
Published: September 2022

Frost heave is an important factor affecting the safety and practicability of buildings in cold regions or artificial freezing engineering. In order to reduce frost heave, frost-susceptible silty clay was used in a one-dimensional frost heave testing system in three different freezing modes. The results show that, compared with the continuous freezing mode, frost heave in the intermittent freezing mode and the continuous-intermittent freezing mode is reduced by 14.4% and 43.6%, respectively. These results clearly demonstrate that frost heave can be restrained in the continuous-intermittent freezing mode more effectively than in the other two freezing modes. The periodic step growth on the frost heave curves in the continuous-intermittent freezing mode is the main reason for this, as explained by the frost heave theory in this paper. To acquire appropriate settings on the cold end temperature, frost heave tests were carried out at different amplitudes and periods of temperature change in the continuous-intermittent freezing mode. The frost heave decreases with the increase of the amplitude of temperature change and period of temperature change. The power function growth, periodic step growth and periodic polyline growth are shown on the frost heave curves at different periods of temperature change of 2, 4, and 8 h, respectively. Due to the good inhibition effect of frost heave, periodic step growth will be a better way to reduce frost heave, which is of great significance to the life cycle safety of buildings.