bluuebunny/crossref_metadata_2025 huggingface dataset:
Fen Eğitiminde 5E Öğrenme Modeli İle İlgili Çalışmaların İncelenmesi
Authors: Şeremet Şeyma , Kızılay Esra , Öner Armağan Fulya
Published: April 2022

Bu çalışmada 2010-2020 yılları arasında fen eğitiminde 5E öğrenme modeli üzerine yapılan çalışmaların çeşitli değişkenlere göre incelenmesi amaçlanmıştır. 2010- 2020 yılları arasında yapılan makale ve tez çalışmaları YÖK TEZ ve TR Dizin veri tabanlarından taranmış ve bu araştırmaya 55 çalışma dahil edilmiştir. Bu çalışmaların yıllara göre dağılımı, araştırmanın türü, araştırma modeli, örneklem türü, örneklem sayısı, araştırmalarda kullanılan veri toplama araçları, araştırmaların analiz yöntemleri ve konuları açısından dağılımları incelenmiştir. 2017 yılı itibariyle 5E öğrenme modelinin fen alanında kullanımında bir artış olduğu, bu konuda yapılan çalışmaların genellikle nicel araştırma modeline uygun olarak yapıldığı, araştırmaların yarı deneysel yöntemle yapıldığı görülmüştür. Ayrıca çalışmaların örneklem grubunun genellikle ortaokul öğrencilerinden oluştuğu, veri toplama aracı olarak testlerin kullanıldığı ve veri analiz yöntemi olarak ise sıklıkla t testi kullanıldığı görülmüştür. Yine incelenen çalışmalarda 5E öğrenme modelinin fen alanında kullanımı sonucunda öğrencilerin tutumun ve akademik başarısındaki değişimin sık araştırılan konular olduğu görülmüştür.
THE EFFECT OF HEALTH LITERACY ON RATIONAL DRUG USE BEHAVIOR
Authors: YALMAN Fuat , YILDIZ Mehmet Selami , VURAL Nazmi
Published: April 2022

The main purpose of this study is to determine the effects of the factors affecting the health literacy levels of individuals on the factors affecting their rational drug use levels using path analysis and to reveal the path coefficients according to the degree of importance. The study population of the research consisted of patients and their relatives who received health services from pharmacies operating in Sakarya city centres. A population-based cross-sectional research design was applied. Frequency analysis, explanatory factor analysis and path analysis techniques were applied to the research data. IBM SPSS 23 V and AMOS package programs were used in the analysis of the data. Functional health literacy levels of individuals has affected their; correct drug use, effective drug use and safe drug use levels in a statistically significantly and positive manner. In addition, it has been determined that the communicative health literacy levels of individuals affected their; correct drug use, effective drug use and safe drug use levels in a statistically significant and negative way. In this research, it is recommended to provide education and information programs to increase the health literacy level of the society and to raise awareness about the correct rational use of drugs.
COMPARISON OF THE MICROHARDNESS OF BULK FILL COMPOSITES
Authors: ŞİŞMAN Reyhan , DAYI Burak , TURGUT Hacer , ŞİMŞEK Enis
Published: April 2022

The aim of this study is to compare the microhardness of five different bulk fill composites (SDR, TEC, XTF, SF, FBF). A total of 25 cylindrical molds were prepared. Composite resin was placed in each mold in sequence, at one time, by condensing it thoroughly. Then, the polymerization of the composites was achieved with the LED light device which was applied for 20 seconds. Microhardness measurements of the samples were made with the classical Vicker's test. The data of our study were evaluated by using the Kruskal Wallis H test with the SPSS 20.0 package program. When the measured surface microhardness values were compared between the groups; microhardness values SDR and FBF groups were found to be significantly lower than TEC, XTF and KSF groups (p<0.05). When the sub-surface microhardness values were compared between the groups; the microhardness value of the SDR group was found to be significantly higher than the FBF group, and significantly lower than the TEC, XTF and KSF groups (p<0.05). When both the lower and upper surface microhardness values were compared between the groups, XTF was found to be the bulk fill composite group with the best microhardness.
Analyzing the Effect of Covid-19 Pandemic on Tourists’ Psyche and Effective Implications for the Public Transport System for Safe-Travel: A Case Study on India
Authors: RANGA Bindu , SİNGH Kuldeep , RANGA Indu , GANTAİT Arnab
Published: April 2022

In the process of unlocking India after the COVID-19 outbreak, the Indian tourism and transport industry is resuming to revive the economy. In this scenario, it is substantial to examine the impact of Covid-19 pandemic on the travel pattern of the Indians. At the same time, making public transports safe to prevent mass transmission of the Corona-virus is equally important to ensure safe-travel. The present study investigates the impact of COVID-19 on the travel behaviour of the Indians, their readiness for availing public transports, as well as their stand on the reoperation of public transport. A total of 212 responses are collected through convenience sampling method for this purpose. The study reveals that COVID-19 pandemic has deeply affected the travel pattern of the Indians. The transport sector has been considered as one of the major causes of transmission of Corona-virus whereas; railway has been identified as the riskiest mode of transport. Though many Indians are ready to avail public transport, the majority still prefer private vehicles more than anything. The Indian respondents are also found doubtful regarding the effective implementation of rules and regulations, which is no doubt crucial for safe travelling. This study will provide useful understandings to the Indian transportation authorities as well as to the Tour Operators regarding the Indian travelers’ concern for transport sector amid COVID-19.
The Potential Role of Mitochondrial Acetaldehyde Dehydrogenase 2 in Urological Cancers From the Perspective of Ferroptosis and Cellular Senescence
Authors: Zhu Weizhen , Feng Dechao , Shi Xu , Wei Qiang , Yang Lu
Published: April 2022

Overproduction of reactive oxygen species (ROS) and superlative lipid peroxidation promote tumorigenesis, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is associated with the detoxification of ROS-mediated lipid peroxidation-generated reactive aldehydes such as 4-hydroxy-2-nonenal (4-HNE), malondialdehyde, and acrolein due to tobacco smoking. ALDH2 has been demonstrated to be highly associated with the prognosis and chemoradiotherapy sensitivity of many types of cancer, including leukemia, lung cancer, head and neck cancer, esophageal cancer, hepatocellular cancer, pancreatic cancer, and ovarian cancer. In this study, we explored the possible relationship between ALDH2 and urological cancers from the aspects of ferroptosis, epigenetic alterations, proteostasis, mitochondrial dysfunction, and cellular senescence.
Ferroptosis-Related Gene MT1G as a Novel Biomarker Correlated With Prognosis and Immune Infiltration in Colorectal Cancer
Authors: Peng Bi , Peng Jinwu , Kang Fanhua , Zhang Wenqin , Peng Emin , He Qingchun
Published: April 2022

Ferroptosis, a newly discovered way of cell death, has been proved to be involved in the oncogenesis and development of cancers, including colorectal cancer (CRC). Here, by identifying the differentially expressed genes (DEGs) from three CRC transcriptome microarray datasets (GSE20842, GSE23878, and GSE25070), we found that the expression of MT1G was significantly decreased in CRC tissues, and the patients with a high level of MT1G displayed a poor prognosis. Quantitative PCR (qPCR) further confirmed the downregulated MT1G in two CRC cells, HCT8 and HCT116. The colony-forming assay indicated that the MT1G overexpression exhibited a remarkable inhibition of cell proliferation in HCT8 and HCT116 cells. In addition, we explored the co-expressed genes of MT1G to gain a better understanding of its potential signaling pathways. Aberrantly expressed MT1G also affected the immune response of CRC patients. Collectively, these findings might deepen our comprehension on the potential biological implications of MT1G in CRC.
Transcriptomic Responses of Salmonella enterica Serovars Enteritidis in Sodium Hypochlorite
Authors: Wang Sheng , Xiao Xingning , Qiu Mengjia , Wang Wensi , Xiao Yingping , Yang Hua , Dang Yali , Wang Wen
Published: April 2022

Salmonella enterica serovars Enteritidis (S. Enteritidis) can survive extreme food processing environments including bactericidal sodium hypochlorite (NaClO) treatments generally recognized as safe. In order to reveal the molecular regulatory mechanisms underlying the phenotypes, the overall regulation of genes at the transcription level in S. Enteritidis after NaClO stimulation were investigated by RNA-sequencing. We identified 1399 differentially expressed genes (DEG) of S. Enteritidis strain CVCC 1806 following treatment in liquid culture with 100 mg/L NaClO for 20 min (915 upregulated and 484 downregulated). NaClO stress affects the transcription of genes related to a range of important biomolecular processes such as membrane damage, membrane transport function, energy metabolism, oxidative stress, DNA repair, and other important processes in Salmonella enterica. First, NaClO affects the structural stability of cell membranes, which induces the expression of a range of outer and inner membrane proteins. This may lead to changes in cell membrane permeability, accelerating the frequency of DNA conversion and contributing to the production of drug-resistant bacteria. In addition, the expression of exocytosis pump genes (emrB, yceE, ydhE, and ydhC) was able to expel NaClO from the cell, thereby increasing bacterial tolerance to NaClO. Secondly, downregulation of genes related to the Kdp-ATPase transporter system (kdpABC) and the amino acid transporter system (aroP, brnQ and livF) may to some extent reduce active transport by bacterial cells, thereby reducing their own metabolism and the entry of disinfectants. Downregulation of genes related to the tricarboxylic acid (TCA) cycle may drive bacterial cells into a viable but non-culturable (VBNC) state, resisting NaClO attack by reducing energy metabolism. In addition, significant upregulation of genes related to oxidative stress could mitigate damage caused by disinfectants by eliminating alkyl hydroperoxides, while upregulation of genes related to DNA repair could repair damage to bacterial cells caused by oxidative stress. Therefore, this study indicated that S. Enteritidis has genomic mechanisms to adapt to NaClO stress.
Minimal Intervention Dentistry: Biocompatibility and Mechanism of Action of Products for Chemical-Mechanical Removal of Carious Tissue
Authors: Leme Roberta Duarte , Lamarque Giuliana de Campos Chaves , Bastos Laura Alves , Arnez Maya Fernanda Manfrin , Paula-Silva Francisco Wanderley Garcia
Published: April 2022

Conventional method for removal of carious tissue using low speed drills usually induce noise and vibration, in addition to thermal and pressure effects that can be harmful to the pulp tissue and cause fear in children. Therefore, several alternative methods are being developed to try to minimize the unpleasant perception of the patient during caries removal. Chemical-mechanical removal of carious tissue goal is to selectively remove the carious lesion, which reduces the amount of bacteria inside the cavity without removing the tissue susceptible to remineralization. This method is also able to minimize the tactile perception by the patient during the manipulation of the lesion compared to the conventional method, and, therefore, it has been widely accepted among phobic patients, children and special needs patients. Due to the close relationship between dentin and pulp tissue, all injuries imposed on this dentin may have repercussions on the underlying pulp connective tissue. The morphological aspects of remaining dentin favor the diffusion of chemical components of dental materials, which can be toxic to the pulp tissue or even negatively interfere in the reparative process. Thus, considering the proximity between the applied material and the underlying pulp tissue, especially in deep cavities, there is a need to assess the biological behavior of dental materials against pulp cells, since aggressions to the pulp tissue can be caused not only by metabolites from microorganisms involved in dental caries but also by components that are released from these products. This subject was explored in this narrative literature review.
Residual Risk of Coronary Atherosclerotic Heart Disease and Severity of Coronary Atherosclerosis Assessed by ApoB and LDL-C in Participants With Statin Treatment: A Retrospective Cohort Study
Authors: Yao Tianci , Lu Weilin , Ke Jinshan , Zhang Hao , Zhao Xiaofang , Song Bei , Liu Ting , Ke Qinmei , Liu Chengyun
Published: April 2022

Background

Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy on the management of hypercholesterolemia in the United States and European guidelines, while apolipoprotein B (apoB) is the secondary target. The objective was to determine if elevated levels of apoB is superior to LDL-C in assessing residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment.

Methods

This study included 131 participants with statin treatment. The generalized linear model and relative risk regression (generalized linear Poisson model with robust error variance) were used to analyze the association of the levels of apoB and LDL-C with the severity of coronary atherosclerosis and residual risk of coronary atherosclerotic heart disease.

Results

Categorizing apoB and LDL-C based on tertiles, higher levels of apoB were significantly associated with the severity of coronary atherosclerosis (Ptrend = 0.012), whereas no such associations were found for elevated levels of LDL-C (Ptrend = 0.585). After multivariate adjustment, higher levels of apoB were significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level apoB (≤0.66 g/L), the multivariate adjusted RR and 95% CI of intermediate-level apoB (0.67–0.89 g/L) and high-level apoB (≥0.90 g/L) were 1.16 (1.01, 1.33) and 1.31 (1.08, 1.60), respectively (Ptrend = 0.011). There was a 45% increased residual risk of coronary atherosclerotic heart disease per unit increment in natural log-transformed apoB (Ptrend <0.05). However, higher levels of LDL-C were not significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level LDL-C (≤1.56 mmol/L), the multivariate adjusted RR and 95% CI of intermediate-level LDL-C (1.57–2.30 mmol/L) and high-level LDL-C (≥2.31 mmol/L) were 0.99 (0.84, 1.15) and 1.10 (0.86, 1.42), respectively (Ptrend = 0.437). Similar results were observed in the stratified analyses and sensitivity analyses. No significant interactions were detected for both apoB and LDL-C (all Pinteraction>0.05).

Conclusions

Elevated apoB are superior in assessing the residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment.
Scalability of Nek5000 on High-Performance Computing Clusters Toward Direct Numerical Simulation of Molten Pool Convection
Authors: Bian Boshen , Gong Jing , Villanueva Walter
Published: April 2022

In a postulated severe accident, a molten pool with decay heat can form in the lower head of a reactor pressure vessel, threatening the vessel’s structural integrity. Natural convection in molten pools with extremely high Rayleigh (Ra) number is not yet fully understood as accurate simulation of the intense turbulence remains an outstanding challenge. Various models have been implemented in many studies, such as RANS (Reynolds-averaged Navier–Stokes), LES (large-eddy simulation), and DNS (direct numerical simulation). DNS can provide the most accurate results but at the expense of large computational resources. As the significant development of the HPC (high-performance computing) technology emerges, DNS becomes a more feasible method in molten pool simulations. Nek5000 is an open-source code for the simulation of incompressible flows, which is based on a high-order SEM (spectral element method) discretization strategy. Nek5000 has been performed on many supercomputing clusters, and the parallel performance of benchmarks can be useful for the estimation of computation budgets. In this work, we conducted scalability tests of Nek5000 on four different HPC clusters, namely, JUWELS (Atos Bullsquana X1000), Hawk (HPE Apollo 9000), ARCHER2 (HPE Cray EX), and Beskow (Cray XC40). The reference case is a DNS of molten pool convection in a hemispherical configuration with Ra = 1011, where the computational domain consisted of 391 million grid points. The objectives are (i) to determine if there is strong scalability of Nek5000 for the specific problem on the currently available systems and (ii) to explore the feasibility of obtaining DNS data for much higher Ra. We found super-linear speed-up up to 65536 MPI-rank on Hawk and ARCHER2 systems and around 8000 MPI-rank on JUWELS and Beskow systems. We achieved the best performance with the Hawk system with reasonably good results up to 131072 MPI-rank, which is attributed to the hypercube technique on its interconnection. Given the current HPC technology, it is feasible to obtain DNS data for Ra = 1012, but for cases higher than this, significant improvement in hardware and software HPC technology is necessary.
Octopus Fishing and New Information on Ecology and Fishing of the Shallow-Water Octopus Callistoctopus furvus (Gould, 1852) Based on the Local Ecological Knowledge of Octopus Fishers in the Marine Ecoregions of Brazil
Authors: Jesus Manuella Dultra , Zapelini Cleverson , Santana Romário Oliveira de , Schiavetti Alexandre
Published: April 2022

Studies that compile local ecological knowledge (LEK) on some of the various species of living beings observe biological data and are notably fundamental for effectively managing fisheries, supporting management strategies for protected areas, species conservation, and other factors. In this study, ethnoecological approaches were used to focus on the octopus Callistoctopus furvus (Gould, 1852), recently re-described and re-presented to the academic community more than a century after its discovery. The LEK of octopus fishers from different marine ecoregions of Brazil was compared to identify the distribution limits of the species along the Brazilian coast. Semi-structured interviews were conducted in 16 municipalities across four marine ecoregions located between the states of Ceará (northern limit) and Santa Catarina (southern limit), between March 2018 and August 2019. The results of the 187 interviews indicated a traditionality of fishing among artisanal octopus fishers, who are mostly men, although some are women who also share information on the fishing of C. furvus and hold leadership positions in the fishing colony. Cronbach’s alpha was used to analyze reliability of the form used in the interviews. A logistic regression model with binomial distribution was used to assess whether the probability of capturing the “eastern octopus” was associated with some of the interview variables. A cluster analysis based only on the respondents who caught the “eastern octopus” indicated the formation of groups and revealed greater dissimilarities among the fishers from the southeastern marine ecoregion of Brazil due to the fishing method used in the region. Heat maps showed that most of the information on the species was obtained in the eastern marine ecoregion of Brazil. The occurrence of the “eastern octopus” was recorded in all the studied Brazilian marine ecoregions. Moreover, this study revealed the relevant contribution of fishers’ knowledge to the distribution diagnosis of species with scarce scientific information.
Microparticles in Autoimmunity: Cause or Consequence of Disease?
Authors: Rother Nils , Yanginlar Cansu , Pieterse Elmar , Hilbrands Luuk , van der Vlag Johan
Published: April 2022

Microparticles (MPs) are small (100 nm – 1 um) extracellular vesicles derived from the plasma membrane of dying or activated cells. MPs are important mediators of intercellular communication, transporting proteins, nucleic acids and lipids from the parent cell to other cells. MPs resemble the state of their parent cells and are easily accessible when released into the blood or urine. MPs also play a role in the pathogenesis of different diseases and are considered as potential biomarkers. MP isolation and characterization is technically challenging and results in different studies are contradictory. Therefore, uniform guidelines to isolate and characterize MPs should be developed. Our understanding of MP biology and how MPs play a role in different pathological mechanisms has greatly advanced in recent years. MPs, especially if derived from apoptotic cells, possess strong immunogenic properties due to the presence of modified proteins and nucleic acids. MPs are often found in patients with autoimmune diseases where MPs for example play a role in the break of immunological tolerance and/or induction of inflammatory conditions. In this review, we describe the main techniques to isolate and characterize MPs, define the characteristics of MPs generated during cell death, illustrate different mechanism of intercellular communication via MPs and summarize the role of MPs in pathological mechanisms with a particular focus on autoimmune diseases.
AHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer
Authors: Park Hong-Jai , Boo Sunjin , Park Inkeun , Shin Min Sun , Takahashi Tsukasa , Takanari Jun , Homma Kohei , Kang Insoo
Published: April 2022

Treatment strategies combining immune checkpoint blockade (ICB) with other agents have emerged as a promising approach in the treatment of cancers. AHCC®, a standardized extract of cultured Lentinula edodes mycelia, has been reported to inhibit tumor growth and enhance immune cell function. Here we investigated whether AHCC® promotes the therapeutic effect of immunotherapy in cancers. A combination of oral AHCC® and dual immune checkpoint blockade (DICB), including PD-1/CTLA-4 blockade, had reduced tumor growth and increased granzyme B and Ki-67 expression by tumor-infiltrating CD8+ T cells in MC38 colon cancer bearing mice compared to a combination of water and DICB. In the same tumor bearing mice, AHCC® and DICB treatment also altered the composition of the gut microbiome with the increased abundance of the species of Ruminococcaceae family which is associated with increased therapeutic efficacy of immunotherapy. The anti-tumor effect of AHCC® and DICB was not found in MC38 tumor-bearing mice treated with antibiotics. These data suggest that AHCC® increases the anti-tumor effect of DICB by enhancing T cell function and affecting the gut microbiome.
Serum Antigenome Profiling Reveals Diagnostic Models for Rheumatoid Arthritis
Authors: Han Peng , Hou Chao , Zheng Xi , Cao Lulu , Shi Xiaomeng , Zhang Xiaohui , Ye Hua , Pan Hudan , Liu Liang , Li Tingting , Hu Fanlei , Li Zhanguo
Published: April 2022

Objective

The study aimed to investigate the serum antigenomic profiling in rheumatoid arthritis (RA) and determine potential diagnostic biomarkers using label-free proteomic technology implemented with machine-learning algorithm.

Method

Serum antigens were captured from a cohort consisting of 60 RA patients (45 ACPA-positive RA patients and 15 ACPA-negative RA patients), together with sex- and age-matched 30 osteoarthritis (OA) patients and 30 healthy controls. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was then performed. The significantly upregulated and downregulated proteins with fold change > 1.5 (p < 0.05) were selected. Based on these differentially expressed proteins (DEPs), a machine learning model was trained and validated to classify RA, ACPA-positive RA, and ACPA-negative RA.

Results

We identified 62, 71, and 49 DEPs in RA, ACPA-positive RA, and ACPA-negative RA, respectively, as compared to OA and healthy controls. Typical pathway enrichment and protein–protein interaction networks were shown among these DEPs. Three panels were constructed to classify RA, ACPA-positive RA, and ACPA-negative RA using random forest models algorithm based on the molecular signature of DEPs, whose area under curve (AUC) were calculated as 0.9949 (95% CI = 0.9792–1), 0.9913 (95% CI = 0.9653–1), and 1.0 (95% CI = 1–1).

Conclusion

This study illustrated the serum auto-antigen profiling of RA. Among them, three panels of antigens were identified as diagnostic biomarkers to classify RA, ACPA-positive, and ACPA-negative RA patients.
Transdisciplinary Research: Can Citizen Science Support Effective Decision-Making for Coastal Infrastructure Management?
Authors: Agnew Sonya , Kopke Kathrin , Power Orla-Peach , Troya María Del Camino , Dozier Amy
Published: April 2022

Stakeholder engagement is increasingly recognised as imperative for developing effective climate change adaptation policy within the EU, particularly for delivering sustainable coastal infrastructure. This perspective discusses how current transdisciplinary research (TDR) approaches concerning ecoengineering solutions for artificial coastal structures are insufficient in ensuring adequate stakeholder engagement to facilitate coherent and enduring decision-making and policy development processes. Socio-cultural analysis focussing on how people view and feel about artificial coastal infrastructure within coastal infrastructure research has been recognised as a large knowledge gap. We suggest that citizen science (CS) methodologies as part of a cultural ecosystem services (CES) research approach can adequately inform and support the implementation of ecoengineering solutions for hard artificial coastal structures whilst addressing existing barriers associated with stakeholder engagement in current TDR approaches.
Case Report: Unusual Varicella-Zoster Virus Meningoencephalitis With Meningomyelitis Mimicking Central Nervous System Leukemia
Authors: Tu Ranran , Liu Jianyang , Cheng Fan , Weng Weipin , Zhang Hainan , Shu Yi , Wu Xiaomei , Hu Zhiping , Zhang Jie
Published: April 2022

Background

Varicella-Zoster Virus (VZV) is a human pathogen from the α-subfamily of herpesviruses. In immunocompromised patients, VZV may produce disease of the central nervous system (CNS). Clinical manifestations of CNS infection with VZV are non-specific and can mimic other infectious and non-infectious diseases. Due to similar symptoms, CNS infection with VZV represents a diagnostic challenge. Here, we report a case of a patient who showed laboratory and imaging manifestations mimicking the neoplastic etiology.

Case

A 31-year-old man presented with a 3-day history of headache, 5-h of confusion, generalized tonic-clonic seizures, and transient fever. The patient has a history of acute myelogenous leukemia (AML). His cerebrospinal fluid (CSF) studies revealed markedly elevated protein (10.326 g/L) and atypical cells. Meanwhile, the MRI of brain, cervical, and thoracic spine was reported as extensive (frontal, parieto-occipital and temporal pachymeningeal, and falx cerebri) enhancement and irregular thickening. These examinations suggested a suspicion of CNS involvement of AML. However, based on further investigations with metagenomic next-generation sequencing, a final diagnosis of VZV meningoencephalitis with meningomyelitis was made. With acyclovir and foscarnet sodium therapy, repeated CSF studies revealed normal cell count and protein. No atypical cells were found. The repeated brain MRI also revealed obvious resolution of the previous abnormal pachymeningeal enhancement.

Conclusion

This case highlights the importance of recognizing the unusual phenomenon of traditional tests in VZV meningoencephalitis with meningomyelitis, and timely using of further precise examinations to detect viral DNA, which is required to prevent missed diagnosis.
Co-Translational Folding of Multi-Domain Proteins
Authors: Rajasekaran Nandakumar , Kaiser Christian M.
Published: April 2022

The majority of proteins in nature are composed of multiple domains connected in a single polypeptide. How these long sequences fold into functional structures without forming toxic misfolds or aggregates is poorly understood. Their folding is inextricably linked to protein synthesis and interactions with cellular machinery, making mechanistic studies challenging. Recent progress has revealed critical features of multi-domain protein folding in isolation and in the context of translation by the ribosome. In this review, we discuss challenges and progress in understanding multi-domain protein folding, and highlight how molecular interactions shape folding and misfolding pathways. With the development of new approaches and model systems, the stage is now set for mechanistically exploring the folding of large multi-domain proteins.
Associations Between Age and Resting State Connectivity Are Partially Dependent Upon Cardiovascular Fitness
Authors: Gust Charleen J. , Moe Erin N. , Seals Douglas R. , Banich Marie T. , Andrews-Hanna Jessica R. , Hutchison Kent E. , Bryan Angela D.
Published: April 2022

Previous research suggests a marked impact of aging on structural and functional connectivity within the frontoparietal control network (FPCN) and default mode network (DMN). As aging is also associated with reductions in cardiovascular fitness, age-related network connectivity differences reported by past studies could be partially due to age-related declines in fitness. Here, we use data collected as part of a 16-week exercise intervention to explore relationships between fitness and functional connectivity. Young and older adults completed baseline assessments including cardiovascular fitness, health and functioning measures, and an fMRI session. Scan data were acquired on a Siemens 3T MRI scanner with a 32-channel head coil. Results from regression analyses indicated that average connectivity did not differ between young and older adults. However, individual ROI-to-ROI connectivity analyses indicated weaker functional correlations for older adults between specific regions in the FPCN and DMN and, critically, many of these differences were attenuated when fitness was accounted for. Taken together, findings suggest that fitness exerts regional rather than global effects on network connectivity.
Generalized Net Model of the Foreign Object Principle and its Network Physiology Interpretations
Authors: Atanassov Krassimir , Staneva Galya , Pencheva Tania
Published: April 2022

The Foreign Object Principle has been introduced in a formalized form for first time. Proven as a suitable tool for modelling of parallel processes flowing in real time, the generalized nets have been used for an interpretation of the Foreign Object Principle. It is illustrated by some examples from network physiology.
Neural Evidence for Different Types of Position Coding Strategies in Spatial Working Memory
Authors: Purg Nina , Starc Martina , Slana Ozimič Anka , Kraljič Aleksij , Matkovič Andraž , Repovš Grega
Published: April 2022

Sustained neural activity during the delay phase of spatial working memory tasks is compelling evidence for the neural correlate of active storage and maintenance of spatial information, however, it does not provide insight into specific mechanisms of spatial coding. This activity may reflect a range of processes, such as maintenance of a stimulus position or a prepared motor response plan. The aim of our study was to examine neural evidence for the use of different coding strategies, depending on the characteristics and demands of a spatial working memory task. Thirty-one (20 women, 23 ± 5 years) and 44 (23 women, 21 ± 2 years) participants performed a spatial working memory task while we measured their brain activity using fMRI in two separate experiments. Participants were asked to remember the position of a briefly presented target stimulus and, after a delay period, to use a joystick to indicate either the position of the remembered target or an indicated non-matching location. The task was designed so that the predictability of the response could be manipulated independently of task difficulty and memory retrieval process. We were particularly interested in contrasting conditions in which participants (i) could use prospective coding of the motor response or (ii) had to rely on retrospective sensory information. Prospective motor coding was associated with activity in somatomotor, premotor, and motor cortices and increased integration of brain activity with and within the somatomotor network. In contrast, retrospective sensory coding was associated with increased activity in parietal regions and increased functional connectivity with and within secondary visual and dorsal attentional networks. The observed differences in activation levels, dynamics of differences over trial duration, and integration of information within and between brain networks provide compelling evidence for the use of complementary spatial working memory strategies optimized to meet task demands.
Multi-Source Domain Adaptation Techniques for Mitigating Batch Effects: A Comparative Study
Authors: Panda Rohan , Kalmady Sunil Vasu , Greiner Russell
Published: April 2022

The past decade has seen an increasing number of applications of deep learning (DL) techniques to biomedical fields, especially in neuroimaging-based analysis. Such DL-based methods are generally data-intensive and require a large number of training instances, which might be infeasible to acquire from a single acquisition site, especially for data, such as fMRI scans, due to the time and costs that they demand. We can attempt to address this issue by combining fMRI data from various sites, thereby creating a bigger heterogeneous dataset. Unfortunately, the inherent differences in the combined data, known as batch effects, often hamper learning a model. To mitigate this issue, techniques such as multi-source domain adaptation [Multi-source Domain Adversarial Networks (MSDA)] aim at learning an effective classification function that uses (learned) domain-invariant latent features. This article analyzes and compares the performance of various popular MSDA methods [MDAN, Domain AggRegation Networks (DARN), Multi-Domain Matching Networks (MDMN), and Moment Matching for MSDA (M3SDA)] at predicting different labels (illness, age, and sex) of images from two public rs-fMRI datasets: ABIDE 1and ADHD-200. It also evaluates the impact of various conditions such as class imbalance, the number of sites along with a comparison of the degree of adaptation of each of the methods, thereby presenting the effectiveness of MSDA models in neuroimaging-based applications.
Digital Brain Maps and Virtual Neuroscience: An Emerging Role for Light-Sheet Fluorescence Microscopy in Drug Development
Authors: Perens Johanna , Hecksher-Sørensen Jacob
Published: April 2022

The mammalian brain is by far the most advanced organ to have evolved and the underlying biology is extremely complex. However, with aging populations and sedentary lifestyles, the prevalence of neurological disorders is increasing around the world. Consequently, there is a dire need for technologies that can help researchers to better understand the complexity of the brain and thereby accelerate therapies for diseases with origin in the central nervous system. One such technology is light-sheet fluorescence microscopy (LSFM) which in combination with whole organ immunolabelling has made it possible to visualize an intact mouse brain with single cell resolution. However, the price for this level of detail comes in form of enormous datasets that often challenges extraction of quantitative information. One approach for analyzing whole brain data is to align the scanned brains to a reference brain atlas. Having a fixed spatial reference provides each voxel of the sample brains with x-, y-, z-coordinates from which it is possible to obtain anatomical information on the observed fluorescence signal. An additional and important benefit of aligning light sheet data to a reference brain is that the aligned data provides a digital map of gene expression or cell counts which can be deposited in databases or shared with other scientists. This review focuses on the emerging field of virtual neuroscience using digital brain maps and discusses some of challenges incurred when registering LSFM recorded data to a standardized brain template.
High-Resolution Digital Panorama of Multiple Structures in Whole Brain of Alzheimer's Disease Mice
Authors: Yin Xianzhen , Zhang Xiaochuan , Zhang Jingjing , Yang Weicheng , Sun Xian , Zhang Haiyan , Gao Zhaobing , Jiang Hualiang
Published: April 2022

Simultaneously visualizing Amyloid-β (Aβ) plaque with its surrounding brain structures at the subcellular level in the intact brain is essential for understanding the complex pathology of Alzheimer's disease, but is still rarely achieved due to the technical limitations. Combining the micro-optical sectioning tomography (MOST) system, whole-brain Nissl staining, and customized image processing workflow, we generated a whole-brain panorama of Alzheimer's disease mice without specific labeling. The workflow employed the steps that include virtual channel splitting, feature enhancement, iso-surface rendering, direct volume rendering, and feature fusion to extract and reconstruct the different signals with distinct gray values and morphologies. Taking advantage of this workflow, we found that the denser-distribution areas of Aβ plaques appeared with relatively more somata and smaller vessels, but show a dissimilar distributing pattern with nerve tracts. In addition, the entorhinal cortex and adjacent subiculum regions present the highest density and biggest diameter of plaques. The neuronal processes in the vicinity of these Aβ plaques showed significant structural alternation such as bending or abrupt branch ending. The capillaries inside or adjacent to the plaques were observed with abundant distorted micro-vessels and abrupt ending. Depicting Aβ plaques, somata, nerve processes and tracts, and blood vessels simultaneously, this panorama enables us for the first time, to analyze how the Aβ plaques interact with capillaries, somata, and processes at a submicron resolution of 3D whole-brain scale, which reveals potential pathological effects of Aβ plaques from a new cross-scale view. Our approach opens a door to routine systematic studies of complex interactions among brain components in mouse models of Alzheimer's disease.
Application of Subperineural Resection Technique in Vestibular Schwannomas: Surgical Efficacy and Outcomes in 124 patients
Authors: Wu Yingxi , Wei Chen , Wang Ping , Zhang Yunze , Wu Yang , Xue Yafei , Zhao Tianzhi , Qu Yan
Published: April 2022

Objective

We aimed to explore the application and prospects of the subperineural resection technique for tumor separation and removal under the perineurium during surgery for vestibular schwannomas (VSs).

Methods

This study retrospectively analyzed 124 patients with VSs who underwent surgery via a retrosigmoid approach from July 2015 to October 2020 in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University. The data will be discussed with regard to the following aspects: clinical features, surgical strategies, tumor resection extent, facial–acoustic function preservation, and postoperative complications.

Results

Gross total resection (GTR) of the tumor was achieved in 104 patients, with a GTR rate of 83.9%, and subtotal resection (STR) of the tumor was achieved in 20 patients. There was no significant difference in facial and acoustic nerve functional preservation between GTR and STR, as well as in tumor resection between solid and cystic tumors. The retention rate reached 97.6% in terms of complete anatomical facial nerve preservation. Facial nerve function was assessed using the House–Brackmann (HB) grading score. Consequently, HB grades of I–II, III–IV, and V–VI were determined for 96 (77.4%), 25 (20.2%), and 3 (2.4%) cases, respectively, 1 week postoperatively and accounted for 110 cases (88.7%), 13 cases (10.5%), and 1 case (0.8%), respectively, at 6 months. Fifteen of 35 (42.9%) patients with serviceable hearing before the operation still had serviceable hearing at 6 months postoperatively. There were 5 cases of cerebellar or brainstem bleeding after the operation, and one patient died. Multivariate logistic regression analysis showed that older age (≥60 years, p = 0.011), large tumor (>3 cm, p = 0.004), and cystic tumor (p = 0.046) were independent risk factors associated with the extent of adhesion between the tumor and the brainstem and facial–acoustic nerve.

Conclusion

We successfully applied the subperineural resection technique to a large series of patients with VSs and achieved satisfactory results. Accurate identification of the perineurium and subperineural resection of the tumor can effectively reduce the disturbance of the facial–acoustic nerve during the operation and provide an intuitive basis for judging the tumor boundary. The subperineural resection technique may be conducive to improving the rate of total tumor resection and facial–acoustic nerve functional preservation in the surgical treatment of VSs.
Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy
Authors: Xie Li-Yun , Wang Kun , Chen Hai-Lu , Shi Yan-Xia , Zhang Yuan-Qi , Lin Hao-Yu , Liang Yuan-Ke , Xiao Ying-Sheng , Wu Zhi-Yong , Yuan Zhong-Yu , Qiu Si-Qi
Published: April 2022

Background

Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population.

Methods

A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients’ outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients’ survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker.

Results

Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066]).

Conclusions

Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.
Multiphase Dual-Energy Spectral CT-Based Deep Learning Method for the Noninvasive Prediction of Head and Neck Lymph Nodes Metastasis in Patients With Papillary Thyroid Cancer
Authors: Jin Dan , Ni Xiaoqiong , Zhang Xiaodong , Yin Hongkun , Zhang Huiling , Xu Liang , Wang Rui , Fan Guohua
Published: April 2022

Purpose

To develop deep learning (DL) models based on multiphase dual-energy spectral CT for predicting lymph nodes metastasis preoperatively and noninvasively in papillary thyroid cancer patients.

Methods

A total of 293 lymph nodes from 78 papillary thyroid cancer patients who underwent dual-energy spectral CT before lymphadenectomy were enrolled in this retrospective study. The lymph nodes were randomly divided into a development set and an independent testing set following a 4:1 ratio. Four single-modality DL models based on CT-A model, CT-V model, Iodine-A model and Iodine-V model and a multichannel DL model incorporating all modalities (Combined model) were proposed for the prediction of lymph nodes metastasis. A CT-feature model was also built on the selected CT image features. The model performance was evaluated with respect to discrimination, calibration and clinical usefulness. In addition, the diagnostic performance of the Combined model was also compared with four radiologists in the independent test set.

Results

The AUCs of the CT-A, CT-V, Iodine-A, Iodine-V and CT-feature models were 0.865, 0.849, 0.791, 0.785 and 0.746 in the development set and 0.830, 0.822, 0.744, 0.739 and 0.732 in the testing set. The Combined model had outperformed the other models and achieved the best performance with AUCs yielding 0.890 in the development set and 0.865 in the independent testing set. The Combined model showed good calibration, and the decision curve analysis demonstrated that the net benefit of the Combined model was higher than that of the other models across the majority of threshold probabilities. The Combined model also showed noninferior diagnostic capability compared with the senior radiologists and significantly outperformed the junior radiologists, and the interobserver agreement of junior radiologists was also improved after artificial intelligence assistance.

Conclusion

The Combined model integrating both CT images and iodine maps of the arterial and venous phases showed good performance in predicting lymph nodes metastasis in papillary thyroid cancer patients, which could facilitate clinical decision-making.
Fatty Acid β-Oxidation in Kidney Diseases: Perspectives on Pathophysiological Mechanisms and Therapeutic Opportunities
Authors: Gao Zhumei , Chen Xiangmei
Published: April 2022

The kidney is a highly metabolic organ and requires a large amount of ATP to maintain its filtration-reabsorption function, and mitochondrial fatty acid β-oxidation serves as the main source of energy to meet its functional needs. Reduced and inefficient fatty acid β-oxidation is thought to be a major mechanism contributing to kidney diseases, including acute kidney injury, chronic kidney disease and diabetic nephropathy. PPARα, AMPK, sirtuins, HIF-1, and TGF-β/SMAD3 activation have all been shown to play key roles in the regulation of fatty acid β-oxidation in kidney diseases, and restoration of fatty acid β-oxidation by modulation of these molecules can ameliorate the development of such diseases. Here, we disentangle the lipid metabolism regulation properties and potential mechanisms of mesenchymal stem cells and their extracellular vesicles, and emphasize the role of mesenchymal stem cells on lipid metabolism. This review aims to highlight the important role of fatty acid β-oxidation in the progression of kidney diseases, and to explore the fatty acid β-oxidation effects and therapeutic potential of mesenchymal stem cells for kidney diseases.