bluuebunny/crossref_metadata_2025 huggingface dataset:
Rediscovering Teaching in University: A Scoping Review of Teacher Effectiveness in Higher Education
Authors: Mastrokoukou Sofia , Kaliris Andronikos , Donche Vincent , Chauliac Margot , Karagiannopoulou Evangelia , Christodoulides Pavlos , Longobardi Claudio
Published: March 2022

Although teacher effectiveness plays a critical role in the learning process, little is known about its conceptualization and assessment, particularly in higher education (HE). This review aims to fill this gap by (a) listing the literature on teacher effectiveness, (b) identifying the instruments that have been used to assess teacher effectiveness (HE), and (c) highlighting the most effective teaching approaches based on the relevant literature. The selection process considered studies published since 1990 and conducted in higher education contexts with students. The research articles measured instructional processes and faculty effectiveness in terms of student outcomes, focusing on student achievement and student satisfaction. In reviewing the international research, special attention was paid to Southeastern Europe and Greece in particular. After a thorough review, the analysis revealed 26 studies. The results show that there is no universal definition of effective higher education teaching. Effective teaching may manifest itself in high scores on student performance assessments or in rewarding classroom interactions. Based on this principle, the way teacher effectiveness is defined is closely linked to proposed solutions in educational policy. Furthermore, research has shown that student-centered teaching styles are perceived by students as more effective, engaging, and performance-enhancing. However, several studies have not clarified why different teachers use different teaching styles in similar contexts. This review represents a step forward in our understanding of teacher effectiveness in HE. Nonetheless, effective teaching strategies could be better conceptualized through future research aimed at assessing the contextual nature of teaching along with student perceptions of effectiveness and expectations for an effective classroom climate.
Perception of Online Teaching and Learning (T&L) Activities Among Postgraduate Students in Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM)
Authors: Ghazali Ahmad Rohi , Zainodin Elly Liyana , Madhavan Indira , Gnanasundram Linsay Sundram , Nisar Nadia , Abd Rashid Reena , Muniandy Subashini , Tang Wei Wei
Published: March 2022

The COVID-19 pandemic has changed the landscape of teaching pedagogies, assessment methods, supervision, and student engagement in higher education institutions. Exploration of students’ perception on online teaching and learning (T&L) in terms of their level of satisfaction is an important core indicator of their acceptance to enhance the long-term impact of the online (T&L) activities. The objective of the study is to determine the level of satisfaction of online (T&L) activities and its involved technical support among postgraduate students in the Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM). A validated questionnaire was used to conduct the survey. A total of 81 postgraduate students were recruited using purposive sampling in the study. Results showed that more than 86% of the students were satisfied with the online T&L activities except for two areas where 50% of the students felt that the curriculum structure design was too heavy and they felt stressed after attending the first online class and examination. On the other hand, more than 70% of the students were satisfied with the technical support for the online T&L. Although the satisfaction level for both was high, there was no association between them, χ2 (1, N = 162) = 3.8, p = 0.42. In conclusion, the postgraduate students of the Faculty of Health Sciences, UKM are satisfied with the online T&L process, which implies a good reception. A review of curriculum structure and design that considers the psychological and behavior changes among students during online T&L is also recommended for the online T&L continues to be effective in the future.
The Relationship Between Renal Stones and Primary Aldosteronism
Authors: Chang Chun-Kai , Chang Chin-Chen , Wu Vin-Cent , Geng Jiun-Hung , Lee Hsiang-Ying
Published: March 2022

Introduction

The association between primary aldosteronism (PA) and nephrolithiasis is still unclear. The hypercalciuria and hypocitraturia of PA patients might be the reason leading to recurrent calcium nephrolithiasis. This study aimed to evaluate the relationship between PA and renal stones, including stone size and density.

Materials and Methods

From February 2010 to March 2021, we retrospectively collected 610 patients who presented to our medical center with hypertension history, and all these patients, suspicious of PA, had PA data survey. In total, 147 patients had kidney stone and were divided into 44 patients with essential hypertension as group 1 and 103 patients with PA as group 2. Pearson χ2 test and independent Student’s t-test were performed to examine the differences among variables.

Results

The mean age was 54.4 ± 12.0 years in group 1 and 53.0 ± 11.1 years in group 2. The incidence rate of renal stones in the PA group was around 24%. No significant differences between the two groups were found for gender, systolic/diastolic blood pressure, duration of hypertension, diabetes mellitus history, and laterality of kidney stone; however, mean stone size was 4.0 ± 3.3 mm in group 1 and 6.5 ± 7.2 mm in group 2, with a significantly larger renal stone size noted in the PA group than that in the essential hypertension group (p = 0.004). Hounsfield unit (HU) density was higher in the PA group vis-à-vis the essential hypertension cohort, although this did not reach a significant difference (p = 0.204).

Conclusions

Our study revealed that PA patients had a higher incidence rate of renal stones compared to that of the general population. Besides, the PA-related renal stones also presented as larger and harder than those of the essential hypertension group. Further investigation concerning the association between PA and renal stones is warranted.
Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach
Authors: Arriba María , Ezquieta Begoña
Published: March 2022

Adrenal insufficiency in paediatric patients is mostly due to congenital adrenal hyperplasia (CAH), a severe monogenic disease caused by steroid 21-hydroxylase deficiency (21-OHD, encoded by the CYP21A2 gene) in 95% of cases. CYP21A2 genotyping requires careful analyses that guaranty gene-specific PCR, accurate definition of pseudogene-gene chimeras, gene duplications and allele dropout avoidance. A small panel of well-established disease-causing alterations enables a high diagnostic yield in confirming/discarding the disorder not only in symptomatic patients but also in those asymptomatic with borderline/positive results of 17-hydroxyprogesterone. Unfortunately, the complexity of this locus makes it today reluctant to high throughput techniques of massive sequencing. The strong relationship existing between the molecular alterations and the degree of enzymatic deficiency has allowed genetic studies to demonstrate its usefulness in predicting/classifying the clinical form of the disease. Other aspects of interest regarding molecular studies include its independence of physiological variations and analytical interferences, its usefulness in the diagnosis of simple virilizing forms in males and its inherent contribution to the genetic counseling, an aspect of great importance taking into account the high carrier frequency of CAH in the general population. Genetic testing of CYP21A2 constitutes an irreplaceable tool to detect severe alleles not just in family members of classical forms but also in mild late-onset forms of the disease and couples. It is also helpful in areas such as assisted reproduction and preimplantation diagnosis. Molecular diagnosis of 21-OHD under expert knowledge definitely contributes to a better management of the disease in every step of the clinical course.
Genome-Wide Association Studies and Haplotype-Sharing Analysis Targeting the Egg Production Traits in Shaoxing Duck
Authors: Xu Wenwu , Wang Zhenzhen , Qu Yuanqi , Li Qingyi , Tian Yong , Chen Li , Tang Jianhong , Li Chengfeng , Li Guoqin , Shen Junda , Tao Zhengrong , Cao Yongqing , Zeng Tao , Lu Lizhi
Published: March 2022

Age at first egg (AFE) and egg number (EN) are economically important traits related to egg production, as they directly influence the benefits of the poultry industry, but the molecular genetic research that affects those traits in laying ducks is still sparse. Our objective was to identify the genomic regions and candidate genes associated with AFE, egg production at 43 weeks (EP43w), and egg production at 66 weeks (EP66w) in a Shaoxing duck population using genome-wide association studies (GWASs) and haplotype-sharing analysis. Single-nucleotide polymorphism (SNP)-based genetic parameter estimates showed that the heritability was 0.15, 0.20, and 0.22 for AFE, EP43w, and EP66w, respectively. Subsequently, three univariate GWASs for AFE, EP43w, and EP66w were carried out independently. Twenty-four SNPs located on chromosome 25 within a 0.01-Mb region that spans from 4.511 to 4.521 Mb were associated with AFE. There are two CIs that affect EP43w, i.e., twenty-five SNPs were in strong linkage disequilibrium region spanning from 3.186 to 3.247 Mb on chromosome 25, a region spanning from 4.442 to 4.446 Mb on chromosome 25, and two interesting genes, ACAD8 and THYN1, that may affect EP43w in laying ducks. There are also two CIs that affect EP66w, i.e., a 2.412-Mb region that spans from 127.497 to 129.910 Mb on chromosome 2 and a 0.355-Mb region that spans from 4.481 to 4.837 Mb on chromosome 29, and CA2 and GAMT may be the putative candidate genes. Our study also found some haplotypes significantly associated with these three traits based on haplotype-sharing analysis. Overall, this study was the first publication of GWAS on egg production in laying ducks, and our findings will be helpful to provide some candidate genes and haplotypes to improve egg production performance based on breeding in laying duck. Additionally, we learned from a method called bootstrap test to verify the reliability of a GWAS with small experimental samples that users can access at https://github.com/xuwenwu24/Bootstrap-test.
Evolutionary Trajectories of Complex Traits in European Populations of Modern Humans
Authors: Kuijpers Yunus , Domínguez-Andrés Jorge , Bakker Olivier B. , Gupta Manoj Kumar , Grasshoff Martin , Xu Cheng-Jian , Joosten Leo A.B. , Bertranpetit Jaume , Netea Mihai G. , Li Yang
Published: March 2022

Humans have a great diversity in phenotypes, influenced by genetic, environmental, nutritional, cultural, and social factors. Understanding the historical trends of physiological traits can shed light on human physiology, as well as elucidate the factors that influence human diseases. Here we built genome-wide polygenic scores for heritable traits, including height, body mass index, lipoprotein concentrations, cardiovascular disease, and intelligence, using summary statistics of genome-wide association studies in Europeans. Subsequently, we applied these scores to the genomes of ancient European populations. Our results revealed that after the Neolithic, European populations experienced an increase in height and intelligence scores, decreased their skin pigmentation, while the risk for coronary artery disease increased through a genetic trajectory favoring low HDL concentrations. These results are a reflection of the continuous evolutionary processes in humans and highlight the impact that the Neolithic revolution had on our lifestyle and health.
An Individualized Prognostic Signature for Clinically Predicting the Survival of Patients With Bladder Cancer
Authors: Liu Qing , Wang Yunchao , Gao Huayu , Sun Fahai , Wang Xuan , Zhang Huawei , Wang Jianning
Published: March 2022

Background:The tumor immune microenvironment (TIME) plays an important role in the development and prognosis of bladder cancer. It is essential to conduct a risk model to explore the prognostic value of the immunologic genes and establish an individualized prognostic signature for predicting the survival of patients with bladder cancer.

Method:The differentially expressed immunologic genes (DEGs) are identified in The Cancer Genome Atlas (TCGA). The nonnegative matrix factorization (NMF) was used to stratify the DEGs in TCGA. We used the least absolute shrinkage and selection operator (LASSO) Cox regression and univariate Cox analysis to establish a prognostic risk model. A nomogram was used to establish an individualized prognostic signature for predicting survival. The potential pathways underlying the model were explored.

Results:A total of 1,018 DEGs were screened. All samples were divided into two clusters (C1 and C2) by NMF with different immune cell infiltration, and the C2 subtype had poor prognosis. We constructed a 15-gene prognostic risk model from TCGA cohort. The patients from the high-risk group had a poor overall survival rate compared with the low-risk group. Time-dependent ROC curves demonstrated good predictive ability of the signature (0.827, 0.802, and 0.812 for 1-, 3-, and 5-year survival, respectively). Univariate and multivariate Cox regression analyses showed that the immunologic prognostic risk model was an independent factor. The decision curve demonstrated a relatively good performance of the risk model and individualized prognostic signature, showing the best net benefit for 1-, 3-, and 5-year OS. Gene aggregation analysis showed that the high-risk group was mainly concentrated in tumorigenesis and migration and immune signaling pathways.

Conclusion:We established a risk model and an individualized prognostic signature, and these may be useful biomarkers for prognostic prediction of patients with bladder cancer.
Both Natural and Induced Anti-Sda Antibodies Play Important Roles in GTKO Pig-to-Rhesus Monkey Xenotransplantation
Authors: Feng Hao , Li Tao , Du Jiaxiang , Xia Qiangbing , Wang Lu , Chen Song , Zhu Lan , Pan Dengke , Wang Yi , Chen Gang
Published: March 2022

Sda, produced by the B4GALNT2 enzyme, has been recognized as an important xenoantigen for pig-to-nonhuman primate xenotransplantation. However, little is known about Sda expression in pigs and its immunogenicity in xenotransplantation. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from wildtype, GTKO (with high, moderate, and low Sda expression), GTKO/β4GalNT2KO, GTKO/CMAHKO, or GTKO/CMAHKO/β4GalNT2KO pigs. Anti-pig IgM/IgG binding and complement-dependent cytotoxicity (CDC) to pig PBMCs was measured by flow cytometry using pooled rhesus monkey sera (n=20) or human sera (n=20). As compared to wild-type pigs (n=12), GTKO pigs (n=17) had a significantly higher mean level of Sda expression on PBMCs and showed a greater individual difference in expression. Both the overall binding of monkey serum IgM/IgG antibody to GTKO pig PBMCs and CDC against these PBMCs decreased significantly with a progressive reduction in Sda expression, showing a clear dose-effect relationship. Both the monkey serum antibody binding and CDC decreased significantly after the additional deletion of Sda, whereas the binding of human serum antibody and CDC against the GTKO pig PBMCs were markedly reduced after the deletion of Neu5Gc in the pigs. In addition, anti-Sda antibody accounted for > 50% of the induced anti-non-Gal antibody at the time of rejection in two rhesus monkeys that received GTKO/hCD55 pig kidney xenotransplantation, and the anti-Sda antibody showed significant cytotoxic activity against GTKO pig cells. We conclude that both natural and induced anti-Sda antibodies play important roles in GTKO pig-to-rhesus monkey xenotransplantation, thus providing further evidence for GTKO/β4GalNT2KO pigs as the preferred organ source for rhesus monkeys as a preclinical model of xenotransplantation.
Using Unmanned Aerial Vehicle (UAV) Imagery to Characterise Pursuit-Diving Seabird Association With Tidal Stream Hydrodynamic Habitat Features
Authors: Slingsby James , Scott Beth E. , Kregting Louise , McIlvenny Jason , Wilson Jared , Yanez Marion , Langlois Samuel , Williamson Benjamin J.
Published: March 2022

Tidal stream environments exhibit fast current flows and unique turbulent features occurring at fine spatio-temporal scales (metres and seconds). There is now global recognition of the importance of tidal stream environments for marine megafauna. Such areas are also key to the development of marine renewable energy due to the reliable and predictable nature of tidally driven flows. Bed-derived turbulent features, such as kolk-boils, transport organic material to the surface and may increase the availability of prey species (fish) for foraging marine megafauna (seabirds and marine mammals). Quantification of animal association and interactions with turbulent features is required to understand potential environmental impacts of tidal energy developments in these sites. Downward-facing unmanned aerial vehicle (UAV) imagery was collected within the Pentland Firth, UK. Resulting imagery was used to quantify the density distribution of pursuit-diving seabirds, called auks (of the family Alcidae), distribution in comparison relation to concurrent surface imagery of kolk-boils and, analyse evaluate spatial relationships with individual kolk-boil features, and quantify body orientation relative to the water flow. Although variability was present, auk density distribution was generally correlated with that of kolk-boils throughout the study area; however, spatial analysis highlighted an overall trend of finer-scale dispersion between individual auks and kolk-boils. Auk orientation on the surface was primarily observed across the flow throughout ebb and flood tidal phases. These results suggest that auks may be associating with kolk-boil peripheries. Similarly, it may be energetically beneficial to orientate across the flow while maintaining observation of current flow or searching for shallow prey species and potential threats in the environment. This work demonstrates that UAV imagery was appropriate for quantification of fine-scale biophysical interactions. It allowed for concurrent measurement of hydrodynamic and predator metrics in a challenging environment and provided novel insights not possible to collect by conventional survey methodology. This technique can increase the evidence base for assessment of potential impacts of marine renewable energy extraction on key marine species.
Magnesium Isotopes in Pore Water of Active Methane Seeps of the South China Sea
Authors: Jin Meng , Feng Dong , Huang Kangjun , Gong Shanggui , Luo Min , Peckmann Jörn , Wang Xudong , Hu Yu , Chen Duofu
Published: March 2022

The magnesium (Mg) isotopic composition of marine authigenic carbonates is considered as promising archive of ancient seawater geochemistry and paleoenvironments. Previous experimental and theoretical work has shown that Mg isotope fractionation during carbonate mineral formation is a function of mineralogy and precipitation rate. However, information on Mg isotope fractionation is limited for well-defined precipitation rates in natural settings. Here, we investigate pore waters from sediments of an area of active methane seepage in the South China Sea. Low δ13C values (< −48.3‰ VPDB) of dissolved inorganic carbon (DIC) near the sulfate-methane transition zone (SMTZ) indicate that sulfate-driven anaerobic oxidation of methane (SD-AOM) is the predominant biogeochemical process. Pore water composition of dissolved Mg, calcium (Ca), and strontium (Sr) agrees with aragonite as the dominant carbonate mineral at the site ROV1, and high Mg-calcite at sites ROV2 and ROV4. Calculated carbonate precipitation rates are 0.92 μmol cm−2 yr−1 for site ROV2 and 1.24 μmol cm−2 yr−1 for site ROV4; these estimates are similar to previous calculations for seeps from other areas. The pore water δ26Mg values (−0.88‰ to −0.71‰) obtained for the three study sites are similar to those of seawater, in accord with a minor effect of Rayleigh fractionation due to abundant supply of Mg from seawater and insignificant consumption of Mg during carbonate precipitation. The modeled Mg isotope fractionation (ϵ = −2.0‰ to −1.0‰ for core ROV2; ϵ = −1.3‰ to −0.3‰ for core ROV4) can be explained by kinetic isotope fractionation during carbonate precipitation. The calculated carbonate precipitation rates and the degree of fractionation of Mg isotopes support the notion that fractionation is small at high precipitation rates. However, the carbonate precipitation rates calculated for the studied seep environments are much smaller than those in laboratory experiments, documenting a discrepancy of isotopic fractionation between carbonate authigenesis in laboratory experiments and natural environments. These results, including the modeled precipitation rates, provide new constraints for Mg isotope fractionation in natural settings.
Central Venous Pressure Measurement Is Associated With Improved Outcomes in Patients With or at Risk for Acute Respiratory Distress Syndrome: An Analysis of the Medical Information Mart for Intensive Care IV Database
Authors: Tang Rui , Peng Junnan , Wang Daoxin
Published: March 2022

Background

Central venous pressure (CVP) monitoring is widely used in the intensive care unit (ICU). However, the formal utility of CVP measurement to altering patient outcomes among ICU patients with or at risk for acute respiratory distress syndrome (ARDS) has never been investigated. Our study aimed to explore the association of CVP measurement with 28-day mortality specifically in that population.

Methods

This study was based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients were divided into CVP and no CVP groups according to whether they had CVP measurement within 24 h of admission to the ICU. The primary outcome was 28-day mortality. Multivariate regression was used to elucidate the association between CVP measurement and 28-day mortality, and propensity score matching (PSM) and propensity score-based overlap weighting (OW) were employed to verify the stability of our results.

Results

A total of 10,198 patients with or at risk for ARDS were included in our study, of which 4,647 patients (45.6%) belonged to the CVP group. Multivariate logistic regression showed that the early measurement of CVP was independently associated with lower 28-day mortality (OR: 0.49; 95% CI: 0.42–0.57; p < 0.001). This association remained robust after PSM and OW (both p < 0.001). Patients in the CVP group had shorter ICU stay, lower in-hospital mortality, more fluid on day 1 and higher clearance of blood lactate than those in the no CVP group.

Conclusion

Early CVP measurement is associated with an improvement in 28-day mortality among a general population of critically ill patients with or at risk for ARDS.
Microbial Associations of Abyssal Gorgonians and Anemones (>4,000 m Depth) at the Clarion-Clipperton Fracture Zone
Authors: Quintanilla Elena , Rodrigues Clara F. , Henriques Isabel , Hilário Ana
Published: March 2022

Deep coral-dominated communities play paramount roles in benthic environments by increasing their complexity and biodiversity. Coral-associated microbes are crucial to maintain fitness and homeostasis at the holobiont level. However, deep-sea coral biology and their associated microbiomes remain largely understudied, and less from remote and abyssal environments such as those in the Clarion-Clipperton Fracture Zone (CCZ) in the tropical Northeast (NE) Pacific Ocean. Here, we study microbial-associated communities of abyssal gorgonian corals and anemones (>4,000 m depth) in the CCZ; an area harboring the largest known global reserve of polymetallic nodules that are commercially interesting for the deep-sea nodule mining. Coral samples (n = 25) belonged to Isididae and Primnoidae families, while anemones (n = 4) to Actinostolidae family. Significant differences in bacterial community compositions were obtained between these three families, despite sharing similar habitats. Anemones harbored bacterial microbiomes composed mainly of Hyphomicrobiaceae, Parvibaculales, and Pelagibius members. Core microbiomes of corals were mainly dominated by different Spongiibacteraceae and Terasakiellaceae bacterial members, depending on corals’ taxonomy. Moreover, the predicted functional profiling suggests that deep-sea corals harbor bacterial communities that allow obtaining additional energy due to the scarce availability of nutrients. This study presents the first report of microbiomes associated with abyssal gorgonians and anemones and will serve as baseline data and crucial insights to evaluate and provide guidance on the impacts of deep-sea mining on these key abyssal communities.
Effect of 6-Methoxybenzoxazolinone on the Cecal Microbiota of Adult Male Brandt’s Vole
Authors: Dai Xin , Chen Lin , Liu Mengyue , Liu Ying , Jiang Siqi , Xu Tingting , Wang Aiqin , Yang Shengmei , Wei Wanhong
Published: March 2022

The anti-microbial effects of plant secondary metabolite (PSM) 6-methoxybenzoxazolinone (6-MBOA) have been overlooked. This study investigated the effect of 6-MBOA on the cecal microbiota of adult male Brandt’s voles (Lasiopodomys brandtii), to evaluate its effect on the physiology of mammalian herbivores. The growth of voles was inhibited by 6-MBOA. A low dose of 6-MBOA enhanced the observed species, as well as the Chao1 and abundance-based coverage estimator (ACE) indices and introduced changes in the structure of cecal microbiota. The abundance of the phylum Tenericutes, classes Mollicutes and Negativicutes, order Selenomonadales, families Ruminococcaceae and Veillonellaceae, genera Quinella, Caproiciproducens, Anaerofilum, Harryflintia, and unidentified Spirochaetaceae in the cecal microbiota was enhanced upon administration of a low dose of 6-MBOA, which also inhibited glucose metabolism and protein digestion and absorption in the cecal microbiota. 6-MBOA treatment also stimulated butyrate production and dose-dependently enhanced the metabolism of xenobiotics in the cecal microbiome. Our findings indicate that 6-MBOA can affect Brandt’s voles by inducing changes in the abundance of cecal bacteria, thereby, altering the contents of short-chain fatty acids (SCFAs) and pathway intermediates, ultimately inhibiting the growth of voles. Our research suggests that 6-MBOA could potentially act as a digestion-inhibiting PSM in the interaction between mammalian herbivores and plants.
Recent Approaches to the Identification of Novel Microtubule-Targeting Agents
Authors: Eli Susanna , Castagna Rossella , Mapelli Marina , Parisini Emilio
Published: March 2022

Microtubules are key components of the eukaryotic cytoskeleton with essential roles in cell division, intercellular transport, cell morphology, motility, and signal transduction. They are composed of protofilaments of heterodimers of α-tubulin and β-tubulin organized as rigid hollow cylinders that can assemble into large and dynamic intracellular structures. Consistent with their involvement in core cellular processes, affecting microtubule assembly results in cytotoxicity and cell death. For these reasons, microtubules are among the most important targets for the therapeutic treatment of several diseases, including cancer. The vast literature related to microtubule stabilizers and destabilizers has been reviewed extensively in recent years. Here we summarize recent experimental and computational approaches for the identification of novel tubulin modulators and delivery strategies. These include orphan small molecules, PROTACs as well as light-sensitive compounds that can be activated with high spatio-temporal accuracy and that represent promising tools for precision-targeted chemotherapy.
The Role of Anti-EGFR Monoclonal Antibody in mCRC Maintenance Therapy
Authors: Yuan Meiqin , Wang Zeng , Lv Wangxia , Pan Hongming
Published: March 2022

Background: Epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) combined with chemotherapy in patients with RAS (rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer (mCRC) can alleviate and stabilize the disease, effectively prolong the progression-free survival (PFS) and overall survival (OS), and improve the overall response rate (ORR), which is the first-line treatment standard scheme for RAS wild-type mCRC currently. However, whether anti-EGFR mAb can be used for the maintenance treatment after the first-line treatment of mCRC remains controversial. We reviewed the recent studies on anti-EGFR mAb. The contents include five parts, introduction, anti-EGFR mAb in mCRC and its status in first-line therapy, establishment of the maintenance treatment pattern after the standard first-line treatment for mCRC, research progress of anti-EGFR mAb in mCRC maintenance therapy, and conclusion. More studies support the maintenance treatment of anti-EGFR mAb, but some researchers raise the problems about high cost and drug resistance. Despite lack of the maintenance evidence of anti-EGFR mAb, especially lack of large-scale phase III prospective clinical trials, with the emergence of new evidence and more accurate screening of treatment-dominant groups, maintenance therapy with anti-EGFR mAb monotherapy or anti-EGFR mAb combined with fluorouracil-based schemes after first-line chemotherapy combined with anti-EGFR mAb therapy might strive for more treatment opportunities, optimize treatment strategies and prolong treatment continuity, and finally, lead to more survival benefit for suitable patients.
Aberrant Volume-Wise and Voxel-Wise Concordance Among Dynamic Intrinsic Brain Activity Indices in Parkinson’s Disease: A Resting-State fMRI Study
Authors: Tian Yuan , Chen Hai-Bo , Ma Xin-Xin , Li Shu-Hua , Li Chun-Mei , Wu Shao-Hui , Liu Feng-Zhi , Du Yu , Li Kai , Su Wen
Published: March 2022

Researches using resting-state functional magnetic resonance imaging (rs-fMRI) have applied different regional measurements to study the intrinsic brain activity (IBA) of patients with Parkinson’s disease (PD). Most previous studies have only examined the static characteristics of IBA in patients with PD, neglecting the dynamic features. We sought to explore the concordance between the dynamics of different rs-fMRI regional indices. This study included 31 healthy controls (HCs) and 57 PD patients to calculate the volume-wise (across voxels) and voxel-wise (across periods) concordance using a sliding time window approach. This allowed us to compare the concordance of dynamic alterations in frequently used metrics such as degree centrality (DC), global signal connectivity (GSC), voxel-mirrored heterotopic connectivity (VMHC), the amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo). We analyzed the changes of concordance indices in the PD patients and investigated the relationship between aberrant concordance values and clinical/neuropsychological assessments in the PD patients. We found that, compared with the HCs, the PD patients had lower volume concordance in the whole brain and lower voxel-wise concordance in the posterior cerebellar lobe, cerebellar tonsils, superior temporal gyrus, and supplementary motor region. We also found negative correlations between these concordance alterations and patients’ age. The exploratory results contribute to a better understanding of IBA alterations and pathophysiological mechanisms in PD.
Inter-Individual Differences in Cognitive Tasks: Focusing on the Shaping of Decision-Making Strategies
Authors: Pittaras Elsa , Hamelin Héloïse , Granon Sylvie
Published: March 2022

In this paper, we review recent (published and novel) data showing inter-individual variation in decision-making strategies established by mice in a gambling task (MGT for Mouse Gambling Task). It may look intriguing, at first, that congenic animals develop divergent behaviors. However, using large groups of mice, we show that individualities emerge in the MGT, with about 30% of healthy mice displaying risk-averse choices while about 20-25% of mice make risk-prone choices. These strategies are accompanied by different brain network mobilization and individual levels of regional -prefrontal and striatal- monoamines. We further illustrate three ecological ways that influence drastically cognitive strategies in healthy adult mice: sleep deprivation, sucrose or artificial sweetener exposure, and regular exposure to stimulating environments. Questioning how to unmask individual strategies, what are their neural/neurochemical bases and whether we can shape or reshape them with different environmental manipulations is of great value, first to understand how the brain may build flexible decisions, and second to study behavioral plasticity, in healthy adult, as well as in developing brains. The latter may open new avenues for the identification of vulnerability traits to adverse events, before the emergence of mental pathologies.
Altered Structural Brain Network Topology in Patients With Primary Craniocervical Dystonia
Authors: Wang Xiu , Hu Wenhan , Wang Huimin , Gao Dongmei , Liu Yuye , Zhang Xin , Jiang Yin , Mo Jiajie , Meng Fangang , Zhang Kai , Zhang Jian-guo
Published: March 2022

Purpose

Regional cortical thickness or volume analyses based upon structural MRI scans have been employed to study the pathophysiology of primary craniocervical dystonia (CCD). In the present study, brain connectivity network analyses based upon morphological distribution similarities among different brain areas were used to study the network disruption in individuals affected by CCD.

Methods

The T1 MRI scans were completed for 37 patients with CCD and 30 healthy controls, with individual brain structural networks being constructed based upon gray matter (GM) similarities in 90 regions within the brain. Area under the curve (AUC) values for each network parameter were determined, and the GRETNA program was used to conduct a graph theory-based measurement of nodal and global network properties. These properties were then compared between healthy controls and those with CCD. In addition, relationships between nodal properties and the severity of clinical dystonia were assessed through Spearman's correlation analyses.

Results

Relative to individuals in the control group, patients with CCD exhibited decreased local nodal properties in the right globus pallidus, right middle frontal gyrus, and right superior temporal pole. The degree of centrality as well as the node efficiency of the right globus pallidus were found to be significantly correlated with ocular dystonic symptom. The node efficiency of right middle frontal gyrus was significantly related to the total motor severity. No nodal properties were significantly correlated with oral dystonic motor scores. Among CCD patients, the right hemisphere exhibited more widespread decreases in connectivity associated with the motor related brain areas, associative cortex, and limbic system, particularly in the middle frontal gyrus, globus pallidus, and cingulate gyrus.

Conclusions

The assessment of morphological correlations between different areas in the brain may represent a sensitive approach for detecting alterations in brain structures and to understand the mechanistic basis for CCD at the network level. Based on the nodal properties identified in this study, the right middle frontal gyrus and globus pallidus were the most severely affected in patients with CCD. The widespread alterations in morphological connectivity, such as the cortico-cortical and cortico-subcortical networks, further support the network mechanism as a basis for CCD.
A New Scoring System to Differentially Diagnose and Distinguish Tuberculous Meningitis and Bacterial Meningitis in South China
Authors: Wen An , Liu Shi-Min , Cao Wen-Feng , Zhou Yong-Liang , Luo Chao-Qun , Xiang Zheng-bing , Hu Fan , Zhang Ping , Leng Er-Ling
Published: March 2022

Background

Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China.

Methods

A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule.

Results

Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively.

Conclusion

The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.
The MMT of Elbow Flexion and the AFE Predict Impairment and Disability at 3 Weeks in Patients With Acute Stroke
Authors: Ueda Shujiro , Aoki Hiroko , Yasuda Yumiko , Nishiyama Ayumi , Hayashi Yusuke , Honaga Kaoru , Tanuma Akira , Takakura Tomokazu , Kurosu Akihiro , Hatori Kozo , Hayashi Akito , Fujiwara Toshiyuki
Published: March 2022

Objective

This study aimed to investigate whether upper extremity motor function assessment within 72 h from stroke onset can predict the functional outcomes of the upper extremity.

Design

This was a prospective, cohort study of patients with a first unilateral hemispheric stroke between May 2018 and March 2020. The motor arm item of the National Institutes of Health Stroke Scale, manual muscle testing of the elbow and forearm, and active finger extension scale were assessed within 72 h after stroke onset. The Fugl-Meyer assessment upper extremity motor score and action research arm test were assessed at discharge from the acute hospital. Multiple regression analysis was used to study predictors of upper extremity motor function at discharge from the acute hospital. The adjustment variables included age, sex, thumb localizing test, and visuospatial function.

Results

Sixty acute stroke patients were recruited. The model with the highest coefficient of determination for the Fugl-Meyer assessment upper extremity motor score at discharge was the elbow flexion model (R2= 0.76), followed by the active finger extension model (R2= 0.69). For the action research arm test, the highest model was the active finger extension model (R2= 0.64), followed by the elbow flexion model (R2= 0.63).

Conclusion

The manual muscle testing of elbow flexion and the active finger extension may be useful for predicting impairment and disability at 3 weeks in patients with acute stroke.
The Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cognition in Patients With Traumatic Brain Injury: A Protocol for a Randomized Controlled Trial
Authors: Zhang Han , Zhao Yu , Qu Yun , Huang Yunyun , Chen Zhu , Lan Hong , Peng Yi , Ren Hongying
Published: March 2022

Cognitive impairment, defined as a decline in memory and executive function, is one of the most severe complications of traumatic brain injury (TBI). Patients with TBI are often unable to return to work due to cognitive impairment and their overall quality of life is reduced. TBI can bring a serious economic burden to patient's families and to society. Reported findings on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving cognitive impairment following TBI are inconsistent. The purpose of the proposed study is to investigate whether rTMS can improve memory and executive function in patients with TBI. Herein, we propose a prospective randomized placebo-controlled (rTMS, sham rTMS, cognitive training), parallel-group, single-center trial. 36 participants with a TBI occurring at least 6 months prior will be recruited from an inpatient rehabilitation center. Participants will be randomly assigned to the real rTMS, sham rTMS, or cognitive training groups with a ratio of 1:1:1. A 20-session transcranial magnetic stimulation protocol will be applied to the left and right dorsolateral prefrontal cortices (DLPFC) at frequencies of 10 Hz and 1 Hz, respectively. Neuropsychological assessments will be performed at four time points: baseline, after the 10th rTMS session, after the 20th rTMS session, and 30 days post-intervention. The primary outcome is change in executive function assessed using the Shape Trail Test (STT). The secondary outcome measures are measures from neuropsychological tests: the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test (BVMT), the Digit Span Test (DST). We report on positive preliminary results in terms of improving memory and executive function as well as beneficial changes in brain connectivity among TBI patients undergoing rTMS and hypothesize that we will obtain similar results in the proposed study.
Requirements for Eliciting a Spastic Response With Passive Joint Movements and the Influence of Velocity on Response Patterns: An Experimental Study of Velocity-Response Relationships in Mild Spasticity With Repeated-Measures Analysis
Authors: Fujimura Kenta , Mukaino Masahiko , Itoh Shota , Miwa Haruna , Itoh Ryoka , Narukawa Daisuke , Tanikawa Hiroki , Kanada Yoshikiyo , Saitoh Eiichi , Otaka Yohei
Published: March 2022

Background

Spasticity is defined as a velocity-dependent increase in tonic stretch reflexes and is manually assessed in clinical practice. However, the best method for the clinical assessment of spasticity has not been objectively described. This study analyzed the clinical procedure to assess spasticity of the elbow joint using an electrogoniometer and investigated the appropriate velocity required to elicit a spastic response and the influence of velocity on the kinematic response pattern.

Methods

This study included eight healthy individuals and 15 patients with spasticity who scored 1 or 1+ on the modified Ashworth Scale (MAS). Examiners were instructed to manually assess spasticity twice at two different velocities (slow and fast velocity conditions). During the assessment, velocity, deceleration value, and angle [described as the % range of motion (%ROM)] at the moment of resistance were measured using an electrogoniometer. Differences between the slow and fast conditions were evaluated. In addition, variations among the fast condition such as the responses against passive elbow extension at <200, 200–300, 300–400, 400°/s velocities were compared between the MAS 1+, MAS 1, and control groups.

Results

Significant differences were observed in the angular deceleration value and %ROM in the fast velocity condition (417 ± 80°/s) between patients and healthy individuals, but there was no difference in the slow velocity condition (103 ± 29°/s). In addition, the deceleration values were significantly different between the MAS 1 and MAS 1+ groups in velocity conditions faster than 300°/s. In contrast, the value of %ROM plateaued when the velocity was faster than 200°/s.

Conclusion

The velocity of the passive motion had a significant effect on the response pattern of the elbow joint. The velocity-response pattern differed between deceleration and the angle at which the catch occurred; the value of deceleration value for passive motion was highly dependent on the velocity, while the %ROM was relatively stable above a certain velocity threshold. These results provide clues for accurate assessment of spasticity in clinical practice.
Structural Characteristics and Immunomodulatory Effects of a Long-Chain Polysaccharide From Laminaria japonica
Authors: Cui Jiamei , Wang Yunpeng , Kim Eunyoung , Zhang Chongyu , Zhang Guiguo , Lee Yunkyoung
Published: March 2022

Polysaccharides derived from Laminaria japonica (LJPS) have shown a variety of beneficial effects on improving human health; however, the structural features and bioactivities of long-chain LJPS remain unclear. This study aimed to investigate the structural characteristics and bioactivities of a novel long-chain LJPS. Results showed that the LJPS was composed of Fuc, Rha, Ara, Gal, Glc, Xyl, Man, Fru, Rib, GalA, GluA, GlcA, and ManA, with a molar ratio of 35.71:1.48:0.28:13.16:0.55:2.97:6.92:0.58:0.41:0.14:3.16:15.84:18.79. Of these, Fuc, Gal, Man, GlcA, and ManA were the predominant components with an accumulated proportion of 93.6%. The LJPS was found to consist of seven types of the monomer residues, and the main interchain glycosidic linkages were β -D-(1 → 2), α -D-(1 → 3), (1 → 4), and (1 → 6), and the molecular mass was 5.79 × 104 g/mol. Regarding the molecular conformation, LJPS was a multi-branched, long-chain macromolecule, and appeared in a denser crosslinking network with highly branched and helix domains in the terms of morphology. Additionally, the LJPS had no toxicity to mouse macrophage cells and exhibited biphasic immuno-modulating capacity. The present findings suggested that the long-chain LJPS might be an attractive candidate as an immunopotentiating and anti-inflammatory functional food, and this study also provides a feasible approach to decipher the structural characteristics and spatial conformations of plant-derived polysaccharides.
Causal Association Between Tea Consumption and Kidney Function: A Mendelian Randomization Study
Authors: Zhang Yangchang , Xiong Yang , Shen Shisi , Yang Jialu , Wang Wei , Wu Tingting , Chen Li , Yu Qiuhua , Zuo Hangjia , Wang Xu , Lei Xun
Published: March 2022

Background

Causal research concerning the consumption of tea and the risk of chronic kidney disease (CKD) is limited. This study identified the potential causal effects of tea intake on CKD, the estimated glomerular filtration rate (eGFR), and albuminuria.

Methods

Genome-wide association studies (GWASs) from UK Biobank were able to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea each day. The summary statistics for the kidney function from the CKDGen consortium include 11,765 participants (12,385 cases of CKD) and 54,116 participants for the urinary albumin-to-creatinine ratio who were mostly of European descent. A two-sample Mendelian randomization (MR) analysis was performed to test the relationship between the selected SNPs and the risk of CKD.

Results

A total of 2,672 SNPs associated with tea consumption (p < 5 × 10–8) were found, 45 of which were independent and usable in CKDGen. Drinking more cups of tea per day indicates a protective effect for CKD G3-G5 [odds ratio (OR) = 0.803; p = 0.004] and increases eGFR (β = 0.019 log ml/min/1.73 m2 per cup per day; p = 2.21 × 10–5). Excluding two SNPs responsible for directional heterogeneity (Cochran Q p = 0.02), a high consumption of tea was also negatively correlated with a lower risk of albuminuria (OR = 0.758; p = 0.002).

Conclusion

From the perspective of genes, causal relationships exist between daily extra cup of tea and the reduced risk of CKD and albuminuria and increased eGFR.