bluuebunny/crossref_metadata_2025 huggingface dataset:
Capecitabine Can Induce T Cell Apoptosis: A Potential Immunosuppressive Agent With Anti-Cancer Effect
Authors: Zhang Sai , Wang Zhenglu , Fan Shunli , Liu Tao , Yoshida Sei , Yang Shuang , Liu Lei , Hou Wen , Cao Lei , Wang Jianxi , Song Zhuolun , Li Shanni , Zhang Sirui , Wang Hao , Li Jianghong , Zheng Hong , Shen Zhongyang
Published: September 2021

Capecitabine (CAP) is now widely used in the comprehensive treatment of digestive system tumors. Some clinical observations have shown that CAP may have immunosuppressive effects, but there is still a lack of clear experimental verification. In this study, different doses of CAP were administered to normal mice by gavage. Our results confirmed that CAP did not cause myelosuppression in bone marrow tissue; CAP selectively reduced the proportion of T cells and the concentration of related pro-inflammatory cytokines, while it increased the concentration of anti-inflammatory cytokines. Thymidylate phosphorylase (TP) is the key enzyme for the transformation of CAP in vivo; this study confirmed that T cells express TP, but the bone marrow tissue lacks TP expression, which explains the selectivity in pharmacodynamic effects of CAP. In addition, it was confirmed that CAP can induce T cell apoptosis in vivo and in vitro. In vitro experiments showed that CAP-induced T cell apoptosis was related to TP expression, endoplasmic reticulum stress (ERS) induction, reactive oxygen species (ROS) production, and mitochondria-mediated apoptosis activation. Therefore, this study confirmed that the differential expression of TP in cells and tissues explains why CAP avoids the toxic effects of myelosuppression while inducing T cell apoptosis to exert the immunosuppressive effect. Therefore, CAP may become an immunosuppressive agent with a simultaneous anti-cancer effect, which is worthy of further studies.
Quantifying Patterns in Fish Assemblages and Habitat Use Along a Deep Submarine Canyon-Valley Feature Using a Remotely Operated Vehicle
Authors: Saunders Benjamin J. , Galaiduk Ronen , Inostroza Karina , Myers Elisabeth M. V. , Goetze Jordan S. , Westera Mark , Twomey Luke , McCorry Denise , Harvey Euan S.
Published: September 2021

The aim of this study was to document the composition and distribution of deep-water fishes associated with a submarine canyon-valley feature. A work-class Remotely Operated Vehicle (ROV) fitted with stereo-video cameras was used to record fish abundance and assemblage composition along transects at water depths between 300 and 900 metres. Three areas (A, B, C) were sampled along a submarine canyon-valley feature on the continental slope of tropical north-western Australia. Water conductivity/salinity, temperature, and depth were also collected using an ROV mounted Conductivity Temperature and Depth (CTD) instrument. Multivariate analyses were used to investigate fish assemblage composition, and species distribution models were fitted using boosted regression trees. These models were used to generate predictive maps of the occurrence of four abundant taxa over the survey areas. CTD data identified three water masses, tropical surface water, South Indian Central Water (centred ∼200 m depth), and a lower salinity Antarctic Intermediate Water (AAIW) ∼550 m depth. Distinct fish assemblages were found among areas and between canyon-valley and non-canyon habitats. The canyon-valley habitats supported more fish and taxa than non-canyon habitats. The fish assemblages of the deeper location (∼700–900 m, Area A) were different to that of the shallower locations (∼400–700 m, Areas B and C). Deep-water habitats were characterised by a Paraliparis (snail fish) species, while shallower habitats were characterised by the family Macrouridae (rat tails). Species distribution models highlighted the fine-scale environmental niche associations of the four most abundant taxa. The survey area had a high diversity of fish taxa and was dominated by the family Macrouridae. The deepest habitat had a different fish fauna to the shallower areas. This faunal break can be attributed to the influence of AAIW. ROVs provide a platform on which multiple instruments can be mounted and complementary streams of data collected simultaneously. By surveying fish in situ along transects of defined dimensions it is possible to produce species distribution models that will facilitate a greater insight into the ecology of deep-water marine systems.
Investigations Exploring the Use of an Unstructured-Grid, Finite-Volume Modelling Approach to Simulate Coastal Circulation in Remote Island Settings—Case Study Region, Vanuatu/New Caledonia
Authors: Lee Serena Blyth , Zhang Fan , Lemckert Charles James , Tomlinson Rodger
Published: September 2021

Understanding coastal circulation and how it may alter in the future is important in island settings, especially in the South West Pacific, where communities rely heavily upon marine resources, and where sea level rise (SLR) is higher than the global average. In this study we explore the use of an unstructured-mesh finite-volume modelling approach to assist in filling the knowledge gaps with respect to coastal circulation in remote island locations—selecting the Vanuatu and New Caledonia archipelagos as our example study site. Past limited observations and modelling studies are leveraged to construct and verify a regional/coastal ocean model based on the Finite-Volume Community Ocean Model (FVCOM). Following verification with respect to tidal behaviour, we investigate how changes in wind speed and direction, and SLR, alter coastal water levels and coastal currents. Results showed tidal residual circulation was typically associated with flow separation at headlands and islands. Trade winds had negligible effect on water levels at the coast, however, wind-residual circulation was sensitive to both wind speed and direction. Wind-residual currents were typically strongest close to coastlines. Wind residual circulation patterns were strongly influenced by Ekman flow, while island blocking, topographic steering and geostrophic currents also appear to influence current patterns. Tidal amplitudes and phases were unchanged due to SLR of up to 2 m, while maximum current speeds altered by as much as 20 cm/s within some coastal embayments. Non-linear relationships between SLR and maximum current speeds were seen at some coastal reef platform sites. Under higher sea levels, tidal residual currents altered by less than ±2 cm/s which is relatively significant given maximum tidal residual current speeds are typically below 10 cm/s. Our findings indicate that under higher sea levels, coastal processes governing sediment transport, pollutant dispersal and larval transport are likely to alter, which may have implications for coastal environments and ecosystems. Given winds influence coastal circulation and subsequent coastal processes, changes in trade winds due to climate change may act to further alter coastal processes. It is felt that the current modelling approach can be applied to other regions to help fill critical knowledge gaps.
Staphylococcus aureus Strain-Dependent Biofilm Formation in Bone-Like Environment
Authors: Lamret Fabien , Varin-Simon Jennifer , Velard Frédéric , Terryn Christine , Mongaret Céline , Colin Marius , Gangloff Sophie C. , Reffuveille Fany
Published: September 2021

Staphylococcus aureus species is an important threat for hospital healthcare because of frequent colonization of indwelling medical devices such as bone and joint prostheses through biofilm formations, leading to therapeutic failure. Furthermore, bacteria within biofilm are less sensitive to the host immune system responses and to potential antibiotic treatments. We suggested that the periprosthetic bone environment is stressful for bacteria, influencing biofilm development. To provide insights into S. aureus biofilm properties of three strains [including one methicillin-resistant S. aureus (MRSA)] under this specific environment, we assessed several parameters related to bone conditions and expected to affect biofilm characteristics. We reported that the three strains harbored different behaviors in response to the lack of oxygen, casamino acids and glucose starvation, and high concentration of magnesium. Each strain presented different biofilm biomass and live adherent cells proportion, or matrix production and composition. However, the three strains shared common responses in a bone-like environment: a similar production of extracellular DNA and engagement of the SOS response. This study is a step toward a better understanding of periprosthetic joint infections and highlights targets, which could be common among S. aureus strains and for future antibiofilm strategies.
Taxonomy and SSU rDNA-Based Phylogeny of Two Heterotrich Ciliates (Ciliophora, Heterotrichea) Collected From Subtropical Wetlands of China, Including the Description of a New Species, Linostomella pseudovorticella n. sp.
Authors: Jin Didi , Zhao Xuetong , Ye Tingting , Huang Jie , Warren Alan , Al-Farraj Saleh A. , Chen Xiangrui
Published: September 2021

The Heterotrichea Stein, 1859 are a group of ciliated protists (single-celled eukaryotes) that occur in a wide variety of aquatic habitat where they play important roles in the flow of nutrients and energy within the microbial food web. Many species are model organisms for research in cytology and regenerative biology. In the present study, the morphology and phylogeny of two heterotrich ciliates, namely, Linostomella pseudovorticella n. sp. and Peritromus kahli Villeneuve-Brachon, 1940, collected from subtropical wetlands of China, were investigated using morphological and molecular methods. L. pseudovorticella n. sp. differs from its only known congener, Linostomella vorticella Ehrenberg, 1833 Aescht in Foissner et al., 1999, by having more ciliary rows (48–67, mean about 56 vs. 26–51, mean about 42) and its small-subunit (SSU) rDNA sequence, which shows a 15-bp divergence. Although P. kahli has been reported several times in recent decades, its infraciliature has yet to be described. A redescription and improved diagnosis of this species based on a combination of previous and present data are here supplied. Phylogenetic analyses based on SSU rDNA sequences revealed that the genus Linostomella is positioned within Condylostomatidae, and Peritromidae is sister to Climacostomidae with relatively low support, and the family Spirostomidae is the root branch of the class Heterotrichea.
Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice
Authors: Alamri Sawsan S. , Alluhaybi Khalid A. , Alhabbab Rowa Y. , Basabrain Mohammad , Algaissi Abdullah , Almahboub Sarah , Alfaleh Mohamed A. , Abujamel Turki S. , Abdulaal Wesam H. , ElAssouli M-Zaki , Alharbi Rahaf H. , Hassanain Mazen , Hashem Anwar M.
Published: September 2021

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. The spike (S) glycoprotein of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) is a major immunogenic and protective protein and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2, denoted VIU-1005. The design was based on a codon-optimized coding sequence of a consensus full-length S glycoprotein. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models 4 weeks after three injections with 100 μg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Such immunization induced long-lasting IgG and memory T cell responses in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower or fewer doses were able to elicit significantly high levels of Th1-biased systemic S-specific immune responses, as demonstrated by the significant levels of binding IgG antibodies, nAbs and IFN-γ, TNF and IL-2 cytokine production from memory CD8+ and CD4+ T cells in BALB/c mice. Furthermore, compared to intradermal needle injection, which failed to induce any significant immune response, intradermal needle-free immunization elicited a robust Th1-biased humoral response similar to that observed with intramuscular immunization. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting Th1-skewed humoral and cellular immunity in mice. Furthermore, we show that the use of a needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.
A New Subfamily of Glycoside Hydrolase Family 30 with Strict Xylobiohydrolase Function
Authors: Crooks Casey , Bechle Nathan J. , St John Franz J.
Published: September 2021

The Acetivibrioclariflavus (basonym: Clostridium clariflavum) glycoside hydrolase family 30 cellulosomal protein encoded by the Clocl_1795 gene was highly represented during growth on cellulosic substrates. In this report, the recombinantly expressed protein has been characterized and shown to be a non-reducing terminal (NRT)-specific xylobiohydrolase (AcXbh30A). Biochemical function, optimal biophysical parameters, and phylogeny were investigated. The findings indicate that AcXbh30A strictly cleaves xylobiose from the NRT up until an α-1,2-linked glucuronic acid (GA)-decorated xylose if the number of xyloses is even or otherwise a single xylose will remain resulting in a penultimate GA-substituted xylose. Unlike recently reported xylobiohydrolases, AcXbh30A has no other detectable hydrolysis products under our optimized reaction conditions. Sequence analysis indicates that AcXbh30A represents a new GH30 subfamily. This new xylobiohydrolase may be useful for commercial production of industrial quantities of xylobiose.
Expression of IL-20 Receptor Subunit β Is Linked to EAE Neuropathology and CNS Neuroinflammation
Authors: Dayton Jacquelyn R. , Yuan Yinyu , Pacumio Lisa P. , Dorflinger Bryce G. , Yoo Samantha C. , Olson Mariah J. , Hernández-Suárez Sara I. , McMahon Moira M. , Cruz-Orengo Lillian
Published: September 2021

Considerable clinical evidence supports that increased blood–brain barrier (BBB) permeability is linked to immune extravasation of CNS parenchyma during neuroinflammation. Although BBB permeability and immune extravasation are known to be provoked by vascular endothelial growth factor-A (i.e., VEGF-A) and C-X-C motif chemokine ligand 12 (CXCL12), respectively, the mechanisms that link both processes are still elusive. The interleukin-20 (i.e., IL-20) cytokine signaling pathway was previously implicated in VEGF-mediated angiogenesis and is known to induce cellular response by way of signaling through IL-20 receptor subunit β (i.e., IL-20RB). Dysregulated IL-20 signaling is implicated in many inflammatory pathologies, but it’s contribution to neuroinflammation has yet to be reported. We hypothesize that the IL-20 cytokine, and the IL cytokine subfamily more broadly, play a key role in CNS neuroinflammation by signaling through IL-20RB, induce VEGF activity, and enhance both BBB-permeability and CXCL12-mediated immune extravasation. To address this hypothesis, we actively immunizedIL-20RB–/–mice and wild-type mice to induce experimental autoimmune encephalomyelitis (EAE) and found thatIL-20RB–/–mice showed amelioration of disease progression compared to wild-type mice. Similarly, we passively immunizedIL-20RB–/–mice and wild-type mice with myelin-reactive Th1 cells from eitherIL-20RB–/–and wild-type genotype. HostIL-20RB–/–mice showed lesser disease progression than wild-type mice, regardless of the myelin-reactive Th1 cells genotype. Using multianalyte bead-based immunoassay and ELISA, we found distinctive changes in levels of pro-inflammatory cytokines betweenIL-20RB–/–mice and wild-type mice at peak of EAE. We also found detectable levels of all cytokines of the IL-20 subfamily within CNS tissues and specific alteration to IL-20 subfamily cytokines IL-19, IL-20, and IL-24, expression levels. Immunolabeling of CNS region-specific microvessels confirmed IL-20RB protein at the spinal cord microvasculature and upregulation during EAE. Microvessels isolated from macaques CNS tissues also expressed IL-20RB. Moreover, we identified the expression of all IL-20 receptor subunits: IL-22 receptor subunit α-1 (IL-22RA1), IL-20RB, and IL-20 receptor subunit α (IL-20RA) in human CNS microvessels. Notably, human cerebral microvasculature endothelial cells (HCMEC/D3) treated with IL-1β showed augmented expression of the IL-20 receptor. Lastly, IL-20-treated HCMEC/D3 showed alterations on CXCL12 apicobasal polarity consistent with a neuroinflammatory status. This evidence suggests that IL-20 subfamily cytokines may signal at the BBBviaIL-20RB, triggering neuroinflammation.
Early Intervention via Stimulation of the Medial Septal Nucleus Improves Cognition and Alters Markers of Epileptogenesis in Pilocarpine-Induced Epilepsy
Authors: Izadi Ali , Schedlbauer Amber , Ondek Katelynn , Disse Gregory , Ekstrom Arne D. , Cowen Stephen L. , Shahlaie Kiarash , Gurkoff Gene G.
Published: September 2021

Over one-third of patients with temporal lobe epilepsy are refractory to medication. In addition, anti-epileptic drugs often exacerbate cognitive comorbidities. Neuromodulation is an FDA treatment for refractory epilepsy, but patients often wait >20 years for a surgical referral for resection or neuromodulation. Using a rodent model, we test the hypothesis that 2 weeks of theta stimulation of the medial septum acutely following exposure to pilocarpine will alter the course of epileptogenesis resulting in persistent behavioral improvements. Electrodes were implanted in the medial septum, dorsal and ventral hippocampus, and the pre-frontal cortex of pilocarpine-treated rats. Rats received 30 min/day of 7.7 Hz or theta burst frequency on days 4–16 post-pilocarpine, prior to the development of spontaneous seizures. Seizure threshold, spikes, and oscillatory activity, as well as spatial and object-based learning, were assessed in the weeks following stimulation. Non-stimulated pilocarpine animals exhibited significantly decreased seizure threshold, increased spikes, and cognitive impairments as compared to vehicle controls. Furthermore, decreased ventral hippocampal power (6–10 Hz) correlated with both the development of spikes and impaired cognition. Measures of spikes, seizure threshold, and cognitive performance in both acute 7.7 Hz and theta burst stimulated animals were statistically similar to vehicle controls when tested during the chronic phase of epilepsy, weeks after stimulation was terminated. These data indicate that modulation of the septohippocampal circuit early after pilocarpine treatment alters the progression of epileptic activity, resulting in elevated seizure thresholds, fewer spikes, and improved cognitive outcome. Results from this study support that septal theta stimulation has the potential to serve in combination or as an alternative to high frequency thalamic stimulation in refractory cases and that further research into early intervention is critical.
Information Bottleneck as Optimisation Method for SSVEP-Based BCI
Authors: Ingel Anti , Vicente Raul
Published: September 2021

In this study, the information bottleneck method is proposed as an optimisation method for steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI). The information bottleneck is an information-theoretic optimisation method for solving problems with a trade-off between preserving meaningful information and compression. Its main practical application in machine learning is in representation learning or feature extraction. In this study, we use the information bottleneck to find optimal classification rule for a BCI. This is a novel application for the information bottleneck. This approach is particularly suitable for BCIs since the information bottleneck optimises the amount of information transferred by the BCI. Steady-state visual evoked potential-based BCIs often classify targets using very simple rules like choosing the class corresponding to the largest feature value. We call this classifier the arg max classifier. It is unlikely that this approach is optimal, and in this study, we propose a classification method specifically designed to optimise the performance measure of BCIs. This approach gives an advantage over standard machine learning methods, which aim to optimise different measures. The performance of the proposed algorithm is tested on two publicly available datasets in offline experiments. We use the standard power spectral density analysis (PSDA) and canonical correlation analysis (CCA) feature extraction methods on one dataset and show that the current approach outperforms most of the related studies on this dataset. On the second dataset, we use the task-related component analysis (TRCA) method and demonstrate that the proposed method outperforms the standard argmax classification rule in terms of information transfer rate when using a small number of classes. To our knowledge, this is the first time the information bottleneck is used in the context of SSVEP-based BCIs. The approach is unique in the sense that optimisation is done over the space of classification functions. It potentially improves the performance of BCIs and makes it easier to calibrate the system for different subjects.
Characterizing the Retinal Phenotype of the Thy1-h[A30P]α-syn Mouse Model of Parkinson’s Disease
Authors: Veys Lien , Devroye Joyce , Lefevere Evy , Cools Lien , Vandenabeele Marjan , De Groef Lies
Published: September 2021

Despite decades of research, disease-modifying treatments of Parkinson’s disease (PD), the second most common neurodegenerative disease worldwide, remain out of reach. One of the reasons for this treatment gap is the incomplete understanding of how misfolded alpha-synuclein (α-syn) contributes to PD pathology. The retina, as an integral part of the central nervous system, recapitulates the PD disease processes that are typically seen in the brain, and retinal manifestations have emerged as prodromal symptoms of the disease. The timeline of PD manifestations in the visual system, however, is not fully elucidated and the underlying mechanisms are obscure. This highlights the need for new studies investigating retinal pathology, in order to propel its use as PD biomarker, and to develop validated research models to investigate PD pathogenesis. The present study pioneers in characterizing the retina of the Thy1-h[A30P]α-syn PD transgenic mouse model. We demonstrate widespread α-syn accumulation in the inner retina of these mice, of which a proportion is phosphorylated yet not aggregated. This α-syn expression coincides with inner retinal atrophy due to postsynaptic degeneration. We also reveal abnormal retinal electrophysiological responses. Absence of selective loss of melanopsin retinal ganglion cells or dopaminergic amacrine cells and inflammation indicates that the retinal manifestations in these transgenic mice diverge from their brain phenotype, and questions the specific cellular or molecular alterations that underlie retinal pathology in this PD mouse model. Nevertheless, the observed α-syn accumulation, synapse loss and functional deficits suggest that the Thy1-h[A30P]α-syn retina mimics some of the features of prodromal PD, and thus may provide a window to monitor and study the preclinical/prodromal stages of PD, PD-associated retinal disease processes, as well as aid in retinal biomarker discovery and validation.
Optimized Extraction and Characterization of Folates From Date Palm Fruits and Their Tracking During Fruits Wine Fermentation
Authors: Meng Ziyi , Yi Ling , Hu Qingxin , Lin Zhiyi , Ramaswamy Hosahalli S. , Wang Chao
Published: September 2021

Folates belong to the essential B vitamins group and participate in one-carbon metabolism. Date palm fruits (Phoenix dactilyfera L. family Arecaceae) are consumed by millions of people and are good sources of folates. To date, no detailed study has been carried out on suitable methods for folate extraction from date palm fruits. In the present study, an experimental design using response surface methodology (RSM) was used to maximize the extraction yield of folates from date palm fruits by including enzymatic depectinization. By applying this new strategy and a UHPLC-MS/MS technique for analysis, total folate and different folate vitamers of three cultivars of date palm fruits (Muzafti, Zahdi, and Rubai), brewer's yeast, and fermented date wine were analyzed. The optimized extraction conditions of folates from date palm fruits were found to be a pectinase activity of 47.7 U, an incubation temperature of 40°C, and an incubation time of 38 min, which yielded a total folate content of 191–301 μg/100 g. In brewer's yeast, the extracted total folate content was very high (4,870 μg/100 g), and, in the resulting date wine, it reached a maximum of 700 μg/L on the fifth day. The predominant folate vitamers in date fruit and fruit wine were 5-formyltetrahydrofolate (5-CHO-THF) and 5-methyltetrahydrofolate (5-CH3-THF). During date palm fruit fermentation for up to 8 days, the 5-CHO-THF content gradually decreased by 20%, while 5-CH3-THF increased linearly from day 1 to day 5 (y = 0.058 x + 0.0284, R2 = 0.9614). This study shows that date palm fruit and fruit wine are excellent sources of folate, and further study can be focused on different methods to improve folate stability during wine storage.
Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
Authors: Lu Xiuqin , Li Chuanyu , Xu Wenhao , Wu Yuanyuan , Wang Jian , Chen Shuxian , Zhang Hailiang , Huang Huadong , Huang Haineng , Liu Wangrui
Published: September 2021

The tumor microenvironment (TME) contributes to the initiation and progression of many neoplasms. However, the impact of low-grade glioma (LGG) purity on carcinogenesis remains to be elucidated. We selected 509 LGG patients with available genomic and clinical information from the TCGA database. The percentage of tumor infiltrating immune cells and the tumor purity of LGG were evaluated using the ESTIMATE and CIBERSORT algorithms. Stromal-related genes were screened through Cox regression, and protein-protein interaction analyses and survival-related genes were selected in 487 LGG patients from GEO database. Hub genes involved in LGG purity were then identified and functionally annotated using bioinformatics analyses. Prognostic implications were validated in 100 patients from an Asian real-world cohort. Elevated tumor purity burden, immune scores, and stromal scores were significantly associated with poor outcomes and increased grade in LGG patients from the TCGA cohort. In addition,CD3Ewas selected with the most significant prognostic value (Hazard Ratio=1.552,P<0.001). Differentially expressed genes screened according toCD3Eexpression were mainly involved in stromal related activities. Additionally, significantly increasedCD3Eexpression was found in 100 LGG samples from the validation cohort compared with adjacent normal brain tissues. HighCD3Eexpression could serve as an independent prognostic indicator for survival of LGG patients and promotes malignant cellular biological behaviors of LGG. In conclusion, tumor purity has a considerable impact on the clinical, genomic, and biological status of LGG.CD3E, the gene for novel membrane immune biomarker deeply affecting tumor purity, may help to evaluate the prognosis and develop individual immunotherapy strategies for LGG patients. Evaluating the ratio of differential tumor purity andCD3Eexpression levels may provide novel insights into the complex structure of the LGG microenvironment and targeted drug development.
The Significance of MET Expression and Strategies of Targeting MET Treatment in Advanced Gastric Cancer
Authors: Liao Haiyan , Tian Tiantian , Sheng Yuling , Peng Zhi , Li Zhongwu , Wang Jingyuan , Li Yanyan , Zhang Cheng , Gao Jing
Published: September 2021

Background

Accurate assessment of predictive biomarker expression is critical in patient selection in clinical trials or clinical practice. However, changes in biomarker expression may occur after treatment. The aim of the present study was to evaluate the effects of chemotherapy on MET expression in gastric cancer (GC).

Methods

MET expression was examined immunohistochemically before and after treatment in 122 patients with unresectable or recurrent GC, and was evaluated according to H-score or the scoring criteria used in the MetMAb trial. MET gene amplification was assessed by chromogenic in situ hybridization (CISH). The antitumor effect of MET targeted therapy was investigated in human gastric cancer cells in vitro and in vivo, and the underlying molecular mechanisms were analyzed by western blot.

Results

MET expression was associated with Lauren classification as well as tumor differentiation by either scoring system. MET amplification was not associated with clinical characteristics. Of the 71 patients who had paired pre- and post-treatment tumor tissues, 28 patients (39%) were initially positive for MET expression, and 43 (61%) were negative. Twenty-five patients (35%) showed significant changes in MET expression after treatment (P=0.007). Additionally, there was a concomitant overexpression of MET and HER2 in a subset of GC patients. MET inhibitor volitinib could significantly inhibit cell proliferation and xenograft growth in vitro and in vivo in MKN45 cells with MET and phosphorylated MET (pMET) high expressions via suppressing downstream PI3K/Akt and MAPK signaling pathways. Furthermore, combination therapy targeting both MET and HER2 demonstrated a synergistic antitumor activity.

Conclusions

MET expression is altered post chemotherapy and MET status should be evaluated in real-time. Both MET and pMET expressions might need to be considered for patients suitable for volitinib treatment.
Perspective of Human Condensins Involved in Colorectal Cancer
Authors: Wang Hongzhen , Chen Yao , Yang Dawei , Ma Liang
Published: September 2021

Although many important roles are played by human condesins in condensation and segregation of mitotic chromosomes, what roles of human condensins play in colorectal cancer are still unclear at present. Recently, abnormal expressions of all eight subunits of human condensins have been found in colorectal cancer and they are expected to become potential biomarkers and therapeutic targets for colorectal cancer in the future. However, there are still no reviews on the significance of abnormal expression of human condensin subunits and colorectal cancer until now. Based on a brief introduction to the discovery and composition of human condensins, the review summarized all abnormally expressed human subunits found in colorectal cancer based on publicly published papers. Moreover, Perspective of application on abnormally expressed human subunits in colorectal cancer is further reviewed.
Comparison of Rifabutin-Based Versus Rifampin-Based Regimens for the Treatment of Mycobacterium avium Complex: A meta-Analysis Study
Authors: Hajikhani Bahareh , Nasiri Mohammad Javad , Adkinson Brian C. , Azimi Taher , Khalili Farima , Goudarzi Mehdi , Dadashi Masoud , Murthi Mukunthan , Mirsaeidi Mehdi
Published: September 2021

Background: The incidence of Mycobacterium avium complex (MAC) increases as immunosuppressed conditions become more common. MAC's standard treatment regimen includes a macrolide, ethambutol, and a rifamycin, among which rifampin and rifabutin are the most commonly used. Although current guidelines recommend initial therapy for MAC with rifampin, it has been theorized to be less efficacious than rifabutin.

Methods: We reviewed the relevant scientific literature published up to February 18, 2020. Statistical analyses were performed with Comprehensive Meta-Analysis Software Version 2.0 (Biostat, Englewood, NJ). The pooled frequency with 95% confidence intervals (CI) was assessed using a random-effect model. We considered P <0.05 as statistically significant for publication bias.

Results: After reviewing 3665 records, we identified 24 studies that satisfied the inclusion criteria. Among these studies, 8 had rifabutin in their regimens (rifabutin group) and 16 had rifampin in their regimens (rifampin group). The estimated pooled treatment success rate was found to be 54.7% (95% CI 41.0-67.0%) in rifabutin groups and 67.5% (95% CI 55.7-77.4%) in rifampin groups. There was no evidence of publication bias among the included studies (Egger’s test p-value was 0.7).

Conclusion: In this study, it was shown that in comparison to Rifabutin, rifampin has similar treatment success rates in treating MAC. In order to determine the exact preference of each of these drugs, double-blind clinical trial studies are recommended.
The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews
Authors: Pyrgidis Nikolaos , Mykoniatis Ioannis , Haidich Anna-Bettina , Tirta Maria , Talimtzi Persefoni , Kalyvianakis Dimitrios , Ouranidis Andreas , Hatzichristou Dimitrios
Published: September 2021

Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic.

Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews.

Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups.

Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: −0.8, 95% CI: −1.65-0.06).

Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile.

Systematic Review Registration: PROSPERO, identifier [CRD42020216754].
Identification of VCAN as Hub Gene for Diabetic Kidney Disease Immune Injury Using Integrated Bioinformatics Analysis
Authors: Xu Qiannan , Li Binjue , Wang Yucheng , Wang Cuili , Feng Shi , Xue Lu , Chen Jianghua , Jiang Hong
Published: September 2021

Background: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China. Tubular injury contributes to the progression of DKD. Our study was conducted to explore the differential gene expression profiles between kidneys from patients with DKD and kidney living donors (LDs).

Methods: In total, seven DKD and eighteen LD gene expression profiles from the GSE104954 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed in R with the limma package. DEGs were uploaded to the g:Profiler online database to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Ingenuity pathway analysis (IPA) was carried out using online IPA software. Weighted gene co-expression network analysis (WGCNA) was performed using the WGCNA R package. By integrating DEGs and genes from the top 1 phenotype-gene associated module, we determined the hub gene. We next tested the hub gene, VCAN, in the GSE30122 dataset. We also validated the versican levels in human kidney tissues, explored immune cell type enrichment using an online database xCell, and investigated the correlation between cell types and VCAN expression.

Results: A total of 563 DEGs was identified. A large number of pathways were involved in the immune response process according to the results of GO, KEGG, and IPA. Using WGCNA, we selected the lightcyan module in which genes showed the strongest correlation with the phenotype and smallest P-value. We also identified VCAN as a hub gene by integrating DEG analysis and WGCNA. Versican expression was upregulated in human diabetic kidney tissue. Moreover, versican was speculated to play a role in immune injury according to the enrichment of functions and signaling pathways. VCAN transcript levels correlate with the assembly of immune cells in the kidney.

Conclusion: Immune processes played an essential role in DKD tubulointerstitium injury. The hub gene VCAN contributed to this process.
Dynamic Development of White Lupin Rootlets Along a Cluster Root
Authors: Le Thanh Tamara , Hufnagel Bárbara , Soriano Alexandre , Divol Fanchon , Brottier Laurent , Casset Célia , Péret Benjamin , Doumas Patrick , Marquès Laurence
Published: September 2021

White lupin produces cluster roots in response to phosphorus deficiency. Along the cluster root, numerous short rootlets successively appear, creating a spatial and temporal gradient of developmental stages that constitutes a powerful biological model to study the dynamics of the structural and functional evolution of these organs. The present study proposes a fine histochemical, transcriptomic and functional analysis of the rootlet development from its emergence to its final length. Between these two stages, the tissue structures of the rootlets were observed, the course of transcript expressions for the genes differentially expressed was monitored and some physiological events linked to Pi nutrition were followed. A switch between (i) a growing phase, in which a normal apical meristem is present and (ii) a specialized phase for nutrition, in which the rootlet is completely differentiated, was highlighted. In the final stage of its determinate growth, the rootlet is an organ with a very active metabolism, especially for the solubilization and absorption of several nutrients. This work discusses how the transition between a growing to a determinate state in response to nutritional stresses is found in other species and underlines the fundamental dilemma of roots between soil exploration and soil exploitation.
Systematic Review of Efficacy of Interventions for Social Isolation of Older Adults
Authors: Tong Feng , Yu ChengLin , Wang LinSen , Chi Iris , Fu Fang
Published: September 2021

Background: The social isolation of older people is a growing public health concern. The proportion of older people in society has increased in recent decades, and it is estimated that ~40% of the population will be aged 50 or above within the next few decades. This systematic review aims to summarize and renew knowledge of the effectiveness of existing interventions for alleviating social isolation of older adults.

Methods: Relevant electronic databases, including Cochrane Library, CINAHL, SCOPUS, and Web of Science, were searched by a systematic evaluation method. Eligible randomized controlled trial (RCT) studies were published between 1978 and 2021 in English or Chinese. The primary and secondary outcomes were social isolation and loneliness. The quality of the included RCTs was scored by the Cochrane risk-of-bias tool to assess their quality. Two independent reviewers extracted data, using a standardized form. Narrative synthesis and vote-counting methods were used to summarize and interpret study data.

Results: Twenty-four RCTs were finally included in this review. There was evidence of substantial heterogeneity in the interventions delivered. The overall quality of included studies indicated a low-to-medium risk of bias. Eighteen of 24 RCTs showed at least one dimension effect on reducing social isolation. The interventions with accurate targeting of clients in social and public places had more obvious effect. The interventions in which older people are active participants also appeared more likely to be effective. In addition, group intervention activities and individual intervention interviews were effective in improving structural social support; mixed intervention, and group intervention on training support significantly improved functional social support.

Conclusions: This study suggests that group and mixed intervention targeting of older adults could be helpful for alleviating social isolation problems. The use of modern technology for remote services could also present good results. More well-conducted RCTs of the effectiveness of social interventions for alleviating social isolation are needed to improve the evidence base. Especially as the debating results of remote interventions, further research in this field should be conducted.
Fear of COVID 19 Infection Across Different Cohorts: A Scoping Review
Authors: Quadros Shalini , Garg Shalini , Ranjan Rupesh , Vijayasarathi Guruprasad , Mamun Mohammed A.
Published: September 2021

Background: Psychological stressors like panic, fear, phobia, etc., are being substantially reported during the COVID-19 outbreak. In the prior outbreaks, fear of being infected was reported as the prominent suicide stressor. Therefore, fear of infection has become a concern in the context of the COVID-19 pandemic because it worsens emotion, cognition, and behavioral responses. Understanding the extent of fear of COVID-19 infection in various cohorts would aid in gauging the mental health services, which was a remedy in the present review.

Methods: Adhering to Arksey and O'Malley's framework for conducting a scoping review, a systematic search was performed in the month of September 2020 in several databases, including Scopus, PubMed, Web of Science, etc. Considering the inclusion criteria, a total of 14 articles were included in the present review.

Results: All of the included studies were conducted via online platforms, whereas all but one of the studies were cross-sectional in nature (including a mixed-method study, and a comparative study). Most of the studies were conducted among the general population (n = 12), within March and May 2020 (n = 9), from Asian countries (n = 7), and considered a self-developed item for fear of COVID-19 assessment (n = 8; whereas the Fear of COVID-19 Scale was used in 6-studies). The prevalence of fear of COVID-19 was reported to be 18.1–45.2%, although no cutoff point or criteria was mentioned for such a prevalence estimation of the Fear of COVID-19 Scale. However, females, younger adults, urban residents, divorcees, healthcare workers, those in quarantine settings, those in suspicion of being infected, and those with mental health problems, etc., were found to be at an increased risk of COVID-19 fear.

Conclusions: Being one of the first reviews in this context, the findings are anticipated to be helpful to predict the possible solutions for reducing fear of COVID-19 and facilitate further studies on strategies of how to alleviate such a stressful situation.
Sedentary Behavior and Associated Factors Among Working Adults in Eastern Ethiopia
Authors: Motuma Aboma , Gobena Tesfaye , Roba Kedir Teji , Berhane Yemane , Worku Alemayehu
Published: September 2021

Background:Sedentary behavior is a major risk factor for non-communicable diseases. Due to changes in lifestyle, sedentary behavior is increasing in sub-Saharan Africa. However, information on the extent of sedentarism among various segments of the population is scant in low-income countries. The objective of this study was to assess the extent of high sedentary behavior and associated factors among working adults in eastern Ethiopia.

Methods:A crosssectional study was conducted among 1,164 working adults at Haramaya University from December 2018 to February 2019. Data were collected through face-to-face interviews using the WHO STEPS and sedentary behavior questionnaire. All reported sedentary activities were added to calculate the total number of hours spent on sedentary behavior, which was then dichotomized into two categories. Those who had ≥8 sedentary hours per day were categorized as having high sedentary behavior. The prevalence ratio (PR) with 95% confidence intervals (CIs) was calculated. Factors associated with outcome variables were identified using Poisson regression with a robust variance statistical model.

Results:The prevalence of high sedentary behavior was 20.3% (95% CI, 18.0–22.7%) among the study participants. The prevalence of high sedentary behavior was associated with age 45–54 years adjusted PR (APR: 2.00; 95% CI = 1.01–3.97) and 55–64 years (APR: 2.16; 95% CI = 1.03–4.57), being a non-manual worker (APR: 2.11; 95% CI = 1.46–3.05), frequent khat chewers (APR: 1.57; 95% CI = 1.22–2.01), with body mass index of ≥25 kg/m2(APR: 1.93; 95% CI = 1.53–2.44), and regular alcohol drinker (APR: 1.39; 95% CI = 1.11–1.76).

Conclusion:One-fifth of working adults had high sedentary behavior. Factors associated with high sedentary behaviors were older age, being a non-manual worker, substance-use behaviors, and having a high body mass index.
Prediction of Mental Health in Medical Workers During COVID-19 Based on Machine Learning
Authors: Wang Xiaofeng , Li Hu , Sun Chuanyong , Zhang Xiumin , Wang Tan , Dong Chenyu , Guo Dongyang
Published: September 2021

Mental health prediction is one of the most essential parts of reducing the probability of serious mental illness. Meanwhile, mental health prediction can provide a theoretical basis for public health department to work out psychological intervention plans for medical workers. The purpose of this paper is to predict mental health of medical workers based on machine learning by 32 factors. We collected the 32 factors of 5,108 Chinese medical workers through questionnaire survey, and the results of Self-reporting Inventory was applied to characterize mental health. In this study, we propose a novel prediction model based on optimization algorithm and neural network, which can select and rank the most important factors that affect mental health of medical workers. Besides, we use stepwise logistic regression, binary bat algorithm, hybrid improved dragonfly algorithm and the proposed prediction model to predict mental health of medical workers. The results show that the prediction accuracy of the proposed model is 92.55%, which is better than the existing algorithms. This method can be used to predict mental health of global medical worker. In addition, the method proposed in this paper can also play a role in the appropriate work plan for medical worker.