bluuebunny/crossref_metadata_2025 huggingface dataset:
The future role of MFCs in biomass energy
Authors: Ieropoulos Ioannis , Greenman John
Published: March 2023

Microbial fuel cells (MFC) are an emerging green technology which offers several comparative advantages over other technologies for utilizing biomass. It is a technology that treats (cleans) wet organic waste, converting chemical energy to electricity that is used for connected peripherals and target applications. The main advantage is the technology’s ability to utilise wet biomass in suspension or in solution (i.e., too wet to burn) and change the biomass directly into bioenergy in the form of electricity. All other technologies either combust the biomass directly (e.g., wood fuel) or change the biomass into refined fuels which are then combusted or fed to chemical fuel cells to generate heat or electricity. Excluding methane production from biomass, and fermentation leading to hydrogen production, all other biomass/biofuel technologies utilize dry plant matter, which mainly consists of cellulose or lignocellulose and they cannot directly utilize sludge or slurries of organic detritus material. The substrates used for MFCs are not traditionally made into organic fuels, as with other biomass technologies, but are used directly as fuel, recasting the “waste” suspensions and solutions, and promoting them into fuels themselves. To a stack of MFCs, a polluted river, landfill leachate or farmland run-off, can all be reassigned as fuel. This wet fuel is widespread around the planet, the amounts found and the energy contained within are significant, and the cost as a fuel is close to zero. This review gives a general overview of biomass energy along with extraction techniques and compares advantages and disadvantages of MFCs with other biomass technologies for producing electrical energy.
Optimization of the offshore wind power grid-connected structure based on an improved genetic algorithm
Authors: Li Haibo , Jiang Keteng , Lu Zongxiang , Hou Junhao , Xu Sixuan , Qi Wanchun , Cai Hui
Published: March 2023

Large-scale offshore wind power generation has become one of the research hotspots in the development of new energy in the world. However, the planning of far-reaching offshore wind power is faced with many technical difficulties, such as the need to consider the optimization of line transmission capacity caused by the truncation effect in combination with the wind power output probability, and solve the problem that traditional algorithms cannot solve the dynamic programming problem, and the greedy algorithm for solving the dynamic programming problem cannot solve the global optimal solution. Therefore, in order to solve the above problems, based on the full life cycle (FLC) investment calculation of the collecting and transmission system, the topology optimization model of the offshore wind power system is established. In addition, in order to solve the grid-connection problem of offshore wind farms, an improved topology optimization algorithm based on greedy idea is proposed. The optimization results show that the critical values of economic transmission distance of HVAC, FFTS and HVDC are usually 50 km and 170 km respectively. Finally, the collection scheme of the wind farm cluster including three far-reaching offshore wind farms are analyzed, and the results show that the total cost of the optimized point-to-point scheme is reduced by 5.6% and 10.2% respectively compared with the star topology and the circular collection topology, with significant economic benefits.
How the Freshwater Biodiversity Information System (FBIS) is supporting national freshwater fish conservation decisions in South Africa
Authors: Kajee Mohammed , Henry Dominic A. W. , Dallas Helen F. , Griffiths Charles L. , Pegg Josephine , Van der Colff Dewidine , Impson Dean , Chakona Albert , Raimondo Domitilla C. , Job Nancy M. , Paxton Bruce R. , Jordaan Martine S. , Bills Roger , Roux Francois , Zengeya Tsungai A. , Hoffman Andre , Rivers-Moore Nick , Shelton Jeremy M.
Published: March 2023

In South Africa, anthropogenic pressures such as water over-abstraction, invasive species impacts, land-use change, pollution, and climate change have caused widespread deterioration of the health of river ecosystems. This comes at great cost to both people and biodiversity, with freshwater fishes ranked as the country’s most threatened species group. Effective conservation and management of South Africa’s freshwater ecosystems requires access to reliable and comprehensive biodiversity data. Despite the existence of a wealth of freshwater biodiversity data, access to these data has been limited. The Freshwater Biodiversity Information System (FBIS) was built to address this knowledge gap by developing an intuitive, accessible and reliable platform for freshwater biodiversity data in South Africa. The FBIS hosts high quality, high accuracy biodiversity data that are freely available to a wide range of stakeholders, including researchers, conservation practitioners and policymakers. We describe how the system is being used to provide freshwater fish data to a national conservation decision-support tool—The Department of Forestry, Fisheries, and the Environment (DFFE) National Environmental Screening Tool (NEST). The NEST uses empirical and modelled biodiversity data to guide Environmental Impact Assessment Practitioners in conducting environmental assessments of proposed developments. Occurrence records for 34 threatened freshwater fishes occurring in South Africa were extracted from the FBIS and verified by taxon specialists, resulting in 6 660 records being used to generate modelled and empirical national distribution (or sensitivity) layers. This represents the first inclusion of freshwater biodiversity data in the NEST, and future iterations of the tool will incorporate additional freshwater taxa. This case study demonstrates how the FBIS fills a pivotal role in the data-to-decision pipeline through supporting data-driven conservation and management decisions at a national level.
Matching for HLA-DR excluding diabetogenic HLA-DR3 and HLA-DR4 predicts insulin independence after pancreatic islet transplantation
Authors: Ballou Cassandra , Barton Franca , Payne Elizabeth H. , Berney Thierry , Villard Jean , Meier Raphael P. H. , Baidal David , Alejandro Rodolfo , Robien Mark , Eggerman Thomas L. , Kamoun Malek , Muller Yannick D.
Published: March 2023

Introduction

In pancreatic islet transplantation, the exact contribution of human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets may be exposed to allogenic rejection but also the recurrence of type 1 diabetes (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic HLA-DR3 or HLA-DR4 matches.

Methods

We retrospectively examined the HLA profile in 965 transplant recipients and 2327 islet donors. The study population was obtained from patients enrolled in the Collaborative Islet Transplant Registry. We then identified 87 recipients who received a single-islet infusion. Islet-kidney recipients, 2nd islet infusion, and patients with missing data were excluded from the analysis (n=878).

Results

HLA-DR3 and HLA-DR4 were present in 29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group A), 11 with 1 or 2 HLA-DR-matches but excluding HLA-DR3 and HLA- DR4 (group B), and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was maintained in a significantly higher percentage of group B recipients from year one through five post-transplantation (p<0.01). At five-year post-transplantation, 78% of group B was insulin-independent compared to 24% (group A) and 35% (group C). Insulin-independence correlated with significantly better glycemic control (HbA1c <7%), fasting blood glucose, and reduced severe hypoglycemic events. Matching HLA-A-B-DR (≥3) independently of HLA- DR3 or HLA-DR4 matching did not improve graft survival.

Conclusion

This study suggests that matching HLA-DR but excluding the diabetogenic HLA-DR3 and/or 4 is a significant predictor for long-term islet survival.
Tocilizumab-coated solid lipid nanoparticles loaded with cannabidiol as a novel drug delivery strategy for treating COVID-19: A review
Authors: Zielińska Aleksandra , Eder Piotr , Karczewski Jacek , Szalata Marlena , Hryhorowicz Szymon , Wielgus Karolina , Szalata Milena , Dobrowolska Agnieszka , Atanasov Atanas G. , Słomski Ryszard , Souto Eliana B.
Published: March 2023

Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflammatory responses in COVID-19 patients. TCZ, as an immunosuppressive drug, is mainly used to treat rheumatoid arthritis, although several attempts have been made to use it in the active hyperinflammatory phase of COVID-19, with promising outcomes. TCZ is currently administered intravenously. It this review, we discuss the potential advances on the use of SLN for oral administration of TCZ-tailored CBD-loaded SLN, as an innovative platform for managing SARS-CoV-2 and related infections.
Pancreatic cancer and fibrosis: Targeting metabolic reprogramming and crosstalk of cancer-associated fibroblasts in the tumor microenvironment
Authors: Li Xin , Zhou Jianbo , Wang Xue , Li Chunxi , Ma Zifan , Wan Qiaoling , Peng Fu
Published: March 2023

Pancreatic cancer is one of the most dangerous types of cancer today, notable for its low survival rate and fibrosis. Deciphering the cellular composition and intercellular interactions in the tumor microenvironment (TME) is a necessary prerequisite to combat pancreatic cancer with precision. Cancer-associated fibroblasts (CAFs), as major producers of extracellular matrix (ECM), play a key role in tumor progression. CAFs display significant heterogeneity and perform different roles in tumor progression. Tumor cells turn CAFs into their slaves by inducing their metabolic dysregulation, exacerbating fibrosis to acquire drug resistance and immune evasion. This article reviews the impact of metabolic reprogramming, effect of obesity and cellular crosstalk of CAFs and tumor cells on fibrosis and describes relevant therapies targeting the metabolic reprogramming.
Longitudinal choroidal thickness changes among Chinese young adults with various refractive errors
Authors: Duan Fang , Chen Ziyan , Wang Zhenyu , Deng Jiayu , Yeo Anna C.H. , Yang Adeline , Drobe Björn , Wong Yee Ling , Chen Xiang
Published: March 2023

Purpose

To determine the characteristics of longitudinal choroidal thickness (CT) and axial length (AL) changes in a group of Chinese young adults with various refractive errors.

Methods

In this 2 year prospective cohort study, a total of 291 (314 enrolled at baseline) Chinese medical freshmen aged 18 to 22 years (mean age, 18.7 ± 0.9 years) underwent eye examinations at baseline and follow-up visits, including cycloplegic refraction, ocular biometry measurements, and swept-source optical coherence tomography. Choroidal thickness measurements were performed at nine locations in the macular area.

Results

At baseline, the CT and AL was significant differences among groups of emmetropia, mild to moderate myopia and high myopia. During a two-year period, there were significant differences found in the changes of the subfoveal CT (p < 0.001) and parafoveal CT of 7 locations between emmetropia and mild to moderate myopia, and the changes of the subfoveal CT (p = 0.002) and parafoveal CT of 6 locations between emmetropia and high myopia. But there were no differences for AL and SE (p > 0.05). The multivariable linear regression analysis showed that baseline subfoveal CT (per 1 μm) was a significant factor affecting the changes of subfoveal CT (p < 0.001), whereas age, gender, and baseline AL were not significantly associated.

Conclusion

The longitudinal change in CT varies with refractive errors in Chinese young adults aged 18 to 22 years over a two-year period. The changes of subfoveal CT were significantly associated with the baseline subfoveal CT, but not associated with baseline AL.
Glutathione: Pharmacological aspects and implications for clinical use in non-alcoholic fatty liver disease
Authors: Santacroce Giovanni , Gentile Antonella , Soriano Simone , Novelli Andrea , Lenti Marco Vincenzo , Di Sabatino Antonio
Published: March 2023

Glutathione is a tripeptide synthesized at cytosolic level, that exists in cells in a reduced form (thiol-reduced-GSH-) and in an oxidized form (disulfide-oxidized). The antioxidant function of GSH has led to speculation about its therapeutic role in numerous chronic diseases characterized by altered redox balance and reduced GSH levels, including, for instance, neurodegenerative disorders, cancer, and chronic liver diseases. Among these latter, non-alcoholic fatty liver disease (NAFLD), characterized by lipid accumulation in hepatocytes, in the absence of alcohol abuse or other steatogenic factors, is one of the most prevalent. The umbrella term NAFLD includes the pure liver fat accumulation, the so-called hepatic steatosis or non-alcoholic fatty liver, and the progressive form with inflammation, also known as non-alcoholic steatohepatitis, which is related to the increase in oxidative stress and reactive oxygen species, eventually leading to liver fibrosis. Although the pathogenetic role of oxidative stress in these diseases is well established, there is still limited evidence on the therapeutic role of GSH in such conditions. Hence, the aim of this review is to depict the current molecular and pharmacological knowledge on glutathione, focusing on the available studies related to its therapeutic activity in NAFLD.
CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases
Authors: Chevalier Kevin , Genin Michaël , Jean Thomas Petit , Avouac Jerôme , Flipo Rene-Marc , Georgin-Lavialle Sophie , El Mahou Soumaya , Pertuiset Edouard , Pham Thao , Servettaz Amelie , Marotte Hubert , Domont Fanny , Chazerain Pascal , Devaux Mathilde , Mekinian Arsene , Sellam Jérémie , Fautrel Bruno , Rouzaud Diane , Ebstein Esther , Costedoat-Chalumeau Nathalie , Richez Christophe , Hachulla Eric , Mariette Xavier , Seror Raphaèle
Published: March 2023

Introduction

Autoimmune/inflammatory rheumatic diseases (AIRDs) patients might be at-risk of severe COVID-19. However, whether this is linked to the disease or to its treatment is difficult to determine. This study aimed to identify factors associated with occurrence of severe COVID-19 in AIRD patients and to evaluate whether having an AIRD was associated with increased risk of severe COVID-19 or death.

Materials and methods

Two databases were analyzed: the EDS (Entrepôt des Données de Santé, Clinical Data Warehouse), including all patients followed in Paris university hospitals and the French multi-center COVID-19 cohort [French rheumatic and musculoskeletal diseases (RMD)]. First, in a combined analysis we compared patients with severe and non-severe COVID-19 to identify factors associated with severity. Then, we performed a propensity matched score case–control study within the EDS database to compare AIRD cases and non-AIRD controls.

Results

Among 1,213 patients, 195 (16.1%) experienced severe COVID-19. In multivariate analysis, older age, interstitial lung disease (ILD), arterial hypertension, obesity, sarcoidosis, vasculitis, auto-inflammatory diseases, and treatment with corticosteroids or rituximab were associated with increased risk of severe COVID-19. Among 35,741 COVID-19 patients in EDS, 316 having AIRDs were compared to 1,264 Propensity score-matched controls. AIRD patients had a higher risk of severe COVID-19 [aOR = 1.43 (1.08–1.87), p = 0.01] but analysis restricted to rheumatoid arthritis and spondyloarthritis found no increased risk of severe COVID-19 [aOR = 1.11 (0.68–1.81)].

Conclusion

In this multicenter study, we confirmed that AIRD patients treated with rituximab or corticosteroids and/or having vasculitis, auto-inflammatory disease, and sarcoidosis had increased risk of severe COVID-19. Also, AIRD patients had, overall, an increased risk of severe COVID-19 compares general population.
Association between the vaginal and uterine microbiota and the risk of early embryonic arrest
Authors: Wang Li , Chen Junyu , He Lin , Liu Hanbo , Liu Yan , Luan Zonghui , Li Hong , Liu Weixin , Luo Mengjun
Published: March 2023

The aim of this study was to explore the microecological distribution and differences in the uterus and vaginal microbiome in women with early embryonic arrest and those with normal pregnancy by high-throughput sequencing. We systematically sampled the vaginal and uterine microbiomes of 56 pregnant women, namely, 38 patients with early embryonic arrest and 18 pregnant women with normal pregnancy-induced abortion. We obtained colonization data by 16S rRNA gene amplicon sequencing. In the vagina, Lactobacillus, Bacteroidetes and Helicobacter exhibited significant differences between the groups. We further found that Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri and Lactobacillus jensenii were the most dominant Lactobacillus species and that L. iners was significantly different between the groups. Receiver operating characteristic (ROC) curve analysis confirmed that Ensifer had the highest predictive value for early embryonic arrest. In the uterine cavity, we determined that Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria were the dominant bacteria at the phylum level and that Bacteroides, Pseudarthrobacter, Lactobacillus and Ralstonia were the dominant genera. Further classification of Lactobacillus revealed that L. iners, L. crispatus, L. gasseri, and L. jensenii were the main species. There was a significant difference in L. jensenii between the normal pregnancy group and early embryonic arrest group. Random forest analysis revealed 18 different genera in the uterus, and ROC curve analysis indicated that Candidatus Symbiobacter, Odoribacter, Blautia, Nocardioides and Ileibacterium had a certain predictive value.
Growth rate-associated transcriptome reorganization in response to genomic, environmental, and evolutionary interruptions
Authors: Matsui Yuichiro , Nagai Motoki , Ying Bei-Wen
Published: March 2023

The genomic, environmental, and evolutionary interruptions caused the changes in bacterial growth, which were stringently associated with changes in gene expression. The growth and gene expression changes remained unclear in response to these interruptions that occurred combinative. As a pilot study, whether and how bacterial growth was affected by the individual and dual interruptions of genome reduction, environmental stress, and adaptive evolution were investigated. Growth assay showed that the presence of the environmental stressors, i.e., threonine and chloramphenicol, significantly decreased the growth rate of the wild-type Escherichia coli, whereas not that of the reduced genome. It indicated a canceling effect in bacterial growth due to the dual interruption of the genomic and environmental changes. Experimental evolution of the reduced genome released the canceling effect by improving growth fitness. Intriguingly, the transcriptome architecture maintained a homeostatic chromosomal periodicity regardless of the genomic, environmental, and evolutionary interruptions. Negative epistasis in transcriptome reorganization was commonly observed in response to the dual interruptions, which might contribute to the canceling effect. It was supported by the changes in the numbers of differentially expressed genes (DEGs) and the enriched regulons and functions. Gene network analysis newly constructed 11 gene modules, one out of which was correlated to the growth rate. Enrichment of DEGs in these modules successfully categorized them into three types, i.e., conserved, responsive, and epistatic. Taken together, homeostasis in transcriptome architecture was essential to being alive, and it might be attributed to the negative epistasis in transcriptome reorganization and the functional differentiation in gene modules. The present study directly connected bacterial growth fitness with transcriptome reorganization and provided a global view of how microorganisms responded to genomic, environmental, and evolutionary interruptions for survival from wild nature.
Antimicrobial activity of antidepressants on normal gut microbiota: Results of the in vitro study
Authors: Rukavishnikov Grigory , Leonova Lubov , Kasyanov Evgeny , Leonov Vadim , Neznanov Nikholay , Mazo Galina
Published: March 2023

Currently, there is little published data on the effects of antidepressants on normal gut microbiota and the consequences of such effects on treatment outcomes.

The aim of the study: was to evaluate the growth kinetics of normal human gut microorganisms with antidepressants most common in routine clinical practice.

Materials and methods: Research objects were species of microorganisms representing normal gut microbiota: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Candida albicans ATCC 24433, Bifidobacterium 791, Enterococcus faecalis ATCC 29212, Lactobacillus rhamnosus ATCC 53103. All microorganisms were cultivated in Schaedler broth (HiMedia) under aerobic/anaerobic conditions. The active substances of all studied antidepressants (fluvoxamine, fluoxetine, escitalopram, duloxetine, venlafaxine, mirtazapine) were extracted from ground preparations by dimethyl sulfoxide and centrifuged. Each solution of antidepressants was added to a Schaedler broth containing a certain microorganism’s strain and diluted to final concentrations—200 μg/ml, 500 μg/ml, and 700 μg/ml. For a quantitative assessment of the effect, the specific growth rates (μ, h-1) of microorganisms were calculated as the slope of the initial part of the growth curve in coordinates (lnA, t). To evaluate the antidepressant effects on representatives of the normal microbiota in vitro, the following parameters were chosen: specific growth rate and IC50.

Results: All antidepressants had an inhibitory effect on the growth of all studied microorganisms. Fluvoxamine and venlafaxine had the least effect on the growth activity of all studied microorganisms. Fluoxetine showed a pronounced effect on growth activity against E. coli, E. feacalis, S. aureus, and the least effect against C. albicans. Escitalopram had a greater effect on the growth rate of E. coli, E. feacalis, B. bifidum, L. rhamnosus, and C. albicans, which puts it among the leaders in terms of its effect on the growth activity of the microorganisms we studied. Mirtazapine, according to the results of our experiment, showed the greatest activity against L. rhamnosus and C. albicans.

Conclusions: Our results confirm the effects of antidepressants on the growth activity of the normal gut microbiota individual strains. Further study of the antimicrobial activity of antidepressants may become one of the new directions for optimizing the personalized therapy of patients with depression.
A nomogram for predicting the risk of poor prognosis in patients with poor-grade aneurysmal subarachnoid hemorrhage following microsurgical clipping
Authors: Zhou Zhaopeng , Liu Zhuanghua , Yang Hongqiao , Zhang Chunlei , Zhang Chenxu , Chen Junhui , Wang Yuhai
Published: March 2023

Objective

Aneurysmal subarachnoid hemorrhage (aSAH) is a common and potentially fatal cerebrovascular disease. Poor-grade aSAH (Hunt-Hess grades IV and V) accounts for 20–30% of patients with aSAH, with most patients having a poor prognosis. This study aimed to develop a stable nomogram model for predicting adverse outcomes at 6 months in patients with aSAH, and thus, aid in improving the prognosis.

Method

The clinical data and imaging findings of 150 patients with poor-grade aSAH treated with microsurgical clipping of intracranial aneurysms on admission from December 2015 to October 2021 were retrospectively analyzed. Least absolute shrinkage and selection operator (LASSO), logistic regression analyses, and a nomogram were used to develop the prognostic models. Receiver operating characteristic (ROC) curves and Hosmer–Lemeshow tests were used to assess discrimination and calibration. The bootstrap method (1,000 repetitions) was used for internal validation. Decision curve analysis (DCA) was performed to evaluate the clinical validity of the nomogram model.

Result

LASSO regression analysis showed that age, Hunt-Hess grade, Glasgow Coma Scale (GCS), aneurysm size, and refractory hyperpyrexia were potential predictors for poor-grade aSAH. Logistic regression analyses revealed that age (OR: 1.107, 95% CI: 1.056–1.116, P < 0.001), Hunt-Hess grade (OR: 8.832, 95% CI: 2.312–33.736, P = 0.001), aneurysm size (OR: 6.871, 95% CI: 1.907–24.754, P = 0.003) and refractory fever (OR: 3.610, 95% CI: 1.301–10.018, P < 0.001) were independent predictors of poor outcome. The area under the ROC curve (AUC) was 0.909. The calibration curve and Hosmer–Lemeshow tests showed that the nomogram had good calibration ability. Furthermore, the DCA curve showed better clinical utilization of the nomogram.

Conclusion

This study provides a reliable and valuable nomogram that can accurately predict the risk of poor prognosis in patients with poor-grade aSAH after microsurgical clipping. This tool is easy to use and can help physicians make appropriate clinical decisions to significantly improve patient prognosis.
Brain diffusion tensor imaging reveals altered connections and networks in epilepsy patients
Authors: Wang Meixia , Cheng Xiaoyu , Shi Qianru , Xu Bo , Hou Xiaoxia , Zhao Huimin , Gui Qian , Wu Guanhui , Dong Xiaofeng , Xu Qinrong , Shen Mingqiang , Cheng Qingzhang , Xue Shouru , Feng Hongxuan , Ding Zhiliang
Published: March 2023

Introduction

Accumulating evidence shows that epilepsy is a disease caused by brain network dysfunction. This study explored changes in brain network structure in epilepsy patients based on graph analysis of diffusion tensor imaging data.

Methods

The brain structure networks of 42 healthy control individuals and 26 epilepsy patients were constructed. Using graph theory analysis, global and local network topology parameters of the brain structure network were calculated, and changes in global and local characteristics of the brain network in epilepsy patients were quantitatively analyzed.

Results

Compared with the healthy control group, the epilepsy patient group showed lower global efficiency, local efficiency, clustering coefficient, and a longer shortest path length. Both healthy control individuals and epilepsy patients showed small-world attributes, with no significant difference between groups. The epilepsy patient group showed lower nodal local efficiency and nodal clustering coefficient in the right olfactory cortex and right rectus and lower nodal degree centrality in the right olfactory cortex and the left paracentral lobular compared with the healthy control group. In addition, the epilepsy patient group showed a smaller fiber number of edges in specific regions of the frontal lobe, temporal lobe, and default mode network, indicating reduced connection strength.

Discussion

Epilepsy patients exhibited lower global and local brain network properties as well as reduced white matter fiber connectivity in key brain regions. These findings further support the idea that epilepsy is a brain network disorder.
Association between vitamin K intake and depressive symptoms in US adults: Data from the National Health and Nutrition Examination Survey (NHANES) 2013–2018
Authors: Zhang Yuyi , Tan Weiliang , Xi Xiaolan , Yang Hui , Zhang Ke , Li Shengnan , Chen Xuefen , Zuo Hui
Published: March 2023

Background

The relationship between vitamin intake and depression has attracted increasing attention. However, several studies examining such relationship among populations at different age groups have produced inconsistent findings. This study was aimed to investigate the cross-sectional association between vitamin K intake and depressive symptoms in US adults.

Methods

We used the data from a nationally representative sample of 11,687 adults from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES). Vitamin K intake was assessed by the 24-h dietary recall at the first day. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Logistic regression and generalized additive model were used to examine the association between vitamin K intake and depressive symptoms.

Results

The weighted prevalence of depressive symptoms was 10.2% (8.0% in men and 12.0% in women). We observed a significant inverse linear relationship between vitamin K intake and depressive symptoms in models adjusted for age, sex, race/ethnicity, marital status, educational status, family poverty income ratio (PIR), home status, body mass index (BMI), smoking status, physical activity, sleep disorders, hypertension, hyperlipidemia, and diabetes. The odds ratios (OR) (95% CI) for the highest compared with the lowest quartile of vitamin K intake was 0.68 (95% CI: 0.52, 0.89, p-trend < 0.05). The association was similar in subgroups stratified by age, sex, race/ethnicity, marital status, educational status, PIR, home status, BMI, smoking status, physical activity, sleep disorders, hypertension, hyperlipidemia, and diabetes.

Conclusion

Vitamin K intake was inversely and independently associated with the odds of depressive symptoms in the US adults. Prospective studies are warranted to confirm our findings.
Severe immune thrombocytopenia that developed immediately after COVID-19 in a school-aged patient: A case report
Authors: Shinno Kazuma , Banno Yoshinori , Kamimaki Isamu
Published: March 2023

Immune thrombocytopenia (ITP) is an autoimmune disorder that is sometimes triggered by a preceding viral infection and is characterized by a transient or persistent decrease in the platelet (Plt) count. Herein, we report the first pediatric case of severe ITP that developed immediately after the diagnosis of coronavirus disease 2019 (COVID-19) in a school-aged girl. A previously healthy six-year-old girl was diagnosed with COVID-19 a day before experiencing a high fever, sore throat, and headache. She also presented with gingival hemorrhage, petechiae around both eyes and on the chest, and ecchymosis on her right leg. Based on the mucosal hemorrhage and a very low Plt count of 3 × 103/µl, we diagnosed her with severe ITP and urgently treated her with intravenous immunoglobulin (IVIG) to prevent life-threatening hemorrhage. The Plt count increased to 266 × 103/µl one week after treatment with IVIG. Given the possibility of severe ITP secondary to COVID-19, patients with COVID-19 should be carefully examined for the signs of ITP, such as mucosal hemorrhage. Their Plt counts should also be monitored.
Improvement of solubility and pharmacokinetic profile of hepatoprotector icariin through complexation with HP-γ-cyclodextrin
Authors: Ding Yili , Yu Bo , Zhou Shuzhen , Ding Charles , Zhang Zhiyuan , Xu Shufeng , Xu Zhe
Published: March 2023

Icariin as a hepatoprotector from Herba epimedii can expand the cardiovascular and cerebral blood vessels, promote hematopoietic functions, enhance the immune system and show anti-liver tumor activities. However, its low solubility (0.02 mg/mL) limits its clinical applications as food and medical supplements. Through complexation with HP-γ-cyclodextrin by using a trace amount of water-soluble polymer, the water solubility of icariin was increased by 654 times, which is the best result to date for the water solubility study of icariin. In an in vitro pharmacokinetic study, the complexation increased the dissolution rate of icariin by 80 times, and the icariin complex can be 100% released in the first few minutes. Through complexation, in an in vivo dog pharmacokinetic study, the Cmax of icariin was increased about 5 times, the AUC0-120 was increased about 20 times and the clearance of icariin was changed from 11.17 L/h/kg to 0.65 L/h/kg. The half-life time was changed from 0.68 h to 6.38 h and the relative bioavailability was increased by nearly 20 times, indicating that less drug is needed for the same therapeutic effect by using the icariin complex, and the complex can be used as a potential potent hepatoprotector or anti-liver cancer drug.
HZ-A-018, a novel inhibitor of Bruton tyrosine kinase, exerts anti-cancer activity and sensitizes 5-FU in gastric cancer cells
Authors: Liu Danjing , Xu Wei , Lin Bin , Ji Cong , Shen Minmin , Shen Shuying , Ma Junjie , Zhou Xinglu , Yan Youyou , Zhang Bo , Lin Nengming
Published: March 2023

Gastric cancer is the third leading cause of cancer related death worldwide. Due to the complexity and heterogeneity of gastric cancer, the development of targeted drugs is somehow limited, but is urgently needed. Since the expression of Bruton tyrosine kinase (BTK) was significantly associated with the prognosis of gastric cancer patients, we aimed to determine the anti-cancer activity of HZ-A-018, which was a novel derivative of ACP-196, in gastric cancer cells. As a result, HZ-A-018 presented a stronger anti-proliferation activity than ACP-196 via the substantial suppression of AKT/S6 pathway. In addition, HZ-A-018, but not ACP-196, exerted the synergistic effects in combined treatment with 5-FU both in vitro and in vivo, without exacerbating the adverse effects of 5-FU. Mechanismly, the combination of HZ-A-018 and 5-FU remarkably reduced the expression of RRM2, which played an essential role in proliferation and drug sensitivity in gastric cancer cells. In summary, our work demonstrated the stronger anti-cancer activity of HZ-A-018 than ACP-196 in gastric cancer cells, and revealed synergistic effects of HZ-A-018 and 5-FU combination probably through the inhibition of RRM2 via AKT/S6 pathway, thereby providing a promising therapeutic strategy in gastric cancer.
The role of β-catenin in cardiac diseases
Authors: Ni Beibei , Sun Meijuan , Zhao Jun , Wang Jiao , Cao Zhanqi
Published: March 2023

The Wnt/β-catenin signaling pathway is a classical Wnt pathway that regulates the stability and nuclear localization of β-catenin and plays an important role in adult heart development and cardiac tissue homeostasis. In recent years, an increasing number of researchers have implicated the dysregulation of this signaling pathway in a variety of cardiac diseases, such as myocardial infarction, arrhythmias, arrhythmogenic cardiomyopathy, diabetic cardiomyopathies, and myocardial hypertrophy. The morbidity and mortality of cardiac diseases are increasing, which brings great challenges to clinical treatment and seriously affects patient health. Thus, understanding the biological roles of the Wnt/β-catenin pathway in these diseases may be essential for cardiac disease treatment and diagnosis to improve patient quality of life. In this review, we summarize current research on the roles of β-catenin in human cardiac diseases and potential inhibitors of Wnt/β-catenin, which may provide new strategies for cardiac disease therapies.
Hematologic side effects of immune checkpoint inhibitor with or without chemotherapy in patients with advanced and metastatic gastrointestinal cancer: A systematic review and network meta-analysis of phase 3 trials
Authors: Hou Jingyi , Xie Ruiyang , Zhang Zhuo , Liu Qianxin , Xiang Qian , Cui Yimin
Published: March 2023

Background: The regimens of immune checkpoint inhibitors (ICIs) alone or with chemotherapy are emerging as systemic therapy for patients with advanced and metastatic gastrointestinal cancers. However, the risk of treatment-related hematologic toxicity stays unclear.

Methods: We enrolled in phase 3 randomized clinical trials (RCTs) comparing PD-1, PD-L1, and CTLA-4 inhibitors in advanced and metastatic gastrointestinal cancers. The incidences of overall treatment-related adverse events (TRAEs), discontinuation, leukopenia, neutropenia, thrombocytopenia, and anemia were extracted for the Bayesian network meta-analysis. Analyses with poor convergence or low incidence were reported as incidences with 95% CIs instead.

Results: Sixteen phase 3 RCTs with 9732 patients who received systemic therapy were included. A total of 150 (1.54% [95% CI 1.31–1.80]) treatment-related death events were recorded, whereas 13 (0.13% [95% CI 0.08–0.22]) of them were hematologic. 0.24% (95% CI 0.12–0.48) patients received ICI plus chemotherapy were recorded for hematological deaths, 0.09% (95% CI 0.01–0.23) were for chemotherapy alone, and 0.05% were for ICI alone (95% CI 0.01–0.29). Febrile neutropenia was the most frequent cause of death in ICI with chemotherapy. For grade ≥3 TRAEs, we found nivolumab plus chemotherapy (OR 1.63 [95% CI 0.84–3.17]) had a higher risk than other treatments. Overall, ICI monotherapy led to fewer AEs than chemotherapy-based regimens in the analyses of leukopenia, neutropenia, thrombocytopenia, and anemia. Among the 11 treatments, toripalimab plus chemotherapy possessed the highest risk in any-grade leukopenia (OR 1.84 [95% CI 0.48, 6.82]) and neutropenia (OR 1.71 [95% CI 0.17, 17.40]) respectively. For grade ≥3 hematologic AEs, neutropenia (20.08% [95% CI 18.67–21.56]) related to ICI plus chemotherapy was the most dominant. ICI plus chemotherapy was likely to increase the incidence than dosing these drugs alone.

Conclusion: Using ICI alone had a low incidence of causing hematologic mortality and AEs, while the combination with chemotherapy might magnify the side effects. Comprehensively, pembrolizumab plus chemotherapy and sintilimab plus chemotherapy were the safest regimens in terms of leukopenia and neutropenia respectively. This study will guide clinical practice for ICI-based chemotherapy.

Systematic Review Registration: PROSPERO, identifier CRD42022380150
PlotCam: A handheld proximal phenomics platform
Authors: Morrison Malcolm J. , Gahagan A. Claire , Hotte T. , Lefebvre M. B. , Kenny M. , Saumure A.
Published: March 2023

Future crop varieties must be higher yielding, stress resilient and climate agile to feed a larger population, and overcome the effects of climate change. This will only be achieved by a fusion of plant breeding with multiple “omic” sciences. Field-based, proximal phenomics assesses plant growth and responses to stress and agronomic treatments, in a given environment, over time and requires instruments capable of capturing data, quickly and reliably. We designed the PlotCam following the concepts of cost effective phenomics, being low-cost, light-weight (6.8 kg in total) and portable with rapid and repeatable data collection at high spatial resolution. The platform consisted of a telescoping, square carbon fiber unipod, which allowed for data collection from many heights. A folding arm held the sensor head at the nadir position over the plot, and an accelerometer in the arm ensured the sensor head was level at the time of data acquisition. A computer mounted on the unipod ran custom software for data collection. RGB images were taken with an 18 MP, WiFi controlled camera, infrared thermography data was captured with a 0.3 MP infrared camera, and canopy height measured with a 0.3 MP stereo depth camera. Incoming light and air temperature were logged with every image. New operators were quickly trained to gather reliable and repeatable data and an experienced operator could image up to 300 plots per hour. The PlotCam platform was not limited by field design or topography. Multiple identical PlotCams permitted the study of larger populations generating phenomic information useful in variety improvement. We present examples of data collected with the PlotCam over field soybean experiments to show the effectiveness of the platform.
Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
Authors: Zhong Jiu-Gen , Lan Wan-Ting , Feng Yan-Qing , Li Yin-Hua , Shen Ying-Ying , Gong Jia-Heng , Zou Zhi , Hou Xiaohui
Published: March 2023

Introduction: The microbiota–gut–brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats.

Methods: The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography–mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC).

Results: The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and Lactobacillus intestinalis. Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids.

Discussion: According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota–gut–brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.
Deciphering plant health status: The link between secondary metabolites, fungal community and disease incidence in olive tree
Authors: Gomes Teresa , Pereira José Alberto , Moya-Laraño Jordi , Poveda Jorge , Lino-Neto Teresa , Baptista Paula
Published: March 2023

Plant-associated microorganisms are increasingly recognized to play key roles in host health. Among several strategies, associated microorganisms can promote the production of specific metabolites by their hosts. However, there is still a huge gap in the understanding of such mechanisms in plant-microorganism interaction. Here, we want to determine whether different levels of olive leaf spot (OLS) disease incidence were related to differences in the composition of fungal and secondary metabolites (i.e. phenolic and volatile compounds) in leaves from olive tree cultivars with contrasting OLS susceptibilities (ranging from tolerant to highly susceptible). Accordingly, leaves with three levels of OLS incidence from both cultivars were used to assess epiphytic and endophytic fungal communities, by barcoding of cultivable isolates, as well as to evaluate leaf phenolic and volatile composition. Fungal and metabolite compositions variations were detected according to the level of disease incidence. Changes were particularly noticed for OLS-tolerant cultivars, opposing to OLS-susceptible cultivars, suggesting that disease development is linked, not only to leaf fungal and metabolite composition, but also to host genotype. A set of metabolites/fungi that can act as predictive biomarkers of plant tolerance/susceptibility to OLS disease were identified. The metabolites α-farnesene and p-cymene, and the fungi Fusarium sp. and Alternaria sp. were more related to disease incidence, while Pyronema domesticum was related to the absence of disease symptoms. Cultivar susceptibility to OLS disease is then suggested to be driven by fungi, volatile and phenolic host leaves composition, and above all to plant-fungus interaction. A deeper understanding of these complex interactions may unravel plant defensive responses.
The use of a candidate gene approach to study Botrytis cinerea resistance in Gerbera hybrida
Authors: Fu Yiqian , Song Yin , van Tuyl Jaap M. , Visser Richard G. F. , Arens Paul
Published: March 2023

Candidate genes (CG) for Botrytis cinerea resistance described in literature were mapped on gerbera linkage maps for which several QTL for Botrytis resistance had been found previously using a rapid, low-cost platform for SNP genotyping. In total, 29 CGs were mapped in either of two mapping populations. Four CGs were mapped within the previous identified QTL intervals and three co-localized with QTL. Two of these CGs for resistance against B. cinerea, PG1 (polygalacturonase gene) and sit (sitiens, ABA-aldehyde oxidase gene) that mapped in QTL regions for the ray floret disease resistance test were studied in detail. Virus-induced gene silencing (VIGS) was used for gene function analysis to determine the CGs’ role in gerbera resistance to Botrytis. Ray florets, of which the CGs were silenced, showed a significantly delayed growth of lesions upon Botrytis infection compared to controls. Combining QTL analysis, candidate gene mapping and VIGS showed to be an useful combination to identify possible causal genes and for understanding the molecular mechanisms of Botrytis resistance in gerbera. The two genes seem to act as partial S-genes and are likely among the determining genes leading to the variation observed for B. cinerea resistance in gerbera.
Does correlation heuristic dependence reduce due to classroom teaching? A case study from India
Authors: Choudhary Gitanshu , Rao Akash K. , Dutt Varun
Published: March 2023

Introduction

People worldwide have problems understanding the basic stock-flow principles (e.g., correlation heuristic), which govern many everyday tasks. Perhaps, teaching system dynamic concepts in classroom settings might reduce people’s dependence on the correlation heuristic. However, limited literature exists on the effectiveness of classroom curricula in reducing reliance on the correlation heuristic. The present research aims to bridge this gap and empirically understand the effects of classroom teaching programs on reducing people’s reliance on correlation heuristic and improving people’s ability to understand stock-flow concepts. By taking a case from a reputed technology Institute in India, the present research examines how classroom teaching of system dynamics concepts might help students reduce their dependence on the correlation heuristic.

Methods

The experiment consisted of two between-subjects conditions: the experimental and the control (N = 45 in each condition). The experimental condition consisted of randomly registered students that were taught system dynamics principles over 5-months of classroom training. Though, no teaching took place in the control condition. Participants in both conditions were evaluated on their ability to solve stock-flow problems.

Results

Participants in the experimental condition were found to perform better in solving stock-flow problems than subjects in the control condition, and they also relied less on the correlation heuristic.

Discussion

We emphasize the relevance of system dynamics education in graduate curricula in alleviating reliance on the correlation heuristic.