bluuebunny/crossref_metadata_2025 huggingface dataset:
The diagnostic performance of machine learning based on resting-state functional magnetic resonance imaging data for major depressive disorders: a systematic review and meta-analysis
Authors: Chen Yanjing , Zhao Wei , Yi Sijie , Liu Jun
Published: September 2023

Objective

Machine learning (ML) has been widely used to detect and evaluate major depressive disorder (MDD) using neuroimaging data, i.e., resting-state functional magnetic resonance imaging (rs-fMRI). However, the diagnostic efficiency is unknown. The aim of the study is to conduct an updated meta-analysis to evaluate the diagnostic performance of ML based on rs-fMRI data for MDD.

Methods

English databases were searched for relevant studies. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the methodological quality of the included studies. A random-effects meta-analytic model was implemented to investigate the diagnostic efficiency, including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Regression meta-analysis and subgroup analysis were performed to investigate the cause of heterogeneity.

Results

Thirty-one studies were included in this meta-analysis. The pooled sensitivity, specificity, DOR, and AUC with 95% confidence intervals were 0.80 (0.75, 0.83), 0.83 (0.74, 0.82), 14.00 (9, 22.00), and 0.86 (0.83, 0.89), respectively. Substantial heterogeneity was observed among the studies included. The meta-regression showed that the leave-one-out cross-validation (loocv) (sensitivity: p < 0.01, specificity: p < 0.001), graph theory (sensitivity: p < 0.05, specificity: p < 0.01), n > 100 (sensitivity: p < 0.001, specificity: p < 0.001), simens equipment (sensitivity: p < 0.01, specificity: p < 0.001), 3.0T field strength (Sensitivity: p < 0.001, specificity: p = 0.04), and Beck Depression Inventory (BDI) (sensitivity: p = 0.04, specificity: p = 0.06) might be the sources of heterogeneity. Furthermore, the subgroup analysis showed that the sample size (n > 100: sensitivity: 0.71, specificity: 0.72, n < 100: sensitivity: 0.81, specificity: 0.79), the different levels of disease evaluated by the Hamilton Depression Rating Scale (HDRS/HAMD) (mild vs. moderate vs. severe: sensitivity: 0.52 vs. 0.86 vs. 0.89, specificity: 0.62 vs. 0.78 vs. 0.82, respectively), the depression scales in patients with comparable levels of severity. (BDI vs. HDRS/HAMD: sensitivity: 0.86 vs. 0.87, specificity: 0.78 vs. 0.80, respectively), and the features (graph vs. functional connectivity: sensitivity: 0.84 vs. 0.86, specificity: 0.76 vs. 0.78, respectively) selected might be the causes of heterogeneity.

Conclusion

ML showed high accuracy for the automatic diagnosis of MDD. Future studies are warranted to promote the potential use of these classification algorithms in clinical settings.
Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly
Authors: Sokol Deborah K. , Lahiri Debomoy K.
Published: September 2023

Recent studies promote new interest in the intersectionality between autism spectrum disorder (ASD) and Alzheimer’s Disease. We have reported high levels of Amyloid-β Precursor Protein (APP) and secreted APP-alpha (sAPPa) and low levels of amyloid-beta (Aβ) peptides 1–40 and 1–42 (Aβ40, Aβ42) in plasma and brain tissue from children with ASD. A higher incidence of microcephaly (head circumference less than the 3rd percentile) associates with ASD compared to head size in individuals with typical development. The role of Aβ peptides as contributors to acquired microcephaly in ASD is proposed. Aβ may lead to microcephaly via disruption of neurogenesis, elongation of the G1/S cell cycle, and arrested cell cycle promoting apoptosis. As the APP gene exists on Chromosome 21, excess Aβ peptides occur in Trisomy 21-T21 (Down’s Syndrome). Microcephaly and some forms of ASD associate with T21, and therefore potential mechanisms underlying these associations will be examined in this review. Aβ peptides’ role in other neurodevelopmental disorders that feature ASD and acquired microcephaly are reviewed, including dup 15q11.2-q13, Angelman and Rett syndrome.
Assessing daily energy intake in adult women: validity of a food-recognition mobile application compared to doubly labelled water
Authors: Serra Michele , Alceste Daniela , Hauser Florian , Hulshof Paul J. M. , Meijer Harro A. J. , Thalheimer Andreas , Steinert Robert E. , Gerber Philipp A. , Spector Alan C. , Gero Daniel , Bueter Marco
Published: September 2023

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland–Altman plots, paired difference tests, and Pearson’s correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = −329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = −543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p < 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings.

Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).
A nomogram based on the preoperative neutrophil-to-lymphocyte ratio to distinguish sarcomatoid renal cell carcinoma from clear cell renal cell carcinoma
Authors: Wu Yijian , Qi Tienan , Qin Xin , Zhao Zhongwei , Zheng Jianguo , Du Qinglong , Yu Nengwang
Published: September 2023

Objective

Our study aimed to assess the predictive value of the preoperative neutrophil-to-lymphocyte ratio(NLR) in distinguishing sarcomatoid renal cell carcinoma (SRCC) from clear cell renal cell carcinoma(CCRCC) and to developing a nomogram based on the preoperative NLR and other factors to distinguish SRCC from CCRCC.

Materials and methods

The database involved 280 patients, including 46 SRCC and 234 CCRCC. logistic analysis was conducted to select the variables associated with identifying SRCC preoperatively, and subgroup analysis was used to further validate the ability of NLR with preoperative identification of SRCC.In addition, The data were randomly separated into a training cohort(n=195) and a validation cohort(n=85). And an NLR-based nomogram was plotted based on the logistic analysis results. The nomogram was evaluated according to its discrimination, consistency, and clinical benefits.

Results

Multivariate analysis indicated that NLR, flank pain, tumor size, and total cholesterol(TC) were independent risk factors for identifying SRCC. The results of subgroup analysis showed that higher NLR was associated with a higher probability of SRCC in most subgroups. The area under the curve(AUC) of the training and validation cohorts were 0.801 and 0.738, respectively. The results of the calibration curve show high consistency between predicted and actual results. Decision Curve Analysis(DCA) showed clinical intervention based on the model was beneficial over most of the threshold risk range.

Conclusion

NLR is a potential indicator for preoperative differentiation of SRCC and CCRCC, and the predictive model constructed based on NLR has a good predictive ability. The new model could provide suggestions for the early identification of SRCC.
Molecular triaging options for women testing HPV positive with self-collected samples
Authors: Taghavi Katayoun , Zhao Fanghui , Downham Laura , Baena Armando , Basu Partha
Published: September 2023

We review developments in molecular triaging options for women who test positive for high-risk human papillomavirus (hrHPV) on self-collected samples in the context of cervical cancer elimination. The World Health Organization (WHO) recommends hrHPV screening as the primary test for cervical screening due to its high sensitivity compared to other screening tests. However, when hrHPV testing is used alone for treatment decisions, a proportion of women of childbearing age receive unnecessary treatments. This provides the incentive to optimize screening regimes to minimize the risk of overtreatment in women of reproductive age. Molecular biomarkers can potentially enhance the accuracy and efficiency of screening and triage. HrHPV testing is currently the only screening test that allows triage with molecular methods using the same sample. Additionally, offering self-collected hrHPV tests to women has been reported to increase screening coverage. This creates an opportunity to focus health resources on linking screen-positive women to diagnosis and treatment. Adding an additional test to the screening algorithm (a triage test) may improve the test’s positive predictive value (PPV) and offer a better balance of benefits and risks for women. Conventional triage methods like cytology and visual inspection with acetic acid (VIA) cannot be performed on self-collected samples and require additional clinic visits and subjective interpretations. Molecular triaging using methods like partial and extended genotyping, methylation tests, detection of E6/E7 proteins, and hrHPV viral load in the same sample as the hrHPV test may improve the prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and invasive cancer, offering more precise, efficient, and cost-effective screening regimes. More research is needed to determine if self-collected samples are effective and cost-efficient for diverse populations and in comparison to other triage methods. The implementation of molecular triaging could improve screening accuracy and reduce the need for multiple clinical visits. These important factors play a crucial role in achieving the global goal of eliminating cervical cancer as a public health problem.
Development, quality, and influencing factors of colonoscopy in China: results from the national census in 2013 and 2020
Authors: Jiao Yun-Fei , Cheng Zhi-Yuan , Gao Ye , Yu Chu-Ting , Jiang Hui-Shan , Wang Ting-Lu , Deng Ying , Lin Han , Wang Tian-Jiao , Wang Wei , Wan Rong , Li Zhao-Shen , Xin Lei , Wang Luo-Wei
Published: September 2023

Background and Aim

With the increasing burden of colorectal cancer (CRC), the practice of colonoscopy is gaining attention worldwide. However, it exhibits distinct trends between developing and developed countries. This study aims to explore its development and identify influencing factors in China.

Methods

The Chinese Digestive Endoscopy Censuses were conducted twice in mainland China under the supervision of health authorities. Information regarding the practice of colonoscopy was collected through a structured online questionnaire. The authenticity of the data was evaluated through logical tests, and a random selection of endoscopic reports underwent manual validation by Quality Control Centers. Potential factors associated with colonoscopy were analyzed using real-world information.

Results

From 2012 to 2019, the number of hospitals that performed colonoscopy increased from 3,210 to 6,325 (1.97-fold), and the volume increased from 5.83 to 12.92 million (2.21-fold). The utilization rate rose from 436.0 to 914.8 per 100,000 inhabitants (2.10-fold). However, there was an exacerbation of regional inequality in the adequacy of colonoscopy. Regions with higher incidence of CRC, higher gross domestic product per capita, more average numbers of endoscopists and tertiary hospitals tended to provide more accessible colonoscopy (P<0.001). Nationwide, the cecal intubation rate improved from 83.9% to 94.4% and the unadjusted adenoma detection rate (ADR) improved from 16.3% to 18.1%. Overall, hospital grading, educational background of endoscopists, economic income, and colonoscopy volume were observed as the significantly positive factors affecting ADR (P<0.05), but not the incidence of CRC or the number of endoscopists.

Conclusions

Tremendous progress in colonoscopy has been made in China, but some issues needed timely reflection. Our findings provide timely evidence for better colonoscopy strategies and measures, such as quality control and medical education of endoscopists.
Chagas disease treatment efficacy markers: experiences from a Phase III study with nifurtimox in children
Authors: Grossmann Ulrike , Rodriguez Maria-Luisa
Published: September 2023

Determining the success of antitrypanosomal therapy for Chagas disease is challenging, particularly in the chronic phase of the disease, because seropositivity persists for a long time after successful antitrypanosomal treatment and is known to be related to the duration of Trypanosoma cruzi infection. Seroconversion to negative by two or more conventional serologic tests is the currently accepted measure of efficacy, and studies suggest no significant change in seropositivity if left untreated. However, there is no guidance for industry on how to establish the effectiveness of drugs intended for the treatment of Chagas disease. Due to the lack of validated sensitive, specific, easy-to-use markers that allow early monitoring of the efficacy of antitrypanosomal treatment in an efficient manner, we used seroreduction measured by two conventional enzyme-linked immunosorbent assays in addition to the currently accepted criterion for what constitutes a cure, seroconversion to negative, as a surrogate parameter for efficacy in a Phase III pediatric trial with nifurtimox. The measures for confirmation of the antitrypanosomal efficacy of nifurtimox were discussed with US FDA. In this perspective article, we present our experiences obtained from a pediatric study on Chagas disease with an established drug using a surrogate efficacy parameter in addition to the established criterion for a cure.
Evaluation of the impact of oximeter averaging times on automated FiO2 control in routine NICU care: a randomized cross-over study
Authors: Janota J. , Dornakova J. , Karadyova V. , Brabec R. , Rafl-Huttova V. , Bachman T. , Rozanek M. , Rafl J.
Published: September 2023

Objective

Changes in oximeter averaging times have been noted to affect alarm settings. Automated algorithms (A-FiO2) assess FiO2 faster than oximeter averaging, potentially impacting their effectiveness.

Methods

In a single NICU routinely using 15 fabian-PRICO A-FiO2 systems, neonates were randomly exposed to SpO2 averaging time settings switched every 12 h among short (2–4 s), medium (10 s), and long (16 s) oximeter averaging times for the entire duration of their A-FiO2 exposure. Primary endpoints were the percent time in the set SpO2 target range (dependent on PMA), SpO2 < 80%, and SpO2 > 98%, excluding FiO2 = 0.21.

Results

Ten VLBW neonates were enrolled over 11 months. At entry, they were 17 days old (IQR: 14–19), with an adjusted gestational age of 29 weeks (IQR: 27–30). The study included data from 272 days of A-FiO2 control (34% short, 32% medium, and 34% long). Respiratory support was predominantly non-invasive (53% NCPAP, 40% HFNC, and 6% NIPPV). The aggregate SpO2 exposure levels were 67% (IQR: 55–82) in the target range, 5.4% (IQR: 2.0–10) with SpO2 < 80%, and 1.2% (IQR: 0.4–3.1) with SpO2 > 98%. There were no differences in the target range time between the SpO2 averaging time settings. There were differences at the SpO2 extremes (p ≤ 0.001). The medium and long averaging were both lower than the short, with the difference larger than predicted. Multivariate analysis revealed that these findings were independent of subject, ventilation mode, target range, and overall stability.

Conclusions

This A-FiO2 algorithm is effective regardless of the SpO2 averaging time setting. There is an advantage to the longer settings, which suggest an interaction with the controller.
Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor
Authors: Liu Yahong , Cheng Ying , Huang Gongchao , Xia Xiangying , Wang Xingkai , Tian Hongqi
Published: September 2023

Background: Aberrant activation of RAS-RAF-MEK-ERK signaling pathway has been implicated in more than one-third of all malignancies. MEK inhibitors are promising therapeutic approaches to target this signaling pathway. Though four MEK inhibitors have been approved by FDA, these compounds possess either limited efficacy or unfavorable PK profiles with toxicity issues, hindering their broadly application in clinic. Our efforts were focused on the design and development of a novel MEK inhibitor, which subsequently led to the discovery of tunlametinib.

Methods: This study verified the superiority of tunlametinib over the current MEK inhibitors in preclinical studies. The protein kinase selectivity activity of tunlametinib was evaluated against 77 kinases. Anti-proliferation activity was analyzed using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) or (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay. ERK and phospho-ERK levels were evaluated by Western blot analysis. Flow cytometry analysis was employed to investigate cell cycle and arrest. Cell-derived xenograft (CDX) and Patient-derived xenograft (PDX) models were used to evaluate the tumor growth inhibition. The efficacy of tunlametinib as monotherapy treatment was evaluated in KRAS/BRAF mutant or wild type xenograft model. Furthermore, the combination studies of tunlametinib with BRAF/KRASG12C/SHP2 inhibitors or chemotherapeutic agent were conducted by using the cell proliferation assay in vitro and xenograft models in vivo.

Results:In vitro, tunlametinib demonstrated high selectivity with approximately 19-fold greater potency against MEK kinase than MEK162, and nearly 10–100-fold greater potency against RAS/RAF mutant cell lines than AZD6244. In vivo, tunlametinib resulted in dramatic tumor suppression and profound inhibition of ERK phosphorylation in tumor tissue. Mechanistic study revealed that tunlametinib induced cell cycle arrest at G0/G1 phase and apoptosis of cells in a dose-proportional manner. In addition, tunlametinib demonstrated a favorable pharmacokinetic profile with dose-proportionality and good oral bioavailability, with minimal drug exposure accumulation. Furthermore, tunlametinib combined with BRAF/KRASG12C/SHP2 inhibitors or docetaxel showed synergistically enhanced response and marked tumor inhibition.

Conclusion: Tunlametinib exhibited a promising approach for treating RAS/RAF mutant cancers alone or as combination therapies, supporting the evaluation in clinical trials. Currently, the first-in-human phase 1 study and pivotal clinical trial of tunlametinib as monotherapy have been completed and pivotal trials as combination therapy are ongoing.
Dense metal corrosion depth estimation
Authors: Li Yanping , Li Honggang , Guan Yong , Zhang Xinyu , Zhao Xiaomei
Published: September 2023

Introduction: Metal corrosion detection is important for protecting lives and property. X-ray inspection systems are widely used because of their good penetrability and visual presentation capability. They can visually display both external and internal corrosion defects. However, existing X-ray-based defect detection methods cannot present and estimate the dense corrosion depths. To solve this problem, we propose a dense metal corrosion depth estimation method based on image segmentation and inpainting.

Methods: The proposed method employs an image segmentation module to segment metal corrosion defects and an image inpainting module to remove these segmented defects. It then calculates the pixel-level dense corrosion depths using the X-ray images before and after inpainting. Moreover, to address the difficulty of acquiring training images with ground-truth dense corrosion depth annotations, we propose a virtual data generation method for creating virtual corroded metal X-ray images and their corresponding ground-truth annotations.

Results: Experiments on both virtual and real datasets show that the proposed method successfully achieves accurate dense metal corrosion depth estimation.

Discussion: In conclusion, the proposed virtual data generation method can provide effective and sufficient training samples, and the proposed dense metal corrosion depth estimation framework can produce accurate dense corrosion depths.
Metabolic pathways engineering for drought or/and heat tolerance in cereals
Authors: Liu Songtao , Zenda Tinashe , Tian Zaimin , Huang Zhihong
Published: September 2023

Drought (D) and heat (H) are the two major abiotic stresses hindering cereal crop growth and productivity, either singly or in combination (D/+H), by imposing various negative impacts on plant physiological and biochemical processes. Consequently, this decreases overall cereal crop production and impacts global food availability and human nutrition. To achieve global food and nutrition security vis-a-vis global climate change, deployment of new strategies for enhancing crop D/+H stress tolerance and higher nutritive value in cereals is imperative. This depends on first gaining a mechanistic understanding of the mechanisms underlying D/+H stress response. Meanwhile, functional genomics has revealed several stress-related genes that have been successfully used in target-gene approach to generate stress-tolerant cultivars and sustain crop productivity over the past decades. However, the fast-changing climate, coupled with the complexity and multigenic nature of D/+H tolerance suggest that single-gene/trait targeting may not suffice in improving such traits. Hence, in this review-cum-perspective, we advance that targeted multiple-gene or metabolic pathway manipulation could represent the most effective approach for improving D/+H stress tolerance. First, we highlight the impact of D/+H stress on cereal crops, and the elaborate plant physiological and molecular responses. We then discuss how key primary metabolism- and secondary metabolism-related metabolic pathways, including carbon metabolism, starch metabolism, phenylpropanoid biosynthesis, γ-aminobutyric acid (GABA) biosynthesis, and phytohormone biosynthesis and signaling can be modified using modern molecular biotechnology approaches such as CRISPR-Cas9 system and synthetic biology (Synbio) to enhance D/+H tolerance in cereal crops. Understandably, several bottlenecks hinder metabolic pathway modification, including those related to feedback regulation, gene functional annotation, complex crosstalk between pathways, and metabolomics data and spatiotemporal gene expressions analyses. Nonetheless, recent advances in molecular biotechnology, genome-editing, single-cell metabolomics, and data annotation and analysis approaches, when integrated, offer unprecedented opportunities for pathway engineering for enhancing crop D/+H stress tolerance and improved yield. Especially, Synbio-based strategies will accelerate the development of climate resilient and nutrient-dense cereals, critical for achieving global food security and combating malnutrition.
Phytomediated selenium nanoparticles and light regimes elicited in vitro callus cultures for biomass accumulation and secondary metabolite production in Caralluma tuberculata
Authors: Ali Amir , Mashwani Zia-ur-Rehman , Raja Naveed Iqbal , Mohammad Sher , Luna-Arias Juan Pedro , Ahmad Ajaz , Kaushik Prashant
Published: September 2023

Introduction

Caralluma tuberculata holds significant importance as a medicinal plant due to its abundance of bioactive metabolites, which offer a wide range of therapeutic potentials. However, the sustainable production of this plant is challenged by overexploitation, changes in natural conditions, slow growth rate, and inadequate biosynthesis of bioactive compounds in wild populations. Therefore, the current study was conducted to establish an in vitro based elicitation strategy (nano elicitors and light regimes) for the enhancement of biomass and production of secondary metabolites.

Methods

Garlic clove extract was employed as a stabilizing, reducing, or capping agent in the green formulation of Selenium nanoparticles (SeNPs) and various physicochemical characterization analyses such as UV visible spectroscopy, scanning electron microscopy (SEM), energy dispersive X-Ray (EDX) Spectroscopy, fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were performed. Furthermore, the effects of phytosynthesized SeNPs at various concentrations (0, 50, 100, 200, and 400 µg/L on callus proliferation and biosynthesis of medicinal metabolites under different light regimes were investigated.

Results and discussion

Cultures grown on Murashige and Skoog (MS) media containing SeNPs (100 µg/L), in a dark environment for two weeks, and then transferred into normal light, accumulated maximum fresh weight (4,750 mg/L FW), phenolic contents (TPC: 3.91 mg/g DW), flavonoid content (TFC: 2.04 mg/g DW) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity (85%). Maximum superoxide dismutase (SOD: 4.36 U/mg) and peroxide dismutase activity (POD: 3.85 U/mg) were determined in those cultures exposed to SeNPs (100 µg/L) under complete dark conditions. While the callus cultures proliferate on media augmented with SeNPs (200 µg/L) and kept under dark conditions for two weeks and then shifted to normal light conditions exhibited the highest catalase (CAT: 3.25 U/mg) and ascorbate peroxidase (APx: 1.93 U/mg) activities. Furthermore, LC-ESI-MS/MS analysis confirmed the effects of SeNPs and light conditions that elicited the antidiabetic metabolites (cumarins, gallic acid, caffeic acid, ferulic acid, catechin, querctin and rutin). This protocol can be scaled up for the industrial production of plant biomass and pharmacologically potent metabolites using in vitro callus cultures of C. tuberculata.
Methylome changes in Lolium perenne associated with long-term colonisation by the endophytic fungus Epichloë sp. LpTG-3 strain AR37
Authors: Forte Flavia Pilar , Malinowska Marta , Nagy Istvan , Schmid Jan , Dijkwel Paul , Hume David E. , Johnson Richard D. , Simpson Wayne R. , Asp Torben
Published: September 2023

Epichloë spp. often form mutualistic interactions with cool-season grasses, such as Lolium perenne. However, the molecular mechanisms underlying this interaction remain poorly understood. In this study, we employed reduced representation bisulfite sequencing method (epiGBS) to investigate the impact of the Epichloë sp. LpTG-3 strain AR37 on the methylome of L. perenne across multiple grass generations and under drought stress conditions. Our results showed that the presence of the endophyte leads to a decrease in DNA methylation across genomic features, with differentially methylated regions primarily located in intergenic regions and CHH contexts. The presence of the endophyte was consistently associated with hypomethylation in plants across generations. This research sheds new light on the molecular mechanisms governing the mutualistic interaction between Epichloë sp. LpTG-3 strain AR37 and L. perenne. It underscores the role of methylation changes associated with endophyte infection and suggests that the observed global DNA hypomethylation in L. perenne may be influenced by factors such as the duration of the endophyte-plant association and the accumulation of genetic and epigenetic changes over time.
Transcriptomics combined with physiological analysis reveals the mechanism of cadmium uptake and tolerance in Ligusticum chuanxiong Hort. under cadmium treatment
Authors: Zhang Zhanling , Zhong Lele , Xiao Wanting , Du Yaping , Han Guiqi , Yan Zhuyun , He Dongmei , Zheng Chuan
Published: September 2023

Introduction

Ligusticum chuanxiong Hort. is a widely used medicinal plant, but its growth and quality can be negatively affected by contamination with the heavy metal cadmium (Cd). Despite the importance of understanding how L. chuanxiong responds to Cd stress, but little is currently known about the underlying mechanisms.

Methods

To address this gap, we conducted physiological and transcriptomic analyses on L. chuanxiong plants treated with different concentrations of Cd2+ (0 mg·L−1, 5 mg·L−1, 10 mg·L−1, 20 mg·L−1, and 40 mg·L−1).

Results

Our findings revealed that Cd stress inhibited biomass accumulation and root development while activating the antioxidant system in L. chuanxiong. Root tissues were the primary accumulation site for Cd in this plant species, with Cd being predominantly distributed in the soluble fraction and cell wall. Transcriptomic analysis demonstrated the downregulation of differential genes involved in photosynthetic pathways under Cd stress. Conversely, the plant hormone signaling pathway and the antioxidant system exhibited positive responses to Cd regulation. Additionally, the expression of differential genes related to cell wall modification was upregulated, indicating potential enhancements in the root cell wall’s ability to sequester Cd. Several differential genes associated with metal transport proteins were also affected by Cd stress, with ATPases, MSR2, and HAM3 playing significant roles in Cd passage from the apoplast to the cell membrane. Furthermore, ABC transport proteins were found to be key players in the intravesicular compartmentalization and efflux of Cd.

Discussion

In conclusion, our study provides preliminary insights into the mechanisms underlying Cd accumulation and tolerance in L. chuanxiong, leveraging both physiological and transcriptomic approaches. The decrease in photosynthetic capacity and the regulation of plant hormone levels appear to be major factors contributing to growth inhibition in response to Cd stress. Moreover, the upregulation of differential genes involved in cell wall modification suggests a potential mechanism for enhancing root cell wall capabilities in isolating and sequestering Cd. The involvement of specific metal transport proteins further highlights their importance in Cd movement within the plant.
Deciphering the underlying immune network of the potato defense response inhibition by Phytophthora infestans nuclear effector Pi07586 through transcriptome analysis
Authors: Xiong Yumeng , Zhao Di , Chen Shengnan , Yuan Lan , Zhang Die , Wang Hongyang
Published: September 2023

Phytophthora infestans, a highly destructive plant oomycete pathogen, is responsible for causing late blight in potatoes worldwide. To successfully infect host cells and evade immunity, P. infestans secretes various effectors into host cells and exclusively targets the host nucleus. However, the precise mechanisms by which these effectors manipulate host gene expression and reprogram defenses remain poorly understood. In this study, we focused on a nuclear-targeted effector, Pi07586, which has been implicated in immune suppression. Quantitative real-time PCR (qRT-PCR) analysis showed Pi07586 was significant up-regulation during the early stages of infection. Agrobacterium-induced transient expression revealed that Pi07586 localized in the nucleus of leaf cells. Overexpression of Pi07586 resulted in increased leaf colonization by P. infestans. RNA-seq analysis revealed that Pi07586 effectively suppressed the expression of PR-1C-like and photosynthetic antenna protein genes. Furthermore, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) analysis indicated that Pi07586 overexpression led to a substantial decrease in abscisic acid (ABA), jasmonic acid (JA), and jasmonoyl-isoleucine (JA-Ile) levels, while not affecting salicylic acid (SA) and indole-3-acetic acid (IAA) production. These findings shed new light on the modulation of plant immunity by Pi07586 and enhance our understanding of the intricate relationship between P. infestans and host plants.
Taking the unreal seriously: enriching cognitive science with the notion of fictionality
Authors: Gander Pierre , Szita Kata , Falck Andreas , Thompson William Hedley
Published: September 2023

Fictionality and fictional experiences are ubiquitous in people’s everyday lives in the forms of movies, novels, video games, pretense and role playing, and digital technology use. Despite this ubiquity, though, the field of cognitive science has traditionally been dominated by a focus on the real world. Based on the limited understanding from previous research on questions regarding fictional information and the cognitive processes for distinguishing reality from fiction, we argue for the need for a comprehensive and systematic account that reflects on related phenomena, such as narrative comprehension or imagination embedded into general theories of cognition. This is important as incorporating cognitive processing of fictional events into memory theory reshapes the conceptual map of human memory. In this paper, we highlight future challenges for the cognitive studies of fictionality on conceptual, neurological, and computational levels. Taking on these challenges requires an interdisciplinary approach between fields like developmental psychology, philosophy, and the study of narrative comprehension. Our aim is to build on such interdisciplinarity and provide conclusions on the ways in which new theoretical frameworks of fiction cognition can aid understanding human behaviors in a wide range of aspects of people’s daily lives, media consumption habits, and digital encounters. Our account also has the potential to inform technological innovations related to training intelligent digital systems to distinguish fact and fiction in the source material.
The effect of study-abroad experience on lexical translation among interpreting students
Authors: Wang Ruiyuan , Han Jing , Di Biase Bruno , Antoniou Mark
Published: September 2023

This study investigates the impact of study-abroad experience (SAE) on lexical translation among 50 Chinese (L1)-English (L2) interpreting students. Participants were divided into two groups based on their experience abroad. Both groups consisted of 25 unbalanced L2 learners who were matched in age, working memory, length of interpreting training, and L2 proficiency. Bidirectional word translation recognition tasks, from L1 to L2 and L2 to L1, highlighted several key findings: (1) both groups were significantly more accurate and faster from L2 to L1 than in the reverse direction; (2) the study abroad (SA) group was more inclined to respond quickly at the risk of making errors, whereas the non-study abroad (NSA) group tended to be more cautious, prioritising accuracy over speed; (3) the SA group were more balanced and consistent in their performance across lexical translations in both directions than the NSA group. These results emphasise the potent effect of SAE in resolving bilinguals’ language competition, especially in streamlining language switching, a cognitive process critical for interpreting students engaging daily with dual languages.
Interoception, alexithymia, and anxiety among individuals with alcohol use disorder
Authors: Wiśniewski Paweł , Jakubczyk Andrzej , Trucco Elisa M. , Kobyliński Paweł , Suszek Hubert , Zaorska Justyna , Rydzewska Małgorzata , Kopera Maciej
Published: September 2023

Background

Interoception (i.e., the ability to recognize bodily signals), alexithymia (i.e., the inability to recognize emotional states) and negative affect (i.e., unpleasant feelings such as anxiety) have been associated with alcohol use disorder (AUD). Previous research suggests that interoception may underlie alexithymia, which in turn may be associated with negative affectivity. However, this remains to be empirically tested. This study investigates whether alexithymia mediates the association between interoception and anxiety and whether this association differs across individuals with AUD and a healthy control (HC) comparison group.

Methods

The AUD group consisted of 99 participants enrolled in an 8-week abstinence-based inpatient treatment program. The HC group included 103 healthy individuals. The heartbeat counting task (HCT) was used to assess interoception (cardiac interoceptive accuracy). The Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia. The Brief Symptom Inventory (BSI) was used to assess anxiety.

Results

The moderated mediation model with interoception as the predictor, alexithymia as the mediator, and negative affect (i.e., state anxiety) as the dependent variable was tested. The analysis showed that the conditional indirect effect of interoception on anxiety via alexithymia was significant for individuals with AUD [ab= −0.300, bootstrap 95% CI = (−0.618, −0.088)], as well as for HCs [ab= −0.088, bootstrap 95% CI = (−0.195, −0.014)]; however, the conditional indirect effect significantly differed across HCs and individuals with AUD. Namely, the mediated effect was greater among individuals with AUD compared to the HC group.

Conclusion

The results suggests that interoceptive impairment contributes to greater negative affect (i.e., state anxiety) via alexithymia especially for individuals with AUD. Improving emotion recognition via therapeutic methods focused on strengthening interoceptive abilities could improve outcomes for individuals receiving treatment for AUD.
Prevalence and risk factors associated with the occurrence of Campylobacter sp. in children aged 6–24 months in peri-urban Nairobi, Kenya
Authors: Kiarie Alice , Bebora Lilly , Gitao George , Ochien’g Linnet , Okumu Noah , Mutisya Christine , Wasonga Joseph , Masudi Sherril Phyllis , Moodley Arshnee , Amon-Tanoh Maud A. , Watson Julie , Cumming Oliver , Cook Elizabeth A. J.
Published: September 2023

Introduction

Campylobacter bacteria is a major cause of foodborne-related bacterial gastroenteritis in humans worldwide. It is known to cause diarrhea in young children which has been shown to directly affect their weight and height as a result of malnutrition. Severe cases of diarrhea can also lead to death. Most of the burden is experienced in resource-limited countries in Africa and Southeast Asia where the disease is linked to poor hygiene and sanitation. The objective of this study was to determine the prevalence of Campylobacter in children aged between 6 and 24 months in Nairobi, Kenya and identify potential risk factors associated with their occurrence.

Methods

A cross-sectional study was carried out between May to December 2021. A total of 585 randomly selected households were visited in two wards (Uthiru/Ruthimitu and Riruta) in Dagoretti South sub-county, Nairobi. A questionnaire regarding how children’s food is handled, the major foods consumed, sanitation and hygiene, and animal ownership was conducted among caregivers to identify associated risk factors. Stool samples were collected from 540/585 children and screened for the presence of Campylobacter using culture-based methods and confirmed through PCR.

Results

Of the 540 children’s stool samples processed, Campylobacter isolates were detected in 4.8% (26/540). Campylobacter jejuni (C. jejuni) was the most common species in 80.8% of positive samples compared to Campylobacter coli (C. coli) in 26.9% of samples. In six samples, both C. jejuni and C. coli were isolated, while in four samples, it was not possible to speciate the Campylobacter. Drinking cow’s milk (OR 4.2, 95% CI 1.4 – 12.6) and the presence of animal feces in the compound (OR 3.4, 95% CI 1.1 – 10.3) were found to be statistically associated with Campylobacter carriage in children.

Discussion

The carriage of Campylobacter in children in this community indicates a need for further investigation on source attribution to understand transmission dynamics and inform where to target interventions. Awareness creation among caregivers on good personal and food hygiene is needed, including boiling milk before consumption. Implementation of biosecurity measures at the household level is highly recommended to reduce contact between animals and humans.
Seroepidemiology of Chagas disease in at-risk individuals in Caraíbas, a city with high endemicity in Bahia State, Brazil
Authors: Pavan Tycha Bianca Sabaini , Dias Deorlan Pereira , Cangussú Márcia Moraes , Dutra Vilquenia Porto Pacheco , Sampaio Daniel Dias , Santos Fred Luciano Neves
Published: September 2023

Introduction

In Brazil, an estimated 1.1 million people are infected with Trypanosoma cruzi, the causative agent of Chagas disease (CD). Despite the high number of cases, the estimated prevalence of infection per 100 inhabitants is low (0.03). However, the actual number of chronically infected individuals is still unknown. Therefore, we sought to determine the prevalence of chronic CD in at-risk individuals in Caraíbas (Bahia, Brazil) through active case finding.

Methods

A total of 572 individuals living in rural or urban areas of Caraíbas were eligible for the study. A serum sample was collected from 226 individuals, and the diagnosis performed according to international guidelines.

Results

The overall prevalence of anti-T. cruzi IgG was 4.42%. The median age of anti-T. cruzi IgG-positive individuals was 54.5 years, and the female-to-male ratio was 1.5:1. The prevalence of anti-T. cruzi IgG was similar in rural (4.29%) and urban areas (4.65%).

Discussion

Compared with national estimates, we concluded that Caraíbas had a high prevalence for chronic CD and a high risk for persistent transmission. Through our study, it was possible to monitor individuals who were unaware of their clinical condition, thus improving their quality of life.
Applications of VirScan to broad serological profiling of bat reservoirs for emerging zoonoses
Authors: Ruhs Emily Cornelius , Chia Wan Ni , Foo Randy , Peel Alison J. , Li Yimei , Larman H. Benjamin , Irving Aaron T. , Wang Linfa , Brook Cara E.
Published: September 2023

Introduction

Bats are important providers of ecosystem services such as pollination, seed dispersal, and insect control but also act as natural reservoirs for virulent zoonotic viruses. Bats host multiple viruses that cause life-threatening pathology in other animals and humans but, themselves, experience limited pathological disease from infection. Despite bats’ importance as reservoirs for several zoonotic viruses, we know little about the broader viral diversity that they host. Bat virus surveillance efforts are challenged by difficulties of field capture and the limited scope of targeted PCR- or ELISA-based molecular and serological detection. Additionally, virus shedding is often transient, thus also limiting insights gained from nucleic acid testing of field specimens. Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a broad serological tool used previously to comprehensively profile viral exposure history in humans, offers an exciting prospect for viral surveillance efforts in wildlife, including bats.

Methods

Here, for the first time, we apply PhIP-Seq technology to bat serum, using a viral peptide library originally designed to simultaneously assay exposures to the entire human virome.

Results

Using VirScan, we identified past exposures to 57 viral genera—including betacoronaviruses, henipaviruses, lyssaviruses, and filoviruses—in semi-captive Pteropus alecto and to nine viral genera in captive Eonycteris spelaea. Consistent with results from humans, we find that both total peptide hits (the number of enriched viral peptides in our library) and the corresponding number of inferred past virus exposures in bat hosts were correlated with poor bat body condition scores and increased with age. High and low body condition scores were associated with either seropositive or seronegative status for different viruses, though in general, virus-specific age-seroprevalence curves defied assumptions of lifelong immunizing infection, suggesting that many bat viruses may circulate via complex transmission dynamics.

Discussion

Overall, our work emphasizes the utility of applying biomedical tools, like PhIP-Seq, first developed for humans to viral surveillance efforts in wildlife, while highlighting opportunities for taxon-specific improvements.
MeaningBERT: assessing meaning preservation between sentences
Authors: Beauchemin David , Saggion Horacio , Khoury Richard
Published: September 2023

In the field of automatic text simplification, assessing whether or not the meaning of the original text has been preserved during simplification is of paramount importance. Metrics relying on n-gram overlap assessment may struggle to deal with simplifications which replace complex phrases with their simpler paraphrases. Current evaluation metrics for meaning preservation based on large language models (LLMs), such as BertScore in machine translation or QuestEval in summarization, have been proposed. However, none has a strong correlation with human judgment of meaning preservation. Moreover, such metrics have not been assessed in the context of text simplification research. In this study, we present a meta-evaluation of several metrics we apply to measure content similarity in text simplification. We also show that the metrics are unable to pass two trivial, inexpensive content preservation tests. Another contribution of this study is MeaningBERT (https://github.com/GRAAL-Research/MeaningBERT), a new trainable metric designed to assess meaning preservation between two sentences in text simplification, showing how it correlates with human judgment. To demonstrate its quality and versatility, we will also present a compilation of datasets used to assess meaning preservation and benchmark our study against a large selection of popular metrics.
Treatment performance and microbial community structure in an aerobic granular sludge sequencing batch reactor amended with diclofenac, erythromycin, and gemfibrozil
Authors: Bodle Kylie B. , Mueller Rebecca C. , Pernat Madeline R. , Kirkland Catherine M.
Published: September 2023

This study characterizes the effects of three commonly detected pharmaceuticals—diclofenac, erythromycin, and gemfibrozil—on aerobic granular sludge. Approximately 150 µg/L of each pharmaceutical was fed in the influent to a sequencing batch reactor for 80 days, and the performance of the test reactor was compared with that of a control reactor. Wastewater treatment efficacy in the test reactor dropped by approximately 30-40%, and ammonia oxidation was particularly inhibited. The relative abundance of active Rhodocyclaceae, Nitrosomonadaceae, and Nitrospiraceae families declined throughout exposure, likely explaining reductions in wastewater treatment performance. Pharmaceuticals were temporarily removed in the first 12 days of the test via both sorption and degradation; both removal processes declined sharply thereafter. This study demonstrates that aerobic granular sludge may successfully remove pharmaceuticals in the short term, but long-term tests are necessary to confirm if pharmaceutical removal is sustainable.