bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable development goals applied to digital pathology and artificial intelligence applications in low- to middle-income countries
Authors: Piya Sumi , Lennerz Jochen K.
Published: May 2023

Digital Pathology (DP) and Artificial Intelligence (AI) can be useful in low- and middle-income countries; however, many challenges exist. The United Nations developed sustainable development goals that aim to overcome some of these challenges. The sustainable development goals have not been applied to DP/AI applications in low- to middle income countries. We established a framework to align the 17 sustainable development goals with a 27-indicator list for low- and middle-income countries (World Bank/WHO) and a list of 21 essential elements for DP/AI. After categorization into three domains (human factors, IT/electronics, and materials + reagents), we permutated these layers into 153 concatenated statements for prioritization on a four-tiered scale. The two authors tested the subjective ranking framework and endpoints included ranked sum scores and visualization across the three layers. The authors assigned 364 points with 1.1–1.3 points per statement. We noted the prioritization of human factors (43%) at the indicator layer whereas IT/electronic (36%) and human factors (35%) scored highest at the essential elements layer. The authors considered goal 9 (industry, innovation, and infrastructure; average points 2.33; sum 42), goal 4 (quality education; 2.17; 39), and goal 8 (decent work and economic growth; 2.11; 38) most relevant; intra-/inter-rater variability assessment after a 3-month-washout period confirmed these findings. The established framework allows individual stakeholders to capture the relative importance of sustainable development goals for overcoming limitations to a specific problem. The framework can be used to raise awareness and help identify synergies between large-scale global objectives and solutions in resource-limited settings.
Multidrug-resistant non-typhoidal Salmonella of public health significance recovered from migratory birds in Bangladesh
Authors: Card Roderick M. , Chisnall Thomas , Begum Ruhena , Sarker Md Samun , Hossain Muhammad Sazzad , Sagor Md Shahjalal , Mahmud Mohammad Asheak , Uddin A. S. M. Ashab , Karim Md Rezaul , Lindahl Johanna F. , Samad Mohammed Abdus
Published: May 2023

Non-typhoidal Salmonella provides an exemplar for the One Health approach as it encompasses public and animal health, food safety, and environmental considerations. The contribution of environmental aspects is currently less well-defined. The purpose of this study was to determine the carriage occurrence of non-typhoidal Salmonella in migratory birds in Bangladesh and assess the potential significance to public and animal health. Cloacal swabs (N = 453) were collected in the years 2018–2020 from Tanguar and Hakaluki Haors, important wetland ecosystems in Northeastern Bangladesh. The prevalence of Salmonella was 13.5% (61 positive swabs). Classical serotyping identified six serovars: Salmonella enterica subsp. enterica serovars Perth, Kentucky, Albany, Infantis, Weltevreden, and Brancaster. Resistance towards 14 antimicrobials was assessed by broth microdilution minimum inhibitory concentration determination and the antimicrobial resistance (AMR) genotype established by whole-genome sequencing. S. Perth and S. Weltevreden isolates were susceptible and harbored no acquired AMR genes. Isolates from the remaining serovars were multidrug resistant, commonly possessing resistance to tetracycline, ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and ciprofloxacin. Salmonella resistant to ciprofloxacin meets WHO criteria for priority pathogens. There was excellent concordance between resistance phenotype and the presence of corresponding AMR genes, many of which reside on Salmonella Genomic Islands. High-level ciprofloxacin resistance correlated with the presence of mutations in the chromosomal gyrB and/or parC genes. The S. Kentucky isolates were ST198, a widely distributed multidrug-resistant lineage reported in humans and animals, and constituting an ongoing risk to public health worldwide. We have demonstrated that multidrug-resistant non-typhoidal Salmonella of public health significance can be recovered from migratory birds. A potential for risk can manifest through direct interaction, transmission to food-producing livestock on farms, and dissemination via the long range migratory movements of birds. Risks can be mitigated by measures including continued surveillance and implementation of good farm biosecurity practices.
Capturing the dynamics of microbial interactions through individual-specific networks
Authors: Yousefi Behnam , Melograna Federico , Galazzo Gianluca , van Best Niels , Mommers Monique , Penders John , Schwikowski Benno , Van Steen Kristel
Published: May 2023

Longitudinal analysis of multivariate individual-specific microbiome profiles over time or across conditions remains dauntin. Most statistical tools and methods that are available to study microbiomes are based on cross-sectional data. Over the past few years, several attempts have been made to model the dynamics of bacterial species over time or across conditions. However, the field needs novel views on handling microbial interactions in temporal analyses. This study proposes a novel data analysis framework, MNDA, that combines representation learning and individual-specific microbial co-occurrence networks to uncover taxon neighborhood dynamics. As a use case, we consider a cohort of newborns with microbiomes available at 6 and 9 months after birth, and extraneous data available on the mode of delivery and diet changes between the considered time points. Our results show that prediction models for these extraneous outcomes based on an MNDA measure of local neighborhood dynamics for each taxon outperform traditional prediction models solely based on individual-specific microbial abundances. Furthermore, our results show that unsupervised similarity analysis of newborns in the study, again using the notion of a taxon's dynamic neighborhood derived from time-matched individual-specific microbial networks, can reveal different subpopulations of individuals, compared to standard microbiome-based clustering, with potential relevance to clinical practice. This study highlights the complementarity of microbial interactions and abundances in downstream analyses and opens new avenues to personalized prediction or stratified medicine with temporal microbiome data.
Population response of intestinal microbiota to acute Vibrio alginolyticus infection in half-smooth tongue sole (Cynoglossus semilaevis)
Authors: Hao Yaotong , Zhao Yaxian , Zhang Yitong , Liu Yufeng , Wang Guixing , He Zhongwei , Cao Wei , Han Tian , Zhang Xun , Zhang Ziying , Wang Yufen , Gong Chunguang , Hou Jilun
Published: May 2023

Introduction

Vibriosis causes enormous economic losses of marine fish. The present study investigated the intestinal microbial response to acute infection of half-smooth tongue sole with different-dose Vibrio alginolyticus within 72 h by metagenomic sequencing.

Methods

The inoculation amount of V. alginolyticus for the control, low-dose, moderate-dose, and high-dose groups were 0, 8.5 × 101, 8.5 × 104, and 8.5 × 107 cells/g respectively, the infected fish were farmed in an automatic seawater circulation system under a relatively stable temperature, dissolved oxygen and photoperiod, and 3 ~ 6 intestinal samples per group with high-quality DNA assay were used for metagenomics analysis.

Results

The acute infections with V. alginolyticus at high, medium, and low doses caused the change of different-type leukocytes at 24 h, whereas the joint action of monocytes and neutrophils to cope with the pathogen infection only occurred in the high-dose group at 72 h. The metagenomic results suggest that a high-dose V. alginolyticus infection can significantly alter the intestinal microbiota, decrease the microbial α-diversity, and increase the bacteria from Vibrio and Shewanella, including various potential pathogens at 24 h. High-abundance species of potential pathogens such as V. harveyii, V. parahaemolyticus, V. cholerae, V. vulnificus, and V. scophthalmi exhibited significant positive correlations with V. alginolyticus. The function analysis revealed that the high-dose inflection group could increase the genes closely related to pathogen infection, involved in cell motility, cell wall/ membrane/envelope biogenesis, material transport and metabolism, and the pathways of quorum sensing, biofilm formation, flagellar assembly, bacterial chemotaxis, virulence factors and antibiotic resistances mainly from Vibrios within 72 h.

Discussion

It indicates that the half-smooth tongue sole is highly likely to be a secondary infection with intestinal potential pathogens, especially species from Vibrio and that the disease could become even more complicated because of the accumulation and transfer of antibiotic-resistance genes in intestinal bacteria during the process of V. alginolyticus intensified infection.
Improvement of crAssphage detection/quantification method and its extensive application for food safety
Authors: Lee So-Young , Yang Jihye , Lee Ju-Hoon
Published: May 2023

Water-borne diseases are usually caused by the fecal–oral transmission of human fecal pathogens. Traditionally, coliforms and enterococci are widely used as indicator bacteria, but they do not allow to differentiate between human and animal fecal contamination. Owing to its presence only in the human gut environment, crAssphage has been suggested as an alternative indicator of human fecal contamination to overcome the above challenges. In this study, 139 human and 89 animal fecal samples (e.g., chicken, cow, dog, pig, pigeon, and mouse) were collected. For the rapid detection of human crAssphage in fecal samples, quantitative real-time PCR (qPCR) was performed using five different oligonucleotide primer/probe combinations. These included three previously reported oligonucleotide primer/probe combinations (RQ, CPQ056, and CrAssBP) and two newly developed combinations (ORF00018-targeting CrAssPFL1 and ORF00044-targeting CrAssPFL2). The detection rate (crAssphage-positive rate) in human fecal samples were 23.0, 30.2, 28.8, 20.1, and 30.9%, respectively, suggesting CrAssPFL2 showed the highest detection rate. Furthermore, the lowest copy numbers (436.16 copy numbers) could be detected using the CrAssPFL2 combination. Interestingly, no difference in crAssphage detection rates was found between healthy people and intestinal inflammatory patients. As expected, no crAssphage was detected in any animal fecal samples, indicating its human specificity. Furthermore, qPCR analysis of sewage samples collected from five different sewage treatment plants revealed that they were all contaminated with 105.71 copy numbers/mL of crAssphage on average. The simulation test of crAssphage-contaminated food samples also confirmed that the detection limit was from 107.55 copy numbers of crAssphage in foods. Therefore, the newly developed and optimized qPCR would be useful for the sensitive detection of crAssphage while identifying the source of human fecal contamination.
Antimicrobial activity of photosensitizers: arrangement in bacterial membrane matters
Authors: Batishchev Oleg V. , Kalutskii Maksim A. , Varlamova Ekaterina A. , Konstantinova Anna N. , Makrinsky Kirill I. , Ermakov Yury A. , Meshkov Ivan N. , Sokolov Valerij S. , Gorbunova Yulia G.
Published: May 2023

Porphyrins are well-known photosensitizers (PSs) for antibacterial photodynamic therapy (aPDT), which is still an underestimated antibiotic-free method to kill bacteria, viruses, and fungi. In the present work, we developed a comprehensive tool for predicting the structure and assessment of the photodynamic efficacy of PS molecules for their application in aPDT. We checked it on a series of water-soluble phosphorus(V) porphyrin molecules with OH or ethoxy axial ligands and phenyl/pyridyl peripheral substituents. First, we used biophysical approaches to show the effect of PSs on membrane structure and their photodynamic activity in the lipid environment. Second, we developed a force field for studying phosphorus(V) porphyrins and performed all-atom molecular dynamics simulations of their interactions with bacterial lipid membranes. Finally, we obtained the structure-activity relationship for the antimicrobial activity of PSs and tested our predictions on two models of Gram-negative bacteria, Escherichia coli and Acinetobacter baumannii. Our approach allowed us to propose a new PS molecule, whose MIC50 values after an extremely low light dose of 5 J/cm2 (5.0 ± 0.4 μg/mL for E. coli and 4.9 ± 0.8 μg/mL for A. baumannii) exceeded those for common antibiotics, making it a prospective antimicrobial agent.
Women and stroke: disparities in clinical presentation, severity, and short- and long-term outcomes
Authors: Naveed Hiba , Almasri Muna , Kazani Bahram , Nauman Areej , Akhtar Naveed , Singh Rajvir , Kamran Saadat , Al Jerdi Salman , Thermalingem Sathvika , Shuaib Ashfaq
Published: May 2023

Objectives

There are limited data from the Middle East on sex-related differences in short- and long-term stroke outcomes. We present 8 years of experience based on the Qatar stroke database.

Setting

The Qatar stroke database prospectively collects data on all stroke patients admitted to Hamad General Hospital. For this study, we compared female and male acute ischemic stroke patients on their characteristics at admission, short-term outcomes [modified Rankin Scale (mRS) score], and long-term outcomes [incidence of major adverse cardiovascular events (MACEs)].

Participants

A total of 7,300 patients [F: 1,406 (19.3%), M: 5,894 (80.7%); mean age 55.1 ± 13.3 (F: 61.6 ± 15.1, M: 53.5 ± 12.3; p < 0.001)] were admitted with acute ischemic stroke.

Results

Significantly fewer women presented within 4.5 h of onset (F: 29% vs. M: 32.8%; p = 0.01). Although women were more likely to experience severe stroke (NIHSS >10; F: 19.9% vs. M: 14.5%; p < 0.001), fewer were treated with thrombolysis (F: 9.8% vs. M: 12.1%; p = 0.02). Women experienced more medical complications (F: 11.7% vs. M: 7.4%; p < 0.001) and tended to have a more prolonged length of stay in the hospital (F: 6.4 ± 7.6 days vs. M: 5.5 ± 6.8 days; p < 0.001).

Primary and secondary outcome measures

Good outcomes at 90 days (mRS score of 0–2) were less frequent in women (F: 53.3% vs. M: 71.2%; p < 0.001). Fewer female patients were taking antiplatelets (F: 78% vs. M: 84.8%; p < 0.001) or statins (F: 81.2% vs. M: 85.7%; p < 0.001). Significantly more female patients experienced a MACE (F: 12.6% vs. M: 6.5%; p < 0.001).

Conclusion

Older age at presentation contributes to poor outcomes following acute stroke in women. Other contributing factors include delays in admission to the hospital, lower rates of thrombolysis, and lower rates of provision of preventative treatments.
Initial results of the INSPIRE clinical trial—investigating radiation dosimetry for differentiated thyroid cancer patients
Authors: Taprogge Jan , Abreu Carla , Vávrová Lenka , Carnegie-Peake Lily , Rushforth Dominic , Gape Paul , Gear Jonathan , Murray Iain , Wong Kee H. , Newbold Kate , Yusuf Siraj , Flux Glenn
Published: May 2023

Introduction

The optimal strategy for differentiated thyroid cancer (DTC) patients treated with radioiodine (RAI) following thyroidectomy remains controversial. Multi-centre clinical studies are essential to identify strategies to improve patient outcomes while minimising treatment-induced toxicity.

Materials and Methods

The INSPIRE clinical trial (ClinicalTrials.gov Identifier: NCT04391244) aims to investigate patient-specific dosimetry for DTC patients and to determine the range of absorbed doses delivered to target and non-target tissues and their relationship with treatment outcome and toxicity.

Results

We report here initial results of the first 30 patients enrolled onto the INSPIRE trial. A large range of absorbed doses are observed for both thyroid remnants and salivary glands, with median values of 4.8 Gy (Range 0.2 – 242 Gy) and 0.3 Gy (Range 0.1 to 1.7 Gy), respectively.

Discussion

The preliminary study results are encouraging and could help to improve our understanding of absorbed doses to thyroid remnants and normal organs following RAI therapy. Such knowledge could potentially enable patient-specific treatment planning with improved clinical outcomes and quality-of-life of patients.
A proteomic study of the effect of UV-B on the regulatory mechanism of flavonoids metabolism in pea seedlings
Authors: Fu Xin , Xu Yinghao , Lu Ming
Published: May 2023

This study aimed to investigate the mechanism of response of pea seedlings to UV-B stress from a proteomic perspective. In this experiment, we measured the growth of pea seedlings in two groups affected by UV-B and unaffected by UV-B and conducted proteomic analysis. The results showed that the ascorbic acid content of UV-B-irradiated pea seedlings increased by 19.0%; the relative content of flavonoids increased by 112.4%; the length of edible parts decreased by 14.2%, and the elongation of roots increased by 11.4%. Proteomics studies showed a significant increase in the levels of CHI, F3'5'H, F3H, F3'H, C4H, and CHR, which are key enzymes for flavonoid synthesis. RT-qPCR indicated that the expression of the regulatory genes of these enzymes was significantly upregulated. This study provided a basis for further studies on the flavonoid response mechanism in pea seedlings during UV stress.
RUNX2 promotes gastric cancer progression through the transcriptional activation of MGAT5 and MMP13
Authors: Wang Ying , Tan Zhibo , Li Xiaoyu , Zhang Lili , Pei Xiaojuan
Published: May 2023

Introduction

RUNX2 is overexpressed in gastric cancer but the mechanism(s) through which it promotes tumor progression remain undefined. Here, we investigated the role of RUNX2 on gastric cancer pathogenesis at the molecular level.

Methods

The qRT-PCR and western bolt were utilized to examine the mRNA and protein levels. CCK-8, Transwell and wound healing assays were used to measure cell proliferation, invasion and migration. CHIP-PCR gel electrophoresis was used to verify RUNX2 as a transcription factor for MMP13 and MGAT5. The in vivo assay was utilized to assess tumor growth. In vivo assay was used to evaluate tumor growth, aberrant expression of RUNX2 and lung metastasis of gastric cancer.

Results

RUNX2 is overexpressed in MKN-45 and AGS cells. Genetic RUNX2 silencing reduced the proliferation, invasion and migration of MKN-45 and AGS cells. Analysis of the gastric cancer samples from the database revealed a significant positive correlation between MGAT5, MMP13, and RUNX2 expression. JASPAR analysis revealed that there was a potential binding site of RUNX2 in the promoter regions of MGAT5 and MMP13, and the experimental results confirmed that RUNX2 could regulate the expression of MGAT5 and MMP13 respectively. In vivo assays confirmed the aberrant expression of RUNX2 in mouse models of gastric cancer and reduced growth and lung metastasis in RUNX2 silenced xenograft tumors assessed.

Conclusion

Collectively, these data reveal that RUNX2 enhances MGAT5 and MMP13 expression in gastric cancer cells and represents a biomarker and potential therapeutic target for gastric cancer therapy.
Association of early immune-related adverse events with treatment efficacy of neoadjuvant Toripalimab in resectable advanced non-small cell lung cancer
Authors: Tao Ye , Li Xiang , Liu Bing , Wang Jia , Lv Chao , Li Shaolei , Wang Yuzhao , Chen Jinfeng , Yan Shi , Wu Nan
Published: May 2023

Background

Neoadjuvant immunotherapy with anti-PD-1 was proved promising in resectable non-small cell lung cancer (NSCLC). Immune-related adverse events (irAEs) have been preliminarily implicated their association with treatment efficacy. Here we elucidated the early onset of irAEs associated with better clinical outcomes in a prospective study (Renaissance study).

Methods

We conducted the prospective study of NSCLC patients treated by neoadjuvant Toripalimab (240mg, every 3 weeks) plus double platinum-based chemotherapy from December 2020 to March 2022 at Peking University Cancer Hospital. Patients were enrolled if they have resectable IIB-IIIB NSCLC without EGFR/ALK mutation. Data were analyzed to explore the relationship between clinical outcome and irAEs after neoadjuvant treatment. A multidisciplinary team including physicians, surgeons, and radiologists, confirmed the irAEs according to the clinical manifestation. The relationship between irAEs and pathological outcomes was analyzed. The Renaissance study was approved by the Peking University Ethic board (2020YJZ58) and registered at https://clinicaltrials.gov/ as NCT04606303.

Results

Fifty-five consecutive patients were enrolled with a male-to-female ratio of 10:1, the median age was 62 years old (IQR: 45-76), of which 44 patients (80%) were diagnosed with squamous cell carcinoma. Forty-eight of 55 patients finally received thoracic surgery with a median preoperative waiting time of 67 days (IQR 39-113 days). Pathological results demonstrated that 31 (64.6%) patients achieved major pathological response (MPR) and 24 (50.0%) achieved complete pathological response (pCR). Among 48 patients who received R0 resection, immunotherapy-related thyroid dysfunction, rash/pruritus and enteritis occurred in 11 patients (22.9%), 7 patients (14.6%), and 1 patient (2.1%), respectively. Six patients (54.5%) with thyroid dysfunction achieved MPR with 5 (45.5%) achieved pCR, and a median time to onset was 45 days (IQR 21-91 days). Six patients (85.7%) with rash or pruritus achieved MPR and 5 patients (71.4%) achieved pCR, with median time to onset being 8 days (IQR 6-29 days). Furthermore, irAEs had no significant influence on operation time (170.6 min vs 165.7 min, P=0.775), intraoperative blood loss (67.4 mL vs 64.3 mL, P=0.831) and preoperative waiting time (93 days vs 97 days, P=0.630) when comparing with patients without irAEs (Figure 1).

Conclusion

The immunotherapy-related rash is potentially associated with pathological outcomes in NSCLC patients after neoadjuvant chemo-immunotherapy, suggesting easy-to-find irAEs, such as rash, can be used as indicators to predict response to neoadjuvant chemo-immunotherapy.

Clinical trial registration

clinicaltrials.gov/, identifier NCT04606303.
Development of a machine learning framework for radiation biomarker discovery and absorbed dose prediction
Authors: Andersson Björn , Langen Britta , Liu Peidi , Dávila López Marcela
Published: May 2023

Background

Molecular radiation biomarkers are an emerging tool in radiation research with applications for cancer radiotherapy, radiation risk assessment, and even human space travel. However, biomarker screening in genome-wide expression datasets using conventional tools is time-consuming and underlies analyst (human) bias. Machine Learning (ML) methods can improve the sensitivity and specificity of biomarker identification, increase analytical speed, and avoid multicollinearity and human bias.

Aim

To develop a resource-efficient ML framework for radiation biomarker discovery using gene expression data from irradiated normal tissues. Further, to identify biomarker panels predicting radiation dose with tissue specificity.

Methods

A strategic search in the Gene Expression Omnibus database identified a transcriptomic dataset (GSE44762) for normal tissues radiation responses (murine kidney cortex and medulla) suited for biomarker discovery using an ML approach. The dataset was pre-processed in R and separated into train and test data subsets. High computational cost of Genetic Algorithm/k-Nearest Neighbor (GA/KNN) mandated optimization and 13 ML models were tested using the caret package in R. Biomarker performance was evaluated and visualized via Principal Component Analysis (PCA) and dose regression. The novelty of ML-identified biomarker panels was evaluated by literature search.

Results

Caret-based feature selection and ML methods vastly improved processing time over the GA approach. The KNN method yielded overall best performance values on train and test data and was implemented into the framework. The top-ranking genes were Cdkn1a, Gria3, Mdm2 and Plk2 in cortex, and Brf2, Ccng1, Cdkn1a, Ddit4l, and Gria3 in medulla. These candidates successfully categorized dose groups and tissues in PCA. Regression analysis showed that correlation between predicted and true dose was high with R2 of 0.97 and 0.99 for cortex and medulla, respectively.

Conclusion

The caret framework is a powerful tool for radiation biomarker discovery optimizing performance with resource-efficiency for broad implementation in the field. The KNN-based approach identified Brf2, Ddit4l, and Gria3 mRNA as novel candidates that have been uncharacterized as radiation biomarkers to date. The biomarker panel showed good performance in dose and tissue separation and dose regression. Further training with larger cohorts is warranted to improve accuracy, especially for lower doses.
Association of maternal personality traits with medication use during pregnancy to appraise unmeasured confounding in long-term pharmacoepidemiological safety studies
Authors: Lupattelli Angela , Trinh Nhung T. H. , Nordeng Hedvig
Published: May 2023

Maternal personality is a possible confounder on the association between prenatal medication exposure and long-term developmental outcomes in offspring, but it is often unmeasured. This study aimed to (i) estimate the association between five maternal personality traits and prenatal use of acetaminophen (including extended use), opioid analgesics, antidepressants, benzodiazepines/z-hypnotics, and antipsychotics; (ii) evaluate, using an applied example, whether unmeasured confounding by maternal neuroticism would make the association between prenatal antidepressant-child ADHD null, using the E-value framework. We used data from 8,879 pregnant women and recent mothers who participated in the Multinational Medication Use in Pregnancy Study, a web-based cross-sectional study performed within the period from 1-Oct-2011 to 29-Feb-2012 in Europe, North America and Australia. Medication use in pregnancy was self-reported by the women. Personality was assessed with the Big Five Inventory, capturing the dimensions of neuroticism, extraversion, openness, agreeableness, and conscientiousness. Adjusted logistic regression analyses were conducted for each trait-medication pair, using the survey weighting. There was a strong association between having high neuroticism and prenatal use of antidepressants (Odds Ratio (OR): 5.63, 95% Confidence Interval (CI): 3.96-8.01), benzodiazepines/z-hypnotics (OR: 6.66, 95% CI: 4.05-10.95), and analgesic opioids (OR: 2.24, 95% CI: 1.41-3.56), but not with antipsychotics. Among women with mental illness, this association attenuated for benzodiazepines/z-hypnotics, but decreased to the null for antidepressants. High neuroticism (OR: 1.31, 95% CI: 1.08-1.59) and high openness (OR: 0.77, 95% CI: 0.64-0.93) were associated with extended use of acetaminophen. The E-value for the Hazard Ratio 1.93 in the applied example was 3.27. If the example study was conducted using a population comparison group, high maternal neuroticism could have explained away the association antidepressant-ADHD. Because the example study included only women with a mental illness, this risk of bias was assessed as minimal. Various personality dispositions in the mother are associated, with a different degree, to prenatal use of medication. The strength of these association can aid researchers in evaluating the influence of uncontrolled confounding by maternal personality in long-term safety studies in pregnancy, using the E-value. This assessment should always be performed in addition to a rigorous study design using approaches to triangulate the evidence.
Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease
Authors: Yang Keungmo , Kim Hee-Hoon , Shim Young-Ri , Ryu Tom , Kim Chang Wook
Published: May 2023

Introduction: The continuous rise in the prevalence of nonalcoholic fatty liver disease (NAFLD) is emerging as a global health issue. Although the protective effects of N-acetylcysteine (NAC), an antioxidant, against various diseases have been reported, it is still unclear whether NAC has therapeutic potential in NAFLD. Thus, the present meta-analysis aimed to investigate the efficacy of NAC on NAFLD in preclinical studies.

Methods: By searching PubMed, Web of Science, and Cochrane Library, 13 studies were included. The methodological quality was assessed based on the SYstematic Review Centre for Laboratory animal Experimentation guideline, and heterogeneity was evaluated with I2 and p values. Publication bias was assessed by Egger’s test and sensitivity analysis was performed.

Results: The results showed that NAC treatment significantly improved systemic and hepatic lipid metabolism (p < 0.01), inflammation-related liver injury (p < 0.01), glucose intolerance (p < 0.05), and hepatic steatosis (p < 0.01) by restoring hepatic glutathione (GSH) (p < 0.05) and GSH reductase (p < 0.05) levels compared to controls in NAFLD-induced animals. Consistently, in bulk, single-cell, and spatial transcriptomics data, the abovementioned target pathways of NAC were strongly associated with NAFLD development in mice and patients.

Conclusion: Our study suggests that NAC has therapeutic potential for NAFLD and should be considered for future clinical trials.
Exploring the dynamics of nonlocal nonlinear waves: Analytical insights into the extended Kadomtsev–Petviashvili model
Authors: Sakkaravarthi Karuppaiya , Singh Sudhir , Karjanto Natanael
Published: May 2023

The study of nonlocal nonlinear systems and their dynamics is a rapidly increasing field of research. In this study, we take a closer look at the extended nonlocal Kadomtsev–Petviashvili (enKP) model through a systematic analysis of explicit solutions. Using a superposed bilinearization approach, we obtained a bilinear form of the enKP equation and constructed soliton solutions. Our findings show that the nature of the resulting solitons, such as the amplitude, width, localization, and velocity, can be controlled by arbitrary solution parameters. The solutions exhibited both symmetric and asymmetric characteristics, including localized bell-type bright solitons, superposed kink-bell-type and antikink-bell-type soliton profiles. The solitons arising in this nonlocal model only undergo elastic interactions while maintaining their initial identities and shifting phases. Additionally, we demonstrated the possibility of generating bound-soliton molecules and breathers with appropriately chosen soliton parameters. The results of this study offer valuable insights into the dynamics of localized nonlinear waves in higher-dimensional nonlocal nonlinear models.
Molecular interaction between plants and Trichoderma species against soil-borne plant pathogens
Authors: Dutta Pranab , Mahanta Madhusmita , Singh Soibam Basanta , Thakuria Dwipendra , Deb Lipa , Kumari Arti , Upamanya Gunadhya K. , Boruah Sarodee , Dey Utpal , Mishra A. K. , Vanlaltani Lydia , VijayReddy Dumpapenchala , Heisnam Punabati , Pandey Abhay K.
Published: May 2023

Trichoderma spp. (Hypocreales) are used worldwide as a lucrative biocontrol agent. The interactions of Trichoderma spp. with host plants and pathogens at a molecular level are important in understanding the various mechanisms adopted by the fungus to attain a close relationship with their plant host through superior antifungal/antimicrobial activity. When working in synchrony, mycoparasitism, antibiosis, competition, and the induction of a systemic acquired resistance (SAR)-like response are considered key factors in deciding the biocontrol potential of Trichoderma. Sucrose-rich root exudates of the host plant attract Trichoderma. The soluble secretome of Trichoderma plays a significant role in attachment to and penetration and colonization of plant roots, as well as modulating the mycoparasitic and antibiosis activity of Trichoderma. This review aims to gather information on how Trichoderma interacts with host plants and its role as a biocontrol agent of soil-borne phytopathogens, and to give a comprehensive account of the diverse molecular aspects of this interaction.
A combined approach of DNA metabarcoding collectively enhances the detection efficiency of medicinal plants in single and polyherbal formulations
Authors: Travadi Tasnim , Shah Abhi P. , Pandit Ramesh , Sharma Sonal , Joshi Chaitanya , Joshi Madhvi
Published: May 2023

Introduction

Empirical research has refined traditional herbal medicinal systems. The traditional market is expanding globally, but inadequate regulatory guidelines, taxonomic knowledge, and resources are causing herbal product adulteration. With the widespread adoption of barcoding and next-generation sequencing, metabarcoding is emerging as a potential tool for detecting labeled and unlabeled plant species in herbal products.

Methods

This study validated newly designed rbcL and ITS2 metabarcode primers for metabarcoding using in-house mock controls of medicinal plant gDNA pools and biomass pools. The applicability of the multi-barcode sequencing approach was evaluated on 17 single drugs and 15 polyherbal formulations procured from the Indian market.

Results

The rbcL metabarcode demonstrated 86.7% and 71.7% detection efficiencies in gDNA plant pools and biomass mock controls, respectively, while the ITS2 metabarcode demonstrated 82.2% and 69.4%. In the gDNA plant pool and biomass pool mock controls, the cumulative detection efficiency increased by 100% and 90%, respectively. A 79% cumulative detection efficiency of both metabarcodes was observed in single drugs, while 76.3% was observed in polyherbal formulations. An average fidelity of 83.6% was observed for targeted plant species present within mock controls and in herbal formulations.

Discussion

In the present study, we achieved increasing cumulative detection efficiency by combining the high universality of the rbcL locus with the high-resolution power of the ITS2 locus in medicinal plants, which shows applicability of multilocus strategies in metabarcoding as a potential tool for the Pharmacovigilance of labeled and unlabeled plant species in herbal formulations.
Role of SEC14-like phosphatidylinositol transfer proteins in membrane identity and dynamics
Authors: Montag Karolin , Ivanov Rumen , Bauer Petra
Published: May 2023

Membrane identity and dynamic processes, that act at membrane sites, provide important cues for regulating transport, signal transduction and communication across membranes. There are still numerous open questions as to how membrane identity changes and the dynamic processes acting at the surface of membranes are regulated in diverse eukaryotes in particular plants and which roles are being played by protein interaction complexes composed of peripheral and integral membrane proteins. One class of peripheral membrane proteins conserved across eukaryotes comprises the SEC14-like phosphatidylinositol transfer proteins (SEC14L-PITPs). These proteins share a SEC14 domain that contributes to membrane identity and fulfills regulatory functions in membrane trafficking by its ability to sense, bind, transport and exchange lipophilic substances between membranes, such as phosphoinositides and diverse other lipophilic substances. SEC14L-PITPs can occur as single-domain SEC14-only proteins in all investigated organisms or with a modular domain structure as multi-domain proteins in animals and streptophytes (comprising charales and land plants). Here, we present an overview on the functional roles of SEC14L-PITPs, with a special focus on the multi-domain SEC14L-PITPs of the SEC14-nodulin and SEC14-GOLD group (PATELLINs, PATLs in plants). This indicates that SEC14L-PITPs play diverse roles from membrane trafficking to organism fitness in plants. We concentrate on the structure of SEC14L-PITPs, their ability to not only bind phospholipids but also other lipophilic ligands, and their ability to regulate complex cellular responses through interacting with proteins at membrane sites.
Core microbiota of wheat rhizosphere under Upper Indo-Gangetic plains and their response to soil physicochemical properties
Authors: Kumar Murugan , Ansari Waquar Akhter , Zeyad Mohammad Tarique , Singh Arjun , Chakdar Hillol , Kumar Adarsh , Farooqi Mohammad Samir , Sharma Anu , Srivastava Sudhir , Srivastava Alok Kumar
Published: May 2023

Wheat is widely cultivated in the Indo-Gangetic plains of India and forms the major staple food in the region. Understanding microbial community structure in wheat rhizosphere along the Indo-Gangetic plain and their association with soil properties can be an important base for developing strategies for microbial formulations. In the present study, an attempt was made to identify the core microbiota of wheat rhizosphere through a culture-independent approach. Rhizospheric soil samples were collected from 20 different sites along the upper Indo-Gangetic plains and their bacterial community composition was analyzed based on sequencing of the V3-V4 region of the 16S rRNA gene. Diversity analysis has shown significant variation in bacterial diversity among the sites. The taxonomic profile identified Proteobacteria, Chloroflexi, Actinobacteria, Bacteroidetes, Acidobacteria, Gemmatimonadetes, Planctomycetes, Verrucomicrobia, Firmicutes, and Cyanobacteria as the most dominant phyla in the wheat rhizosphere in the region. Core microbiota analysis revealed 188 taxa as core microbiota of wheat rhizosphere with eight genera recording more than 0.5% relative abundance. The order of most abundant genera in the core microbiota isRoseiflexus>Flavobacterium> Gemmatimonas>Haliangium>Iamia>Flavisolibacter>Ohtaekwangia>Herpetosiphon.Flavobacterium,Thermomonas,Massilia, UnclassifiedRhizobiaceae, and Unclassified Crenarchaeota were identified as keystone taxa of the wheat rhizosphere. Correlation studies revealed, pH, organic carbon content, and contents of available nitrogen, phosphorus, and iron as the major factors driving bacterial diversity in the wheat rhizosphere. Redundancy analysis has shown the impact of different soil properties on the relative abundance of different genera of the core microbiota. The results of the present study can be used as a prelude to be developing microbial formulations based on core microbiota.
Monitoring weed mechanical and chemical damage stress based on chlorophyll fluorescence imaging
Authors: Quan Longzhe , Chen Keyong , Chen Tianbao , Li Hailong , Li Wenchang , Cheng Tianyu , Xia Fulin , Lou Zhaoxia , Geng Tianyu , Sun Deng , Jiang Wei
Published: May 2023

Currently, mechanical and chemical damage is the main way to carry out weed control. The use of chlorophyll fluorescence (CF) technology to nondestructively monitor the stress physiological state of weeds is significant to reveal the damage mechanism of mechanical and chemical stresses as well as complex stresses. Under simulated real field environmental conditions, different species and leaf age weeds (Digitaria sanguinalis 2-5 leaf age, and Erigeron canadensis 5-10 leaf age) were subjected to experimental treatments for 1-7 days, and fluorescence parameters were measured every 24 h using a chlorophyll fluorometer. The aim of this study was to investigate the changes in CF parameters of different species of weeds (Digitaria sanguinalis, Erigeron canadensis) at their different stress sites under chemical, mechanical and their combined stresses. The results showed that when weeds (Digitaria sanguinalis and Erigeron canadensis) were chemically stressed in different parts, their leaf back parts were the most severely stressed after 7 days, with photosynthetic inhibition reaching R=75%. In contrast, mechanical stress differs from its changes, and after a period of its stress, each parameter recovers somewhat after 1 to 2 days of stress, with heavy mechanical stress R=11%. Complex stress had the most significant effect on CF parameters, mainly in the timing and efficiency of changes in Fv/Fm, Fq’/Fm’, ETR, Rfd, NPQ and Y(NO), with R reaching 71%-73% after only 3-4 days of complex stress, and its changes in complex stress were basically consistent with the pattern of changes in its chemical stress. The results of the study will help to understand the effects of mechanical and chemical stresses and combined stresses on CF parameters of weeds and serve as a guide for efficient weed control operations and conducting weed control in the future.
Moderate nitrogen application improved salt tolerance by enhancing photosynthesis, antioxidants, and osmotic adjustment in rapeseed (Brassica napus L.)
Authors: Wang Long , Zheng Jingdong , Zhou Guisheng , Li Jing , Qian Chen , Lin Guobin , Li Yiyang , Zuo Qingsong
Published: May 2023

Salt stress is a major adverse environmental factor limiting plant growth. Nitrogen (N) application is an effective strategy to alleviate the negative effects of salt stress on plants. To improve the knowledge of the mechanism of N application on alleviating salt stress on rapeseed seedlings, a pot experiment was conducted with four N application treatments (0, 0.1, 0.2, and 0.3 g N kg−1 soil, referred to as N0, N1, N2, and N3, respectively) and exposed to non-salt stress (0 g NaCl kg−1 soil, referred to as S0) and salt stress (3 g NaCl kg−1 soil, referred to as S1) conditions. The results indicated that in comparison with non-salt stress, salt stress increased the Na content (236.53%) and reactive oxygen species (ROS) production such as hydrogen peroxide (H2O2) (30.26%), resulting in cell membrane lipid peroxidation characterized by an increased content of malondialdehyde (MDA) (122.32%) and suppressed photosynthetic rate (15.59%), finally leading to inhibited plant growth such as shorter plant height, thinner root neck, lower leaf area, and decreased dry weight. N application improved the plant growth, and the improvement by N application under salt stress was stronger than that under non-salt stress, suggesting that rapeseed seedlings exposed to salt stress are more sensitive to N application and require N to support their growth. Moreover, seedlings exposed to salt stress under N application showed lower ROS accumulation; increased photosynthesis; higher antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and ascorbic acid (AsA); and greater accumulation of osmotic substances including soluble protein, soluble sugar, and proline, as compared with seedlings without N application. In particular, the best improvement by N application under salt stress occurred at the N2 level, while too high N application could weaken the improvement due to inhibited N metabolism. In summary, this study suggests that moderate N application can improve photosynthesis, antioxidants, and osmoregulation to alleviate the adverse effects of salt stress in rapeseed seedlings.
Implementing the Bashayer chatbot in Saudi higher education: measuring the influence on students' motivation and learning strategies
Authors: Al-Abdullatif Ahlam Mohammed , Al-Dokhny Amany Ahmed , Drwish Amr Mohammed
Published: May 2023

Since the fourth industrial revolution, intelligent software and applications that attempt to mimic human behavior have become increasingly common. The chatbot is an example of an artificial intelligence-based computer program that simulates human behavior by having a conversation and interacting with users using natural language. The implementation of chatbot technology in the educational context is still in its nascent stage, and further investigation into measuring its effectiveness in supporting learning and teaching processes is required, particularly in the context of higher education. Thus, this study presents the design and implementation of a task-oriented chatbot, that is embedded into the WhatsApp application, called Bashayer. It aims at supporting postgraduate students' motivation and learning strategies in Saudi Arabia. A quasi-experimental design with a single-subject experimental approach was adopted with a sample of 60 Saudi postgraduate students. The descriptive analysis of the collected data showed promising results of postgraduate students utilized the Bashayer chatbot system. Participants in the experimental group that used Bashayer were more motivated to learn than those in the control group. Participants also practiced more cognitive and metacognitive learning strategies while utilizing the chatbot compared to the control group. The results of this study are encouraging for the development of chatbot systems similar to Bashayer to support postgraduate students' successful learning. These results contribute to bridging the research gap and adding to the literature on chatbots use in postgraduate educational contexts.
Effects of neurofeedback on the self-concept of children with learning disorders
Authors: Martínez-Briones Benito Javier , Flores-Gallegos Rodrigo , Cárdenas Sonia Y. , Barrera-Díaz Bertha Elena , Fernández Thalía , Silva-Pereyra Juan
Published: May 2023

Children with learning disorders (LDs) often have a lower self-concept than their typically developing peers. Neurofeedback (NFB) treatments seem to improve the cognitive and academic performance of these children, but the effects on self-concept have not been studied. In this exploratory study, 34 right-handed children (8–11 y.o.) with LD and delayed electroencephalographic maturation responded to the Piers–Harris Children’s Self-Concept Scale. One group received NFB (n = 20), and another group (n = 14) served as control, which included 9 children treated with sham-NFB and 5 on a waiting-list. A nonparametric permutation approach was used to compare the academic performance and self-concept difference (postscores – prescores) between the NFB and control groups. Given the smaller size of the control subgroups, a comparison of the percent changes between sham-NFB and the waiting-list was performed with the non-overlap of all pairs (NAP) technique. In the NFB group, the scores of reading, math, and global self-concept increased significantly, highlighting the self-concept subdomains of physical appearance, nonanxiety, popularity, and happiness. Additionally, the sham-NFB subgroup showed better outcomes than the waiting-list subgroup, perhaps due to noncontrolled factors. We found improved academic performance and self-concept in children with LDs who received NFB treatment. This study is an important exploratory step in studying a relevant treatment that seems to ameliorate symptoms of LDs such as anxiety and low self-concept.
Active screen time and imagination in 5–6-years-old children
Authors: Bukhalenkova Daria , Almazova Olga
Published: May 2023

This research focused on the connection between such factors of the active screen time of preschoolers as the time spent playing computer games and parental participation in children’s computer games on imagination in 5–6 years old children. The mothers of 772 children were asked to fill out questionnaires where they described how their children interact with gadgets. 371 of these children also participated in the test that assessed productive imagination using complete the drawing task (such parameters as flexibility, originality, elaboration were assessed). As a result of the study, no relationship was found between imagination and the time spent by preschoolers playing computer games. At the same time, this study revealed significant relationships between imagination and the characteristics of parental participation in the gadgets’ usage by preschoolers. The research showed that imagination flexibility scores are significantly higher in children who use gadgets with siblings or peers than in those who often play alone or with an adult.