bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study
Authors: Zhao Yuheng , Pang Jinglin , Fang Xingyi , Yan Zhaohua , Yang Haili , Deng Qinghua , Ma Tianzhong , Lv Mengqi , Li Yingying , Tu Ziying , Zou Lin
Published: May 2024

Background

Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework.

Methods

After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots.

Results

We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS.

Conclusion

This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.
Extent to which weight loss contributes to improving metabolic dysfunction-associated and metabolic and alcohol related/associated steatotic liver disease: a study on Japanese participants undergoing health checkups
Authors: Fukuda Tatsuya , Okamoto Takahiro , Fukaishi Takahiro , Kawakami Akio , Tanaka Makoto , Yamada Tetsuya , Monzen Koshiro
Published: May 2024

Introduction

The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups.

Methods

This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves.

Results

Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction.

Discussion

Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population.
Integrative assessment of in situ combined bioremediation strategies applied to remediate soils spilled with sewage sludges
Authors: Pérez-Vázquez A. , Urionabarrenetxea E. , Artetxe U. , Rutkoski C. F. , Gomez-Sagasti M. T. , Garcia-Velasco N. , Zaldibar B. , Anza M. , Epelde L. , Garbisu C. , Becerril J. M. , Soto M.
Published: May 2024

Landfills and waste disposal sites in the Basque Country are summarized in the inventory of soils that either currently support or have supported potentially polluting activities or facilities (Law 4/2015). Notably, “Landfill 17,” located in Gernika-Lumo, has been receiving, for decades, sewage sludges from the local wastewater treatment plant (WWTP) as agricultural amendment. In order to decontaminate and recover soil functionality, a combination of bioremediation (which involved bioagumentation and phyto- and vermitechnologies) and complementary bioremediation strategy (i.e., promotion and maintenance of the native vegetation) was implemented in situ. Physicochemical and ecotoxicological characterization were achieved. Furthermore, an ecotoxicological assessment of the soils upon flora and fauna was carried out through the application of different bioassays and biomarkers. Additionally, an integrative biomarker response (IBR/n) index was calculated to provide a holistic view of the soil general status. Critical pollutants [Cd, Cr, Ni, Pb, benzo(a)pyrene, and dieldrin] were observed in most of the treated sites. Microbial parameters did not present remarkable differences among sites. However, plant indicators pointed the non-treated site (MN8) as the unhealthiest. This was also observed in earthworms’ immune system, where cytotoxicity appears when exposed to non-treated soils. In conclusion, this field study showed that the combination of bioaugmentation, phytoremediation with native species, and vermiremediation is highly useful in eliminating mixed contamination, improving soil health, and ultimately restoring ecosystem functionality and biodiversity.
IL-38 promotes the development of prostate cancer
Authors: Wu Huiyan , Yang Jing , Yuan Liuhong , Tan Zhenyu , Zhang Xiuqin , Hambly Brett D. , Bao Shisan , Tao Kun
Published: May 2024

Introduction

Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment.

Materials and methods

The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics.

Results

There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients.

Conclusion

These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.
Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease
Authors: Li Yang , Li Xiao-meng , Duan Hao-yu , Yang Kai-di , Ye Jun-feng
Published: May 2024

In the advancement of Inflammatory Bowel Disease (IBD) treatment, existing therapeutic methods exhibit limitations; they do not offer a complete cure for IBD and can trigger adverse side effects. Consequently, the exploration of novel therapies and multifaceted treatment strategies provides patients with a broader range of options. Within the framework of IBD, gut microbiota plays a pivotal role in disease onset through diverse mechanisms. Bacteriophages, as natural microbial regulators, demonstrate remarkable specificity by accurately identifying and eliminating specific pathogens, thus holding therapeutic promise. Although clinical trials have affirmed the safety of phage therapy, its efficacy is prone to external influences during storage and transport, which may affect its infectivity and regulatory roles within the microbiota. Improving the stability and precise dosage control of bacteriophages—ensuring robustness in storage and transport, consistent dosing, and targeted delivery to infection sites—is crucial. This review thoroughly explores the latest developments in IBD treatment and its inherent challenges, focusing on the interaction between the microbiota and bacteriophages. It highlights bacteriophages’ potential as microbiome modulators in IBD treatment, offering detailed insights into research on bacteriophage encapsulation and targeted delivery mechanisms. Particular attention is paid to the functionality of various carrier systems, especially regarding their protective properties and ability for colon-specific delivery. This review aims to provide a theoretical foundation for using bacteriophages as microbiome modulators in IBD treatment, paving the way for enhanced regulation of the intestinal microbiota.
Comparison of linear and nonlinear modeling approaches to develop an abundance index based on voyage and market data for a data-limited fishery
Authors: Yuan Tzu-Lun , Xu Haikun , Lu Bing-Jing , Chang Shui-Kai
Published: May 2024

Introduction

Worldwide coastal fish resources face severe threats from fisheries overexploitation. However, the evaluation of abundance trends in most coastal fisheries is constrained by limited data. This study took blackmouth croaker (Atrobucca nibe), a stock depleted by coastal trawl fishery in southwestern Taiwan, as an example to showcase the development of a relative abundance index from data-limited fishery (only landing data were available).

Methods

This study employed unique data sourcing from voyage data recorders (VDRs) to estimate fishing effort (in combination with landing data to estimate the catch per unit effort, CPUE) that demonstrated the potential application in global data-limited fisheries and assessed alternative approaches for predictors of fishery-targeting practices to condition effort for producing more accurate metrics of relative abundance. The nominal CPUE was standardized using three statistical models: generalized linear model, generalized additive model (GAM), and vector-autoregressive spatiotemporal models (VASTs) with two treatments of each of the four effects: environmental (sea temperature, salinity, density of mixing layer, seafloor temperature, and chlorophyll), vessel, spatial, and targeting effects. A total of 15 models were designed and compared for these effects, and their explanatory power (EP) was evaluated using cross-validation R2 and other metrics.

Results and discussion

Results indicated that the targeting effect exerted the most significant influence on standardization and was suggested to be addressed through the principal component analysis (PCA) approach. Both vessel and spatial effects demonstrated considerable influence, whereas the environmental effect exhibited a limited impact, possibly due to the small fishing area in this study. Regarding models’ EP, given the nonlinear nature of the PCA algorithm and environmental data, the study highlighted the superiority of the GAM over linear-based models. However, incorporating nonlinear features in VAST (M15) makes it the most effective model in terms of predictive power in this study. Concerning the stock status, despite variations in relative CPUE trends among major models, a general declining trend since 2015 signals the potential decline of the blackmouth stock and urges fishery managers to consider further design of management measures.
Exploratory insights into prefrontal cortex activity in continuous glucose monitoring: findings from a portable wearable functional near-infrared spectroscopy system
Authors: Chen Jiafa , Yu Kaiwei , Zhuang Songlin , Zhang Dawei
Published: May 2024

The escalating global prevalence of diabetes highlights an urgent need for advancements in continuous glucose monitoring (CGM) technologies that are non-invasive, accurate, and user-friendly. Here, we introduce a groundbreaking portable wearable functional near-infrared spectroscopy (fNIRS) system designed to monitor glucose levels by assessing prefrontal cortex (PFC) activity. Our study delineates the development and application of this novel fNIRS system, emphasizing its potential to revolutionize diabetes management by providing a non-invasive, real-time monitoring solution. Fifteen healthy university students participated in a controlled study, where we monitored their PFC activity and blood glucose levels under fasting and glucose-loaded conditions. Our findings reveal a significant correlation between PFC activity, as measured by our fNIRS system, and blood glucose levels, suggesting the feasibility of fNIRS technology for CGM. The portable nature of our system overcomes the mobility limitations of traditional setups, enabling continuous, real-time monitoring in everyday settings. We identified 10 critical features related to blood glucose levels from extensive fNIRS data and successfully correlated PFC function with blood glucose levels by constructing predictive models. Results show a positive association between fNIRS data and blood glucose levels, with the PFC exhibiting a clear response to blood glucose. Furthermore, the improved regressive rule principal component analysis (PCA) method outperforms traditional PCA in model prediction. We propose a model validation approach based on leave-one-out cross-validation, demonstrating the unique advantages of K-nearest neighbor (KNN) models. Comparative analysis with existing CGM methods reveals that our paper’s KNN model exhibits lower RMSE and MARD at 0.11 and 8.96%, respectively, and the fNIRS data were highly significant positive correlation with actual blood glucose levels (r = 0.995, p < 0.000). This study provides valuable insights into the relationship between metabolic states and brain activity, laying the foundation for innovative CGM solutions. Our portable wearable fNIRS system represents a significant advancement in effective diabetes management, offering a promising alternative to current technologies and paving the way for future advancements in health monitoring and personalized medicine.
Advances in determining the gross tumor target volume for radiotherapy of brain metastases
Authors: Du Shanshan , Gong Guanzhong , Liu Rui , Meng Kangning , Yin Yong
Published: May 2024

Brain metastases (BMs) are the most prevalent intracranial malignant tumors in adults and are the leading cause of mortality attributed to malignant brain diseases. Radiotherapy (RT) plays a critical role in the treatment of BMs, with local RT techniques such as stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) showing remarkable therapeutic effectiveness. The precise determination of gross tumor target volume (GTV) is crucial for ensuring the effectiveness of SRS/SBRT. Multimodal imaging techniques such as CT, MRI, and PET are extensively used for the diagnosis of BMs and GTV determination. With the development of functional imaging and artificial intelligence (AI) technology, there are more innovative ways to determine GTV for BMs, which significantly improve the accuracy and efficiency of the determination. This article provides an overview of the progress in GTV determination for RT in BMs.
Leveraging radiomics and AI for precision diagnosis and prognostication of liver malignancies
Authors: Haghshomar Maryam , Rodrigues Darren , Kalyan Aparna , Velichko Yury , Borhani Amir
Published: May 2024

Liver tumors, whether primary or metastatic, have emerged as a growing concern with substantial global health implications. Timely identification and characterization of liver tumors are pivotal factors in order to provide optimum treatment. Imaging is a crucial part of the detection of liver tumors; however, conventional imaging has shortcomings in the proper characterization of these tumors which leads to the need for tissue biopsy. Artificial intelligence (AI) and radiomics have recently emerged as investigational opportunities with the potential to enhance the detection and characterization of liver lesions. These advancements offer opportunities for better diagnostic accuracy, prognostication, and thereby improving patient care. In particular, these techniques have the potential to predict the histopathology, genotype, and immunophenotype of tumors based on imaging data, hence providing guidance for personalized treatment of such tumors. In this review, we outline the progression and potential of AI in the field of liver oncology imaging, specifically emphasizing manual radiomic techniques and deep learning-based representations. We discuss how these tools can aid in clinical decision-making challenges. These challenges encompass a broad range of tasks, from prognosticating patient outcomes, differentiating benign treatment-related factors and actual disease progression, recognizing uncommon response patterns, and even predicting the genetic and molecular characteristics of the tumors. Lastly, we discuss the pitfalls, technical limitations and future direction of these AI-based techniques.
Correlation study of serum lipid levels and lipid metabolism-related genes in cervical cancer
Authors: Cheng Lin , Li Zhuo , Zheng Qingmei , Yao Qin
Published: May 2024

Objective

Lipid metabolism plays an important role in cancer. The aim of this study was to investigate the relationship between lipid metabolism and the development of cervical cancer, and to explore the prognostic significance of lipid metabolism-related genes in patients with cervical cancer.

Methods

Initially, we retrospectively collected data from 1589 cervical cancer patients treated at the Affiliated Hospital of Qingdao University, with 1589 healthy individuals from the physical examination center serving as the control group. The correlation between their serum lipid levels and cervical cancer was analyzed. Subsequently, leveraging public databases, we conducted comprehensive studies on lipid metabolism-related genes. Additionally, we analyzed RNA expression profiling and clinical information sourced from TCGA and GTEx databases. Finally, we established a prognostic model integrating 9 genes associated with lipid metabolism and generated a nomogram model using R. GO and KEGG were performed to explore the functions and pathways of lipid metabolism-related genes.

Results

Our findings revealed that patients with cervical cancer exhibited dyslipidemia, characterized by elevated levels of TC, TG, and LDL-C, alongside reduced HDL-C levels compared to controls (P<0.05). Interestingly, compared with early-stage patients, advanced patients had lower HDL-C level and higher LDL-C level. Regression analysis further highlighted high TC, TG, and LDL-C as significant risk factors for cervical cancer. Then a total of 188 lipid metabolism-related genes were identified and a prognostic signature based on 9 genes was established and validated. The results of the GO and KEGG functional analysis indicated that the lipid metabolism-related genes are primarily concentrated on pathways associated with fatty acid metabolism.

Conclusion

Our study underscores the varying degrees of dyslipidemia observed in patients with cervical cancer, emphasizing the relevance of serum lipids in disease development. Our prognostic riskScore model predicted the overall survival time of patients based on 9 genes associated with lipid metabolism. These 9 genes may be tumor biomarkers and new targets for the treatment of cervical cancer.
Case report: Increased efficacy of cetuximab after pembrolizumab failure in cutaneous squamous cell carcinoma
Authors: Morecroft Renee , Phillipps Jordan , Zhou Alice , Butt Omar , Khaddour Karam , Johanns Tanner , Ansstas George
Published: May 2024

Immunotherapy is the first-line option for treating advanced cutaneous squamous cell carcinoma (cSCC). However, up to half of patients experience no benefit and treatment resistance, warranting newer therapeutic approaches. Combinatory approaches, including cetuximab, may help overcome immunotherapy resistance and improve response rates in advanced cSCC. We report three cases of metastatic cSCC that achieved significant clinical responses after cetuximab therapy following initial progression on pembrolizumab. We have retrospectively reviewed these cases at a single academic center between 2018 and 2023. All patients initially progressed on pembrolizumab, after which cetuximab (mono- or combination therapy) was added with two complete responses and one partial response. Initial responses were noted within 2 to 7 months of starting cetuximab. While the benefit of cetuximab and immunotherapy in head-and-neck squamous cell carcinoma has growing evidence, information regarding cSCC remains limited. This study adds three cases to the underreported literature on treating advanced cSCC with cetuximab after initially failing immunotherapy.
Kinetics of BCR::ABL1 transcript levels and molecular relapse after tyrosine kinase inhibitors discontinuation in chronic myeloid leukemia patients: preliminary results from the DES-CML study
Authors: Murbach Bruna , Duarte Gislaine , Palma Leonardo Carvalho , Miranda Eliana , Duffles Guilherme , Furlin Graziele Pavan , Toni Isabella , De Souza Carmino , Binelli Larissa , Bassan Vitor Leonardo , de Castro Fabiola Attie , Figueiredo-Pontes Lorena Lobo de , Pagnano Katia Borgia Barbosa
Published: May 2024

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia. Patients who achieve sustained deep molecular response are eligible for treatment discontinuation. DES-CML is an ongoing, phase 2 multicentric discontinuation trial. Adult patients with CML in chronic phase with typical BCR::ABL1 transcripts, stable deep molecular response (MR4.5 IS) for two years, and no previous resistance were eligible. Patients underwent a phase of TKI dose de-escalation for six months before discontinuation. TKI was reintroduced at the previous dose if the patient lost major molecular response (MMR) at any time. This study aimed to assess the impact of BCR-ABL transcript kinetics during TKI de-escalation and discontinuation phases on treatment-free survival. So far, the study recruited 41 patients, and 38 patients discontinued therapy (4 were in the second discontinuation attempt). Eleven patients lost MMR, one during the de-escalation phase and ten after discontinuation. 24-month treatment-free survival was 66% (95% CI: 48-84%) in a median follow-up of 7 (1–30) months. No patient lost hematological response or had disease progression. A higher rate of molecular relapses occurred in patients with fluctuating BCR::ABL1 levels after the discontinuation phase (with loss of MR4.5, but no loss of MMR) (P=0.04, HR-4.86 (1.03-22.9) but not confirmed in the multivariate analysis. The longer duration of TKI treatment (P=0.03, HR-1.02, 95%CI - 1.00-1.04) and MMR (P=0.004, HR-0.95, 95%CI - 0.92-098) were independent factors of a lower relapse rate.
Fibrinogen and tumors
Authors: Wu Xinyuan , Yu Xiaomin , Chen Cheng , Chen Chenlu , Wang Yuxin , Su Dongyan , Zhu Liqing
Published: May 2024

Elevated plasma fibrinogen (Fg) levels consistently correlate with an unfavorable prognosis in various tumor patient cohorts. Within the tumor microenvironment, aberrant deposition and expression of Fg have been consistently observed, interacting with multiple cellular receptors and thereby accentuating its role as a regulator of inflammatory processes. Specifically, Fg serves to stimulate and recruit immune cells and pro-inflammatory cytokines, thereby contributing to the promotion of tumor progression. Additionally, Fg and its fragments exhibit dichotomous effects on tumor angiogenesis. Notably, Fg also facilitates tumor migration through both platelet-dependent and platelet-independent mechanisms. Recent studies have illuminated several tumor-related signaling pathways influenced by Fg. This review provides a comprehensive summary of the intricate involvement of Fg in tumor biology, elucidating its multifaceted role and the underlying mechanisms.
Stratifying risk of disease in haematuria patients using machine learning techniques to improve diagnostics
Authors: Drożdż Anna , Duggan Brian , Ruddock Mark W. , Reid Cherith N. , Kurth Mary Jo , Watt Joanne , Irvine Allister , Lamont John , Fitzgerald Peter , O’Rourke Declan , Curry David , Evans Mark , Boyd Ruth , Sousa Jose
Published: May 2024

Background

Detailed and invasive clinical investigations are required to identify the causes of haematuria. Highly unbalanced patient population (predominantly male) and a wide range of potential causes make the ability to correctly classify patients and identify patient-specific biomarkers a major challenge. Studies have shown that it is possible to improve the diagnosis using multi-marker analysis, even in unbalanced datasets, by applying advanced analytical methods. Here, we applied several machine learning algorithms to classify patients from the haematuria patient cohort (HaBio) by analysing multiple biomarkers and to identify the most relevant ones.

Materials and methods

We applied several classification and feature selection methods (k-means clustering, decision trees, random forest with LIME explainer and CACTUS algorithm) to stratify patients into two groups: healthy (with no clear cause of haematuria) or sick (with an identified cause of haematuria e.g., bladder cancer, or infection). The classification performance of the models was compared. Biomarkers identified as important by the algorithms were also analysed in relation to their involvement in the pathological processes.

Results

Results showed that a high unbalance in the datasets significantly affected the classification by random forest and decision trees, leading to the overestimation of the sick class and low model performance. CACTUS algorithm was more robust to the unbalance in the dataset. CACTUS obtained a balanced accuracy of 0.747 for both genders, 0.718 for females and 0.803 for males. The analysis showed that in the classification process for the whole dataset: microalbumin, male gender, and tPSA emerged as the most informative biomarkers. For males: age, microalbumin, tPSA, cystatin C, BTA, HAD and S100A4 were the most significant biomarkers while for females microalbumin, IL-8, pERK, and CXCL16.

Conclusions

CACTUS algorithm demonstrated improved performance compared with other methods such as decision trees and random forest. Additionally, we identified the most relevant biomarkers for the specific patient group, which could be considered in the future as novel biomarkers for diagnosis. Our results have the potential to inform future research and provide new personalised diagnostic approaches tailored directly to the needs of the individuals.
Examination of the role of mutualism in immune evasion
Authors: Gourmet Lucie , Walker-Samuel Simon , Mallick Parag
Published: May 2024

Though the earliest stages of oncogenesis, post initiation, are not well understood, it is generally appreciated that a successful transition from a collection of dysregulated cells to an aggressive tumour requires complex ecological interactions between cancer cells and their environment. One key component of tumorigenesis is immune evasion. To investigate the interplay amongst the ecological behaviour of mutualism and immune evasion, we used a computational simulation framework. Sensitivity analyses of the growth of a virtual tumour implemented as a 2D-hexagonal lattice model suggests tumour survival depends on the interplay between growth rates, mutualism and immune evasion. In 60% of simulations, cancer clones with low growth rates, but exhibiting mutualism were able to evade the immune system and continue progressing suggesting that tumours with equivalent growth rates and no mutualism are more likely to be eliminated than tumours with mutualism. Tumours with faster growth rates showed a lower dependence upon mutualism for progression. Geostatistical analysis showed decreased spatial heterogeneity over time for polyclonal tumours with a high division rate. Overall, these results suggest that in slow growing tumours, mutualism is critical for early tumorigenesis.
Exploring the putative microRNAs cross-kingdom transfer in Solanum lycopersicum-Meloidogyne incognita interactions
Authors: Leonetti Paola , Dallera Debora , De Marchi Davide , Candito Pamela , Pasotti Lorenzo , Macovei Anca
Published: May 2024

Introduction

Plant-pathogen interaction is an inexhaustible source of information on how to sustainably control diseases that negatively affect agricultural production. Meloidogyne incognita is a root-knot nematode (RKN), representing a pest for many crops, including tomato (Solanum lycopersicum). RKNs are a global threat to agriculture, especially under climate change, and RNA technologies offer a potential alternative to chemical nematicides. While endogenous microRNAs have been identified in both S. lycopersicum and M. incognita, and their roles have been related to the regulation of developmental changes, no study has investigated the miRNAs cross-kingdom transfer during this interaction.

Methods

Here, we propose a bioinformatics pipeline to highlight potential miRNA-dependent cross-kingdom interactions between tomato and M. incognita.

Results

The obtained data show that nematode miRNAs putatively targeting tomato genes are mostly related to detrimental effects on plant development and defense. Similarly, tomato miRNAs putatively targeting M. incognita biological processes have negative effects on digestion, mobility, and reproduction. To experimentally test this hypothesis, an in vitro feeding assay was carried out using sly-miRNAs selected from the bioinformatics approach. The results show that two tomato miRNAs (sly-miRNA156a, sly-miR169f) soaked by juvenile larvae (J2s) affected their ability to infect plant roots and form galls. This was also coupled with a significant downregulation of predicted target genes (Minc11367, Minc00111), as revealed by a qRT-PCR analysis.

Discussions

Therefore, the current study expands the knowledge related to the cross-kingdom miRNAs involvement in host-parasite interactions and could pave the way for the application of exogenous plant miRNAs as tools to control nematode infection.
Biobehavioral approach to distinguishing panic symptoms from medical illness
Authors: Tunnell Natalie C. , Corner Sarah E. , Roque Andres D. , Kroll Juliet L. , Ritz Thomas , Meuret Alicia E.
Published: May 2024

Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.
Development of portfolio management tools in crop breeding programs: a case study of cassava in sub-Saharan Africa
Authors: Egesi Chiedozie , Mbanjo Edwige Gaby Nkouaya , Kawuki Robert , Teeken Béla , Rabbi Ismail Yusuf , Prempeh Ruth , Jiwuba Lydia , Njoku Damian , Kulembeka Heneriko , Gwandu Francisca , Woyengo Vincent , Parkes Elizabeth , Ofei Richard , Banda Vishnuvardhan Reddy , Ntawuruhunga Pheneas , Derera John , Weber Steffen , Kulakow Peter
Published: May 2024

The response to the diverse needs along the cassava value chain, the urge to increase genetic gain, and the need for rapid varietal turnover will necessitate not only technological innovations but also transformation of public breeding programs in sub-Saharan Africa (SSA). We developed guiding, flexible and adaptative tools for portfolio management of cassava breeding. The cassava breeding and product development pipeline process was mapped to illustrate activities of each stage, as well as to clarify key decision points. Stakeholders involved at all stages of breeding were identified. This allowed for identification of gaps and new crucial functions. To clarify accountability and reduce complexity in the decision-making at key decision points, the roles were mapped against decision-rights at each stage-gate. Cassava crop calendars for the different regions in SSA were developed to facilitate better planning. A product advancement template was developed to guide product advancement. The tools that have been developed and stage-gate mapping, will support regional efforts to establish more structured, transparent, participatory, efficient, inclusive, and demand-driven cassava breeding in the region. These approaches could be customized to other commodities.
Transcriptomics reveals age-related changes in ion transport–related factors in yak lungs
Authors: Xie Xiating , Wei Yating , Cui Yan , Zhang Qian , Lu Hongqin , Chen Liang , He Junfeng
Published: May 2024

Yaks inhabit high-altitude, low-oxygen regions, where ion transport functions play a crucial role in maintaining intracellular and extracellular ionic balance and regulating pulmonary vascular tension. These functions affect pulmonary ventilation and blood flow rate, aiding tissue development and enhancing oxygen transfer efficiency, thus facilitating better adaptation to hypoxic environments. To investigate the regulatory mechanisms of ion transport-related factors on the growth and development of yak lungs, we employed RNA sequencing (RNA-seq)for sequencing the transcriptome in the lung tissues of neonatal (1-day-old), juvenile (1-year-old), and adult (4-year-old) yaks. We also performed differential gene expression and functional analyses. The results yielded 26 genes associated with ion transport, mainly enriched in the salivary and pancreatic secretion pathways. Finally, we used several methods including quantitative polymerase chain reaction (qRT-PCR), and Western blotting (WB), immunohistochemical (IHC) and immunofluorescence (IF) staining to determine the distribution of the expression of the ion transport genes FOXI1, KCNMA1, and SLC12A2 in yak lung tissues. qRT-PCR and WB results indicated that mRNA and protein relative expression levels of FOXI1 and SLC12A2 were significantly higher in neonatal yaks than in juvenile and adult yaks (all p < 0.05), whereas those of KCNMA1 were significantly higher in adult yaks than in neonatal and juvenile yaks (all p < 0.05). IHC and IF results demonstrated that FOXI1, KCNMA1, and SLC12A2 were distributed among the epithelial mucosal layers (including ciliated, goblet, and Clara cells) of the yaks’ bronchi and their branches in the lungs across different age groups of yak. Therefore, our results suggested that FOXI1, KCNMA1, and SLC12A2 may be strongly associated with the development and aging processes in yak lungs. These results provide insights into the molecular mechanisms underlying the yak’s adaptation to high-altitude environments and valuable references for further research.
Three Cube Packing for All Dimensions
Authors: Adamko Peter
Published: May 2024

Let Vn(d) denote the least number, such that every collection of n d-cubes with total volume 1 in d-dimensional (Euclidean) space can be packed parallelly into some d-box of volume Vn(d). We show that V3(d)=r1−dd if d≥11 and V3(d)=1r+1rd+1r−rd+1 if 2≤d≤10, where r is the only solution of the equation 2(d−1)kd+dkd−1=1 on 22,1 and (k+1)d(1−k)d−1dk2+d+k−1=kddkd+1+dkd+kd+1 on 22,1, respectively. The maximum volume is achieved by hypercubes with edges x, y, z, such that x=2rd+1−1/d, y=z=rx if d≥11, and x=rd+(1r−r)d+1−1/d, y=rx, z=(1r−r)x if 2≤d≤10. We also proved that only for dimensions less than 11 are there two different maximum packings, and for all dimensions greater than 10, the maximum packing has the same two smallest cubes.
Collaboration to Address the Challenges Faced by Smallholders in Practicing Organic Agriculture: A Case Study of the Organic Sorghum Industry in Zunyi City, China
Authors: Wu Sheng , Li Shanwei
Published: May 2024

In many developing countries, organic agriculture is increasingly recognized as a key strategy for promoting rural economic development and improving farmer welfare. It is primarily smallholders who form the foundation of organic production in these areas. However, these farmers face significant challenges in adopting organic farming methods. The aim of this paper is to investigate solutions to the challenges encountered by smallholders. This research utilizes an integrated approach and includes a case study of the organic sorghum sector in Zunyi, China. The findings indicate that (1) a robust partnership has been established between enterprises, government, and farmers in the organic sorghum industry in Zunyi. Enterprises purchase the sorghum, cover organic certification costs, and partially fund material inputs, while local government facilitates organization, coordination, and technical support, with farmers responsible for production. (2) This collaboration has catalyzed high-quality development in the industry, benefiting all stakeholders. (3) Through this collaborative model, common challenges faced by smallholders, such as obstacles in obtaining certification, income fluctuations, and unfair market conditions, have been mitigated. Consequently, smallholders secure stable and reliable income as they benefit from favorable contract prices for organic sorghum and the assumption by enterprises of most material input costs. This study offers valuable empirical evidence that can guide the expansion of organic agriculture in similar regions and countries.
Do Factor Misallocations Affect Food Security? Evidence from China
Authors: Jiang Tuanbiao , Zhong Min , Gao Anrong , Ma Guoqun
Published: May 2024

The reasonable allocation of grain production factors is of vital importance to food security and agricultural development. To assess the impact of agricultural factor misallocation on food security, this paper, based on the panel data from China spanning from 2005 to 2019, conducted a comprehensive evaluation of agricultural factor misallocation and food security coefficients across 31 provinces in China, using a spatial Durbin model to examine the effects of factor misallocations on food security. The findings are as follows: (1) Production factor misallocation has significant negative impacts on food security, among them, capital misallocation and labor misallocation inhibiting food security in the local and neighboring areas, and land misallocation has a significant negative impact on food security in local areas, while its spatial spillover effect is no longer significant. (2) Mechanism analysis shows that capital misallocation and labor misallocation hinder the development of transportation infrastructure and the transfer of rural labor, thereby reducing food security. Land misallocation has accelerated the construction of transportation infrastructure, promoted the migration of rural labor, and helped ensure food security. (3) The regional heterogeneity test reveals that capital misallocation and labor misallocation hinder food security in major grain-producing areas and both sides of the Hu Huanyong Line (Hu Line). Meanwhile, land misallocation hinders food security development in various grain-producing areas, as well as the southeast of the Hu Line. Based on the above conclusions, this paper proposes suggestions to improve the efficiency of land and labor resource allocation, accelerate the construction of transportation infrastructure, and encourage the transfer speed of surplus agricultural labor.
Low Red to Far-Red Light Ratio Promoted Growth and Fruit Quality in Salt-Stressed Tomato Plants Based on Metabolomic Analysis
Authors: Miao Yanxiu , Li Ruochan , Li Caixia , Zhou Xiaolin , Xu Xinxin , Sun Meihua , Bai Longqiang , Hou Leiping
Published: May 2024

Salt stress poses a serious threat to tomato production. Red to far-red light ratio (R/FR) is actively involved in the regulation of tomato growth and development; however, it is still uncertain whether and how R/FR improves fruit quality under salt stress. Thus, we conducted metabolomic analysis of tomato fruits under four treatments, including R/FR = 7 (CK), R/FR = 0.7 (L), R/FR = 7 and 100 mmol·L−1 NaCl (Na), and R/FR = 0.7 and 100 mmol·L−1 NaCl (Na+L). Metabolomic analysis indicated that both low R/FR and salt stress enhanced organic acids and phenols accumulation; however, additional low R/FR mainly improved carbohydrates, organic acids, phenols and amino acids accumulation in salt-stressed tomato fruit. Physiological studies were consistent with the above results and further revealed that additional low R/FR drastically promoted plant growth, soluble sugar, total phenol and flavonoid contents, improved osmotic pressure balance and antioxidant capacity, and notably relieved the salt stress-induced suppressions. This study proved the importance of applying light quality regulation in salt-resistant tomato production.
Soybean CEP6 Signaling Peptides Positively Regulate Nodulation
Authors: Wu Shuai , Wang Xiaoli , Qin Jie , Tian Wenqing , Wang Min , Yue Aiqin , Wang Lixiang , Du Weijun , Zhao Jinzhong
Published: May 2024

Nodulation is the most efficient nitrate assimilation system in the ecosystem, while excessive fertilization has an increased nitrate inhibition effect; deciphering the nitrate signal transduction mechanism in the process is of the utmost importance. In this study, genome-wide analyses of the GmCEP genes were applied to identify nodulation-related CEP genes; 22 GmCEP family members were identified, while GmCEP6 was mainly expressed in nodules and significantly responded to nitrate treatment and rhizobium infection, especially in later stages. Overexpression and CRISPR-Cas9 were used to validate its role in nodulation. We found that GmCEP6 overexpression significantly increased the nodule number, while GmCEP6 knock-out significantly decreased the nodule number, which suggests that GmCEP6 functions as a positive regulator in soybean nodulation. qRT-PCR showed that alterations in the expression of GmCEP6 affected the expression of marker genes in the Nod factor signaling pathway. Lastly, the function of GmCEP6 in nitrate inhibition of nodulation was analyzed; nodule numbers in the GmCEP6-overexpressed roots significantly increased under nitrogen treatments, which suggests that GmCEP6 functions in the resistance to nitrate inhibition. The study helps us understand that GmCEP6 promotes nodulation and participates in the regulation of nitrate inhibition of nodulation, which is of great significance for high efficiency utilization of nitrogen in soybeans.
Different Land-Use Effects on Soil Aggregates and Aggregate-Associated Organic Carbon in Eastern Qinghai–Tibet Plateau
Authors: Zhang Yongkun , Li Ying , Ma Zhanming , Cui Zilong , Sheng Haiyan , Li Runjie
Published: May 2024

Land use changes modify soil properties, including aggregate structure, and thus, profoundly affect soil quality and health. However, the effects of land use changes originating from alpine grassland on soil aggregates and aggregate-associated organic carbon have received little attention. Soil aggregate fraction, aggregate-associated organic carbon and relevant influencing factors were determined at 0–20, 20–40 cm soil layers for alpine grassland, cropland and abandoned land in the eastern Qinghai–Tibet Plateau (QTP), and their relationships were analyzed by partial least square regression (PLSR). Results showed the following: (1) conversion from alpine grassland to cropland resulted in a significant decline macroaggregate fraction (R0.25), mean weight diameter (MWD), mean weight diameter (GMD), soil organic carbon (SOC), and microaggregate-associated SOC; (2) almost all aggregate stability indexes, SOC, and aggregate-associated SOCs were significantly positively correlated with silt and glomalin, suggesting that the binding of fine particles (silt) with the organic cementing agent (glomalin) was probably a key mechanism of SOC formation and aggregate stability in the studied region; (3) compared with biotic factors such as SOC, glomalin and root biomass, abiotic factors including silt and sand can better predict aggregate stability and SOC fraction using the PLSR model. The above results indicated that the conversion of alpine grassland to other land use types in high altitude areas would destroy soil structure and decrease soil organic carbon content, and then reduce soil quality.