bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying physiological and genetic determinants of faba bean transpiration response to evaporative demand
Authors: Mandour Hend , Khazaei Hamid , Stoddard Frederick L , Dodd Ian C 
Published: January 2023

AbstractBackground and AimsLimiting maximum transpiration rate (TR) under high vapour pressure deficit (VPD) works as a water conservation strategy. While some breeding programmes have incorporated this trait into some crops to boost yields in water-limited environments, its underlying physiological mechanisms and genetic regulation remain unknown for faba bean (Vicia faba). Thus, we aimed to identify genetic variation in the TR response to VPD in a population of faba bean recombinant inbred lines (RILs) derived from two parental lines with contrasting water use (Mélodie/2 and ILB 938/2).MethodsPlants were grown in well-watered soil in a climate-controlled glasshouse with diurnally fluctuating VPD and light conditions. Whole plant transpiration was measured in a gas exchange chamber that tightly regulated VPD around the shoot under constant light, while whole-plant hydraulic conductance and its components (root and stem hydraulic conductance) were calculated from dividing TR by water potential gradients measured with a pressure chamber.Key ResultsAlthough TR of Mélodie/2 increased linearly with VPD, ILB 938/2 limited its TR above 2.0 kPa. Nevertheless, Mélodie/2 had a higher leaf water potential than ILB 938/2 at both low (1.0 kPa) and high (3.2 kPa) VPD. Almost 90 % of the RILs limited their TR at high VPD with a break-point (BP) range of 1.5–3.0 kPa and about 10 % had a linear TR response to VPD. Thirteen genomic regions contributing to minimum and maximum transpiration, and whole-plant and root hydraulic conductance, were identified on chromosomes 1 and 3, while one locus associated with BP transpiration was identified on chromosome 5.ConclusionsThis study provides insight into the physiological and genetic control of transpiration in faba bean and opportunities for marker-assisted selection to improve its performance in water-limited environments.
Allometric relationships between leaf and petiole traits across 31 floating-leaved plants reveal a different adaptation pattern from terrestrial plants
Authors: Liu Yang , Liu Hui , Baastrup-Spohr Lars , Li Zhizhong , Li Wei , Pan Junfeng , Cao Yu 
Published: January 2023

AbstractBackground and AimsAllometric scaling between stomata and xylem for terrestrial woody plants is a widely observed pattern that may be constrained by water transport. Floating-leaved plants, a particular life form of aquatic plants, have leaves in direct contact with both air and water and a poorly developed xylem that may not be limited by water supply as for terrestrial plants. However, whether such an allometric scaling relationship still exists in floating-leaved plants has not been explored.MethodsWe analysed 31 floating-leaved species/varieties with a range in leaf area covering six orders of magnitude. For all 31 floating-leaved plants, we studied the allometric relationships between leaf area and petiole transverse area, and between total stomatal area and petiole vascular area.Key ResultsThe slopes of both relationships were similar to the slope of the allometric relationship (1.23) between total stomatal area and xylem area of 53 terrestrial plants. However, for ten of them with xylem that can be clearly defined, the strong positive relationship between total stomatal area and petiole xylem area had a significantly smaller slope than that of terrestrial plants (0.64 vs. 1.23). Furthermore, after considering phylogeny, the scaling relationships between total stomatal area and petiole traits in floating-leaved plants remained significant.ConclusionsWe speculated that for floating-leaved plants, the hyperallometric relationship (slope &gt;1) between the construction of leaf/stoma and petiole was promoted by the high demand for photosynthesis and thus more leaves/stomata. While the hypoallometric relationship (slope &lt;1) between stomatal and xylem area was related more to hydraulic processes, the selection pressure on stomata was lower than xylem of floating-leaved plants. Allometric relationships among the hydraulic traits on water transport of aquatic plants are the result of natural selection to achieve maximum carbon gain, which is similar to terrestrial plants.
Remote, Computerised Cognitive Assessment for Breast Cancer- and Treatment-Related Cognitive Dysfunction: Psychometric Characteristics of the Cogsuite Neurocognitive Battery
Authors: Root James C , Gaynor Alexandra M , Ahsan Anam , Jung Duane , Schofield Elizabeth , Ryan Elizabeth , Li Yuelin , Ahles Tim A 
Published: January 2023

Abstract

Objective
Cancer-related cognitive dysfunction (CRCD) is a significant concern for breast cancer survivors. The Cogsuite battery was developed to improve sensitivity to CRCD with the use of cognitive experimental measures, clarify specific cognitive processes impacted and to be capable of being administered either in-office or remotely.

Methods
In sum, 357 breast cancer survivors and non-cancer controls completed the Cogsuite Battery in-office (n = 76) or remotely (n = 281). Measure validity, sensitivity to demographic factors, correlations with standard neuropsychological measures and intercorrelations of Cogsuite variables were assessed. Test-retest reliability was evaluated in-office (n = 24) and remotely (n = 80).

Results
Test-retest reliability for most variables assessed was adequate to strong. Internal validity, as indicated by the confirmation of expected condition effects within each measure, was established for all measures. Assessment of external validity found age, but not education, was a significant predictor in the majority of measures. Assessment of criterion validity found that Cogsuite variables were correlated with standard measures in psychomotor speed, working memory and executive function, but not associated with self-reported cognition or mood.

Conclusions
Cogsuite is reliable and valid, and is sensitive to the effects of increasing age on cognition. The addition of the Cogsuite battery to standard assessment may improve sensitivity to CRCD and identify underlying processes that may be affected. Remote use of the Cogsuite battery in appropriate settings will lessen the burden for providers, researchers and survivors in research and clinical contexts.
DIST: spatial transcriptomics enhancement using deep learning
Authors: Zhao Yanping , Wang Kui , Hu Gang 
Published: January 2023

AbstractSpatially resolved transcriptomics technologies enable comprehensive measurement of gene expression patterns in the context of intact tissues. However, existing technologies suffer from either low resolution or shallow sequencing depth. Here, we present DIST, a deep learning-based method that imputes the gene expression profiles on unmeasured locations and enhances the gene expression for both original measured spots and imputed spots by self-supervised learning and transfer learning. We evaluate the performance of DIST for imputation, clustering, differential expression analysis and functional enrichment analysis. The results show that DIST can impute the gene expression accurately, enhance the gene expression for low-quality data, help detect more biological meaningful differentially expressed genes and pathways, therefore allow for deeper insights into the biological processes.
DrTransformer: heuristic cotranscriptional RNA folding using the nearest neighbor energy model
Authors: Badelt Stefan , Lorenz Ronny , Hofacker Ivo L 
Published: January 2023

Abstract

Motivation
Folding during transcription can have an important influence on the structure and function of RNA molecules, as regions closer to the 5′ end can fold into metastable structures before potentially stronger interactions with the 3′ end become available. Thermodynamic RNA folding models are not suitable to predict structures that result from cotranscriptional folding, as they can only calculate properties of the equilibrium distribution. Other software packages that simulate the kinetic process of RNA folding during transcription exist, but they are mostly applicable for short sequences.

Results
We present a new algorithm that tracks changes to the RNA secondary structure ensemble during transcription. At every transcription step, new representative local minima are identified, a neighborhood relation is defined and transition rates are estimated for kinetic simulations. After every simulation, a part of the ensemble is removed and the remainder is used to search for new representative structures. The presented algorithm is deterministic (up to numeric instabilities of simulations), fast (in comparison with existing methods), and it is capable of folding RNAs much longer than 200 nucleotides.

Availability and implementation
This software is open-source and available at https://github.com/ViennaRNA/drtransformer.

Supplementary information
Supplementary data are available at Bioinformatics online.
DiffCircaPipeline: a framework for multifaceted characterization of differential rhythmicity
Authors: Xue Xiangning , Zong Wei , Huo Zhiguang , Ketchesin Kyle D , Scott Madeline R , Petersen Kaitlyn A , Logan Ryan W , Seney Marianne L , McClung Colleen , Tseng George 
Published: January 2023

Abstract

Summary
Circadian oscillations of gene expression regulate daily physiological processes, and their disruption is linked to many diseases. Circadian rhythms can be disrupted in a variety of ways, including differential phase, amplitude and rhythm fitness. Although many differential circadian biomarker detection methods have been proposed, a workflow for systematic detection of multifaceted differential circadian characteristics with accurate false positive control is not currently available. We propose a comprehensive and interactive pipeline to capture the multifaceted characteristics of differentially rhythmic biomarkers. Analysis outputs are accompanied by informative visualization and interactive exploration. The workflow is demonstrated in multiple case studies and is extensible to general omics applications.

Availability and implementation
R package, Shiny app and source code are available in GitHub (https://github.com/DiffCircaPipeline) and Zenodo (https://doi.org/10.5281/zenodo.7507989)

Supplementary information
Supplementary data are available at Bioinformatics online.
FungiExp: a user-friendly database and analysis platform for exploring fungal gene expression and alternative splicing
Authors: Liu Jinding , Zhang Yaru , Shi Yapin , Zheng Yiqing , Zhu Yali , Guan Zhuoran , Shen Danyu , Dou Daolong 
Published: January 2023

Abstract

Summary
Fungi form a large and heterogeneous group of eukaryotic organisms with diverse ecological niches. The high importance of fungi contrasts with our limited understanding of fungal lifestyle and adaptability to environment. Over the last decade, the high-throughput sequencing technology produced tremendous RNA-sequencing (RNA-seq) data. However, there is no comprehensive database for mycologists to conveniently explore fungal gene expression and alternative splicing. Here, we have developed FungiExp, an online database including 35 821 curated RNA-seq samples derived from 220 fungal species, together with gene expression and alternative splicing profiles. It allows users to query and visualize gene expression and alternative splicing in the collected RNA-seq samples. Furthermore, FungiExp contains several online analysis tools, such as differential/specific, co-expression network and cross-species gene expression conservation analysis. Through these tools, users can obtain new insights by re-analyzing public RNA-seq data or upload personal data to co-analyze with public RNA-seq data.

Availability and implementation
The FungiExp is freely available at https://bioinfo.njau.edu.cn/fungiExp.

Supplementary information
Supplementary data are available at Bioinformatics online.
Adversarial dense graph convolutional networks for single-cell classification
Authors: Wang Kangwei , Li Zhengwei , You Zhu-Hong , Han Pengyong , Nie Ru 
Published: January 2023

Abstract

Motivation
In single-cell transcriptomics applications, effective identification of cell types in multicellular organisms and in-depth study of the relationships between genes has become one of the main goals of bioinformatics research. However, data heterogeneity and random noise pose significant difficulties for scRNA-seq data analysis.

Results
We have proposed an adversarial dense graph convolutional network architecture for single-cell classification. Specifically, to enhance the representation of higher-order features and the organic combination between features, dense connectivity mechanism and attention-based feature aggregation are introduced for feature learning in convolutional neural networks. To preserve the features of the original data, we use a feature reconstruction module to assist the goal of single-cell classification. In addition, HNNVAT uses virtual adversarial training to improve the generalization and robustness. Experimental results show that our model outperforms the existing classical methods in terms of classification accuracy on benchmark datasets.

Availability and implementation
The source code of HNNVAT is available at https://github.com/DisscLab/HNNVAT.

Supplementary information
Supplementary data are available at Bioinformatics online.
Anti-amyloid antibody therapies in Alzheimer’s disease
Authors: Perneczky Robert , Jessen Frank , Grimmer Timo , Levin Johannes , Flöel Agnes , Peters Oliver , Froelich Lutz 
Published: January 2023

AbstractAfter years of failed attempts to develop a disease-modifying therapy for Alzheimer’s disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-β protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-β lowering on PET also underpin the positive results of the trial.In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer’s disease failed. We compare the safety profiles of the different antibodies and highlight cautionary measures for their routine clinical use. Last, we discuss the role of blood-based biomarkers in transforming the clinical care pathway to facilitate the uptake of antibody treatments, proposing an integrated case-finding and treatment model crossing the different healthcare sectors.Taken together, a real breakthrough may have been achieved by proving that amyloid-β reduction results in clinical benefits, rather than just biomarker changes. At the same time, routine use of the new generation of drugs will show if statistical efficacy translates into clinically meaningful change. This may just be the beginning of a new era of Alzheimer’s disease drug development.
Interleukin-18 as a severity marker and novel potential therapeutic target for epidermolytic ichthyosis
Authors: Ansai Osamu , Miyauchi Toshinari , Hayashi Ryota , Katsumi Tatsuya , Nishiguchi Tomoki , Hasegawa Akito , Shinkuma Satoru , Natsuga Ken , Nomura Toshifumi , Shimomura Yutaka , Abe Riichiro 
Published: January 2023

Abstract

Background
Epidermolytic ichthyosis (EI) is a major form of nonsyndromic inherited ichthyosis, characterized by erythroderma, marked hyperkeratosis and scale, bulla and erosion at birth, associated with KRT1/KRT10 mutations. The cytokine and chemokine profiles in EI are poorly understood, and specific treatment options have not been established.

Aim
To explore novel biomarkers and therapeutic targets in patients with EI.

Methods
We analysed cytokine levels in serum and skin samples from 10 patients with inherited ichthyosis, including seven patients with EI. Wild-type and mutant KRT1 constructs were established and transfected into HaCaT cells, an immortalized keratinocyte cell line, for in vitro immunoblotting and immunocytochemistry analyses.

Results
Multiplex cytokine/chemokine analysis revealed that 10 cytokines/chemokines [interleukin (IL)-1β, IL-4, IL-17A, IL-16, IL-18, IL-1 receptor-α, macrophage colony-stimulating factor, interferon-α2, basic fibroblast growth factor and monocyte chemotactic protein-3] were significantly increased in patients with EI. Furthermore, IL-18 levels were significantly higher in patients with EI [n = 7; 2714.1 (1438.0) pg mL−1] than in healthy controls [n = 11; 218.4 (28.4) pg mL−1, P &lt; 0.01]. Immunohistochemical analyses showed that IL-18 expression was elevated in skin samples from patients with EI. Serum IL-18 levels correlated with the severity of ichthyosis, as measured by the Ichthyosis Scoring System. Immunoblotting analysis revealed that mature IL-18 levels were increased in the supernatant of mutant KRT1 expressing HaCaT cells. Additionally, these cells showed NLRP3 aggregation in the cytoplasm and ASC clustered around mutant keratin aggregations. These findings suggest that mutant keratin might promote the activation of the NLRP3 inflammasome and its downstream caspase-1-mediated IL-18 release in keratinocytes from patients with EI.

Conclusions
Our results suggest that serum IL-18 is a severity marker released from the skin of patients with EI. Blockade of IL-18 may be a useful novel therapeutic option for patients with EI.
Effects of metformin on clinical, hormonal and relevant gene expression parameters in patients with acne: an observational study
Authors: Kamboj Parul , Kaushik Akanksha , Handa Sanjeev , Dutta Pinaki , Saikia Uma Nahar , Pal Arnab , De Dipankar 
Published: January 2023

Abstract

Background
Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with polycystic ovarian syndrome (PCOS). However, the benefits of metformin in patients with acne in general are not well established.

Aim
To study the effectiveness of metformin treatment in patients with acne but who do not have PCOS and to understand the mechanisms of action of metformin in acne not related to PCOS.

Method
In this observational study, 30 patients with clinically confirmed acne vulgaris were treated with metformin (1000 mg daily) for 3 months without any other topical or systemic active intervention for their acne. The effect of metformin at the clinical, hormonal and genetic level was assessed.

Results
Metformin monotherapy significantly (P &lt; 0.001) decreased the global acne grading score for acne followed by a marginal increase in insulin; with a significant (P = 0.03) increase in insulin-like growth factor-1 (IGF-1). A significant (P &lt; 0.001) decrease in free androgen index resulting from a significant (P &lt; 0.001) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. Homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box protein O1 (FOXO1) expression was significantly (P = 0.006) downregulated with metformin treatment at the mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely HMGCR, SQLE and ACSL5 (P = 0.001, P = 0.03, P = 0.03, respectively) were also downregulated.

Conclusion
Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FOXO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.
Chloroquine reduces neutrophil extracellular trap (NET) formation through inhibition of peptidyl arginine deiminase 4 (PAD4)
Authors: Ivey Abby D , Matthew Fagan B , Murthy Pranav , Lotze Michael T , Zeh Herbert J , Hazlehurst Lori A , Geldenhuys Werner J , Boone Brian A 
Published: January 2023

AbstractNeutrophil extracellular traps (NETs) occur when chromatin is decondensed and extruded from the cell, generating a web-like structure. NETs have been implicated in the pathogenesis of several sterile disease states and thus are a potential therapeutic target. Various pathways have been shown to induce NETs, including autophagy, with several key enzymes being activated like peptidyl arginine deiminase 4 (PAD4), an enzyme responsible for citrullination of histones, allowing for DNA unwinding and subsequent release from the cell. Pre-clinical studies have already demonstrated that chloroquine (CQ) and hydroxychloroquine (HCQ) are able to reduce NETs and slow disease progression. The exact mechanism as to how these drugs reduce NETs has yet to be elucidated. CQ and HCQ decrease NET formation from various NET activators, independent of their autophagy inhibitory function. CQ and HCQ were found to inhibit PAD4 exclusively, in a dose-dependent manner, confirmed with reduced CitH3+ NETs after CQ or HCQ treatment. Circulating CitH3 levels were reduced in pancreatic cancer patients after HCQ treatment. In silico screening of PAD4 protein structure identified a likely binding site interaction at Arg639 for CQ and Trp347, Ser468, and Glu580 for HCQ. SPR analysis confirmed the binding of HCQ and CQ with PAD4 with KD values of 54.1 µM (CQ) and 88.1 µM (HCQ). This data provide evidence of direct PAD4 inhibition as a mechanism for CQ/HCQ inhibition of NETs. We propose that these drugs likely reduce NET formation through multiple mechanisms; the previously established TLR9 and autophagy inhibitory mechanism and the novel PAD4 inhibitory mechanism.
Activation of brain arousal networks coincident with eye blinks during resting state
Authors: Demiral Şükrü Barış , Kure Liu Christopher , Benveniste Helene , Tomasi Dardo , Volkow Nora D 
Published: January 2023

Abstract
Eye-blinking has been implicated in arousal and attention. Here we test the hypothesis that blinking-moments represent arousal surges associated with activation of the ascending arousal network (AAN) and its thalamic projections. For this purpose, we explored the temporal relationship between eye-blinks and fMRI BOLD activity in AAN and thalamic nuclei, as well as whole brain cluster corrected activations during eyes-open, resting-state fMRI scanning. We show that BOLD activations in the AAN nuclei peaked prior to the eye blinks and in thalamic nuclei peaked prior to and during the blink, consistent with the role of eye blinking in arousal surges. Additionally, we showed visual cortex peak activation prior to the eye blinks, providing further evidence of the visual cortex’s role in arousal, and document cerebellar peak activation post eye blinks, which might reflect downstream engagement from arousal surges.
Bone marrow inflammatory memory in cardiometabolic disease and inflammatory comorbidities
Authors: Mitroulis Ioannis , Hajishengallis George , Chavakis Triantafyllos 
Published: January 2023

Abstract
Cardiometabolic disorders are chief causes of morbidity and mortality, with chronic inflammation playing a crucial role in their pathogenesis. The release of differentiated myeloid cells with elevated pro-inflammatory potential, as a result of maladaptively trained myelopoiesis may be a crucial factor for the perpetuation of inflammation. Several cardiovascular risk factors, including sedentary lifestyle, unhealthy diet, hypercholesterolemia, and hyperglycemia, may modulate bone marrow hematopoietic progenitors, causing sustained functional changes that favour chronic metabolic and vascular inflammation. In the present review, we summarize recent studies that support the function of long-term inflammatory memory in progenitors of the bone marrow for the development and progression of cardiometabolic disease and related inflammatory comorbidities, including periodontitis and arthritis. We also discuss how maladaptive myelopoiesis associated with the presence of mutated hematopoietic clones, as present in clonal hematopoiesis, may accelerate atherosclerosis via increased inflammation.