bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative Synergistic Effects of Drought and Heat During Flowering and Seed Setting in Soybean
Authors: Poudel Sadikshya , Vennam Ranadheer Reddy , Sankarapillai Lekshmy V. , Liu Jinbo , Reddy K. Raja , Wijewardane Nuwan K. , Mukhtar M. Shahid , Bheemanahalli Raju 
Published: January 2024

AbstractRising temperatures and intense heatwaves combined with lower precipitations are the new norms of current global scenarios. These altered climatic conditions negatively impact soybean yield potential and quality. Ten soybean cultivars were subjected to four different growing conditions: control, drought, heat, and combined heat and drought to understand the physiological, yield, and molecular changes. Stomatal conductance was reduced by 62% and 10% under drought and heat, respectively. This reduction was further exacerbated to 93% when exposed to both stresses simultaneously. The highest canopy temperature was recorded at +8 °C with combinatorial treatments, whereas heat and drought exhibited +5.4 °C and +2 °C, respectively. Furthermore, combined stress displayed a more pronounced negative impact on greenness-associated vegetative index; the gene expression analysis further corroborated these findings. Particularly, each °C increase in temperature during flowering-seed filling reduced seed weight by ∼7% and ∼4% with and without drought, respectively. The seed protein increased under drought, whereas the oil showed a converse trend under drought and combined stresses. Most physiology and yield traits showed no significant correlations between control or individual and combined stress. This suggests that selection for combinatorial stress may not be appropriate based on nonstress or individual stress performance. Thus, incorporating stress-resilient traits into elite soybean cultivars could significantly boost soybean production under hot and dry climatic conditions.
Evaluation of the efficacy of a full-spectrum medicinal cannabis plant extract with less than 0.3% Δ9-tetrahydrocannabinol inin vitromodels of inflammation and excitotoxicity
Authors: Ross-Munro Emily , Isikgel Esra , Fleiss Bobbi 
Published: January 2024

AbstractThe rapid development of research on the therapeutic benefits of medicinal cannabis, in parallel with an increased understanding of the endocannabinoid system, has driven research ofCannabis sativaconstituents for managing neurological conditions. While most studies have focused on the therapeutic potential of the major components of cannabis plant extract isolated or combined, limited research has explored the pharmacological benefits of whole cannabis plant extract. In this study, we investigated the potential anti-inflammatory and neuroprotective effects of NTI-164, a novel full-spectrum cannabis extract with negligible Δ9-tetrahydrocannabinol (THC), compared with cannabidiol (CBD) alone in BV-2 microglial and SHSY-5Y neuronal cells. The inflammation-induced upregulation of microglial inflammatory mediators, being tumour necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS), and Arginase-1 (Arg-1), were significantly attenuated by NTI-164. This immunomodulatory effect was not observed upon treatment with isolated CBD. Compared to CBD alone, NTI-164 prevented elevated mitochondrial activity while normalising cell numbers in immune-activated microglia cells. NTI-164 also promoted the proliferation of undifferentiated neurons and the survival of differentiated neurons under excitotoxic conditions. Overall, our work shows that the anti-inflammatory and neuroprotective effects of NTI-164 as a full-spectrum cannabis extract are enhanced relative to that of CBD alone, highlighting the potential therapeutic efficacy of NTI-164 for the treatment of neuropathologies such as autism spectrum disorder (ASD) and related neuropathologies. This study has further shown that understanding the synergistic effect of phytocannabinoids is integral to realising the therapeutic potential of full-spectrum cannabis extract to inform the design of botanical-derived treatments for managing neurological disorders.
Early detection and treatment of postpartum haemorrhage: a cost-effectiveness analysis of the E-MOTIVE trial
Authors: Williams E.V. , Goranitis I. , Oppong R. , Perry S.J. , Devall A. , Martin J.T. , Mammoliti K-M. , Beeson L. , Sindhu K.N. , Galadanci H. , Alwy Al‑beity F. , Qureshi Z. , Hofmeyr G.J. , Moran N. , Fawcus S. , Mandondo S. , Middleton L. , Hemming K. , Oladapo O. , Gallos I. , Coomarasamy A. , Roberts T.E. 
Published: January 2024

AbstractBackgroundTimely detection and treatment of postpartum haemorrhage (PPH) are crucial to prevent complications or death. A calibrated blood-collection drape can help provide objective, accurate, and early diagnosis of PPH and a treatment bundle can address delays or inconsistencies in the use of effective interventions.MethodsWe conducted an incremental cost-effectiveness analysis alongside the E-MOTIVE trial, an international, parallel cluster-randomised trial with a baseline control phase, designed to assess a multi-component intervention for PPH in patients having vaginal delivery. We compared the E-MOTIVE intervention, which included a calibrated blood-collection drape for early detection of PPH and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), with usual care. We used multilevel modelling to estimate incremental cost-effectiveness ratios from the perspective of the public healthcare system for outcomes of cost per case of severe PPH (blood loss ≥1000 mL) prevented and cost per disability-adjusted life-year (DALY) averted.ResultsA total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the E-MOTIVE group or the usual-care group. Among hospitals and patients with data, severe PPH was diagnosed in 1.6% of patients in the E-MOTIVE group and 4.3% of patients in the usual-care group (risk difference, -2.6%; 95% CI -3.1% to -2.1%). Mean DALYs per patient were lower for the E-MOTIVE group (-0.0027; 95% CI -0.0081 to 0.0029) whilst mean costs per patient were slightly higher compared with the usual-care group (0.30 USD; 95% CI -2.31 to 2.78). The E-MOTIVE intervention was deemed cost-effective at contemporary willingness-to-pay thresholds and remained cost-effective across the full range of sensitivity and country-level analyses.InterpretationUse of a calibrated blood-collection drape for early detection of PPH and bundled first-response treatment is cost-effective and should be perceived by decision makers as a worthwhile use of healthcare budgets.FundingBill & Melinda Gates Foundation (NCT04341662).
The pandemic, COVID-19 disease and perinatal health
Authors: Jung Shelley , Liu Emily F , Goin Dana E , Rudolph Kara E , Mujahid Mahasin S , Dow William H , Ahern Jennifer 
Published: January 2024

ABSTRACTAdverse effects of COVID-19 on perinatal health have been documented, however there is a lack of research that separates individual disease from other changing risks during the pandemic period. We linked California statewide birth and hospital discharge data for 2019-2020, and compared health indicators among 3 groups of pregnancies: [a] 2020 delivery with COVID-19, [b] 2020 delivery with no documented COVID-19, and [c] 2019 pre-pandemic delivery. We aimed to quantify the links between COVID-19 and perinatal health, separating individual COVID-19 disease (a vs b) from the pandemic period (b vs c). We examined the following health indicators: preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus and severe maternal morbidity. We applied model based standardization to estimate “average effect of treatment on the treated” risk differences (RD), and adjusted for individual and community-level confounders. Among pregnancies in 2020, those with COVID-19 disease had higher burdens of preterm birth (RD[95% confidence interval (CI)]=2.8%[2.1,3.5]), hypertension (RD[95% CI]=3.3%[2.4,4.1]), and severe maternal morbidity (RD[95% CI]=2.3%[1.9,2.7]) compared with pregnancies without COVID-19 (a vs b) adjusted for confounders. Pregnancies in 2020 without COVID-19 had a lower burden of preterm birth (RD[95% CI]=-0.4%[-0.6,-0.3]), particularly spontaneous preterm, and a higher burden of hypertension (RD[95% CI]=1.0%[0.9,1.2]) and diabetes RD[95%CI]=0.9%[0.8,1.1] compared with pregnancies in 2019 (b vs c) adjusted for confounders. Protective associations of the pandemic period for spontaneous preterm birth may be explained by socioenvironmental and behavioral modifications, while increased maternal conditions may be due to stress and other behavioral changes. To our knowledge, our study is the first to distinguish between individual COVID-19 disease and the pandemic period in connection with perinatal outcomes.
Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation
Authors: Vella Laura A. , Berna Amalia Z. , Blatz Allison M. , Logan Joey , Sharma Priya , Liu Yang , Tedesco Jonathan , Toland Cara , Babiker Leena , Hafertepe Kathryn , Kammerman Shane , Novacek Josef , Akaho Elikplim , Gonzalez Alexander K. , Taylor Deanne , Diorio Caroline , Balamuth Fran , Bassiri Hamid , Odom John Audrey R. 
Published: January 2024

AbstractMultisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVβ21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.
Diagnostic Performance of Radiomics in Prediction of Ki-67 Index Status in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Shahidi Ramin , Hassannejad Ehsan , Baradaran Mansoureh , Klontzas Michail E. , HajiEsmailPoor Zanyar , Chong Weelic , Broomand Nima , Alizadeh Mohammadreza , Sadeghsalehi Hamidreza , Mozafari Navid , Teimoori Soraya , Farhadi Akram , Nouri Hamed , Shobeiri Parnian , Sotoudeh Houman 
Published: January 2024

AbstractBackgroundLung cancer is a global health concern, in part due to its high prevalence and invasiveness. The Ki-67 index, indicating cellular proliferation, is pivotal for assessing lung cancer aggressiveness. Radiomics is the inference of quantifiable data features from medical images through algorithms and may offer insights into tumor behavior. Here, we perform a systematic review and meta-analysis to assess the performance of radiomics for predicting Ki-67 status in Non-small Cell Lung Cancer (NSCLC) on CT scan.Methods and materialsA comprehensive search of the current literature was conducted using relevant keywords in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception to November 16, 2023. Original studies discussing the performance of CT-based radiomics for predicting Ki-67 status in NSCLC cohorts were included. The quality assessment involved quality assessment of diagnostic accuracy studies (QUADAS-2) and radiomics quality score (RQS). Quantitative meta-analysis, using R, assessed pooled sensitivity and specificity in NSCLC cohorts.ResultsWe identified 10 studies that met the inclusion criteria, involving 2279 participants, with 9 of these studies included in quantitative meta-analysis. The overall quality of the included studies was moderate to high based on QUADAS-2 and RQS assessment. The pooled sensitivity and specificity of radiomics-based models for predicting the Ki-67 status of NSCLC training cohorts were 0.78 (95% CI [0.73; 0.83]) and 0.76 (95% CI [0.70; 0.82]), respectively. The pooled sensitivity and specificity of radiomics-based models for predicting the Ki-67 status of NSCLC validation cohorts were 0.79 (95% CI [0.73; 0.84]) and 0.69 (95% CI [0.61; 0.76]), respectively. Substantial heterogeneity was noted in the pooled sensitivity and specificity of training cohorts and the pooled specificity of validation cohorts (I2> 40%). It was identified that utilizing ITK-SNAP as a segmentation software contributed to a significantly higher pooled sensitivity.ConclusionThis meta-analysis indicates promising diagnostic accuracy of radiomics in predicting Ki-67 in NSCLC. The study underscores radiomics’ potential in personalized lung cancer management, advocating for prospective studies with standardized methodologies and larger samples.
Macromolecular toolbox to elucidate CLE-RLK binding, signaling and downstream effects
Authors: Narasimhan Madhumitha , Jahnke Nina , Kallert Felix , Bahafid Elmehdi , Böhmer Franziska , Hartmann Laura , Simon Rüdiger 
Published: January 2024

SummaryPlant peptides communicate by binding to a large family of receptor-like kinases (RLKs) and they share a conserved binding mechanism, which may account for their promiscuous interaction with several RLKs. In order to understand the in vivo binding specificity of CLE peptide family, we have developed a novel set of CLAVATA 3 (CLV3) based peptide tools. After carefully evaluating the CLE peptide binding characteristics, using solid phase synthesis process, we have modified the CLV3 peptide and attached a fluorophore and a photoactivable side group. We observed that the labeled CLV3 shows binding specificity within CLAVATA1 clade of RLKs while avoiding the distantly-related PEP RECEPTOR clade, thus resolving the contradictory results obtained previously by many in vitro methods. Furthermore, we observed that the RLK-bound CLV3 undergoes clathrin-mediated endocytosis and gets trafficked to vacuole via ARA7-labeled endosomes. Additionally, modifying CLV3 for light-controlled activation enabled spatial and temporal control over CLE signalling. Hence our CLV3 macromolecular toolbox can be used to study rapid cell specific down-stream effects. Given the conserved binding properties, in the future our toolbox can also be used as a template to modify other CLE peptides.HighlightA macromolecular tool box consisting of modified CLE peptide with fluorescent molecule and photoactivable group offers reliable insights into its in vivo binding characteristics, localization and signaling.
Transcriptional responses of brain endothelium toPlasmodium falciparumpatient-derived isolatesin vitro
Authors: Askonas Caroline , Storm Janet , Camarda Grazia , Craig Alister , Pain Arnab 
Published: January 2024

AbstractA hallmark of cerebral malaria (CM) is sequestration ofPlasmodium falciparuminfected erythrocytes (IE) within the brain microvasculature. Binding of IE to endothelium reduces microvascular flow and combined with an inflammatory response perturbs endothelial barrier function, resulting in breakdown of the blood- brain barrier (BBB). Cytoadherence leads to activation of the endothelium and alters a range of cell processes affecting signalling pathways, receptor expression, coagulation, and disruption of BBB integrity. Here, we investigated whether CM derived parasites elicit differential effects on human brain microvascular endothelial cells (HBMECs), as compared to uncomplicated malaria (UM) derived parasites. Patient-derived IE from UM and CM clinical cases, as well as non-binding skeleton-binding protein 1 knockout parasites, were overlaid onto TNF-activated HBMECs. Gene expression analysis of endothelial responses was performed using probe-based assays of a panel of genes involved in inflammation, apoptosis, endothelial barrier function, and prostacyclin synthesis pathway. We observed a significant effect on endothelial transcriptional responses in the presence of IE, yet there was no significant correlation between HBMEC responses and type of clinical syndrome (UM or CM). Further, there was no correlation between HBMEC gene expression and both binding itself and level of IE binding to HBMEC, as we detected the same change in endothelial responses when employing both binding and non-binding parasites. Our results suggest that interaction of IE with endothelial cells in this co-culture model induce some endothelial responses that are independent of clinical origin and independent of the expression of the major variant antigenPfEMP1 on the IE surface.
Single nuclei multiomics reveals the drought-driven gene regulatory atlas in Arabidopsis
Authors: Liu Jinbao , Majeed Aqsa , Kumar Nilesh , Pajerowska-Mukhtar Karolina M. , Mukhtar M. Shahid 
Published: January 2024

AbstractThe regulation of gene expression in plant responses to drought has been thoroughly investigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lacking. In this study, we report the use of single-nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis delineated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly enriched in pathways responsive to drought, heat, and light. Motif enrichment analysis and gene regulatory network (GRN) inference highlighted key transcription factors (TFs) and regulatory networks related to ethylene signaling pathways in endodermis as well as circadian rhythms in both endodermis and guard cells. Pseudotime analysis identified critical transcriptomic progression from metabolic process to stress response within three cell types. Overall, this study elucidates drought-related regulatory mechanisms in Arabidopsis at single-cell resolution, providing valuable insights into the fundamental regulatory events involved in stress responses. It also serves as a reference for future single-cell multiomic investigations in crop plants.One Sentence SummarySingle cell multiomic analysis under drought stress
Transcriptomic analysis of pubertal and adult virgin mouse mammary epithelial and stromal cell populations
Authors: Heijmans Nika , Wiese Katrin E. , Jonkers Jos , van Amerongen Renée 
Published: January 2024

AbstractConflicting data exist as to how mammary epithelial cell proliferation changes during the reproductive cycle. To study the effect of endogenous hormone fluctuations on gene expression in the mouse mammary gland, we performed bulk RNAseq analyses of epithelial and stromal cell populations that were isolated either during puberty or at different stages of the adult virgin estrous cycle. Our data confirm prior findings that proliferative changes do not occur in every mouse in every cycle. We also show that during the estrous cycle the main gene expression changes occur in adipocytes and other stromal cells. Finally, we present a comprehensive overview of theWntgene expression landscape in different mammary gland cell types in pubertal and adult mice. This work contributes to understanding the effects of physiological hormone fluctuations and locally produced signaling molecules on gene expression changes in the mammary gland during the reproductive cycle and should be a useful resource for future studies investigating gene expression patterns in different cell types across different developmental timepoints.
Evaluating Evapotranspiration in a Commercial Greenhouse: A Comparative Study of Microclimatic Factors and Machine-Learning Algorithms
Authors: Averbuch Nir , Moshelion Menachem 
Published: January 2024

AbstractThe FAO-56 Penman-Monteith equation (FPME) is commonly used to calculate evapotranspiration and apply necessary irrigation, based on environmental data usually taken from a single measuring station. In this study, we hypothesized that the accuracy of the FPME is affected by microclimatic changes over time and space within the target area. Therefore, we tested the impact of numerous spatial and temporal environmental measurement points in a commercial greenhouse on the accuracy of the FPME, by comparing its evapotranspiration evaluation to the actual evaporation measured by dozens of weighing lysimeters throughout the year. Additionally, we harnessed the capabilities of machine-learning algorithms to utilize the extensive data acquired for predicting evapotranspiration. Our results revealed that the daily FPME exhibited a -22% to +22% discrepancy in accuracy, as compared to the lysimeters, with overestimation in the winter and underestimation in the summer. Interestingly, using more data points per day led to less accurate FPME evaluation. The conflict between an increased number of data points and a reduction in accuracy was explained by daily hysteresis. Machine-learning algorithms (Decision Tree, Random Forest, XGBoost and Neural Network) showed impressive accuracy in predicting evapotranspiration, when the model dataset contained temporal parameters (R2> 0.918). Furthermore, we demonstrated that spatial sampling had a stronger effect on the accuracy of predictions than the amount of the data collected. Specifically, when we used 10% of the original dataset (3.01e5 entries) with high consideration of spatial measurements, the best-performing models (Random Forest and XGBoost) were highly accurate (R2= 0.913 andR2= 0.935, respectively). The top three most influential features of all models were light, day and hour, underscoring the importance of the temporal dimension. This approach allowed us to explore the potential of leveraging advanced computational methods to improve the estimation of water loss under various environmental conditions.
The Zymoseptoria tritici avirulence factor AvrStb6 accumulates in hyphae close to stomata and triggers a wheat defense response hindering fungal penetration
Authors: Alassimone Julien , Praz Coraline , Lorrain Cécile , Francesco Agustina De , Carrasco-López Cristian , Faino Luigi , Meile Lukas , Sánchez-Vallet Andrea 
Published: January 2024

ABSTRACTZymoseptoria tritici, the causal agent of septoria tritici blotch, is one of Europe’s most damaging wheat pathogens, causing significant economic losses. Genetic resistance is a common strategy to control the disease,Stb6being a resistance gene used for over 100 years in Europe. This study investigates the molecular mechanisms underlying Stb6-mediated resistance. Utilizing confocal microscopy imaging, we identified thatZ. triticiepiphytic hyphae mainly accumulates the corresponding avirulence factor AvrStb6 in close proximity to stomata. Consequently, the progression of AvrStb6-expressing avirulent strains is hampered during penetration. The fungal growth inhibition co-occurs with a transcriptional reprogramming in wheat characterized by an induction of immune responses, genes involved in stomata regulation, and cell wall-related genes. Overall, we shed light on the gene-for-gene resistance mechanisms in the wheat -Z. triticipathosystem at the cytological and transcriptomic level, and our results highlight that stomata penetration is a critical process for pathogenicity and resistance.