bluuebunny/crossref_metadata_2025 huggingface dataset:
Food fraud threats in UK post-harvest seafood supply chains; an assessment of current vulnerabilities
Authors: Lawrence Sophie , Elliott Christopher , Huisman Wim , Dean Moira , van Ruth Saskia
Published: May 2024

Seafood fraud is commonly reported on food fraud databases and deceptive practices are highlighted by numerous studies, with impacts on the economy, health and marine conservation. Food fraud assessments are a widely accepted fraud mitigation and prevention activity undertaken to identify possible points of deception within a supply chain. This study aims to understand the food fraud vulnerability of post-harvest seafood supply chains in the UK and determine if there are differences according to commodity, supply chain node, business size and certification status. The SSAFE food fraud vulnerability assessment tool was used to assess 48 fraud factors relating to opportunities, motivations and controls. The analysis found seafood supply chains to have a medium vulnerability to food fraud, with the highest perceived vulnerability in technical opportunities. Certification status was a stronger determinant of vulnerability than any other factor, particularly in the level of controls, a factor that also indicated a higher perceived level of vulnerability in smaller companies and the food service industry. This paper also reviews historic food fraud trends in the sector to provide additional insights and the analysis indicates that certain areas of the supply chain, including uncertified prawn supply chains, salmon supply chains and food service companies, may be at higher risk of food fraud. This study conducts an in-depth examination of food fraud vulnerability relating to the UK and for seafood supply chains and contributes to a growing body of literature identifying areas of vulnerability and resilience to food related criminality within the global food system.
A geographically disaggregated approach to integrate low-carbon technologies across local electricity networks
Authors: Few Sheridan , Djapic Predrag , Strbac Goran , Nelson Jenny , Candelise Chiara
Published: May 2024

Meeting climate targets requires widespread deployment of low-carbon technologies such as distributed photovoltaics, heat pumps and electric vehicles. Without mitigating actions, changing power flows associated with these technologies would adversely impact some local networks. The extent of these impacts, and the optimal means of avoiding them, remains unclear. Here we use local-level data and network simulation to estimate variation in future network upgrade costs in over 40,000 geographical regions comprising all of Great Britain. We find that costs vary substantially between localities, and are typically highest in urban areas, and areas with highest deployment of heat pumps and electric vehicles. We estimate reductions in required upgrades associated with local flexibility, which vary substantially between localities. We show that using geographically disaggregated data to inform flexibility deployment across the country could reduce network upgrade costs by hundreds of millions of pounds relative to an approach that treats localities as homogeneous.
Evolutionary–developmental (evo-devo) dynamics of hominin brain size
Authors: González-Forero Mauricio
Published: May 2024

Brain size tripled in the human lineage over four million years, but why this occurred remains uncertain. Here, to study what caused this brain expansion, I mathematically model the evolutionary and developmental (evo-devo) dynamics of hominin brain size. The model recovers (1) the evolution of brain and body sizes of seven hominin species starting from brain and body sizes of the australopithecine scale, (2) the evolution of the hominin brain–body allometry and (3) major patterns of human development and evolution. I show that the brain expansion recovered is not caused by direct selection for brain size but by its genetic correlation with developmentally late preovulatory ovarian follicles. This correlation is generated over development if individuals experience a challenging ecology and seemingly cumulative culture, among other conditions. These findings show that the evolution of exceptionally adaptive traits may not be primarily caused by selection for them but by developmental constraints that divert selection.
Deep history of cultural and linguistic evolution among Central African hunter-gatherers
Authors: Padilla-Iglesias Cecilia , Blanco-Portillo Javier , Pricop Bogdan , Ioannidis Alexander G. , Bickel Balthasar , Manica Andrea , Vinicius Lucio , Migliano Andrea Bamberg
Published: May 2024

Human evolutionary history in Central Africa reflects a deep history of population connectivity. However, Central African hunter-gatherers (CAHGs) currently speak languages acquired from their neighbouring farmers. Hence it remains unclear which aspects of CAHG cultural diversity results from long-term evolution preceding agriculture and which reflect borrowing from farmers. On the basis of musical instruments, foraging tools, specialized vocabulary and genome-wide data from ten CAHG populations, we reveal evidence of large-scale cultural interconnectivity among CAHGs before and after the Bantu expansion. We also show that the distribution of hunter-gatherer musical instruments correlates with the oldest genomic segments in our sample predating farming. Music-related words are widely shared between western and eastern groups and likely precede the borrowing of Bantu languages. In contrast, subsistence tools are less frequently exchanged and may result from adaptation to local ecologies. We conclude that CAHG material culture and specialized lexicon reflect a long evolutionary history in Central Africa.
Human ventromedial prefrontal cortex is necessary for prosocial motivation
Authors: Lockwood Patricia L. , Cutler Jo , Drew Daniel , Abdurahman Ayat , Jeyaretna Deva Sanjeeva , Apps Matthew A. J. , Husain Masud , Manohar Sanjay G.
Published: May 2024

Ventromedial prefrontal cortex (vmPFC) is vital for decision-making. Functional neuroimaging links vmPFC to processing rewards and effort, while parallel work suggests vmPFC involvement in prosocial behaviour. However, the necessity of vmPFC for these functions is unknown. Patients with rare focal vmPFC lesions (n = 25), patients with lesions elsewhere (n = 15) and healthy controls (n = 40) chose between rest and exerting effort to earn rewards for themselves or another person. vmPFC damage decreased prosociality across behavioural and computational measures. vmPFC patients earned less, discounted rewards by effort more, and exerted less force when another person benefited, compared to both control groups. Voxel-based lesion mapping revealed dissociations between vmPFC subregions. While medial damage led to antisocial behaviour, lateral damage increased prosocial behaviour relative to patients with damage elsewhere. vmPFC patients also showed reduced effort sensitivity overall, but reward sensitivity was limited to specific subregions. These results reveal multiple causal contributions of vmPFC to prosocial behaviour, effort and reward.
Dissecting cell membrane tension dynamics and its effect on Piezo1-mediated cellular mechanosensitivity using force-controlled nanopipettes
Authors: Lüchtefeld Ines , Pivkin Igor V. , Gardini Lucia , Zare-Eelanjegh Elaheh , Gäbelein Christoph , Ihle Stephan J. , Reichmuth Andreas M. , Capitanio Marco , Martinac Boris , Zambelli Tomaso , Vassalli Massimo
Published: May 2024

The dynamics of cellular membrane tension and its role in mechanosensing, which is the ability of cells to respond to physical stimuli, remain incompletely understood, mainly due to the lack of appropriate tools. Here, we report a force-controlled nanopipette-based method that combines fluidic force microscopy with fluorescence imaging for precise manipulation of the cellular membrane tension while monitoring the impact on single-cell mechanosensitivity. The force-controlled nanopipette enables control of the indentation force imposed on the cell cortex as well as of the aspiration pressure applied to the plasma membrane. We show that this setup can be used to concurrently monitor the activation of Piezo1 mechanosensitive ion channels via calcium imaging. Moreover, the spatiotemporal behavior of the tension propagation is assessed with the fluorescent membrane tension probe Flipper-TR, and further dissected using molecular dynamics modeling. Finally, we demonstrate that aspiration and indentation act independently on the cellular mechanobiological machinery, that indentation induces a local pre-tension in the membrane, and that membrane tension stays confined by links to the cytoskeleton.
NG2 glia protect against prion neurotoxicity by inhibiting microglia-to-neuron prostaglandin E2 signaling
Authors: Liu Yingjun , Guo Jingjing , Matoga Maja , Korotkova Marina , Jakobsson Per-Johan , Aguzzi Adriano
Published: May 2024

Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. Here, we identify a neuroprotective role for NG2 glia against prion toxicity. NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia enhanced the biosynthesis of prostaglandin E2 (PGE2) by microglia, which augmented prion neurotoxicity through binding to the EP4 receptor. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.
Multi-source remote sensing-based landslide investigation: the case of the August 7, 2020, Gokseong landslide in South Korea
Authors: Choi Shin-Kyu , Ramirez Ryan Angeles , Lim Hwan-Hui , Kwon Tae-Hyuk
Published: May 2024

Landslides pose a growing concern worldwide, emphasizing the need for accurate prediction and assessment to mitigate their impact. Recent advancements in remote sensing technology offer unprecedented datasets at various scales, yet practical applications demand further case studies to fully integrate these technologies into landslide analysis. This study presents a case study approach to fully leverage variety of multi-source remote sensing technologies for analyzing the characteristics of a landslide. The selected case is a landslide with a long runout debris flow that occurred in Gokseong County, South Korea, on August 7, 2020. The chosen multi-source technologies encompass digital photogrammetry using RGB and multi-spectral imageries, 3D point clouds acquired by light detection and ranging (LiDAR) mounted on an unmanned aerial vehicle (UAV), and satellite interferometric synthetic aperture radar (InSAR). The satellite InSAR analysis identifies the initial displacement, triggered by rainfall and later transforming into a debris flow. The utilization of digital photogrammetry, employing UAV-RGB and multi-spectral image data, precisely delineates the extent affected by the landslide. The landslide encompassed a runout distance of 678 m, featuring an initiation zone characterized by an average slope of 35°. Notably, the eroded and deposited areas measured 2.55 × 104 m2 and 1.72 × 104 m2, respectively. The acquired UAV-LiDAR data further reveal the eroded and deposited landslide volumes approximately measuring 5.60 × 104 m3 and 1.58 × 104 m3, respectively. This study contributes a valuable dataset on a rainfall-induced landslide with a long runout debris flow, underscoring the effectiveness of multi-source remote sensing technology in monitoring and comprehending complex landslide events.
Metabolomic-derived endotypes of age-related macular degeneration (AMD): a step towards identification of disease subgroups
Authors: Mendez Kevin , Lains Ines , Kelly Rachel S. , Gil João , Silva Rufino , Miller John , Vavvas Demetrios G. , Kim Ivana , Miller Joan , Liang Liming , Lasky-Su Jessica A. , Husain Deeba
Published: May 2024

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a complex pathophysiology and phenotypic diversity. Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both Endotype 3 and 4 were associated with more severe AMD and exhibited low levels of fatty acid metabolites and elevated levels of sphingomyelins and fatty acid metabolites, respectively. These preliminary findings indicate that metabolomics-derived endotyping may offer a refined strategy for categorizing AMD patients based on their specific pathophysiological underpinnings, rather than relying solely on traditional observational clinical indicators.
Coupling control technology of anchoring and unloading in deep intense-mining and large-deformation roadway: a case study
Authors: Wang En , Yin Shuaifeng , Kang Qingtao , Zhao Xubo , Lan Qiankun , Sheng Hongyuan , Liang Huiyang
Published: May 2024

In order to control the deformation of surrounding rock in deep high-stress and intense-mining roadways, taking a deep coal roadway with continuous deformation as an example, the characteristics of crustal stress, coal strength, and mining influence of roadway are obtained by underground tests. The combined failure mechanism of coal roadway surrounding-rock is revealed by differential stress of deep and shallow anchor cables. We propose that the improvement of surrounding rock control for coal roadway is adopting the coupling control technology of anchoring and unloading. The stress distribution and evolution laws of lateral surrounding rock of unloading holes are obtained by numerical simulation and theoretical calculation, and reasonable unloading-hole spacing of 4.0 m is comprehensively determined. A mechanical model of roadway roof beam under fixed support at both ends is constructed and the important role of anchor cable beam-truss in controlling the stability of coal roadway is obtained. The rationality of coupling control technology of anchoring and unloading and parameters has been verified by engineering test and mine pressure observation, providing technical references for surrounding rock control in deep intense-mining and large-deformation roadways.
Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective
Authors: Xie Chengzhi , Zhang Ying , Zhu Baochen , Yang Lin , Ren Jianxun , Lang Na
Published: May 2024

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein–protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.
HER2 quantitative continuous scoring for accurate patient selection in HER2 negative trastuzumab deruxtecan treated breast cancer
Authors: Kapil Ansh , Spitzmüller Andreas , Brieu Nicolas , Haneder Susanne , Shumilov Anatoliy , Meier Armin , Cecchi Fabiola , Barkell Alice , Harder Nathalie , Mittermaier Katrin , Hidalgo-Sastre Ana , Alleze Regina , Schick Markus , Schmidt Günter , Sade Hadassah , Tsuchihashi Zenta , Suto Fumitaka , Gustavson Mark , Barrett J. Carl , Carroll Danielle
Published: May 2024

Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes. Using data from trastuzumab deruxtecan-treated patients with HER2-positive and HER2-negative breast cancer from a phase 1 study (NCT02564900; DS8201-A-J101; N = 151), QCS-based patient stratification showed longer progression-free survival (14.8 vs 8.6 months) with higher prevalence of patient selection (76.4 vs 56.9%) and a better cross-validated log-rank p value (0.026 vs 0.26) than manual scoring based on the American Society of Clinical Oncology / College of American Pathologists guidelines. QCS-based features enriched the HER2-negative subgroup by correctly predicting 20 of 26 responders.
A novel combinatorial approach using sulforaphane- and withaferin A-rich extracts for prevention of estrogen receptor-negative breast cancer through epigenetic and gut microbial mechanisms
Authors: Rahman Mohammad Mijanur , Wu Huixin , Tollefsbol Trygve O.
Published: May 2024

Estrogen receptor-negative [ER(−)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(−)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(−) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.
Predicting the stereoselectivity of chemical reactions by composite machine learning method
Authors: Chung Jihoon , Li Justin , Saimon Amirul Islam , Hong Pengyu , Kong Zhenyu
Published: May 2024

Stereoselective reactions have played a vital role in the emergence of life, evolution, human biology, and medicine. However, for a long time, most industrial and academic efforts followed a trial-and-error approach for asymmetric synthesis in stereoselective reactions. In addition, most previous studies have been qualitatively focused on the influence of steric and electronic effects on stereoselective reactions. Therefore, quantitatively understanding the stereoselectivity of a given chemical reaction is extremely difficult. As proof of principle, this paper develops a novel composite machine learning method for quantitatively predicting the enantioselectivity representing the degree to which one enantiomer is preferentially produced from the reactions. Specifically, machine learning methods that are widely used in data analytics, including Random Forest, Support Vector Regression, and LASSO, are utilized. In addition, the Bayesian optimization and permutation importance tests are provided for an in-depth understanding of reactions and accurate prediction. Finally, the proposed composite method approximates the key features of the available reactions by using Gaussian mixture models, which provide suitable machine learning methods for new reactions. The case studies using the real stereoselective reactions show that the proposed method is effective and provides a solid foundation for further application to other chemical reactions.
Exploring shared molecular signatures and regulatory mechanisms in nonalcoholic steatohepatitis and inflammatory bowel disease using integrative bioinformatics analysis
Authors: Zhong Zixuan , Xu Minxuan , Ge Chenxu , Tan Jun
Published: May 2024

The co-existence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH) has raised interest in identifying shared molecular mechanisms and potential therapeutic targets. However, the relationship between these two diseases remains unclear and effective medical treatments are still lacking. Through the bioinformatics analysis in this study, 116 shared differentially expressed genes (SDEGs) were identified between IBD and NASH datasets. GO and KEGG pathway analyses revealed significant involvement of SDEGs in apoptotic processes, cell death, defense response, cytokine and chemokine activity, and signaling pathways. Furthermore, weighted gene co-expression network analysis (WGCNA) identified five shared signature genes associated specifically with IBD and NASH, they were CXCL9, GIMAP2, ADAMTS5, GRAP, and PRF1. These five genes represented potential diagnostic biomarkers for distinguishing patients with diseases from healthy individuals by using two classifier algorithms and were positively related to autophagy, ferroptosis, angiogenesis, and immune checkpoint factors in the two diseases. Additionally, single-cell analysis of IBD and NASH samples highlighted the expression of regulatory genes in various immune cell subtypes, emphasizing their significance in disease pathogenesis. Our work elucidated the shared signature genes and regulatory mechanisms of IBD and NASH, which could provide new potential therapies for patients with IBD and NASH.
Novel gene-specific Bayesian Gaussian mixture model to predict the missense variants pathogenicity of Sanfilippo syndrome
Authors: Mohammed Eman E. A. , Fayez Alaaeldin G. , Abdelfattah Nabil M. , Fateen Ekram
Published: May 2024

MPS III is an autosomal recessive lysosomal storage disease caused mainly by missense variants in the NAGLU, GNS, HGSNAT, and SGSH genes. The pathogenicity interpretation of missense variants is still challenging. We aimed to develop unsupervised clustering-based pathogenicity predictor scores using extracted features from eight in silico predictors to predict the impact of novel missense variants of Sanfilippo syndrome. The model was trained on a dataset consisting of 415 uncertain significant (VUS) missense NAGLU variants. Performance The SanfilippoPred tool was evaluated by validation and test datasets consisting of 197-labelled NAGLU missense variants, and its performance was compared versus individual pathogenicity predictors using receiver operating characteristic (ROC) analysis. Moreover, we tested the SanfilippoPred tool using extra-labelled 427 missense variants to assess its specificity and sensitivity threshold. Application of the trained machine learning (ML) model on the test dataset of labelled NAGLU missense variants showed that SanfilippoPred has an accuracy of 0.93 (0.86–0.97 at CI 95%), sensitivity of 0.93, and specificity of 0.92. The comparative performance of the SanfilippoPred showed better performance (AUC = 0.908) than the individual predictors SIFT (AUC = 0.756), Polyphen-2 (AUC = 0.788), CADD (AUC = 0.568), REVEL (AUC = 0.548), MetaLR (AUC = 0.751), and AlphMissense (AUC = 0.885). Using high-confidence labelled NAGLU variants, showed that SanfilippoPred has an 85.7% sensitivity threshold. The poor correlation between the Sanfilippo syndrome phenotype and genotype represents a demand for a new tool to classify its missense variants. This study provides a significant tool for preventing the misinterpretation of missense variants of the Sanfilippo syndrome-relevant genes. Finally, it seems that ML-based pathogenicity predictors and Sanfilippo syndrome-specific prediction tools could be feasible and efficient pathogenicity predictors in the future.
First external validity study of the Fagotti score in ovarian cancer
Authors: Aida Sarah , Levaillant Mathieu , Azaïs Henri , Ballester Marcos , Canlorbe Geoffroy , Chauvet Pauline , Gauthier Tristan , Huchon Cyrille , Kerbage Yohan , Koskas Martin , Lecointre Lise , Ouldamer Lobna , Raimond Émilie , Lavoué Vincent , Legendre Guillaume
Published: May 2024

Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75–0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score.
Correlation of the total superoxide dismutase activity between joint fluid and synovium in end-stage knee osteoarthritis
Authors: Koike Masato , Nojiri Hidetoshi , Kanazawa Hiroaki , Sawa Mamiko , Miyagawa Kei , Yamaguchi Hiroto , Iwase Yoshiyuki , Kurosawa Hisashi , Kaneko Kazuo , Ishijima Muneaki
Published: May 2024

Recently, we found significantly reduced total superoxide dismutase (SOD) activity in the cartilage of patients with end-stage knee osteoarthritis (OA). In this study, we aimed to evaluate the SOD activity in serum, joint fluid, cartilage, and synovial membrane samples collected from 52 patients with end-stage knee OA who underwent total knee arthroplasty. The relationship between the total SOD activity in each tissue was evaluated using Spearman’s rank correlation coefficient. The joint fluid total SOD activity was used as the objective variable, and its association with the serum, cartilage, and synovial total SOD activities was evaluated using multiple linear regression analysis. Univariate analysis revealed that joint fluid total SOD activity was positively correlated with synovial total SOD activity. Multiple linear regression analysis using joint fluid total SOD activity as the objective variable showed a positive association with synovial total SOD activity (β = 0.493, adjusted R2 = 0.172, P < 0.01). In patients with end-stage knee OA, the state of the synovial total SOD activity is better reflected by the total SOD activity in the joint fluid than that in the cartilage. Joint fluid total SOD activity may serve as a biomarker for the treatment and prevention of synovitis.
Micropeptide AF127577.4-ORF hidden in a lncRNA diminishes glioblastoma cell proliferation via the modulation of ERK2/METTL3 interaction
Authors: Du Baoshun , Zhang Zheying , Jia Linlin , Zhang Huan , Zhang Shuai , Wang Haijun , Cheng Zhenguo
Published: May 2024

Micropeptides hidden in long non-coding RNAs (lncRNAs) have been uncovered to program various cell-biological changes associated with malignant transformation-glioblastoma (GBM) cascade. Here, we identified and characterized a novel hidden micropeptide implicated in GBM. We screened potential candidate lncRNAs by establishing a workflow involving ribosome-bound lncRNAs, publicly available MS/MS data, and prognosis-related lncRNAs. Micropeptide expression was detected by western blot (WB), immunofluorescence (IF), and immunohistochemistry (IHC). Cell proliferation rate was assessed by calcein/PI staining and EdU assay. Proteins interacted with the micropeptide were analyzed by proteomics after co-immunoprecipitation (Co-IP). We discovered that lncRNA AF127577.4 indeed encoded an endogenous micropeptide, named AF127577.4-ORF. AF127577.4-ORF was associated with GBM clinical grade. In vitro, AF127577.4-ORF could suppress GBM cell proliferation. Moreover, AF127577.4-ORF reduced m6A methylation level of GBM cells. Mechanistically, AF127577.4-ORF diminished ERK2 interaction with m6A reader methyltransferase like 3 (METTL3) and downregulated phosphorylated ERK (p-ERK) level. The ERK inhibitor reduced p-ERK level and downregulated METTL3 protein expression. AF127577.4-ORF weakened the stability of METTL3 protein by ERK. Also, AF127577.4-ORF suppressed GBM cell proliferation via METTL3. Our study identifies a novel micropeptide AF127577.4-ORF hidden in a lncRNA, with a potent anti-proliferating function in GBM by diminishing METTL3 protein stability by reducing the ERK2/METTL3 interaction. This micropeptide may be beneficial for development of therapeutic strategies against GBM.
Interspecific selection in a diverse mycorrhizal symbiosis
Authors: Rúa Megan A. , Hoeksema Jason D.
Published: May 2024

Coevolution describes evolutionary change in which two or more interacting species reciprocally drive each other’s evolution, potentially resulting in trait diversification and ecological speciation. Much progress has been made in analysis of its dynamics and consequences, but relatively little is understood about how coevolution works in multispecies interactions, i.e., those with diverse suites of species on one or both sides of an interaction. Interactions among plant hosts and their mutualistic ectomycorrhizal fungi (ECM) may provide an ecologically unique arena to examine the nature of selection in multispecies interactions. Using native genotypes of Monterey pine (Pinus radiata), we performed a common garden experiment at a field site that contains native stands to investigate selection from ECM fungi on pine traits. We planted seedlings from all five native populations, as well as inter-population crosses to represent intermediate phenotypes/genotypes, and measured seedling traits and ECM fungal traits to evaluate the potential for evolution in the symbiosis. We then combined field estimates of selection gradients with estimates of heritability and genetic variance–covariance matrices for multiple traits of the mutualism to determine which fungal traits drive plant fitness variation. We found evidence that certain fungal operational taxonomic units, families and species-level morphological traits by which ECM fungi acquire and transport nutrients exert selection on plant traits related to growth and allocation patterns. This work represents the first field-based, community-level study measuring multispecific coevolutionary selection in nutritional symbioses.
Evolutionary dynamics of canine kobuvirus in Vietnam and Thailand reveal the evidence of viral ability to evade host immunity
Authors: Van Nguyen Tin , Kasantikul Tanit , Piewbang Chutchai , Techangamsuwan Somporn
Published: May 2024

Canine kobuvirus (CaKoV) is a pathogen associated with canine gastrointestinal disease (GID). This study examined 327 rectal swabs (RS), including 113 from Vietnam (46 healthy, 67 with GID) and 214 from Thailand (107 healthy and 107 with GID). CaKoV was detected in both countries, with prevalences of 28.3% (33/113) in Vietnam and 7.9% (17/214) in Thailand. Additionally, CaKoV was found in both dogs with diarrhea and healthy dogs. CaKoV was mainly found in puppies under six months of age (30.8%). Co-detection with other canine viruses were also observed. The complete coding sequence (CDS) of nine Vietnamese and four Thai CaKoV strains were characterized. Phylogenetic analysis revealed a close genetic relationship between Vietnamese and Thai CaKoV strains, which were related to the Chinese strains. CDS analysis indicated a distinct lineage for two Vietnamese CaKoV strains. Selective pressure analysis on the viral capsid (VP1) region showed negative selection, with potential positive selection sites on B-cell epitopes. This study, the first of its kind in Vietnam, provides insights into CaKoV prevalence in dogs of different ages and healthy statuses, updates CaKoV occurrence in Thailand, and sheds light on its molecular characteristics and immune evasion strategies.
HIF2α-dependent Dock4/Rac1-signaling regulates formation of adherens junctions and cell polarity in normoxia
Authors: Raykhel I. , Ronkainen V.-P. , Myllyharju J. , Manninen A.
Published: May 2024

Hypoxia-inducible factors (HIF) 1 and 2 regulate similar but distinct sets of target genes. Although HIFs are best known for their roles in mediating the hypoxia response accumulating evidence suggests that under certain conditions HIFs, particularly HIF2, may function also under normoxic conditions. Here we report that HIF2α functions under normoxic conditions in kidney epithelial cells to regulate formation of adherens junctions. HIF2α expression was required to induce Dock4/Rac1/Pak1-signaling mediating stability and compaction of E-cadherin at nascent adherens junctions. Impaired adherens junction formation in HIF2α- or Dock4-deficient cells led to aberrant cyst morphogenesis in 3D kidney epithelial cell cultures. Taken together, we show that HIF2α functions in normoxia to regulate epithelial morphogenesis.
Deciphering anoikis resistance and identifying prognostic biomarkers in clear cell renal cell carcinoma epithelial cells
Authors: Li Junyi , Cao Qingfei , Tong Ming
Published: May 2024

This study tackles the persistent prognostic and management challenges of clear cell renal cell carcinoma (ccRCC), despite advancements in multimodal therapies. Focusing on anoikis, a critical form of programmed cell death in tumor progression and metastasis, we investigated its resistance in cancer evolution. Using single-cell RNA sequencing from seven ccRCC patients, we assessed the impact of anoikis-related genes (ARGs) and identified differentially expressed genes (DEGs) in Anoikis-related epithelial subclusters (ARESs). Additionally, six ccRCC RNA microarray datasets from the GEO database were analyzed for robust DEGs. A novel risk prognostic model was developed through LASSO and multivariate Cox regression, validated using BEST, ULCAN, and RT-PCR. The study included functional enrichment, immune infiltration analysis in the tumor microenvironment (TME), and drug sensitivity assessments, leading to a predictive nomogram integrating clinical parameters. Results highlighted dynamic ARG expression patterns and enhanced intercellular interactions in ARESs, with significant KEGG pathway enrichment in MYC + Epithelial subclusters indicating enhanced anoikis resistance. Additionally, all ARESs were identified in the spatial context, and their locational relationships were explored. Three key prognostic genes—TIMP1, PECAM1, and CDKN1A—were identified, with the high-risk group showing greater immune infiltration and anoikis resistance, linked to poorer prognosis. This study offers a novel ccRCC risk signature, providing innovative approaches for patient management, prognosis, and personalized treatment.
Population-based nanopore sequencing of the HIV-1 pangenome to identify drug resistance mutations
Authors: Ode Hirotaka , Matsuda Masakazu , Shigemi Urara , Mori Mikiko , Yamamura Yoshimi , Nakata Yoshihiro , Okazaki Reiko , Kubota Mai , Setoyama Yuka , Imahashi Mayumi , Yokomaku Yoshiyuki , Iwatani Yasumasa
Published: May 2024

HIV-1 drug resistance genotypic tests have primarily been performed by Sanger sequencing of gene segments encoding different drug target proteins. Since the number of targets has increased with the addition of a new class of antiretroviral drugs, a simple high-throughput system for assessing nucleotide sequences throughout the HIV-1 genome is required. Here, we developed a new solution using nanopore sequencing of viral pangenomes amplified by PCR. Benchmark tests using HIV-1 molecular clones demonstrated an accuracy of up to 99.9%. In addition, validation tests of our protocol in 106 clinical samples demonstrated high concordance of drug resistance and tropism genotypes (92.5% and 98.1%, respectively) between the nanopore sequencing-based results and archived clinical determinations made based on Sanger sequencing data. These results suggest that our new approach will be a powerful solution for the comprehensive survey of HIV-1 drug resistance mutations in clinical settings.
Reagent-free detection of Plasmodium falciparum malaria infections in field-collected mosquitoes using mid-infrared spectroscopy and machine learning
Authors: Mwanga Emmanuel P. , Kweyamba Prisca A. , Siria Doreen J. , Mshani Issa H. , Mchola Idrisa S. , Makala Faraja E. , Seleman Godian , Abbasi Said , Mwinyi Sophia H. , González-Jiménez Mario , Waynne Klaas , Baldini Francesco , Babayan Simon A. , Okumu Fredros O.
Published: May 2024

Field-derived metrics are critical for effective control of malaria, particularly in sub-Saharan Africa where the disease kills over half a million people yearly. One key metric is entomological inoculation rate, a direct measure of transmission intensities, computed as a product of human biting rates and prevalence of Plasmodium sporozoites in mosquitoes. Unfortunately, current methods for identifying infectious mosquitoes are laborious, time-consuming, and may require expensive reagents that are not always readily available. Here, we demonstrate the first field-application of mid-infrared spectroscopy and machine learning (MIRS-ML) to swiftly and accurately detect Plasmodium falciparum sporozoites in wild-caught Anopheles funestus, a major Afro-tropical malaria vector, without requiring any laboratory reagents. We collected 7178 female An. funestus from rural Tanzanian households using CDC-light traps, then desiccated and scanned their heads and thoraces using an FT-IR spectrometer. The sporozoite infections were confirmed using enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), to establish references for training supervised algorithms. The XGBoost model was used to detect sporozoite-infectious specimen, accurately predicting ELISA and PCR outcomes with 92% and 93% accuracies respectively. These findings suggest that MIRS-ML can rapidly detect P. falciparum in field-collected mosquitoes, with potential for enhancing surveillance in malaria-endemic regions. The technique is both fast, scanning 60–100 mosquitoes per hour, and cost-efficient, requiring no biochemical reactions and therefore no reagents. Given its previously proven capability in monitoring key entomological indicators like mosquito age, human blood index, and identities of vector species, we conclude that MIRS-ML could constitute a low-cost multi-functional toolkit for monitoring malaria risk and evaluating interventions.
The role of laboratory indices on treatment response and survival in breast cancer receiving neoadjuvant chemotherapy
Authors: Yildirim Sedat , Dogan Akif , Akdag Goncagul , Yüksel Yasar Zeynep , Bal Hamit , Kinikoglu Oguzcan , Oksuz Sila , Ozkerim Ugur , Tunbekici Salih , Yildiz Hacer Sahika , Alan Ozkan , Coban Kokten Sermin , Isik Deniz , Surmeli Heves , Basoglu Tugba , Sever Ozlem Nuray , Odabas Hatice , Yildirim Mahmut Emre , Turan Nedim
Published: May 2024

Neoadjuvant chemotherapy (NACT) is the standard treatment for locally advanced, high-risk breast cancer. Pathological complete response (pCR) improves survival. Peripheral blood-derived indices reflecting systemic inflammation and nutritional status have long been used as predictive and prognostic markers in solid malignancies. This retrospective study investigates whether eight commonly used indices in patients receiving NACT affect pCR and survival. This study includes 624 locally advanced breast cancer patients who received NACT. The biomarker indices were calculated from peripheral blood samples taken two weeks before starting chemotherapy. The indices’ optimal cut-off values were determined using ROC Curve analysis. During a median follow-up period of 42 months, recurrence was detected in 146 patients, and 75 patients died. pCR was observed in 166 patients (26.6%). In univariate analysis, NLR, PLR, SII, PNI, HALP, and HRR were statistically significantly associated (p = 0.00; p = 0.03; p = 0.03; p = 0.02; p = 0.00; p = 0.02 respectively), but in multivariate analysis, only NLR was significantly predictive for pCR(p = 0.04). In multivariate analysis, the HGB/RDW score significantly predicted DFS(p = 0.04). The PNI score was identified as a marker predicting survival for both OS and PFS (p = 0.01, p = 0.01, respectively). In conclusion, peripheral blood-derived indices have prognostic and predictive values on pCR and survival. However, further studies are needed to validate our findings.
The social stratification of internal migration and daily mobility during the COVID-19 pandemic
Authors: Elejalde Erick , Ferres Leo , Navarro Victor , Bravo Loreto , Zagheni Emilio
Published: May 2024

This study leverages mobile data for 5.4 million users to unveil the complex dynamics of daily mobility and longer-term relocations in and from Santiago, Chile, during the COVID-19 pandemic, focusing on socioeconomic differentials. We estimated a relative increase in daily mobility, in 2020, for lower-income compared to higher-income regions. In contrast, longer-term relocation rose primarily among higher-income groups. These shifts indicate nuanced responses to the pandemic across socioeconomic classes. Compared to 2017, economic factors in 2020 had a stronger influence on the decision to relocate and the selection of destinations, suggesting transformations in mobility behaviors. Contrary to previously held beliefs, there was no evidence supporting a preference for rural over urban destinations, despite the surge in emigration from Santiago during the pandemic. This study enhances our understanding of how varying socioeconomic conditions interact with mobility decisions during crises and provides insights for policymakers aiming to enact fair and evidence-based measures in rapidly changing circumstances.
Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure
Authors: Hessel Anthony L. , Kuehn Michel N. , Han Seong-Won , Ma Weikang , Irving Thomas C. , Momb Brent A. , Song Taejeong , Sadayappan Sakthivel , Linke Wolfgang A. , Palmer Bradley M.
Published: May 2024

In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2-/-) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2−/− fibers present deficits in force production and calcium sensitivity. Structurally, passive C2-/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2-/-, which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.