bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive modeling and simulation of photovoltaic system performance by using matlab/simulink: integrating dynamic meteorological parameters for enhanced accuracy
Authors: Nfaoui Mohamed , Ihfa Fatima Ezzahra , Bougtaib Ayoub , Harfouf Amine El , Hayani-Mounir Sanaa , Bennai Mohamed , El-Hami Khalil
Published: July 2024

Studying the operation of photovoltaic panels in the presence of varying meteorological parameters is a complex undertaking that requires the development of models to understand the physical phenomena associated with different meteorological factors. The main aim of this study is to examine the impact of meteorological factors, such as illuminance, temperature, and wind speed, on the performance of photovoltaic modules. Our goal is to develop precise models that illustrate how these factors affect the output of a photovoltaic system at a specific location. To achieve this, we utilized a rigorously validated mathematical model, previously tested with photovoltaic simulation software such as PVsyst, enabling accurate prediction of photovoltaic installation output. We compared the results of our simulations, conducted with the chosen mathematical model, with those obtained from PVsyst software. Subsequently, we validated the accuracy of our proposed model using real operating conditions simulated by PVsyst. Additionally, we incorporated additional curves, not available in the PVsyst database, accounting for wind speed as a meteorological parameter.
Suicide attempts and correlates among in-school adolescents in Benin City, Nigeria
Authors: Jegede T. O. , Jegede T. O. , Omoaregba J. O. , Arigbede O. O.
Published: July 2024

We aim to add to the literature on suicidality in Africa by estimating the prevalence and exploring the behavioural correlates of suicide attempts among in-school adolescents in Benin City, Nigeria. Utilising a cross-sectional design, participants were a random, stratified sample of students who filled out questionnaires to identify various determinants of suicidal attempts among adolescents between the ages of 10 and 19. We used bivariate and multivariate analyses to determine associations between suicide attempts and other variables. A total of 725 adolescents completed the instruments. Over 13.5% reported suicidal ideation, and approximately 10.5% reported that they had attempted suicide in the last year. At the multivariate level, adolescents who attempted suicide had significantly greater odds of being anxious, lonely, or victims of bullying behaviour. Individuals experiencing persistently sad moods, suicidal thoughts and plans were significantly associated with suicide attempts. Suicidal ideation and attempts are prevalent among adolescents. Assessment of anxiety, loneliness, and persistently sad moods as risk factors for suicide attempts among adolescents is vital. Indicators of bullying appear to be particularly relevant to the risk of suicide attempts among adolescents and should be given attention as part of risk assessments. We suggest that bullying prevention programs and early identification of the risk factors be a vital part of strategies for initiating and maintaining public health interventions pitched toward suicide prevention in Nigeria and Africa. This study will, in addition, provide a baseline for future studies on suicidal behaviour.
Die S3-Leitlinie zur Therapie von Sprachentwicklungsstörungen
Authors: Freitag Christine M.
Published: July 2024

Zusammenfassung: Die S3-Leitlinie zur Therapie von Sprachentwicklungsstörungen (AWMF: Nr. 049-015), die Ende 2022 auf der Homepage der AWMF veröffentlich wurde, ist unter Federführung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie in Kooperation mit zahlreichen Sprachwissenschaftler_innen und Sprachtherapeut_innen entwickelt und von zahlreichen wissenschaftlichen medizinischen Fachgesellschaften konsentiert worden. Die Leitliniengruppe hat erstmalig für den deutschen Sprachraum versucht, die internationale Studienlage zur Therapie unterschiedlicher Sprach- und Sprechstörungen aufzuarbeiten und darauf basierend Evidenz- oder auch Konsensus-basierte Empfehlungen für die klinische Versorgung zu formulieren. In dem vorliegenden Artikel werden diese Empfehlungen zusammenfassend dargestellt, und es wird eine Wertung der Leitlinie aus Kinder- und Jugendpsychiatrischer Sicht vorgenommen.
The Role of Continental Alkaline Magmatism in Mantle Carbon Outflux Constrained by a Machine Learning Analysis of Zircon
Authors: Wang Lu , Liu Jia , Spencer Christopher J. , Wu Sensen , Li Anzhou , Qiu Chengfeng , Wu Qi , Jia Zubing , Wang Zizhen , Sun Hao , Xia Qun‐Ke
Published: July 2024

Continental alkaline magmatism has been suggested to play a significant role in releasing deep mantle carbon into the atmosphere, which can greatly impact the global climate. However, the temporal variations of alkaline magmatism and their potential to modulate climate over geologic time remain poorly constrained. The detrital zircon record is a frequently used proxy for tracking secular variations in particular magmatism. Here, we use a novel machine‐learning technique to discriminate zircon from carbonatites, kimberlites, and other alkaline rocks. A global compilation of detrital zircon yields continental alkaline magmatic flare‐ups between 1,050−850, 650−500, 250−200, and 50−0 Ma. Our estimates indicate relatively elevated contributions of total magmatic carbon outgassing from alkaline magmatism during the aforementioned magmatic flare‐ups. We infer that anomalous alkaline magmatism may influence global warming during specific intervals of geologic time, but when they are not that voluminous or persistent extensive arc magmatism may drive warming conditions.
Is El Niño‐Southern Oscillation a Tipping Element in the Climate System?
Authors: Bayr Tobias , Lübbecke Joke F. , Fiedler Stephanie
Published: July 2024

Observed El Niño‐Southern Oscillation (ENSO) varies between decades with high ENSO amplitude and more extreme Eastern Pacific (EP) El Niño events and decades with low ENSO amplitude and mainly weak El Niño events. Based on experiments with the CESM1 model, ENSO may lock‐in into an extreme EP El Niño‐dominated state in a +3.7 K warmer climate, while in a −4.0 K cooler climate ENSO may lock‐in into a weak El Niño‐dominated state. The state shift of ENSO with global warming can be explained by the location and amplitude of the strongest warming over the eastern equatorial Pacific, which amplifies the Bjerknes feedback and allows a southward migration of the Intertropical Convergence Zone onto the equator, a prerequisite of extreme EP El Niños. In light of these results, we discuss to what extent the state of ENSO may be a tipping element in the climate system.
Supersharp Images Reveal Scars of Major Eruption on Io
Authors: Stanley Sarah
Published: July 2024

Jupiter’s volcanic moon is captured in exquisite detail by an instrument atop a mountain in Arizona.
Impact of a rash management guide in patients receiving apalutamide for high-risk localized prostate cancer in the Apa-RP study
Authors: Shore Neal , Hafron Jason , Saltzstein Daniel , Bhaumik Amitabha , Aggarwal Pankaj , Phillips Jennifer , McGowan Tracy
Published: July 2024

Background/objectives

Based on the SPARTAN and TITAN studies, apalutamide is approved for patients with nonmetastatic castration-resistant and metastatic castration-sensitive prostate cancer. Skin rash was a common adverse reaction across indications. We hypothesized that earlier identification and intervention could improve rash outcomes.

Subjects/methods

A prespecified rash management guide outlining recommended skin care practices was provided to all patients enrolled in Apa-RP (NCT04523207). Rash-related safety data from Apa-RP were compared descriptively with data from SPARTAN and TITAN.

Results

Patients in Apa-RP experienced improved rash-related outcomes vs those in SPARTAN and TITAN.

Conclusions

Increased vigilance and proactive management may reduce the incidence, severity, and duration of rash during apalutamide treatment.
Phase separation of RNF214 promotes the progression of hepatocellular carcinoma
Authors: He Zheng-Jie , He Ke , Cai Song-Wang , Zhang Rui , Shao Zhong-Bao , Wang Sheng-Te , Li Xiao-Peng , Li Yan-Chi , Liu Wei-Jing , Zhu You-Qing , Zeng Shi-Jie , Su Yu-Bin , Shi Zhi
Published: July 2024

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.
Facile and efficient synthesis of N-benzyl chitosan via a one-pot reductive amination utilizing 2-picoline borane
Authors: Miyake Junpei
Published: July 2024

In this paper, the use of 2-picoline borane (pic-BH3) as a reducing agent for the reductive amination of chitosan is reported for the first time. By optimizing the feed molar ratio of chitosan, benzaldehyde and pic-BH3, a high yield of isolated N-benzyl chitosan with a nearly perfect degree of substitution is successfully obtained. This material has rarely been obtained with previous methods. The newly developed synthetic method herein has many advantages, including being more facile, more efficient, and less harmful than conventional methods; thus, this method is applicable to other aldehydes or ketones, leading to wide varieties of N-modified chitosan in the future.
Atmospheric oxidation drove climate change on Noachian Mars
Authors: Liu Jiacheng , Michalski Joseph R. , Wang Zhicheng , Gao Wen-Sheng
Published: July 2024

Modern Mars is bipolar, cold, and oxidizing, while early Mars was characterized by icy highlands, episodic warmth and reducing atmosphere. The timing and association of the climate and redox transitions remain inadequately understood. Here we examine the spatiotemporal distribution of the low surface iron abundance in the ancient Martian terrains, revealing that iron abundance decreases with elevation in the older Noachian terrains but with latitude in the younger Noachian terrains. These observations suggest: (a) low-temperature conditions contribute to surface iron depletion, likely facilitated by anoxic leaching through freeze-thaw cycles under a reducing atmosphere, and (b) temperature distribution mode shifted from elevation-dominant to latitude-dominant during the Noachian period. Additionally, we find iron leaching intensity decreases from the Early to Late Noachian epoch, suggesting a gradual atmospheric oxidation coupled with temperature mode transition during the Noachian period. We think atmospheric oxidation led to Mars becoming cold and bipolar in its early history.
A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics
Authors: Arora Pragya , Sadhukhan Souvik , Nandi Saroj Kumar , Bi Dapeng , Sood A. K. , Ganapathy Rajesh
Published: July 2024

Many critical biological processes, like wound healing, require densely packed cell monolayers/tissues to transition from a jammed solid-like to a fluid-like state. Although numerical studies anticipate changes in the cell shape alone can lead to unjamming, experimental support for this prediction is not definitive because, in living systems, fluidization due to density changes cannot be ruled out. Additionally, a cell’s ability to modulate its motility only compounds difficulties since even in assemblies of rigid active particles, changing the nature of self-propulsion has non-trivial effects on the dynamics. Here, we design and assemble a monolayer of synthetic cell-mimics and examine their collective behaviour. By systematically increasing the persistence time of self-propulsion, we discovered a cell shape-driven, density-independent, re-entrant jamming transition. Notably, we observed cell shape and shape variability were mutually constrained in the confluent limit and followed the same universal scaling as that observed in confluent epithelia. Dynamical heterogeneities, however, did not conform to this scaling, with the fast cells showing suppressed shape variability, which our simulations revealed is due to a transient confinement effect of these cells by their slower neighbors. Our experiments unequivocally establish a morphodynamic link, demonstrating that geometric constraints alone can dictate epithelial jamming/unjamming.
Numerical simulations suggest asteroids (101955) Bennu and (162173) Ryugu are likely second or later generation rubble piles
Authors: Walsh K. J. , Ballouz R-L. , Bottke W. F. , Avdellidou C. , Connolly Jr H. C. , Delbo M. , DellaGiustina D. N. , Jawin E. R. , McCoy T. , Michel P. , Morota T. , Nolan M. C. , Schwartz S. R. , Sugita S. , Lauretta D. S.
Published: July 2024

Rubble pile asteroids are widely understood to be composed of reaccumulated debris following a catastrophic collision between asteroids in the main asteroid belt, where each disruption can make a family of new asteroids. Near-Earth asteroids Ryugu and Bennu have been linked to collisional families in the main asteroid belt, but surface age analyses of each asteroid suggest these bodies are substantially younger than their putative families. Here we show, through a coupled collisional and dynamical evolution of members of these families, that neither asteroid was likely to have been created at the same time as the original family breakups, but rather are likely remnants of later disruptions of original family members, making them second, or later, generation remnants. Our model finds about 80% and 60% of asteroids currently being delivered to near-Earth orbits from the respective families of New Polana and Eulalia are second or later generation. These asteroids delivered today in the 0.5-1 km size range have median ages since their last disruption that are substantially younger than the family age, reconciling their measured crater retention ages with membership in these families.
Surface photogalvanic effect in Ag2Te
Authors: Xie Xiaoyi , Leng Pengliang , Ding Zhenyu , Yang Jinshan , Yan Jingyi , Zhou Junchen , Li Zihan , Ai Linfeng , Cao Xiangyu , Jia Zehao , Zhang Yuda , Zhao Minhao , Zhu Wenguang , Gao Yang , Dong Shaoming , Xiu Faxian
Published: July 2024

The bulk photovoltaic effect (BPVE) in non-centrosymmetric materials has attracted significant attention in recent years due to its potential to surpass the Shockley-Queisser limit. Although these materials are strictly constrained by symmetry, progress has been made in artificially reducing symmetry to stimulate BPVE in wider systems. However, the complexity of these techniques has hindered their practical implementation. In this study, we demonstrate a large intrinsic photocurrent response in centrosymmetric topological insulator Ag2Te, attributed to the surface photogalvanic effect (SPGE), which is induced by symmetry reduction of the surface. Through diverse spatially-resolved measurements on specially designed devices, we directly observe that SPGE in Ag2Te arises from the difference between two opposite photocurrent flows generated from the top and bottom surfaces. Acting as an efficient SPGE material, Ag2Te demonstrates robust performance across a wide spectral range from visible to mid-infrared, making it promising for applications in solar cells and mid-infrared detectors. More importantly, SPGE generated on low-symmetric surfaces can potentially be found in various systems, thereby inspiring a broader range of choices for photovoltaic materials.
A data science roadmap for open science organizations engaged in early-stage drug discovery
Authors: Edfeldt Kristina , Edwards Aled M. , Engkvist Ola , Günther Judith , Hartley Matthew , Hulcoop David G. , Leach Andrew R. , Marsden Brian D. , Menge Amelie , Misquitta Leonie , Müller Susanne , Owen Dafydd R. , Schütt Kristof T. , Skelton Nicholas , Steffen Andreas , Tropsha Alexander , Vernet Erik , Wang Yanli , Wellnitz James , Willson Timothy M. , Clevert Djork-Arné , Haibe-Kains Benjamin , Schiavone Lovisa Holmberg , Schapira Matthieu
Published: July 2024

The Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery. We present here the recommendations of a working group composed of experts from both the public and private sectors. Robust data management requires precise ontologies and standardized vocabulary while a centralized database architecture across laboratories facilitates data integration into high-value datasets. Lab automation and opening electronic lab notebooks to data mining push the boundaries of data sharing and data modeling. Important considerations for building robust machine-learning models include transparent and reproducible data processing, choosing the most relevant data representation, defining the right training and test sets, and estimating prediction uncertainty. Beyond data-sharing, cloud-based computing can be harnessed to build and disseminate machine-learning models. Important vectors of acceleration for hit and chemical probe discovery will be (1) the real-time integration of experimental data generation and modeling workflows within design-make-test-analyze (DMTA) cycles openly, and at scale and (2) the adoption of a mindset where data scientists and experimentalists work as a unified team, and where data science is incorporated into the experimental design.
Economic segregation is associated with reduced concerns about economic inequality
Authors: Davidai Shai , Goya-Tocchetto Daniela , Lawson M. Asher
Published: July 2024

Economic segregation is the geographical separation of people with different economic means. In this paper, we employ an archival study of attitudes in regions with varying degrees of economic segregation and a series of experimental studies measuring reactions to hypothetical levels of segregation to examine how segregation affects concerns about inequality. Combining correlational and experimental methods and examining attitudes about economic inequality in both the United States and South Africa, we show that when individuals of different means are segregated from each other, people are less likely to engage in economic comparisons and are therefore less concerned by inequality. Moreover, we find that this is true even when people are exposed to (and are aware of) the same levels of inequality, suggesting that segregation in and of itself affects attitudes about inequality. Our findings highlight the importance of economic segregation in shaping public attitudes about organizational and societal economic inequality.
Alternative molecular mechanisms for force transmission at adherens junctions via β-catenin-vinculin interaction
Authors: Morales-Camilo Nicole , Liu Jingzhun , Ramírez Manuel J. , Canales-Salgado Patricio , Alegría Juan José , Liu Xuyao , Ong Hui Ting , Barrera Nelson P. , Fierro Angélica , Toyama Yusuke , Goult Benjamin T. , Wang Yilin , Meng Yue , Nishimura Ryosuke , Fong-Ngern Kedsarin , Low Christine Siok Lan , Kanchanawong Pakorn , Yan Jie , Ravasio Andrea , Bertocchi Cristina
Published: July 2024

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, β-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that β-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and β-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving β-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.
tracerDB: a crowdsourced fluorescent tracer database for target engagement analysis
Authors: Dopfer Johannes , Vasta James D. , Müller Susanne , Knapp Stefan , Robers Matthew B. , Schwalm Martin P.
Published: July 2024

Investigating ligand-protein complexes is essential in the areas of chemical biology and drug discovery. However, detailed information on key reagents such as fluorescent tracers and associated data for the development of widely used bioluminescence resonance energy transfer (BRET) assays including NanoBRET, time-resolved Förster resonance energy transfer (TR-FRET) and fluorescence polarization (FP) assays are not easily accessible to the research community. We created tracerDB, a curated database of validated tracers. This resource provides an open access knowledge base and a unified system for tracer and assay validation. The database is freely available at https://www.tracerdb.org/.
CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice
Authors: Colella Pasqualina , Sayana Ruhi , Suarez-Nieto Maria Valentina , Sarno Jolanda , Nyame Kwamina , Xiong Jian , Pimentel Vera Luisa Natalia , Arozqueta Basurto Jessica , Corbo Marco , Limaye Anay , Davis Kara L. , Abu-Remaileh Monther , Gomez-Ospina Natalia
Published: July 2024

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.
Future trends of marine fish biomass distributions from the North Sea to the Barents Sea
Authors: Gordó-Vilaseca Cesc , Costello Mark John , Coll Marta , Jüterbock Alexander , Reiss Henning , Stephenson Fabrice
Published: July 2024

Climate warming is one of the facets of anthropogenic global change predicted to increase in the future, its magnitude depending on present-day decisions. The north Atlantic and Arctic Oceans are already undergoing community changes, with warmer-water species expanding northwards, and colder-water species retracting. However, the future extent and implications of these shifts remain unclear. Here, we fitted a joint species distribution model to occurrence data of 107, and biomass data of 61 marine fish species from 16,345 fishery independent trawls sampled between 2004 and 2022 in the northeast Atlantic Ocean, including the Barents Sea. We project overall increases in richness and declines in relative dominance in the community, and generalised increases in species’ ranges and biomass across three different future scenarios in 2050 and 2100. The projected decline of capelin and the practical extirpation of polar cod from the system, the two most abundant species in the Barents Sea, drove an overall reduction in fish biomass at Arctic latitudes that is not replaced by expanding species. Furthermore, our projections suggest that Arctic demersal fish will be at high risk of extinction by the end of the century if no climate refugia is available at eastern latitudes.
Global biogeographic regions for ants have complex relationships with those for plants and tetrapods
Authors: Wang Runxi , Kass Jamie M. , Chaudhary Chhaya , Economo Evan P. , Guénard Benoit
Published: July 2024

On a global scale, biodiversity is geographically structured into regions of biotic similarity. Delineating these regions has been mostly targeted for tetrapods and plants, but those for hyperdiverse groups such as insects are relatively unknown. Insects may have higher biogeographic congruence with plants than tetrapods due to their tight ecological and evolutionary links with the former, but it remains untested. Here, we develop a global regionalization for a major and widespread insect group, ants, based on the most comprehensive distributional and phylogenetic information to date, and examine its similarity to regionalizations for tetrapods and vascular plants. Our ant regionalization supports the newly proposed Madagascan and Sino-Japanese realms based on tetrapod delineations, and it recovers clusters observed in plants but not in tetrapods, such as the Holarctic and Indo-Pacific realms. Quantitative comparison suggests strong associations among different groups—plants showed a higher congruence with ants than with tetrapods. These results underscore the wide congruence of diverse distribution patterns across the tree of life and the similarities shared by insects and plants that are not captured by tetrapod groups. Our analysis highlights the importance of developing global biogeographic maps for insect groups to obtain a more comprehensive geographic picture of life on Earth.
Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models
Authors: Wang Jun , Wang Meng , Moshiri Ala , Harris R. Alan , Raveendran Muthuswamy , Nguyen Tracy , Kim Soohyun , Young Laura , Wang Keqing , Wiseman Roger , O’Connor David H. , Johnson Zach , Martinez Melween , Montague Michael J. , Sayers Ken , Lyke Martha , Vallender Eric , Stout Tim , Li Yumei , Thomasy Sara M. , Rogers Jeffrey , Chen Rui
Published: July 2024

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.
TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer
Authors: Sim Nicholas , Carter Jean-Michel , Deka Kamalakshi , Tan Benita Kiat Tee , Sim Yirong , Tan Suet-Mien , Li Yinghui
Published: July 2024

Triple Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype suffering from limited targeted treatment options. Following recent reports correlating Fibroblast growth factor-inducible 14 (Fn14) receptor overexpression in Estrogen Receptor (ER)-negative breast cancers with metastatic events, we show that Fn14 is specifically overexpressed in TNBC patients and associated with poor survival. We demonstrate that constitutive Fn14 signalling rewires the transcriptomic and epigenomic landscape of TNBC, leading to enhanced tumour growth and metastasis. We further illustrate that such mechanisms activate TNBC-specific super enhancers (SE) to drive the transcriptional activation of cancer dependency genes via chromatin looping. In particular, we uncover the SE-driven upregulation of Nicotinamide phosphoribosyltransferase (NAMPT), which promotes NAD+ and ATP metabolic reprogramming critical for filopodia formation and metastasis. Collectively, our study details the complex mechanistic link between TWEAK/Fn14 signalling and TNBC metastasis, which reveals several vulnerabilities which could be pursued for the targeted treatment of TNBC patients.
Unveiling the mechanism of triphos-Ru catalysed C–O bond disconnections in polymers
Authors: Ahrens Alexander , Batista Gabriel Martins Ferreira , Hammershøj Hans Christian D. , Schwibinger Emil Vincent , Nova Ainara , Skrydstrup Troels
Published: July 2024

Ruthenium complexes with facially coordinating tripodal phosphine ligands are privileged catalysts for a broad range of (de-)hydrogenation-based transformations. Among these, C–O bond hydrogenolysis holds potential for the depolymerisation of both the biopolymer lignin and epoxy resins applied in wind turbine blades, aircrafts and more. However, this methodology is poorly understood in mechanistic terms. Here, we present a detailed investigation on the triphos-Ru catalysed C–O bond scission on a molecular level. A combination of experimental, spectroscopical and theoretical studies elucidates the reactivity of the ruthenium trimethylenemethane precatalyst, revealing the key roles of ruthenium phenolates in both catalyst activation as well as the catalytic cycle itself. Furthermore, a Ru(0)/Ru(II) oxidative addition into the C–O bond is disclosed, with a triphos-Ru(0) dihydrogen complex as entry point. With the molecular nature of the operating triphos-Ru species and the thermodynamics and kinetics of the catalysis unravelled, improvements of established methods as well as design of related transformations may become possible.
Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation
Authors: Su Kexin , Shi Lu , Sheng Tao , Yan Xinxin , Lin Lixin , Meng Chaoyang , Wu Shiqi , Chen Yuxuan , Zhang Yao , Wang Chaorong , Wang Zichuan , Qiu Junjie , Zhao Jiahui , Xu Tengfei , Ping Yuan , Gu Zhen , Liu Shuai
Published: July 2024

Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.
Stable peptide-assembled nanozyme mimicking dual antifungal actions
Authors: Yuan Ye , Chen Lei , Song Kexu , Cheng Miaomiao , Fang Ling , Kong Lingfei , Yu Lanlan , Wang Ruonan , Fu Zhendong , Sun Minmin , Wang Qian , Cui Chengjun , Wang Haojue , He Jiuyang , Wang Xiaonan , Liu Yuan , Jiang Bing , Jiang Jing , Wang Chenxuan , Yan Xiyun , Zhang Xinzheng , Gao Lizeng
Published: July 2024

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.
Quantifying mechanical forces during vertebrate morphogenesis
Authors: Maniou Eirini , Todros Silvia , Urciuolo Anna , Moulding Dale A. , Magnussen Michael , Ampartzidis Ioakeim , Brandolino Luca , Bellet Pietro , Giomo Monica , Pavan Piero G. , Galea Gabriel L. , Elvassore Nicola
Published: July 2024

Morphogenesis requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these force fields can lead to congenital malformations. Understanding these dynamic processes requires the quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis. Here we describe elastic spring-like force sensors with micrometre-level resolution, fabricated by intravital three-dimensional bioprinting directly in the closing neural tubes of growing chicken embryos. Integration of calibrated sensor read-outs with computational mechanical modelling allows direct quantification of the forces and work performed by the embryonic tissues. As they displace towards the embryonic midline, the two halves of the closing neural tube reach a compression of over a hundred nano-newtons during neural fold apposition. Pharmacological inhibition of Rho-associated kinase to decrease the pro-closure force shows the existence of active anti-closure forces, which progressively widen the neural tube and must be overcome to achieve neural tube closure. Overall, our approach and findings highlight the intricate interplay between mechanical forces and tissue morphogenesis.
The way we look at an image or a webpage can reveal personality traits
Authors: Le Bras Thomas , Allibe Benoit , Doré-Mazars Karine
Published: July 2024

Personality is a central concept and a cross-domain explanatory factor in psychology to characterize and differentiate individuals. Surprisingly, among the many studies on oculomotor behavior, only a few have investigated how personality influences the exploration of a visual stimulus. Due to the limited number of existing studies, it is still uncertain if markers of personality in eye movements are always observable in eye movements across various exploration contexts. Here, introducing a novel concept of gaze-based signatures of personality, we used visual exploration metrics to detect personality signatures across various exploration contexts (visual search and free-viewing on images and webpages) in 91 participants. Personality data were collected as in the reference paper that validated the French version of the Big Five Inventory. Linear regression analyses demonstrated that while Extraversion and Openness to Experience did not correlate with any particular exploration metric, the other three traits–Conscientiousness, Agreeableness, and Neuroticism–correlated robustly with all exploration metrics in different visual exploration contexts. Our study provides evidence for the capture of the gaze-based signature of personality from very brief eye movement recordings.
Biomechanical factors associated with patellofemoral pain in children and adolescents
Authors: Sanchis Gerônimo J. B. , Nascimento Jeisyane A. S. do , Santana Rebeca de C. , Santos Vagner M. dos , Cunha Vitor L. da , Assis Sanderson J. C. de , Cavalcanti Rafael L. , Guedes Thaís S. R. , Oliveira Angelo G. R. da C. , Guedes Marcello B. O. G.
Published: July 2024

To investigate the biomechanical factors associated with patellofemoral pain in children and adolescents. A cross-sectional, population-based study conducted in Brazil from 2019 to 2023, involving students from public schools. Adjusted prevalence ratios and their respective 95% confidence intervals for the outcome in relation to independent variables were calculated for association analysis, adopting a significance level of 5%. Out of the total of 283 students, 152 were female and 182 were aged between 16 and 18 years old. A positive association was observed between the presence of patellofemoral pain and a poor movement quality in both lower limbs (right side: p = 0.04 and left side: p = 0.04) as well as with dynamic valgus of the left lower limb (p < 0.01). Patellofemoral pain in children and adolescents is associated with poor movement quality in the lower limbs and dynamic valgus of the left lower limb. Actions targeting these biomechanical factors may be crucial for early diagnosis and clinical treatment of this disfunction.
Enhancing aromatic rice production through agronomic and nutritional management for improved yield and quality
Authors: Patra Partha Sarathi , Saha Rajesh , Ahmed Arju Sahid , Kanjilal Bratati , Debnath Manoj Kanti , Paramanik Bappa , Hoque Akramul , Kundu Arindam , Adhikary Pabitra , Biswas Amiya , Dey Prithwiraj , Biswas Asim
Published: July 2024

To meet the growing international demand for aromatic rice, this study, conducted at Uttar Banga Krishi Viswavidyalaya in Cooch Behar, West Bengal, aimed to enhance the yield and quality of the ‘Tulaipanji’ rice cultivar through advanced establishment methods and the use of organic nutrients over two years. The research tested three planting techniques: mechanical transplanting, wet direct seeding (using a drum seeder), and traditional methods, alongside four nutrient management strategies: vermicompost, farmyard manure, a mix of both, and conventional fertilizers. Findings revealed that mechanical transplanting significantly increased yield by over 31.98% and 71.05% compared to traditional methods and wet direct seeding, respectively. Using vermicompost alone as a nutrient source not only boosted yields by 21.31% over conventional fertilizers but also enhanced the rice's nutritional value and cooking quality. Moreover, soils treated with vermicompost showed higher dehydrogenase activity, indicating better soil health. Economically, mechanical transplanting with vermicompost was the most beneficial, yielding the highest net returns and benefit–cost ratios in both years studied. This approach presents a viable model for improving the sustainability of aromatic rice production globally, emphasizing the economic and environmental advantages of adopting mechanical planting techniques and organic fertilization methods.
Multicentric short term and safety study of ineffective esophageal motility patients treated with RefluxStop device
Authors: Feka J. , Saad M. , Boyle N. , Paireder M. , Kristo I. , Rieder E. , Asari R. , Schoppmann S. F.
Published: July 2024

Gastroesophageal reflux disease (GERD) presents a general health problem with a variety of symptoms and an impairment of life quality. Conservative therapies do not offer sufficient symptom relief in up to 30% of patients. Patients who suffer from ineffective esophageal motility (IEM) and also GERD may exhibit symptoms ranging from mild to severe. In cases where surgical intervention becomes necessary for this diverse group of patients, it is important to consider the potential occurrence of postoperative dysphagia. RefluxStop is a new alternative anti-reflux surgery potentially reducing postoperative dysphagia rates. In this bicentric tertiary hospital observational study consecutive patients diagnosed with PPI refractory GERD and IEM that received RefluxStop implantation were included. A first safety and efficacy evaluation including clinical examination and GERD-HRQL questionnaire was conducted. 40 patients (25 male and 15 female) were included. 31 patients (77.5%) were on PPI at time of surgery, with mean acid exposure time of 8.14% ± 2.53. The median hospital stay was 3 days. Postoperative QoL improved significantly measured by GERD HRQL total score from 32.83 ± 5.08 to 6.6 ± 3.71 (p < 0.001). A 84% reduction of PPI usage (p < 0.001) was noted. 36 patients (90%) showed gone or improved symptoms and were satisfied at first follow-up. Two severe adverse events need mentioning: one postoperative slipping of the RefluxStop with need of immediate revisional operation on the first postoperative day (Clavien–Dindo Score 3b) and one device migration with no necessary further intervention. RefluxStop device implantation is safe and efficient in the short term follow up in patients with GERD and IEM. Further studies and longer follow-up are necessary to prove long-lasting positive effects.
Metabolomics-based search for lung cancer markers among patients with different smoking status
Authors: Klupczynska-Gabryszak Agnieszka , Daskalaki Evangelia , Wheelock Craig E. , Kasprzyk Mariusz , Dyszkiewicz Wojciech , Grabicki Marcin , Brajer-Luftmann Beata , Pawlak Magdalena , Kokot Zenon J. , Matysiak Jan
Published: July 2024

Tobacco smoking is the main etiological factor of lung cancer (LC), which can also cause metabolome disruption. This study aimed to investigate whether the observed metabolic shift in LC patients was also associated with their smoking status. Untargeted metabolomics profiling was applied for the initial screening of changes in serum metabolic profile between LC and chronic obstructive pulmonary disease (COPD) patients, selected as a non-cancer group. Differences in metabolite profiles between current and former smokers were also tested. Then, targeted metabolomics methods were applied to verify and validate the proposed LC biomarkers. For untargeted metabolomics, a single extraction-dual separation workflow was applied. The samples were analyzed using a liquid chromatograph-high resolution quadrupole time-of-flight mass spectrometer. Next, the selected metabolites were quantified using liquid chromatography-triple-quadrupole mass spectrometry. The acquired data confirmed that patients’ stratification based on smoking status impacted the discriminating ability of the identified LC marker candidates. Analyzing a validation set of samples enabled us to determine if the putative LC markers were truly robust. It demonstrated significant differences in the case of four metabolites: allantoin, glutamic acid, succinic acid, and sphingosine-1-phosphate. Our research showed that studying the influence of strong environmental factors, such as tobacco smoking, should be considered in cancer marker research since it reduces the risk of false positives and improves understanding of the metabolite shifts in cancer patients.
Loop-mediated isothermal amplification (LAMP) assay coupled with gold nanoparticles for colorimetric detection of Trichoderma spp. in Agaricus bisporus cultivation substrates
Authors: Djisalov Mila , Janjušević Ljiljana , Léguillier Vincent , Šašić Zorić Ljiljana , Farre Carole , Anba-Mondoloni Jamila , Vidic Jasmina , Gadjanski Ivana
Published: July 2024

One of the significant challenges in organic cultivation of edible mushrooms is the control of invasive Trichoderma species that can hinder the mushroom production and lead to economic losses. Here, we present a novel loop-mediated isothermal amplification (LAMP) assay coupled with gold nanoparticles (AuNPs) for rapid colorimetric detection of Trichoderma spp. The specificity of LAMP primers designed on the tef1 gene was validated in silico and through gel-electrophoresis on Trichoderma harzianum and non-target soil-borne fungal and bacterial strains. LAMP amplification of genomic DNA templates was performed at 65 °C for only 30 min. The results were rapidly visualized in a microplate format within less than 5 min. The assay is based on salt-induced aggregation of AuNPs that is being prevented by the amplicons produced in case of positive LAMP reaction. As the solution color changes from red to violet upon nanoparticle aggregation can be observed with the naked eye, the developed LAMP-AuNPs assay can be easily operated to provide a simple initial screening for the rapid detection of Trichoderma in button mushroom cultivation substrate.
Concomitant decrease of E- and A-FABP expression predicts worse survival in urothelial bladder cancer patients
Authors: Saizonou Inès , Lascombe Isabelle , Monnien Franck , Bedgedjian Isabelle , Kleinclauss François , Algros Marie-Paule , Fauconnet Sylvie
Published: July 2024

Non-muscle invasive bladder cancers (NMIBC) pTa-pT1 are depicted by a high risk of recurrence and/or progression with an unpredictable clinical evolution. Our aim was to identify, from the original resection specimen, tumors that will progress to better manage patients. We previously showed that A-FABP (Adipocyte- Fatty Acid Binding Protein) loss predicted NMIBC progression. Here we determined by immunohistochemistry the prognostic value of E-FABP (Epidermal-Fatty Acid Binding Protein) expression in 210 tumors (80 pTa, 75 pT1, 55 pT2-T4). Thus, E-FABP low expression was correlated with a high grade/stage, the presence of metastatic lymph nodes, and visceral metastases (p < 0.001). Unlike A-FABP in NMIBC, E-FABP low expression was not associated with RFS or PFS in Kaplan–Meier analysis. But patients of the overall cohort with a high E-FABP expression had a longer mOS (53.8 months vs. 29.3 months, p = 0.029). The immunohistochemical analysis on the same NMIBC tissue sections revealed that when A-FABP is absent, a high E-FABP expression is detected. E-FABP could compensate A-FABP loss. Interestingly, patients, whose original tumor presents both low E-FABP and negative A-FABP, had the worse survival, those maintaining the expression of both markers had better survival. To conclude, the combined evaluation of A- and E-FABP expression allowed to stratify patients with urothelial carcinoma for optimizing treatment and follow-up.