bluuebunny/crossref_metadata_2025 huggingface dataset:
MpoxPlex: a high-throughput and versatile multiplexed immunoassay for assessing and discriminating between IgG responses to Mpox infection and vaccination
Authors: Jones Scott , Hicks Bethany , Callaby Helen , Bailey Daniel , Gordon Claire , Rampling Tommy , Houlihan Catherine , Jones Rachael , Pond Marcus , Mehta Ravi , Wright Deborah , Oeser Clarissa , Tonge Simon , Linley Ezra , Rowe Cathy , Hallis Bassam , Otter Ashley
Published: June 2024

The summer of 2022 saw the first global outbreak of Mpox disease (formerly ‘monkeypox’), primarily within gay, bisexual, and other men who have sex with men (GBMSM). In response, public health agencies in the UK have offered smallpox vaccines to those individuals deemed at highest risk of infection. With Mpox cases still being detected globally, novel tools are required to aid with diagnosis, serosurveillance and the evaluation of immune responses following infection and vaccination. Here, we describe the development of a multiplexed immunoassay that is able to measure IgG responses to twelve immunogenic Orthopoxvirus proteins concurrently and distinguish between responses to infection and vaccination.

Using the Luminex platform, antibody responses to vaccinia virus (VACV) proteins B5, A27, A33 and Monkeypox virus (MPXV) proteins E8, B6, B2, M1, A27, A35, H3, A29, A5 were assessed in serum from individuals post-MPXV infection (n=24) and post-vaccination (n=75) with modified vaccinia virus Ankara-Bavarian Nordic (MVA-BN, “IMVANEX”). Negative sera (n=435) were run alongside to assess appropriate assay cut-offs and characteristics.

Using the results from a combination of eight of the twelve proteins within the immunoassay we were able to classify samples as either post-vaccination or infection, from negative samples with a sensitivity of 98.39% (9.72-99.22%) and specificity of 95.24% (86.91-98.70%). IgG responses to VACV A27, MPXV A29 and MPXV A5 provided little diagnostic advantage. IgG responses to the MPXV protein A27 were able to distinguish post-MPXV infection from negative and post-vaccination samples with a sensitivity of 87.5% (69.00-95.66%) and specificity of 96.84% (94.84-98.07%).

There is an ongoing need to utilise Mpox serology to conduct disease surveillance, assess the efficacy of current and new vaccine candidates, and further understand immune responses to Mpox infection. We believe this assay will provide substantial insight into the current global outbreak of Mpox, with additional benefits over current serological assays.
A staged screening protocol identifies people with biomarkers related to neuronal alpha-synuclein disease
Authors: Brown Ethan G. , Chahine Lana M. , Siderowf Andrew , Gochanour Caroline , Kurth Ryan , Marshall Micah J. , Caspell-Garcia Chelsea , Brumm Michael C. , Coffey Christopher S. , Stanley Craig E. , Korell Monica , McMahon Bridget , Kuhl Maggie , Fabrizio Kimberly , Heathers Laura , Foroud Tatiana M. , Concha-Marambio Luis , Soto Claudio , Chowdhury Sohini , Simuni Tanya , Marek Kenneth , Tanner Caroline M. ,   the Parkinson Progression Marker Initiative
Published: June 2024

Importance

Identifying individuals in the earliest stages of synucleinopathy is essential to evaluate drugs aimed to slow progression or prevent manifest disease. Remote identification of hyposmic individuals may enable scalable recruitment of participants with underlying alpha-synuclein pathology.

Objective

To evaluate the performance of a staged screening paradigm using smell testing to enrich for deficit on dopaminergic transporter (DAT) imaging and pathologic alpha-synuclein aggregation.

Design

Cross-sectional analysis of data from the Parkinson’s Progression Markers Initiative (PPMI).

Setting

Screening activities were completed both at home and local PPMI sites.

Participants

Individuals aged 60 and older without a diagnosis of Parkinson’s diseaseInterventions or Exposures:Participants were asked to complete a University of Pennsylvania Smell Identification Test (UPSIT) remotely. Participants with hyposmia were invited to complete DAT imaging, which determined eligibility for enrollment in longitudinal assessments and further biomarker evaluation including cerebrospinal fluid synuclein seed amplification assay (synSAA).

Main Outcomes and Measures

We determined the proportion of people with hyposmia, impaired DAT binding, and positive synSAA and explored determinants of these biomarkers.

Results

As of January 29, 2024, 49,843 participants were sent an UPSIT and 31,293 (63%) completed it. Of UPSIT completers, 8,301 (27%) scored <15th%ile. Of 1,546 who completed DAT, 19% had DAT binding < 65% expected for age and sex. Self-reported features were independently associated with severe hyposmia (UPSIT <10th%ile), such as REM sleep behavior disorder (RBD) or dream enactment behavior (DEB) (aOR: 1.9, 95% CI 1.7–2.1) and subjective smell loss (aOR: 15.0, 95% CI 13.7–16.3). Participants with an UPSIT <10th%ile (N=1,221) had greater likelihood of low DAT binding compared to participants with an UPSIT in the 10th– 15th%ile (OR 3.01, 95% CI 1.85–4.91). Among remotely recruited participants with synSAA results obtained, 198/363 (55%) had positive synSAA at baseline. This proportion increased when the cohort was limited to an UPSIT<10th%ile (182/257, 71%).

Conclusion and Relevance

Remote screening for severe hyposmia identifies participants with a high proportion of positive synSAA and reduced DAT binding. This staged screening protocol is an effective approach to identify cohorts for therapeutic trials aiming to slow progression in alpha-synucleinopathy.
Genetic Evidence for a Causal Link between Intra-Pancreatic Fat Deposition and Pancreatitis: a Mendelian Randomization Study
Authors: Yamazaki Hajime , Heni Martin , Wagner Róbert , Fukuhara Shunichi , Grossman Steven R. , Han Sihao , Wu Lang , Streicher Samantha A. , Huang Brian Z.
Published: June 2024

Introduction

Recent associative studies have linked intra-pancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear.

Methods

Utilizing Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach utilized genetic variants from genome-wide association studies of IPFD (n=25,617), acute pancreatitis (n=6,787 cases/361,641 controls), and chronic pancreatitis (n=3,875 cases/361,641 controls).

Results

Genetically predicted IPFD was significantly associated with acute pancreatitis (OR per 1-SD increase: 1.40[95%CI:1.12-1.76], p=0.0032) and chronic pancreatitis (OR:1.64[95%CI:1.13-2.39], p=0.0097).

Discussion

Our findings support a causal role of IPFD in pancreatitis, suggesting that reducing IPFD could lower the risk of pancreatitis.
Lifestyles and their relative contribution to biological aging across multiple organ systems: change analysis from the China Multi-Ethnic Cohort Study
Authors: Zhang Yuan , Tang Dan , Zhang Ning , Xiang Yi , Hu Yifan , Qian Wen , Baima Yangji , Ding Xianbin , Wang Ziyun , Yin Jianzhong , Xiao Xiong , Zhao Xing
Published: June 2024

Background

Biological aging exhibits heterogeneity across multi organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China.

Objective

To examine the associations of healthy lifestyle with comprehensive and organ-specific biological ages and which lifestyle factors contribute most.

Methods

This study involved 8,396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) Study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera-Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation.

Results

About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in healthy lifestyle index showed a protective association with the acceleration of all biological ages, with a mean shift of –0.19 (95%CI: –0.34, –0.03) in the comprehensive biological age acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively.

Conclusions

Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Machine Learning Assisted Web Application for Identifying Beneficial Drug Candidates for Genetic Alterations in Cancer Patients
Authors: Bozcuk Hakan Şat
Published: June 2024

Background

Precision medicine in oncology relies heavily on molecular genetic data, primarily obtained from Next-generation sequencing (NGS) tests. However, the complexity of these data and the need to match genetic alterations with specific drug candidates pose significant challenges for clinicians. To simplify this process, a user-friendly web application has been developed. This app facilitates the matching, graphical presentation, and clustering of treatment options for specific genetic alterations, making it easier for clinicians to interpret and apply the results in patient care.

Materials and Methods

Utilizing the application programming interface (API) of the Drug-Gene Interaction Database (DGIdb 4.0), a web application was developed in Python to list drugs that interact with specific genetic changes. The application features a user-friendly display achieved through graphical representation and web scraping for gene-related information. Additionally, unsupervised machine learning, specifically K-means cluster analysis, was employed to categorize drug candidates based on their interaction scores with the genetic alteration in question. To enhance the interpretability of the results, the web app also provides key references and web links to the relevant drug interactions.

Results

The developed web application successfully filtered, listed, and displayed the gene interaction results. Utilizing an unsupervised machine learning algorithm, the app identified three optimal clusters of drug candidates based on their efficacy potentials using the Elbow Method. The cluster analysis demonstrated strong performance, evidenced by the following metrics for BRAF mutations: a Silhouette score of 0.74, a Davies-Bouldin index of 0.44, and a Calinski-Harabasz index of 475.96. Additionally, the web app effectively extracted and defined relevant gene information and identified key references for each genetic alteration within the cloud database.

Conclusion

The web application developed in this study provides a user-friendly platform for classifying and interpreting drug candidates based on the presence of specific genetic alterations in cancer patients. This tool is expected to enhance the accessibility and usability of genetic data, aiding clinicians in making informed treatment decisions.
Current-use and legacy contaminants evidence dissolved organic matter transfer and dynamics across a fractured-rock groundwater recharge area
Authors: Zerfaß Christian , Lehmann Robert , Ueberschaar Nico , Totsche Kai Uwe , Pohnert Georg
Published: June 2024

Anthropogenic activities cause the release of vast amounts of contaminants into the environment which eventually reach even groundwater resources. With usually sparse regulatory monitoring of limited priority compounds, the large spectrum of contaminants, and the intricacies of intra- and inter-annual contaminant dynamics, such as the emergence and mobilisation of contaminants, are easily overlooked. Utilizing an 6-year record of untargeted LC-MS assessment of dissolved organic, we report the detection and tracing of selected environmental chemicals in the Hainich Critical Zone Exploratory (central Germany), representing a model groundwater flow system under different land use. The insect repellent DEET (N,N-diethyl-m-toluamide) and the coniferous resin acid 7-ODAA (7-oxodehydroabietic acids) show phases of seasonal dynamics in line with their expected periods of release. The legacy herbicides simazine, the triazine transformation product hydroxypropazine, and the flame retardant/plasticiser TPP (triphenyl phosphate) occurred episodically at various locations in the fractured sedimentary bedrock. Within the period of monitoring, extreme weather events (i.e., the severe 2018 drought) and extreme subsurface responses (i.e., 5-year groundwater highstand 2018) likely contributed to long-term organic matter dynamics, potentially causing re-emergence of legacy agrochemicals. This investigation points to the persistence and mobilisation of anthropogenic contaminants, and highlights the importance of long-term combined untargeted and targeted analysis of the groundwater dissolved organic matter for understanding subsurface ecosystems processes. The results add a note of caution for regulatory monitoring since also legacy contaminant levels may considerably vary over time.

Highlights

6 years of monitoring with non-target LC-MS screenings; 4-weekly samplings

5 current-use and legacy compounds that evidence dissolved organic matter transfer

Compounds comprise regularly targeted and non-monitored features in groundwater

Pronounced phases of non-detects help to further investigate surface-subsurface coupling

This illustrates the need for spatiotemporally highly resolved non-target monitoring
Loss of FBXO31-mediated γH2AX foci formation impairs initiation of NHEJ and HR repair pathways, and sensitizes breast cancer to therapy
Authors: Sahay Osheen , Barik Ganesh Kumar , Dey Samya , Islam Sehbanul , Paul Debasish , Bhavsar Praneeta Pradip , Nath Somsubhra , Rapole Srikanth , Santra Manas Kumar
Published: June 2024

In response to genotoxic stress, cell initiates complex signalling cascades to combat genomic insults through simultaneous initiation of growth arrest and DNA damage repair process. γH2AX functions as a crucial initiator in DNA double strand damage repair process. Therefore, γH2AX foci formation onto the damage sites is essential to initiate the recruitment of repair proteins involved in NHEJ (Non-homologous DNA-end joining) or HR (Homologous recombination) repair process. However, molecular events associated with γH2AX foci formation onto the DNA damage sites are poorly understood. Here, we show that FBXO31, the first ubiquitin ligase, mediated Lys-63-linked ubiquitination of γH2AX is essential for its foci formation onto the DNA damage sites to initiate recruitment of proteins involved in NHEJ and HR-mediated DNA damage repair. Therefore, tumors with FBXO31 deficiency show enhanced growth suppression following chemotherapeutic drug treatment because of synthetic lethality, indicating that FBXO31 could be used as a marker for predicting the outcome of chemotherapy treatment.
GCN5L1 regulates glucose and ketone body metabolism during cardiac ischemia-reperfusion injury
Authors: Bugga Paramesha , Stoner Michael W , Manning Janet R , Mushala Bellina , Bhattarai Nisha , Sharifi-Sanjani Maryam , Scott Iain
Published: June 2024

Ischemic heart diseases are the leading cause of death among cardiovascular diseases. Reperfusion of the ischemic myocardium is the only way to treat IHD. However, reperfusion can damage the ischemic myocardium if it does not happen at the right time. Therefore, understanding the pathophysiology of cardiac ischemic reperfusion injury is essential to identifying new therapeutic targets. We reported the cardioprotective role of GCN5L1 in ex-vivo cardiac ischemic reperfusion injury through the regulation of cytoprotective signaling by reducing oxidative stress. The current study investigated the role of GCN5L1 in in-vivo cardiac ischemic reperfusion injury and in-vitro H/R injury in AC16 cells. The cardiac-specific GCN5L1 KO did not further deteriorate the cardiac function and infarct size. We measured the glucose metabolism-related protein expression among all experimental groups and found that GCN5L1 KO significantly decreases glucose metabolism by PDH phosphorylation. We further evaluated the role of GCN5L1 in in-vitro H/R injury in genetically modified AC16 cells (GCN5L1 KD and overexpressed and control). GCN5L1 KD in AC16 cells promotes phosphorylation of PDH; similarly, overexpression reduces the p-PDH levels. We identified that the regulation of PDH phosphorylation via PDK4/PDP1/PDPR and GCN5L1 regulates the PDK4 expression. We measured the ketone body metabolism related to protein expression in control and KD cells after H/R injury and found the upregulation of ketone body metabolism-related protein expression in KD cells compared to control AC16 cells. Altogether, our in vivo and in vitro studies findings conclude that GCN5L1 is required for glucose metabolism in ischemic reperfusion injury, and in the absence of GCN5L1, ketone body metabolism accomplishes the cardiac energy requirements and prevents I/R induced cardiac damage and infarct size.

Graphical Abstract

Graphical abstract of the manuscript

Altogether, our results conclude that Cardiomyocyte-specific GCN5L1 KO in-vivo cardiac ischemic reperfusion injury and in-vitro Hypoxia-reoxygenation stress significantly affect glucose metabolism by suppressing glucose metabolism. Cardiac-specific GCN5L1 KO mice in-vivo and knockdown in AC16 cells invitro upregulates the expression of enzymes that are involved in the ketone body metabolism to rescue from in-vivo cardiac ischemic reperfusion injury and invitro H/R stress.
Immunoinformatics design of a novel multiepitope vaccine candidate against non-typhoidal salmonellosis caused bySalmonellaKentucky using outer membrane proteins A, C, and F
Authors: Igomu Elayoni E. , Mamman Paul H. , Adamu Jibril , Muhammad Maryam , Woziri Abubarkar O. , Sugun Manasa Y. , Benshak John A. , Anyika Kingsley C. , Sam-Gyang Rhoda , Ehizibolo David O.
Published: June 2024

The global public health risk posed bySalmonellaKentucky, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations, is rising. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we utilized a bioinformatics approach to design a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F ofSalmonellaKentucky, with thefliCprotein fromSalmonellaTyphimurium serving as an adjuvant. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. When used in vaccine formulations, the predicted epitopes are expected to achieve a population coverage of 94.91%. Additionally, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To enhance the immunogenicity of the peptide construct, thefliCprotein fromSalmonellaTyphimurium was included at the N-terminal as an adjuvant. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-γ, TGF-β, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in silico results, further validation through preclinical and clinical trials is necessary to confirm the vaccine’s protective efficacy and safety.
Genome-wide mapping of native co-localized G4s and R-loops in living cells
Authors: Liu Ting , Shen Xing , Ren Yijia , Lu Hongyu , Liu Yu , Chen Chong , Yu Lin , Xue Zhihong
Published: June 2024

The non-B DNA structures can act as dynamic functional genomic elements regulating gene expression. Among them, G4s and R-loops are two of the best studied. The interplay between R-loops and G4s are emerging in regulating DNA repair, replication and transcription. A comprehensive picture of native co-localized G4s and R-loops in living cells is currently lacking. Here, we describe the development of HepG4-seq and an optimized HBD-seq methods, which robustly capture native G4s and R-loops, respectively, in living cells. We successfully employed these methods to establish comprehensive maps of native co-localized G4s and R-loops in human HEK293 cells and mouse embryonic stem cells (mESCs). We discovered that co-localized G4s and R-loops are dynamically altered in a cell type-dependent manner and are largely localized at active promoters and enhancers of transcriptional active genes. We further demonstrated the helicase Dhx9 as a direct and major regulator that modulates the formation and resolution of co-localized G4s and R-loops. Depletion of Dhx9 impaired the self-renewal and differentiation capacities of mESCs by altering the transcription of co-localized G4s and R-loops - associated genes. Taken together, our work established that the endogenous co-localized G4s and R-loops are prevalently persisted in the regulatory regions of active genes and are involved in the transcriptional regulation of their linked genes, opening the door for exploring broader roles of co-localized G4s and R-loops in development and disease.
Chioso: Segmentation-free Annotation of Spatial Transcriptomics Data at Sub-cellular Resolution via Adversarial Learning
Authors: Yu Ji
Published: June 2024

Recent advances in spatial transcriptomics technology have produced full-transcriptomic scale dataset with subcellular spatial resolutions. Here we present a new computational algorithm, chioso, that can transfer cell-level labels from a reference dataset (typically a single-cell RNA sequencing dataset) to a target spatial dataset by assigning a label to every spatial location at sub-cellular resolution. Importantly, we do this without requiring single cell segmentation inputs, thereby simplifying the experiments, and allowing for a more streamlined, and potentially more accurate, analysis pipeline. Using a generative neural network as the underlying algorithmic engine, chioso is very fast and scales well to large datasets. We validated the performance of chioso using synthetic data and further demonstrated its scalability by analyzing the complete MOSTA dataset acquired using the Stereo-Seq technology.

Abstract Figure
Annotating publicly-available samples and studies using interpretable modeling of unstructured metadata
Authors: Yuan Hao , Hicks Parker , Ahmadian Mansooreh , Johnson Kayla , Valtadoros Lydia , Krishnan Arjun
Published: June 2024

Reusing massive collections of publicly available biomedical data can significantly impact knowledge discovery. However, these public samples and studies are typically described using unstructured plain text, hindering the findability and further reuse of the data. To combat this problem, we proposetxt2onto 2.0, a general-purpose method based on natural language processing and machine learning for annotating biomedical unstructured metadata to controlled vocabularies of diseases and tissues. Compared to the previous version (txt2onto 1.0), which uses numerical embeddings as features, this new version uses words as features, resulting in improved interpretability and performance, especially when few positive training instances are available.Txt2onto 2.0uses embeddings from a large language model during prediction to deal with unseen-yet-relevant words related to each disease and tissue term being predicted from the input text, thereby explaining the basis of every annotation. We demonstrate the generalizability oftxt2onto 2.0by accurately predicting disease annotations for studies from independent datasets, using proteomics and clinical trials as examples. Overall, our approach can annotate biomedical text regardless of experimental types or sources. Code, data, and trained models are available athttps://github.com/krishnanlab/txt2onto2.0.

Key points

We developedtxt2onto 2.0, a computational method that combines language models and machine learning to annotate public samples and studies with standardized tissue and disease terms, with a focus on interpretability and explainability.

Txt2onto 2.0uses word/phrase occurrence statistics to represent sample/study metadata, train machine learning models, and predict terms in controlled vocabularies to annotate each sample and study. This approach allows the model to keep track of predictive words related to model decisions and easily separate informative from uninformative words.

Txt2onto 2.0outperforms its predecessor,txt2onto 1.0, in tissue and disease annotation, especially when training data is limited.

The predictive features learned bytxt2onto 2.0are highly interpretable. These features not only include explicit mentions of the actual disease or tissue terms but also related biomedical concepts, including words that are unseen by the model during training.

Although trained on metadata of transcriptomes,txt2onto 2.0is capable of annotating disease and tissue for any kind of biomedical metadata, making it a versatile tool for sample and study annotation.
TC10 differently controls the dynamics of Exo70 in growth cones of cortical and hippocampal neurons
Authors: Gosain Hiteshika , Busch Karin B.
Published: June 2024

The exocyst is an octameric protein complex that acts as a tether for GOLGI-derived vesicles at the plasma membrane during exocytosis. It is involved in membrane expansion during axonal outgrowth. Exo70 is a major subunit of the exocyst complex and is controlled by TC10, a Rho family GTPase. How TC10 affects the dynamics of Exo70 at the plasma membrane is not well understood. There is also evidence that TC10 controls Exo70 dynamics differently in nonpolar cells and axons. To address this, we used super-resolution microscopy to study the spatially resolved effects of TC10 on Exo70 dynamics in HeLa cells and the growth cone of cortical and hippocampal neurons. We generated single particle localization and trajectory maps and extracted mean square displacements, diffusion coefficients, and alpha coefficients to characterize Exo70 diffusion. We found that the diffusivity of Exo70 was different in nonpolar cells and in the growth cone of neurons. TC10 stimulated the mobility of Exo70 in HeLa cells, but decreased the diffusion of Exo70 in the growth cone of cortical neurons. In contrast to cortical neurons, TC10 overexpression did not affect the mobility of Exo70 in the axonal growth cone of hippocampal neurons. These data suggest that mainly exocyst tethering in cortical neurons was under the control of TC10.
TCA Cycle Dysfunction and Amino Acid Catabolism Drive Hepatic Steatosis in Mice with HFpEF
Authors: Mushala Bellina A.S. , Stoner Michael W. , Manning Janet R. , Bugga Paramesha , Bhattarai Nisha , Sharifi-Sanjani Maryam , McMahon Brenda , Vandevender Amber , Mullet Steven J. , Kaufman Brett A. , Shiva Sruti S. , Gelhaus Stacy L. , Jurczak Michael J. , Scott Iain
Published: June 2024

The prevalence of cardiometabolic heart failure with preserved ejection fraction (HFpEF) continues to grow worldwide, and now represents over half of current heart failure cases in the United States (1). Due to a lack of specific approved therapies, current treatment guidelines focus on the management of comorbidities related to metabolic syndrome (e.g. obesity, diabetes, hypertension) that promote HFpEF progression (1). The same comorbidities also drive cardiometabolic disease in non-cardiac tissues, and links between disease presentations in different organs are increasingly being recognized in the clinic. However, mechanistic studies examining the underlying pathophysiological connections have not kept pace, particularly in the cardio-hepatic disease axis (2). To address this, we used a recently developed and validated preclinical model of HFpEF (3) to examine how this disease impacts the liver. The development of HFpEF in mice leads to the simultaneous development of widespread hepatic steatosis that is consistent with human non-alcoholic fatty liver disease (NAFLD). Mechanistically, we show that the liver steatosis observed is driven by excess glucogenic amino acid entry into the TCA cycle, which promotes hepatic glucose production and de novo lipogenesis. Our findings suggest that HFpEF development is a multi-organ event, with implications for both preclinical and translational research.
Quantifying Contributions from Topological Cycles in the Brain Network towards Cognition
Authors: Garai Sumita , Vo Sandra , Blank Lucy , Xu Frederick , Chen Jiong , Duong-Tran Duy , Zhao Yize , Shen Li
Published: June 2024

This study proposes a novel metric called Homological Vertex Importance Profile (H-VIP), utilizing topological data analysis tool persistent homology, to analyze human brain structural and functional connectomes. Persistent homology is a useful tool for identifying topological features such as cycles and cavities within a network. The salience of persistent homology lies in the fact that it offers a global view of the network as a whole. However, it falls short in precisely determining the relative relevance of the vertices of the network that contribute to these topological features. Our aim is to quantify the contribution of each individual vertex in the formation of homological cycles and provide insight into local connectivity. Our proposed H-VIP metric captures, quantifies, and compresses connectivity information from vertices even at multiple degrees of separation and projects back onto each vertex. Using this metric, we analyze two independent datasets: structural connectomes from the Human Connectome Project and functional connectomes from the Alzheimer’s Disease Neuroimaging Initiative. Our findings indicate a positive correlation between various cognitive measures and H-VIP, in both anatomical and functional brain networks. Our study also demonstrates that the connectivity in the frontal lobe has a higher correlation with cognitive performance compared to the whole brain network. Furthermore, the H-VIP provides us with a metric to easily locate, quantify, and visualize potentially impaired connectivity for each subject and may have applications in the context of personalized medicine for neurological diseases and disorders.
Muscone-specific olfactory protein reveals the putative scent-marking pheromone in the Sunda pangolin (Manis javanica)
Authors: Yu Zhongbo , Meng Tao , Yu Luyao , Zhou Yichen , Que Tengcheng , He Meihong , Wang Haijing , Li Yingjiao , Liu Liling , Liu Wenjian , Wang Yinliang , Ren Bingzhong
Published: June 2024

The Sunda pangolin (Manis javanica) is a burrowing and nocturnal animal, and they have poor vision, thus, intraspecies communication relies on olfaction, such as mating, warning, and scent-marking. However, the intraspecies pheromone in pangolins remains unknown. In this study, all the odorant-binding proteins in Sunda pangolins were functionally expressed, and they were screened against a panel of 32 volatiles that were derived from the pangolin’s urine, feces, and anal gland secretions. Reverse chemical ecology identified thatM. javanicaodorant-binding protein 3 (MjavOBP3) possesses the highest binding affinity to muscone. A subsequent behavior-tracking assay showed that only males can sense muscone; thus, we hypothesize that muscone is a male-specific scent-marking pheromone. Meanwhile, the structural study showed that Tyr117 contributes the most to muscone’s binding, which was further validated by site-directed mutagenesis. The findings clarify the scent-marking mechanism in pangolins, and muscone could potentially be used to support the monitoring and conservation of this endangered animal.

Author Summary

The Sunda pangolin is an endangered mammal that is native to Southeast Asia and is threatened due to its economic value. They are cave-living and nocturnal, poor vision; thus, their intraspecies communication is highly reliant on olfaction. Although they are generally solitary, they have been observed to have some social aspects in the wild, such as breeding and territorial behaviors, which are mediated by scents. However, no previous study has investigated the type of pheromones and how they are detected. Using the reverse chemical ecology approach, MjavOBP3 was found to bind to muscone with high affinity, and behavior-tracking assay was performed under well-controlled artificial rearing conditions, which showed only male pangolins can recognize muscone, suggesting its potential male-specific pheromone role.
Leptogenesis consequences of trimaximal mixing and
μ−τ
reflection symmetry in the most minimal seesaw model
Authors: Zhao Zhen-hua , Shi Hong-Yu , Shao Yan
Published: June 2024

In this paper, we have studied the realizations of the popular first trimaximal neutrino mixing and neutrino μ−τ reflection symmetry (which are well motivated from the neutrino oscillation data and lead to interesting phenomenological consequences) in the most minimal seesaw model with a pseudo-Dirac pair of right-handed neutrinos and their consequences for leptogenesis. In order to realize the low-scale resonant leptogenesis scenario, we have considered two possible ways of generating the tiny mass splitting between the two right-handed neutrinos: one way is to modify their Majorana mass matrix to a form as shown in Eq. (25); the other way is to consider the renormalization-group corrections for their masses. For the μ−τ reflection symmetry, in order for leptogenesis to work, we have further considered the flavor-dependent conversion efficiencies from the lepton asymmetry to the baryon asymmetry during the sphaleron processes and its breaking via the renormalization-group corrections.

Published by the American Physical Society
2024
Black holes and Marchenko-Pastur distribution
Authors: Mück Wolfgang
Published: June 2024

The universal eigenvalue distribution characterizing the Gram matrix of semiclassical ensembles of black hole microstates is recognized as the Marchenko-Pastur distribution, which plays a prominent role as the universal limit distribution in a large class of random matrix and vector models. It is proposed that this distribution also universally determines the energy spectral density of black holes, which allows one to construct a Krylov space for the time evolution of typical black hole states and calculate their state complexity. It is checked that the state complexity growth at late times saturates Lloyd’s bound. Some implications of the proposed spectral density for the generation of Hawking radiation and black hole evaporation are discussed.

Published by the American Physical Society
2024
Impacts of credit constraints on adoption of risk management strategies and income of maize farmers in Northern Nigeria
Authors: Ogunleye Ayodeji , Akinloye Mercy Olajumoke , Kehinde Ayodeji , Ajayi Oluseyi Moses , Wongnaa Camillus Abawiera
Published: June 2024

Purpose

A correlation has been shown in the literature between credit constraints and the adoption of agricultural technologies, technical efficiencies and measures for adapting to climate change. The relationship between credit constraints, risk management strategy adoption and income, however, is not well understood. Consequently, the purpose of this study was to investigate how credit constraints affect the income and risk management practices adopted by Northern Nigerian maize farmers.

Design/methodology/approach

Cross-sectional data were collected from 300 maize farmers in Northern Nigeria using a multi-stage sampling technique. Descriptive statistics, seemingly unrelated regression and double hurdle regression models were the analysis methods.

Findings

The results showed that friends and relatives, banks, “Adashe”, cooperatives and farmer groups were the main sources of credit in the study area. The findings also revealed that the sources of risk in the study area included production risk, economic risk, financial risk, institutional risk, technological risk and human risk. In addition, the risk management strategies used to mitigate observed risks were fertilizer application, insecticides, planting of disease-resistant varieties, use of herbicides, practising mixed cropping, modern planning, use of management tools as well as making bunds and channels. Furthermore, we found that interest rate, farm size, level of education, gender and marital status were significant determinants of statuses of credit constraints while the age of the farmer, gender, household size, primary occupation, access to extension services and income from maize production affected the choice and intensity of adoption of risk management strategies among the farmers.

Research limitations/implications

The study concluded that credit constrained status condition of farmers negatively affected the adoption of some risk management strategies and maize farmers’ income.

Practical implications

The study concluded that credit constrained status condition of farmers negatively affected the adoption of some risk management strategies and maize farmers’ income. It therefore recommends that financial service providers should be engaged to design financial products that are tailored to the needs of smallholder farmers in the study area.

Originality/value

This paper incorporates the role of constraints in influencing farmers’ decisions to uptake credits and subsequently their adoption behaviours on risk management strategies. The researcher approached the topic with a state-of-the-art method which allows for obtaining more reliable results and hence more specific contributions to research and practice.
How semiotic product packaging, brand image, perceived brand quality influence brand loyalty and purchase intention: a stimulus-organism-response perspective
Authors: Rehman Anis Ur , Elahi Yasir Arafat
Published: June 2024

Purpose

The present study, underpinned by the stimulus-organism-response (SOR) theory, aims to examine the impact of packaging semiotics on brand image, perceived brand quality, brand loyalty and purchase intention of well-established food brands.

Design/methodology/approach

A self-administered questionnaire was disseminated to participants residing in the Lucknow region of India. We conducted an experiment in which 374 participants evaluated the factors on a stimulus (chips packaging) using an online survey. Collected data were analysed through structural equation modelling (SEM).

Findings

The result suggests that packaging semiotics exhibits a positive influence on brand image and perceived brand quality of consumers. The brand image significantly impacts brand loyalty and consumers’ purchase intention. In addition, the perceived brand quality has a positive significant impact on brand loyalty, but a negative and insignificant influence on purchase intention. The results show that both brand image and perceived brand quality significantly mediate the relation between packaging semiotics and brand loyalty. Brand image significantly mediates but perceived brand quality does not mediate the relation between packaging semiotics and purchase intention.

Practical implications

The results of the study will assist food brands in determining how to utilise semiotics in packaging to positively influence brand image, perceived brand quality, brand loyalty and consumers’ intent to purchase.

Originality/value

The study is unique in the sense that it assesses the role of packaging semiotics as antecedent in mapping of brand loyalty and purchase intention through brand image and perceived product quality. This study takes a lead as these constructs have been less explored relatively from the lens of packaging semiotics in an emerging Asian market.
Maximizing solar energy generation: guidelines for optimizing photovoltaic panel placement on building facades
Authors: Reffat Rabee , Ezzat Radwa
Published: June 2024

Purpose

This purpose of this paper is to address the research problem of optimizing photovoltaic (PV) panel placement on building facades to maximize solar energy generation.

Design/methodology/approach

The study examines the significance of various design configurations and their implications for PV system performance. The research involves analysis of relevant literature and energy simulations. An exemplary case study is conducted in a hot climate zone to quantify the impacts of PV panel placement on energy generation. Various application scenarios are developed, resulting in 28 scenarios for PV on building facades. Energy simulations using Grasshopper Rhino software and Ladybug plugin components are performed.

Findings

The paper identifies key factors influencing PV panel placement and energy generation through qualitative analysis. It introduces an appropriateness matrix as a decision-making framework to evaluate placement options. The study identifies design configurations and external features impacting PV location selection and performs a qualitative classification to determine their impact on energy generation.

Practical implications

The results and decision-making framework enable informed choices based on solar radiation levels, shading conditions, and building requirements. Optimizing PV panel placement enhances solar energy harvesting in buildings, benefiting architects and engineers.

Originality/value

The novel contributions of this paper include practical insights and guidance for strategically placing PV panels on building facades.
The engagement of the UK construction industry towards achievement of the Sustainable Development Goals
Authors: Watts Greg
Published: June 2024

Purpose

The Sustainable Development Goals (SDGs) provide a blueprint for UN member states to achieve prosperity and peace. A resilient construction industry should positively contribute to the achievement of all SDGs. Yet it is currently unclear if the industry helps or hinders SDG achievement. This research aims to explore if the industry is positively engaging with all SDGs.

Design/methodology/approach

This research is split into two phases. The first is an objectivist Qualitative Content Analysis (QCA) of sustainability reports from the ten leading UK contractors to identify direct and indirect SDG references. The second research phase adopts a subjectivist ontological position consisting of twenty-one semi-structured interviews with a range of construction industry project-based professionals. Narrative analysis is used to structure the interview questions and analyse the data gained.

Findings

Many SDGs are excluded from sustainability reports, and where discussed, only some are engaged with substantially. The SDG knowledge held by construction professionals is reduced further still, and SDG progress is rarely measured. The ambiguity surrounding the SDGs enables discrepancies between reporting and professional perceptions. There is also a lack of regard for fellow contractor collaboration through fear of reduced competitive advantage.

Originality/value

This paper addresses a gap in the literature between contractor SDG knowledge and action. This serves as a platform for future research agendas regarding how the SDGs can be better understood and actioned in a construction management context. For industry, inconsistencies between organisational sustainability reporting and the knowledge and awareness of staff are exposed, due to the lack of collaborative practices currently adopted.
Performance of concrete containing waste demolished concrete powder as a partial substitute for cement
Authors: Haroon Muhammad , Khan Raja Bilal Nasar , Khitab Anwar
Published: June 2024

Purpose

Present work deals with the partial substitution of cement by waste demolished concrete powder (WDP) for reducing the carbon footprints of concrete.

Design/methodology/approach

Control specimens and the specimens with 20% WDP as fractional substitute of cement were prepared. The waste powder was thermally activated at 825 °C prior to its use in the mix. The prepared specimens were evaluated in terms of density, workability, mechanical strength, Ultrasonic pulse velocity (UPV) and rebound hammer (RH).

Findings

The results showed that with the substitution, the workability of the mix increased, while the density decreased. A decrement within a 20% limit was found in compressive strength. The UPV and RH results were closely linked to the other results as mentioned above.

Research limitations/implications

The study deals with only M15 concrete and the substitution level of only 20% as a baseline.

Practical implications

The concrete containing 20% WDP is lightweight and more workable. Moreover, its strength at 28 days is 14 MPa, only 1 MPa lesser than the characteristic strength.

Social implications

The WDP can be recycled and the dumping in landfills can be reduced. This is an important effort towards the decarbonation of concrete.

Originality/value

Previous literature indicates that the WDP has been frequently used as a partial replacement of aggregates. However, some traces of secondary hydration were also reported. This work considers the effect of partial substitution of cement by the WDP.
Effective health systems facing pandemic crisis: lessons from COVID-19 in Europe for next emergencies
Authors: Coccia Mario , Benati Igor
Published: June 2024

Purpose

The investigation goal is the analysis of the relation between healthcare expenditures and other resources, and COVID-19 fatality rates among European countries to design effective health policies for crisis management.

Design/methodology/approach

Research methodology is based on descriptive statistics and various parametric methods, also including a linear model of regression to analyze basic relationships of variables under study.

Findings

Results show that a lower COVID-19 fatality rate is associated with higher levels of health expenditure (% GDP), of healthcare expenditure per capita, health expenditure in preventive care (% GDP), hospitals per million inhabitants, physicians, nurses, hospital beds and curative acute care beds per 1,000 inhabitants. Regression analysis shows that a 1% increase in healthcare expenditures per capita of countries, it reduces the level of COVID-19 fatality rate by 0.74%. In fact, many countries in Eastern Europe with low healthcare expenditures per capita in 2019 (e.g., Bulgaria, Romania, Hungary, Poland, Latvia, Slovakia, Lithuania, etc.), they have experienced high COVID-19 fatality rates. Instead, a lot of countries in Western Europe, with high healthcare expenditures per capita, such as Germany, Denmark, Austria, and the Netherlands, they had resilient health systems to face pandemic crisis and lower COVID-19 fatality rates.

Practical implications

These findings suggest strategies of systematic and continuous investments in healthcare, medical technologies, and ICT infrastructures to support effective health policy of crisis management in countries to face future pandemic crisis and other emergencies in society.

Originality/value

The explanation of critical role of high health expenditure (% GDP) and healthcare expenditure per capita to support robust health systems that bolster the resilience in nations to face health emergencies and worldwide crises.