bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Focal Muscle Vibrations in Improving Sensorimotor Performance, Mobility and Strength in Spinal Cord Injury Population: A Systematic Review
Authors: Ashfaque Moeez , Pujari Amit N. , Niazi Imran Khan , Amjad Imran , Haavik Heidi , Farmer Simon F
Published: December 2023

Introduction: The pathophysiology of spinal cord injury (SCI) is still not completely understood. Current SCI rehabilitation strategies remain ineffective. Focal muscle vibrations (FMVs), through afferent nerve stimulation, modulate peripheral and central pathways and have potential as a complementary and easy to administer rehabilitation tool in treating SCI populations, however the exact effectiveness of FMVs remains unknown. Methods: This study is a systematic review on the use of FMVs in SCIs. Sensorimotor function, and mobility and strength were the main outcomes considered. Science Direct, PubMed, Cochrane library, PEDro, Google Scholar and Springer databases were searched for original studies until June 2023. The PEDro scale was used to assess the methodological quality of the studies. Results: Twenty-three studies were included. Nine studies using FMV in the upper limb and fourteen in the lower limb. The analysis includes 422 SCI patients and 132 non-disabled participants, with a focus on male, chronic SCI cases, and a prevalence in North American studies. Conclusion: Our findings suggest potential benefits of FMV on sensory perception, motor function, mobility, and strength in both upper and lower limbs of SCI patients. However, there is acute need for further research to optimize the application of FMV through its vibration parameters, location, duration and understanding its long-term effects. Due to the lack larger sample sizes and longitudinal studies, any conclusions derived here and within these studies should be interpreted with caution.
Classifying breast cancer and fibroadenoma tissue biopsies from paraffined stain-free slides by fractal biomarkers in Fourier Ptychographic Microscopy
Authors: Bianco Vittorio , Valentino Marika , Pirone Daniele , Miccio Lisa , Memmolo Pasquale , Brancato Valentina , Coppola Luigi , Smaldone Giovanni , D’Aiuto Massimiliano , Mossetti Gennaro , Salvatore Marco , Ferraro Pietro
Published: December 2023

Breast cancer is one of the most spread and monitored pathologies in high-income countries. After breast biopsy, histological tissue is stored in paraffin, sectioned and mounted. Conventional inspection of tissue slides under benchtop light microscopes involves paraffin removal and staining, typically with H&E. Then, expert pathologists are called to judge the stained slides. However, paraffin removal and staining are operator-dependent, time and resources consuming processes that can generate ambiguities due to non-uniform staining. Here we propose a novel method that can work directly on paraffined stain-free slides. The method is automatic, independent from the operator, and provides classification of different portions of the tissue image with very high accuracy. Besides, it returns a guide map to help pathologist to judge the different tissue portions based on the likelihood these can be associated to a breast cancer or fibroadenoma biomarker. We use Fourier Ptychography as a quantitative phase-contrast microscopy method, which allows accessing a very wide field of view (i.e., square millimeters) in one single image while guaranteeing at the same time high lateral resolution (i.e., 0.5 microns). This imaging method is multi-scale, since it enables looking at the big picture, i.e. the complex tissue structure and connections, with the possibility to zoom-in up to the single cell level. In order to handle this informative image content, we introduce elements of fractal geometry as a multi-scale analysis method. We show the effectiveness of fractal features in describing fibroadenoma and breast cancer from six patients with very high accuracy. The proposed method could significantly simplify the steps of tissue analysis and make it independent from the sample preparation, the skills of the lab operator and the pathologist.
Biodiversity in mountain soils above the treeline
Authors: Praeg Nadine , Steinwandter Michael , Urbach Davnah , Snethlage Mark A. , Alves Rodrigo P. , Apple Martha E. , Britton Andrea J. , Bruni Estelle P. , Chen Ting-Wen , Dumack Kenneth , Fernandez-Mendoza Fernando , Freppaz Michele , Frey Beat , Fromin Nathalie , Geisen Stefan , Grube Martin , Guariento Elia , Guisan Antoine , Ji Qiao-Qiao , Jiménez Juan J. , Maier Stefanie , Malard Lucie A. , Minor Maria A. , Mc Lean Cowan C. , Mitchell Edward A. D. , Peham Thomas , Pizzolotto Roberto , Taylor Andy F. S. , Vernon Philippe , van Tol Johan J. , Wu Yunga , Wu Donghui , Xie Zhijing , Weber Bettina , Illmer Paul , Seeber Julia
Published: December 2023

Despite the importance of healthy soils for human livelihood, wellbeing, and safety, current gaps in our knowledge and understanding of biodiversity in soil are numerous, undermining conservation efforts. These gaps are particularly wide in mountain regions where healthy soils are especially important for human safety and yet evidence is accumulating of ongoing degradation, posing significant threats to ecosystem functioning and human settlements.

To analyse these gaps in detail, we synthesise current research on the global diversity of microorganisms, cryptogams, and invertebrates in mountain soils above the treeline. This synthesis is based on a semi-quantitative survey of the literature and an expert-based analysis. Our work reveals not only deficiencies in geographic cover but also significant gaps in taxonomic coverage, particularly among soil protists and invertebrates, and a lack of (functional and ecological) description of the uncultivated majority of prokaryotes, fungi, and protists. We subsequently build on this overview to highlight opportunities for research on mountain soils as systems of co-occurring species that interact in complex environmental matrices to fulfil critical functions and make essential contributions to life on land.

Closing gaps in biodiversity research in mountain soil is crucial to enhance our understanding and to promote laws and guidelines advancing international soil biodiversity conservation targets in mountains. Addressing sparse and biased data, recognizing the impact of environmental changes on mountain ecosystems, and advocating dedicated policies are essential strategies to safeguard mountain soils and their biodiversity.

GLOSSARY
The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders
Authors: Smith Samuel S. , Jahn Kelly N. , Sugai Jenna A. , Hancock Ken E. , Polley Daniel B.
Published: December 2023

Sound is jointly processed along acoustic and emotional dimensions. These dimensions can become distorted and entangled in persons with sensory disorders, producing a spectrum of loudness hypersensitivity, phantom percepts, and – in some cases – debilitating sound aversion. Here, we looked for objective signatures of disordered hearing (DH) in the human face. Pupil dilations and micro facial movement amplitudes scaled with sound valence in neurotypical listeners but not DH participants with chronic tinnitus (phantom ringing) and sound sensitivity. In DH participants, emotionally evocative sounds elicited abnormally large pupil dilations but blunted and invariant facial reactions that jointly provided an accurate prediction of individual tinnitus and hyperacusis questionnaire handicap scores. By contrast, EEG measures of central auditory gain identified steeper neural response growth functions but no association with symptom severity. These findings highlight dysregulated affective sound processing in persons with bothersome tinnitus and sound sensitivity disorders and introduce approaches for their objective measurement.
ANTIPASTI: interpretable prediction of antibody binding affinity exploiting Normal Modes and Deep Learning
Authors: Michalewicz Kevin , Barahona Mauricio , Bravi Barbara
Published: December 2023

The high binding affinity of antibodies towards their cognate targets is key to eliciting effective immune responses, as well as to the use of antibodies as research and therapeutic tools. Here, we propose ANTIPASTI, a Convolutional Neural Network model that achieves state-of-the-art performance in the prediction of antibody binding affinity using as input a representation of antibody-antigen structures in terms of Normal Mode correlation maps derived from Elastic Network Models. This representation captures not only structural features but energetic patterns of local and global residue fluctuations. The learnt representations are interpretable: they reveal similarities of binding patterns among antibodies targeting the same antigen type, and can be used to quantify the importance of antibody regions contributing to binding affinity. Our results show the importance of the antigen imprint in the Normal Mode landscape, and the dominance of cooperative effects and long-range correlations between antibody regions to determine binding affinity.
The clouded mother-of-pearlProtogoniomorpha anacardiiLinnaeus, 1758 (Lepidoptera: Nymphalidae) – an updated record of butterfly for Saudi Arabia
Authors: Alfakih Ateah , Al Faify Eisa Ali
Published: December 2023

The record of the clouded mother-of-pearlProtogoniomorpha anacardiiLinnaeus, 1758 (Lepidoptera: Nymphalidae) was updated in Saudi Arabia. At this stage, we confirmed the presence of this species in the southernmost part of Saudi Arabia based on photographs taken between 2020–2023 from Fayfa and the adjacent mountains in Jazan. The photographs match the descriptions and remarks made by Dr Torben Larsen in multiple publications, which suggest that this taxon represents the widespread subspeciesP. a. nebulosaTrimen, 1881. Here, we discuss the Saudi Arabian populations ofP. a. nebulosaand its conservation in depth and encourage more research on butterflies in Saudi Arabia.
Horizontal transfers between fungalFusariumspecies contributed to successive outbreaks of coffee wilt disease
Authors: Peck Lily D. , Llewellyn Theo , Bennetot Bastien , O’Donnell Samuel , Nowell Reuben W. , Ryan Matthew J. , Flood Julie , Rodŕıguez de la Vega Ricardo C. , Ropars Jeanne , Giraud Tatiana , Spanu Pietro D. , Barraclough Timothy G.
Published: December 2023

Outbreaks of fungal disease have devastated plants and animals throughout history. Over the past century, the repeated emergence of coffee wilt disease caused by the fungal pathogenFusarium xylarioidesseverely impacted coffee production across sub-Saharan Africa. To improve the disease management of such pathogens, it is crucial to understand their genetic structure and evolutionary potential. We compared the genomes of 13 historic strains spanning six decades and multiple disease outbreaks to investigate population structure and host specialisation. We foundF. xylarioidescomprises at least four distinct lineages: one host-specific toCoffea arabica, one toC. canephoravar.robusta, and two historic lineages isolated from variousCoffeaspecies. Mapping variation onto a new long-read reference genome showed that host-specificity appears to be acquired through horizontal transfer of effector genes from members of theF. oxysporumspecies complex. This species complex is known to cause wilt disease in over 100 plant species. Multiple transfers into theF. xylarioidespopulations matched to different parts of theF. oxysporummobile pathogenicity chromosome and were enriched in effector genes and transposons. Effector genes in this region and other horizontally transferred carbohydrate-active enzymes important in the breakdown of plant cell walls were shown by transcriptomics to be highly expressed during infection ofC. arabicaby the fungal arabica strains. Widespread sharing of specific transposons betweenF. xylarioidesandF. oxysporum, and the presence of largeStarshipelements, indicate that transposons were involved in horizontal transfers. Our results support the hypothesis that horizontal gene transfers contributed to the repeated emergence of this fungal disease.
The Brain Image Library: A Community-Contributed Microscopy Resource for Neuroscientists
Authors: Kenney Mariah , Vasylieva Iaroslavna , Hood Greg , Cao-Berg Ivan , Tuite Luke , Laghaei Rozita , Smith Megan C. , Watson Alan M. , Ropelewski Alexander J.
Published: December 2023

Advancements in microscopy techniques and computing technologies have enabled researchers to digitally reconstruct brains at micron scale. As a result, community efforts like the BRAIN Initiative Cell Census Network (BICCN) have generated thousands of whole-brain imaging datasets to trace neuronal circuitry and comprehensively map cell types. This data holds valuable information that extends beyond initial analyses, opening avenues for variation studies and robust classification of cell types in specific brain regions. However, the size and heterogeneity of these imaging data have historically made storage, sharing, and analysis difficult for individual investigators and impractical on a broad community scale. Here, we introduce the Brain Image Library (BIL), a public resource serving the neuroscience community that provides a persistent centralized repository for brain microscopy data. BIL currently holds thousands of brain datasets and provides an integrated analysis ecosystem, allowing for exploration, visualization, and data access without the need to download, thus encouraging scientific discovery and data reuse.
Single-nucleus transcriptome atlas of orbitofrontal cortex in amyotrophic lateral sclerosis with a deep learning-based decoding of alternative polyadenylation mechanisms
Authors: McKeever Paul M. , Sababi Aiden M. , Sharma Raghav , Xu Zhiyu , Xiao Shangxi , McGoldrick Philip , Ketela Troy , Sato Christine , Moreno Danielle , Visanji Naomi , Kovacs Gabor G. , Keith Julia , Zinman Lorne , Rogaeva Ekaterina , Goodarzi Hani , Bader Gary D. , Robertson Janice
Published: December 2023

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two age-related and fatal neurodegenerative disorders that lie on a shared disease spectrum. While both disorders involve complex interactions between neuronal and glial cells, the specific cell-type alterations and their contributions to disease pathophysiology remain incompletely understood. Here, we applied single-nucleus RNA sequencing of the orbitofrontal cortex, a region affected in ALS-FTLD, to map cell-type specific transcriptional signatures in C9orf72-related ALS (with and without FTLD) and sporadic ALS cases. Our findings reveal disease- and cell-type-specific transcriptional changes, with neurons exhibiting the most pronounced alterations, primarily affecting mitochondrial function, protein homeostasis, and chromatin remodeling. A comparison with independent datasets from different cortical regions of C9orf72 and sporadic ALS cases showed concordance in several pathways, with neuronal STMN2 and NEFL showing consistent up-regulation between brain regions and disease subtypes. We also interrogated alternative polyadenylation (APA) as an additional layer of transcriptional regulation, demonstrating that APA events are not correlated with identified gene expression changes. To interpret these events, we developed APA-Net, a deep learning model that integrates transcript sequences with RNA-binding protein expression profiles, revealing cell type-specific patterns of APA regulation. Our atlas illuminates cell type-specific pathomechanisms of ALS/FTLD, providing a valuable resource for further investigation.
Precise 3D Localization of Intracerebral Implants with a simple Brain Clearing Method
Authors: Catanese Julien , Murakami Tatsuya , Kenny Paul J. , Ibanez-Tallon Ines
Published: December 2023

Determining the localization of intracerebral implants in rodent brain stands as a critical final step in most physiological and behaviroral studies, especially when targeting deep brain nuclei. Conventional histological approaches, reliant on manual estimation through sectioning and slice examination, are error-prone, potentially complicating data interpretation.

Leveraging recent advances in tissue-clearing techniques and light-sheet fluorescence microscopy, we introduce a method enabling virtual brain slicing in any orientation, offering precise implant localization without the limitations of traditional tissue sectioning.

To illustrate the method’s utility, we present findings from the implantation of linear silicon probes into the midbrain interpeduncular nucleus (IPN) of anesthetized transgenic mice expressing chanelrhodopsin-2 and enhanced yellow fluorescent protein under the choline acetyltransferase (ChAT) promoter/enhancer regions (ChAT-Chr2-EYFP mice). Utilizing a fluorescent dye applied to the electrode surface, we visualized both the targeted area and the precise localization, enabling enhanced inter-subject comparisons. Three dimensional (3D) brain renderings, presented effortlessly in video format across various orientations, showcase the versatility of this approach.
DNA Nanostar Structures with Tunable Auxetic Properties
Authors: Du Yancheng , Li Ruixin , Madhvacharyula Anirudh S. , Swett Alexander A. , Choi Jong Hyun
Published: December 2023

Auxetic structures are unique with a negative Poisson’s ratio. Unlike regular materials, they response to external loading with simultaneous expansion or compression in all directions, rendering powerful properties advantageous in diverse applications from manufacturing to space engineering. The auxetic behaviors are determined by structural design and architecture. Such structures have been discovered in natural crystals and demonstrated synthetically with bulk materials. Recent development of DNA-based structures has pushed the unit cell size to nanometer scale. DNA nanotechnology utilizes sequence complementarity between nucleotides. By combining sequence designs with programmable self-assembly, it is possible to construct complex structures with nanoscale accuracy and to perform dynamic reconfigurations. Herein, we report a novel design of auxetic nanostars with sliding behaviors using DNA origami. Our proposed structure, inspired by an Islamic pattern, demonstrates a unit cell with two distinct reconfigurations by programming directed sliding mechanisms. Compared to previous metamaterials, the DNA nanostars show an architecture with tunable auxetic properties for the first time. We envision that this strategy may form the basis of novel metastructures with adaptability and open new possibilities in bioengineering.
Systematic analysis of cotranscriptional RNA folding using transcription elongation complex display
Authors: Kelly Skyler L. , Strobel Eric J.
Published: December 2023

RNA can fold into structures that mediate diverse cellular functions. Understanding how RNA primary sequence directs the formation of functional structures requires methods that can comprehensively assess how changes in an RNA sequence affect its structure and function. Here we have developed a platform for performing high-throughput cotranscriptional RNA biochemical assays, calledTranscriptionElongationComplex display (TECdisplay). TECdisplay measures RNA function by fractionating a TEC library based on the activity of cotranscriptionally displayed nascent RNA. In this way, RNA function is measured as the distribution of template DNA molecules between fractions of the transcription reaction. This approach circumvents typical RNA sequencing library preparation steps that can cause technical bias. We used TECdisplay to characterize the transcription antitermination activity of 32,768 variants of theClostridium beijerinckii pflZTP riboswitch designed to perturb steps within its cotranscriptional folding pathway. Our findings establish TECdisplay as an accessible platform for high-throughput RNA biochemical assays.
Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates
Authors: Amjad Usamma , Choi Jiwon , Gibson Daniel J. , Murray Raymond , Graybiel Ann M. , Schwerdt Helen N.
Published: December 2023

Measuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. Here, we developed methods to measure concurrently dopamine and extracellular action potentials (i.e., spikes) and applied these in a monkey performing a behavioral task. Standard fast-scan cyclic voltammetric (FSCV) electrochemical (EChem) and electrophysiological (EPhys) recording systems are combined and used to collect spike and dopamine signals, respectively, from an array of carbon fiber (CF) sensors implanted in the monkey striatum. FSCV requires the application of small voltages at the implanted sensors to measure redox currents generated from target molecules, such as dopamine. These applied voltages create artifacts at neighboring EPhys-measurement sensors, producing signals that may falsely be classified as physiological spikes. Therefore, simple automated temporal interpolation algorithms were designed to remove these artifacts and enable accurate spike extraction. We validated these methods using simulated artifacts and demonstrated an average spike recovery rate of 84.5%. This spike extraction was performed on data collected from concurrent EChem and EPhys recordings made in a task-performing monkey to discriminate cell-type specific striatal units. These identified units were shown to correlate to specific behavioral task parameters related to reward size and eye-movement direction. Synchronous measures of spike and dopamine signals displayed contrasting relations to the behavioral task parameters, as taken from our small set of representative data, suggesting a complex relationship between these two modes of neural signaling. Future application of our methods will help advance our understanding of the interactions between neuromodulator signaling and neuronal activity, to elucidate more detailed mechanisms of neural circuitry and plasticity mediating behaviors in health and in disease.

Significance statement

We present a simple method for recording synchronous molecular and neuronal spike signals. Conventional electrophysiological and electrochemical instruments are combined without the need for additional hardware. A custom-designed algorithm was made and validated for extracting neuronal action potential signals with high fidelity. We were able to compute cell-type specific spike activity along with molecular dopamine signals related to reward and movement behaviors from measurements made in the monkey striatum. Such combined measurements of neurochemical and extracellular action potentials may help pave the way to elucidating mechanisms of plasticity, and how neuromodulators and neurons are orchestrated to mediate behavior.
Iterative Prompt Refinement for Mining Gene Relationships from ChatGPT
Authors: Chen Yibo , Gao Jeffrey , Petruc Marius , Hammer Richard D. , Popescu Mihail , Xu Dong
Published: December 2023

ChatGPT has demonstrated its potential as a surrogate knowledge graph. Trained on extensive data sources, including open-access publications, peer-reviewed research articles and biomedical websites, ChatGPT extracted information on gene relationships and biological pathways. However, a major challenge is model hallucination, i.e., high false positive rates. To assess and address this challenge, we systematically evaluated ChatGPT’s capacity for predicting gene relationships using GPT-3.5-turbo and GPT-4. Benchmarking against the KEGG Pathway Database as the ground truth, we experimented with diverse prompting strategies, targeting gene relationships of activation, inhibition, and phosphorylation. We introduced an innovative iterative prompt refinement technique. By assessing prompt efficacy using metrics like F-1 score, precision, and recall, GPT-4 was re-engaged to suggest improved prompts. A refined prompt, which combines a specialized role with explanatory text, significantly enhances the performance. Going beyond pairwise gene relationships, we also deciphered complex gene interplays, such as gene interaction chains and pathways pertinent to diseases like non-small cell lung cancer. Direct prompts showed limited success, but “least-to-most” prompting exhibited significant potentials for such network constructions. The methods in this study may be used for some other bioinformatics prediction problems.
Exogenous mitochondrial transfer increases energy expenditure and attenuates adiposity gains in mice with diet-induced obesity
Authors: Namwanje Maria , Mazumdar Soumi , Stayton Amanda , Patel Prisha S. , Watkins Christine , White Catrina , Brown Chester , Eason James D. , Mozhui Khyobeni , Kuscu Cem , Pabla Navjot , Stephenson Erin J. , Bajwa Amandeep
Published: December 2023

Obesity is associated with chronic multi-system bioenergetic stress that may be improved by increasing the number of healthy mitochondria available across organ systems. However, treatments capable of increasing mitochondrial content are generally limited to endurance exercise training paradigms, which are not always sustainable long-term, let alone feasible for many patients with obesity. Recent studies have shown that local transfer of exogenous mitochondria from healthy donor tissues can improve bioenergetic outcomes and alleviate the effects of tissue injury in recipients with organ specific disease. Thus, the aim of this project was to determine the feasibility of systemic mitochondrial transfer for improving energy balance regulation in the setting of diet-induced obesity. We found that transplantation of mitochondria from lean mice into mice with diet-induced obesity attenuated adiposity gains by increasing energy expenditure and promoting the mobilization and oxidation of lipids. Additionally, mice that received exogenous mitochondria demonstrated improved glucose uptake, greater insulin responsiveness, and complete reversal of hepatic steatosis. These changes were, in part, driven by adaptations occurring in white adipose tissue. Together, these findings are proof-of-principle that mitochondrial transplantation is an effective therapeutic strategy for limiting the deleterious metabolic effects of diet-induced obesity in mice.
Effect of habitat degradation on hantavirus infection among introduced and endemic small mammals of Madagascar
Authors: Dubrulle Jérémy , Kauffman Kayla , Soarimalala Voahangy , Randriamoria Toky , Goodman Steven M. , Herrera James , Nunn Charles , Tortosa Pablo
Published: December 2023

Hantaviruses are globally distributed zoonotic pathogens capable of causing fatal disease in humans. Rodents and other small mammals are the typical reservoirs of hantaviruses, though the particular host varies regionally. Addressing the risk of hantavirus spillover from animal reservoirs to humans requires identifying the local mammal reservoirs and the predictors of infection in those animals, such as their population density and habitat characteristics. We screened native and non-native small mammals and bats in northeastern Madagascar for hantavirus infection to investigate the influence of habitat, including effects of human land use on viral prevalence. We trapped 227 bats and 1663 small mammals over 5 successive years in and around Marojejy National Park across a range of habitat types including villages, agricultural fields, regrowth areas, and secondary and semi-intact forests. Animals sampled included endemic tenrecs (Tenrecidae), rodents (Nesomyidae) and bats (6 families), along with non-native rodents (Muridae) and shrews (Soricidae). A hantavirus closely related to the previously described Anjozorobe virus infected 9.5% ofRattus rattussampled. We did not detect hantaviruses in any other species. Habitat degradation had a complex impact on hantavirus prevalence in our study system: more intensive land use increase the abundance ofR. rattus. The average body size of individuals varied between agricultural and non-agricultural land-use types, which in turn affected infection prevalence. SmallerR.rattushad lower probability of infection and were captured more commonly in villages and forests. Thus, infection prevalence was highest in agricultural areas. These findings provide new insights to the gradients of hantavirus exposure risk for humans in areas undergoing rapid land use transformations associated with agricultural practices.
Molecular Group and Correlation Guided Structural Learning for Multi-Phenotype Prediction
Authors: Zhou Xueping , Cai Manqi , Yue Molin , Celedón Juan , Ding Ying , Chen Wei , Li Yanming
Published: December 2023

We propose a supervised learning algorithm to perform feature selection and outcome prediction for genomic data with multi-phenotypic responses. Our algorithm particularly incorporates the genome and/or phenotype grouping structures and phenotype correlation structures in feature selection, effect estimation, and outcome prediction under a penalized multi-response linear regression model. Extensive simulations demonstrate its superior performance over its competing methods. We apply the proposed algorithm to two omics studies. In the first study, we identified novel association signals between multivariate gene expressions and high-dimensional DNA methylation profiles, providing biological insights into how CpG sites regulate gene expressions. The second study is for cell type deconvolution. Using the proposed algorithm, we were able to achieve better cell type fraction predictions using high-dimensional gene expression data.
Discovery of genomic and transcriptomic pleiotropy between kidney function and soluble receptor for advanced glycation end-products using correlated meta-analyses: The Long Life Family Study (LLFS)
Authors: Feitosa Mary F. , Lin Shiow J. , Acharya Sandeep , Thyagarajan Bharat , Wojczynski Mary K. , Kuipers Allison L. , Kulminski Alexander , Christensen Kaare , Zmuda Joseph M. , Brent Michael R. , Province Michael A.
Published: December 2023

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGE). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genomewide association study (GWAS)p-values in 4,182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of 1,209 individuals. We identified 59 pleiotropic GWAS loci (p<5×10-8) and 17 TWAS genes (Bonferroni-p<2.73×10-6) for eGFR traits and sRAGE. TWAS genes,LSP1andMIR23AHG, were associated with eGFR and sRAGE located within GWAS loci, lncRNA-KCNQ1OT1andCACNA1A/CCDC130, respectively. GWAS variants were eQTLs in the kidney glomeruli and tubules, and GWAS genes predicted kidney carcinoma. TWAS genes harbored eQTLs in the kidney, predicted kidney carcinoma, and connected enhancer-promoter variants with kidney function-related phenotypes atp<5×10-8. Additionally, higher allele frequencies of protective variants for eGFR traits were detected in LLFS than in ALFA-Europeans and TOPMed, suggesting better kidney function in healthy-aging LLFS than in general populations. Integrating genomic annotation and transcriptional gene activity revealed the enrichment of genetic elements in kidney function and kidney diseases. The identified pleiotropic loci and gene expressions for eGFR and sRAGE suggest their underlying shared genetic effects and highlight their roles in kidney- and aging-related signaling pathways.
Signatures of transmission in within-hostM. tuberculosisvariation
Authors: Walter Katharine S. , Cohen Ted , Mathema Barun , Colijn Caroline , Sobkowiak Benjamin , Comas Iñaki , Goig Galo A. , Croda Julio , Andrews Jason R.
Published: December 2023

Background

BecauseM. tuberculosisevolves slowly, transmission clusters often contain multiple individuals with identical consensus genomes, making it difficult to reconstruct transmission chains. Finding additional sources of sharedM. tuberculosisvariation could help overcome this problem. Previous studies have reportedM. tuberculosisdiversity within infected individuals; however, whether within-host variation improves transmission inferences remains unclear.

Methods

To evaluate the transmission information present in within-hostM. tuberculosisvariation, we re-analyzed publicly available sequence data from three household transmission studies, using household membership as a proxy for transmission linkage between donor-recipient pairs.

Findings

We found moderate levels of minority variation present inM. tuberculosissequence data from cultured isolates that varied significantly across studies (mean: 6, 7, and 170 minority variants above a 1% minor allele frequency threshold, outside of PE/PPE genes). Isolates from household members shared more minority variants than did isolates from unlinked individuals in the three studies (mean 98 shared minority variants vs. 10; 0.8 vs. 0.2, and 0.7 vs. 0.2, respectively). Shared within-host variation was significantly associated with household membership (OR: 1.51 [1.30,1.71], for one standard deviation increase in shared minority variants). Models that included shared within-host variation improved the accuracy of predicting household membership in all three studies as compared to models without within-host variation (AUC: 0.95versus0.92, 0.99versus0.95, and 0.93versus0.91).

Interpretation

Within-hostM. tuberculosisvariation persists through culture and could enhance the resolution of transmission inferences. The substantial differences in minority variation recovered across studies highlights the need to optimize approaches to recover and incorporate within-host variation into automated phylogenetic and transmission inference.

Funding

NIAID: 5K01AI173385
Preliminary Analysis of the Melanoma Multimedia Educational programme for general practitioners on behalf of the Italian Melanoma Intergroup
Authors: Zamagni Federica , Falcini Fabio , Magi Serena , Bucchi Lauro , Mancini Silvia , Vattiato Rosa , Crocetti Emanuele , Falcinelli Stefano , Feliciani Claudio , Lombardo Maurizio , Melandri Davide , Re Patrizia , Ricci Francesco , Satta Rosanna Rita , Gandini Sara , Stanganelli Ignazio ,   FAD MelaMEd Working Group
Published: December 2023

Introduction

According to the National Oncological Plan 2023-2027 on the importance of multidisciplinary and interactive e-learning training, the Italian Melanoma Intergroup (IMI) has developed MelaMEd (Melanoma Multimedia Education), a national project for general practitioners (GPs) on the prevention and detection of cutaneous melanoma through an online platform and an online course. MelaMEd enables participants to (1) recognize skin lesions that require specialist dermatological assessment, (2) select patients at high risk of melanoma and (3) be informed of the diagnosis and treatment pathway of patients with melanoma.

Methods

A free online platform and online course were developed and launched in June 2022. Before starting the course, enrolled participants fill out a pre-training questionnaire concerning the basic knowledge of the disease and the recognition and management of suspicious lesions. After the course, participants will fill out the same questionnaire again. The online course will end in December 2023. Here we present a preliminary analysis of the pre-training results (January 2023-July 2023). The data have been analyzed descriptively.

Results

So far, five healthcare centers have participated in the project for a total of 1320 participants. Of these, 298 compiled the pre-training questionnaire. Forty-seven percent of them were aged <40 years. Respondents were almost divided between GPs (47%) and resident GPs (48%). Among the theoretical questions, the “ABCDE” rule and “ugly duckling” sign are well known (96% and 91% of correct answers, respectively), but a lower percentage (68%) of respondents knows the “EFG” rule for the recognition of nodular melanomas and the statement of Breslow thickness (29%).

Regarding the series of clinical images of pigmented skin lesions and their management, the percentages rate of accuracy varied from 33% to 87%: melanoma (5 cases) ranges from 36% to 71%, melanocytic nevi (3 cases) from 33% to 84%, whereas the percentages rate of referral for dermatological evaluation varied from 44% to 99%. Melanoma cases referred to dermatologist ranges from 67% to 99%.

Conclusions

This preliminary analysis on pre-training questionnaire mainly showed a lack of knowledge of the two major points of melanoma diagnosis (EFG) and management (Breslow thickness), as well as a low rate of participants. We will compare the proportions of correct answers to the questionnaires before and after the course once available.
Investigations on Clinical Validation of mutated ANKRD36 as a Novel Molecular Biomarker for Monitoring Early Progression and Timely Therapeutic Interventions in Blast Crisis CML
Authors: Alanazi Nawaf , Siyal Abdulaziz , Absar Muhammad , Shammas Masood , Mahmood Amer , Basit Sulman , AlMukhaylid Sarah , Iqbal Zafar
Published: December 2023

Background

Chronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression.

Materials and Methods

The study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2020 and September 2023. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved by scientific and ethical review committees of all participating centers.

Sanger sequencing was employed to detect ANKRD36 mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36. Data was analyzed using SPSS version 26.

Results

During our study, 17% of CML patients progressed to advanced phases AP-CML n= 11 (8.9%) and BC-CML n=10 (8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c.1183_1184 delGC and c.1187_1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML.

Conclusions

The study confirms ANKRD36 as a novel genomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells and correlation with high WBC count. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.
Bifurcation analysis of a two-infection transmission model with explicit vector dynamics
Authors: Srivastav Akhil Kumar , Steindorf Vanessa , Guerrero Bruno V. , Stollenwerk Nico , Kooi Bob W. , Aguiar Maíra
Published: December 2023

The investigation of epidemiological scenarios characterized by chaotic dynamics is crucial for understanding disease spread and improving disease control strategies. Motivated by dengue fever epidemiology, in this study we introduce the SIRSIR-UV model, which accounts for differences between primary and secondary infections and explicit disease vector dynamics. Our analysis, employing nonlinear dynamics and bifurcation theory, provides key insights into how vectors contribute to the overall system dynamics. In this paper, the formalization of backward bifurcation using center manifold theory, computation of Hopf and global homoclinic bifurcation curves, and derivation of analytical expressions for transcritical and tangent bifurcations deepen the understanding. The observation of chaotic behavior with the inclusion of seasonal forcing in the vector population underscores the importance of considering external factors like climate in disease spread. Our findings align with those from previous models, emphasizing the significance of simplifying assumptions, such as implicit vector dynamics, when constructing models without vector control. This study brings significant insights to the mathematical modeling of vector-borne diseases, providing a manageable framework for exploring complex epidemiological scenarios and identifying key factors influencing disease spread. While the absence of strain structure may limit predictive power in certain scenarios, the SIRSIR-UV model serves as a starting point for understanding vector-borne infectious disease dynamics.
Nascent RNA kinetics with complex promoter architecture: Analytic results and parameter inference
Authors: Shi Changhong , Yang Xiyan , Zhou Tianshou , Zhang Jiajun
Published: December 2023

Transcription is a stochastic process that involves several downstream operations, which make it difficult to model and infer transcription kinetics from mature RNA numbers in individual cell. However, recent advances in single-cell technologies have enabled a more precise measurement of the fluctuations of nascent RNA that closely reflect transcription kinetics. In this paper, we introduce a general stochastic model to mimic nascent RNA kinetics with complex promoter architecture. We derive the exact distribution and moments of nascent RNA using queuing theory techniques, which provide valuable insights into the effect of the molecular memory created by the multistep activation and deactivation on the stochastic kinetics of nascent RNA. Moreover, based on the analytical results, we develop a statistical method to infer the promoter memory from stationary nascent RNA distributions. Data analysis of synthetic data and a realistic example, theHIV-1gene, verifies the validity of this inference method.
Dollar or percentage? The effect of reward presentation on referral likelihood
Authors: Chen Hao , Hao Shuangkang
Published: December 2023

Purpose

Addressing the significant differences between referral programs and traditional promotional marketing, this paper aims to investigate and examine the impact of how reward-related information is presented within referral programs and how it interacts with reward size and reward allocation.

Design/methodology/approach

This study adopts framing effect and equity theory to build the relationship between reward presentation, reward size and reward allocation. Then, two scenario-based experimental studies are designed and conducted on Amazon Mechanical Turk.

Findings

The results show that there is no direct impact of reward presentation on referral likelihood, while the effect relies on reward size. As the levels of reward size increase, the referral likelihood gradually shifts from percentage form to dollar form as perceived size mediates the interaction effect on referral likelihood. Further, adding information about reward allocation also indicate the different impacts of equity and inequity on influencing the above findings.

Originality/value

The study contributes to the literature by introducing reward presentation and emphasizes its impact on individual’s behavior decisions in the context of referral programs. This study extends and broadens the scope and effectiveness of the framing effect on traditional promotional marketing strategies, while also bridging the gap in the literature by examining the combined role of information about rewards.
Restaurant containment measures and perceived service quality: implications for future pandemics
Authors: Ribeiro Paulo , Ramos Ricardo F. , Moro Sérgio
Published: December 2023

Purpose

This study aims to identify the impact of restaurant pandemic mitigation measures on perceived service quality.

Design/methodology/approach

A total of 15,251 reviews were collected from 300 TripAdvisor Lisbon restaurant Web pages between March 2020 and December 2021, when Covid-19 contingency measures were in place. Grounded on the online reviews, a word frequency matrix was created and used as input on partial least squares–structural equation modeling to test the proposed hypotheses.

Findings

The results suggest that precaution measures, such as the Vaccination Certificate, negative tests and restaurant layout configuration, positively influenced perceived service quality and consumer satisfaction, moderated by consumers’ beliefs.

Originality/value

This study provides relevant information for restaurant managers, which will help them implement strategies to guarantee service quality, consumer satisfaction and revisit intentions in future pandemic scenarios.
Optimized aspect and self-attention aware LSTM for target-based semantic analysis (OAS-LSTM-TSA)
Authors: Vasavi B. , Dileep P. , Srinivasarao Ulligaddala
Published: December 2023

Purpose

Aspect-based sentiment analysis (ASA) is a task of sentiment analysis that requires predicting aspect sentiment polarity for a given sentence. Many traditional techniques use graph-based mechanisms, which reduce prediction accuracy and introduce large amounts of noise. The other problem with graph-based mechanisms is that for some context words, the feelings change depending on the aspect, and therefore it is impossible to draw conclusions on their own. ASA is challenging because a given sentence can reveal complicated feelings about multiple aspects.

Design/methodology/approach

This research proposed an optimized attention-based DL model known as optimized aspect and self-attention aware long short-term memory for target-based semantic analysis (OAS-LSTM-TSA). The proposed model goes through three phases: preprocessing, aspect extraction and classification. Aspect extraction is done using a double-layered convolutional neural network (DL-CNN). The optimized aspect and self-attention embedded LSTM (OAS-LSTM) is used to classify aspect sentiment into three classes: positive, neutral and negative.

Findings

To detect and classify sentiment polarity of the aspect using the optimized aspect and self-attention embedded LSTM (OAS-LSTM) model. The results of the proposed method revealed that it achieves a high accuracy of 95.3 per cent for the restaurant dataset and 96.7 per cent for the laptop dataset.

Originality/value

The novelty of the research work is the addition of two effective attention layers in the network model, loss function reduction and accuracy enhancement, using a recent efficient optimization algorithm. The loss function in OAS-LSTM is minimized using the adaptive pelican optimization algorithm, thus increasing the accuracy rate. The performance of the proposed method is validated on four real-time datasets, Rest14, Lap14, Rest15 and Rest16, for various performance metrics.