bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene PointNet for Tumor Classification
Authors: Lu Hao , Rezapour Mostafa , Baha Haseebullah , Niazi Muhammad Khalid Khan , Narayanan Aarthi , Gurcan Metin Nafi 
Published: June 2024

AbstractThe rising incidence of cancer underscores the imperative for innovative diagnostic and prognostic methodologies. This study delves into the potential of RNA-Seq gene expression data to enhance cancer classification accuracy. Introducing a pioneering approach, we model gene expression data as point clouds, capitalizing on the data’s intrinsic properties to bolster classification performance. Utilizing PointNet, a typical technique for processing point cloud data, as our framework’s cornerstone, we incorporate inductive biases pertinent to gene expression and pathways. This integration markedly elevates model efficacy, culminating in developing an end-to-end deep learning classifier with an accuracy rate surpassing 99%. Our findings not only illuminate the capabilities of AI-driven models in the realm of oncology but also highlight the criticality of acknowledging biological dataset nuances in model design. This research provides insights into application of deep learning in medical science, setting the stage for further innovation in cancer classification through sophisticated biological data analysis. The source code for our study is accessible at:https://github.com/cialab/GPNet.
The divergent responses of salinity generalists to hyposaline stress provide insights into the colonization of freshwaters by diatoms
Authors: Judy Kathryn J. , Pinseel Eveline , Downey Kala M. , Lewis Jeffrey A. , Alverson Andrew J. 
Published: June 2024

ABSTRACTEnvironmental transitions, such as the salinity divide separating marine and fresh waters, shape biodiversity over both shallow and deep timescales, opening up new niches and creating opportunities for accelerated speciation and adaptive radiation. Understanding the evolutionary genetic underpinnings behind habitat transitions is therefore a central question in evolutionary biology. We used time-resolved transcriptomics to contrast the hyposalinity stress responses of two ecologically important diatoms:Skeletonema marinoihas a deep marine ancestry but recently invaded brackish waters, whereasCyclotella crypticahas deep freshwater ancestry and can withstand a much broader salinity range.S. marinoiis less adept at mitigating even mild salinity stress compared toC. cryptica, which has distinct mechanisms for rapid mitigation of hyposaline stress and long-term growth in low salinity. We show that the cellular mechanisms underlying low salinity tolerance, which has allowed diversification across freshwater habitats worldwide, includes elements that are both conserved and variable across the diatom lineage. The balance between ancestral and lineage-specific environmental responses in phytoplankton have likely shaped marine–freshwater transitions on evolutionary timescales and, on contemporary timescales, will likely determine which lineages survive and adapt to changing ocean conditions.
A semidwarf and late-flowering isogenic Kosihihikari d60Hd16: development, productivity, and regional suitability revealed by correlation-based network analysis
Authors: Tomita Motonori , Honda Hiroshi 
Published: June 2024

AbstractBreeding rice varieties that are tolerant to weather variability and optimizing cultivation methods for each developed variety are challenging issues for global food problems. In this study, the late-flowering geneHd16of Koganebare was introduced into Koshihikari through backcrossing to create ’Koshihikari Hd16’. It was then crossed with ’Koshihikari d60’ to develop an isogenic Koshihikari containing bothHd16andd60. Productivity tests were conducted in nine prefectures in Japan for two homogeneous rice genotypes,Hd16(late flowering) andd60Hd16(short culm and late flowering). By analyzing the relationship between genotype, traits, and accumulation temperature, we reexamined the characteristics of each genotype and inferred the optimal growing areas. Correlation-based network analysis among yield, grain quality, and value of taste and traits showed that quality was positively correlated with panicle length and 1000-grain weight, and yield was strongly positively correlated with 1000-grain weight. d60 genotype was negatively correlated with culm length and lodging degree. These correlations were supported by partial correlation analysis and significant differences compared to the wildtype was identified. Principal component analysis ofd60Hd16revealed that Yamanashi and Ehime, which have longer panicle length and culm length, were suitable in terms of yield and quality, while Shimane, which is warmer and has shorter panicle length and culm length, was suitable in terms of eating quality. Moreover, Koshihikari d60Hd16 could express traits that are less prone to lodging degree while maintaining the same quality and yield as the wild type in cultivation of late-flowering strains. Thus, thed60andH16genotypes express stable traits adapted to a wide range of Japanese climatic conditions and growing environments. This study provides fundamental information for promoting new smart agriculture, in which improved varieties are deployed in different regions with different climatic conditions.
Interplay of EGFR, JNK and ROS signalling in soma-germline communication in theDrosophilatestis
Authors: Alvarez Maria , Papagiannouli Fani 
Published: June 2024

AbstractCell communication via signalling exchange plays a pivotal role in multicellular development for building functional tissues and organs. In theDrosophilatestis, a pair of somatic cyst cells (CCs) encapsulate the germline that differentiates through close-range EGFR signalling activation. The conserved Dlg/Scrib/Lgl cortical polarity complex and clathrin-mediated endocytosis attenuate EGFR signalling in CCs and loss of their function leads to EGFR overactivation and non-autonomous death of the neighbouring germ cells. Here we show that EGFR overactivation results in upregulation of JNK and p38 signalling in CCs and ROS levels in the germ cells that are destined to die. Our data uncover a bidirectional feedback between JNK signalling and ROS who regulate each other within the CC-germline microenvironment, while reducing the levels of either JNK or ROS restores germ cell survival. This study provides a framework of how polarity and cellular trafficking regulate the output of multiple signalling responses cell-intrinsically and in adjacent cells, to coordinate tissue-specific responses and maintain homeostasis.
Frameshifts in Tandem Repeats: Consequences on Protein Physicochemical Properties and Function
Authors: Osmanli Zarifa , Aldrian Gudrun , Leclercq Jeremy , Falgarone Theo , Gomez Bergna Santiago M. , Gori Denis N. Prada , Oleinikov Andrew V. , Shahmuradov Ilham , Kajava Andrey V. 
Published: June 2024

ABSTRACTThe genetic code uses three-nucleotide units to encode each amino acid in proteins. Insertions or deletions of nucleotides not divisible by three shift the reading frames, resulting in significantly different protein sequences. These events are disruptive but can also create variability important for evolution. Previous studies suggest that genetic code and gene sequences evolve to minimize frameshift effects, maintaining similar physicochemical properties to their reference proteins. Here, we focused on tandem repeat sequences, known as frameshift hotspots. Using cutting-edge bioinformatics tools, we compared reference and frameshifted protein sequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes. Our analysis revealed several intriguing sequence-structure-function correlations. We showed that in contrast to the general tendency, frameshifts within these regions, especially with short repeats, lead to significant changes: increased hydrophobicity and arginine content, new aggregation-prone and transmembrane regions. Overall, frameshifts have stronger effects on tandem repeat regions compared to non-repetitive sequences, and therefore can be a primary cause of altered functions, cellular localization, and the development of various pathologies.
Genomic alterations and transcriptional phenotypes in circulating tumor DNA and matched metastatic tumor
Authors: Takahashi Nobuyuki , Pongor Lorinc , Agrawal Shivam P. , Shtumpf Mariya , Rajapakse Vinodh N. , Shafiei Ahmad , Schultz Christopher W. , Kim Sehyun , Roame Diana , Carter Paula , Vilimas Rasa , Nichols Samantha , Desai Parth , Figg William Douglas , Bagheri Mohammad , Teif Vladimir B. , Thomas Anish 
Published: June 2024

AbstractBackgroundProfiling circulating cell-free DNA (cfDNA) has become a fundamental practice in cancer medicine, but the effectiveness of cfDNA at elucidating tumor-derived molecular features has not been systematically compared to standard single-lesion tumor biopsies in prospective cohorts of patients. The use of plasma instead of tissue to guide therapy is particularly attractive for patients with small cell lung cancer (SCLC), a cancer whose aggressive clinical course making it exceedingly challenging to obtain tumor biopsies.MethodsHere, a prospective cohort of 49 plasma samples obtained before, during, and after treatment from 20 patients with recurrent SCLC, we study cfDNA low pass whole genome (0.1X coverage) and exome (130X) sequencing in comparison with time-point matched tumor, characterized using exome and transcriptome sequencing.ResultsDirect comparison of cfDNA versus tumor biopsy reveals that cfDNA not only mirrors the mutation and copy number landscape of the corresponding tumor but also identifies clinically relevant resistance mechanisms and cancer driver alterations not found in matched tumor biopsies. Longitudinal cfDNA analysis reliably tracks tumor response, progression, and clonal evolution. Genomic sequencing coverage of plasma DNA fragments around transcription start sites shows distinct treatment-related changes and captures the expression of key transcription factors such as NEUROD1 and REST in the corresponding SCLC tumors, allowing prediction of SCLC neuroendocrine phenotypes and treatment responses.ConclusionsThese findings have important implications for non-invasive stratification and subtype-specific therapies for patients with SCLC, now treated as a single disease.
Electrochemically controlled switching of dyes for enhanced super-resolution optical fluctuation imaging (SOFI)
Authors: Yang Ying , Ma Yuanqing , Tilley Richard D. , Gooding J. Justin 
Published: June 2024

AbstractIn super-resolution optical fluctuation imaging (SOFI), the locations of molecules spaced closer than the diffraction limit of light can be identified through spatial and temporal correlation analysis of the fluorescence intensity fluctuation. Using organic dyes as fluorophore probes, the fast but stochastic switching of the individual dyes is favourable for improving SOFI imaging resolution and speed, especially in the case of high-order cumulant analysis. While in practice, fluorophore switching can be non-uniform, with some fluorophores remaining in ON or OFF state for extended periods. Furthermore, in some cases the overall rate of switching of the fluorophores can be too slow, presenting practical limitations for high-resolution and fast SOFI imaging. In this work, we demonstrate how to overcome these challenges using electrochemical controlled fluorophore switching. The oscillating electrochemical potential setting with high frequency increases the switching rate and reduces the switching heterogeneity of fluorophores. The dye Alexa Fluor 647, applied here as an example, exhibits over 3-fold decrease in average ON time and over 2-fold decrease in switching variance, resulting in significantly improved SOFI image resolution with fewer frames. We demonstrated that this new electrochemically controlled SOFI imaging modality can achieve a SOFI image with ∼130 nm resolution in 2 seconds of acquisition time, and 80 nm resolution in 6 seconds. This advancement enables fast, large area tile-scan super-resolution imaging, which opens the full potential of SOFI imaging.
BIT: Bayesian Identification of Transcriptional Regulators from Epigenomics-Based Query Region Sets
Authors: Lu Zeyu , Xu Lin , Wang Xinlei 
Published: June 2024

AbstractTranscriptional regulators (TRs) are master controllers of gene expression and play a critical role in both normal tissue development and disease progression. However, existing computational methods for identification of TRs regulating specific biological processes have significant limitations, such as relying on distance on a linear chromosome or binding motifs that have low specificity. Many also use statistical tests in ways that lack interpretability and rigorous confidence measures. We introduce BIT, a novel Bayesian hierarchical model forin-silicoTR identification. Leveraging a comprehensive library of TR ChIP-seq data, BIT offers a fully integrated Bayesian approach to assess genome-wide consistency between user-provided epigenomic profiling data and the TR binding library, enabling the identification of critical TRs while quantifying uncertainty. It avoids estimation and inference in a sequential manner or numerous isolated statistical tests, thereby enhancing accuracy and interpretability. BIT successfully identified critical TRs in perturbation experiments, functionally essential TRs in various cancer types, and cell-type-specific TRs within heterogeneous cell populations, offering deeper biological insights into transcriptional regulation.
Skeletal Muscle Specific PolG Dysfunction Activates the Integrated Stress Response and Promotes a Cachexia like Phenotype
Authors: Bond Simon T , King Emily J , Walker Shannen M , Yang Christine , Liu Yingying , Liu Kevin H , Zhuang Aowen , Jurrjens Aaron W , Fang Haoyun A , Formosa Luke E , Nath Artika P , Carmona Sergio Ruiz , Inouye Michael , Huynh Kevin , Meikle Peter J , Doomun Nadeem Elahee , de Souza David P , Rudler Danielle L , Calkin Anna C , Filipovska Aleksandra , Greening David W , Henstridge Darren C , Drew Brian G 
Published: June 2024

ABSTRACTDuring mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses to preserve cellular health. One such pathway is the mitochondrial integrated stress response (mtISR), which is specifically activated by mitochondrial DNA (mtDNA) damage. However, the causal molecular signals responsible for this activation remain elusive. A gene often associated with mtDNA mutations/deletions isPolg1, which encodes the mitochondrial DNA Polymerase γ (PolG). Here, we describe what is to our knowledge the first conditional muscle specific model of PolG mutation, and demonstrate a rapid development of mitochondrial dysfunction and cachexia in these animals from ∼5 months of age. Detailed molecular profiling of muscles demonstrated robust activation of the mtISR, likely mediated upstream by the HRI/DELE1 stress pathway. This was accompanied by striking alterations to the mitochondrial folate cycle and its metabolites, strongly implying imbalanced folate intermediates as a previously unrecognised pathology driving the mtISR in mitochondrial disease.
Benchmarking Imputed Low Coverage Genomes in a Human Population Genetics Context
Authors: Purnomo Gludhug A. , Teixeira João C. , Sudoyo Herawati , Llamas Bastien , Tobler Raymond 
Published: June 2024

ABSTRACTOngoing advances in population genomic methodologies have recently made it possible to study millions of loci across hundreds of genomes at a relatively low cost, by leveraging a combination of low-coverage shotgun sequencing and innovative genotype imputation methods. This approach has the potential to provide economical access to genotype information that is similar to most widely used low-cost genotyping approach – i.e. SNP panels – while avoiding potential issues related to loci being ascertained in distantly related populations. Nonetheless, adoption of imputation methods has been constrained by the lack of suitable reference panels of phased genomes, as performance degrades when panel individuals are distantly related to the target populations. Recent advances in imputation algorithms now allow genetic information from the target population to be used in the imputation process, however, potentially mitigating the lack of a suitable reference panel. Here we assess the performance of the recently released GLIMPSE imputation software on a set of 250 low coverage genomes (∼3x) from populations from Island Southeast Asia and Near Oceania that are poorly represented in publicly available datasets, comparing the use of imputed genotypes against other common genotype calling methods for a range of standard population genomic analyses. We find that imputation performance and inference both greatly improved when genetic information from the 250 target individuals was leveraged, with comparable results to pseudo-haploid calls that trade off improved precision with reduced accuracy. Our study shows that imputed genotypes are a cost effective and robust basis for population genomic studies of groups, especially those that are poorly represented in publicly available data.
Risk factors for atopic and non-atopic asthma in school-aged children from high-, and low-and-middle-income countries
Authors: Rutter Charlotte E , Mpairwe Harriet , Figueiredo Camila A , Njoroge Mary , Robertson Steven , Ali Hajar , Brooks Collin , Douwes Jeroen , Cooper Philip J , Chico Martha , Romero-Sandoval Natalia , Cruz Alvaro A , Tumwesige Pius , Barreto Mauricio L , Pearce Neil , Pembrey Lucy ,   the CAMERA Study Group
Published: June 2024

AbstractBackgroundIt is well established that there are different asthma phenotypes, but whereas determinants of atopic asthma are well studied, little is known about non-atopic asthma. We compared risk factors for atopy, atopic asthma (AA) in atopics, and non-atopic asthma (NAA) in non-atopics, in children in a wide variety of countries.MethodsUsing four studies, across 23 countries, we assessed asthma status and atopy (skin prick tests) for children aged 6-17, plus risk factors from housing, heating, pets, family, diet, and air-quality categories. Using mixed effects logistic regression models we assessed 4 pathways to asthma: Pathway 1: comparing NAA with non-atopic non-asthma (risk factors for NAA); Pathway 2: comparing atopic non-asthma with non-atopic non-asthma (risk factors for atopy); Pathway 3: comparing AA with atopic non-asthma (risk factors for AA); Pathway 4: comparing AA with non-atopic non-asthma (risk factors for atopy and AA together).ResultsOur final sample of 32741 children comprised 67% with neither atopy nor asthma, 15% with atopybut without asthma, 8% with AA and 10% with NAA. Risk factors were similar for AA in atopic children and NAA in non-atopic children (Pearson’s correlation = 0.81, 95% confidence interval = [0.68, 0.94]). In contrast, risk factors for atopy in children without asthma differed from those for AA in atopic children (−0.06, [−0.29, 0.17]).DiscussionThese findings indicate that although atopy increases the risk of asthma, the risk factors for subsequently developing asthma are generally the same in those with and without atopy. This raises important questions about the role of atopy in asthma, particularly whether it is an inherent part of the aetiological process or is coincidental.Key messagesWhat is already known on this topicIt is well established that there are different phenotypes of asthma but little is known about risk factors for non-atopic asthma.What this study addsUsing a novel approach, we found that lifestyle and environmental risk factors for developing asthma are generally similar in atopic children and non-atopic children but the risk factors for atopy are quite different.How this study might affect research, practice or policyOur findings suggest that atopy and asthma may be coincidental in a large proportion of children who are defined as having atopic asthma. This has important implications for our understanding of the causes and mechanisms of different asthma phenotypes, and therefore prevention and treatment of asthma.
Factors influencing uptake of COVID-19 diagnostics in Sub-Saharan Africa: a rapid scoping review
Authors: Phiri Mackwellings Maganizo , Dunkley Yasmin , Di Giacomo Elizabeth , Lora Wezzie , Kumwenda Moses , Kabonga Itai , Isere Elvis , Bimba John , Sibanda Euphemia , Choko Augustine , Hatzold Karin , Corbett Liz , Desmond Nicola 
Published: June 2024

AbstractBackgroundDiagnostics are critical for preventing COVID-19 transmission, enabling disease management and engagement with care. However, COVID-19 testing uptake remained low in low- and middle- income countries in Sub-Saharan Africa (SSA) during the recent pandemic, due to issues of supply, access and acceptability. Early studies conducted outside of the region provide insight into uptake of COVID-19 testing, however there has been no systematic research within the region. The aim of this scoping review is to investigate factors influencing uptake of COVID-19 testing in different settings across SSA.MethodsInclusion criteria was any study employing qualitative or mixed methodologies, addressing uptake of COVID-19 testing conducted in SSA. MEDLINE, PubMed, Google Scholar, Web of Science, and Africa-Wide Information were searched.Thematic content analysis was conducted across all included articles until saturation was attained.ResultsIn total 2994 articles were identified and fourteen reviewed. Structural, social, epidemiological, informational, and political elements affected how publics interacted with COVID-19 testing. Coverage was limited by insufficient diagnostic capabilities caused by a shortage of laboratory resources and trained personnel. False information spread through social media led to testing misperceptions and apprehension. Testing hesitancy was ascribed to fear of restrictive measures and the possibility of social harms if positive. Facility-based testing was physically inaccessible and perceived as lacking privacy, whereas self-testing distributed by the community removed lengthy distances and prevented stigma. Perceptions that COVID-19 was not severe and low numbers of confirmed cases in comparison to other settings undermined public urgency for testing. Low testing frequency led to low-rate assumptions, which in turn generated denial and othering narratives. Politicians’ acceptance or denial of COVID-19 affected the mobilization of the health system, and their model actions—such as testing openly—promoted public confidence and involvement in interventions.ConclusionsThis review emphasizes the necessity of strong political commitments to enhancing health systems for future pandemic preparedness. Response plans should consider contextual elements that affect how people react to interventions and perceive health emergencies. Community-driven self-testing distribution could enhance the uptake of diagnostics through addressing socio-economic constraints impacting facility-delivered testing.