bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour suppressor WT1 and its interacting protein RNA helicase DDX5 regulate the microRNA let7/Igf1r axis in the kidney mesenchyme
Authors: Dey Sourav , Slight Joan , Aitken Stuart , Joseph Iwin , Bhore Utkarsh , vonKriegshiem Alex , Petrovich Giulia , Charlton Jocelyn , Stancheva Viktoriya , Mohapatra Debasis , Essafi Abdelkader , Pritchard-Jones Kathy , Hastie Nicholas D , Bharathavikru Ruthrothaselvi 
Published: January 2025

AbstractGermline mutations in tumour suppressor, Wilms Tumour 1 (WT1) as well as somatic and germline mutations in microRNA processing genes (MIRPG) have been identified in Wilms’ Tumours (WT), where upregulation of IGF2 through genetic and/or epigenetic mechanisms is commonly seen. Whether these different epigenetic and genetic causes converge on common targets is still unclear. WT1 is also involved in RNA binding and regulates the stability of these developmental mRNAs. We now show that WT1 interacts with microRNA let-7 and proteins involved in microRNA processing wherein DDX5 is found to be an important regulator. WT1 absence results in decreased microRNA levels in cell lines and kidney mesenchyme, which is further downregulated in a WT1 and DDX5 double knockdown, ultimately modulatingIgf1rexpression. These findings suggest a plausible mechanism by whichWT1mutations lead to WT, and converge on microRNA pathway and IGF signalling pathway, which are important contributing factors in the aetiology of WT.
Regulation of transcription elongation anticipates alternative gene expression strategies across the cell cycle
Authors: Maya-Miles Douglas , García-Martínez José , Cases Ildefonso , Pasión Rocío , de la Cruz Jesús , Pérez-Ortín José E. , de la Cruz Muñoz-Centeno María , Chávez Sebastián 
Published: January 2025

ABSTRACTIncreasing evidence supports that the activity of RNA polymerase II (RNA pol II) during transcription elongation can be regulated to control transcription rates. Using genomic run-on (GRO) and RNA pol II chromatin immunoprecipitation (RPCC), we have respectively measured active and total RNA pol II present in the body of genes at 3 different stages of the mitotic cell cycle ofSaccharomyces cerevisiae: G1, S and G2/M. Comparison of active and total RNA pol II values at these three points defined different patterns of transcription elongation control across the cell cycle. Previously characterized cycling genes were found associated to some of these elongation patterns. A cluster of genes with very divergent GRO and RPCC patterns was significantly enriched in genes functionally related to ribosome biogenesis (RiBi) and the structural components of the ribosome. We confirmed that RiBi mRNA expression upregulates after START but decreases after mitosis. Finally, we analysed the contribution of mRNA stability to each cluster and found that concerted control of RNA pol II activity and mRNA decay is needed to fully understand alternative strategies of gene expression across the cell cycle.
Performance of the VISITECT® CD4 Test for Rapid Identification of Advanced HIV Disease at AHF-Supported Sites in Zambia: A Diagnostic Accuracy Analysis in a Zambian Population
Authors: Mulumba Eric Mpoyi , Kayembe Mazinga F. , Chewe Webster C. , Chanda Chitalu , Dube Nduduzo , Chituta Clifford , Hamooya Benson M. , Kasweka Freddy T. , Matabishi Martin , Assani Muyungila Bob 
Published: January 2025

AbstractBackgroundAdvanced HIV disease (AHD), defined as a CD4 count below 200 cells/mm³ or the presence of WHO Stage 3 or 4 clinical conditions, poses significant diagnostic challenges in resource-limited settings such as Zambia. Early identification of AHD is essential for improving outcomes for recipients of care (ROCs). The VISITECT® CD4 test, a point-of-care tool, offers potential for addressing these challenges; however, its diagnostic performance in Zambia remains under-evaluated. This study aimed to assess the sensitivity and specificity of the VISITECT® CD4 test for identifying AHD among ROCs at five AIDS Healthcare Foundation (AHF)-supported clinics in Zambia.MethodologyA cross-sectional study was conducted between January 8 to May 31, 2024, at five AHF-supported clinics in Zambia. Participants included individuals who were newly diagnosed with HIV, re-engaging in HIV care, or presenting with unsuppressed HIV viral loads. Baseline clinical and demographic data were collected, and the diagnostic performance of the VISITECT® CD4 test was compared to the flow cytometry CD4 test (the gold standard) using STATA v15 to determine sensitivity, specificity, and other diagnostic accuracy metrics.ResultsAmong 231 participants, 24.7% (57/231) had AHD based on the flow cytometry CD4 test, whereas 47.6% (110/231) were classified with AHD by the VISITECT® CD4 test. The VISITECT® CD4 test demonstrated a sensitivity of 96.5% and a specificity of 68.4%. The Negative Predictive Value was 98.4%, and the Positive Predictive Value was 50.0%. The overall diagnostic accuracy, as indicated by the area under the curve, was 0.82 (95% CI: 0.78, 0.87). AHD was significantly associated with age according to flow cytometry (p=0.029) but not according to the VISITECT® CD4 test (p=0.277). A significantly higher proportion of individuals with anemia had AHD across both tests (p<0.05).ConclusionThe VISITECT® CD4 test demonstrated strong diagnostic accuracy for detecting AHD, making it a valuable rapid point-of-care tool in resource-limited settings. Its wider implementation could enhance early AHD detection and facilitate timely clinical interventions, warranting further exploration.
Non-Contact Optical Blood Pressure Biometry Using AI-Based Analysis of Non-Mydriatic Fundus Imaging
Authors: Bressler Idan , Dollberg Dolev , Aviv Rachelle , Margalit Danny , Harris Alon , Siesky Brent , Ianchulev Tsontcho , Dvey-Aharon Zack 
Published: January 2025

AbstractBackgroundThis study was developed to determine whether a machine learning model could be developed to assess blood pressure with accuracy comparable to arm cuff measurements.MethodsA deep learning model was developed based on the UK Biobank dataset and was trained to detect both systolic and diastolic pressure. The hypothesis was formulated after data collection and before the development of the model. Comparison was conducted between arm cuff measurements, as ground truth, and results from the model, using Mean Absolute Error, Mean Squared Error, and Coefficient of Determination (R^2).ResultsSystolic pressure was measured with 9.81 Mean Absolute Error, 165.13 Mean Squared Error and 0.36 R^2. Diastolic pressure was measured with 6.00 Mean Absolute Error, 58.21 and 0.30 R^2.ConclusionsThis model improves on existing research and shows errors comparable to the variability of hand cuff measurements. The use of fundus images to assess blood pressure may be more indicative of long-term hypertension. Additional trials in clinical settings may be necessary, as well as additional prospective studies to validate results.
HD2Net: A Deep Learning Framework for Simultaneous Denoising and Deaberration in Fluorescence Microscopy
Authors: Hou Xuekai , Li Yue , Hobson Chad M. , Shroff Hari , Guo Min , Liu Huafeng 
Published: January 2025

AbstractFluorescence microscopy is essential for biological research, offering high-contrast imaging of microscopic structures. However, the quality of these images is often compromised by optical aberrations and noise, particularly in low signal-to-noise ratio (SNR) conditions. While adaptive optics (AO) can correct aberrations, it requires costly hardware and slows down imaging; whereas current denoising approaches boost the SNR but leave out the aberration compensation. To address these limitations, we introduce HD2Net, a deep learning framework that enhances image quality by simultaneously denoising and suppressing the effect of aberrations without the need for additional hardware. Building on our previous work, HD2Net incorporates noise estimation and aberration removal modules, effectively restoring images degraded by noise and aberrations. Through comprehensive evaluation of synthetic phantoms and biological data, we demonstrate that HD2Net outperforms existing methods, significantly improving image resolution and contrast. This framework offers a promising solution for enhancing biological imaging, particularly in challenging aberrating and low-light conditions.
Carbon monoxide exposure in pregnant women in the UK – results from the IPPCO study
Authors: Place Elsie , Wareing Hilary , Herigstad Mari 
Published: January 2025

ABSTRACTCarbon monoxide (CO) is a colourless, odourless gas that poses a threat to life at concentrations of just a few hundred ppm. The developing foetus is particularly vulnerable to CO exposure, and maternal exposure to much lower levels of the gas is associated with adverse outcomes such as low birth weight. This study aimed to quantify CO exposure in pregnant women’s homes and assess whether breath CO levels could be linked to home-based CO exposure and sociodemographic factors.CO levels were monitored continuously over two weeks in 161 households selected for indicators of lower socio-economic status and proximity to gas appliances, a risk factor for environmental CO exposure. Exhaled breath CO measurements were taken before and after the monitoring period. Of the households monitored, 57.8% had detectable CO levels, with 31.7% experiencing levels above 4ppm and 14.3% above 10ppm. CO exposure varied significantly across households, with both chronic low-level and intermittent high-level exposures observed. Six households included in the study exceeded current World Health Organisation recommended limits of 3.5ppm for ≥24 hours, and three exceeded the limit of 9ppm for ≥8 hours. Higher CO levels in the household were associated with the use of gas for cooking. Higher exhaled CO levels were associated with number of smokers in the household and eligibility for the UK government NHS Healthy Start scheme. Following the monitoring period, exhaled CO levels were only associated with number of smokers in the household, suggesting an intervention effect.This study indicates that a high proportion of pregnant women are exposed to CO within the home, albeit predominantly within current recommended limits, and that exposure may be linked to socio-economic factors in addition to smoking. This study highlights the need for improved CO monitoring and mitigation strategies, particularly in vulnerable populations, to protect maternal and foetal health.
Unraveling the molecular mechanism underlying the anticancer activity of CISD2/NAF-144-67
Authors: Rowland Linda , Alfoni Itai , Neumann Ehud , Karmi Ola , Nechushtai Rachel , Mittler Ron 
Published: January 2025

AbstractWe recently reported on the development of a unique cancer-targeting peptide called NAF-144-67(derived from CISD2/NAF-1). NAF-144-67selectively permeates the plasma membrane (PM) of cancer cells, but not healthy cells, causing the activation of apoptotic and ferroptotic cell death pathways specifically in cancer cells. NAF-144-67also targets and shrinks human breast and ovarian cancer tumors in a xenograft mice model system without any apparent side effects. Although the specific permeation of NAF-144-67through cancer cell PMs was studied, and its cancer killing effects validatedin vitroandin vivo, little is known about how NAF-144-67exerts its biological activity once it enters cancer cells. Here, we report that NAF-144-67targets the CISD2/NAF-1 protein of cancer cells and disrupts its homodimeric structure. We further reveal that a peptide derived from the same domain of the human CISD1 (mitoNEET; mNT19-42) protein, a close family member to CISD2, has no killing activity towards cancer cells, and that dimers of NAF-144-67(at two different orientations) have higher anticancer activity compared to monomeric NAF-144-67. Our findings shed new light on the biological activity of NAF-144-67and bring it closer to becoming a potential new anticancer drug.
PROTAC molecule-mediated SpCas9 protein degradation for precise genome editing
Authors: Sun Shengnan , Sun Renhong , Tan Minkang , Kip Maarten , Yang Xiaobao , Pang Baoxu 
Published: January 2025

AbstractCRISPR (clustered regularly interspaced short palindromic repeats) technology has revolutionized both fundamental research and genomic medicine. The need for precise control of SpCas9-based CRISPR genome editing has resulted in a number of methods to control the function and activity of Cas9 proteins to minimize off-target editing effects. Proteolysis-targeting chimeras (PROTACs) are an emerging technology using the ubiquitin-proteasome system to selectively degrade the target proteins. Here, we developed CASPROTAC 6, a reversible and cell-permeable degrader directly targeting SpCas9 proteins for degradation. The warhead of CASPROTACs was derived by bridging a known SpCas9 binder BRD7087 with an S-substituted Lenalidomide cereblon (CRBN) ligand via the 6-carbon alkyl linker. Our data showed that CASPROTAC 6 is a broad-spectrum degrader of SpCas9 and SpCas9 variants such as dCas9 and Cas9 nickases. The CASPROTAC 6 degraded SpCas9 and the SpCas9-guide-RNA complex via the proteasome system by ∼50%. As a result, the CASPROTAC 6 molecule can reduce the CRISPR/Ca9-mediated genome editing by 30%. The CASPROTAC 6 molecules could be used to regulate the CRISPR/SpCas9-associated nucleases for precise genome editing to reduce off-target effects and strengthen biosafety.
Cell-death induced immune response and coagulopathy promote cachexia inDrosophila
Authors: Singh Ankita , Hu Yanhui , Lopes Raphael Fragoso , Lane Liz , Woldemichael Hilina , Xu Charles , Udeshi Namrata D. , Carr Steven A. , Perrimon Norbert 
Published: January 2025

AbstractTumors can exert a far-reaching influence on the body, triggering systemic responses that contribute to debilitating conditions like cancer cachexia. To characterize the mechanisms underlying tumor-host interactions, we utilized a BioID-based proximity labeling method to identify proteins secreted by YkiactadultDrosophilagut tumors into the bloodstream/hemolymph. Among the major proteins identified are coagulation and immune-responsive factors that contribute to the systemic wasting phenotypes associated with Ykiacttumors. The effect of innate immunity factors is mediated by NFκB transcription factors Relish, dorsal, and Dif, which in turn upregulate the expression of the cachectic factors Pvf1, Impl2, and Upd3. In addition, Ykiacttumors secrete Eiger, a TNF-alpha homolog, which activates the JNK signaling pathway in neighboring non-tumor cells, leading to cell death. The release of damage-associated molecular patterns (DAMPs) from these dying cells presumably amplifies the inflammatory response, exacerbating systemic wasting. Targeting the inflammatory response, the JNK pathway, or the production of cachectic factors could potentially alleviate the debilitating effects of cancer cachexia.
LncPTPred: Predicting lncRNA-Protein Interaction based on Crosslinking and Immunoprecipitation (CLIP-Seq) Data
Authors: Das Gourab , Das Troyee , Ghosh Zhumur 
Published: January 2025

ABSTRACTLong non-coding RNA (lncRNA)-Protein Interaction (LPI) across diverse biological systems directly and indirectly regulates various cellular processes. Experimental assays to recognize the protein binding partners of lncRNAs is highly time consuming and expensive.In-silicopredictive approaches involving pattern recognition technique provides a promising alternative to it by reducing the search space. Our work identifies such hidden pattern from within the Cross-linking immunoprecipitation sequencing (CLIP-Seq) data which aids to overcome the problem of obtaining real negative dataset and thus offers a state-of-the-art machine learning (ML) based prediction algorithm to predict LPI. Initial phase of this work involves preparation of the training dataset and the next phase is devoted towards developing the ML based model to perform prediction operation. In order to show the efficacy of our model, its performance has been compared against that of the contemporary prediction tools, where the result clearly shows the outperformance of our model. Moreover it also provides the segments of interaction within the lncRNA loci which acts as a roadmap for precise designing of the validation experiment. The LncPTPred tool has been provided in terms of web server as well as standalone version in github.Web server Link:http://bicresources.jcbose.ac.in/zhumur/lncptpred/Github Link:https://github.com/zglabDIB/lncptpred.git
Calcium-triggered apoplastic ROS bursts balance gravity and mechanical signals to navigate soil
Authors: Kulich Ivan , Vladimirtsev Dmitrii , Randuch Marek , Gao Shiqiang , Citterico Matteo , Konrad Kai R. , Nagel Georg , Wrzaczek Michael , Friml Jiri 
Published: January 2025

AbstractReactive oxygen species (ROS) have been implicated repeatedly in multiple signaling processes in plants but the underlying mechanisms and roles remain enigmatic. Here, we developed live imaging of apoplastic ROS at the root surface. Different signals, including auxin, extracellular ATP and RALF1 peptide, all induce cytosolic calcium transients and apoplastic ROS bursts. Genetic and optogenetic manipulations identified calcium transients as necessary and sufficient for ROS bursts via activation of NADPH oxidases RBOHC and RBOHF. Apoplastic ROS bursts are not required but rather limit the gravity-induced root bending. Root bending is sensed by stretch-activated calcium channel MCA1 leading to NADPH oxidase activation at the stretched side. The resulting ROS production stiffens cell wall for better soil penetration. Apoplastic ROS thus provides a means to balance tissue flexibility and stiffness to efficiently navigate soil.
AAVone: A Cost-Effective, Single-Plasmid Solution for Efficient AAV Production with Reduced DNA Impurities
Authors: Yang Rongze , Tran Ngoc Tam , Chen Taylor , Cui Mengtian , Wang Yuyan , Sharma Tapan , Liu Yu , Zhang Jiantao , Yuan Xinxu , Zhang Danmeng , Chen Cuiping , Shi Zhen , Wang Leming , Dai Yuling , Zaidi Haniya , Liang Jiarui , Chen May , Jaijyan Dabbu , Hu Huan , Wang Bing , Xu Cheng , Hu Wenhui , Gao Guangping , Yu Daozhan , Tai Phillip W.L. , Wang Qizhao 
Published: January 2025

ABSTRACTCurrently, the most common approach for manufacturing GMP-grade adeno-associated virus (AAV) vectors involves transiently transfecting mammalian cells with three plasmids that carry the essential components for production. The requirement for all three plasmids to be transfected into a single cell and the necessity for high quantities of input plasmid DNA, limits AAV production efficiency, introduces variability between production batches, and increases time and labor costs. Here, we developed an all-in-one, single-plasmid AAV production system, called AAVone. In this system, the adenovirus helper genes (E2A,E4orf6, andVA RNA), packaging genes (repandcap), and the vector transgene cassette are consolidated into a single compact plasmid with a 13-kb backbone. The AAVone system achieves a two- to four-fold increase in yields compared to the traditional triple-plasmid system. Furthermore, the AAVone system exhibits low batch-to-batch variation and eliminates the need for fine-tuning the ratios of the three plasmids, simplifying the production process. In terms of vector quality, AAVs generated by the AAVone system show similarin vitroandin vivotransduction efficiency, but a substantial reduction in sequences attributed to plasmid backbones and a marked reduction in non-functional snap-back genomes. In Summary, the AAVone platform is a straightforward, cost-effective, and highly consistent AAV production system – making it particularly suitable for GMP-grade AAV vectors.
Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization
Authors: Tang Gechlang , Carr Alex V. , Perez Crystal , Ramos Sarmiento Katherine , Levy Lisa , Lampe Johanna W. , Diener Christian , Gibbons Sean M. 
Published: January 2025

AbstractAbsolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, qPCR, or spike-ins (i.e., adding cells or DNA from an organism not normally found in a sample), can be labor-intensive, costly, and confounded by factors like water content, DNA extraction efficiency, PCR inhibitors, and other technical challenges that add bias and noise. We propose a simple, cost-effective approach that circumvents some of these technical challenges: directly estimating bacterial biomass from metagenomes using bacterial-to-host (B:H) read ratios. We compare B:H ratios to the standard methods outlined above, demonstrating that B:H ratios are useful proxies for bacterial biomass in stool and possibly in other host-associated substrates. We show how B:H ratios can be used to track antibiotic treatment response and recovery in both mice and humans, which showed 403-fold and 45-fold reductions in bacterial biomass during antibiotic treatment, respectively. Our results indicate that host and bacterial metagenomic DNA fractions in human stool fluctuate longitudinally around a stable mean in healthy individuals, and the average host read fraction varies across healthy individuals by < 8-9 fold. B:H ratios offer a convenient alternative to other absolute biomass quantification methods, without the need for additional measurements, experimental design considerations, or machine learning algorithms, enabling retrospective absolute biomass estimates from existing stool metagenomic data.
Quantifying the spatiotemporal dynamics of the first two epidemic waves of SARS-CoV-2 infections in the United States
Authors: Lopes Rafael , Swartwood Nicole A. , Lan Yu , Chitwood Melanie H. , Klaassen Fayette , Salomon Joshua A. , Menzies Nicolas A. , Warren Joshua L. , Grubaugh Nathan D. , Cohen Ted 
Published: January 2025

AbstractSARS-CoV-2 infection rates displayed striking temporal and spatial variation during the emergence of new variants globally and within the United States. While spatiotemporal “waves” of infection have been observed, quantitative assessments of their spread remain limited. Here, we estimate and compare the speed and spatial extent of the first two major infection waves in the United States, illustrating these dynamics through detailed visualizations. Our findings reveal that the origins of these waves coincide with large gatherings and the relaxation of masking mandates. Notably, the second wave spread more rapidly than the first, driven by multiple, non-contiguous origins of infection. This highlights the role of regional heterogeneity in epidemic dynamics and underscores the importance of localized public health measures in mitigating ongoing outbreaks.Author SummaryOver the pandemic of SARS-CoV-2, efforts to identify and visualize the disease progression were made. However, quantitative visualization of the infections spreading are limited until today. Here we developed tools to visualize the spatial and temporal spreading of SARS-CoV-2 first two waves of infections over the Contiguous United States. We generated novels figures and movies that captures the dynamics of spreading and developed a new mapping of incidence of SARS-CoV-2 that goes below county-level. These outputs can help public health understanding and control efforts of the disease.