bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of clinically-relevant genetic alterations in uveal melanoma using RNA sequencing
Authors: Nell R.J. , Versluis M. , Cats D. , Mei H. , Verdijk R.M. , Kroes W.G.M. , Luyten G.P.M. , Jager M.J. , van der Velden P.A. 
Published: December 2023

AbstractIntroductionUveal melanoma is a lethal intraocular tumour, in which the presence of certain genetic alterations correlates with the risk of metastatic dissemination and patient survival. RNA data is typically used to transcriptionally characterise tumours and their micro-environment. In this study, we tested the detectability of all key genetic alterations in uveal melanoma from RNA sequencing data.MethodsCohort-wide gene expression profiling was used to classify tumours at the transcriptional level. In individual samples, copy number alterations affecting chromosomes 3 and 8q were analysed by measuring expressed allelic imbalances of heterozygous common single nucleotide polymorphisms. Mutations inGNAQ, GNA11, CYSLTR2, PLCB4, BAP1, SF3B1andEIF1AXwere identified by screening of hotspot regions and by evaluating their transcriptional effects. All findings were cross-validated with DNA-derived data in a training cohort of 80 primary uveal melanomas studied by The Cancer Genome Atlas (TCGA) initiative, and in five prospectively analysed cases from our institution.ResultsUnsupervised gene expression profiling strongly correlated to the presence of chromosome 3 alterations, but was not reliable in identifying other (clinically-)relevant genetic alterations. However, the presence of both chromosome 3 and 8q copy number alterations could be successfully inferred from expressed allelic imbalances in most tumours. The majority of mutations were adequately recognised at the RNA level by their nucleotide changes (all genes), alternative splicing around the mutant position (BAP1) and transcriptome-wide aberrant splice junction usage (SF3B1). Notably, in the TCGA cohort we detected previously unreported mutations inBAP1(n=3) andEIF1AX(n=5), that were missed by the original DNA sequencing. In our prospective cohort, all mutations and copy number alterations were successfully identified at the RNA level by combining the described approaches.ConclusionIn addition to providing gene expression levels and profiles, RNA from uveal melanomas presents insights into the expressed tumour genotype and its phenotypic consequences. Such complete analysis of transcriptional data may augment or even substitute current DNA-based approaches, and has potential applicability in both research and clinical practice.
Genomic Profiling and Spatial SEIR Modeling of COVID-19 Transmission in Western New York
Authors: Bard Jonathan E , Jiang Na , Emerson Jamaal , Bartz Madeleine , Lamb Natalie A. , Marzullo Brandon J. , Pohlman Alyssa , Boccolucci Amanda , Nowak Norma J. , Yergeau Donald A. , Crooks Andrew T. , Surtees Jennifer A. 
Published: December 2023

AbstractThe COVID-19 pandemic has prompted an unprecedented global effort to understand and mitigate the spread of the SARS-CoV-2 virus. In this study, we present a comprehensive analysis of COVID-19 in Western New York, integrating individual patient-level genomic sequencing data with a spatially informed agent-based disease Susceptible-Exposed-Infectious-Removed (SEIR) computational model. The integration of genomic and spatial data enables a multi-faceted exploration of the factors influencing the transmission patterns of COVID-19, including population density, movement dynamics, and genetic variations in the viral genomes replicating in New York State (NYS). Our findings shed light on local dynamics of the pandemic, revealing potential hotspots of transmission. Additionally, the genomic analysis provides insights into the genetic heterogeneity of SARS-CoV-2 within a single lineage at a region-specific level. This interdisciplinary approach, bridging genomics and spatial modeling, contributes to a more holistic understanding of COVID-19 dynamics. The results of this study have implications for future public health strategies, guiding targeted interventions and resource allocation to effectively control the spread of similar viruses in the Western New York region.
Lupus Nephritis Subtype Classification with only Slide Level labels
Authors: Sharma Amit , Chauhan Ekansh , Uppin Megha S , Rajasekhar Liza , Jawahar C V , Vinod P K 
Published: December 2023

AbstractLupus Nephritis classification has historically relied on labor-intensive and meticulous glomerular-level labeling of renal structures in whole slide images (WSIs). However, this approach presents a formidable challenge due to its tedious and resource-intensive nature, limiting its scalability and practicality in clinical settings. In response to this challenge, our work introduces a novel methodology that utilizes only slide-level labels, eliminating the need for granular glomerular-level labeling. A comprehensive multi-stained lupus nephritis digital histopathology WSI dataset was created from the Indian population, which is the largest of its kind.LupusNet, a deep learning MIL-based model, was developed for the sub-type classification of LN. The results underscore its effectiveness, achieving an AUC score of 91.0%, an F1-score of 77.3%, and an accuracy of 81.1% on our dataset in distinguishing membranous and diffused classes of LN.
DeePNAP: A deep learning method to predict protein-nucleic acids binding affinity from sequence
Authors: Pandey Uddeshya , Behara Sasi M. , Sharma Siddhant , Patil Rachit S. , Nambiar Souparnika , Koner Debasish , Bhukya Hussain 
Published: December 2023

ABSTRACTPredicting the protein-nucleic acid (PNA) binding affinity solely from their sequences is of paramount importance for the experimental design and analysis of PNA interactions (PNAIs). A large number of currently developed models for binding affinity prediction are limited to specific PNAIs, while also relying on both sequence and structural information of the PNA complexes for both train/test and also as inputs. As PNA complex structures available are scarce, this significantly limits the diversity and generalizability due to a small training dataset. Additionally, a majority of the tools predict a single parameter such as binding affinity or free energy changes upon mutations, rendering a model less versatile for usage. Hence, we propose DeePNAP, a machine learning-based model trained on a vast and heterogeneous dataset with 14,401 entries (from both eukaryotes and prokaryotes) of ProNAB database, consisting of wild-type and mutant PNA complex binding parameters. Our model precisely predicts the binding affinity and free energy changes due to the mutation(s) of PNAIs exclusively from the sequences. While other similar tools extract features from both sequence and structure information, DeePNAP employs sequence-based features to yield high correlation coefficients between the predicted and experimental values with low root mean squared errors for PNA complexes in predicting theKDand ΔΔG implying the generalizability of DeePNAP. Additionally, we have also developed a web interface hosting DeePNAP that can serve as a powerful tool to rapidly predict binding affinities for a myriad of PNAIs with high precision toward developing a deeper understanding of their implications in various biological systems. Web interface:http://14.139.174.41:8080/
Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy
Authors: Rabbani Rozhan , Najafiaghdam Hossein , Roschelle Micah , Papageorgiou Efthymios Philip , Zhao Biqi Rebekah , Ghanbari Mohammad Meraj , Muller Rikky , Stojanovic Vladimir , Anwar Mekhail 
Published: December 2023

AbstractWe present a mm-sized, ultrasonically powered lensless CMOS image sensor as a progress towards wireless fluorescence microscopy. Access to biological information within the tissue has the potential to provide insights guiding diagnosis and treatment across numerous medical conditions including cancer therapy. This information, in conjunction with current clinical imaging techniques that have limitations in obtaining images continuously and lack wireless compatibility, can improve continual detection of multicell clusters deep within tissue. The proposed platform incorporates a 2.4×4.7 mm2integrated circuit (IC) fabricated in TSMC 0.18 μm, a micro laser diode (μLD), a single piezoceramic and off-chip storage capacitors. The IC consists of a 36×40 array of capacitive trans-impedance amplifier-based pixels, wireless power management and communication via ultrasound and a laser driver all controlled by a Finite State Machine. The piezoceramic harvests energy from the acoustic waves at a depth of 2 cm to power up the IC and transfer 11.5 kbits/frame via backscattering. DuringCharge-Up, the off-chip capacitor stores charge to later supply a high-power 78 mW μLD duringImaging. Proof of concept of the imaging front end is shown by imaging distributions of CD8 T-cells, an indicator of the immune response to cancer,ex vivo, in the lymph nodes of a functional immune system (BL6 mice) against colorectal cancer consistent with the results of a fluorescence microscope. The overall system performance is verified by detecting 140 μm features on a USAF resolution target with 32 ms exposure time and 389 ms ultrasound backscattering.
Neutron capture enhances dose and reduces cancer cell viability in and out of beam during helium and carbon ion therapy
Authors: Howell Nicholas , Middleton Ryan J. , Sierro Frederic , Wyatt Naomi A. , Chacon Andrew , Fraser Benjamin H. , Bambery Keith , Livio Elle , Dobie Christopher , Bevitt Joseph J. , Davies Justin , Dosseto Anthony , Franklin Daniel R. , Garbe Ulf , Guatelli Susanna , Hirayama Ryoichi , Matsufuji Naruhiro , Mohammadi Akram , Mutimer Karl , Rendina Louis M. , Rosenfeld Anatoly B. , Safavi-Naeini Mitra 
Published: December 2023

PurposeNeutron Capture Enhanced Particle Therapy (NCEPT) is a proposed augmentation of charged particle therapy which exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with two different targeted neutron capture agents (NCAs).Materials and MethodsHuman glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs, [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a PMMA phantom either laterally adjacent to, or within, a 100×100×60 mm spread out Bragg peak (SOBP). The impact of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in six independent experiments. Neutron fluence within the phantom was characterised by quantifying the neutron activation of gold foil.ResultsCells placed inside the treatment volume reached 10% survival by 2 Gy of C or 2-3 Gy of He in the presence of NCAs compared to 5 Gy of C and 7 Gy of He with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of C or He (to the treatment volume), compared to a no detectable effect on cells without NCA. The mean thermal neutron fluence at the centre of the SOBP was approximately 2.2×109n/cm2/Gy(RBE) for the carbon beam and 5.8×109n/cm2/Gy(RBE) for the helium beam and gradually decreased in all directions.ConclusionsThe addition of NCAs to cancer cells during C and He beam irradiation has a measurable impact on cell survival and growthin-vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumours, by targeting this dose to micro-infiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumour tissue within the treatment volume, with a reduction in radiation doses to off target tissue.
Temperament in early childhood is associated with gut microbiota composition and diversity
Authors: Ueda Eriko , Matsunaga Michiko , Fujihara Hideaki , Kajiwara Takamasa , Takeda Aya K. , Watanabe Satoshi , Hagihara Keisuke , Myowa Masako 
Published: December 2023

AbstractTemperament is a key predictor of human mental health, and cognitive and emotional development. While human fear behavior is reportedly associated with gut microbiome in infancy, infant gut microbiota changes dramatically during the first five years, when the diversity and composition of gut microbiome are established. This period is crucial for developing human executive functioning, including emotion regulation. Therefore, this study investigated the relationship between temperament and gut microbiota in 284 preschool children aged 3–4 years. Child temperament was assessed by maternal reports of the Children’s Behavior Questionnaire. Gut microbiota (alpha/beta diversity and genera abundance) was evaluated using 16S rRNA sequencing of stool samples. A high abundance of anti-inflammatory bacteria (e.g., Faecalibacterium) and low abundance of inflammatory bacteria (e.g., Eggerthella, Flavonifractor) were associated with higher positive emotionality and reward-seeking (i.e., Surgency/Extraversion, β =0.15, p = 0.013), and lower negative emotionality and behavioral inhibition (i.e., Negative Affectivity, β = -0.17, p = 0.004). Additionally, gut microbiota diversity was associated with a more active approach and exploration (i.e., Impulsivity, a specific aspect of Surgency/Extraversion, β = 0.16, p = 0.008). This study provides insight into the biological mechanisms of temperament and takes important steps toward identifying predictive markers of psychological/emotional risk.
Fibroblast Growth Factor-induced lens fiber cell elongation is driven by the stepwise activity of Rho and Rac
Authors: Sugiyama Yuki , Reed Daniel A. , Herrmann David , Lovicu Frank J. , Robinson Michael L. , Timpson Paul , Masai Ichiro 
Published: December 2023

AbstractThe spheroidal shape of the eye lens is critical for precise light focusing onto the retina. This shape is determined by concentrically aligned, convexly elongated lens fiber cells along the anterior and posterior axis of the lens. Upon differentiation at the lens equator, the fiber cells increase in height as their apical and basal tips migrate towards the anterior and posterior poles, respectively. The forces driving this elongation and migration remain unclear. We found that membrane protrusions or lamellipodia are observed only in the maturing fibers undergoing cell curve conversion, indicating lamellipodium is not the primary driver of earlier fiber migration. We demonstrated that elevated levels of fibroblast growth factor (FGF) suppressed the extension of Rac-dependent protrusions, suggesting changes in the activity of FGF controling Rac activity, switching to lamellipodium-driven migration. Inhibitors of ROCK, myosin, and actin reduced the height of both early and later fibers, indicating elongation of these fibers relies on actomyosin contractility. Consistently, active RhoA was detected throughout these fibers. Given that FGF promotes fiber elongation, we propose it to do so through regulation of Rho activity.Summary statementFGF differentially regulates Rho- and Rac-activity at the lens equator to promote lens fiber cell elongation and migration.
Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 and BA.5 subvariant predominance: a systematic literature review
Authors: Drysdale Myriam , Berktas Mehmet , Gibbons Daniel C. , Rolland Catherine , Lavoie Louis , Lloyd Emily J. 
Published: December 2023

AbstractBackgroundEmerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab, with variable fold changes in neutralization potency reported for Omicron BA.2 and subsequent variants. We performed a systematic literature review (SLR) to evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance.MethodsElectronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022–February 27, 2023.ResultsThe 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions, and comprised >1.7 million high-risk patients with COVID-19, of whom approximately 41,000 received sotrovimab (range n=20– 5979 during BA.2 and n=76–1383 during BA.5 predominance). Studies were from the US, UK, Italy, Denmark, France, Qatar, and Japan. Four studies compared the effectiveness of sotrovimab with untreated or no monoclonal antibody treatment controls, two compared sotrovimab with other treatments, and three single-arm studies compared outcomes during BA.2 and/or BA.5 versus BA.1. The remaining five studies descriptively reported rates of clinical outcomes in patients treated with sotrovimab. Rates of COVID-19-related hospitalization or mortality among sotrovimab-treated patients were consistently low (0.95% to 4.0% during BA.2; 0.5% to 2.0% during BA.5). All-cause hospitalization or mortality was also low (1.7% to 2.0% during BA.2; 3.4% during combined BA.2 and BA.5 periods). During BA.2, a lower risk of all-cause hospitalization or mortality was reported across studies with sotrovimab versus untreated cohorts. Compared with other treatments, sotrovimab was associated with a lower (molnupiravir) or similar (nirmatrelvir/ritonavir) risk of COVID-19-related hospitalization or mortality during BA.2 and BA.5. There was no significant difference in outcomes between the BA.1, BA.2 and BA.5 periods.ConclusionsThe studies included in this SLR suggest continued effectiveness of sotrovimab in preventing severe clinical outcomes during BA.2 and BA.5 predominance, both against an active/untreated comparator and compared with BA.1 predominance.
Epidemiological overlaps in COVID-19 and malaria within healthcare and community settings of Southern Ghana
Authors: Amegatcher Gloria , Acquah Maame E. , Tetteh Deborah , Obeng Rachael , Debrah Ethel , Quist Bridget , Acquah-Jackson Priscilla , Boateng Kyerewaa A. , Twieku Gideon , Armoo Samuel , Awandare Gordon A. , Mosi Lydia , Narh Charles A. 
Published: December 2023

AbstractBackgroundCOVID-19 disruptions in Africa in 2020-2022 contributed to reductions in malaria control activities including antimalarial surveillance programs. This study investigated the malaria burden and distribution on the background of active transmission of SARS-CoV-2 in Southern Ghana. Specifically, it aimed to identify epidemiological factors that can maximise programmatic control for both diseases, utilising community health education and medical screening (CHEMS).MethodsBetween October-December 2022, prospective cross-sectional surveys, with CHEMS were conducted in Greater Accra and Central regions, where 994 participants enrolled either at a hospital or community setting provided demographic and clinical data including history of clinical malaria infection and antimalarial treatment in the past two weeks. Of this study population, 953 provided nasal/throat swabs for COVID-19 RT-PCR testing, with a subset of 136 participants also providing finger-prick blood for malaria RDT testing.ResultsThe study population comprised of 73.6% adults, with 54.6% COVID-19 vaccination rate. Overall, 18.1% of participants had a history of clinical malaria, which was associated (adjusted odds ratio > 1.50, P-value ≤ 0.022) with COVID-19 symptoms and positivity, study area and hospital setting, suggestive of overlaps in the epidemiological risk for malaria. On a background of widespread SARS-CoV-2 infections (12-37%), malaria parasitaemia was detected in 6%, with 2% being co-infections. Among the malaria positives, 9.5% had a history of antimalarial treatment, which suggested that their infections were recrudescent parasitaemia.ConclusionThe overlaps in the epidemiological risk for malaria and COVID-19 indicate that innovative surveillance programs, with community engagement are needed to maximise control interventions including treatment of asymptomatic malaria infections.
CRISPR-based multiplex detection of human papillomaviruses for one-pot point-of-care diagnostics
Authors: Ghouneimy Ahmed , Ali Zahir , Aman Rashid , Jiang Wenjun , Aouida Mustapha , Mahfouz Magdy 
Published: December 2023

AbstractThe World Health Organization’s global initiative toward eliminating high-risk Human Papillomavirus (hrHPV)-related cancers recommends DNA testing over visual inspection in all settings for primary cancer screening and HPV eradication by 2100. However, multiple hrHPV types cause different types of cancers, and there is a pressing need for a, easy-to-use, multiplex point-of-care diagnostic platform for detecting different hrHPV types. Recently, CRISPR-Cas systems have been repurposed for point-of-care detection. Here, we established aCRISPR-Cas multiplexeddiagnostic assay (CRISPRD) to detect cervical cancer-causing hrHPVs in one reaction (one-pot assay). We harnessed the compatibility of thermostable AapCas12b, TccCas13a, and HheCas13a nucleases with isothermal amplification and successfully detected HPV16 and HPV18, along with an internal control in a single-pot assay with a limit of detection of 10 copies and 100% specificity. This platform offers a rapid and practical solution for multiplex detection of hrHPVs, facilitating large-scale hrHPV point-of-care screening, guiding effective treatment and policy development, and supporting global health initiatives. Furthermore, the CRISPRD platform’s programmability enables it to be adapted for simultaneously detecting hrHPVs-causing cancer, strengthening the scope of early diagnosis of HPV in the fight against infectious disease.
Beyond defense: Glucosinolate structural diversity shapes recruitment of a metabolic network of leaf-associated bacteria
Authors: Unger Kerstin , Raza Ali K. , Mayer Teresa , Reichelt Michael , Stuttmann Johannes , Hielscher Annika , Wittstock Ute , Gershenzon Jonathan , Agler Matthew T. 
Published: December 2023

AbstractLeaf bacteria are critical for plant health, but little is known about how plant traits control their recruitment. Aliphatic glucosinolates (GLSs) are secondary metabolites present in leaves of Brassicaceae plants in genotypically-defined mixtures. Upon damage, they are broken down to products that deter herbivory and inhibit pathogens. Using twoA. thalianagenotypes with different aliphatic GLS profiles, we find that structural variants differentially affect commensal leaf bacteria: In the model genotype Col-0, GLS breakdown products (mostly from 4-methylsulfinylbutyl-glucosinolate) are potentially highly toxic to bacteria but have no effect on natural leaf colonization. In contrast, in anA. thalianagenotype from a wild population, GLS (mostly allyl-GLS) enriches Burkholderiales bacteria, an effect also detected in nature. Indeed,in-vitroas a carbon source, intact allyl-GLS specifically enriches a Burkholderiales-containing community in which Burkholderiales depend on other bacteria but in turn increase community growth rates. Metabolism of different GLSs is linked to breakdown product detoxification, helping explain GLS structural control of community recruitment.