bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imputation of the continuous arterial line blood pressure waveform from non-invasive measurements using deep learning
Authors: Hill Brian L. , Rakocz Nadav , Rudas Ákos , Chiang Jeffrey N. , Wang Sidong , Hofer Ira , Cannesson Maxime , Halperin Eran 
Published: August 2021

AbstractIn two-thirds of intensive care unit (ICU) patients and 90% of surgical patients, arterial blood pressure (ABP) is monitored non-invasively but intermittently using a blood pressure cuff. Since even a few minutes of hypotension increases the risk of mortality and morbidity, for the remaining (high-risk) patients ABP is measured continuously using invasive devices, and derived values are extracted from the recorded waveforms. However, since invasive monitoring is associated with major complications (infection, bleeding, thrombosis), the ideal ABP monitor should be both non-invasive and continuous. With large volumes of high-fidelity physiological waveforms, it may be possible today to impute a physiological waveform from other available signals. Currently, the state-of-the-art approaches for ABP imputation only aim at intermittent systolic and diastolic blood pressure imputation, and there is no method that imputes the continuous ABP waveform. Here, we developed a novel approach to impute the continuous ABP waveform non-invasively using two continuously-monitored waveforms that are currently part of the standard-of-care, the electrocardiogram (ECG) and photo-plethysmogram (PPG), by adapting a deep learning architecture designed for image segmentation. Using over 150,000 min of data collected at two separate health systems from 463 patients, we demonstrate that our model provides a highly accurate prediction of the continuous ABP waveform (root mean square error 5.823 (95% CI 5.806–5.840) mmHg), as well as the derived systolic (mean difference 2.398 ± 5.623 mmHg) and diastolic blood pressure (mean difference − 2.497 ± 3.785 mmHg) compared to arterial line measurements. Our approach can potentially be used to measure blood pressure continuously and non-invasively for all patients in the acute care setting, without the need for any additional instrumentation beyond the current standard-of-care.
Heavy-ion production of 77Br and 76Br
Authors: McGuinness Sean R. , Wilkinson John T. , Peaslee Graham F. 
Published: August 2021

AbstractMany radioisotopes with potential medical applications are difficult to produce routinely, especially those on the proton-rich side of the valley of stability. Current production methods typically use light-ion (protons or deuteron) reactions on materials of similar mass to the target radioisotope, which limits the elemental target material available and may require the use of targets with poor thermal properties (as is the case for the production of radiobromine). These reactions may also create significant amounts of proton-rich decay products which require chemical separation from the desired product in a highly radioactive environment. A promising alternative method using heavy-ion fusion-evaporation reactions for the production of the medically relevant bromine radioisotopes 76Br (t1/2 = 16.2 h) and 77Br (t1/2 = 57.0 h) is presented. Heavy-ion beams of 28Si and 16O were used to bombard natural chromium and copper targets just above the Coulomb barrier at the University of Notre Dame's Nuclear Science Laboratory to produce these bromine and precursor radioisotopes by fusion-evaporation reactions. Production yields for these reactions were measured and compared to PACE4 calculations. In addition to using more robust targets for irradiation, a simple physical–chemical separation method is proposed that will lead to very high radiopurity yields. A summary of accelerator facility requirements needed for routine production of these radioisotopes is also presented.
Machine learning-based prediction of acute kidney injury after nephrectomy in patients with renal cell carcinoma
Authors: Lee Yeonhee , Ryu Jiwon , Kang Min Woo , Seo Kyung Ha , Kim Jayoun , Suh Jungyo , Kim Yong Chul , Kim Dong Ki , Oh Kook-Hwan , Joo Kwon Wook , Kim Yon Su , Jeong Chang Wook , Lee Sang Chul , Kwak Cheol , Kim Sejoong , Han Seung Seok 
Published: August 2021

AbstractThe precise prediction of acute kidney injury (AKI) after nephrectomy for renal cell carcinoma (RCC) is an important issue because of its relationship with subsequent kidney dysfunction and high mortality. Herein we addressed whether machine learning (ML) algorithms could predict postoperative AKI risk better than conventional logistic regression (LR) models. A total of 4104 RCC patients who had undergone unilateral nephrectomy from January 2003 to December 2017 were reviewed. ML models such as support vector machine, random forest, extreme gradient boosting, and light gradient boosting machine (LightGBM) were developed, and their performance based on the area under the receiver operating characteristic curve, accuracy, and F1 score was compared with that of the LR-based scoring model. Postoperative AKI developed in 1167 patients (28.4%). All the ML models had higher performance index values than the LR-based scoring model. Among them, the LightGBM model had the highest value of 0.810 (0.783–0.837). The decision curve analysis demonstrated a greater net benefit of the ML models than the LR-based scoring model over all the ranges of threshold probabilities. The application of ML algorithms improves the predictability of AKI after nephrectomy for RCC, and these models perform better than conventional LR-based models.
Pre-pregnancy BMI-associated miRNA and mRNA expression signatures in the placenta highlight a sexually-dimorphic response to maternal underweight status
Authors: Clark Jeliyah , Eaves Lauren A. , Gaona Adriana R. , Santos Hudson P. , Smeester Lisa , Bangma Jacqueline T. , Rager Julia E. , O’Shea T. Michael , Fry Rebecca C. 
Published: August 2021

AbstractPre-pregnancy body mass index (BMI) is associated with adverse pregnancy and neonatal health outcomes, with differences in risk observed between sexes. Given that the placenta is a sexually dimorphic organ and critical regulator of development, examining differences in placental mRNA and miRNA expression in relation to pre-pregnancy BMI may provide insight into responses to maternal BMI in utero. Here, genome-wide mRNA and miRNA expression levels were assessed in the placentas of infants born extremely preterm. Differences in expression were evaluated according to pre-pregnancy BMI status (1) overall and (2) in male and female placentas separately. Overall, 719 mRNAs were differentially expressed in relation to underweight status. Unexpectedly, no genes were differentially expressed in relation to overweight or obese status. In male placentas, 572 mRNAs were associated with underweight status, with 503 (70%) overlapping genes identified overall. Notably, 43/572 (8%) of the mRNAs associated with underweight status in male placentas were also gene targets of two miRNAs (miR-4057andmiR-128-1-5p) associated with underweight status in male placentas. Pathways regulating placental nutrient metabolism and angiogenesis were among those enriched in mRNAs associated with underweight status in males. This study is among the first to highlight a sexually dimorphic response to low pre-pregnancy BMI in the placenta.
Atypical DNA methylation, sRNA-size distribution, and female gametogenesis in Utricularia gibba
Authors: Cervantes-Pérez Sergio Alan , Yong-Villalobos Lenin , Florez-Zapata Nathalia M. V. , Oropeza-Aburto Araceli , Rico-Reséndiz Félix , Amasende-Morales Itzel , Lan Tianying , Martínez Octavio , Vielle-Calzada Jean Philippe , Albert Victor A. , Herrera-Estrella Luis 
Published: August 2021

AbstractThe most studied DNA methylation pathway in plants is the RNA Directed DNA Methylation (RdDM), a conserved mechanism that involves the role of noncoding RNAs to control the expansion of the noncoding genome. Genome-wide DNA methylation levels have been reported to correlate with genome size. However, little is known about the catalog of noncoding RNAs and the impact on DNA methylation in small plant genomes with reduced noncoding regions. Because of the small length of intergenic regions in the compact genome of the carnivorous plant Utricularia gibba, we investigated its repertoire of noncoding RNA and DNA methylation landscape. Here, we report that, compared to other angiosperms, U. gibba has an unusual distribution of small RNAs and reduced global DNA methylation levels. DNA methylation was determined using a novel strategy based on long-read DNA sequencing with the Pacific Bioscience platform and confirmed by whole-genome bisulfite sequencing. Moreover, some key genes involved in the RdDM pathway may not represented by compensatory paralogs or comprise truncated proteins, for example, U. gibba DICER-LIKE 3 (DCL3), encoding a DICER endonuclease that produces 24-nt small-interfering RNAs, has lost key domains required for complete function. Our results unveil that a truncated DCL3 correlates with a decreased proportion of 24-nt small-interfering RNAs, low DNA methylation levels, and developmental abnormalities during female gametogenesis in U. gibba. Alterations in female gametogenesis are reminiscent of RdDM mutant phenotypes in Arabidopsis thaliana. It would be interesting to further study the biological implications of the DCL3 truncation in U. gibba, as it could represent an initial step in the evolution of RdDM pathway in compact genomes.
Establishment of HLA class I and MICA/B null HEK-293T panel expressing single MICA alleles to detect anti-MICA antibodies
Authors: Jeon Ji-Ho , Baek In-Cheol , Hong Cheol-Hwa , Park Ki Hyun , Lee Hyeyoung , Oh Eun-Jee , Kim Tai-Gyu 
Published: August 2021

AbstractPre- and post-transplantation anti-MICA antibody detection development are associated with an increased rejection risk and low graft survival. We previously generated HLA class I null HEK-293T using CRISPR/Cas9, while MICA and MICB genes were removed in this study. A panel of 11 cell lines expressing single MICA alleles was established. Anti-MICA antibody in the sera of kidney transplant patients was determined using flow cytometric method (FCM) and the Luminex method. In the 44 positive sera, the maximum FCM value was 2879 MFI compared to 28,135 MFI of Luminex method. Eleven sera (25%) were determined as positive by FCM and 32 sera (72%) were positive by the Luminex method. The sum of total MICA antigens, MICA*002, *004, *009, *019, and *027 correlation showed a statistically significant between the two methods (P = 0.0412, P = 0.0476, P = 0.0019, P = 0.0098, P = 0.0467, and P = 0.0049). These results demonstrated that HEK-293T-based engineered cell lines expressing single MICA alleles were suitable for measuring specific antibodies against MICA antigens in the sera of transplant patients. Studies of antibodies to MICA antigens may help to understand responses in vivo and increase clinical relevance at the cellular level such as complement-dependent cytotoxicity.
Evolution of a key enzyme of aerobic metabolism reveals Proterozoic functional subunit duplication events and an ancient origin of animals
Authors: Bezerra Bruno Santos , Belato Flavia Ariany , Mello Beatriz , Brown Federico , Coates Christopher J. , de Moraes Leme Juliana , Trindade Ricardo I. F. , Costa-Paiva Elisa Maria 
Published: August 2021

AbstractThe biological toolkits for aerobic respiration were critical for the rise and diversification of early animals. Aerobic life forms generate ATP through the oxidation of organic molecules in a process known as Krebs’ Cycle, where the enzyme isocitrate dehydrogenase (IDH) regulates the cycle's turnover rate. Evolutionary reconstructions and molecular dating of proteins related to oxidative metabolism, such as IDH, can therefore provide an estimate of when the diversification of major taxa occurred, and their coevolution with the oxidative state of oceans and atmosphere. To establish the evolutionary history and divergence time of NAD-dependent IDH, we examined transcriptomic data from 195 eukaryotes (mostly animals). We demonstrate that two duplication events occurred in the evolutionary history of NAD-IDH, one in the ancestor of eukaryotes approximately at 1967 Ma, and another at 1629 Ma, both in the Paleoproterozoic Era. Moreover, NAD-IDH regulatory subunits β and γ are exclusive to metazoans, arising in the Mesoproterozoic. Our results therefore support the concept of an ‘‘earlier-than-Tonian’’ diversification of eukaryotes and the pre-Cryogenian emergence of a metazoan IDH enzyme.
Using normative modelling to detect disease progression in mild cognitive impairment and Alzheimer’s disease in a cross-sectional multi-cohort study
Authors: Pinaya Walter H. L. , Scarpazza Cristina , Garcia-Dias Rafael , Vieira Sandra , Baecker Lea , F da Costa Pedro , Redolfi Alberto , Frisoni Giovanni B. , Pievani Michela , Calhoun Vince D. , Sato João R. , Mechelli Andrea 
Published: August 2021

AbstractNormative modelling is an emerging method for quantifying how individuals deviate from the healthy populational pattern. Several machine learning models have been implemented to develop normative models to investigate brain disorders, including regression, support vector machines and Gaussian process models. With the advance of deep learning technology, the use of deep neural networks has also been proposed. In this study, we assessed normative models based on deep autoencoders using structural neuroimaging data from patients with Alzheimer’s disease (n = 206) and mild cognitive impairment (n = 354). We first trained the autoencoder on an independent dataset (UK Biobank dataset) with 11,034 healthy controls. Then, we estimated how each patient deviated from this norm and established which brain regions were associated to this deviation. Finally, we compared the performance of our normative model against traditional classifiers. As expected, we found that patients exhibited deviations according to the severity of their clinical condition. The model identified medial temporal regions, including the hippocampus, and the ventricular system as critical regions for the calculation of the deviation score. Overall, the normative model had comparable cross-cohort generalizability to traditional classifiers. To promote open science, we are making all scripts and the trained models available to the wider research community.
Genome-wide approaches for the identification of markers and genes associated with sugarcane yellow leaf virus resistance
Authors: Pimenta Ricardo José Gonzaga , Aono Alexandre Hild , Burbano Roberto Carlos Villavicencio , Coutinho Alisson Esdras , da Silva Carla Cristina , dos Anjos Ivan Antônio , Perecin Dilermando , Landell Marcos Guimarães de Andrade , Gonçalves Marcos Cesar , Pinto Luciana Rossini , de Souza Anete Pereira 
Published: August 2021

AbstractSugarcane yellow leaf (SCYL), caused by the sugarcane yellow leaf virus (SCYLV) is a major disease affecting sugarcane, a leading sugar and energy crop. Despite damages caused by SCYLV, the genetic base of resistance to this virus remains largely unknown. Several methodologies have arisen to identify molecular markers associated with SCYLV resistance, which are crucial for marker-assisted selection and understanding response mechanisms to this virus. We investigated the genetic base of SCYLV resistance using dominant and codominant markers and genotypes of interest for sugarcane breeding. A sugarcane panel inoculated with SCYLV was analyzed for SCYL symptoms, and viral titer was estimated by RT-qPCR. This panel was genotyped with 662 dominant markers and 70,888 SNPs and indels with allele proportion information. We used polyploid-adapted genome-wide association analyses and machine-learning algorithms coupled with feature selection methods to establish marker-trait associations. While each approach identified unique marker sets associated with phenotypes, convergences were observed between them and demonstrated their complementarity. Lastly, we annotated these markers, identifying genes encoding emblematic participants in virus resistance mechanisms and previously unreported candidates involved in viral responses. Our approach could accelerate sugarcane breeding targeting SCYLV resistance and facilitate studies on biological processes leading to this trait.
Lentiviral and AAV-mediated expression of palivizumab offer protection against Respiratory Syncytial Virus infection
Authors: Antepowicz Agata , Habib Omar , Kirsebom Freja , Johansson Cecilia , Gill Deborah R. , Hyde Stephen C. 
Published: August 2021

AbstractRespiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations.
Comprehensive analysis of the expression and prognosis for TNFAIPs in head and neck cancer
Authors: Lan Gaochen , Yu Xiaoling , Sun Xin , Li Wan , Zhao Yanna , Lan Jinjian , Wu Xiaolong , Gao Ruilan 
Published: August 2021

AbstractHead and neck cancer (HNC) tumorigenesis involves a combination of multiple genetic alteration processes. Tumour necrosis factor-alpha-induced proteins (TNFAIPs) are involved in tumour development and progression, but few studies have been conducted on these factors in HNC. We aimed to analyse TNFAIPs and assess their potential as prognostic biomarkers and therapeutic targets using the Oncomine, UALCAN, Human Protein Atlas, LinkedOmics, cBioPortal, GeneMANIA, Enrichr, and Tumor IMmune Estimation Resource databases. We found that the transcript levels of TNFAIP1, TNFAIP3, EFNA1, TNFAIP6 and TNFAIP8 were increased, while those of TNFAIP8L3 and STEAP4 were reduced in HNC tissues versus normal tissues. The EFNA1, TNFAIP8 and TNFAIP8L3 expression levels were significantly correlated with the pathological stage. In HNC patients, high PTX3 and TNFAIP6 transcript levels were significantly associated with shorter overall survival (OS). Moreover, genetic alterations in TNFAIP1, TNFAIP6, and STEAP4 resulted in poorer disease-free survival, progression-free survival, and OS, respectively. TNFAIPs may mediate HNC tumorigenesis by regulating PI3K-Akt, Ras and other signalling pathways. TNFAIPs are also closely correlated with the infiltration of immune cells, including B cells, CD8+ T cells, CD4+ T cells, etc. The data above indicate that TNFAIPs may be potential biomarkers and therapeutic targets for HNC.
Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
Authors: Rouchka Eric C. , Chariker Julia H. , Alejandro Brian , Adcock Robert S. , Singhal Richa , Ramirez Julio , Palmer Kenneth E. , Lasnik Amanda B. , Carrico Ruth , Arnold Forest W. , Furmanek Stephen , Zhang Mei , Wolf Leslie A. , Waigel Sabine , Zacharias Wolfgang , Bordon Jose , Chung Donghoon 
Published: August 2021

AbstractKey elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.
Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds
Authors: Alqahtani Alaa M. 
Published: August 2021

AbstractNovel tri-and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were synthesized, and their antimicrobial activity was estimated. The obtained results evidenced the substantial efficiencies of pyrano-thiadiazolopyrimidine compounds 8a–b and 9a–b toward the two strains of gram-positive bacteria (S. aureus and B. cereus). Besides, tetracyclic pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a–b and 17a–b displayed prominent efficiencies toward the two strains of gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a–b and 9a–b displayed good efficacy toward C. albicans. The activity of antiquorum sensing (anti-QS) inhibition of the newly synthesized thiadiazolopyrimidine-based compounds toward C. violaceum was tested, suggesting satisfactory activity for derivatives 16a–b, 17a–b, 8b, and 9a. The cytotoxic activity of these derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2, and HepG2) and standard normal fibroblast cells (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b17a, and 17b showed potent cytotoxic efficacy against the MCF-7 cells with the IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) of the inspected thiadiazolopyrimidine derivatives provided a correlation between the chemical structure and anticancer efficiency. The in silico docking studies were implemented for silencing the hormonal signaling in the breast (PDB Code-5NQR). The results were found to be consistent with the cytotoxic activity.