bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo
Authors: Kulhankova Katarina , Traore Soumba , Cheng Xue , Benk-Fortin Hadrien , Hallée Stéphanie , Harvey Mario , Roberge Joannie , Couture Frédéric , Kohli Sajeev , Gross Thomas J. , Meyerholz David K. , Rettig Garrett R. , Thommandru Bernice , Kurgan Gavin , Wohlford-Lenane Christine , Hartigan-O’Connor Dennis J. , Yates Bradley P. , Newby Gregory A. , Liu David R. , Tarantal Alice F. , Guay David , McCray Paul B. 
Published: December 2023

AbstractGene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP. Following intratracheal aerosol delivery of Cy5-labeled peptide in rhesus macaques, we confirm delivery throughout the respiratory tract. Subsequently, we target CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieve editing efficiencies of up-to 5.3% in rhesus airway epithelia. Moreover, we document persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restores anion channel function in cultured human airway epithelia. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.
Strong temperature gradients in the ice age North Atlantic Ocean revealed by plankton biogeography
Authors: Jonkers Lukas , Laepple Thomas , Rillo Marina C. , Shi Xiaoxu , Dolman Andrew M. , Lohmann Gerrit , Paul André , Mix Alan , Kucera Michal 
Published: December 2023

AbstractThe cold Last Glacial Maximum, around 20,000 years ago, provides a useful test case for evaluating whether climate models can simulate climate states distinct from the present. However, because of the indirect and uncertain nature of reconstructions of past environmental variables such as sea surface temperature, such evaluation remains ambiguous. Instead, here we evaluate simulations of Last Glacial Maximum climate by relying on the fundamental macroecological principle of decreasing community similarity with increasing thermal distance. Our analysis of planktonic foraminifera species assemblages from 647 sites reveals that the similarity-decay pattern that we obtain when the simulated ice age seawater temperatures are confronted with species assemblages from that time differs from the modern. This inconsistency between the modern temperature dependence of plankton species turnover and the simulations arises because the simulations show globally rather uniform cooling for the Last Glacial Maximum, whereas the species assemblages indicate stronger cooling in the subpolar North Atlantic. The implied steeper thermal gradient in the North Atlantic is more consistent with climate model simulations with a reduced Atlantic meridional overturning circulation. Our approach demonstrates that macroecology can be used to robustly diagnose simulations of past climate and highlights the challenge of correctly resolving the spatial imprint of global change in climate models.
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Authors: Desai Jayesh , Alonso Guzman , Kim Se Hyun , Cervantes Andres , Karasic Thomas , Medina Laura , Shacham-Shmueli Einat , Cosman Rasha , Falcon Alejandro , Gort Eelke , Guren Tormod , Massarelli Erminia , Miller Wilson H. , Paz-Ares Luis , Prenen Hans , Amatu Alessio , Cremolini Chiara , Kim Tae Won , Moreno Victor , Ou Sai-Hong I. , Passardi Alessandro , Sacher Adrian , Santoro Armando , Stec Rafal , Ulahannan Susanna , Arbour Kathryn , Lorusso Patricia , Luo Jia , Patel Manish R. , Choi Yoonha , Shi Zhen , Mandlekar Sandhya , Lin Mark T. , Royer-Joo Stephanie , Chang Julie , Jun Tomi , Dharia Neekesh V. , Schutzman Jennifer L. ,   GO42144 Investigator and Study Group, Han Sae-Won 
Published: December 2023

AbstractKRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS–MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC. Here, we report on divarasib plus cetuximab (epidermal growth factor receptor inhibitor) in patients with KRAS G12C-positive CRC (n = 29) from arm C of an ongoing phase 1b trial. The primary objective was to evaluate safety. Secondary objectives included preliminary antitumor activity. The safety profile of this combination was consistent with those of single-agent divarasib and cetuximab. Treatment-related adverse events led to divarasib dose reductions in four patients (13.8%); there were no treatment withdrawals. The objective response rate was 62.5% (95% confidence interval: 40.6%, 81.2%) in KRAS G12C inhibitor-naive patients (n = 24). The median duration of response was 6.9 months. The median progression-free survival was 8.1 months (95% confidence interval: 5.5, 12.3). As an exploratory objective, we observed a decline in KRAS G12C variant allele frequency associated with response and identified acquired genomic alterations at disease progression that may be associated with resistance. The manageable safety profile and encouraging antitumor activity of divarasib plus cetuximab support the further investigation of this combination in KRAS G12C-positive CRC.ClinicalTrials.gov identifier: NCT04449874
Proximal Molecular Probe Transfer (PROMPT), a new approach for identifying sites of protein/nucleic acid interaction in cells by correlated light and electron microscopy
Authors: Castillon Guillaume A. , Phan Sebastien , Hu Junru , Boassa Daniela , Adams Stephen R. , Ellisman Mark H. 
Published: December 2023

AbstractThe binding and interaction of proteins with nucleic acids such as DNA and RNA constitutes a fundamental biochemical and biophysical process in all living organisms. Identifying and visualizing such temporal interactions in cells is key to understanding their function. To image sites of these events in cells across scales, we developed a method, named PROMPT for PROximal Molecular Probe Transfer, which is applicable to both light and correlative electron microscopy. This method relies on the transfer of a bound photosensitizer from a protein known to associate with specific nucleic acid sequence, allowing the marking of the binding site on DNA or RNA in fixed cells. The method produces a fluorescent mark at the site of their interaction, that can be made electron dense and reimaged at high resolution in the electron microscope. As proof of principle, we labeled in situ the interaction sites between the histone H2B and nuclear DNA. As an example of application for specific RNA localizations we labeled different nuclear and nucleolar fractions of the protein Fibrillarin to mark and locate where it associates with RNAs, also using electron tomography. While the current PROMPT method is designed for microscopy, with minimal variations, it can be potentially expanded to analytical techniques.
IoT and ML approach for ornamental fish behaviour analysis
Authors: Patro K. Suresh Kumar , Yadav Vinod Kumar , Bharti Vidya S. , Sharma Arun , Sharma Arpita , Senthilkumar T. 
Published: December 2023

AbstractOrnamental fish keeping is the second most preferred hobby in the world and it provides a great opportunity for entrepreneurship development and income generation. Controlling the environment in ornamental fish farm is a considerable challenge because it is affected by a variety of parameters like water temperature, dissolved oxygen, pH, and disease occurrences. One particular interesting ornamental fish species is goldfish (Carassius auratus). Machine learning (ML) and deep learning technique have significant potential in analysing voluminous data collected from fish farm. Through this technique, the fish farmers can get insight on feeding behaviour, fish growth patterns, predict diseases/stress, and environmental factors affecting fish health. The aim of the study is to analyze the behavioural changes in goldfish due to alterations in environmental parameters (water temperature and dissolved oxygen). Decision tree, Naïve Bayes classifier, K-nearest neighbour (KNN), and linear discriminant analysis (LDA) were used to analyse the behavioural change data. To compare the performance between all four classifiers, cross validation and confusion matrix used. The cross-validation error of LDA, Naïve Bayes classification, KNN and decision tree was 19.86, 28.08, 30.14 and 13.78 respectively. Decision tree was proved to be the most accurate and effective classifier. Different temperature and DO range were taken to predict fish behaviour. Some findings are, the behaviour of fish was rest between temperature 37.85 °C and 40.535 °C, erratic when temperature was greater than or equal to 40.535 °C, gasping when temperature was between 37.85 and 40.535 °C and when DO concentration was less than 6.58 mg/L. Blood parameter analysis has been done to validate the change in external behaviours with change in physiological parameters.
Comparison of statistical approaches to predicting norovirus laboratory reports before and during COVID-19: insights to inform public health surveillance
Authors: Ondrikova Nikola , Clough Helen , Douglas Amy , Vivancos Roberto , Itturiza-Gomara Miren , Cunliffe Nigel , Harris John P. 
Published: December 2023

AbstractSocial distancing interrupted transmission patterns of contact-driven infectious agents such as norovirus during the Covid-19 pandemic. Since routine surveillance of norovirus was additionally disrupted during the pandemic, traditional naïve forecasts that rely only on past public health surveillance data may not reliably represent norovirus activity. This study investigates the use of statistical modelling to predict the number of norovirus laboratory reports in England 4-weeks ahead of time before and during Covid-19 pandemic thus providing insights to inform existing practices in norovirus surveillance in England. We compare the predictive performance from three forecasting approaches that assume different underlying structure of the norovirus data and utilized various external data sources including mobility, air temperature and relative internet searches (Time Series and Regularized Generalized Linear Model, and Quantile Regression Forest). The performance of each approach was evaluated using multiple metrics, including a relative prediction error against the traditional naive forecast of a five-season mean. Our data suggest that all three forecasting approaches improve predictive performance over the naïve forecasts, especially in the 2020/21 season (30–45% relative improvement) when the number of norovirus reports reduced. The improvement ranged from 7 to 22% before the pandemic. However, performance varied: regularized regression incorporating internet searches showed the best forecasting score pre-pandemic and the time series approach achieved the best results post pandemic onset without external data. Overall, our results demonstrate that there is a significant value for public health in considering the adoption of more sophisticated forecasting tools, moving beyond traditional naïve methods, and utilizing available software to enhance the precision and timeliness of norovirus surveillance in England.
Porcine milk exosomes modulate the immune functions of CD14+ monocytes in vitro
Authors: Ávila Morales Gabriela , De Leonardis Daria , Filipe Joel , Furioso Ferreira Rafaela , Agazzi Alessandro , Sauerwein Helga , Comi Marcello , Mrljak Vladimir , Lecchi Cristina , Ceciliani Fabrizio 
Published: December 2023

AbstractExosomes mediate near and long-distance intercellular communication by transferring their molecular cargo to recipient cells, altering their biological response. Milk exosomes (MEx) are internalized by immune cells and exert immunomodulatory functions in vitro. Porcine MEx can accumulate in the small intestine, rich in macrophages. No information is available on the immunomodulatory ability of porcine MEx on porcine monocytes, which are known precursors of gut macrophages. Therefore, this study aims at (1) assessing the in vitro uptake of porcine MEx by porcine monocytes (CD14+), and (2) evaluating the in vitro impact of porcine MEx on porcine monocytes immune functions. MEx were purified by ultracentrifugation and size exclusion chromatography. The monocytes’ internalization of PKH26-labeled MEx was examined using fluorescence microscopy. Monocytes were incubated with increasing exosome concentrations and their apoptosis and viability were measured. Lastly, the ability of MEx to modulate the cells’ immune activities was evaluated by measuring monocytes’ phagocytosis, the capacity of killing bacteria, chemotaxis, and reactive oxygen species (ROS) production. MEx were internalized by porcine monocytes in vitro. They also decreased their chemotaxis and phagocytosis, and increased ROS production. Altogether, this study provides insights into the role that MEx might play in pigs’ immunity by demonstrating that MEx are internalized by porcine monocytes in vitro and exert immunomodulatory effects on inflammatory functions.
Space, time, and dynamics of binocular interactions
Authors: Yassin Marzouk , Lev Maria , Polat Uri 
Published: December 2023

AbstractBinocular summation (BS), defined as the superiority of binocular over monocular visual performance, shows that thresholds are about 40% (a factor of 1.4) better in binocular than in monocular viewing. However, it was reported that different amounts of BS exist in a range from 1.4 to 2 values because BS is affected by the spatiotemporal parameters of the stimulus. Lateral interactions can be defined as the neuron’s ability to affect the neighboring neurons by either inhibiting or exciting their activity. We investigated the effect of the spatial and temporal domains on binocular interactions and BS under the lateral masking paradigm and how BS would be affected by lateral interactions via a lateral masking experiment. The two temporal alternative forced-choice (2TAFC) method was used. The stimuli consisted of a central vertically oriented Gabor target and high-contrast Gabor flankers positioned in two configurations (orthogonal or collinear) with target-flanker separations of either 2 or 3 wavelengths (λ), presented at 4 different presentation times (40, 80, 120, and 200 ms) using a different order of measurements across the different experiments. Opaque lenses were used to control the monocular and binocular vision. BS is absent at close distances (2λ), depending on the presentation time’s order, for the collinear but not for the orthogonal configuration. However, BS exists at more distant flankers (collinear and orthogonal, 3λ). BS is not uniform (1.4); it depends on the stimulus condition, the presentation times, the order, and the method that was used to control the monocular and binocular vision.
Asthma control and sputum eosinophils in adult patients: a cross-sectional study in southern Brazil
Authors: Barcellos Vanessa Albano , dos Santos Vanessa Cristina Hartmann , Moreira Maria Ângela Fontoura , Dalcin Paulo de Tarso Roth 
Published: December 2023

AbstractAsthma control and health related quality of life are an important goal of asthma management, but their association with sputum eosinophilic inflammation has been less firmly established. To investigate the relationship of asthma control and quality of life with sputum eosinophils in clinical practice. Cross-sectional study with a convenience sample, including patients with asthma, aged between 18 and 65 years, attending to outpatient clinic. Patients underwent sputum induction, pulmonary function tests, Juniper’s Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), Global Initiative for Asthma (GINA) criteria for evaluation of asthma control and severity of the disease, blood count analysis, serum IgE and cutaneous prick test. Sputum sample was considered as eosinophilic if the percentage of eosinophils was ≥ 3%. A total of 45 individuals were enrolled, 15 with eosinophilic sputum (≥ 3% eosinophil cells) and 30 with non-eosinophilic sputum (< 3% eosinophil cells). There were no association of ACT an AQLQ scores with sputum eosinophilia (p > 0.05). This study suggested that the finding of sputum eosinophilia was not related to asthma control neither with health-related quality of life in patients with severe asthma.
Dysregulated wound healing in the pathogenesis of urogynecologic mesh complications
Authors: Artsen Amanda M. , Liang Rui , Meyn Leslie , Bradley Megan S. , Moalli Pamela A. 
Published: December 2023

AbstractTo test the hypothesis that dysregulated wound healing is associated with Urogynecologic mesh complications, we collected vaginal cell secretions using vaginal swabs after polypropylene mesh implantation in patients with (N = 39) and without (N = 40) complication. A customized multiplex immunoassay measured markers of inflammation (MCP-1, IGFBP-1, IL-2, IL-10, IL-17, PDGF-BB, bFGF, IL-1b, IL-6, IL-12p70, TNF-α), neuroinflammation (IL-1RA, TGF-β, IL-15, IL-18, IL-3, M-CSF), angiogenesis (VEGF), and matrix proteins (fibronectin, tenasin c, thrombospondin-2, lumican) between groups. Patients with complications were younger, heavier, implanted with mesh longer, and more likely to be ever smokers. A 5 kg/m2 BMI increase and ever-smoking were associated with a 2.4-fold and sixfold increased risk of complication, respectively. Patients with the highest tertile of bFGF, fibronectin, thrombospondin-2, TNF-β, or VEGF had an odds ratio (OR) of 11.8 for having a mesh complication while ≥ 3 elevated had an OR of 237 while controlling for age, BMI, and smoking. The highest tertile of bFGF, thrombospondin-2, and fibronectin together perfectly indicated a complication (P < 0.0001). A receiver-operator curve for high bFGF, thrombospondin-2, and fibronectin showed excellent discrimination between complications and controls (AUC 0.87). These data provide evidence of dysregulated wound healing in mesh complications. Modifiable factors provide potential targets for patient counseling and interventions.
Correlation between dynamic contrast-enhanced MRI characteristics and apparent diffusion coefficient with Ki-67-positive expression in non-mass enhancement of breast cancer
Authors: Nie Tingting , Feng Mengwei , Yang Kai , Guo Xiaofang , Yuan Zilong , Zhang Zhaoxi , Yan Gen 
Published: December 2023

AbstractAs a remarkably specific characteristic of breast cancer observed on magnetic resonance imaging (MRI), the association between the NME type breast cancer and prognosis, including Ki-67, necessitates comprehensive exploration. To investigate the correlation between dynamic contrast-enhanced MRI (DCE-MRI) characteristics and apparent diffusion coefficient (ADC) values with Ki-67-positive expression in NME type breast cancer. A total of 63 NME type breast cancer patients were retrospectively reviewed. Malignancies were confirmed by surgical pathology. All patients underwent DCE and diffusion-weighted imaging (DWI) before surgery. DCE-MRI characteristics, including tumor distribution, internal enhancement pattern, axillary adenopathy, and time-intensity curve types were observed. ADC values and lesion sizes were also measured. The correlation between these features and Ki-67 expression were assessed using Chi-square test, Fisher’s exact test, and Spearman rank analysis. The receiver operating characteristic curve and area under the curve (AUC) was used to evaluate the diagnostic performance of Ki-67-positive expression. Regional distribution, TIC type, and ipsilateral axillary lymph node enlargement were correlated with Ki-67-positive expression (χ2 = 0.397, 0.357, and 0.357, respectively; P < 0.01). ADC value and lesion size were positively correlated with Ki-67-positive expression (rs = 0.295, 0.392; P < 0.05). The optimal threshold values for lesion size and ADC value to assess Ki-67 expression were determined to be 5.05 (AUC = 0.759) cm and 0.403 × 10–3 s/mm2 (AUC = 0.695), respectively. The best diagnosis performance was the ADC combined with lesion size (AUC = 0.791). The ADC value, lesion size, regional distribution, and TIC type in NME type breast cancer were correlated with Ki-67-positive expression. These features will aid diagnosis and treatment of NME type breast cancer.
Modulation recognition method of mixed signals based on cyclic spectrum projection
Authors: Yang Weichao , Ren Ke , Du Yu , Zheng Jia , Ping Yifan , Wang Sujun , Yang Xinquan , Li Li 
Published: December 2023

AbstractThe signal in the receiver is mainly a combination of different modulation types due to the complex electromagnetic environment, which makes the modulation recognition of the mixed signal a hot topic in recent years. In response to the poor adaptability of existing mixed signals recognition methods, this paper proposes a new recognition method for mixed signals based on cyclic spectrum projection and deep neural network. Firstly, through theoretical derivation, we prove the feasibility of using cyclic spectrum for mixed communication signal identification. Then, we adopt grayscale projections on the two-dimensional cyclic spectrum as identifying representation. And a new nonlinear piecewise mapping and directed pseudo-clustering method are used to enhance the above-mentioned grayscale images, which reduces the impact of energy ratios and symbol rates on signal identification. Finally, we use deep neural networks to extract deep abstract modulation information to achieve effective recognition of mixed signals. Simulation results show that the proposed method is robust against noise. When signal-to-noise ratio is not less than 0 dB, the average recognition rate is greater than 95%. Furthermore, this method exhibits good robustness towards the changes in signal symbol rates and energy ratios between mixed signals.
CT perfusion stroke lesion threshold calibration between deconvolution algorithms
Authors: Chung Kevin J. , De Sarno Danny , Lee Ting-Yim 
Published: December 2023

AbstractCTP is an important diagnostic tool in managing patients with acute ischemic stroke, but challenges persist in the agreement of stroke lesion volumes and ischemic core-penumbra mismatch profiles determined with different CTP post-processing software. We investigated a systematic method of calibrating CTP stroke lesion thresholds between deconvolution algorithms using a digital perfusion phantom to improve inter-software agreement of mismatch profiles. Deconvolution-estimated cerebral blood flow (CBF) and Tmax was compared to the phantom ground truth via linear regression for one model-independent and two model-based deconvolution algorithms. Using the clinical standard of model-independent CBF < 30% and Tmax > 6 s as reference thresholds for ischemic core and penumbra, respectively, we determined that model-based CBF < 15% and Tmax > 6 s were the corresponding calibrated thresholds after accounting for quantitative differences revealed at linear regression. Calibrated thresholds were then validated in 63 patients with large vessel stroke by evaluating agreement (concordance and Cohen’s kappa, κ) between the two model-based and model-independent deconvolution methods in determining mismatch profiles used for clinical decision-making. Both model-based deconvolution methods achieved 95% concordance with model-independent assessment and Cohen’s kappa was excellent (κ = 0.87; 95% confidence interval [CI] 0.72–1.00 and κ = 0.86; 95% CI 0.70–1.00). Our systematic method of calibrating CTP stroke lesion thresholds may help harmonize mismatch profiles determined by different software.