bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid, label-free classification of tumor-reactive T cell killing with quantitative phase microscopy and machine learning
Authors: Kim Diane N. H. , Lim Alexander A. , Teitell Michael A. 
Published: September 2021

AbstractQuantitative phase microscopy (QPM) enables studies of living biological systems without exogenous labels. To increase the utility of QPM, machine-learning methods have been adapted to extract additional information from the quantitative phase data. Previous QPM approaches focused on fluid flow systems or time-lapse images that provide high throughput data for cells at single time points, or of time-lapse images that require delayed post-experiment analyses, respectively. To date, QPM studies have not imaged specific cells over time with rapid, concurrent analyses during image acquisition. In order to study biological phenomena or cellular interactions over time, efficient time-dependent methods that automatically and rapidly identify events of interest are desirable. Here, we present an approach that combines QPM and machine learning to identify tumor-reactive T cell killing of adherent cancer cells rapidly, which could be used for identifying and isolating novel T cells and/or their T cell receptors for studies in cancer immunotherapy. We demonstrate the utility of this method by machine learning model training and validation studies using one melanoma-cognate T cell receptor model system, followed by high classification accuracy in identifying T cell killing in an additional, independent melanoma-cognate T cell receptor model system. This general approach could be useful for studying additional biological systems under label-free conditions over extended periods of examination.
A minimal model for gene expression dynamics of bacterial type II toxin–antitoxin systems
Authors: Kosmidis Kosmas , Hütt Marc-Thorsten 
Published: September 2021

AbstractToxin–antitoxin (TA) modules are part of most bacteria’s regulatory machinery for stress responses and general aspects of their physiology. Due to the interplay of a long-lived toxin with a short-lived antitoxin, TA modules have also become systems of interest for mathematical modelling. Here we resort to previous modelling efforts and extract from these a minimal model of type II TA system dynamics on a timescale of hours, which can be used to describe time courses derived from gene expression data of TA pairs. We show that this model provides a good quantitative description of TA dynamics for the 11 TA pairs under investigation here, while simpler models do not. Our study brings together aspects of Biophysics with its focus on mathematical modelling and Computational Systems Biology with its focus on the quantitative interpretation of ’omics’ data. This mechanistic model serves as a generic transformation of time course information into kinetic parameters. The resulting parameter vector can, in turn, be mechanistically interpreted. We expect that TA pairs with similar mechanisms are characterized by similar vectors of kinetic parameters, allowing us to hypothesize on the mode of action for TA pairs still under discussion.
New segmentation and feature extraction algorithm for classification of white blood cells in peripheral smear images
Authors: Tavakoli Sajad , Ghaffari Ali , Kouzehkanan Zahra Mousavi , Hosseini Reshad 
Published: September 2021

AbstractThis article addresses a new method for the classification of white blood cells (WBCs) using image processing techniques and machine learning methods. The proposed method consists of three steps: detecting the nucleus and cytoplasm, extracting features, and classification. At first, a new algorithm is designed to segment the nucleus. For the cytoplasm to be detected, only a part of it located inside the convex hull of the nucleus is involved in the process. This attitude helps us overcome the difficulties of segmenting the cytoplasm. In the second phase, three shapes and four novel color features are devised and extracted. Finally, by using an SVM model, the WBCs are classified. The segmentation algorithm can detect the nucleus with a dice similarity coefficient of 0.9675. The proposed method can categorize WBCs in Raabin-WBC, LISC, and BCCD datasets with accuracies of 94.65%, 92.21%, and 94.20%, respectively. Besides, we show that the proposed method possesses more generalization power than pre-trained CNN models. It is worth mentioning that the hyperparameters of the classifier are fixed only with the Raabin-WBC dataset, and these parameters are not readjusted for LISC and BCCD datasets.
DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart
Authors: Pantner Yvanna , Polavarapu Rohini , Chin Lih-Shen , Li Lian , Shimizu Yuuki , Calvert John W. 
Published: September 2021

AbstractDJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress—the non-enzymatic glycosylation of proteins. However, specific proteins protected from glycative stress by DJ-1 are not known. Given that mitochondrial electron transport proteins have a propensity for being targets of glycative stress, we investigated if DJ-1 regulates the glycation of Complex I and Complex III after myocardial ischemia–reperfusion (I/R) injury. Initial studies found that DJ-1 localized to the mitochondria and increased its interaction with Complex I and Complex III 3 days after the onset of myocardial I/R injury. Next, we investigated the role DJ-1 plays in modulating glycative stress in the mitochondria. Analysis revealed that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of glycative stress following I/R. Additionally, Complex I and Complex III glycation were found to be at higher levels in DJ-1 KO hearts. This corresponded with reduced complex activities, as well as reduced mitochondrial oxygen consumption ant ATP synthesis in the presence of pyruvate and malate. To further determine if DJ-1 influenced the glycation of the complexes, an adenoviral approach was used to over-express the active form of DJ-1(AAV9-DJ1ΔC). Under I/R conditions, the glycation of Complex I and Complex III were attenuated in hearts treated with AAV9-DJ1ΔC. This was accompanied by improvements in complex activities, oxygen consumption, and ATP production. Together, this data suggests that cardiac DJ-1 maintains Complex I and Complex III efficiency and mitochondrial function during the recovery from I/R injury. In elucidating a specific mechanism for DJ-1’s role in the post-ischemic heart, these data break new ground for potential therapeutic strategies using DJ-1 as a target.
Effect of ondansetron on reducing ICU mortality in patients with acute kidney injury
Authors: Guo Xiaojiang , Qi Xiguang , Fan Peihao , Gilbert Michael , La Andrew D. , Liu Zeyu , Bertz Richard , Kellum John A. , Chen Yu , Wang Lirong 
Published: September 2021

AbstractThe purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients’ baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug’s molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.
A 390 million-year-old hyper-compound eye in Devonian phacopid trilobites
Authors: Schoenemann B. , Clarkson E. N. K. , Bartels C. , Südkamp W. , Rössner G. E. , Ryck U. 
Published: September 2021

AbstractTrilobites, extinct arthropods that dominated the faunas of the Palaeozoic, since their appearance c 523 million years ago, were equipped with elaborate compound eyes. While most of them possessed apposition compound eyes (in trilobites called holochroal eyes), comparable to the compound eyes of many diurnal crustaceans and insects living today, trilobites of the suborder Phacopina developed atypical large eyes with wide lenses and wide interspaces in between (schizochroal eyes). Here, we show that these compound eyes are highly sophisticated systems—hyper-compound eyes hiding an individual compound eye below each of the big lenses. Thus, each of the phacopid compound eyes comprises several tens, in cases even hundreds of small compound eye systems composing a single visual surface. We discuss their development, phylogenetic position of this hyper-compound eye, and its neuronal infrastructure. A hyper-compound eye in this form is unique in the animal realm.
Cardiac involvement in hospitalized patients with COVID-19 and its incremental value in outcomes prediction
Authors: Pournazari Payam , Spangler Alison L. , Ameer Fawzi , Hagan Kobina K. , Tano Mauricio E. , Chamsi-Pasha Mohammed , Chebrolu Lakshmi H. , Zoghbi William A. , Nasir Khurram , Nagueh Sherif F. 
Published: September 2021

AbstractRecent reports linked acute COVID-19 infection in hospitalized patients to cardiac abnormalities. Studies have not evaluated presence of abnormal cardiac structure and function before scanning in setting of COVD-19 infection. We sought to examine cardiac abnormalities in consecutive group of patients with acute COVID-19 infection according to the presence or absence of cardiac disease based on review of health records and cardiovascular imaging studies. We looked at independent contribution of imaging findings to clinical outcomes. After excluding patients with previous left ventricular (LV) systolic dysfunction (global and/or segmental), 724 patients were included. Machine learning identified predictors of in-hospital mortality and in-hospital mortality + ECMO. In patients without previous cardiovascular disease, LV EF < 50% occurred in 3.4%, abnormal LV global longitudinal strain (< 16%) in 24%, and diastolic dysfunction in 20%. Right ventricular systolic dysfunction (RV free wall strain < 20%) was noted in 18%. Moderate and large pericardial effusion were uncommon with an incidence of 0.4% for each category. Forty patients received ECMO support, and 79 died (10.9%). A stepwise increase in AUC was observed with addition of vital signs and laboratory measurements to baseline clinical characteristics, and a further significant increase (AUC 0.91) was observed when echocardiographic measurements were added. The performance of an optimized prediction model was similar to the model including baseline characteristics + vital signs and laboratory results + echocardiographic measurements.
Absolute contrast estimation for soft X-ray photon fluctuation spectroscopy using a variational droplet model
Authors: Burdet N. G. , Esposito V. , Seaberg M. H. , Yoon C. H. , Turner J. J. 
Published: September 2021

AbstractX-ray photon fluctuation spectroscopy using a two-pulse mode at the Linac Coherent Light Source has great potential for the study of quantum fluctuations in materials as it allows for exploration of low-energy physics. However, the complexity of the data analysis and interpretation still prevent recovering real-time results during an experiment, and can even complicate post-analysis processes. This is particularly true for high-spatial resolution applications using CCDs with small pixels, which can decrease the photon mapping accuracy resulting from the large electron cloud generation at the detector. Droplet algorithms endeavor to restore accurate photon maps, but the results can be altered by their hyper-parameters. We present numerical modeling tools through extensive simulations that mimic previous x-ray photon fluctuation spectroscopy experiments. By modification of a fast droplet algorithm, our results demonstrate how to optimize the precise parameters that lift the intrinsic counting degeneracy impeding accuracy in extracting the speckle contrast. These results allow for an absolute determination of the summed contrast from multi-pulse x-ray speckle diffraction, the modus operandi by which the correlation time for spontaneous fluctuations can be measured.
ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression
Authors: Naboulsi Rakan , Larsson Mårten , Andersson Leif , Younis Shady 
Published: September 2021

AbstractThe expression of Igf2 in mammals shows a complex regulation involving multiple promoters and epigenetic mechanisms. We previously identified a novel regulatory mechanism based on the interaction between the transcriptional factor ZBED6 and Igf2 intron. Disruption of the ZBED6-Igf2 interaction leads to a dramatic up-regulation of IGF2 expression postnatally. In the current study we characterize an additional layer of regulation involving miR483 encoded by another Igf2 intron. We found a highly significant up-regulation of miR483 expression when the ZBED6-Igf2 axis is disrupted in transgenic mice. Furthermore, CRISPR/Cas9 mediated knock-out of miR483 in C2C12 myoblast cells, both wild-type and cells with disrupted ZBED6-Igf2 axis (Igf2dGGCT), resulted in down-regulation of Igf2 expression and a reduced proliferation rate. This was further validated using miR483 mimics and inhibitors. RNA-seq analysis revealed a significant enrichment of genes involved in the PI3K-Akt signaling pathway among genes down-regulated in miR483−/− cells, including Igf2 down-regulation. The opposite pattern was observed in Igf2dGGCT cells, where Igf2 is up-regulated. Our data suggest a positive feedback between miR483 and Igf2 promoter activity, strongly affecting how ZBED6 controls Igf2 expression in various cell types.
COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19
Authors: Menestrina Luca , Cabrelle Chiara , Recanatini Maurizio 
Published: September 2021

AbstractThe COVID-19 pandemic poses a huge problem of public health that requires the implementation of all available means to contrast it, and drugs are one of them. In this context, we observed an unmet need of depicting the continuously evolving scenario of the ongoing drug clinical trials through an easy-to-use, freely accessible online tool. Starting from this consideration, we developed COVIDrugNet (http://compmedchem.unibo.it/covidrugnet), a web application that allows users to capture a holistic view and keep up to date on how the clinical drug research is responding to the SARS-CoV-2 infection. Here, we describe the web app and show through some examples how one can explore the whole landscape of medicines in clinical trial for the treatment of COVID-19 and try to probe the consistency of the current approaches with the available biological and pharmacological evidence. We conclude that careful analyses of the COVID-19 drug-target system based on COVIDrugNet can help to understand the biological implications of the proposed drug options, and eventually improve the search for more effective therapies.
Washing load influences the microplastic release from polyester fabrics by affecting wettability and mechanical stress
Authors: Volgare Michela , De Falco Francesca , Avolio Roberto , Castaldo Rachele , Errico Maria Emanuela , Gentile Gennaro , Ambrogi Veronica , Cocca Mariacristina 
Published: September 2021

AbstractMicroplastics released from textiles during the washing process represent the most prevalent type of microparticles found in different environmental compartments and ecosystems around the world. Release of microfibres during the washing process of synthetic textiles is due to the mechanical and chemical stresses that clothes undergo in washing machines. Several washing process parameters, conditions, formulations of laundering additives have been correlated to microfibre release and some of them have been identified to affect microfibre release during washing process, while no correlation has been evaluated between microfibre release and washing load. In the present study, microfibre release was evaluated as function of the washing load in a real washing process, indicating a progressive decrease of microfibre release with increasing washing load. The quantity of released microfibres increased by around 5 times by decreasing the washing load due to a synergistic effect between water-volume to fabric ratio and mechanical stress during washing. Moreover, the higher mechanical stress to which the fabric is subjected in the case of a low washing load, hinders the discrimination of the effect on the release of other washing parameters like the type of detergent and laundry additives used.
Feasibility of a surveillance programme based on gargle samples and pool testing to prevent SARS-CoV-2 outbreaks in schools
Authors: Sweeney-Reed Catherine M. , Wolff Doreen , Hörnschemeyer Sarah , Faßhauer Henriette , Haase Antonia , Schomburg Dirk , Niggel Jakob , Kabesch Michael , Apfelbacher Christian 
Published: September 2021

AbstractSchool closures have a negative impact on physical and mental well-being, and education, of children and adolescents. A surveillance programme to detect asymptomatic SARS-CoV-2 infection could allow schools to remain open, while protecting the vulnerable. We assessed the feasibility of a programme employing gargle samples and pool testing of individually extracted RNA using rRT-qPCR in a primary and a secondary school in Germany, based on programme logistics and acceptance. Twice a week, five participants per class were selected to provide samples, using an algorithm weighted by a risk-based priority score to increase likelihood of case detection. The positive response rate was 54.8% (550 of 1003 pupils). Logistics evaluation revealed the rate-limiting steps: completing the regular pre-test questionnaire and handing in the samples. Acceptance questionnaire responses indicated strong support for research into developing a surveillance programme and a positive evaluation of gargle tests. Participation was voluntary. As not all pupils participated, individual reminders could lead to participant identification. School-wide implementation of the programme for infection monitoring purposes would enable reminders to be given to all school pupils to address these steps, without compromising participant anonymity. Such a programme would provide a feasible means to monitor asymptomatic respiratory tract infection in schools.
Predicting intestinal viability by consecutive photoacoustic monitoring of oxygenation recovery after reperfusion in acute mesenteric ischemia in rats
Authors: Sugiura Takumi , Okumura Kenichiro , Matsumoto Junichi , Sakaguchi Maki , Komori Takahiro , Ogi Takahiro , Inoue Dai , Koda Wataru , Kobayashi Satoshi , Gabata Toshifumi 
Published: September 2021

AbstractThe purpose was to assess whether consecutive monitoring of oxygenation by photoacoustic imaging (PAI) can objectively predict intestinal viability during surgery for acute mesenteric ischemia (AMI). PAI uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in intestinal tissue. In 30 rats, AMI was induced by clamping the mesenteric and marginal vessels of the ileum for 0 min in the control group, 30 min in the mild group, and 180 min in the severe group (10 rats per group). After 60 min of reperfusion, intestinal damage was evaluated pathologically. Oxygenation of the intestine was monitored throughout the procedure in real time by a commercially available PAI system and compared among the groups. All rats showed irreversible (i.e. transmucosal or transmural infarction) damage in the severe group. After reperfusion, the oxygenation in the mild group recovered immediately and was significantly higher than in the severe group at 1, 5, 10, 30, and 60 min (P = .011, 002, < .001, 001, and 001, respectively). Oxygenation showed a significant strong negative correlation with pathological severity (rs =  − 0.7783, − 0.7806, − 0.7422, − 0.7728, and − 0.7704, respectively). In conclusion, PAI could objectively predict irreversible ischemic damage immediately after reperfusion, which potentially prevents inadequate surgery.
Performance of a scalable RNA extraction-free transcriptome profiling method for adherent cultured human cells
Authors: Ghimire Shreya , Stewart Carley G. , Thurman Andrew L. , Pezzulo Alejandro A. 
Published: September 2021

AbstractRNA sequencing enables high-content/high-complexity measurements in small molecule screens. Whereas the costs of DNA sequencing and RNA-seq library preparation have decreased consistently, RNA extraction remains a significant bottleneck to scalability. We evaluate the performance of a bulk RNA-seq library prep protocol optimized for analysis of many samples of adherent cultured cells in parallel. We combined a low-cost direct lysis buffer compatible with cDNA synthesis (in-lysate cDNA synthesis) with Smart-3SEQ and examine the effects of calmidazolium and fludrocortisone-induced perturbation of primary human dermal fibroblasts. We compared this method to normalized purified RNA inputs from matching samples followed by Smart-3SEQ or Illumina TruSeq library prep. Our results show the minimal effect of RNA loading normalization on data quality, measurement of gene expression patterns, and generation of differentially expressed gene lists. We found that in-lysate cDNA synthesis combined with Smart-3SEQ RNA-seq library prep generated high-quality data with similar ranked DEG lists when compared to library prep with extracted RNA or with Illumina TruSeq. Our data show that small molecule screens or experiments based on many perturbations quantified with RNA-seq are feasible at low reagent and time costs.
The effects of different frequencies of rhythmic acoustic stimulation on gait stability in healthy elderly individuals: a pilot study
Authors: Minino Roberta , Troisi Lopez Emahnuel , Sorrentino Pierpaolo , Rucco Rosaria , Lardone Anna , Pesoli Matteo , Tafuri Domenico , Mandolesi Laura , Sorrentino Giuseppe , Liparoti Marianna 
Published: September 2021

AbstractThe efficacy of rhythmic acoustic stimulation (RAS) to improve gait and balance in healthy elderly individuals is controversial. Our aim was to investigate, through 3D gait analysis, the effect of different types of RAS (fixed frequency and based on subject-specific cadence), using conventional gait parameters and the trunk displacement as readouts. Walking at a fixed frequency of 80 bpm, the subjects showed extended duration of gait cycle and increased gait variability while the same individuals, walking at a fixed frequency of 120 bpm, showed reduced trunk sway and gait cycle duration. With regard to the RAS at subject-specific frequencies, walking at 90% of the subject-specific average cadence did not significantly modify the gait parameters, except for the speed, which was reduced. In contrast, walking at 100% and 110% of the mean cadence caused increased stride length and a slight reduction of temporal parameters and trunk sway. In conclusion, this pilot study shows that using RAS at fixed frequencies might be an inappropriate strategy, as it is not adjusted to individual gait characteristics. On the other hand, RAS frequencies equal to or slightly higher than each subject's natural cadence seem to be beneficial for gait and stability.