bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient CO2 electroreduction on facet-selective copper films with high conversion rate
Authors: Zhang Gong , Zhao Zhi-Jian , Cheng Dongfang , Li Huimin , Yu Jia , Wang Qingzhen , Gao Hui , Guo Jinyu , Wang Huaiyuan , Ozin Geoffrey A. , Wang Tuo , Gong Jinlong
Published: September 2021

Tuning the facet exposure of Cu could promote the multi-carbon (C2+) products formation in electrocatalytic CO2 reduction. Here we report the design and realization of a dynamic deposition-etch-bombardment method for Cu(100) facets control without using capping agents and polymer binders. The synthesized Cu(100)-rich films lead to a high Faradaic efficiency of 86.5% and a full-cell electricity conversion efficiency of 36.5% towards C2+ products in a flow cell. By further scaling up the electrode into a 25 cm2 membrane electrode assembly system, the overall current can ramp up to 12 A while achieving a single-pass yield of 13.2% for C2+ products. An insight into the influence of Cu facets exposure on intermediates is provided by in situ spectroscopic methods supported by theoretical calculations. The collected information will enable the precise design of CO2 reduction reactions to obtain desired products, a step towards future industrial CO2 refineries.
A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination
Authors: Ambjørn Sara M. , Duxin Julien P. , Hertz Emil P. T. , Nasa Isha , Duro Joana , Kruse Thomas , Lopez-Mendez Blanca , Rymarczyk Beata , Cressey Lauren E. , van Overeem Hansen Thomas , Kettenbach Arminja N. , Oestergaard Vibe H. , Lisby Michael , Nilsson Jakob
Published: September 2021

Mutations in the tumour suppressor gene BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD51 nucleoprotein filament formation on resected single-stranded DNA, but how BRCA2 activity is regulated during HR is not fully understood. Here, we delineate a pathway where ATM and ATR kinases phosphorylate a highly conserved region in BRCA2 in response to DSBs. These phosphorylations stimulate the binding of the protein phosphatase PP2A-B56 to BRCA2 through a conserved binding motif. We show that the phosphorylation-dependent formation of the BRCA2-PP2A-B56 complex is required for efficient RAD51 filament formation at sites of DNA damage and HR-mediated DNA repair. Moreover, we find that several cancer-associated mutations in BRCA2 deregulate the BRCA2-PP2A-B56 interaction and sensitize cells to PARP inhibition. Collectively, our work uncovers PP2A-B56 as a positive regulator of BRCA2 function in HR with clinical implications for BRCA2 and PP2A-B56 mutated cancers.
Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease
Authors: Roberts Kevin J. , Cubitt Marion F. , Carlton Timothy M. , Rodrigues-Duarte Lurdes , Maggiore Luana , Chai Ray , Clare Simon , Harcourt Katherine , MacDonald Thomas T. , Ray Keith P. , Vossenkämper Anna , West Michael R. , Crowe J. Scott
Published: September 2021

Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn’s disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration. Incubation of V56B2 with trypsin or human faecal supernatant resulted in a complete separation of the V565 and V900 monomers without loss of neutralising potency. Following oral administration of V900 and V565 in mice, high levels of each domain antibody were detected in the faeces, demonstrating stability in the intestinal milieu. In ex vivo cultures of colonic biopsies from IBD patients, treatment with V565 or V900 inhibited tissue phosphoprotein levels and with a combination of the two, inhibition was even greater. These results support further development of V56B2 as an oral therapy for IBD with improved safety and efficacy in a greater proportion of patients as well as greater convenience for patients compared with traditional monoclonal antibody therapies.
The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus
Authors: Rathnasinghe Raveen , Jangra Sonia , Miorin Lisa , Schotsaert Michael , Yahnke Clifford , Garcίa-Sastre Adolfo
Published: September 2021

The germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit their use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) and influenza A virus to 405 nm, visible light in the absence of exogenous photosensitizers thereby indicating a potential alternative porphyrin-independent mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are considered safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.
Dental replacement in Mesozoic birds: evidence from newly discovered Brazilian enantiornithines
Authors: Wu Yun-Hsin , Chiappe Luis M. , Bottjer David J. , Nava William , Martinelli Agustín G.
Published: September 2021

Polyphyodonty—multiple tooth generations—in Mesozoic birds has been confirmed since the nineteenth century. Their dental cycle had been assessed through sparse data from tooth roots revealed through broken jawbones and disattached teeth. However, detailed descriptions of their tooth cycling are lacking, and the specifics of their replacement patterns remain largely unknown. Here we present unprecedented µCT data from three enantiornithine specimens from the Upper Cretaceous of southeastern Brazil. The high resolution µCT data show an alternating dental replacement pattern in the premaxillae, consistent with the widespread pattern amongst extinct and extant reptiles. The dentary also reveals dental replacement at different stages. These results strongly suggest that an alternating pattern was typical of enantiornithine birds. µCT data show that new teeth start lingually within the alveoli, resorb roots of functional teeth and migrate labially into their pulp cavities at an early stage, similar to modern crocodilians. Our results imply that the control mechanism for tooth cycling is conserved during the transition between non-avian reptiles and birds. These first 3D reconstructions of enantiornithine dental replacement demonstrate that 3D data are essential to understand the evolution and deep homology of archosaurian tooth cycling.
Adverse outcomes after noncardiac surgery in patients with aortic stenosis
Authors: Tai Ying-Hsuan , Chang Chuen-Chau , Yeh Chun-Chieh , Cherng Yih-Giun , Chen Ta-Liang , Liao Chien-Chang
Published: September 2021

Whether aortic stenosis (AS) increases perioperative risk in noncardiac surgery remains controversial. Limited information is available regarding adequate anesthetic techniques for patients with AS. Using the reimbursement claims data of Taiwan’s National Health Insurance, we performed propensity score matching analyses to evaluate the risk of adverse outcomes in patients with or without AS undergoing noncardiac surgery between 2008 and 2013. We also compared the perioperative risk of AS patients undergoing general anesthesia or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for postoperative mortality and major complications. The matching procedure generated 9741 matched pairs for analyses. AS was significantly associated with 30-day in-hospital mortality (aOR 1.31, 95% CI 1.03–1.67), acute renal failure (aOR 1.42, 95% CI 1.12–1.79), pneumonia (aOR 1.16, 95% CI 1.02–1.33), stroke (aOR 1.14, 95% CI 1.01–1.29), and intensive care unit stay (aOR 1.38, 95% CI 1.27–1.49). Compared with neuraxial anesthesia, general anesthesia was associated with increased risks of acute myocardial infarction (aOR 3.06, 95% CI 1.22–7.67), pneumonia (aOR 1.80, 95% CI 1.32–2.46), acute renal failure (aOR 1.82, 95% CI 1.11–2.98), and intensive care (aOR 4.05, 95% CI 3.23–5.09). The findings were generally consistent across subgroups. AS was an independent risk factor for adverse events after noncardiac surgery. In addition, general anesthesia was associated with greater postoperative complications in AS patients compared to neuraxial anesthesia. This real-world evidence suggests that neuraxial anesthesia should not be contraindicated in patients with AS.
Effect of functional oils or probiotics on performance and microbiota profile of newly weaned piglets
Authors: Vieira Alexandre Maciel , Sessin Amanda Pires , Soratto Tatiany Aparecida Teixeira , Pires Paula Gabriela da Silva , Cardinal Kátia Maria , Wagner Glauber , Hauptli Lucélia , Lima André Luis Ferreira , Dahlke Fabiano , Netto Diego Peres , Moraes Priscila de Oliveira
Published: September 2021

The study aimed to evaluate a commercial blend of functional oils based on liquid from the cashew nutshell and castor oil as a growth promoter in newly weaned piglets. A total of 225 piglets, castrated males and females with 28 days of age were randomly distributed in pens with 15 animals composing three treatments and five repetitions. The treatments were: control (without the inclusion of additives), probiotics, or functional oils. The performance was evaluated. At 50 days of age, a pool of fresh feces from 3 animals/repetition was collected to perform the sequencing of microbiota using the Illumina MiSeq platform. Supplementation with functional oils improved the piglets' daily weight gain and feed conversion ratio (P < 0.05) in the first weeks of the experiment, which resulted in higher final live weight (P < 0.05) in the phase when compared to the control treatment (24.34 kg and 21.55 kg, respectively). The animals that received probiotics showed an intermediate performance (23.66 kg final live weight) at the end of the 38 experimental days. Both additives were effective in increasing groups essential for intestinal health, such asRuminococcaceaeandLachnospiraceae. The functional oils were more effective in reducing pathogenic bacteria, such asCampylobacterandEscherichia coli. In conclusion, the use of functional oils optimized performance and effectively modulated the microbiota of newly weaned piglets.
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

Quantitative 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

Toxin–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

This 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

DJ-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

The 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

Trilobites, 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

Recent 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

X-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

The 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

The 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

Microplastics 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

School 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

The 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

RNA 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

The 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.
Effectiveness of human-origin Lactobacillus plantarum PL-02 in improving muscle mass, exercise performance and anti-fatigue
Authors: Lee Mon-Chien , Hsu Yi-Ju , Ho Hsieh‐Hsun , Kuo Yi‐Wei , Lin Wen-Yang , Tsai Shin-Yu , Chen Wei-Ling , Lin Che-Li , Huang Chi-Chang
Published: September 2021

Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 109, 4.10 × 109 and 1.03 × 1010 CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect.
Remdesivir is efficacious in rhesus monkeys exposed to aerosolized Ebola virus
Authors: Warren Travis K. , Kane Christopher D. , Wells Jay , Stuthman Kelly S. , Van Tongeren Sean A. , Garza Nicole L. , Donnelly Ginger , Steffens Jesse , Gomba Laura , Weidner Jessica M. , Norris Sarah , Zeng Xiankun , Bannister Roy , Cihlar Tomas , Bavari Sina , Porter Danielle P. , Iversen Patrick L.
Published: September 2021

Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.
Low-spin ferric iron in primordial bridgmanite crystallized from a deep magma ocean
Authors: Okuda Yoshiyuki , Ohta Kenji , Nishihara Yu , Hirao Naohisa , Wakamatsu Tatsuya , Suehiro Sho , Kawaguchi Saori I. , Ohishi Yasuo
Published: September 2021

The crystallization of the magma ocean resulted in the present layered structure of the Earth’s mantle. An open question is the electronic spin state of iron in bridgmanite (the most abundant mineral on Earth) crystallized from a deep magma ocean, which has been neglected in the crystallization history of the entire magma ocean. Here, we performed energy-domain synchrotron Mössbauer spectroscopy measurements on two bridgmanite samples synthesized at different pressures using the same starting material (Mg0.78Fe0.13Al0.11Si0.94O3). The obtained Mössbauer spectra showed no evidence of low-spin ferric iron (Fe3+) from the bridgmanite sample synthesized at relatively low pressure of 25 gigapascals, while that directly synthesized at a higher pressure of 80 gigapascals contained a relatively large amount. This difference ought to derive from the large kinetic barrier of Fe3+ rearranging from pseudo-dodecahedral to octahedral sites with the high-spin to low-spin transition in experiments. Our results indicate a certain amount of low-spin Fe3+ in the lower mantle bridgmanite crystallized from an ancient magma ocean. We therefore conclude that primordial bridgmanite with low-spin Fe3+ dominated the deeper part of an ancient lower mantle, which would contribute to lower mantle heterogeneity preservation and call for modification of the terrestrial mantle thermal evolution scenarios.
Hemoglobin-mediated lipid oxidation of herring filleting co-products during ensilaging and its inhibition by pre-incubation in antioxidant solutions
Authors: Sajib Mursalin , Wu Haizhou , Fristedt Rikard , Undeland Ingrid
Published: September 2021

The aims of this study were to investigate the role of hemoglobin (Hb) in lipid oxidation development during ensilaging of herring filleting co-products, and, to inhibit this reaction by pre-incubating the co-products in water or physiological salt, with/without different antioxidants. Results showed that both peroxide value (PV) and 2-thiobarbituric acid reactive substances (TBARS) gradually increased during 7 days of ensilaging at 22 °C in absence of antioxidants. The increase in TBARS was proportional to the Hb levels present, while PV was less affected. A Hb-fortified Tris-buffer model system adjusted to pH 3.50 confirmed that Hb changed immediately from its native oxyHb to the metHb state, which facilitated heme group release and thus probably explains the increased PV and TBARS during ensilaging. Pre-incubating the co-products for 30 s in a solution containing 0.5% rosemary extract was the most promising strategy to inhibit lipid oxidation both in the co-products during pre-processing storage and during the actual ensilaging. The solution could be re-used up to ten times without losing its activity, illustrating that this methodology can be a scalable and cost-effective strategy to extend the oxidative stability of herring co-products allowing for further value adding e.g., into a high-quality silage.
Powerful use of automated prioritization of candidate variants in genetic hearing loss with extreme etiologic heterogeneity
Authors: Kim So Young , Lee Seungmin , Seo Go Hun , Kim Bong Jik , Oh Doo Yi , Han Jin Hee , Park Moo Kyun , Lee So min , Kim Bonggi , Yi Nayoung , Kim Namju Justin , Koh Doo Hyun , Hwang Sohyun , Keum Changwon , Choi Byung Yoon
Published: September 2021

Variant prioritization of exome sequencing (ES) data for molecular diagnosis of sensorineural hearing loss (SNHL) with extreme etiologic heterogeneity poses a significant challenge. This study used an automated variant prioritization system (“EVIDENCE”) to analyze SNHL patient data and assess its diagnostic accuracy. We performed ES of 263 probands manifesting mild to moderate or higher degrees of SNHL. Candidate variants were classified according to the 2015 American College of Medical Genetics guidelines, and we compared the accuracy, call rates, and efficiency of variant prioritizations performed manually by humans or using EVIDENCE. In our in silico panel, 21 synthetic cases were successfully analyzed by EVIDENCE. In our cohort, the ES diagnostic yield for SNHL by manual analysis was 50.19% (132/263) and 50.95% (134/263) by EVIDENCE. EVIDENCE processed ES data 24-fold faster than humans, and the concordant call rate between humans and EVIDENCE was 97.72% (257/263). Additionally, EVIDENCE outperformed human accuracy, especially at discovering causative variants of rare syndromic deafness, whereas flexible interpretations that required predefined specific genotype–phenotype correlations were possible only by manual prioritization. The automated variant prioritization system remarkably facilitated the molecular diagnosis of hearing loss with high accuracy and efficiency, fostering the popularization of molecular genetic diagnosis of SNHL.
Defining the Gothic Arch Angle (GAA) as a radiographic diagnostic tool for instability in hip dysplasia
Authors: Zimmerer A. , Löchel J. , Schoon J. , Janz V. , Wassilew G. I.
Published: September 2021

In recent years, there has been a controversial discussion about whether borderline dysplastic hips should be treated with an arthroscopic procedure or rather with an acetabular reorientation. New research suggests that a classification into stable and unstable hips may be helpful. The aim of the study was to validate (1) the intra- and interobserver reliability of a newly defined radiographic parameter named the Gothic Arch Angle, (2) the association between the GAA and previously existing measurements used to define severity of acetabular dysplasia, and (3) the correlation between radiographic measurements of acetabular dysplasia with MRI findings previously suggestive of hip instability. We defined and validated the GAA in 10 standardized radiographs of asymptomatic hips by two observers and calculated intra- and interobserver coefficients at two individual dates. Subsequently, a consecutive series of 100 patients with dysplastic hips (LCEA < 25°, Toennis grade ≤ 1) were evaluated for signs of instability on anteroposterior (a.p.) pelvic radiographs and direct MR arthrography and were divided in two groups: stable and unstable. In these patients the LCEA, the AI, the FEAR index and the GAA were radiographically evaluated. Correlation analyses and a logistic regression analysis was performed to identify the predictive value of instability for each radiographic parameter. Cutoff probabilities analysis was performed using standard receiver operating characteristic (ROC) curves to rate the predictive efficiency value of the GAA. The GAA showed excellent inter- and intraobserver reliability. A correlation was found between GAA and FEAR index. A logistic regression analysis showed that LCEA, FEAR index and GAA are distinct predictors of instability in hip dysplasia. The GAA showed the largest area under the curve (AUC 0.96), indicating it to be the best predictor of instability with an optimal cutoff value of 90° (sensitivity, 0.95; specificity, 0.93). The GAA is a new available indicator for instability and is thus suggested to be used as a future radiographic parameter for the stability of dysplastic hips. Further studies are needed to understand how this parameter might additionally predict clinical outcome in the treatment of hip dysplasia.

Level of evidence: Level III, diagnostic study.
A novel flow-based geometrical upscaling method for representing fault zones with two-phase fault rock properties into a dynamic reservoir model
Authors: Islam Md Saiful , Manzocchi Tom
Published: September 2021

Faults are generally represented in conventional upscaled models as 2D planar surfaces with transmissibility multipliers used to represent single-phase fault properties. However, faults are structurally complex 3D zones in which both single-phase and two-phase fault rock properties can be significant. Ignoring this structural and petrophysical complexity within faults may impart considerable inaccuracy on the predictive performance of upscaled models. This study has developed a two-phase flow-based geometrical upscaling method capable of representing simultaneously the complex geometry and saturation-dependent two-phase flow properties of realistic fault zones. In this approach, high-resolution sector models are built of small portions of the fault zones and assigned appropriate single-phase and two-phase fault rock properties. Steady state two-phase flow simulations at different fractional flows of oil and water are used to determine the saturation dependent upscaled pseudo relative permeability functions which are incorporated into upscaled models. The method is applied to an example model containing two 3D fault zone components and tested by comparing the flow results of upscaled model with those of a high-resolution truth model. Results show that two-phase flow-based geometrical upscaling is a promising method for representing the effects of two-phase fault rock properties and complex 3D fault zone structure simultaneously.