bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidating the network features and evolutionary attributes of intra- and interspecific protein–protein interactions between human and pathogenic bacteria
Authors: Acharya Debarun , Dutta Tapan K.
Published: January 2021

Host–pathogen interaction is one of the most powerful determinants involved in coevolutionary processes covering a broad range of biological phenomena at molecular, cellular, organismal and/or population level. The present study explored host–pathogen interaction from the perspective of human–bacteria protein–protein interaction based on large-scale interspecific and intraspecific interactome data for human and three pathogenic bacterial species, Bacillus anthracis, Francisella tularensis and Yersinia pestis. The network features revealed a preferential enrichment of intraspecific hubs and bottlenecks for both human and bacterial pathogens in the interspecific human–bacteria interaction. Analyses unveiled that these bacterial pathogens interact mostly with human party-hubs that may enable them to affect desired functional modules, leading to pathogenesis. Structural features of pathogen-interacting human proteins indicated an abundance of protein domains, providing opportunities for interspecific domain-domain interactions. Moreover, these interactions do not always occur with high-affinity, as we observed that bacteria-interacting human proteins are rich in protein-disorder content, which correlates positively with the number of interacting pathogen proteins, facilitating low-affinity interspecific interactions. Furthermore, functional analyses of pathogen-interacting human proteins revealed an enrichment in regulation of processes like metabolism, immune system, cellular localization and transport apart from divulging functional competence to bind enzyme/protein, nucleic acids and cell adhesion molecules, necessary for host-microbial cross-talk.
Evaluating the course of the saphenous vein and nerve for risk assessment in the suture button technique
Authors: Hamada Tomo , Matsubara Hidenori , Hikichi Toshifumi , Tsuchiya Hiroyuki
Published: January 2021

The suture button technique can cause damage to the saphenous vein and nerve. We examined the location and course of the great saphenous vein using magnetic resonance imaging and determined its position at 10, 20, 30, or 40 mm proximal to the tibial plafond. We divided the region from the anterior to the posteromedial tibial edges into segments A, B, C, D, and E, and compared baseline data and vein parameters between 56 healthy (group H) and 296 symptomatic limbs (group D). At 10, 20, 30, and 40 mm proximal to the tibial plafond, segments A (53.4%), B (45.7%), C (50.0%), and D (52.6%), respectively, had the highest probability of the presence of the great saphenous vein. The mean angle of the great saphenous vein from the distal anterior to the proximal posterior side of the tibia in relation to the tibial axis was 32.4° ± 4.8°. There were no significant differences between groups H and D. These findings indicate that the position of the saphenous vein and nerve should be determined prior to performing the suture button technique on the medial side of the tibia. This can be achieved under direct visualization through a small skin incision or via ultrasound.
Exploring gene knockout strategies to identify potential drug targets using genome-scale metabolic models
Authors: Paul Abhijit , Anand Rajat , Karmakar Sonali Porey , Rawat Surender , Bairagi Nandadulal , Chatterjee Samrat
Published: January 2021

Research on new cancer drugs is performed either through gene knockout studies or phenotypic screening of drugs in cancer cell-lines. Both of these approaches are costly and time-consuming. Computational framework, e.g., genome-scale metabolic models (GSMMs), could be a good alternative to find potential drug targets. The present study aims to investigate the applicability of gene knockout strategies to be used as the finding of drug targets using GSMMs. We performed single-gene knockout studies on existing GSMMs of the NCI-60 cell-lines obtained from 9 tissue types. The metabolic genes responsible for the growth of cancerous cells were identified and then ranked based on their cellular growth reduction. The possible growth reduction mechanisms, which matches with the gene knockout results, were described. Gene ranking was used to identify potential drug targets, which reduce the growth rate of cancer cells but not of the normal cells. The gene ranking results were also compared with existing shRNA screening data. The rank-correlation results for most of the cell-lines were not satisfactory for a single-gene knockout, but it played a significant role in deciding the activity of drug against cell proliferation, whereas multiple gene knockout analysis gave better correlation results. We validated our theoretical results experimentally and showed that the drugs mitotane and myxothiazol can inhibit the growth of at least four cell-lines of NCI-60 database.
Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes
Authors: Wan Chengyao , Wen Jing , Liang Xiaolin , Xie Qiongni , Wu Wenqi , Wu Meiqing , Liu Zhenfang
Published: January 2021

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P < 0.0001), 0.7515 (P = 0.0002), 0.9647 (P < 0.0001), 0.8064 (P < 0.0001) and 0.9019 (P < 0.0001). Regarding Kaplan–Meier analysis, high miR-320c and miR-320d expression were related to shorter overall survival (OS). Moreover, multivariate analysis revealed the independent prognostic value of miR-320d for OS in MDS. The expression of miR-320 family members was up-regulated in MDS, and miR-320 family members could serve as candidate diagnostic biomarkers for MDS. High expression of miR-320d was an independent prognostic factor for OS in MDS.
Investigating the influence of physiologically relevant hydrostatic pressure on CHO cell batch culture
Authors: Shang Menglin , Kwon Taehong , Hamel Jean-Francois P. , Lim Chwee Teck , Khoo Bee Luan , Han Jongyoon
Published: January 2021

Chinese hamster ovary (CHO) cells have been the most commonly used mammalian host for large-scale commercial production of therapeutic proteins, such as monoclonal antibodies. Enhancement of productivity of these CHO cells is one of the top priorities in the biopharmaceutical industry to reduce manufacturing cost. Although there are many different methods (e.g. temperature, pH, feed) to improve protein production in CHO cells, the role of physiologically relevant hydrostatic pressure in CHO cell culture has not been reported yet. In this study, four different hydrostatic pressures (0, 30, 60, and 90 mmHg) were applied to batch CHO cells, and their cell growth/metabolism and IgG1 production were examined. Our results indicate that hydrostatic pressure can increase the maximum cell concentration by up to 50%. Moreover, overall IgG1 concentration on Day 5 showed that 30 mmHg pressure can increase IgG1 production by 26%. The percentage of non-disulphide-linked antibody aggregates had no significant change under pressure. Besides, no significant difference was observed between 30 mmHg and no pressure conditions in terms of cell clumping formation. All these findings are important for the optimization of fed-batch or perfusion culture for directing cell growth and improving antibody production.
Measurement of emotional states of zebrafish through integrated analysis of motion and respiration using bioelectric signals
Authors: Soh Zu , Matsuno Motoki , Yoshida Masayuki , Furui Akira , Tsuji Toshio
Published: January 2021

Fear, anxiety, and preference in fish are generally evaluated by video-based behavioural analyses. We previously proposed a system that can measure bioelectrical signals, called ventilatory signals, using a 126-electrode array placed at the bottom of an aquarium and achieved cameraless real-time analysis of motion and ventilation. In this paper, we propose a method to evaluate the emotional state of fish by combining the motion and ventilatory indices obtained with the proposed system. In the experiments, fear/anxiety and appetitive behaviour were induced using alarm pheromone and ethanol, respectively. We also found that the emotional state of the zebrafish can be expressed on the principal component (PC) space extracted from the defined indices. The three emotional states were discriminated using a model-based machine learning method by feeding the PCs. Based on discrimination performed every 5 s, the F-score between the three emotional states were as follows: 0.84 for the normal state, 0.76 for the fear/anxiety state, and 0.59 for the appetitive behaviour. These results indicate the effectiveness of combining physiological and motional indices to discriminate the emotional states of zebrafish.
Synthesis of SiC/SiO2 core–shell nanowires with good optical properties on Ni/SiO2/Si substrate via ferrocene pyrolysis at low temperature
Authors: Chen Bo-Yu , Chi Chong-Chi , Hsu Wen-Kuang , Ouyang Hao
Published: January 2021

In this study, the high-density SiC/SiO2 core–shell nanowires were synthesized on the nickel coated SiO2 (100 nm)/Si substrate by chemical vapor deposition (CVD) method with ferrocene precursor at temperature 1000 °C compared to previous studies (1300–1600 °C). The present work provides an efficient strategy for the production of SiC/SiO2 nanowires with uniform morphology and good optical properties, where the Ni layer plays important roles for this fabrication at low temperature which reduces the decomposition temperature of hydrocarbon gases and improves the growth quality of SiC nanowires. The as-synthesized SiC/SiO2 nanowires consist of single crystal 3C structures as well as 3C structures with defects along [111] direction. In the photoluminescence (PL) spectrum, the SiC/SiO2 core–shell nanowires revealed an obvious blueshift. The blueshift is due to the formation of nanoscale silicon carbide polytypism caused by the stacking faults in 3C–SiC and the nanoscale polytypism also caused the transition from indirect to direct bandgap which explains why the stacking faults percentage in SiC confirmed from X-ray diffraction (XRD) is 19%, but ultimately makes the strongest emission intensity. Finally, the PL characteristics are further improved by changing the diameter of the SiC nanowire and etching and an approximate model followed by the vapor–liquid–solid (VLS) mechanism was proposed to explain the possible growth mechanism of the SiC/SiO2 nanowires.
Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
Authors: Kadelka Sarah , Dahari Harel , Ciupe Stanca M.
Published: January 2021

The RNA interference (RNAi) drug ARC-520 was shown to be effective in reducing serum hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HBeAg-positive patients treated with a single dose of ARC-520 and daily nucleosidic analogue (entecavir). To provide insights into HBV dynamics under ARC-520 treatment and its efficacy in blocking HBV DNA, HBsAg, and HBeAg production we developed a multi-compartmental pharmacokinetic–pharamacodynamic model and calibrated it with frequent measured HBV kinetic data. We showed that the time-dependent single dose ARC-520 efficacies in blocking HBsAg and HBeAg are more than 96% effective around day 1, and slowly wane to 50% in 1–4 months. The combined single dose ARC-520 and entecavir effect on HBV DNA was constant over time, with efficacy of more than 99.8%. The observed continuous HBV DNA decline is entecavir mediated, the strong but transient HBsAg and HBeAg decays are ARC-520 mediated. The modeling framework may help assess ongoing RNAi drug development for hepatitis B virus infection.
Technical feasibility of radiomics signature analyses for improving detection of occult tonsillar cancer
Authors: Lee Jeong Hoon , Ha Eun Ju , Roh Jin , Lee Su Jin , Jang Jeon Yeob
Published: January 2021

Diagnosis of occult palatine tonsil squamous cell carcinoma (SCC) using conventional magnetic resonance imaging (MRI) is difficult in patients with cervical nodal metastasis from an unknown primary site at presentation. We aimed to establish a radiomics approach based on MRI features extracted from the volume of interest in these patients. An Elastic Net model was developed to differentiate between normal palatine tonsils and occult palatine tonsil SCC. The diagnostic performances of the model with radiomics features extracted from T1-weighted image (WI), T2WI, contrast-enhanced T1WI, and an apparent diffusion coefficient (ADC) map had area under the receiver operating characteristic (AUROC) curve values of 0.831, 0.840, 0.781, and 0.807, respectively, for differential diagnosis. The model with features from the ADC alone showed the highest sensitivity of 90.0%, while the model with features from T1WI + T2WI + contrast-enhanced T1WI showed the highest AUROC of 0.853. The added sensitivity of the radiomics feature analysis were 34.6% over that of conventional MRI to detect occult palatine tonsil SCC. Therefore, we concluded that adding radiomics feature analysis to MRI may improve the detection sensitivity for occult palatine tonsil SCC in patients with a cervical nodal metastasis from cancer of an unknown primary site.
Respiration characteristics and its responses to hydrothermal seasonal changes in reconstructed soils
Authors: Lei Na , Li Juan , Chen Tianqing
Published: January 2021

Seasonal changes in respiration and the components of four reconstructed soils (gravel + meteorite + lou; gravel + shale + lou; gravel + sand + lou; and gravel + soft rock + lou) in barren gravel land were monitored using the soil carbon flux measurement system. The results showed that (1) the monthly average respiration rate and the rates of the components in the four reconstructed soils were the highest in summer and lowest in winter. In winter, the monthly average respiration rates of the four reconstructed soils were not different (p > 0.05). In summer, the monthly average respiration rate of the sand or meteorite reconstructed soil was different from that of the other three (p < 0.05). (2) The heterotrophic and autotrophic respiration rates were different between the four reconstructed soils (p < 0.05). The contribution of heterotrophic respiration to total respiration in the four reconstructed soils was greater than that of autotrophic respiration throughout the year. In winter, autotrophic respiration accounts for the smallest proportion of total respiration. As the temperature rises, the proportion of autotrophic respiration to total respiration gradually increases and peaks in summer. In summer, the proportion of heterotrophic respiration in the total respiration is the smallest. With the decrease in temperature, the proportion of heterotrophic respiration in total respiration gradually increases and peaks in winter. (3) The maximum and minimum values of the monthly average respiration rate of the four reconstructed soils coincided with the months of maximum and minimum soil temperature. The soil volumetric water content changed with the amount of precipitation. The correlation between soil respiration and temperature was greater than that between soil respiration and volumetric water content. (4) The correlation in seasonal variation between respiration of the four remodelled soils and hydrothermal factors in the study area can be characterised by an exponential function and power-exponential function.
Response of bacterial and fungal communities to high petroleum pollution in different soils
Authors: Galitskaya Polina , Biktasheva Liliya , Blagodatsky Sergey , Selivanovskaya Svetlana
Published: January 2021

Petroleum pollution of soils is a major environmental problem. Soil microorganisms can decompose a significant fraction of petroleum hydrocarbons in soil at low concentrations (1–5%). This characteristic can be used for soil remediation after oil pollution. Microbial community dynamics and functions are well studied in cases of moderate petroleum pollution, while cases with heavy soil pollution have received much less attention. We studied bacterial and fungal successions in three different soils with high petroleum contents (6 and 25%) in a laboratory experiment. The proportion of aliphatic and aromatic compounds decreased by 4–7% in samples with 6% pollution after 120 days of incubation but remained unchanged in samples with 25% hydrocarbons. The composition of the microbial community changed significantly in all cases. Oil pollution led to an increase in the relative abundance of bacteria such as Actinobacteria and the candidate TM7 phylum (Saccaribacteria) and to a decrease in that of Bacteroidetes. The gene abundance (number of OTUs) of oil-degrading bacteria (Rhodococcus sp., candidate class TM7-3 representative) became dominant in all soil samples, irrespective of the petroleum pollution level and soil type. The fungal communities in unpolluted soil samples differed more significantly than the bacterial communities. Nonmetric multidimensional scaling revealed that in the polluted soil, successions of fungal communities differed between soils, in contrast to bacterial communities. However, these successions showed similar trends: fungi capable of lignin and cellulose decomposition, e.g., from the genera Fusarium and Mortierella, were dominant during the incubation period.
Potential use of molecular and structural characterization of the gut bacterial community for postmortem interval estimation in Sprague Dawley rats
Authors: Li Huan , Zhang Siruo , Liu Ruina , Yuan Lu , Wu Di , Yang E. , Yang Han , Ullah Shakir , Ishaq Hafiz Muhammad , Liu Hailong , Wang Zhenyuan , Xu Jiru
Published: January 2021

Once the body dies, the indigenous microbes of the host begin to break down the body from the inside and play a key role thereafter. This study aimed to investigate the probable shift in the composition of the rectal microbiota at different time intervals up to 15 days after death and to explore bacterial taxa important for estimating the time since death. At the phylum level, Proteobacteria and Firmicutes showed major shifts when checked at 11 different intervals and emerged at most of the postmortem intervals. At the species level, Enterococcus faecalis and Proteus mirabilis showed a downward and upward trend, respectively, after day 5 postmortem. The phylum-, family-, genus-, and species-taxon richness decreased initially and then increased considerably. The turning point occurred on day 9, when the genus, rather than the phylum, family, or species, provided the most information for estimating the time since death. We constructed a prediction model using genus-level data from high-throughput sequencing, and seven bacterial taxa, namely, Enterococcus, Proteus, Lactobacillus, unidentified Clostridiales, Vagococcus, unidentified Corynebacteriaceae, and unidentified Enterobacteriaceae, were included in this model. The abovementioned bacteria showed potential for estimating the shortest time since death.
Highly efficient self-powered perovskite photodiode with an electron-blocking hole-transport NiOx layer
Authors: Afzal Amir Muhammad , Bae In-Gon , Aggarwal Yushika , Park Jaewoo , Jeong Hye-Ryeon , Choi Eun Ha , Park Byoungchoo
Published: January 2021

Hybrid organic–inorganic perovskite materials provide noteworthy compact systems that could offer ground-breaking architectures for dynamic operations and advanced engineering in high-performance energy-harvesting optoelectronic devices. Here, we demonstrate a highly effective self-powered perovskite-based photodiode with an electron-blocking hole-transport layer (NiOx). A high value of responsivity (R = 360 mA W−1) with good detectivity (D = 2.1 × 1011 Jones) and external quantum efficiency (EQE = 76.5%) is achieved due to the excellent interface quality and suppression of the dark current at zero bias voltage owing to the NiOx layer, providing outcomes one order of magnitude higher than values currently in the literature. Meanwhile, the value of R is progressively increased to 428 mA W−1 with D = 3.6 × 1011 Jones and EQE = 77% at a bias voltage of − 1.0 V. With a diode model, we also attained a high value of the built-in potential with the NiOx layer, which is a direct signature of the improvement of the charge-selecting characteristics of the NiOx layer. We also observed fast rise and decay times of approximately 0.9 and 1.8 ms, respectively, at zero bias voltage. Hence, these astonishing results based on the perovskite active layer together with the charge-selective NiOx layer provide a platform on which to realise high-performance self-powered photodiode as well as energy-harvesting devices in the field of optoelectronics.
Particulate matter emission sources and meteorological parameters combine to shape the airborne bacteria communities in the Ligurian coast, Italy
Authors: Palladino Giorgia , Morozzi Pietro , Biagi Elena , Brattich Erika , Turroni Silvia , Rampelli Simone , Tositti Laura , Candela Marco
Published: January 2021

Aim of the present study is to explore how the chemical composition of particulate matter (PM) and meteorological conditions combine in shaping the air microbiome in Savona (Italy), a medium-size, heavily inhabited urban settlement, hosting a wide range of industrial activities. In particular, the air microbiome and PM10 were monitored over six months in 2012. During that time, the air microbiome was highly dynamic, fluctuating between different compositional states, likely resulting from the aerosolization of different microbiomes emission sources. According to our findings, this dynamic process depends on the combination of local meteorological parameters and particle emission sources, which may affect the prevalent aerosolized microbiomes, thus representing further fundamental tools for source apportionment in a holistic approach encompassing chemical as well as microbiological pollution. In particular, we showed that, in the investigated area, industrial emissions and winds blowing from the inlands combine with an airborne microbiome which include faecal microbiomes components, suggesting multiple citizens’ exposure to both chemicals and microorganisms of faecal origin, as related to landscape exploitation and population density. In conclusion, our findings support the need to include monitoring of the air microbiome compositional structure as a relevant factor for the final assessment of local air quality.
LAMP-based foldable microdevice platform for the rapid detection of Magnaporthe oryzae and Sarocladium oryzae in rice seed
Authors: Prasannakumar M. K. , Parivallal P. Buela , Pramesh Devanna , Mahesh H. B. , Raj Edwin
Published: January 2021

Rice blast (caused by Magnaporthe oryzae) and sheath rot diseases (caused by Sarocladium oryzae) are the most predominant seed-borne pathogens of rice. The detection of both pathogens in rice seed is essential to avoid production losses. In the present study, a microdevice platform was designed, which works on the principles of loop-mediated isothermal amplification (LAMP) to detect M. oryzae and S. oryzae in rice seeds. Initially, a LAMP, polymerase chain reaction (PCR), quantitative PCR (qPCR), and helicase dependent amplification (HDA) assays were developed with primers, specifically targeting M. oryzae and S. oryzae genome. The LAMP assay was highly efficient and could detect the presence of M. oryzae and S. oryzae genome at a concentration down to 100 fg within 20 min at 60 °C. Further, the sensitivity of the LAMP, HDA, PCR, and qPCR assays were compared wherein; the LAMP assay was highly sensitive up to 100 fg of template DNA. Using the optimized LAMP assay conditions, a portable foldable microdevice platform was developed to detect M. oryzae and S. oryzae in rice seeds. The foldable microdevice assay was similar to that of conventional LAMP assay with respect to its sensitivity (up to 100 fg), rapidity (30 min), and specificity. This platform could serve as a prototype for developing on-field diagnostic kits to be used at the point of care centers for the rapid diagnosis of M. oryzae and S. oryzae in rice seeds. This is the first study to report a LAMP-based foldable microdevice platform to detect any plant pathogens.
Chlamydia trachomatis intra-bacterial and total plasmid copy number in clinical urogenital samples
Authors: Dirks J. A. M. C. , Janssen K. , Hoebe C. J. P. A. , Geelen T. H. B. , Lucchesi M. , Dukers-Muijrers N. H. T. M. , Wolffs P. F. G.
Published: January 2021

Chlamydia trachomatis (CT) increases its plasmid numbers when stressed, as occurs in clinical trachoma samples. Most CT tests target the plasmid to increase the test sensitivity, but some only target the chromosome. We investigated clinical urogenital samples for total plasmid copy numbers to assess its diagnostic value and intra-bacterial plasmid copy numbers to assess its natural variation. Both plasmid and chromosome copies were quantified using qPCR, and the plasmid:chromosome ratio (PCr) calculated in two cohorts: (1) 383 urogenital samples for the total PCR (tPCr), and (2) 42 vaginal swabs, with one half treated with propium-monoazide (PMA) to prevent the quantification of extracellular DNA and the other half untreated to allow for both tPCr and intra-bacterial PCr (iPCr) quantification. Mann–Whitney U tests compared PCr between samples, in relation to age and gender. Cohort 1: tPCr varied greatly (1–677, median 16). Median tPCr was significantly higher in urines than vaginal swabs (32 vs. 11, p < 0.001). Cohort 2: iPCr was more stable than tPCr (range 0.1–3 vs. 1–11). To conclude, tPCr in urogenital samples was much more variable than previously described. Transport time and temperature influences DNA degradation, impacting chromosomal DNA more than plasmids and urine more than vaginal samples. Data supports a plasmid target in CT screening assays to increase clinical sensitivity.
An experimental validation of partial discharge localization using electromagnetic time reversal
Authors: Karami Hamidreza , Azadifar Mohammad , Rubinstein Marcos , Rachidi Farhad
Published: January 2021

The localization of partial discharge (PD) sources is of importance for the monitoring and maintenance of power transformers. Time difference of arrival (TDoA) based methods are widely adopted in the literature for the localization of PDs. Recently, time reversal (TR) was suggested as an efficient means to locate PD sources. As opposed to TDoA, which needs at least 4 sensors, TR is able to locate PD sources in power transformers with only one sensor. Moreover, it needs neither line-of-sight wave propagation from the PD sources to the sensor nor time synchronization. In this study, we present for the first time an experimental demonstration of the ability of the TR process to locate PD sources. A typical TR process includes three steps: (1) recording the PD-emitted field by a sensor, (2) time reversing and back injecting the signal into the medium, (3) using a proper criterion to obtain the focusing point which corresponds to the location of the PD source. In this work, we present a laboratory setup in which steps one and two are performed experimentally, both in the frequency and in the time domain. The obtained peak electric field value is used as a criterion in the third step. It is found that the accuracy of the proposed method is better than 2.5 cm in a transformer tank model with dimensions 73 × 73 × 103 cm3. The effects of the presence of scatterers such as transformer windings are also investigated experimentally and found not to affect the location accuracy of the method.
Identification of a novel QTL and candidate gene associated with grain size using chromosome segment substitution lines in rice
Authors: Wang Dianwen , Sun Wenqiang , Yuan Zhiyang , Sun Qiang , Fan Kai , Zhang Chaopu , Yu Sibin
Published: January 2021

Rice is one of the staple crops in the world. Grain size is an important determinant of rice grain yield, but the genetic basis of the grain size remains unclear. Here, we report a set of chromosome segment substitution lines (CSSL) developed in the genetic background of the genome-sequenced indica cultivar Zhenshan 97. Genotyping of the CSSLs by single nucleotide polymorphism array shows that most carry only one or two segments introduced from the genome-sequenced japonica cultivar Nipponbare. Using this population and the high-density markers, a total of 43 quantitative trait loci were identified for seven panicle- and grain-related traits. Among these loci, the novel locus qGL11 for grain length and thousand-grain weight was validated in a CSSL-derived segregating population and finely mapped to a 25-kb region that contains an IAA-amido synthetase gene OsGH3.13, This gene exhibited a significant expression difference in the young panicle between the near-isogenic lines that carry the contrasting Zhenshan 97 and Nipponbare alleles at qGL11. Expression and sequence analyses suggest that this gene is the most likely candidate for qGL11. Furthermore, several OsGH3.13 mutants induced by a CRISPR/Cas9 approach in either japonica or indica exhibit an increased grain length and thousand-grain weight, thus enhancing the final grain yield per plant. These findings provide insights into the genetic basis of grain size for the improvement of yield potential in rice breeding programs.
Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
Authors: Matsumoto Kotaro , Yasuoka Hidekata , Yoshimoto Keiko , Suzuki Katsuya , Takeuchi Tsutomu
Published: January 2021

Neutrophils form neutrophil extracellular traps (NETs), which are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Recent reports suggest that platelets stimulated via toll-like receptor (TLR) pathways can induce NETs formation. However, the mechanism underlying the involvement of platelets in NETs formation in AAV is unknown. We investigated the role of platelets in the pathogenesis of AAV. Platelets from AAV patients and healthy controls (HCs) were co-cultured with peripheral neutrophils, and NETs formation was visualized and quantified. The expression levels of TLRs on platelets were examined by flow cytometry. Platelets were treated with a TLR agonist, platelet-derived humoral factor, CXCL4 (platelet factor 4: PF4), and/or anti-CXCL4 antibody to investigate the effects of TLR–CXCL4 signaling on NETs formation. Platelets from AAV significantly upregulated NETs formation in vitro. Flow cytometric analysis revealed that the proportion of TLR9 positive platelets was significantly higher in AAV than HCs. CXCL4 released from TLR9 agonist-stimulated platelets was significantly enhanced in AAV, which subsequently increased NETs formation. Further, neutralizing anti-CXCL4 antibody significantly inhibited NETs formation enhanced by platelets from AAV. TLR9 signaling and CXCL4 release underlie the key role that platelets play in NETs formation in the pathogenesis of AAV.
Elevated temperatures diminish the effects of a highly resistant rice variety on the brown planthopper
Authors: Horgan Finbarr G. , Arida Arriza , Ardestani Goli , Almazan Maria Liberty P.
Published: January 2021

This study compares the effects of temperature (constant at 15, 20, 25, 30 and 35 °C) on adult longevity, oviposition, and nymph development of the brown planthopper, Nilaparvata lugens, on susceptible and resistant rice varieties. The resistant variety contained the BPH32 gene. In our experiments, nymphs failed to develop to adults at 15, 20 and 35 °C on either variety. Host resistance had its greatest effect in reducing adult survival at 20–25 °C and its greatest effect in reducing nymph weight gain at 25 °C. This corresponded with optimal temperatures for adult survival (20–25 °C) and nymph development (25–30 °C). At 25 and 30 °C, adult females achieved up to three oviposition cycles on the susceptible variety, but only one cycle on the resistant variety. Maximum egg-laying occurred at 30 °C due to larger numbers of egg batches produced during the first oviposition cycle on both the susceptible and resistant varieties, and larger batches during the second and third oviposition cycles on the susceptible variety; however, resistance had its greatest effect in reducing fecundity at 25 °C. This revealed a mismatch between the optimal temperatures for resistance and for egg production in immigrating females. Increasing global temperatures could reduce the effectiveness of anti-herbivore resistance in rice and other crops where such mismatches occur.
Discrimination of standing postures between young and elderly people based on center of pressure
Authors: Fujio Kimiya , Takeuchi Yahiko
Published: January 2021

Posturography is utilized to assess the influence of aging on postural control. Although this measurement is advantageous for finding group-level differences between the young and the elderly, it is unclear whether it has the potential to differentiate elderly individuals who are affected by various impacts of aging. The purpose of this study was to determine the utility of posturography to discriminate elderly individuals from young adults. We investigated the performances of the random forest classifiers constructed from center of pressure (COP) indices for discriminating standing postures between healthy elderly and young people. Postural sways in 19 young and 31 community-dwelling elderly participants were measured using force plates in 4 standing conditions: bipedal standing, standing on a narrow base, standing on foam rubber, and standing with eyes closed. We further verified the informative predictors that contributed to the prediction model. As the results, the classifier based on the COP indices for standing on foam rubber showed the best performance (accuracy: 93.4%, sensitivity: 94.4%, specificity: 93.6%, area under the curve of receiving operator characteristics: 0.95), followed by the classifier for standing with eyes closed. The informative predictors varied depending on the postural conditions. Our findings demonstrated the potential of posturography for identifying elderly postures. The evaluation of sensory re-weighting using the appropriate COP indices would be a useful clinical tool for detecting the progress of aging on postural control.
A study on the bio-applicability of aqueous-dispersed van der Waals 1-D material Nb2Se9 using poloxamer
Authors: Chae Sudong , Oh Seungbae , Choi Kyung Hwan , Lee Jin Woong , Jeon Jiho , Liu Zhixiang , Wang Cong , Lim Changmo , Dong Xue , Woo Chaeheon , Asghar Ghulam , Shi Liyi , Kang Joohoon , Kim Sung Jae , Song Si Young , Lee Jung Heon , Yu Hak Ki , Choi Jae-Young
Published: January 2021

In this research, dispersion of a new type of one-dimensional inorganic material Nb2Se9, composed of van der Waals bonds, in aqueous solution for bio-application study were studied. To disperse Nb2Se9, which exhibits hydrophobic properties in water, experiments were carried out using a block copolymer (poloxamer) as a dispersant. It was confirmed that PPO, the hydrophobic portion of Poloxamer, was adsorbed onto the surface of Nb2Se9, and PEO, the hydrophilic portion, induced steric hinderance to disperse Nb2Se9 to a size of 10 nm or less. To confirm the adaptability of muscle cells C2C12 to the dispersed Nb2Se9 using poloxamer 188 as dispersant, a MTT assay and a live/dead assay were performed, demonstrating improvement in the viability and proliferation of C2C12 cells.
Elastic flow instabilities and macroscopic textures in graphene oxide lyotropic liquid crystals
Authors: Wychowaniec Jacek K. , Iliut Maria , Borek Bartłomiej , Muryn Christopher , Mykhaylyk Oleksandr O. , Edmondson Steve , Vijayaraghavan Aravind
Published: January 2021

Graphene oxide (GO) forms a well-aligned lyotropic liquid crystal (LC) phase in aqueous dispersions at relatively low concentrations. Under a remarkably wide range of shear rates, we report hitherto unobserved shear-induced polarized light image patterns, a Maltese cross combined with shear banding, recorded in real time and in situ during rheological measurements. This is shown to be a result of elastic flow instabilities that manifest as a helical flow in alternating bands of left- and right-handed helices, arising from a combination of shear flow and Taylor-type vortex flow. The instability is observed for LCs formed from large aspect ratio GO particles owing to their unique viscoelastic properties, but not for smaller aspect ratio particles. This phenomenon coincides with rheopecty and anomalous small-angle X-ray scattering patterns under shear flow, which confirm the instabilities. The results presented here could lead to advanced control over macroscopic periodic alignment in technologically relevant dispersions of two-dimensional material particles.
Deep learning-enabled medical computer vision
Authors: Esteva Andre , Chou Katherine , Yeung Serena , Naik Nikhil , Madani Ali , Mottaghi Ali , Liu Yun , Topol Eric , Dean Jeff , Socher Richard
Published: January 2021

A decade of unprecedented progress in artificial intelligence (AI) has demonstrated the potential for many fields—including medicine—to benefit from the insights that AI techniques can extract from data. Here we survey recent progress in the development of modern computer vision techniques—powered by deep learning—for medical applications, focusing on medical imaging, medical video, and clinical deployment. We start by briefly summarizing a decade of progress in convolutional neural networks, including the vision tasks they enable, in the context of healthcare. Next, we discuss several example medical imaging applications that stand to benefit—including cardiology, pathology, dermatology, ophthalmology–and propose new avenues for continued work. We then expand into general medical video, highlighting ways in which clinical workflows can integrate computer vision to enhance care. Finally, we discuss the challenges and hurdles required for real-world clinical deployment of these technologies.
Development and validation of an interpretable neural network for prediction of postoperative in-hospital mortality
Authors: Lee Christine K. , Samad Muntaha , Hofer Ira , Cannesson Maxime , Baldi Pierre
Published: January 2021

While deep neural networks (DNNs) and other machine learning models often have higher accuracy than simpler models like logistic regression (LR), they are often considered to be “black box” models and this lack of interpretability and transparency is considered a challenge for clinical adoption. In healthcare, intelligible models not only help clinicians to understand the problem and create more targeted action plans, but also help to gain the clinicians’ trust. One method of overcoming the limited interpretability of more complex models is to use Generalized Additive Models (GAMs). Standard GAMs simply model the target response as a sum of univariate models. Inspired by GAMs, the same idea can be applied to neural networks through an architecture referred to as Generalized Additive Models with Neural Networks (GAM-NNs). In this manuscript, we present the development and validation of a model applying the concept of GAM-NNs to allow for interpretability by visualizing the learned feature patterns related to risk of in-hospital mortality for patients undergoing surgery under general anesthesia. The data consists of 59,985 patients with a feature set of 46 features extracted at the end of surgery to which we added previously not included features: total anesthesia case time (1 feature); the time in minutes spent with mean arterial pressure (MAP) below 40, 45, 50, 55, 60, and 65 mmHg during surgery (6 features); and Healthcare Cost and Utilization Project (HCUP) Code Descriptions of the Primary current procedure terminology (CPT) codes (33 features) for a total of 86 features. All data were randomly split into 80% for training (n = 47,988) and 20% for testing (n = 11,997) prior to model development. Model performance was compared to a standard LR model using the same features as the GAM-NN. The data consisted of 59,985 surgical records, and the occurrence of in-hospital mortality was 0.81% in the training set and 0.72% in the testing set. The GAM-NN model with HCUP features had the highest area under the curve (AUC) 0.921 (0.895–0.95). Overall, both GAM-NN models had higher AUCs than LR models, however, had lower average precisions. The LR model without HCUP features had the highest average precision 0.217 (0.136–0.31). To assess the interpretability of the GAM-NNs, we then visualized the learned contributions of the GAM-NNs and compared against the learned contributions of the LRs for the models with HCUP features. Overall, we were able to demonstrate that our proposed generalized additive neural network (GAM-NN) architecture is able to (1) leverage a neural network’s ability to learn nonlinear patterns in the data, which is more clinically intuitive, (2) be interpreted easily, making it more clinically useful, and (3) maintain model performance as compared to previously published DNNs.
Clinical outcomes of digital sensor alerting systems in remote monitoring: a systematic review and meta-analysis
Authors: Iqbal Fahad M. , Lam Kyle , Joshi Meera , Khan Sadia , Ashrafian Hutan , Darzi Ara
Published: January 2021

Advances in digital technologies have allowed remote monitoring and digital alerting systems to gain popularity. Despite this, limited evidence exists to substantiate claims that digital alerting can improve clinical outcomes. The aim of this study was to appraise the evidence on the clinical outcomes of digital alerting systems in remote monitoring through a systematic review and meta-analysis. A systematic literature search, with no language restrictions, was performed to identify studies evaluating healthcare outcomes of digital sensor alerting systems used in remote monitoring across all (medical and surgical) cohorts. The primary outcome was hospitalisation; secondary outcomes included hospital length of stay (LOS), mortality, emergency department and outpatient visits. Standard, pooled hazard ratio and proportion of means meta-analyses were performed. A total of 33 studies met the eligibility criteria; of which, 23 allowed for a meta-analysis. A 9.6% mean decrease in hospitalisation favouring digital alerting systems from a pooled random effects analysis was noted. However, pooled weighted mean differences and hazard ratios did not reproduce this finding. Digital alerting reduced hospital LOS by a mean difference of 1.043 days. A 3% mean decrease in all-cause mortality from digital alerting systems was noted. There was no benefit of digital alerting with respect to emergency department or outpatient visits. Digital alerts can considerably reduce hospitalisation and length of stay for certain cohorts in remote monitoring. Further research is required to confirm these findings and trial different alerting protocols to understand optimal alerting to guide future widespread implementation.
Backslide or forward progress? Virtual care at U.S. healthcare systems beyond the COVID-19 pandemic
Authors: Dorn Spencer D.
Published: January 2021

The COVID-19 pandemic forced most U.S. healthcare systems to quickly pivot to virtual care. However, since peaking in late April, care has largely shifted back to in-person. Health systems are now challenged to further develop and integrate useful, usable, and sustainable virtual care tools into their broader care model in ways that benefit their organizations and the communities they serve.
Peptide signaling without feedback in signal production operates as a true quorum sensing communication system in Bacillus subtilis
Authors: Dogsa Iztok , Spacapan Mihael , Dragoš Anna , Danevčič Tjaša , Pandur Žiga , Mandic-Mulec Ines
Published: January 2021

Bacterial quorum sensing (QS) is based on signal molecules (SM), which increase in concentration with cell density. At critical SM concentration, a variety of adaptive genes sharply change their expression from basic level to maximum level. In general, this sharp transition, a hallmark of true QS, requires an SM dependent positive feedback loop, where SM enhances its own production. Some communication systems, like the peptide SM-based ComQXPA communication system of Bacillus subtilis, do not have this feedback loop and we do not understand how and if the sharp transition in gene expression is achieved. Based on experiments and mathematical modeling, we observed that the SM peptide ComX encodes the information about cell density, specific cell growth rate, and even oxygen concentration, which ensure power-law increase in SM production. This enables together with the cooperative response to SM (ComX) a sharp transition in gene expression level and this without the SM dependent feedback loop. Due to its ultra-sensitive nature, the ComQXPA can operate at SM concentrations that are 100–1000 times lower than typically found in other QS systems, thereby substantially reducing the total metabolic cost of otherwise expensive ComX peptide.
Combinatorial targeting of multiple myeloma by complementing T cell engaging antibody fragments
Authors: Geis Maria , Nowotny Boris , Bohn Marc-Dominic , Kouhestani Dina , Einsele Hermann , Bumm Thomas , Stuhler Gernot
Published: January 2021

Bispecific T cell engaging antibodies (BiTEs) address tumor associated antigens that are over-expressed on cancer but that can also be found on healthy tissues, causing substantial on-target/off-tumor toxicities. To overcome this hurdle, we recently introduced hemibodies, a pair of complementary antibody fragments that redirect T cells against cancer-defining antigen combinations. Here we show that hemibodies addressing CD38 and SLAMF7 recruit T cells for the exquisite elimination of dual antigen positive multiple myeloma cells while leaving single antigen positive bystanders unharmed. Moreover, CD38 and SLAMF7 targeting BiTEs, but not hemibodies induce massive cytokine release and T cell fratricide reactions, a major drawback of T cell recruiting strategies. Together, we provide evidence in vitro and in vivo that hemibodies can be developed for the effective and highly specific immunotherapy of multiple myeloma.