bluuebunny/crossref_metadata_2025_split huggingface dataset:
The global population of SARS-CoV-2 is composed of six major subtypes
Authors: Morais Ivair José , Polveiro Richard Costa , Souza Gabriel Medeiros , Bortolin Daniel Inserra , Sassaki Flávio Tetsuo , Lima Alison Talis Martins 
Published: October 2020

AbstractThe World Health Organization characterized COVID-19 as a pandemic in March 2020, the second pandemic of the twenty-first century. Expanding virus populations, such as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms, imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for robust clustering. Here, we propose subdividing the global SARS-CoV-2 population into six well-defined subtypes and 10 poorly represented genotypes named tentative subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons and structural (spike and nucleocapsid) and accessory (ORF8) genes. The six subtypes and the additional genotypes showed amino acid replacements that might have phenotypic implications. Notably, three mutations (one of them in the Spike protein) were responsible for the geographical segregation of subtypes. We hypothesize that the virus subtypes detected in this study are records of the early stages of SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing candidate vaccines or drugs.
Systematic investigation of promoter substitutions resulting from somatic intrachromosomal structural alterations in diverse human cancers
Authors: Alaei-Mahabadi Babak , Elliott Kerryn , Larsson Erik 
Published: October 2020

AbstractOne of the ways in which genes can become activated in tumors is by somatic structural genomic rearrangements leading to promoter swapping events, typically in the context of gene fusions that cause a weak promoter to be substituted for a strong promoter. While identifiable by whole genome sequencing, limited availability of this type of data has prohibited comprehensive study of the phenomenon. Here, we leveraged the fact that copy number alterations (CNAs) arise as a result of structural alterations in DNA, and that they may therefore be informative of gene rearrangements, to pinpoint recurrent promoter swapping at a previously intractable scale. CNA data from nearly 9500 human tumors was combined with transcriptomic sequencing data to identify several cases of recurrent activating intrachromosomal promoter substitution events, either involving proper gene fusions or juxtaposition of strong promoters to gene upstream regions. Our computational screen demonstrates that a combination of CNA and expression data can be useful for identifying novel fusion events with potential driver roles in large cancer cohorts.
A device for surveillance of vascular access sites for bleeding: results from a clinical evaluation trial
Authors: Chionh Chang Yin , Soh Desilyn Yuqing , Tan Chee How , Khaw Jien-Yi , Wong Ying Ching ,   CREMERE Group, Roy Debajyoti Malakar , Koduri Sreekanth , Ng Alvin Kok Heong , Poh Cheng Boon , Ng Chee Yong , Yeon Wenxiang , Foong Shaohui 
Published: October 2020

AbstractPost-procedural wound haemorrhage is a potentially life-threatening complication. For haemodialysis patients, bleeding is often encountered after vascular access procedures and fatal episodes have been reported. Visual monitoring for bleeding is manpower intensive and bleeding episodes may still be missed between inspections. A device, Blood WArning Technology with Continuous Haemoglobin sensor (BWATCH), was developed to detect bleeding from wounds. This a prospective, observational clinical trial on patients who have had a dialysis catheter inserted or removed. The battery-powered, disc-shaped device (43 mm diameter, 12 mm height) was placed over the dressing for at least six hours. The device detects reflected light with characteristics specific for haemoglobin and an alarm would be triggered if bleeding occurs. There were 250 participants (177 post-insertion, 73 post-removal) and 36 episodes of bleeding occurred. The device alarm was triggered in all instances but there were also 9 false alarms. Specificity was 95.8%, false positive rate was 4.2% and positive predictive value was 80.0%. Sensitivity and negative predictive value were 100% but detection failure may still occur due to improper application or device maintenance. The use of technological aids for monitoring improves patient safety and may reduce demand on manpower.
Fabrication of tri-layered electrospun polycaprolactone mats with improved sustained drug release profile
Authors: Kamath S. Manjunath , Sridhar K. , Jaison D. , Gopinath V. , Ibrahim B. K. Mohamed , Gupta Nilkantha , Sundaram A. , Sivaperumal P. , Padmapriya S. , Patil S. Shantanu 
Published: October 2020

AbstractModulation of initial burst and long term release from electrospun fibrous mats can be achieved by sandwiching the drug loaded mats between hydrophobic layers of fibrous polycaprolactone (PCL). Ibuprofen (IBU) loaded PCL fibrous mats (12% PCL-IBU) were sandwiched between fibrous polycaprolactone layers during the process of electrospinning, by varying the polymer concentrations (10% (w/v), 12% (w/v)) and volume of coat (1 ml, 2 ml) in flanking layers. Consequently, 12% PCL-IBU (without sandwich layer) showed burst release of 66.43% on day 1 and cumulative release (%) of 86.08% at the end of 62 days. Whereas, sandwich groups, especially 12% PCLSW-1 & 2 (sandwich layers—1 ml and 2 ml of 12% PCL) showed controlled initial burst and cumulative (%) release compared to 12% PCL-IBU. Moreover, crystallinity (%) and hydrophobicity of the sandwich models imparted control on ibuprofen release from fibrous mats. Further, assay for cytotoxicity and scanning electron microscopic images of cell seeded mats after 5 days showed the mats were not cytotoxic. Nuclear Magnetic Resonance spectroscopic analysis revealed weak interaction between ibuprofen and PCL in nanofibers which favors the release of ibuprofen. These data imply that concentration and volume of coat in flanking layer imparts tighter control on initial burst and long term release of ibuprofen.
Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer
Authors: Tsai Hsin-Tien , Huang Ching-Shui , Tu Chao-Chiang , Liu Chih-Yi , Huang Chi-Jung , Ho Yuan-Soon , Tu Shih-Hsin , Tseng Ling-Ming , Huang Chi-Cheng 
Published: October 2020

AbstractMicrocalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.
An analytical approach to determine the optimal duration of continuous glucose monitoring data required to reliably estimate time in hypoglycemia
Authors: Camerlingo Nunzio , Vettoretti Martina , Facchinetti Andrea , Sparacino Giovanni , Mader Julia K. , Choudhary Pratik , Del Favero Simone 
Published: October 2020

AbstractDiabetes is a chronic metabolic disease that causes blood glucose (BG) concentration to make dangerous excursions outside its physiological range. Measuring the fraction of time spent by BG outside this range, and, specifically, the time-below-range (TBR), is a clinically common way to quantify the effectiveness of therapies. TBR is estimated from data recorded by continuous glucose monitoring (CGM) sensors, but the duration of CGM recording guaranteeing a reliable indicator is under debate in the literature. Here we framed the problem as random variable estimation problem and studied the convergence of the estimator, deriving a formula that links the TBR estimation error variance with the CGM recording length. Validation is performed on CGM data of 148 subjects with type-1-diabetes. First, we show the ability of the formula to predict the uncertainty of the TBR estimate in a single patient, using patient-specific parameters; then, we prove its applicability on population data, without the need of parameters individualization. The approach can be straightforwardly extended to other similar metrics, such as time-in-range and time-above-range, widely adopted by clinicians. This strengthens its potential utility in diabetes research, e.g., in the design of those clinical trials where minimal CGM monitoring duration is crucial in cost-effectiveness terms.
Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles
Authors: Rodriguez Blanca V. , Kuehn Meta J. 
Published: October 2020

AbstractBacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such asStaphylococcus aureusand their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells.S. aureusproduce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show thatS. aureussecretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses.
Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains
Authors: Diallo Ousmane Oumou , Baron Sophie Alexandra , Dubourg Gregory , Chaudet Hervé , Halfon Philippe , Camiade Sabine , Comte Béatrice , Joubert Stéphanie , François Arnaud , Seyral Philippe , Parisot François , Casalta Jean-Paul , Ruimy Raymond , Maruejouls Christophe , Achiardy Jean-Christophe , Burignat Sophie , Carvajal Joseph , Delaunay Edouard , Meyer Sandra , Levy Pierre-Yves , Roussellier Patricia , Brunet Patrick , Bosi Claude , Stolidi Philippe , Arzouni Jean-Pierre , Gay Gisele , Hance Pierre , Colson Philippe , Raoult Didier , Rolain Jean-Marc 
Published: October 2020

AbstractThe burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann–Whitney U test, the χ2 test or the Fisher’s exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19–12.27%; p = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9–24.03%; p = 0.001) and Enterobacter cloacae (24.05–42.05%; p = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.
The vertical stratification of potential bridge vectors of mosquito-borne viruses in a central Amazonian forest bordering Manaus, Brazil
Authors: Hendy Adam , Hernandez-Acosta Eduardo , Valério Danielle , Mendonça Claudia , Costa Edson Rodrigues , Júnior José Tenaçol Andes , Assunção Flamarion Prado , Scarpassa Vera Margarete , Gordo Marcelo , Fé Nelson Ferreira , Buenemann Michaela , de Lacerda Marcus Vinícius Guimarães , Hanley Kathryn A. , Vasilakis Nikos 
Published: October 2020

AbstractThe emergence of Zika virus (ZIKV) in Latin America brought to the fore longstanding concerns that forests bordering urban areas may provide a gateway for arbovirus spillback from humans to wildlife. To bridge urban and sylvatic transmission cycles, mosquitoes must co-occur with both humans and potential wildlife hosts, such as monkeys, in space and time. We deployed BG-Sentinel traps at heights of 0, 5, 10, and 15 m in trees in a rainforest reserve bordering Manaus, Brazil, to characterize the vertical stratification of mosquitoes and their associations with microclimate and to identify potential bridge vectors. Haemagogus janthinomys and Sabethes chloropterus, two known flavivirus vectors, showed significant stratification, occurring most frequently above the ground. Psorophora amazonica, a poorly studied anthropophilic species of unknown vector status, showed no stratification and was the most abundant species at all heights sampled. High temperatures and low humidity are common features of forest edges and microclimate analyses revealed negative associations between minimum relative humidity, which was inversely correlated with maximum temperature, and the occurrence of Haemagogus and Sabethes mosquitoes. In this reserve, human habitations border the forest while tamarin and capuchin monkeys are also common to edge habitats, creating opportunities for the spillback of mosquito-borne viruses.
Mineral soil conditioner requirement and ability to adjust soil acidity
Authors: Yang Xiangdong , Feng Yashuang , Zhang Xiaohong , Sun Mingxue , Qiao Dan , Li Juan , Li Xiaoyan 
Published: October 2020

AbstractMineral soil conditioners (MSCs) are used to regulate soil acidity and improve soil quality; they are often made in sintering potassium feldspar, limestone, or dolomite, and are alkaline materials rich in silicon, calcium, potassium, and magnesium. The key point of how to apply them into farmlands is their ability to adjust soil acidity and the MSCs requirement (MSCR). In this study, inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis and X-ray diffraction (XRD) were firstly used to determine the elemental and phase compositions of the MSCs in order to establish its equivalent relationship for the depletion of soil activity (H+) and its conversion relationship with CaCO3. Secondly, the soil culture method and the improved Shoemaker Mclean Peatt–Double Buffer (SMP–DB) method were compared using a group of 14 typical acid soils in MSCR. It is investigated that the MSCs contained four alkali/alkaline earth–metal elements: Ca, Mg, K, and Na in the bound aluminosilicate form (Ca2MgAlSi2O7, Ca3(SiO3)3, KAlSiO4, and KAlSi2O6); and the depletion of 2.31 mol of H+ required 100 g of MSCs and the amount of Si–Ca–K–Mg MSC needed to deplete the same quantity of H+ was only 0.87 times that of CaCO3. Based on the calculations by using the SMP-DB method and the soil culture method, the MSCR for treating the 14 typical acid soils were in the range of 0.56–8.27 t hm−2 and 0–10.8 t hm−2, respectively. Data from both methods were highly correlated with each other and there was a good linear correlation between them, and the equation: $${{MSC}_{R}}^{{\prime}}=30.29d-0.77$$

MSC

R

′

=
30.29
d
-
0.77

could be used to calculate the MSCs requirement. The recommended MSCR was approximately 4–8, 2–6, and 1–3 t hm−2 when soil pH < 4.50, 4.50 < pH < 5.50, and pH > 5.50, respectively. The experimental and computational methods established in this study could serve as the scientific basis and theoretical guidance for the production and agricultural use of MSCs.
Using chemiluminescence imaging of cells (CLIC) for relative protein quantification
Authors: Fisher Jane , Sørensen Ole E. , Abu-Humaidan Anas H. A. 
Published: October 2020

AbstractCell physiology and cellular responses to external stimuli are partly controlled through protein binding, localization, and expression level. Thus, quantification of these processes is pivotal in understanding cellular biology and disease pathophysiology. However, it can be methodologically challenging. Immunofluorescence is a powerful technique, yet quantification by this method can be hampered by auto-fluorescence. Here we describe a simple, sensitive and robust chemiluminescence-based immunoassay (chemiluminescence imaging of cells; CLIC) for relative quantification of proteins. We first employed this method to quantify complement activation in cultured mammalian cells, and to quantify membrane protein expression, shedding, binding and internalization. Moreover, through specific membrane permeabilization we were able to quantify both cytosolic and nuclear proteins, and their translocation. We validated the CLIC quantification method by performing parallel experiments with other quantification methods like ELISA, qPCR, and immunofluorescence microscopy. The workflow of the immunoassay was found to be advantageous in certain instances when compared to these quantification methods. Since the reagents used for CLIC are common to other immunoassays with no need for specialized equipment, and due to the good linearity, dynamic range and signal stability inherent to chemiluminescence, we suggest that this assay is suitable for both small scale and high throughput relative protein quantification studies in whole cells.
Rotational symmetry of photonic bound states in the continuum
Authors: Li Liangsheng , Li Yunzhou , Zhu Yong , Yin Hongcheng 
Published: October 2020

AbstractThe bound states in the continuum (BICs) have been investigated by simulating the optical reflectivity of a tri-layer photonic crystal slab. We found that optical BICs can occur in a class of photonic crystal systems with $$c_{1}^{z}$$

c

1

z

, $$c_{2}^{z}$$

c

2

z

or $$c_{4}^{z}$$

c

4

z

rotational symmetries, which are constructed by three identical photonic crystal slabs. By applying the two mode coupled model, we obtain the reflectivity formula to fit the numerical data and evaluate the lifetime of radiation decay. In vicinity of BIC, the lifetime diverges as a power law form, when approaching the BIC point. The infinity life time of $$c_{1}^{z} {\text{ } - \text{ BIC}}$$

c

1

z

-

BIC

in the tri-layer structure indicate that it is a true BIC. The $$c_{1}^{z} {\text{ } - \text{ BIC}}$$

c

1

z

-

BIC

occurs robustly in tri-layer structures, but the resonance frequency of the BICs is dependent on the permittivity of slab, air-hole size and hole shape.
The water chemistry and microbiome of household wells in Medawachchiya, Sri Lanka, an area with high prevalence of chronic kidney disease of unknown origin (CKDu)
Authors: McDonough Liza K. , Meredith Karina T. , Nikagolla Chandima , Middleton Ryan J. , Tan Jian K. , Ranasinghe Asanga V. , Sierro Frederic , Banati Richard B. 
Published: October 2020

AbstractChronic kidney disease (CKD) of unknown etiology (CKDu) mostly affects agricultural communities in Central America, South Asia, Africa, but likely also in North America and Australia. One such area with increased CKDu prevalence is the Medawachchiya District Secretariat Division of the Anuradhapura District in the North Central Province of Sri Lanka. Recent research has focused on the presence of various microbial pathogens in drinking water as potential causal or contributing factors to CKDu, yet no study to date has performed a more comprehensive microbial and water chemistry assessment of household wells used for domestic water supply in areas of high CKDu prevalence. In this study, we describe the chemical composition and total microbial content in 30 domestic household wells in the Medawachchiya District Secretariat Division. While the chemical composition in the tested wells mostly lies within standard drinking water limits, except for high levels of fluoride (F), magnesium (Mg), sodium (Na), chloride (Cl) and calcium (Ca) in some samples, we find a frequent presence of cyanotoxin-producing Microcystis, confirming earlier studies in Sri Lanka. Since the total microbial content of drinking water also directly influences the composition of the human gut microbiome, it can be considered an important determinant of health. Several bacterial phyla were previously reported in the gut microbiome of patients with CKD. Using these bacteria phyla to define operational taxonomic units, we found that these bacteria also occur in the microbiome of the sampled well water. Based on available environmental data, our study demonstrates associations between the abundances of these bacteria with geographical distribution, well water temperature and likely fertilizer use in the local surface water catchment area of the individual household wells. Our results reinforce the recommendation that household wells with stagnant or infrequently used water should be purged prior to use for drinking water, bathing and irrigation. The latter is suggested because of the reported potential accumulation of bacterial toxins by agricultural crops. The observation that bacteria previously found in chronic kidney disease patients are also present in household wells requires a more detailed systematic study of both the human gut and drinking water microbiomes in CKDu patients, in relation to disease prevalence and progression.