bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene editing and elimination of latent herpes simplex virus in vivo
Authors: Aubert Martine , Strongin Daniel E. , Roychoudhury Pavitra , Loprieno Michelle A. , Haick Anoria K. , Klouser Lindsay M. , Stensland Laurence , Huang Meei-Li , Makhsous Negar , Tait Alexander , De Silva Feelixge Harshana S. , Galetto Roman , Duchateau Philippe , Greninger Alexander L. , Stone Daniel , Jerome Keith R. 
Published: August 2020

AbstractWe evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection. Here we show that AAV-delivered meganucleases, but not CRISPR/Cas9, mediate highly efficient gene editing of HSV, eliminating over 90% of latent virus from superior cervical ganglia. Single-cell RNA sequencing demonstrates that both HSV and individual AAV serotypes are non-randomly distributed among neuronal subsets in ganglia, implying that improved delivery to all neuronal subsets may lead to even more complete elimination of HSV. As predicted, delivery of meganucleases using a triple AAV serotype combination results in the greatest decrease in ganglionic HSV loads. The levels of HSV elimination observed in these studies, if translated to humans, would likely significantly reduce HSV reactivation, shedding, and lesions. Further optimization of meganuclease delivery and activity is likely possible, and may offer a pathway to a cure for HSV infection.
High intensity training during spaceflight: results from the NASA Sprint Study
Authors: English Kirk L. , Downs Meghan , Goetchius Elizabeth , Buxton Roxanne , Ryder Jeffrey W. , Ploutz-Snyder Robert , Guilliams Mark , Scott Jessica M. , Ploutz-Snyder Lori L. 
Published: August 2020

AbstractHistorically, International Space Station (ISS) exercise countermeasures have not fully protected astronauts’ musculoskeletal and cardiorespiratory fitness. Although these losses have been reduced on more recent missions, decreasing the time required to perform in-flight exercise would permit reallocation of that time to other tasks. To evaluate the effectiveness of a new training prescription, ISS crewmembers performed either the high intensity/lower volume integrated Sprint resistance (3 d wk−1) and aerobic (interval and continuous workouts, each 3 d wk−1 in alternating fashion) exercise program (n = 9: 8M/1F, 48 ± 7 y, 178 ± 5 cm, 77.7 ± 12.0 kg) or the standard ISS countermeasure consisting of daily resistance and aerobic exercise (n = 17: 14M/3F, 46 ± 6 y, 176 ± 6 cm, 80.6 ± 10.5 kg) during long-duration spaceflight. Bone mineral density (dual energy X-ray absorptiometry (DXA)), muscle strength (isokinetic dynamometry), muscle function (cone agility test), and cardiorespiratory fitness (VO2peak) were assessed pre- and postflight. Mixed-effects modeling was used to analyze dependent measures with alpha set at P < 0.05. After spaceflight, femoral neck bone mineral density (−1.7%), knee extensor peak torque (−5.8%), cone agility test time (+7.4%), and VO2peak (−6.1%) were decreased in both groups (simple main effects of time, all P < 0.05) with a few group × time interaction effects detected for which Sprint experienced either attenuated or no loss compared to control. Although physiologic outcomes were not appreciably different between the two exercise programs, to conserve time and optimally prepare crewmembers for the performance of physically demanding mission tasks, high intensity/lower volume training should be an indispensable component of spaceflight exercise countermeasure prescriptions.
Band gap crossover and insulator–metal transition in the compressed layered CrPS4
Authors: Susilo Resta A. , Jang Bo Gyu , Feng Jiajia , Du Qianheng , Yan Zhipeng , Dong Hongliang , Yuan Mingzhi , Petrovic Cedomir , Shim Ji Hoon , Kim Duck Young , Chen Bin 
Published: August 2020

AbstractTwo-dimensional van der Waals (vdW) magnetic materials have emerged as possible candidates for future ultrathin spintronic devices, and finding a way to tune their physical properties is desirable for wider applications. Owing to the sensitivity and tunability of the physical properties to the variation of interatomic separations, this class of materials is attractive to explore under pressure. Here, we present the observation of direct to indirect band gap crossover and an insulator–metal transition in the vdW antiferromagnetic insulator CrPS4 under pressure through in-situ photoluminescence, optical absorption, and resistivity measurements. Raman spectroscopy experiments revealed no changes in the spectral feature during the band gap crossover whereas the insulator–metal transition is possibly driven by the formation of the high-pressure crystal structure. Theoretical calculations suggest that the band gap crossover is driven by the shrinkage and rearrangement of the CrS6 octahedra under pressure. Such high tunability under pressure demonstrates an interesting interplay between structural, optical and magnetic degrees of freedom in CrPS4, and provides further opportunity for the development of devices based on tunable properties of 2D vdW magnetic materials.
A framework for monitoring the safety of water services: from measurements to security
Authors: Charles Katrina J. , Nowicki Saskia , Bartram Jamie K. 
Published: August 2020

AbstractThe sustainable developments goals (SDGs) introduced monitoring of drinking water quality to the international development agenda. At present, Escherichia coli are the primary measure by which we evaluate the safety of drinking water from an infectious disease perspective. Here, we propose and apply a framework to reflect on the purposes of and approaches to monitoring drinking water safety. To deliver SDG 6.1, universal access to safe drinking water, a new approach to monitoring is needed. At present, we rely heavily on single measures of E. coli contamination to meet a normative definition of safety. Achieving and sustaining universal access to safe drinking water will require monitoring that can inform decision making on whether services are managed to ensure safety and security of access.
Dual-modal magnetic resonance and photoacoustic tracking and outcome of transplanted tendon stem cells in the rat rotator cuff injury model
Authors: Cheng Xueqing , Xu Jinshun , Hu Ziyue , Jiang Jingzhen , Wang Zhigang , Lu Man 
Published: August 2020

AbstractStem cells have been used to promote the repair of rotator cuff injury, but their fate after transplantation is not clear. Therefore, contrast agents with good biocompatibility for labeling cell and a reliable technique to track cell are necessary. Here, we developed a micron-sized PLGA/IO MPs to label tendon stem cells (TSCs) and demonstrated that PLGA/IO MPs were safe and efficient for long-term tracking of TSCs by using dual-modal MR and Photoacoustic (PA) imaging both in vitro and in rat rotator cuff injury. Moreover, TSCs improved the repair of injury and the therapeutic effect was not affected by PLGA/IO MPs labeling. We concluded that PLGA/IO particle was a promising dual-modal MR/PA contrast for noninvasive long-term stem cell tracking.
Variational Hilbert Quantitative Phase Imaging
Authors: Trusiak Maciej , Cywińska Maria , Micó Vicente , Picazo-Bueno José Ángel , Zuo Chao , Zdańkowski Piotr , Patorski Krzysztof 
Published: August 2020

AbstractUtilizing the refractive index as the endogenous contrast agent to noninvasively study transparent cells is a working principle of emerging quantitative phase imaging (QPI). In this contribution, we propose the Variational Hilbert Quantitative Phase Imaging (VHQPI)—end-to-end purely computational add-on module able to improve performance of a QPI-unit without hardware modifications. The VHQPI, deploying unique merger of tailored variational image decomposition and enhanced Hilbert spiral transform, adaptively provides high quality map of sample-induced phase delay, accepting particularly wide range of input single-shot interferograms (from off-axis to quasi on-axis configurations). It especially promotes high space-bandwidth-product QPI configurations alleviating the spectral overlapping problem. The VHQPI is tailored to deal with cumbersome interference patterns related to detailed locally varying biological objects with possibly high dynamic range of phase and relatively low carrier. In post-processing, the slowly varying phase-term associated with the instrumental optical aberrations is eliminated upon variational analysis to further boost the phase-imaging capabilities. The VHQPI is thoroughly studied employing numerical simulations and successfully validated using static and dynamic cells phase-analysis. It compares favorably with other single-shot phase reconstruction techniques based on the Fourier and Hilbert–Huang transforms, both in terms of visual inspection and quantitative evaluation, potentially opening up new possibilities in QPI.
Magma fragmentation and particle size distributions in low intensity mafic explosions: the July/August 2015 Piton de la Fournaise eruption
Authors: Edwards Matthew J. , Pioli Laura , Harris Andrew J. L. , Gurioli Lucia , Thivet Simon 
Published: August 2020

AbstractUnderstanding magma fragmentation mechanisms in explosive eruptions is a key requirement for volcanic hazard assessment, eruption management and risk mitigation. This paper focuses on a type case small explosivity eruption (July–August 2015 eruption of Piton de la Fournaise). These eruptions, despite being often overlooked, are exceedingly frequent on local-to-global scales and constitute a significant hazard in vent-proximal areas, which are often populated by guides, tourists and, indeed, volcanologists due to their accessibility. The explosions presented here are ideal cases for the study of the dynamics of magma fragmentation and how it relates to the size distribution of scoria generated at the vent. We documented these events visually and thermally, and characterised the products through sample-return. This allowed us to describe small-scale gas bursts sending ejecta up to 30 m during intermittent lava fountains. Surface tension instabilities and inertial forces played a major role in fragmentation processes and generated particles with coarse-skewed distributions and median diameters ranging from − 8 to − 10 ϕ. However, with time distributions of particles in the most energetic fountains shifted towards more symmetrical shapes as median grains sizes became finer. Analyses of sequences of images demonstrate that the evolution of particle size distributions with time is due to instability of magma droplets and (in-flight) fragmentation.
Rapid repair of human disease-specific single-nucleotide variants by One-SHOT genome editing
Authors: Yokouchi Yuji , Suzuki Shinichi , Ohtsuki Noriko , Yamamoto Kei , Noguchi Satomi , Soejima Yumi , Goto Mizuki , Ishioka Ken , Nakamura Izumi , Suzuki Satoru , Takenoshita Seiichi , Era Takumi 
Published: August 2020

AbstractMany human diseases ranging from cancer to hereditary disorders are caused by single-nucleotide mutations in critical genes. Repairing these mutations would significantly improve the quality of life for patients with hereditary diseases. However, current procedures for repairing deleterious single-nucleotide mutations are not straightforward, requiring multiple steps and taking several months to complete. In the current study, we aimed to repair pathogenic allele-specific single-nucleotide mutations using a single round of genome editing. Using high-fidelity, site-specific nuclease AsCas12a/Cpf1, we attempted to repair pathogenic single-nucleotide variants (SNVs) in disease-specific induced pluripotent stem cells. As a result, we achieved repair of the Met918Thr SNV in human oncogene RET with the inclusion of a single-nucleotide marker, followed by absolute markerless, scarless repair of the RET SNV with no detected off-target effects. The markerless method was then confirmed in human type VII collagen-encoding gene COL7A1. Thus, using this One-SHOT method, we successfully reduced the number of genetic manipulations required for genome repair from two consecutive events to one, resulting in allele-specific repair that can be completed within 3 weeks, with or without a single-nucleotide marker. Our findings suggest that One-SHOT can be used to repair other types of mutations, with potential beyond human medicine.
Using Relaxation Time to characterize biological effects of different mutagens
Authors: Li Xinglin , Sun Shuguang , Yao Jingxia , Sun Zhengfeng 
Published: August 2020

AbstractAll kinds of mutagenic factors may cause physiological, biochemical and genetic changes of all organisms. To characterize their characteristic biology effects, the concept of Relaxation Time (RT) was introduced for the first time, and the specific process was as follows. After mutation of organisms, the offsprings will be continuingly cultured (or cultivated) to the next generation (Rx). Once a biological effect began to show no significant difference compared to the untreated controls, the Rx was defined as the RT of the effect. In this paper, three kinds of mutagenic factors were selected to treat the seeds or seedlings of Astragalus sinicus L., subsequently, the corresponding RT was calibrated. The results showed that the RT was diverse not only among different biological effects but also among different mutagenic factors. For the RT of chemical mutagens and gamma rays, most of which are concentrated on R1, whereas the heavy ion beams have significant differences among different tracks. Among biological effects, the SOD activity and superoxide anion free radical content in the Peak region are more prominent, and their RT reaches R3 and R4, respectively. Thus, the RT may characterize the characteristic biological effects from differently mutagenic factors.
Seasonal variation of intra-ocular pressure in glaucoma with and without dry eye
Authors: Kuze Manami , Ayaki Masahiko , Yuki Kenya , Kawashima Motoko , Uchino Miki , Tsubota Kazuo , Negishi Kazuno 
Published: August 2020

AbstractThe management of intra-ocular pressure (IOP) is important for glaucoma treatment. IOP is recognized for showing seasonal fluctuation. Glaucoma patients can be at high risk of dry eye disease (DED). We thus evaluated seasonal variation of IOP with and without DED in glaucoma patients. This study enrolled 4,708 patients, with mean age of 55.2 years, who visited our clinics in Japan from Mar 2015 to Feb 2017. We compared the seasonal variation in IOP (mean ± SD) across spring (March–May), summer (June–August), fall (September–November), and winter (December–February). IOP was highest in winter and lowest in summer, at 14.2/13.7 for non-glaucoma without DED group (n = 2,853, P = 0.001), 14.5/13.6 for non-glaucoma with DED group (n = 1,500, P = 0.000), 14.0/13.0 for glaucoma without DED group (n = 240, P = 0.051), and 15.4/12.4 for glaucoma with DED group (n = 115, P = 0.015). Seasonal variation was largest across the seasons in the glaucoma with DED group. IOP was also inversely correlated with corneal staining score (P = 0.000). In conclusion, the seasonal variation was significant in most of study groups and IOP could tend to be low in summer.
Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting
Authors: Hoel Ida Marie , Syre Heidi , Skarstein Ingerid , Mustafa Tehmina 
Published: August 2020

AbstractThe diagnosis of extrapulmonary tuberculosis (EPTB) is often challenging due to paucibacillary nature of the disease. Xpert MTB/RIF Ultra (Ultra) has been developed to improve detection of Mycobacterium tuberculosis complex (MTC) in paucibacillary specimens. The objective of the study was to assess the performance of Ultra for the diagnosis of EPTB in a high-income low TB prevalence country. Extrapulmonary samples received for TB diagnostics at two hospitals in Norway between January 2015 and January 2016 were prospectively and consecutively included. Defrosted samples were subjected to Ultra. Culture and routine PCR tests were used as reference standard. A total of 82 samples, 10 culture and/or routine PCR positive (confirmed TB) samples and 72 culture and routine PCR negative samples were included in analysis. The overall sensitivity and specificity of Ultra were 90% (9/10, 95% CI 56–100) and 99% (71/72, 95% CI 93–100), respectively. Ultra was positive in 6/7 smear negative confirmed TB samples. To conclude, Ultra showed a high sensitivity and specificity in extrapulmonary specimens and may contribute to a rapid diagnosis of EPTB in a low TB prevalence setting.
ENaC regulation by phospholipids and DGK explained through mathematical modeling
Authors: Olivença Daniel V. , Voit Eberhard O. , Pinto Francisco R. 
Published: August 2020

AbstractCystic fibrosis is a condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). It is also thought to increase the activity of epithelial sodium channels (ENaC). The altered function of these ion channels is one of the causes of the thick dehydrated mucus that characterizes the disease and is partially responsible for recurrent pulmonary infections and inflammation events that ultimately destroy the lungs of affected subjects. Phosphoinositides are signaling lipids that regulate numerous cellular processes and membrane proteins, including ENaC. Inhibition of diacylglycerol kinase (DGK), an enzyme of the phosphoinositide pathway, reduces ENaC function. We propose a computational analysis that is based on the combination of two existing mathematical models: one representing the dynamics of phosphoinositides and the other explaining how phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) influences ENaC activity and, consequently, airway surface liquid. This integrated model permits, for the first time, a detailed assessment of the intricate interactions between DGK and ENaC and is consistent with available literature data. In particular, the computational approach allows comparisons of two competing hypotheses regarding the regulation of ENaC. The results strongly suggest that the regulation of ENaC is primarily exerted through the control of PI(4,5)P2 production by type-I phosphatidylinositol-4-phosphate 5-kinase (PIP5KI), which in turn is controlled by phosphatidic acid (PA), the product of the DGK reaction.
Understanding of metals dysregulation in patients with systolic and diastolic dysfunction in ischemic heart disease
Authors: Khan Noman , Hashmi Satwat , Siddiqui Amna Jabbar , Farooq Sabiha , Sami Shahid Ahmed , Basir Nageeb , Bokhari Syeda Saira , Sharif Hasanat , Junejo Sanaullah , El-Seedi Hesham R. , Musharraf Syed Ghulam 
Published: August 2020

AbstractIschemic heart disease (IHD) is the leading cause of death and chronic disability in the world. IHD affects both the systolic and diastolic function of the heart which progressively leads to heart failure; a structural and functional impairment of filling or ejection of blood from the heart. In this study, the progression of systolic and diastolic dysfunction characterized according to their echocardiographic parameters including left ventricular ejection fraction (EF), grades of diastolic dysfunction and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/eʹ), were correlated with differential regulation of various metals in patients sera samples (n = 62) using inductive coupled plasma-mass spectrometry (ICP-MS). Chromium, nickel and selenium were found significant (p < 0.05) in patients having EF < 45% compared with EF > 45%. In patients with systolic dysfunction (EF < 45%), the level of selenium was decreased while the level of chromium and nickel was increased compared to patients with EF > 45%. Selenium level was also decreased significantly (p < 0.05) in grade 1A and 2 patients that are considered as higher grades of diastole dysfunction in comparison to grade 0–1. Overall, selenium deficiency was identified in both systolic and diastolic dysfunctions of IHD patients corresponding to the progression of disease that could be related to many metabolic and translational pathways specifically which involve selenoproteins.
LncRNA and mRNA expression profiles and functional networks of hyposalivation of the submandibular gland in hypertension
Authors: Shen Zhu-Jun , Han Ye-Chen , Wang Yi-Ning , Xie Hong-Zhi 
Published: August 2020

AbstractHyposalivation is a complication of hypertension. However, little is known about the role of long non-coding RNAs (lncRNAs) in salivary glands in hypertension. This study aimed to compare the lncRNA and mRNA expression profiles between spontaneous hypertension rats (SHRs) and Wistar-Kyoto (WKY) rats through microarray analysis and apple bioinformatics methods to analyse their potential roles in hyposalivation. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Compared with WKY rats, 225 DE lncRNAs and 473 DE mRNAs were identified in the SMG of SHRs. The pathway analyses of DE mRNAs showed that inflammatory mediator regulation of transient receptor potential channels was involved in hyposalivation in SHRs. Ten DE lncRNAs were chosen for further research. A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network analysis revealed that the potential functions of these 10 DE lncRNAs were closely connected with the processes of the immune response. This study showed abundant DE lncRNAs and mRNAs in hypertensive SMGs. Furthermore, our results indicated strong associations between the immune response and hyposalivation and showed the potential of immune-related genes as novel and therapeutic targets for hyposalivation.
Implications of back-and-forth motion and powerful propulsion for spirochetal invasion
Authors: Abe Keigo , Kuribayashi Toshiki , Takabe Kyosuke , Nakamura Shuichi 
Published: August 2020

AbstractThe spirochete Leptospira spp. can move in liquid and on a solid surface using two periplasmic flagella (PFs), and its motility is an essential virulence factor for the pathogenic species. Mammals are infected with the spirochete through the wounded dermis, which implies the importance of behaviors on the boundary with such viscoelastic milieu; however, the leptospiral pathogenicity involving motility remains unclear. We used a glass chamber containing a gel area adjoining the leptospiral suspension to resemble host dermis exposed to contaminated water and analyzed the motility of individual cells at the liquid-gel border. Insertion of one end of the cell body to the gel increased switching of the swimming direction. Moreover, the swimming force of Leptospira was also measured by trapping single cells using an optical tweezer. It was found that they can generate $$\sim $$
∼
17 pN of force, which is $$\sim $$
∼
30 times of the swimming force of Escherichia coli. The force-speed relationship suggested the load-dependent force enhancement and showed that the power (the work per unit time) for the propulsion is $$\sim $$
∼
3.1 × 10–16 W, which is two-order of magnitudes larger than the propulsive power of E. coli. The powerful and efficient propulsion of Leptospira using back-and-forth movements could facilitate their invasion.