bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical and Experimental Validation of the Applicability of Active‐DTS Experiments to Estimate Thermal Conductivity and Groundwater Flux in Porous Media
Authors: Simon N. , Bour O. , Lavenant N. , Porel G. , Nauleau B. , Pouladi B. , Longuevergne L. , Crave A.
Published: December 2020

Groundwater flow depends on the heterogeneity of hydraulic properties whose field characterization is challenging. Recently developed active‐Distributed Temperature Sensing (DTS) experiments offer the possibility to directly measure groundwater fluxes resulting from heterogeneous flow fields. Here, based on fundamental principles and numerical simulations, two interpretation methods of active‐DTS experiments are proposed to estimate both the porous media thermal conductivities and the groundwater fluxes in sediments. These methods rely on the interpretation of the temperature increase measured along a single heated fiber‐optic (FO) cable and consider heat transfer processes occurring both through the FO cable itself and through the porous media. The first method relies on the Moving Instantaneous Line Source model that reproduces the temperature increase and provides estimates of thermal conductivity and groundwater flux as well as an evaluation of the temperature rise due to the FO cable. The second method, based on the graphical identification of three characteristic times, provides complementary estimates of flux, fully independent of the effect of the FO cable. Sandbox experiments provide an experimental validation of the interpretation methods, demonstrate the excellent accuracy of groundwater flux estimates (<5%), and highlight the complementarity of both methods. Active‐DTS experiments allow investigating groundwater fluxes over a large range spanning 1 × 10−6−5 × 10−2 m/s, depending on the duration of the experiment. Considering the applicability of active‐DTS experiments in different contexts, we propose a general experimental framework for the application of both interpretation methods in the field, making active‐DTS field experiments especially promising for many subsurface applications.
Computerized Cognitive Training and Evidence-Based Practice in Pediatric Psychology
Authors: Schwartz David D.
Published: December 2020

Objective: Cognitive dysfunction is associated with common pediatric conditions, including attention-deficit/hyperactivity disorder, traumatic brain injury, and acquired brain injuries secondary to acute and chronic illness. There is substantial interest in computerized cognitive training (CCT) as a way to remediate these deficits, but use of CCT has been the subject of ongoing debate regarding its effectiveness. This invited commentary describes the current evidence base and potential benefits and costs of CCT, discusses clinical decision-making from the perspective of evidence-based practice, and offers suggestions for future development and research. Method: A selective review of reviews of the recent CCT literature, with a focus on pediatric conditions. Results: Large claims have been made for the effectiveness of CCT, but research to date indicates only limited and circumscribed benefits. Improvements have been demonstrated in trained tasks and closely related skills, but generalization to other cognitive domains has not convincingly been shown. On the other hand, unequivocally beneficial treatment alternatives are lacking or have their own limitations. This state of affairs raises practical and ethical concerns for clinicians interested in using this intervention. CCT does show promise: It can be delivered at home, potentially increasing access to care, and may be improved by coaching or as an adjunct to other treatments. Conclusions: CCT may provide limited benefits for some pediatric patients, but further research and development is needed before it can considered an effective intervention for cognitive dysfunction. Clinicians considering its use should be sure that patients and families are well informed about its benefits and limitations.

Implications for Impact Statement

Computerized cognitive training (CCT) is increasingly being promoted as a way to remediate cognitive dysfunction in pediatric patients. This article describes the current evidence-base for CCT, discusses clinical decision-making from the perspective of evidence-based practice in psychology, and offers suggestions for future development and research.
ZFP804A mutant mice display sex-dependent schizophrenia-like behaviors
Authors: Huang Ying , Huang Jing , Zhou Qi-Xin , Yang Chun-Xian , Yang Cui-Ping , Mei Wan-Ying , Zhang Lei , Zhang Qiong , Hu Ling , Hu Yun-Qing , Song Ning-Ning , Wu Sheng-Xi , Xu Lin , Ding Yu-Qiang
Published: December 2020

Genome-wide association studies uncovered the association ofZNF804A(Zinc-finger protein 804A) with schizophrenia (SZ). In vitro data have indicated thatZNF804Amight exert its biological roles by regulating spine and neurite morphogenesis. However, no in vivo data are available for the role ofZNF804Ain psychiatric disorders in general, SZ in particular. We generatedZFP804Amutant mice, and they showed deficits in contextual fear and spatial memory. We also observed the sensorimotor gating impairment, as revealed by the prepulse inhibition test, but only in femaleZFP804Amutant mice from the age of 6 months. Notably, the PPI difference between the female mutant and control mice was no longer existed with the administration of Clozapine or after the ovariectomy. Hippocampal long-term potentiation was normal in both genders of the mutant mice. Long-term depression was absent in male mutants, but facilitated in the female mutants. Protein levels of hippocampal serotonin-6 receptor and GABAB1 receptor were increased, while those of cortical dopamine 2 receptor were decreased in the female mutants with no obvious changes in the male mutants. Moreover, the spine density was reduced in the cerebral cortex and hippocampus of the mutant mice. Knockdown ofZFP804Aimpaired the neurite morphogenesis of cortical and hippocampal neurons, while its overexpression enhanced neurite morphogenesis only in the cortical neurons in vitro. Our data collectively support the idea thatZFP804A/ZNF804Aplays important roles in the cognitive functions and sensorimotor gating, and its dysfunction may contribute to SZ, particularly in the female patients.
Evading the host response: Staphylococcus “hiding” in cortical bone canalicular system causes increased bacterial burden
Authors: Zoller Stephen D. , Hegde Vishal , Burke Zachary D. C. , Park Howard Y. , Ishmael Chad R. , Blumstein Gideon W. , Sheppard William , Hamad Christopher , Loftin Amanda H. , Johansen Daniel O. , Smith Ryan A. , Sprague Marina M. , Hori Kellyn R. , Clarkson Samuel J. , Borthwell Rachel , Simon Scott I. , Miller Jeff F. , Nelson Scott D. , Bernthal Nicholas M.
Published: December 2020

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this “limb salvage” surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection ofStaphylococcus aureus(the most common infecting agent) into the host lacunar–canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-timeStaphylococciinfection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by whichStaphylococcievasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.
Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project
Authors: Millen Gerard C. , Arnold Roland , Cazier Jean-Baptiste , Curley Helen , Feltbower Richard G. , Gamble Ashley , Glaser Adam W. , Grundy Richard G. , Lee Lennard Y. W. , McCabe Martin G. , Phillips Robert S. , Stiller Charles A. , Várnai Csilla , Kearns Pamela R.
Published: December 2020

Background

Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK.

Methods

Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital.

Results

Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%.

Conclusions

Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.
BMSC-derived exosomes from congenital polydactyly tissue alleviate osteoarthritis by promoting chondrocyte proliferation
Authors: Zhou Xinghua , Liang Hansi , Hu Xiaohan , An JinNan , Ding Sisi , Yu Shuichang , Liu Cuiping , Li Fang , Xu Yunyun
Published: December 2020

In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and exosomes may play a major role. Here, we acquired a special kind of MSCs from the bone marrow of surgically resected tissue from the hand of a patient with polydactyly. Experiments were focused on the role of polydactyly bone marrow-derived MSCs (pBMSCs) in osteoarthritis. The results showed that the pBMSCs had a greater ability than the BMSCs to differentiate into chondrocytes. Mechanistically, the expression of BMP4 was significantly higher in the pBMSCs than it was in the BMSCs. Furthermore, we showed that the migration and proliferation of chondrocytes were stimulated by exosomes secreted by pBMSC (pBMSC-EXOs). Notably, the downregulation of BMP4 in pBMSCs by siRNA inhibited both the chondrogenic differentiation potential of the MSCs and the function of the chondrocytes. In addition, the injection of pBMSC-EXOs and BMSC-EXOs attenuated OA in an OA mouse model, but the pBMSC-EXOs had a superior therapeutic effect compared with that of the BMSC-EXOs. Taken together, the data indicate that pBMSCs have greater ability to differentiate into chondrocytes and regulate chondrocyte formation through BMP4 signaling. Therefore, pBMSC-EXOs may represent a novel treatment for OA.
Publisher Correction: The understanding of congruent and incongruent referential gaze in 17-month-old infants: an eye-tracking study comparing human and robot
Authors: Manzi F. , Ishikawa M. , Di Dio C. , Itakura S. , Kanda T. , Ishiguro H. , Massaro D. , Marchetti A.
Published: December 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A fluorescence immunoassay for a rapid detection of Listeria monocytogenes on working surfaces
Authors: Capo Alessandro , D’Auria Sabato , Lacroix Monique
Published: December 2020

Listeria monocytogenes is a foodborne pathogen responsible for human listeriosis. The increasing incidence of listeriosis induced governments and food manufacturing enterprises to act to diminish the problem. Several methods for the detection of Listeria monocytogenes in food industries were developed. However, they are time-consuming and require the use of specialized equipment. To reduce the detection time of Listeria monocytogenes in food, in this work we developed a fluorescence sandwich immunoassay based on the use of an innovative chitosan-cellulose nanocrystal (CNC) membrane that improves the antigen capture during bacterial growth. The combined use of CNC film for the capture of p60 protein-specific antigen together with the use of fluorescence detection reduced the time of analysis from 24 to 12 h with a limit of detection (LOD) of the assay of 102 CFU/mL (2 Log). In addition, the use of monoclonal anti-PepD covalently immobilized to a CNC membrane assured a high specificity of the assay. Interestingly, the obtained results show no cross-reactivity with the five most diffused pathogen bacteria strains tested.
Nonreciprocal elasticity and the realization of static and dynamic nonreciprocity
Authors: Shaat Mohamed
Published: December 2020

The realization of the mechanical nonreciprocity requires breaking either the time-reversal symmetry or the material deformation symmetry. The time-reversal asymmetry was the commonly adopted approach to realize dynamic nonreciprocity. However, a static nonreciprocity requires—with no any other option—breaking the material deformation symmetry. By virtue of the Maxwell–Betti reciprocal theorem, the achievement of the static nonreciprocity seems to be conditional by the use of a nonlinear material. Here, we further investigate this and demonstrate a novel “nonreciprocal elasticity” concept. We investigated the conditions of the attainment of effective static nonreciprocity. We revealed that the realization of static nonreciprocity requires breaking the material deformation symmetry under the same kinematical and kinetical conditions, which can be achieved only and only if the material exhibits a nonreciprocal elasticity. By means of experimental and topological mechanics, we demonstrate that the realization of static nonreciprocity requires nonreciprocal elasticity no matter what the material is linear or nonlinear. We experimentally demonstrated linear and nonlinear metamaterials with nonreciprocal elasticities. The developed metamaterials were used to demonstrate that nonreciprocal elasticity is essential to realize static nonreciprocal-topological systems. The nonreciprocal elasticity developed here will open new venues of the design of metamaterials that can effectively break the material deformation symmetry and achieve, both, static and dynamic nonreciprocity.
Comprehensive analysis of liver and blood miRNA in precancerous conditions
Authors: Umezu Tomohiro , Tsuneyama Koichi , Kanekura Kohsuke , Hayakawa Michiyo , Tanahashi Toshihito , Kawano Mitsuoki , Taguchi Y-h , Toyoda Hidenori , Tamori Akihiro , Kuroda Masahiko , Murakami Yoshiki
Published: December 2020

Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from STZ-mice and non-treated mice (CTL-mice) at 6, 10, and 12 W. The exosome enriched fraction extracted from serum was used. Hepatic histological examination and hepatic and exosomal miRNA expression analysis were serially performed using next-generation sequencing (NGS). Human miRNA expression analysis of chronic hepatitis liver tissue and exosomes, which were collected before starting the antiviral treatment, were also performed. No inflammation or fibrosis was found in the liver of CTL-mice during the observation period. In STZ-mice, regeneration and inflammation of hepatocytes was found at 6 W and nodules of atypical hepatocytes were found at 10 and 12 W. In the liver tissue, during 6–12 W, the expression levels of let-7f-5p, miR-143-3p, 148a-3p, 191-5p, 192-5p, 21a-5p, 22-3p, 26a-5p, and 92a-3p was significantly increased in STZ-mice, and anti-oncogenes of their target gene candidates were down-regulated. miR-122-5p was also significantly down-regulated in STZ-mice. Fifteen exosomal miRNAs were upregulated in STZ-mice. Six miRNAs (let-7f-5p, miR-10b-5p, 143-3p, 191-5p, 21a-5p, and 26a-5p) were upregulated, similarly to human HCC cases. From the precancerous state, aberrant expression of hepatic miRNAs has already occurred, and then, it can promote carcinogenesis. In exosomes, the expression pattern of common miRNAs between mice and humans before carcinogenesis was observed and can be expected to be developed as a cancer predictive marker.
Intercalation of Mn in graphene/Cu(111) interface: insights to the electronic and magnetic properties from theory
Authors: Guo Qilin , Dedkov Yuriy , Voloshina Elena
Published: December 2020

The effect of Mn intercalation on the atomic, electronic and magnetic structure of the graphene/Cu(111) interface is studied using state-of-the-art density functional theory calculations. Different structural models of the graphene–Mn–Cu(111) interface are investigated. While a Mn monolayer placed between graphene and Cu(111) (an unfavorable configuration) yields massive rearrangement of the graphene-derived $$\pi $$
π
bands in the vicinity of the Fermi level, the possible formation of a $$\hbox {Cu}_2$$

Cu
2

Mn alloy at the interface (a favorable configuration) preserves the linear dispersion for these bands. The deep analysis of the electronic states around the Dirac point for the graphene/$$\hbox {Cu}_2$$

Cu
2

Mn/Cu(111) system allows to discriminate between contributions from three carbon sublattices of a graphene layer in this system and to explain the bands’ as well as spins’ topology of the electronic states around the Fermi level.
Self-healable soft shield for γ-ray radiation based on polyacrylamide hydrogel composites
Authors: Park Jinwoo , Kim Minseok , Choi Sooseok , Sun Jeong-Yun
Published: December 2020

With the growing risk of radiation exposure, there are growing interests in radiation shielding. Because most radiation shields are made from heavy metals, a need to develop a soft shield is raised to protect human body. However, because the shield can easily undergo a mechanical damage by an impact, it would be better to have self-repairing system in the shield. Here, we have fabricated an intrinsic self-healable soft shield for gamma ray by making acrylamide based hydrogel composite. The composite contains lead dioxide nanoparticles for gamma ray shielding and Laponite clays for self-repairing. Although the hydrogel contained a large amount of lead dioxide nanoparticles (3.23 M), the fabricated composites stretched beyond 1400% while showing a high attenuation coefficient of 0.1343 cm−1against gamma ray from a cobalt-60 source. Then a systematic study was performed to analyze self-healing properties and the 96.55% of maximum self-healing efficiency was obtained. We also analyzed a storage modulus of hydrogel and molecular weight of polyacrylamide to study an effect of gamma ray on the self-healing. The self-healing efficiency was decreased by a gamma ray because the radiation induces scissioning or covalent crosslinking in the chains.
Unravelling the intricate cooperativity of subunit gating in P2X2 ion channels
Authors: Sattler Christian , Eick Thomas , Hummert Sabine , Schulz Eckhard , Schmauder Ralf , Schweinitz Andrea , Unzeitig Christopher , Schwede Frank , Benndorf Klaus
Published: December 2020

Ionotropic purinergic (P2X) receptors are trimeric channels that are activated by the binding of ATP. They are involved in multiple physiological functions, including synaptic transmission, pain and inflammation. The mechanism of activation is still elusive. Here we kinetically unraveled and quantified subunit activation in P2X2 receptors by an extensive global fit approach with four complex and intimately coupled kinetic schemes to currents obtained from wild type and mutated receptors using ATP and its fluorescent derivative 2-[DY-547P1]-AET-ATP (fATP). We show that the steep concentration-activation relationship in wild type channels is caused by a subunit flip reaction with strong positive cooperativity, overbalancing a pronounced negative cooperativity for the three ATP binding steps, that the net probability fluxes in the model generate a marked hysteresis in the activation-deactivation cycle, and that the predicted fATP binding matches the binding measured by fluorescence. Our results shed light into the intricate activation process of P2X channels.
Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19
Authors: Jøntvedt Jørgensen Marthe , Holter Jan Cato , Christensen Erik Egeland , Schjalm Camilla , Tonby Kristian , Pischke Søren Erik , Jenum Synne , Skeie Linda G. , Nur Sarah , Lind Andreas , Opsand Hanne , Enersen Tone Burvald , Grøndahl Ragnhild , Hermann Anne , Dudman Susanne , Muller Fredrik , Ueland Thor , Mollnes Tom Eirik , Aukrust Pål , Heggelund Lars , Holten Aleksander Rygh , Dyrhol-Riise Anne Ma
Published: December 2020

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2–5 and 7–10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79–0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.
Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
Authors: Lepez Anouk , Pirnay Tiphène , Denanglaire Sébastien , Perez-Morga David , Vermeersch Marjorie , Leo Oberdan , Andris Fabienne
Published: December 2020

The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMPK is dispensable for early TCR signaling and short-term proliferation but required for sustained long-term T cell proliferation and effector/memory T cell survival. In particular, AMPK promoted accumulation of effector/memory T cells in competitive homeostatic proliferation settings. Transplantation of AMPK-deficient hematopoïetic cells into allogeneic host recipients led to a reduced graft-versus-host disease, further bolstering a role for AMPK in the expansion and pathogenicity of effector T cells. Mechanistically, AMPK expression enhances the mitochondrial membrane potential of T cells, limits reactive oxygen species (ROS) production, and resolves ROS-mediated toxicity. Moreover, dampening ROS production alleviates the proliferative defect of AMPK-deficient T cells, therefore indicating a role for an AMPK-mediated ROS control of T cell fitness.
Hop flower extracts mitigate retinal ganglion cell degeneration in a glaucoma mouse model
Authors: Hasegawa Tomoko , Ikeda Hanako O. , Iwai Sachiko , Sasaoka Norio , Kakizuka Akira , Tsujikawa Akitaka
Published: December 2020

In glaucoma, retinal ganglion cells degenerate progressively, leading to visual field loss and blindness. Presently, the only treatment strategy for glaucoma is lowering the intraocular pressure. However, there are cases in which patients develop progressive visual field loss even though their intraocular pressures are within normal ranges. Therefore, the development of novel therapeutic strategies is an urgent endeavor. Besides high intraocular pressure, several other factors have been proposed to be associated with glaucoma progression, e.g., myopia, blood flow impairment, and amyloid β accumulation. We have previously reported that hop flower extracts possess γ-secretase inhibitory activities and reduce amyloid β deposition in the brains of Alzheimer’s disease model mice. In the current study, we showed that administration of hop flower extracts to glutamate-aspartate transporter (GLAST) knockout mice, the glaucoma model mice, attenuated glaucomatous retinal ganglion cell degeneration. Preservation of retinal ganglion cells in hop flower extract-administered mice was confirmed using optical coherence tomography, confocal scanning laser ophthalmoscopy, and retinal flatmount and histological evaluations. Hop flower extracts are, therefore, deemed a possible candidate as a novel therapeutic agent to treat glaucoma.
Tracking the early depleting transmission dynamics of COVID-19 with a time-varying SIR model
Authors: Law Kian Boon , Peariasamy Kalaiarasu M. , Gill Balvinder Singh , Singh Sarbhan , Sundram Bala Murali , Rajendran Kamesh , Dass Sarat Chandra , Lee Yi Lin , Goh Pik Pin , Ibrahim Hishamshah , Abdullah Noor Hisham
Published: December 2020

The susceptible-infectious-removed (SIR) model offers the simplest framework to study transmission dynamics of COVID-19, however, it does not factor in its early depleting trend observed during a lockdown. We modified the SIR model to specifically simulate the early depleting transmission dynamics of COVID-19 to better predict its temporal trend in Malaysia. The classical SIR model was fitted to observed total (I total), active (I) and removed (R) cases of COVID-19 before lockdown to estimate the basic reproduction number. Next, the model was modified with a partial time-varying force of infection, given by a proportionally depleting transmission coefficient, $$\beta_{t}$$

β
t

and a fractional term, z. The modified SIR model was then fitted to observed data over 6 weeks during the lockdown. Model fitting and projection were validated using the mean absolute percent error (MAPE). The transmission dynamics of COVID-19 was interrupted immediately by the lockdown. The modified SIR model projected the depleting temporal trends with lowest MAPE for I total, followed by I, I daily and R. During lockdown, the dynamics of COVID-19 depleted at a rate of 4.7% each day with a decreased capacity of 40%. For 7-day and 14-day projections, the modified SIR model accurately predicted I total, I and R. The depleting transmission dynamics for COVID-19 during lockdown can be accurately captured by time-varying SIR model. Projection generated based on observed data is useful for future planning and control of COVID-19.
Association between positive history of essential tremor and disease progression in patients with Parkinson's disease
Authors: Ou Ruwei , Wei Qianqian , Hou Yanbing , Zhang Lingyu , Liu Kuncheng , Lin Junyu , Jiang Zheng , Song Wei , Cao Bei , Shang Huifang
Published: December 2020

This study aimed to explore the effect of pre-existing essential tremor (ET) history on the disease progression of Parkinson’s disease (PD). We recruited and followed-up a group of PD patients from March 2009 to July 2020. The ET history of each patient was obtained by retrospective interviews or past medical records. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the hazard ratio (HR) with 95% confidence intervals (CIs). Of 785 patients who completed the followed-up visits, 61 patients (7.8%) reported a history of pre-existing ET. Cox regression models after IPTW indicated that the positive ET history in patients with PD was protective against time to United PD Rating Scale III 14-point increase (HR = 0.301, 95% CI = 0.134–0.678, P = 0.004), time to akinesia and rigidity 8-point increase (HR = 0.417, 95% CI = 0.218–0.796, P = 0.008), time to conversion to Hoehn and Yahr stage 3 (HR = 0.356, 95% CI = 0.131–0.969, P = 0.043), time to develop dyskinesia (HR = 0.160, 95% CI = 0.037–0.698, P = 0.015), and time to Montreal Cognitive Assessment 3-point decrease (HR = 0.389, 95% CI = 0.160–0.946, P = 0.037), but had no relationship with time to tremor 4-point increase (HR = 1.638, 95% CI = 0.822–3.266, P = 0.161) and time to death (HR = 0.713, 95% CI = 0.219–2.319, P = 0.574). Our study indicated that ET history in patients with PD is associated with a benign prognosis with slower motor and non-motor progression.
Dazomet application suppressed watermelon wilt by the altered soil microbial community
Authors: Zhu Feiying , Xiao Jiling , Zhang Yi , Wei Lin , Liang Zhihuai
Published: December 2020

Fusarium wilt disease causes severe decline of watermelon yield and quality. Researches have been reported that soil fumigation with dazomet can help control crop disease. Firstly, we discovered that the dazomet application suppressed watermelon wilt in field experiment compared to the control group. While the importance of microbial community in regulating plant health has been rising up, we therefore focused on examining the soil microbial diversity at six different sampling times after dazomet application by using Illumina MiSeq platform. Remarkably, our research results showed that some beneficial microbial genera have been altered, and these beneficial microbial genera have dominated the entire community, such as Nitrolancea, Pseudomonas and Penicillium after dazomet application. Instead, the relative abundance of Fusarium genus and the pathogen FON (Fusarium oxysporum f. sp. niveum, FON) had the decreased. As there was a significant accumulation of AP (available soil phosphorus) after dazomet application, we noticed that the beneficial microbes as Bacillus, Nitrolancea, Paenibacillus and Penicillium have significant positive correlation with AP but negatively related to morbidity. Together, these results demonstrate that the altered soil microbial community structure by dazomet application is critical to suppress watermelon Fusarium wilt. Thus, our results will drive investigations aimed to deploy interaction of microbiota contribute and plant immunity.
Multiple scattering effects on intercept, size, polydispersity index, and intensity for parallel (VV) and perpendicular (VH) polarization detection in photon correlation spectroscopy
Authors: Ragheb Ragy , Nobbmann Ulf
Published: December 2020

Dynamic light scattering (DLS) is well established for rapid size, polydispersity, and size distribution determination of colloidal samples. While there are limitations in size range, resolution, and concentration, the technique has found ubiquitous applications from molecules to particles. With the ease of use of today’s commercial DLS instrumentation comes an inherent danger of misinterpretation or misapplication at the borderlines of suitability. In this paper, we show how comparison of different polarization components can help ascertain the presence of unwanted multiple scattering, which can lead to false conclusions about a sample’s mean size and polydispersity. We find that the contribution of multiple scattering events effectively reduces both the measured scattering intensity and the apparent size from the autocorrelation function. The intercept of the correlation function may serve as an indicator of relative strength of single to multiple scattering. Furthermore, the abundance of single scattering events at measurement positions close to the cell wall results in an apparent increase in uniformity yielding a lower polydispersity index which is more representative of the physical system.
Comparative thermal research on tetraazapentalene-derived heat-resistant energetic structures
Authors: Zhou Jing , Ding Li , Zhu Yong , Wang Bozhou , Li Xiangzhi , Zhang Junlin
Published: December 2020

Organic inner salt structures are ideal backbones for heat-resistant energetic materials and systematic studies towards the thermal properties of energetic organic inner salt structures are crucial to their applications. Herein, we report a comparative thermal research of two energetic organic inner salts with different tetraazapentalene backbones. Detailed thermal decomposition behaviors and kinetics were investigated through differential scanning calorimetry and thermogravimetric analysis (DSC-TG) methods, showing that the thermal stability of the inner salts is higher than most of the traditional heat-resistant energetic materials. Further studies towards the thermal decomposition mechanism were carried out through condensed-phase thermolysis/Fourier-transform infrared (in-situ FTIR) spectroscopy and the combination of differential scanning calorimetry-thermogravimetry-mass spectrometry-Fourier-transform infrared spectroscopy (DSC-TG-MS-FTIR) techniques. The experiment and calculation results prove that the arrangement of the inner salt backbones has great influence on the thermal decompositions of the corresponding energetic materials. The weak N4-N5 bond in “y-” pattern tetraazapentalene backbone lead to early decomposition process and the “z-” pattern tetraazapentalene backbone exhibits more concentrated decomposition behaviors.
Microbiome dysbiosis in lung cancer: from composition to therapy
Authors: Liu Ning-Ning , Ma Qiang , Ge Yang , Yi Cheng-Xiang , Wei Lu-Qi , Tan Jing-Cong , Chu Qiao , Li Jing-Quan , Zhang Peng , Wang Hui
Published: December 2020

The correlations between microbiota dysbiosis and cancer have gained extensive attention and been widely explored. As a leading cancer diagnosis worldwide, lung cancer poses a great threat to human health. The healthy human lungs are consistently exposed to external environment and harbor a specific pattern of microbiota, sharing many key pathological and physiological characteristics with the intestinal tract. Although previous findings uncovered the critical roles of microbiota in tumorigenesis and response to anticancer therapy, most of them were focused on the intestinal microbiota rather than lung microbiota. Notably, the considerable functions of microbiota in maintaining lung homeostasis should not be neglected as the microbiome dysbiosis may promote tumor development and progression through production of cytokines and toxins and multiple other pathways. Despite the fact that increasing studies have revealed the effect of microbiome on the induction of lung cancer and different disease status, the underlying mechanisms and potential therapeutic strategies remained unclear. Herein, we summarized the recent progresses about microbiome in lung cancer and further discussed the role of microbial communities in promoting lung cancer progression and the current status of therapeutic approaches targeting microbiome to alleviate and even cure lung cancer.
Phosphatidylinositol synthesis, its selective salvage, and inter-regulation of anionic phospholipids in Toxoplasma gondii
Authors: Ren Bingjian , Kong Pengfei , Hedar Fatima , Brouwers Jos F. , Gupta Nishith
Published: December 2020

Phosphatidylinositol (PtdIns) serves as an integral component of eukaryotic membranes; however, its biosynthesis in apicomplexan parasites remains poorly understood. Here we show that Toxoplasma gondii—a common intracellular pathogen of humans and animals—can import and co-utilize myo-inositol with the endogenous CDP-diacylglycerol to synthesize PtdIns. Equally, the parasite harbors a functional PtdIns synthase (PIS) containing a catalytically-vital CDP-diacylglycerol phosphotransferase motif in the Golgi apparatus. Auxin-induced depletion of PIS abrogated the lytic cycle of T. gondii in human cells due to defects in cell division, gliding motility, invasion, and egress. Isotope labeling of the PIS mutant in conjunction with lipidomics demonstrated de novo synthesis of specific PtdIns species, while revealing the salvage of other lipid species from the host cell. Not least, the mutant showed decline in phosphatidylthreonine, and elevation of selected phosphatidylserine and phosphatidylglycerol species, indicating a rerouting of CDP-diacylglycerol and homeostatic inter-regulation of anionic phospholipids upon knockdown of PIS. In conclusion, strategic allocation of own and host-derived PtdIns species to gratify its metabolic demand features as a notable adaptive trait of T. gondii. Conceivably, the dependence of T. gondii on de novo lipid synthesis and scavenging can be exploited to develop new anti-infectives.
Identification of MLH2/hPMS1 dominant mutations that prevent DNA mismatch repair function
Authors: Reyes Gloria X. , Zhao Boyu , Schmidt Tobias T. , Gries Kerstin , Kloor Matthias , Hombauer Hans
Published: December 2020

Inactivating mutations affecting key mismatch repair (MMR) components lead to microsatellite instability (MSI) and cancer. However, a number of patients with MSI-tumors do not present alterations in classical MMR genes. Here we discovered that specific missense mutations in the MutL homolog MLH2, which is dispensable for MMR, confer a dominant mutator phenotype in S. cerevisiae. MLH2 mutations elevated frameshift mutation rates, and caused accumulation of long-lasting nuclear MMR foci. Both aspects of this phenotype were suppressed by mutations predicted to prevent the binding of Mlh2 to DNA. Genetic analysis revealed that mlh2 dominant mutations interfere with both Exonuclease 1 (Exo1)-dependent and Exo1-independent MMR. Lastly, we demonstrate that a homolog mutation in human hPMS1 results in a dominant mutator phenotype. Our data support a model in which yeast Mlh1-Mlh2 or hMLH1-hPMS1 mutant complexes act as roadblocks on DNA preventing MMR, unraveling a novel mechanism that can account for MSI in human cancer.
Substrate-binding destabilizes the hydrophobic cluster to relieve the autoinhibition of bacterial ubiquitin ligase IpaH9.8
Authors: Ye Yuxin , Xiong Yuxian , Huang Hao
Published: December 2020

IpaH enzymes are bacterial E3 ligases targeting host proteins for ubiquitylation. Two autoinhibition modes of IpaH enzymes have been proposed based on the relative positioning of the Leucine-rich repeat domain (LRR) with respect to the NEL domain. In mode 1, substrate-binding competitively displaces the interactions between theLRR and NEL to relieve autoinhibition. However, the molecular basis for mode 2 is unclear. Here, we present the crystal structures of Shigella IpaH9.8 and the LRR of IpaH9.8 in complex with the substrate of human guanylate-binding protein 1 (hGBP1). A hydrophobic cluster in the C-terminus of IpaH9.8LRR forms a hydrophobic pocket involved in binding the NEL domain, and the binding is important for IpaH9.8 autoinhibition. Substrate-binding destabilizes the hydrophobic cluster by inducing conformational changes of IpaH9.8LRR. Arg166 and Phe187 in IpaH9.8LRR function as sensors for substrate-binding. Collectively, our findings provide insights into the molecular mechanisms for the actication of IpaH9.8 in autoinhibition mode 2.
Temperature dependence of adsorption hysteresis in flexible metal organic frameworks
Authors: Rahman Shamsur , Arami-Niya Arash , Yang Xiaoxian , Xiao Gongkui , Li Gang , May Eric F.
Published: December 2020

“Breathing” and “gating” are striking phenomena exhibited by flexible metal-organic frameworks (MOFs) in which their pore structures transform upon external stimuli. These effects are often associated with eminent steps and hysteresis in sorption isotherms. Despite significant mechanistic studies, the accurate description of stepped isotherms and hysteresis remains a barrier to the promised applications of flexible MOFs in molecular sieving, storage and sensing. Here, we investigate the temperature dependence of structural transformations in three flexible MOFs and present a new isotherm model to consistently analyse the transition pressures and step widths. The transition pressure reduces exponentially with decreasing temperature as does the degree of hysteresis (c.f. capillary condensation). The MOF structural transition enthalpies range from +6 to +31 kJ·mol−1 revealing that the adsorption-triggered transition is entropically driven. Pressure swing adsorption process simulations based on flexible MOFs that utilise the model reveal how isotherm hysteresis can affect separation performance.
CRISPR/Cas-based Functional Genomic Approaches to Phenotypic Screening
Authors: Isherwood Beverley , Peel Samantha , Dunn Shanade , McDermott Ultan
Published: December 2020

Arguably, one of the most exciting new technologies for drug discovery in recent years has been that of CRISPR. The ability to efficiently silence or activate gene expression at genome scale using CRISPR/Cas vectors coupled with a lower false-positive rate than previous gene editing approaches has the potential to revolutionise the search for novel drug targets. Here we describe how this technology is transforming target identification, and what the future holds for the integration of genome editing into phenotypic drug discovery. We will guide readers through the process of applying CRISPR technology to phenotypic drug discovery, from project start to completion, describing key considerations and technological advances to maximise success.
Use of Phenotypic Screening in Mice in the Development of a Novel Non-D2-Receptor-Targeting Drug for the Treatment of Schizophrenia
Authors: Leahy E. , Varney M. , Brunner D.
Published: December 2020

SEP-363856, a novel, first-in-class drug treatment being developed by Sunovion Pharmaceuticals, showed robust therapeutic effects in patients diagnosed with schizophrenia across a broad range of disabling symptoms including positive, negative, depressive, and general psychopathology symptoms, with a safety profile similar to placebo. SmartCube® – PsychoGenics’ proprietary mouse-based phenotypic platform, in combination with anti-target screening, was used as part of a phenotypic screening effort that identified SEP-363856. SmartCube® employs computer vision and artificial intelligence to extract and analyze behavioral data for central nervous system disorders. SEP-363856 does not interact with dopamine D2 nor with 5HT2A receptors that mediate the effects of currently available antipsychotic agents. The SmartCube® platform thus represents an effective approach to the discovery and development of the next generation of breakthrough treatments for schizophrenia and other neuropsychiatric disorders.
Phenotypic Screening for Drug Discovery in Tuberculosis
Authors: Delorme V.
Published: December 2020

Tuberculosis is still a terrible human disease, killing over 1 million people every year worldwide. Better antibiotics that could shorten treatment duration and provide a relief to the emergence and spread of drug-resistant strains are definitely needed. In this chapter, we give an overview of the phenotypic screening systems available for drug discovery in tuberculosis, highlighting their potential strengths and weaknesses. In addition, we illustrate with examples how phenotypic screenings have contributed to the field, discuss the role they can play in the future and how some specific gaps could be addressed.
Electroenzymatic choline sensing at near the theoretical performance limit
Authors: Huang I-wen , Clay Mackenzie , Cao Yan , Nie Jingjing , Guo Yuwan , Monbouquette Harold G.
Published: December 2020

Using detailed simulations as a guide, an implantable, electroenzymatic choline sensor with sensitivity approaching the theoretical and unprecedented response time has been created.
Self-absorption corrected non-invasive transmission Raman spectroscopy (of biological tissue)
Authors: Gardner Benjamin , Matousek Pavel , Stone Nicholas
Published: December 2020

Higher contrast of subsurface Raman spectra is achievable with self-absorption corrected transmission Raman spectroscopy. (Desired signal in red, interfering matrix artefacts in blue.)
A potential-resolved electrochemiluminescence resonance energy transfer strategy for the simultaneous detection of neuron-specific enolase and the cytokeratin 19 fragment
Authors: Mo Guichun , He Xuanming , Qin Dongmiao , Jiang Xiaohua , Zheng Xiangfei , Deng Biyang
Published: December 2020

An electrochemiluminescence resonance energy transfer immunosensor was developed based on the potential-resolved technology for the simultaneous detection of NSE and CYFRA21-1.
Straightforward neuron micropatterning and neuronal network construction on cell-repellent polydimethylsiloxane using microfluidics-guided functionalized Pluronic modification
Authors: Liu Wenming , Fu Wenzhu , Sun Meilin , Han Kai , Hu Rui , Liu Dan , Wang Jinyi
Published: December 2020

We present straightforward neuron patterning and neuronal network construction on polydimethylsiloxane based on functionalized Pluronic modification using microfluidics-guided flow deposition.
Using machine learning and liquid crystal droplets to identify and quantify endotoxins from different bacterial species
Authors: Jiang Shengli , Noh JungHyun , Park Chulsoon , Smith Alexander D. , Abbott Nicholas L. , Zavala Victor M.
Published: December 2020

Detection and quantification of bacterial endotoxins is important in a range of health-related contexts, including during pharmaceutical manufacturing of therapeutic proteins and vaccines.
A preliminary study on the potential of front face fluorescence spectroscopy for the discrimination of Moroccan virgin olive oils and the prediction of their quality
Authors: Zaroual Hicham , El Hadrami El Mestafa , Karoui Romdhane
Published: December 2020

This study examines the feasibility of using front face fluorescence spectroscopy (FFFS) to authenticate 41 virgin olive oil (VOO) samples collected from 5 regions in Morocco during 2 consecutive crop seasons.
A FRET aptasensor for sensitive detection of aflatoxin B1 based on a novel donor–acceptor pair between ZnS quantum dots and Ag nanocubes
Authors: Wang Chengquan , Zhang Wuhao , Qian Jing , Wang Li , Ren Yi , Wang Yu , Xu Mengqi , Huang Xingyi
Published: December 2020

A FRET aptasensor based on a novel donor–acceptor pair between ZnS QDs and Ag nanocubes was developed for AFB1 detection.
Hierarchical and heterogeneous hydrogel system as a promising strategy for diversified interfacial tissue regeneration
Authors: Zhang Liwen , Fu Lei , Zhang Xin , Chen Linxin , Cai Qing , Yang Xiaoping
Published: December 2020

A state-of-the-art review on the design and preparation of hierarchical and heterogeneous hydrogel systems for interfacial tissue regeneration.
Dual effect of molecular mobility and functional groups of polyrotaxane surfaces on the fate of mesenchymal stem cells
Authors: Sekiya-Aoyama Ruriko , Arisaka Yoshinori , Hakariya Masahiro , Masuda Hiroki , Iwata Takanori , Yoda Tetsuya , Yui Nobuhiko
Published: December 2020

Mesenchymal stem cells on polyrotaxane surfaces underwent enhanced osteoblast and adipocyte differentiation. Two independent parameters, high molecular mobility and negative charge on the surfaces, may not offset the effect to promote both differentiation.