bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning the Low Frequency Earthquake Activity on the Central San Andreas Fault
Authors: Johnson Christopher W. , Johnson Paul A.
Published: June 2021

Low frequency earthquakes (LFEs) originating below the central San Andreas Fault are associated with slow‐slip beneath the seismogenic zone within the more ductile portion of the crust. Monitoring efforts over 15 years detected >1 million LFEs. We train a gradient boosted tree model using statistical features describing the seismic waveforms to estimate the hourly LFE event count. The burst‐like LFE behavior is reproduced, while lower amplitudes are predicted during the most active periods. The hourly event counts are up to 18% greater than the catalog. The ability to continuously monitor LFE activity provides insight to when geodetic measurements of slow slip are possible, without the need for developing a computational‐intensive template‐matching catalog. Similar waveform statistical features are found between detecting LFEs and tremors, which provides additional evidence tremors are composed of LFEs. The approach extracts information contained in continuous seismic waveforms that might benefit detecting precursory signals.
Expanding the environmental scope: an environment-wide association study for mental well-being
Authors: van de Weijer Margot P. , Baselmans Bart M. L. , Hottenga Jouke-Jan , Dolan Conor V. , Willemsen Gonneke , Bartels Meike
Published: June 2021

Background

Identifying modifiable factors associated with well-being is of increased interest for public policy guidance. Developments in record linkage make it possible to identify what contributes to well-being from a myriad of factors. To this end, we link two large-scale data resources; the Geoscience and Health Cohort Consortium, a collection of geo-data, and the Netherlands Twin Register, which holds population-based well-being data.

Objective

We perform an Environment-Wide Association Study (EnWAS), where we examine 139 neighbourhood-level environmental exposures in relation to well-being.

Methods

First, we performed a generalized estimation equation regression (N = 11,975) to test for the effects of environmental exposures on well-being. Second, to account for multicollinearity amongst exposures, we performed principal component regression. Finally, using a genetically informative design, we examined whether environmental exposure is driven by genetic predisposition for well-being.

Results

We identified 21 environmental factors that were associated with well-being in the domains: housing stock, income, core neighbourhood characteristics, livability, and socioeconomic status. Of these associations, socioeconomic status and safety are indicated as the most important factors to explain differences in well-being. No evidence of gene-environment correlation was found.

Significance

These observed associations, especially neighbourhood safety, could be informative for policy makers and provide public policy guidance to improve well-being. Our results show that linking databases is a fruitful exercise to identify determinants of mental health that would remain unknown by a more unilateral approach.
Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair
Authors: Zhang Yu , Wang Yan , Zhou Ding , Wang Kai , Wang Xu , Wang Xiang , Jiang Yang , Zhao Min , Yu Rutong , Zhou Xiuping
Published: June 2021

Although radiotherapy is a well-known effective non-surgical treatment for malignant gliomas, the therapeutic efficacy is severely limited due to the radioresistance of tumor cells. Previously, we demonstrated that Yes-associated protein (YAP) promotes glioma malignant progression. However, whether YAP plays a role in radioresistance and its potential value in cancer treatment are still unclear. In this study, we found that high YAP expression is associated with poor prognosis in malignant glioma patients undergoing radiotherapy. Research in immortalized cell lines and primary cells from GBM patients revealed that YAP exhibited a radioresistant effect on gliomas via promoting DNA damage repair. Mechanistically, after radiation, YAP was translocated into the nucleus, where it promoted the expression and secretion of FGF2, leading to MAPK–ERK pathway activation.FGF2is a novel target gene of YAP. Inhibition of YAP–FGF2–MAPK signaling sensitizes gliomas to radiotherapy and prolongs the survival of intracranial cell-derived and patient-derived xenograft models. These results suggest that YAP–FGF2–MAPK is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy.
Congenital hypothyroidism impairs spine growth of dentate granule cells by downregulation of CaMKIV
Authors: Tang Qingying , Chen Shuxia , Wu Hui , Song Honghua , Wang Yongjun , Shi Jinlong , Wu Youjia
Published: June 2021

Congenital hypothyroidism (CH), a common neonatal endocrine disorder, can result in cognitive deficits if delay in diagnose and treatment. Dentate gyrus (DG) is the severely affected subregion of the hippocampus by the CH, where the dentate granule cells (DGCs) reside in. However, how CH impairs the cognitive function via affecting DGCs and the underlying mechanisms are not fully elucidated. In the present study, the CH model of rat pups was successfully established, and the aberrant dendrite growth of the DGCs and the impaired cognitive behaviors were observed in the offspring. Transcriptome analysis of hippocampal tissues following rat CH successfully identified that calcium/calmodulin-dependent protein kinase IV (CaMKIV) was the prominent regulator involved in mediating deficient growth of DGC dendrites. CaMKIV was shown to be dynamically regulated in the DG subregion of the rats following drug-induced CH. Interference of CaMKIV expression in the primary DGCs significantly reduced the spine density of dendrites, while addition of T3 to the primary DGCs isolated from CH pups could facilitate the spine growth of dendrites. Insights into relevant mechanisms revealed that CH-mediated CaMKIV deficiency resulted in the significant decrease of phosphorylated CREB in DGCs, in association with the abnormality of dendrites. Our results have provided a distinct cell type in hippocampus that is affected by CH, which would be beneficial for the treatment of CH-induced cognitive deficiency.
The role of auxin during early berry development in grapevine as revealed by transcript profiling from pollination to fruit set
Authors: Godoy Francisca , Kühn Nathalie , Muñoz Mindy , Marchandon Germán , Gouthu Satyanarayana , Deluc Laurent , Delrot Serge , Lauvergeat Virginie , Arce-Johnson Patricio
Published: June 2021

Auxin is a key phytohormone that modulates fruit formation in many fleshy fruits through the regulation of cell division and expansion. Auxin content rapidly increases after pollination and the manipulation in its levels may lead to the parthenocarpic development. lnVitis viniferaL., little is known about the early fruit development that encompasses from pollination to fruit set. Pollination/fertilization events trigger fruit formation, and auxin treatment mimics their effect in grape berry set. However, the role of auxin in this process at the molecular level is not well understood. To elucidate the participation of auxin in grapevine fruit formation, morphological, reproductive, and molecular events from anthesis to fruit set were described in sequential days after pollination. Exploratory RNA-seq analysis at four time points from anthesis to fruit set revealed that the highest percentage of genes induced/repressed within the hormone-related gene category were auxin-related genes. Transcript profiling showed significant transcript variations in auxin signaling and homeostasis-related genes during the early fruit development. Indole acetic acid and several auxin metabolites were present during this period. Finally, application of an inhibitor of auxin action reduced cell number and the mesocarp diameter, similarly to unpollinated berries, further confirming the key role of auxin during early berry development. This work sheds light into the molecular features of the initial fruit development and highlights the auxin participation during this stage in grapevine.
Tight docking of membranes before fusion represents a metastable state with unique properties
Authors: Witkowska Agata , Heinz Leonard P. , Grubmüller Helmut , Jahn Reinhard
Published: June 2021

Membrane fusion is fundamental to biological processes as diverse as membrane trafficking or viral infection. Proteins catalyzing membrane fusion need to overcome energy barriers to induce intermediate steps in which the integrity of bilayers is lost. Here, we investigate the structural features of tightly docked intermediates preceding hemifusion. Using lipid vesicles in which progression to hemifusion is arrested, we show that the metastable intermediate does not require but is enhanced by divalent cations and is characterized by the absence of proteins and local membrane thickening. Molecular dynamics simulations reveal that thickening is due to profound lipid rearrangements induced by dehydration of the membrane surface.
Ultrahigh energy-dissipation elastomers by precisely tailoring the relaxation of confined polymer fluids
Authors: Huang Jin , Xu Yichao , Qi Shuanhu , Zhou Jiajia , Shi Wei , Zhao Tianyi , Liu Mingjie
Published: June 2021

Energy-dissipation elastomers relying on their viscoelastic behavior of chain segments in the glass transition region can effectively suppress vibrations and noises in various fields, yet the operating frequency of those elastomers is difficult to control precisely and its range is narrow. Here, we report a synergistic strategy for constructing polymer-fluid-gels that provide controllable ultrahigh energy dissipation over a broad frequency range, which is difficult by traditional means. This is realized by precisely tailoring the relaxation of confined polymer fluids in the elastic networks. The symbiosis of this combination involves: elastic networks forming an elastic matrix that displays reversible deformation and polymer fluids reptating back and forth to dissipate mechanical energy. Using prototypical poly (n-butyl acrylate) elastomers, we demonstrate that the polymer-fluid-gels exhibit a controllable ultrahigh energy-dissipation property (loss factor larger than 0.5) with a broad frequency range (10−2 ~ 108 Hz). Energy absorption of the polymer-fluid-gels is over 200 times higher than that of commercial damping materials under the same dynamic stress. Moreover, their modulus is quasi-stable in the operating frequency range.
Prognostic implications of troponin T variations in inherited cardiomyopathies using systems biology
Authors: Shakur Rameen , Ochoa Juan Pablo , Robinson Alan J. , Niroula Abhishek , Chandran Aneesh , Rahman Taufiq , Vihinen Mauno , Monserrat Lorenzo
Published: June 2021

The cardiac troponin T variations have often been used as an example of the application of clinical genotyping for prognostication and risk stratification measures for the management of patients with a family history of sudden cardiac death or familial cardiomyopathy. Given the disparity in patient outcomes and therapy options, we investigated the impact of variations on the intermolecular interactions across the thin filament complex as an example of an unbiased systems biology method to better define clinical prognosis to aid future management options. We present a novel unbiased dynamic model to define and analyse the functional, structural and physico-chemical consequences of genetic variations among the troponins. This was subsequently integrated with clinical data from accessible global multi-centre systematic reviews of familial cardiomyopathy cases from 106 articles of the literature: 136 disease-causing variations pertaining to 981 global clinical cases. Troponin T variations showed distinct pathogenic hotspots for dilated and hypertrophic cardiomyopathies; considering the causes of cardiovascular death separately, there was a worse survival in terms of sudden cardiac death for patients with a variation at regions 90–129 and 130–179 when compared to amino acids 1–89 and 200–288. Our data support variations among 90–130 as being a hotspot for sudden cardiac death and the region 131–179 for heart failure death/transplantation outcomes wherein the most common phenotype was dilated cardiomyopathy. Survival analysis into regions of high risk (regions 90–129 and 130–180) and low risk (regions 1–89 and 200–288) was significant for sudden cardiac death (p = 0.011) and for heart failure death/transplant (p = 0.028). Our integrative genomic, structural, model from genotype to clinical data integration has implications for enhancing clinical genomics methodologies to improve risk stratification.
A twilight for the complete nitrogen removal via synergistic partial-denitrification, anammox, and DNRA process
Authors: Ahmad Hafiz Adeel , Guo Beibei , Zhuang Xuming , Zhao Yiyi , Ahmad Shakeel , Lee Taeho , Zhu Jiegao , Dong Yuliang , Ni Shou-Qing
Published: June 2021

The prolonged start-up time and low total nitrogen removal of anammox hinder its full-scale application. Herein, application of nano-zerovalent iron and low strength magnetic field in sole and in combination to abbreviate the start-up period and long-term process stability of anammox was carried out. The reactor’s anammox start-up with the only magnetic field (R3) was 34 days, saving 43.3% time compared with the control. The increase of nitrogen removal efficiency over the control was 43.7% during the start-up period. However, the reactor with the coupled treatment of nano-zerovalent iron and magnetic field (R4) was more stable with higher nitrogen removal efficiency (80%) at high nitrogen loading (5.28 kg/m3/d). Anammox gene copy number in R4 was highest after 180 days of culture, followed by nano-zerovalent iron (R2) and R3 reactor. The functional genes of denitrifying bacteria (nirK and nirS) were also identified in all reactors with higher copy numbers in R2, followed by R4 and R3. Furthermore, high throughput analysis showed that the Thauera performing partial denitrification, Ignavibacterium performing dissimilatory nitrate reduction to ammonium or nitrite were also present in all reactors, more abundant in R4, confirming that the higher nitrogen removal efficiency in R4 was attributed to the synergistic relationship of other nitrogenous genera with anammox. The higher abundance of PD and DNRA in the reactor with the coupled treatment of nano-zero valent iron and magnetic field, achieved in this research, opens the opportunity of complete nitrogen removal via synergistic partial-denitrification, anammox, and DNRA (SPDAD) process.
Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection
Authors: Wang Zijun , Muecksch Frauke , Schaefer-Babajew Dennis , Finkin Shlomo , Viant Charlotte , Gaebler Christian , Hoffmann Hans- Heinrich , Barnes Christopher O. , Cipolla Melissa , Ramos Victor , Oliveira Thiago Y. , Cho Alice , Schmidt Fabian , Da Silva Justin , Bednarski Eva , Aguado Lauren , Yee Jim , Daga Mridushi , Turroja Martina , Millard Katrina G. , Jankovic Mila , Gazumyan Anna , Zhao Zhen , Rice Charles M. , Bieniasz Paul D. , Caskey Marina , Hatziioannou Theodora , Nussenzweig Michel C.
Published: June 2021

More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals2,5–8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.
Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals
Authors: Kustin Talia , Harel Noam , Finkel Uriah , Perchik Shay , Harari Sheri , Tahor Maayan , Caspi Itamar , Levy Rachel , Leshchinsky Michael , Ken Dror Shifra , Bergerzon Galit , Gadban Hala , Gadban Faten , Eliassian Eti , Shimron Orit , Saleh Loulou , Ben-Zvi Haim , Keren Taraday Elena , Amichay Doron , Ben-Dor Anat , Sagas Dana , Strauss Merav , Shemer Avni Yonat , Huppert Amit , Kepten Eldad , Balicer Ran D. , Netzer Doron , Ben-Shachar Shay , Stern Adi
Published: June 2021

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.
Statistical and sequence learning lead to persistent memory in children after a one-year offline period
Authors: Tóth-Fáber Eszter , Janacsek Karolina , Németh Dezső
Published: June 2021

Extraction of environmental patterns underlies human learning throughout the lifespan and plays a crucial role not only in cognitive but also perceptual, motor, and social skills. At least two types of regularities contribute to acquiring skills: (1) statistical, probability-based regularities, and (2) serial order-based regularities. Memory performance of probability-based and/or serial order-based regularities over short periods (from minutes to weeks) has been widely investigated across the lifespan. However, long-term (months or year-long) memory performance of such knowledge has received relatively less attention and has not been assessed in children yet. Here, we aimed to test the long-term memory performance of probability-based and serial order-based regularities over a 1-year offline period in neurotypical children between the age of 9 and 15. Participants performed a visuomotor four-choice reaction time task designed to measure the acquisition of probability-based and serial order-based regularities simultaneously. Short-term consolidation effects were controlled by retesting their performance after a 5-h delay. They were then retested on the same task 1 year later without any practice between the sessions. Participants successfully acquired both probability-based and serial order-based regularities and retained both types of knowledge over the 1-year period. The successful retention was independent of age. Our study demonstrates that the representation of probability-based and serial order-based regularities remains stable over a long period of time. These findings offer indirect evidence for the developmental invariance model of skill consolidation.
Cyclotide host-defense tailored for species and environments in violets from the Canary Islands
Authors: Slazak Blazej , Kaltenböck Klara , Steffen Karin , Rogala Martyna , Rodríguez-Rodríguez Priscila , Nilsson Anna , Shariatgorji Reza , Andrén Per E. , Göransson Ulf
Published: June 2021

Cyclotides are cyclic peptides produced by plants. Due to their insecticidal properties, they are thought to be involved in host defense. Violets produce complex mixtures of cyclotides, that are characteristic for each species and variable in different environments. Herein, we utilized mass spectrometry (LC–MS, MALDI-MS), transcriptomics and biological assays to investigate the diversity, differences in cyclotide expression based on species and different environment, and antimicrobial activity of cyclotides found in violets from the Canary Islands. A wide range of different habitats can be found on these islands, from subtropical forests to dry volcano peaks at high altitudes. The islands are inhabited by the endemic Viola palmensis, V. cheiranthifolia, V. anagae and the common V. odorata. The number of cyclotides produced by a given species varied in plants from different environments. The highest diversity was noted in V. anagae which resides in subtropical forest and the lowest in V. cheiranthifolia from the Teide volcano. Transcriptome sequencing and LC–MS were used to identify 23 cyclotide sequences from V. anagae. Cyclotide extracts exhibited antifungal activities with the lowest minimal inhibitory concentrations noted for V. anagae (15.62 μg/ml against Fusarium culmorum). The analysis of the relative abundance of 30 selected cyclotides revealed patterns characteristic to both species and populations, which can be the result of genetic variability or environmental conditions in different habitats. The current study exemplifies how plants tailor their host defense peptides for various habitats, and the usefulness of cyclotides as markers for chemosystematics.
The joint involvement in adult onset Still's disease is characterised by a peculiar magnetic resonance imaging and a specific transcriptomic profile
Authors: Ruscitti Piero , Barile Antonio , Berardicurti Onorina , Iafrate Sonia , Di Benedetto Paola , Vitale Antonio , Caso Francesco , Costa Luisa , Bruno Federico , Ursini Francesco , Navarini Luca , Sensini Federica , Scarpa Raffaele , Frediani Bruno , Cantarini Luca , Masciocchi Carlo , Giacomelli Roberto , Cipriani Paola
Published: June 2021

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed.
Improved dynamic imaging of multiphase flow by constrained tomographic reconstruction
Authors: Rasmussen Peter Winkel , Sørensen Henning Osholm , Bruns Stefan , Dahl Anders Bjorholm , Christensen Anders Nymark
Published: June 2021

Dynamic tomography has become an important technique to study fluid flow processes in porous media. The use of laboratory X-ray tomography instruments is, however, limited by their low X-ray brilliance. The prolonged exposure times, in turn, greatly limit temporal resolution. We have developed a tomographic reconstruction algorithm that maintains high image quality, despite reducing the exposure time and the number of projections significantly. Our approach, based on the Simultaneous Iterative Reconstruction Technique, mitigates the problem of few and noisy exposures by utilising a high-quality scan of the system before the dynamic process is started. We use the high-quality scan to initialise the first time step of the dynamic reconstruction. We further constrain regions of the dynamic reconstruction with a segmentation of the static system. We test the performance of the algorithm by reconstructing the dynamics of fluid separation in a multiphase system. The algorithm is compared quantitatively and qualitatively with several other reconstruction algorithms and we show that it can maintain high image quality using only a fraction of the normally required number of projections and with a substantially larger noise level. By robustly allowing fewer projections and shorter exposure, our algorithm enables the study of faster flow processes using laboratory tomography instrumentation but it can also be used to improve the reconstruction quality of dynamic synchrotron experiments.
Changes in the geometry of modern daily disposable soft contact lenses during wear
Authors: Mlyniuk Patryk , Stachura Joanna , Jiménez-Villar Alfonso , Grulkowski Ireneusz , Kaluzny Bartlomiej J.
Published: June 2021

The geometry of contact lenses can be altered by wear but determining the changes that occur in soft contact lenses (SCLs) is challenging. This study aimed to investigate the shape alterations of daily disposable SCLs after wear using swept-source optical coherence tomography (SS-OCT). Forty-five eyes with myopia of − 3.00 diopters (D) were enrolled. The participants wore three types of SCLs: hydrogel lens (nesofilcon A) and silicone hydrogel lenses (delefilcon A and stenfilcon A). The SCLs were scanned 3–6 min after lens removal. We found a significant decrease in the SCL anterior curvature: 0.24 ± 0.17 mm for nesofilcon A, 0.44 ± 0.21 mm for delefilcon A, and 0.53 ± 0.29 mm for stenfilcon A. The changes in the anterior curvature of SCLs correlated moderately with the mean corneal keratometry; Pearson’s correlation coefficients for nesofilcon A and delefilcon A were 0.57 and 0.52, respectively (P < 0.001). A statistically significant change in the total diameter was observed in SCL made of stenfilcon A (0.39 mm, P < 0.001). To conclude, the central radii of curvature decreased after a wearing period for all three types of daily disposable SCLs to imitate the anterior corneal surface, however, the changes in other geometrical parameters measured with SS-OCT were lens-specific.
Heat transfer intensification of nanomaterial with involve of swirl flow device concerning entropy generation
Authors: Shah Zahir , Jafaryar M. , Sheikholeslami M. , Ikramullah  , Kumam Poom
Published: June 2021

The thermal features of hybrid nano-powder turbulent motion through a pipe employing helical turbulator is numerically simulated via Finite Volume Method (FVM). The hybrid nanofluid (MWCNTs + Fe3O4 + H2O) is obtained by uniformly dispersing MWCNTs + Fe3O4 nanomaterials in H2O. The characteristics features of thermal energy transfer of hybrid nanofluid are investigated by varying the pitch ratio (P) of the helical turbulator and Reynolds number (Re) of the fluid. The outputs of the study are depicted in terms of contour plots of temperature, velocity, frictional irreversibility Sgen,f, and thermal irreversibility Sgen,th. The variation of Sgen,f, and Sgen,th with changing P and Re are also displayed by 3D plots. It is found that making the fluid more turbulent by increasing Re, the temperature of the fluid drops whereas the fluid velocity augments. The frictional irreversibility enhances, whereas the thermal irreversibility drops with the increasing turbulent motion. The decreasing P causes to drop the temperature of the higher turbulent fluid flow, while opposite effect is observed for smaller Re. The decreasing P causes to enhance the fluid mixing and thus augments the fluid velocity. Sgen,f and Sgen,th both augment with decreasing P. The comparison of current outputs with the older article shows an acceptable accuracy. The results of the present investigation will be useful in modelling of efficient thermal energy transfer systems.
A feasibility study of dual-task strategy training to improve gait performance in patients with Parkinson’s disease
Authors: Wollesen Bettina , Rudnik Silvan , Gulberti Alessandro , Cordes Thomas , Gerloff Christian , Poetter-Nerger Monika
Published: June 2021

Gait disorders in patients with Parkinson’s disease (PD) impact their mobility and self-dependence. Gait training and dual-task (DT)-training improve gait quality. This study aims to assess the feasibility of a specific, gradually intensified DT-training for PD patients with a special focus on gait performance under single task (ST) and DT conditions. Correlations to Freezing of Gait (FoG) were examined. 17 PD patients (70.1 ± 7.4 years, H&Y Stadium 2–3, FoG-Q 9.0 ± 5.5) participated in a four-week DT-training (1x/week, 60 min) with progressively increasing task difficulty and number of tasks. Gait performance (spatiotemporal parameters) was assessed during ST and DT conditions. The training improved DT gait performance, especially gait velocity + 0.11 m/s; (F(2,16) = 7.163; p = .0171; η2part = .309) and step length (+ 5.73 cm). Also, physical well-being and absolved walking distance improved significantly. Correlation analyses of the FoG score at baseline with relative change of gait metrics post-training revealed significant correlations with training-induced changes of step length and improvement of gait velocity. Overall, the developed DT-training was feasible and effective. Further studies should examine the long-term benefits and the optimal setting to achieve the highest impact. The study was registered in the DRKS (ID DRKS00018084, 23.1.20).
Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML
Authors: Modarres Parastoo , Mohamadi Farsani Farzaneh , Nekouie Amir Abas , Vallian Sadeq
Published: June 2021

The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be differentially expressed in the chemo-resistance compared to the chemo-sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug-resistance development in AML.
Retraction Note: A Chinese herbal formula, Jian-Pi-Yi-Shen decoction, improves muscle atrophy via regulating mitochondrial quality control process in 5/6 nephrectomised rats
Authors: Wang Dongtao , Chen Jianping , Liu Xinhui , Zheng Ping , Song Gaofeng , Yi Tiegang , Li Shunmin
Published: June 2021

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-91869-x.
Facile fabrication of antibacterial and antiviral perhydrolase-polydopamine composite coatings
Authors: Wang Li-Sheng , Xu Shirley , Gopal Sneha , Kim Eunsol , Kim Domyoung , Brier Matthew , Solanki Kusum , Dordick Jonathan S.
Published: June 2021

In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA). In the presence of AcT and its two substrates, propylene glycol diacetate and H2O2, sufficient and continuous PAA is generated over an extended time to kill a wide range of bacteria with the enzyme dissolved in aqueous buffer. For extended self-disinfection, however, active and stable AcT bound onto or incorporated into a surface coating is necessary. In the current study, an active, stable and reusable AcT-based coating was developed by incorporating AcT into a polydopamine (PDA) matrix in a single step, thereby forming a biocatalytic composite onto a variety of surfaces. The resulting AcT-PDA composite coatings on glass, metal and epoxy surfaces yielded up to 7-log reduction of Gram-positive and Gram-negative bacteria when in contact with the biocatalytic coating. This composite coating also possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing. As a result, this enzyme-polymer composite technique may serve as a general strategy for preparing antibacterial and antiviral surfaces for applications in health care and common infrastructure safety, such as in schools, the workplace, transportation, etc.
Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
Authors: Aceves-Sánchez Michel de Jesús , Flores-Valdez Mario Alberto , Pedroza-Roldán César , Creissen Elizabeth , Izzo Linda , Silva-Angulo Fabiola , Dawson Clinton , Izzo Angelo , Bielefeldt-Ohmann Helle , Segura-Cerda Cristian Alfredo , López-Romero Wendy , Bravo-Madrigal Jorge , Barrios-Payán Jorge Alberto , de la Cruz Miguel Ángel , Ares Miguel , Jorge-Espinoza María Guadalupe
Published: June 2021

A single intradermal vaccination with an antibiotic-less version of BCGΔBCG1419c given to guinea pigs conferred a significant improvement in outcome following a low dose aerosol exposure to M. tuberculosis compared to that provided by a single dose of BCG Pasteur. BCGΔBCG1419c was more attenuated than BCG in murine macrophages, athymic, BALB/c, and C57BL/6 mice. In guinea pigs, BCGΔBCG1419c was at least as attenuated as BCG and induced similar dermal reactivity to that of BCG. Vaccination of guinea pigs with BCGΔBCG1419c resulted in increased anti-PPD IgG compared with those receiving BCG. Guinea pigs vaccinated with BCGΔBCG1419c showed a significant reduction of M. tuberculosis replication in lungs and spleens compared with BCG, as well as a significant reduction of pulmonary and extrapulmonary tuberculosis (TB) pathology measured using pathology scores recorded at necropsy. Evaluation of cytokines produced in lungs of infected guinea pigs showed that BCGΔBCG1419c significantly reduced TNF-α and IL-17 compared with BCG-vaccinated animals, with no changes in IL-10. This work demonstrates a significantly improved protection against pulmonary and extrapulmonary TB provided by BCGΔBCG1419c in susceptible guinea pigs together with an increased safety compared with BCG in several models. These results support the continued development of BCGΔBCG1419c as an effective vaccine for TB.
Spectral-domain optical coherence tomography for evaluating palisades of Vogt in ocular surface disorders with limbal involvement
Authors: Chen Ying-Yi , Sun Yi-Chen , Tsai Chia-Ying , Chu Hsiao-Sang , Wu Jo-Hsuan , Chang Huai-Wen , Chen Wei-Li
Published: June 2021

Spectral-domain optical coherence tomography (SD-OCT) has been used to observe the morphology of the palisades of Vogt (POV) with satisfactory resolutions. In this study, we used SD-OCT to examine the microstructure of the POV in ocular surface disorders with limbal involvement. We detect subclinical limbal pathologies based on five parameters, including (1) decreased epithelial thickness, (2) loss of the sharp stromal tip, (3) loss of the smooth epithelial-stromal interface, (4) dilated stromal vessels, and (5) decreased POV density. Eighteen eyes of 10 patients with advancing wavelike epitheliopathy (AWE) and 15 eyes of 9 patients with phlyctenular keratitis/ocular rosacea were recruited. SD-OCT could detect abnormal changes in the POV in 100% of the lesion sites. In presumed-healthy areas of the diseased eyes diagnosed by slit-lamp biomicroscopy, SD-OCT detected abnormal changes in the POV in 100% of the eyes in both groups. In patients with unilateral disease, abnormal changes in the POV were detected by SD-OCT in 50% and 100% of presumed-healthy eyes diagnosed by slit-lamp biomicroscopy in the AWE group and phlyctenular keratitis/ocular rosacea group, respectively. SD-OCT is powerful in detecting POV changes in ocular surface disorders and can provide useful information that cannot be provided by slit-lamp biomicroscopy.
Biomolecular changes and subsequent time-dependent recovery in hippocampal tissue after experimental mild traumatic brain injury
Authors: Ustaoglu Sebnem Garip , Ali Mohamed H. M. , Rakib Fazle , Blezer Erwin L. A. , Van Heijningen Caroline L. , Dijkhuizen Rick M. , Severcan Feride
Published: June 2021

Traumatic brain injury (TBI) is the main cause of disability and mortality in individuals under the age of 45 years. Elucidation of the molecular and structural alterations in brain tissue due to TBI is crucial to understand secondary and long-term effects after traumatic brain injury, and to develop and apply the correct therapies. In the current study, the molecular effects of TBI were investigated in rat brain at 24 h and 1 month after the injury to determine acute and chronic effects, respectively by Fourier transform infrared imaging. This study reports the time-dependent contextual and structural effects of TBI on hippocampal brain tissue. A mild form of TBI was induced in 11-week old male Sprague Dawley rats by weight drop. Band area and intensity ratios, band frequency and bandwidth values of specific spectral bands showed that TBI causes significant structural and contextual global changes including decrease in carbonyl content, unsaturated lipid content, lipid acyl chain length, membrane lipid order, total protein content, lipid/protein ratio, besides increase in membrane fluidity with an altered protein secondary structure and metabolic activity in hippocampus 24 h after injury. However, improvement and/or recovery effects in these parameters were observed at one month after TBI.
Dietary intake and plasma levels of polyunsaturated fatty acids in early-stage Parkinson’s disease
Authors: Yoo Dallah , Lim Yunsook , Son Yiseul , Rho Hyunkyung , Shin Chaewon , Ahn Tae-Beom
Published: June 2021

Polyunsaturated fatty acids (PUFA) are important for neuronal function and may contribute to the development of neurodegenerative diseases. Here, we investigated the correlation between dietary intake and plasma concentrations of PUFA and their associations with clinical severity in early-stage Parkinson’s disease (PD). In a case–control study with 38 patients with PD and 33 controls, we assessed dietary intake using food frequency questionnaires and simultaneously measured the plasma levels of five PUFA. No differences were observed in dietary total energy and lipid intake, including PUFA, between patients with PD and controls. However, α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) plasma levels were lower in patients with PD. The association between dietary intake and plasma PUFA concentrations was not significant in patients with PD. ALA and LA plasma levels were inversely correlated with motor severity in patients with PD, while docosahexaenoic acid and AA plasma levels were positively correlated with non-motor symptoms after controlling for age and sex.
Long-term mortality due to infection associated with elevated liver enzymes: a population-based cohort study
Authors: Oh Tak Kyu , Jang Eun Sun , Song In-Ae
Published: June 2021

We aimed to investigate whether elevated liver enzymes in the adult population were associated with mortality due to infection. As a population-based cohort study, data from the National Health Insurance Service Health Screening Cohort were used. Adult individuals (aged ≥ 40 years) who underwent standardized medical examination between 2002 and 2003 were included, and infectious mortality was defined as mortality due to infection between 2004 and 2015. Aspartate transaminase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), AST/ALT ratio, and dynamic AST/ALT ratio (dAAR) were included in multivariable Cox modeling. A total of 512,746 individuals were included in this study. Infectious mortality occurred in 2444 individuals (0.5%). In the multivariable model, moderate and severe elevation in AST was associated with 1.94-fold [hazard ratio (HR):1.94, 95% confidence interval (CI) 1.71–2.19; P < 0.001] and 3.93-fold (HR: 3.93, 95% CI 3.05–5.07; P < 0.001) higher infectious mortality respectively, compared with the normal AST group. Similar results were observed for moderate and severe elevation in ALT and mild, moderate, and severe elevation in γ-GTP. Additionally, a 1-point increase in the AST/ALT ratio and dAAR was associated with higher infection mortality. Elevated liver enzymes (AST, ALT, AST/ALT ratio, γ-GTP, and dAAR) were associated with increased infectious mortality.
Quantitative assessment of normal middle deltoid muscle elasticity at various arm abduction using ultrasound shear wave elastography
Authors: Wang Lei , Guo Xuanyan , Tan Li , Chen Qin
Published: June 2021

The objective of this study is to assess the change in the normal MD elasticity using shear wave elastography (SWE) through measuring the middle deltoid (MD) elasticity in healthy participants at various arm abduction (with bilateral arms at 0 degrees abduction and 90 degrees active abduction) and analyzing the factors affecting normal MD elasticity. Mean shear wave velocity (SWV) of the MD in healthy right-handed participants were evaluated using SWE at different arm abduction, and potential factors (gender, MD thickness, age, body mass index) affecting MD elasticity were analyzed. Different arm abduction positions of each participant were as follows: (i) 0° abduction of bilateral arm (L0° and R0°), (ii) 90° active abduction of bilateral arm (L90° and R90°). Mean SWV was significantly higher at L90° than L0°, higher at R90° than R0°, higher at R0° than L0°, and higher at R90° than L90° (all P < 0.0001). SWV was significantly higher in males at both L0° (P < 0.05) and R0° (P < 0.01) than in females. Neither MD thickness, age nor body mass index influenced MD elasticity. Reference ranges of normal MD elasticity were 2.4–3.1 m/s in males and 2.2–2.9 m/s in females at L0° and 2.5–3.3 m/s in males and 2.4–3.2 m/s in females at R0°, and were 4.9–6.7 m/s at L90°, 5.2–7.1 m/s at R90° for both males and females. SWE is a feasible technique to assess normal MD elasticity at various arm abduction. Our results suggest that normal MD elasticity at L0°, R0°, L90°, and R90° with SWE are different. Moreover, these reference ranges may serve as quantitative baseline measurements for assessment of normal MD elasticity in the future.
Pan-cancer analysis of SETD2 mutation and its association with the efficacy of immunotherapy
Authors: Lu Mingdong , Zhao Bin , Liu Mengshan , Wu Le , Li Yingying , Zhai Yingna , Shen Xian
Published: June 2021

Histone methyltransferase SETD2 plays a critical role in maintaining genomic integrity and stability. Here, we investigated the characteristics of SETD2 somatic mutation in the cancer genome atlas pan-cancer cohort. Our data revealed that, compared with SETD2 nonmutant patients, SETD2 mutant patients had higher tumor mutation burden and microsatellite instability. In addition, the transcriptions of most genes related to immune activities were upregulated in patients with SETD2 mutant tumors. Further examination of cancer patients treated with immune checkpoint inhibitors suggested SETD2 mutation was associated with favorable clinical outcomes. These results have implication for the personalization of cancer immunotherapy.
A simulation-based evaluation of machine learning models for clinical decision support: application and analysis using hospital readmission
Authors: Mišić Velibor V. , Rajaram Kumar , Gabel Eilon
Published: June 2021

The interest in applying machine learning in healthcare has grown rapidly in recent years. Most predictive algorithms requiring pathway implementations are evaluated using metrics focused on predictive performance, such as the c statistic. However, these metrics are of limited clinical value, for two reasons: (1) they do not account for the algorithm’s role within a provider workflow; and (2) they do not quantify the algorithm’s value in terms of patient outcomes and cost savings. We propose a model for simulating the selection of patients over time by a clinician using a machine learning algorithm, and quantifying the expected patient outcomes and cost savings. Using data on unplanned emergency department surgical readmissions, we show that factors such as the provider’s schedule and postoperative prediction timing can have major effects on the pathway cohort size and potential cost reductions from preventing hospital readmissions.