bluuebunny/crossref_metadata_2025 huggingface dataset:
Early myocardial damage (EMD) and valvular dysfunction after femur fracture in pigs
Authors: Weber Birte , Lackner Ina , Miclau Theodore , Stulz Jonathan , Gebhard Florian , Pfeifer Roman , Cinelli Paolo , Halvachizadeh Sascha , Teuben Michel , Pape Hans-Christoph , Lipiski Miriam , Cesarovic Nikola , Kalbitz Miriam
Published: April 2021

Musculoskeletal injuries are the most common reason for surgery in severely injured patients. In addition to direct cardiac damage after physical trauma, there is rising evidence that trauma induces secondary cardiac structural and functional damage. Previous research associates hip fractures with the appearance of coronary heart disease: As 25% of elderly patients developed a major adverse cardiac event after hip fracture. 20 male pigs underwent femur fracture with operative stabilization via nailing (unreamed, reamed, RIA I and a new RIA II; each group n = 5). Blood samples were collected 6 h after trauma and the concentration of troponin I and heart-type fatty acid binding protein (HFABP) as biomarkers for EMD were measured. At baseline and 6 h after trauma, transesophageal ECHO (TOE) was performed; and invasive arterial and left ventricular blood pressure were measured to evaluate the cardiac function after femur fracture. A systemic elevation of troponin I and HFABP indicate an early myocardial damage after femur fracture in pigs. Furthermore, various changes in systolic (ejection fraction and cardiac output) and diastolic (left ventricular end-diastolic pressure, mitral valve deceleration time and E/A ratio) parameters illustrate the functional impairment of the heart. These findings were accompanied by the development of valvular dysfunction (pulmonary and tricuspid valve). To the best of our knowledge, we described for the first time the development of functional impairment of the heart in the context of EMD after long bone fracture in pigs. Next to troponin and HFABP elevation, alterations in the systolic and diastolic function occurred and were accompanied by pulmonary and tricuspid valvular insufficiency. Regarding EMD, none of the fracture stabilization techniques (unreamed nailing, reaming, RIA I and RIA II) was superior.
Green phosphorescent organic light-emitting diode exhibiting highest external quantum efficiency with ultra-thin undoped emission layer
Authors: Kang Shin Woo , Baek Dong-Hyun , Ju Byeong-Kwon , Park Young Wook
Published: April 2021

In this study, we report highly efficient green phosphorescent organic light-emitting diodes (OLEDs) with ultra-thin emission layers (EMLs). We use tris[2-phenylpyridinato-C2,N]iridium(III) (Ir(ppy)3), a green phosphorescent dopant, for creating the OLEDs. Under systematic analysis, the peak external quantum efficiency (EQE) of an optimized device based on the ultra-thin EML structure is found to be approximately 24%. This result is highest EQE among ultra-thin EML OLEDs and comparable to the highest efficiency achieved by OLEDs using Ir(ppy)3 that are fabricated via conventional doping methods. Moreover, this result shows that OLEDs with ultra-thin EML structures can achieve ultra-high efficiency.
Facile preparation and highly efficient sorption of magnetic composite graphene oxide/Fe3O4/GC for uranium removal
Authors: Yang Aili , Wang Zhijun , Zhu Yukuan
Published: April 2021

In this work, we reported for the first time a novel magnetic composite graphene oxide/Fe3O4/glucose-COOH (GO/Fe3O4/GC) that was facilely prepared from glucose through the hydrothermal carbonization and further combination with graphene oxide (GO). The chemical and structural properties of the samples were investigated. By the batch uranium adsorption experiments, the magnetic composite GO/Fe3O4/GC exhibits an excellent adsorption performance and fast solid–liquid separation for uranium from aqueous solution. GO/Fe3O4/GC (the maximum adsorption capacity (Qm) was 390.70 mg g−1) exhibited excellent adsorption capacity and higher removal rate (> 99%) for U(VI) than those of glucose-COOH (GC) and magnetic GC (MGC). The effect of the coexisting ions, such as Na+, K+, Mg2+, Ca2+, and Al3+, on the U(VI) removal efficiency of GO/Fe3O4/GC was examined. The equilibrium sorption and sorption rate for the as-prepared adsorbents well fit the Langmuir model and pseudo second-order kinetic model, respectively. The thermodynamic parameters (ΔH0 = 11.57 kJ mol−1 and ΔG0 < 0) for GO/Fe3O4/GC indicate that the sorption process of U(VI) was exothermic and spontaneous. Thus, this research provides a facile strategy for the preparation of the magnetic composite with low cost, high efficiency and fast separation for the U(VI) removal from aqueous solution.
Metagenomic shotgun sequencing reveals host species as an important driver of virome composition in mosquitoes
Authors: Thongsripong Panpim , Chandler James Angus , Kittayapong Pattamaporn , Wilcox Bruce A. , Kapan Durrell D. , Bennett Shannon N.
Published: April 2021

High-throughput nucleic acid sequencing has greatly accelerated the discovery of viruses in the environment. Mosquitoes, because of their public health importance, are among those organisms whose viromes are being intensively characterized. Despite the deluge of sequence information, our understanding of the major drivers influencing the ecology of mosquito viromes remains limited. Using methods to increase the relative proportion of microbial RNA coupled with RNA-seq we characterize RNA viruses and other symbionts of three mosquito species collected along a rural to urban habitat gradient in Thailand. The full factorial study design allows us to explicitly investigate the relative importance of host species and habitat in structuring viral communities. We found that the pattern of virus presence was defined primarily by host species rather than by geographic locations or habitats. Our result suggests that insect-associated viruses display relatively narrow host ranges but are capable of spreading through a mosquito population at the geographical scale of our study. We also detected various single-celled and multicellular microorganisms such as bacteria, alveolates, fungi, and nematodes. Our study emphasizes the importance of including ecological information in viromic studies in order to gain further insights into viral ecology in systems where host specificity is driving both viral ecology and evolution.
Development and virtual validation of a novel digital workflow to rehabilitate palatal defects by using smartphone-integrated stereophotogrammetry (SPINS)
Authors: Farook Taseef Hasan , Jamayet Nafij Bin , Asif Jawaad Ahmed , Din Abdul Sattar , Mahyuddin Muhammad Nasiruddin , Alam Mohammad Khursheed
Published: April 2021

Palatal defects are rehabilitated by fabricating maxillofacial prostheses called obturators. The treatment incorporates taking deviously unpredictable impressions to facsimile the palatal defects into plaster casts for obturator fabrication in the dental laboratory. The casts are then digitally stored using expensive hardware to prevent physical damage or data loss and, when required, future obturators are digitally designed, and 3D printed. Our objective was to construct and validate an economic in-house smartphone-integrated stereophotogrammetry (SPINS) 3D scanner and to evaluate its accuracy in designing prosthetics using open source/free (OS/F) digital pipeline. Palatal defect models were scanned using SPINS and its accuracy was compared against the standard laser scanner for virtual area and volumetric parameters. SPINS derived 3D models were then used to design obturators by using (OS/F) software. The resultant obturators were virtually compared against standard medical software designs. There were no significant differences in any of the virtual parameters when evaluating the accuracy of both SPINS, as well as OS/F derived obturators. However, limitations in the design process resulted in minimal dissimilarities. With further improvements, SPINS based prosthetic rehabilitation could create a viable, low cost method for rural and developing health services to embrace maxillofacial record keeping and digitised prosthetic rehabilitation.
An approach using ddRADseq and machine learning for understanding speciation in Antarctic Antarctophilinidae gastropods
Authors: Moles Juan , Derkarabetian Shahan , Schiaparelli Stefano , Schrödl Michael , Troncoso Jesús S. , Wilson Nerida G. , Giribet Gonzalo
Published: April 2021

Sampling impediments and paucity of suitable material for molecular analyses have precluded the study of speciation and radiation of deep-sea species in Antarctica. We analyzed barcodes together with genome-wide single nucleotide polymorphisms obtained from double digestion restriction site-associated DNA sequencing (ddRADseq) for species in the family Antarctophilinidae. We also reevaluated the fossil record associated with this taxon to provide further insights into the origin of the group. Novel approaches to identify distinctive genetic lineages, including unsupervised machine learning variational autoencoder plots, were used to establish species hypothesis frameworks. In this sense, three undescribed species and a complex of cryptic species were identified, suggesting allopatric speciation connected to geographic or bathymetric isolation. We further observed that the shallow waters around the Scotia Arc and on the continental shelf in the Weddell Sea present high endemism and diversity. In contrast, likely due to the glacial pressure during the Cenozoic, a deep-sea group with fewer species emerged expanding over great areas in the South-Atlantic Antarctic Ridge. Our study agrees on how diachronic paleoclimatic and current environmental factors shaped Antarctic communities both at the shallow and deep-sea levels, promoting Antarctica as the center of origin for numerous taxa such as gastropod mollusks.
Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
Authors: Hariri Hadla , Addison William N. , St-Arnaud René
Published: April 2021

We have previously shown that parathyroid hormone (PTH) induces the phosphorylation of the DNA-binding protein Nascent polypeptide associated complex And Coregulator alpha (NACA), leading to nuclear translocation of NACA and activation of target genes. Using ChIP-Seq against NACA in parallel with RNA-sequencing, we report the identification of Ubiquitin Specific Peptidase 53 (Usp53) as a target gene of PTH-activated NACA in osteoblasts. A binding site for NACA within the ChIP fragment from the Usp53 promoter was confirmed by electrophoretic mobility shift assay. Activity of the Usp53 promoter (− 2325/+ 238 bp) was regulated by the JUN-CREB complex and this activation relied on activated PKA and the presence of NACA. Usp53 knockdown in ST2 stromal cells stimulated expression of the osteoblastic markers Bglap2 (Osteocalcin) and Alpl (Alkaline phosphatase) and inhibited expression of the adipogenic markers Pparg and Cebpa. A similar effect was measured when knocking down Naca. During osteoblastogenesis, the impact of Usp53 knockdown on PTH responses varied depending on the maturation stage of the cells. In vivo implantation of Usp53-knockdown bone marrow stromal cells in immunocompromised mice showed an increase in osteoblast number and a decrease in adipocyte counts. Our data suggest that Usp53 modulates the fate of mesenchymal cells by impacting lineage selection.
Influence of bone conduction transducer type and placement on ocular and cervical vestibular evoked myogenic potentials
Authors: Fröhlich Laura , Wilke Maira , Plontke Stefan K. , Rahne Torsten
Published: April 2021

Evaluating the effectiveness of different bone conduction (BC) transducers with controlled coupling force to elicit cervical and ocular vestibular evoked myogenic potentials (cVEMPs, oVEMPs) in healthy subjects by comparing response rates, amplitudes, latencies, thresholds and asymmetry ratios. Prospective experimental study including healthy participants. VEMPs were measured to different stimulation modes; the BC transducer coupling force was controlled to 5.4 (± 0.5) Newton. cVEMPs: to bone conducted vibration (BCV) with the B81 transducer on the mastoid; oVEMPs: to BCV with the B81 on the mastoid, BCV with the B81 on the forehead, and BCV with the Mini-Shaker 4810 on the forehead. Air conducted sound (ACS) with insert earphones was used as reference. Data of 24 normal subjects (mean age 25.3 (± 3.0) years) were analyzed. ACS and BCV with the B81on the mastoid evoked cVEMPs in 100% of ears. The highest oVEMP response rates were obtained with the B81 on the mastoid (83–92%), the lowest with the B81 on the forehead (17–22%). The Mini-Shaker elicited lower response rates (65%) compared to results from the literature without coupling force control and compared to ACS (78–87%). Amplitudes were higher for BCV than ACS. ACS and BCV on the mastoid caused higher asymmetry compared to BCV forehead stimulation. The B81 was feasible to elicit VEMPs with mastoid placement and can be used as an approved medical device to measure BCV VEMPs in a clinical set-up. Normative asymmetry values have to be established due to higher variability for mastoid stimulation.
Lupeol acetate as a potent antifungal compound against opportunistic human and phytopathogenic mold Macrophomina phaseolina
Authors: Javed Shabnam , Mahmood Zaid , Khan Khalid Mohammed , Sarker Satyajit D. , Javaid Arshad , Khan Iqra Haider , Shoaib Amna
Published: April 2021

Antifungal activity of Monothecabuxifolia methanolic extract and its various fractions were assessed against Macrophominaphaseolina, a soil-borne fungal pathogen of more than 500 vegetal species as well as rare and emerging opportunistic human pathogen. Different concentrations of methanolic extract (3.125 to 200 mg mL−1) inhibited fungal biomass by 39–45%. Isolated n-hexane, chloroform and ethyl acetate fractions suppressed fungal biomass by 32–52%, 29–50% and 29–35%, respectively. Triterpenes lupeol and lupeol acetate (1, 2) were isolated from n-hexane while betulin, β-sitosterol, β-amyrin, oleanolic acid (3–6) were isolated from chloroform fraction. Vanillic acid, protocatechuic acid, kaempferol and quercetin (7–10) were isolated from the ethyl acetate fraction and identified using various spectroscopic techniques namely mass spectroscopy and NMR. Antifungal activity of different concentrations (0.0312 to 2 mg mL−1) of the isolated compounds was evaluated and compared with the activity of a broad spectrum fungicide mancozeb. Different concentrations of mencozeb reduced fungal biomass by 83–85%. Among the isolated compounds lupeol acetate (2) was found the highest antifungal against M.phaseolina followed by betulin (3), vanillic acid (7), protocatechuic acid (8), β-amyrin (5) and oleanolic acid (6) resulting in 79–81%, 77–79%, 74–79%, 67–72%, 68–71% and 68–71%, respectively. Rest of the compounds also showed considerable antifungal activity and reduced M.phaseolina biomass by 41–64%.
Task-related brain functional network reconfigurations relate to motor recovery in chronic subcortical stroke
Authors: Cheng Hsiao-Ju , Ng Kwun Kei , Qian Xing , Ji Fang , Lu Zhong Kang , Teo Wei Peng , Hong Xin , Nasrallah Fatima Ali , Ang Kai Keng , Chuang Kai-Hsiang , Guan Cuntai , Yu Haoyong , Chew Effie , Zhou Juan Helen
Published: April 2021

Stroke leads to both regional brain functional disruptions and network reorganization. However, how brain functional networks reconfigure as task demand increases in stroke patients and whether such reorganization at baseline would facilitate post-stroke motor recovery are largely unknown. To address this gap, brain functional connectivity (FC) were examined at rest and motor tasks in eighteen chronic subcortical stroke patients and eleven age-matched healthy controls. Stroke patients underwent a 2-week intervention using a motor imagery-assisted brain computer interface-based (MI-BCI) training with or without transcranial direct current stimulation (tDCS). Motor recovery was determined by calculating the changes of the upper extremity component of the Fugl–Meyer Assessment (FMA) score between pre- and post-intervention divided by the pre-intervention FMA score. The results suggested that as task demand increased (i.e., from resting to passive unaffected hand gripping and to active affected hand gripping), patients showed greater FC disruptions in cognitive networks including the default and dorsal attention networks. Compared to controls, patients had lower task-related spatial similarity in the somatomotor–subcortical, default–somatomotor, salience/ventral attention–subcortical and subcortical–subcortical connections, suggesting greater inefficiency in motor execution. Importantly, higher baseline network-specific FC strength (e.g., dorsal attention and somatomotor) and more efficient brain network reconfigurations (e.g., somatomotor and subcortical) from rest to active affected hand gripping at baseline were related to better future motor recovery. Our findings underscore the importance of studying functional network reorganization during task-free and task conditions for motor recovery prediction in stroke.
The combination of fluoxetine and environmental enrichment reduces postpartum stress-related behaviors through the oxytocinergic system and HPA axis in mice
Authors: Bashiri Hamideh , Houwing Danielle J. , Homberg Judith R. , Salari Ali-Akbar
Published: April 2021

Gestational stress can increase postpartum depression in women. To treat maternal depression, fluoxetine (FLX) is most commonly prescribed. While FLX may be effective for the mother, at high doses it may have adverse effects on the fetus. As environmental enrichment (EE) can reduce maternal stress effects, we hypothesized that a subthreshold dose of FLX increases the impact of EE to reduce anxiety and depression-like behavior in postpartum dams exposed to gestational stress. We evaluated this hypothesis in mice and to assess underlying mechanisms we additionally measured hypothalamic–pituitary–adrenal (HPA) axis function and brain levels of the hormone oxytocin, which are thought to be implicated in postpartum depression. Gestational stress increased anxiety- and depression-like behavior in postpartum dams. This was accompanied by an increase in HPA axis function and a decrease in whole-brain oxytocin levels in dams. A combination of FLX and EE remediated the behavioral, HPA axis and oxytocin changes induced by gestational stress. Central administration of an oxytocin receptor antagonist prevented the remediating effect of FLX + EE, indicating that brain oxytocin contributes to the effect of FLX + EE. These findings suggest that oxytocin is causally involved in FLX + EE mediated remediation of postpartum stress-related behaviors, and HPA axis function in postpartum dams.
Differences in glycated hemoglobin levels and cholesterol levels in individuals with diabetes according to Helicobacter pylori infection
Authors: Haj Saeda , Chodick Gabriel , Goren Sophy , Na’amnih Wasef , Shalev Varda , Muhsen Khitam
Published: April 2021

This study examined differences in glycated hemoglobin (HbA1c), fasting plasma glucose and cholesterol levels between H. pylori infected and uninfected persons with diabetes. Anonymized data of Maccabi Healthcare Services in Israel were analyzed, of 12,207 individuals (50.0% H. pylori positive) aged 25–95 years who underwent the urea breath test. The data included HbA1c, fasting plasma glucose and cholesterol levels. The inverse probability of treatment weighting approach was used to account for confounders. Differences between individuals who were H. pylori positive and negative, in HbA1c (> or ≤ 7.0%) and in cholesterol levels were assessed using weighted generalized estimating equations. For men, but not women, the likelihood of having HbA1c > 7.0% was increased in those infected than uninfected with H. pylori: prevalence ratio 1.11 (95% CI 1.00, 1.24), P = 0.04. For both sexes, total cholesterol (P = 0.004) and low-density lipoprotein (LDL) levels (P = 0.006) were higher among those infected than uninfected with H. pylori. No significant differences were found in glucose and HDL levels according to H. pylori infection. The results were consistent in unweighted multivariable analyses. In conclusion, H. pylori infection might be related to worse glycemic control in men, and higher total cholesterol and LDL cholesterol levels in both sexes.
Fast and effective pseudo transfer entropy for bivariate data-driven causal inference
Authors: Silini Riccardo , Masoller Cristina
Published: April 2021

Identifying, from time series analysis, reliable indicators of causal relationships is essential for many disciplines. Main challenges are distinguishing correlation from causality and discriminating between direct and indirect interactions. Over the years many methods for data-driven causal inference have been proposed; however, their success largely depends on the characteristics of the system under investigation. Often, their data requirements, computational cost or number of parameters limit their applicability. Here we propose a computationally efficient measure for causality testing, which we refer to as pseudo transfer entropy (pTE), that we derive from the standard definition of transfer entropy (TE) by using a Gaussian approximation. We demonstrate the power of the pTE measure on simulated and on real-world data. In all cases we find that pTE returns results that are very similar to those returned by Granger causality (GC). Importantly, for short time series, pTE combined with time-shifted (T-S) surrogates for significance testing strongly reduces the computational cost with respect to the widely used iterative amplitude adjusted Fourier transform (IAAFT) surrogate testing. For example, for time series of 100 data points, pTE and T-S reduce the computational time by $$82\%$$

82
%

with respect to GC and IAAFT. We also show that pTE is robust against observational noise. Therefore, we argue that the causal inference approach proposed here will be extremely valuable when causality networks need to be inferred from the analysis of a large number of short time series.
Microscopic imbibition characterization of sandstone reservoirs and theoretical model optimization
Authors: Xu Xuan , Wan Yujin , Li Xizhe , Hu Yong , Tian Shanshan , Mei Qingyan , Jiao Chunyan , Guo Changmin
Published: April 2021

Traditional porous media imbibition models deviate from the actual imbibition process in oil and gas reservoirs. Experimental studies on gas–water imbibition in reservoirs were carried out to describe the dynamic profile variation process of wet phase saturation in reservoirs and to further reveal the variation of the imbibition front and the imbibition amount. Optimization and correction methods were established, and experimental verifications were performed. Studies have shown the following: (1) Unlike homogeneous porous media, the water phase imbibition process in oil and gas reservoirs is more complicated, and it is impossible for the maximum saturation of imbibition to reach 100%. (2) Contrary to the theoretical hypothesis, the imbibition of water is not piston-like, and there is a clear transition zone at the imbibition front. This transition zone is the main cause of water saturation variations in the imbibition zone; with the expansion of the imbibition zone, the influence of the transition zone on water saturation weakens. (3) Traditional theoretical models predict a positive correlation between the imbibition amount and the measurements; however, there is a large deviation in the numerical values, which must be corrected. (4) The L-W model was optimized and the parameter group fluid factor F and the reservoir factor R were proposed to characterize the properties of the fluid and the reservoir, respectively. These two parameters have a clear physical significance and are easy to accurately test. After experimental correction, the optimized model is favourably suitable for oil and gas reservoirs.
A paradoxical knowledge gap in science for critically endangered fishes and game fishes during the sixth mass extinction
Authors: Guy Christopher S. , Cox Tanner L. , Williams Jacob R. , Brown Colter D. , Eckelbecker Robert W. , Glassic Hayley C. , Lewis Madeline C. , Maskill Paige A. C. , McGarvey Lauren M. , Siemiantkowski Michael J.
Published: April 2021

Despite unprecedented scientific productivity, Earth is undergoing a sixth mass extinction. The disconnect between scientific output and species conservation may be related to scientists studying the wrong species. Given fishes have a high extinction rate, we assessed the paradox between scientific productivity and science needed for conservation by comparing scientific output created for critically endangered fishes and game fishes. We searched 197,866 articles (1964–2018) in 112 journals for articles on 460 critically endangered fishes, 297 game fishes, and 35 fishes classified as critically endangered and game fish—our analysis included freshwater and marine species. Only 3% of the articles in the final database were on critically endangered fishes; 82% of critically endangered fishes had zero articles. The difference between the number of articles on game fishes and critically endangered fishes increased temporally with more articles on game fishes during the extinction crisis. Countries with 10 or more critically endangered fishes averaged only 17 articles from 1964 to 2018. Countries with the most critically endangered fishes are most in need of science. More scientific knowledge is needed on critically endangered fishes to meet the challenges of conserving fishes during the sixth mass extinction.
A 3 pJ/bit free space optical interlink platform for self-powered tetherless sensing and opto-spintronic RF-to-optical transduction
Authors: Wheaton Skyler , Lopez-Dominguez Victor , Almasi Hamid , Cai Jialin , Zeng Zhongming , Khalili Amiri Pedram , Mohseni Hooman
Published: April 2021

Tetherless sensors have long been positioned to enable next generation applications in biomedical, environmental, and industrial sectors. The main challenge in enabling these advancements is the realization of a device that is compact, robust over time, and highly efficient. This paper presents a tetherless optical tag which utilizes optical energy harvesting to realize scalable self-powered devices. Unlike previous demonstrations of optically coupled sensor nodes, the device presented here amplifies signals and encodes data on the same optical beam that provides its power. This optical interrogation modality results in a highly efficient data link. These optical tags support data rates up to 10 Mb/s with an energy consumption of ~ 3 pJ/bit. As a proof-of-concept application, the optical tag is combined with a spintronic microwave detector based on a magnetic tunnel junction (MTJ). We used this hybrid opto-spintronic system to perform self-powered transduction of RF waves at 1 GHz to optical frequencies at ~ 200 THz, while carrying an audio signal across (see Supplementary Data for audio files).
Image-based personalization of computational models for predicting response of high-grade glioma to chemoradiation
Authors: Hormuth David A. , Al Feghali Karine A. , Elliott Andrew M. , Yankeelov Thomas E. , Chung Caroline
Published: April 2021

High-grade gliomas are an aggressive and invasive malignancy which are susceptible to treatment resistance due to heterogeneity in intratumoral properties such as cell proliferation and density and perfusion. Non-invasive imaging approaches can measure these properties, which can then be used to calibrate patient-specific mathematical models of tumor growth and response. We employed multiparametric magnetic resonance imaging (MRI) to identify tumor extent (via contrast-enhanced T1-weighted, and T2-FLAIR) and capture intratumoral heterogeneity in cell density (via diffusion-weighted imaging) to calibrate a family of mathematical models of chemoradiation response in nine patients with unresected or partially resected disease. The calibrated model parameters were used to forecast spatially-mapped individual tumor response at future imaging visits. We then employed the Akaike information criteria to select the most parsimonious member from the family, a novel two-species model describing the enhancing and non-enhancing components of the tumor. Using this model, we achieved low error in predictions of the enhancing volume (median: − 2.5%, interquartile range: 10.0%) and a strong correlation in total cell count (Kendall correlation coefficient 0.79) at 3-months post-treatment. These preliminary results demonstrate the plausibility of using multiparametric MRI data to inform spatially-informative, biologically-based predictive models of tumor response in the setting of clinical high-grade gliomas.
Olfactory signals and fertility in olive baboons
Authors: Vaglio Stefano , Minicozzi Pamela , Kessler Sharon E. , Walker David , Setchell Joanna M.
Published: April 2021

Female primates signal impending ovulation with a suite of sexual signals. Studies of these signals have focussed on visual, and to a lesser extent, acoustic signals, neglecting olfactory signals. We aimed to investigate the information content of female olfactory signals in captive olive baboons (Papio anubis) and relate these to the female fertile period. We studied eight adult females living in four groups at the CNRS Station de Primatologie, Rousset-sur-Arc, France. We used vaginal cytology to detect ovulation. We investigated the volatile component of odour signals using solid-phase microextraction and gas chromatography-mass spectrometry. We found a total of 74 volatile compounds, of which we tentatively identified 25, including several ketones, alcohols, aldehydes, terpenes, volatile fatty acids and hydrocarbons that have been identified in odour profiles of other primates. Our results show that vaginal odour intensity differs with sexual cycle stage suggesting that odour might play a role in signalling female baboon fertility. We found differences in vaginal odour between females living in all-female and in mixed sex groups but we could not distinguish the effects of group composition, female age and identity. This study of olfactory signalling improves our understanding of how female primates advertise their sexual receptivity.
Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
Authors: Nascimento-Carvalho Gustavo C. , Nascimento-Carvalho Eduardo C. , Ramos Clara L. , Vilas-Boas Ana-Luisa , Moreno-Carvalho Otávio A. , Vinhaes Caian L. , Barreto-Duarte Beatriz , Queiroz Artur T. L. , Andrade Bruno B. , Nascimento-Carvalho Cristiana M.
Published: April 2021

Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015–2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017–2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1β, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1β, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.
Multiscale investigation on the chemical and anatomical changes of lignocellulosic biomass for different severities of hydrothermal treatment
Authors: Lancha Julia P. , Perré Patrick , Colin Julien , Lv Pin , Ruscassier Nathalie , Almeida Giana
Published: April 2021

The chemical changes sustained by lignocellulosic biomass during hydrothermal treatment are reflected at multiple scales. This study proposes to benefit from this multiscale nature in order to provide a global understanding of biomass alterations during hydrothermal treatment. For this purpose, complementary imaging techniques—confocal Raman microscopy and X-ray nano-tomography—analysed by image processing and coupled to chemical measurements were used. This unique combination of analyses provided valuable information on topochemical and morphological changes of poplar samples, without the artefacts of sample preparation. At the cell wall level, holocellulose hydrolysis and lignin modifications were observed, which corresponded to anatomical modifications observed at higher scales. Overall, after treatment, samples shrank and had thinner cell walls. When subjected to more severe pre-treatments, cells were disrupted and detached from adjacent cells. Anatomical changes were then used to obtain quantitative indicators of the treatment severity. The effects of treatment at different scales can thus be quantitatively connected in both directions, from micro to macro and from macro to micro.
Induced pluripotent stem cells from subjects with Lesch-Nyhan disease
Authors: Sutcliffe Diane J. , Dinasarapu Ashok R. , Visser Jasper E. , Hoed Joery den , Seifar Fatemeh , Joshi Piyush , Ceballos-Picot Irene , Sardar Tejas , Hess Ellen J. , Sun Yan V. , Wen Zhexing , Zwick Michael E. , Jinnah H. A.
Published: April 2021

Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine–guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 lines had the characteristics of pluripotent stem cells, as assessed by immunostaining for pluripotency markers, expression of pluripotency genes, and differentiation into the 3 primary germ cell layers. Gene expression profiling with RNAseq demonstrated significant heterogeneity among the lines. Despite this heterogeneity, several anticipated abnormalities were readily detectable across all LND lines, including reduced HPRT1 mRNA. Several unexpected abnormalities were also consistently detectable across the LND lines, including decreases in FAR2P1 and increases in RNF39. Shotgun proteomics also demonstrated several expected abnormalities in the LND lines, such as absence of HGprt protein. The proteomics study also revealed several unexpected abnormalities across the LND lines, including increases in GNAO1 decreases in NSE4A. There was a good but partial correlation between abnormalities revealed by the RNAseq and proteomics methods. Finally, functional studies demonstrated LND lines had no HGprt enzyme activity and resistance to the toxic pro-drug 6-thioguanine. Intracellular purines in the LND lines were normal, but they did not recycle hypoxanthine. These cells provide a novel resource to reveal insights into the relevance of heterogeneity among iPSC lines and applications for modeling LND.
Toxicity of biogenic zinc oxide nanoparticles to soil organic matter cycling and their interaction with rice-straw derived biochar
Authors: Shemawar  , Mahmood Abid , Hussain Sabir , Mahmood Faisal , Iqbal Muhammad , Shahid Muhammad , Ibrahim Muhammad , Ali Muhammad Arif , Shahzad Tanvir
Published: April 2021

Given the rapidly increasing use of metal oxide nanoparticles in agriculture as well as their inadvertent addition through sewage sludge application to soils, it is imperative to assess their possible toxic effects on soil functions that are vital for healthy crop production. In this regard, we designed a lab study to investigate the potential toxicity of one of the most produced nanoparticles, i.e. zinc oxide nanoparticles (nZnO), in a calcareous soil. Microcosms of 80 g of dry-equivalent fresh soils were incubated in mason jars for 64 days, after adding 100 or 1000 mg of biogenically produced nZnO kg−1 soil. Moreover, we also added rice-straw derived biochar at 1 or 5% (w: w basis) hypothesizing that the biochar would alleviate nZnO-induced toxicity given that it has been shown to adsorb and detoxify heavy metals in soils. We found that the nZnO decreased microbial biomass carbon by 27.0 to 33.5% in 100 mg nZnO kg−1 soil and by 39.0 to 43.3% in 1000 mg nZnO kg−1 soil treatments across biochar treatments in the short term i.e. 24 days after incubation. However, this decrease disappeared after 64 days of incubation and the microbial biomass in nZnO amended soils were similar to that in control soils. This shows that the toxicity of nZnO in the studied soil was ephemeral and transient which was overcome by the soil itself in a couple of months. This is also supported by the fact that the nZnO induced higher cumulative C mineralization (i.e. soil respiration) at both rates of addition. The treatment 100 mg nZnO kg−1 soil induced 166 to 207%, while 1000 mg nZnO kg−1 soil induced 136 to 171% higher cumulative C mineralization across biochar treatments by the end of the experiment. However, contrary to our hypothesis increasing the nZnO addition from 100 to 1000 mg nZnO kg−1 soil did not cause additional decrease in microbial biomass nor induced higher C mineralization. Moreover, the biochar did not alleviate even the ephemeral toxicity that was observed after 24d of incubation. Based on overall results, we conclude that the studied soil can function without impairment even at 1000 mg kg−1 concentration of nZnO in it.
Antifreeze protein from Ammopiptanthus nanus functions in temperature-stress through domain A
Authors: Yu HaoQiang , Zheng HongYing , Liu Yuan , Yang QingQing , Li WanChen , Zhang YuanYuan , Fu FengLing
Published: April 2021

Temperature stress restricts plant growth and development. Antifreeze protein (AFP) can improve plants antifreeze ability. In our previous study, the AnAFP gene cloned from Ammopiptanthus nanus was confirmed to be an excellent candidate enhancing plant cold resistance. But, AnAFP protein shared similar structures with KnS type dehydrins including K, N and S domains except ice crystal binding domain A. Here, we generated AnAFPΔA, AnAFPΔK, AnAFPΔN and AnAFPΔS, and transformed them into ordinary and cold sensitive strains of E. coli, and Arabidopsis KS type dehydrin mutant to evaluate their function. Expression of AnAFPΔA decreases cold and heat tolerance in E. coli, meanwhile, AnAFP enhances heat tolerance in Arabidopsis, suggesting that domain A is a thermal stable functional domain. AnAFP, AnAFPΔA and AnAFPΔS localize in whole cell, but AnAFPΔK and AnAFPΔN only localizes in nucleus and cytoplasm, respectively, exhibiting that K and N domains control localization of AnAFP. Likewise, K domain blocks interaction between AnAFP and AnICE1. The result of RT-qPCR showed that expression of AnAFP, AnICE1 and AnCBF genes was significantly induced by high-temperature, indicating that the AnAFP is likely regulated by ICE1-CBF-COR signal pathway. Taken together, the study provides insights into understanding the mechanism of AnAFP in response to temperature stress and gene resource to improve heat or cold tolerance of plants in transgenic engineering.
High throughput viscoelastic particle focusing and separation in spiral microchannels
Authors: Kumar Tharagan , Ramachandraiah Harisha , Iyengar Sharath Narayana , Banerjee Indradumna , Mårtensson Gustaf , Russom Aman
Published: April 2021

Passive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported. We show that the balance between dominant inertial lift force, dean drag force and elastic force enables stable 3D particle focusing at dynamically high Reynolds numbers. Using a two-turn spiral, we show that particles, initially pinched towards the inner wall using an elasticity enhancer, PEO (polyethylene oxide), as sheath migrate towards the outer wall strictly based on size and can be effectively separated with high precision. As a proof of principle for high resolution particle separation, 15 µm particles were effectively separated from 10 µm particles. A separation efficiency of 98% for the 10 µm and 97% for the 15 µm particles was achieved. Furthermore, we demonstrate sheath-less, high throughput, separation using a novel integrated two-spiral device and achieved a separation efficiency of 89% for the 10 µm and 99% for the 15 µm particles at a sample flow rate of 1 mL/min—a throughput previously only reported for inertial microfluidics. We anticipate the ability to precisely control particles in 3D at extremely high flow rates will open up several applications, including the development of ultra-high throughput microflow cytometers and high-resolution separation of rare cells for point of care diagnostics.
Shifting and reducing breathing disturbance in patients with very severe obstructive sleep apnea by modified Z-palatoplasty with one-layer closure in one-stage multilevel surgery
Authors: Huang Ethan I. , Lin Yu-Ching , Huang Shu-Yi , Lin Chin-Kuo , Lin Chieh-Mo
Published: April 2021

Very severe obstructive sleep apnea (OSA) with apnea–hypopnea index (AHI) ≥ 60 events/h differs in several areas from OSA with other severities, including having a low-level daytime partial pressure of oxygen and residual on-CPAP (continuous positive airway pressure) AHIs greater than 20/h. Patients with very severe OSA show narrow retroglossal space and confined framework, which is difficult to be enlarged via conventional Uvulopalatopharyngoplasty (UPPP) surgery, resulting in poor response to non-framework surgeries. Our latest report showed efficacy and efficiency for subjects undergoing modified Z-palatoplasty (ZPP) with one-layer closure in a one-stage multilevel surgery. It is unclear whether and how this procedure could help patients with very severe OSA characterized with confined framework. From Mar. 2015 to May 2018, we enrolled 12 patients with very severe OSA receiving one-stage multi-level surgery with modified ZPP with one-layer closure, CO2 laser partial tongue-base glossectomy, and bilateral septomeatoplasty. Our results show that the surgery reduced AHI from 73.8 ± 10.7 to 30.8 ± 23.2 events/h and achieved a mean AHI reduction of 58.3% (p < 0.001 against 0 reduction or no surgery). The surgery shifted components of the breathing disturbances. It reduced more apnea than hypopnea and might convert some apnea to hypopnea.
Exogenous sex hormones, menstrual and reproductive history, and risk of non-melanoma skin cancer among women: a systematic literature review and meta-analysis
Authors: Caini Saverio , De Angelis Simone Pietro , Corso Federica , Fantini Carolina , Raimondi Sara , Pala Laura , Stanganelli Ignazio , de Giorgi Vincenzo , Gandini Sara
Published: April 2021

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88–1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87–1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.
Molecular characterization and transcriptional regulation of two types of H+-pyrophosphatases in the scuticociliate parasite Philasterides dicentrarchi
Authors: Folgueira I. , Lamas J. , Sueiro R. A. , Leiro J. M.
Published: April 2021

Proton-translocating inorganic pyrophosphatases (H+-PPases) are an ancient family of membrane bound enzymes that couple pyrophosphate (PPi) hydrolysis to H+ translocation across membranes. In this study, we conducted a molecular characterization of two isoenzymes (PdVP1 and PdVP2) located in respectively the alveolar sacs and in the membranes of the intracellular vacuoles of a scuticociliate parasite (Philasterides dicentrarchi) of farmed turbot. We analyzed the genetic expression of the isoenzymes after administration of antiparasitic drugs and after infection in the host. PdVP1 and PdVP2 are encoded by two genes of 2485 and 3069 bp, which respectively contain 3 and 11 exons and express proteins of 746 and 810 aa of molecular mass 78.9 and 87.6 kDa. Topological predictions from isoenzyme sequences indicate the formation of thirteen transmembrane regions (TMRs) for PdVP1 and seventeen TMRs for PdVP2. Protein structure modelling indicated that both isoenzymes are homodimeric, with three Mg2+ binding sites and an additional K+ binding site in PdVP2. The levels of identity and similarity between the isoenzyme sequences are respectively 33.5 and 51.2%. The molecular weights of the native proteins are 158 kDa (PdVP1) and 178 kDa (PdVP2). The isoenzyme sequences are derived from paralogous genes that form a monophyletic grouping with other ciliate species. Genetic expression of the isoenzymes is closely related to the acidification of alveolar sacs (PdVP1) and intracellular vacuoles (PdVP2): antiparasitic drugs inhibit transcription, while infection increases transcription of both isoenzymes. The study findings show that P. dicentrarchi possesses two isoenzymes with H+-PPase activity which are located in acidophilic cell compartment membranes and which are activated during infection in the host and are sensitive to antiparasitic drugs. The findings open the way to using molecular modelling to design drugs for the treatment of scuticociliatosis.