bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Topography, Bedrock Weathering, and Water Storage Across a Sequence of Ridges and Valleys
Authors: Pedrazas Michelle A. , Hahm W. Jesse , Huang Mong‐Han , Dralle David , Nelson Mariel D. , Breunig Rachel E. , Fauria Kristen E. , Bryk Alexander B. , Dietrich William E. , Rempe Daniella M.
Published: March 2021

Bedrock weathering regulates nutrient mobilization, water storage, and soil production. Relative to the mobile soil layer, little is known about the relationship between topography and bedrock weathering. Here, we identify a common pattern of weathering and water storage across a sequence of three ridges and valleys in the sedimentary Great Valley Sequence in Northern California that share a tectonic and climate history. Deep drilling, downhole logging, and characterization of chemistry and porosity reveal two weathering fronts. The shallower front is ∼7 m deep at the ridge of all three hillslopes, and marks the extent of pervasive fracturing and oxidation of pyrite and organic carbon. A deeper weathering front marks the extent of open fractures and discoloration. This front is 11 m deep under two ridges of similar ridge‐valley spacing, but 17.5 m deep under a ridge with nearly twice the ridge‐valley spacing. Hence, at ridge tops, the fraction of the hillslope relief that is weathered scales with hillslope length. In all three hillslopes, below this second weathering front, closed fractures and unweathered bedrock extend about one‐half the hilltop elevation above the adjacent channels. Neutron probe surveys reveal that seasonally dynamic moisture is stored to approximately the same depth as the shallow weathering front. Under the channels that bound our study hillslopes, the two weathering fronts coincide and occur within centimeters of the ground surface. Our findings provide evidence for feedbacks between erosion and weathering in mountainous landscapes that result in systematic subsurface structuring and water routing.
Selection of Multiple Donor Gauges via Graphical Lasso for Estimation of Daily Streamflow Time Series
Authors: Villalba German A. , Liang Xu , Liang Yao
Published: March 2021

A fundamental challenge in estimations of daily streamflow time series at sites with incomplete records is how to effectively and efficiently select reference/donor gauges from an existing gauge network to infer the missing data. While research on estimating missing streamflow time series is not new, the existing approaches either use a single reference streamflow gauge or employ a set of “ad hoc” reference gauges, leaving a systematic selection of reference gauges as a long‐standing open question. In this work, a novel method is introduced that facilitates a systematic selection of multiple reference gauges from any given streamflow network. The idea is to mathematically characterize the network‐wise correlation structure of a streamflow network via graphical Markov modeling and to further transform a dense network into a sparsely connected one. The resulted underlying sparse graph from the graphical model encodes conditional independence conditions among all reference gauges from the streamflow network, allowing determination of an optimum subset of the donor gauges. The sparsity is discovered by using the Graphical Lasso algorithm with an L1 norm regularization parameter and a thresholding parameter. These two parameters are determined by a multi‐objective optimization process. Furthermore, the graphical modeling approach is employed to solve another open problem in gauge removal planning decision (e.g., due to operation budget constraints): which gauges to remove would statistically guarantee the least loss of information by estimations from the remaining gauges? Our graphical model‐based method is demonstrated with daily streamflow data from a network of 34 gauges over the Ohio River basin region.
Unexpected Consequences of River Engineering on the Carbon Cycle
Authors: Repasch Marisa
Published: March 2021

Rivers around the world have been heavily engineered, and these man‐made changes are affecting important biogeochemical cycles. Rivers play a key role in the global carbon cycle, by mobilizing organic carbon from land and delivering it to the oceans. River engineering techniques, like levees that prevent flooding, change the way carbon is cycled through rivers, but it is difficult to identify and quantify these changes. Shen et al. (2021) were able to quantify changes in river organic carbon fluxes induced by bank stabilization in the Mississippi River. The authors compared the age distribution of organic carbon in modern river sediment and old river sediment deposited before the construction of extensive levee systems. They found that bank stabilization significantly reduces the amount of time organic carbon spends in the river system before being exported to the Gulf of Mexico. As a result, less organic carbon is oxidized to CO2 and more organic carbon is exported to the ocean, ultimately reducing atmospheric CO2. This study highlights an important effect of anthropogenic activity on river carbon fluxes that should be considered in global carbon cycle models.
C�mo combatir el acoso y la discriminaci�n en las geociencias
Authors: Popp Andrea , Hall Caitlyn , Yılmaz Yeliz
Published: March 2021

Aqu� hay 10 pasos pr�cticos que los cient�ficos pueden tomar para contrarrestar los efectos perjudiciales de entornos laborales acad�micos abusivos.
The accuracy of laser fluorescence (DIAGNOdent) in assessing caries lesion activity on root surfaces, around crown margins, and in furcations in older adults
Authors: Mitchell Chelsea , Zaku Hiba , Milgrom Peter , Mancl Lloyd , Prince David B.
Published: March 2021

The authors conducted a case series to assess accuracy of DIAGNOdent (DD) in assessment of activity of dental caries lesions in root surfaces and in furcations and at crown margins. The study was a prospective, single center case series. The patients were 123 adults (age ≥ 55 years). To be included, a patient needed to have at least one active root caries lesion. The study was conducted at the Roseman College of Dental Medicine in South Jordan, Utah, USA and at area nursing homes. Lesions were rinsed and dried with air, and DD readings were obtained. Lesions were then isolated and 38% silver diamine fluoride was applied repeatedly for two minutes with a microbrush. DD readings and treatments were repeated every six months. Mean DD values were significantly different between active (unarrested) and inactive (arrested) caries for all comparisons, p-value < 0.0001. The optimal cut-off values for DD were between 20 and 35 except optimal cut-offs were higher for furcation and crown margin surfaces, particularly in the posterior (optimal cut-offs 40–45). This study demonstrates DD is a potentially valuable tool for assessing lesion activity in root surfaces, at restoration margins, and in furcations.
The Groningen electrocardiographic criteria for left ventricular hypertrophy: a sex-specific analysis
Authors: van der Ende M. Yldau , Hendriks Tom , van de Vegte Yordi , Lipsic Erik , Snieder Harold , van der Harst Pim
Published: March 2021

The sensitivity of electrocardiogram (ECG) criteria to detect left ventricular hypertrophy (LVH) is low, especially in women. We determined sex-specific sensitivities of ECG-LVH criteria, and developed new criteria, using cardiovascular magnetic resonance imaging (CMR). Sensitivities of ECG-LVH criteria were determined in participants of the UK Biobank (N = 3632). LVH was defined when left ventricular mass was > 95% confidence interval (CI) according to age and sex. In a training cohort (75%, N = 2724), sex-specific ECG-LVH criteria were developed by investigating all possible sums of QRS-amplitudes in all 12 leads, and selecting the sum with the highest pseudo-R2 and area under the curve to detect LVH. Performance was assessed in a validation cohort (25%, N = 908), and association with blood pressure change was investigated in an independent cohort. Sensitivities of ECG-LVH criteria were low, especially in women. Newly developed Groningen-LVH criterion for women (QV2 + RI + RV5 + RV6 + SV2 + SV4 + SV5 + SV6) outperformed all ECG-LVH criteria with a sensitivity of 42% (95% CI 35–49%). In men, newly developed criterion ((RI + RV5 + SII + SV2 + SV6) × QRS duration) was equally sensitive as 12-lead sum with a sensitivity of 44% (95% CI 37–51%) and outperformed the other criteria. In an independent cohort, the Groningen-LVH criteria were strongest associated with change in systolic blood pressure. Our proposed CMR sex-specific Groningen-LVH criteria improve the sensitivity to detect LVH, especially in women. Further validation and its association with clinical outcomes is warranted.
Gibberellic acid and nitrogen efficiently protect early seedlings growth stage from salt stress damage in Sorghum
Authors: Ali Adam Yousif Adam , Ibrahim Muhi Eldeen Hussien , Zhou Guisheng , Nimir Nimir Eltyb Ahmed , Elsiddig Aboagla Mohammed Ibrahim , Jiao Xiurong , Zhu Guanglong , Salih Ebtehal Gabralla Ibrahim , Suliman Mohamed Suliman Eltyeb Suliman , Elradi Safiya Babiker Mustafa
Published: March 2021

Salinity one of environmental factor that limits the growth and productivity of crops. This research was done to investigate whether GA3(0, 144.3, 288.7 and 577.5 μM) and nitrogen fertilizer (0, 90 and 135 kg N ha−1) could mitigate the negative impacts of NaCl (0, 100, and 200 mM NaCl) on emergence percentage, seedling growth and some biochemical parameters. The results showed that high salinity level decreased emergence percentage, seedling growth, relative water content, chlorophyll content (SPAD reading), catalase (CAT) and peroxide (POD), but increased soluble protein content, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The SOD activity was decreased by nitrogen. However, the other measurements were increased by nitrogen. The interactive impact between nitrogen and salinity was significant in most parameters except EP, CAT and POD. The seedling length, dry weight, fresh weight, emergence percentage, POD, soluble protein and chlorophyll content were significantly affected by the interaction between GA3and salinity. The GA3and nitrogen application was successful mitigating the adverse effects of salinity. The level of 144.3 and 288.7 μm GA3and the rate of 90 and 135 kg N ha−1were most effective on many of the attributes studied. Our study suggested that GA3and nitrogen could efficiently protect early seedlings growth from salinity damage.
Test conditions can significantly affect the results of in vitro cytotoxicity testing of degradable metallic biomaterials
Authors: Jablonská Eva , Kubásek Jiří , Vojtěch Dalibor , Ruml Tomáš , Lipov Jan
Published: March 2021

In vitro cytotoxicity testing is an indispensable part of the development of new biomaterials. However, the standard ISO 10993-5 enables variability in the testing conditions, which makes the results of the test incomparable. We studied the influence of media composition on the results of the cytotoxicity test. Solutions of ZnCl2 served as simulated extracts and we also used extracts of three types of Zn-based and Mg-based degradable metals. We incubated the cells with the solutions prepared in two types of media with two concentrations of serum (5 and 10%). We compared the toxic effect of the extracts on L929 murine fibroblast-derived cell line, which is recommended by ISO standard and on “osteoblast-like cells” U-2 OS. We also compared two methods of exposition: solutions were added either to a sub-confluent layer or to the cell suspension. We evaluated the metabolic activity of the cells using the resazurin test. We found out that in vitro cytotoxicity is dramatically influenced by the concentration of serum and by the type of the medium as well as by the type of exposition and type of cells. Therefore, when performing in vitro cytotoxicity testing of biomaterials, the authors should carefully specify the conditions of the test and comparison of different studies should be carried out with caution.
Energy transfer to the phonons of a macromolecule through light pumping
Authors: Faraji Elham , Franzosi Roberto , Mancini Stefano , Pettini Marco
Published: March 2021

In the present paper we address the problem of the energy downconversion of the light absorbed by a protein into its internal vibrational modes. We consider the case in which the light receptors are fluorophores either naturally co-expressed with the protein or artificially covalently bound to some of its amino acids. In a recent work [Phys. Rev. X 8, 031061 (2018)], it has been experimentally found that by shining a laser light on the fluorophores attached to a protein the energy fed to it can be channeled into the normal mode of lowest frequency of vibration thus making the subunits of the protein coherently oscillate. Even if the phonon condensation phenomenon has been theoretically explained, the first step - the energy transfer from electronic excitation into phonon excitation - has been left open. The present work is aimed at filling this gap.
Multiwave pandemic dynamics explained: how to tame the next wave of infectious diseases
Authors: Cacciapaglia Giacomo , Cot Corentin , Sannino Francesco
Published: March 2021

Pandemics, like the 1918 Spanish Influenza and COVID-19, spread through regions of the World in subsequent waves. Here we propose a consistent picture of the wave pattern based on the epidemic Renormalisation Group (eRG) framework, which is guided by the global symmetries of the system under time rescaling. We show that the rate of spreading of the disease can be interpreted as a time-dilation symmetry, while the final stage of an epidemic episode corresponds to reaching a time scale-invariant state. We find that the endemic period between two waves is a sign of instability in the system, associated to near-breaking of the time scale-invariance. This phenomenon can be described in terms of an eRG model featuring complex fixed points. Our results demonstrate that the key to control the arrival of the next wave of a pandemic is in the strolling period in between waves, i.e. when the number of infections grows linearly. Thus, limiting the virus diffusion in this period is the most effective way to prevent or delay the arrival of the next wave. In this work we establish a new guiding principle for the formulation of mid-term governmental strategies to curb pandemics and avoid recurrent waves of infections, deleterious in terms of human life loss and economic damage.
Using RNA-seq to characterize pollen–stigma interactions for pollination studies
Authors: Lobaton Juan , Andrew Rose , Duitama Jorge , Kirkland Lindsey , Macfadyen Sarina , Rader Romina
Published: March 2021

Insects are essential for the reproduction of pollinator-dependent crops and contribute to the pollination of 87% of wild plants and 75% of the world’s food crops. Understanding pollen flow dynamics between plants and pollinators is thus essential to manage and conserve wild plants and ensure yields are maximized in food crops. However, the determination of pollen transfer in the field is complex and laborious. We developed a field experiment in a pollinator-dependent crop and used high throughput RNA sequencing (RNA-seq) to quantify pollen flow by measuring changes in gene expression between pollination treatments across different apple (Malus domestica Borkh.) cultivars. We tested three potential molecular indicators of successful pollination and validated these results with field data by observing single and multiple visits by honey bees (Apis mellifera) to apple flowers and measured fruit set in a commercial apple orchard. The first indicator of successful outcrossing was revealed via differential gene expression in the cross-pollination treatments after 6 h. The second indicator of successful outcrossing was revealed by the expression of specific genes related to pollen tube formation and defense response at three different time intervals in the stigma and the style following cross-pollination (i.e. after 6, 24, and 48 h). Finally, genotyping variants specific to donor pollen could be detected in cross-pollination treatments, providing a third indicator of successful outcrossing. Field data indicated that one or five flower visits by honey bees were insufficient and at least 10 honey bee flower visits were required to achieve a 25% probability of fruit set under orchard conditions. By combining the genotyping data, the differential expression analysis, and the traditional fruit set field experiments, it was possible to evaluate the pollination effectiveness of honey bee visits under orchards conditions. This is the first time that pollen-stigma-style mRNA expression analysis has been conducted after a pollinator visit (honey bee) to a plant (in vivo apple flowers). This study provides evidence that mRNA sequencing can be used to address complex questions related to stigma–pollen interactions over time in pollination ecology.
Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer’s disease
Authors: Rosales Jubal Eduardo , Schwalm Miriam , dos Santos Guilherme Malena , Schuck Florian , Reinhardt Sven , Tose Amanda , Barger Zeke , Roesler Mona K. , Ruffini Nicolas , Wierczeiko Anna , Schmeisser Michael J. , Schmitt Ulrich , Endres Kristina , Stroh Albrecht
Published: March 2021

Aberrant activity of local functional networks underlies memory and cognition deficits in Alzheimer’s disease (AD). Hyperactivity was observed in microcircuits of mice AD-models showing plaques, and also recently in early stage AD mutants prior to amyloid deposition. However, early functional effects of AD on cortical microcircuits remain unresolved. Using two-photon calcium imaging, we found altered temporal distributions (burstiness) in the spontaneous activity of layer II/III visual cortex neurons, in a mouse model of familial Alzheimer’s disease (5xFAD), before plaque formation. Graph theory (GT) measures revealed a distinct network topology of 5xFAD microcircuits, as compared to healthy controls, suggesting degradation of parameters related to network robustness. After treatment with acitretin, we observed a re-balancing of those network measures in 5xFAD mice; particularly in the mean degree distribution, related to network development and resilience, and post-treatment values resembled those of age-matched controls. Further, behavioral deficits, and the increase of excitatory synapse numbers in layer II/III were reversed after treatment. GT is widely applied for whole-brain network analysis in human neuroimaging, we here demonstrate the translational value of GT as a multi-level tool, to probe networks at different levels in order to assess treatments, explore mechanisms, and contribute to early diagnosis.
Estimating the asphaltene critical nanoaggregation concentration region using ultrasonic measurements and Bayesian inference
Authors: Svalova Aleksandra , Walshaw David , Lee Clement , Demyanov Vasily , Parker Nicholas G. , Povey Megan J. , Abbott Geoffrey D.
Published: March 2021

Bayesian inference and ultrasonic velocity have been used to estimate the self-association concentration of the asphaltenes in toluene using a changepoint regression model. The estimated values agree with the literature information and indicate that a lower abundance of the longer side-chains can cause an earlier onset of asphaltene self-association. Asphaltenes constitute the heaviest and most complicated fraction of crude petroleum and include a surface-active sub-fraction. When present above a critical concentration in pure solvent, asphaltene “monomers” self-associate and form nanoaggregates. Asphaltene nanoaggregates are thought to play a significant role during the remediation of petroleum spills and seeps. When mixed with water, petroleum becomes expensive to remove from the water column by conventional methods. The main reason of this difficulty is the presence of highly surface-active asphaltenes in petroleum. The nanoaggregates are thought to surround the water droplets, making the water-in-oil emulsions extremely stable. Due to their molecular complexity, modelling the self-association of the asphaltenes can be a very computationally-intensive task and has mostly been approached by molecular dynamic simulations. Our approach allows the use of literature and experimental data to estimate the nanoaggregation and its credible intervals. It has a low computational cost and can also be used for other analytical/experimental methods probing a changepoint in the molecular association behaviour.
Gnrh2 maintains reproduction in fasting zebrafish through dynamic neuronal projection changes and regulation of gonadotropin synthesis, oogenesis, and reproductive behaviors
Authors: Marvel Miranda , Levavi-Sivan Berta , Wong Ten-Tsao , Zmora Nilli , Zohar Yonathan
Published: March 2021

Restricted food intake, either from lack of food sources or endogenous fasting, during reproductive periods is a widespread phenomenon across the animal kingdom. Considering previous studies show the canonical upstream regulator of reproduction in vertebrates, the hypothalamic Gonadotropin-releasing hormone (Gnrh), is inhibited in some fasting animals, we sought to understand the neuroendocrine control of reproduction in fasted states. Here, we explore the roles of the midbrain neuropeptide, Gnrh2, in inducing reproduction via its pituitary prevalence, gonadotropin synthesis, gametogenesis, and reproductive outputs in the zebrafish model undergoing different feeding regimes. We discovered a fasting-induced four-fold increase in length and abundance of Gnrh2 neuronal projections to the pituitary and in close proximity to gonadotropes, whereas the hypothalamic Gnrh3 neurons are reduced by six-fold in length. Subsequently, we analyzed the functional roles of Gnrh2 by comparing reproductive parameters of a Gnrh2-depleted model, gnrh2−/−, to wild-type zebrafish undergoing different feeding conditions. We found that Gnrh2 depletion in fasted states compromises spawning success, with associated decreases in gonadotropin production, oogenesis, fecundity, and male courting behavior. Gnrh2 neurons do not compensate in other circumstances by which Gnrh3 is depleted, such as in gnrh3−/− zebrafish, implying that Gnrh2 acts to induce reproduction specifically in fasted zebrafish.
Transcriptomic insight into the translational value of two murine models in human atopic dermatitis
Authors: Kim Young-Won , Ko Eun-A , Jung Sung-Cherl , Lee Donghee , Seo Yelim , Kim Seongtae , Kim Jung-Ha , Bang Hyoweon , Zhou Tong , Ko Jae-Hong
Published: March 2021

This study sought to develop a novel diagnostic tool for atopic dermatitis (AD). Mouse transcriptome data were obtained via RNA-sequencing of dorsal skin tissues of CBA/J mice affected with contact hypersensitivity (induced by treatment with 1-chloro-2,4-dinitrobenzene) or brush stimulation-induced AD-like skin condition. Human transcriptome data were collected from German, Swedish, and American cohorts of AD patients from the Gene Expression Omnibus database. edgeR and SAM algorithms were used to analyze differentially expressed murine and human genes, respectively. The FAIME algorithm was then employed to assign pathway scores based on KEGG pathway database annotations. Numerous genes and pathways demonstrated similar dysregulation patterns in both the murine models and human AD. Upon integrating transcriptome information from both murine and human data, we identified 36 commonly dysregulated differentially expressed genes, which were designated as a 36-gene signature. A severity score (AD index) was applied to each human sample to assess the predictive power of the 36-gene AD signature. The diagnostic power and predictive accuracy of this signature were demonstrated for both AD severity and treatment outcomes in patients with AD. This genetic signature is expected to improve both AD diagnosis and targeted preclinical research.
The toxic effects of chloroquine and hydroxychloroquine on skeletal muscle: a systematic review and meta-analysis
Authors: Biguetti Claudia Cristina , Junior Joel Ferreira Santiago , Fiedler Matthew William , Marrelli Mauro Toledo , Brotto Marco
Published: March 2021

The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles. We collected data published from 1990 to April 2020 using PubMed, Cochrane Library, EMBASE, and SciELO. Risk of bias for observational studies was assessed regarding the ROBIN-I scale. Studies with less than five patients (case reports) were selected for an additional qualitative analysis. We used the software Comprehensive Meta-Analysis at the confidence level of 0.05. We identified 23 studies for qualitative analysis (17 case-reports), and five studies were eligible for quantitative analysis. From case reports, 21 patients presented muscle weakness and confirmatory biopsy for CQ/HCQ induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of CQ/HCQ, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy. No study presented randomized samples. The chronic use of CQ/HCQ may be a risk for drug-induced myopathy. There is substantiated need for proper randomized trials and controlled prospective studies needed to assess the clinical and subclinical stages of CQ/HCQ -induced muscle myopathy.
CT based radiomic approach on first line pembrolizumab in lung cancer
Authors: Zerunian Marta , Caruso Damiano , Zucchelli Alberto , Polici Michela , Capalbo Carlo , Filetti Marco , Mazzuca Federica , Marchetti Paolo , Laghi Andrea
Published: March 2021

Clinical evaluation poorly predicts outcomes in lung cancer treated with immunotherapy. The aim of the study is to assess whether CT-derived texture parameters can predict overall survival (OS) and progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) treated with first line Pembrolizumab. Twenty-one patients with NSLC were prospectively enrolled; they underwent contrast enhanced CT (CECT) at baseline and during Pembrolizumab treatment. Response to therapy was assessed both with clinical and iRECIST criteria. Two radiologists drew a volume of interest of the tumor at baseline CECT, extracting several texture parameters. ROC curves, a univariate Kaplan-Meyer analysis and Cox proportional analysis were performed to evaluate the prognostic value of texture analysis. Twelve (57%) patients showed partial response to therapy while nine (43%) had confirmed progressive disease. Among texture parameters, mean value of positive pixels (MPP) at fine and medium filters showed an AUC of 72% and 74% respectively (P < 0.001). Kaplan-Meyer analysis showed that MPP < 56.2 were significantly associated with lower OS and PFS (P < 0.0035). Cox proportional analysis showed a significant correlation between MPP4 and OS (P = 0.0038; HR = 0.89[CI 95%:0.83,0.96]). In conclusion, MPP could be used as predictive imaging biomarkers of OS and PFS in patients with NSLC with first line immune treatment.
Multi-decadal trends in contingent mixing of Atlantic mackerel (Scomber scombrus) in the Northwest Atlantic from otolith stable isotopes
Authors: Arai Kohma , Castonguay Martin , Secor David H.
Published: March 2021

The Atlantic mackerel (Scomber scombrus) in the Northwest Atlantic is comprised of northern and southern components that have distinct spawning sites off Canada (northern contingent) and the US (southern contingent), and seasonally overlap in US fished regions. Thus, assessment and management of this population can be sensitive to levels of mixing between contingents, which remain unknown. Multi-decadal trends in contingent mixing levels within the US fisheries region were assessed, and the contingent composition across seasons, locations, ages, and size classes were characterized using archived otoliths and developing a classification baseline based on juvenile otolith carbon and oxygen stable isotopes (δ13C/δ18O values). Classification of age ≥ 2 adults demonstrated that northern contingent mixing was prevalent within the US continental shelf waters during the past 2 decades (2000–2019), providing an important seasonal subsidy to the US winter fishery despite substantial depletion in spawning stock biomass of the dominant northern contingent. While the majority of older fish were of the northern contingent during the early 2000s, the southern contingent contribution increased with age/size class during the recent period (2013–2019). Spatial mixing was most prevalent during February and March when the northern contingent occurred as far south as the Delmarva Peninsula, but were mostly absent from US waters in May. A positive relationship (albeit not significant; r = 0.60, p = 0.07) occurred between northern contingent mixing and US fisheries landings, which could imply that higher contingent mixing levels might be associated with greater landings for the US winter mackerel fishery. The yield of the Northwest Atlantic mackerel depends upon the status of the northern contingent, with the southern contingent possibly more prone to depletion. Spatially explicit stock assessment models are recommended to conserve both productivity and stability in this two-component population.
Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
Authors: Horita Shoichiro , Ono Tomoyuki , Gonzalez-Resines Saul , Ono Yuko , Yamachi Megumi , Zhao Songji , Domene Carmen , Maejima Yuko , Shimomura Kenju
Published: March 2021

Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, the most severe end of neonatal diabetes mellitus, is caused by mutation in the ATP-sensitive potassium (KATP) channel. In addition to diabetes, DEND patients present muscle weakness as one of the symptoms, and although the muscle weakness is considered to originate in the brain, the pathological effects of mutated KATP channels in skeletal muscle remain elusive. Here, we describe the local effects of the KATP channel on muscle by expressing the mutation present in the KATP channels of the DEND syndrome in the murine skeletal muscle cell line C2C12 in combination with computer simulation. The present study revealed that the DEND mutation can lead to a hyperpolarized state of the muscle cell membrane, and molecular dynamics simulations based on a recently reported high-resolution structure provide an explanation as to why the mutation reduces ATP sensitivity and reveal the changes in the local interactions between ATP molecules and the channel.
Effect of disease modifying anti-rheumatic drugs on major cardiovascular events: a meta-analysis of randomized controlled trials
Authors: Thanigaimani Shivshankar , Phie James , Krishna Smriti Murali , Moxon Joseph , Golledge Jonathan
Published: March 2021

Disease modifying anti-rheumatic drugs (DMARDs) were developed to treat joint inflammation. There is growing evidence that anti-inflammatory drugs prevent major cardiovascular events (MACE). The aim of this systematic review and meta-analysis was to examine whether DMARDs reduce the risk of MACE. A systematic literature search was performed to identify randomized controlled trials (RCTs) testing the effect of DMARDs on cardiovascular events. The primary outcome was MACE defined as the first occurrence of non-fatal myocardial infarction (MI), non-fatal stroke or cardiovascular death. Secondary outcomes were myocardial infarction or stroke alone and all-cause mortality. Safety was assessed by fatal or life threatening infection. Meta-analyses were performed using random effect models and reported as risk ratios (RR) and 95% confidence intervals (CI). Study quality and publication bias were assessed using the Cochrane Collaboration’s tool for assessing risk of bias and funnel plots. Twelve RCTs involving 18,056 participants testing three different DMARDs subclasses (Tumor Necrosis Factor inhibitors—4 trials; Janus Kinase inhibitors—5 trials; Interleukin inhibitors—3 trials) were included. Meta-analysis suggested that none of the DMARD subclasses had any effect on MACE, MI alone, stroke alone, risk of fatal or life threatening infection or death. Risk of bias was high, low and unclear in five, six and one studies respectively. Funnel plots suggested a low possibility of publication bias. This meta-analysis suggests that DMARDs do not affect the incidence of MACE. More trials are needed for firm conclusions.
Percutaneous nephrostomy versus retrograde ureteral stenting for acute upper obstructive uropathy: a systematic review and meta-analysis
Authors: Zul Khairul Azwadi Ismail , Norhayati Mohd Noor , Abdullah Mohd Shafie
Published: March 2021

Acute obstructive uropathy is associated with significant morbidity among patients with any condition that leads to urinary tract obstruction. Immediate urinary diversion is necessary to prevent further damage to the kidneys. In many centres, the two main treatment options include percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS). The purpose of this study if to compare the efficacy and safety of PCN and RUS for the treatment of acute obstructive uropathy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE, the World Health Organisation International Clinical Trials Registry Platform and ClinicalTrials.gov. We also searched the reference lists of included studies to identify any additional trials. We included randomised controlled trials and controlled clinical trials comparing the outcomes of clinical improvement (septic parameters), hospitalisation duration, quality of life, urinary-related symptoms, failure rates, post-procedural pain [measured using a visual analogue scale (VAS)] and analgesics use. We conducted statistical analyses using random effects models and expressed the results as risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). Seven trials were identified that included 667 patients. Meta-analysis of the data revealed no difference in the two methods in improvement of septic parameters, quality of life, failure rates, post-procedural pain (VAS), or analgesics use. Patients receiving PCN had lower rates of haematuria and dysuria post-operatively and longer hospitalisation duration than those receiving RUS. PCN and RUS are effective for the decompression of an obstructed urinary system, with no significant difference in most outcomes. However, PCN is preferable to RUS because of its reduced impact on the patient’s post-operative quality of life due to haematuria and dysuria, although it is associated with slightly longer hospitalisation duration.
Furry is required for cell movements during gastrulation and functionally interacts with NDR1
Authors: Cervino Ailen S. , Moretti Bruno , Stuckenholz Carsten , Grecco Hernán E. , Davidson Lance A. , Cirio M. Cecilia
Published: March 2021

Gastrulation is a key event in animal embryogenesis during which germ layer precursors are rearranged and the embryonic axes are established. Cell polarization is essential during gastrulation, driving asymmetric cell division, cell movements, and cell shape changes. The furry (fry) gene encodes an evolutionarily conserved protein with a wide variety of cellular functions, including cell polarization and morphogenesis in invertebrates. However, little is known about its function in vertebrate development. Here, we show that in Xenopus, Fry plays a role in morphogenetic processes during gastrulation, in addition to its previously described function in the regulation of dorsal mesoderm gene expression. Using morpholino knock-down, we demonstrate a distinct role for Fry in blastopore closure and dorsal axis elongation. Loss of Fry function drastically affects the movement and morphological polarization of cells during gastrulation and disrupts dorsal mesoderm convergent extension, responsible for head-to-tail elongation. Finally, we evaluate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis.
An analysis of the population of Cryptococcus neoformans strains isolated from animals in Poland, in the years 2015–2019
Authors: Florek Magdalena , Nawrot Urszula , Korzeniowska-Kowal Agnieszka , Włodarczyk Katarzyna , Wzorek Anna , Woźniak-Biel Anna , Brzozowska Magdalena , Galli Józef , Bogucka Anna , Król Jarosław
Published: March 2021

Fungi belonging to the Cryptococcus neoformans/C. gattii species complex (CNGSC) are pathogens causing severe infections in humans and animals, that for humans may result in a mortality rate ranging up to 70%. The CNGSC is divided into eight major molecular types, that may differ in their virulence and susceptibility. In order to fully understand the epidemiology of cryptococcosis, it is important to study the world distribution and population structure of these pathogens. The present study is the first presenting a population of strains isolated in Poland and one of the few using a multi-species animal group as a source of the specimen. The pathogen was present in 2.375% of the tested animals. The URA5-RFLP and MALDI-TOF MS analyses have revealed that the population consisted exclusively of C. neoformans strains, with a predominance of major molecular type VNIV (C. neoformans var. neoformans). The MALDI-TOF MS was used to perform the CNGSC strains identification on both the species and sub-species level. Despite the fact that the animals providing the specimens were not treated with 5-fluorocytosine, around 10% of the tested population presented MIC values exceeding 64 mg/L, indicating the existence of the 5-fluorocytosine-resistant strains in the environment.
Characterization of the bacterial microbiome of Rhipicephalus (Boophilus) microplus collected from Pecari tajacu “Sajino” Madre de Dios, Peru
Authors: Rojas-Jaimes Jesús , Lindo-Seminario David , Correa-Núñez Germán , Diringer Benoit
Published: March 2021

Ticks are arthropods that can host and transmit pathogens to wild animals, domestic animals, and even humans. The bacterial microbiome of adult (males and females) and nymph Rhipicephalus microplus ticks collected from a collared peccary, Pecari tajacu, captured in the rural area of Botijón Village in the Amazon region of Madre de Dios, Peru, was evaluated using metagenomics. The Chao1 and Shannon–Weaver analyses indicated greater bacterial richness and diversity in female ticks (GARH; 375–4.15) and nymph ticks (GARN; 332–4.75) compared to that in male ticks (GARM; 215–3.20). Taxonomic analyses identified 185 operational taxonomic units representing 147 bacterial genera. Of the 25 most prevalent genera, Salmonella (17.5%) and Vibrio (15.0%) showed the highest relative abundance followed by several other potentially pathogenic genera, such as Paracoccus (7.8%), Staphylococcus (6.8%), Pseudomonas (6.6%), Corynebacterium (5.0%), Cloacibacterium (3.6%), and Acinetobacter (2.5%). In total, 19.7% of the detected genera are shared by GARH, GARM, and GARN, and they can be considered as the core microbiome of R. microplus. To the best of our knowledge, this study is the first to characterize the microbiome of ticks collected from P. tajacu and to report the presence of Salmonella and Vibrio in R. microplus. The pathogenic potential and the role of these bacteria in the physiology of R. microplus should be further investigated due to the possible implications for public health and animal health in populations neighboring the habitat of P. tajacu.
Association of metabolic syndrome with mobility in the older adults: a Korean nationwide representative cross-sectional study
Authors: Son Ki Young , Shin Dong Wook , Lee Ji Eun , Kim Sang Hyuck , Yun Jae Moon , Cho Belong
Published: March 2021

We aimed to examine whether metabolic syndrome (MetS) is associated with mobility in the older adults, using the timed up and go (TUG) test which is one of the most widely used tests for evaluating mobility. This is population-based study with the National Health Insurance Service–National Health Screening Cohort database of National Health Information Database. Participants included were those who completed the TUG as part of the National Screening Program for Transitional Ages. An abnormal TUG result was defined as a time ≥ 10 s. Multiple logistic regression models were used to assess the associations between MetS and TUG results. We constructed three models with different levels of adjustment. Furthermore, we conducted a stratified analysis according to the risk. Among the 40,767 participants included, 19,831 (48.6%) were women. Mean TUG value was 8.34 ± 3.07 s, and abnormal TUG test results were observed in 4,391 (10.8%) participants; 6,888 (16.9%) participants were categorised to have MetS. The worst TUG test results were obtained in participants with three or four MetS features, and a J-shaped relationship of each MetS feature, except triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C), with TUG test was found. Participants with MetS had 18% higher likelihood of showing abnormal TUG test results in a fully adjusted model (adjusted odds ratio 1.183, 95% confidence interval 1.115–1.254). The stratified analysis revealed that participants with central obesity, high blood pressure, and normal HDL-C and TG were more likely to have abnormal TUG times. Participants with MetS had a higher risk of exhibiting abnormal TUG results, and except for HDL-C and TG, all other MetS features had a J-shaped relationship with TUG. Preventive lifestyle such as lower carbohydrate and higher protein intake, and endurance exercise is needed.
Identification of deleterious recessive haplotypes and candidate deleterious recessive mutations in Japanese Black cattle
Authors: Sasaki Shinji , Watanabe Toshio , Ibi Takayuki , Hasegawa Kiyotoshi , Sakamoto Yoichi , Moriwaki Shunsuke , Kurogi Kazuhito , Ogino Atsushi , Yasumori Takanori , Wakaguri Hiroyuki , Muraki Eiji , Miki Youko , Yoshida Yuichi , Inoue Yoshinobu , Tabuchi Ichiro , Iwao Ken , Arishima Taichi , Kawashima Keisuke , Watanabe Manabu , Sugano Sumio , Sugimoto Yoshikazu , Suzuki Yutaka
Published: March 2021

Intensive use of a few elite sires has increased the risk of the manifestation of deleterious recessive traits in cattle. Substantial genotyping data gathered using single-nucleotide polymorphism (SNP) arrays have identified the haplotypes with homozygous deficiency, which may compromise survival. We developed Japanese Black cattle haplotypes (JBHs) using SNP array data (4843 individuals) and identified deleterious recessive haplotypes using exome sequencing of 517 sires. We identified seven JBHs with homozygous deficiency. JBH_10 and JBH_17 were associated with the resuming of estrus after artificial insemination, indicating that these haplotypes carried deleterious mutations affecting embryonic survival. The exome data of 517 Japanese Black sires revealed that AC_000165.1:g.85341291C>G of IARS in JBH_8_2, AC_000174.1:g.74743512G>T of CDC45 in JBH_17, and a copy variation region (CNVR_27) of CLDN16 in JBH_1_1 and JBH_1_2 were the candidate mutations. A novel variant AC_000174.1:g.74743512G>T of CDC45 in JBH_17 was located in a splicing donor site at a distance of 5 bp, affecting pre-mRNA splicing. Mating between heterozygotes of JBH_17 indicated that homozygotes carrying the risk allele died around the blastocyst stage. Analysis of frequency of the CDC45 risk allele revealed that its carriers were widespread throughout the tested Japanese Black cattle population. Our approach can effectively manage the inheritance of recessive risk alleles in a breeding population.
Serum biomarkers confirming stable remission in inflammatory bowel disease
Authors: Kessel Christoph , Lavric Miha , Weinhage Toni , Brueckner Markus , de Roock Sytze , Däbritz Jan , Weber Jakob , Vastert Sebastiaan J. , Foell Dirk
Published: March 2021

Crohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for the confirmation of disease remission in patients with IBD. We retrospectively analyzed samples of 40 IBD patients (30 UC, 10 CD) enrolled in a tight-control follow-up study. Half of the patients had a flare during follow up. Serum was analyzed for S100A12 as well as S100A8/A9 and for 50 further biomarkers in a bead-based multiplex assay. The concentrations of 9 cytokines/chemokines and S100A8/A9 significantly differed in IBD patients with unstable remission (before flares) when compared to IBD patients with stable remission. Although the number of patients was small, ROC curve analyses revealed a number of biomarkers (IL-1β, IL-1RA, IL-8, IL13, IL-15, IL-21, IL-25, IFN-β, CXCL9, CXCL10, CXCL11, Galectin-1, G-CSF and S100A8/A9) that were elevated in patients with later occurring relapses. While earlier studies on peripheral biomarkers in IBD are limited to only few analytes, our study using a broad screening approach identified serum biomarkers with the potential to indicate unstable disease control in IBD, which may help to steer individual therapies to maintain remission.
Business-as-usual will lead to super and ultra-extreme heatwaves in the Middle East and North Africa
Authors: Zittis George , Hadjinicolaou Panos , Almazroui Mansour , Bucchignani Edoardo , Driouech Fatima , El Rhaz Khalid , Kurnaz Levent , Nikulin Grigory , Ntoumos Athanasios , Ozturk Tugba , Proestos Yiannis , Stenchikov Georgiy , Zaaboul Rashyd , Lelieveld Jos
Published: March 2021

Global climate projections suggest a significant intensification of summer heat extremes in the Middle East and North Africa (MENA). To assess regional impacts, and underpin mitigation and adaptation measures, robust information is required from climate downscaling studies, which has been lacking for the region. Here, we project future hot spells by using the Heat Wave Magnitude Index and a comprehensive ensemble of regional climate projections for MENA. Our results, for a business-as-usual pathway, indicate that in the second half of this century unprecedented super- and ultra-extreme heatwave conditions will emerge. These events involve excessively high temperatures (up to 56 °C and higher) and will be of extended duration (several weeks), being potentially life-threatening for humans. By the end of the century, about half of the MENA population (approximately 600 million) could be exposed to annually recurring super- and ultra-extreme heatwaves. It is expected that the vast majority of the exposed population (>90%) will live in urban centers, who would need to cope with these societally disruptive weather conditions.
Boundary conditions investigation to improve computer simulation of cerebrospinal fluid dynamics in hydrocephalus patients
Authors: Gholampour Seifollah , Fatouraee Nasser
Published: March 2021

Three-D head geometrical models of eight healthy subjects and 11 hydrocephalus patients were built using their CINE phase-contrast MRI data and used for computer simulations under three different inlet/outlet boundary conditions (BCs). The maximum cerebrospinal fluid (CSF) pressure and the ventricular system volume were more effective and accurate than the other parameters in evaluating the patients’ conditions. In constant CSF pressure, the computational patient models were 18.5% more sensitive to CSF volume changes in the ventricular system under BC “C”. Pulsatile CSF flow rate diagrams were used for inlet and outlet BCs of BC “C”. BC “C” was suggested to evaluate the intracranial compliance of the hydrocephalus patients. The results suggested using the computational fluid dynamic (CFD) method and the fully coupled fluid-structure interaction (FSI) method for the CSF dynamic analysis in patients with external and internal hydrocephalus, respectively.