bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual n-back working memory training evinces superior transfer effects compared to the method of loci
Authors: Li Wenjuan , Zhang Qiuzhu , Qiao Hongying , Jin Donggang , Ngetich Ronald K. , Zhang Junjun , Jin Zhenlan , Li Ling
Published: February 2021

Working memory (WM) training is a prevalent intervention for multiple cognitive deficits, however, the transfer effects to other cognitive tasks from gains in WM induced by different training techniques still remains controversial. Therefore, the current study recruited three groups of young adults to investigate the memory training transference, with N-back group (NBG) (n = 50) training on dual n-back task, Memory Palace group (MPG) (n = 50) on method of loci, and a blank control group (BCG) (n = 48) receiving no training. Our results showed that both training groups separately improved WM capacity on respective trained task. For untrained tasks, both training groups enhanced performance on digit-span task, while on change detection task, significant improvement was only observed in NBG. In conclusion, while both techniques can be used as effective training methods to improve WM, the dual n-back task training method, perhaps has a more prominent transfer effect than that of method of loci.
Evaluation of quasi-static and dynamic nanomechanical properties of bone-metastatic breast cancer cells using a nanoclay cancer testbed
Authors: Kar Sumanta , Katti Dinesh R. , Katti Kalpana S.
Published: February 2021

In recent years, there has been increasing interest in investigating the mechanical properties of individual cells to delineate disease mechanisms. Reorganization of cytoskeleton facilitates the colonization of metastatic breast cancer at bone marrow space, leading to bone metastasis. Here, we report evaluation of mechanical properties of two breast cancer cells with different metastatic ability at the site of bone metastases, using quasi-static and dynamic nanoindentation methods. Our results showed that the significant reduction in elastic modulus along with increased liquid-like behavior of bone metastasized MCF-7 cells was induced by depolymerization and reorganization of F-actin to the adherens junctions, whereas bone metastasized MDA-MB-231 cells showed insignificant changes in elastic modulus and F-actin reorganization over time, compared to their respective as-received counterparts. Taken together, our data demonstrate evolution of breast cancer cell mechanics at bone metastases.
Identification of sources resistant to a virulent Fusarium wilt strain (VCG 0124) infecting Cavendish bananas
Authors: Thangavelu R. , Saraswathi M. S. , Uma S. , Loganathan M. , Backiyarani S. , Durai P. , Raj E. Edwin , Marimuthu N. , Kannan G. , Swennen R.
Published: February 2021

Bananas are vital for food security in many countries, and half of banana production relies solely on ‘Cavendish’ (AAA), which is presently threatened by the fungal pathogenFusarium oxysporumf. sp.cubense(Foc) tropical race 4. This particular virulentFocstrain was also found to attack other banana varieties of commercial importance. As there is no single effective management practice available so far, this study was undertaken to determine resistant sources from the genotype collection available at the ICAR-National Research Centre for Banana, Tiruchirappalli, Tamil Nadu, India for direct use by farmers and/or in breeding programmes to develop resistant hybrids. A total of 258 genotypes of different ploidies and genomic constitutions were tested againstFocrace 1 (VCG 0124). In total, 19 genotypes (AA Unique-6, BB type-2, AAA Unique-1, AAA Cavendish-1, AAB Mysore-3, AAB Pome-1, AAB Plantain-4 and AAAB-1) were found to be immune; eight genotypes (AA Unique-1, BB type-3, AAA Cavendish-1, AAB Mysore-1, AAB Unique-1, AAB Plantain-1) were highly resistant; and nine genotypes (AA Unique-1, AAA Cavendish-3, AAB Silk-1, AAB Pome-4) were resistant. The genotypes that are resistant to the virulentFocrace 1 (VCG 0124) strain can be exploited directly for commercialization and/or in breeding programs to develop resistant hybrids.
Lifestyle and behavioral modifications made by patients with interstitial cystitis
Authors: Lin Krystal Bay-San , Wu Ming-Ping , Lin Yen-Kuang , Yen Yu-Chun , Chuang Yao-Chi , Chin Hung-Yen
Published: February 2021

Interstitial cystitis/bladder pain syndrome (IC/BPS) negatively affects the quality of life. In this study, we investigated the lifestyle behavioral changes patients with IC/BPS make to cope with their symptoms. This prospective study was conducted between August 2018 and June 2019. All patients had a primary symptom of suprapubic pain with a full bladder and other lower urinary tract symptoms for more than 6 weeks as well as cystoscopic findings. All participants completed our self-developed questionnaire, which included informations about their living and work environment, occupational garments, dietary habits, and personal habits. Continuous variables were compared using an independent sample t test, and categorical variables were compared using a chi-square test. We recruited 86 patients with IC/BPS and age-matched 86 controls without IC/BPS. In our study, patients with IC/BPS had more cranberry intake (45.34% vs. 5.81%, P < 0.05) than non-IC/BPS controls; the IC/BPS group had decreased consumption of coffee and spicy food; and wore less makeup or special work garments. In conclusion, patients with IC/BPS tend to make several lifestyle behavioral changes to cope with their symptoms.
Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation
Authors: Deng Rongkang , Kao Joseph P. Y. , Kanold Patrick O.
Published: February 2021

The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.
Comparative risk assessment for the development of cardiovascular diseases in the Hungarian general and Roma population
Authors: Piko Peter , Kosa Zsigmond , Sandor Janos , Adany Roza
Published: February 2021

Cardiovascular diseases (CVDs) are the number one cause of death globally, and the early identification of high risk is crucial to prevent the disease and to reduce healthcare costs. Short life expectancy and increased mortality among the Roma are generally accepted (although not indeed proven by mortality analyses) which can be partially explained by the high prevalence of cardiovascular risk factors (CVRF) among them. This study aims to elaborate on the prevalence of the most important CVD risk factors, assess the estimation of a 10-year risk of development of fatal and nonfatal CVDs based on the most used risk assessment scoring models, and to compare the Hungarian general (HG) and Roma (HR) populations. In 2018 a complex health survey was accomplished on the HG (n = 380) and HR (n = 347) populations. The prevalence of CVRS was defined and 10-year cardiovascular risk was estimated for both study populations using the following systems: Framingham Risk Score for hard coronary heart disease (FRSCHD) and for cardiovascular disease (FRSCVD), Systematic COronary Risk Evaluation (SCORE), ACC/AHA Pooled Cohort Equations (PCE) and Revised Pooled Cohort Equations (RPCE). After the risk scores had been calculated, the populations were divided into risk categories and all subjects were classified. For all CVD risk estimation scores, the average of the estimated risk was higher among Roma compared to the HG independently of the gender. The proportion of high-risk group in the Hungarian Roma males population was on average 1.5–3 times higher than in the general one. Among Roma females, the average risk value was higher than in the HG one. The proportion of high-risk group in the Hungarian Roma females population was on average 2–3 times higher compared to the distribution of females in the general population. Our results show that both genders in the Hungarian Roma population have a significantly higher risk for a 10-year development of cardiovascular diseases and dying from them compared to the HG one. Therefore, cardiovascular interventions should be focusing not only on reducing smoking among Roma but on improving health literacy and service provision regarding prevention, early recognition, and treatment of lipid disorders and diabetes among them.
Objective characterization of hip pain levels during walking by combining quantitative electroencephalography with machine learning
Authors: Kimura Atsushi , Mitsukura Yasue , Oya Akihito , Matsumoto Morio , Nakamura Masaya , Kanaji Arihiko , Miyamoto Takeshi
Published: February 2021

Pain is an undesirable sensory experience that can induce depression and limit individuals’ activities of daily living, in turn negatively impacting the labor force. Affected people frequently feel pain during activity; however, pain is subjective and difficult to judge objectively, particularly during activity. Here, we developed a system to objectively judge pain levels in walking subjects by recording their quantitative electroencephalography (qEEG) and analyzing data by machine learning. To do so, we enrolled 23 patients who had undergone total hip replacement for pain, and recorded their qEEG during a five-minute walk via a wearable device with a single electrode placed over the Fp1 region, based on the 10–20 Electrode Placement System, before and three months after surgery. We also assessed subject hip pain using a numerical rating scale. Brain wave amplitude differed significantly among subjects with different levels of hip pain at frequencies ranging from 1 to 35 Hz. qEEG data were also analyzed by a support vector machine using the Radial Basis Functional Kernel, a function used in machine learning. That approach showed that an individual’s hip pain during walking can be recognized and subdivided into pain quartiles with 79.6% recognition Accuracy. Overall, we have devised an objective and non-invasive tool to monitor an individual’s pain during walking.
Optical performance of progressive addition lenses (PALs) with astigmatic prescription
Authors: De Lestrange-Anginieur E. , Kee C. S.
Published: February 2021

The progressive addition lens (PAL) is a spectacle lens design with progressive refractive power changes across the lens surface to provide sharp vision at different viewing distances for patients with reduced accommodative strength. It has gained in popularity not just for presbyopic patients, but also patients with occupational (office, driving, or digital device) and therapeutic (e.g., myopia control) needs. However, despite the increasing prevalence of astigmatism in adults > 40 years old who rely on PAL correction, no metric is available to reflect the optical variation in PALs with astigmatic prescriptions. Based on recent studies, four novel optical metrics sensitive to variation of refractive power across the lens surface of PALs have been developed. These metrics were used to compare the optical performance of PALs of various prescriptions, designs, and manufacturers. For each lens, the refractive power profile was first measured with a Moire-deflectometry-based instrument.The data was then exported and analyzed using a two-dimensional error map for each of the four metrics. The results revealed significant impacts of astigmatic prescription, providing evidence for the usefulness of these metrics in quantifying the optical performance of PALs for patients with astigmatic prescriptions.
Phase-transition-induced jumping, bending, and wriggling of single crystal nanofibers of coronene
Authors: Takazawa Ken , Inoue Jun-ichi , Mitsuishi Kazutaka , Yoshida Yukihiro , Kishida Hideo , Tinnemans Paul , Engelkamp Hans , Christianen Peter C. M.
Published: February 2021

For decades, it has been reported that some organic crystals suddenly crack, break, or jump when they are heated from room temperature. Recently, such crystals have been intensively studied both in fundamental science and for high-speed mechanical device applications. According to these studies, the sudden crystal motions have been attributed to structural phase transitions induced by heating. Stress created by the phase transition is released through the sudden and rapid motion of the crystals. Here we report that single crystal nanofibers of coronene exhibit a new type of ultrafast motion when they are cooled from room temperature and subsequently heated to room temperature. The nanofibers make centimeter-scale jumps accompanied by surprisingly unique behaviors such as sharp bending and wriggling. We found that the motions are caused by a significantly fast structural phase transition between two polymorphs of coronene. A theoretical investigation revealed that the sudden force generated by the phase transition together with the nanoscale dimensions and elastic properties create dynamical instability in the nanofibers that results in the motions. Our finding demonstrates the novel mechanism that leads to ultrafast, large deformation of organic crystals.
Remote sensing image description based on word embedding and end-to-end deep learning
Authors: Wang Yuan , Ma Hongbing , Alifu Kuerban , Lv Yalong
Published: February 2021

This study proposes an end-to-end image description generation model based on word embedding technology to realise the classification and identification of Populus euphratica and Tamarix in complex remote sensing images by providing descriptions in precise and concise natural sentences. First, category ambiguity over large-scale regions in remote sensing images is addressed by introducing the co-occurrence matrix and global vectors for word representation to generate the word vector features of the object to be identified. Second, a new multi-level end-to-end model is employed to further describe the content of remote sensing images and to better advance the description tasks for P. euphratica and Tamarix in remote sensing images. Experimental results reveal that the natural language sentences generated using this method can better describe P. euphratica and Tamarix in remote sensing images compared with conventional deep learning methods.
Evaluation of an in vitro assay to screen for the immunotoxic potential of chemicals to fish
Authors: Rehberger Kristina , Escher Beate I. , Scheidegger Andreas , Werner Inge , Segner Helmut
Published: February 2021

A wide variety of environmental contaminants has been shown to disrupt immune functions of fish and may compromise their defense capability against pathogens. Immunotoxic effects, however, are rarely considered in ecotoxicological testing strategies. The aim of this study was to systematically evaluate the suitability of an in vitro immuno-assay using selected fish immune parameters to screen for chemicals with known immunotoxic potential and to differentiate them from non-immunotoxicants. Non-stimulated and lipopolysaccharide-stimulated head kidney leukocytes of rainbow trout (Oncorhynchus mykiss) were exposed for 3 h or 19 h to chemicals with different modes of action. As immune parameters, phagocytosis activity, oxidative burst activity and cytokine transcription (IL-1β, TNFα, IL-10) were examined, accompanied by in silico modelling. The immunotoxicants dexamethasone, benzo(a)pyrene, ethinylestradiol and bisphenol A significantly altered the immune parameters at non-cytotoxic concentrations whereas diclofenac had only weak effects. However, the two baseline chemicals with no known immunotoxic potential, butanol and ethylene glycol, caused significant effects, too. From our results it appears that the in vitro fish leukocyte assay as performed in the present study has only a limited capacity for discriminating between immunotoxicants and non-immunotoxicants.
Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study
Authors: Seral-Cortes Miguel , Sabroso-Lasa Sergio , De Miguel-Etayo Pilar , Gonzalez-Gross Marcela , Gesteiro Eva , Molina-Hidalgo Cristina , De Henauw Stefaan , Gottrand Frederic , Mavrogianni Christina , Manios Yannis , Plada Maria , Widhalm Kurt , Kafatos Anthony , Erhardt Éva , Meirhaeghe Aline , Salazar-Tortosa Diego , Ruiz Jonatan , Moreno Luis A. , Esteban Luis Mariano , Labayen Idoia
Published: February 2021

Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11–19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual’s predisposition to overweight/obesity in European adolescents.
Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies
Authors: Carmeli Cristian , Kutalik Zoltán , Mishra Pashupati P. , Porcu Eleonora , Delpierre Cyrille , Delaneau Olivier , Kelly-Irving Michelle , Bochud Murielle , Dhayat Nasser A. , Ponte Belen , Pruijm Menno , Ehret Georg , Kähönen Mika , Lehtimäki Terho , Raitakari Olli T. , Vineis Paolo , Kivimäki Mika , Chadeau-Hyam Marc , Dermitzakis Emmanouil , Vuilleumier Nicolas , Stringhini Silvia
Published: February 2021

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
Free radical degradation in aqueous solution by blowing hydrogen and carbon dioxide nanobubbles
Authors: Fujita Toyohisa , Kurokawa Hiromi , Han Zhenyao , Zhou Yali , Matsui Hirofumi , Ponou Josiane , Dodbiba Gjergj , He Chunlin , Wei Yuezou
Published: February 2021

The main findings are the hydroxyl radical scavenging and the superoxide anion diminishing by mixing the carbon dioxide (CO2) nanobubbles after hydrogen nanobubble blowing in water and alcohol aqueous solution. The nanobubbles produce the hydroxyl radical by ultrasonic waves, changing the pH and catalyst and so on, while the nanobubble is very reactive to scavenge free radicals. In this research especially hydrogen (4% H2 in argon) and CO2 nanobubbles have been blown into hydrogen peroxide (H2O2) added pure water, ethanol, and ethylene glycol aqueous solution through a porous ceramic sparger from the gas cylinder. The aqueous solutions with H2O2 are irradiated by ultraviolet (UV) light and the produced hydroxyl radical amount is measured with spin trapping reagent and electron spin resonance (ESR). The CO2 nanobubble blowing extremely has reduced the hydroxyl radical in water, ethanol, and ethylene glycol aqueous solution. On the other hand, when H2 nanobubbles are brown after CO2 nanobubble blowing, the hydroxyl radical amount has increased. For the disinfection test, the increase of hydroxyl radicals is useful to reduce the bacteria by the observation in the agar medium. Next, when the superoxide anion solution is mixed with nanobubble containing water, ethanol, and ethylene glycol aqueous solution, H2 nanobubble has reduced the superoxide anion slightly. The water containing both CO2 and H2 nanobubble reduces the superoxide anion. The less than 20% ethanol and the 30% ethylene glycol aqueous solution containing CO2 nanobubbles generated after H2 nanobubble blowing can diminish the superoxide anion much more. While the H2 nanobubble blowing after CO2 nanobubble blowing scavenges the superoxide anion slightly. The experimental results have been considered using a chemical reaction formula.
Predictors for the severe coronavirus disease 2019 (COVID-19) infection in patients with underlying liver disease: a retrospective analytical study in Iran
Authors: Bahardoust Mansour , Heiat Mohammad , Khodabandeh Mehrdad , Karbasi Ashraf , Bagheri-Hosseinabadi Zahra , Ataee Mohammad Hossein , Seidalian Narjes , Babazadeh Amirhossein , Agah Shahram , Abyazi Mohammad Ali
Published: February 2021

Risk factors for clinical outcomes of COVID-19 pneumonia have not yet been well established in patients with underlying liver diseases. Our study aimed to describe the clinical characteristics and outcomes of COVID-19 infection among patients with underlying liver diseases and determine the risk factors for severe COVID-19 among them. In a retrospective analytical study, 1002 patients with confirmed COVID-19 pneumonia were divided into two groups: patients with and without underlying liver diseases. The admission period was from 5 March to 14 May 2020. The prevalence of underlying conditions, Demographic data, clinical parameters, laboratory data, and participants' outcomes were evaluated. Logistic regression was used to estimate the predictive factors. Eighty-one (8%) of patients had underlying liver diseases. The frequencies of gastrointestinal symptoms such as diarrhea and vomiting were significantly higher among patients with liver diseases (48% vs. 25% and 46.1% vs. 30% respectively, both P < 0.05). Moreover, ALT and AST were significantly higher among patients with liver diseases (54.5 ± 45.6 vs. 37.1 ± 28.4, P = 0.013 and 41.4 ± 27.2 vs. 29.2 ± 24.3, P = 0.028, respectively). Additionally, the mortality rate was significantly high in patients with liver disease (12.4% vs. 7%, P = 0.018). We also observed that the parameters such as neutrophil to leukocyte ratio [Odds Ratio Adjusted (ORAdj) 1.81, 95% CI 1.21–3.11, P = 0.011] and blood group A (ORAdj 1.59, 95% CI 1.15–2.11, P = 0.001) were associated with progression of symptoms of COVID-19. The presence of underlying liver diseases should be considered one of the poor prognostic factors for worse outcomes in patients with COVID-19.
Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice
Authors: Weisell Jonna , Ruotsalainen Anna-Kaisa , Näpänkangas Juha , Jauhiainen Matti , Rysä Jaana
Published: February 2021

In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD.LDLr−/−ApoB100/100male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemicLDLr−/−ApoB100/100mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.
The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
Authors: Vázquez-Moreno Miguel , Locia-Morales Daniel , Valladares-Salgado Adan , Sharma Tanmay , Perez-Herrera Aleyda , Gonzalez-Dzib Roxana , Rodríguez-Ruíz Francisco , Wacher-Rodarte Niels , Cruz Miguel , Meyre David
Published: February 2021

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35–2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13–2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14–3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10–6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10–5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.
Mating system evolution and genetic structure of diploid sexual populations of Cyrtomium falcatum in Japan
Authors: Imai Ryosuke , Tsuda Yoshiaki , Ebihara Atsushi , Matsumoto Sadamu , Tezuka Ayumi , Nagano Atsushi J. , Ootsuki Ryo , Watano Yasuyuki
Published: February 2021

Evolution of mating systems has become one of the most important research areas in evolutionary biology. Cyrtomium falcatum is a homosporous fern species native to eastern Asia. Two subspecies belonging to a sexual diploid race of C. falcatum are recognized: subsp. littorale and subsp. australe. Subspecies littorale shows intermediate selfing rates, while subsp. australe is an obligate outcrosser. We aimed to evaluate the process of mating system evolution and divergence for the two subspecies using restriction site associated DNA sequencing (RAD-seq). The results showed that subsp. littorale had lower genetic diversity and stronger genetic drift than subsp. australe. Fluctuations in the effective population size over time were evaluated by extended Bayesian skyline plot and Stairway plot analyses, both of which revealed a severe population bottleneck about 20,000 years ago in subsp. littorale. This bottleneck and the subsequent range expansion after the LGM appear to have played an important role in the divergence of the two subspecies and the evolution of selfing in subsp. littorale. These results shed new light on the relationship between mating system evolution and past demographic change in fern species.
Comparison of treatment outcomes for native tissue repair and sacrocolpopexy as apical suspension procedures at the time of hysterectomy for uterine prolapse
Authors: Oh Sumin , Shin E. Kyung , Hyun Sowoon , Jeon Myung Jae
Published: February 2021

Concomitant apical suspension should be performed at the time of hysterectomy for uterine prolapse to reduce the risk of recurrent prolapse. Native tissue repair (NTR) and sacrocolpopexy (SCP) are commonly used apical suspension procedures; however, it remains unclear which one is preferred. This study aimed to compare the treatment outcomes of NTR and SCP in terms of surgical failure, complication and reoperation rates. Surgical failure was defined as the presence of vaginal bulge symptoms, any prolapse beyond the hymen, or retreatment for prolapse. This retrospective cohort study included 523 patients who had undergone NTR (n = 272) or SCP (n = 251) along with hysterectomy for uterine prolapse and who had at least 4-month follow-up visits. During the median 3-year follow-up period, the surgical failure rate was higher in the NTR group (21.3% vs 6.4%, P < 0.01), with a low rate of retreatment in both groups. Overall complication rates were similar, but complications requiring surgical correction under anesthesia were more common in the SCP group (7.2% vs 0.4%, P < 0.01). As a result, the total reoperation rate was significantly higher in the SCP group (8.0% vs 2.6%, P = 0.02). Taken together, NTR may be a preferred option for apical suspension when hysterectomy is performed for uterine prolapse.
Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
Authors: Youssef Lina , Miranda Jezid , Blasco Miquel , Paules Cristina , Crovetto Francesca , Palomo Marta , Torramade-Moix Sergi , García-Calderó Héctor , Tura-Ceide Olga , Dantas Ana Paula , Hernandez-Gea Virginia , Herrero Pol , Canela Nuria , Campistol Josep Maria , Garcia-Pagan Joan Carles , Diaz-Ricart Maribel , Gratacos Eduard , Crispi Fatima
Published: February 2021

Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC–MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein–protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit (R2X = 0.99, p < 0.001) and a strong predictive ability (Q2Y = 0.8, p < 0.001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0.05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3.17e−07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway.
Coinfection of porcine deltacoronavirus and porcine epidemic diarrhea virus increases disease severity, cell trophism and earlier upregulation of IFN-α and IL12
Authors: Saeng-chuto Kepalee , Madapong Adthakorn , Kaeoket Kampon , Piñeyro Pablo Enrique , Tantituvanont Angkana , Nilubol Dachrit
Published: February 2021

Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) cause an enteric disease characterized by diarrhea clinically indistinguishable. Both viruses are simultaneously detected in clinical cases, but a study involving the co-infection has not been reported. The study was therefore conducted to investigate the disease severity following a co-infection with PEDV and PDCoV. In the study, 4-day-old pigs were orally inoculated with PEDV and PDCoV, either alone or in combination. Following challenge, fecal score was monitored on a daily basis. Fecal swabs were collected and assayed for the presence of viruses. Three pigs per group were necropsied at 3 and 5 days post inoculation (dpi). Microscopic lesions and villous height to crypt depth (VH:CD) ratio, together with the presence of PEDV and PDCoV antigens, were evaluated in small intestinal tissues. Expressions of interferon alpha (IFN-α) and interleukin 12 (IL12) were investigated in small intestinal mucosa. The findings indicated that coinoculation increased the disease severity, demonstrated by significantly prolonged fecal score and virus shedding and decreasing VH:CD ratio in the jejunum compared with pigs inoculated with either PEDV or PDCoV alone. Notably, in single-inoculated groups, PEDV and PDCoV antigens were detected only in villous enterocytes wile in the coinoculated group, PDCoV antigen was detected in both villous enterocytes and crypts. IFN-α and IL12 were significantly up-regulated in coinoculated groups in comparison with single-inoculated groups. In conclusion, co-infection with PEDV and PDCoV exacerbate clinical signs and have a synergetic on the regulatory effect inflammatory cytokines compared to a single infection with either virus.
Foxes fertilize the subarctic forest and modify vegetation through denning
Authors: Lang Jessica A. , Roth James D. , Markham John H.
Published: February 2021

Ecosystem engineers modify habitats through processes other than trophic interactions, such as by regulating soil nutrients, and can influence resource availability and quality for other organisms. Predator-mediated elemental cycling may be especially important in determining plant diversity and growth in ecosystems where soil fertility and primary productivity are low. Red foxes (Vulpes vulpesL.), top predators in the Subarctic, could engineer local ecosystems through denning, which could create biogeochemical hotspots of nutrients due to continual input of feces, urine and prey remains. We examined soil and vegetation characteristics on red fox dens and paired control sites in woodland habitats near the Arctic treeline in Manitoba, Canada. The organic soil layer on den sites had 81% more inorganic nitrogen and 250% more extractable phosphorus than in control areas. Denning also increased soil respiration and pH in the organic layer, suggesting improved soil quality and nutrient availability for plants. By enriching nutrients and disturbing soils through digging, den sites had a higher plant species ß-diversity and a greater cover of erect woody shrubs (Salixspp.), grasses (Leymus mollis(Trinius) Pilger) and weedy ephemerals compared to control sites, resulting in a regional increase in plant species richness. Our research highlights the importance of considering impacts of predators other than through their consumption of prey, and provides insight into the role of red foxes in modifying plant diversity and productivity in the Subarctic.
The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
Authors: Kovacevic Katarina D. , Greisenegger Stefan , Langer Agnes , Gelbenegger Georg , Buchtele Nina , Pabinger Ingrid , Petroczi Karin , Zhu Shuhao , Gilbert James C. , Jilma Bernd
Published: February 2021

The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.
Evaluation of dose-volume histogram prediction for organ-at risk and planning target volume based on machine learning
Authors: Jiao Sheng xiu , Wang Ming li , Chen Li xin , Liu Xiao-wei
Published: February 2021

The purpose of this work is to evaluate the performance of applying patient dosimetric information induced by individual uniform-intensity radiation fields in organ-at risk (OAR) dose-volume histogram (DVH) prediction, and extend to DVH prediction of planning target volume (PTV). Ninety nasopharyngeal cancer intensity-modulated radiation therapy (IMRT) plans and 60 rectal cancer volumetric modulated arc therapy (VMAT) plans were employed in this study. Of these, 20 nasopharyngeal cancer cases and 15 rectal cancer cases were randomly selected as the testing data. The DVH prediction was performed using two methods. One method applied the individual dose-volume histograms (IDVHs) induced by a series of fields with uniform-intensity irradiation and the other method applied the distance-to-target histogram and the conformal-plan-dose-volume histogram (DTH + CPDVH). The determination coefficient R2 and mean absolute error (MAE) were used to evaluate DVH prediction accuracy. The PTV DVH prediction was performed using the IDVHs. The PTV dose coverage was evaluated using D98, D95, D1 and uniformity index (UI). The OAR dose was compared using the maximum dose, V30 and V40. The significance of the results was examined with the Wilcoxon signed rank test. For PTV DVH prediction using IDVHs, the clinical plan and IDVHs prediction method achieved mean UI values of 1.07 and 1.06 for nasopharyngeal cancer, and 1.04 and 1.05 for rectal cancer, respectively. No significant difference was found between the clinical plan results and predicted results using the IDVHs method in achieving PTV dose coverage (D98,D95,D1 and UI) for both nasopharyngeal cancer and rectal cancer (p-values ≥ 0.052). For OAR DVH prediction, no significant difference was found between the IDVHs and DTH + CPDVH methods for the R2, MAE, the maximum dose, V30 and V40 (p-values ≥ 0.087 for all OARs). This work evaluates the performance of dosimetric information of several individual fields with uniform-intensity radiation for DVH prediction, and extends its application to PTV DVH prediction. The results indicated that the IDVHs method is comparable to the DTH + CPDVH method in accurately predicting the OAR DVH. The IDVHs method quantified the input features of the PTV and showed reliable PTV DVH prediction, which is helpful for plan quality evaluation and plan generation.
Near-infrared fundus autofluorescence alterations correlate with swept-source optical coherence tomography angiography findings in patients with retinitis pigmentosa
Authors: Nassisi Marco , Lavia Carlo , Mohand-Said Saddek , Smirnov Vasily , Antonio Aline , Condroyer Christel , Sancho Serge , Varin Juliette , Gaudric Alain , Zeitz Christina , Sahel José-Alain , Audo Isabelle
Published: February 2021

Thirty-eight patients from 37 families with retinitis pigmentosa (RP) underwent macular 6 × 6-mm swept-source optical coherence tomography angiography (SS-OCTA) and 30° near-infrared fundus autofluorescence (NIR-FAF) acquisitions in one eye. Superficial vascular complex (SVC), deep capillary complex (DCC) and choriocapillaris (CC) angiograms were registered with NIR-FAF acquisitions to comparatively assess subjects with and without central area of preserved NIR-FAF (APA). On the subset of patients showing an APA, the vessel densities for SVC and DCC and flow deficits for CC were assessed in three directions (superior, inferior and temporal) from the fovea and compared to healthy 1:1 age-matched controls. Nine patients with no APA had evidence of severe central OCTA alterations at all levels, especially in the DCC. In the other 29 subjects presenting APA, all OCTA parameters were similar to healthy eyes within the APA, where the retina preserves its structural integrity. Outside the APA, both the DCC and CC were significantly reduced in all directions. These alterations are probably related to the outer retinal atrophy outside the APA. Comparing OCTA to other imaging modalities is helpful to determine the potential interest of OCTA findings as an outcome measure for disease status and progression.
Simultaneous, efficient and continuous oil–water separation via antagonistically functionalized membranes prepared by atmospheric-pressure cold plasma
Authors: Kim Dong-hyun , Mauchauffé Rodolphe , Kim Jongwoon , Moon Se Youn
Published: February 2021

For decades, oil and water separation has remained a challenge. Not only oil spills but also industrial oily wastewaters are threatening our environment. Over the years, oil–water separation methods have been developed, however, there are still considerable hurdles to overcome to provide a low cost and efficient process able to treat a large amount of liquid. In this work, we suggest a continuous, simultaneous and effective oil–water separation method based on the antagonistic functionalization of meshes using atmospheric pressure cold plasmas. Using this robust plasma method, superhydrophobic/underwater-superoleophilic or superhydrophilic/underwater-superoleophobic functionalized meshes are obtained. Antagonistically functionalized meshes can simultaneously separate oil and water and show continuous separation flow rates of water (900 L m−2 h−1) and oil (400 L m−2 h−1) with high purities (> 99.9% v/v). This fast, low-cost and continuous plasma-based process can be readily and widely adopted for the selective functionalization of membranes at large scale for oil-spill cleanup and water purification.
Growth, clinical and neurodevelopmental outcomes at school age are similar for children who received 1-year lamivudine or lopinavir/ritonavir HIV prophylaxis in early life
Authors: Nagot Nicolas , Singata-Madliki Mandisa , Cournil Amandine , Nalugya Joyce , Tassembedo Souleymane , Quillet Catherine , Tonga Melany W. , Tumwine James , Meda Nicolas , Kankasa Chipepo , Mwiya Mwiya , Bangirana Paul , Peries Marianne , Batting Joanne , Engebretsen Ingunn M. S. , Tylleskär Thorkild , Perre Philippe Vande , Ndeezi Grace , Molès Jean-Pierre
Published: February 2021

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5–7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.
Sample pooling as a strategy for community monitoring for SARS-CoV-2
Authors: Sawicki Rafal , Korona-Glowniak Izabela , Boguszewska Anastazja , Stec Agnieszka , Polz-Dacewicz Malgorzata
Published: February 2021

Sample pooling strategy was intended to determine the optimal parameters for group testing of pooled specimens for the detection of SARS-CoV-2 and process them without significant loss of test usability. Standard molecular diagnostic laboratory equipment, and commercially available centrifugal filters, RNA isolation kits and SARS Cov2 PCR tests were used. The basic idea was to combine and concentrate several samples to the maximal volume, which can be extracted with the single extraction column. Out of 16 tested pools, 12 were positive with cycle threshold (Ct) values within 0.5 and 3.01 Ct of the original individual specimens. The analysis of 112 specimens determined that 12 pools were positive, followed by identification of 6 positive individual specimens among the 112 tested. This testing was accomplished with the use of 16 extractions/PCR tests, resulting in saving of 96 reactions but adding the 40 centrifugal filters. The present study demonstrated that pool testing could detect even up to a single positive sample with Ct value as high as 34. According to the standard protocols, reagents and equipment, this pooling method can be applied easily in current clinical testing laboratories.