bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, characterization, and imaging of radiopaque bismuth beads for image-guided transarterial embolization
Authors: Negussie Ayele H. , de Ruiter Quirina M. B. , Britton Hugh , Donahue Danielle R. , Boffi Quentin , Kim Young-Seung , Pritchard William F. , Moonen Chrit , Storm Gert , Lewis Andrew L. , Wood Bradford J.
Published: January 2021

Current therapy for hypervascular cancers, e.g., hepatocellular carcinoma, includes occlusion of the tumor blood supply by arterial infusion of embolic microspheres (beads) suspended in iodine-based contrast under fluoroscopic guidance. Available radiopaque, imageable beads use iodine as the radiopacifier and cannot be differentiated from contrast. This study aimed to synthesize and characterize imageable beads using bismuth as the radiopacifier that could be distinguished from iodine contrast based upon the difference in the binding energy of k-shell electrons (k-edge). Radiodense bismuth beads were successfully synthesized some with uniform bismuth distribution across the beads. The beads were spherical and could be infused through clinical microcatheters. The bismuth beads could be imaged with clinical dual-energy computed tomography (CT), where iodine-based contrast could be distinguished from the microspheres. The ability to separate iodine from bismuth may enhance the diagnostic information acquired on follow-up CT, identifying the distribution of the embolic beads separately from the contrast. Furthermore, with sequential use of iodine- and bismuth-based beads, the two radiopaque beads could be spatially distinguished on imaging, which may enable the development of dual drug delivery and dual tracking.
3D imaging using scanning diffractometry
Authors: Siavashani Morteza J. , Naghedi Iman , Abbasian Vahid , Akhlaghi Ehsan A. , Charsooghi Mohammad A. , Tavassoly Mohammad Taghi , Moradi Ali-Reza
Published: January 2021

Imaging of cells is a challenging problem as they do not appreciably change the intensity of the illuminating light. Interferometry-based methods to do this task suffer from high sensitivity to environmental vibrations. We introduce scanning diffractometry as a simple non-contact and vibration-immune methodology for quantitative phase imaging. Fresnel diffractometry by a phase step has led to several applications such as high-precision measurements of displacement. Additional scanning may lead to 3D imaging straightforwardly. We apply the technique to acquire 3D images of holographic grating, red blood cell, neuron, and sperm cell. Either visibility of the diffraction fringes or the positions of extrema may be used for phase change detection. The theoretical analysis through the Fresnel diffraction from one-dimensional phase step is presented and the experimental results are validated with digital holographic microscopy. The presented technique can be suggested to serve as a robust device for 3D phase imaging and biomedical measurements.
Parametric shift from rational to irrational decisions in mice
Authors: Schneider Nathan A. , Ballintyn Benjamin , Katz Donald , Lisman John , Pi Hyun-Jae
Published: January 2021

In the classical view of economic choices, subjects make rational decisions evaluating the costs and benefits of options in order to maximize their overall income. Nonetheless, subjects often fail to reach optimal outcomes. The overt value of an option drives the direction of decisions, but covert factors such as emotion and sensitivity to sunk cost are thought to drive the observed deviations from optimality. Many questions remain to be answered as to (1) which contexts contribute the most to deviation from an optimal solution; and (2) the extent of these effects. In order to tackle these questions, we devised a decision-making task for mice, in which cost and benefit parameters could be independently and flexibly adjusted and for which a tractable optimal solution was known. Comparing mouse behavior with this optimal solution across parameter settings revealed that the factor most strongly contributing to suboptimal performance was the cost parameter. The quantification of sensitivity to sunk cost, a covert factor implicated in our task design, revealed it as another contributor to reduced optimality. In one condition where the large reward option was particularly unattractive and the small reward cost was low, the sensitivity to sunk cost and the cost-led suboptimality almost vanished. In this regime and this regime only, mice could be viewed as close to rational (here, ‘rational’ refers to a state in which an animal makes decisions basing on objective valuation, not covert factors). Taken together, our results suggest that “rationality” is a task-specific construct even in mice.
Patterns and risk of HIV-1 transmission network among men who have sex with men in Guangxi, China
Authors: Pang Xianwu , Wei Hui , Huang Jinghua , He Qin , Tang Kailing , Fang Ningye , Zhou Xinjuan , Zhu Qiuying , Wu Xiuling , Lan Guanghua , Shen Zhiyong , Lin Mei , Liang Shujia
Published: January 2021

The prevalence of HIV-1 in Guangxi is very high, and the rate of HIV-1 infection among men who have sex with men (MSM) has been increasing. Therefore, it is necessary to explore the patterns and risk factors of HIV transmission in Guangxi. For this purpose, individuals diagnosed with HIV-1 during 2013–2018 in Guangxi were recruited. Phylogenetic relationship, transmission clusters, and genotypic drug resistance analyses were performed based on HIV-1 pol sequences. Related factors were analysed to assess for their association with HIV-1 transmission. CRF07_BC (50.4%) and CRF01_AE (33.4%) were found to be the predominant subtypes. The analysed 1633 sequences (50.15%, Guangxi; 49.85%, other provinces) were segregated into 80 clusters (size per cluster, 2–704). We found that 75.3% of the individuals were in three clusters (size ˃ 100), and 73.8% were high-risk spreaders (links ≥ 4). Infection time, marital status, and subtype were significantly associated with HIV-1 transmission. Additionally, 80.2% of recent infections were linked to long-term infections, and 46.2% were linked to other provinces. A low level of transmitted drug resistance was detected (4.8%). Our findings indicated superclusters and high-risk HIV-1 spreaders among the MSM in Guangxi. Effective strategies blocking the route of transmission should be developed.
Future thermal regimes for epaulette sharks (Hemiscyllium ocellatum): growth and metabolic performance cease to be optimal
Authors: Wheeler Carolyn R. , Rummer Jodie L. , Bailey Barbara , Lockwood Jamie , Vance Shelby , Mandelman John W.
Published: January 2021

Climate change is affecting thermal regimes globally, and organisms relying on their environment to regulate biological processes face unknown consequences. In ectotherms, temperature affects development rates, body condition, and performance. Embryonic stages may be the most vulnerable life history stages, especially for oviparous species already living at the warm edge of their distribution, as embryos cannot relocate during this developmental window. We reared 27 epaulette shark (Hemiscyllium ocellatum) embryos under average summer conditions (27 °C) or temperatures predicted for the middle and end of the twenty-first century with climate change (i.e., 29 and 31 °C) and tracked growth, development, and metabolic costs both in ovo and upon hatch. Rearing sharks at 31 °C impacted embryonic growth, yolk consumption, and metabolic rates. Upon hatch, 31 °C-reared sharks weighed significantly less than their 27 °C-reared counterparts and exhibited reduced metabolic performance. Many important growth and development traits in this species may peak after 27 °C and start to become negatively impacted nearing 31 °C. We hypothesize that 31 °C approximates the pejus temperature (i.e., temperatures at which performance of a trait begin to decline) for this species, which is alarming, given that this temperature range is well within ocean warming scenarios predicted for this species’ distribution over the next century.
Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy
Authors: Ura Katsuro , Yamada Katsuhisa , Tsujimoto Takeru , Ukeba Daisuke , Iwasaki Norimasa , Sudo Hideki
Published: January 2021

Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.
Endophytic fungal community structure in olive orchards with high and low incidence of olive anthracnose
Authors: Martins Fátima , Mina Diogo , Pereira José Alberto , Baptista Paula
Published: January 2021

Fungal endophytes have been increasingly recognized to promote host plant protection to pathogens, but knowledge of the multiple effects that they could have in crop diseases is still scarce. This work attempts to understand the role of fungal endophytes in crop diseases, specifically in reducing disease development and interfering on lifestyle transition of the pathogen. To accomplish this, the endophytic fungal community of reproductive organs of olive tree from two orchards showing different levels of anthracnose incidence, a major disease of olive fruits, was characterized and compared between them. The two orchards showed distinct endophytic communities, differing in species richness, abundance and composition, with highest isolation rates and richness of endophytes in the orchard with low anthracnose incidence. These differences among orchards were greater on fruits than on flowers, suggesting that these changes in endophytic fungal composition may influence the lifestyle shifts in pathogen (from latent to pathogen). A number of fungal taxa were found to be positively associated to one of the two orchards. The fungal endophytes best correlated with high incidence of anthracnose are pathogens, while endophytes-associated to low anthracnose incidence are described to protect plants. Altogether, the results suggest varying pathogen–endophyte interactions among the two orchards.
Natural sonic crystal absorber constituted of seagrass (Posidonia Oceanica) fibrous spheres
Authors: Barguet L. , Romero-García V. , Jiménez N. , Garcia-Raffi L. M. , Sánchez-Morcillo V. J. , Groby J.-P.
Published: January 2021

We present a 3-dimensional fully natural sonic crystal composed of spherical aggregates of fibers (called Aegagropilae) resulting from the decomposition of Posidonia Oceanica. The fiber network is first acoustically characterized, providing insights on this natural fiber entanglement due to turbulent flow. The Aegagropilae are then arranged on a principal cubic lattice. The band diagram and topology of this structure are analyzed, notably via Argand representation of its scattering elements. This fully natural sonic crystal exhibits excellent sound absorbing properties and thus represents a sustainable alternative that could outperform conventional acoustic materials.
Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice
Authors: Zhang Wenchao , Miikeda Aika , Zuckerman Jonathan , Jia Xun , Charugundla Sarada , Zhou Zhiqiang , Kaczor-Urbanowicz Karolina Elżbieta , Magyar Clara , Guo Fangfei , Wang Zeneng , Pellegrini Matteo , Hazen Stanley L. , Nicholas Susanne B. , Lusis Aldons J. , Shih Diana M.
Published: January 2021

Patients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.
The perception of interpersonal distance is distorted by the Müller-Lyer illusion
Authors: Bunce Carl , Gray Katie L. H. , Cook Richard
Published: January 2021

There is growing interest in how human observers perceive social scenes containing multiple people. Interpersonal distance is a critical feature when appraising these scenes; proxemic cues are used by observers to infer whether two people are interacting, the nature of their relationship, and the valence of their current interaction. Presently, however, remarkably little is known about how interpersonal distance is encoded within the human visual system. Here we show that the perception of interpersonal distance is distorted by the Müller-Lyer illusion. Participants perceived the distance between two target points to be compressed or expanded depending on whether face pairs were positioned inside or outside the to-be-judged interval. This illusory bias was found to be unaffected by manipulations of face direction. These findings aid our understanding of how human observers perceive interpersonal distance and may inform theoretical accounts of the Müller-Lyer illusion.
The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome
Authors: Rathinam Elanagai , Govindarajan Srinath , Rajasekharan Sivaprakash , Declercq Heidi , Elewaut Dirk , De Coster Peter , Martens Luc , Leybaert Luc
Published: January 2021

Calcium (Ca2+) signalling plays an indispensable role in dental pulp and dentin regeneration, but the Ca2+ responses of human dental pulp stem cells (hDPSCs) stimulated with tricalcium silicate-based (TCS-based) dental biomaterials remains largely unexplored. The objective of the present study was to identify and correlate extracellular Ca2+ concentration, intracellular Ca2+ dynamics, pH, cytotoxicity, gene expression and mineralization ability of human dental pulp stem cells (hDPSCs) stimulated with two different TCS-based biomaterials: Biodentine and ProRoot white MTA. The hDPSCs were exposed to the biomaterials, brought in contact with the overlaying medium, with subsequent measurements of extracellular Ca2+ and pH, and intracellular Ca2+ changes. Messenger RNA expression (BGLAP, TGF-β, MMP1 and BMP2), cytotoxicity (MTT and TUNEL) and mineralization potential (Alizarin red and Von Kossa staining) were then evaluated. Biodentine released significantly more Ca2+ in the α-MEM medium than ProRoot WMTA but this had no cytotoxic impact on hDPSCs. The larger Biodentine-linked Ca2+ release resulted in altered intracellular Ca2+ dynamics, which attained a higher maximum amplitude, faster rise time and increased area under the curve of the Ca2+ changes compared to ProRoot WMTA. Experiments with intracellular Ca2+ chelation, demonstrated that the biomaterial-triggered Ca2+ dynamics affected stem cell-related gene expression, cellular differentiation and mineralization potential. In conclusion, biomaterial-specific Ca2+ dynamics in hDPSCs determine differentiation and mineralization outcomes, with increased Ca2+ dynamics enhancing mineralization.
Endovascular management of giant visceral artery aneurysms
Authors: Tipaldi Marcello Andrea , Krokidis Miltiadis , Orgera Gianluigi , Pignatelli Matteo , Ronconi Edoardo , Laurino Florindo , Laghi Andrea , Rossi Michele
Published: January 2021

Endovascular management of small visceral artery aneurysms is an established treatment with satisfactory outcomes. However, when size exceeds 5 cm visceral aneurysms are considered as “giant” (giant visceral artery aneurysms or GVAAs) and management is significantly more complex. Between August 2007 and June 2019 eleven cases of GVAAs that were endovascularly treated were retrospectively reviewed and included in this single center study. Mean size was 80 mm (± 26.3 mm) x 46 mm (+ \-11.8 mm). Nine of the lesions were true aneurysms, and two were pseudoaneurysms. In 8 patients, the lesion was causing compression symptoms in the surrounding organs, one patient developed a contained rupture while 2 patients were completely asymptomatic. However, all patients were hemodynamically stable at the time of treatment. Technical success was defined as immediate complete exclusion of the aneurysmal sac, and clinical success as complete relief from clinical symptoms. Follow-up was performed with CT angiography, ultrasound and clinical examination. Mean follow-up was 45 months (range 6–84). Technical and clinical success were both 91%. Complications were one lack of control of contained rupture that was subsequently operated, one case of self-limiting non-target spleen embolization and one case of splenic abscess. Three patients died, one due to the contained rupture 15 days after procedure, the other two for other causes and occurred during the long-term follow-up. This series suggests that endovascular treatment of giant visceral artery aneurysms and pseudoaneuryms is a valid minimally invasive solution with very satisfactory immediate and long-term outcomes unless the aneurysm is already ruptured. A variety of endovascular tools may be required for successful treatment.
Multi-level remodelling of chromatin underlying activation of human T cells
Authors: Bediaga Naiara G. , Coughlan Hannah D. , Johanson Timothy M. , Garnham Alexandra L. , Naselli Gaetano , Schröder Jan , Fearnley Liam G. , Bandala-Sanchez Esther , Allan Rhys S. , Smyth Gordon K. , Harrison Leonard C.
Published: January 2021

Remodelling of chromatin architecture is known to regulate gene expression and has been well characterized in cell lineage development but less so in response to cell perturbation. Activation of T cells, which triggers extensive changes in transcriptional programs, serves as an instructive model to elucidate how changes in chromatin architecture orchestrate gene expression in response to cell perturbation. To characterize coordinate changes at different levels of chromatin architecture, we analyzed chromatin accessibility, chromosome conformation and gene expression in activated human T cells. T cell activation was characterized by widespread changes in chromatin accessibility and interactions that were shared between activated CD4+ and CD8+ T cells, and with the formation of active regulatory regions associated with transcription factors relevant to T cell biology. Chromatin interactions that increased and decreased were coupled, respectively, with up- and down-regulation of corresponding target genes. Furthermore, activation was associated with disruption of long-range chromatin interactions and with partitioning of topologically associating domains (TADs) and remodelling of their TAD boundaries. Newly formed/strengthened TAD boundaries were associated with higher nucleosome occupancy and lower accessibility, linking changes in lower and higher order chromatin architecture. T cell activation exemplifies coordinate multi-level remodelling of chromatin underlying gene transcription.
Effects of stimulus and task structure on temporal perceptual learning
Authors: Xu Rannie , Church Russell M. , Sasaki Yuka , Watanabe Takeo
Published: January 2021

Our ability to discriminate temporal intervals can be improved with practice. This learning is generally thought to reflect an enhancement in the representation of a trained interval, which leads to interval-specific improvements in temporal discrimination. In the present study, we asked whether temporal learning is further constrained by context-specific factors dictated through the trained stimulus and task structure. Two groups of participants were trained using a single-interval auditory discrimination task over 5 days. Training intervals were either one of eight predetermined values (FI group), or random from trial to trial (RI group). Before and after the training period, we measured discrimination performance using an untrained two-interval temporal comparison task. Our results revealed a selective improvement in the FI group, but not the RI group. However, this learning did not generalize between the trained and untrained tasks. These results highlight the sensitivity of TPL to stimulus and task structure, suggesting that mechanisms of temporal learning rely on processes beyond changes in interval representation.
Identification of significantly mutated subnetworks in the breast cancer genome
Authors: Ajwad Rasif , Domaratzki Michael , Liu Qian , Feizi Nikta , Hu Pingzhao
Published: January 2021

Recent studies showed that somatic cancer mutations target genes that are in specific signaling and cellular pathways. However, in each patient only a few of the pathway genes are mutated. Current approaches consider only existing pathways and ignore the topology of the pathways. For this reason, new efforts have been focused on identifying significantly mutated subnetworks and associating them with cancer characteristics. We applied two well-established network analysis approaches to identify significantly mutated subnetworks in the breast cancer genome. We took network topology into account for measuring the mutation similarity of a gene-pair to allow us to infer the significantly mutated subnetworks. Our goals are to evaluate whether the identified subnetworks can be used as biomarkers for predicting breast cancer patient survival and provide the potential mechanisms of the pathways enriched in the subnetworks, with the aim of improving breast cancer treatment. Using the copy number alteration (CNA) datasets from the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study, we identified a significantly mutated yet clinically and functionally relevant subnetwork using two graph-based clustering algorithms. The mutational pattern of the subnetwork is significantly associated with breast cancer survival. The genes in the subnetwork are significantly enriched in retinol metabolism KEGG pathway. Our results show that breast cancer treatment with retinoids may be a potential personalized therapy for breast cancer patients since the CNA patterns of the breast cancer patients can imply whether the retinoids pathway is altered. We also showed that applying multiple bioinformatics algorithms at the same time has the potential to identify new network-based biomarkers, which may be useful for stratifying cancer patients for choosing optimal treatments.
Characterization of Bacillus velezensis AK-0 as a biocontrol agent against apple bitter rot caused by Colletotrichum gloeosporioides
Authors: Kim Young Soo , Lee Younmi , Cheon Wonsu , Park Jungwook , Kwon Hyeok-Tae , Balaraju Kotnala , Kim Jungyeon , Yoon Yeo Jun , Jeon Yongho
Published: January 2021

Bacillusgenus produces several secondary metabolites with biocontrol ability against various phytopathogens.Bacillus velezensisAK-0 (AK-0), an antagonistic strain isolated from Korean ginseng rhizospheric soil, was found to exhibit antagonistic activity against several phytopathogens. To further display the genetic mechanism of the biocontrol traits of AK-0, we report the complete genome sequence of AK-0 and compared it with complete genome sequences of closely related strains. We report the biocontrol activity of AK-0 against apple bitter rot caused byColletotrichum gloeosporioides, which could lead to commercialization of this strain as a microbial biopesticide in Korea. To retain its biocontrol efficacy for a longer period, AK-0 has been formulated with ingredients for commercialization, named AK-0 product formulation (AK-0PF). AK-0PF played a role in the suppression of the mycelial growth of the fungicide-resistant pathogenC. gloeosporioidesYCHH4 at a greater level than the non-treated control. Moreover, AK-0PF exhibited greater disease suppression of bitter rot in matured under field conditions. Here, we report the complete genome sequence of the AK-0 strain, which has a 3,969,429 bp circular chromosome with 3808 genes and a G+C content of 46.5%. The genome sequence of AK-0 provides a greater understanding of theBacillusspecies, which displays biocontrol activity via secondary metabolites. The genome has eight potential secondary metabolite biosynthetic clusters, among which,ituDandbacDgenes were expressed at a greater level than other genes. This work provides a better understanding of the strain AK-0, as an effective biocontrol agent (BCA) against phytopathogens, including bitter rot in apple.
Effect of gallic acid on the larvae of Spodoptera litura and its parasitoid Bracon hebetor
Authors: Punia Abhay , Chauhan Nalini Singh , Singh Drishtant , Kesavan Anup Kumar , Kaur Sanehdeep , Sohal Satwinder Kaur
Published: January 2021

The antibiosis effect of gallic acid onSpodoptera lituraF. (Lepidoptera: Noctuidae) and its parasitoid evaluated by feeding six days old larvae on artificial diet incorporated with different concentrations (5 ppm, 25 ppm, 125 ppm, 625 ppm, 3125 ppm) of the phenolic compound revealed higher concentration (LC50) of gallic acid had a negative impact on the survival and physiology ofS. lituraand its parasitoidBracon hebetor(Say) (Hymenoptera:Braconidae). The mortality ofS. lituralarvae was increased whereas adult emergence declined with increasing concentration of gallic acid. The developmental period was delayed significantly and all the nutritional indices were reduced significantly with increase in concentration. Higher concentration (LC50) of gallic acid adversely affected egg hatching, larval mortality, adult emergence and total development period ofB. hebetor.At lower concentration (LC30) the effect onB. hebetoradults and larvae was non-significant with respect to control. Gene expression for the enzymes viz.,Superoxide dismutase, Glutathione peroxidase, Peroxidase, Esterases and Glutathione S transferases increased while the total hemocyte count ofS. lituralarvae decreased with treatment. Our findings suggest that gallic acid even at lower concentration (LC30) can impair the growth ofS. lituralarvae without causing any significant harm to its parasitoidB. hebetorand has immense potential to be used as biopesticides.
White-naped mangabeys’ viable insurance population within European Zoo Network
Authors: Iglesias Pastrana Carlos , Navas González Francisco Javier , Ruiz Aguilera María Josefa , Dávila García José Antonio , Delgado Bermejo Juan Vicente , Abelló María Teresa
Published: January 2021

The success and viability of an ex-situ conservation program lie in the establishment and potential maintenance of a demographically and genetically viable insurance population. Such population reserve may support reintroduction and reinforcement activities of wild populations. White-naped mangabeys are endangered restricted-range African primates which have experienced a dramatic population decrease in their natural habitats over the last few decades. Since 2001, some European zoos singularly monitor an ex-situ population aiming to seek the recovery of the current wild population. The aim of the present paper is to evaluate the genetic status and population demographics of European zoo-captive white-naped mangabeys based on pedigree data. The captive population is gradually growing and preserves specific reproductive and demographic parameters linked to the species. The intensive management program that is implemented has brought about the minimization of inbreeding and average relatedness levels, thus maintaining high levels of genetic diversity despite the existence of fragmented populations. This finding suggests white-naped mangabey ex-situ preservation actions may be a good example of multifaceted conservation throughout studbook management which could be used as a model for other ex-situ live-animal populations.
The additive nature of the human multisensory evoked pupil response
Authors: Van der Stoep Nathan , Van der Smagt M. J. , Notaro C. , Spock Z. , Naber M.
Published: January 2021

Pupillometry has received increased interest for its usefulness in measuring various sensory processes as an alternative to behavioural assessments. This is also apparent for multisensory investigations. Studies of the multisensory pupil response, however, have produced conflicting results. Some studies observed super-additive multisensory pupil responses, indicative of multisensory integration (MSI). Others observed additive multisensory pupil responses even though reaction time (RT) measures were indicative of MSI. Therefore, in the present study, we investigated the nature of the multisensory pupil response by combining methodological approaches of previous studies while using supra-threshold stimuli only. In two experiments we presented auditory and visual stimuli to observers that evoked a(n) (onset) response (be it constriction or dilation) in a simple detection task and a change detection task. In both experiments, the RT data indicated MSI as shown by race model inequality violation. Still, the multisensory pupil response in both experiments could best be explained by linear summation of the unisensory pupil responses. We conclude that the multisensory pupil response for supra-threshold stimuli is additive in nature and cannot be used as a measure of MSI, as only a departure from additivity can unequivocally demonstrate an interaction between the senses.
A novel retinal ganglion cell quantification tool based on deep learning
Authors: Masin Luca , Claes Marie , Bergmans Steven , Cools Lien , Andries Lien , Davis Benjamin M. , Moons Lieve , De Groef Lies
Published: January 2021

Glaucoma is a disease associated with the loss of retinal ganglion cells (RGCs), and remains one of the primary causes of blindness worldwide. Major research efforts are presently directed towards the understanding of disease pathogenesis and the development of new therapies, with the help of rodent models as an important preclinical research tool. The ultimate goal is reaching neuroprotection of the RGCs, which requires a tool to reliably quantify RGC survival. Hence, we demonstrate a novel deep learning pipeline that enables fully automated RGC quantification in the entire murine retina. This software, called RGCode (Retinal Ganglion Cell quantification based On DEep learning), provides a user-friendly interface that requires the input of RBPMS-immunostained flatmounts and returns the total RGC count, retinal area and density, together with output images showing the computed counts and isodensity maps. The counting model was trained on RBPMS-stained healthy and glaucomatous retinas, obtained from mice subjected to microbead-induced ocular hypertension and optic nerve crush injury paradigms. RGCode demonstrates excellent performance in RGC quantification as compared to manual counts. Furthermore, we convincingly show that RGCode has potential for wider application, by retraining the model with a minimal set of training data to count FluoroGold-traced RGCs.
Outcome of TACE treatment in HIV infected patients with hepatocellular carcinoma
Authors: Kong Lingxiang , Wei Guo , Lv Tao , Jiang Li , Yang Jian , Zhao Yong , Yang Jiayin
Published: January 2021

The surgical treatment and transcatheter arterial chemoembolization (TACE) rate of human immunodeficiency virus (HIV)-infected hepatocellular carcinoma (HCC) patients is relatively low in West China. For various reasons, most patients do not receive timely surgical treatment. Upon transfer to an infectious disease centralized hospital, they were already classified in the Barcelona Clinic Liver Cancer (BCLC)-B stage. A total of 2249 BCLC-B HCC patients were analyzed. The eligible population was divided into three groups for analysis of survival and prognostic factors; These were 21 HIV infected (HIV+) HCC patients treated with TACE (TACE+), 1293 non-HIV-infected (HIV−) HCC patients treated with TACE, and 150 HIV− HCC patients who only receive medication (TACE−) as a second control group. After 1:2 matching, 1- and 2-year survival of HIV+ TACE+ and HIV− TACE+ groups was 64.3% and 76.5% (P = 0.453) and 45.5% vs. 50.0% (P = 0.790) respectively. We also compared one and two-year survival between HIV+ TACE+ and HIV− TACE−. One-year overall survival was 64.3% vs. 45.7% (P = 0.097) and 2-year survival was 45.5% vs. 7.1% (P = 0.004). Multivariate analysis showed that the most important prognostic factors for survival were serum alpha-fetoprotein (AFP) and Child–Pugh score and tumor size, while HIV status had no significant effect on prognosis statistically. CD4 levels below 200 may increase the risk of opportunistic infection after surgery, but after anti-infection and systematic supportive therapy, it has no effect on survival. HIV+ patients should have the same treatment opportunities as HIV− patients. If the patient's immune status permits, we suggest that early TACE treatment should be administered to BCLC-B HCC patients, regardless of HIV infection.
Templating the morphology of soft microgel assemblies using a nanolithographic 3D-printed membrane
Authors: Linkhorst John , Lölsberg Jonas , Thill Sebastian , Lohaus Johannes , Lüken Arne , Naegele Gerhard , Wessling Matthias
Published: January 2021

Filter cake formation is the predominant phenomenon limiting the filtration performance of membrane separation processes. However, the filter cake’s behavior at the particle scale, which determines its overall cake behavior, has only recently come into the focus of scientists, leaving open questions about its formation and filtration behavior. The present study contributes to the fundamental understanding of soft filter cakes by analyzing the influence of the porous membrane’s morphology on crystal formation and the compaction behavior of soft filter cakes under filtration conditions. Microfluidic chips with nanolithographic imprinted filter templates were used to trigger the formation of crystalline colloidal filter cakes formed by soft microgels. The soft filter cakes were observed via confocal laser scanning microscopy (CLSM) under dead-end filtration conditions. Colloidal crystal formation in the cake, as well as their compaction behavior, were analyzed by optical visualization and pressure data. For the first time, we show that exposing the soft cake to a crystalline filter template promotes the formation of colloidal crystallites and that soft cakes experience gradient compression during filtration.
Chemical enhanced oil recovery and the dilemma of more and cleaner energy
Authors: Farajzadeh Rouhi , Kahrobaei Siavash , Eftekhari Ali Akbari , Mjeni Rifaat A. , Boersma Diederik , Bruining Johannes
Published: January 2021

A method based on the concept of exergy-return on exergy-investment is developed to determine the energy efficiency and CO2 intensity of polymer and surfactant enhanced oil recovery techniques. Exergy is the useful work obtained from a system at a given thermodynamics state. The main exergy investment in oil recovery by water injection is related to the circulation of water required to produce oil. At water cuts (water fraction in the total liquid produced) greater than 90%, more than 70% of the total invested energy is spent on injection and lift pumps, resulting in large CO2 intensity for the produced oil. It is shown that injection of polymer with or without surfactant can considerably reduce CO2 intensity of the mature waterflood projects by decreasing the volume of produced water and the exergy investment associated with its circulation. In the field examples considered in this paper, a barrel of oil produced by injection of polymer has 2–5 times less CO2 intensity compared to the baseline waterflood oil. Due to large manufacturing exergy of the synthetic polymers and surfactants, in some cases, the unit exergy investment for production of oil could be larger than that of the waterflooding. It is asserted that polymer injection into reservoirs with large water cut can be a solution for two major challenges of the energy transition period: (1) meet the global energy demand via an increase in oil recovery and (2) reduce the CO2 intensity of oil production (more and cleaner energy).
Alterations observed in the interferon α and β signaling pathway in MDD patients are marginally influenced by cis-acting alleles
Authors: Magri Chiara , Giacopuzzi Edoardo , Sacco Chiara , Bocchio-Chiavetto Luisella , Minelli Alessandra , Gennarelli Massimo
Published: January 2021

Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. Pieces of evidence indicate that inflammation and immune activation may contribute to the onset of MDD playing a role in the pathogenetic mechanism. To date, it is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Both components were tested for association with MDD. Many genes belonging to the α/β interferon signaling pathway showed an association between MDD and EReX, only two between MDD and GReX. Also other MDD differentially expressed genes were more influenced by the EReX than by GReX. These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway.
Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis
Authors: Dodge James C. , Yu Jinlong , Sardi S. Pablo , Shihabuddin Lamya S.
Published: January 2021

Aberrant cholesterol homeostasis is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease that is due to motor neuron (MN) death. Cellular toxicity from excess cholesterol is averted when it is enzymatically oxidized to oxysterols and bile acids (BAs) to promote its removal. In contrast, the auto oxidation of excess cholesterol is often detrimental to cellular survival. Although oxidized metabolites of cholesterol are altered in the blood and CSF of ALS patients, it is unknown if increased cholesterol oxidation occurs in the SC during ALS, and if exposure to oxidized cholesterol metabolites affects human MN viability. Here, we show that in the SOD1G93A mouse model of ALS that several oxysterols, BAs and auto oxidized sterols are increased in the lumbar SC, plasma, and feces during disease. Similar changes in cholesterol oxidation were found in the cervical SC of sporadic ALS patients. Notably, auto-oxidized sterols, but not oxysterols and BAs, were toxic to iPSC derived human MNs. Thus, increased cholesterol oxidation is a manifestation of ALS and non-regulated sterol oxidation likely contributes to MN death. Developing therapeutic approaches to restore cholesterol homeostasis in the SC may lead to a treatment for ALS.
Association of nocebo hyperalgesia and basic somatosensory characteristics in a large cohort
Authors: Feldhaus Mari Hanna , Horing Björn , Sprenger Christian , Büchel Christian
Published: January 2021

Medical outcomes are strongly affected by placebo and nocebo effects. Prediction of who responds to such expectation effects has proven to be challenging. Most recent approaches to prediction have focused on placebo effects in the context of previous treatment experiences and expectancies, or personality traits. However, a recent model has suggested that basic somatosensory characteristics play an important role in expectation responses. Consequently, this study investigated not only the role of psychological variables, but also of basic somatosensory characteristics. In this study, 624 participants underwent a placebo and nocebo heat pain paradigm. Additionally, individual psychological and somatosensory characteristics were assessed. While no associations were identified for placebo responses, nocebo responses were associated with personality traits (e.g. neuroticism) and somatosensory characteristics (e.g. thermal pain threshold). Importantly, the associations between somatosensory characteristics and nocebo responses were among the strongest. This study shows that apart from personality traits, basic somatosensory characteristics play an important role in individual nocebo responses, in agreement with the novel idea that nocebo responses result from the integration of top-down expectation and bottom-up sensory information.
Spatiotemporal dynamic characteristics of typical temperate glaciers in China
Authors: Shijin Wang , Yanjun Che , Yanqiang Wei
Published: January 2021

China’s temperate glaciers have a relatively warm and humid climate and hydrothermal conditions at low latitudes. Temperate glaciers, however, have larger ablation, higher ice temperatures, relatively fast movement speeds, and a significant sliding process at the bottom. As a result, these glaciers are more significantly affected by climate change. On the basis of topographic maps, aerial photography, and Landsat OLI images, and combined with existing research results, this paper systematically analyzed the temporal and spatial dynamic characteristics of typical temperate glaciers. The results are as follows: (1) From the 1950s to the 1970s, compared with other types of glaciers, temperate glaciers showed strong retreat and ablation trends in terms of area, length, speed, and mass balance. (2) The reduction rates of glacier areas of Kangri Garpo, Dagu Snow Mountain, Yulong Snow Mountain (YSM), and Meili Snow Mountain (MSM) in China’s temperate glacier areas all exceeded 38%, which was far above the national average of 18% from the 1950s to the 2010s. (3) The recent length retreat rates of Azha Glacier, Kangri Garpo, and Mingyong Glacier, MSM, Hailuogou Glacier (HG), Gongga Snow Mountain (GSM), and Baishui River Glacier No. 1 (BRGN1), YSM were above 22 m/a, which was faster than the retreat rates of other regions. (4) Consistent with glacier retreat, temperate glaciers also had a faster ice flow speed. The ice flow velocities of the BGN1, HG, Parlung River Glaciers No. 4 and 94, and Nyainqêntanglha were, respectively, 6.33–30.78 m/a, 41–205 m/a, 15.1–86.3 m/a, and 7.5–18.4 m/a, which was much faster than the velocity of other types of glaciers. (5) Mass loss of temperate glaciers was most dramatic during the observation period (1959–2015). The annual mass balance from eight typical temperate glaciers fluctuated between − 2.48 and 0.44 m w.e., and the annual average change rate of mass balance (− 0.037 m w.e./a) was much higher than that in China (− 0.015 m w.e./a, p < 0.0001) and globally (− 0.013 m w.e./a, p < 0.0001).
Near-term climate change impacts on sub-national malaria transmission
Authors: Lubinda Jailos , Haque Ubydul , Bi Yaxin , Hamainza Busiku , Moore Adrian J.
Published: January 2021

The role of climate change on global malaria is often highlighted in World Health Organisation reports. We modelled a Zambian socio-environmental dataset from 2000 to 2016, against malaria trends and investigated the relationship of near-term environmental change with malaria incidence using Bayesian spatio-temporal, and negative binomial mixed regression models. We introduced the diurnal temperature range (DTR) as an alternative environmental measure to the widely used mean temperature. We found substantial sub-national near-term variations and significant associations with malaria incidence-trends. Significant spatio-temporal shifts in DTR/environmental predictors influenced malaria incidence-rates, even in areas with declining trends. We highlight the impact of seasonally sensitive DTR, especially in the first two quarters of the year and demonstrate how substantial investment in intervention programmes is negatively impacted by near-term climate change, most notably since 2010. We argue for targeted seasonally-sensitive malaria chemoprevention programmes.
Probiotic lactobacilli as a promising strategy to ameliorate disorders associated with intestinal inflammation induced by a non-steroidal anti-inflammatory drug
Authors: Monteros María José Martínez , Galdeano Carolina Maldonado , Balcells María Florencia , Weill Ricardo , De Paula Juan Andrés , Perdigón Gabriela , Cazorla Silvia Inés
Published: January 2021

Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. Hence, we investigated whether probiotics can control the onset of this severe condition in a murine model of intestinal inflammation induced by the NSAID, indomethacin. Probiotic supplementation to mice reduce the body weight loss, anemia, shortening of the small intestine, cell infiltration into the intestinal tissue and the loss of Paneth and Goblet cells associated with intestinal inflammation. Furthermore, a high antimicrobial activity in the intestinal fluids of mice fed with probiotics compared to animals on a conventional diet was elicited against several pathogens. Interestingly, probiotics dampened the oxidative stress and several local and systemic markers of an inflammatory process, as well as increased the secretion of IL-10 by regulatory T cells. Even more importantly, probiotics induced important changes in the large intestine microbiota characterized by an increase in anaerobes and lactobacilli, and a significant decrease in total enterobacteria. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis.