bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission
Authors: He Qixin , Pilosof Shai , Tiedje Kathryn E. , Day Karen P. , Pascual Mercedes
Published: May 2021

In high-transmission endemic regions, local populations of Plasmodium falciparum exhibit vast diversity of the var genes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial antigenic diversity is common to other hyperdiverse pathogens. It underlies a series of fundamental epidemiological characteristics, including large reservoirs of transmission from high prevalence of asymptomatics and long-lasting infections. Previous theory has shown that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity of var gene repertoires, or strains, in a pattern of limiting similarity that is both non-random and non-neutral. A combination of stochastic agent-based models and network analyses has enabled the development and testing of theory in these complex adaptive systems, where assembly of local parasite diversity occurs under frequency-dependent selection and large pools of variation. We show here the application of these approaches to theory comparing the response of the malaria transmission system to intervention when strain diversity is assembled under (competition-based) selection vs. a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections. The transmission system is considerably more persistent under NFDS, exhibiting a lower extinction probability despite comparable prevalence during intervention. We explain this pattern on the basis of the structure of strain diversity, in particular the more pronounced fraction of highly dissimilar parasites. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreased var gene diversity reduces parasite transmission. A Principal Component Analysis of network features describing parasite similarity reveals that despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence. Given the described enhanced persistence under perturbation, intervention efforts will likely require longer times than the usual practice to eliminate P. falciparum populations. We discuss implications of our findings and potential analogies for ecological communities with non-neutral assembly processes involving frequency-dependence.
Chemical Similarity of Co-occurring Trees Decreases With Precipitation and Temperature in North American Forests
Authors: Sedio Brian E. , Spasojevic Marko J. , Myers Jonathan A. , Wright S. Joseph , Person Maria D. , Chandrasekaran Hamssika , Dwenger Jack H. , Prechi María Laura , López Christian A. , Allen David N. , Anderson-Teixeira Kristina J. , Baltzer Jennifer L. , Bourg Norman A. , Castillo Buck T. , Day Nicola J. , Dewald-Wang Emily , Dick Christopher W. , James Timothy Y. , Kueneman Jordan G. , LaManna Joseph , Lutz James A. , McGregor Ian R. , McMahon Sean M. , Parker Geoffrey G. , Parker John D. , Vandermeer John H.
Published: May 2021

Plant diversity varies immensely over large-scale gradients in temperature, precipitation, and seasonality at global and regional scales. This relationship may be driven in part by climatic variation in the relative importance of abiotic and biotic interactions to the diversity and composition of plant communities. In particular, biotic interactions may become stronger and more host specific with increasing precipitation and temperature, resulting in greater plant species richness in wetter and warmer environments. This hypothesis predicts that the many defensive compounds found in plants’ metabolomes should increase in richness and decrease in interspecific similarity with precipitation, temperature, and plant diversity. To test this prediction, we compared patterns of chemical and morphological trait diversity of 140 woody plant species among seven temperate forests in North America representing 16.2°C variation in mean annual temperature (MAT), 2,115 mm variation in mean annual precipitation (MAP), and from 10 to 68 co-occurring species. We used untargeted metabolomics methods based on data generated with liquid chromatography-tandem mass spectrometry to identify, classify, and compare 13,480 unique foliar metabolites and to quantify the metabolomic similarity of species in each community with respect to the whole metabolome and each of five broad classes of metabolites. In addition, we compiled morphological trait data from existing databases and field surveys for three commonly measured traits (specific leaf area [SLA], wood density, and seed mass) for comparison with foliar metabolomes. We found that chemical defense strategies and growth and allocation strategies reflected by these traits largely represented orthogonal axes of variation. In addition, functional dispersion of SLA increased with MAP, whereas functional richness of wood density and seed mass increased with MAT. In contrast, chemical similarity of co-occurring species decreased with both MAT and MAP, and metabolite richness increased with MAT. Variation in metabolite richness among communities was positively correlated with species richness, but variation in mean chemical similarity was not. Our results are consistent with the hypothesis that plant metabolomes play a more important role in community assembly in wetter and warmer climates, even at temperate latitudes, and suggest that metabolomic traits can provide unique insight to studies of trait-based community assembly.
The Plot Thickens: Haploid and Triploid-Like Thalli, Hybridization, and Biased Mating Type Ratios in Letharia
Authors: Ament-Velásquez Sandra Lorena , Tuovinen Veera , Bergström Linnea , Spribille Toby , Vanderpool Dan , Nascimbene Juri , Yamamoto Yoshikazu , Thor Göran , Johannesson Hanna
Published: May 2021

The study of the reproductive biology of lichen fungal symbionts has been traditionally challenging due to their complex lifestyles. Against the common belief of haploidy, a recent genomic study found a triploid-like signal in Letharia. Here, we infer the genome organization and reproduction in Letharia by analyzing genomic data from a pure culture and from thalli, and performing a PCR survey of the MAT locus in natural populations. We found that the read count variation in the four Letharia specimens, including the pure culture derived from a single sexual spore of L. lupina, is consistent with haploidy. By contrast, the L. lupina read counts from a thallus' metagenome are triploid-like. Characterization of the mating-type locus revealed a conserved heterothallic configuration across the genus, along with auxiliary genes that we identified. We found that the mating-type distributions are balanced in North America for L. vulpina and L. lupina, suggesting widespread sexual reproduction, but highly skewed in Europe for L. vulpina, consistent with predominant asexuality. Taken together, we propose that Letharia fungi are heterothallic and typically haploid, and provide evidence that triploid-like individuals are hybrids between L. lupina and an unknown Letharia lineage, reconciling classic systematic and genetic studies with recent genomic observations.
The Dissensus Protocol: Governing Differences in Online Peer Communities
Authors: Brekke Jaya Klara , Beecroft Kate , Pick Francesca
Published: May 2021

Peer-to-peer networks and protocols have inspired new ideas and ideologies about governance, with the aim of using technology to enable horizontal and decentralized decision-making at scale. This article introduces the concept of “dissensus” from political theory to debates about peer governance in online communities. Dissensus describes the emergence of incompatible differences. Among peer-to-peer technologies, blockchain stands out as a set of ideas that explicitly seek to resolve dissensus through consensus protocols. In this article, we propose dissensus as a “protocol” for foregrounding the often sidelined yet productive aspects of incompatible differences. The concept highlights that there might not always be consensus about a consensus algorithm, and that indeed, dissensus is the precondition for new possibilities and perspectives to emerge. We discuss the concept in relation to the histories of governance ideas in blockchain, namely, a “materialist,” “design,” and “emergent” approach. We then describe moments of dissensus in practice through two cases of online communities, Genesis DAO and Ouishare, discussing their different ways of recognizing and navigating dissensus. Finally, we give a critical overview of consensus algorithms, voting, staking, and forking as the mechanisms that make out blockchain governance ideologies. In conclusion, we argue that dissensus can serve as a useful concept for pointing attention to governance as it is conducted in practice, as historically and culturally specific practices, rather than as a problem to be solved through supposedly universal mechanisms.
Reconciling Behavioural, Bioenergetic, and Oceanographic Views of Bowhead Whale Predation on Overwintering Copepods at an Arctic Hotspot (Disko Bay, Greenland)
Authors: Banas Neil S. , Møller Eva Friis , Laidre Kristin L. , Simon Malene , Ellingsen Ingrid H. , Nielsen Torkel Gissel
Published: May 2021

Bowhead whales (Balaena mysticetus) visit Disko Bay, West Greenland in winter and early spring to feed onCalanusspp., at a time of year when the copepods are still mostly in diapause and concentrated in near-bottom patches. Combining past observations of copepod abundance and distribution with detailed observations of bowhead whale foraging behaviour from telemetry suggests that if the whales target the highest-density patches, they likely consume 26–75% of theCalanusstanding stock annually. A parallel bioenergetic calculation further suggests that the whales' patch selection must be close to optimally efficient at finding hotspots of high density copepods near the sea floor in order for foraging in Disko Bay to be a net energetic gain. AnnualCalanusconsumption by bowhead whales is similar to median estimates of consumption by each of three zooplankton taxa (jellies, chaetognaths, and predatory copepods), and much greater than the median estimate of consumption by fish larvae, as derived from seasonal abundance and specific ingestion rates from the literature. The copepods' self-concentration during diapause, far from providing a refuge from predation, is the behaviour that makes this strong trophic link possible. Because the grazing impact of the whales comes 6–10 months later than the annual peak in primary production, and because Disko Bay sits at the end of rapid advective pathways (here delineated by a simple numerical particle-tracking experiment), it is likely that theseCalanuspopulations act in part as a long-distance energetic bridge between the whales and primary production hundreds or thousands of km away.
A Review on Coastal Urban Ecology: Research Gaps, Challenges, and Needs
Authors: Graells Giorgia , Nakamura Nao , Celis-Diez Juan L. , Lagos Nelson A. , Marquet Pablo A. , Pliscoff Patricio , Gelcich Stefan
Published: May 2021

Coastal urban areas have dramatically increased during the last decades, however, coastal research integrating the impacts and challenges facing urban areas is still scarce. To examine research advances and critical gaps, a review of the literature on coastal urban ecology was performed. Articles were selected following a structured decision tree and data were classified into study disciplines, approaches, type of analysis, main research objectives, and Pickett's paradigms in-, of-, and for- the city, among other categories. From a total of 237 publications, results show that most of the research comes from the USA, China, and Australia, and has been carried out mostly in large cities with populations between 1 and 5 million people. Focus has been placed on ecological studies, spatial and quantitative analysis and pollution in coastal urban areas. Most of the studies on urban ecology in coastal zones were developed at nearshore terrestrial environments and only 22.36% included the marine ecosystem. Urban ecological studies in coastal areas have mainly been carried out under the paradigm in the city with a focus on the disciplines of biology and ecology. Results suggest a series of disciplinary, geographical, and approach biases which can present a number of risks. Foremost among these is a lack of knowledge on social dimensions which can impact on sustainability. A key risk relates to the fact that lessons and recommendations of research are mainly from developed countries and large cities which might have different institutional, planning and cultural settings compared to developing and mid-income countries. Scientific research on coastal urban areas needs to diversify toward an ecology of and for the cities, in order to support coastal development in a diversity of countries and settings.
Influence of Spawning Ground Dynamics on the Long-Term Abundance of Japanese Flying Squid (Todarodes pacificus) Winter Cohort
Authors: Liu Yang , Xia Xinmei , Tian Yongjun , Alabia Irene D. , Ma Shuyang , Sun Peng , Saitoh Sei-Ichi
Published: May 2021

Japanese flying squid (Todarodes pacificus) is one of the most commercially important resources in the Pacific Ocean and its abundance is largely affected by environmental conditions. We examined the influence of environmental factors in potential spawning grounds of the winter cohort, approximated from Japanese and South Korean catch and catch per unit effort (CPUE) data of Japanese flying squid. Annual spawning ground dynamics were constructed using sea surface temperature (SST), submarine elevation and mean Kuroshio axis data from 1979 to 2018. Based on these information, we generated a suite of spawning ground indices including suitability SST-weighted area of potential spawning ground (SSWA), mean values (January–April) of suitable SST (MVSS), and the meridional position (MP) of SST isolines (18–24°C). Comparable interannual-decadal variability patterns were detected between the squid abundance and spawning ground indices, with abrupt shifts around 1990/1991 and in recent decades. In particular, the Pacific Decadal Oscillation is negatively correlated with spawning ground indices, suggesting its role in regulating the environmental dynamics in the area. Further, the gradient forest model underpinned the importance of SSWA, SSWA_Lag1 and MVSS_Lag1 on squid abundance. The CPUE is also shown to be a better abundance index than the annual catch in modeling the species’ response to environmental variability in its spawning grounds. Our findings suggest that it is imperative to pay more and timely attention to the relationship between the abundance of Japanese flying squid and environmental changes, especially under adverse environmental conditions.
Development of a New Silica Aerogel-Polypropylene Foam Composite as a Highly Flexible Thermal Insulation Material
Authors: Yoda Satoshi , Takeshita Satoru , Ono Takumi , Tada Ryosuke , Ota Hideo
Published: May 2021

A new flexible thermal insulation sheet, a composite of silica aerogel with polypropylene (PP) foam, has been developed. Even though a large volume ratio of silica aerogel (97%) was included, the composite showed high flexibility. Thermal conductivity of the composite was 0.016 W/(m⋅K) at 298 K, which is as low as silica aerogel monolith. Silica aerogel flaking, which has been a problem in practical applications, is very low in this composite due to skin layers of the polymer-foam composite. A supercritical drying process for rolled sheets of the material for large-scale production is also described. Simulations of extraction of 2-propanol from a silica alcogel revealed that rolled composite sheets with small spaces between the sheet composite are able to dry in a reasonable extraction time. These findings led to effective on production of this material on a pilot industrial scale.
Interleukin-10 Attenuates Liver Fibrosis Exacerbated by Thermoneutrality
Authors: Nga Ha Thi , Moon Ji Sun , Tian Jingwen , Lee Ho Yeop , Kim Seok-Hwan , Lee Young-Sun , Jeon Jae-Han , Yi Hyon-Seung
Published: May 2021

Background: Crosstalk between brown adipose tissue (BAT) and the liver is receiving increasing attention. This study investigated the effect of BAT dysfunction by thermoneutral (TN) housing on liver fibrosis in mice and examined the effect of secreted factors from brown adipocytes on the activation of hepatic stellate cells (HSCs).

Methods: The carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was used to evaluate fibrotic changes in the livers of mice housed under standard and TN conditions. The effect of BAT on the activation of HSCs was examined using cultured cells treated with conditioned media from brown adipocytes.

Results: Under TN conditions, mice with CCl4-induced liver fibrosis exhibited increased liver injury, collagen deposition, and alpha smooth muscle actin (α-SMA) expression in the liver compared with mice maintained at room temperature. The numbers of liver-infiltrating immune cells and T cells producing IL-17A and IFN-γ were also significantly increased in the livers of mice housed under TN conditions. Treatment of HSCs with conditioned media from brown adipocytes markedly attenuated HSC activation, as shown by down-regulated α-SMA expression at day 4, day 7 and day 10 of culture. At thermoneutrality, with CCl4 administration, IL-10-deficient mice exhibited more severe liver fibrosis than wild-type mice. Interestingly, conditioned media from IL-10-deficient brown adipocytes could up-regulate the expression of α-SMA and induce HSCs activation.

Conclusions: BAT inactivation by thermoneutrality contributes to the activation of pro-inflammatory and pro-fibrotic pathways in mice with CCl4-induced liver fibrosis. Normal brown adipocytes secreted factors that impair the activation of HSCs, while this protective effect was lost in IL-10-deficient brown adipocytes. Thus, the BAT–liver axis may serve as a potential therapeutic target for liver fibrosis, and IL-10 may be a key factor regulating the activation of HSCs by BAT.
Genetic Differentiation and Mixed Reproductive Strategies in the Northern Corn Leaf Blight Pathogen Setosphaeria turcica From Sweet Corn in Fujian Province, China
Authors: Dai Yuli , Gan Lin , Lan Chengzhong , Lu Xuesong , Yang Xiujuan , Gao Zhimou
Published: May 2021

The northern corn leaf blight (NCLB) pathogen Setosphaeria turcica (Luttrell) Leonard and Suggs is one of the main biotic constraints on sweet corn (Zea mays L.) yield and quality in Fujian Province, China. Currently, however, there is comparatively little information available regarding the distribution of mating types, population genetics, and reproductive strategies of this pathogen in Fujian. In this study, we investigated the distribution of mating types and population genetics of 117 isolates of S. turcica collected from seven of the main sweet corn-growing regions in Fujian Province, based on multiple polymerase chain reaction analyses using two mating type-specific primer pairs and 11 inter-simple sequence repeat markers. Furthermore, we examined the mode of reproduction of Fujian S. turcica populations. Both MAT1-1 and MAT1-2 mating types were detected throughout all seven sampling locations. The majority of MAT1-2 isolates were detected from Dongyou, Jian’ou, Pingnan, Songxi, and Longyan, whereas a large proportion of the detected MAT1-1 isolates were among those collected from Dongfeng and Nanjing. Furthermore, we detected five shared multi-locus haplotypes among S. turcica isolates from Dongyou, Jian’ou, Pingnan, Nanjing, and Songxi, whereas no shared haplotypes were observed between the Dongfeng (or Longyan) population and these five populations. Pairwise comparisons of the indices ΦPT and Nm, and population structure and principal coordinate analyses indicated genetic differentiation between both the regional and the mating type populations of S. turcica in Fujian. The skewed mating type ratio associated with low a haplotypic diversity and evident linkage disequilibrium reveals a mixed reproductive strategy for S. turcica populations in Fujian Province. The findings of this study advance our current understanding of the genetic diversity, population structure, and reproductive strategies of S. turcica populations infecting sweet corn in Fujian Province, and will potentially contribute to further resistance breeding efforts.
Pulse Frequency in Crop Rotations Alters Soil Microbial Community Networks and the Relative Abundance of Fungal Plant Pathogens
Authors: Yang Tony , Evans Bianca , Bainard Luke D.
Published: May 2021

Including pulse crops in cereal-based cropping systems has become a widely accepted and useful agronomic practice to increase crop diversification and biologically fixed nitrogen in agroecosystems. However, there is a lack of knowledge regarding how the intensification of pulses in crop rotations influence soil microbial communities. In this study, we used an amplicon sequencing approach to examine the bulk and rhizosphere soil bacterial and fungal communities from the wheat (Triticum aestivum L.) phase (final year of 4 years rotations) of a long-term pulse intensification field trial in the semi-arid region of the Canadian Prairies. Our results revealed pulse frequency had a minimal impact on microbial α-diversity, but caused a significant shift in the composition of the fungal (rhizosphere and bulk soil) and bacterial (bulk soil) communities. This effect was the most pronounced in the Ascomycete and Bacteroidete communities. Increasing pulse frequency also promoted a higher proportion of fungal pathotrophs in the bulk soil, particularly those putatively identified as plant pathogens. The network analysis revealed that rotations with higher pulse frequency promoted increased competition within the soil microbial networks in the rhizosphere and bulk soil. However, we also detected more negative interactions among the dominant pathotrophic taxa with increased pulse frequency, suggesting higher soil-borne disease potential. These findings highlight the potential drawbacks and reduced sustainability of increasing pulse frequency in crop rotations in semiarid environments.
Artificial Intelligence Can Effectively Predict Early Hematoma Expansion of Intracerebral Hemorrhage Analyzing Noncontrast Computed Tomography Image
Authors: Teng Linyang , Ren Qianwei , Zhang Pingye , Wu Zhenzhou , Guo Wei , Ren Tianhua
Published: May 2021

This study aims to develop and validate an artificial intelligence model based on deep learning to predict early hematoma enlargement (HE) in patients with intracerebral hemorrhage. A total of 1,899 noncontrast computed tomography (NCCT) images of cerebral hemorrhage patients were retrospectively analyzed to establish a predicting model and 1,117 to validate the model. And a total of 118 patients with intracerebral hemorrhage were selected based on inclusion and exclusion criteria so as to validate the value of the model for clinical prediction. The baseline noncontrast computed tomography images within 6 h of intracerebral hemorrhage onset and the second noncontrast computed tomography performed at 24 ± 3 h from the onset were used to evaluate the prediction of intracerebral hemorrhage growth. In validation dataset 1, the AUC was 0.778 (95% CI, 0.768–0.786), the sensitivity was 0.818 (95% CI, 0.790–0.843), and the specificity was 0.601 (95% CI, 0.565–0.632). In validation dataset 2, the AUC was 0.780 (95% CI, 0.761–0.798), the sensitivity was 0.732 (95% CI, 0.682–0.788), and the specificity was 0.709 (95% CI, 0.658–0.759). The sensitivity of intracerebral hemorrhage hematoma expansion as predicted by an artificial intelligence imaging system was 89.3%, with a specificity of 77.8%, a positive predictive value of 55.6%, a negative predictive value of 95.9%, and a Yoden index of 0.671, which were much higher than those based on the manually labeled noncontrast computed tomography signs. Compared with the existing prediction methods through computed tomographic angiography (CTA) image features and noncontrast computed tomography image features analysis, the artificial intelligence model has higher specificity and sensitivity in the prediction of early hematoma enlargement in patients with intracerebral hemorrhage.
Decreased Resting-State Functional Connectivity of Periaqueductal Gray in Temporal Lobe Epilepsy Comorbid With Migraine
Authors: Wang Long , Cai Xin-Ting , Zu Mei-Dan , Zhang Juan , Deng Zi-Ru , Wang Yu
Published: May 2021

Objective: Patients with temporal lobe epilepsy (TLE) are at high risk for having a comorbid condition of migraine, and these two common diseases are proposed to have some shared pathophysiological mechanisms. Our recent study indicated the dysfunction of periaqueductal gray (PAG), a key pain-modulating structure, contributes to the development of pain hypersensitivity and epileptogenesis in epilepsy. This study is to investigate the functional connectivity of PAG network in epilepsy comorbid with migraine.

Methods: Thirty-two patients with TLE, including 16 epilepsy patients without migraine (EwoM) and 16 epilepsy patients with comorbid migraine (EwM), and 14 matched healthy controls (HCs) were recruited and underwent resting functional magnetic resonance imaging (fMRI) scans to measure the resting-state functional connectivity (RsFC) of PAG network. The frequency and severity of migraine attacks were assessed using the Migraine Disability Assessment Questionnaire (MIDAS) and Visual Analog Scale/Score (VAS). In animal experiments, FluoroGold (FG), a retrograde tracing agent, was injected into PPN and its fluorescence detected in vlPAG to trace the neuronal projection from vlPAG to PPN. FG traced neuron number was used to evaluate the neural transmission activity of vlPAG-PPN pathway. The data were processed and analyzed using DPARSF and SPSS17.0 software. Based on the RsFC finding, the excitatory transmission of PAG and the associated brain structure was studied via retrograde tracing in combination with immunohistochemical labeling of excitatory neurons.

Results: Compared to HCs group, the RsFC between PAG and the left pedunculopontine nucleus (PPN), between PAG and the corpus callosum (CC), was decreased both in EwoM and EwM group, while the RsFC between PAG and the right PPN was increased only in EwoM group but not in EwM group. Compared to EwoM group, the RsFC between PAG and the right PPN was decreased in EwM group. Furthermore, the RsFC between PAG and PPN was negatively correlated with the frequency and severity of migraine attacks. In animal study, a seizure stimulation induced excitatory transmission from PAG to PPN was decreased in rats with chronic epilepsy as compared to that in normal control rats.

Conclusion: The comorbidity of epilepsy and migraine is associated with the decreased RsFC between PAG and PPN.
The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?
Authors: MacMahon Copas Adina N. , McComish Sarah F. , Fletcher Jean M. , Caldwell Maeve A.
Published: May 2021

Parkinson's disease (PD), the second most common neurodegenerative disease, is characterised by the motor symptoms of bradykinesia, rigidity and resting tremor and non-motor symptoms of sleep disturbances, constipation, and depression. Pathological hallmarks include neuroinflammation, degeneration of dopaminergic neurons in the substantia nigra pars compacta, and accumulation of misfolded α-synuclein proteins as intra-cytoplasmic Lewy bodies and neurites. Microglia and astrocytes are essential to maintaining homeostasis within the central nervous system (CNS), including providing protection through the process of gliosis. However, dysregulation of glial cells results in disruption of homeostasis leading to a chronic pro-inflammatory, deleterious environment, implicated in numerous CNS diseases. Recent evidence has demonstrated a role for peripheral immune cells, in particular T lymphocytes in the pathogenesis of PD. These cells infiltrate the CNS, and accumulate in the substantia nigra, where they secrete pro-inflammatory cytokines, stimulate surrounding immune cells, and induce dopaminergic neuronal cell death. Indeed, a greater understanding of the integrated network of communication that exists between glial cells and peripheral immune cells may increase our understanding of disease pathogenesis and hence provide novel therapeutic approaches.
High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling
Authors: Chakraborti Ayanabha , Graham Christopher , Chehade Sophie , Vashi Bijal , Umfress Alan , Kurup Pradeep , Vickers Benjamin , Chen H. Alexander , Telange Rahul , Berryhill Taylor , Van Der Pol William , Powell Mickie , Barnes Stephen , Morrow Casey , Smith Daniel L. , Mukhtar M. Shahid , Watts Stephen , Kennedy Gregory , Bibb James
Published: May 2021

The neurobiological mechanisms that mediate psychiatric comorbidities associated with metabolic disorders such as obesity, metabolic syndrome and diabetes remain obscure. High fructose corn syrup (HFCS) is widely used in beverages and is often included in food products with moderate or high fat content that have been linked to many serious health issues including diabetes and obesity. However, the impact of such foods on the brain has not been fully characterized. Here, we evaluated the effects of long-term consumption of a HFCS-Moderate Fat diet (HFCS-MFD) on behavior, neuronal signal transduction, gut microbiota, and serum metabolomic profile in mice to better understand how its consumption and resulting obesity and metabolic alterations relate to behavioral dysfunction. Mice fed HFCS-MFD for 16 weeks displayed enhanced anxiogenesis, increased behavioral despair, and impaired social interactions. Furthermore, the HFCS-MFD induced gut microbiota dysbiosis and lowered serum levels of serotonin and its tryptophan-based precursors. Importantly, the HFCS-MFD altered neuronal signaling in the ventral striatum including reduced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β), increased expression of ΔFosB, increased Cdk5-dependent phosphorylation of DARPP-32, and reduced PKA-dependent phosphorylation of the GluR1 subunit of the AMPA receptor. These findings suggest that HFCS-MFD-induced changes in the gut microbiota and neuroactive metabolites may contribute to maladaptive alterations in ventral striatal function that underlie neurobehavioral impairment. While future studies are essential to further evaluate the interplay between these factors in obesity and metabolic syndrome-associated behavioral comorbidities, these data underscore the important role of peripheral-CNS interactions in diet-induced behavioral and brain function. This study also highlights the clinical need to address neurobehavioral comorbidities associated with obesity and metabolic syndrome.
Liver Transplantation Versus Liver Resection for Stage I and II Hepatocellular Carcinoma: Results of an Instrumental Variable Analysis
Authors: Li Wei , Xiao Haitao , Wu Hong , Xu Xuewen , Zhang Yange
Published: May 2021

Background

This study aimed to compare the long-term outcomes of liver transplantation (LT) and liver resection (LR) among patients with stage I and II hepatocellular carcinoma (HCC).

Methods

SEER 18 registry from 2004 to 2015 was retrieved for this study. We included 1,765 and 1,746 cases with stage I–II (AJCC, 7th) HCC in the multivariable analyses and instrumental variable (IV) analyses, respectively. Propensity score matching (PSM) was further carried out to ensure comparability. Propensity score to receive LT was adjusted by stabilized inverse probability of treatment weighting (IPTW) and standardized mortality ratio weighting (SMRW) methods. In addition, IV analysis was performed to adjust both measured and unmeasured confounding factors.

Results

We identified 1,000 (56.7%) and 765 (43.3%) patients treated with LR and LT, respectively. In the multivariable adjusted cohort, after adjusting potential confounders, patients undergoing LT offered significant prognostic advantages over LR in overall survival (OS, P < 0.001) and disease-free survival (DSS, P < 0.001). The instrument variable in this study is LT rates in various Health Service Areas (HSAs). Results from the IV analysis showed that cases treated with LT had significantly longer OS (P = 0.001) and DSS (P < 0.001). In IV analysis stratified by clinicopathologic variables, the treatment effect of LT vs. LR in OS was consistent across all subgroups. Regarding DSS in IV analyses, the subgroup analyses observed that LT had better DSS across all subgroups, except for similar results in the older patients (interaction P value = 0.039) and the non-White patients (interaction P value = 0.041). In the propensity-matched cohort, patients with LT still had better OS (P < 0.001) and DSS (P < 0.001) in comparison to cases who underwent LR. In both IPTW and SMRW cohorts, patients who underwent LT had better OS (both P values < 0.001) and DSS (both P values < 0.001).

Conclusions

LT provided a survival benefit for cases with stage I–II HCC. These results indicated that if LT rate was to increase in the future, average long-term survival may also increase. However, for some special populations such as the elderly patients, owing to the similar outcomes between LT and LR, the selection of LT should be cautious.
Correlation Between Lung Density Changes Under Different Dose Gradients and Radiation Pneumonitis—Based on an Analysis of Computed Tomography Scans During Esophageal Cancer Radiotherapy
Authors: Du Feng , Liu Hong , Wang Wei , Zhang Yingjie , Li Jianbin
Published: May 2021

Purpose

To assess the relationship between different doses of radiation and lung density changes and to determine the ability of this correlation to identify esophageal cancer (EC) patients who develop radiation pneumonitis (RP) and the occurrence time of RP.

Methods

A planning computed tomography (CT) scan and a re-planning CT scan were retrospectively collected under institutional review board approval for each of 103 thoracic segment EC patients who underwent radiotherapy (RT). The isodose curve was established on the planning CT with an interval of 5 Gy, which was used as the standard for dividing different gradient doses. Planning CT and re-planning CT scans were matched and the mean lung CT value (HU) between different doses gradients was automatically obtained by the software system. The density change value (ΔHU) was the difference of CT value between each dose gradient before and after treatment. The correlation between ΔHU and the corresponding dose was calculated, as well as the regression coefficients. Additionally the correlation between ΔHU and the occurrence and time of RP (< 4 weeks, 4–12 weeks, > 12 weeks) was calculated.

Results

The radiation dose and ΔHU was positively correlated, but the correlation coefficient and regression coefficient were lower, 0.261 (P <0.001) and 0.127 (P <0.001), respectively. With the increase of radiation dose gradient, ΔHU in RP≥2 group was higher than that in RP<2 group, and there was significant difference between two groups in ΔHU20-25, ΔHU25-30, ΔHU30-35, ΔHU35-40, ΔHU40-45, ΔHU45-50 (p<0.05). The occurrence time of RP was negatively correlated with the degree of ΔHU (P<0.05), with a high correlation coefficient (Y = week actual value −0.521, P < 0.001) (Y = week grade value −0.381, P = 0.004) and regression coefficient (Y = week actual value −0.503, P<0.001) (Y = week rating value −0.401, P=0.002).

Conclusions

A relationship between radiation dose and lung density changes was observed. For most dose intervals, there was an increase of ΔHU with an increased radiation dose, although low correlation coefficient. ΔHU were obvious after irradiation with dose ≥20 Gy which was closely related to the occurrence of RP. For patients with RP, the more obvious ΔHU, the earlier the occurrence of RP, there was a significant negative correlation between them.
Case Report: Concurrent Occurrence of Abdominal Double Expressor Lymphoma and Jejunum Follicular Lymphoma
Authors: Takada Ryutaro , Watanabe Tomohiro , Sekai Ikue , Yoshikawa Keisuke , Hara Akane , Otsuka Yasuo , Yoshikawa Tomoe , Kamata Ken , Minaga Kosuke , Komeda Yoriaki , Chikugo Takaaki , Arai Yasuyuki , Yamashita Kohei , Kudo Masatoshi
Published: May 2021

Double expressor lymphoma (DEL), defined as overexpression of BCL2 and MYC, is an aggressive subtype of diffuse large B cell lymphoma (DLBCL). Here we report a case of a 64-year-old female diagnosed with abdominal DEL transformed from jejunum follicular lymphoma (FL). 18F-fluorodeoxyglucose (FDG)-positron emission tomography showed diffuse accumulation of FDG into the peritoneum and small bowel wall. Double balloon-assisted enteroscopy revealed whitish submucosal tumors in the proximal jejunum. Aggregation of atypical lymphocytes positive for CD20, CD79a, and BCL2 was seen in the jejunal biopsy samples. These atypical lymphocytes were monoclonal since cell surface expression of Ig light chains was limited to κ chain by flow-cytometry. Thus, immunohistochemical and flowcytometric analyses data were consistent with FL of the jejunum. Neoplastic lymphocytes obtained from ascites were positive for CD10, CD20, CD79a, BCL2, and BCL6. Fluorescence in situ hybridization (FISH) showed formation of BCL2/IgH fusion gene and extra copies of MYC, the former of which is a characteristic chromosomal abnormality of FL. These genetic alterations and protein expression profiles of ascitic fluid cells were consistent with those of DEL transformed from FL. Given that a significant population of patients with indolent FL of the gastrointestinal tract developed into aggressive DLBCL, it is likely that primary FL of the jejunum transformed into the abdominal aggressive DEL in this case. This case is unique in that concurrent occurrence of FL and DEL was confirmed by immunohistochemical and FISH analyses and that abdominal DEL transformed from jejunal FL was highly suspected.
Identification of an m6A-Related lncRNA Signature for Predicting the Prognosis in Patients With Kidney Renal Clear Cell Carcinoma
Authors: Yu JunJie , Mao WeiPu , Sun Si , Hu Qiang , Wang Can , Xu ZhiPeng , Liu RuiJi , Chen SaiSai , Xu Bin , Chen Ming
Published: May 2021

Purpose

This study aimed to construct an m6A-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data obtained from The Cancer Genome Atlas (TCGA) database.

Methods

The KIRC patient data were downloaded from TCGA database and m6A-related genes were obtained from published articles. Pearson correlation analysis was implemented to identify m6A-related lncRNAs. Univariate, Lasso, and multivariate Cox regression analyses were used to identifying prognostic risk-associated lncRNAs. Five lncRNAs were identified and used to construct a prognostic signature in training set. Kaplan–Meier curves and receiver operating characteristic (ROC) curves were applied to evaluate reliability and sensitivity of the signature in testing set and overall set, respectively. A prognostic nomogram was established to predict the probable 1-, 3-, and 5-year overall survival of KIRC patients quantitatively. GSEA was performed to explore the potential biological processes and cellular pathways. Besides, the lncRNA/miRNA/mRNA ceRNA network and PPI network were constructed based on weighted gene co-expression network analysis (WGCNA). Functional Enrichment Analysis was used to identify the biological functions of m6A-related lncRNAs.

Results

We constructed and verified an m6A-related lncRNAs prognostic signature of KIRC patients in TCGA database. We confirmed that the survival rates of KIRC patients with high-risk subgroup were significantly poorer than those with low-risk subgroup in the training set and testing set. ROC curves indicated that the prognostic signature had a reliable predictive capability in the training set (AUC = 0.802) and testing set (AUC = 0.725), respectively. Also, we established a prognostic nomogram with a high C-index and accomplished good prediction accuracy. The lncRNA/miRNA/mRNA ceRNA network and PPI network, as well as functional enrichment analysis provided us with new ways to search for potential biological functions.

Conclusions

We constructed an m6A-related lncRNAs prognostic signature which could accurately predict the prognosis of KIRC patients.
Arterial Infusion Chemotherapy for Neoplastic Esophagogastric Anastomotic Strictures After Esophagectomy
Authors: Xie Pengfei , Yin Meipan , He Wei , Ma Yaozhen , Li Chunxia , Li Zhen , Li Xiaobing , Wang Shuai , Wu Gang
Published: May 2021

Background

Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer is a very difficult problem in clinical practice. We aim at to investigate the safety and feasibility of arterial infusion chemotherapy in treatment of neoplastic esophagogastric anastomotic strictures after esophagectomy.

Methods

From October 2014 to December 2019, 50 patients with Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer were assessed retrospectively. Preoperative dysphagia was grade III in 34 cases and grade IV in 16 cases. Thirty-eight patients had different degrees of dyspnea before surgery Twenty-five patients had intolerable (grade IV) dyspnea and airway stenting was undertaken before surgery. Thirteen patients had tolerable dyspnea that did not require airway stenting, and preoperative dyspnea was grade III.

Results

All patients were successfully treated with arterial infusion chemotherapy, no paraplegia or death occurred. The dysphagia grade of 50 patients after AIC was compared: one case had grade I, 40 cases had grade II, and nine cases had grade III. Thirteen patients had tolerable dyspnea that did not necessitate airway stenting. Dyspnea was classified as grade I in five cases and grade II in eight cases. After 1–3 courses of AIC, 50 patients were followed up for a complete response (eight cases), partial response (28) and stable disease (14 cases). Total objective effective rate (complete response+ partial response) and disease control rate(complete response + partial response + stable disease)were 72.0% and 100.0%, respectively. The median duration of follow-up was 8.5 months. One-year survival was 46.0%.

Conclusion

Arterial infusion chemotherapy is safe and efficacious treatment for Neoplastic esophagogastric anastomotic strictures after esophagectomy.
Clinical Factors and Outcomes of Atypical Meningioma: A Population-Based Study
Authors: Zhang Gui-Jun , Liu Xiao-Yin , You Chao
Published: May 2021

Objective

Atypical meningioma is a non-benign tumor, and its prognostic factors and treatment strategies are unclear.

Methods

Patients with atypical meningioma, between 2004 and 2016, were collected from the Surveillance, Epidemiology, and End Results database. Then, we randomly divided patients into a training set and a validation set at a ratio of 8:2. The nomogram was constructed based on the multivariate Cox regression analyses. And the concordance index, calibration curves, and receiver operating character were used to assess the predictive ability of the nomogram. We divided the patient scores into three groups and constructed a survival curve using Kaplan–Meier analysis.

Results

After our inclusion and exclusion criteria, 2358 patients were histologically diagnosed of atypical meningioma. The prognostic nomogram comprised factors of overall survival, including age, tumor size and surgery. The concordance index was 0.715 (95%CI=0.688-0.742) for overall survival in the training set and 0.688 (95%CI=0.629-0.747) for overall survival in the validation set. The calibration curves and receiver operating character also indicated the good predictability of the nomogram. Risk stratification revealed a statistically significant difference among the three groups of patients according to quartiles of risk score.

Conclusion

Gross total resection is an independent factor for survival, and radiation after non-gross total resection potentially confers a survival advantage for patients with atypical meningioma.
Impact of Non-steroidal Anti-inflammatory Drug Administration for 12 Months on Renal Function
Authors: Hayashi Kazuhiro , Miki Kenji , Kajiyama Hiroshi , Ikemoto Tatsunori , Yukioka Masao
Published: May 2021

Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of renal complications. Resolution of renal adverse effects after NSAID administration has been observed after short-term use. Thus, the present study aimed to investigate a series of patients with chronic musculoskeletal pain who underwent long-term NSAID administration followed by switching to tramadol hydrochloride/acetaminophen (TA) combination tablets to study the impact of NSAID-induced renal adverse effects.

Methods: This was a longitudinal retrospective study of 99 patients with chronic musculoskeletal pain. The patients were administrated with NSAIDs daily during the first 12 months, followed by daily TA combination tablets for 12 months. Estimated glomerular filtration rate (eGFR) and serum levels of aspartate aminotransferase and alanine transaminase were measured at baseline, after NSAID administration and after TA administration.

Results: eGFR was significantly reduced after 12-month NSAID administration (median, from 84.0 to 72.8 ml/min/1.73 m2), and the reduction was not shown after the subsequent 12-month TA administration (median, 71.5 ml/min/1.73 m2). Reduction in eGFR was less in patients who received celecoxib (median, −1.8 ml/min/1.73 m2) during the first 12 months. There was no significant difference in aspartate aminotransferase and alanine transaminase in each period.

Conclusions: Thus, patients receiving NSAIDs for 12 months displayed both reversible and irreversible reduction of eGFR upon cessation of NSAIDs and switching to TA. Our data highlight the potential safety benefit of utilizing multimodal analgesic therapies to minimize the chronic administration of NSAIDs.
Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia
Authors: Hsiao Chien-Chou , Lee Cheng-Han , Yang Rei-Cheng , Chen Jia-Yuh , Su Tzu-Cheng , Chang Yu-Jun , Lin Ching-Yuang , Tsai Yi-Giien
Published: May 2021

Background: Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD).

Methods: This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay.

Results: Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 (r = 0.47) and Day 28 of life (r = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death.

Conclusions: Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.