bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Genomic Analysis and a Novel Set of Missense Mutation of the Leptospira weilii Serogroup Mini From the Urine of Asymptomatic Dogs in Thailand
Authors: Kurilung Alongkorn , Perreten Vincent , Prapasarakul Nuvee
Published: October 2021

Leptospira weilii belongs to the pathogenic Leptospira group and is a causal agent of human and animal leptospirosis in many world regions. L. weilii can produce varied clinical presentations from asymptomatic through acute to chronic infections and occupy several ecological niches. Nevertheless, the genomic feature and genetic basis behind the host adaptability of L. weilii remain elusive due to limited information. Therefore, this study aimed to examine the complete circular genomes of two new L. weilii serogroup Mini strains (CUDO6 and CUD13) recovered from the urine of asymptomatic dogs in Thailand and then compared with the 17 genomes available for L. weilii. Variant calling analysis (VCA) was also undertaken to gain potential insight into the missense mutations, focusing on the known pathogenesis-related genes. Whole genome sequences revealed that the CUDO6 and CUD13 strains each contained two chromosomes and one plasmid, with average genome size and G+C content of 4.37 Mbp and 40.7%, respectively. Both strains harbored almost all the confirmed pathogenesis-related genes in Leptospira. Two novel plasmid sequences, pDO6 and pD13, were identified in the strains CUDO6 and CUD13. Both plasmids contained genes responsible for stress response that may play important roles in bacterial adaptation during persistence in the kidneys. The core-single nucleotide polymorphisms phylogeny demonstrated that both strains had a close genetic relationship. Amongst the 19 L. weilii strains analyzed, the pan-genome analysis showed an open pan-genome structure, correlated with their high genetic diversity. VCA identified missense mutations in genes involved in endoflagella, lipopolysaccharide (LPS) structure, mammalian cell entry protein, and hemolytic activities, and may be associated with host-adaptation in the strains. Missense mutations of the endoflagella genes of CUDO6 and CUD13 were associated with loss of motility. These findings extend the knowledge about the pathogenic molecular mechanisms and genomic evolution of this important zoonotic pathogen.
Creation of a Novel Nomogram Based on the Direct Bilirubin-To-Indirect Bilirubin Ratio and Lactate Dehydrogenase Levels in Resectable Colorectal Cancer
Authors: Ma Yifei , Shi Lulu , Lu Ping , Yao Shuang , Xu Hongli , Hu Junjie , Liang Xin , Liang Xinjun , Wei Shaozhong
Published: October 2021

Background: Recently, many studies have suggested that bilirubin is associated with the prognosis of colorectal cancer (CRC). Conversely, there is substantial evidence that lactate dehydrogenase (LDH) levels are associated with the prognosis of cancer. Therefore, we sought to find a novel marker based on the above to predict prognosis in patients with resectable CRC.

Methods: A total of 702 patients from Hubei Cancer Hospital were included. The whole population was randomly divided into training (n = 491) and testing (n = 211) cohorts. Next, we established a new index based on direct bilirubin, indirect bilirubin and LDH levels. Chi-square tests, Kaplan-Meier survival analyses, and Cox regression analyses were used to evaluate prognosis. The prediction accuracies of models for overall survival (OS) and disease-free survival (DFS) were estimated through Harrell’s concordance index (C-index) and the Brier score.

Results: The median DFS duration was 32 months (range: 0–72.6 months), whereas the median OS duration was 35 months (range: 0 months–73.8 months). In addition, a new indicator, (DIR.LDH) (HR: 1.433; 95% CI, 1.069–1.920) could independently predict outcomes in CRC patients. Moreover, the module based on DIR. LDH was found to have exceptional performance for predicting OS and DFS. The C-index of the nomogram for OS was 0.802 (95% CI, 0.76–0.85) in the training cohort and 0.829 (95% CI, 0.77–0.89) in the testing cohort. The C-index of the nomogram for DFS was 0.774 (95% CI, 0.74–0.81) in the training cohort and 0.775 (95% CI, 0.71–0.84) in the testing cohort.

Conclusion: We successfully established a novel module to guide clinical decision-making for CRC.
Daidzein Alleviates Hypothalamic-Pituitary-Adrenal Axis Hyperactivity, Ameliorates Depression-Like Behavior, and Partly Rectifies Circulating Cytokine Imbalance in Two Rodent Models of Depression
Authors: Chen Long , Wang Xiaokun , Zhang Yunpeng , Zhong Hequan , Wang Cuiting , Gao Pengfei , Li Bing
Published: October 2021

Depression is one very common mental health disorder which can cause morbidity and mortality if not addressed. Recent studies have provided strong evidence that depression may be accompanied by immune activation, secondary inflammatory reaction, and hyperactivity of the Hypothalamic Pituitary Adrenal (HPA) axis. It is well-known that it takes at least 2 weeks for conventional antidepressants, especially SSRIs (Selective serotonin reuptake inhibitors) to produce effects. To better understand the mechanism of antidepressant effects on depression and subsequently further elucidate the pathogenesis of depression, we selected phytestrogen daidzein (DD) to observe its effects on the depression-like and anxiety-like behavior in two different rodent models of depression which were induced by learned helplessness and chronic mild stress (CMS) and then simultaneous evaluation of the depression-like behavior, the activity of HPA axis, and circulatory cytokines. Our results showed that daidzein attenuated depression-like behaviors through alleviating HPA axis hyperactivity, decreasing the levels of stress-related hormones, and partly rectifying some inflammatory cytokines imbalance in both the rodent models of depression.
Beyond Single Discrete Responses: An Integrative and Multidimensional Analysis of Behavioral Dynamics Assisted by Machine Learning
Authors: León Alejandro , Hernandez Varsovia , Lopez Juan , Guzman Isiris , Quintero Victor , Toledo Porfirio , Avendaño-Garrido Martha Lorena , Hernandez-Linares Carlos A. , Escamilla Esteban
Published: October 2021

Understanding behavioral systems as emergent systems comprising the environment and organism subsystems, include spatial dynamics as a primary dimension in natural settings. Nevertheless, under the standard approaches, the experimental analysis of behavior is based on the single response paradigm and the temporal distribution of discrete responses. Thus, the continuous analysis of spatial behavioral dynamics is a scarcely studied field. The technological advancements in computer vision have opened new methodological perspectives for the continuous sensing of spatial behavior. With the application of such advancements, recent studies suggest that there are multiple features embedded in the spatial dynamics of behavior, such as entropy, and that they are affected by programmed stimuli (e.g., schedules of reinforcement) at least as much as features related to discrete responses. Despite the progress, the characterization of behavioral systems is still segmented, and integrated data analysis and representations between discrete responses and continuous spatial behavior are exiguous in the experimental analysis of behavior. Machine learning advancements, such ast-distributed stochastic neighbor embeddingandvariable ranking, provide invaluable tools to crystallize an integrated approach for analyzing and representing multidimensional behavioral data. Under this rationale, the present work (1) proposes a multidisciplinary approach for the integrative and multilevel analysis of behavioral systems, (2) provides sensitive behavioral measures based on spatial dynamics and helpful data representations to study behavioral systems, and (3) reveals behavioral aspects usually ignored under the standard approaches in the experimental analysis of behavior. To exemplify and evaluate our approach, the spatial dynamics embedded in phenomena relevant to behavioral science, namely, water-seeking behavior and motivational operations, are examined, showing aspects of behavioral systems hidden until now.
A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies
Authors: Cahill Branden , Poelker-Wells Samuel , Prather Jonathan F. , Li Yun
Published: October 2021

Depression is an umbrella term used to describe a mood disorder with a broad spectrum of symptoms including a persistent feeling of sadness, loss of interest, and deficits in social behavior. Epigenetic research bridges the environmental and genetic landscape and has the potential to exponentially improve our understanding of such a complex disorder. Depression is also a sexually dimorphic disorder and variations exist within epigenetic modification sites between sexes. These sex-specific mediators may impact behavioral symptomology and could serve as therapeutic targets for treatments to improve behavioral deficits. This mini review will focus on the social behavior perspective of depression and specifically explore the sexually different epigenetic modifications on depression.
A Novel CNTNAP2 Mutation Results in Abnormal Neuronal E/I Balance
Authors: Lu Ping , Wang Fengpeng , Zhou Shuixiu , Huang Xiaohua , Sun Hao , Zhang Yun-Wu , Yao Yi , Zheng Honghua
Published: October 2021

CNTNAP2 (coding for protein Caspr2), a member of the neurexin family, plays an important role in the balance of excitatory and inhibitory post-synaptic currents (E/I balance). Here, we describe a novel pathogenic missense mutation in an infant with spontaneous recurrent seizures (SRSs) and intellectual disability. Genetic testing revealed a missense mutation, c.2329 C>G (p. R777G), in the CNTNAP2 gene. To explore the effect of this novel mutation, primary cultured neurons were transfected with wild type homo CNTNAP2 or R777G mutation and the morphology and function of neurons were evaluated. When compared with the vehicle control group or wild type group, the neurites and the membrane currents, including spontaneous excitatory post-synaptic currents (sEPSCs) and inhibitory post-synaptic currents (sIPSCs), in CNTNAP2 R777G mutation group were all decreased or weakened. Moreover, the action potentials (APs) were also impaired in CNTNAP2 R777G group. Therefore, CNTNAP2 R777G may lead to the imbalance of excitatory and inhibitory post-synaptic currents in neural network contributing to SRSs.
The Influence of Transcranial Magnetoacoustic Stimulation Parameters on the Basal Ganglia-Thalamus Neural Network in Parkinson’s Disease
Authors: Zhang Yanqiu , Zhang Mohan , Ling Zichao , Wang Peiguo , Jian Xiqi
Published: October 2021

Objective: Parkinson’s disease (PD) is a degenerative disease of the nervous system that frequently occurs in the aged. Transcranial magnetoacoustic stimulation (TMAS) is a neuronal adjustment method that combines sound fields and magnetic fields. It has the characteristics of high spatial resolution and noninvasive deep brain focusing.

Methods: This paper constructed a simulation model of TMAS based on volunteer’s skull computer tomography, phased controlled transducer and permanent magnet. It simulates a transcranial focused sound pressure field with the Westervelt equation and builds a basal ganglia and thalamus neural network model in the PD state based on the Hodgkin-Huxley model.

Results: A biased sinusoidal pulsed ultrasonic TMAS induced current with 0.3 T static magnetic field induction and 0.2 W⋅cm–2 sound intensity can effectively modulate PD states with RI ≥ 0.633. The magnitude of magnetic induction strength was changed to 0.2 and 0.4 T. The induced current was the same when the sound intensity was 0.4 and 0.1 W⋅cm–2. And the sound pressure level is in the range of −1 dB (the induced current difference is less than or equal to 0.019 μA⋅cm–2). TMAS with a duty cycle of approximately 50% can effectively modulates the error firings in the PD neural network with a relay reliability not less than 0.633.

Conclusion: TMAS can modulates the state of PD.
Sex Differences in Odor Hedonic Perception: An Overview
Authors: Bontempi Charlotte , Jacquot Laurence , Brand Gérard
Published: October 2021

Odor hedonic evaluation (pleasant/unpleasant) is considered as the first and one of the most prominent dimension in odor perception. While sex differences in human olfaction have been extensively explored, gender effect in hedonic perception appears to be less considered. However, a number of studies have included comparisons between men and women, using different types of measurements (psychophysical, psychophysiological,…). This overview presents experimental works with non-specific and body odors separately presented as well as experimental studies comparing healthy participants vs patients with psychiatric disorders. Contrary to sensitivity, identification or discrimination, the overall literature tends to prove that no so clear differences occur in odor hedonic judgment between men and women. On the whole, gender effect appears more marked for body than non-specific odors and is almost never reported in psychiatric diseases. These findings are discussed in relation to the processes classically implied in pleasantness rating and emotional processes.
Comparisons and Impacts of the Basic Components of Sarcopenia Definition and Their Pairwise Combinations in Gastric Cancer: A Large-Scale Study in a Chinese Population
Authors: Zhang Feng-Min , Zhang Xian-Zhong , Shi Han-Ping , Zhang Zhao , Wang Su-Lin , Shen Zi-Le , Chen Xiao-Lei , Shen Xian , Yu Zhen , Zhuang Cheng-Le
Published: October 2021

Background and Aims: Sarcopenia is negatively associated with clinical outcomes. However, the definitions of sarcopenia are inconsistent across international consensuses. Thus, the purpose of this study is to compare the impact of the basic definition components of sarcopenia and their combinations in post-operative complications and overall survival, aiming to find the best sarcopenia definition to stratify the prognosis in an Asian population.

Methods: A total of 1,307 patients who underwent curative surgery for gastric cancer from July 2014 to May 2019 were prospectively included. The basic sarcopenia components were measured pre-operatively, including low skeletal muscle mass index (LSMI), low skeletal muscle radiodensity (LSMD), low handgrip strength (LHGS), and low gait speed (LGS). Among them, LSMI and LSMD were measured using a CT post-processing software, LHGS was measured using an electronic hand dynamometer, and LGS was represented by a 6-m walk speed.

Results: For the single basic component, the muscle function parameters (LHGS or LGS) but not the muscle composition parameters (LSMI or LSMD) showed associations with post-operative complications and mortality. For the combination of the basic combinations, all statistically significant combinations included at least one muscle function parameter. The combination of muscle composition (LSMI or LSMD) and muscle function (LHGS or LGS) had a significantly higher area under the curve in the prediction of post-operative complications compared with the combinations of two muscle function parameters (LSMI plus LSMD) or two muscle composition parameters (LHGS plus LGS).

Conclusions: Compared with muscle composition parameters (LSMI and LSMD), muscle function parameters (LHGS and LGS) are better predictors of post-operative complications and overall survival, which should be considered as the principal determinant in the sarcopenia definition. The definition of sarcopenia consists of muscle function (LHGS or LGS) and muscle composition (LSMI or LSMD) separately, which is better than the combination of the two muscle function parameters (LHGS plus LGS) or two muscle composition parameters (LSMI plus LSMD).
Camrelizumab Plus Sorafenib Versus Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Analysis
Authors: Liu Qinqin , You Nan , Li Jing , Wu Ke , Peng Xuehui , Wang Zheng , Wang Liang , Zhu Yinan , Zheng Lu
Published: October 2021

Background

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Immunotherapy has gained great interest for various solid tumors due to its promising clinical efficacy. Targeted therapy also plays a crucial role in anticancer treatment. However, studies on the combination of immunotherapy and targeted therapy for advanced HCC are limited. Thus, the objective of this study was to investigate the efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced HCC.

Methods

From January 2019 to January 2021, 100 consecutive patients with advanced HCC in our hospital were enrolled for this study. Patients were assigned into two groups: a combined-therapy group (camrelizumab + sorafenib) and a sorafenib-only group. Progression-free survival (PFS), overall survival (OS), treatment response, and relevant adverse effects (AEs) were evaluated and recorded.

Results

Of a total of 100 patients, 35 received a combination of camrelizumab and sorafenib, and 65 were treated with sorafenib alone. After 1:1 propensity score matching (PSM), each group had 34 patients. The overall response rate (ORR) of the combined-therapy group was statistically significantly higher than that of the sorafenib-only group (before PSM, p = 0.037; after PSM, p = 0.010). However, there was no significant difference in disease control rate (DCR) between the two groups (before PSM, p = 0.695; after PSM, p = 1.000). Patients who received the combination therapy had significantly longer PFS than those who received the sorafenib monotherapy (before PSM, p = 0.041; after PSM, p = 0.043). However, the two groups exhibited comparable median OS (before PSM, p = 0.135; after PSM, p = 0.105). Although the combined-therapy group showed a higher incidence of AEs such as thrombocytopenia than the sorafenib-only group after PSM, most of these AEs were easily controlled after treatment.

Conclusion

Camrelizumab plus sorafenib showed favorable efficacy and manageable toxicity for patients with advanced HCC. However, more prospective randomized trials are necessary to further verify the potential clinical benefits of this combination therapy.
The Impact of Diabetes on the Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Systematic Review and Meta-Analysis
Authors: Gao Xiaoshuai , Zhou Liang , Ai Jianzhong , Wang Wei , Di Xingpeng , Peng Liao , Liao Banghua , Jin Xi , Li Hong , Wang Kunjie
Published: October 2021

Background

Studies have reported that diabetes is related to the prognosis of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU), but this conclusion is still controversial. Here, we performed a meta-analysis to comprehensively explore the association between diabetes and UTUC prognosis.

Methods

In November 2020, we searched PubMed, Web of science and the Cochrane Library to find relevant studies that evaluated the effect of diabetes on the prognosis of UTUC. The Newcastle Ottawa Scale was used to assess the quality of the literature. Review Manager 5.3 was used to pool cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and intravesical recurrence (IVR).

Results

A total of 10 studies with 11,303 patients were included in this meta-analysis. Our pooled results showed that diabetes did not affect the survival outcome of UTUC, including CSS (HR: 1.33, 95% CI: 0.89-1.98; P = 0.16), OS (HR: 1.18, 95% CI: 0.77-1.80; P = 0.45) and RFS (HR: 1.37, 95% CI: 0.91-2.05; P = 0.13). However, diabetes increased the risk of IVR of UTUC patients (HR: 1.26, 95% CI: 1.11-1.43; P = 0.0004).

Conclusion

Although diabetes has no significant impact on the survival outcomes of UTUC after RNU, it increases the risk of IVR. Therefore, special attention should be paid to monitoring the IVR for UTUC patients with diabetes and the necessity of appropriate intravesical adjuvant treatment when needed.
Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy
Authors: Elbanna May , Chowdhury Nayela N. , Rhome Ryan , Fishel Melissa L.
Published: October 2021

In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have the potential to dramatically enhance the radiation therapeutic ratio. The increased ability to molecularly profile tumors both at diagnosis and at relapse and the co-incident progress in the field of radiogenomics could potentially pave the way for a more personalized approach to radiation treatment in contrast to the current ‘‘one size fits all’’ paradigm. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiation therapy, however, most have failed to show benefit, which is arguably due to limited preclinical data. Several key molecular pathways could theoretically enhance therapeutic effect of radiation when rationally targeted either by directly enhancing tumor cell kill or indirectly through the abscopal effect of radiation when combined with novel immunotherapies. The timing of combining molecular targeted therapy with radiation is also important to determine and could greatly affect the outcome depending on which pathway is being inhibited.
Metabolomics and Transcriptomics Analysis on Metabolic Characteristics of Oral Lichen Planus
Authors: Xin Ming-zhe , Shi Ying-ying , Li Chun-shen , Zuo Li-hua , Li Na , Liu Li-wei , Ma He-xin , Du Qiu-zheng , Xue Peng , Sun Zhi , Zhao Hong-yu
Published: October 2021

Objective

To explore metabolic biomarkers related to erosive and reticulated oral lichen planus (OLP) by non-targeted metabolomics methods and correlate metabolites with gene expression, and to investigate the pathological network pathways of OLP from the perspective of metabolism.

Methods

A total of 153 individuals were enrolled in this study, including 50 patients with erosive oral lichen planus (EOLP), 51 patients with reticulated oral lichen planus (ROLP), and 52 healthy controls (HC). The ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to analyze the metabolites of 40 EOLP, 40 ROLP, and 40 HC samples, and the differential metabolic biomarkers were screened and identified. The regulatory genes were further screened through the shared metabolites between EOLP and ROLP, and cross-correlated with the OLP-related differential genes in the network database. A “gene-metabolite” network was constructed after finding the key differential genes. Finally, the diagnostic efficiency of the biomarkers was verified in the validation set and a diagnostic model was constructed.

Result

Compared with HC group, a total of 19 and 25 differential metabolites were identified in the EOLP group and the ROLP group, respectively. A total of 14 different metabolites were identified between EOLP and ROLP. Two diagnostic models were constructed based on these differential metabolites. There are 14 differential metabolites shared by EOLP and ROLP. The transcriptomics data showed 756 differentially expressed genes, and the final crossover network showed that 19 differential genes were associated with 12 metabolites. Enrichment analysis showed that alanine, aspartate and glutamate metabolism were closely associated with the pathogenesis of OLP.

Conclusion

The metabolic change of different types of OLP were clarified. The potential gene perturbation of OLP was provided. This study provided a strong support for further exploration of the pathogenic mechanism of OLP.
Genomics of Obsessive-Compulsive Disorder—Toward Personalized Medicine in the Era of Big Data
Authors: Szejko Natalia , Dunalska Anna , Lombroso Adam , McGuire Joseph F. , Piacentini John
Published: October 2021

Pathogenesis of obsessive-compulsive disorder (OCD) mainly involves dysregulation of serotonergic neurotransmission, but a number of other factors are involved. Genetic underprints of OCD fall under the category of “common disease common variant hypothesis,” that suggests that if a disease that is heritable is common in the population (a prevalence >1–5%), then the genetic contributors—specific variations in the genetic code—will also be common in the population. Therefore, the genetic contribution in OCD is believed to come from multiple genes simultaneously and it is considered a polygenic disorder. Genomics offers a number of advanced tools to determine causal relationship between the exposure and the outcome of interest. Particularly, methods such as polygenic risk score (PRS) or Mendelian Randomization (MR) enable investigation of new pathways involved in OCD pathogenesis. This premise is also facilitated by the existence of publicly available databases that include vast study samples. Examples include population-based studies such as UK Biobank, China Kadoorie Biobank, Qatar Biobank,All of USProgram sponsored by National Institute of Health or Generations launched by Yale University, as well as disease-specific databases, that include patients with OCD and co-existing pathologies, with the following examples: Psychiatric Genomics Consortium (PGC), ENIGMA OCD, The International OCD Foundation Genetics Collaborative (IOCDF-GC) or OCD Collaborative Genetic Association Study. The aim of this review is to present a comprehensive overview of the available Big Data resources for the study of OCD pathogenesis in the context of genomics and demonstrate that OCD should be considered a disorder which requires the approaches offered by personalized medicine.
Magnetic Field Intensity Modification to Force Free Model of Magnetic Clouds: Website of Wind Examples From Launch to July of 2015
Authors: Wu Chin-Chun , Lepping R. P. , Berdichevsky D. B.
Published: October 2021

We describe a new NASA website that shows normalized magnetic field (B) magnitude profiles withinWindmagnetic clouds (MCs) (i.e., observationsversusbasic modelversusmodified model) for 209 MCs observed from launch in late 1994 to July of 2015, where model modification is based on the studies of Lepping et al. (Solar Phys, 2017, 292:27) and Lepping et al. (Solar Phys, 2018, 293:162); the basic force free magnetic cloud parameter fitting model employing Bessel functions (Lepping et al., J. Geophys. Res., 1990, 95:11957) is called the LJB model here. The fundamental principles should be applicable to theB-data from any spacecraft at 1 AU. Earlier (in the LJB study), we justified why the field magnitude can be thought of as decoupled from the field direction within an MC, and further, we justified this idea in terms of actual observations seen over a few decades with examples of MCs fromWinddata. The model modification is achieved by adding a correction (“Quad”) value to the LJB model (Bessel function) value in the following manner:B(est)/B0≈ [LJB Model + Quad (CA,u)], whereB0is the LJB-estimated field magnitude value on the MC’s axis,CAis the relative closest approach (SeeSupplementary Appendix A), anduis the distance that the spacecraft travels through the MC from its entrance point. In an average sense, the Quad technique is shown to be successful for 82% of the past modeled MCs, when Quality (Q0) is good or excellent (seeSupplementary Appendix A). The Quad technique is successful for 78% of MCs when all cases are considered. SoQ0of the MC LJB-fit is not a big factor when the success of the Quad scheme is considered. In addition, it is found that the Quad technique does not work better for MC events with higher solar wind speed. Yearly occurrence frequency of all MC events (NYearly) and those MC events with ΔσN/σN2≥ 0.5 (NΔσN/σN2≥0.5) are well correlated, but there is no solar cycle dependence for normalizing NΔσN/σN2≥0.5with NYearly.
Resilience of Nematode Connectomes Based on Network Dimension-reduced Method
Authors: Dongli Duan , Xixi Wu , Shubin Si
Published: October 2021

The whole map of nematode connectomes provides important structural data for exploring the behavioral mechanism of nematodes, but to further reveal the functional importance and resilience pattern of nematode neurons, it is necessary to effectively couple the regulatory relationship between neurons and their topology. Here, with a typical signal excitation function we propose a model to capture the interacting relationship between the neurons, because a differential equation depicts the activity of a neuron, n neurons mean we need high-D differential equations to capture the neural network. With mean-field theory, we decouple this N-dimension question into a one-dimension problem mathematically. In our framework, we emphatically analyze the characteristics, similarities and differences of the structure and dynamical behaviors of the neuronal system for Caenorhabditis elegans and Pristionchus pacificus. The comparing results of simulating method and theoretical approach show that the most important homologous neurons between C.elegans and P.pacificus are I2 and NSM, which may lead to their different behavior characteristics of predation and prey. At the same time, we expect that the xeff index can be used to reveal the importance of neurons for the functional evolution and degeneration of neural networks from a dynamic perspective. In the hermaphroditic and male C.elegans, we test the control level of the intermediate neuron groups over the output neuron groups and the single neuron. These results suggest that our theoretical approach can be used to reveal the effects of bio-connectivity groups, potentially enabling us to explore the interaction relationship of neural networks in humans and animals.
Bidirectional Mechanical Response Between Cells and Their Microenvironment
Authors: Mierke Claudia Tanja
Published: October 2021

Cell migration and invasion play a role in many physiological and pathological processes and are therefore subject of intensive research efforts. Despite of the intensively investigated biochemical processes associated with the migration and invasion of cells, such as cancer cells, the contribution of mechanobiological processes to the migratory capacity of cells as well as the role of physical polymeric phase transitions is not yet clearly understood. Unfortunately, these experiments are not very informative because they completely disregard the influence of the three-dimensional cell environment. Despite this data situation, it was possible to adequately demonstrate that there exists a direct mechanical interplay between cells and their microenvironment in both directions, where both elements can be mechanically altered by one another. In line with these results, it has turned out that the mechanobiological molecular processes through which cells interact with each other and additionally sense their nearby microenvironment have an impact on cellular functions such as cellular motility. The mechanotransduction processes have become the major focus of biophysical research and thereby, diverse biophysical approaches have been developed and improved to analyze the mechanical properties of individual cells and extracellular matrix environments. Both, the cell mechanics and matrix environment mechanics regulate the cell migration types in confined microenvironments and hence it seems to be suitable to identify and subsequently present a common bidirectional interplay between cells and their matrix environment. Moreover, hallmarks of the mechanophenotype of invasive cells and extracellular matrices can be defined. This review will point out how on the one hand the intracellular cytoskeletal architecture and on the other hand the matrix architecture contribute to cellular stiffness or contractility and thereby determines the migratory phenotype and subsequently the emergence of a distinct migration mode. Finally, in this review it is discussed whether universal hallmarks of the migratory phenotype can be defined.
Enhanced Store-Operated Ca2+ Signal of Small Intestinal Smooth Muscle Cells Accelerates Small Bowel Transit Speed in Type 1 Diabetic Mouse
Authors: Dai Fang , Guo Jizheng , Wang Yang , Jiang Tian , Chen Hongbo , Hu Ying , Du Juan , Xia Xianming , Zhang Qiu , Shen Bing
Published: October 2021

Aims: The underlying mechanism of diabetic enteropathy, a common complication of type 1 diabetes, remains unclear. Store-operated Ca2+ entry (SOCE) is a ubiquitous type of Ca2+ influx involved in various cellular functions. Here, we show that SOCE-related stromal interaction molecule 1 (STIM1) and Orai1 participate in inappropriate cellular Ca2+ homeostasis, augmenting agonist-induced small intestinal smooth muscle contraction and small bowel transit speed in a mouse model of type 1 diabetes.

Methods and Results: We used small interfering (si)RNA to suppress STIM1 and Orai1 proteins, and employed intracellular Ca2+, small intestinal contraction and intestinal transit speed measurement to investigate the functional change. We found that SOCE activity and Orai1 and STIM1 expression levels of small intestinal smooth muscle were significantly increased in cells cultured in high glucose medium or in diabetic mice. Gastrointestinal transit speed and SOCE-mediated contractions were markedly increased in diabetic mice; Knocking down Orai1 or STIM1 with siRNA rescued both alterations in diabetic mice. However, the Orai1-large conductance Ca2+-activated K+ (BKCa) channel interaction was decreased in diabetic mice, and suppressing Orai1 expression or inhibiting the BKCa channel increased agonist-induced small intestinal contractions in normal mice.

Conclusion: We concluded that the increased SOCE caused by excessive STIM1 and Orai1 expression and decreased Orai1-BKCa interaction augmented small intestinal smooth muscle contraction and accelerated small bowel transit speed in diabetic mice. This finding demonstrates a pathological role for SOCE in diabetic enteropathy and provides a potential therapeutic target for diabetic enteropathy.
Extrapolation of Ventricular Activation Times From Sparse Electroanatomical Data Using Graph Convolutional Neural Networks
Authors: Meister Felix , Passerini Tiziano , Audigier Chloé , Lluch Èric , Mihalef Viorel , Ashikaga Hiroshi , Maier Andreas , Halperin Henry , Mansi Tommaso
Published: October 2021

Electroanatomic mapping is the gold standard for the assessment of ventricular tachycardia. Acquiring high resolution electroanatomic maps is technically challenging and may require interpolation methods to obtain dense measurements. These methods, however, cannot recover activation times in the entire biventricular domain. This work investigates the use of graph convolutional neural networks to estimate biventricular activation times from sparse measurements. Our method is trained on more than 15,000 synthetic examples of realistic ventricular depolarization patterns generated by a computational electrophysiology model. Using geometries sampled from a statistical shape model of biventricular anatomy, diverse wave dynamics are induced by randomly sampling scar and border zone distributions, locations of initial activation, and tissue conduction velocities. Once trained, the method accurately reconstructs biventricular activation times in left-out synthetic simulations with a mean absolute error of 3.9 ms ± 4.2 ms at a sampling density of one measurement sample per cm2. The total activation time is matched with a mean error of 1.4 ms ± 1.4 ms. A significant decrease in errors is observed in all heart zones with an increased number of samples. Without re-training, the network is further evaluated on two datasets: (1) an in-house dataset comprising four ischemic porcine hearts with dense endocardial activation maps; (2) the CRT-EPIGGY19 challenge data comprising endo- and epicardial measurements of 5 infarcted and 6 non-infarcted swines. In both setups the neural network recovers biventricular activation times with a mean absolute error of less than 10 ms even when providing only a subset of endocardial measurements as input. Furthermore, we present a simple approach to suggest new measurement locations in real-time based on the estimated uncertainty of the graph network predictions. The model-guided selection of measurement locations allows to reduce by 40% the number of measurements required in a random sampling strategy, while achieving the same prediction error. In all the tested scenarios, the proposed approach estimates biventricular activation times with comparable or better performance than a personalized computational model and significant runtime advantages.
Biogeography of Argylia D. Don (Bignoniaceae): Diversification, Andean Uplift and Niche Conservatism
Authors: Glade-Vargas Nataly S. , Rojas Carla , Jara-Arancio Paola , Vidal Paula , Arroyo Mary T. Kalin , Hinojosa Luis Felipe
Published: October 2021

Andean uplift and the concomitant formation of the Diagonal Arid of South America is expected to have promoted species diversification through range expansions into this novel environment. We evaluate the evolution of Argylia, a genus belonging to the Bignoniaceae family whose oldest fossil record dates back to 49.4 Ma. Today, Argylia is distributed along the Andean Cordillera, from 15°S to 38.5°S and from sea level up to 4,000 m.a.s.l. We ask whether Argylia’s current distribution is a result of a range expansion along the Andes Cordillera (biological corridor) modulated by climatic niche conservatism, considering the timing of Andean uplift (30 Ma – 5 Ma). To answer this question, we reconstructed the phylogenetic relationships of Argylia species, estimated divergence times, estimated the realized climatic niche of the genus, reconstructed the ancestral climatic niche, evaluated its evolution, and finally, performed an ancestral range reconstruction. We found strong evidence for climatic niche conservatism for moisture variables, and an absence of niche conservatism for most of the temperature variables considered. Exceptions were temperature seasonality and winter temperature. Results imply that Argylia had the capacity to adapt to extreme temperature conditions associated with the Andean uplift and the new climatic corridor produced by uplift. Ancestral range reconstruction for the genus showed that Argylia first diversified in a region where subtropical conditions were already established, and that later episodes of diversification were coeval with the of Andean uplift. We detected a second climatic corridor along the coastal range of Chile-Peru, the coastal lomas, which allowed a northward range expansion of Argylia into the hyperarid Atacama Desert. Dating suggests the current distribution and diversity of Argylia would have been reached during the Late Neogene and Pleistocene.
Factor Structure, Validity, and Reliability of the STarT Back Screening Tool in Italian Obese and Non-obese Patients With Low Back Pain
Authors: Giusti Emanuele Maria , Varallo Giorgia , Abenavoli Alessandra , Manzoni Gian Mauro , Aletti Luca , Capodaglio Paolo , Castelnuovo Gianluca , Maggiani Alberto
Published: October 2021

Background: The STarT Back Screening Tool (SBST) is a self-report questionnaire developed for prognostic purposes which evaluates risk factors for disability outcomes in patients with chronic low back pain. Previous studies found that its use enables to provide a cost-effective stratified care. However, its dimensionality has been assessed only using exploratory approaches, and reports on its psychometric properties are conflicting.

Objective: The objective of this study was to assess the factorial structure and the psychometric properties of the Italian version of the STarT Back Screening Tool (SBST).

Materials and Methods: Patients with medical diagnosis of low back pain were enrolled from a rehabilitation unit of a tertiary care hospital specialized in obesity care (Sample 1) and from a clinical internship center of an osteopathic training institute (Sample 2). At baseline and after 7 days patients were asked to fill a battery of self-report questionnaires. The factorial structure, internal consistency, test-retest reliability, and construct validity of the SBST were assessed.

Results: One hundred forty-six patients were enrolled (62 from Sample 1 and 84 from Sample 2). The confirmatory factor analysis showed that the fit of the original two-correlated factors model was adequate (CFI = 0.98, TLI = 0.99, RMSEA = 0.03). Cronbach's α of the total scale (α = 0.64) and of the subscales (physical subscale α = 0.55; psychological subscale α = 0.61) was below the cutoffs, partly because of the low correlation of item 2 with the other items. Test-retest reliability was adequate (ICC = 0.84). The SBST had moderate correlations with comparisons questionnaires, except for the Roland-Morris Disability Questionnaire, which had a high correlation (r = 0.65).

Discussion: The SBST has adequate psychometric properties and can be used to assess prognostic factors for disability in low back pain patients.
Investigating Care Dependency and Its Relation to Outcome (ICARE): Results From a Naturalistic Study of an Intensive Day Treatment Program for Depression
Authors: Glanert Sarah , Sürig Svenja , Grave Ulrike , Fassbinder Eva , Schwab Sebastian , Borgwardt Stefan , Klein Jan Philipp
Published: October 2021

Background: This study explores the association of experienced dependency in psychotherapy as measured with the CDQ (Care Dependency Questionnaire) and treatment outcome in depression. Furthermore, the course of care dependency and differences in the CDQ scores depending on the received type of treatment, MCT (metacognitive therapy), or CBASP (cognitive behavioral analysis system of psychotherapy), were investigated.

Methods: The study follows a prospective, parallel group observational design. Patients suffering from depression received an 8-week intensive day clinic program, which was either CBASP or MCT. The treatment decision was made by clinicians based on the presented symptomatology and with regard to the patients' preferences. The patients reported depressive symptoms with the QIDS-SR16 (Quick Inventory of Depressive Symptomatology) and levels of experienced care dependency with the German version of the CDQ on a weekly basis. Mixed-model analyses were run to account for the repeated-measures design.

Results: One hundred patients were included in the analyses. Results indicate that higher levels of care dependency might predict a less favorable outcome of depressive symptomatology. Levels of care dependency as well as depressive symptoms decreased significantly over the course of treatment. There was no significant between-group difference in care dependency between the two treatment groups.

Conclusion: The results suggest that care dependency might be associated with a worse treatment outcome in depressed patients. In general, care dependency seems to be a dynamic construct, as it is changing over time, while the levels of care dependency seem to be independent from the received type of treatment. Future research should continue investigating the mechanisms of care dependency in a randomized controlled design.

Clinical Trial Registration:https://www.drks.de/drks_web/, identifier: DRKS00023779.
Study Protocol for “Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study”
Authors: Spriggs Meg J. , Douglass Hannah M. , Park Rebecca J. , Read Tim , Danby Jennifer L. , de Magalhães Frederico J. C. , Alderton Kirsty L. , Williams Tim M. , Blemings Allan , Lafrance Adele , Nicholls Dasha E. , Erritzoe David , Nutt David J. , Carhart-Harris Robin L.
Published: October 2021

Background:Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin.

Methods:(1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of “recovery”from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21–65 years old, body mass index (BMI) 15 kg/m2or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity.

Discussion:The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition.

Clinical Trial Registration:identifier: NCT04505189.
Identification of Neuromuscular Performance Parameters as Risk Factors of Non-contact Injuries in Male Elite Youth Soccer Players: A Preliminary Study on 62 Players With 25 Non-contact Injuries
Authors: Kolodziej Mathias , Nolte Kevin , Schmidt Marcus , Alt Tobias , Jaitner Thomas
Published: October 2021

Introduction: Elite youth soccer players suffer increasing numbers of injuries owing to constantly increasing physical demands. Deficits in neuromuscular performance may increase the risk of injury. Injury risk factors need to be identified and practical cut-off scores defined. Therefore, the purpose of the study was to assess neuromuscular performance parameters within a laboratory-based injury risk screening, to investigate their association with the risk of non-contact lower extremity injuries in elite youth soccer players, and to provide practice-relevant cut-off scores.

Methods: Sixty-two elite youth soccer players (age: 17.2 ± 1.1 years) performed unilateral postural control exercises in different conditions, isokinetic tests of concentric and eccentric knee extension and knee flexion (60°/s), isometric tests of hip adduction and abduction, and isometric tests of trunk flexion, extension, lateral flexion and transversal rotation during the preseason period. Non-contact lower extremities injuries were documented throughout 10 months. Risk profiling was assessed using a multivariate approach utilizing a Decision Tree model [Classification and Regression Tree (CART) method].

Results: Twenty-five non-contact injuries were registered. The Decision Tree model selected the COP sway, the peak torque for knee flexion concentric, the functional knee ratio and the path of the platform in that hierarchical order as important neuromuscular performance parameters to discriminate between injured and non-injured players. The classification showed a sensitivity of 0.73 and a specificity of 0.91. The relative risk was calculated at 4.2, meaning that the risk of suffering an injury is four times greater for a player, who has been classified as injured by the Decision Tree model.

Conclusion: Measuring static postural control, postural control under unstable condition and the strength of the thigh seem to enable a good indication of injury risk in elite youth soccer players. However, this finding has to be taken with caution due to a small number of injury cases. Nonetheless, these preliminary results may have practical implications for future directions in injury risk screening and in planning and developing customized training programs to counteract intrinsic injury risk factors in elite youth soccer players.