bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-Scale Landslide Susceptibility Mapping Using an Integrated Machine Learning Model: A Case Study in the Lvliang Mountains of China
Authors: Xing Yin , Yue Jianping , Guo Zizheng , Chen Yang , Hu Jia , Travé Anna
Published: August 2021

Integration of different models may improve the performance of landslide susceptibility assessment, but few studies have tested it. The present study aims at exploring the way to integrating different models and comparing the results among integrated and individual models. Our objective is to answer this question: Will the integrated model have higher accuracy compared with individual model? The Lvliang mountains area, a landslide-prone area in China, was taken as the study area, and ten factors were considered in the influencing factors system. Three basic machine learning models (the back propagation (BP), support vector machine (SVM), and random forest (RF) models) were integrated by an objective function where the weight coefficients among different models were computed by the gray wolf optimization (GWO) algorithm. 80 and 20% of the landslide data were randomly selected as the training and testing samples, respectively, and different landslide susceptibility maps were generated based on the GIS platform. The results illustrated that the accuracy expressed by the area under the receiver operating characteristic curve (AUC) of the BP-SVM-RF integrated model was the highest (0.7898), which was better than that of the BP (0.6929), SVM (0.6582), RF (0.7258), BP-SVM (0.7360), BP-RF (0.7569), and SVM-RF models (0.7298). The experimental results authenticated the effectiveness of the BP-SVM-RF method, which can be a reliable model for the regional landslide susceptibility assessment of the study area. Moreover, the proposed procedure can be a good option to integrate different models to seek an “optimal” result.
Hollow Mesoporous Silica by Ion Exchange-Induced Etching Strategy for High Temperature Proton Exchange Membrane
Authors: Zhang Aijing , Jiang Shengjuan , Shan Xuefei , Wang Jia , Zhou Mingzheng , Chai Maorong
Published: August 2021

Hollow mesoporous silica (HMS) has attracted significant attention for fuel cell applications. The mesopores in the shell can accelerate proton transport and the void in the center of the particle is advantageous for proton storage. However, the conventional methods for HMS fabrication are complicated, which is not conducive to scaling up the fabrication of HMS. In this work, a new, simple strategy to synthesize HMS has been developed via OH− ion exchange-induced etching of mesoporous silica (mSiO2). The mSiO2 immersed in an alkaline Na2CO3 solution led to an exchange of the Br− ions in the surfactant with the OH− ions in the solution, resulting in a high concentration of OH− ions in the mesoporous channels of mSiO2 close to the core, and a low concentration of OH− ions close to the surface. This demonstrated that the etching of the core of mSiO2 was induced, which extended from the core to the surface of the nanoparticles. Furthermore, the success of the ion exchange-induced etching process was demonstrated by the gradient distribution of the Na+ ion in mesoporous silica microspheres through microscopy. In addition, the proton conductivity of the phosphoric acid-impregnated HMS membrane at 180°C under anhydrous conditions was found to be 0.025 S.cm−1. These results demonstrate the simplicity of the ion exchange-induced etching strategy for the fabrication of HMS microspheres and its promising application in high temperature proton exchange membrane fuel cells.
Leaf Anatomical Traits of Lianas and Trees at the Canopy of Two Contrasting Lowland Tropical Forests in the Context of Leaf Economic Spectrum
Authors: Harrison Dominica , Guzmán Q. J. Antonio , Sánchez-Azofeifa G. Arturo
Published: August 2021

The leaf economic spectrum describes a comprehensive framework of how the surrounding environment modulates leaf functional traits (LFT) and how these are associated between them. This framework has traditionally focused on physiological, chemical, and biomass assignation traits, but rarely in leaf anatomical traits. Here we compare leaf anatomical metrics and traits of 40 liana and tree species from two lowland tropical forests in Panama with contrasting rainfall regimes: Parque Natural Metropolitano (dry-forest) and Parque Nacional San Lorenzo (wet-forest). Then we evaluate how anatomical traits are associated with well-established LFTs. Anatomical metrics were collected from leaf cross-section images estimating the area, thickness, cell count, and size of the upper and lower epidermis and palisade and spongy mesophyll. Ratios between metrics were performed as potential anatomical traits to reduce the leaf size effect between species. Our results suggest that anatomical changes between life forms are associated with increases in the palisade area and thickness of trees in comparison with lianas, while anatomical changes between forest type species are related to increases in the spongy area and thickness of wet-forest species than dry-forest. These differences could be associated with the high photosynthetic rates of trees or the need to enhance the gas exchange in humid environments. Our results also suggest that anatomical traits are related to well-established LFT; however, the degree of association between them may depend on the life forms and forest type. For example, our results suggest that reductions in the palisade and spongy cell density are associated with increases in leaf mass area and maximum photosynthetic capacity, but this association was not observed when we compared life forms or forest types. The use of leaf anatomical information may facilitate to describe the mechanism that drives the leaf economy, improving our understanding of the resource allocation strategies embedded in functional groups.
Neutrophils Affect IL-33 Processing in Response to the Respiratory Allergen Alternaria alternata
Authors: Van Nevel Sharon , van Ovost Judith , Holtappels Gabriele , De Ruyck Natalie , Zhang Nan , Braun Harald , Maes Tania , Bachert Claus , Krysko Olga
Published: August 2021

Future precision medicine requires further clarifying the mechanisms of inflammation in the severe endotypes of chronic airway diseases such as asthma and chronic rhinosinusitis (CRS). The presence of neutrophils in the airways is often associated with severe airway inflammation, while their precise contribution to the severe inflammation is largely unknown. We aimed to study the role of neutrophils in BALB/c and C57BL/6 mice exposed to Alternaria alternata (Alt). The mice were exposed to Alt extract for twelve hours or ten days to induce allergic airway inflammation. C57BL/6 mice exposed to Alt responded with eosinophilic infiltration and the characteristic IL-5 upregulation. In contrast, the inflammatory response to Alt extract in BALB/c mice was characterized by a neutrophilic response, high levels of G-CSF, and elastase in the lungs. The lack of neutrophils affected the processing of IL-33 in BALB/c mice, as was demonstrated by depletion of neutrophils through intraperitoneal injections of anti-Ly6G antibody. Our data identifies the key role of neutrophils in airway inflammation through IL-33 cleavage in the Alt-induced airway inflammation in mice, which could potentially underline the different endotypes in human disease.
Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome
Authors: Chatzis Loukas , Goules Andreas V. , Stergiou Ioanna E. , Voulgarelis Michael , Tzioufas Athanasios G. , Kapsogeorgou Efstathia K.
Published: August 2021

Recent studies suggest that elevated CXCL13 serum levels in patients with primary Sjögren’s syndrome (pSS) associate with minor salivary gland (MSG) histologic features, disease severity, as well as high-risk status for non-Hodgkin lymphoma (NHL) development and NHL itself. In contrast, limited discriminative value of CXCL13 saliva levels has been reported. Prompt by these reports, we sought to validate the clinical utility of CXCL13 by investigating potential correlations of serum and saliva levels with MSG histopathologic [including CXCL13+-cell number, severity of infiltrates and germinal center (GC) formation], serologic and clinical parameters, as well as NHL. CXCL13 levels were evaluated in paired serum and saliva specimens of 45 pSS patients (15 with NHL; pSS-associated NHL: SSL), 11 sicca-controls (sicca-complaining individuals with negative MSG biopsy and negative autoantibody profile), 10 healthy individuals (healthy-controls) and 6 non-SS-NHLs. CXCL13+-cells were measured in paired MSG-tissues of 22 of pSS patients studied (including 7 SSLs) and all sicca-controls. CXCL13 serum levels were significantly increased in pSS and SSL patients compared to sicca- and healthy-controls and were positively correlated with the CXCL13+-cell number and biopsy focus-score. Serum CXCL13 was significantly higher in pSS patients with GCs, rheumatoid factor, hypocomplementemia, high disease activity, NHL and in high-risk patients for NHL development. CXCL13 saliva levels were significantly increased in SSL patients (compared to non-SS-NHLs), patients with GCs and in high-risk for NHL patients. Univariate analysis revealed that CXCL13 serum, but not saliva, levels were associated with lymphoma, an association that did not survive multivariate analysis. Conclusively, our findings confirm that serum, but not saliva, levels of CXCL13 are associated with histologic, serologic and clinical features indicative of more severe pSS.
Integrated Research for Integrated Ocean Management
Authors: Rölfer Lena , Liconti Arianna , Prinz Natalie , Klöcker Clara Antonia
Published: August 2021

With the start of the United Nations (UN) Decade of Ocean Science for Sustainable Development in 2021, research priorities to support the sustainable use of coastal and ocean resources and their conservation are in the spotlight. However, to date comprehensive regulation and management of multifaceted and multi-used ecosystems has proven challenging. This is partly due to the complexity of coastal and ocean social-ecological systems (SES), as well as the multitude of approaches to manage those spaces. In order to address such challenges, magnified by often-conflicting interests between economic activities and nature conservation, there is an urgent need for integrated approaches that bridge the gap between science, policy and society, as well as across different epistemological boundaries set by various management approaches. Consequently, the interest in multi-, inter-, and transdisciplinary research approaches at the national and international levels has been growing. In light of the recently started Decade of Ocean Science, this paper aims at providing key considerations for research approaches that tackle the outlined challenges in managing the ocean space. From a survey targeted at projects and initiatives that apply multi-, inter-, and transdisciplinary approaches, we draw examples of challenges and good-practices. Based on this, we propose three key considerations for an integrated research approach, including (1) target setting, resource management, and adaptive planning; (2) knowledge production and responsiveness toward policy and society; and (3) co-design, co-development, cooperation, as well as effective communication. The considerations laid out in this paper are aimed at the effective translation between science, policy, and society in support of sustainable coastal and ocean governance within the Decade of Ocean Science.
Invasion and Extirpation Potential of Native and Invasive Spartina Species Under Climate Change
Authors: Borges Francisco O. , Santos Catarina P. , Paula José R. , Mateos-Naranjo Enrique , Redondo-Gomez Susana , Adams Janine Barbara , Caçador Isabel , Fonseca Vanessa F. , Reis-Santos Patrick , Duarte Bernardo , Rosa Rui
Published: August 2021

Coastal areas host some of the planet’s most productive ecosystems, providing life-sustaining ecological services and several benefits to humankind, while also being some of the most threatened areas (e.g., by globalization, climate change, and biological invasion). Salt marshes are coastal habitats with a key role in food and shelter provisioning, sediment deposition, nutrient cycling and carbon storage. Spartina spp. is a genus of grass halophytes which occurs in salt marshes worldwide, and includes species with different invasive potential. We evaluated the effect of climate change in the distribution and invasion potential of five Spartina species (S. anglica, S. alterniflora, S. densiflora, S. patens, and S. maritima) at a global scale. Species distribution models (SDMs) were applied on species occurrence data and atmospheric environmental predictors (WorldClim 2.1) to project potential changes in habitat suitability and associated changes in distribution and species co-occurrence until the end of the century, across four Shared Socioeconomic Pathway scenarios (i.e., SSP1-2.6 to SSP5-8.5). Projections showed a global trend for increasing species co-occurrence, with a general range expansion potentiated by increasing pathway severity. This study suggests that Spartina species can potentially benefit from climate change, predicting poleward expansions in the Northern Hemisphere for most species, with results pointing at increased conflict and invasion potential in Northern Europe and East Asian shorelines, already under strong invasive pressure. S. anglica is projected to remain a successful invader, with more severe scenarios likely favoring greater expansions. S. alterniflora exhibits very low expansion comparatively, despite exhibiting the same northward distribution shift. SSP1-2.6 produced the smallest change to species co-occurrence, suggesting a smaller potential for invasion-related conflicts, although still registering a potential net expansion for the Genus. Despite their limitations, SDMs can help establish general trends in climate change ecology and inform policymakers and environmental agents to ensure the correct management of these habitats and, ultimately, ecosystems.
Residual Pain in the Context of Selecting and Switching Biologic Therapy in Inflammatory Rheumatic Diseases
Authors: Berghea Florian , Berghea Camelia Elena , Zaharia Dumitru , Trandafir Andreea Iulia , Nita Elena Cristina , Vlad Violeta Maria
Published: August 2021

For many years, inflammatory rheumatic diseases (IRDs) represented a source of disappointment in medical care caused by the mediocre efficacy of the available treatments. Some of these diseases, like Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS), caused fear in the general population, especially due to associated joint deformities and subsequent disabilities. However, in the last 20 years, a new successful class of antirheumatic drugs has become available: biologic Disease-Modifying Antirheumatic Drugs (bDMARDs). Due to this innovative treatment, the days are over when joint and spine deformities defined the condition of a person with RA or AS. Nonetheless, expectations are higher today, and other clinical problems, (not entirely solved by bDMARDs), seem to drive the drug selection during the span of rheumatic diseases. Most of these issues are covered by the term “unmet needs.” One of the most intriguing of such needs is the residual pain (RP) in patients that are otherwise in the biological remission of the disease. Present in a significant proportion of the patients that enter remission status, RP is poorly understood and managed. In recent years, new data has become available in this area and new conceptual clarifications have occurred. In this review, we explain the various nature of RP and the necessity of treatment diversification in such situations. All in all, we believe this condition is far more complex than simple pain and includes other clinical aspects, too (like fatigue or mood changes) so the terms Post-Remission Syndrome (PRS), and PRS pain might be more appropriate.
Pacbio Sequencing of PLC/PRF/5 Cell Line and Clearance of HBV Integration Through CRISPR/Cas-9 System
Authors: Chen Chia-Chen , Guan Guiwen , Qi Xuewei , Abulaiti Abudurexiti , Zhang Ting , Liu Jia , Lu Fengmin , Chen Xiangmei
Published: August 2021

The integration of HBV DNA is one of the carcinogenic mechanisms of HBV. The clearance of HBV integration in hepatocyte is of great significance to cure chronic HBV infection and thereby prevent the occurrence of HBV-related hepatocellular carcinoma (HCC). However, the low throughput of traditional methods, such as Alu-PCR, results in low detecting sensitivity of HBV integration. Although the second-generation sequencing can obtain a large amount of sequencing data, but the sequencing fragments are extremely short, so it cannot fully explore the characteristics of HBV integration. In this study, we used the third-generation sequencing technology owning advantages both in sequencing length and in sequencing depth to analyze the HBV integration characteristics in PLC/PRF/5 cells comprehensively. A total of 4,142,311 cleaning reads was obtained, with an average length of 18,775.6 bp, of which 84 reads were fusion fragments of the HBV DNA and human genome. These 84 fragments located in seven chromosomes, including chr3, chr4, chr8, chr12, chr13, chr16, and chr17. We observed lots of DNA rearrangement both in the human genome and in HBV DNA fragments surrounding the HBV integration site, indicating the genome instability causing by HBV integration. By analyzing HBV integrated fragments of PLC/PRF/5 cells that can potentially express HBsAg, we selected three combinations of sgRNAs targeting the integrated fragments to knock them out with CRISPR/Cas9 system. We found that the sgRNA combinations could significantly decrease the level of HBsAg in the supernatant of PLC/PRF/5 cells, while accelerated cell proliferation. This study proved the effectiveness of third-generation sequencing to detect HBV integration, and provide a potential strategy to reach HBsAg clearance for chronic HBV infection patients, but the knock-out of HBV integration from human genome by CRISPR/Cas9 system may have a potential of carcinogenic risk.
Early Warning Value of ASL-MRI to Estimate Premorbid Variations in Patients With Early Postoperative Cognitive Dysfunctions
Authors: Du Xue , Gao Yan , Liu Su , Zhang Jingya , Basnet Diksha , Yang Junjun , Liu Jiehui , Deng Yijie , Hu Jiayong , Wang Peijun , Liu Jianhui
Published: August 2021

Background: Postoperative cognitive dysfunction (POCD) is a general complication following cardiac and major non-cardiac surgery amongst the elderly, yet its causes and mechanisms are still unknown. The present study aimed to detect whether regional cerebral blood flow (CBF) is altered in the brain before surgery in POCD patients compared with non-POCD (NPOCD) patients, thus, CBF variation may potentially predict the occurrence of early POCD.

Methods: Fifty patients scheduled for spinal stenosis surgery were enrolled in the study. All study participants completed a battery of neuropsychological tests (NPTs) by a well-trained neuropsychologist before the surgery and 1 week after the surgery. POCD was defined when the preoperative to postoperative difference of at least two of the NPTs’ |Z|-scores with reference to a control group exceeded 1.96. Pulsed arterial spin-labeling (ASL) MRI was scanned at least 1 day before surgery. The ASLtbx toolkit and SPM12 were applied to preprocess and correct the images, which were then normalized to the MNI brain template space to obtain standardized cerebral perfusion images.

Results: POCD was identified in 11 out of 50 patients (22%). The CBF of the right superior temporal lobe, right and left middle cingulate gyrus, and the right hippocampus, and parahippocampal gyrus in POCD group was lower than that in NPOCD group (P < 0.001). The CBF of the pars triangularis of inferior frontal gyrus in POCD group was higher than that in NPOCD group (P < 0.001).

Conclusions: These preliminary findings suggest that CBF premorbid alterations may happen in cognitively intact elderly patients that develop early POCD. Alterations of preoperative CBF might be a bio-marker for early POCD that can be detected by noninvasive MRI scans.
Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior
Authors: Felippe Renata M. , Oliveira Gabriel M. , Barbosa Rafaela S. , Esteves Betina D. , Gonzaga Beatriz M. S. , Horita Samuel I. M. , Garzoni Luciana R. , Beghini Daniela G. , Araújo-Jorge Tânia C. , Fragoso Viviane M. S.
Published: August 2021

Aggression is defined as hostile behavior that results in psychological damage, injury and even death among individuals. When aggression presents itself in an exacerbated and constant way, it can be considered escalating or pathological. The association between social stress and the emergence of exacerbated aggressiveness is common and is suggested to be interconnected through very complex neurobiological factors. For example, alterations in the expression of the dopaminergic receptors D1 and D2, reactive oxygen species (ROS) and the c-Fos protein in the cortex have been observed. Our objective was to analyze which factors are involved at the neurobiological level in the highly aggressive response of Swiss Webster adult male mice in a vivarium. In this work, we investigated the relationship among dopaminergic receptors, the production of ROS and the expression of c-Fos. Mice with exacerbated aggression were identified by the model of spontaneous aggression (MSA) based on the grouping of young mice and the regrouping of the same animals in adulthood. During the regrouping, we observed different categories of behavior resulting from social stress, such as (i) highly aggressive animals, (ii) defeated animals, and (iii) harmonic groups. To evaluate the dopaminergic system and the c-Fos protein, we quantified the expression of D1 and D2 dopaminergic receptors by Western blotting and fluorescence immunohistochemistry and that of the c-Fos protein by fluorescence immunohistochemistry. The possible production of ROS was also evaluated through the dihydroethidium (DHE) assay. The results showed that aggressive and subordinate mice showed a reduction in the expression of the D1 receptor, and no significant difference in the expression of the D2 receptor was observed between the groups. In addition, aggressive mice exhibited increased production of ROS and c-Fos protein. Based on our results, we suggest that exacerbated aggression is associated with social stress, dysregulation of the dopaminergic system and exacerbated ROS production, which leads to a state of cellular oxidative stress. The overexpression of c-Fos due to social stress suggests an attempt by the cell to produce antioxidant agents to reduce the toxic cellular concentration of ROS.
Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings
Authors: Coffin Allison B. , Boney Robert , Hill Jordan , Tian Cong , Steyger Peter S.
Published: August 2021

Over 100 drugs and chemicals are associated with permanent hearing loss, tinnitus, and vestibular deficits, collectively known as ototoxicity. The ototoxic potential of drugs is rarely assessed in pre-clinical drug development or during clinical trials, so this debilitating side-effect is often discovered as patients begin to report hearing loss. Furthermore, drug-induced ototoxicity in adults, and particularly in elderly patients, may go unrecognized due to hearing loss from a variety of etiologies because of a lack of baseline assessments immediately prior to novel therapeutic treatment. During the current pandemic, there is an intense effort to identify new drugs or repurpose FDA-approved drugs to treat COVID-19. Several potential COVID-19 therapeutics are known ototoxins, including chloroquine (CQ) and lopinavir-ritonavir, demonstrating the necessity to identify ototoxic potential in existing and novel medicines. Furthermore, several factors are emerging as potentiators of ototoxicity, such as inflammation (a hallmark of COVID-19), genetic polymorphisms, and ototoxic synergy with co-therapeutics, increasing the necessity to evaluate a drug's potential to induce ototoxicity under varying conditions. Here, we review the potential of COVID-19 therapies to induce ototoxicity and factors that may compound their ototoxic effects. We then discuss two models for rapidly detecting the potential for ototoxicity: mammalian auditory cell lines and the larval zebrafish lateral line. These models offer considerable value for pre-clinical drug development, including development of COVID-19 therapies. Finally, we show the validity ofin silicoscreening for ototoxic potential using a computational model that compares structural similarity of compounds of interest with a database of known ototoxins and non-ototoxins. Preclinical screening atin silico, in vitro, andin vivolevels can provide an earlier indication of the potential for ototoxicity and identify the subset of candidate therapeutics for treating COVID-19 that need to be monitored for ototoxicity as for other widely-used clinical therapeutics, like aminoglycosides and cisplatin.
Prefrontal tDCS Attenuates Self-Referential Attentional Deployment: A Mechanism Underlying Adaptive Emotional Reactivity to Social-Evaluative Threat
Authors: Allaert Jens , Erdogan Maide , Sanchez-Lopez Alvaro , Baeken Chris , De Raedt Rudi , Vanderhasselt Marie-Anne
Published: August 2021

Social-evaluative threat (SET) – a situation in which one could be negatively evaluated by others – elicits profound (psycho)physiological reactivity which, if chronically present and not adaptively regulated, has deleterious effects on mental and physical health. Decreased self-awareness and increased other-awareness are understood to be an adaptive response to SET. Attentional deployment – the process of selectively attending to certain aspects of emotional stimuli to modulate emotional reactivity – is supported by fronto-parietal and fronto-limbic networks, with the dorsolateral prefrontal cortex being a central hub. The primary aim of the current study was to investigate the effects of active (versus sham) prefrontal transcranial direct current stimulation (tDCS) on self and other-attentional deployment during the exposure to a SET context. Seventy-four female participants received active or sham tDCS and were subsequently exposed to a rigged social feedback paradigm. In this paradigm a series of social evaluations were presented together with a photograph of the supposed evaluator and a self- photograph of the participant, while gaze behavior (time to first fixation, total fixation time) and skin conductance responses (SCRs; a marker of emotional reactivity) were measured. For half of the evaluations, participants could anticipate the valence (negative or positive) of the evaluation a priori. Analyses showed that participants receiving active tDCS were (a) slower to fixate on their self-photograph, (b) spent less time fixating on their self-photograph, and (c) spent more time fixating on the evaluator photograph. During unanticipated evaluations, active tDCS was associated with less time spent fixating on the evaluation. Furthermore, among those receiving active tDCS, SCRs were attenuated as a function of slower times to fixate on the self-photograph. Taken together, these results suggest that in a context of SET, prefrontal tDCS decreases self-attention while increasing other-attention, and that attenuated self-referential attention specifically may be a neurocognitive mechanism through which tDCS reduces emotional reactivity. Moreover, the results suggest that tDCS reduces vigilance toward stimuli that possibly convey threatening information, corroborating past research in this area.
Effect of Anesthesia/Surgery on Gut Microbiota and Fecal Metabolites and Their Relationship With Cognitive Dysfunction
Authors: Lian Xinrong , Zhu Qianmei , Sun Li , Cheng Yaozhong
Published: August 2021

Aims: Post-operative cognitive dysfunction (POCD) is the decline in cognitive function of the central nervous system (CNS) after anesthesia/surgery. The present study explored whether anesthesia/surgery altered gut microbiota and fecal metabolites, examining their associations with risk factors of cognitive dysfunction in aged mice.

Methods: Sixteen-month-old C57BL/6 mice underwent abdominal surgery under isoflurane anesthesia to establish an animal model of POCD. The Morris water maze test (MWMT) was used as an indicator of memory after surgery. The effects of anesthesia/surgical interventions on gut microbiota, fecal metabolites, hippocampus, and serum levels of inflammatory factors were examined.

Results: The anesthesia/surgery induced more serious POCD behavior, increasing brain interleukin (IL)-6, and IL-1β levels than sham control mice. The relative abundance of bacterial genera Bacteroidales_unclassified, Mucispirillum, and Clostridiales_unclassified declined, whereas that of Escherichia–Shigella, actinomyces, Ruminococcus_gnavus_group, and Lachnospiraceae_FCS020_group were enriched after anesthesia/surgery compared to the baseline controls. Liquid chromatography–mass spectrometry (LC–MS) showed that the metabolites differed between post-anesthesia+surgery (post_A + S) and baseline samples and were associated with the fecal metabolism of tryptophan, kynurenic acid, N-oleoyl γ-aminobutyric acid (GABA), 2-indolecarboxylic acid, and glutamic acid. Furthermore, the differential metabolites were associated with alterations in the abundance of specific bacteria. These results indicate that the POCD intervention may be achieved by targeting specific bacteria associated with neurotransmitter metabolism.

Conclusions: A transient cognitive disturbance induced by anesthesia/surgery may be associated with unfavorable alterations in gut microbiota and fecal metabolites, thereby contributing to the POCD development.
Changes in Vegetable Consumption in Times of COVID-19—First Findings From an International Civil Science Project
Authors: Jordan Irmgard , Keding Gudrun B. , Stosius Lena , Hawrysz Iwona , Janiszewska Katarzyna , Heil Eleonore A.
Published: August 2021

The crisis related to the COVID-19 pandemic influenced food security and nutrition through both direct and indirect pathways. This ranged from short-term to long-term impacts, not only on health but also on food systems and thus on nutrition. This study aimed to identify how the observed constraints affected the food intake of populations across the globe. Here, special attention was paid to the consumption of vegetables and legumes and the diversity within these food groups. An online survey on Food and COVID-19 was conducted using a semi-structured questionnaire translated into several languages. Binary logistic regression models and Poisson regression models were calculated to evaluate changes in consumption patterns and to test potential determinants for the changes. For more detailed information on reasons for changes open ended questions were analysed qualitatively. Time spend at home, working from home, and mental stress were important drivers for changes in dietary intake according to the 1,042 respondents included in this analysis. The participants observed a change in food quantity (38%) and vegetable intake (27%). No changes were observed for the number of vegetable groups consumed, while significant reductions in diversity were detected within all vegetable groups. Moreover, associations between the number of consumed vegetable types during the COVID-19 pandemic and income regions as well as gender were found. The regression analysis showed that the level of decrease in vegetable diversity in the different vegetable groups were often depending on educational and occupational status, gender and household environment. Changes in food prices were related to changes in vegetable intake per se, overall vegetable diversity, and diversity within the provitamin A rich vegetable group. Food systems are not static and are transitioning quickly as could be observed during the Covid-19 pandemic. There is a need for a nutrition strategy to strengthen the resilience of vulnerable households to consume a diverse diet in adequate amount even in times of a pandemic.
Bioaccessibility and Intestinal Transport of Deltamethrin in Pacific Oyster (Magallana Gigas) Using Simulated Digestion/NCM460 Cell Models
Authors: Jiao Yadan , Liu Chune , Feng Chunsong , Regenstein Joe M. , Luo Yongkang , Tan Yuqing , Hong Hui
Published: August 2021

Deltamethrin (DEL) can be introduced into the food chain through bioaccumulation in Pacific oysters, and then potentially threaten human health. The objective of this study was to investigate the bioaccessibility of DEL in oysters with different cooking methods after simulated digestion. DEL content in different tissues of oysters going from high to low were gills, mantle, viscera, and adductor muscle. Bioaccessibility of DEL in oysters decreased after steaming (65%) or roasting (51%) treatments compared with raw oysters (82%), which indicated that roasting can be used as a recommended cooking method for oysters. In the simulated digestion process, the concentration of DEL in the digestive juice and the bioaccessibility of DEL were affected by the pH in the gastric phase. And the transport efficiency of DEL through the monolayer molecular membrane of NCM460 cells ranged from 35 to 45%. These results can help assess the potential harm to consumers of DEL in shellfish. Furthermore, it provides a reference for the impact of lipophilic toxins in seafood.
Evaluation of the Impact of Intratumoral Heterogeneity of Esophageal Cancer on Pathological Diagnosis and P16 Methylation and the Representativity of Endoscopic Biopsy
Authors: Qin Yu , Zhou Jing , Fan Zhiyuan , Gu Jianhua , Li Xinqing , Lin Dongmei , Deng Dajun , Wei Wenqiang
Published: August 2021

Background

P16 methylation is expected to be potential diagnostic and therapeutic targets for esophageal cancer (EC). The intratumoral heterogeneity (ITH) of EC has been mentioned but has not been quantitatively measured yet. We aimed to clarify the impact of ITH on pathological diagnosis and P16 methylation, and the concordance between endoscopic biopsy and the corresponding surgically resected tissue.

Methods

We designed a systematic sampling method (SSM) compared with a general sampling method (GSM) to obtain EC tumor tissue, tumor biopsy, and normal squamous epithelium biopsy. MethyLight assay was utilized to test P16 methylation. All specimens obtained by the SSM were pathologically diagnosed.

Results

A total of 81 cases were collected by the GSM, and 91.4% and 8.6% of them were esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EADs), respectively. Nine SSM cases were 100.0% ESCCs. The positive rates of P16 methylation of the GSM tumor and normal tissues were 63.0% (51/81) and 32.1% (26/81), respectively. For SSM samples, tumor tissues were 100.0% (40/40) EC and 85.0% (34/40) P16 methylated; tumor biopsy was 64.4% (29/45) diagnosed of EC and 68.9% P16 methylated; the corresponding normal biopsies were 15.7% (8/51) dysplasia and 54.9% (28/51) P16 methylated. The concordance of pathological diagnosis and P16 methylation between tumor biopsy and the corresponding tumor tissue was 75.0% and 62.5%, respectively.

Conclusion

The SSM we designed was efficient in measuring the ITH of EC. We found inadequate concordance between tumor biopsy and tissue in pathological diagnosis and P16 methylation.
Aggresome–Autophagy Associated Gene HDAC6 Is a Potential Biomarker in Pan-Cancer, Especially in Colon Adenocarcinoma
Authors: Zhang Zhiyong , Zhang Xin , Huang Aimin
Published: August 2021

Background

Histone deacetylase 6 (HDAC6) regulates cytoplasmic signaling networks through the deacetylation of various cytoplasmic substrates. Recent studies have identified the role of HDAC6 in tumor development and immune metabolism, but its specific function remains unclear.

Methods

The current study determined the role of HDAC6 in tumor metabolism and tumor immunity through a multi-database pan-cancer analysis. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) datasets were used to determine the expression levels, prognosis, tumor progression, immune checkpoints, and immune metabolism of HDAC6 in 33 tumors. Pathways, immune checkpoints, immune neoantigens, immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), DNA mismatch repair (MMR), and the value of methyltransferases. The R package was used for quantitative analysis and panoramic description.

Results

In the present study, we determined that HDAC6 is differentially expressed in pan carcinomas, and by survival, we found that HDAC6 was generally associated with the prognosis of pancreatic adenocarcinoma, Thymoma, and uveal melanoma, where low expression of HDAC6 had a significantly worse prognosis. Secondly, through this experiment, we confirmed that HDAC6 expression level was associated with tumor immune infiltration and tumor microenvironment, especially in PAAD. Finally, HDAC6 was associated with immune neoantigen and immune checkpoint gene expression profiles in all cancers in addition to TMB and MSI in pan-cancers.

Conclusion

HDAC6 is differentially expressed in pan-cancers and plays an essential role in tumor metabolism and immunity. HDAC6 holds promise as a tumor potential prognostic marker, especially in colon cancer.
Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review
Authors: Chitsike Lennox , Duerksen-Hughes Penelope J.
Published: August 2021

The treatment landscape of locally advanced HPV-oropharyngeal squamous cell carcinoma (OPSCC) is undergoing transformation. This is because the high cures rates observed in OPSCC are paired with severe treatment-related, long-term toxicities. These significant adverse effects have led some to conclude that the current standard of care is over-treating patients, and that de-intensifying the regimens may achieve comparable survival outcomes with lower toxicities. Consequently, several de-escalation approaches involving locally advanced OPSCC are underway. These include the reduction of dosage and volume of intensive cytotoxic regimens, as well as elimination of invasive surgical procedures. Such de-intensifying treatments have the potential to achieve efficacy and concurrently alleviate morbidity. Targeted therapies, given their overall safer toxicity profiles, also make excellent candidates for de-escalation, either alone or alongside standard treatments. However, their role in these endeavors is currently limited, because few targeted therapies are currently in clinical use for head and neck cancers. Unfortunately, cetuximab, the only FDA-approved targeted therapy, has shown inferior outcomes when paired with radiation as compared to cisplatin, the standard radio-sensitizer, in recent de-escalation trials. These findings indicate the need for a better understanding of OPSCC biology in the design of rational therapeutic strategies and the development of novel, OPSCC-targeted therapies that are safe and can improve the therapeutic index of standard therapies. In this review, we summarize ongoing research on mechanism-based inhibitors in OPSCC, beginning with the salient molecular features that modulate tumorigenic processes and response, then exploring pharmacological inhibition and pre-clinical validation studies of candidate targeted agents, and finally, summarizing the progression of those candidates in the clinic.
Dysregulated lncRNAs are Involved in the Progress of Sepsis by Constructing Regulatory Networks in Whole Blood Cells
Authors: Cheng Yanwei , Cao Xue , Zhang Jiange , Chen Dong , Zhu Juan , Xu Lijun , Qin Lijie
Published: August 2021

Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced host response to an infection. Long noncoding RNAs (lncRNAs) have been reported to exert regulatory roles in a variety of biological processes, and became potential biomarkers and therapeutic targets for diverse diseases. However, current understanding on the roles of lncRNAs in sepsis is extremely limited. Herein, to decipher the underlying functions of lncRNAs, we reexplored the 83 transcriptome datasets from specimens with sepsis, no_sepsis by final diagnosis, and control. The results of differentially expressed genes (DEGs), differentially expressed lncRNA (DElncRNA) analysis, and co-expression analysis of lncRNA–mRNA pairs were obtained. We found that the expression pattern of lncRNAs was significantly activated in sepsis specimens, which was clearly distinguished in sepsis from no_sepsis and control specimens. By performing co-expression analysis, we found DElncRNAs were closely related to T-cell activation and immune response–related terms in sepsis by regulating mRNA expression in the trans manner. The lncRNA–mRNA network and the qRT-PCR test revealed that lncRNAs LINC00861, RP11-284N8.3, and CTB-61M7.2 were significantly correlated with the pathogenesis of sepsis. In addition, weighted gene co-expression analysis (WGCNA) and cis-regulation analysis also revealed sepsis-specific lncRNAs were highly associated with important biological processes correlated with sepsis. In summary, the systematic dysregulation of lncRNAs is tightly involved in the remodeling of gene expression regulatory network in sepsis, and the lncRNA–mRNA expression network may be used to refine biomarker predictions for developing novel therapeutic approaches in sepsis.
Advanced Computational Methodologies Used in the Discovery of New Natural Anticancer Compounds
Authors: Chavda Vivek P. , Ertas Yavuz Nuri , Walhekar Vinayak , Modh Dharti , Doshi Avani , Shah Nirav , Anand Krishna , Chhabria Mahesh
Published: August 2021

Natural chemical compounds have been widely investigated for their programmed necrosis causing characteristics. One of the conventional methods for screening such compounds is the use of concentrated plant extracts without isolation of active moieties for understanding pharmacological activity. For the last two decades, modern medicine has relied mainly on the isolation and purification of one or two complicated active and isomeric compounds. The idea of multi-target drugs has advanced rapidly and impressively from an innovative model when first proposed in the early 2000s to one of the popular trends for drug development in 2021. Alternatively, fragment-based drug discovery is also explored in identifying target-based drug discovery for potent natural anticancer agents which is based on well-defined fragments opposite to use of naturally occurring mixtures. This review summarizes the current key advancements in natural anticancer compounds; computer-assisted/fragment-based structural elucidation and a multi-target approach for the exploration of natural compounds.
Lactate and Myocardiac Energy Metabolism
Authors: Dong Shuohui , Qian Linhui , Cheng Zhiqiang , Chen Chang , Wang Kexin , Hu Sanyuan , Zhang Xiang , Wu Tongzhi
Published: August 2021

The myocardium is capable of utilizing different energy substrates, which is referred to as “metabolic flexibility.” This process assures ATP production from fatty acids, glucose, lactate, amino acids, and ketones, in the face of varying metabolic contexts. In the normal physiological state, the oxidation of fatty acids contributes to approximately 60% of energy required, and the oxidation of other substrates provides the rest. The accumulation of lactate in ischemic and hypoxic tissues has traditionally be considered as a by-product, and of little utility. However, recent evidence suggests that lactate may represent an important fuel for the myocardium during exercise or myocadiac stress. This new paradigm drives increasing interest in understanding its role in cardiac metabolism under both physiological and pathological conditions. In recent years, blood lactate has been regarded as a signal of stress in cardiac disease, linking to prognosis in patients with myocardial ischemia or heart failure. In this review, we discuss the importance of lactate as an energy source and its relevance to the progression and management of heart diseases.
Evaluation of Before Operational Stress: A Program to Support Mental Health and Proactive Psychological Protection in Public Safety Personnel
Authors: Stelnicki Andrea M. , Jamshidi Laleh , Fletcher Amber J. , Carleton R. Nicholas
Published: August 2021

Public safety personnel (PSP; e.g., communications officials, corrections workers, firefighters, paramedics, and police officers) are at risk of developing mental health problems due to experiencing potentially psychologically traumatic events during their career. Research examining evidence-based treatments for psychological injuries resulting from operational duties (also known as operational stress injuries) has not yielded robust results that would indicate ongoing interventions as the best solution for managing PSP mental health injuries; as such, proactive psychological interventions designed to bolster resilience are being considered potentially beneficial for mitigating the impact of occupational stress on PSP. Despite the growing popularity of resilience programs, most are delivered in a single session after an event deemed particularly problematic with no follow-up. Longer interventions may better support sustained resiliency, mitigate the impact of operational stress, and increase positive PSP workplace outcomes. The current article introduces the Before Operational Stress (BOS) program, which was designed for delivery early in a PSP career to enhance self-awareness and healthy relationships. The year-long program is derived from cognitive behavior therapy and group therapeutic techniques to meet program objectives. The current BOS program evaluation demonstrated small, statistically significant improvements in symptoms of PTSD, quality of life, stigma, and perceived social support from baseline (Time 1) to 6 months (Time 4). There were also non-significant improvements observed in symptoms of depression, anxiety, stress, alcohol use, as well as in emotional regulation and resilience. Qualitative results indicated participants positively perceived the BOS program, with participants reporting specific improvements in self-awareness, avoidant behaviors, and relationships with family and colleagues. The BOS program content (e.g., functional disconnection and functional reconnection) and processes (e.g., psychoeducation within a supportive learning structure; mutually empowering group interactions) appear unique relative to other PSP resilience programs, with promising initial results in support of PSP mental health. Recommendations for future research and program development are provided.