bluuebunny/crossref_metadata_2025 huggingface dataset:
The Presence of Leishmania braziliensis DNA in the Nasal Mucosa of Cutaneous Leishmaniasis Patients and the Search for Possible Clinical and Immunological Patterns of Disease Progression: A Cross Sectional Study
Authors: Barroso Daniel Holanda , Nóbrega Otávio de Toledo , de Araújo Carla Nunes , Freire Gustavo Subtil Magalhães , Martins Sofia Sales , Rodrigues Bruna Côrtes , Gomes Ciro Martins , Sampaio Raimunda Nonata Ribeiro
Published: October 2021

Leishmania braziliensis is the most important causal agent of American tegumentary leishmaniasis (ATL), and 3 to 5% of patients develop mucosal lesions. The mechanisms related to parasite and host immune interactions and the parasite life cycle that lead to dissemination to the mucosa are poorly understood. We aimed to detect L. braziliensis DNA in the nasal mucosa of cutaneous leishmaniasis (CL) patients with early mucous dissemination and to relate those findings to specific inflammatory responses. Nasal swabs were collected from patients with the cutaneous form of ATL. L. braziliensis DNA was investigated using TaqMan-based real-time PCR. The levels of serum cytokines (IL-12, IL-6, TNF-α, IL-10, IL-1β and IL-8) were measured by a multiplex cytometric array. A Poisson regression model was used to test prevalence ratios (PRs) and multivariate interactions of clinical and laboratory characteristics. Of the 79 CL patients, 24 (30%) had L. braziliensis DNA in the nasal mucosa. In the multivariate model, parasite DNA presence in mucosa was associated with a reduction in IL-12 levels (PR = 0.440; p=0.034), increased IL-6 levels (PR = 1.001; p=0.002) and a higher number of affected body segments (PR = 1.65; p<0.001). In this study, we observed a higher rate of early dissemination to the nasal mucosa than what was previously described. We suggest that an enhanced Th1 profile characterized by higher IL-12 is important for preventing dissemination of L. braziliensis to the mucosa. Further evaluation of parasite-related interactions with the host immunological response is necessary to elucidate the dissemination mechanisms of Leishmania.
Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?
Authors: Xu Xiaolin , Chen Rongmin , Zhan Gaofeng , Wang Danning , Tan Xi , Xu Hui
Published: October 2021

In recent years, increasing studies have been conducted on the mechanism of gut microbiota in neuropsychiatric diseases and non-neuropsychiatric diseases. The academic community has also recognized the existence of the microbiota-gut-brain axis. Chronic pain has always been an urgent difficulty for human beings, which often causes anxiety, depression, and other mental symptoms, seriously affecting people’s quality of life. Hyperalgesia is one of the main adverse reactions of chronic pain. The mechanism of gut microbiota in hyperalgesia has been extensively studied, providing a new target for pain treatment. Enterochromaffin cells, as the chief sentinel for sensing gut microbiota and its metabolites, can play an important role in the interaction between the gut microbiota and hyperalgesia through paracrine or neural pathways. Therefore, this systematic review describes the role of gut microbiota in the pathological mechanism of hyperalgesia, learns about the role of enterochromaffin cell receptors and secretions in hyperalgesia, and provides a new strategy for pain treatment by targeting enterochromaffin cells through restoring disturbed gut microbiota or supplementing probiotics.
The Long-Term Results of Three Catheter Ablation Methods in Patients With Paroxysmal Atrial Fibrillation: A 4-Year Follow-Up Study
Authors: You Ling , Zhang Xiaohong , Yang Jing , Wang Lianxia , Zhang Yan , Xie Ruiqin
Published: October 2021

Aims: Catheter ablation of paroxysmal atrial fibrillation (PAF) has been shown to be effective and safe. However, recurrence of PAF varies between 10 and 30% for radiofrequency ablation. There have been no reports comparing long-term recurrence rates following radiofrequency ablation, cryoablation, and three-dimensional guided cryoablation plus radiofrequency ablation. The aim of this study was to observe the long-term recurrence rate of PAF when treated by these three catheter ablation methods, and to explore clinical factors that can potentially predict PAF recurrence following catheter ablation.

Methods: There were 238 patients involved in this study, including 106 radiofrequency (RF) ablation cases (RF group), 66 cryoablation cases (Freeze group), and 66 cases treated by three-dimensional guided cryoablation combined with radiofrequency ablation (Freeze-plus-RF group). All patients underwent standardized follow-up. The recurrence rate of atrial fibrillation (AF) in the three groups was calculated. Predictive factors for the recurrence of AF were also investigated.

Results: At 48 months (the median follow-up period), the sinus rhythm maintenance rate was 77.4% in the RF group, 72.7% in the Freeze group, and 81.8% in the Freeze-plus-RF group. The maintenance rate of sinus rhythm was highest in the Freeze-plus-RF group, but differences among the three groups were not statistically significant. Further analysis found that the preoperative left atrial appendage emptying velocity (LAAEV) (recurrence vs. no recurrence, 56.58 ± 18.37 vs. 65.59 ± 18.83, respectively, p = 0.003), left atrial (LA) anteroposterior dimension (recurrence vs. no recurrence, 36.56 ± 4.65 vs. 35.00 ± 4.37, respectively; p = 0.028), and LA vertical dimension (recurrence vs. no recurrence, 56.31 ± 6.96 vs. 53.72 ± 6.52, respectively; p = 0.035) were related to postoperative recurrence. Multiple Cox regression analysis showed that only LAAEV was predictive of postoperative recurrence of PAF (hazard ratio: 0.979; 95% confidence interval: 0.961–0.997).

Conclusion: Our study found that there was no statistically significant difference in long-term recurrence rates among the RF, Freeze, and Freeze-plus-RF groups. Preoperative LAAEV is an independent predictor of postoperative recurrence of PAF.
Electromagnetic Field Associated With Dermoscope Magnets May Affect the Safety of Cardiac Implanted Electronic Devices Patients
Authors: Sławiński Grzegorz , Sławińska Martyna , Usarek Zbigniew , Sobjanek Michał , Kempa Maciej , Liżewska-Springer Aleksandra , Lewicka Ewa , Nowicki Roman J. , Raczak Grzegorz
Published: October 2021

Dermoscopy is currently used as an auxiliary tool in general dermatology. Since some commercially available dermoscopes have built-in magnets, electromagnetic interference (EMI) may occur when examining cardiac implantable electronic devices (CIED) patients. The aim of the study was to create maps of electromagnetic fields defining a safe distance in terms of EMI. The study was performed in laboratory conditions using measuring equipment specially designed for this purpose. The following dermoscopes have been tested: Illuco IDS-1100, Visiomed Luminis, Visiomed Luminis 2, Heine NC2 with and without a contact plate, DermLite DL4, and DermLite Handyscope. Measurements were made for the following set of lift-off distances: 5, 10, 20, 30, 40, 50, and 150 mm. Each 2D scan consisted of 10-line scans shifted from each other by 10 mm. The strength of the magnetic field decreased with the distance from the faceplate. The distribution of the magnetic field differed depending on the position of the magnets. The highest magnetic field was recorded in the center of the Heine NC2 faceplate (up to 8 mT). In most cases, at a distance of 10 mm, the magnetic field strength was measured below 1 mT, with the exception of Heine NC2 and Heine NC2 with a contact plate. All tested dermoscopes generated a magnetic field of <1 mT at the distance of 20 mm. The use of dermoscopes with built-in magnets may affect the functioning of CIEDs, and the impact may vary depending on the type of dermoscope.
A Data-Driven Personalized Lighting Recommender System
Authors: Zarindast Atousa , Wood Jonathan
Published: October 2021

Recommender systems attempt to identify and recommend the most preferable item (product-service) to individual users. These systems predict user interest in items based on related items, users, and the interactions between items and users. We aim to build an auto-routine and color scheme recommender system for home-based smart lighting that leverages a wealth of historical data and machine learning methods. We utilize an unsupervised method to recommend a routine for smart lighting. Moreover, by analyzing users’ daily logs, geographical location, temporal and usage information, we understand user preferences and predict their preferred light colors. To do so, users are clustered based on their geographical information and usage distribution. We then build and train a predictive model within each cluster and aggregate the results. Results indicate that models based on similar users increases the prediction accuracy, with and without prior knowledge about user preferences.
Effect of Pre-Adsorbed Water on Methane Adsorption Capacity in Shale-Gas Systems
Authors: Chen Lei , Jiang Zhenxue , Jiang Shu , Guo Song , Tan Jingqiang
Published: October 2021

The presence and content of water will certainly affect the gas adsorption capacity of shale and the evaluation of shale gas content. In order to reasonably evaluate the gas adsorption capacity of shale under actual reservoir conditions, the effect of water on methane adsorption capacity needs to be investigated. Taking the Da’anzhai Member of the Lower Jurassic Ziliujing Formation in the northeastern Sichuan Basin, China as an example, this study attempts to reveal the effect of pre-adsorbed water on methane adsorption capacity in shale-gas systems by conducting methane adsorption experiments in two sequences, firstly at different temperatures under dry condition and secondly at different relative humidity levels under the same temperature. The results show that temperature and relative humidity (i.e., water saturation) are the main factors affecting the methane adsorption capacity of shale for a single sample. The key findings of this study include: 1) Methane adsorption capacity of shale first increases then decreases with depth, reaching a peak at about 1,600–2,400 m. 2) Lower relative humidity correlates to greater maximum methane adsorption capacity and greater depth to reach the maximum methane adsorption capacity. 3) 20% increase of relative humidity results in roughly 10% reduction of maximum methane adsorption capacity. As a conclusion, methane adsorption capacity of shale is predominately affected by water saturation, pore type and pore size of shale. This study could provide a theoretical basis for the establishment of a reasonable evaluation method for shale adsorbed gas content.
Research and Application of a Clear Diamond-Shaped Distribution Network Structure
Authors: Shengli Liu , Jun Wu , Longjiang Xue , Di Wu , Haiqing Lu , Wenlong Li , Shaofang Wang , Wenqi Li
Published: October 2021

Aiming at the problems of low power supply reliability, poor transfer capacity between stations, and low line utilization in the current distribution network, this paper proposes a diamond-shaped distribution network structure with a clear structure. First, we investigated the typical wiring patterns of medium-voltage distribution networks in Tokyo, Japan, Paris, France, and China’s developed cities, and summarized experience and shortcomings. Secondly, combining the typical wiring patterns of distribution networks in China and abroad, construct a diamond-shaped distribution network structure, and study its adaptability, safety and flexibility, power supply reliability, and economy. Finally, take the transformation of the wiring mode of a regional distribution network in a certain city as an example, compare the use of the diamond-shaped distribution network structure in this article with the use of cable double-ring network wiring, cable “double petal” wiring, and Shanghai diamond-type wiring distribution network grid reconstruction The effect verifies the superiority of the diamond-shaped distribution network structure in this paper.
Zonal Patterns of Meteorological Drought on the Yunnan-Guizhou Plateau, China
Authors: Yu Hang , Wang Long , Yang Maoling
Published: October 2021

Drought is a natural phenomenon caused by a shortage of water resources and has a great impact on agriculture, the economy, and the environment. To study the Spatio-temporal distribution and explore the zonal patterns of drought, this paper took the Yunnan-Guizhou Plateau (YGP) as the research region, selected the air temperature, relative humidity, sunshine duration, wind speed, and precipitation data from 47 meteorological stations on the YGP. First, the standardized precipitation evapotranspiration index (SPEI) was calculated, and then the Spatio-temporal distribution of YGP drought was analyzed with the SPEI, Mann–Kendall test, and principal component analysis (PCA). Finally, the correlations between the average SPEI, drought characteristics extracted from the SPEI, and longitude/elevation/latitude were analyzed with the linear regression method, and then the zonal patterns of the YGP drought were obtained. The results revealed that the annual and seasonal SPEI values mainly decreased. Because the first component of the SPEI (the largest eigenvalue makes it the most important component) in annual and winter had a poor relationship with longitude/elevation, its correlation was weak, while the average SPEI values in other seasons were significantly correlated with longitude/elevation (α = 0.001), and the absolute value of the correlation coefficient was between 0.6879–0.9453. Except for PC1 in annual and winter, PC1 and PC2 were significantly correlated with longitude/elevation (α = 0.001), and the absolute value of the correlation coefficient was between 0.5087–0.9501. The duration, severity, intensity, frequency of drought were significantly correlated with longitude/elevation (α = 0.001) in most situations. The average SPEI values and drought characteristics showed a good multivariate linear correlation with longitude, latitude, and elevation, indicating that drought exhibited strong zonal patterns. This study will provide new ideas for drought research and technical support for regional industrial layouts, planting structure adjustments, and drought and disaster reduction.
Kelp Forests: Catastrophes, Resilience, and Management
Authors: Wilman Elizabeth A.
Published: October 2021

Resilient kelp forests provide foundation habitat for marine ecosystems and are indicators of the ecosystems’ sustainable natural capital. Loss of resilience and imperfectly reversible catastrophic shifts from kelp forests to urchin barrens, due to pollution or loss of a top predator, are part of an ecological tipping point phenomenon, and involve a loss in sustainable natural capital. Management controls to prevent or reverse these shifts and losses are classified in a number of ways. Systemic controls eliminate the cause of the problem. Symptomatic controls use leverage points for more direct control of the populations affected, urchin harvesting or culling, or kelp enhancement. There is a distinction between ongoing structural (press) controls versus temporary or intermittent perturbation (pulse) controls, and one between shift preventing versus shift reversing or restorative controls. Adaptive management and the options it creates both focus on reductions in uncertainty and control policies with the flexibility to take advantage of those reductions. The various management distinctions are most easily understood by modeling the predator-urchin-kelp marine ecosystem. This paper develops a mathematical model of the ecosystem that has the potential for two different catastrophic shifts between equilibria. Pulse disturbances, originating from exogenous abiotic factors or population dynamics elsewhere in the metacommunity, can activate shifts. A measure of probabilistic resilience is developed and used as part of an assessment of the ecosystem’s sustainable stock of natural capital. With perturbation outcomes clustered around the originating equilibrium, hysteresis is activated, resulting imperfect reversibility of catastrophic shifts, and a loss in natural capital. The difficulty of reversing a shift from kelp forest to urchin barren, with an associated loss in sustainable natural capital, is an example. Management controls are modeled. I find that systemic and symptomatic, and press and pulse, controls can be complementary. Restorative controls tend to be more difficult or costly than preventative ones. Adaptive management, favoring flexible, often preventative, controls, creates option value, lowering control costs and/or losses in sustainable natural capital. Two cases are used to illustrate, Tasmania, Australia and Haida Gwaii, Canada.
Regulatory Non-Coding RNAs Modulate Transcriptional Activation During B Cell Development
Authors: Attaway Mary , Chwat-Edelstein Tzippora , Vuong Bao Q.
Published: October 2021

B cells play a significant role in the adaptive immune response by secreting immunoglobulins that can recognize and neutralize foreign antigens. They develop from hematopoietic stem cells, which also give rise to other types of blood cells, such as monocytes, neutrophils, and T cells, wherein specific transcriptional programs define the commitment and subsequent development of these different cell lineages. A number of transcription factors, such as PU.1, E2A, Pax5, and FOXO1, drive B cell development. Mounting evidence demonstrates that non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), modulate the expression of these transcription factors directly by binding to the mRNA coding for the transcription factor or indirectly by modifying cellular pathways that promote expression of the transcription factor. Conversely, these transcription factors upregulate expression of some miRNAs and lncRNAs to determine cell fate decisions. These studies underscore the complex gene regulatory networks that control B cell development during hematopoiesis and identify new regulatory RNAs that require additional investigation. In this review, we highlight miRNAs and lncRNAs that modulate the expression and activity of transcriptional regulators of B lymphopoiesis and how they mediate this regulation.
Case Report: Autoimmune Psychosis in Chromosome 22q11.2 Deletion Syndrome
Authors: Ciano-Petersen Nicolás Lundahl , Hamad-Cueto Omar , Drissi-Reyes Hania , Doña-Díaz Álvaro , García-Martín Guillermina
Published: October 2021

Chromosome 22q11.2 deletion syndrome (22q11DS) is characterized by congenital cardiac abnormalities, hypoplastic thymus, palatal abnormalities, and hypocalcemia, although other clinical features are frequent such as autoimmune and psychiatric disorders. One-third of the patients have psychotic disorders, frequently followed by developmental regression and long-term cognitive disturbances. Despite humoral and cellular immunodeficiency are common in 22q11DS, it is associated with an increased prevalence of autoimmune disorders such as idiopathic thrombocytopenic purpura and juvenile idiopathic arthritis, likely due to immune dysregulations associated with thymic abnormalities, which plays a major role in self-tolerance. We report an unique case of a 14-year-old girl with 22q11DS that presented with subacute psychotic symptoms, intolerance to antipsychotics, CSF pleocytosis, and EEG abnormalities, that was successfully treated with empiric immunotherapy after fulfilling criteria for probable seronegative autoimmune encephalitis and probable autoimmune psychosis. The autoimmune etiology of these clinical features of 22q11DS has never been postulated despite the predisposition of this syndrome to present autoimmune disorders. We suggest the systematic evaluation with serum and CSF neuronal antibodies, MRI, and EEG of patients with 22q11DS that develop subacute psychotic symptoms or rapidly progressive cognitive decline. Early immunomodulatory therapies should be carefully considered if criteria of probable autoimmune psychosis or possible autoimmune encephalitis are fulfilled, as it may prevent long-term disabilities. Further studies are required to assess the autoimmune origin of psychosis and cognitive impairment associated with 22q11DS.
Gene-Specific Sex Effects on Susceptibility to Infectious Diseases
Authors: Lipoldová Marie , Demant Peter
Published: October 2021

Inflammation is an integral part of defense against most infectious diseases. These pathogen-induced immune responses are in very many instances strongly influenced by host’s sex. As a consequence, sexual dimorphisms were observed in susceptibility to many infectious diseases. They are pathogen dose-dependent, and their outcomes depend on pathogen and even on its species or subspecies. Sex may differentially affect pathology of various organs and its influence is modified by interaction of host’s hormonal status and genotype: sex chromosomes X and Y, as well as autosomal genes. In this Mini Review we summarize the major influences of sex in human infections and subsequently focus on 22 autosomal genes/loci that modify in a sex-dependent way the response to infectious diseases in mouse models. These genes have been observed to influence susceptibility to viruses, bacteria, parasites, fungi and worms. Some sex-dependent genes/loci affect susceptibility only in females or only in males, affect both sexes, but have stronger effect in one sex; still other genes were shown to affect the disease in both sexes, but with opposite direction of effect in females and males. The understanding of mechanisms of sex-dependent differences in the course of infectious diseases may be relevant for their personalized management.
Cholesterol Regulates Exosome Release in Cultured Astrocytes
Authors: Abdullah Mohammad , Nakamura Tomohisa , Ferdous Taslima , Gao Yuan , Chen Yuxin , Zou Kun , Michikawa Makoto
Published: October 2021

Exosomes are vesicles secreted by various kinds of cells, and they are rich in cholesterol, sphingomyelin (SM), phosphatidylcholine, and phosphatidylserine. Although cellular sphingolipid-mediated exosome release has been reported, the involvement of other lipid components of cell membranes in the regulation of exosome release is poorly understood. Here, we show that the level of exosome release into conditioned media is significantly reduced in cultured astrocytes prepared from apolipoprotein E (ApoE) knock-out mice when compared to those prepared from wild-type (WT) mice. The reduced level of exosome release was accompanied by elevated levels of cellular cholesterol. The addition of cholesterol to WT astrocytes significantly increased the cellular cholesterol levels and reduced exosome release. PI3K/Akt phosphorylation was enhanced in ApoE-deficient and cholesterol-treated WT astrocytes. In contrast, the depletion of cholesterol in ApoE-deficient astrocytes due to treatment with β-cyclodextrin recovered the exosome release level to a level similar to that in WT astrocytes. In addition, the reduced levels of exosome release due to the addition of cholesterol recovered to the control levels after treatment with a PI3K inhibitor (LY294002). The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.
Short-Chain Fatty Acids Calibrate RARα Activity Regulating Food Sensitization
Authors: Yuan Xiefang , Tang Hongmei , Wu Renlan , Li Xingjie , Jiang Hongyu , Liu Zhigang , Zhang Zongde
Published: October 2021

Gut-microbiota dysbiosis links to allergic diseases. The mechanism of the exacerbation of food allergy caused by gut-microbiota dysbiosis remains unknown. Regulation of retinoic acid receptor alpha (RARα) signaling is critical for gut immune homeostasis. Here we clarified that RARα in dendritic cells (DCs) promotes Th2 cell differentiation. Antibiotics treatment stimulates retinoic acid signaling in mucosal DCs. We found microbiota metabolites short-chain fatty acids (SCFAs) maintain IGF-1 levels in serum and mesenteric lymph nodes. The IGF-1/Akt pathway is essential for regulating the transcription of genes targeted by RARα. And RARα in DCs affects type I interferon (IFN-I) responses through regulating transcription of IFN-α. Our study identifies SCFAs crosstalk with RARα in dendritic cells as a critical modulator that plays a core role in promoting Th2 cells differentiation at a state of modified/disturbed microbiome.
MALT1-Dependent Cleavage of HOIL1 Modulates Canonical NF-κB Signaling and Inflammatory Responsiveness
Authors: Fung Shan-Yu , Lu Henry Y. , Sharma Mehul , Sharma Ashish A. , Saferali Aabida , Jia Alicia , Abraham Libin , Klein Theo , Gold Michael R. , Noterangelo Luigi D. , Overall Christopher M. , Turvey Stuart E.
Published: October 2021

Nuclear factor kappa B (NF-κB) is a critical transcription factor involved in regulating cell activation, inflammation, and survival. The linear ubiquitin chain assembly complex (LUBAC) which consists of HOIL1, HOIP, and SHARPIN, catalyzes the linear ubiquitination of target proteins—a post-translational modification that is essential for NF-κB activation. Human germline pathogenic variants that dysregulate linear ubiquitination and NF-κB signaling are associated with immunodeficiency and/or autoinflammation including dermatitis, recurrent fevers, systemic inflammation and enteropathy. We previously identified MALT1 paracaspase as a novel negative regulator of LUBAC by proteolytic cleavage of HOIL1. To directly investigate the impact of HOIL1 cleavage activity on the inflammatory response, we employed a stable transduction system to express and directly compare non-cleavable HOIL1 with wild-type HOIL1 in primary HOIL1-deficient patient skin fibroblasts. We discovered that non-cleavable HOIL1 resulted in enhanced NF-κB signaling in response to innate stimuli. Transcriptomics revealed enrichment of inflammation and proinflammatory cytokine-related pathways after stimulation. Multiplexed cytokine assays confirmed a ‘hyperinflammatory’ phenotype in these cells. This work highlights the physiological importance of MALT1-dependent cleavage and modulation of HOIL1 on NF-κB signaling and inflammation, provides a mechanism for the autoinflammation observed in MALT1-deficient patients, and will inform the development of therapeutics that target MALT1 paracaspase and LUBAC function in treating autoinflammatory skin diseases.
Environmental Considerations for the Management of the Bivalve Fisheries of Bahía Magdalena (Mexico), a Coastal Lagoon at the Southern End of the California Current
Authors: Jiménez-Quiroz María del Carmen , Barrón-Barraza Francisco Javier , Cervantes-Duarte Rafael , Funes-Rodríguez René
Published: October 2021

This study presents an overview of bivalve assemblages in Bahia Magdalena (BM, México) and the possible impact of environmental variability on these populations, constantly stressed by fishing. This lagoon is responsible for a high proportion of harvest of regional bivalves. First, we list the bivalve species reported in public biogeographic databases. Based on eight commercially exploited species, we described the composition of the bivalve assemblage and its biological characteristics, the history of fishery, and environmental variability in the marine area adjacent to the lagoon (1970–2019) and the habitat of bivalves (2002–2020). Sources of data were public databases and published literature. The enlisted species (n = 184) belong to six orders, and most are small and infaunal, but the structure of the assemblage is unknown. The fisheries began at different times and focused on the most valuable resources. Almost all harvest of bivalves had wide variations because of intensive fishing and a weak regulation frame. After 2015, the main resources were the Pacific wing-oyster (a new resource since 2017) and the geoduck clam due to the declining abundance of other resources (e.g., pen shells, Pacific calico scallop). There was a warming trend in the region since the 1970's, but the strongest El Niño-Southern Oscillation (ENSO) phases caused the most notable changes before 2013; after that year, a combination of large-scale phenomena increased the temperature significantly. The trend of chlorophyll-a abundance negatively correlated with temperature, but there was an almost constant supply of particulate organic matter in the interior of Bahia Magdalena (BM). After 2015, the quality of lagoon water gradually deteriorated, and in 2017 and 2019, harmful algal blooms developed, but the impact was not fully assessed. The challenges faced by the fishery are multiple (institutional weakness and regional warming); however, permanent monitoring programs of environmental conditions and critical biological variables should be implemented to design scenarios that allow fishery sustainability.
Dynamic Regulation of Ions and Amino Acids in Adult Asian Hard Clams Meretrix lusoria Upon Hyperosmotic Salinity
Authors: Lin Chia-Hao , Yeh Po-Ling , Wang Yu-Chun , Lee Tsung-Han
Published: October 2021

The dynamic regulation of ions and amino acids in the gills and mantle of the Asian hard clam, Meretrix lusoria, following the exposure to a hyperosmotic environment was hitherto unclear. The present study revealed that the osmolality as well as the Na+ and Cl– concentrations in the hemolymph were significantly increased 3 h after transferring the clams from an environment with the salinity of their natural habitat (brackish water; BW; 20‰) to one with hyperosmotic salinity (seawater; 35‰). In addition, we found that the specific activities of Na+/K+-ATPase, a key enzyme that plays a significant role in cell osmoregulation, in the gills and mantle of clams were significantly increased at 72 and 12 h post-transfer, respectively, during acclimation to hyperosmotic salinity. Similarly, the contents of free amino acids (FAAs) such as taurine, alanine, and glycine were significantly elevated during hyperosmotic salinity acclimation. Previous research indicates that taurine is the most abundant FAA in the gills and mantles of Asian hard clams and that the taurine transporter (TAUT) plays an important role in taurine accumulation. The present study showed that TAUT mRNA and protein expression were significantly and transiently increased in the mantle of Asian hard clams following exposure to seawater; although the expression of TAUT mRNA in the gills of Asian hard clams was also transiently stimulated by exposure to hyperosmotic salinity, the relative TAUT protein abundance decreased only at later stages. Accordingly, the findings of this study improve our understanding of the dynamic processes of ion and amino acid regulation in the peripheral tissues of bivalves under hyperosmotic stress.
Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries: The Pathfinder Feasibility Trial
Authors: Shanker Akshay , Abel John H. , Narayanan Shilpa , Mathur Pooja , Work Erin , Schamberg Gabriel , Sharkey Aidan , Bose Ruma , Rangasamy Valluvan , Senthilnathan Venkatachalam , Brown Emery N. , Subramaniam Balachundhar
Published: October 2021

Multimodal general anesthesia (MMGA) is a strategy that utilizes the well-known neuroanatomy and neurophysiology of nociception and arousal control in designing a rational and clinical practical paradigm to regulate the levels of unconsciousness and antinociception during general anesthesia while mitigating side effects of any individual anesthetic. We sought to test the feasibility of implementing MMGA for seniors undergoing cardiac surgery, a high-risk cohort for hemodynamic instability, delirium, and post-operative cognitive dysfunction. Twenty patients aged 60 or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries were enrolled in this non-randomized prospective observational feasibility trial, wherein we developed MMGA specifically for cardiac surgeries. Antinociception was achieved by a combination of intravenous remifentanil, ketamine, dexmedetomidine, and magnesium together with bupivacaine administered as a pecto-intercostal fascial block. Unconsciousness was achieved by using electroencephalogram (EEG)-guided administration of propofol along with the sedative effects of the antinociceptive agents. EEG-guided MMGA anesthesia was safe and feasible for cardiac surgeries, and exploratory analyses found hemodynamic stability and vasopressor usage comparable to a previously collected cohort. Intraoperative EEG suppression events and postoperative delirium were found to be rare. We report successful use of a total intravenous anesthesia (TIVA)-based MMGA strategy for cardiac surgery and establish safety and feasibility for studying MMGA in a full clinical trial.

Clinical Trial Number:www.clinicaltrials.gov; identifier NCT04016740 (https://clinicaltrials.gov/ct2/show/NCT04016740).
Design and Validation of a Multi-Point Injection Technology for MR-Guided Convection Enhanced Delivery in the Brain
Authors: Prezelski Kayla , Keiser Megan , Stein Joel M. , Lucas Timothy H. , Davidson Beverly , Gonzalez-Alegre Pedro , Vitale Flavia
Published: October 2021

Convection enhanced delivery (CED) allows direct intracranial administration of neuro-therapeutics. Success of CED relies on specific targeting and broad volume distributions (VD). However, to prevent off-target delivery and tissue damage, CED is typically conducted with small cannulas and at low flow rates, which critically limit the maximum achievable VD. Furthermore, in applications such as gene therapy requiring injections of large fluid volumes into broad subcortical regions, low flow rates translate into long infusion times and multiple surgical trajectories. The cannula design is a major limiting factor in achieving broad VD, while minimizing infusion time and backflow. Here we present and validate a novel multi-point cannula specifically designed to optimize distribution and delivery time in MR-guided intracranial CED of gene-based therapeutics. First, we evaluated the compatibility of our cannula with MRI and common viral vectors for gene therapy. Then, we conducted CED tests in agarose brain phantoms and benchmarked the results against single-needle delivery. 3T MRI in brain phantoms revealed minimal susceptibility-induced artifacts, comparable to the device dimensions. Benchtop CED of adeno-associated virus demonstrated no viral loss or inactivation. CED in agarose brain phantoms at 3, 6, and 9 μL/min showed >3x increase in volume distribution and 60% time reduction compared to single-needle delivery. This study confirms the validity of a multi-point delivery approach for improving infusate distribution at clinically-compatible timescales and supports the feasibility of our novel cannula design for advancing safety and efficacy of MR-guided CED to the central nervous system.
Predominant Biphenyl Dioxygenase From Legacy Polychlorinated Biphenyl (PCB)-Contaminated Soil Is a Part of Unusual Gene Cluster and Transforms Flavone and Flavanone
Authors: Suman Jachym , Strejcek Michal , Zubrova Andrea , Capek Jan , Wald Jiri , Michalikova Klara , Hradilova Miluse , Sredlova Kamila , Semerad Jaroslav , Cajthaml Tomas , Uhlik Ondrej
Published: October 2021

In this study, the diversity of bphA genes was assessed in a 13C-enriched metagenome upon stable isotope probing (SIP) of microbial populations in legacy PCB-contaminated soil with 13C-biphenyl (BP). In total, 13 bphA sequence variants (SVs) were identified in the final amplicon dataset. Of these, one SV comprised 59% of all sequences, and when it was translated into a protein sequence, it exhibited 87, 77.4, and 76.7% identity to its homologs from Pseudomonas furukawaii KF707, Cupriavidus sp. WS, and Pseudomonas alcaliphila B-367, respectively. This same BphA sequence also contained unusual amino acid residues, Alanine, Valine, and Serine in region III, which had been reported to be crucial for the substrate specificity of the corresponding biphenyl dioxygenase (BPDO), and was accordingly designated BphA_AVS. The DNA locus of 18 kbp containing the BphA_AVS-coding sequence retrieved from the metagenome was comprised of 16 ORFs and was most likely borne by Paraburkholderia sp. The BPDO corresponding to bphAE_AVS was cloned and heterologously expressed in E. coli, and its substrate specificity toward PCBs and a spectrum of flavonoids was assessed. Although depleting a rather narrow spectrum of PCB congeners, the efficient transformation of flavone and flavanone was demonstrated through dihydroxylation of the B-ring of the molecules. The homology-based functional assignment of the putative proteins encoded by the rest of ORFs in the AVS region suggests their potential involvement in the transformation of aromatic compounds, such as flavonoids. In conclusion, this study contributes to the body of information on the involvement of soil-borne BPDOs in the metabolism of flavonoid compounds, and our paper provides a more advanced context for understanding the interactions between plants, microbes and anthropogenic compounds in the soil.
Cultivar Contributes to the Beneficial Effects of Bacillus subtilis PTA-271 and Trichoderma atroviride SC1 to Protect Grapevine Against Neofusicoccum parvum
Authors: Leal Catarina , Richet Nicolas , Guise Jean-François , Gramaje David , Armengol Josep , Fontaine Florence , Trotel-Aziz Patricia
Published: October 2021

Grapevine trunk diseases (GTDs) are a big threat for global viticulture. Without effective chemicals, biocontrol strategies are developed as alternatives to better cope with environmental concerns. A combination of biological control agents (BCAs) could even improve sustainable disease management through complementary ways of protection. In this study, we evaluated the combination ofBacillus subtilis(Bs) PTA-271 andTrichoderma atroviride(Ta) SC1 for the protection of Chardonnay and Tempranillo rootlings againstNeofusicoccum parvumBt67, an aggressive pathogen associated to Botryosphaeria dieback (BD). Indirect benefits offered by each BCA and their combination were then characterizedin planta, as well as their direct benefitsin vitro. Results provide evidence that (1) the cultivar contributes to the beneficial effects ofBsPTA-271 andTaSC1 againstN. parvum, and that (2) thein vitroBCA mutual antagonism switches to the strongest fungistatic effect towardNp-Bt67 in a three-way confrontation test. We also report for the first time the beneficial potential of a combination of BCA againstNp-Bt67 especially in Tempranillo. Our findings highlight a common feature for both cultivars: salicylic acid (SA)-dependent defenses were strongly decreased in plants protected by the BCA, in contrast with symptomatic ones. We thus suggest that (1) the high basal expression of SA-dependent defenses in Tempranillo explains its highest susceptibility toN. parvum, and that (2) the cultivar-specific responses to the beneficialBsPTA-271 andTaSC1 remain to be further investigated.
Preponderance of blaKPC-Carrying Carbapenem-Resistant Enterobacterales Among Fecal Isolates From Community Food Handlers in Kuwait
Authors: Moghnia Ola H. , Rotimi Vincent O. , Al-Sweih Noura A.
Published: October 2021

Carbapenem-resistant Enterobacterales (CRE) are pathogens that have been found in several countries, with a significant public health concern. Characterizing the mode of resistance and determining the prevailing clones are vital to the epidemiology of CRE in our community. This study was conducted to characterize the molecular mode of resistance and to determine the clonality of the CRE fecal isolates among community food handlers (FHs) vs. infected control patients (ICPs) in Kuwait. Fecal CRE isolates obtained from FHs and ICPs from September 2016 to September 2018 were analyzed for their resistance genes. Gene characterization was carried out by polymerase chain reaction (PCR) assays and sequencing. Clonality of isolates was established by multilocus sequence typing (MLST). Of the 681 and 95 isolates of the family Enterobacterales isolated from FHs and ICPs, 425 (62.4%) and 16 (16.8%) were Escherichia coli, and 18 (2.6%) and 69 (72.6%) were Klebsiella pneumoniae, respectively. A total of 36 isolates were CRE with a prevalence of 5.3% among FH isolates and 87 (91.6%) among the ICPs. Of these, carbapenemase genes were detected in 22 (61.1%) and 65 (74.7%) isolates, respectively (p < 0.05). The detected specific genes among FHs and ICPs were positive for blaKPC 19 (86.4%) and 35 (40.2%), and blaOXA 10 (45.5%) and 59 (67.8%), in addition to blaNDM 2 (9.1%) and 32 (36.8%), respectively. MLST assays of the E. coli and K. pneumoniae isolates revealed considerable genetic diversity and polyclonality as well as demonstrated multiple known ST types and eight novel sequence types. The study revealed a relatively high number of CRE harboring predominantly blaKPC-mediated CRE among the community FH isolates vs. predominant blaOXA genes among the ICPs. Those heterogeneous CRE isolates raise concerns and mandate more efforts toward molecular surveillance. A multinational study is recommended to monitor the spread of genes mediating CRE in the community of Arabian Peninsula countries.
Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome
Authors: Zhao Jing , Lu Qing-Bin , Li Hao , Yuan Yang , Cui Ning , Yuan Chun , Zhang Xiao-Ai , Yang Zhen-Dong , Ruan Shi-Man , Liu Lan-Zheng , Du Juan , Fang Li-Qun , Liu Wei
Published: October 2021

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities.

Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011–2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way.

Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00–1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75–8.84) vs. 5.30 (3.54–7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40–2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16–4.46) in ≤60 years, to 2.06 (1.34–3.18) in 60–70 years and further to 1.55 (0.97–2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female.

Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.
Transcriptomic and Ultrastructural Analyses of Pyricularia Oryzae Treated With Fungicidal Peptaibol Analogs of Trichoderma Trichogin
Authors: Sella Luca , Govind Rakshita , Caracciolo Rocco , Quarantin Alessandra , Vu Van V. , Tundo Silvio , Nguyen Hung Minh , Favaron Francesco , Musetti Rita , De Zotti Marta
Published: October 2021

Eco-friendly analogs of Trichogin GA IV, a short peptaibol produced by Trichoderma longibrachiatum, were assayed against Pyricularia oryzae, the causal agent of rice blast disease. In vitro and in vivo screenings allowed us to identify six peptides able to reduce by about 70% rice blast symptoms. One of the most active peptides was selected for further studies. Microscopy analyses highlighted that the treated fungal spores could not germinate and the fluorescein-labeled peptide localized on the spore cell wall and in the agglutinated cytoplasm. Transcriptomic analysis was carried out on P. oryzae mycelium 3 h after the peptide treatment. We identified 1,410 differentially expressed genes, two-thirds of which upregulated. Among these, we found genes involved in oxidative stress response, detoxification, autophagic cell death, cell wall biogenesis, degradation and remodeling, melanin and fatty acid biosynthesis, and ion efflux transporters. Molecular data suggest that the trichogin analogs cause cell wall and membrane damages and induce autophagic cell death. Ultrastructure observations on treated conidia and hyphae confirmed the molecular data. In conclusion, these selected peptides seem to be promising alternative molecules for developing effective bio-pesticides able to control rice blast disease.
Harmonisation and Between-Country Differences of the Lifetime of Experiences Questionnaire in Older Adults
Authors: Ourry Valentin , Marchant Natalie L. , Schild Ann-Katrin , Coll-Padros Nina , Klimecki Olga M. , Krolak-Salmon Pierre , Goldet Karine , Reyrolle Leslie , Bachelet Romain , Sannemann Lena , Meiberth Dix , Demnitz-King Harriet , Whitfield Tim , Botton Maëlle , Lebahar Julie , Gonneaud Julie , de Flores Robin , Molinuevo José Luis , Jessen Frank , Vivien Denis , de la Sayette Vincent , Valenzuela Michael J. , Rauchs Géraldine , Wirth Miranka , Chételat Gaël , Arenaza-Urquijo Eider M. ,   The Medit-Ageing Research Group
Published: October 2021

Background: The Lifetime of Experiences Questionnaire (LEQ) assesses complex mental activity across the life-course and has been associated with brain and cognitive health. The different education systems and occupation classifications across countries represent a challenge for international comparisons. The objectives of this study were four-fold: to adapt and harmonise the LEQ across four European countries, assess its validity across countries, explore its association with brain and cognition and begin to investigate between-country differences in life-course mental activities.

Method: The LEQ was administered to 359 cognitively unimpaired older adults (mean age and education: 71.2, 13.2 years) from IMAP and EU-funded Medit-Ageing projects. Education systems, classification of occupations and scoring guidelines were adapted to allow comparisons between France, Germany, Spain and United Kingdom. We assessed the LEQ's (i) concurrent validity with a similar instrument (cognitive activities questionnaire - CAQ) and its structural validity by testing the factors' structure across countries, (ii) we investigated its association with cognition and neuroimaging, and (iii) compared its scores between countries.

Results: The LEQ showed moderate to strong positive associations with the CAQ and revealed a stable multidimensional structure across countries that was similar to the original LEQ. The LEQ was positively associated with global cognition. Between-country differences were observed in leisure activities across the life-course.

Conclusions: The LEQ is a promising tool for assessing the multidimensional construct of cognitive reserve and can be used to measure socio-behavioural determinants of cognitive reserve in older adults across countries. Longitudinal studies are warranted to test further its clinical utility.