bluuebunny/crossref_metadata_2025 huggingface dataset:
High Prevalence of HIV-Related Cryptococcosis and Increased Resistance to Fluconazole of the Cryptococcus neoformans Complex in Jiangxi Province, South Central China
Authors: Yang Chunxi , Bian Zeyuan , Blechert Oliver , Deng Fengyi , Chen Hui , Li Yueting , Yang Yunhong , Chen Min , Zhan Ping
Published: November 2021

Background

Cryptococcosis is caused by a fungi of the Cryptococcus neoformans/Cryptococcus gattii complex and is a severe concern for public health worldwide. C. neoformans species are globally distributed, and C. gattii species are mostly found in America, Australia, and Sub-Saharan Africa. Cryptococcus usually infects an immunocompromised population; however, the majority of cryptococcosis in China has been reported in patients without any recognizable immunosuppression, i.e., HIV infection. To date, very few studies investigated this disease in South Central China.

Methods

The present study recruited 230 clinically suspected cryptococcosis cases in the last 5 years at two hospitals in Jiangxi Province, South Central China. All isolated strains were subjected to multilocus sequence typing (MLST) and phylogenetic analysis. Serotype and mating type were assessed by PCR, in vitro antifungal susceptibility was assessed by the CLSI-M27-A3 protocol.

Results

A total of 230 patients were identified as infected by C. neoformans, including 12 cases with Talaromyces marneffei coinfection. All seven MLST markers were successfully amplified and used to identify the ST genotype in 199 strains. C. gattii strains were not detected. In contrast to previous studies, 59.3% of the patients had an immunocompromised status, and 61.9% of these patients were infected with HIV. All isolates manifested serotype A and mating type α. The ST5 genotype was common (89.5%) in the Jiangxi region, and three novel genotypes (ST656, ST657, and ST658 in six isolates) were detected in the present study. A total of 86 of the isolates (43.2%) were not sensitive to fluconazole at a MIC50 ≥ 8 μg/ml, most of the isolates were resistant to amphotericin B, and nearly all isolates were resistant to itraconazole and posaconazole. Resistances to 5-Flucytosine and voriconazole were very rare.

Conclusions

The results of the present study indicated that C. neoformans is the predominant species for cryptococcosis in Jiangxi Province, and a large proportion of the strains were not sensitive to fluconazole, which may be related to treatment failure and relapse. A high percentage of HIV-related C. neoformans infections was reported in Jiangxi, supporting a previous hypothesis that cryptococcosis is more frequent among the HIV-infected population in China. Continuous monitoring of species distribution and antifungal sensitivity is important for the investigation of this severe disease in the Jiangxi region.
Circulating Vascular Cell Adhesion Molecule-1 (sVCAM-1) Is Associated With Left Atrial Remodeling in Long-Distance Runners
Authors: Contreras-Briceño Felipe , Herrera Sebastián , Vega-Adauy Julian , Salinas Manuel , Ocaranza María Paz , Jalil Jorge E. , Mandiola Jorge , García Lorena , Chiong Mario , Castro Pablo F. , Lavandero Sergio , Gabrielli Luigi
Published: November 2021

Introduction: An increased risk of atrial fibrillation (AF) has been demonstrated in high-performance athletes. Soluble vascular adhesion molecule-1 (sVCAM-1), a biomarker involved in inflammation and cardiac remodeling, is associated with the development of AF in the general population. However, the relationship between sVCAM-1 and left atrial (LA) remodeling has been poorly investigated in long-distance runners (LDR).

Aim: To determine the association between LA remodeling and sVCAM-1 levels in LDR during the training period before a marathon race.

Methods: Thirty-six healthy male LDR (37.0 ± 5.3 years; 174.0 ± 7.0 height; BMI: 23.8 ± 2.8; V°O2-peak: 56.5 ± 7.3 mL·kg−1·min−1) were evaluated in this single-blind and cross-sectional study. The LDR were separated into two groups according to previous training levels: high-training (HT) (n = 18) ≥100 km·week−1 and low-training (LT) (n = 18) ≥70 and <100 km·week−1. Also, 18 healthy non-active subjects were included as a control group (CTR). In all participants, transthoracic echocardiography was performed. sVCAM-1 blood levels were measured baseline and immediately finished the marathon race in LDR.

Results: HT showed increased basal levels of sVCAM-1 (651 ± 350 vs. 440 ± 98 ng·mL−1 CTR, p = 0.002; and vs. 533 ± 133 ng·mL−1 LT; p = 0.003) and a post-marathon increase (ΔsVCAM-1) (651 ± 350 to 905 ± 373 ng·mL−1; p = 0.002), that did not occur in LT (533 ± 133 to 651 ± 138 ng·mL−1; p = 0.117). In LDR was a moderate correlation between LA volume and sVCAM-1 level (rho = 0.510; p = 0.001).

Conclusions: In male long-distance runners, sVCAM-1 levels are directly associated with LA remodeling. Also, the training level is associated with basal sVCAM-1 levels and changes after an intense and prolonged exercise (42.2 km). Whether sVCAM-1 levels predict the risk of AF in runners remains to be established.
Screening for Asymptomatic Coronary Artery Disease via Exercise Stress Testing in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Dun Yaoshan , Wu Shaoping , Cui Ni , Thomas Randal J. , Olson Thomas P. , Zhou Nanjiang , Li Qiuxia , Liu Suixin
Published: November 2021

Objectives: This meta-analysis aims to investigate the diagnostic value of exercise stress testing (EST) for asymptomatic coronary artery disease (CAD) among patients with type 2 diabetes mellitus (T2DM) and to ascertain the influence of different variables on the sensitivity and specificity of EST.

Background: Asymptomatic CAD occurs in >1 in five diabetes mellitus patients, and it is associated with an increased risk of complications. Methods for screening asymptomatic CAD in T2DM patients are still not unified.

Methods: MEDLINE (via Ovid), Embase (via Ovid), Cochrane Library, SCOPUS, PubMed, Ovid, EBSCO ASP, and Web of Science were systematically searched on June 8 and 9, 2021, for diagnostic cohort and case-control studies. We included studies that used EST to screen for CAD in asymptomatic patients with T2DM, and that used coronary angiography to diagnose CAD and had reported the basic diagnostic indicators. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess study quality. The combined effect sizes were calculated by overall analysis and multiple variable effects were explored by regression analysis and subgroup analysis.

Results: Nine groups of data from eight diagnostic cohort studies, totaling 515 participants, were included. Included studies showed a low risk of bias in most items, except for flow and timing. The combined sensitivity and specificity of EST for asymptomatic CAD in patients with T2DM were 55 (48 to 61%) and 66 (61 to 70%), respectively. When non-diagnostic tests were excluded, sensitivity increased to 73 (56 to 88%). The proportion receiving angiography also significantly affected sensitivity. No significant difference was found in the duration of diabetes or other additional risk factors.

Conclusions: EST is a tool of moderate sensitivity and specificity to be used for the initial screening of asymptomatic CAD in T2DM. It has the advantage of being non-invasive, relatively inexpensive, easily available in most settings, and has no radiation associated with its use. Additional research with higher quality studies in which tests that are non-diagnostic are included and flow and timing is described clearly, will be important to further our understanding of EST for asymptomatic CAD detection in patients with T2DM.

Systematic review registration: PROSPERO CRD42021259555.
Early Warning Indicators of Landslides Based on Deep Displacements: Applications on Jinping Landslide and Wendong Landslide, China
Authors: Chen He , Li Guo , Fang Rui , Zheng Min
Published: November 2021

Real-time monitoring and early warning have great significance in reducing/avoiding the consequences caused by landslides. The deep displacement-based monitoring method has been proven to be a suitable solution for landslide risk management. However, the early warning indicators based on the deep displacement method need to be fully understood. This paper reports on an investigation into early warning indicators and deformation monitoring of several natural landslides. A series of indicators using the profiles of the accumulative displacement, kinetic energy, and their rates against time for early warning are developed and calibrated by monitoring and analyzing a natural landslide. The early warning indicators are then applied to monitor and identify the different deformation stages of the Jinping County North Landslide and the Wendong Town Landslide.
Hypothesis and Theory: Evaluating the Co-Evolution of the Melanocortin-2 Receptor and the Accessory Protein MRAP1
Authors: Dores Robert M. , Chapa Emilia
Published: November 2021

The melanocortin receptors (MCRs) and the MRAP accessory proteins belong to distinct gene families that are unique to the chordates. During the radiation of the chordates, the melancortin-2 receptor paralog (MC2R) and the MRAP1 paralog (melanocortin-2 receptor accessory protein 1) have co-evolved to form a heterodimer interaction that can influence the ligand selectivity and trafficking properties of MC2R. This apparently spontaneous interaction may have begun with the ancestral gnathostomes and has persisted in both the cartilaginous fishes and the bony vertebrates. The ramifications of this interaction had profound effects on the hypothalamus/anterior pituitary/adrenal-interrenal axis of bony vertebrates resulting in MC2R orthologs that are exclusively selective for the anterior pituitary hormone, ACTH, and that are dependent on MRAP1 for trafficking to the plasma membrane. The functional motifs within the MRAP1 sequence and their potential contact sites with MC2R are discussed. The ramifications of the MC2R/MRAP1 interaction for cartilaginous fishes are also discussed, but currently the effects of this interaction on the hypothalamus/pituitary/interrenal axis is less clear. The cartilaginous fish MC2R orthologs have apparently retained the ability to be activated by either ACTH or MSH-sized ligands, and the effect of MRAP1 on trafficking varies by species. In this regard, the possible origin of the dichotomy between cartilaginous fish and bony vertebrate MC2R orthologs with respect to ligand selectivity and trafficking properties is discussed in light of the evolution of functional amino acid motifs within MRAP1.
Quantitative Genetics of Smoltification Status at the Time of Seawater Transfer in Atlantic Salmon (Salmo Salar)
Authors: Khaw Hooi Ling , Gjerde Bjarne , Boison Solomon A. , Hjelle Elise , Difford Gareth F.
Published: November 2021

High mortality during grow out in the sea is a challenge for farmed Atlantic salmon production in Norway and globally, which is partly attributed to suboptimal smolt quality. In this study, two groups of pre-smolts were put on a standard light smoltification regime with alternating 12L:12D per day for 6 weeks (Phase I), followed by 24L:0D per day for 6 weeks (Phase II); one group was 0 + smolt (EXP1) and the other 1 + smolt (EXP2). To monitor the smoltification status of the fish, 100 (EXP1) and 60 (EXP2) fish were randomly sampled per week during Phase II. The following phenotypes for smoltification status were studied: RT-qPCR relative mRNA expression of values of two alpha catalytic subunits of the variants of the Na+K+ATPase (NKA) expressed in the sampled gill tissues of each fish. The first variant, alpha1a with increased expression in freshwater (FW) and the second variant alpha1b with increased expression in seawater variant (SW), as well as their ratio SW/FW. At the optimal time for seawater transfer based on the SW/FW trait, 1,000 (at sixth sampling of EXP1) and 1,500 (at fifth sampling of EXP2) fish were sampled for genetic parameter estimation. The individual variation in FW, SW, and SW/FW was very large at each of the seven samplings indicating a large variation among individuals in the optimum time of transfer to seawater. SW/FW showed significant genetic variation in both 0+ and 1+ smolts, which indicates the possibility for selection for improved synchronization of smoltification status of Atlantic salmon at the time where the largest proportion of the fish is considered to be smolt. However, the genetic correlation between SW/FW of 0+ and 1+ was not significantly different from zero indicating very little shared genetic variation in SW/FW in 0+ and 1+ fish. Smoltification phenotypes showed temporal progression over the smoltification period, and this progression varied between 0+ and 1+ smolt highlighting the importance of correctly timing the major sampling point, and when cohorts are transferred to seawater. This also highlighted the need for further research into noninvasive methods of objectively measuring individual smoltification through time and subsequent smolt survival and growth rate at sea.
Association Between RSK2 and Clinical Indexes of Primary Breast Cancer: A Meta-Analysis Based on mRNA Microarray Data
Authors: Zheng Kun , Yao Shuo , Yao Wei , Li Qianxia , Wang Yali , Zhang Lili , Chen Xiuqiong , Xiong Huihua , Yuan Xianglin , Wang Yihua , Zou Yanmei , Xiong Hua
Published: November 2021

Background: Although ribosomal protein S6 kinases, 90 kDa, polypeptide 3 (RSK2, RPS6KA3) has been reported to play an important role in cancer cell proliferation, invasion, and migration, including breast cancer, its clinical implication in primary breast cancer patients is not well understood, and there were not many studies to explore the relationship between RSK2 and breast cancer on a clinical level.

Methods: A systematic series matrix file search uploaded from January 1, 2008 to November 31, 2017 was undertaken using ArrayExpress and Gene Expression Omnibus (GEO) databases. Search filters were breast cancer, RNA assay, and array assay. Files eligible for inclusion met the following criteria: a) sample capacity is over 100, b) tumor sample comes from unselected patient’s primary breast tumor tissue, and c) expression of RSK2 and any clinical parameters of patients were available from the files. We use median as the cutoff value to assess the association between the expression of RSK2 and the clinical indexes of breast cancer patients.

Finding: The meta-analysis identified 13 series matrix files from GEO database involving 3,122 samples that come from patients’ primary breast cancer tissue or normal tissue. The expression of RSK2 in tumor tissues is lower than that in normal tissues [odds ratio (OR), 0.54; 95% credible interval (CI), 0.44–0.67; Cochran’s Q test p = 0.14; I2 = 41.7%]. Patients with a high expression of RSK2 showed more favorable overall survival [hazard ratio (HR), 0.71; 95% CI, 0.49–0.94; Cochran’s Q test p = 0.95; I2 = 0.0%] and less potential of distant metastasis (OR, 0.59; 95% CI, 0.41–0.87; Cochran’s Q test p = 0.88; I2 = 0.0%) and lymph node infiltration (OR, 0.81; 95% CI, 0.65–0.998; Cochran’s Q test p = 0.09; I2 = 42.8%). Besides, the expression of RSK2 in luminal breast cancer is lower than Cochran’s Q test p = 0.06; I2 = 63.5%). RSK2 overexpression corresponded with higher histological grade (OR, 1.329; 95% CI, 1.03–1.721; Cochran’s Q test p = 0.69; I2 = 0.0%). RSK2 expression is also associated with estrogen receptor (ER) and age.

Conclusion: The meta-analysis provides evidence that RSK2 is a potential biomarker in breast cancer patients. The expression of RSK2 is distinctive in different intrinsic subtypes of breast cancer, indicating that it may play an important role in specific breast cancer. Further study is needed to uncover the mechanism of RSK2 in breast cancer.

Systematic Review Registration: (website), identifier (registration number).
Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain
Authors: Vassallo Amy , Shajahan Sultana , Harris Katie , Hallam Laura , Hockham Carinna , Womersley Kate , Woodward Mark , Sheel Meru
Published: November 2021

Since the start of the COVID-19 pandemic there has been a global call for sex/gender-disaggregated data to be made available, which has uncovered important findings about COVID-19 testing, incidence, severity, hospitalisations, and deaths. This mini review scopes the evidence base for efficacy, effectiveness, and safety of COVID-19 vaccines from both experimental and observational research, and asks whether (1) women and men were equally recruited and represented in vaccine research, (2) the outcomes of studies were presented or analysed by sex and/or gender, and (3) there is evidence of sex and/or gender differences in outcomes. Following a PubMed search, 41 articles were eligible for inclusion, including seven randomised controlled trials (RCTs), 11 cohort studies, eight cross-sectional surveys, eight routine surveillance studies, and seven case series. Overall, the RCTs contained equal representation of women and men; however, the observational studies contained a higher percentage of women. Of 10 studies with efficacy data, only three (30%) presented sex/gender-disaggregated results. Safety data was included in 35 studies and only 12 (34%) of these presented data by sex/gender. For those that did present disaggregated data, overall, the majority of participants reporting adverse events were women. There is a paucity of reporting and analysis of COVID-19 vaccine data by sex/gender. Research should be designed in a gender-sensitive way to present and, where possible analyse, data by sex/gender to ensure that there is a robust and specific evidence base of efficacy and safety data to assist in building public confidence and promote high vaccine coverage.
COVID-19 Mechanisms in the Human Body—What We Know So Far
Authors: Kumar Ashutosh , Narayan Ravi K. , Prasoon Pranav , Kumari Chiman , Kaur Gurjot , Kumar Santosh , Kulandhasamy Maheswari , Sesham Kishore , Pareek Vikas , Faiq Muneeb A. , Pandey Sada N. , Singh Himanshu N. , Kant Kamla , Shekhawat Prakash S. , Raza Khursheed , Kumar Sujeet
Published: November 2021

More than one and a half years have elapsed since the commencement of the coronavirus disease 2019 (COVID-19) pandemic, and the world is struggling to contain it. Being caused by a previously unknown virus, in the initial period, there had been an extreme paucity of knowledge about the disease mechanisms, which hampered preventive and therapeutic measures against COVID-19. In an endeavor to understand the pathogenic mechanisms, extensive experimental studies have been conducted across the globe involving cell culture-based experiments, human tissue organoids, and animal models, targeted to various aspects of the disease, viz., viral properties, tissue tropism and organ-specific pathogenesis, involvement of physiological systems, and the human immune response against the infection. The vastly accumulated scientific knowledge on all aspects of COVID-19 has currently changed the scenario from great despair to hope. Even though spectacular progress has been made in all of these aspects, multiple knowledge gaps are remaining that need to be addressed in future studies. Moreover, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged across the globe since the onset of the first COVID-19 wave, with seemingly greater transmissibility/virulence and immune escape capabilities than the wild-type strain. In this review, we narrate the progress made since the commencement of the pandemic regarding the knowledge on COVID-19 mechanisms in the human body, including virus–host interactions, pulmonary and other systemic manifestations, immunological dysregulations, complications, host-specific vulnerability, and long-term health consequences in the survivors. Additionally, we provide a brief review of the current evidence explaining molecular mechanisms imparting greater transmissibility and virulence and immune escape capabilities to the emerging SARS-CoV-2 variants.
Targeting Macrophage Dysregulation for Viral Infections: Novel Targets for Immunomodulators
Authors: Reece Monica D. , Taylor Ruby R. , Song Colin , Gavegnano Christina
Published: November 2021

A major barrier to human immunodeficiency virus (HIV-1) cure is the latent viral reservoir, which persists despite antiretroviral therapy (ART), including across the non-dividing myeloid reservoir which is found systemically in sanctuary sites across tissues and the central nervous system (CNS). Unlike activated CD4+ T cells that undergo rapid cell death during initial infection (due to rapid viral replication kinetics), viral replication kinetics are delayed in non-dividing myeloid cells, resulting in long-lived survival of infected macrophages and macrophage-like cells. Simultaneously, persistent inflammation in macrophages confers immune dysregulation that is a key driver of co-morbidities including cardiovascular disease (CVD) and neurological deficits in people living with HIV-1 (PLWH). Macrophage activation and dysregulation is also a key driver of disease progression across other viral infections including SARS-CoV-2, influenza, and chikungunya viruses, underscoring the interplay between macrophages and disease progression, pathogenesis, and comorbidity in the viral infection setting. This review discusses the role of macrophages in persistence and pathogenesis of HIV-1 and related comorbidities, SARS-CoV-2 and other viruses. A special focus is given to novel immunomodulatory targets for key events driving myeloid cell dysregulation and reservoir maintenance across a diverse array of viral infections.
Refractory Gastroesophageal Reflux Disease: A Management Update
Authors: Rettura Francesco , Bronzini Francesco , Campigotto Michele , Lambiase Christian , Pancetti Andrea , Berti Ginevra , Marchi Santino , de Bortoli Nicola , Zerbib Frank , Savarino Edoardo , Bellini Massimo
Published: November 2021

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.
Diversity and Biogeography of Bathyal and Abyssal Seafloor Bacteria and Archaea Along a Mediterranean—Atlantic Gradient
Authors: Trouche Blandine , Brandt Miriam I. , Belser Caroline , Orejas Covadonga , Pesant Stéphane , Poulain Julie , Wincker Patrick , Auguet Jean-Christophe , Arnaud-Haond Sophie , Maignien Loïs
Published: November 2021

Seafloor sediments cover the majority of planet Earth and microorganisms inhabiting these environments play a central role in marine biogeochemical cycles. Yet, description of the biogeography and distribution of sedimentary microbial life is still too sparse to evaluate the relative contribution of processes driving this distribution, such as the levels of drift, connectivity, and specialization. To address this question, we analyzed 210 archaeal and bacterial metabarcoding libraries from a standardized and horizon-resolved collection of sediment samples from 18 stations along a longitudinal gradient from the eastern Mediterranean to the western Atlantic. Overall, we found that biogeographic patterns depended on the scale considered: while at local scale the selective influence of contemporary environmental conditions appeared strongest, the heritage of historic processes through dispersal limitation and drift became more apparent at regional scale, and ended up superseding contemporary influences at inter-regional scale. When looking at environmental factors, the structure of microbial communities was correlated primarily with water depth, with a clear transition between 800 and 1,200 meters below sea level. Oceanic basin, water temperature, and sediment depth were other important explanatory parameters of community structure. Finally, we propose increasing dispersal limitation and ecological drift with sediment depth as a probable factor for the enhanced divergence of deeper horizons communities.
Environmental Occurrence, Toxicity Concerns, and Degradation of Diazinon Using a Microbial System
Authors: Wu Xiaozhen , Li Jiayi , Zhou Zhe , Lin Ziqiu , Pang Shimei , Bhatt Pankaj , Mishra Sandhya , Chen Shaohua
Published: November 2021

Diazinon is an organophosphorus pesticide widely used to control cabbage insects, cotton aphids and underground pests. The continuous application of diazinon in agricultural activities has caused both ecological risk and biological hazards in the environment. Diazinon can be degraded via physical and chemical methods such as photocatalysis, adsorption and advanced oxidation. The microbial degradation of diazinon is found to be more effective than physicochemical methods for its complete clean-up from contaminated soil and water environments. The microbial strains belonging to Ochrobactrum sp., Stenotrophomonas sp., Lactobacillus brevis, Serratia marcescens, Aspergillus niger, Rhodotorula glutinis, and Rhodotorula rubra were found to be very promising for the ecofriendly removal of diazinon. The degradation pathways of diazinon and the fate of several metabolites were investigated. In addition, a variety of diazinon-degrading enzymes, such as hydrolase, acid phosphatase, laccase, cytochrome P450, and flavin monooxygenase were also discovered to play a crucial role in the biodegradation of diazinon. However, many unanswered questions still exist regarding the environmental fate and degradation mechanisms of this pesticide. The catalytic mechanisms responsible for enzymatic degradation remain unexplained, and ecotechnological techniques need to be applied to gain a comprehensive understanding of these issues. Hence, this review article provides in-depth information about the impact and toxicity of diazinon in living systems and discusses the developed ecotechnological remedial methods used for the effective biodegradation of diazinon in a contaminated environment.
Low Serum Testosterone Concentrations Are Associated With Poor Cognitive Performance in Older Men but Not Women
Authors: Dong Xue , Jiang Hong , Li Suyun , Zhang Dongfeng
Published: November 2021

Objective: Current evidence on the association between serum testosterone and cognitive performance has been inconsistent, especially in older adults. To investigate the associations between serum testosterone and cognitive performance in a nationally representative sample of older men and women.

Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. 1,303 men and 1,349 women aged 60 years or older were included in the study. Serum total testosterone was preformed via isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method. Free testosterone was calculated by Vermeulen’s formula. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). Binary logistic regression and restricted cubic spline models were applied to evaluate the association of testosterone and cognitive performance.

Results: In men, higher concentrations of total testosterone were associated with better performance on CERAD test (OR = 0.51; 95%CI = 0.27–0.95) and DSST (OR = 0.54; 95%CI = 0.30–0.99) in adjusted group. Similarly, higher concentrations of free testosterone were associated with better performance on CERAD test (OR = 0.32; 95%CI = 0.17–0.61) and DSST (OR = 0.41; 95%CI = 0.17–0.96) in men. These associations were not seen in women.

Conclusion: Serum testosterone concentrations were inversely associated with cognitive performance in older men but not women in the United States.
Path Planning and Impedance Control of a Soft Modular Exoskeleton for Coordinated Upper Limb Rehabilitation
Authors: Liu Quan , Liu Yang , Li Yi , Zhu Chang , Meng Wei , Ai Qingsong , Xie Sheng Q.
Published: November 2021

The coordinated rehabilitation of the upper limb is important for the recovery of the daily living abilities of stroke patients. However, the guidance of the joint coordination model is generally lacking in the current robot-assisted rehabilitation. Modular robots with soft joints can assist patients to perform coordinated training with safety and compliance. In this study, a novel coordinated path planning and impedance control method is proposed for the modular exoskeleton elbow–wrist rehabilitation robot driven by pneumatic artificial muscles (PAMs). A convolutional neural network-long short-term memory (CNN-LSTM) model is established to describe the coordination relationship of the upper limb joints, so as to generate adaptive trajectories conformed to the coordination laws. Guided by the planned trajectory, an impedance adjustment strategy is proposed to realize active training within a virtual coordinated tunnel to achieve the robot-assisted upper limb coordinated training. The experimental results showed that the CNN-LSTM hybrid neural network can effectively quantify the coordinated relationship between the upper limb joints, and the impedance control method ensures that the robotic assistance path is always in the virtual coordination tunnel, which can improve the movement coordination of the patient and enhance the rehabilitation effectiveness.
Juxtacellular Labeling of Stellate, Disk and Basket Neurons in the Central Nucleus of the Guinea Pig Inferior Colliculus
Authors: Wallace Mark N. , Shackleton Trevor M. , Thompson Zoe , Palmer Alan R.
Published: November 2021

We reconstructed the intrinsic axons of 32 neurons in the guinea pig inferior colliculus (IC) following juxtacellular labeling. Biocytin was injected into cells in vivo, after first analyzing physiological response properties. Based on axonal morphology there were two classes of neuron: (1) laminar cells (14/32, 44%) with an intrinsic axon and flattened dendrites confined to a single fibrodendritic lamina and (2) translaminar cells (18/32, 56%) with axons that terminated in two or more laminae in the central nucleus (ICc) or the surrounding cortex. There was also one small, low-frequency cell with bushy-like dendrites that was very sensitive to interaural timing differences. The translaminar cells were subdivided into three groups of cells with: (a) stellate dendrites that crossed at least two laminae (8/32, 25%); (b) flattened dendrites confined to one lamina and that had mainly en passant axonal swellings (7/32, 22%) and (c) short, flattened dendrites and axons with distinctive clusters of large terminal boutons in the ICc (3/32, 9%). These terminal clusters were similar to those of cortical basket cells. The 14 laminar cells all had sustained responses apart from one offset response. Almost half the non-basket type translaminar cells (7/15) had onset responses while the others had sustained responses. The basket cells were the only ones to have short-latency (7–9 ms), chopper responses and this distinctive temporal response should allow them to be studied in more detail in future. This is the first description of basket cells in the auditory brainstem, but more work is required to confirm their neurotransmitter and precise post-synaptic targets.
Time-Based Decision Making for Reperfusion in Acute Ischemic Stroke
Authors: Grøan Mathias , Ospel Johanna , Ajmi Soffien , Sandset Else Charlotte , Kurz Martin W. , Skjelland Mona , Advani Rajiv
Published: November 2021

Decision making in the extended time windows for acute ischemic stroke can be a complex and time-consuming process. The process of making the clinical decision to treat has been compounded by the availability of different imaging modalities. In the setting of acute ischemic stroke, time is of the essence and chances of a good outcome diminish by each passing minute. Navigating the plethora of advanced imaging modalities means that treatment in some cases can be inefficaciously delayed. Time delays and individually based non-programmed decision making can prove challenging for clinicians. Visual aids can assist such decision making aimed at simplifying the use of advanced imaging. Flow charts are one such visual tool that can expedite treatment in this setting. A systematic review of existing literature around imaging modalities based on site of occlusion and time from onset can be used to aid decision making; a more program-based thought process. The use of an acute reperfusion flow chart helping navigate the myriad of imaging modalities can aid the effective treatment of patients.
Quality of Life in Young Adults With Cerebral Palsy: A Longitudinal Analysis of the SPARCLE Study
Authors: Vidart d'Egurbide Bagazgoïtia Nicolas , Ehlinger Virginie , Duffaut Carine , Fauconnier Jérôme , Schmidt-Schuchert Silke , Thyen Ute , Himmelmann Kate , Marcelli Marco , Arnaud Catherine
Published: November 2021

Introduction: While most people with cerebral palsy (CP) will have a life expectancy similar to that of the general population, international research has primarily focused on childhood and adolescence; and knowledge about the quality of life (QoL) of young adults with CP, its trajectories, and associated factors remains scarce.

Methods: This longitudinal study included young adults with CP living in five European regions and who had previously participated in the SPARCLE cohort as children and/or adolescents. Their QoL in the psychological well-being and social relationships domains was estimated using age-appropriate validated instruments (KIDSCREEN-52 in childhood/adolescence and WHOQOL-Bref in young adulthood). We used generalized linear mixed-effect models with random intercept to estimate long-term trajectories of QoL in both domains and to investigate whether severity of impairment, pain, and seizure influenced these trajectories. We sought to identify potentially different trajectories of QoL from childhood to adulthood using a shape-based clustering method.

Results: In total, 164 young adults with CP aged 22–27 years participated in the study. Psychological well-being linearly decreased by 0.78 points (scale 0–100) per year (95% confidence interval (CI) −0.99 to −0.56) from childhood to young adulthood, whereas QoL in the social relationships domain increased (β coefficient 1.24, 95% CI 0.92–1.55). Severity of impairment was associated with reduced QoL in all life periods of the study (childhood, adolescence, and young adulthood): motor impairment with social relationships, and more nuancedly intellectual disability with psychological well-being and social relationships. At all periods, frequent pain significantly reduced psychological well-being, and seizures were associated with lower QoL in the social relationships domain. In both domains, we identified a group of individuals with CP who presented a reverse trajectory compared with the general QoL trajectory.

Conclusion: Identification of QoL trajectories and their associated factors yields improved knowledge about the experience of individuals with CP until young adulthood. Further studies are needed to better understand the determinants that have the greatest influence on the different shapes of long-term trajectories of QoL.
Current Incidence and Risk Factors of Fecal Incontinence After Acute Stroke Affecting Functionally Independent People
Authors: Lucente Giuseppe , Corral Javier , Rodríguez-Esparragoza Luis , Castañer Sara , Ortiz Hector , Piqueras Anna , Broto Joaquim , Hernández-Pérez María , Domenech Sira , Martinez-Piñeiro Alicia , Serra Jordi , Almendrote Miriam , Parés David , Millán Mònica
Published: November 2021

Background: Previously published retrospective series show a high prevalence of fecal incontinence (FI) in stroke patients. We aimed to analyze in a prospective series the current incidence of FI in acute stroke in functionally independent patients and its evolution over time and the patient characteristics associated with the appearance of FI in acute stroke.

Methods: We included consecutive patients with acute stroke admitted in our stroke unit who fulfilled the following inclusion criteria: a first episode of stroke, aged >18 years, with no previous functional dependency [modified Rankin Scale (mRS) ≤ 2] and without previous known FI. FI was assessed by a multidisciplinary trained team using dedicated questionnaires at 72 ± 24 h (acute phase) and at 90 ± 15 days (chronic phase). Demographic, medical history, clinical and stroke features, mortality, and mRS at 7 days were collected.

Results: Three hundred fifty-nine (48.3%) of 749 patients (mean age 65.9 ± 10, 64% male, 84.1% ischemic) fulfilled the inclusion criteria and were prospectively included during a 20-month period. FI was identified in 23 patients (6.4%) at 72 ± 24 h and in 7 (1.9%) at 90 days ± 15 days after stroke onset. FI was more frequent in hemorrhagic strokes (18 vs. 5%, p 0.007) and in more severe strokes [median National Institute of Health Stroke Scale (NIHSS) 18 (14–22) vs. 5 (3–13), p < 0.0001]. No differences were found regarding age, sex, vascular risk factors, or other comorbidities, or affected hemisphere. Patients with NIHSS ≥12 (AUC 0.81, 95% CI 0.71 to 0.89) had a 17-fold increase for the risk of FI (OR 16.9, IC 95% 4.7–60.1) adjusted for covariates.

Conclusions: At present, the incidence of FI in acute stroke patients without previous functional dependency is lower than expected, with an association of a more severe and hemorrhagic stroke. Due to its impact on the quality of life, it is necessary to deepen the knowledge of the underlying mechanisms to address therapeutic strategies.
Concussion Among Children in the United States General Population: Incidence and Risk Factors
Authors: Cook Nathan E. , Iverson Grant L.
Published: November 2021

The objective of this study was to examine the incidence of concussion and risk factors for sustaining concussion among children from the United States general population. This prospective cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study®. Children were recruited from schools across the US, sampled to reflect the sociodemographic variation of the US population. The current sample includes 11,013 children aged 9 to 10 years old (47.6% girls; 65.5% White) who were prospectively followed for an average of 1 year (mean = 367.9 days, SD = 40.8, range 249–601). The primary outcome was caregiver-reported concussion during a 1 year follow-up period. Logistic regression was used to determine which potential clinical, health history, and behavioral characteristics (assessed at baseline) were prospectively associated with concussion. In the 1 year follow-up period between ages 10 and 11, 1 in 100 children (n = 123, 1.1%) sustained a concussion. In univariate models, three baseline predictors (ADHD, prior concussion, and accident proneness) were significantly associated with sustaining a concussion. In a multivariate model, controlling for all other predictors, only prior concussion remained significantly associated with the occurrence of a concussion during the observation period (Odds Ratio = 5.49, 95% CI: 3.40–8.87). The most robust and only independent prospective predictor of sustaining a concussion was history of a prior concussion. History of concussion is associated with 5.5 times greater odds of sustaining concussion between ages 10 and 11 among children from the general US population.
Dissociating the Impact of Movement Time and Energy Costs on Decision-Making and Action Initiation in Humans
Authors: Saleri Lunazzi Clara , Reynaud Amélie J. , Thura David
Published: November 2021

Recent theories and data suggest that adapted behavior involves economic computations during which multiple trade-offs between reward value, accuracy requirement, energy expenditure, and elapsing time are solved so as to obtain rewards as soon as possible while spending the least possible amount of energy. However, the relative impact of movement energy and duration costs on perceptual decision-making and movement initiation is poorly understood. Here, we tested 31 healthy subjects on a perceptual decision-making task in which they executed reaching movements to report probabilistic choices. In distinct blocks of trials, the reaching duration (“Time” condition) and energy (“Effort” condition) costs were independently varied compared to a “Reference” block, while decision difficulty was maintained similar at the block level. Participants also performed a simple delayed-reaching (DR) task aimed at estimating movement initiation duration in each motor condition. Results in that DR task show that long duration movements extended reaction times (RTs) in most subjects, whereas energy-consuming movements led to mixed effects on RTs. In the decision task, about half of the subjects decreased their decision durations (DDs) in the Time condition, while the impact of energy on DDs were again mixed across subjects. Decision accuracy was overall similar across motor conditions. These results indicate that movement duration and, to a lesser extent, energy expenditure, idiosyncratically affect perceptual decision-making and action initiation. We propose that subjects who shortened their choices in the time-consuming condition of the decision task did so to limit a drop of reward rate.
The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation
Authors: Huang Linyuan , Zhang Jun , Zhu Xinyun , Mi Xue , Li Qiujie , Gao Jing , Zhou Jianheng , Zhou Jun , Liu Xiao-Min
Published: November 2021

Adipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of rhein on adipogenesis at both the transcriptional and posttranscriptional levels. Rhein remarkably suppresses adipogenesis in the stage-specific and dose-dependent manners. Rhein has been identified to inhibit fat mass and obesity-associated (FTO) demethylase activity. Surprisingly, side-by-side comparison analysis revealed that the rhein treatment and Fto knockdown triggered the differential gene regulatory patterns, resulting in impaired adipocyte formation. Specifically, rhein treatment mildly altered the transcriptome with hundreds of genes dysregulated. N6-methyladenosine (m6A) methylome profile showed that, although the supply of rhein induced increased m6A levels on a small subset of messenger RNAs (mRNAs), few of them showed dramatic transcriptional response to this compound. Moreover, the specific rhein-responsive mRNAs, which are linked to mitotic pathway, are barely methylated or contain m6A peaks without dramatic response to rhein, suggesting separate regulation of global m6A pattern and adipogenesis mediated by rhein. Further identification of m6A-independent pathways revealed a positive regulator, receptor expressing-enhancing protein 3 (REEP3), in guidance of adipogenesis. Hence, this study provides the mechanistic view of the cellular actions of rhein in the modulation of adipogenesis and identifies a potential novel target for obesity therapeutic research.
BI-RADS Reading of Non-Mass Lesions on DCE-MRI and Differential Diagnosis Performed by Radiomics and Deep Learning
Authors: Zhou Jiejie , Liu Yan-Lin , Zhang Yang , Chen Jeon-Hor , Combs Freddie J. , Parajuli Ritesh , Mehta Rita S. , Liu Huiru , Chen Zhongwei , Zhao Youfan , Pan Zhifang , Wang Meihao , Yu Risheng , Su Min-Ying
Published: November 2021

Background

A wide variety of benign and malignant processes can manifest as non-mass enhancement (NME) in breast MRI. Compared to mass lesions, there are no distinct features that can be used for differential diagnosis. The purpose is to use the BI-RADS descriptors and models developed using radiomics and deep learning to distinguish benign from malignant NME lesions.

Materials and Methods

A total of 150 patients with 104 malignant and 46 benign NME were analyzed. Three radiologists performed reading for morphological distribution and internal enhancement using the 5th BI-RADS lexicon. For each case, the 3D tumor mask was generated using Fuzzy-C-Means segmentation. Three DCE parametric maps related to wash-in, maximum, and wash-out were generated, and PyRadiomics was applied to extract features. The radiomics model was built using five machine learning algorithms. ResNet50 was implemented using three parametric maps as input. Approximately 70% of earlier cases were used for training, and 30% of later cases were held out for testing.

Results

The diagnostic BI-RADS in the original MRI report showed that 104/104 malignant and 36/46 benign lesions had a BI-RADS score of 4A–5. For category reading, the kappa coefficient was 0.83 for morphological distribution (excellent) and 0.52 for internal enhancement (moderate). Segmental and Regional distribution were the most prominent for the malignant group, and focal distribution for the benign group. Eight radiomics features were selected by support vector machine (SVM). Among the five machine learning algorithms, SVM yielded the highest accuracy of 80.4% in training and 77.5% in testing datasets. ResNet50 had a better diagnostic performance, 91.5% in training and 83.3% in testing datasets.

Conclusion

Diagnosis of NME was challenging, and the BI-RADS scores and descriptors showed a substantial overlap. Radiomics and deep learning may provide a useful CAD tool to aid in diagnosis.