bluuebunny/crossref_metadata_2025 huggingface dataset:
Thromboinflammation Supports Complement Activation in Cancer Patients With COVID-19
Authors: Peerschke Ellinor I. , Valentino Alisa , So Rachel J. , Shulman Scott , Ravinder  
Published: August 2021

Background

COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients.

Objective

This study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation.

Methods

Markers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 μg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response.

Results

Increases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU.

Conclusion

Complement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.
Immunoregulatory Functions of Interferons During Genital HSV-2 Infection
Authors: Feng Emily , Balint Elizabeth , Vahedi Fatemah , Ashkar Ali A.
Published: August 2021

Herpes simplex virus type 2 (HSV-2) infection is one of the most prevalent sexually transmitted infections that disproportionately impacts women worldwide. Currently, there are no vaccines or curative treatments, resulting in life-long infection. The mucosal environment of the female reproductive tract (FRT) is home to a complex array of local immune defenses that must be carefully coordinated to protect against genital HSV-2 infection, while preventing excessive inflammation to prevent disease symptoms. Crucial to the defense against HSV-2 infection in the FRT are three classes of highly related and integrated cytokines, type I, II, and III interferons (IFN). These three classes of cytokines control HSV-2 infection and reduce tissue damage through a combination of directly inhibiting viral replication, as well as regulating the function of resident immune cells. In this review, we will examine how interferons are induced and their critical role in how they shape the local immune response to HSV-2 infection in the FRT.
The Transcriptome of Schistosoma mansoni Developing Eggs Reveals Key Mediators in Pathogenesis and Life Cycle Propagation
Authors: Lu Zhigang , Sankaranarayanan Geetha , Rawlinson Kate A. , Offord Victoria , Brindley Paul J. , Berriman Matthew , Rinaldi Gabriel
Published: August 2021

Schistosomiasis, the most important helminthic disease of humanity, is caused by infection with parasitic flatworms of the genus Schistosoma. The disease is driven by parasite eggs becoming trapped in host tissues, followed by inflammation and granuloma formation. Despite abundant transcriptome data for most developmental stages of the three main human-infective schistosome species—Schistosoma mansoni, S. japonicum and S. haematobium—the transcriptomic profiles of developing eggs remain under unexplored. In this study, we performed RNAseq of S. mansoni eggs laid in vitro during early and late embryogenesis, days 1-3 and 3-6 post-oviposition, respectively. Analysis of the transcriptomes identified hundreds of up-regulated genes during the later stage, including venom allergen-like (VAL) proteins, well-established host immunomodulators, and genes involved in organogenesis of the miracidium larva. In addition, the transcriptomes of the in vitro laid eggs were compared with existing publicly available RNA-seq datasets from S. mansoni eggs collected from the livers of rodent hosts. Analysis of enriched GO terms and pathway annotations revealed cell division and protein synthesis processes associated with early embryogenesis, whereas cellular metabolic processes, microtubule-based movement, and microtubule cytoskeleton organization were enriched in the later developmental time point. This is the first transcriptomic analysis of S. mansoni embryonic development, and will facilitate our understanding of infection pathogenesis, miracidial development and life cycle progression of schistosomes.
Bioenergetic Model Sensitivity to Diet Diversity Across Space, Time and Ontogeny
Authors: Lawson Christopher L. , Taylor Matthew D. , Smith James A. , Payne Nicholas L. , Semmens Jayson M. , Suthers Iain M. , Brodie Stephanie
Published: August 2021

Consumption is the primary trophic interaction in ecosystems and its accurate estimation is required for reliable ecosystem modeling. When estimating consumption, species’ diets are commonly assumed to be the average of those that occur among habitats, seasons, and life stages which introduces uncertainty and error into consumption rate estimates. We present a case study of a teleost (Yellowfin Bream Acanthopagrus australis) that quantifies the potential error in consumption (in mass) and growth rate estimates when using diet data from different regions and times and ignoring ontogenetic variability. Ontogenetic diet trends were examined through gut content analysis (n = 1,130 fish) and incorporated into a bioenergetic model (the “primary” model) that included diet variability (n = 144 prey sources) and ontogenetic changes in metabolism (1–7 year) to estimate lifetime consumption. We quantified error by building nine model scenarios that each incorporated different spatiotemporal diet data of four published studies. The model scenarios produced individual lifetime consumption estimates that were between 25% lower and 15% higher than the primary model (maximum difference was 53%, range 11.7–17.8 kg). When consumption (in mass) was held constant, differences in diet quality among models caused a several-fold range in growth rate (0.04–1.07 g day–1). Our findings showcase the large uncertainty in consumption rate estimates due to diet diversity, and illustrate that caution is required when considering bioenergetic results among locations, times, and ontogeny.
Through the Boundaries: Environmental Factors Affecting Reef Benthic Cover in Marine Protected Areas in the Philippines
Authors: Panga Fleurdeliz M. , Anticamara Jonathan A. , Quibilan Miledel Christine C. , Atrigenio Michael P. , Aliño Porfirio M.
Published: August 2021

Philippine coral reefs have been on the decline since the 1970s, and this degradation has posed a risk to biodiversity, food security, and livelihood in the country. In an effort to arrest this degradation, marine protected areas (MPAs) were established across the country. MPAs are known to improve fish biomass, but their effect on live coral cover and other benthos is not yet well documented and understood. In this study, 28 MPAs across the Philippines were surveyed comparing benthic cover and indices between protected reefs and adjacent unprotected reefs. No consistent differences were found between reefs inside and outside MPAs through all the benthic categories and reef health indices considered that are indicative of protection effects or recovery within MPAs. However, there were notable site-specific differences in benthic cover across the study MPAs-suggesting that factors other than protection play important roles in influencing benthic cover inside and outside of MPAs. Storm frequency and proximity to rivers, as a proxy for siltation, were the strongest negative correlates to live coral cover. Also, high coastal population, a proxy for pollution, and occurrence of blast and poison fishing positively correlated with high dead coral cover. The lack of significant difference in benthic cover between reefs inside and outside MPAs suggests that protection does not necessarily guarantee immediate improvement in benthic condition. Correlations between benthic condition and storm frequency, siltation, and pollution suggest that it is necessary to augment MPAs with other management strategies that will address the multiple stressors that are usually indiscriminate of MPA boundaries. Supplementing long-term and systematic monitoring of benthic cover and biodiversity inside and outside of MPAs with data on other important environmental and human impact variables will help improve understanding of benthic cover and biodiversity dynamics inside and outside of MPA boundaries.
The Emergence and Initial Impact of Stony Coral Tissue Loss Disease (SCTLD) in the United States Virgin Islands
Authors: Brandt Marilyn E. , Ennis Rosmin S. , Meiling Sonora S. , Townsend Joseph , Cobleigh Kathryn , Glahn Adam , Quetel Jason , Brandtneris Viktor , Henderson Leslie M. , Smith Tyler B.
Published: August 2021

Coral communities in the Caribbean face a new and deadly threat in the form of the highly virulent multi-host stony coral tissue loss disease (SCTLD). In late January of 2019, a disease with signs and characteristics matching that of SCTLD was found affecting a reef off the coast of St. Thomas in the U.S. Virgin Islands (USVI). Identification of its emergence in the USVI provided the opportunity to document the initial evolution of its spatial distribution, coral species susceptibility characteristics, and its comparative impact on coral cover at affected and unaffected coral reef locations. Re-assessments at sentinel sites and long-term monitoring locations were used to track the spread of the disease, assess species affected, and quantify its impact. The disease was initially limited to the southwest of St. Thomas for several months, then spread around the island and to the neighboring island of St. John to the east. Differences in disease prevalence among species were similar to reports of SCTLD from other regions. Highly affected species included Colpophyllia natans, Eusmilia fastigiata, Montastraea cavernosa, Orbicella spp., and Pseudodiploria strigosa. Dendrogyra cylindrus and Meandrina meandrites were also highly affected but showed more variability in disease prevalence, likely due to initial low abundances and the rapid loss of colonies due to disease. Siderastrea spp. were less affected and showed lower prevalence. Species previously reported as unaffected or data deficient that were found to be affected by SCTLD included Agaricia spp., Madracis spp., and Mycetophyllia spp. We also observed multi-focal lesions at SCTLD-affected sites on colonies of Porites astreoides, despite that poritids have previously been considered low or not susceptible to SCTLD. Loss of coral cover due to acute tissue loss diseases, which were predominantly SCTLD, was significant at several monitoring locations and was more impactful than previous mass bleaching events at some sites. There are no signs that the USVI SCTLD outbreak is abating, therefore it is likely that this disease will become widespread across the U.S. Caribbean and British Virgin Islands in the near future.
Research on Improving the Working Current of NbOx-Based Selector by Inserting a Ti Layer
Authors: Liu Chunlei , Ma Guokun , Zeng Junpeng , Tan Qiuyang , Zhang Ziqi , Chen Ao , Liu Nengfan , Wan Houzhao , Wang Baoyuan , Tao Li , Rao Yiheng , Shen Liangping , Wang Hanbin , Zhang Jun , Wang Hao
Published: August 2021

To achieve the highest possible integration storage density in the V-point structure, the working current of the selector in the one-selection one-resistance (1S1R) structure should match with the resistance random access memory (RRAM). In this study, a selector device is designed with a Ti/NbOx/Ti/Pt structure through the magnetron sputtering method and achieves excellent performance of threshold switching under ultra-large compliance current (CC) up to 100 mA. Furthermore, both the switching voltages and the OFF-state resistance of the device demonstrate excellent stability even when CC is increased to a milliampere level, attributed from the existence of metallic NbO in the switching layer. This study provides evidence that a Ti/NbOx/Ti/Pt device has a great potential to drive RRAM in the V-point structure.
Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in Aspergillus niger in Peanuts
Authors: Xu Manlin , Zhang Xia , Yu Jing , Guo Zhiqing , Li Ying , Song Xinying , He Kang , Li Guowei , Chi Yucheng
Published: August 2021

Aspergillus niger is a very destructive pathogen causing severe peanut root rot, especially in the seeding stage of peanuts (Arachis hypogaea), and often leading to the death of the plant. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly detected post-translational modification identified in several species. In this study, we identified 5041 Khib sites on 1,453 modified proteins in A. niger. Compared with five other species, A. niger has conserved and novel proteins. Bioinformatics analysis showed that Khib proteins are widely distributed in A. niger and are involved in many biological processes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that Khib proteins were significantly enriched in many cellular compartments and pathways, such as ribosomes and proteasome subunits. A total of 223 Khib proteins were part of the PPI network, thus, suggesting that Khib proteins are associated with a large range of protein interactions and diverse pathways in the life processes of A. niger. Several identified proteins are involved in pathogenesis regulation. Our research provides the first comprehensive report of Khib and an extensive database for potential functional studies on Khib proteins in this economically important fungus.
The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity
Authors: Zhai Zhenya , Niu Kai-Min , Liu Yichun , Lin Chong , Wu Xin
Published: August 2021

Eucommia ulmoides leaves (EL) are rich in phenolic acids and flavonoids, showing enhancing intestinal health effects. The intestinal microbiota-bile acid axis plays important roles in the occurrence and recovery of inflammatory bowel disease (IBD). However, whether EL extract (ELE) has regulatory effects on the intestinal microbiota, bile acid metabolism, and IBD is still unclear. To fill this gap, 2% dextran sulfate sodium (DSS)-induced mild IBD in a C57BL/6J mouse model that was treated with 200 or 400 mg/kg (intake dose/body weight) ELE was used. Oral ELE supplementation alleviated DSS-induced shortening of colon and colonic epithelial injury. Compared with the DSS group, ELE supplementation significantly decreased Toll-like receptor 4 (TLR4) and interlukin-6 (IL-6) and increased occludin and claudin-1 mRNA expression level in the colon (p < 0.05). Combined 16S rRNA gene sequencing and targeted metabolomic analyses demonstrated that ELE significantly improved the diversity and richness of the intestinal microbiota, decreased the abundance of Bacteroidaceae, and increased Akkermansiaceae and Ruminococcaceae abundance (p < 0.05) compared with DSS-induced IBD mice. Moreover, ELE significantly increased the serum contents of deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA), which were highly positively correlated with Akkermansia and unidentified_Ruminococccaceae relative to the DSS group. We then found that ELE increased Takeda G-protein coupled receptor 5 (TGR5), claudin-1, and occludin mRNA expression levels in the colon. In the Caco-2 cell model, we confirmed that activation of TGR5 improved the reduction in transepithelial electoral resistance (TEER) and decreased the permeability of FITC-dextran on monolayer cells induced by LPS (p < 0.05). siRNA interference assays showed that the decrease in TGR5 expression led to the decrease in TEER, an increase in FITC-dextran permeability, and a decrease in claudin-1 protein expression in Caco-2 cells. In summary, ELE alleviated IBD by influencing the intestinal microbiota structure and composition of bile acids, which in turn activated the colonic TGR5 gene expression in the colon and promoted the expression of tight junction proteins. These findings provide new insight for using ELE as a functional food with adjuvant therapeutic effects in IBD.
Antimicrobial, Antibiofilm, and Anti-persister Activities of Penfluridol Against Staphylococcus aureus
Authors: Liu Yaqian , She Pengfei , Xu Lanlan , Chen Lihua , Li Yimin , Liu Shasha , Li Zehao , Hussain Zubair , Wu Yong
Published: August 2021

Staphylococcus aureus has increasingly attracted global attention as a major opportunistic human pathogen owing to the emergence of biofilms (BFs) and persisters that are known to increase its antibiotic resistance. However, there are still no effective antimicrobial agents in clinical settings. This study investigated the antimicrobial activity of penfluridol (PF), a long-acting antipsychotic drug, against S. aureus and its clinical isolates via drug repurposing. PF exhibited strong bactericidal activity against S. aureus, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 4–8 and 16–32 μg/ml, respectively. PF could significantly inhibit biofilm formation and eradicate 24 h preformed biofilms of S. aureus in a dose-dependent manner. Furthermore, PF could effectively kill methicillin-resistant S. aureus (MRSA) persister cells and demonstrated considerable efficacy in a mouse model of subcutaneous abscess, skin wound infection, and acute peritonitis caused by MRSA. Notably, PF exerted almost no hemolysis activity on human erythrocytes, with limited cytotoxicity and low tendency to cause resistance. Additionally, PF induced bacterial membrane permeability and ATP release and further caused membrane disruption, which may be the underlying antibacterial mechanism of PF. In summary, our findings suggest that PF has the potential to serve as a novel antimicrobial agent against S. aureus biofilm- or persister-related infections.
SGnn: A Web Server for the Prediction of Prion-Like Domains Recruitment to Stress Granules Upon Heat Stress
Authors: Iglesias Valentín , Santos Jaime , Santos-Suárez Juan , Pintado-Grima Carlos , Ventura Salvador
Published: August 2021

Proteins bearing prion-like domains (PrLDs) are essential players in stress granules (SG) assembly. Analysis of data on heat stress-induced recruitment of yeast PrLDs to SG suggests that this propensity might be connected with three defined protein biophysical features: aggregation propensity, net charge, and the presence of free cysteines. These three properties can be read directly in the PrLDs sequences, and their combination allows to predict protein recruitment to SG under heat stress. On this basis, we implemented SGnn, an online predictor of SG recruitment that exploits a feed-forward neural network for high accuracy classification of the assembly behavior of PrLDs. The simplicity and precision of our strategy should allow its implementation to identify heat stress-induced SG-forming proteins in complete proteomes.
Association Between Antibiotic Treatment of Chlamydia pneumoniae and Reduced Risk of Alzheimer Dementia: A Nationwide Cohort Study in Taiwan
Authors: Ou Hsun , Chien Wu-Chien , Chung Chi-Hsiang , Chang Hsin-An , Kao Yu-Chen , Wu Pei-Chuan , Tzeng Nian-Sheng
Published: August 2021

Background:Chlamydia pneumoniae (CPn) is a common community-acquired pneumonia. In the literature, CPn infection is demonstrated to exhibit an association with Alzheimer dementia (AD). We executed the present nationwide, population-based research with the goal of probing the association of CPn infection and antibiotic therapy with AD risk.

Methods: We conducted a cohort study using a database extracted from Taiwan's National Health Insurance Research Database (NHIRD). All medical conditions for each enrolled individuals were categorized using the International Classification of Diseases, ninth Revision classifications. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CPn pneumonia-associated hospitalizations and AD were estimated using Fine and Gray's survival analysis and adjusted for comorbidities. The effects of the antibiotics on the HRs for AD in the patients with CPn pneumonia-associated hospitalization were also analyzed.

Results: Our analyses included 6,628 individuals, including 1,657 CPn-infected patients, as well as 4,971 controls matched by age, index date, and sex (1:3). In this study, patients hospitalized for CPn pneumonia exhibited a significantly higher AD risk (adjusted HR = 1.599, 95% CI = 1.284–1.971, p < 0.001). We also noted an association of macrolide use (≥15 days) and fluoroquinolone use (≥15 days) with decreased AD risk.

Conclusions: We determined CPn pneumonia to be associated with a relatively high AD risk. The result in this study confirmed the findings from previous literatures, by using a large, nationwide, population-based database. Appropriate macrolide and fluoroquinolone treatment may attenuate this risk.
Cognitive Decline Assessment: A Review From Medical Imaging Perspective
Authors: Dartora Caroline Machado , Borelli Wyllians Vendramini , Koole Michel , Marques da Silva Ana Maria
Published: August 2021

Aging is a complex process that involves changes at both molecular and morphological levels. However, our understanding of how aging affects brain anatomy and function is still poor. In addition, numerous biomarkers and imaging markers, usually associated with neurodegenerative diseases such as Alzheimer's disease (AD), have been clinically used to study cognitive decline. However, the path of cognitive decline from healthy aging to a mild cognitive impairment (MCI) stage has been studied only marginally. This review presents aspects of cognitive decline assessment based on the imaging differences between individuals cognitively unimpaired and in the decline spectrum. Furthermore, we discuss the relationship between imaging markers and the change in their patterns with aging by using neuropsychological tests. Our goal is to delineate how aging has been studied by using medical imaging tools and further explore the aging brain and cognitive decline. We find no consensus among the biomarkers to assess the cognitive decline and its relationship with the cognitive decline trajectory. Brain glucose hypometabolism was found to be directly related to aging and indirectly to cognitive decline. We still need to understand how to quantify an expected hypometabolism during cognitive decline during aging. The Aβ burden should be longitudinally studied to achieve a better consensus on its association with changes in the brain and cognition decline with aging. There exists a lack of standardization of imaging markers that highlight the need for their further improvement. In conclusion, we argue that there is a lot to investigate and understand cognitive decline better and seek a window for a suitable and effective treatment strategy.
Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress
Authors: Parker Kaila N. , Donovan Michael H. , Smith Kylee , Noble-Haeusslein Linda J.
Published: August 2021

Despite the high incidence of brain injuries in children, we have yet to fully understand the unique vulnerability of a young brain to an injury and key determinants of long-term recovery. Here we consider how early life stress may influence recovery after an early age brain injury. Studies of early life stress alone reveal persistent structural and functional impairments at adulthood. We consider the interacting pathologies imposed by early life stress and subsequent brain injuries during early brain development as well as at adulthood. This review outlines how early life stress primes the immune cells of the brain and periphery to elicit a heightened response to injury. While the focus of this review is on early age traumatic brain injuries, there is also a consideration of preclinical models of neonatal hypoxia and stroke, as each further speaks to the vulnerability of the brain and reinforces those characteristics that are common across each of these injuries. Lastly, we identify a common mechanistic trend; namely, early life stress worsens outcomes independent of its temporal proximity to a brain injury.
Prospective Study of a Multimodal Convulsive Seizure Detection Wearable System on Pediatric and Adult Patients in the Epilepsy Monitoring Unit
Authors: Onorati Francesco , Regalia Giulia , Caborni Chiara , LaFrance W. Curt , Blum Andrew S. , Bidwell Jonathan , De Liso Paola , El Atrache Rima , Loddenkemper Tobias , Mohammadpour-Touserkani Fatemeh , Sarkis Rani A. , Friedman Daniel , Jeschke Jay , Picard Rosalind
Published: August 2021

Background:Using machine learning to combine wrist accelerometer (ACM) and electrodermal activity (EDA) has been shown effective to detect primarily and secondarily generalized tonic-clonic seizures, here termed as convulsive seizures (CS). A prospective study was conducted for the FDA clearance of an ACM and EDA-based CS-detection device based on a predefined machine learning algorithm. Here we present its performance on pediatric and adult patients in epilepsy monitoring units (EMUs).

Methods:Patients diagnosed with epilepsy participated in a prospective multi-center clinical study. Three board-certified neurologists independently labeled CS from video-EEG. The Detection Algorithm was evaluated in terms of Sensitivity and false alarm rate per 24 h-worn (FAR) on all the data and on only periods of rest. Performance were analyzed also applying the Detection Algorithm offline, with a less sensitive but more specific parameters configuration (“Active mode”).

Results:Data from 152 patients (429 days) were used for performance evaluation (85 pediatric aged 6–20 years, and 67 adult aged 21–63 years). Thirty-six patients (18 pediatric) experienced a total of 66 CS (35 pediatric). The Sensitivity (corrected for clustered data) was 0.92, with a 95% confidence interval (CI) of [0.85-1.00] for the pediatric population, not significantly different (p> 0.05) from the adult population's Sensitivity (0.94, CI: [0.89–1.00]). The FAR on the pediatric population was 1.26 (CI: [0.87–1.73]), higher (p< 0.001) than in the adult population (0.57, CI: [0.36–0.81]). Using the Active mode, the FAR decreased by 68% while reducing Sensitivity to 0.95 across the population. During rest periods, the FAR's were 0 for all patients, lower than during activity periods (p< 0.001).

Conclusions:Performance complies with FDA's requirements of a lower bound of CI for Sensitivity higher than 0.7 and of a FAR lower than 2, for both age groups. The pediatric FAR was higher than the adult FAR, likely due to higher pediatric activity. The high Sensitivity and precision (having no false alarms) during sleep might help mitigate SUDEP risk by summoning caregiver intervention. The Active mode may be advantageous for some patients, reducing the impact of the FAR on daily life. Future work will examine the performance and usability outside of EMUs.
Sustained Effects of Acute Resistance Exercise on Executive Function in Healthy Middle-Aged Adults
Authors: Chou Chien-Chih , Hsueh Ming-Chun , Chiu Yi-Hsiang , Wang Wen-Yi , Huang Mei-Yao , Huang Chung-Ju
Published: August 2021

The present study examined the sustained effects of acute resistance exercise on inhibitory function in healthy middle-aged adults. Seventy healthy middle-aged adults (mean age = 46.98 ± 5.70 years) were randomly assigned to exercise or control groups, and the Stroop test was administered before, immediately after, and 40 min after exercise. The resistance exercise protocol involved two sets of seven exercises performed for a maximum of 10 repetitions, with 60 s between sets and exercises. Acute resistance exercise resulted in higher Stroop test performance under the incongruent (inhibition) and interference conditions immediately post-exercise and 40 min post-exercise. Furthermore, the difference in scores after 40 min was significant. The findings indicate that a moderately intensive acute resistance exercise could facilitate Stroop performance and has a more beneficial effect on sustaining of cognition that involves executive control at least 40 min.
Leveraging Neuroimaging Tools to Assess Precision and Accuracy in an Alzheimer’s Disease Neuropathologic Sampling Protocol
Authors: Webster Jason M. , Grabowski Thomas J. , Madhyastha Tara M. , Gibbons Laura E. , Keene C. Dirk , Latimer Caitlin S.
Published: August 2021

Introduction

The study of Alzheimer’s disease investigates topographic patterns of degeneration in the context of connected networks comprised of functionally distinct domains using increasingly sophisticated molecular techniques. Therefore, obtaining high precision and accuracy of neuropathologic tissue sampling will enhance the reliability of molecular studies and contribute to the understanding of Alzheimer’s disease pathology. Neuroimaging tools can help assess these aspects of current sampling protocols as well as contribute directly to their improvement.

Methods

Using a virtual sampling method on magnetic resonance images (MRIs) from 35 participants (21 women), we compared the precision and accuracy of traditional neuropathologic vs. neuroimaging-guided sampling. The impact of the resulting differences was assessed by evaluating the functional connectivity pattern of regions selected by each approach.

Results

Virtual sampling using the traditional neuropathologic approach had low neuroanatomical precision and accuracy for all cortical regions tested. Neuroimaging-guided strategies narrowed these gaps. Discrepancies in the location of traditional and neuroimaging-guided samples corresponded to differences in fMRI measures of functional connectivity.

Discussion

Integrating neuroimaging tools with the neuropathologic assessment will improve neuropathologic-neuroimaging correlations by helping to ensure specific functional domains are accurately sampled for quantitative molecular neuropathologic applications. Our neuroimaging-based simulation of current sampling practices provides a benchmark of precision and accuracy against which to measure improvements when using novel tissue sampling approaches. Our results suggest that relying on gross landmarks alone to select samples at autopsy leads to significant variability, even when sampled by the same neuropathologist. Further, this exercise highlights how sampling precision could be enhanced if neuroimaging were integrated with the standard neuropathologic assessment. More accurate targeting and improved biological homogeneity of sampled brain tissue will facilitate the interpretation of neuropathological analyses in AD and the downstream research applications of brain tissue from biorepositories.
Differences in Mechanical Parameters of Keyboard Switches Modulate Motor Preparation: A Wearable EEG Study
Authors: Watanabe Hiroki , Nakajima Kae , Takagi Shunsuke , Mizuyama Ryo , Saito Mayumi , Furusawa Koichi , Nakatani Kunio , Yokota Yusuke , Kataoka Hirotaka , Nakajima Hiroshi , Naruse Yasushi
Published: August 2021

The mechanical parameters of keyboard switches affect the psychological sense of pressing. The effects of different mechanical parameters on psychological sense have been quantified using questionnaires, but these subjective evaluations are unable to fully clarify the modulation of information processing in the brain due to these differences. This study aimed to elucidate the ability of electroencephalography (EEG) measurements to detect the modulation of subconscious information processing according to mechanical parameter values. To this end, we prepared five mechanical switches with linearly increasing values of pretravel (PT: the distance from the free position until the operating position). We hypothesized that the differences in PTs would subconsciously affect the motor preparation prior to pressing switches because switches with PTs that deviated from those commonly used were predicted to increase the users' attention level when pressing. Differences in motor preparation were quantified using the mean amplitudes of the late contingent negative variation (CNV). We recorded EEGs of 25 gamers during a reaction task for fast switch pressing after a response cue preceded by a pre-cue for response preparation; we also measured the reaction time feedback on each switch pressing trial. Participants performed five sessions (60 trials per session) in total. For the analysis, trials were divided into first (session 1, 2, and 3) and second half sessions (session 4 and 5). In the latter session, CNV amplitudes were significantly higher for the switch with the highest PT than for that with a medium PT, which is closest to that commonly used in commercial mechanical switches. On the other hand, the questionnaire did not detect any significant differences between PTs in their subjective rankings of the psychological effects of switch pressing. These results suggest that differences in PTs modulate motor preparation to press switches, and that EEG measurements may provide a novel objective evaluation of the mechanical parameters of keyboard switches.
Endocannabinoids Released in the Ventral Tegmental Area During Copulation to Satiety Modulate Changes in Glutamate Receptors Associated With Synaptic Plasticity Processes
Authors: Rodríguez-Manzo Gabriela , González-Morales Estefanía , Garduño-Gutiérrez René
Published: August 2021

Endocannabinoids modulate mesolimbic (MSL) dopamine (DA) neurons firing at the ventral tegmental area (VTA). These neurons are activated by copulation, increasing DA release in nucleus accumbens (NAcc). Copulation to satiety in male rats implies repeated ejaculation within a short period (around 2.5 h), during which NAcc dopamine concentrations remain elevated, suggesting continuous neuronal activation. During the 72 h that follow copulation to satiety, males exhibit long-lasting changes suggestive of brain plasticity processes. Enhanced DA neuron activity triggers the synthesis and release of endocannabinoids (eCBs) in the VTA, which participate in several long-term synaptic plasticity processes. Blockade of cannabinoid type 1 receptors (CB1Rs) during copulation to satiety interferes with the appearance of the plastic changes. Glutamatergic inputs to the VTA express CB1Rs and contribute to DA neuron burst firing and synaptic plasticity. We hypothesized that eCBs, released during copulation to satiety, would activate VTA CB1Rs and modulate synaptic plasticity processes involving glutamatergic transmission. To test this hypothesis, we determined changes in VTA CB1R density, phosphorylation, and internalization in rats that copulated to satiety 24 h earlier as compared both to animals that ejaculated only once and to sexually experienced unmated males. Changes in glutamate AMPAR and NMDAR densities and subunit composition and in ERK1/2 activation were determined in the VTA of males that copulated to satiety in the presence or absence of AM251, a CB1R antagonist. The CB1R density decreased and the proportion of phosphorylated CB1Rs increased in the animals that copulated compared to control rats. The CB1R internalization was detected only in sexually satiated males. A decrease in α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) density, blocked by AM251 pretreatment, and an increase in the proportion of GluA2-AMPARs occurred in sexually satiated rats. GluN2A- N-methyl-D-aspartate receptor (NMDAR) expression decreased, and GluN2B-NMDARs increased in these animals, both of which were prevented by AM251 pre-treatment. An increase in phosphorylated ERK1/2 emerged in males copulating to satiety in the presence of AM251. Results demonstrate that during copulation to satiety, eCBs activate CB1Rs in the VTA, producing changes in glutamate receptors compatible with a reduced neuronal activation. These changes could play a role in the induction of the long-lasting physiological changes that characterize sexually satiated rats.
Relationship Between Serum Albumin and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis
Authors: Wang Yali , Du Peng , Xiao Qi , Li Jianfeng , Liu Xiao , Tan Jinfeng , Zhang Xingjian
Published: August 2021

Background: The dose–response association between serum albumin and atrial fibrillation is not well known. This study aims to assess the relationship between albumin and atrial fibrillation and the potential dose–response effect.

Methods: Studies reported that the serum albumin and AF were identified by searching the EMBASE, PubMed, and Cochrane Library databases. The potential dose–response effect was performed by using a stage robust error meta-regression.

Results: Nine studies were included with a total of 32,130 individuals. Patients with high albumin level were associated with a decreased risk of atrial fibrillation compared with patients with low serum albumin (OR[odds ratio]: 0.62, 95% CI [0.44, 0.89]; I2 = 76%; P = 0.009). In the dose–response analysis, for each 10 g/L increase in serum albumin level, the risk of atrial fibrillation decreased by 36% (95% CI: 0.51–0.81, I2 = 87%, P < 0.001). Furthermore, a significant negative linear relationship between serum albumin and the risk of atrial fibrillation (Pnonlinearity = 0.33) was found.

Conclusion: Our dose–response meta-analysis suggests that low serum albumin level is associated with an increased risk of atrial fibrillation. Further studies are needed to explore the effect of induction of elevated serum albumin levels on the prevention of atrial fibrillation.
Recent Progress on Primary Central Nervous System Lymphoma—From Bench to Bedside
Authors: Shao Liang , Xu Chengshi , Wu Huijing , Jamal Muhammad , Pan Shan , Li Sirui , Chen Fei , Yu Ding , Liu Kui , Wei Yongchang
Published: August 2021

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extra-nodal lymphoma. The high relapse rate of PCNSL remains a major challenge to the hematologists, even though patients exhibit high sensitivity to the methotrexate-based chemotherapeutic regimens. Recently, the advent of Bruton’s tyrosine kinase inhibitor (BTKi) and CAR T treatment has made more treatment options available to a proportion of patients. However, whether BTKi monotherapy should be given alone or in combination with conventional chemotherapy is still a clinical question. The status of CAR T therapy for PCNSLs also needs to be elucidated. In this review, we summarized the latest progress on the epidemiology, pathology, clinical manifestation, diagnosis, and treatment options for PCNSLs.
Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer
Authors: Yang Liqiong , Bai Yun , Li Qing , Chen Jie , Liu Fangfang , Weng Xiechuan , Xu Fan
Published: August 2021

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.
A Real-World Observation of Eltrombopag and Recombinant Human Thrombopoietin (rhTPO) in Lymphoma Patients With Chemotherapy Induced Thrombocytopenia
Authors: Zhu Qiuhua , Yang Shimei , Zeng Wenbin , Li Mingjie , Guan Zebing , Zhou Lanlan , Wang Hong , Liu Yanan , Gao Yanmin , Qiu Shiqiu , Chen Chaolun , Li Huan , Zheng Shanshan , Yuan Yuemei , Zhang Hanling , Pan Xueyi
Published: August 2021

This real-world, observational study aimed to assess and compare the clinical efficacy and safety of eltrombopag with recombinant human thrombopoietin (rhTPO) in the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma. One hundred and fifty-three patients who experienced grade 3 or 4 thrombocytopenia after chemotherapy for lymphoma were enrolled, 51 of which were treated with eltrombopag, 50 with rhTPO, and 52 patients with no drug treatment were served as the control group. The lowest platelet level and mean platelet counts at Day 5, Day 7, and Day 10 were significantly higher in both the eltrombopag group (P=.041,.003,.000,.000) and rhTPO group (P=.005,.005,.000,.000) than the control, but there was no difference between treatment with eltrombopag and rhTPO. Similarly, days required for the recovery of platelet counts to ≥50×109/L and ≥75×109/L were not different between the two treatment groups but significantly higher than the control group (P <.05). Rates of bleeding and platelet transfusion were all significantly reduced in patients treated with eltrombopag (P=.031,.032) or rhTPO (P=.017,.009) when compared to the control. Treatment-related adverse events (AEs) were reported in 7 (13.7%) and 6 (12.0%) patients in the eltrombopag and rhTPO groups, respectively, all being mild and transient in nature. In conclusion, both eltrombopag and rhTPO were effective and safe in the treatment of thrombocytopenia after chemotherapy for lymphoma.
How to Facilitate Decision-Making for Hematopoietic Stem Cell Transplantation in Patients With Hemoglobinopathies. The Perspectives of Healthcare Professionals
Authors: Mekelenkamp Hilda , Zanten Herma van , Vries Martine de , Lankester Arjan , Smiers Frans
Published: August 2021

Hematopoietic stem cell transplantation decision-making for hemoglobinopathy patients is a complex process, and it remains difficult for health care professionals to decide whether and when a hematopoietic stem cell transplantation should be offered. Gaining insight into health care professionals' considerations is required to understand and optimize this decision-making process. A qualitative interview study using semi-structured interviews with eighteen health care professionals. Data were thematically analyzed. Two main themes emerged from the data: (1) Experiencing the influence of a frame of reference and (2) Feeling responsible for a guided decision-making. The frame of reference, meaning the health care professionals' knowledge and experiences regarding hematopoietic stem cell transplantation, influenced the guided decision-making process. Subsequently, three subthemes evolved from the second theme: (a) weighing up disease severity against possible complications, (b) making an effort to inform, and (c) supporting the best fitting decision for the individual patient. The health care professionals' frame of reference determined the hematopoietic stem cell transplantation decision-making process. This demands reflection on the health care professionals' own frame of reference and its influence on decision-making. Furthermore, reflection on the frame of reference is needed by exchange of knowledge and experiences between referring and referred-to healthcare professionals in an open and two-way direction. The transplantation teams have a responsibility of keeping the frame of reference of their referring colleagues up to date and referring health care professionals should share their feelings regarding hematopoietic stem cell transplantation. To guide patients, a shared decision-making approach is supportive, in which eliciting the patients' preferences is highly important. Health care professionals can refine the decision-making process by guiding patients in eliciting their preferences and including these in the decision.
Anti-Adipogenic Effect of Alchemilla monticola is Mediated Via PI3K/AKT Signaling Inhibition in Human Adipocytes
Authors: Mladenova Saveta G. , Vasileva Liliya V. , Savova Martina S. , Marchev Andrey S. , Tews Daniel , Wabitsch Martin , Ferrante Claudio , Orlando Giustino , Georgiev Milen I.
Published: August 2021

Obesity is a persistent and continuously expanding social health concern. Excessive fat mass accumulation is associated with increased risk of chronic diseases including diabetes, atherosclerosis, non-alcoholic steatohepatitis, reproductive dysfunctions and certain types of cancer. Alchemilla monticola Opiz. is a perennial plant of the Rosaceae family traditionally used to treat inflammatory conditions and as a component of weight loss herbal mixtures. In the search for bioactive leads with potential anti-adipogenic effect from A. monticola extract (ALM), we have employed nuclear magnetic resonance (NMR) based metabolomics to obtain data for the phytochemical profile of the extract. Further, molecular docking simulation was performed against key adipogenic targets for selected pure compounds, present in the ALM extract. Evaluation of the biological activity was done in human adipocytes exposed to ALM (5, 10 and 25 μg/ml), pure astragalin (AST) or quercitrin (QUE) both at the concentrations of 5, 10 and 25 μM. Investigation of the molecular pathways involved was performed through real-time quantitative PCR and Western blot analyses. According to the docking predictions strong putative affinity was revealed for both AST and QUE towards peroxisome proliferator-activated receptor gamma (PPARγ) and phosphoinositide 3-kinase (PI3K). Assessment of the intracellular lipid accumulation revealed anti-adipogenic activity of ALM. Correspondingly, the expression of the adipogenic genes CCAAT/enhancer-binding protein alpha (CEBPA) and PPARG was downregulated upon ALM and AST treatment. The Western blotting results exposed protein kinase B (AKT), PI3K and PPARγ as targets for the inhibitory effect of ALM and AST on adipogenesis. Collectively, we provide a broader insight of the phytochemical composition of A. monticola. Additionally, we demonstrate the anti-adipogenic effect of ALM and its active compound AST in human adipocytes. Furthermore, PI3K/AKT signaling pathway is identified to mediate the ALM anti-adipogenic action. Hence, the ALM extract and its secondary metabolite AST are worth further exploration as potentially active agents in obesity management.
The LAC Score Indicates Significant Fibrosis in Patients With Chronic Drug-Induced Liver Injury: A Large Biopsy-Based Study
Authors: Li Zhong-Bin , Chen Dan-Dan , He Qing-Juan , Li Le , Zhou Guangde , Fu Yi-Ming , Deng Ya , Niu Xiao-Xia , Chu Fang , Gao Xiao-Pan , Zou Zhengsheng , Chen Guofeng , Ji Dong
Published: August 2021

Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.