bluuebunny/crossref_metadata_2025 huggingface dataset:
Image Descriptors for Weakly Annotated Histopathological Breast Cancer Data
Authors: Stanitsas Panagiotis , Cherian Anoop , Morellas Vassilios , Tejpaul Resha , Papanikolopoulos Nikolaos , Truskinovsky Alexander
Published: December 2020

Introduction: Cancerous Tissue Recognition (CTR) methodologies are continuously integrating advancements at the forefront of machine learning and computer vision, providing a variety of inference schemes for histopathological data. Histopathological data, in most cases, come in the form of high-resolution images, and thus methodologies operating at the patch level are more computationally attractive. Such methodologies capitalize on pixel level annotations (tissue delineations) from expert pathologists, which are then used to derive labels at the patch level. In this work, we envision a digital connected health system that augments the capabilities of the clinicians by providing powerful feature descriptors that may describe malignant regions.

Material and Methods: We start with a patch level descriptor, termed Covariance-Kernel Descriptor (CKD), capable of compactly describing tissue architectures associated with carcinomas. To leverage the recognition capability of the CKDs to larger slide regions, we resort to a multiple instance learning framework. In that direction, we derive the Weakly Annotated Image Descriptor (WAID) as the parameters of classifier decision boundaries in a Multiple Instance Learning framework. The WAID is computed on bags of patches corresponding to larger image regions for which binary labels (malignant vs. benign) are provided, thus obviating the necessity for tissue delineations.

Results: The CKD was seen to outperform all the considered descriptors, reaching classification accuracy (ACC) of 92.83%. and area under the curve (AUC) of 0.98. The CKD captures higher order correlations between features and was shown to achieve superior performance against a large collection of computer vision features on a private breast cancer dataset. The WAID outperform all other descriptors on the Breast Cancer Histopathological database (BreakHis) where correctly classified malignant (CCM) instances reached 91.27 and 92.00% at the patient and image level, respectively, without resorting to a deep learning scheme achieves state-of-the-art performance.

Discussion: Our proposed derivation of the CKD and WAID can help medical experts accomplish their work accurately and faster than the current state-of-the-art.
Post-Depositional Fluid Flow in Jurassic Sandstones of the Uncompahgre Uplift: Insights From Magnetic Fabrics
Authors: Ejembi John I. , Ferré Eric C. , Satolli Sara , Friedman Sarah A.
Published: December 2020

The anisotropy of magnetic susceptibility (AMS) in sedimentary rocks results from depositional, diagenetic, syn- and post-sedimentary processes that affect magnetic grains. Some studies have also shown the potential role played by post-depositional fluid flow in detrital and carbonate formations. Here we present a new case study of Middle-Upper Jurassic sandstones where secondary iron oxides, precipitated from fluids that migrated through pores, give rise to the AMS. These sandstones are well exposed in the Uncompahgre Uplift region of the Central Colorado Trough, Colorado. The magnetic foliation of these undeformed, subhorizontal strata consistently strike NE-SW over a large distance with an average 45° dip to the SE. This steep AMS fabric is oblique with respect to the regional subhorizontal bedding and therefore does not reflect the primary sedimentary fabric. Also, outcrop-scale and microscopic observations show a lack of post-depositional plastic (undulose extinction) or pressure-solution (stylolites) deformation microstructures in these sandstones, hence precluding a tectonic origin. The combination of magnetic hysteresis, isothermal remanent magnetization, and thermal demagnetization of the natural remanent magnetization indicate that these rocks carry a chemical remanent magnetization born primarily by hematite and goethite. High-field magnetic hysteresis and electron microscopy indicate that detrital magnetite and authigenic hematite are the main contributors to the AMS. These results show that post-depositional iron remobilization through these porous sandstones took place due to the action of percolating fluids which may have started as early as Late Cretaceous along with the Uncompahgre Uplift. The AMS fabric of porous sandstones does not systematically represent depositional or deformation processes, and caution is urged in the interpretation of magnetic fabrics in these types of reservoir rock. Conversely, understanding these fabrics may advance our knowledge of fluid flow in porous sandstones and may have applications in hydrocarbon exploration.
Six-Week Exercise Training With Dietary Restriction Improves Central Hemodynamics Associated With Altered Gut Microbiota in Adolescents With Obesity
Authors: Huang Junhao , Liao Jingwen , Fang Yang , Deng Hailin , Yin Honggang , Shen Bing , Hu Min
Published: December 2020

Purpose

Obesity in children and in adolescents can lead to adult cardiovascular diseases, and the gut microbiota plays a crucial role in obesity pathophysiology. Exercise and diet interventions are typical approaches to improve physical condition and to alter the gut microbiota in individuals with obesity. However, whether central hemodynamic parameters including subendocardial viability ratio, the augmentation index standardized to a heart rate of 75/min (AIx75), resting heart rate, and blood pressure, correlate with gut microbiota changes associated with exercise and diet is unclear.

Methods

Adolescents (n = 24, 12.88 ± 0.41 years) with obesity completed our 6-week program of endurance and strength exercises along with dietary restriction. Blood and fecal samples were collected, and physical parameters were measured before and 24 h after the last session of the intervention program. Pulse wave analysis using applanation tonometry provided the subendocardial viability ratio, a surrogate measure of microvascular myocardial perfusion, and AIx75, a measure of arterial stiffness and peripheral arteriolar resistance. Correlation analysis detected any associations of anthropometric or central hemodynamic parameters with gut microbiome composition.

Results

Exercise and diet interventions significantly reduced body weight, body mass index, body fat, and waist-to-hip ratio, and lowered levels of fasting blood glucose, serum triglycerides, and high-density lipoprotein cholesterol. AIx75 and resting heart rate were also significantly reduced after the intervention without changes to systolic or diastolic blood pressure. The ratio of intestinal microbiota Firmicutes to Bacteroidetes displayed a marked increase after intervention. Interventional changes in gut microbiota members were significantly associated with anthropometric and metabolic parameters. Microbial changes were also significantly correlated with central hemodynamic parameters, including subendocardial viability ratio, AIx75, and resting heart rate.

Conclusion

Exercise and diet interventions significantly improved measures of central hemodynamics, including subendocardial viability ratio, AIx75, and resting heart rate, which were correlated with altered gut microbiota in adolescents with obesity. Our findings shed light on the effects and mechanisms underlying exercise and diet interventions on obesity and suggest this approach for treating patients with both cardiovascular disease and obesity.
Glycemic Control Improvement in Italian Children and Adolescents With Type 1 Diabetes Followed Through Telemedicine During Lockdown Due to the COVID-19 Pandemic
Authors: Predieri Barbara , Leo Francesco , Candia Francesco , Lucaccioni Laura , Madeo Simona F. , Pugliese Marisa , Vivaccia Valentina , Bruzzi Patrizia , Iughetti Lorenzo
Published: December 2020

Background/Objective

To minimize the wide spread of coronavirus disease (COVID-19) pandemic, Italy was placed in an almost complete lockdown state that forced people to “stay at home”. Aim of this study was to evaluate the effects of lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) followed through telemedicine.

Subjects/Methods

This observational study involved patients with T1D using the real-time continuous glucose monitoring (CGM) Dexcom G6®. Ambulatory glucose profile data from the 3-months before schools closure (November 26, 2019–February 23, 2020; T0) and from the 3-months of consecutive lockdown (February 24–May 18, 2020; T1) were compared.

Results

Sixty-two children and adolescents (11.1 ± 4.37 years, 50% males) with T1D (median time disease 3.67 years) were enrolled in the study. Insulin total daily dose was unchanged, while time spent on physical activities was decreased (p<0.0001). Despite the lack of statistical significance, median value of the glucose management indicator decreased from 7.4% to 7.25%. Glucose standard deviation (p<0.0001) and coefficient of variation (p=0.001) improved across the study. Median time in range increased from 60.5% to 63.5% (p=0.008), time above range decreased from 37.3% to 34.1% (p=0.048), and time below range decreased from 1.85% to 1.45% (p=0.001).

Conclusions

Overall, in our children and adolescents with T1D glycemic control improved during lockdown. Despite patients were confined to their homes and limited to exercise, our data suggest that the use of real-time CGM, the continuous parental management, and the telemedicine can display beneficial effects on T1D care.
Strontium Uptake and Intra-Population 87Sr/86Sr Variability of Bones and Teeth—Controlled Feeding Experiments With Rodents (Rattus norvegicus, Cavia porcellus)
Authors: Weber Michael , Tacail Théo , Lugli Federico , Clauss Marcus , Weber Katrin , Leichliter Jennifer , Winkler Daniela E. , Mertz-Kraus Regina , Tütken Thomas
Published: December 2020

Strontium isotopes in biogenic apatite, especially enamel, are widely employed to determine provenance and track migration in palaeontology and archaeology. Body tissues record the 87Sr/86Sr of bioavailable Sr of ingested food and water. To identify non-local individuals, knowledge of the 87Sr/86Sr of a non-migratory population is required. However, varying factors such as tissue turnover rates, feeding selectivity, Sr content, digestibility of food, and the ingestion of mineral dust can influence body tissue 87Sr/86Sr. To evaluate the Sr contribution of diet and water to mammalian hard tissues 87Sr/86Sr, controlled feeding studies are necessary. Here we present 87Sr/86Sr from controlled feeding experiments with two rodent species (Rattus norvegicus, Cavia porcellus). Due to the continuous and fast incremental growth of rat and guinea pig incisors (~0.1 – 0.5 mm/day), their enamel is expected to record isotopic dietary changes. For Experiment-1: Diet Switch, animals were switched from their respective supplier food to a pelleted experimental diet containing either insect-, plant-, or meat-meal and a staggered-sampling approach was used to monitor the 87Sr/86Sr changes in rat incisor enamel and bone over the course of the experiment. In Experiment-2: Basic Diets, separated cohorts (n = 6) of rats and guinea pigs were fed one of the three pelleted diets and received tap water for 54 days. While the rat incisors showed a complete tissue turnover, the slower-growing guinea pig incisors partially retained supplier diet-related isotopic compositions. In addition, one group of rats fed plant-meal pellets received Sr-rich mineral water, demonstrating that drinking water can be an important Sr source in addition to diet. Additionally, a leaching experiment showed that only a small fraction of diet-related Sr is bioavailable. Finally, in Experiment-3: Dust Addition, guinea pigs were fed pellets with and without addition of 4% of isotopically distinct dust (loess or kaolin). Animals that received kaolin-containing pellets displayed increased enamel 87Sr/86Sr. Intra-population 87Sr/86Sr variability within each feeding group was small and thus we conclude that it should not affect interpretations of 87Sr/86Sr in provenance studies. However, the differences between bulk food and leachate 87Sr/86Sr highlight the importance of Sr bioavailability for provenance studies and Sr isoscapes.
The Elephant in the Lab (and Field): Contamination in Aquatic Environmental DNA Studies
Authors: Sepulveda Adam J. , Hutchins Patrick R. , Forstchen Meghan , Mckeefry Madeline N. , Swigris Anna M.
Published: December 2020

The rapid evolution of environmental (e)DNA methods has resulted in knowledge gaps in smaller, yet critical details like proper use of negative controls to detect contamination. Detecting contamination is vital for confident use of eDNA results in decision-making. We conducted two literature reviews to summarize (a) the types of quality assurance measures taken to detect contamination of eDNA samples from aquatic environments, (b) the occurrence, frequency and attribution (i.e., putative sources) of unexpected amplification in these quality assurance samples, and (c) how results were interpreted when contamination occurred. In the first literature review, we reviewed 156 papers and found that 91% of targeted and 73% of metabarcoding eDNA studies reported inclusion of negative controls within their workflows. However, a large percentage of targeted (49%) and metabarcoding (80%) studies only reported negative controls for laboratory procedures, so results were potentially blind to field contamination. Many of the 156 studies did not provide critical methodological information and amplification results of negative controls. In our second literature review, we reviewed 695 papers and found that 30 targeted and 32 metabarcoding eDNA studies reported amplification of negative controls. This amplification occurred at similar proportions for field and lab workflow steps in targeted and metabarcoding studies. These studies most frequently used amplified negative controls to delimit a detection threshold above which is considered significant or provided rationale for why the unexpected amplifications did not affect results. In summary, we found that there has been minimal convergence over time on negative control implementation, methods, and interpretation, which suggests that increased rigor in these smaller, yet critical details remains an outstanding need. We conclude our review by highlighting several studies that have developed especially effective quality assurance, control and mitigation methods.
Population Genetic Structure and Connectivity of the European Lobster Homarus gammarus in the Adriatic and Mediterranean Seas
Authors: Pavičić Mišo , Žužul Iva , Matić-Skoko Sanja , Triantafyllidis Alexandros , Grati Fabio , Durieux Eric D. H. , Celić Igor , Šegvić-Bubić Tanja
Published: December 2020

Highly selective fishing has the potential to permanently change the characteristics within a population and could drive the decline of genetic diversity. European lobster is an intensively fished crustacean species in the Adriatic Sea which reaches high market value. Since knowledge of population structure and dynamics is important for effective fisheries management, in this study, we used 14 neutral microsatellites loci and partial mitochondrial COI region sequencing to explore population connectivity and genetic structure by comparing samples from the Adriatic Sea and the adjacent basins of the Mediterranean Sea. The obtained results suggest that neutral genetic diversity has not been significantly affected by decrease in population size due to overfishing, habitat degradation and other anthropogenic activities. Global genetic differentiation across all populations was low (FST= 0.0062). Populations from the Adriatic Sea were panmictic, while genetic differentiation was found among populations from different Mediterranean basins. Observed gene flow for European lobster suggest that populations in the north eastern Adriatic act as a source for surrounding areas, emphasizing the need to protect these populations by establishing interconnected MPAs that will be beneficial for both fisheries and conservation management.
Insights Into Mucosal Innate Immune Responses in House Dust Mite-Mediated Allergic Asthma
Authors: Abu Khweek Arwa , Kim Eunsoo , Joldrichsen Marisa R. , Amer Amal O. , Boyaka Prosper N.
Published: December 2020

The prevalence of asthma has been rising steadily for several decades, and continues to be a major public health and global economic burden due to both direct and indirect costs. Asthma is defined as chronic heterogeneous inflammatory diseases characterized by airway obstruction, mucus production and bronchospasm. Different endotypes of asthma are being recognized based on the distinct pathophysiology, genetic predisposition, age, prognosis, and response to remedies. Mucosal innate response to environmental triggers such as pollen, cigarette smoke, fragrances, viral infection, and house dust mite (HDM) are now recognized to play an important role in allergic asthma. HDM are the most pervasive allergens that co-habitat with us, as they are ubiquitous in-house dusts, mattress and bedsheets, and feed on a diet of exfoliated human skin flakes.Dermatophagoides pteronyssinus, is one among several HDM identified up to date. During the last decade, extensive studies have been fundamental in elucidating the interactions between HDM allergens, the host immune systems and airways. Moreover, the paradigm in the field of HDM-mediated allergy has been shifted away from being solely a Th2-geared to a complex response orchestrated via extensive crosstalk between the epithelium, professional antigen presenting cells (APCs) and components of the adaptive immunity. In fact, HDM have several lessons to teach us about their allergenicity, the complex interactions that stimulate innate immunity in initiating and perpetuating the lung inflammation. Herein, we review main allergens ofDermatophagoides pteronyssinusand their interactions with immunological sentinels that promote allergic sensitization and activation of innate immunity, which is critical for the development of the Th2 biased adaptive immunity to HDM allergens and development of allergic asthma.
Molecular and Immune Characteristics for Lung Adenocarcinoma Patients With ERLIN2 Overexpression
Authors: Liu Yifei , Xie Pengfei , Jiang Daishang , Liu Jian , Zhang Jianguo , Bian Tingting , Shi Jiahai
Published: December 2020

Background

Endoplasmic reticulum lipid raft-associated protein 2 (ERLIN2) is protein contained in the membrane of the endoplasmic reticulum. In lung adenocarcinoma (LUAD), the molecular function of ERLIN2 and the correlation between ERLIN2 and tumor-infiltrating immune cells have been unclear. The aim of our study was to determine the role of ERLIN2 in LUAD development to provide a better understanding of the molecular pathogenesis of this disease and identify new therapeutic targets for its treatment.

Methods

Immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to detect protein and mRNA levels of ERLIN2 in LUAD and adjacent normal tissues. Using the A549, H1299 cell line, ERLIN2-short hairpin RNA was applied to silence ERLIN2 to determine its role in LUAD cell proliferation and invasion. Based on mRNA expression of ERLIN2 from the Cancer Genome Atlas (TCGA) database, we identified ERLIN2-related protein-coding genes and analyzed the Kyoto Encyclopedia of Genes and Genomes pathway to explore its potential biological functions and determined the correlation between ERLIN2 and tumor-infiltrating immune cells.

Results

ERLIN2 was abnormally expressed in a variety of tumor tissues and is highly expressed in LUAD. This overexpression was associated with histological grade (P = 0.044), TNM stage (P = 0.01), and lymph node metastasis (P = 0.038). Patient overall survival was poorer with ERLIN2 overexpression. Downregulation of ERLIN2 inhibited LUAD cell proliferation and invasion in vitro. Based on mRNA expression of ERLIN2 from the TCGA database, 13 ERLIN2-related genes and 10 pathways were identified and showed a correlation between ERLIN2 and naive B cells and neutrophils.

Conclusion

ERLIN2 could serve as a potential diagnostic and prognostic biomarker for LUAD and has demonstrated to be correlated with immune infiltrates, which suggests that it may represent a new therapeutic target for LUAD.
Distinct Molecular Mechanisms Underlying Potassium Efflux for NLRP3 Inflammasome Activation
Authors: Xu Ziwei , Chen Zi-mo , Wu Xiaoyan , Zhang Linjie , Cao Ying , Zhou Pingzheng
Published: December 2020

The NLRP3 inflammasome is a core component of innate immunity, and dysregulation of NLRP3 inflammasome involves developing autoimmune, metabolic, and neurodegenerative diseases. Potassium efflux has been reported to be essential for NLRP3 inflammasome activation by structurally diverse pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Thus, the molecular mechanisms underlying potassium efflux to activate NLRP3 inflammasome are under extensive investigation. Here, we review current knowledge about the distinction channels or pore-forming proteins underlying potassium efflux for NLRP3 inflammasome activation with canonical/non-canonical signaling or following caspase-8 induced pyroptosis. Ion channels and pore-forming proteins, including P2X7 receptor, Gasdermin D, pannexin-1, and K2P channels involved present viable therapeutic targets for NLRP3 inflammasome related diseases.
Detrital Subsidies in the Diet of Mytilus edulis; Macroalgal Detritus Likely Supplements Essential Fatty Acids
Authors: Both Adrianus , Byron Carrie J. , Costa-Pierce Barry , Parrish Christopher C. , Brady Damian C.
Published: December 2020

Detritus is a frequent, poorly defined, component of bivalve growth and carrying capacity models. The purpose of this study was to determine the proportional contributions of detrital material derived from primary producers (phytoplankton, macroalgae,Spartina alterniflora, and terrestrial leaf litter) to particulate organic matter (POM) and blue mussel’s (Mytilus edulis) diet within a temperate bay (Saco Bay, ME, United States). We assessed which detrital sources, if any, warranted incorporation into modeling efforts. Stable isotopes (δ13C and δ15N) and fatty acid biomarkers (FA) of mussels, size fractionated (<100 μm) POM, and primary producer endmembers (phytoplankton,Saccharina latissima, Ascophyllum nodosum, Chondrus crispus, Spartina alternifloraand leaf litter) collected between 2016 and 2017 were used to estimate endmember contributions to POM and mussel diets. Based on FAs dinoflagellates were the most abundant phytoplankton in Saco Bay, even during the fall diatom bloom. Diatoms within the bay were primarily centric, but pennate diatoms were at times present in the water column (e.g., in September). Following abundances of dinoflagellates, and centric and pennate diatoms, 22:6ω3 (DHA) was the most abundant essential FA (8.6 ± 0.1% total FAs), followed by 20:5ω3 (EPA: 7.0 ± 0.1%) and 20:4ω6 (ARA: 0.3 ± 0.1%). On average, phytoplankton derived organic matter contributed 22.1 ± 0.3% of the total POM in the bay. The concentration of non-fresh phytoplankton organic matter, or remaining organic matter (REMORG), was positively correlated with all endmember biomarkers. However, the proportion (%) of vascular plant, macroalgal, and detrital FAs was negatively correlated with the concentration of REMORG. This finding suggests in periods of low productivity, vascular plant and macroalgal detritus are proportionally more important contributors to POM. Mussels were broad spectrum omnivores, consuming phytoplankton, zooplankton, and detrital material. Detrital contributions to mussel diets were important (minimum of 16% of diet). Although small, macroalgae’s dietary contribution (8%) toM. edulismay be important. Macroalgal detritus contained essential FAs (20:5ω3 and 20:4ω6) that could supplement mussel diets, asM. edulisin Saco Bay were likely limited by 20:5ω3. Consideration of how macroalgal detritus affects the availability of essential FAs in POM may be useful to incorporate into aquaculture site selection.
Thermal Transport in Two-Dimensional Heterostructures
Authors: Chen Xue-Kun , Zeng Yu-Jia , Chen Ke-Qiu
Published: December 2020

Heterostructures based on two-dimensional (2D) materials have attracted intense attention in recent decades due to their unusual and tunable physics/chemical properties, which can be converted into promising engineering applications ranging from electronics, photonics, and phononics to energy recovery. A fundamental understanding of thermal transport in 2D heterostructures is crucial importance for developing micro-nano devices based on them. In this review, we summarized the recent advances of thermal transport in 2D heterostructures. Firstly, we introduced diverse theoretical approaches and experimental techniques for thermal transport in low-dimensional materials. Then we briefly reviewed the thermal properties of various 2D single-phase materials beyond graphene such as hexagonal boron nitride (h-BN), phosphorene, transition metal dichalcogenides (TMDs) and borophene, and emphatically discussed various influencing factors including structural defects, mechanical strain, and substrate interactions. Moreover, we highlighted thermal conduction control in tailored nanosystems—2D heterostructures and presented the associated underlying physical mechanisms, especially interface-modulated phonon dynamics. Finally, we outline their significant applications in advanced thermal management and thermoelectrics conversion, and discuss a number of open problems on thermal transport in 2D heterostructures.
Strain Hardening Behavior of Laminate Structure With Stable bcc/fcc Bimetal Interfaces
Authors: Huang Xuqiang , Lu Zhaoyang , Cai Minghui , Hodgson Peter D.
Published: December 2020

This work developed a well-bonded bcc/fcc bimetal interphase, which was produced by a two-step process involving diffusion bonding and conventional rolling. The high-quality interface maintained its integrity even at fracture. The earlier tensile instability in the core steel layer was constrained by the neighboring stable Cu layers on both sides, leading to extra strain hardening and consequently higher ductility. An increase in twin density or slip bands and shear deformation between the layers might be the primary causes for the observed hardening behaviors in the near-interface regions.
Integrating Tumor Stroma Biomarkers With Clinical Indicators for Colon Cancer Survival Stratification
Authors: Chen Yong , Wang Wenlong , Jiang Bo , Yao Lei , Xia Fada , Li Xinying
Published: December 2020

The tumor stroma plays an important role in tumor progression and chemotherapeutic resistance; however, its role in colon cancer (CC) survival prognosis remains to be investigated. Here, we identified tumor stroma biomarkers and evaluated their role in CC prognosis stratification. Four independent datasets containing a total of 1,313 patients were included in this study and were divided into training and testing sets. Stromal scores calculated using the estimation of stromal and immune cells in malignant tumors using expression data (ESTIMATE) algorithm were used to assess the tumor stroma level. Kaplan-Meier curves and the log-rank test were used to identify relationships between stromal score and prognosis. Tumor stroma biomarkers were identified by cross-validation of multiple datasets and bioinformatics methods. Cox proportional hazards regression models were constructed using four prognosis factors (age, tumor stage, the ESTIMATE stromal score, and the biomarker stromal score) in different combinations for prognosis prediction and compared. Patients with high stromal scores had a lower overall survival rate (p = 0.00016), higher risk of recurrence (p < 0.0001), and higher probability of chemotherapeutic resistance (p < 0.0001) than those with low scores. We identified 16 tumor stroma biomarkers and generated a new prognosis indicator termed the biomarker stromal score (ranging from 0 to 16) based on their expression levels. Its addition to an age/tumor stage-based model significantly improved prognosis prediction accuracy. In conclusion, the tumor stromal score is significantly negatively associated with CC survival prognosis, and the new tumor stroma indicator can improve CC prognosis stratification.
The Link Between Autonomic Nervous System and Rheumatoid Arthritis: From Bench to Bedside
Authors: Ingegnoli Francesca , Buoli Massimiliano , Antonucci Flavia , Coletto Lavinia Agra , Esposito Cecilia Maria , Caporali Roberto
Published: December 2020

Neuronal stimulation is an emerging field of research focused on the management and treatment of various diseases through the reestablishment of physiological homeostasis. Electrical vagus nerve stimulation has recently been proposed as a revolutionary therapeutic option for rheumatoid arthritis (RA) in combination with or even as a replacement for conventional and biological drugs. In the past few years, disruption of the autonomic system has been linked to RA onset and activity. Novel research on the link between the autonomic nervous system and the immune system (immune-autonomics) has paved the way for the development of innovative RA management strategies. Clinical evidence supports this approach. Cardiovascular involvement, in terms of reduced baroreflex sensitivity and heart rate variability-derived indices, and mood disorders, common comorbidities in patients with RA, have been linked to autonomic nervous system dysfunction, which in turn is influenced by increased levels of circulating pro-inflammatory cytokines. This narrative review provides an overview of the autonomic nervous system and RA connection, discussing most of the common cardiac and mental health-related RA comorbidities and their potential relationships to systemic and joint inflammation.
The Impact of SARS-CoV-2 Outbreak on Primary Sjögren's Syndrome: An Italian Experience
Authors: Carubbi Francesco , Alunno Alessia , Ferri Claudio , Gerli Roberto , Bartoloni Elena
Published: December 2020

Objective:Since no data is available about the personal experience of people with primary Sjögren's syndrome (pSS) with regard to disease burden and management during the novel Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)-2 outbreak, we aimed to explore these aspects with the ultimate goal to identify unmet needs and priorities.

Methods:A telephone consultation was scheduled with patients with pSS and information regarding the disease status, ongoing treatment and symptoms/diagnosis of coronavirus disease 2019 (COVID-19) were collected. Clinical records were retrospectively evaluated to gather pre-COVID-19 information.

Results:One hundred and two patients with pSS were contacted. Most rheumatology consultations and other pSS-related tests were canceled during the SARS-CoV-2 outbreak. Less than 30% of patients contacted the rheumatologist via telemedicine despite experiencing disease flares or therapy shortage. Disease activity and patient reported symptoms significantly worsened during the closure period. All patients practiced social distancing, most of those employed switched to smart working and different work settings impacted on the type of symptom worsening.

Conclusion:This is the first study addressing the personal experience of pSS patients resulting from the impact of the SARS-CoV2 outbreak and it identifies unmet needs and priorities requiring to be addressed. Our findings may help designing individualized strategies
Advances in the Approaches Using Peripheral Perfusion for Monitoring Hemodynamic Status
Authors: Falotico Julianne M. , Shinozaki Koichiro , Saeki Kota , Becker Lance B.
Published: December 2020

Measures of peripheral perfusion can be used to assess the hemodynamic status of critically ill patients. By monitoring peripheral perfusion status, clinicians can promptly initiate life-saving therapy and reduce the likelihood of shock-associated death. Historically, abnormal perfusion has been indicated by the observation of pale, cold, and clammy skin with increased capillary refill time. The utility of these assessments has been debated given that clinicians may vary in their clinical interpretation of body temperature and refill time. Considering these constraints, current sepsis bundles suggest the need to revise resuscitation guidelines. New technologies have been developed to calculate capillary refill time in the hopes of identifying a new gold standard for clinical care. These devices measure either light reflected at the surface of the fingertip (reflected light), or light transmitted through the inside of the fingertip (transmitted light). These new technologies may enable clinicians to monitor peripheral perfusion status more accurately and may increase the potential for ubiquitous hemodynamic monitoring across different clinical settings. This review will summarize the different methods available for peripheral perfusion monitoring and will discuss the advantages and disadvantages of each approach.
Acute-on-Chronic Liver Failure From Chronic-Hepatitis-B, Who Is the Behind Scenes
Authors: Li Qian , Wang Jun , Lu Mengji , Qiu Yuanwang , Lu Hongzhou
Published: December 2020

Acute-on-chronic liver failure (ACLF) is an acute syndrome accompanied with decompensation of cirrhosis, organ failure with high 28-day mortality rate. Systemic inflammation is the main feature of ACLF, and poor outcome is closely related with exacerbated systemic inflammatory responses. It is well known that severe systemic inflammation is an important event in chronic hepatitis B (CHB)-ACLF, which eventually leads to liver injury. However, the initial CHB-ACLF events are unclear; moreover, the effect of these events on host immunity as well as that of immune imbalance on CHB-ACLF progression are unknown. Here, we investigate the initial events of ACLF progression, discuss possible mechanisms underlying ACLF progression, and provide a new model for ACLF prediction and treatment. We review the characteristics of ACLF, and consider its plausible immune predictors and alternative treatment strategies.
Effect of Lactic Acid Bacteria Addition on the Microbiological Safety of Pasta-Filata Types of Cheeses
Authors: Medved’ová Alžbeta , Koňuchová Martina , Kvočiková Karolína , Hatalová Ivana , Valík L’ubomír
Published: December 2020

In this work, the effects of different combinations of lactic acid bacteria (LAB) on the growth of coagulase-positive staphylococci (CPS) and Escherichia coli were evaluated during ripening of 23 curd cheeses, and their subsequent behavior during the manufacture and storage of pasta-filata cheeses was characterized. Three groups of cheeses were prepared in total: first, control cheeses from raw milk without LAB addition; further pasteurized milk cheeses with LAB, CPS and E. coli intentional inoculation; and finally, raw milk cheeses with LAB added. The aim was to compare the effect of LAB from starter culture, and also in combination with native LAB, and to evaluate the LAB effect as a group, and further to suggest the culture with the best inhibitory potential. Based on the results, counts of CPS increased over 24 h in control curd cheese by 1.76 ± 0.56 log CFU/g. On the other hand, in raw milk cheeses with the addition of starter culture, the increase in CPS counts by 0.76 ± 0.87 log CFU/g was noticed. Counts of E. coli increased during the first 24 h of curd manufacture by 3.56 ± 0.41 log CFU/g in cheeses without LAB addition. Contrary to this, using of LAB cultures resulted in an increase in E. coli counts by only 1.40 ± 1.07 log CFU/g. After steaming at 63.6 ± 1.9°C for 7.2 ± 2.1 min (temperature of heated acidified curd was 54.9 ± 1.7°C), CPS decreased by 0.58 ± 1.12 log CFU/g, and E. coli decreased by 1.23 ± 0.97 log CFU/g in all cheeses, regardless of LAB addition. Finally, during storage of cheeses at 6 ± 0.5°C for 28 days, the levels of E. coli in control cheeses and in raw milk LAB-enriched cheeses reached levels of 2.07 ± 2.28 log CFU/g and 1.20 ± 0.85 log CFU/g, respectively. In addition, the counts of CPS at the end of storage met the criteria of EU Commission Regulation (EC) No. 1441/2007 (2007) (less than 4 log CFU/g) in all manufactured cheeses with added LAB culture, while in the control raw milk cheeses, a level of 3.80 ± 1.22 log CFU/g was observed. Regarding the culture used, the best microbiological inhibitory effect in 28-day-old cheeses was reached by the combination of Fresco culture with Lacticaseibacillus rhamnosus GG, and the best sensory properties were judged to be those for cheeses manufactured with Culture A. A moderate negative effect of storage on overall sensory acceptance was noted, according to the final evaluation of overall acceptability of pasta-filata cheeses. The most satisfactory overall acceptability after 28 days of storage at 6°C was reached for cheese with the addition of culture A.
Homology-Directed Repair in Zebrafish: Witchcraft and Wizardry?
Authors: Prill Kendal , Dawson John F.
Published: December 2020

Introducing desired mutations into the genome of model organisms is a priority for all research focusing on protein function and disease modeling. The need to create stable mutant lines has resulted in the rapid advancement of genetic techniques over the last few decades from chemical mutagenesis and zinc finger nucleases to clustered regularly interspaced short palindromic repeats (CRISPR) and homology-directed repair (HDR). However, achieving consistently high success rates for direct mutagenesis in zebrafish remains one of the most sought-after techniques in the field. Several genes have been modified using HDR in zebrafish, but published success rates range widely, suggesting that an optimal protocol is required. In this review, we compare target genes, techniques, and protocols from 50 genes that were successfully modified in zebrafish using HDR to find the statistically best variables for efficient HDR rates.
m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer
Authors: Xiang Shixin , Ma Yongshun , Shen Jing , Zhao Yueshui , Wu Xu , Li Mingxing , Yang Xiao , Kaboli Parham Jabbarzadeh , Du Fukuan , Ji Huijiao , Zheng Yuan , Li Xiang , Li Jing , Wen Qinglian , Xiao Zhangang
Published: December 2020

5-Methylcytosine (m5C) is a kind of methylation modification that occurs in both DNA and RNA and is present in the highly abundant tRNA and rRNA. It has an important impact on various human diseases including cancer. The function of m5C is modulated by regulatory proteins, including methyltransferases (writers) and special binding proteins (readers). This study aims at comprehensive study of the m5C RNA methylation-related genes and the main pathways under m5C RNA methylation in gastrointestinal (GI) cancer. Our result showed that the expression of m5C writers and reader was mostly up-regulated in GI cancer. The NSUN2 gene has the highest proportion of mutations found in GI cancer. Importantly, in liver cancer, higher expression of almost all m5C regulators was significantly associated with lower patient survival rate. In addition, the expression level of m5C-related genes is significantly different at various pathological stages. Finally, we have found through bioinformatics analysis that m5C regulatory proteins are closely related to the ErbB/PI3K–Akt signaling pathway and GSK3B was an important target for m5C regulators. Besides, the compound termed streptozotocin may be a key candidate drug targeting on GSK3B for molecular targeted therapy in GI cancer.
A Protocol for Cortical Type Analysis of the Human Neocortex Applied on Histological Samples, the Atlas of Von Economo and Koskinas, and Magnetic Resonance Imaging
Authors: García-Cabezas Miguel Ángel , Hacker Julia Liao , Zikopoulos Basilis
Published: December 2020

The human cerebral cortex is parcellated in hundreds of areas using neuroanatomy and imaging methods. Alternatively, cortical areas can be classified into few cortical types according to their degree of laminar differentiation. Cortical type analysis is based on the gradual and systematic variation of laminar features observed across the entire cerebral cortex in Nissl stained sections and has profound implications for understanding fundamental aspects of evolution, development, connections, function, and pathology of the cerebral cortex. In this protocol paper, we explain the general principles of cortical type analysis and provide tables with the fundamental features of laminar structure that are studied for this analysis. We apply cortical type analysis to the micrographs of the Atlas of the human cerebral cortex of von Economo and Koskinas and provide tables and maps with the areas of this Atlas and their corresponding cortical type. Finally, we correlate the cortical type maps with the T1w/T2w ratio from widely used reference magnetic resonance imaging scans. The analysis, tables and maps of the human cerebral cortex shown in this protocol paper can be used to predict patterns of connections between areas according to the principles of the Structural Model and determine their level in cortical hierarchies. Cortical types can also predict the spreading of abnormal proteins in neurodegenerative diseases to the level of cortical layers. In summary, cortical type analysis provides a theoretical and practical framework for directed studies of connectivity, synaptic plasticity, and selective vulnerability to neurologic and psychiatric diseases in the human neocortex.
Endolymphatic Potential Measured From Developing and Adult Mouse Inner Ear
Authors: Li Yi , Liu Huizhan , Zhao Xiaochang , He David Z.
Published: December 2020

The mammalian inner ear has two major parts, the cochlea is responsible for hearing and the vestibular organ is responsible for balance. The cochlea and vestibular organs are connected by a series of canals in the temporal bone and two distinct extracellular fluids, endolymph and perilymph, fill different compartments of the inner ear. Stereocilia of mechanosensitive hair cells in the cochlea and vestibular end organs are bathed in the endolymph, which contains high K+ions and possesses a positive potential termed endolymphatic potential (ELP). Compartmentalization of the fluids provides an electrochemical gradient for hair cell mechanotransduction. In this study, we measured ELP from adult and neonatal C57BL/6J mice to determine how ELP varies and develops in the cochlear and vestibular endolymph. We measured ELP and vestibular microphonic response from saccules of neonatal mice to determine when vestibular function is mature. We show that ELP varies considerably in the cochlear and vestibular endolymph of adult mice, ranging from +95 mV in the basal turn to +87 mV in the apical turn of the cochlea, +9 mV in the saccule and utricle, and +3 mV in the semicircular canal. This suggests that ELP is indeed a local potential, despite the fact that endolymph composition is similar. We further show that vestibular ELP reaches adult-like magnitude around post-natal day 6, ~12 days earlier than maturation of cochlear ELP (i.e., endocochlear potential). Maturation of vestibular ELP coincides with the maturation of vestibular microphonic response recorded from the saccular macula, suggesting that maturation of vestibular function occurs much earlier than maturation of hearing in mice.
Is There Association Between Stress and Bruxism? A Systematic Review and Meta-Analysis
Authors: Chemelo Victória dos Santos , Né Yago Gecy de Sousa , Frazão Deborah Ribeiro , Souza-Rodrigues Renata Duarte de , Fagundes Nathalia Carolina Fernandes , Magno Marcela Baraúna , Silva Cláudia Maria Tavares da , Maia Lucianne Cople , Lima Rafael Rodrigues
Published: December 2020

This systematic review and meta-analysis aimed to investigate a possible association between stress and bruxism in humans. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines under the code CRD42020188862, and the searches were performed on the following databases: PubMed, Scopus, Web of Science, Cochrane, LILACS, OpenGrey, and Google Scholar. This systematic review evaluated observational studies in adult humans with and without stress to verify the association between bruxism and the presence of stress. The risk of bias was evaluated through the Joanna Briggs Institute Critical Appraisal Tools for Analytical Cross-Sectional Studies. In quantitative analysis, the Odds Ratio (OR) and their 95% confidence interval (CI) were calculated through a fixed-effect model. Furthermore, a summary of the overall strength of evidence was presented using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). A total of 1,458 studies were identified, and six were included in this systematic review. Two studies included were classified with a low risk of bias, and the others were classified with a moderate risk of bias. In three articles, a meta-analysis was performed and showed an association between these two factors (OR 2.07 [1.51, 2.83],p< 0.00001,I2= 45%). Besides that, a low certainty of the evidence was detected among this association. Stressed individuals show a higher chance of presenting bruxism when compared to healthy individuals. Despite the low heterogeneity found in the quantitative analysis among the articles reporting an association between stress and bruxism, further studies with similar methods are necessary to understand this relationship better.
Characterization of the Stages of Creative Writing With Mobile EEG Using Generalized Partial Directed Coherence
Authors: Cruz-Garza Jesus G. , Sujatha Ravindran Akshay , Kopteva Anastasiya E. , Rivera Garza Cristina , Contreras-Vidal Jose L.
Published: December 2020

Two stages of the creative writing process were characterized through mobile scalp electroencephalography (EEG) in a 16-week creative writing workshop. Portable dry EEG systems (four channels: TP09, AF07, AF08, TP10) with synchronized head acceleration, video recordings, and journal entries, recorded mobile brain-body activity of Spanish heritage students. Each student's brain-body activity was recorded as they experienced spaces in Houston, Texas (“Preparation” stage), and while they worked on their creative texts (“Generation” stage). We used Generalized Partial Directed Coherence (gPDC) to compare the functional connectivity among both stages. There was a trend of higher gPDC in the Preparation stage from right temporo-parietal (TP10) to left anterior-frontal (AF07) brain scalp areas within 1–50 Hz, not reaching statistical significance. The opposite directionality was found for the Generation stage, with statistical significant differences (p < 0.05) restricted to the delta band (1–4 Hz). There was statistically higher gPDC observed for the inter-hemispheric connections AF07–AF08 in the delta and theta bands (1–8 Hz), and AF08 to TP09 in the alpha and beta (8–30 Hz) bands. The left anterior-frontal (AF07) recordings showed higher power localized to the gamma band (32–50 Hz) for the Generation stage. An ancillary analysis of Sample Entropy did not show significant difference. The information transfer from anterior-frontal to temporal-parietal areas of the scalp may reflect multisensory interpretation during the Preparation stage, while brain signals originating at temporal-parietal toward frontal locations during the Generation stage may reflect the final decision making process to translate the multisensory experience into a creative text.