bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopically-Assisted Scar-Free Midline Neck Mass Excision
Authors: Kim Hyoyeon , Woo Seung Hoon
Published: August 2021

Traditional open surgery is indicated for the treatment of selected tumor subsites in the head and neck. However, it can cause major cosmetic problems and functional pathologies. The endoscopically-assisted transoral approach is increasingly preferred in some surgical fields due to its superior cosmetic and functional outcomes. Nonetheless, endoscopically-assisted transoral approach is not yet standard in the head and neck due to their anatomical complexity. The transoral surgical approach has been used for head and neck masses since the 1960s, and its application continues to evolve with changing disease conditions and recent innovations in surgical instruments. The potential for wide application of transoral surgery continues to be investigated, with a focus on minimizing occurrence of the complications. This review presents details of the surgical procedure and postoperative clinical outcomes, as well as endoscopically-assisted scar-free techniques for the resection of midline neck masses.
Finite Element Modeling And Parametric Optimization of Solidly Mounted Film Bulk Acoustic Resonator For Its Performance Enhancement
Authors: Johar Arun Kishor , Bhatt Jai Kumar , Sharma Gaurav Kumar , Kumar Tangudu Bharat , Varma Tarun , Periasamy C. , Agarwal Ajay , Boolchandani Dharmendar
Published: August 2021

This paper reports, the application of Taguchi Design of Experiments (DoE) and ANOVA (Analysis of Variance) for finding the optimal combinations and analysis of the effect of individual layer thickness on the performance of SMR sensor. The optimum combination of design parameters and its performance as a sensor have been predicted with DoE and validated through the finite element modeling (FEM) simulation. The optimization has been done to achieve enhancement in coupling coefficient of SMR sensor. The best optimized thickness of metal electrodes, piezoelectric, sensing, insulation low and high acoustic impedance layers have been found to be 0.2µm, 2µm, 0.68µm, 0.3µm, 1.028µm and 1.008µm, respectively. The results of the present study show that for the optimized dimension of SMR structure, simulated values of coupling coefficient (K2eff), Quality factor (Q) and figure of merit (FoM) are 0.075596 (or 7.5596%), 1171.6 and ≈ 88, respectively. Optimized structure performance has been compared with the existing SMR sensors and it is observed that proposed SMR exhibits performance enhancement in terms of FoM by ≈ 37 %.
Regional comparative analysis of factors that affect child-birth among women in Ghana after marriage.
Authors: Iddrisu Abdul-Karim , Adams Mustapha , Odametey Akuye-Shika , Mensah Nana Kofi , Kwotua Paul A.
Published: August 2021

Introduction: Infertility or difficulty related to conception and childbirth is still a global health concern including Ghana. Infertility or child-birth associated difficulties after marriage can lead to divorce. However, risk factors associated with child-birth difficulties are often difficult to detect by both the Gynaecologist and the couple involved. This makes proposing solutions to issues related to child-birth usually unsuccessful. Methods: This study seeks to identify risk factors associated with child-birth among married women in Ghana. This was achieved by using a logistic regression model for the dichotomous birth length (birth within 10 months or after 10 months in marriage) variable, adjusting for risk factors of birth length. The data used for the study were obtained from the 2014 Ghana Demographic and Health Survey, consisting of 5,004 complete cases. Statistical analyses were carried out using STATA version 14.1, best-fitting model selected from candidate models using their respective Akaike Information Criterion or Bayesian Information Criterion and the predictive power of such model determined using the Receiver Operating Characteristic curve. Results: Respondents with Akan ethnic background are less likely to deliver their first child after 10 months of marriage, wives who reported that beating is justified if she goes out without her husband's notice are more likely to give birth to their first child after 10 months of marriage, wives who reported that beating is justified when she burns food are less likely to give birth to their first child after 10 months of marriage. A unit increase in the age of respondent at first sex at first cohabitation decreases the likelihood of giving birth to the first child after 10 months in marriage. Rich and middle-class wives are more likely to give birth after 10 months in marriage. Discussion and Conclusions: For wives to conceive within 10 months of marriage, wives and husbands should or are encouraged to have frequent sex, any negative social behaviour or policies must be discouraged. Husbands should openly express their desire and love for their children since this increases the likelihood of wife’s desire to give birth. This leads to frequent sex, which then reduces conception time, and hence, child-birth within the shortest possible time.
Distinction of Consciousness Fields According to Taheri from Other Conventional Physical Fields: Evaluating the Magnetic Properties of Materials
Authors: Taheri Mohammad Ali , Payervand Firouz , Ahmadkhanlou Farzad , Torabi Sara , Semsarha Farid
Published: August 2021

Magnetization hysteresis loop provides important information about the magnetic properties of materials. In this study, by examining the magnetic properties of three paramagnetic and diamagnetic materials in the vicinity of the Consciousness Fields (three types 1,2 and 3), we have investigated the nature of the Consciousness Fields in comparison with magnetic field. The magnetic properties of the materials under the influence of three distinct Consciousness Fields have changed significantly. Furthermore, the Consciousness Field 1 of the present study (with originally named Consciousness Bond Field by Taheri) has changed the magnetic properties of materials toward their physically inherent state in standard laboratory conditions. Based on the conditions and the results of the present study, it can be concluded that the Consciousness Fields are inherently neither electric nor magnetite fields and have a completely different and distinct impact on materials and their properties.
Highly selective behaviour of colon adenoma after administration of EMR composition and its HCT116-based model.
Authors: Jakabčin Patrik , Kello Martin , Záň Jozef , Kolář Josef , Ulicny Jozef
Published: August 2021

When applying the improved composition of solution used during endoscopic mucosal resection (EMR), we have observed unexpectedly large and quantitatively significant differences in adenoma response vs. healthy tissue of surrounding GIT tract, namely the selective reaction enhancing the adenoma volume and differentiated colour. The in vitro experiments on model neoplasia cell line HCT116 suggest that the robust differences in the response of starving cells can be traced down principally to the tetrastarch digestion and enhanced metabolic rate of neoplastic cells. The neoplastic tissue grows into several intestine layers so that submucosal injection of iso-oncotic tetrastarch compound leads to degradation of starch and production of oncotic molecules in submucosa transported by facilitated transport into the neoplastic tissue. The colour distinction is due to concentration differences of the reporting dye between three separated compartments, further enhancing the utility of the contrasting mixture. The diffusion dynamics shall be tuneable by optimizing starch composition, improving desirable pharmacokinetics.
Comparative analysis of the SPL genes among four Ipomoea species and the evidence for a role of some IbSPLs in storage root development in sweet potato (Ipomoea batatas)
Authors: Sun Haoyun , Mei Jingzhao , Hou Wenqian , Zhang Yang , Xu Tao , Wu Shaoyuan , Zhang Lei
Published: August 2021

Background

As a major family of plant-specific transcription factors, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes play crucial regulatory roles in plant growth, development, and stress tolerance. SPL transcription factor family has been widely studied in various plant species, however, there are no systematic studies on SPL genes in genus Ipomoea.
Results

In this study, a total of 29, 27, 26, 23 SPL genes were identified in Ipomoea batatas, Ipomoea trifida, Ipomoea triloba, and Ipomoea nil, respectively. Phylogenetic analysis indicated that Ipomoea SPL genes could be clustered into eight clades. SPL members within the same clade showed similar gene structures, domain organizations, and cis-acting element compositions, suggesting similarity of biological function potentially. Evolutionary analysis revealed that segmental duplication events played a major role in the Ipomoea genus-specific expansion of SPL genes. Of these Ipomoea SPL genes, 69 were predicted as the target genes of miR156, and 7 IbSPL genes were further confirmed by degradome data. Additionally, IbSPL genes showed diverse expression patterns in various tissues, implying their functional conservation and divergence. Finally, by combining the information from expression patterns and regulatory sub-networks, we found that four IbSPL genes (IbSPL16/IbSPL17/IbSPL21/IbSPL28) may be involved in the formation and development of storage roots.
Conclusions

This study not only provides novel insights into the evolutionary and functional divergence of the SPL genes in all available sequenced species in genus Ipomoea, but also lays a foundation for further elucidation of the potential functional roles of IbSPL genes during storage root development.
Anti-Diabetic Activity of Silver Nanoparticles Synthesized From The Hydroethanolic Extract of Myristica Fragrans Seeds
Authors: P Ramya , Krishnadhas Lavanya
Published: August 2021

Myristica fragrans, also known as nutmeg is a spice that cures various diseases. This study aimed to synthesize silver nanoparticles from a hydroethanolic extract of Myristica fragrans seeds (MFHE) and evaluate their anti-diabetic properties. To MFHE, AgNO3 solution was added and exposed to sunlight to produce silver nanoparticles from hydroethanolic seed extract of Myristica fragrans (MFHENP). The MFHENP was characterized by numerous techniques. UV-visible spectroscopy confirmed the formation of silver nanoparticles by the absorption peak at 430nm. Scanning electron microscopy (SEM) studies revealed the shape and size of the particles at the range of 50-60nm. Energy-dispersive X-ray spectroscopy (EDX) disclosed the presence of silver ions. X-ray diffraction spectrum confirmed the crystalline nature of silver nanoparticles by the peak at 39o. FTIR analysis revealed the functional groups present in MFHE as well as in MFHENP and Zeta potential analysis was found to be 14mV. Furthermore, in-vitro anti-diabetic activity was investigated. MFHENP showed significant efficiency against the inhibition of alpha-amylase and alpha-glucosidase enzymes and also MFHENP retarded the glucose transport across the membrane which is analyzed by glucose diffusion and glucose uptake assays. Acarbose is used as a standard for all these methods and MFHENP efficiency proves their therapeutic potential for the treatment of diabetes mellitus.
Advance Directives in Patients With Head and Neck Cancer - Status Quo and Factors Influencing Their Creation
Authors: Allner Moritz , Gostian Magdalena , Balk Matthias , Rupp Robin , Allner Clarissa , Mantsopoulos Konstantin , Ostgathe Christoph , Iro Heinrich , Hecht Markus , Gostian Antoniu-Oreste
Published: August 2021

Background: Advance Care Planning (ACP) including living wills (LWs) and durable powers of attorney for healthcare (DPAHCs) is a highly relevant topic aiming to increase patient autonomy and reduce medical overtreatment. Data from patients with head and neck cancer are not currently available. Methods: In this single center cross-sectional study, we evaluated patients during their regular follow-up consultations at Germany’s largest tertiary referral center for head and neck cancer, regarding the frequency, characteristics, and influencing factors for the creation of advance directives (ADs) using a validated questionnaire tailored to our cohort. The advance directives included living wills, durable powers of attorney for healthcare, and combined documents (CDs). Results: Four hundred and forty-six patients were surveyed from 07/01/2019 to 12/31/2019 (response rate=65.9%). The mean age was 62.4 years (SD 11.9), 26.9% were women (n=120). 46.4% of patients (n=207) reported having authored at least one advance directive. These documents included 16 durable powers of attorney for healthcare (3.6%), 75 living wills (16.8%), and 116 combined documents (26.0%). In multinominal regression analysis, older age (OR≤0.231, 95% CI 0.097-0.548; p<0.001), regular medication (OR=1.862, 95% CI 1.048-3.308; p=0.034), and the marital status (“married”: OR=2.395, 95% CI 1.074-5.337; p=0.033; and “permanent partnership”: OR=4.526, 95% CI 1.100-18.625; p=0.036) emerged as significant factors increasing the likelihood of having an advance directive. In contrast, the stage of disease, the therapeutic regimen, the ECOG status, and the time from initial diagnosis did not correlate with the presence of any type of advance directive. Conclusion: Less than half of head and neck cancer patients had created an advance directive. Older and comorbid patients who were married or in a permanent partnership had a higher likelihood of having an advance directive. This is the first study investigating the current situation in head and neck oncology and providing evidence to identify a patient population in need of appropriate support.
Calculation of the Fine Structure Constant derived from Principle Theory.
Authors: Geilhaupt Manfred
Published: August 2021

Recently we have presented in a paper that the combination of two Principle Theories, General Relativity (GR) and Thermodynamics (TD), is able to derive the restmass (m) of an electron which (surprisingly) depends on the Sommerfeld Fine Structure Constant (FSC). In this paper we present a completed calculation of the FSC number (1/α=137.035999024(9)) from a GR+TD point of view
Efficacy and Safety of Artificial Tears Containing Lipidure and Hypromellose for the Treatment of Moderate Dry Eye Disease in Contact Lens Wearers
Authors: Gagliano Caterina , Amato Roberta , Scollo Davide , Avitabile Alessandro , Foti Roberta , Petrillo Francesco , Longo Antonio
Published: August 2021

Purpose: Dry eye disease (DED) involves up to 50% of the global population. The present study compared efficacy, tolerability and safety of the novel Respilac artificial tears containing Lipidure and hypromellose (HPMC) to the widely used Nextal artificial tears, HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers.Methods: In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED and wearing CL were randomly assigned to Respilac (n=15) or to Nextal group (n=15). Patients self-administrated one drop of Respilac or Nextal in both eyes 3-times daily for 21 days. Changes in endpoints (Visual Analogue Scale (VAS) score for ocular tolerability, Symptom Assessment iN Dry Eye (SANDE) score, Non-Invasive First Break-Up Time (NIF-BUT) results, Tear analysis value, Meibography results, CL tolerability results were investigated, comparing treatment groups and time-points evaluations. Adverse events (AEs) were also recorded and evaluated.Results: VAS scores decreased with time (p<0.001) in both groups showing no statistically significant difference among them (p=0.13). Improvements were also detected, from screening to end-of-treatment, by SANDE scores for severity and frequency (p<0.001) and by Tear analysis results (p<0.001) with no observed difference between Nextal and Respilac arm. NIF-BUT, Meibography and CL tolerability values showed to be non-significantly affected by treatment nor by time. No AEs were detected.Conclusion: According to the study results, Respilac showed to be effective, safe and well-tolerated for the treatment of moderate DED in CL wearers. Lipidure-based ophthalmic solution resulted not inferior to the currently used Nextal.
Risk of COVID-19 Introduction into the Scottish Hebrides and Strategies for Control
Authors: Ruget Anne-Sophie , Banks Christopher J. , Enright Jessica , Kao Rowland R.
Published: August 2021

Background In the context of an outbreak the natural boundaries of islands can allow for control of movements between populations. We estimate the risk of introduction of COVID-19 to each of the Hebridean islands situated off the west coast of mainland Scotland due to individual movements, and explore control strategies to mitigate this risk.Methods We use a combination of real human mobility data and census data to generate seasonally varying patterns of human movements amongst the Hebrides and from elsewhere. We consider three distinct periods: each of summer and winter 2019, illustrating a year prior to the pandemic, and summer 2020 illustrating a "pandemic summer". Movements during these periods serve as input to simulate COVID-19 transmission from the mainland to the archipelago in a stochastic meta-population model allowing us to explore the impact of seasonal variations on the risk of introduction and the effectiveness of non-pharmaceutical interventions.Results Despite strong seasonality in movement patterns, partly driven by tourism, for islands closely connected to the mainland there is evidence of substantial risk of disease introduction even over winter. In summer, when the risk is the highest, some islands can delay the introduction of COVID-19 by over six weeks, i.e. beyond the summer holiday period, through a 70% reduction of movements. Conclusion A high introduction risk in winter will be of particular concern if COVID-19 becomes a seasonal respiratory infection affecting temperate areas in winter concomitantly with other seasonal infections such as flu.For some islands, control of movements in peak summer tourist season has the potential for delaying the introduction risk beyond the summer holiday period, i.e. beyond a period of high mobility of people, potentially inducing a risk for rapid spread. Such measures would be particularly relevant in the occurrence of a variant escaping the vaccine given the current progress of the vaccine roll-out. However, such restrictions must be balanced against indirect negative economic impacts that might result.
Cancer-Related Fatigue On Daily Living Activities in Pediatric Cancer Survivors
Authors: Tanrıverdi Müberra , Çakır Fatma Betül
Published: August 2021

Aim

Cancer-related long term complications such as cardiovascular disease, fatigue, weight-related problems, and emotional disturbances are found to be increased in pediatric cancer survivors (PCS). The relationship between daily living activities (DLA) and such complications is still being investigated. Our aim in this study was to investigate the impact of cancer-related fatigue on DLA in PCS.
Methods

Cancer-related fatigue was assessed by “PedsQL Multidimensional Fatigue Scale (MFS)”, “Visuel Analogue Scale (VAS)” and “Borg Fatigue Scale”. The DLA was evaluated by WeeFIM.
Results

There were 77 PCS (44 boys) with a mean age of 10.76 ± 4.49 years. The mean value of fatigue scales were VAS 2.48 ± 1.48, Borg 0.61 ± 1.00 and MFS total score 71.14 ± 18.74. There was a statistically significant negative relationship between age and VAS scores of PCS (p = 0.047). The girls were found more tired than boys (VAS; p = 0.031). A positive correlation was established between the type of tumor and MFS total score (p = 0.048). WeeFIM total result was 118.64 ± 11.37. While there was a statisticially significant relationship between VAS Fatigue Score and WeeFIM total (p = 0.07), there was no such correlation between MFS total and WeeFIM total (p = 0.080) and Borg Fatigue Scale and WeeFIM total (p = 0.449).
Conclusions

It is established that there is a relationship between level of fatigue and DLA. Risk factors like tumor type or treatment modalities for fatigue should be investigated in larger samples of specific survivor groups. Fatigue and its association with DLA should be screened clinically as a routine surveillence in PCS and treatment options be planned.
Canagliflozin Alleviates Diabetic Cardiovascular Disease via Lipid Lowering, Mitochondrial Homeostasis, and Gut Microbiota Regulation
Authors: Wang Xueliang , Wang Zhe , Liu Di , Jiang Hao , Cai Chao , Li Guoyun , Yu Guangli
Published: August 2021

Background: Type 2 diabetes mellitus (T2DM) is associated with cardiovascular disease (CVD). Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most effective oral drugs for the treatment of T2DM, and have been shown to improve generalized vascular dysfunction. However, it’s effect on improving diabetic CVD and the possible action mechanism are currently unclear.Methods: T2DM was induced by feeding a high-fat diet (HFD) to male C57BL/6J mice for 24 weeks. Afterthat, HFD-fed mice were treated with Cana (50 mg/kg/d) or positive drug metformin (225 mg/kg/d) by oral gavage for 6 weeks. Myocardial mitochondrial morphology and cardiovascular abnormalities were assessed by transmission electron microscope and histological staining; lipids proﬁle and oxidative stress state were assessed by corresponding biochemical assay kits and histological staining; myocardial injury was characterized by H&E staining, TUNEL, and ELISA assays; colonic gut microbiota was assessed by 16S rDNA high-throughput sequencing.Results: Cana reduced the lipid (such as TG, TC, and LDL-C) accumulation in serum, thus decreased atherogenic index of plasma and arteriosclerosis index values. And, Cana reduced the circulating markers of inflammation (such as TNFα, MCP-1, and IL-6). More importantly, Cana improved cardiac mitochondrial homeostasis and relieved oxidative stress. Myocardial injury was alleviated after Cana treatment with decreasing levels of serous cTn I and sCD40L. Thus, cardiovascular abnormality was relieved by elevating the CD31 expression level, and suppressing ﬁbrosis and basement membrane thickening in T2DM mice. Interestingly, Cana administration increased the ratio of Firmicutes/Bacteroidetes and the relative abundance of Olsenella, Alistipes, and Alloprevotella, while decreased the abundance of Proteobacteria, Helicobacter and Mucispirillum at various taxonomic levels.Conclusions: Cana treatment improved CVD by decreasing the risk of atherosclerosis, maintaining a relatively normal haemogram, and reducing the thickness of vascular basement membrane and myocardial injury. Importantly, Cana treatment significantly elevated myocardial mitochondria homeostasis, thus ameliorated the oxidative stress and inflammatory states. Moreover, Cana subtly altered microbiota composition in T2DM mice with CVD, which contributed to the improvement of CVD. Collectively, the improvements of myocardial mitochondrial and gut microbiota homeostasis, may represent an important mechanism underlying the cardiovascular benefits of Cana treatment.
Machine Learning Aided Construction of the Quorum Sensing Communication Network for Human Gut Microbiota
Authors: Wu Shengbo , Feng Jie , Liu Chunjiang , Wu Hao , Qiu Zekai , Ge Jianjun , Sun Shuyang , Hong Xia , Li Yukun , Wang Xiaona , Yang Aidong , Guo Fei , Qiao Jianjun
Published: August 2021

Quorum sensing (QS) is a cell-cell communication mechanism that connects members in various microbial systems. Conventionally, limited QS entries were collected for specific microbes, which is far from being able to fully depict QS-based complex microbial interactions in human gut microbiota. In this study, we proposed a systematic workflow including three modules and the use of machine learning-based ensemble classifiers to collect reported QS entries, expand the QS repository, and mine new potential QS proteins. Furthermore, we developed the Quorum Sensing of Human Gut Microbes (QSHGM) database (http://www.qshgm.lbci.net/) including 28,567 redundancy removal QS entries, to bridge the gap between QS repositories and human gut microbiota. With the help of QSHGM, various QS-based microbial interactions could be predicted and a comprehensive QS communication network was further constructed and analysed for 818 human gut microbes. This work contributes to the establishment of the QS communication network which may form one of the key knowledge maps of the human gut microbiota, supporting future applications such as potential therapies to gut diseases.
Evaluation the Serum Level of Sex Hormones in Patients With Trigeminal Neuralgia
Authors: Lavaee Fatemeh , Zahed Parisa Mohaghegh , Zarei Fateme , Sardo Maryam Shahrokhi
Published: August 2021

Background and Aim: In this study FSH, LH, Testosterone, Estrogen, Progesterone serum levels in women affected by trigeminal neuralgia have been evaluated.Materials and Methods: This study is a cross sectional study during 2017-2018 in which FSH, LH, Testosterone, Estrogen, Progesterone serum levels in women affected by trigeminal neuralgia, who had referred to Emam Reza clinic and Oral and Maxillofacial Disease Department of Shiraz Dental Faculty, have been evaluated. Twenty-six women with trigeminal neuralgia were recruited in trigeminal neuralgia(TN) group and 26 healthy women whom their age were matched with TN group were enrolled in the healthy control group. Data was analyzed by SPSS version 18.Results: Sex hormone serum level was not significantly different between patients with TN and healthy control group (P value ≥0.05). In spite of this finding, the serum level of FSH in non-menopausal (P value=0.002) participants and progesterone in menopausal (P value=0.016) participants of TN and healthy control group, were significantly different. The serum level for both of these hormones were higher in patients with TN. In contrast to healthy control group, the sex hormone profiles of patients with TN, except LH did not follow the natural pattern changes based on menopausal status. Conclusion: In spite of no significant differences in sex hormonal profile of patients with TN and healthy controls, some hormonal disturbance in FSH and progesterone have been detected in TN patients in comparison between non-menopause and menopausal sex hormones profile.
“Prostaglandin E2 Sensitizes the Cough Reflex Centrally via EP3 Receptor-dependent Activation of NaV 1.8 Channels”
Authors: Al-Kandery Al-Shaimaa , Rao Muddana , EL-Hashim Ahmed
Published: August 2021

Background
Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E2 (PGE2), have been implicated in peripheral induction/sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE2 can sensitize the cough reflex via central actions and, if so, via which mechanisms.
Methods
All drugs were administered by intracerebroventricular (i.c.v.) route and whole-body plethysmograph set-up was used for both induction, using aerosolized citric acid (0.2 M), and recording of cough. Immunohistochemistry was performed to confirm the expression of NaV 1.8 channels in the nucleus tractus solitarius (nTS).
Results
We show that both PGE2 and the non-selective EP1/EP3 agonist, sulprostone, dose-dependently enhanced the citric acid-induced cough (P ≤ 0.001, P ≤ 0.01, respectively). Pretreatment with the EP1 antagonist, ONO-8130, did not affect the sulprostone-induced cough sensitization, whilst the EP3 antagonist, L-798,106, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, treatment with either the EP2 agonist, butaprost or the EP4 agonist, L-902,688, had no effect on cough sensitization. Additionally, pretreatment with either the TRPV1 antagonist, JNJ-17203212 or the TRPA1 antagonist, HC-030031, alone or in combination, nor with the NaV 1.1, 1.2, 1.3, 1.4, 1.6 and 1.7 channel blocker, tetrodotoxin, had any effect on the cough. In contrast, pretreatment with the NaV 1.8 antagonist, A-803467, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, NaV 1.8 channels were shown to be expressed in the nTS.
Conclusion
Collectively, our findings show that PGE2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 but independently of TRPV1/TRPA1 and TTX-sensitive sodium channel activation. These results indicate that PGE2 plays an important role in central sensitization of the cough reflex and suggest that central EP3 receptors and/or Nav 1.8 channels may represent novel antitussive molecular targets.
Tissue- and Salinity-specific Na–Cl Cotransporter (NCC) Orthologues Involved in the Sea lamprey (Petromyzon Marinus) Adaptive Osmoregulation
Authors: Barany A. , Shaughnessy C. A. , Pelis R. M. , Fuentes J. , Mancera J. M. , McCormick S. D.
Published: August 2021

The authors have requested that this preprint be removed from Research Square.
De novo human brain enhancers created by single nucleotide mutations
Authors: Li Shan , Hannenhalli Sridhar , Ovcharenko Ivan
Published: August 2021

Advanced human cognition is attributed to increased neocortex size and complexity, but the underlying gene regulatory mechanisms are unknown. Using deep learning model of embryonic neocortical enhancers, and human and macaque embryonic neocortex H3K27ac data, we identified ~4000 enhancers gained in the human, largely attributable to single-nucleotide essential mutations. The genes near gained enhancers exhibit increased expression in human embryonic neocortex, and are involved in critical neural developmental processes, and are expressed specifically in the progenitor cells and interneurons. The gained enhancers, especially the essential mutations, are associated with central nervous system disorders/traits. The essential mutations establish enhancer activities through affecting binding of key transcription factors of embryonic neocortex. Overall, our results suggest that non-coding mutations have led to de novo enhancer gains in the embryonic human neocortex, that orchestrate the expression of genes involved in critical developmental processes associated with human cognition.
Metabolic Regulation of SARS-CoV-2 Infection
Authors: Nahmias Yaakov , Ehrlich Avner , Ioannidis Konstantinos , Nasar Makram , Alkian Ismaeel Abu , Hofree Matan , Tikva Sigal Shafran , Rainy Nir , Houri Inbal , Cicero Arrigo , Pavanello Chiara , Sirtori Cesare , Cohen Jordana , Chirinos Julio , Deutsch Lisa , Gottlieb Amichai , Shibolet Oren , Maayan Shlomo
Published: August 2021

Viruses are efficient metabolic engineers that actively rewire host metabolic pathways to support their lifecycle, presenting attractive metabolic targets for intervention. Here we chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples. Bulk and single-cell analyses show that viral replication induces endoplasmic stress and lipid accumulation. Protein expression screen suggests a role for viral proteins in mediating this metabolic response even in the absence of replication. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication. Analysis of 3,233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective interventional open-label study was carried out in 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate (TriCor®) in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to control patients admitted during the same period and treated with the standard-of-care. Taken together, our data show that elevated lipid metabolism underlies critical aspects of COVID-19 pathogenesis, suggesting that pharmacological modulation of lipid metabolism should be strongly considered for the treatment of coronavirus infection.
Weathering Features of A Five-Story Stone Pagoda Compared To Its Quarrying Site In Geumgolsan Mountain, Korea
Authors: Jo Young Hoon , Lee Chan Hee
Published: August 2021

Understanding the long- and short-term weathering features according to rock type is very important for maintaining the original form of stone heritages. In this study, the material characteristics of a deteriorated five-story stone pagoda were compared with those of fresh rocks from its quarrying site at nearby Geumgolsan Mountain, Korea to diagnose the degree of damage and develop a comprehensive interpretation of the weathering mechanism. The stone pagoda was built from lithic tuff comprising pumice and phenocrysts such as quartz, K-feldspar, plagioclase, and mica based on plagioclase substrates; the mineralogical and geochemical characteristics are similar to those of the fresh rocks. The lithic tuff of the stone pagoda demonstrated a low ultrasonic velocity of 2863 m/s and a high water absorption rate and porosity of 9.5% and 19.2%, respectively, which are poorer than the physical properties of the fresh rocks (i.e., ultrasonic velocity of 3336 m/s, water absorption rate of 8.65%, and porosity of 17.83%). The lithological characteristics and physical properties demonstrated a considerable influence on the weathering and stability of the stone pagoda. In particular, fragments of relatively weak pumice detached from the original rock to form cavities of various sizes. These cavities introduced moisture within the rock, which produced oxides and hydroxides of iron and manganese. In addition, contaminants such as dust, salt crystals, clay minerals, and microorganisms adhering to the surface of the stone pagoda accelerated its physical, chemical, and biological weathering. The results of this study will be important for realizing the stable and long-term conservation of the five-story stone pagoda at Geumgolsan Mountain.
The Additional Effects of Clarithromycin And Pranlukast On The Cytokine Suppression By Corticosteroids Using Murine Allergic Bronchopulmonary Aspergillosis Model
Authors: Fukushima Chizu , Obase Yasushi , Fukahori Susumu , Yamaguchi Hiroyuki , Sakamoto Noriho , Matsuse Hiroto , Mukae Hiroshi
Published: August 2021

Few medicines other than oral corticosteroids and anti-fungal medicines are currently known as reliable treatments for allergic bronchopulmonary aspergillosis (ABPA). The efficacies of macrolide or leukotriene receptor antagonist (LTRA) with or without corticosteroid on ABPA are unknown. Mice were sensitized to Dermatophagoides farinae (Df) allergen intranasally and infected with Aspergillus fumigatus (Af). After Af infection, corticosteroid (Dexamethasone; Dex) was administered for five days in DfAf/Dex group. The effects of macrolide (clarithromycin; CAM) or LTRA (pranlukast; PRN) with or without Dex were also evaluated. Pathologically, the combined treatment with Dex and CAM decreased the airway inflammation. The interleukin (IL)-5, IL-13 and macrophage inflammatory protein (MIP)-2 concentrations in homogenized lungs were significantly elevated in DfAf mice compared to control mice (p < 0.05, each). CAM significantly decreased the elevations of MIP-2 of DfAf mice (p < 0.05). The addition of CAM on Dex suppressed both of the MIP-2 and IL-5 elevation (p < 0.05, each, DfAf/Dex vs DfAf/Dex/CAM group), but the addition of PRN on Dex did not. It was suggested that combination of CAM and corticosteroid enhanced the suppressing effect of both eosinophilic and neutrophilic airway inflammations. This finding will give a new hope for the treatment of severe fungus-related asthma.
Human Rhinoviruses Prevailed Among Children in the Setting of Wearing Face Masks in Shanghai, 2020
Authors: Jia Ran , Lu Lijuan , Li Shu , Liu Pengcheng , Xu Menghua , Cao Lingfeng , Su Liyun , Xu Jin
Published: August 2021

Background Human rhinovirus (HRV) is the predominant etiological agent of the common cold in children and adults. A recent study showed that the inhibitory effect of face masks on viral shedding of HRV was less prominent than that on other respiratory viruses. Considering that most Chinese people have worn face masks in public area since the outbreak of coronavirus disease 2019, we aimed to find out whether HRV prevailed among children in 2020 and demonstrate the details of the epidemiological features of HRV under such a special circumstance. Methods We summarized the incidences of various respiratory virus infections in patients who visited the Children’s Hospital of Fudan University during 2018~2020, and genotyped HRV positive nasopharyngeal specimens collected from 316 inpatients and 72 outpatients that visited the hospital in 2020. Results There was a major prevalence of HRV among children in the latter half of 2020, with a clear seasonality that HRV-As prevailed in summer while HRV-Cs in autumn. HRV-As were more prone to cause severe lower respiratory tract infections (LRTI), while HRV-Cs were closely associated with childhood wheezing. The predominant genotypes were A11, A28, A47, A82, A101, C40 and C43. Notably, A21, A82 and A101 took up larger proportions in severe cases than in non-severe cases. Conclusions Our findings described a major prevalence of HRVs among children in 2020, which highlight the unique transmitting pattern of HRV and help to narrow the targets for antiviral strategies.
Combined Therapy of Platelet-Rich Plasma and Basic Fibroblast Growth Factor Using Gelatin-Hydrogel Sheet for Rotator Cuff Healing in Rat Models
Authors: Kataoka Takeshi , Mifune Yutaka , Inui Atsuyuki , Nishimoto Hanako , Kurosawa Takashi , Yamaura Kohei , Mukohara Shintaro , Matsushita Takehiko , Niikura Takahiro , Tabata Yasuhiko , Kuroda Ryosuke
Published: August 2021

Introduction: Excellent outcomes of arthroscopic rotator cuff repair for small and medium tears have been recently reported. However, re-tears after surgery have been a common complication after surgical repair of large and massive rotator cuff tears andoften occur in early postoperative phase. It was previously reported that basic fibroblastgrowth factor and platelet-rich plasma enhanced rotator cuff tear healing. Wehypothesized that this combined therapy could enhance rotator cuff healing after rotatorcuff repair in a rat model. This study aimed to evaluate the efficacy of combined therapyof platelet-rich plasma and basic fibroblast growth factor with gelatin-hydrogel sheet.Methods: To create a rotator cuff defect, the infraspinatus tendon of Sprague Dawley ratwas resected from the greater tuberosity. The infraspinatus tendons were repaired andcovered with gelatin-hydrogel sheet impregnated with PBS (control group), basicfibroblast growth factor (bFGF group), platelet-rich plasma (PRP group), or both basicfibroblast growth factor and platelet-rich plasma (combined group). Histologicalexaminations were conducted using hematoxylin and eosin, safranin O, andimmunofluorescence staining such as Isolectin B4, type II collagen. For mechanicalanalysis, ultimate failure load of the tendon-humeral head complex was evaluated at41 weeks postoperatively.Results: In the hematoxylin and eosin staining, the tendon maturing score of the combined group was higher than that of the control group postoperativeat 2 weeks. Inthe safranin O staining, stronger proteoglycan staining was observed in the combinedgroup compared with the other groups at postoperative 2 weeks. Vascular staining withisolectin B4 in 3 treatment groups was significantly higher than that in the control group.Type II collagen expression in the combined group was significantly higher than those inthe other groups. The ultimate failure load of the combined group was significantly higherthan that of the control group.Conclusion: Combined therapy of basic fibroblast growth factor and platelet-rich plasmapromoted angiogenesis; tendon maturing and fibrocartilage regeneration at the enthesis,which could be enhance the mechanical strength. It was suggested that basic fibroblastgrowth factor and platelet-rich plasma enhance both tendon and bone-tendon junctionhealing, and basic fibroblast growth factor and platelet-rich plasma were synergistic.
The Association of Household Socioeconomic Status and Neighborhood Support System With Adherence to Cardiovascular Fitness Among Persons With Diabetes Mellitus in Ghana a Hospital-based Cross Sectional Study.
Authors: Doglikuu Be-Ikuu , Abubakari Abdulai , Yaseri Mehdi , Shakibazadeh Elham , Djazayery Abolghassem , Mirzaei Khadijeh
Published: August 2021

Background: Diabetes mellitus (DM) is an independent risk-factor for cardiovascular diseases. Physical activities (PAs) could reverse this risk factor. However some factors could influence adherence to PAs. Our study investigates the association of household socioeconomic status and neighborhood support system with adherence to cardiovascular fitness among persons with diabetes mellitus (DM) in Ghana.Methods: Facility-based cross-sectional-study was conducted among 530 T2DM patients in Ghana. Structured-questionnaires were used to collect demographic, anthropometric, and clinical variables. Household socioeconomic status (SES) was assessed using wealth-composite index and adherence to PAs measured using WHO PA-short form questionnaires. SPSS version-22 was used in data analysis.Results: There were significant mean difference in low (P = 0.010) and high (P = 0.0001) social/neighborhood supports according to place of residence. After adjusting for age and diabetes duration, high SES (quintile 3) Adjusted Odd Ratio (AOR) =0.68, 95% confidence interval (95%CI) (0.22, 0.07), moderate SES (quintile 3), AOR=3.16, 95%CI (1.01, 9.89) and high social support system (quintile 2) AOR =3.29, 95%CI (1.02, 10.58) were significant for adherence to cardiovascular fitness. Furthermore Low SES (quintile 3) AOR= 3.52, 95%CI (1.44, 8.59) and low social support system (quintile 1) AOR=1.05, 95%CI (1.05, 1.09) were significant for adherence to sedentary lifestyle among persons with diabetes mellitus. Conclusion: SES, and Social/neighborhood support systems are associated with adherence to cardiovascular fitness. Health care workers should prioritized these variables as modifiable factors in diseases preventions and health promotion
Integrated Bioinformatic Analysis of DNA Methylation and Immune Infiltration in Endometrial Cancer
Authors: dai fangfang , Deng Zhimin , Tan Wei , Yuan Mengqin , Yang Dongyong , Liu Shiyi , Zheng Yajing , Hu Min , Cheng Yanxiang
Published: August 2021

Background: Endometrial cancer greatly threatens the health of female. Emerging evidences demonstrated that the DNA methylation and immune infiltration involve in the occurrence and development of endometrial cancer. However, the mechanism and prognosis biomarker of endometrial cancer is unclear. In this study, we attempt to assess the DNA methylation and immune infiltration via bioinformatic analysis. Methods: The latest RNA-Seq, DNA methylation data and clinical data of endometrial cancer were download from the UCSC Xena dataset. The methylated driven genes were selected out, and then the risk score was obtained using the “MethylMix” and “corrplot” package. The correction of methylated genes and prognosis values, and the expression of above driven genes were identified by via survminer package and beeswarm package, respectively. Finally, the role of VTCN1 gene in immune infiltration was analyzed via CIBERSORT package. Results: In this study, 179 up-regulated genes, and 311 down-regulated genes are identified, which are related to the extracellular matrix organization, cell-cell junction, and cell adhesion molecular binding. Above them, 13 methylated driven genes were selected out. Meanwhile, it’s obvious that the expression of PGR and VTCN1 are lower in tumor group than that of in normal group. Conversely, VTCN1 gene expresses the opposite. high methylation & low expression of PGR and GYPC are positive correction with the prognosis, while the VTCN1 has the inverse relationship with the prognosis of endometrial cancer. More importantly, the hypomethylation of VTCN1 promoter leads to its high expression, which can cause tumor development by inhibiting CD8+T cell infiltration. Conclusions: In total, our study firstly reveals the mechanism of endometrial cancer combining DNA methylation and immune cell infiltration via integrated bioinformatic analysis. Besides, we found the pivotal prognosis biomarker for this disease. Our study may provide the potential targets for the diagnosis and prognosis of endometrial cancer.
Self-assembled Epitaxial Ferroelectric Oxide Nano-spring with Super-scalability
Authors: Dong Guohua , Hu Yue , Guo Changqing , Wu Haijun , Liu Haixia , Peng Ruobo , Xian Dan , Mao Qi , Dong Yongqi , Zhao Yanan , Peng Bin , Wang Zhiguang , Hu Zhongqiang , Zhang Junwei , Wang Xueyun , Hong Jiawang , Luo Zhenlin , Ren Wei , Ye Zuo-Guang , Jiang Zhuangde , Zhou Ziyao , Huang Houbing , Peng Yong , Liu Ming
Published: August 2021

Oxide nano-springs have attracted many research interests because of their anti-corrosion, high-temperature tolerance, oxidation resistance, and enhanced-mechanic-response from unique helix structures, enabling various nano-manipulators, nano-motors, nano-switches, sensors, and energy harvesters. However, preparing oxide nano-springs is a challenge for their intrinsic nature of lacking elasticity. Here, we developed an approach for preparing self-assembled, epitaxial, ferroelectric nano-springs with built-in strain due to the lattice mismatch in freestanding La0.7Sr0.3MnO3/BaTiO3 (LSMO/BTO) bilayer heterostructures. We find that these LSMO/BTO nano-springs can be extensively pulled or pushed up to their geometry limits back and forth without breaking, exhibiting super-scalability with full recovery capability. The phase-field simulations reveal that the excellent scalability originates from the continuous ferroelastic domain structures, resulting from twisting under co-existing axial and shear strains. In addition, the oxide hetero-structural springs exhibit strong resilience due to the limited plastic deformation nature and the built-in strain between the bilayers. This discovery provides an alternative way for preparing and operating functional oxide nano-springs that can be applied to various technologies.
The Use of Medical Cannabis in Pediatric Palliative Care: A Case Series
Authors: Divisic Antuan , Avagnina Irene , De Tommasi Valentina , Santini Anna , Brogelli Laura , Giacomelli Luca , Benini Franca
Published: August 2021

Background: Medical cannabis may be a useful tool for the management of treatment-resistant epilepsy and chronic pain, which affect many patients who are in PPC; however, little evidence is available in this setting. Case presentation: We aimed to describe a clinical experience, in a setting where high-level evidence may not be obtained. We report our clinical experience in a pediatric palliative care department in Italy. Caregivers reported changes in intensity and frequency of pain and epilepsy events. Six patients received a titrated plant extract of cannabis sativa for 1 year. Only mild and transient adverse events occurred. All patients experienced seizures during the pre-treatment observation period, and obtained a reduction in seizure frequency, although with variable extent while receiving cannabis. In addition, a benefit on pain was observed, based on the caregiver’s evaluation, and a reduction of analgesic use. Conclusion: Our experience suggests that a titrated plant extract preparation of medical cannabis may be useful to control treatment-resistant pain and epilepsy in PPC patients.