bluuebunny/crossref_metadata_2025 huggingface dataset:
A heterogeneous subcontinental mantle under the African-Arabian plate boundary revealed by boron and radiogenic isotopes
Authors: Agostini Samuele , Giuseppe Paolo Di , Manetti Piero , Doglioni Carlo , Conticelli Sandro
Published: July 2020

The north and northwest margins of the Arabian plate are locus of a diffuse and long-lasting (early Miocene to Pleistocene) Na-alkali basaltic volcanism, sourced in the asthenosphere mantle. The occurrence and 20-Ma persistence of magma supply under the study area is explained considering that upwelling asthenosphere produces very limited magma volumes in the axial zone and portions of hot, fertile mantle continue their eastward migration and are stored at shallower depths under the 100-km thick Arabian lithosphere, which is much thinner than the African one (≈175 km). Erupted basalts sampled a continuous variation of the mantle source, with a striking correlation among potential temperature, pressure and isotopic composition shifting between two end members: a 140 km-deep, more depleted source, and a 100 km-deep, more enriched one. In particular, we observed an unusual variation in boron isotopes, which in theory should not vary between more depleted and more enriched domains. This study shows that subcontinental mantle is more heterogeneous than the suboceanic one, and able to record for very long times recycling of shallow material.
Fabrication and Performance of Atmospheric Plasma Spraying Solid Oxide Fuel Cells with Liquid Antimony Anodes
Authors: Jiang Yidong , Mo Wenfei , Cao Tianyu , Shi Yixiang , Cai Ningsheng
Published: July 2020

Solid oxide fuel cells (SOFCs) with liquid antimony anodes (LAAs) are potential energy conversion technology for impurity-containing fuels. Atmospheric plasma spraying (APS) technology has become a promising LAA-SOFC preparation method because of its economy and convenience. In this paper, button SOFCs with different cathode materials and pore former ratio were prepared by the APS method and measured at 750℃. The effect of cathode structure on the electrochemical performance of the LAA-SOFCs was analyzed, and an optimized spraying method for LAA-SOFCs was developed. A tubular LAA-SOFC was prepared by the APS method based on the optimized spraying method and a peak power of 2.5 W was reached. The tubular cell was also measured at a constant current of 2 A for 20 hours and fed with a sulfur-containing fuel to demonstrate the impurity resistance and the long-term stability.
Neoadjuvant systemic and hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery for gastric cancer patients with limited peritoneal metastasis: a prospective cohort study
Authors: Yu Pengfei , Ye Zeyao , Dai Gaiguo , Zhang Yanqiang , Huang Ling , Du Yian , Cheng Xiangdong
Published: July 2020

Background
There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients.
Methods
Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1,and S-1 was administered orally(80 mg/m2/day)on days 1–14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoint was treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS).
Results
A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7–25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3–14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006).
Conclusion
Neoadjuvant systemic chemotherapy and HIPEC combined with CRS was safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted.
Trial registration:
This study is registered with ClinicalTrials.gov as NCT02549911, registered on 15 September 2015.
Integration of RNA-Seq and proteomics data identifies glioblastoma multiforme surfaceome signature
Authors: Syafruddin Saiful Effendi , Nazarie Wan Fahmi Wan Mohamad , Moidu Nurshahirah Ashikin , Soon Bee Hong , Mohtar M. Aiman
Published: July 2020

BackgroundGlioblastoma multiforme (GBM) is a highly lethal, stage IV brain tumor with a prevalence of approximately 2 per 10000 people globally. The cell surface proteins or surfaceome play significant roles in modulating cancer phenotypes and acting as information gateway in many oncogenic signaling pathways. Hence, surfaceome are attractive targets for cancer therapy due to their direct accessibility to drugs. Nonetheless, a comprehensive GBM surfaceome landscape has not been fully defined. Thus, the aim of this study is to define GBM-specific surfaceome genes and identify key cell surface genes that could potentially be developed as novel GBM biomarkers, or therapeutically targeted.MethodsWe integrated the RNA-Seq data from TCGA GBM (n=166) and GTEx normal brain cortex (n=408) databases to identify the significantly dysregulated surfaceome in GBM. This was followed by integrative analysis that combines transcriptomics, proteomics and protein-protein interaction network data to prioritize the high-confidence GBM surfaceome signature.ResultsAmong the 2,381 significantly dysregulated genes in GBM, 395 genes were classified as surfaceome. Via the integrative analysis, we identified 6 high-confidence GBM molecular signature, HLA-DRA, CD44, SLC1A5, EGFR, ITGB2, PTPRJ, which were significantly upregulated in GBM. The expression of these genes were validated in an independent transcriptomics database, which confirmed their upregulated expression in GBM. Importantly, high expression of CD44, PTPRJ and HLA-DRA is significantly associated with poor disease-free survival. Lastly, using the Drugbank database, we identified several clinically-approved drugs targeting the GBM molecular signature suggesting potential drug repurposing.ConclusionsIn summary, we identified and highlighted the key GBM surface-enriched repertoires that could be biologically relevant in supporting GBM pathogenesis. These genes could be further interrogated experimentally in future studies that could lead to efficient GBM diagnostic/prognostic markers or a therapeutic regimen to treat GBM.
The Ecological Cost Of Consumption
Authors: Peterson Isaac , Selinske Matthew , Lenzen Manfred , Moilanen Atte
Published: July 2020

The link between global ecosystem decline, trade, and human consumption suggests that trade-based biodiversity footprints should be regarded as a critical indicator of planetary impacts. Here we integrate a global input-output economic framework that encompasses global trade between 15909 sectors, with range and impact data on 10518 terrestrial plant, 17234 terrestrial animal, 6101 freshwater and 5059 marine species, to specify the biodiversity footprints associated with global trade and consumption across domestic and international supply chains. Our framework characterises global species loss as driven by domestic trade in emerging market economies including China, Brazil, Mexico, India, and Ecuador, and exacerbated by consumption in high-income countries, especially those in the G7, that are driving species loss in emerging markets and low-income nations. We attribute the largest sector-scope footprints to construction in China, Colombia, and India, agriculture commodity trade in Madagascar, Mexico, Tanzania, and Peru, and food manufacture in Mexico, Germany and France.
Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats
Authors: Jo Byung Gon , Namgung Uk
Published: July 2020

Background: Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods: An animal model of hepatitis was generated by intraperitoneal injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN was selectively eliminated by treating animals with capsaicin (CAP). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining.Results: TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). hVNS also induced an increase in phospho-STAT3 in the liver macrophages of ConA-injected animals, suggesting the activation of STAT3 transcription factor associated with cholinergic anti-inflammation. Capsaicin (CAP) treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and also induced an increase in apoptotic caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was reduced by CAP administration. Conclusions: Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.
Long Lasting Insecticide-treated Bed Net Ownership, Utilization and Associated Factors Among School-age Children in Dara Mallo and Uba Debretsehay Districts, Southern Ethiopia
Authors: Zerdo Zerihun , Bastiaens Hilde , Anthierens Sibyl , Massebo Fekadu , Masine Matios , Biresawu Gelila , Shewangizaw Misgun , Tunje Abayneh , Chisha Yilma , Yohannes Tsegaye , geertruyden Jean-Pierre Van
Published: July 2020

Background
Malaria is one of the major causes of morbidity and mortality among school-aged children (SAC) in Sub-Saharan Africa. SAC account for more than 60% of the reservoir of malaria transmission, but they were given less emphasis on prioritizing malaria prevention interventions. This study was aimed at assessing the ownership of bed nets, its utilization and factors associated with ownership of bed nets by households and bed net utilization among SAC in malaria prone areas of Dara Mallo and Uba Debretsehay districts in Southern Ethiopia, October to December 2019.
Methods
This study is part of baseline assessment in a cluster randomized controlled trial. The data were collected through interview and observation following structured questionnaire from 2261 SAC households. Univariable and multivariable logistic regressions were used to assess the association between bed net ownership or utilization and potential predictor variables. Odds Ratio (OR) and corresponding 95% Confidence Interval (CI) were used to determine the strength and statistical significance of association.
Results
The ownership of at least one bed net by households of SAC was about 19.3% (95% CI: 17.7%-21.0%). It was affected by living in altitude ranged from 1100 to 1250 meters above sea level with Adjusted OR (AOR) of 0.5 (95%CI: 0.3–0.9) and presence of child age less than 5 years (AOR = 2.1; 95%CI: 1.2–3.7). About 7.8% (95% CI: 6.7%-10.0%) of all SAC participated in the study and 40.4% (95% CI: 57.4% − 66.7%) of children in households owning at bed net passed the previous night under bed net. Bed net utilization by SAC conditional to its presence was lower among children age > 9 years (AOR = 0.2; 95%CI: 0.03–0.8); higher in children with mothers who had an education level above grade six (AOR = 5.2; 95%CI: 1.8–17.0); and when the household size to bed net ratio was ≤ 2 (AOR = 37.8; 95%CI: 4.1–1106).
Conclusion
Ownership of bed net was lower than universal coverage of at least one bed net for two individuals. It is important to monitor replacement needs and educate mothers with low education level and their SAC on the benefit of consistent utilization of bed nets.
Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury
Authors: Mao Ling , Zhou Ya , Chen Longqing , Hu Lin , Liu Shiming , Zheng Wen , Zhao Juanjuan , Guo Mengmeng , Chen Chao , He Zhixu , Xu Lin
Published: July 2020

Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.
The Path Linking Disease Severity and Cognitive Function with Quality of Life in Parkinson's Disease: the Mediating Effect of Activities of Daily Living and Depression.
Authors: He Yao , Tian Yuling , Han Hongjuan , Cui Jing , Ge Xiaoyan , Qin Yao , Luo Yanhong , Yu Hongmei
Published: July 2020

Background: Research on quality of life (QOL) with Parkinson’s disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence. Methods: We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and physical (PCS) and mental (MCS) QOL. Results:There was a significant mediating effect of PD severity on PCS via ADL and depression (95%CI: −0.669, −0.026), and a significant direct effect (p<0.001). The mediating effect of PD severity on MCS via ADL and depression was significant (95%CI: −2.135, −0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on PCS via ADL and depression (95%CI: 0.025, 0.219) and a significant direct effect (p<0.001). The mediating effect of cognitive function on MCS via ADL and depression was significant (95%CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The PCS models showed a partial mediation, and the MCS models showed a complete mediation, of ADL and depression.Conclusions:PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect PCS and MCS through different pathways.
Role of IL-22 in Persistent Allergic Airway Diseases Caused by House Dust Mite: A Pilot Study
Authors: Tamasauskiene Laura , Gintauskiene Vilte Marija , Bastyte Daina , Sitkauskiene Brigita
Published: July 2020

Background. Persistent allergic airway diseases cause a great burden worldwide. Their pathogenesis is not clear enough. There is evidence that one of the recently described cytokine interleukin (IL) 22 may be involved in the pathogenesis of these diseases. Scientists argue if this cytokine acts as proinflammatory or anti-inflammatory agent. The aim of this study was to investigate IL-22 level in patients with persistent allergic airway diseases caused by house dust mite (HDM) in comparison with healthy individuals and to evaluate its relationship with IL-13 and IL-10 level, symptoms score and quality of life.Methods. Patients with persistent allergic rhinitis caused by HDM and having symptoms for at least 2 years with or without allergic asthma were involved into the study. Measurements of IL-22, IL-13 and IL-10 and in serum and nasal lavage was performed by ELISA. Questionnaires assessing symptoms severity and quality of life were used.Results. A tendency was observed that IL-22 in serum and nasal lavage was higher in patients with allergic airway diseases compared to control group (14.86 pg/ml vs. 7.04 pg/ml and 2.67 pg/ml vs. 1.28 pg/ml, respectively). Positive statistically significant correlation was estimated between serum IL-22 and serum IL-10 (rs=0.57, p<0.01) and IL-13 (rs=0.44, p<0.05) level. Moreover, positive significant correlation was found between IL-22 in nasal lavage and IL-10 in nasal lavage (rs=0.37, p<0.05). There was a negative statistically significant correlation between serum IL-22 and RQLQ (rs=-0.42, p<0.05).Conclusion. Our study showed a possible anti-inflammatory effect of IL-22 in patients with persistent allergic airway diseases caused by HDM.
Plasmodium Falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the Continued Use of Artemether-Lumefantrine in the Region
Authors: Adamu Auwal , Jada Mahmoud Suleiman , Haruna Hauwa Mohammed Sani , Yakubu Bassa Obed , Ibrahim Mohammed Auwal , Balogun Emmanuel Oluwadare , Inaoka Daniel Ken , Kita Kiyoshi , Hirayama Kenji , Culleton Richard , Shuaibu Mohammed Nasir
Published: July 2020

Background
The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of antimalarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria.
Methods
Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analyzed using Pearson Chi-square and Fisher's exact (FE) tests.
Results
The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.5%, 𝜒² = 10.47, P < 0.05), whilst the 184F allele was highest in Kano (73.1%, 𝜒² = 13.20, P < 0.05), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.18, P < 0.05). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 36.05, P < 0.05), followed by NYD with a prevalence of 49% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states.
Conclusion
The present study shows that P. falciparum strains with reduced sensitivity to artemether-lumefantrine exist in Northern Nigeria and predominate in the North-West region.
Comparison of adherence and persistence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare/pharmacy claims database: a retrospective non-interventional cohort study
Authors: Shirai Chikako , Matsuoka Nobushige , Nakazawa Toru
Published: July 2020

Background Adherence and persistence with chronic therapies is crucial to prevent disease progression, such as in glaucoma. However, only a limited number of studies have reported them using real-world data in Japan. This study aimed to evaluate Japanese patients’ adherence and persistence to fixed- and unfixed-combination eye drops as a second-line therapy for glaucoma in real-world practice.Methods This retrospective, non-interventional cohort study utilized a commercially available Japanese healthcare database (MinaCare database). Medical/pharmacy claims data were collected from 2011 to 2016. The primary endpoint was adherence to medications, assessed by proportion of days covered (PDC) with medication during a 12-month post-index period. Meanwhile, the secondary endpoints included the persistence rate.Results A total of 738 patients were included in this study: 309 and 329 in the fixed- and unfixed-combination cohorts, respectively. Prostaglandin analog (PG)/β-blocker (BB) was most commonly claimed in 241/309 (78.0%) patients in the fixed-combination cohort. In the unfixed-combination cohort, PG and BB were claimed in 130/329 (39.5%) patients, whereas PG and α2-agonist were claimed in 87/329 (26.4%) patients. Patients were more adherent to the fixed-combination than the unfixed combinations (mean PDCs [SD], 79.1% [32.1] vs. 62.2% [38.0]; P < 0.0001). The proportion of patients with good adherence (PDC ≥ 80%) was also higher in the fixed-combination cohort (69.6%) than in the unfixed-combination cohort (48.6%) (P < 0.0001). During the 12-month post-index period, the persistence rate was higher in the fixed-combination cohort than in the unfixed-combination cohort (47.6% [95% confidence intervals (CI): 41.9–53.0] vs. 24.9% [95% CI: 20.4–29.7], P < 0.0001).Conclusions Japanese patients with glaucoma preferred the fixed-combination therapies over the unfixed-combination therapies. Hence, fixed-combination therapies would contribute to the improvement of adherence.
RASSF1A Regulates the Abnormal Cell Proliferation in Psoriasis via Inhibition of YAP
Authors: Jia Jinjing , Wang Ning , Zheng Yan , Mo Xiumei , Zhang Yu , Ye Siqi , Liu Junfeng , Yan Fenggen , Li Hongyi , Chen Dacan
Published: July 2020

Background: Psoriasis is a chronic, inflammatory skin disease with high incidence, treatment resistance, and high recurrence. Currently, the exact etiology and pathogenesis are unclear. The goal of this study was to characterize the role of the upstream negative regulator RAS-association domain family 1A (RASSF1A) on Yes-associated protein (YAP) in psoriasis.Methods: Skin lesions of 22 psoriasis patients and 19 normal skin tissue controls were used. Human epidermal keratinocytes were stimulated with M5 (IL-1 α, IL-17, IL-22, TNF-α, oncostatin M), to establish the psoriatic cell model. Methylation inhibitor, 5-Aza-CdR was prepared at different concentrations (5, 10, 20 μmol/L). Cells were infected with lentivirus vector overexpressing RASSF1A. Twenty-five 6-8-week-old female BALB/c mice were used to establish the psoriatic mouse model. Mice were randomly divided into five groups: control (Vaseline applied daily), psoriasis (imiquimod applied daily), and the three different 5-Aza-CdR concentrations (applied daily with imiquimod). Methylation specific PCR (MSP) was used to detect RASSF1A methylation, and immunohistochemistry was used to detect RASSF1A expression in skin lesions. After adding 5-Aza-CdR or lentivirus vector overexpressing RASSF1A, YAP expression, cell proliferation, cell cycle, apoptosis, inflammatory cytokines and related signal pathway activity were detected.Results: As RASSF1A methylation level increased, its expression in psoriasis patients and mice with skin lesions decreased. Addition of 5-Aza-CdR or lentivirus vector overexpressing RASSF1A increased the expression of RASSF1A, reduced the expression of YAP and inflammatory cytokines, cell proliferation, as well as AKT, ERK, STAT3 and NF-κB signaling pathway activities, induced cell cycle arrest in G0/G1 phase, increased apoptosis, and improved skin lesions.Conclusions: RASSF1A inhibited the proliferation of psoriatic cells, induced apoptosis, and reduced the expression of inflammatory factors by inhibiting YAP expression. Based on our findings, targeted drugs that can inhibit RASSF1A methylation and increase its expression may be useful in the treatment of psoriasis.
Acute Q Fever Diagnosed by Metagenomic Next-generation Sequencing and Clinically Compared With Scrub Typhus
Authors: Liu Xi , Lin Ziliang , Zhu Hongqiong , Chen Gongqi , He Pengyuan , Huang Mingxing , Xia Jinyu
Published: July 2020

Background: C. burnetti, the causative agent of Q fever, is considered a potential threat as a biological weapon because of highly infectious and pathogenic. There was an outbreak of Q fever in Zhuhai, P.R. China between December, 2018 and March 2019, although Zhuhai was not the endemic area of Q fever. 46 patients can be detected C. burnetti by metagenomic next-generation sequencing (mNGS). There are many similarities between acute Q fever and scrub typhus in clinical manifestations. Methods: We analyze the differences of clinical manifestations and serological between 46 patients with acute Q fever and 100 patients with scrub typhus. The general information of patients including gender, age, basic disease, days from disease onset and clinical manifestations were evaluated. Results: Their mean age of acute Q fever was 43.6±11.8 (ranging from 32 to 55 years old), younger than scrub typhus patients (53.9±12.7, ranging from 41 to 67 years old) (P<0.001). Males are more susceptible to C. burnetti. There were 45 males (97.8%) in acute Q fever patients and 59 males (59.0%) in scrub typhus patients (P<0.001). Compared with scrub typhus, patients with acute Q fever are more prone to present sore throat (P=0.003), abnormal liver function (P<0.001) and elevated levels of procalcitonin (P<0.001). Meanwhile, skin rash (P<0.001), eschar (P<0.001), lymphadenopathy (P<0.001), leukocytosis (P<0.001), thrombocytopenia (P=0.003), eosinophils reducing or disappearing (P=0.002) and pulmonary involvement on chest imaging (P=0.003) were more common in scrub typhus. There was significant difference between the two groups (P<0.001). Days from minocycline treatment to defervescence in acute Q fever (1.82±1.357, ranging from 0.5 to 3.2 days) were shorter than scrub typhus (2.85±2.801, ranging from 0.0 to 5.7 days) (P=0.008). Conclusions: mNGS is helpful to early diagnosis of acute Q fever. Sex, age, serologic test and physical examination are important in the differentiation of acute Q fever from scrub typhus in Zhuhai, China.
Instrumented gait analysis of stroke patients after FES-cycling therapy.
Authors: BARRIA PATRICIO , AGUILAR ROLANDO , DELGADO DAYA SERRANO , MORIS ANDRE , ANDRADE ASTERIO , AZORIN JOSE M
Published: July 2020

Background: Functional electrical stimulation (FES) is a modality of motor rehabilitation that consists of the programmed application of bursts of electrical current to the a ected neuromuscular region that aims to improve muscle strength, increase the range of motion, facilitate movement control and decrease spasticity. The present study aimed to measure the changes in gait biomechanics of people with Stroke after a FES-cycling rehabilitation program for the lower extremities. Methods: 39 subjects with chronic stroke received 24 sessions of multi-channel FES synchronized with a cycle-ergometer for the lower extremities. The gait of all subjects was evaluated before and after the intervention by an instrumented gait analysis. Results: Signifcant changes were found in the spatio-temporal parameters of gait, mainly in the speed and stride length when considering the general sample. Additionally, in people under 60 years of age, there are signi cant changes in joint kinematics after FES. Conclusions: The rehabilitation using a multi-channel FES-cycling system for lower extremities improve gait biomechanics in people with Stroke. Trial registration: This study was registered as Instrumental Gait Analysis on People With Stroke After Rehabilitation With a Synchronized FES and Cycle-Ergometer System on July 16, 2020 in Clinical Trials with the identier No NCT04473391 (available at https://clinicaltrials.gov/ct2/show/NCT04473391).
Older adults hospitalized with Covid-19: Clinical characteristics and early outcomes from a single center in Istanbul, Turkey
Authors: Medetalibeyoğlu Alpay , Senkal Naci , Kose Murat , Catma Yunus , Caparali Emine Bilge , Erelel Mustafa , Oncul Mustafa Oral , Bahat Gulistan , Tukek Tufan
Published: July 2020

Objective: Older adults have been continuously reported to be at higher risk for adverse outcomes of Covid-19. We aimed to describe clinical characteristics and early outcomes of the older Covid-19 patients hospitalized in our center comparatively with the younger patients, and also to analyze the triage factors that were related to the in-hospital mortality of older adults.Design: Retrospective; observational studySetting: Istanbul Faculty of Medicine hospital, TurkeyParticipants: 362 hospitalized patients with laboratory-confirmed Covid-19 from March 11 to May 11, 2020.Measurements: The demographic information; associated comorbidities; presenting clinical, laboratory, radiological characteristics on admission and outcomes from the electronic medical records were analyzed comparatively between the younger (<65 years) and older (≥65 years) adults. Factors associated with in-hospital mortality of the older adults were analyzed by multivariate regression analyses.Results: The median age was 56 years (interquartile range [IQR], 46-67), and 224 (61.9%) were male. There were 104 (28.7%) patients ≥65 years of age. More than half of the patients (58%) had one or more chronic comorbidity. The three most common presenting symptoms in the older patients were fatigue/myalgia (89.4%), dry cough (72.1%), and fever (63.5%). Cough and fever were significantly less prevalent in older adults compared to younger patients (p=0.001 and 0.008, respectively). Clinically severe pneumonia was present in 31.5% of the study population being more common in older adults (49% vs. 24.4%) (p<0.001). The laboratory parameters that were significantly different between the older and younger adults were as follows: the older patients had significantly higher CRP, D-dimer, TnT, pro-BNP, procalcitonin levels, higher prevalence of lymphopenia, neutrophilia, increased creatinine, and lower hemoglobin, ALT, albumin level (p<0.05). In the radiological evaluation, more than half of the patients (54.6%) had moderate-severe pneumonia, which was more prevalent in older patients (66% vs. 50%) (p=0.006). The adverse outcomes were significantly more prevalent in older adults compared to the younger patients (ICU admission, 28.8% vs. 8.9%; mortality, 23.1% vs. 4.3%, p<0.001). Among the triage evaluation parameters, the only factor associated with higher mortality was the presence of clinically severe pneumonia on admission (Odds Ratio=12.3, 95% confidence interval=2.7-55.5, p=0.001).Conclusion: Older patients presented with more prevalent chronic comorbidities, less prevalent symptomatology but more severe respiratory signs and laboratory abnormalities than the younger patients. Among the triage assessment factors, the clinical evaluation of pulmonary involvement came in front to help clinicians to stratify the patients for mortality risk.
Determinants of increased health care spending: Colombia in the international context
Authors: Piedrahita Juan José Espinal , Zea Jairo Humberto Restrepo , Gaviria Daniel Alberto Grajales
Published: July 2020

Financial sustainability in health refers to the balance over time between income and expenditure, so expenditure is a major fiscal challenge and its determinants require monitoring. The objective of this study is to define and measure the most important determinants that influence increases in health expenditure in 80 countries at different income levels, and to determine how the average level of increase compares with Colombia. A literature review was conducted to define the determinants. Then, a fixed-effects panel regression model was estimated to reveal the contribution of these determinants to the increase in spending. The results indicate that demographic variables and technological innovation have the greatest impact on the increase in health spending (45% and 43%, respectively). In conclusion, the study validates what is reported in the international literature with regard to upper-middle-income countries, where the evidence identifies that demographic and technological factors have the greatest impact on the increase in spending. There is also a need to include institutional and outcome variables to ensure that a fuller array of health spending determinants are considered, quantified, and explored.
Bacterial but no SARS-CoV-2 contamination after terminal disinfection of tertiary care intensive care units treating COVID-19 patients
Authors: Hofmänner Daniel A , Garcia Pedro D Wendel , Duvnjak Branko , Chakrakodi Bhavya , Maier Julian D , Huber Michael , Huder Jon , Wolfensberger Aline , Schreiber Peter W , Schüpbach Reto A. , Zinkernagel Annelies S , Bühler Philipp K , Brugger Silvio D
Published: July 2020

Background: In intensive care units (ICUs) treating patients with Coronavirus disease 2019 (COVID-19) invasive ventilation poses a high risk for aerosol and droplet formation. Surface contamination of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) or bacteria can result in nosocomial transmission.Methods: Two tertiary care COVID-19 intensive care units treating 53 patients for 870 patient days were sampled after terminal cleaning and preparation for regular use to treat non-COVID-19 patients.Results: A total of 176 swabs were sampled of defined locations covering both ICUs. No SARS-CoV-2 ribonucleic acid (RNA) was detected. Gram-negative bacterial contamination was mainly linked to sinks and siphons. Skin flora was isolated from most swabbed areas and Enterococcus faecium was detected on two keyboards.Conclusions: After basic cleaning with standard disinfection measures no remaining SARS-CoV-2 RNA was detected. Bacterial contamination was low and mainly localised in sinks and siphons.
Sub-Lethal Hyperthermia Enhances Anticancer Activity of Doxorubicin in Chronically Hypoxic HepG2 Cells Through ROS-Dependent Mechanism
Authors: Wang Qi , Zhang Hui , Ren Qianqian , Ye Tianhe , Liu Yiming , Zheng Chuansheng , Zhou Guofeng , Xia Xiangwen
Published: July 2020

Background and aims:
Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful anti-tumor effect than thermal ablation alone in hepatocellular carcinoma (HCC) patients. However, the underlying mechanisms remain unclear. The purpose of this study was to evaluate whether sub-lethal hyperthermia encountered in the peri-ablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms.
Methods
HepG2 cells pre-cultured under chronic hypoxic conditions (1% oxygen) were treated in a 42 °C water bath for 15 min or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity.
Results
The results confirmed that sub-lethal hyperthermia enhanced intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells compared to hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of mitochondrial membrane potential. Pretreatment with the ROS scavenger N-acetyl cysteine (NAC) significantly inhibited the apoptotic response suggesting that cell death is ROS-dependent.
Conclusions
These findings suggest that sub-lethal hyperthermia enhanced the anti-cancer activity of doxorubicin in hypoxic HepG2 cells through ROS-dependent mechanism.
Progression Risk Assessment of Post-Surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms
Authors: Wu Mengwei , Liu Rui , Yuan Hongwei , Xu Xiequn , Li Xiaobin , Liu Ziwen
Published: July 2020

BackgroundAccurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circRNAs (DE-circRNAs) via the ceRNA mechanism could help establish a novel assessment tool. MethodsceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. LASSO-Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC.ResultsSix hub DE-mRNAs, namely CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the ATA risk stratification system and MACIS score AJCC staging system.ConclusionsBased on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.
Dynamic Biomarkers Indicate Immunological Benefits Provided by Ganoderma Spore Powder in Post-Operative Breast and Lung Cancer Patients: A Prospective Clinical Trial
Authors: deng yuwei , Ma jianli , Tang dabei , zhang qingyuan
Published: July 2020

Background: T lymphocyte subsets with correlative cytokines, albumin to globulin ratio (AGR) and neutrophil to lymphocyte ratio (NLR), have been linked to inflammatory indicators of immune response and prognosis in various cancer types. The aim of this study was to determine the utility of these biomarkers in predicting the immunological benefits of Ganoderma spore powder in post-operative patients with breast and lung cancer. Methods: We prospectively evaluated 120 consecutive breast and lung cancer patients with or without Ganoderma spore powder. T lymphocyte subsets, as well as relative cytokines were detected and assessed by Pearson correlation analysis. The relationships between AGR and NLR with ganoderma spore powder treatment and prognosis were analyzed using Kaplan–Meier and Cox regression methods.Results: The prevalence of CD3+, CD4+ and CD4+/CD8+, CD3+HLADR-, CD4+HLADR- and CD8+HLADR- cell types was higher in the ganderma spore treated group compared to untreated controls. In addition, the percentage of CD4+CD25+Treg, CD3+HLADR+, CD4+HLADR+ and CD8+HLADR+ cell types was lower in the treated group. IL-2 and IL-12 frequencies were significantly higher during the treatment period which negatively impacted levels of IL-10. Other immunosuppressive factors such as COX2, TGF- 1 and HIF-1A had higher prevalence in non-treated patients. Correlation analysis showed several correlations between the biomarkers, specifically between IL-6 and TGF- 1, CD28 and IL-12R, TGF- 1 and Foxp3, IL-10 and IL-12R with COX2, Foxp3 and CD8, IL-10 and CD28 with IL-12R, COX2 and CD8, IL-12R with COX2, CD3 with CD4 and CD8. A positive relationship was also observed between IL-2 and TGF- 1. Conversely, IL-2 was negatively related to CD3, and HIF-1 negatively related with CD4, CD28 and CD3. Kaplan–Meier analysis suggested that low AGR/high NLR was related to poor progression free survival (PFS, HR=1.572, P=0.038/HR=2.064, P=0.042). A combination of high AGR and low NLR that predicted treatment benefits was also associated with PFS (HR=0.661, P=0.033/HR=1.044, P=0.048).Conclusions: Our findings show that T lymphocyte subsets predominately combined with relevant cytokines and AGR/NLR inflammatory predictors may help to identify patients most likely to benefit from the immunological enhancements from Ganoderma spore powder treatment.
The Glutaminase Inhibitor Compound 968 Exhibits Potent in vitro and in vivo anti-tumor Effects in Endometrial Cancer
Authors: Yuan Lingqin , Guo Hui , Pan Guoyou , Wang Cong , Li Dapeng , Liu Naifu , Wei Ling , Li Peipei , Sheng Xiugui
Published: July 2020

Background: Glutamine is one of the primary nutrients utilized by cancer cells for energy production and biosynthesis. Interfering with glutamine metabolism may impose anti-tumor effects. In this study, we aimed to investigated the anti-tumorigenic effects of GLS1 inhibition in endometrial cancer cells in vitro and in vivo. Methods: In this study, we assessed the relationship between glutaminase-1 enzyme (GLS1) expression and prognosis in endometrial cancer by bioinformatics analyses. Overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method. The effects of compound 968 on cell proliferation, cell cycle, apoptosis, cellular stress, invasion, and AKT/mTOR/S6 pathway inhibition in human endometrial cancer cell lines were assessed. The in vivo therapeutic potential of compound 968 in endometrial cancer was evaluated using tumor xenografts.Results: We found that GLS1 expression is elevated during endometrial cancer progression and is associated with poor prognosis. The GLS1-targeting compound 968 was able to reduce cancer cell proliferation, induce cell cycle arrest at the G1 phase, inhibit cell invasion, as well as promote cellular stress and cancer cell apoptosis. Compound 968 treatment significantly increased the sensitivity of cells to paclitaxel. Moreover, the treatment of endometrial cancer cells with compound 968 resulted in AKT/mTOR/S6 signaling pathway inhibition. In xenograft mouse models of endometrial cancer, compound 968 significantly suppressed tumor growth. Conclusion: We conclude that compound 968 is a promising anti-tumorigenic agent and that combination with paclitaxel may be a valuable strategy for the treatment of endometrial cancer.
Development of a prognostic model for esophageal cancer based on nine immune related genes
Authors: Zhang Zhi , Chen Cheng , Fang Ying , Li Sheng , Wang Xiaohua , Sun Lei , Zhou Guoren , Ye Jinjun
Published: July 2020

Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods: This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results: We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions: These molecules may serve as potential therapeutic targets and biomarkers for the new-immunotherapy of EC.
NKX6.1 Expression is Associated With The Prognosis in Breast Cancer.
Authors: Zhang Jie , Zhang Sujie , Li Xiaoyan , Zhang Fan , Zhao Lei
Published: July 2020

Background: Breast cancer is the most common cancer among women in the world. NKX6.1 is proved to be involved in several human cancers, but fewer researches have reported the functional roles of NKX6.1 in breast cancer. In this study, we investigated the clinical significance of NKX6.1 expression in breast cancer prognosis.Methods: The expression level of NKX6.1 in breast cancer tissues and paired non-cancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was applied to evaluate the relationship between NKX6.1 expression and clinicopathologic parameters. The overall survival of breast cancer patients were analyzed by Kaplan-Meier method with log rank test. Additionally, cox regression analysis was used for prognosis analysis.Results: NKX6.1 expression level is increased in breast cancer tissues (P<0.001). Moreover, the elevated levels were significantly correlated with tumor size (P=0.002), TNM stage (P=0.018) and lymph node metastasis (P=0.007). In addition, breast cancer patients with high NKX6.1 level had a poorer overall survival than those with low level (log rank test, P=0.001). NKX6.1 was an independent prognostic factor for breast cancer (HR=2.961, 95%CI=1.368-6.411, P=0.006).Conclusions: NKX6.1 is up-regulated in breast cancer, which may be a potential prognostic biomarker for the cancer.