bluuebunny/crossref_metadata_2025 huggingface dataset:
Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis
Authors: Hong Wei , Wei Zhanying , Qiu Zhaohui , Li Zheng , Fu Chensheng , Ye Zhibin , xu xiaoya
Published: June 2020

Background: Statins are the most widely used drugs in elderly patients, the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE–/–) mice, and the possible mechanisms involved in these changes. Methods: Twenty-four 60-week-old apoE–/– mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE–/– mice were differentiated into osteoblasts and treated with atorvastatin and Sirt1 inhibitor EX-527. Results: The results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear obviously changes after the treatment of atorvastatin. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE–/– mice were pretreated with EX527, the higher expression of Runx2, ALP and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend. Conclusions: Accordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE−/− mice by regulating the Sirt1–Runx2 axis.
Quantitative characteristics, regeneration status, Physicochemical soil properties within and at different distance of abandoned skid trails in the Hyrcanian forests.
Authors: Abbas-Panah Pouya , Mirkala Seyed Rostam Mousavi , Nikooy Mehrdad , Rad J.Eshaghi
Published: June 2020

The authors have withdrawn this preprint due to author disagreement.
COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
Authors: Malone Robert W. , Tisdall Philip , Fremont-Smith Philip , Liu Yongfeng , Huang Xi-Ping , White Kris M. , Miorin Lisa , Olmo Elena Moreno Del , Alon Assaf , Delaforge Elise , Hennecker Christopher D. , Wang Guanyu , Pottel Joshua , Bona Robert , Smith Nora , Hall Julie M. , Shapiro Gideon , Clark Howard , Mittermaier Anthony , Kruse Andrew C. , García-Sastre Adolfo , Roth Bryan L. , Glasspool-Malone Jill , Francone Victor , Hertzog Norbert , Fremont-Smith Maurice , Ricke Darrell O.
Published: June 2020

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.
RecA protein mediates fitness, virulence and DNA damage response (SOS response) in Riemerella anatipestifer
Authors: Ji Guo , Gong Xiaowei , Chen Qiwei , Liu Yongsheng , Zheng Fuying
Published: June 2020

Background: DNA damage response (SOS response) refers to an important protective mechanism for bacteria to cope with genomic DNA damage. The RecA protein plays a key regulatory role in the induction of SOS responses in many bacteria, and its homologous proteins are widely present in various organisms. However, the biological functions of RecA protein of Riemerella anatipestifer have never been explored.In this work, we constructed the deletion strain RA-GDΔRecA and complemented strain RA-GD△RecA pCPRA::RecA, and the growth ability, drug sensitivity, virulence and SOS response of the parental RA-GD, RA-GDΔRecA and RA-GD△RecA pCPRA::RecA strains were detected. Results: The results showed that the RecA protein reduced the fitness of RA-GD strain, and decreased the resistance of cells to three antibiotics (tetracycline, oxytetracycline and gentamicin sulfate) and the virulence of the strain to ducklings. Within a certain range of ultraviolet irradiation (UV), the transcription level of RecA gene increased significantly with the prolongation of UV time. Furthermore, the deletion of RecA gene reduced significantly the integrity of genomic DNA of RA-GD, indicating that the RecA gene may play a positive regulate role in the SOS response of R. anatipestifer. However, Western blotting showed that the levels of RecA protein in parent strain had no significant change under the condition of UV treatment. Conclusion: This experiment demonstrated for the first time that RecA gene participated in the fitness, resistance, virulence and DNA SOS response in R. anatipestifer.
Surgical management of ulnar styloid fractures: comparison of fixation with anchor suture and tension band wire
Authors: Chen Alvin Chao-Yu , Lin Yi-Hsuan , Weng Chun-Jui , Cheng Chun-Ying
Published: June 2020

Background

Limited reference is available regarding surgical management in symptomatic ulnar styloid fractures with small bony avulsion. The study goal is to report the surgical outcomes using anchor suture fixation with comparison to traditional tension band wire fixation.

Methods

We retrospectively reviewed the medical records in patients who underwent surgical repair for unilateral ulnar styloid fractures with distal radioulnar instability between 2004 and 2017. A total of 31 patients were enrolled including two kinds of fixation methods. Anchor suture fixation plus distal radioulnar joint pinning was performed in ten patients with tiny avulsion bony fragments (group A); tension band wire fixation was performed in 21 patients with big styloid fracture fragments (group B). Patient characteristics and 2-year treatment outcomes were compared between two groups based on Mayo Modified Wrist Score (MMWS), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), visual analog scale (VAS) and surgical complication. Descriptive statistics were used for calculation of key variables; a p-value of < 0.05 was considered statistically significant.

Results

Based on Gaulke classification, there were five subtypes in group A and three subtypes in group B. Incidence of concomitant distal radius fractures was significantly higher in group B; other patient characteristics including age, sex, injury side, and time to surgery showed no significant difference. Outcome assessment regarding MMWS, QuickDASH and VAS was comparable between two groups. Bone-related complications including nonunion, DRUJ subluxation and styloid resorption were analyzed; the difference was not significant. Incidence of implant-related complications including migration and secondary removal surgery was significantly higher in group B (p = 0.021).

Conclusion

Surgical fixation in symptomatic ulnar styloid fractures yields comparable treatment outcomes in both fracture patterns. Implant-related complication with secondary removal surgery is more common in tension band wire group. Anchor suture fixation is a feasible option for tiny styloid avulsion fragments with limited surgical complication.
EgJUB1 and EgERF113 transcription factors as master regulators of defense response in Elaeis guineensis against the hemibiotrophic Ganoderma boninense
Authors: Sakeh Nurshafika Mohd , Abdullah Siti Nor Akmar , Bahari Mohammad Nazri Abdul , Azzeme Azzreena Mohamad , Shaharuddin Noor Azmi , Idris Abu Seman
Published: June 2020

Background
Hemibiotrophic pathogen such as the fungal pathogen Ganoderma boninense that is destructive to oil palm, manipulates host defense mechanism by strategically switching from biotrophic to necrotrophic phase. Our previous study revealed two distinguishable expression profiles of oil palm genes that formed the basis in deducing biotrophic phase at early interaction which switched to necrotrophic phase at later stage of infection.
Results
The present report is a continuing study from our previous published transcriptomic profiling of oil palm seedlings against G. boninense. We focused on identifying differentially expressed genes (DEGs) encoding transcription factors (TFs) from the same RNA-seq data resulting in 106 upregulated and 108 downregulated TFs being identified. DEGs involved in four established defense-related pathways are presented which are responsible in cell wall modification, reactive oxygen species (ROS)-mediated signaling, programmed cell death (PCD) and plant innate immunity. We discovered upregulation of JUNGBRUNNEN 1 (EgJUB1) during fungal biotrophic phase while Ethylene Responsive Factor 113 (EgERF113) demonstrated prominent upregulation when the palm switches to defense against necrotrophic phase. EgJUB1 was shown to have binding activity to a 19 bp palindromic SNBE1 element, WNNYBTNNNNNNNAMGNHW found in the promoter region of co-expressing EgHSFC-2b. Further in silico analysis of promoter regions revealed co-expression of EgJUB1 with TFs containing SNBE1 element with single nucleotide change at either the 5th or 18th position. Meanwhile, EgERF113 binds to both GCC and DRE/CRT elements promoting plasticity in upregulating the downstream defense-related genes. Both TFs were proven to be nuclear localized based on subcellular localization experiment using onion epidermal cells.
Conclusion
Our findings demonstrated unprecedented transcriptional reprogramming of specific TFs potentially to enable regulation of specific set of genes during different infection phases of this hemibiotrophic fungal pathogen. The results propose EgJUB1 and EgERF113 as key TFs in orchestrating the defense mechanisms during biotrophic and during the subsequent transition to necrotrophic phase, respectively. Identification of these phase-specific oil palm TFs is important in designing strategies to tackle or attenuate the progress of infection.
Application of 70kVp in abdominal CT angiography to reduce both radiation and contrast dosage and improve patient comfort for children
Authors: Sun Jihang , Li Haoyan , Yang Lixin , Li Jianying , Zhou Zuofu , Yang Wei , Peng Yun , Li Haiyun
Published: June 2020

Objective To evaluate the application of 70kVp in pediatric abdominal CT angiography (CTA) to reduce radiation and contrast dose and improve patient comfort. Methods Forty-six children needing abdominal CTA were enrolled in the study group using low-dose scanning protocol with 70kVp and 0.7-1.1ml/kg contrast dose, and reconstructed with 50%ASIR-V. They were compared with another 46 children (control group) with matching body weight who underwent conventional CT scans with 100kVp, 1.2-1.8ml/kg contrast dose and reconstructed using 50%ASIR. The image quality of large vessels was evaluated using a 5-point scale, and the number of superior mesenteric artery branches identifiable by CAD was recorded. The CT value and standard deviation of descending aorta (Ao) was measured, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) calculated. Radiation dose, contrast dose, the maximum injection pressure, correlation between flow rate and injection pressure were compared between the two groups. Results The score for displaying large vessels by 70kVp images was 3.91±0.28, and up to 3 superior mesenteric artery branches could be identified, all of which met the diagnostic requirements. The CT value of Ao was 390.87±86.79HU in the study group, higher than 343.93±49.94HU in the control group, while no difference in SNR and CNR between the two groups; the radiation dose, contrast dosage and injection pressure of the study group were 1.23±0.39mGy, 12.67±7.27ml and 43.83±17.16psi respectively, significantly lower than the 1.95±0.37mGy, 22.67±7.39ml, and 77.59±19.68psi of the control group. The correlation coefficients between flow rate and injection pressure were 0.82 and 0.86 in 70kVp group and 100kVp group. Conclusion 70kVp scanning meets the diagnostic requirements in pediatric abdominal CTA while providing significant radiation dose, contrast dose and injection pressure reduction.
Prevalence of HIV Infection Among Foreign Applicant to Residency in Shanghai, China, 2005-2016
Authors: Qin Jia , Xia Jing , Zhu Peiqin , Zhou Ru
Published: June 2020

Background: Shanghai is an international city which has high proportion of entry travelers from all over the world. The HIV infection status of this population can reflect the global trend of HIV prevalence. Thus, a retrospective epidemic investigation was conducted to clarify the prevalence and characteristics of HIV infection among entry travelers who apply to residency in Shanghai. Methods: Totally 50830 entry travelers who applied to residency in Shanghai（2005-2016）were included. The HIV infection rate was confirmed based on the detection of HIV-1 antibody. Results: Among all the recruited entry travelers, 245 persons were determined HIV positive with infection rate of 0.48%. The detection rate of HIV in male was significantly higher than that in female (χ2=62.584, P<0.0001). Those aged 18-30 years, 31-40 years and >40years accounted for 34.3%, 39.6% and 26.1% of the infected population. There was no increase in trend of HIV prevalence rates among the sampling years (Cochran-Armitage Z=2.543, P=0.111). Proportions of individuals infected through homosexual transmission increased over the study period (Cochran-Armitage Z=5.41, P<0.001), while the proportion infected through heterosexual declined over time (Cochran-Armitage Z=3.38, P =0.001). Conclusion: The characteristics of HIV infection among foreign applicant to residency in Shanghai were clarified. The results would provide the necessary epidemiological data for monitoring the HIV epidemic among entry international travelers and contribute to the establishment of relevant policies and regulations for HIV control and prevention.
A Survey on Mental Health Impact Caused by COVID-19 Pandemic in Italian Pediatric Healthcare Workers.
Authors: Filippo Paola Di , Attanasi Marina , Dodi Giulia , Porreca Annamaria , Raso Massimiliano , Pillo Sabrina Di , Chiarelli Francesco
Published: June 2020

Background: Few studies investigated COVID-19 pandemic psychological effects on pediatric healthcare staff. The aim of this study was to evaluate sleep quality and psychological effects of pediatric healthcare workers during COVID-19 epidemic in Italy and to evaluate potential differences between Primary and Secondary Care operators. Methods: Pediatric healthcare workers were involved in an online survey aimed to characterize responders and to define their clinical expertise in the management of suspected or confirmed COVID-19 patients during pandemic. Using validated scores, the online questionnaire assessed sleep quality, stress and anxiety level, self-efficacy and social support in pediatric healthcare workers. Results: During COVID-19 outbreak, 67.43% of our population were suffering sleep disturbance, and we found a positive correlation between sleep disturbances with stress and anxiety. Furthermore, 19.42% of subjects were suffering anxiety and 53% were at risk of developing an acute stress disorder. Stress resulted inversely correlated with self-efficacy and social support.Secondary care operators were more affected than family pediatricians by sleep disturbances, stress but especially by anxiety. Social support was considerably higher in secondary care operators compared to family pediatricians.Conclusions: Despite the less exposure and the less infection probability, much of pediatric healthcare workers were suffered sleep disturbance, anxiety and potential stress disorder. In the Pediatric Units, these psychological effects could be related to other factors compared to frontline departments, such as the early confused situation, the difficulties in workplaces managing and in finding personal protective equipment, as well as the subsequent sense of helplessness and frustration.
LncRNA IMFlnc1 Promotes Porcine Intramuscular Adipocyte Adipogenesis by Sponging Mir-199a-5p to Up-regulate CAV-1
Authors: Wang Jing , Chen Mingyue , Chen Junfeng , Ren Qiaoling , Zhang Jiaqing , Cao Hai , Xing Baosong , Pan Chuanying
Published: June 2020

Background: Local Chinese local pig breeds have thinner muscle fiber and higher intramuscular-fat (IMF) content. But its regulation mechanism has not been discussed in-depth. Studies indicated that long non coding RNAs (lncRNAs) play important role in muscle and fat development.Results: The lncRNAs expressional differences in the longissimus dorsi (LD) muscle were identified between Huainan pigs (local Chinese pigs, fat-type, HN) and Large White pigs (lean-type, LW) at 38, 58, and 78 days post conception (dpc). In total, 2131 novel lncRNAs were identified in 18 samples, and 291, 305, and 683 differentially expressed lncRNAs (DELs) were found between these two breeds at three stages, respectively. GO and KEGG analysis of the DEL co expressed mRNAs showed that muscle development and energy metabolism were more active at 58 dpc in HN, but at 78 dpc in LW pigs. Muscle cell differentiation and myofibril assembly might associated with earlier myogenesis and primary-muscle-fiber assembly in HN, and cell proliferation, insulin, and the MAPK pathway might contribute to longer proliferation in LW pigs. The PI3K/Akt and cAMP pathways were associated with higher IMF deposition in HN. IMFlnc1 was selected for functional verification, and results indicated that it regulated the expressional level of caveolin-1 (CAV-1) by acting as competing endogenous RNA (ceRNA) to sponge miR-199a-5p.Conclusions: Our data contributed to understanding lncRNAs in porcine-muscle development and IMF deposition, and provided valuable information for improving pig-meat quality.
WITHDRAWN: Investigating the Cooperation Status Between the Health System and City Councils and Municipalities in Iran (Documents’ Analysis)
Authors: Khodadadi Najmeh , Khesal Aidin Aryan , Maleki Mohamad Reza
Published: June 2020

Background: The present study is aimed at investigating the cooperation status between the health system and city councils and municipalities in Iran based on rules and documents.Methods: Altheide’s document analysis model (sample selection, data collection, data organization, data analysis, and reporting) was employed in order to prepare and analyze the documents pertaining to the cooperation level between the health system and municipalities and Islamic city councils. The documents were classified at three levels including the national rules, policies, and guidelines; Ministry of Health (MOH) and city council approvals; and eventually Tehran Municipality’s measures.Results: Overall, 78 documents were analyzed including 17 documents at the level of national rules, policies and guidelines; 8 documents at the level of Ministry of Health and city council approvals; and 53 documents at the level of Municipality’s measures.Conclusion: There are adequate legal capacities for designing, planning, executing, as well as creating interaction and cooperation between health system and city councils and municipalities. Moreover, the motive behind creating a purposeful and scheduled cooperation and participation is evident among the officials of health system and city councils and municipalities. Some mechanisms have been established for cross-sectoral cooperation between the health system and other health-related bodies on a cross-sectional basis, but these structures lack the necessary competence, appropriateness and adequacy to create the desired partnership, and especially sufficient attention to existing capacities in municipalities and The city council has not. Accordingly, it is necessary to have a fundamental review on the available structures and enough attention has to be paid to the evident and hidden legal capacities in city councils, and municipalities, as well as Ministry of Health to design an appropriate structure and create competent interaction and also provide more cooperation between the two organizations.
Effect of SGLT-2 Inhibitors on Cardiovascular Outcomes Among Patients With Heart Failure and Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Lu Yuan , Yang Yu , Fan Yong , Li Chenzong , Zhang Min , Duan Yang , Chen Lei , Xi Jue , Chen Minglong , Wang Zhirong
Published: June 2020

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are significantly effective in reducing cardiovascular events in patients with type 2 diabetes mellitus (T2DM). However, the magnitude of the effect of SGLT-2i on cardiovascular outcomes in established heart failure (HF) patients with T2DM remains undefined.
Methods

We systematically searched the PubMed, Embase, Cochrane Central and Web of Science databases for articles published prior to 09 April 2020 to identify randomized controlled trials that compared SGLT-2i with placebo in patients with heart failure concomitant with T2DM. Efficacy outcomes included the composite of cardiovascular death (CVD) or hospitalization for heart failure (HHF), individual CVD, individual HHF, and all-cause mortality (ACM). Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled across trials by using the generic inverse variance method. Sensitivity analyses were conducted by excluding specific studies or using risk ratios (RRs) with 95% CIs as measures of the effect size. Serious adverse events served as safety outcomes.
Results

A total of 5 large trials comprising 6945 patients with HF and T2DM were enrolled. Pooled data demonstrated that SGLT-2i significantly reduced the risk for the primary composite outcome of CVD or HHF by 13% (HR: 0.87, 95% CI: 0.83–0.91, I2: 0%, P < 0.00001) in patients with HF concomitant with T2DM. Similarly, the use of SGLT-2i was associated with a statistically significant 14% reduction in HHF (pooled HR: 0.86, 95% CI: 0.81–0.91, I2: 0%, P < 0.00001) and a 10% reduction in ACM (pooled HR: 0.90, 95% CI: 0.86–0.96, I2: 16%, P < 0.0005) but was not significantly associated with a reduction in CVD (HR: 0.91, 95% CI: 0.81–1.02, I2: 60%, P = 0.11). Sensitivity analyses indicted consistent results. Compared with placebo plus standard care, the SGLT-2i group had a lower proportion of serious adverse events (weighted proportions: 44.3% vs 50.3%; RR 0.88, 95% CI 0.82–0.95, I2: 22%, p = 0∙006).
Conclusions

SGLT-2i significantly reduced the risk of HHF and ACM in a broad range of HF patients concomitant with T2DM. Compared with standard care, SGLT-2i plus standard therapy was associated with a reduction in serious adverse events.
Serum Lactate: Creatinine Ratio as a Prognostic Marker for Liver Failure Patients Treated by artificial liver support systems
Authors: Sun Shuilin , Chen Ling , Zhou Guanlin , Guo Lili , Cai Yunquan , Yang Wenlong , xie baogang
Published: June 2020

Background: To screen potential serum prognostic markers for patients with liver failure treated by artificial liver support systems (ALSSs).Methods: Serum samples were obtained from 57 liver-failure patients before and after ALSSs therapy and analyzed by proton nuclear magnetic resonance. The diagnostic values were evaluated by calculation of the area under a receiver-operating characteristic curve (AUROC). Two retrospective analyses were further employed.Results: Metabonomics analysis showed that ratios of creatine:creatinine, taurine:creatinine, and lactate:creatinine were significantly altered and restored to normal levels after ALSSs treatment. The ratio of lactate:creatinine showed the highest AUROC value (0.650), which was higher than that of the prothrombin time activity (PTA, 0.562). A total of 105 cases of retrospective analysis showed that serum lactate:creatinine ratios among the liver-failure patients were 0.038 ± 0.002 (survival group, n=48), 0.048 ± 0.005 (three-month death group, n=24), and 0.052 ± 0.005 (one-month death group, n=33), which was significantly negatively correlated with survival (r= - 0.26). Another retrospective cohort analysis (n=81) of the early to middle stage liver-failure patients treated by ALSSs showed that the AUROC of the lactate:creatinine ratio for diagnosis of those who survived for one subsequent month was 0.827, which was higher than that of PTA (0.628) and lactate (0.765).Conclusion: The serum lactate:creatinine ratio may be a more sensitive measure than either the PTA or the lactate to evaluate the prognosis of ALSSs treatment in early to middle stage of liver-failure patients. This finding is worthy of further study in clinical applications.
Identification and validation of glycolysis-related signatures for prognosis in patients with breast cancer
Authors: Zhang Ming , Xing Mengying , Ma Yunfei , Yao Bing , Chen Xiang , Ma Changyan
Published: June 2020

Background: Emerging evidence has demonstrated roles of glycolysis in the tumorigenesis and progression of human tumors. However, their underlying clinical implications have not been well elucidated in breast cancer. In present study, we aimed to generate a risk-score from glycolysis-related signatures to predict prognosis of patients with breast cancer. Methods: We acquired mRNAs expression and clinical datasets in patients with breast cancer from The Cancer Genome Atlas (TCGA), then identifying glycolysis-related mRNAs by Gene Set Enrichment Analysis (GSEA), followed by construction of prognostic risk-score. The altered expression of glycolysis-related mRNAs was identified as candidates for further investigation. We constructed a risk-score from the prognostic glycolysis-related mRNAs by Cox regression. Receiver Operating Characteristic (ROC) and clinical subgroups analysis were performed to evaluate the values of risk-score to predict prognosis of breast cancer. Besides, we also compared the expression patterns of the signatures in breast cancer tissues and cell lines.Results: Total of 1208 cases were obtained, including 112 normal tissues and 1096 tumor tissues. We found 4 glycolysis-related pathways significantly involved in breast cancer. And 298 mRNAs involved in the 4 pathways were defined as glycolysis-related mRNAs; of these, 241 dysregulated mRNAs were candidates for further exploration. Then we constructed a risk-score from the 5 candidates (IL13RA1, PGK1, SDC3, NUP43 and SDC1). The area under the curve (AUC) for the risk-score to predict prognosis was 0.729. Patients with high-risk score had poor prognosis among overall or clinical subgroups ( P <0.05). And IL13RA1, PGK1, NUP43 and SDC1 were up-regulated in tumor tissues and cell lines (MDA-MB-231 and BT474) as compared to normal tissues and cell line (MCF-10A), while SDC3 was down-regulated.Conclusions: We construct a risk-score based on 5 glycolysis-related signatures, which can well predict prognosis in breast cancer. Additionally, our findings further unveil the molecular mechanisms of glycolysis in cancer, providing promising directions for the prognostic and therapeutic biomarkers for breast cancer.
Ontogenetic plasticity in cranial morphology is associated with a functional change in the food processing behavior in Alpine newts
Authors: Schwarz Daniel , Konow Nicolai , Porro Laura Beatriz , Heiss Egon
Published: June 2020

Background: Salamander morphology changes substantially during metamorphosis, prompting the hypothesis that larvae need a different processing mechanism than post-metamorphic adults. Salamandrid newts with facultative metamorphosis are suitable for testing this hypothesis, because paedomorphic and metamorphic adults often coexist in the same population. Facultative paedomorphic newts provide a direct comparison of form-function relationships with specimens of the same species sharing similar body size and feeding on overlapping prey spectra, whilst having divergent food-processing morphologies.Methods: We use high-speed videography to quantify the in vivo movements of key anatomical elements during food processing in paedomorphic and metamorphic Alpine newts ( Ichthyosaura alpestris ). Additionally, we use micro-computed tomography (μCT) to analyze morphological differences in the feeding apparatus of paedomorphic and metamorphic Alpine newts and sort them into late-larval, mid-metamorphic and post-metamorphic morphotypes.Results: Paedomorphic and metamorphic individuals exhibited clear morphological differences of their feeding apparatus. Regardless of the paedomorphic state being externally evident, different paedomorphic specimens can conceal different morphotypes (i.e., late-larval and mid-metamorphic morphotypes). Though feeding on the same prey under the same (aquatic) condition, food processing kinematics differed between late-larval, mid-metamorphic and post-metamorphic morphotypes.Conclusions: While the Alpine Newt still lives in water, food processing mechanism changes along with morphology of the feeding apparatus during ontogeny, from a mandible-based to a tongue-based processing mechanism as the mandible’s changing morphology prevents chewing and the tongue allows enhanced protraction. These results could indicate that early tetrapods, in analogy to salamanders, may have developed new feeding mechanisms in their aquatic environment and that these functional innovations may have later paved the way for terrestrial feeding mechanisms.
Ex vivo Inducing Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure
Authors: Le Tien Minh , Morimoto Naoki , Ly Nhung Thi My , Mitsui Toshihito , Notodihardjo Sharon Claudia , Kakudo Natsuko , Kusumoto Kenji
Published: June 2020

Background: Apoptosis was reported to take crucial role in mesenchymal stem cell (MSC)-mediated immunomodulation, in which apoptotic MSCs were shown to be superior compared to living MSCs. Furthermore, extracellular vesicles (Evs) derived from MSCs were revealed more specific advantages for patient safety such as lower propensity to trigger innate and adaptive immune responses. As a safety and simple operation, high hydrostatic pressure (HHP), a physical technique that uses only fluid pressure to inactivate cells or tissues, has been developed and applied in a lot of field of biosciences, including biotechnology, biomaterials, or tissue engineering. Methods: MSCs isolated from human bone marrow were suspended cultured in appropriate medium and subjected to pressurization at 50 MPa for 36 h. Then cells were collected and investigated apoptotic pathway by transmission electron microscopy (TEM), phosphatidylserine membrane translocations, cleaved caspase-3/7 and terminal deoxy-nucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Besides, viability assays and live cell imaging were also used for assessement of cell survival after pressurization. Results: We found that HHP at 50 MPa for ≥36 h completely induced MSC death by Live/Dead assay, live cell imaging and WST-8 assay up to 7 days after pressurization. The large amount of apoptotic MSCs death was found based on morphological changes in TEM, phosphatidylserine exposure, caspase activation and detection of DNA fragmentations via TUNEL staining. Conclusions: In the current study, our data revealed that HHP treatment was convenient processing which safety and effectively induced MSCs undergo apoptosis. Especially, by capable of manufacture expanding, this technique might provide numbers of manipulated products using for industrial cell-based therapies.
The association between serum triglyceride to high-density lipoprotein cholesterol ratio and sarcopenia in community adults: positive or negative?
Authors: Wang Na , Chen Mengjun , Fang Danhong
Published: June 2020

Background
The serum triglyceride to high-density lipoprotein cholesterol(TG/HDL) ratio has been identified to be positively correlated with a higher risk of sarcopenia in elderly Korean males in previous study. In this study, we aimed to discover the association between TG/HDL ratio and sarcopenia in Chinese community adults, including males and females.
Methods
Individuals, who participated in medical examinations at the First Affiliated Hospital of Wenzhou Medical University from May 2016 to August 2017 with the age older than 18 years, were enrolled in the study. We applied univariable and multivariable logistic regression analyses to weigh the effects of TG/HDL ratio on the status of sarcopenia. Besides, we further identified the association by subgroup analysis.
Results
The occurrence of sarcopenia significantly decreased with the TG/HDL ratio increased. The odds ratio(OR) of TG/HDL ratio(high vs. low) for sarcopenia was 0.408(95%CI: 0.323–0.516) by univariable analysis and 0.631 by multivariable analysis(95%CI: 0.494–0.806) respectively. Additionally, the effect of TG/HDL ratio on sarcopenia was favorable(HR < 1.0) across a majority of prespecified subgroups, except age ≥ 65 and overweight population.
Conclusions
TG/HDL ratio was negatively correlated with prevalence of sarcopenia in Chinese community adults, especially in individuals with the age < 65 years old and the BMI < 25 kg/m2.
Immunologic Improvement of Vaccine for Newcastle Disease via Co-Inoculation of Cattle Transfer Factor in Broilers
Authors: Guo Hongrui , Li Xinyang , Li Xiaodan , Jiang Xinyue , Lai Weiming , Wang Kaiyu , Geng Yi , Ouyang Ping , He Ran , Tang Huaqiao , Xie Yue , Yang Guangyou , Gu Xiaobin
Published: June 2020

Background: Transfer factors (TFs), a novel immunostimulatory reagent, have found use as auxiliary or primary therapy for many diseases. The aim of this study was to explore whether TFs are able to strengthen immune responses of Newcastle Disease (ND) vaccines in broilers.Results: The serum antioxidant status was increased in TF-treatment broilers. TF subcutaneous injection could significantly increase (P < 0.5) the antibody titers at 14 and 21 days of the experiment. Moreover, TF treatment increased development of organs of the immune system, such as spleen, thymus, and bursa of Fabricius through inhibition of apoptosis and promotion of proliferation. Cellular immune responses were found to have higher levels in the groups with TF co-inoculation compared to those groups only treated with the ND vaccine, showing phenomena of higher expressions of interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ mRNA in the thymus, spleen, and bursa of Fabricius. Moreover, the immunostimulatory effect of TF subcutaneous injection treatment is better than oral and intramuscular injection.Conclusion: our findings suggest that TF treatment can improve antioxidant status and strengthen immune responses to ND vaccine, including antibody production and cellular immunity (lymphocytes proliferation and cytokines production) of the broilers, and the subcutaneous injection of TF is the appropriate inoculation way. Thus, TFs are a potent adjuvant and can serve as a medicine for immunoregulation.
Individual and Community Level Factors Associated with Early Sexual Initiation Among Female Youth in Ethiopia: A Multilevel Analysis of 2016 Ethiopian Demographic and Health Survey.
Authors: Arefaynie Mastewal , Yalew Melaku , Damtie Yitayish , Kefale Bereket
Published: June 2020

Background: There is limited national representative evidence on determinants of early sexual act among youth (female) especially community level factors are not investigated in Ethiopia. Thus, this study aimed to assess individual and community level factors associated with early sexual initiation among female youth in Ethiopia.Method: A secondary data analysis was done on the 2016 Ethiopian Demographic and Health Survey (EDHS) dataset was collected cross-sectional. A total of 6143 15-24 years’ old females irrespective of their sexual activity were included in the analysis. Multi-level mixed-effect logistic regression analysis was done by STATA version 14.0 to identify individual and community-level factors. Adjusted odds ratio with 95% confidence interval was used to show the strength and direction of association and statistical significance was declared at P value less than 0.05.Result: individual level factors significantly associated with early sexual initiation among female youth were; age group from 19-24 years [AOR=5.77, 95% CI= (4.58, 7.27)], not attend school [AOR=14.1, 95% CI= (8.06, 24.66)], ever chew Chat [AOR= 1.98, 95%CI= (1.32, 2.97)]. From community label variables living in Addis Ababa [AOR= 0.28, 95%CI= (0.17, 0.45)], living in Gambella [AOR=2.7, 95%CI= (1.7, 4.29)] and live in low proportion of poor communities [AOR= 0.66, 95% CI= (0.49, 0.9)] were significantly associated with early initiation of sexual intercourse of female youth. Conclusion: increased age, low educational status, ever chewing Chat, region and live in high proportion of poor community had statistical association with early sexual initiation among female youth. Improving educational coverage, improving community level wealth status are important interventions to delay the age of first sexual act among female youth.
Management of plantar heel pain: a best practice guide synthesising systematic review with expert clinical reasoning and patient values
Authors: Morrissey Dylan , Cotchett Matthew , J’Bari Ahmed Said , Prior Trevor , Vicenzino Bill , Griffiths Ian , Rathleff Michael , Gulle Halime , Barton Christian
Published: June 2020

Objective To develop a Best Practice Guide for managing people with plantar heel pain (PwPHP)Design a mixed methods designData sources Medline, Embase, CINAHL, SportsDiscus, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, reference lists, and citation tracking. Semi-structured interviews with world experts and a patient survey.Eligibility criteria RCTs evaluating any intervention for PwPHP in any language were included subject to strict quality criteria. Trials with a sample size greater than 38 were considered for proof of efficacy. International experts were interviewed using a semi-structured approach and PwPHP surveyed online.Results Forty PwPHP completed the survey and 14 experts were interviewed resulting in 7 themes and 38 sub-themes. Fifty-one eligible trials enrolled 4351 participants, with 10 interventions suitable to determine proof of efficacy. There was good agreement between the interview data and systematic review findings about taping (SMD: -0.47, 95% CI -0.88 to -0.05) and stretching (SMD: 1.21, 95% CI 0.78 to 1.63) for first step pain in the short term, with clinical reasoning guidance to combine these interventions with education and footwear advice as a core approach. There was good agreement to stepped care with focussed shockwave for first step pain in the short term (OR: 1.72, 95% CI 1.14 to 2.61), medium term (SMD -1.31, 95% CI -2.01 to – 0.61) and long term (SMD -1.67, 95% CI -2.45 to -0.88) and radial shockwave for first step pain in the short term (OR: 1.66, 95% CI 1.00 to 2.76) and long term (OR: 1.78, 95% CI 1.07 to 2.96). Good agreement for stepped care was also revealed for custom foot orthoses for pain in the short term (SMD: -0.41, 95% CI -0.74 to – 0.07) and medium term (SMD: -0.55, 95% CI -1.02 to -0.09).ConclusionA best practice guide was formulated based on robust evidence, with application guided by expert reasoning and patients’ perspectives.Systematic review registration Prospero CRD42018102227
COVID-19 Pandemic in Bergamo outbreak: a call to war. Implementation of a “COVID-Hospital” model in ASST Bergamo-Est Trust as a disaster-response strategy.
Authors: Iaculli Edoardo , Marini Michele , Pezzoli Isabella , Spinelli Luisella , Vescovi Lorenzo , Frassini Silvia , Rubertà Francesca , Paderno Nadiane , Nave Rosalba Della , Re Elisa Da , Meneme Hamade Abdel , Bonzi Delia Beatrice , Tedeschi Alberto Mario Guglielmo Leone , Iaculli Alessandro , Nastasi Giuseppe , Mariani Pierpaolo , Albani Antonio Piazzini
Published: June 2020

Background: COVID-19 is a strikingly emerging disease caused by a new coronavirus (SARS-CoV-2) that has rapidly spread across all continents and affecting virtually every country. From a clinical, epidemiological, political and financial perspective, COVID-19 pandemic is now recognized as one of the worst disasters in modern era. In the North of Italy, Bergamo has been the European equal to Chinese City of Wuhan in terms of epidemiological impact of COVID-19. The first case of SARS-Cov-2 infection in Bergamo has been reported in Alzano District General Hospital (DGH), part of ASST Bergamo-Est Multi Hospitals Network. ASST Bergamo-Est comprises four Hospitals serving more than 50% of Bergamo Province and with a patient catchment of 387000 inhabitants. Methods: We retrospectively analyze the challenges and actual impact of the SARS-CoV-2 pandemic on the hospital capacity and performance. Accordingly, we report the specific operational procedures and clinical governance implementation related to the transformation of our Institutions into “COVID-hospitals”. Results: From 1st of March to 20th of April, 4919 consecutive patients were assessed in ASST Bergamo-Est Hospitals as “COVID-Hospital” referral centre, of these 1412 patients were admitted with diagnosis of moderate to severe COVID-19 respiratory insufficiency. Most of patients were high-risk individuals with a median age of 69 years. In-hospital mortality rate was 33.1%. Specific performance improvements under the “COVID-19 Hospital model” capacity-expansion strategy were analysed. Conclusions: This paper informs on the experience of ASST Bergamo-Est Trust and the disaster-response strategy during the COVID-19 pandemic. The ASST Bergamo-Est data reported corroborates the recent call for action to Governments for promoting MCI improved management with focus on COVID-19 pandemic and its possible recurrence.
Comparative therapeutic efficacy of interferon and combination Kaletra plus interferon alpha-2b against SARS-CoV-2
Authors: Liu Jingyuan , Du Chunjing , Pu Lin , Xiong Haofeng , Xiang Pan , Li Chuansheng , Zhang Ming , Xie Wen , Chen Zhihai , Li Ang
Published: June 2020

Background: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people’s attentions. Whether interferon alfa-2b or Kaletra plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown.Methods: This is a retrospective cohort study of 123 laboratory-confirmed COVID-19 patients between Jan.13 2020 and Apr. 23. All patients received standard supportive care and regular clinical monitoring, patients were assigned to standard care group (n=12), interferon alfa-2b group (n=44), and combination Kaletra plus interferon alfa-2b group (n=67) according to their therapies. The primary endpoint for this study was the duration of oxygen-support requirement and virus clearance time. The associations of therapies with these outcomes were assessed by Cox proportional hazards regression. Results: Baseline clinical and laboratory characteristics were similar among 3 groups (p＞0.05). There was no significant association of Kaletra /interferon alfa-2b with faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% CI, 0.45–1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI, 0.32–1.11]; P = 0.10 in Kaletra plus interferon alfa-2b group). The duration of oxygen-support requirement in therapy groups similarly showed no significant association. There were no differences among 3 groups in the incidence of adverse events (p＞0.05).Conclusions: In patients with confirmed SARS-CoV-2 infection, no benefit was observed with interferon alfa-2b and Kaletra plus interferon alfa-2b treatment beyond standard care. Further trials in appropriately randomized design may contribute to validate the effective role and safety profile of the test drugs.
Accuracy of HPV E6/E7 RNA examination using in situ hybridization in diagnosing cervical intraepithelial lesions
Authors: Chang Hui , Bai Huimin , Liu Jun , Lu Xuerong , Wang Shuzhen , Zhang Zhenyu , Jin Mulan , Wang Yue , Liu Yuzhen
Published: June 2020

Background: The consistency of pathologists in the diagnosis of cervical intraepithelial neoplasia (CINs) is not ideal, especially between low- and high-grade squamous intraepithelial lision (LSIL and HSIL). This study was aimed to explore efficient strategies for the grading diagnosis of CINs.Methods: The medical records of patients with high risk HPV (HR-HPV) infections who had undergone cervical biopsy or conization from April 2018 to April 2019 in Beijing Chao-Yang Hospital were collected and examined. HR-HPV E6/E7mRNA in tissues of patients with CINs was detected using RNAscope chromogenic in situ hybridization (RISH). Immunohistochemistry (IHC) was performed to evelute the expression of p16INK4a (P16) and Ki67.Results: HR-HPV E6/E7 mRNA signals were detected in 3/27(11.1%) CIN 1, 32/33(97.0%) CIN 2/3. Mostly staining patterns(27/32, 84.4%) showed full-thickness epithelial layer staining with weak to strong nuclear and cytoplasmic dot-like signals in CIN 2/3, there were also a few special staining patterns significant differences from others. We compared a number of indicators in LISL and HSIL differences. There were statistically significant differences in E6/E7mRNA, p16, Ki67 and cytology between the two groups (P<0.05). According to logistic regression analysis，there was only E6/E7mRNA positivity was significantly associated with CIN2/3(OR: 52.53, 95% CI, P<0.05). In the detection of CIN2/3, The sensitivity and specificity of HPV E6/E7mRNA alone were not sinificantly inferior to that its different combinations with Ki67, p16, and cytology (all P >0.05).Conclusions: RISH was efficient in grading diagnosis of CINs. HPV E6/E7mRNA expressions might reflet the phase HPV infections and its positive pattern might predict the development direction of CINs, which could provide the possibility to realize more accurate treatment for patients.
Cutting Performance of Bionic Cutting tools Based on Surface Microstructures of Blood Clams in Dry Cutting of CFRP
Authors: You Changtang , Xie Chaoping , Chu Xuyang , Zhou Wei , Zhao Guolong , Lian Yunsong
Published: June 2020

Carbon fibre reinforced polymer (CFRP) composites are widely used in high-tech industries like the automobile and aerospace sectors, but the wear resistance of tools is one of the most significant restrictions in machining CFRP. In this study, bionic cutting tools based on surface microstructures of blood clams were fabricated to improve the dry cutting performance of CFRP. Three types of bionic cutting tools with different size parameters were applied in dry cutting test. The three-axis cutting forces and the cutting temperature of the processed workpiece were measured. The average friction coefficient between the rake face and the chip was calculated, and the morphology of the tools wear were observed. The results showed that bionic microstructures with appropriate size parameters can extremely improve the cutting performance of CFRP for tool in turning.