bluuebunny/crossref_metadata_2025 huggingface dataset:
An Implementation History of Primary Health Care Transformation: Alberta’s Primary Care Networks and the People, Time and Culture of change
Authors: Leslie Myles , Khayatzadeh-Mahani Akram , Birdsell Judy , Forest PG , Henderson Rita , Gray Robin Patricia , Schraeder Kyleigh , Seidel Judy , Zwicker Jennifer , Green Lee A.
Published: May 2020

Background: Primary care, and its transformation into Primary Health Care (PHC), hasbecome an area of intense policy interest around the world. As part of this trendAlberta, Canada, has implemented Primary Care Networks (PCNs). These aredecentralized organizations, mandated with supporting the delivery of PHC, fundedthrough capitation, and operating as partnerships between the province’s healthcareadministration system and family physicians. This paper provides an implementationhistory of the PCNs, giving a detailed account of how people, time, and culturehave interacted to implement bottom up, incremental change in a predominantly Fee-For-Service (FFS) environment.Methods: Our implementation history is built out of an analysis of policy documentsand qualitative interviews. We conducted an interpretive analysis of relevant policydocuments (n=20) published since the first PCN was established. We then grounded12 semi-structured interviews in that initial policy analysis. These interviews explored11 key stakeholders’ perceptions of PHC transformation in Alberta generally, and theformation and evolution of the PCNs specifically. The data from the policy review andthe interviews were coded inductively, with participants checking our emerginganalyses. Results: Over time, the PCNs have shifted from an initial Frontier Era thatemphasized local solutions to local problems and featured few rules, to a present Eraof Accountability that features central demands for standardized measures,governance, and co-planning with other elements of the health system. A core groupof people – clinician and administration leaders – emerged to create the PCNs and,over time , to develop a long-term Quality Improvement (QI) vision and governanceplan for them as organizations. The continuing willingness of both these groups towork at understanding and aligning one another’s cultures to achieve thetransformation towards PHC has been central to the PCNs’ survival and success.Conclusions: Generalizable lessons from the implementation history of this emergingpolicy experiment include: The need for flexibility within a broad commitment toimproving quality. The importance of time for individuals and organizations to learnabout: quality improvement; one another’s cultures; and how best to support thetransformation of a system while delivering care locally.
Does the Medical Insurance System Play a Real Role in Reducing Catastrophic Economic Burden in Elderly Patients with Cardiovascular Disease in China? Implication for Accurately Targeting Vulnerable Characteristics.
Authors: Ma Meiyan , Li Ye , Wang Nianshi , Wu Qunhong , Jiao Mingli , Shan Linghan , Sun Tao , Li Heng , Gao Han , Fu Xuelian , Tian Wanxin , Xia Qi , Hao Yanhua , Shi Baoguo
Published: May 2020

Background: The vulnerability of cardiovascular disease (CVD) patients’ health abilities, combined with the severity of the disease and the overlapping risk factors, can cause such people to bear the economic burden of the disease due to the use of medical services.We estimated the economic burden of patients with CVD,and identified the weak link in the design of the medical insurance.Methods: Data from 5,610 middle-aged and elderly with CVD were drawn from the 2015 wave of China Health and Retirement Longitudinal Study (CHARLS). The recommended method of the World Health Organization (WHO) was adopted to calculate catastrophic health expenditure (CHE), impoverishment by medical expenses (IME), and applied the treatment-effect model to analyze the determinants of CHE.Results: The incidence of CHE was 19.9% of the CVD, compared to 7.6% of the sample households trapped in IME. The incidence of CHE in CVD participating in medical insurance was 2.6% higher than for uninsured families (16.3%).Family size, health satisfaction,combine with other chronic diseases, having hospitalization and disabled members, and participating in insurance were found to be significantly associated with the likelihood of CHE.Conclusions: Elderly with physical vulnerabilities were more prone to CHE. The medical insurance only reduced barriers to accessing health resources for elderly with CVD, but lacked policy inclination for high-utilization populations,and had poorly accurate identification of vulnerable characteristics of CVD,which in turn affects the economic protection ability of the medical insurance. The dispersion between the multiple medical security systems leads to the existence of blind spots in the economic risk protection of individuals and families.
Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring
Authors: Li Yu , Lin Peng , Wang Siyao , Li shuang , Wang Rui , Yang Lin , Wang Hongmei
Published: May 2020

BackgroundPsoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis.MethodsThe study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography–mass spectrometry (LC-MS)/MS.ResultsA total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV.ConclusionsThese findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.
Seasonal Variation in the Onset of Acute Calcific Tendinitis of Rotator Cuff
Authors: Furuhata Ryogo , Matsumura Noboru , Yoshiyama Akira , Kamata Yusaku , Takahashi Masaaki , Morioka Hideo
Published: May 2020

BackgroundCalcific tendinitis of the rotator cuff is a common disorder that causes acute onset of shoulder pain when spontaneous resorption of the calcification occurs.However, factors that triggercalcium resorption have not been clarified. The present study aimed to investigate the association between the onset of calcium resorption in calcific tendinitis and the season of onset.MethodsWe retrospectively reviewed200 patients (female, 120; male, 80; mean age, 62.8 ± 14.2 years) diagnosed with acute calcific tendinitis between 2006 and 2018. The onset date of acute calcific tendinitis for each patient was collected from clinical notes. The incidence of acute calcific tendinitis in each season and month and the correlation between the incidence of acute calcific tendinitis and the mean monthly temperature or humidity levels were evaluated.Results The most common season of acute calcific tendinitis onset was summer (35.5%), followed by spring (24.5%), autumn (24.0%), and winter (16.0%) (P = 0.002). Monthly analyses showed the highest peak of onset was in July (15.5%) and the lowest peak was in February (3.0%) (P = 0.018).The incidence of acute calcific tendinitis had a weak association with mean monthly temperature (R2 = 0.074; P = 0.001), but was not associated with mean monthly humidity levels (R2 = 0.024; P = 0.055).ConclusionsThis study provides new information on seasonal variation of acute calcific tendinitis onset. The results of this study indicated that the onset of calcium resorption occurs most frequently in the summer in Japan; however, the reasons for seasonal variation remain unclear, and further studies will be needed.
Response of Groundnut (Arachis hypogaea L.) Genotypes to Combined Application of Phosphorus and Foliar Zinc Fertilizers in Central Tigray, Ethiopia
Authors: Berhe Hintsa Meresa , Abera Dereje Assefa , Yemane Yemane Tsehaye
Published: May 2020

Background: Adequate phosphorus (P) and foliar zinc (Zn) in groundnut required for obtaining Zn-enriched grain and optimum yield. However, it was very low in the area. Due to that, the study investigated the response of groundnut genotypes to combined application of phosphorus and zinc on yield and nutritional content. Methods: A field experiment was conducted at Sheka-Tekli in 2017/18 cropping season. The treatments were consisted of three groundnut genotypes (ICGV00308, ICGV91114 and Sedi) as main plot and four combined (P with Zn) fertilizer levels (00(F 0 ), 10 kg P/ha +0.50 g Zn/L(F 1 ), 20 kg P/ha +1 g Zn/L(F 2 ) and 30 kg P/ha+1.5 g Zn/L(F 3 ) as sub plot was assigned in split plot design. Result: The genotype and combined fertilizer main effect had significance effect on days to 50% flowering and days to 50% maturity. They had also a significant effect on hundred seed weight and leaf length, respectively. Number of pods/plant, pod yield/ha, number of seeds/pod, seed yield kg/ha, shelling percentage, percentage of crude protein and fat content had significantly affected by interaction component. Most of the yield component traits showed a strong positive correlation with seed yield . The highest seed yield (2,529 kg/ha) and protein content (37.79%) was obtained from Sedi with F 3 fertilizer. While the lowest yield was recorded from ICGV00308genotype without fertilizer. The highest fat content (43.95%) had gained from the genotype ICGV00308 with F 3 . A significant MRR (380.58%) was obtained from genotype ICGV00308 with F 1 . In addition, ICGV00308 & sedi with F 3 is the greatest interaction for extract high fat and protein content, respectively. Conclusions: From the result of the study, application of PZn fertilizer increases yield of groundnut. Therefore, based on the MRR result genotype ICGV00308 with F 1 was the best combination to produce groundnut per unit investment in the study area.
Anxiety Prevalence and its Associated Factors Among University Students In Malaysia: A National Cross-Sectional Study
Authors: Mohamad Nurul Elyani , Mohd-Sidik Sherina , Akhtari-Zavare Mehrnoosh , Gani Norsidawati Abdul
Published: May 2020

Background
Anxiety disorder is one of the most common mental health problems worldwide, including Malaysia. With the rising suicide rate nowadays, this issue has gained concern and attention from many, including experts and authorities globally. While average levels of anxiety motivate students to perform well in their studies, a high level of anxiety will significantly affect students' performance and self-esteem.
Methods
A cross-sectional study was conducted at selected government and private universities throughout Malaysia. A total of 1851 students participated in this study. The students were asked to complete self-administered questionnaires, which include information such as socio-demographic, academic, and psychosocial characteristics. The Generalized Anxiety Disorder-7 (GAD-7) questionnaire was used to measure the prevalence of anxiety in this study. Chi-square analysis was conducted to find the relationship between the variables and anxiety, and multivariate logistic regression analysis was used to identify the predictors.
Results
The response rate was 97.90%, where 1821 out of 1860 students participated in the study. The prevalence of anxiety in this study was 29%. The data revealed that race, residency, smoking status, alcohol consumption, sleeping quality, body mass index (BMI), academic year, the field of study, financial support for study and current living arrangement were found to be significantly associated with anxiety; with the academic year as the primary predictor.
Conclusions
Anxiety among university students in Malaysia is mainly impacted by the academic year. The findings highlight the current prevalence of anxiety among university students in Malaysia. The outcome of this study can serve as the evident baseline data and help with the development of specific interventions in addressing and managing the issue appropriately.
Plasma Proteomics Analysis for Screening Anlotinib Responders in Non-small Cell Lung Cancer
Authors: Lu Jun , Zhang Wei , Zhang Lele , Lou Yuqing , Gu Ping , Nei Wei , Qian Jie , Xu Jun , Zhao Xiaodong , Zhong Hua , Wang Huimin , Han Baohui
Published: May 2020

Background Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. The underlying value of proteomics for anlotinib study remains unclear. Methods In this study, plasma samples from 28 anlotinib-treated NSCLC patients (including 14 responders and 14 non-responders) were performed proteomics analysis. LC-MS/MS analysis was performed on those samples with different time points including baseline, best response and progression disease. Bioinformatics analysis was performed to understand the underlying value of those differential proteins. Results Proteomics analysis suggested the differential proteins from responders after anlotinib administration potential play a role in the molecular mechanism characterization and biomarker screening. The differential proteins between responders and non-responders at baseline mainly contribute to biomarker screening. Integrative analysis indicated 43 proteins could be used as underlying biomarkers for clinical practice. Lastly, we selected ARHGDIB and demonstrated that it has potential predictive value for anlotinib. Conclusions This study not only offered the first insight that the proteomic technology potentially be used for anlotinib molecular mechanism characterization, but also provided a basis for anlotinb biomarker screening via proteomics in the future.
In Vivo Length Change of Ligaments of Normal Knees During Dynamic High Flexion
Authors: Kono Kenichi , Konda Shoji , Yamazaki Takaharu , Tanaka Sakae , Sugamoto Kazuomi , Tomita Tetsuya
Published: May 2020

BackgroundNo studies compared the length change of ligaments of normal knees during dynamic activities of daily living. The aim of this study was to investigate in vivo length change of ligaments of the normal knees during high flexion.MethodsEight normal knees were investigated. Each volunteer performed squatting, kneeling, and cross-leg motions. Each sequential motion was performed under fluoroscopic surveillance in the sagittal plane. The femoral, tibial, and fibular attachment areas of the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), deep medial collateral ligament (dMCL), superficial medial collateral ligament (sMCL), and lateral collateral ligament (LCL) were determined according to osseous landmarks. After 2D/3D registration, the direct distance from the femoral attachment to the tibial or fibular attachment was measured as the ligament length. ResultsFrom 20° to 90° withflexion, the ACL was significantly shorter during cross-leg motion than during squatting. For thePCL, dMCL, sMCL, and LCL, there were no significant differences among the 3 motions. ConclusionThe ACL was shorter during cross-leg motion than during squatting in mid-flexion. This suggests that the ACL is looser during cross-leg motion than during squatting. On the other hand, the length change of the PCL, MCL, and LCL did not change even though the high flexion motions were different.
Compared with Electric Cautery, Better Clinical Outcomes can be Obtained by using the Scalpel in Primary Total Knee Arthroplasty
Authors: Lin Wei , Dai Yike , Niu Jinghui , Yang Guangmin , Li Ming , Wang Fei
Published: May 2020

Background: Whether using the scalpel can provide better and faster recovery during the primary total knee arthroplasty (TKA) is still controversial. The aim of this research was to compare the clinical outcomes of using the scalpel and the electric cautery in primary TKA.Methods: From January 2016 to December 2017, a retrospective cohort study was conducted in 313 patients who underwent unilateral primary TKA by using scalpel (group S). Duringthis period, we selected 313 patients who underwent unilateral primary TKA by using electric cautery (group E) for comparison. The tourniquet time, operative time, blood loss, wound complications, visual analog score for pain, range of motion, Knee Society Scorewere assessed between the two groups. The Forgotten Joint Scorewas used to analyze the ability to forget the joint.Results: There were no significant differences intourniquet time, operative time, blood loss between the two groups (p> 0.05). In the group S, the visual analog score for pain, range of motion, Knee Society Score were found better results at 1 month, 3 months, 6 months, 12 months and 24 months after surgery (p< 0.05). In addition, during the follow-up period, the Forgotten Joint Scorewas significantly higher compared with group E (p< 0.05).Conclusion: In this research, the patients who underwent TKA by using the scalpel could achieved better clinical outcomes. In addition, if forgotten artificial joint after TKA was the final goal, the patients who underwent TKA by using the scalpel would acquired better quality of life.
Neutrophil-Lymphocyte Ratio as A Complementary Biomarker of Periprosthetic Joint Infection: A Retrospective Review
Authors: Ye Yongyu , Gu Minghui , Chen Weishen , Xian Guoyan , Zheng Linli , Pan Baiqi , Zhang Ziji , Sheng Puyi
Published: May 2020

Background: Diagnosing a periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the neutrophil-lymphocyte ratio (NLR) in aiding the diagnosis of PJI.Methods: We retrospectively evaluated the medical records of 109 patients who had undergone revision arthroplasty (77 with aseptic mechanic failure and 32 with PJI) from July 2011 to November 2018. Bivariate analysis followed by multivariate logistic regression was applied to compare NLR between two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with C-reactive protein (CRP) and the erythrocyte sedimentation ratio (ESR).Results: NLR was significantly higher in patients with PJI than in patients of the aseptic revision group (3.12 ± 2.45 vs. 2.10 ± 1.03, p < 0.05). ROC curve analysis revealed that NLR had a sensitivity of 56.25% and a specificity of 80.52% with an optimal threshold of 2.52. The diagnostic performance of NLR alone was inferior to that of CRP and ESR as demonstrated by the area under curve, sensitivity, and diagnostic odds ratio. When used in combination with CRP, the diagnostic performance was nearly equal to the combined performance of CRP and ESR or that of all three biomarkers (p > 0.05).Conclusions: NLR is associated with PJI and could be regarded as a complementary marker, which in combination with CRP could improve the diagnostic performance for PJI.
Primarily Treated Patients versus Referred Patients in the Treatment of Native Septic Arthritis of Digits: A Retrospective Comparative Study
Authors: Kwak Sang Ho , Bae Jung Yun , Oh Youngkwang , Jang Hyo Seok , Ahn Tae Young , Lee Sang Hyun
Published: May 2020

Background Septic arthritis of digits needs urgent treatment. When treatments delayed or insufficient, patients may be referred to the upper-level hospital due to uncontrolled infection. We reviewed the treatment history of referred patients and compared the microorganisms and the clinical course of both primary and referred patients as relevant studies are rare. Methods In this retrospective review of consecutive case series, 45 patients (primary, n=11; referred, n=34) were treated with multiple irrigation and debridement. Cefazolin was used as empiric antibiotics, then changed according to microbiologic study. Previously used antibiotics, treatment delay, surgical history of the referred patients were reviewed. Identified microorganisms, required surgical intervention, hospital stay, radiologic outcome, functional outcomes were compared between both groups. Results In the referred patients, methicillin-resistant Staphylococcus aureus (MRSA) was commonly found and cefazolin was susceptible in only 15% of the cases. Longer hospital stay, prolonged antibiotic therapy, more surgical intervention including flap surgery was required to treat the referred patients. Postoperative pain was not severe in daily activities, but the final range of motion was significantly less in the referred patients compared to the primary patients.Conclusions This study suggests that in the treatment of uncontrolled septic arthritis of the digits, antibiotic agents covering MRSA may shorten the duration of antibiotic therapy in areas of high MRSA incidence. Besides, more number of I & D including flap surgery may be required for the referred patients compared with the primary patients. These findings can help the surgeon in setting up a treatment plan or in counseling of referred patients with uncontrolled septic arthritis of the digits.
Mental distress among frontline healthcare workers outside the central epidemic area during the novel coronavirus disease (COVID-19) outbreak in China: A cross-sectional study
Authors: LIU YAYUN , liu xinsheng , gao bai , li chengzhong , Liang XueSong
Published: May 2020

Background and aim:At the initial stage of the fight against COVID-19, a large number of medical staff and materials were dispatched to Wuhan City and Hubei Province to contain the outbreak quickly and effectively.The national infection prevention and control strategy posed a challenge to the physical and psychological resilience of frontline healthcare workers(HCWs) outside the central epidemic area.This study aims to survey frontline HCWs outside the central epidemic area in China to understand their levels of perceived stress, anxiety, and depression during the initial stage of the fight against the COVID-19 outbreak.Methods: From February 11 to February14, 2020, an online survey was conducted in Jinzhong, Shanxi Province using snowball sampling techniques. The survey consisted of two parts, namely, demographic data and psychological screening. Demographic information included gender, age, hospital classification, working department, profession type, and working experience. Perceived stress was assessed by Chinese simple Perceived Stress Scale 10, general anxiety was assessed by the General Anxiety Disorder Scale, and depression was evaluated by the Patient Health Questionnaire-9.Results: A total of 1,315 frontline HCWs were included,of which 646(49.1%) reported a moderate to severe stress(scores≥14), 141(10.7%) reported moderatetosevere anxiety (score≥10), and164(12.4%) reported a major depression (score≥10). Female gender was significantly associated with high levels of perceived stress, anxiety, and depression (P<0.05), and working time was negatively correlated with the level of perceived stress, anxiety, and depression (P<0.05). Statistical difference was observed in perceived stress score among different age groups, levels of hospital group,and working departments (P<0.05).Conclusion:During the initial stage of the fight against COVID-19in China, more than half of the frontline HCWs outside the central epidemic area rated perceived stress as moderatetosevere, and nearly 23% of them reported moderatetosevere anxiety or depression.Female gender, low hospital level, and emergency department were associated with a high level of perceived stress.
Incidence and risks for surgical site infection after closed tibial plateau fractures in adults treated by open reduction and internal fixation: a prospective study
Authors: Li Junyong , Zhu Yanbin , Zhao Kuo , Zhang Junzhe , Meng Hongyu , Jin Zhucheng , Ma Jiangtao , Zhang Yingze
Published: May 2020

Background
Surgical site infection (SSI) was the most common complication of tibial plateau fracture after open reduction and internal fixation (ORIF). Severe infections even required repeat surgeries, which would cause serious psychological harm to patients and increased the economic burden of treatment. In order to identify the characteristics of the SSI and to avoid the occurrence of SSI, we conducted a prospective study to investigate the incidence and independent risk factors of SSI after ORIF for closed tibial plateau fractures in adults.
Methods
This study was performed at a first-level trauma center. From October 2014 to December 2018, the study subjects were adult patients with closed fractures of the tibial plateau, all of whom underwent open reduction and internal fixation (ORIF) treatment. Finally, a total of 1108 patients were followed up. We collected patient demographics information, surgery-related variables and indexes from pre-operative laboratory examinations. Univariate and multivariate logistic analysis models were used to investigate the potential risk factors.
Results
Twenty-five patients (2.3%, 25/1108) developed SSI. A total of 15 of 25 infections (60.0%) were due to Staphylococcus aureus and 3 (12.0%) were due to MRSA. Independent risk factors of SSI identified by multivariate logistic analysis model were bone grafting: autograft (OR, 6.38; 95% CI, 2.155–18.886; p = 0.001) and allograft (OR, 3.215; 95% CI, 1.009–10.247; p = 0.048), fracture type (Schartzker Ⅴ-Ⅵ) (OR, 8.129; 95% CI, 2.961–22.319; p < 0.001), aspartate aminotransferase (> 40 U/L) (OR, 5.500; 95% CI, 2.191–13.807; p < 0.001), white blood cell (> 10*109/L) (OR, 2.498; 95% CI, 1.025–6.092; p = 0.044), and anion gap (> 16 mmol/L) (OR, 8.194; 95% CI, 1.101–60.980).
Conclusions
We should pay enough attention to patients who carried one or more of these factors at admission and adopt more reasonable treatment strategies to reduce or avoid the occurrence of SSI.
Electronic ordering and the management of treatment interdependencies: a qualitative study of paediatric chemotherapy
Authors: Lichtner Valentina , Franklin Bryony Dean , Dalla-Pozza Luciano , Westbrook Johanna I
Published: May 2020

Background
There are serious safety risks associated with chemotherapy, often associated with interdependencies in regimens administered over months or years. Various strategies are used to manage these risks. Computerized provider order entry (CPOE) systems are also implemented to improve medication safety. Little is known regarding the effect of CPOE on how clinicians manage chemotherapy interdependencies and their associated safety strategies.
Methods
We conducted a multi-method qualitative study in a paediatric hospital. We analysed 827 oncology incidents reported following CPOE implementation and carried out semi-structured interviews with doctors (n = 10), nurses (n = 6), a pharmacist, and oncology CPOE team members (n = 2). Results were interpreted according to safety models (ultra-safe, high-reliability organisations [HROs], or ultra-adaptive).
Results
Incident reports highlighted two interrelated types of interdependencies: those within organisation of clinical activities and those inherent in chemotherapy regimens. Clinicians reported strategies to address chemotherapy risks and interdependencies. These included rigid rules and ‘no go’ contexts for treatment to proceed, typical of the ultra-safe model; use of time (e.g. planning only so far ahead) and sensitivity to operations, typical of HROs. CPOE supported ultra-safe strategies through automation and access to rules/standardisation. However, sensitivity to operations was needed to anticipate and resolve uncertainties, hazards, CPOE limitations, and mismatches between CPOE processes and workflow in practice.
Conclusions
Within oncology, CPOE appears to move the ‘mix’ of risk strategies towards ultra-safe models of safety and protocol-mandated care. However, operating ultra-safe strategies embedded in CPOE and staying on protocol necessitate sensitivity to operations in CPOE use. CPOE design can be advanced by better consideration of mechanisms to support interdependencies.
Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE-/- mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage
Authors: Ma Ru , Qi Yi , Zhao Xinying , Li Xueyan , Sun Xuejing , Niu Piye , Li Yanbo , Guo Caixia , Chen Rui , Sun Zhiwei
Published: May 2020

Background
Given the prominent cardiovascular effects of nanosized particulate matter in air pollution, our limited understanding of the potential cardiovascular effects of engineered nanoparticles, in particular, is a pressing concern. Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. However, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown.
Results
Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) in ApoE−/− mice fed by a Western diet after SiNPs exposure via intratracheal instillation compared to the control mice. Histopathological investigation reflected a greater plaque burden with higher lipid load in the aortic root of SiNPs-exposed ApoE−/− mice. When compared to the control, serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress were occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and Bip, CHOP levels. Further, in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment could greatly alleviate SiNPs-induced macrophage lipid accumulation, and reverse the elevated CD36 expression by SiNPs.
Conclusions
Our results firstly revealed the acceleratory effect of SiNPs on atherosclerosis in ApoE−/− mice. SiNPs aggravated the plaque load in the aorta of mice, promoted macrophage infiltration and ER stress inside the lesion, alongside with the exacerbated arterial stiffness and dyslipidemia. Further, ER stress-mediated CD36 upregulation contributed to the formation of macrophage-derived foam cell caused by SiNPs, ultimately contributing to the progression of atherosclerotic plaque.
LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT axis
Authors: Liu Jianmin , Chen Ming , Ma Longyang , Dang Xingbo , Du Gongliang
Published: May 2020

Background: Accumulating evidence has shown that lncRNA growth arrest special 5 (GAS5) is a well‑known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is largely unclear. Here, we explore the role of GAS5 in progression of osteosarcoma. Methods: The expression level of GAS5 was detected in human osteosarcoma tissues and matched adjacent tissues, as well as osteosarcoma cell lines and nonmalignant osteoblast cells. Then, in vitro gain- and loss-of-function experiments, with the pcDNA-GAS5 expression vector and GAS5-siRNA, were performed in U2OS and HOS cells to determine the effect of GAS5 on osteosarcoma cell proliferation and invasion. Subsequently, we searched potential miRNA targets with bioinformatics analysis and confirmed their interaction by using luciferase reporter gene and RNA pull-down assays. The function and mechanism of miR-23a-3p in proliferation and invasion was also investigated in U2OS and HOS cells. Furthermore, rescue experiments were performed to verify the involvement of miR-23a-3p and its target gene in GAS5-mediated cell behaviors. Finally, a xenograft nude mouse model was established by subcutaneous injection with U2OS cells overexpressing GAS5 or not, and the effect of GAS5 on tumor growth in vivo was evaluated. Results: GAS5 was downregulated in human osteosarcoma tissues and cell lines. Overexpression of GAS5 could significantly suppress, and downregulation of GAS5 promoted, proliferation and invasion of osteosarcoma cells. GAS5 could directly bind with and upregulated miR-23a-3p, which post-transcriptionally downregulated the tumor suppressor PTEN and positively regulated proliferation and invasion of osteosarcoma cells. Rescue experiments confirmed the involvement of miR-23a-3p and PTEN in GAS5-mediated cell behaviors by modifying the phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. GAS5 could inhibit tumor growth in vivo. Conclusion: GAS5 functions as a competing endogenous RNA, sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.
Quality of life data for individuals affected by Spinal Muscular Atrophy: A baseline dataset from the Cure SMA Community Update Survey
Authors: Belter Lisa , Cruz Rosángel , Jarecki Jill
Published: May 2020

BACKGROUND Individuals and/or caregivers of individuals affected by Spinal Muscular Atrophy (SMA) completed the 2019 Cure SMA Community Update Survey, online, assessing health-related quality of life (HRQoL), loss of work productivity, and fatigue using the Health Utilities Index Questionnaire (HUI), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Patient Reported Outcomes Measurement Information System Fatigue Short Form (PROMIS Fatigue SF), respectively. The purpose was to collect baseline quality of life results among individuals affected by SMA using the above Patient Reported Outcome Measures (PROMs). RESULTS Of 666 surveys completed between March and May 2019, 478 were included in this analysis, accounting for duplicates, missing data, or deaths. The breakdown across SMA type I, II and III was 25%, 47% and 28%, respectively. Responses were characterized by current functional status/milestone, with subsets for “permanent ventilation,” “non-sitters,” “sitters,” “walk with support,” and “walk alone.” WPAI and HUI respondents included affected adults and caregivers. The PROMIS Fatigue SF was completed by the primary caregiver of affected children. Overall, those affected by a less severe form of SMA and with a higher functional status reported higher HRQoL and lower work productivity and activity impairment. All affected individuals reported higher fatigue levels than the general population. CONCLUSIONS This study offers useful insights into the burden of SMA among affected individuals and their caregivers. The results provide a baseline picture of the patient and caregiver experience with SMA in a post-treatment era from which to measure year-over-year changes in quality of life scores from new therapies and improved care. The WPAI demonstrates the significant impact of work productivity among SMA populations. Aspects of the HUI seem more appropriate to certain SMA sub-populations than others. Measures from the PROMIS Fatigue SF appear to under-represent the burden of fatigue often reported by SMA individuals and caregivers; this may, perhaps be due to a lack of sensitivity in the questions associated with fatigue in the SMA affected population, when compared with other studies on this topic. Overall, these results suggest the need for SMA-specific quality of life outcome measures to fully capture clinically meaningful change in the SMA population.
Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis
Authors: -Vafeiadou Eleni Christodoulou , Geka Christina , Ntari Lydia , Kranidioti Ksanthi , Argyropoulou Eleni , Meier Florian , Armaka Marietta , Mourouzis Iordanis , Pantos Constantinos , Rouchota Maritina , Loudos George , Denis Maria C , Karagianni Niki , Kollias George
Published: May 2020

Background The transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity to human spondyloarthritis we performed detailed characterization of the axial, peripheral and comorbid pathologies of this model. Methods TgA86 bone pathologies were assessed at different ages using CT imaging of the spine, tail vertebrae and hind limbs and characterized in detail by histopathological and immunohistochemical analysis. Cardiac function was examined by echocardiography and electrocardiography and bone structural parameters by µCT analysis. The response of TgA86 mice to either early or late anti-TNF treatment was evaluated clinically, histopathologically and by µCT analysis. Results TgA86 mice developed with 100% penetrance spontaneous axial and peripheral pathology which progressed with time and manifested as reduced body weight and body length, kyphosis, tail bendings as well as swollen and distorted hind joints. Whole body CT analysis at advanced ages revealed bone erosions of sacral and caudal vertebrae as well as of sacroiliac joints and hind limps, and also, new ectopic bone formation and eventually vertebral fusion. The pathology of these mice highly resembled that of SpA patients, as it evolved through an early inflammatory phase, evident as enthesitis and synovitis in the affected joints, characterized by mesenchymal cell accumulation and neutrophilic infiltration. Subsequently, regression of inflammation was accompanied by ectopic bone formation, leading to ankylosis. In addition, both systemic bone loss and comorbid heart valve pathology were evident. Importantly, early anti-TNF treatment, similar to clinical treatment protocols, significantly reduced the inflammatory phase of both the axial and peripheral pathology of TgA86 mice. Conclusions The TgA86 mice develop a spontaneous peripheral and axial biphasic pathology accompanied by comorbid heart valvular dysfunction and osteoporosis, overall faithfully reproducing the progression of pathognomonic features of human spondyloarthritis. Therefore, the TgA86 mouse represents a valuable model for deciphering the pathogenic mechanisms of spondyloarthritis and for assessing the efficacy of human therapeutics targeting different phases of the disease.
EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma
Authors: Huang Weimei , Lin Anqi , Luo Peng , Zhu Weiliang , Wei Ting , Guo Linlang , Zhang Jian
Published: May 2020

Background: Immune checkpoint inhibitor (ICI ) therapy has shown remarkable clinical benefit in lung adenocarcinoma (LUAD) patients. Genomic mutations may be applicable to predict the response to ICIs. Eph receptor A5 (EPHA5) is frequently mutated in breast cancer, lung cancer and other tumors; however, its association with outcome in patients who receive immunotherapy remains unknown. Methods: Somatic mutation data, gene expression data and clinicopathologic information were curated from patients with LUAD who were treated with ICI therapy (MSKCC ICI-treated cohort) and patients with LUAD who did not receive ICI therapy (TCGA-LUAD cohort). The CIBERSORT and gene set enrichment analysis (GSEA) algorithms were separately used to infer the relative abundance of leukocytes and significantly enriched pathways in the defined subgroups. Tumor mutation burden (TMB), tumor neoantigen load, the fraction of copy number variants (CNVs), the mutation frequency of DNA damage repair (DDR) genes, and the prognosis of patients were compared between the EPHA5-mutated subgroup and the EPHA5 wild - type subgroup. Whole-exome sequencing (WES) data and drug sensitivity data downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database were used to evaluate the relationship of the 50% inhibitory concentration (IC50) of multiple drugs and the EPHA5 mutation status in LUAD cells. Results: EPHA5 mutations were associated with increased TMB, neoantigen load, levels of immune - related gene expression signatures, and enhanced tumor-infiltrating lymphocytes (TILs). Patients with EPHA5 mutations in the immunotherapy cohort achieved a longer progression - free survival (PFS) time than patients with wild-type EPHA5. Immune response pathways were among the top enriched pathways in samples with EPHA5 mutations. In addition , patients with EPHA5 mutations tended to be more sensitive to certain targeted molecular inhibitors , including serdemetan, lox2 and PF1-1. Conclusion: Our results suggest that identifying mutations in the EPHA5 gene may provide insight into the genome-wide mutational burden and may serve as a biomarker to predict the immune response of patients with LUAD.
NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC
Authors: Zhang Qiao , Yang Zhe , Ni Yueli , Bai Honggang , Han Qiaoqiao , Yi Zihan , Yi Xiaojia , AGBANA Yannick Luther , Kuang Yingmin , Zhu Yuechun
Published: May 2020

Background Glucose 6-phosphate dehydrogenase (G6PD) serves key roles in cancer cell metabolic reprogramming, and has been reported to be involved in certain carcinogenesis. Previous results from our laboratory demonstrated that overexpressed G6PD was a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. G6PD could stimulate ccRCC growth and invasion through facilitating reactive oxygen species (ROS)-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activation and ROS-MAPK-MMP2 axis pathway, respectively. However, the reasons for ectopic G6PD overexpression and the proliferation repressive effect of G6PD inhibition in ccRCC are still unclear. Methods The impact of ROS accumulation on NK-κB signaling pathway and G6PD expression was determined by real-time RT-PCR and Western blot in ccRCC cells following treatment with ROS stimulator or scavenger. The regulatory function of NK-κB signaling pathway in G6PD transcription was analyzed by real-time RT-PCR, Western blot, luciferase and ChIP assay in ccRCC cells following treatment with NK-κB signaling activator/inhibitor or lentivirus infection. ChIP and Co-IP assay was performed to demonstrate protein-DNA and protein-protein interaction of NK-κB and pSTAT3, respectively. MTS assay, human tissue detection and xenograft model were conducted to characterize the association between NK-κB, pSTAT3, G6PD expression level and proliferation functions. Results ROS-stimulated NF-κB and pSTAT3 signaling over-activation could activate each other, and exhibit cross-talks in G6PD aberrant transcriptional regulation. The underlying mechanism was that NF-κB signaling pathway facilitated G6PD transcription via direct DNA–protein interaction with p65 instead of p50. p65 and pSTAT3 formed a p65/pSTAT3 complex, occupied the pSTAT3-binding site on G6PD promoter, and contributed to ccRCC proliferation following facilitated G6PD overexpression. G6PD, pSTAT3, and p65 were highly expressed and positively correlated with each other in ccRCC tissues, confirming that NF-κB and pSTAT3 synergistically promote G6PD overexpression. Moreover, G6PD inhibitor exhibited tumor-suppressor activities in ccRCC and attenuated the growth of ccRCC cells both in vitro and in vivo . Conclusion ROS-stimulated aberrations of NF-κB and pSTAT3 signaling pathway synergistically drive G6PD transcription through forming a p65/pSTAT3 complex and occupy the pSTAT3-binding site on G6PD promoter. Moreover, G6PD activity inhibition may be a promising therapeutic strategy for ccRCC treatment.
IVF and ICSI outcomes of female patients with X chromosome mosaicism: A 5-year retrospective cohort study
Authors: Liang Shanshan , Yang Jianzhi , Wu Haixia , Xiong Shiyi , Guo Ming , Teng Xiaoming
Published: May 2020

BackgroundThis study focused on the assisted reproductive treatment (ART) outcomes of female patients with X chromosome mosaicism (XM), who underwent their first IVF/ICSI and day 2 or day3 fresh embryo transfer, and the possible impacts of the different mosaic types.Results78 couples with XM female and normal male were included as the X group. 78 couples with normal karyotype were included as the control group. Subgroup X1 included 41 45,X/46,XX cases, Subgroup X2 included 23 47,XXX/46,XX cases, and Subgroup X3 included 13 45,X/47,XXX/46,XX cases. With similar female age and similar body mass index (BMI), the X group had higher total gonadotropin (Gn) dosage than the control group (1800 IU VS 1612 IU). In subgroup analysis, the follical number during oocyte retrieval was less in subgroup X1 than that in X2 or X3. The fertilization rate was lower in subgroup X1 than that in subgroup X2. The utilization rate was higher in subgroup X2 than that in subgroup X3. The implantation rate, clinical pregnancy rate, and miscarriage rate before 12 weeks' gestation were similar in all groups.ConclusionsFemale with 45,X cell line may face higher Gn dosage, less follical number during oocyte retrieval and fewer embryos. But female with X chromosome mosaicism may have similar clinical pregnancy rate and miscarriage rate after fresh embryo transfer.
The common PPARγ2 Pro12Ala polymorphism is associated with an increased risk of coronary artery disease (CAD) in Iranian patients with type 2 diabetes mellitus
Authors: Saremi Leila , Lotfipanah Shirin , Feizy Fatemeh , Avval Fatemeh Rostami , Saltanatpour Zohreh
Published: May 2020

Background. Type 2 diabetes (T2DM) is a risk factor for coronary artery disease (CAD) in patients with type 2 diabetes compared with subjects without diabetes. Many studies have been shown that CAD has resulted from the interaction of genetic markers implicated in dyslipidaemia and oxidative stress. The PPARγ gene is considered as a potential candidate gene for the link between diabetes mellitus and CAD in patients with diabetes mellitus. The purpose of the present study was to determine the association of Pro12Ala PPARγ2 polymorphism (rs1801282) with CAD in Iranian patients with T2DM.Methods. We studied 290 unrelated Iranian subjects, including 145 healthy controls and 145 CAD patients with a history of T2DM. Genomic DNA was isolated from peripheral blood, and the PPARγ2 gene mutations were analyzed using the PCR–RFLP technique.Results. Our results revealed a significant difference between the allele frequencies of PPARγ2 Pro12Ala polymorphism between the case and control subjects. However, no significant association was observed between Pro12Ala genotypes and physiologic variables.Conclusion. In summary, it could be concluded that PPARγ2 Pro12Ala polymorphism may be an essential indicator of the increased risk of CAD in diabetic patients among the Iranian population.Trial Registration. This article does not contain any studies with human participants by any of the authors.