bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Inequality, War Finance and the Pursuit of Tax Fairness
Authors: Chang Chia-Chien
Published: May 2020

It is widely acknowledged that a fair tax system is one of the most crucial foundations for any country to pursue stable development and human values. So how does a country accomplish tax fairness? This article argues that war finance and domestic economic inequality are two critical conditions. Historically, wars usually create opportunities for countries to enact progressive tax reforms. However, countries’ war finance choices are conditioned by domestic economic inequality. When inequality is low, the political leadership is more likely to secure a consensus of ‘equality of fiscal sacrifice’ between domestic wealthy elites and ordinary citizens. As a result, the leadership can more successfully enact progressive taxation, money creation and non-military spending cuts to pay for the war. Conversely, when inequality is high, the societal redistributive conflict could be more serious. Unable to strike a bargain of fiscal sacrifices without severe social instability, the leadership is expected to resort to a debt-financing strategy, which stifles tax progressivity and fairness. This article compares the United States’ war finance in the Korean and Vietnam Wars and finds supportive evidence. This article has important implications for the pursuits of tax fairness, democratic accountability, and the prospect for peace.
Socioecological Factors Affecting Fluid Restriction Adherence Among Korean Patients Receiving Hemodialysis: A Qualitative Study
Authors: Lee Eun Ju , Chang Ae Kyung , Chung Yoon Chung
Published: May 2020

Introduction: To reduce morbidity and mortality rates, hemodialysis patients are advised to restrict their fluid intake. However, fluid restriction is the biggest stressor for the patients. This study explored the barriers and facilitators of fluid restriction among Korean hemodialysis patients. Method: This qualitative descriptive study was guided by the ecological model of health behavior. This study involved five focus group (23 patients) and individual interviews (4 patients) at two hospitals in Korea. Audio-recorded transcripts were analyzed using qualitative content analysis. Results: Six intrapersonal, three interpersonal, and four organization factors affecting fluid restriction adherence were identified. Barriers included physiological symptoms, lack of self-control, social relationships, social stigma, lack of practical education, Korean food culture, and lack of public health and policy support. Facilitators included risk perception, self-assessment, knowledge, stimulated sweating, and social support. Discussion: The findings suggest that socioecological factors should be considered when designing fluid restriction programs for hemodialysis patients.
Delivering healthcare remotely to cardiovascular patients during COVID-19
Authors: Neubeck Lis , Hansen Tina , Jaarsma Tiny , Klompstra Leonie , Gallagher Robyn
Published: May 2020

Background

Although attention is focused on addressing the acute situation created by the COVID-19 illness, it is imperative to continue our efforts to prevent cardiovascular morbidity and mortality, particularly during a period of prolonged social isolation which may limit physical activity, adversely affect mental health and reduce access to usual care. One option may be to deliver healthcare interventions remotely through digital healthcare solutions. Therefore, the aim of this paper is to bring together the evidence for remote healthcare during a quarantine situation period to support people living with cardiovascular disease during COVID-19 isolation.

Methods

The PubMed, CINAHL and Google Scholar were searched using telehealth OR digital health OR mHealth OR eHealth OR mobile apps AND COVID-19 OR quarantine search terms. We also searched for literature relating to cardiovascular disease AND quarantine.

Results

The literature search identified 45 potentially relevant publications, out of which nine articles were included. Three overarching themes emerged from this review: (1) preparing the workforce and ensuring reimbursement for remote healthcare, (2) supporting mental and physical health and (3) supporting usual care.

Conclusion

To support people living with cardiovascular disease during COVID-19 isolation and to mitigate the effects of quarantine and adverse effect on mental and physical well-being, we should offer remote healthcare and provide access to their usual care.
Teasing apart office illumination: Isolating the effects of task illuminance on office workers
Authors: de Vries A , Souman JL , de Kort YAW
Published: May 2020

Task illuminance is one of the most used parameters in office lighting design and is often used as a ‘single number criterion’ to verify that a lighting design meets the requirements. Although other parameters, such as wall luminance, are often highly correlated with task illuminance, not taking these explicitly into account means critical user criteria such as comfort and satisfaction are left to chance. In this study, we investigated the effect of varying desk illuminance(150 lux to 1500 lux) while keeping wall luminance constant, isolating the effects of illuminance on the desk and eye on office users’ overall perception of the space, their mental state and their performance (visual and cognitive). While both visual acuity (paper-based) and perceived brightness increased significantly with higher desk illuminance, the room’s attractiveness did not. Even though illuminance at the eye increased considerably with desk illuminance (from 118 lux to 796 lux), only minor effects were found on subjective alertness and cognitive performance. This suggests that focusing on horizontal task illuminance as a design parameter is appropriate in view of visual acuity but has little to no effect on the space’s attractiveness, nor on cognitive performance or mental state of the office worker.
Development and current challenges of language courses for immigrants in Sweden
Authors: Öbrink Hobzová Milena
Published: May 2020

Sweden has been the target country for migrants and refugees for many decades now. One important tool for the integration of newcomers is the language classes called ‘Svenska för invandrare’ (Swedish for Immigrants). The aim of this article is to answer how Swedish for Immigrants has developed to respond to changes in attitudes to integration and to migration patterns since the 60s (not only as a result of European migration crisis in 2015) and analyse the challenges the system is currently facing. The article outlines the development of the language courses, explores the challenges against the current model and discusses the current state today. It also gives an insight into problems connected with the marginalisation of immigrants in Sweden. The article uses official documents and statistics to draw a picture of the system itself, while analysing the contemporary situation with the help of up-to-date sources, reports and newspaper articles to show that Sweden, often used as a model state for its integration policy, has got limits in this type of education.
PRKCSH Alternative Splicing Involves in Silica-Induced Expression of Epithelial–Mesenchymal Transition Markers and Cell Proliferation
Authors: Huang Ruixue , Liu Xiaodan , Li He , Ning Huacheng , Zhou Ping-Kun
Published: May 2020

Background:

Mounting evidence suggests that alternative splicing is one of the ways for cells to adapt to environmental stress insults. The aim of this study was firstly to examine the effect of silica on the alternative splicing of lung fibrosis–associated genes.

Methods:

Microarray analysis was used to construct the alternative splicing profile. Functional experiments were conducted using Cell Counting Kit-8, cell cycle, apoptosis, and epithelial–mesenchymal transition (EMT) analyses. Alternative splicing variants were verified by quantitative real-time polymerase chain reaction (qRT-PCR) polymerase chain reaction method.

Results:

A total of 1850 genes that have alternative splices in response to silica insult were identified. PCDHB11, MALAT1, MT2A, RP11-126D17.1, and RP11-415I12.2 are the top 5 upregulated genes with occurrence of alternative splice, whereas NDE1, RNPEPL1, TREML2, CSF2RB, and PRKCSH are the top 5 downregulated genes with occurrence of alternative splice. Bioinformatic analysis showed these genes with the occurrence of alternative splice mainly are associated with EMT pathway, N-Glycan biosynthesis, and leukocyte transendothelial migration. Further study indicated that PRKCSH-2 knockdown promotes A549 cell proliferation potential by partially promoting EMT signals.

Conclusions:

Significant changes in alternative splicing of silicosis-associated genes occur in patients with silicosis in silica conditions. Our study provides basic founding for further investigation into the detail molecular mechanisms underlying silica-induced silicosis.
Electrolytes and Cardiovascular Disease Risk
Authors: Bennett Jonathan , Deslippe Alysha L. , Crosby Christine , Belles Sally , Banna Jinan
Published: May 2020

The relationship between sodium intake and blood pressure is a well-studied phenomenon; however, the impact of sodium intake on cardiovascular disease risk and mortality is controversial. Recent studies conclude that weak evidence exists to support sodium restriction for the prevention of cardiovascular mortality in normotensive and hypertensive adults, suggesting that sodium restriction may be an ineffective strategy for disease prevention. Further evidence points to the importance of balancing sodium and potassium intake, a balance commonly achieved with a healthier diet containing greater quantities of fruits and vegetables. The purpose of this article is to highlight dietary strategies that may prove to be more effective in reducing cardiovascular disease risk. Limitations of current methods used to estimate nutrient intake are described as they relate to this topic. Further research is needed to advance understanding of various aspects of dietary intake that are health protective and allow for the development of more effective public education strategies.
Safety and outcomes of mechanical thrombectomy for acute stroke related to infective endocarditis: A case–control study
Authors: Marnat Gaultier , Sibon Igor , Gory Benjamin , Richard Sébastien , Olindo Stéphane , Consoli Arturo , Bourcier Romain , Kyheng Maeva , Labreuche Julien , Darganzali Cyril , Schiporst Adrien ter , Gariel Florent , Blanc Raphaël , Lapergue Bertrand ,   ETIS Registry Investigators
Published: May 2020

Background and purpose

Successful reperfusion can be achieved in more than two-thirds of patients with usual large-vessel occlusion stroke causes treated with mechanical thrombectomy. However, the safety and outcomes after mechanical thrombectomy in the setting of large-vessel occlusion related to infective endocarditis is not known. In this study, we investigated the impact of mechanical thrombectomy in infective endocarditis patients on angiographic and clinical outcomes.

Methods

This was a multicenter study from five comprehensive stroke centers. We compared the outcomes of mechanical thrombectomy treated stroke patients due to infective endocarditis with patients presenting atrial fibrillation. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage, and mortality.

Results

Between June 2013 and March 2019, 28 patients presenting large-vessel occlusion stroke due to IE were included. These cases were matched with 84 large-vessel occlusion stroke related to atrial fibrillation. Successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) was obtained in 85.7%. Symptomatic intracranial hemorrhage, favorable outcome and mortality rates were respectively 8.0%, 25.9%, and 25.9%. In the case–control analysis, we demonstrated no difference in terms of successful reperfusion, procedural complication, symptomatic intracranial hemorrhage, and mortality rates. Three-month favorable outcome was less often achieved in the infective endocarditis group.

Conclusions

Mechanical thrombectomy of infective endocarditis patients presents similar safety and angiographic results compared to patients suffering from atrial fibrillation.
Predicting outcome in liver patients admitted to intensive care: A dual-centre non-specialist hospital external validation of the Liver injury and Failure evaluation score
Authors: de Sausmarez Eleanor , Crowest Paul , Fry Steve , Hodgson Luke
Published: May 2020

Background

Acute hepatic dysfunction in the critically ill population with pre-existing liver cirrhosis is associated with a high mortality. Several prediction models have been developed to risk stratify patients with liver disease.

Methods

This UK dual-centre non-specialist hospital retrospective study (2015–2019) externally validated the Liver injury and Failure evaluation score (incorporating lactate, bilirubin and International Normalised Ratio), alongside two other general intensive care unit prediction models (Intensive Care National Audit and Research Centre and Acute Physiology and Chronic Health Evaluation II). Inclusion criteria matched a recent UK-wide study including at least one of biopsy proven cirrhosis, imaging suggestive of cirrhosis, hepatic encephalopathy or portal hypertension.

Results

One hundred and ninety-nine admissions met inclusion criteria over the study period (n = 169), mean age 57( ±13). In-hospital mortality was 40% in this cohort compared to 18% of all intensive care unit individuals during the same period. Variceal bleeding was associated with a lower short-term (18% versus 47%, P < 0.001, odds ratio 0.3 (95% confidence interval 0.1–0.5)) and longer-term mortality (log rank P = 0.015). In-patient mortality was higher in cases requiring renal replacement therapy (82% versus 29%, odds ratio 11.1 (95% confidence interval 4.6–26.9), P < 0.001) or ventilation (47% versus 32%, odds ratio 1.9 (1.1–3.4), P = 0.03). For in-patient mortality, area under the receiver operating characteristic curves were Liver injury and Failure evaluation 0.69 (95% confidence interval 0.62–0.77), Intensive Care National Audit and Research Centre 0.80 (0.74–0.86) and Acute Physiology and Chronic Health Evaluation II 0.73 (0.65–0.81). Forty-one per cent of cases were alive at one-year follow-up. Area under the receiver operating characteristic curves for one-year survival were Liver injury and Failure evaluation 0.69 (0.61–0.77), Intensive Care National Audit and Research Centre 0.75 (0.67–0.82) and Acute Physiology and Chronic Health Evaluation II 0.69 (0.61–0.77).

Conclusion

This first Liver injury and Failure evaluation score validation in a UK non-specialist hospital setting suggests this parsimonious, easy to calculate model may have utility in prediction of short-term and one-year mortality. As with previous studies variceal haemorrhage was associated with lower mortality.
Polymer nanoparticle-assisted chemotherapy of pancreatic cancer
Authors: Su Tianqi , Yang Bo , Gao Tianren , Liu Tongjun , Li Jiannan
Published: May 2020

Pancreatic cancer is a lethal disease characterized by highly dense stroma fibrosis. Only 15–20% of patients with pancreatic cancer have resectable tumors, and only around 20% of them survive to 5 years. Traditional cancer treatments have little effect on their prognosis, and successful surgical resection combined with effective perioperative therapy is the main method for maximizing long-term survival. For this reason, chemotherapy is an adjunct treatment for resectable cancer and is the main therapy for incurable pancreatic cancer, including metastatic pancreatic adenocarcinoma. However, there are various side effects of chemotherapeutic medicine and low drug penetration because the complex tumor microenvironment limits the application of chemotherapy. As a novel strategy, polymer nanoparticles make it possible to target the tumor microenvironment, release cytotoxic agents through various responsive reactions, and thus overcome the treatment barrier. As drug carriers, polymer nanoparticles show marked advantages, such as increased drug delivery and efficiency, controlled drug release, decreased side effects, prolonged half-life, and evasion of immunogenic blockade. In this review, we discuss the factors that cause chemotherapy obstacles in pancreatic cancer, and introduce the application of polymer nanoparticles to treat pancreatic cancer.
Insulin-delivery methods for children and adolescents with type 1 diabetes
Authors: Zuberi Zavuga , Sauli Elingarami , Cun Liu , Deng Jing , Li Wen-Jun , He Xu-Liang , Li Wen
Published: May 2020

Efforts directed toward restoring normal metabolic levels by mimicking the physiological insulin secretion, thereby ensuring safety, efficacy, minimal invasiveness and conveniences, are of great significance in the management of type 1 diabetes among children and adolescents. Regardless of the various technologies being discovered in addressing invasiveness and enhancing medication adherence in the management of type 1 diabetes, yet limited success had been observed among children and adolescents. The multiple daily subcutaneous insulin injections route using vial and syringe, and occasionally insulin pens, remain the most predictable route for insulin administration among children and adolescents. However, this route has been associated with compromised patient compliance, fear of injections and unacceptability, resulting in poor glycemic control, which promote the demand for alternative routes of insulin administration. Alternative routes for delivering insulin are being investigated in children and adolescents with type 1 diabetes; these include the hybrid closed-loop ‘artificial pancreas’ system, oral, inhalation, intranasal routes, and others. This review article explores the current advances in insulin-delivery methods that address the needs of children and adolescents in the treatment of type 1 diabetes.
How effective are antidepressants for depression over the long term? A critical review of relapse prevention trials and the issue of withdrawal confounding
Authors: Hengartner Michael P.
Published: May 2020

The aim of this article is to discuss the validity of relapse prevention trials and the issue of withdrawal confounding in these trials. Recommendations for long-term antidepressant treatment are based almost exclusively on discontinuation trials. In these relapse prevention trials, participants with remitted depression are randomised either to have the antidepressant abruptly discontinued and replaced by inert placebo or to continue active treatment. The drug–placebo difference in relapse rates at the end of the maintenance phase is then interpreted as a prophylactic drug effect. These trials consistently produce remarkable benefits for maintenance treatment. However, the internal validity of this trial protocol is compromised, as research has shown that abruptly stopping antidepressants can cause severe withdrawal reactions that lead to (or manifest as) depression relapses. That is, there is substantial withdrawal confounding in discontinuation trials, which renders their findings uninterpretable. It is not clear to what degree the drug–placebo separation in relapse prevention (discontinuation) trials is due to withdrawal reactions, but various estimations suggest that it is presumably the majority. A review of findings based on other methodologies, including real-world long-term effectiveness trials like STAR*D and various naturalistic cohort studies, do not indicate that antidepressants have considerable prophylactic effects. As absence of evidence does not imply evidence of absence, no definitive conclusions can be drawn from the literature. To enable a thorough risk–benefit evaluation, real-world effectiveness trials should not only focus on relapse prevention, but also assess antidepressants’ long-term effects on social functioning and quality of life. Thus far, reliable long-term data on these outcome domains are lacking.
Cyberbullying Considerations for School Counselors: A Social Media Content Analysis
Authors: Tinstman Jones Jessica L. , Campbell Laurie O. , Stickl Haugen Jaimie , Sutter Claudia C.
Published: May 2020

Researchers conducted a content analysis of nine social media platforms’ bullying policies based on the American School Counseling Association position statement on bullying to determine the content of the social media platforms’ bullying policies as they connect to school counseling guidelines. Main findings indicated (a) common terms are often unclear and vary, (b) language in policies was mainly negative and punitive, (c) cultural awareness was limited to anti-discrimination, and (d) mental health concerns were addressed but rarely associated with cyberbullying. School counselors can utilize these findings to inform training and prevention efforts to build and maintain safe schools and aid students impacted by cyberbullying.
Sexual Exchange and Cross-Border Trade: Implications for HIV/AIDS in Nigeria
Authors: Jawando Jubril O. , Adeyemi Ezekiel Oluwagbemiga
Published: May 2020

In West African countries, borders create opportunities for informal networks of trade and exchange. Some of the women involved in activities across the borders operate without official permit. Thus, they engage in transactional sex with those who may facilitate their movement across borders. The study examines sexual relations in cross-border trade and their implications for HIV spread in Nigeria. The study was carried out at Seme, a border town between Lagos, Nigeria, and Republic of Benin. The qualitative method was used to collect data for the study. Forty women who were cross-border traders were selected for focus group discussions; they were stratified into four sessions based on the type of goods, age, and years of experience. In-depth interviews (IDIs) were used to elicit information from three drivers and 16 security agents. The study revealed that some of these women used sex as a means of negotiation with border officials to avoid their goods being confiscated, whereas others had extramarital affairs with some of the officials for financial gains and protection. None of the women interviewed used condom during her last sexual intercourse preceding the survey. More than two-thirds of the respondents had heard about HIV/AIDS, but believed that they were not at risk of infection due to their ignorance. The study concluded that the observed sexual relationships may act as conduit for HIV and sexually transmitted infections (STIs) into both Nigeria and Benin, as these create sexual networks that may stretch over a wide geographical area. There is a need for mobile education programs targeted at this high-risk group.
Women’s Decision on Contraceptive Use in Ethiopia: Multinomial Analysis of Evidence From Ethiopian Demographic and Health Survey
Authors: Edossa Zerihun Kura , Debela Tilahun Fufa , Mizana Biru Abdissa
Published: May 2020

Background:

Women are left out of the conversation on contraceptive use due to a variety of reasons. One of the reasons women have reported for their nonuse of family planning method is that they do not decide to use or not to use it. This study aimed to assess the women’s decision-making on contraceptive use and identify its associated factors.

Methods:

Data for this study were extracted from the national representative 2016 Ethiopian Demographic and Health Survey. Data were collected using 2-stage cluster design, in which enumeration areas forming the first stage and households making the second stage. The analysis was done using multinomial logistic regression using STATA software version 14.

Results:

The study revealed that one-fourth (24.3%) 95% CI (23.7%-25.1%) decision was made by women. The multinomial analysis demonstrated women’s decision-making on contraceptive use was influenced by the age of women 15 to 19 years (adjusted odd ratio [AOR] = 0.327, 95% CI: 0.175-0.613), 20 to 24 years (AOR = 0.510, 95% CI: 0.390-0.666), and 25 to 29 (AOR = 0.557 95% CI: 0.460-0.675); place of residence (urban; AOR = 1.637, 95% CI: 1.331-2.015) and region in which the women dwell and husbands education; occupation of both woman and her husband; and number of children ever born were the factors significantly associated with the outcome variable.

Conclusions:

Women’s decision-making on contraceptive utilization was low. It was influenced by age, place of residence and region, education, occupation, and number of children ever born.
Cancer Patient Perspectives on Sharing of Medical Records and Mobile Device Data for Research Purposes
Authors: Franklin Elizabeth F , Nichols Helen M , House Linda , Buzaglo Joanne , Thiboldeaux Kim
Published: May 2020

Sharing data is critical to advancing science, improving health, and creating advances in the delivery of health care services. The value of sharing data for cancer research purposes is well established, and there are multiple initiatives under way that address this need. However, there has been less focus on cancer patient perspectives regarding the sharing of their health information for research purposes. This study examined cancer patient perspectives on the sharing of de-identified health data for research purposes including both data from medical records and mobile applications. This cross-sectional study used survey methodology to collect data from cancer patients/survivors (N = 677). Overall, we found that participants were largely willing (71%) to share de-identified medical data and were most motivated (88%) by a desire to help other cancer patients. Patients were less likely to be comfortable sharing mobile application data (34%). It is vital that we understand patient perspectives on data sharing and work with them as partners, valuing their unique contributions, and attending to their preferences.
Jahnsite-(CaMnZn) from the Hagendorf-Süd pegmatite, Oberpfalz, Bavaria, and structural flexibility of jahnsite-group minerals
Authors: Grey Ian E. , Keck Erich , Kampf Anthony R. , MacRae Colin M. , Cashion John D. , Glenn A. Matt
Published: May 2020

Jahnsite-(CaMnZn), CaMn2+Zn2Fe3+2(PO4)4(OH)2⋅8H2O, is a new jahnsite-group mineral associated with alteration of phosphophyllite at the Hagendorf-Süd pegmatite, Bavaria. It forms as thin yellow crusts and brown epitactic growths on altered phosphophyllite, both of which comprise lath-like crystals in orthogonal orientation, up to 100 μm long. The crystals contain intergrowths of jahnsite-(CaMnZn) and jahnsite-(CaMnMn) on a scale of ~50 μm. The calculated density is 2.87 g cm−3 based on the empirical formula. Optically it is biaxial (–), with α = 1.675(2), β = 1.686(2) and γ = 1.691(2) (white light). The calculated 2V is 68°. Dispersion could not be observed, and the optical orientation is Z = b. Pleochroism was imperceptible. Electron microprobe analyses together with results from Mössbauer spectroscopy gives the formula (Ca0.59Mn0.24)Σ0.83Mn(Zn0.74Mn2+0.48Mg0.18Fe2+0.13Fe3+0.47)Σ2Fe3+2(P0.995O4)4(OH)2.03(H2O)7.97.

Jahnsite-(CaMnZn) is monoclinic, P2/a, with a = 15.059(1), b = 7.1885(6), c = 10.031(2) Å, β = 111.239(8)° and V = 1012.1(2) Å3. The recent International Mineralogical Association approved nomenclature system for jahnsite-group minerals was applied to establish jahnsite-(CaMnZn) from the empirical formula. The structural flexibility of jahnsite-group minerals to accommodate cations of quite different sizes in the X and M1 sites is discussed in terms of rotations about the 7 Å axis of two independent octahedra centred at the M3 sites.
The endoplasmic reticulum protein SEC22B interacts with NBEAL2 and is required for megakaryocyte α-granule biogenesis
Authors: Lo Richard W. , Li Ling , Pluthero Fred G. , Leung Richard , Eto Koji , Kahr Walter H. A.
Published: May 2020

Studies of inherited platelet disorders have provided many insights into platelet development and function. Loss of function of neurobeachin-like 2 (NBEAL2) causes gray platelet syndrome (GPS), where the absence of platelet α-granules indicates NBEAL2 is required for their production by precursor megakaryocytes. The endoplasmic reticulum is a dynamic network that interacts with numerous intracellular vesicles and organelles and plays key roles in their development. The megakaryocyte endoplasmic reticulum is extensive, and in this study we investigated its role in the biogenesis of α-granules by focusing on the membrane-resident trafficking protein SEC22B. Coimmunoprecipitation (co-IP) experiments using tagged proteins expressed in human HEK293 and megakaryocytic immortalized megakaryocyte progenitor (imMKCL) cells established binding of NBEAL2 with SEC22B, and demonstrated that NBEAL2 can simultaneously bind SEC22B and P-selectin. NBEAL2-SEC22B binding was also observed for endogenous proteins in human megakaryocytes using co-IP, and immunofluorescence microscopy detected substantial overlap. SEC22B binding was localized to a region of NBEAL2 spanning amino acids 1798 to 1903, where 2 GPS-associated missense variants have been reported: E1833K and R1839C. NBEAL2 containing either variant did not bind SEC22B coexpressed in HEK293 cells. CRISPR/Cas9-mediated knockout of SEC22B in imMKCL cells resulted in decreased NBEAL2, but not vice versa. Loss of either SEC22B or NBEAL2 expression resulted in failure of α-granule production and reduced granule proteins in imMKCL cells. We conclude that SEC22B is required for α-granule biogenesis in megakaryocytes, and that interactions with SEC22B and P-selectin facilitate the essential role of NBEAL2 in granule development and cargo stability.
The ectodomain of matriptase-2 plays an important nonproteolytic role in suppressing hepcidin expression in mice
Authors: Enns Caroline A. , Jue Shall , Zhang An-Sheng
Published: May 2020

Matriptase-2 (MT2), encoded by TMPRSS6, is a membrane-anchored serine protease that plays a key role in suppressing hepatic hepcidin expression. MT2 is synthesized as a zymogen and undergoes autocleavage for activation. Previous studies suggest that MT2 suppresses hepcidin by cleaving hemojuvelin and other components of the bone morphogenetic protein–signaling pathway. However, the underlying mechanism is still debatable. Here we dissected the contributions of the nonproteolytic and proteolytic activities of Mt2 by taking advantage of Mt2 mutants and Tmprss6−/− mice. Studies of the protease-dead full-length Mt2 (Mt2S762A) and the truncated Mt2 that lacks the catalytic domain (Mt2mask) indicate that the catalytic domain, but not its proteolytic activity, was required for Mt2 to suppress hepcidin expression. This process was likely accomplished by the binding of Mt2 ectodomain to Hjv and Hfe. We found that Mt2 specifically cleaved the key components of the hepcidin-induction pathway, including Hjv, Alk3, ActRIIA, and Hfe, when overexpressed in hepatoma cells. Nevertheless, studies of a murine iron-refractory iron-deficiency anemia–causing mutant (Mt2I286F) in the complement protein subcomponents C1r/C1s, urchin embryonic growth factor, and bone morphogenetic protein 1 domain indicate that Mt2I286F can be activated, but it exhibited a largely compromised ability to suppress hepcidin expression. Coimmunoprecipitation analysis revealed that Mt2I286F, but not Mt2S762A, had reduced interactions with Hjv, ActRIIA, and Hfe. In addition, increased expression of a serine protease inhibitor, the hepatocyte growth factor activator inhibitor-2, in the liver failed to alter hepcidin. Together, these observations support the idea that the substrate interaction with Mt2 plays a determinant role and suggest that the proteolytic activity is not an appropriate target to modulate the function of MT2 for clinical applications.
Abscisic acid mediated proline biosynthesis and antioxidant ability in roots of two different rice genotypes under hypoxic stress
Authors: Cao Xiaochuang , Wu Longlong , Wu Meiyan , Zhu Chunquan , Jin Qianyu , Zhang Junhua
Published: May 2020

Background

Abscisic acid (ABA) and proline play important roles in rice acclimation to different stress conditions. To study whether cross-talk exists between ABA and proline, their roles in rice acclimation to hypoxia, rice growth, root oxidative damage and endogenous ABA and proline accumulation were investigated in two different rice genotypes (‘Nipponbare’ (Nip) and ‘Upland 502’ (U502)).

Results

Compared with U502 seedlings, Nip seedlings were highly tolerant to hypoxic stress, with increased plant biomass and leaf photosynthesis and decreased root oxidative damage. Hypoxia significantly stimulated the accumulation of proline and ABA in the roots of both cultivars, with a higher ABA level observed in Nip than in U502, whereas the proline levels showed no significant difference in the two cultivars. The time course variation showed that the root ABA and proline contents under hypoxia increased 1.5- and 1.2-fold in Nip, and 2.2- and 0.7-fold in U502, respectively, within the 1 d of hypoxic stress, but peak ABA production (1 d) occurred before proline accumulation (5 d) in both cultivars. Treatment with an ABA synthesis inhibitor (norflurazon, Norf) inhibited proline synthesis and simultaneously aggravated hypoxia-induced oxidative damage in the roots of both cultivars, but these effects were reversed by exogenous ABA application. Hypoxia plus Norf treatment also induced an increase in glutamate (the main precursor of proline). This indicates that proline accumulation is regulated by ABA-dependent signals under hypoxic stress. Moreover, genes involved in proline metabolism were differentially expressed between the two genotypes, with expression mediated by ABA under hypoxic stress. In Nip, hypoxia-induced proline accumulation in roots was attributed to the upregulation of OsP5CS2and downregulation of OsProDH, whereas upregulation of OsP5CS1combined with downregulation of OsProDHenhanced the proline level in U502.

Conclusion

These results suggest that the high tolerance of the Nip cultivar is related to the high ABA level and ABA-mediated antioxidant capacity in roots. ABA acts upstream of proline accumulation by regulating the expression of genes encoding the key enzymes in proline biosynthesis, which also partly improves rice acclimation to hypoxic stress. However, other signaling pathways enhancing tolerance to hypoxia in the Nip cultivar still need to be elucidated.
Concurrent cardiac sarcoidosis and obstructive sleep apnea presenting as arrhythmias
Authors: Malli Foteini , Bardaka Fotini , Gourgoulianis Konstantinos I. , Daniil Zoe
Published: May 2020

Background

Cardiac involvement is a rare and potentially fatal presentation of sarcoidosis. Obstructive sleep apnea may complicate sarcoidosis.

Case presentation

We report a case of a sarcoidosis patient with cardiac involvement presenting with ventricular arrhythmias. Besides medical and invasive measures of therapy, the patient failed to respond fully. The patient was subjected to overnight polysomnography and diagnosed with concurrent obstructive sleep apnea syndrome. Following continuous positive airway pressure therapy, we observed a significant improvement of ventricular arrhythmias while methylprednisolone was further tapered.

Conclusions

To our knowledge, this is the first report of cardiac sarcoidosis further implicated by OSAHS and presenting as ventricular arrhythmias that underlies the need for extensive testing in cardiac sarcoidosis in patients not responding to immunosuppressive therapy.
Definitions of unfavorable surgical outcomes and their risk factors based on disability score after spine surgery for lumbar spinal stenosis
Authors: Kim Gang-Un , Park Jiwon , Kim Ho-Joong , Shen Feng , Cho Jaewoo , Chang Bong-Soon , Lee Choon-Ki , Chun Heoung-Jae , Yeom Jin S.
Published: May 2020

Background

Risk factors for unfavorable surgical outcomes are dependent on the definitions of the unfavorable surgical outcomes. The aims of this study were to compare risk factors for each unfavorable surgical outcome according to two different definitions of “unfavorable” surgical outcomes after surgery for lumbar spinal stenosis (LSS) as well as compare the clinical course from the preoperative period to 3 years postoperatively between cases with favorable and unfavorable outcomes according to the two different definitions.

Methods

Overall, 295 patients who underwent spine surgery for LSS and a follow-up evaluation at 3 years postoperatively were enrolled and divided into favorable and unfavorable groups, based on two different definitions for unfavorable surgical outcomes, as evaluated at 12 months postoperatively: the patient-reported outcome (PRO) and minimal clinically important difference (MCID) methods. In the PRO method, patients with a postoperative Oswestry Disability Index (ODI) score > 22 were considered as having an “unfavorable” outcome, whereas in the MCID method, those with a postoperative ODI score that changed < 12.8 points from the preoperative value were classified as having an “unfavorable” outcome. As a primary outcome, risk factors for unfavorable surgical outcomes according to each definition were investigated at 12 months postoperatively.

Results

In the PRO method, female sex (P = 0.011; odds ratio (OR): 2.340), elementary school attainment (vs. university attainment; P = 0.035; OR: 2.875), and higher preoperative ODI score (P = 0.028; OR: 2.340) were associated with higher odds for an unfavorable surgical outcome. In the MCID method, a higher preoperative ODI score was associated with higher odds (P <  0.001; OR: 0.920) of a favorable surgical outcome. In the PRO method, the favorable outcome group demonstrated significantly lower visual analog scale for back and leg pain and lower ODI scores than the unfavorable outcome group at 3 years postoperatively, whereas in the MCID method, clinical outcomes were not different between the two groups at 3 years postoperatively.

Conclusion

A higher preoperative ODI score may be a risk factor for postoperative ODI > 22 after surgery for LSS. It may also be associated with higher odds for improvements in the ODI score of > 12.8.
Patient involvement in healthcare workers’ practices: how does it operate? A mixed-methods study in a French university hospital
Authors: Malloggi Lucie , Leclère Brice , Le Glatin Clément , Moret Leïla
Published: May 2020

Background

The present challenge for patient involvement is the improvement of healthcare efficiency through a deeper consideration of the patient experience. In hospitals, numerous interventions promoting patient involvement are informally implemented by healthcare workers (HCWs). The first aim of this study was to conduct an overview of hospital HCWs’ experiences of the involvement of patients or their representatives. This overview included the involvement of patients in the domains of healthcare provision and support for other patients, healthcare quality and safety improvement, training and research. The second aim was to describe the challenges and conditions for the development of participative interventions by HCWs.

Methods

We conducted a mixed-methods sequential study at Nantes University Hospital from September 2017 to May 2018. To achieve the first aim, we performed a descriptive analysis of quantitative data collected via a questionnaire survey of 1290 HCWs. To achieve the second aim, we conducted a thematic analysis of qualitative data collected via eight semi-structured interviews with HCWs who reported involving patients or their representatives (family and patient association members) in healthcare.

Results

Among the 213 survey participants (16.5%), 133 reported a total of 424 participative interventions, mostly in the domains of care quality and safety (37%) and care provision and support (29%). The analysis of the qualitative data evidenced three types of factors determining the implementation of such interventions: the profiles of patients and their representatives, the beliefs and attitudes of HCWs, and organisational factors. While leadership from patients and HCWs was a central element in the development of patient involvement interventions, organisations’ capacities to foster a sustainable partnership culture appeared to be the next challenge to promote the patient-as-partner model in health systems. Our results also highlighted numerous benefits of patient and representative involvement for patients and HCWs.

Conclusions

The numerous initiatives reported show that patients and patient representatives participate alongside HCWs in hospitals. It is essential to take into account the facilitating and hindering factors of patient involvement in hospital HCWs’ practices for the further development of current initiatives. Additional studies, especially from the point of view of patients, are needed to complement our findings.
MicroRNA-15a-5p serves as a potential biomarker and regulates the viability and apoptosis of hippocampus neuron in children with temporal lobe epilepsy
Authors: Li Na , Pan Jingmei , Liu Wei , Li Yuanyuan , Li Feng , Liu Min
Published: May 2020

Background

Temporal lobe epilepsy (TLE) is the most common type of epilepsy, usually starting in childhood. The dysregulation of microRNAs (miRNAs) has been identified in neurological disorders. The current study investigated the expression level and clinical significance of miR-15a-5p in TLE children, and explored its function in regulating cell behaviors of hippocampal neurons.

Methods

The expression level of miR-15a-5p was examined in the serum of 63 TLE children. Primary hippocampal cells were cultured in magnesium-free medium to mimic TLE condition in children. The effect of miR-15a-5p on the viability and apoptosis of hippocampus neuron was assessed using MTT or flow cytometric apoptosis assay.

Results

TLE children had significantly low expression of miR-15a-5p. MiR-15a-5p was of great value for the diagnosis of TLE in children, with high specificity and sensitivity. The expression level of miR-15a-5p was decreased significantly in hippocampal cells treated in the magnesium-free medium. Overexpression of miR-15a-5p attenuated TLE-induced reduction for cell viability, and reversed the cell apoptosis induced by TLE.

Conclusions

MiR-15a-5p is downregulated in children with TLE, and overexpression of miR-15a-5p promoted the viability and inhibited the apoptosis of hippocampal neuron. MiR-15a-5p may be a promising biomarker for the diagnosis of children TLE.
Correction to: Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response
Authors: Lee Joo Youn , Park Jin Kyun , Lee Eun Young , Lee Eun Bong , Song Yeong Wook
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Aromatic clusters in protein–protein and protein–drug complexes
Authors: Lanzarotti Esteban , Defelipe Lucas A. , Marti Marcelo A. , Turjanski Adrián G.
Published: May 2020

Aromatic rings are important residues for biological interactions and appear to a large extent as part of protein–drug and protein–protein interactions. They are relevant for both protein stability and molecular recognition processes due to their natural occurrence in aromatic aminoacids (Trp, Phe, Tyr and His) as well as in designed drugs since they are believed to contribute to optimizing both affinity and specificity of drug-like molecules. Despite the mentioned relevance, the impact of aromatic clusters on protein–protein and protein–drug complexes is still poorly characterized, especially in those that go beyond a dimer. In this work, we studied protein–drug and protein–protein complexes and systematically analyzed the presence and structure of their aromatic clusters. Our results show that aromatic clusters are highly prevalent in both protein–protein and protein–drug complexes, and suggest that protein–protein aromatic clusters have idealized interactions, probably because they were optimized by evolution, as compared to protein–drug clusters that were manually designed. Interestingly, the configuration, solvent accessibility and secondary structure of aromatic residues in protein–drug complexes shed light on the relation between these properties and compound affinity, allowing researchers to better design new molecules.
Role of apolipoprotein E epsilon 4 (APOE*ε4) as an independent risk factor for incident depression over a 12-year period in cognitively intact adults across the lifespan
Authors: Burns Richard Andrew , Andrews Shea , Cherbuin Nicolas , Anstey Kaarin Jane
Published: May 2020

Background

The apolipoprotein E ε4 allele (APOE*ε4) is indicated as a risk for Alzheimer's disease and other age-related diseases. The risk attributable toAPOE*ε4 for depression is less clear and may be because of confounding of the relationship between dementia and depression.

Aims

We examined the risk ofAPOE*ε4 for incident depression and depressive symptomology over a 12-year period across the adult lifespan.

Method

Participants were from the Personality and Total Health Through Life study, aged 20 to 24 (n= 1420), 40 to 44 (n= 1592) or 60–64 (n= 1768) at baseline, and interviewed every 4 years since 1999. Ethnicities other than White, those without genotyping and those with depression at baseline, or who reported strokes and scores on the Mini-Mental State Examination <27 at any observation, were excluded.

Results

Over the study period, there was no evidence thatAPOE*ε4+was a risk factor for depression, including any depression (odds ratio (OR) = 0.94, 95% CI 0.77–1.16,P= 0.573), major depression (OR = 0.96, 95% CI 0.60–1.53,P= 0.860), minor depression (OR = 0.94, 95% CI 0.67–1.30,P= 0.695) or depressive symptomology (incidence rate ratio (IRR) = 1.02, 95% CI 0.97–1.08,P= 0.451).APOE*ε4 was unrelated to incident depression. Findings were consistent for all age cohorts.

Conclusions

Among cognitively intact Australian adults who were free of depression at baseline, there was little evidence thatAPOE*ε4+carriers are at increased risk for depression over a 12-year period among those who are cognitively intact.
Interactive Exploration of Longitudinal Cancer Patient Histories Extracted From Clinical Text
Authors: Yuan Zhou , Finan Sean , Warner Jeremy , Savova Guergana , Hochheiser Harry
Published: May 2020

PURPOSE

Retrospective cancer research requires identification of patients matching both categorical and temporal inclusion criteria, often on the basis of factors exclusively available in clinical notes. Although natural language processing approaches for inferring higher-level concepts have shown promise for bringing structure to clinical texts, interpreting results is often challenging, involving the need to move between abstracted representations and constituent text elements. Our goal was to build interactive visual tools to support the process of interpreting rich representations of histories of patients with cancer.

METHODS

Qualitative inquiry into user tasks and goals, a structured data model, and an innovative natural language processing pipeline were used to guide design.

RESULTS

The resulting information visualization tool provides cohort- and patient-level views with linked interactions between components.

CONCLUSION

Interactive tools hold promise for facilitating the interpretation of patient summaries and identification of cohorts for retrospective research.