bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese students’ access to media information in Australia and France: a comparative perspective
Authors: Astarita Claudia , Patience Allan
Published: February 2020

The ongoing growth of China’s economy and the premium attached to quality education within its culture has seen students from China become one of the largest groups of international students enrolling in schools and institutes of higher education around the developed world. Given the rising numbers of these students in overseas higher education institutions, their experiences in their host countries deserve more nuanced research. Little is known about what sources of information they rely on; whether, as students coming from a country with non-transparent access to information, their views and media habits are challenged, transformed or consolidated during their overseas experience; and whether they consider overseas media as a trustworthy source to expand their knowledge on China or an instrument of Western propaganda. Drawing from research conducted in Melbourne in 2016/2017, this article explores why Chinese international students in an Australian university, despite the impact of their international experience, prefer Chinese media sources, especially when looking for information about China. This contrasts with Chinese students enrolled in a university in France. Where does the broad scepticism about the reliability of non-Chinese media in reporting Chinese news come from? What do students mean when they refer to an ‘alleged incapacity of foreign media to understand what is good for China?’ In our conclusion, we propose some possible ways to address the perceived biases and offer some ideas to foreign media on how to better engage Chinese international students’ communities.
Digital visibility and the role of mutual interaction expectations: Reframing the journalist–audience relationship through the lens of interpersonal communication
Authors: Wilhelm Claudia , Stehle Helena , Detel Hanne
Published: February 2020

In the light of a new level of reciprocal visibility in the digital age, the journalist–audience relationship has fundamentally changed. Mutual expectations become visible or evolve anew. The question arises as to how these expectations and their (non-)fulfillment influence the journalist–audience relationship. Taking an interpersonal communication perspective by following expectancy violations theory, we focus on the level of interactions and propose a theoretical framework explaining how the interplay of journalists’ and audience’s mutual expectations affects their relationship. Our aim is to contribute to a better understanding of the journalist–audience relationship in digital media environments—and to provide indications for its functioning or failure.
On the necessity of school punishment
Authors: Hand Michael
Published: February 2020

The question of the necessity of school punishment was raised, but not satisfactorily answered, in an exchange some time ago between John Wilson and James Marshall. Wilson argued that social interaction in schools must be governed by rules and that rules only exist if violations of them are normally punished. Marshall objected that there are some rules whose existence plainly does not depend on punishment of violations. Here I revisit and try to resolve the disagreement between Wilson and Marshall. I contend that, while it is not true of rules per se that they must be backed by punishment, there is an important subset of rules that do require this backing, and that subset includes at least some of the rules governing social interaction in schools.
Structural reforms and business ethos in universities under Estonia’s post-2008 austerity regime
Authors: Aidnik Martin
Published: February 2020

The year 2018 marked the 10th anniversary of the global economic crisis of 2008. In Europe, austerity has been a constant ever since the crisis. This article critically engages with recent institutional and ideological developments in the small Baltic state of Estonia. The article investigates the structural reforms and prevailing ideology in Estonian universities under conditions of the post-2008 economic crisis austerity regime. How has austerity impacted academia and what have been the responses to it? How has the university been approached in the context of post-crisis socio-economic challenges? Structural reforms and business ethos coupled with decreased public funding have been part and parcel of the European higher education landscape, from Greece to the British Isles. Expanding the research done on this subject, I explore these issues in the Estonian context with a particular focus on the political economy and institutional governance. I seek to show how Estonia’s consolidation politics in the field of higher education governance has led to a decline of the university as a public (sector) institution and limited the opportunities to undertake independent, critical research. I conclude with recent attempts to contest austerity in universities at a time of a conservative turn in Estonian politics.
Endovascular Treatment of Ischemic Stroke in a Developing Country
Authors: Marquez-Romero Juan Manuel , Góngora-Rivera Fernando , Hernández-Curiel Bernardo César , Aburto-Murrieta Yolanda , García-Cazares Ricardo , Delgado-Garzón Primo , Murillo-Bonilla Luis Manuel , Ochoa-Solórzano Marco Antonio
Published: February 2020

Background:

There is inequality in access to recent advancements in endovascular treatment of acute ischemic stroke (AIS), and Mexico is unusually sensitive to such inequality.

Aims:

To report the initial experience of the Mexican Endovascular Reperfusion Registry (MERR).

Methods:

The MERR is an academic, independent, prospective, multicenter, observational registry of patients treated with endovascular reperfusion techniques in Mexican hospitals. The registry includes information on demographic and clinical characteristics, diagnostic procedures, treatments, selected time metrics, and outcomes.

Results:

In all, 49 (57.1% female) patients from 8 centers were included and had the following characteristics: median National Institute of Health Stroke Scale score, 16; median Alberta Stroke Program Early CT Score score, 9; received intravenous tissue-type plasminogen activator, 49%; and treated with mechanical devices, 39 (79.6%), including 20 treated with stent retriever alone, 2 with retriever and intra-arterial thrombolysis (IAt), 10 with catheter aspiration (4 in combination with IAt), 6 with a combination of catheter aspiration and stent retriever, and 1 with IAt followed by balloon angioplasty. Recanalization (TICI 2b or better) was achieved in 69.4% of the patients. The median clot to recanalization time was 30 minutes. A modified Rankin scale ≤2 was achieved in 44.9% of the patients, and 68.2% of these were treated with stent retriever ( P = .011). Procedure-related morbidity was 12.2%, 7 patients presented intracerebral hemorrhage (71.4% asymptomatic), and all-cause mortality was 6.1%.

Conclusions:

Endovascular treatment of AIS in Mexico is feasible and has an efficacy comparable to that of other countries. Still, many challenges remain, especially pertaining to high costs and difficulties in equality in access to treatment.
School Nurses’ Role in Self-Management, Anticipatory Guidance, and Advocacy for Students With Chronic Illness
Authors: McCabe Ellen M.
Published: February 2020

This article offers tangible support for school nurses to understand, recognize, and integrate self-management promotion, anticipatory guidance, and advocacy into practice. The article utilizes the chronic condition of asthma as a case exemplar, but many of the recommendations apply to other aspects of chronic illness self-management promotion. School nurses are in an ideal position to advocate for students and families and to support evidence-based self-management promotion. In the school setting, gaps currently exist regarding best practices for the promotion of self-management and anticipatory guidance for children with chronic illnesses. Future interventions within school settings should focus on multisystem level collaboration with care coordination efforts between providers and social support systems, internal and external, to the school system. These policies and this resource development will ultimately support the promotion of self-management for children with chronic illness in the school environment and maximize health outcomes.
iCOPE, a multi-level, cluster randomized, 36-month, parallel-group study to assess the efficacy of HIV disclosure intervention in HIV parental disclosure among parents living with HIV in China
Authors: Li Xiaoming , Qiao Shan , Zhou Yuejiao
Published: February 2020

Objectives:

Parents living with HIV who disclose their HIV status to their children could benefit from the parental HIV disclosure. However, it is also very challenging because of persistent stigma and discrimination against HIV. This report describes the study design and protocol of the “Interactive Communication with Openness, Passion, and Empowerment (iCOPE)” randomized controlled trial aimed at assisting parents living with HIV in conducting culturally and developmentally appropriate disclosure to their uninfected children in China through trainings among both parents living with HIV and healthcare providers.

Methods:

A total of 791 parents living with HIV with children aged between 6 and 15 years and 357 healthcare providers were randomized into either the intervention group or control group. Intervention package for parents consisted of five 2-h sessions focusing on positive coping, disclosure decision making, developing a developmentally appropriate disclosure plan, and accessing social support and post-disclosure counseling. The intervention for healthcare providers was made up of two 45-min sessions organized around two primary themes: knowledge of child cognitive development and effective parent–child communication skills in the context of parental disclosure. The control group received nutritional education of either five 2-h sessions (parents) or two 45-min sessions (healthcare providers). The outcome assessments were conducted at baseline, 6, 12, 18, 24, 30, and 36 months.

Conclusion:

The iCOPE study is among the first efforts to develop and evaluate a theory-based and multi-level intervention to promote culturally and developmentally appropriate parental HIV disclosure in China. It has implications for healthcare providers, social workers, and policy makers as it will provide efficacy data on how to enhance appropriate parental HIV disclosure and will shed light on developing a clinical guideline regarding parental HIV disclosure in China and other low- and middle-income countries.
The Need for Cross-Cultural Communication Instruction in U.S. Business Communication Courses
Authors: Smallwood Margaret Garnett
Published: February 2020

U.S. undergraduate business communication (BCOM) classes teach students workplace communication fundamentals, but may not build the cross-cultural communication (CCC) skills that learners will need in today’s global workplace. This project surveyed BCOM instructors and students about the importance of including cross-cultural material in BCOM classes. While all instructors considered it at least moderately important to include CCC material, most covered the subject briefly. Students showed interest in receiving CCC training in their BCOM courses but received limited information about it in their classes. Incorporating CCC comprehensively and systematically into BCOM classrooms may help students become competent intercultural communicators.
Negotiating Quality and Productivity: An Experiential Exercise
Authors: Albright Robert R. , Finn Dale
Published: February 2020

This article presents an active experiential exercise that requires participants to negotiate over scarce resources while assigned separate managerial responsibilities. Students explore concepts associated with integrative and distributive bargaining while engaging in a realistic workplace role-play. Students form pairs and assume the role of either (1) a business line manager charged with product line production and profit/loss responsibilities or (2) a corporate finance manager who is tasked with achieving overarching corporate financial goals. Both face budgetary pressures and feel great responsibility for the achievement of their individual departmental goals. Participants must negotiate with each other to attempt to come to some resolution. Teaching notes are provided. The exercise is designed for undergraduate students and can readily be used in courses such as Organizational Behavior, Negotiations, and Leadership.
Statistical analysis of earthquake debris extent from wood-frame buildings and its use in road networks in Japan
Authors: Moya Luis , Mas Erick , Yamazaki Fumio , Liu Wen , Koshimura Shunichi
Published: February 2020

Debris scattering is one of the main causes of road/street blockage after earthquakes in dense urban areas. Therefore, the evaluation of debris scattering is crucial for decision makers and for producing an effective emergency response. In this vein, this article presents the following: (1) statistical data concerning the debris extent of collapsed buildings caused by the 2016 Mw 7.0 Kumamoto earthquake in Japan; (2) an investigation of the factors influencing the extent of debris; (3) probability functions for the debris extent; and (4) applications in the evaluation of road networks. To accomplish these tasks, LiDAR data and aerial photos acquired before and after the mainshock (16 April 2016) were used. This valuable dataset gives us the opportunity to accurately quantify the relationship between the debris extent and the geometrical properties of buildings.
Plasma Hsa-miR-92a-3p in correlation with lipocalin-2 is associated with sepsis-induced coagulopathy
Authors: Wang Yishan , Wang Huijuan , Zhang Chunfang , Zhang Chao , Yang Huqin , Gao Ruiyue , Tong Zhaohui
Published: February 2020

Background

Sepsis is a life-threatening situation, and it can be rendered more severe by coagulopathy. We here examine a novel plasma biomarker for sepsis-induced coagulopathy.

Methods

A total of 116 patients diagnosed with sepsis were recruited and divided into two groups by whether they also had coagulopathy. Plasma samples were collected on arrival at the intensive care unit. Fifteen sepsis-alone and 15 sepsis-induced coagulopathy plasma samples were mixed and sent for microRNA sequencing. Differently expressed microRNAs were then validated by quantitative reverse transcriptase polymerase chain reaction in 52 sepsis-alone and 34 sepsis-induced coagulopathy patients; plasma lipocalin-2 was measured as well.

Results

Four microRNAs were selected from microRNA sequencing. Only hsa-mir-92a-3p was differently expressed in the validation set. Its level of expression was significantly lower in sepsis-induced coagulopathy group. Hsa-mir-92a-3p had an area under a receiver operating characteristic curve of 0.660 (95% confidence interval, 0.537, 0.782). The plasma Hsa-mir-92a-3p level was related to activated partial thromboplastin time, prothrombin activity, and plasma lipocalin-2 level. A binary logistic model showed an association between hsa-mir-92a-3p and fibrinogen with SIC.

Conclusions

The utility of hsa-mir-92a-3p as a biomarker for sepsis-induced coagulopathy needs more verification, and the regulatory mechanism of hsa-mir-92a-3p in coagulation disorder and its potency as a therapeutic target must be confirmed.
Mucopolysaccharidosis type VI: case report with first neonatal presentation with ascites fetalis and rapidly progressive cardiac manifestation
Authors: Honjo Rachel Sayuri , Vaca Evelyn Cristina Nuñez , Leal Gabriela Nunes , Abellan Deipara Monteiro , Ikari Nana Miura , Jatene Marcelo Biscegli , Martins Ana Maria , Kim Chong Ae
Published: February 2020

Background

The Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome (OMIM 253200) is an autosomal recessive lysosomal disorder, caused by the deficiency of the enzyme N-acetylgalactosamine 4-sulfatase (also known as arylsulfatase B) due to mutations of the ARSB gene. Cardiologic features are well recognized, and are always present in MPS VI patients. Generally, the onset and the progression of the cardiologic symptoms are insidious, and just a few patients have developed a rapidly progressive disease. Cardiac involvement in MPS VI is a common and progressive feature. For MPS patients, cardiac evaluations are recommended every 1 to 2 years, including blood pressure measurement, electrocardiography and echocardiography. However, congestive heart failure and valvular surgical repair are not frequently seen, and if so, they are performed in adults. Here we report on an atypical MPS VI case with ascites fetalis and a rapidly progressive cardiac disease.

Case presentation

A 6-month-old Brazilian male, only child of a Brazilian healthy non-consanguineous couple. During pregnancy, second trimester ultrasonography observed fetal ascites and bilateral hydrocele. Physical exam at 6 months-old revealed a typical gibbus deformity and MPS was suspected. Biochemical investigation revealed a diagnosis of MPS type VI, confirmed by molecular test. Baseline echocardiogram revealed discrete tricuspid regurgitation and a thickened mitral valve with posterior leaflet prolapse, causing moderate to severe regurgitation. The patient evolved with mitral insufficiency and congestive heart failure, eventually requiring surgical repair by the first year of age.

Conclusions

We report the first case of MPS VI whose manifestations started in the prenatal period with fetal ascites, with severe cardiac valvular disease that eventually required early surgical repair. Moreover, in MPS with neonatal presentation, including fetal hydrops, besides MPS I, IVA and VII, clinicians should include MPS VI in the differential diagnosis.
Estimation of the adolescent pregnancy rate in Thailand 2008–2013: an application of capture-recapture method
Authors: Sukrat Bunyarit , Okascharoen Chusak , Rattanasiri Sasivimol , Aekplakorn Wichai , Arunakul Jiraporn , Saejeng Kittipong , Böhning Dankmar , Thakkinstian Ammarin
Published: February 2020

Background

Adolescent pregnancy is an important health and social issue that affects both individual and social well-being. However, deriving a national estimate is challenging in a country with multiple incomplete national databases especially the abortion statistics. The objective of this study was to estimate the adolescent pregnancy rates in Thailand using capture-recapture method.

Methods

An application of capture-recapture method was conducted using two cross-sectional databases (i.e., the national birth registration and the Ministry of Public Health standard health databases) and one hospital-based data source from medical record reviews. A 3-sources capture-recapture with log-linear model was applied to estimate adolescent pregnancy rates.

Results

A total number of 741,084, 290,922 and 25,478 records were respectively identified from the birth registrations, standard health databases and hospital-based survey data during 2008 to 2013. The estimated adolescent pregnancy rates /1000 adolescent women (95% confidence intervals (CI)) ranged from 56.3 (49.4, 66.9) to 70.3 (60.3, 76.6). The estimated rates were about 12–31% higher than adolescent birth rates reported by the Thailand Public Health Statistics.

Conclusions

With the capture-recapture method, more accurate adolescent pregnancy rates were estimated. This method should be able to apply to any setting with similar context.
Spinal epidural hematoma without significant trauma in children: two case reports and review of the literature
Authors: Carlhan-Ledermann Audrey , Laubscher Bernard , Steinlin Maja , Ulrich Christian T. , Verma Rajeev Kumar , Rizzi Mattia , Maduri Rodolfo , Grunt Sebastian
Published: February 2020

Background

Spinal epidural hematoma without significant trauma is a rare condition with potentially severe outcome. This case report and systematic review of the literature illustrates the clinical presentation, risk factors, evaluation, treatment and outcomes of spinal epidural hematoma without significant trauma in children.

Case presentation

We report one case of a 7-year-old girl who developed a neck pain after minor cervical sprain. MRI showed a right posterior epidural hematoma extending from C2/3 to T1. The hematoma was surgically evacuated, and the histopathology showed an arteriovenous malformation. Postoperative MRI showed complete evacuation of the hematoma and no residual vascular malformation. We report a second ASE with idiopathic spinal epidural hematoma of a 4½-year-old boy presenting with neck pain. MRI showed a right-sided latero-posterior subacute spinal epidural hematoma at C3–C5. Owing to the absence of any neurological deficit, the patient was treated conservatively. MRI at 3 months showed complete resolution of the hematoma.

Conclusions

Spinal epidural hematoma without significant trauma in children is a rare condition. It may present with unspecific symptoms. Screening for bleeding diathesis is warranted and neuroradiologic follow-up is essential to rule out vascular malformation. Whereas most children have a favorable outcome, some do not recover, and neurological follow-up is required.
Exploring factors of diagnostic delay for patients with bipolar disorder: a population-based cohort study
Authors: Lublóy Ágnes , Keresztúri Judit Lilla , Németh Attila , Mihalicza Péter
Published: February 2020

Background

Bipolar disorder if untreated, has severe consequences: severe role impairment, higher health care costs, mortality and morbidity. Although effective treatment is available, the delay in diagnosis might be as long as 10–15 years. In this study, we aim at documenting the length of the diagnostic delay in Hungary and identifying factors associated with it.

Methods

Kaplan-Meier survival analysis and Cox proportional hazards model was employed to examine factors associated with the time to diagnosis of bipolar disorder measured from the date of the first presentation to any specialist mental healthcare institution. We investigated three types of factors associated with delays to diagnosis: demographic characteristics, clinical predictors and patient pathways (temporal sequence of key clinical milestones). Administrative data were retrieved from specialist care; the population-based cohort includes 8935 patients from Hungary.

Results

In the sample, diagnostic delay was 6.46 years on average. The mean age of patients at the time of the first bipolar diagnosis was 43.59 years. 11.85% of patients were diagnosed with bipolar disorder without any delay, and slightly more than one-third of the patients (35.10%) were never hospitalized with mental health problems. 88.80% of the patients contacted psychiatric care for the first time in outpatient settings, while 11% in inpatient care. Diagnostic delay was shorter, if patients were diagnosed with bipolar disorder by non-specialist mental health professionals before. In contrast, diagnoses of many psychiatric disorders received after the first contact were coupled with a delayed bipolar diagnosis. We found empirical evidence that in both outpatient and inpatient care prior diagnoses of schizophrenia, unipolar depression without psychotic symptoms, and several disorders of adult personality were associated with increased diagnostic delay. Patient pathways played an important role as well: the hazard of delayed diagnosis increased if patients consulted mental healthcare specialists in outpatient care first or they were hospitalized.

Conclusions

We systematically described and analysed the diagnosis of bipolar patients in Hungary controlling for possible confounders. Our focus was more on clinical variables as opposed to factors controllable by policy-makers. To formulate policy-relevant recommendations, a more detailed analysis of care pathways and continuity is needed.
The association of delta neutrophil index with the prognosis of acute exacerbation of chronic obstructive pulmonary disease
Authors: Park Sunmin , Lee Sang Jun , Shin Beomsu , Lee Seok Jeong , Kim Sang-Ha , Kwon Woo Cheol , Kim Jihye , Lee Myoung Kyu
Published: February 2020

Background

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is associated with infective triggers including bacterial or viral in many cases, and pneumonia is a major contributor to hospitalization for AECOPD and has a close relationship with poor outcomes. Increased delta neutrophil index (DNI) can be useful in the detection of COPD patients with pneumonia.

Methods

A retrospective cohort study was performed to investigate the mortality rate of the patients who were re-admitted within 6 months after discharge from the hospital due to AECOPD with or without CAP. We analyzed the difference of cumulative survival rate according to serum DNI level and readmission duration.

Results

Finally, 140 AECOPD patients with community-acquired pneumonia (CAP) and 174 AECOPD patients without CAP were enrolled during 6 months, respectively. The mean age was 72.2 ± 9.4 year-old, and 240 patients (76.4%) were male. When comparing the cumulative survival rate according to readmission duration (≤ 30 vs >  30 days) and DNI level (< 3.5 vs ≥ 3.5%), AECOPD patients with readmission ≤30 days and DNI ≥ 3.5% showed the lowest cumulative survival rate compared to other groups (P <  0.001). Multivariate analysis revealed readmission duration ≤30 days (HR 7.879, 95% CI 4.554–13.632, P <  0.001); and serum DNI level (HR 1.086, 95% CI 1.043–1.131, P <  0.001) were significantly associated with the mortality of AECOPD patients during 6 months. The area under the curve for readmission (≤ 30 days) + DNI level (≥ 3.5%) was 0.753 (95% CI 0.676–0.830, P <  0.001) with a sensitivity of 73.7% and a specificity of 67.3%.

Conclusion

AECOPD patients who were readmitted ≤30 days and DNI ≥ 3.5% showed higher mortality. DNI level can be used as a predictor of prognosis in AECOPD patients who were readmitted after discharge.
Polyphyllin VII attenuated RANKL-induced osteoclast differentiation via inhibiting of TRAF6/c-Src/PI3K pathway and ROS production
Authors: Zhou Long , Song Hanyi , Zhang Yiqi , Ren Zhaozhou , Li Minghe , Fu Qin
Published: February 2020

Background

Osteoporosis is a worldwide severe bone disease. This study aimed to evaluate the effect of polyphyllin VII on the genesis of osteoclasts from bone marrow macrophages (BMMs) and its potentiality as a therapeutic drug for osteoporosis.

Methods

BMMs were induced to differentiate into osteoclasts by RANKL and M-CSF. The cells were then treated with various concentrations of polyphyllin VII. Intracellular reactive oxygen species (ROS) measurement assay, resorption pit formation assay, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity assessment, cell viability assay, active GTPase pull-down assay, immunofluorescent staining, immunoblotting, and RT-PCR were performed.

Results

RANKL + M-CSF significantly increased TRAP activity, number of osteoclasts, number and area of lacunae, intracellular content of ROS, protein levels of Nox1, TRAF6, c-Src and p-PI3K, as well as the content of activated GTP-Rac1, which were significantly blocked by polyphyllin VII in a concentration-dependent manner.

Conclusion

These findings suggested that polyphyllin VII inhibited differentiation of BMMs into osteoclasts through suppressing ROS synthesis, which was modulated by TRAF6–cSrc–PI3k signal transduction pathway including GTP-Rac1 and Nox1. Polyphyllin VII could be a therapeutic drug for osteoporosis.
Different effects of Wnt/β-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing
Authors: Liu Daocheng , Qin Hao , Yang Jiazhi , Yang Lei , He Sihao , Chen Sixu , Bao Quanwei , Zhao Yufeng , Zong Zhaowen
Published: February 2020

Background

Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/β-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years. The study is to observe whether there is a difference in adult and aged situations by activating two signal paths.

Methods

A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnblox(ex3) mice and wild-type mice. The fracture healing effects of CA (Wnt/β-catenin activation) and PTH (activated by PTH (1–34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of β-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase).

Result

Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice.

Conclusion

The application of Wnt/β-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.
Promotion of compound K production in Saccharomyces cerevisiae by glycerol
Authors: Nan Weihua , Zhao Fanglong , Zhang Chuanbo , Ju Haiyan , Lu Wenyu
Published: February 2020

Background

Ginsenoside compound K (CK), one of the primary active metabolites of protopanaxadiol-type ginsenosides, is produced by the intestinal flora that degrade ginseng saponins and exhibits diverse biological properties such as anticancer, anti-inflammatory, and anti-allergic properties. However, it is less abundant in plants. Therefore, enabling its commercialization by construction of a Saccharomyces cerevisiae cell factory is of considerable significance.

Results

We induced overexpression of PGM2, UGP1, and UGT1 genes in WLT-MVA5, and obtained a strain that produces ginsenoside CK. The production of CK at 96 h was 263.94 ± 2.36 mg/L, and the conversion rate from protopanaxadiol (PPD) to ginsenoside CK was 64.23 ± 0.41%. Additionally, it was observed that the addition of glycerol was beneficial to the synthesis of CK. When 20% glucose (C mol) in the YPD medium was replaced by the same C mol glycerol, CK production increased to 384.52 ± 15.23 mg/L, which was 45.68% higher than that in YPD medium, and the PPD conversion rate increased to 77.37 ± 3.37% as well. As we previously observed that ethanol is beneficial to the production of PPD, ethanol and glycerol were fed simultaneously in the 5-L bioreactor fed fermentation, and the CK levels reached 1.70 ± 0.16 g/L.

Conclusions

In this study, we constructed an S. cerevisiae cell factory that efficiently produced ginsenoside CK. Glycerol effectively increased the glycosylation efficiency of PPD to ginsenoside CK, guiding higher carbon flow to the synthesis of ginsenosides and effectively improving CK production. CK production attained in a 5-L bioreactor was 1.7 g/L after simultaneous feeding of glycerol and ethanol.
Transcranial direct-current stimulation combined with attention increases cortical excitability and improves motor learning in healthy volunteers
Authors: Yamaguchi Tomofumi , Moriya Kouhei , Tanabe Shigeo , Kondo Kunitsugu , Otaka Yohei , Tanaka Satoshi
Published: February 2020

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has the potential to induce motor cortical plasticity in humans. It is well known that motor cortical plasticity plays an essential role in motor learning and recovery in patients with stroke and neurodegenerative disorders. However, it remains unclear how cognitive function influences motor cortical plasticity induced by tDCS. The present study aimed to investigate whether anodal tDCS combined with attention to a target muscle could enhance motor cortical plasticity and improve motor learning in healthy individuals.

Methods

Thirty-three healthy volunteers were assigned to two experiments. In experiment 1, there were three interventional conditions: 1) anodal tDCS was applied while participants paid attention to the first dorsal interosseous (FDI) muscle, 2) anodal tDCS was applied while participants paid attention to the sound, and 3) anodal tDCS was applied without the participants paying attention to the FDI muscle or the sound. Anodal tDCS (2 mA, 10 min) was applied over the primary motor cortex (M1). Changes in motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were assessed before and immediately after (0 min), and then 10 min, 30 min, and 60 min after each intervention. In experiment 2, we investigated whether the combination of anodal tDCS and attention to the abductor pollicis brevis (APB) muscle could facilitate the learning of a ballistic thumb movement.

Results

Anodal tDCS increased cortical excitability in all conditions immediately after the stimulation. Significant increases in MEPs and significant decreases in SICI were observed for at least 60 min after anodal tDCS, but only when participants paid attention to the FDI muscle. In contrast, no significant changes in ICF were observed in any condition. In experiment 2, the combination of tDCS and attention to the APB muscle significantly enhanced the acquisition of a ballistic thumb movement. The higher performance was still observed 7 days after the stimulation.

Conclusions

This study shows that anodal tDCS over M1 in conjunction with attention to the target muscle enhances motor cortex plasticity and improves motor learning in healthy adults. These findings suggest that a combination of attention and tDCS may be an effective strategy to promote rehabilitation training in patients with stroke and neurodegenerative disorders.

Trial registration

Retrospectively registered (UMIN000036848).
Parkinson’s disease-related Leucine-rich repeat kinase 2 modulates nuclear morphology and genomic stability in striatal projection neurons during aging
Authors: Chen Xi , Xie Chengsong , Tian Wotu , Sun Lixin , Zheng Wang , Hawes Sarah , Chang Lisa , Kung Justin , Ding Jinhui , Chen Shengdi , Le Weidong , Cai Huaibin
Published: February 2020

Background

Multiple missense mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with familial forms of late onset Parkinson’s disease (PD), the most common age-related movement disorder. The dysfunction of dopamine transmission contributes to PD-related motor symptoms. Interestingly, LRRK2 is more abundant in the dopaminoceptive striatal spiny projection neurons (SPNs) compared to the dopamine-producing nigrostriatal dopaminergic neurons. Aging is the most important risk factor for PD and other neurodegenerative diseases. However, whether LRRK2 modulates the aging of SPNs remains to be determined.

Methods

We conducted RNA-sequencing (RNA-seq) analyses of striatal tissues isolated from Lrrk2 knockout (Lrrk2−/−) and control (Lrrk2+/+) mice at 2 and 12 months of age. We examined SPN nuclear DNA damage and epigenetic modifications; SPN nuclear, cell body and dendritic morphology; and the locomotion and motor skill learning of Lrrk2+/+ and Lrrk2−/− mice from 2 to 24 months of age. Considering the strength of cell cultures for future mechanistic studies, we also performed preliminary studies in primary cultured SPNs derived from the Lrrk2+/+ and Lrrk2−/− mice as well as the PD-related Lrrk2 G2019S and R1441C mutant mice.

Results

Lrrk2-deficiency accelerated nuclear hypertrophy and induced dendritic atrophy, soma hypertrophy and nuclear invagination in SPNs during aging. Additionally, increased nuclear DNA damage and abnormal histone methylations were also observed in aged Lrrk2−/− striatal neurons, together with alterations of molecular pathways involved in regulating neuronal excitability, genome stability and protein homeostasis. Furthermore, both the PD-related Lrrk2 G2019S mutant and LRRK2 kinase inhibitors caused nuclear hypertrophy, while the Lrrk2 R1441C mutant and γ-Aminobutyric acid type A receptor (GABA-AR) inhibitors promoted nuclear invagination in the cultured SPNs. On the other hand, inhibition of neuron excitability prevented the formation of nuclear invagination in the cultured Lrrk2−/− and R1441C SPNs.

Conclusions

Our findings support an important physiological function of LRRK2 in maintaining nuclear structure integrity and genomic stability during the normal aging process, suggesting that PD-related LRRK2 mutations may cause the deterioration of neuronal structures through accelerating the aging process.
Towards a European health research and innovation cloud (HRIC)
Authors: Aarestrup F. M. , Albeyatti A. , Armitage W. J. , Auffray C. , Augello L. , Balling R. , Benhabiles N. , Bertolini G. , Bjaalie J. G. , Black M. , Blomberg N. , Bogaert P. , Bubak M. , Claerhout B. , Clarke L. , De Meulder B. , D’Errico G. , Di Meglio A. , Forgo N. , Gans-Combe C. , Gray A. E. , Gut I. , Gyllenberg A. , Hemmrich-Stanisak G. , Hjorth L. , Ioannidis Y. , Jarmalaite S. , Kel A. , Kherif F. , Korbel J. O. , Larue C. , Laszlo M. , Maas A. , Magalhaes L. , Manneh-Vangramberen I. , Morley-Fletcher E. , Ohmann C. , Oksvold P. , Oxtoby N. P. , Perseil I. , Pezoulas V. , Riess O. , Riper H. , Roca J. , Rosenstiel P. , Sabatier P. , Sanz F. , Tayeb M. , Thomassen G. , Van Bussel J. , Van den Bulcke M. , Van Oyen H.
Published: February 2020

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.
Unusual recurrent metastasizing benign breast papilloma: a case report
Authors: Jain Amit L. , Mullins Janice , Smith Justin R. , Valasareddy Poojitha , Miller Emily , Chaudhry Amina , Ryder Julie , Hare Felicia , Ranganath Harsha , Berry Michael , Robins David , Schwartzberg Lee , Vidal Gregory A.
Published: February 2020

Background

Papillary breast lesions may be benign, atypical, and malignant lesions. Pathological and clinical differentiation of breast papillomas can be a challenge. Unlike malignant lesions, benign breast papillomas are not classically associated with lymph node and distant metastasis. We report a unique case of a recurrent, benign breast papilloma presenting as an aggressive malignant tumor.

Case presentation

Our patient was a 56-year-old postmenopausal African American woman who was followed in the breast clinic with a long history of multiple breast papillomas. She underwent multiple resections over the course of 7–9 years. After being lost to follow-up for 2 years, she once again presented with a slowly enlarging left breast mass. Subsequent imaging revealed a predominantly cystic mass in the left breast, as well as a suspicious hypermetabolic internal mammary node and a hypermetabolic nodule in the pretracheal space. Biopsy of the internal mammary node demonstrated papillary neoplasm with benign morphology and immunostains positive for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/Neu. Due to the clinical picture concerning for malignancy, the patient was then started on endocrine therapy with palbociclib and letrozole before surgery. She then underwent simple mastectomy and sentinel lymph node dissection with negative nodes and pathology once again revealing benign papillary neoplasm. She underwent adjuvant chest wall radiation for 6 weeks and received letrozole following completion of her radiation therapy. She was without evidence of disease 30 months after surgery.

Conclusions

We present an unusual case of multiple recurrent peripheral papillomas with entirely benign histologic features exhibiting malignant behavior over a protracted period of many years, with an invasion of pectoralis musculature and possibly internal mammary and mediastinal nodes. Her treatment course included multiple surgeries (ultimately mastectomy), radiation therapy, and endocrine therapy.
An SGBM-XVA demonstrator: a scalable Python tool for pricing XVA
Authors: Chau Ki Wai , Tang Jok , Oosterlee Cornelis W.
Published: February 2020

In this work, we developed a Python demonstrator for pricing total valuation adjustment (XVA) based on the stochastic grid bundling method (SGBM). XVA is an advanced risk management concept which became relevant after the recent financial crisis. This work is a follow-up work on Chau and Oosterlee in (Int J Comput Math 96(11):2272–2301, 2019), in which we extended SGBM to numerically solving backward stochastic differential equations (BSDEs). The motivation for this work is basically two-fold. On the application side, by focusing on a particular financial application of BSDEs, we can show the potential of using SGBM on a real-world risk management problem. On the implementation side, we explore the potential of developing a simple yet highly efficient code with SGBM by incorporating CUDA Python into our program.
Multiple transmit antennas for low PAPR spatial modulation in SC-FDMA: single vs. multiple streams
Authors: Sinanović Darko , Šišul Gordan , Kurdija Adrian Satja , Ilić Željko
Published: February 2020

The main reason for the selection of single-carrier frequency division multiple access (SC-FDMA) modulation technique in mobile high data rate communications lays in its low value of peak-to-average power ratio (PAPR). If spatial modulation, a multiple-input multiple-output technique that achieves bitrate increase, is applied to the SC-FDMA system in its conventional form, the PAPR level is increased. Hence, based on previously mentioned, in this paper, we provide the general design criteria for low PAPR spatial modulation (LPSM) implemented in SC-FDMA systems with multiple transmit antennas. The straightforward generalization of LPSM is derived and it is shown that it requires the number of transmit antennas to be doubled in order to add another bit in the spatial component. Based on that, the alternative generalized technique with higher number of spatial bits is proposed. As these techniques present single-stream generalizations, the approach with multiple-streams is proposed as well. After PAPR and performance comparisons, it is concluded that single-stream techniques outperform multiple-stream techniques in the cases of low overall data rate, whereas multiple-stream approach is better in high overall data rate scenarios. All proposed techniques maintain low PAPR level on all transmit antennas.
Social innovation in diagnostics: three case studies
Authors: Srinivas Megan L. , Yang Eileen J. , Shrestha Priyanka , Wu Dan , Peeling Rosanna W. , Tucker Joseph D.
Published: February 2020

Background

Diagnostics are essential for identifying and controlling diseases. However, limited access to diagnostics hinders public health efforts in many settings. Social innovation may provide a framework for expanding access to diagnostics in the global south. Here social innovation is defined as implementing a known public health tool via a novel, community-driven technique.

Main Body

In this article, we discuss three diverse cases that show the potential for using social innovation in diagnostics. The cases chosen for inclusion here demonstrate the importance of social innovation in diagnostics across different geographic, cultural, and health system contexts. They include malaria testing via schools in Malawi, cervical human papillomavirus (HPV) sample self-collection in Peru, and crowdsourcing human immunodeficiency virus (HIV) testing in China. For each case, we present the public health problem and the impact of using social innovation to increase accessibility of diagnostics. We discuss implications of each diagnostic approach and the importance of social innovation in creating these potential solutions. We argue that social innovation is useful in improving the delivery of essential diagnostic tools in low- and middle-income countries.

Conclusions

Interventions in Malawi, Peru, and China suggest social innovation increases uptake of diagnostics. The same tools and principles utilized in these cases can be adapted for use in other contexts. Such diagnostic innovations may help improve identification of and linkage to care for many diseases. The approach presents a unique opportunity to better address public health issues and increase accessibility in LMIC health systems.
Particle interspacing effects on the mechanical behavior of a Fe–TiB2 metal matrix composite using FFT-based mesoscopic field dislocation mechanics
Authors: Genée J. , Berbenni S. , Gey N. , Lebensohn R. A. , Bonnet F.
Published: February 2020

This paper presents an application to metal matrix composites (MMCs) of an enhanced elasto-viscoplastic Fast Fourier Transform (EVP-FFT) formulation coupled with a phenomenological continuum Mesoscale Field Dislocation Mechanics (MFDM) theory. Contrary to conventional crystal plasticity, which only accounts for plastic flow and hardening induced by statistically stored dislocations (SSDs), MFDM-EVP-FFT also describes the evolution of polarized geometrically necessary dislocation (GND) density and its effect on both plastic flow and hardening. Numerical results for a Fe–TiB2MMC made of a ferrite matrix (α-Fe) and elastic ceramic particles (TiB2) are presented. Full-field simulations are performed using synthetic periodic unit cells representative of the MMC, with single-crystalline and polycrystalline matrix, for different particle interspacing distances. A strong dependence of the predicted equivalent stress, cumulated plastic strain and GND density fields with particle interspacing distance is observed, in contrast with conventional crystal plasticity. Correlations between these mechanical fields and microstructural features, and their influence on local and global mechanical behavior are examined for the different MMC microstructures.
Limit behaviour of the minimal solution of a BSDE with singular terminal condition in the non Markovian setting
Authors: Marushkevych Dmytro , Popier Alexandre
Published: February 2020

We use the functional Itô calculus to prove that the solution of a BSDE with singular terminal condition verifies at the terminal time: $\liminf _{t\to T} Y(t) = \xi = Y(T)$liminft→TY(t)=ξ=Y(T). Hence, we extend known results for a non-Markovian terminal condition.