bluuebunny/crossref_metadata_2025 huggingface dataset:
Breaking time control of back-to-back double E-type alternating current contactor
Authors: Qi Lei , Zong Ming , Hao Shuyi , Wang Xuejie
Published: June 2020

The arc generated by breaking the main circuit exacerbates the ablation of the contact, which affects the life of the contactor seriously. By controlling the breaking time of the contactor and making contact break in the optimum time zone are the effective ways to weaken the arc. In this article, the contact movement characteristic is concerned directly in order to control the contact breaking time. A back-to-back double-E alternating current contactor is proposed, and its structural parameters are optimized by particle swarm optimization algorithm. The mathematical model of circuit and magnetic is established. A closed-loop control system based on velocity feedback is proposed. The simulation results show that the designed contactor and the proposed control method are correct, and the actual velocity curve of the contact is consistent with the planned motion curve. It can realize zero-crossing breaking of the main circuit to achieve the effect of no-arc breaking.
A virtual prototype for performance analysis of electropneumatic brake on metro trains
Authors: Zuo Jianyong , Ding Jingxian , Liu Cheng , Luo Zhuojun
Published: June 2020

In order to facilitate system design and performance analysis, a virtual prototype for metro train electropneumatic brakes is proposed. A virtual braking environment that consists of a three-car train model and six electropneumatic brakes model is elaborated. The virtual braking environment can be used to research the relation between braking response and electropneumatic brake’s parameters and to simulate axle loading transfer. By comparing the simulation results with bench test data, the electropneumatic brake model is proven to be quite accurate. Based on the proposed virtual prototype, a test train brake is designed, and a couple of field tests are carried out. The average deceleration of electropneumatic compound service brake at the initial speed of 45 km/h is 0.83 m/s2, the braking distance is 94 m, and that of pure air service brake at the speed of 43 km/h is 0.64 m/s2, the braking distance is 111 m. The field test results satisfy the test train requirements, which further proves the effectiveness of the proposed virtual prototype.
SI engine performance, lubricant oil deterioration, and emission: A comparison of liquid and gaseous fuel
Authors: Usman Muhammad , Saleem Muhammad Wajid , Saqib Syed , Umer Jamal , Naveed Ahmad , Hassan Zain Ul
Published: June 2020

Considering the importance of alternative fuels in IC engines for environment safety, compressed natural gas has been extensively employed in SI engines. However, scarce efforts have been made to investigate the effect of compressed natural gas on engine lubricant oil for a long duration. In this regard, a comprehensive analysis has been made on the engine performance, emissions, and lubricant oil conditions using gasoline ( G)92 and compressed natural gas at different operating conditions using reliable sampling methods. The key parameters of the engine performance like brake power and brake-specific energy consumption were investigated at 80% throttle opening within 1500–4500 range of r/min. For the sake of emission tests, speed was varied uniformly by varying the load at a constant throttle. Furthermore, the engine was run at high and low loads for lubricant oil comparison. Although compressed natural gas showed a decrease in brake-specific energy consumption (7.94%) and emissions content, ( G)92 performed relatively better in the case of brake power (39.93% increase). Moreover, a significant improvement was observed for wear debris, lubricant oil physiochemical characteristics, and additives depletion in the case of compressed natural gas than those of ( G)92. The contents of metallic particles were decreased by 23.58%, 36.25%, 42.42%, and 66.67% for iron, aluminum, copper, and lead, respectively, for compressed natural gas.
Additive manufacturing of Ti-alloy: Thermal analysis and assessment of properties
Authors: Keles Omer , Shuja SZ , Yilbas Bekir Sami , Al-Qahtani H , Hassan G , Adesina AY , Rinaldi Ali , Khaled M , Al-Sharafi Abdullah
Published: June 2020

In this study, 3D printing of Ti6Al4V alloy is realized and the characteristics of the printed layer are examined. The morphological structures and metallurgical changes in the printed layer are assessed. Temperature and stress fields are simulated in line with the experimental conditions. Since the air gaps are present in between the loose alloy powders prior to the printing, the effective properties incorporating the air fraction are determined and the effective properties are used in the simulations. Thermal conductivity of the loose alloy powders with the presence of air gaps is determined by incorporating the virtual experimental technique. It is found that the printed layer is free from micro-cracks and large scale asperities; however, some small pores sites are observed because of the release of air around the loose powders during the printing. Microhardness of the printed surface is higher in the top surface of the printed layer than that of as-received solid alloy. In addition, the friction coefficient of the printed surface remains lower than that of the conventionally produced solid surface. The columnar structures are formed in the mid-section of the printed layer and slanted grains are developed in the region of the top and the bottom surface of the printed layer.
How Do Scientific Views Change? Notes From an Extended Adversarial Collaboration
Authors: Cowan Nelson , Belletier Clément , Doherty Jason M. , Jaroslawska Agnieszka J. , Rhodes Stephen , Forsberg Alicia , Naveh-Benjamin Moshe , Barrouillet Pierre , Camos Valérie , Logie Robert H.
Published: June 2020

There are few examples of an extended adversarial collaboration, in which investigators committed to different theoretical views collaborate to test opposing predictions. Whereas previous adversarial collaborations have produced single research articles, here, we share our experience in programmatic, extended adversarial collaboration involving three laboratories in different countries with different theoretical views regarding working memory, the limited information retained in mind, serving ongoing thought and action. We have focused on short-term memory retention of items (letters) during a distracting task (arithmetic), and effects of aging on these tasks. Over several years, we have conducted and published joint research with preregistered predictions, methods, and analysis plans, with replication of each study across two laboratories concurrently. We argue that, although an adversarial collaboration will not usually induce senior researchers to abandon favored theoretical views and adopt opposing views, it will necessitate varieties of their views that are more similar to one another, in that they must account for a growing, common corpus of evidence. This approach promotes understanding of others’ views and presents to the field research findings accepted as valid by researchers with opposing interpretations. We illustrate this process with our own research experiences and make recommendations applicable to diverse scientific areas.
Absolute pitch learning in adults speaking non-tonal languages
Authors: Wong Yetta Kwailing , Ngan Vince SH , Cheung Leo YT , Wong Alan C-N
Published: June 2020

Absolute pitch (AP) refers to labelling individual pitches in the absence of external reference. A widely endorsed theory regards AP as a privileged ability enjoyed by selected few with rare genetic makeup and musical training starting in early childhood. However, recent evidence showed that even adults can learn AP, and some can attain a performance level comparable to natural AP possessors. These training studies involved native tonal language speakers, whose acquisition of AP might be facilitated by tonal language exposure during early childhood. In this study, adults speaking non-tonal languages went through AP training that was 20-hr long, computerised and personalised. Performance on average improved, which was accompanied by enhanced working memory for tones, whereas relative pitch judgement and sensitivity to small pitch differences remained unchanged. Notably, two out of 13 learned to label all 12 pitches within an octave, with accuracy and response time comparable to natural AP possessors. Overall, the findings suggest that tonal language exposure is not a prerequisite for AP learning in adulthood. The understanding of the origin of AP would benefit from considering the role of lifelong learning instead of focusing only on early childhood experience.
Diagramming the uncertainties of COVID-19: Scales, spatialities, and aesthetics
Authors: Barry Kaya
Published: June 2020

Diagrams of COVID-19 inform individuals how to enact specific spatial, mobile, and bodily practices. This commentary employs a non-representational lens to show how certain aesthetics used in diagramming the virus may accentuate existing public feelings of uncertainty, emergency, or threat.
Meaningful life in the time of Corona-economics
Authors: Tyner James , Rice Stian
Published: June 2020

The COVID-19 pandemic offers an opportunity to think more deeply about who and what we value in society, with value determined not on conditions set by capital but instead on achieving meaning in life. In this commentary, we pose a series of interconnected questions to geography: What does it mean to live a meaningful life? Furthermore, is such a life possible under capitalism? And what does a society that prioritizes meaningful life look like?
In the eye of the storm: the right ventricle in COVID‐19
Authors: Park John F. , Banerjee Somanshu , Umar Soban
Published: June 2020

The corona virus disease of 2019 pandemic caused by the SARS‐CoV‐2 virus continues to inflict significant morbidity and mortality around the globe. A variety of cardiovascular presentations of SARS‐CoV‐2 infection have been described so far. However, the impact of SARS‐CoV‐2 on the right ventricle is largely unknown. Due to its pathophysiologic relevance, the right ventricle finds itself in the eye of the storm of corona virus disease of 2019, placing it at higher risk of failure. Increased afterload from acute respiratory distress syndrome and pulmonary embolism, negative inotropic effects of cytokines, and direct angiotensin converting enzyme 2‐mediated cardiac injury from SARS‐CoV‐2 are potential mechanisms of right ventricle dysfunction in corona virus disease of 2019. Early detection and treatment of right ventricle dysfunction may lead to decreased mortality and improved patient outcomes in corona virus disease of 2019.
Incident pulmonary arterial hypertension associated with Bosutinib
Authors: Yo Shaun , Thenganatt John , Lipton Jeffrey , Granton John
Published: June 2020

Pulmonary arterial hypertension is associated with tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia. Dasatinib is a known cause of drug‐induced pulmonary arterial hypertension. There have been case reports linking Bosutinib with deterioration of pre‐existing pulmonary arterial hypertension. Here, we present a case of a 37‐year‐old woman with chronic myeloid leukemia treated with Bosutinib who was diagnosed with pulmonary arterial hypertension. Prior to Bosutinib, she had received Dasatinib without documented cardiopulmonary toxicity. Withdrawal of Bosutinib led to partial reversal of pulmonary arterial hypertension, and with the addition of pulmonary arterial hypertension‐targeted treatment, there was near normalization of hemodynamics.
An assessment of personal financial literacy teaching and learning in Ontario high schools
Authors: Matheson Murdoch N , DeLuca Christopher , Matheson Ian A
Published: June 2020

The purpose of the study was to examine the experiences of current high school students and teachers in Ontario regarding their experiences with personal financial curriculum and teaching at the secondary level, and to identify the ways in which this important educational experience may have helped prepare students to become financially literate. We considered this overarching issue using a transdisciplinary lens from the perspective of the three stakeholder groups. Using a case study research design, the first of its kind in Ontario or Canada on this topic, We utilized interviews and artifacts to uncover student and teacher experiential data across three high schools in southeastern Ontario. The major findings were that current students and teachers perceived curriculum and teaching experiences as seriously lacking in effectively preparing them to be financially literate, and that a fundamental reorientation around transdisciplinary, student-led learning was key to transforming such learning into a more meaningful and valuable educational experience. With mandatory, properly supported, student-oriented (transdisciplinary) instruction, the potential exists for more effective and valuable learning, resulting in better equipped high school students who were properly prepared to successfully navigate financial issues and the path ahead.
Held Down and Held Back: Systematically Delayed Principal Promotions by Race and Gender
Authors: Bailes Lauren P. , Guthery Sarah
Published: June 2020

Recent scholarship highlights the many benefits of diversity among principals, including improved teacher retention and student outcomes. We use survival analysis to assess the probability and time to promotion for 4,689 assistant principals in Texas from 2001 to 2017. We find that race and gender are associated with the probability of promotion to school leadership. Holding education, experience, school level, and urbanicity constant, Black principals are least likely to be promoted and wait longer for promotion when compared to White assistant principals. Additionally, findings suggest that even though women have over a year more experience on average before being promoted to assistant principal, they are less likely to be promoted to high school principal, and when they are, it is after a longer assistant principalship.
Promoting Sleep in the Intensive Care Unit
Authors: Beck Edvardsen Jorunn , Hetmann Fredrik
Published: June 2020

Introduction

Intensive care nurses face several challenges to facilitating sleep in their critically ill patients. With its high noise levels, hectic around-the-clock activity and constant artificial lights, the intensive care environment does not foster sleep. Intensive care unit patients have significant alterations in their sleep architecture with frequent awakenings and lighter sleep; up to 50% of this sleep also occurs during the daytime. Sleep loss increases the risk of developing delirium (especially in elderly patients) and immune system impairment, which prolongs healing. The aim of this article was to develop an evidence-based bundle of nursing care activities that promote adult intensive care patients’ sleep.

Methods

A broad search was conducted in PubMed, CINAHL, Cochrane Library, and McMaster plus using search words and Medical Subject Headings terms, such as sleep, intensive care unit, intensive care, critical care nursing, sleep promotion, music, white noise, earplugs, pain relief, absence of pain, nonpharmacological intervention, and mechanical ventilation. Eight recommendations emerged from this review: reduce noise, use earplugs and eye masks, use music, promote a natural circadian rhythm, manage pain, use quiet time, cluster nursing care activities at night, and optimize ventilator modes.

Conclusion

Promoting sleep within this patient population needs to be a higher priority for intensive care nurses. Sleep should be a focus throughout the day and night, in order to sustain patients’ natural circadian rhythms. Novel research in this field could change the strength of these recommendations and add new recommendations to the bundle.
Training Faculty in Entrepreneurship and Innovation: An Evaluation of the National Science Foundation Innovation-Corps™ Program
Authors: Duval-Couetil Nathalie , Huang-Saad Aileen , Wheadon Mandy
Published: June 2020

Evaluating the impact of entrepreneurship education is difficult given the heterogeneity of programming which presents challenges related to the generalizability of findings. The National Science Foundation’s Innovation-Corps (I-Corps) program, which incentivizes academic researchers to explore the commercialization potential of their research, offers a unique opportunity to examine the outcomes of entrepreneurship and technology commercialization training from an educational perspective given its standardization across populations and settings. We used the four-level Kirkpatrick Model for evaluating the impact of training and education programs to examine faculty experiences with I-Corps in depth. Using a qualitative inquiry methodology, we conducted 26 interviews with faculty innovators across three large public research institutions. Findings revealed that faculty had positive impressions of the program overall and attributed specific knowledge gains to participation. They also described behavioral changes impacting both their research and teaching. However, participants also identified challenges with I-Corps pedagogy and identified opportunities to improve training. This program evaluation and description of specific learning outcomes (skills, knowledge, attitude, and behaviors) contributes to best practices associated with delivering technology commercialization and entrepreneurship training to academic researchers.
Anomalies in Special Permutation Flow Shop Scheduling Problems
Authors: Gui Lin , Gao Liang , Li Xinyu
Published: June 2020

Recent researches show that there are some anomalies, which are not satisfied with common sense, appearing in some special permutation flow shop scheduling problems (PFSPs). These anomalies can be divided into three different types, such as changing the processing time of some operations, changing the number of total jobs and changing the number of total machines. This paper summarizes these three types of anomalies showing in the special PFSPs and gives some examples to make them better understood. The extended critical path is proposed and the reason why these anomalies happen in special PFSPs is given: anomalies will occur in these special PFSPs when the time of the operations on the reverse critical path changes. After that, the further reason for these anomalies is presented that when any one of these three types of anomalies happens, the original constraint in the special PFSPs is destroyed, which makes the anomalies appear. Finally, the application of these anomalies in production practice is given through examples and also with the possible research directions. The main contribution of this research is analyzing the intial reason why the anomalies appear in special PFSPs and pointing out the application and the possible research directions of all these three types of anomalies.
Silibinin suppresses epithelial–mesenchymal transition in human non-small cell lung cancer cells by restraining RHBDD1
Authors: Xu Suyan , Zhang Hongyan , Wang Aifeng , Ma Yongcheng , Gan Yuan , Li Guofeng
Published: June 2020

Background

Rhomboid domain containing 1 (RHBDD1) plays a crucial role in tumorigenesis. Silibinin, which is a natural extract from milk thistle, has shown anti-tumor effects against various tumors. Here, we investigate whether silibinin affects the function of RHBDD1 in non-small cell lung cancer (NSCLC) cell proliferation, migration and invasion.

Methods

The Oncomine database and an immunohistochemistry (IHC) assay were used to determine the RHBDD1 expression levels in lung cancer tissues. The associations between RHBDD1 and overall survival rate or clinicopathological parameters were respectively assessed using the Kaplan-Meier overall survival analysis or Chi-squared test. CCK-8 and Transwell assays were applied to analyze cell proliferation, migration and invasion. A549 cells were incubated with increasing concentrations of silibinin. RHBDD1 knockdown and overexpression were achieved via transfection with si-RHBDD1 or RHBDD1 overexpression plasmid, respectively. Western blotting was performed to measure the expressions of epithelial–mesenchymal transition (EMT) markers.

Results

We found that overexpression of RHBDD1 in lung cancer tissues correlates with a poor prognosis of survival. Clinical specimen analysis showed that upregulation of RHBDD1 correlates remarkably well with TNM stage and lymph node metastasis. Silibinin suppresses A549 cell proliferation, migration, invasion and EMT in a dose-dependent manner. Importantly, RHBDD1 was downregulated in silibinin-treated A549 cells. RHBDD1 overexpression reversed the suppressive effects of silibinin on A549 cell proliferation, migration, invasion and EMT expression, while its knockdown enhanced them.

Conclusions

These findings shown an anti-tumor impact of silibinin on NSCLC cells via repression of RHBDD1.
Research and Development Strategies for Hybrid japonica Rice
Authors: Zheng Wenjing , Ma Zuobin , Zhao Mingzhu , Xiao Minggang , Zhao Jiaming , Wang Changhua , Gao Hong , Bai Yuanjun , Wang Hui , Sui Guomin
Published: June 2020

The utilization of heterosis has resulted in significant breakthroughs in rice breeding. However, the development of hybrid japonica has been slow in comparison with that of hybrid indica. The present review explores the history and current status of hybrid japonica breeding. With the creation of japonica cytoplasmic male sterility and photo-thermo-sensitive genic male sterile lines, both three-line and two-line systems of hybrid rice have been created, and a series of hybrid japonica rice varieties have been developed and cultivated widely. At the same time, some progress has been made in genetic research of molecular mechanism for heterosis and QTL mapping for traits such as fertility, stigma exposure and flower time. In addition, genomics and transcriptome have been widely used in the research of hybrid rice, which provides a strong support for its development. Although the research on hybrid japonica has made many advances, there are still some restrictive problems. Based on the research and production of hybrid japonica rice, the prospect and development strategies of hybrid japonica rice are analyzed.
Correction to: The Peacock study: feasibility of the dynamic characterisation of the paediatric hypothalamic-pituitary-adrenal function during and after cardiac surgery
Authors: Fudulu Daniel Paul , Angelini Gianni Davide , Papadopoulou Fani Fanoula , Evans Jonathan , Walker-Smith Terrie , Kema Ido , Van Faassen Martijn , Stoica Serban , Caputo Massimo , Lightman Stafford , Gibbison Benjamin
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum
Authors: Hu Wei , Liu Yidong , Kan Shunli , Zhang Tengfei , Jiang Zehua , Zhu Rusen
Published: June 2020

Background

Lumbar spinal stenosis (LSS) is a common degenerative disease, which can lead to neurological dysfunction and requires surgical treatment. In the previous study, we used H&E staining and immunohistochemistry to qualitatively analyze the expression of S100 and P16 in the pathological process of ligamentum flavum (LF) hypertrophy in patients with LSS. To further explore the relationship between P16, S100 and LF hypertrophy in patients with LSS, we quantitatively detected S100 and P16 and their expressed products based on molecular biology techniques, and analyzed their imaging correlation.

Methods

Before posterior lumbar surgery, LF thickness was measured by Magnetic Resonance Imaging (MRI). Through the operation, we obtained the specimens of LF from 120 patients, all of whom were L4/5 LF. They were designated: simple lumbar disc herniation (LDH), single-segment spinal stenosis (SLSS), and double-segment LSS (DLSS). The detection of each side of LF was assessed. S100 and P16 and their expression products were detected by western blot and quantitative polymerase chain reaction (qPCR).

Results

The dorsal mRNA expression of P16 in DLSS group was significantly higher than that in SLSS group. On the dorsal and dural side of LF, the expression of P16 mRNA and proteins in the LDH group was significantly lower than that in SLSS and DLSS groups. We found a correlation between the thickness of LF and the expression of P16. However, there was no significant difference in the expression of S100 mRNA and S100 protein on both sides of the ligament and among the three groups, and no significant correlation between the expression of S100 and the thickness of LF.

Conclusions

P16 is involved in the process of LF hypertrophy in patients with LSS, and the imaging thickness of LF is related to the expression of P16. No obvious evidence proves that S100 may be related to the hypertrophy of LF in patients with LSS.
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside induces autophagy of liver by activating PI3K/Akt and Erk pathway in prediabetic rats
Authors: Wang Xuanbin , Zeng Jing , Wang Xiao , Li Ju , Chen Jin , Wang Ning , Zhang Miao , Feng Yibin , Guo Huailan
Published: June 2020

Background

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is an active compound derived from Polygonum multiflorum Thunb., a Chinese Taoist herbal medicine, which exerts lipid lowering, anti-cancer, anti-aging, anti-inflammatory and hepatoprotective effects. However, its role in protecting hepatocytes under pre-diabetic condition remains unclear.

Methods

In this study, we developed prediabetic SD rats by feeding high-fat and high-sugar diet. The body weight, blood lipid, blood glucose, and fasting insulin (FINS) and insulin resistance index (HOMA-IR) were detected and calculated to assess the potential risk of prediabetes. HE and Oil Red O staining was used, and blood level of biochemical index was detected to observe the liver injury. The autophagic cell death-associated signaling proteins, and the potential signaling factors p-Akt/Akt and p-Erk/Erk were detected using western blot to explore the potential effects of TSG on pre-diabetic liver and the underlying mechanisms.

Results

The results showed that the body weight in TSG-treated group was significantly decreased vs. the model group. The blood glucose, the level of FINS and HOMA-IR, TC and TG were decreased in TSG-treated group as well. Furthermore, TSG treatment significantly ameliorated lipid droplet accumulation, enhanced liver anti-oxidative response which may be associated with an increased activity of SOD and GSH-Px, and a decrease of LDLC and MDA. The autophagic cell death-associated proteins, p-AMPK, ATG12, LC3 II, and Beclin 1 were up-regulated in the TSG-treated group, while the upstream signaling pathway, PI3K/Akt and Erk, were activated.

Conclusions

TSG induced liver autophagic cell death to protect liver from prediabetic injury by activating PI3K/Akt and Erk.

Graphical abstract
Accommodating conscientious objection in the midwifery workforce: a ratio-data analysis of midwives, birth and late abortions in 18 European countries in 2016
Authors: Fleming Valerie , Maxwell Clare , Ramsayer Beate
Published: June 2020

Background

In recent years, the role of a midwife has expanded to include the provision of abortion-related care. The laws on abortion in many European countries allow for those who hold a conscientious objection to participating to refrain from such participation. However, some writers have expressed concerns that this may have a detrimental effect on the workforce and limit women’s access to the service.

Method

The aim of this study was to provide a picture of the potential exposure midwives in Europe have to late abortions, an important factor in the integration of accommodation of conscientious objection to abortion by midwives into workload planning. We collected data from Ministries of Health or government statistical departments in 32 European countries on numbers of births, abortions, late abortions and midwives in 2016. We conducted a ratio-data analysis in those countries that met the inclusion criteria.

Results

Eighteen of the 32 countries provided full data; thus, our calculations are based on a total of 4 036 633 live births, 49 834 late abortions and a total of 132 071 midwives. The calculated ratios of live births to midwife, abortions to midwife and late abortions to midwife illustrate the wide variations between countries in relation to ratios of midwives to live births (15.22–53.99) and late abortions (0.17–1.47)

Conclusions

This study provides the first comprehensive insight to ratios relating to birth and abortion, especially late abortion services, with regard to the midwifery workforce. It is essential to improve the reporting of abortion data and access to it within Europe to support evidence-informed decisions on optimising the contribution of the midwifery workforce especially within highly contentious fields such as abortion services. The study’s findings suggest that there should be neither be any difficulty for those who are responsible for workload allocation nor compromises to a women’s right to abortion services.
Clinical application of the AUC-guided dosage adjustment of docetaxel-based chemotherapy for patients with solid tumours: a single centre, prospective and randomised control study
Authors: Sun Ning , Shen Bo , Zhu Jiali , Zhang Xiaomei , Zhu Huayun , Liang Geyu , Yang Deliang , Lu Jianwei , Zhang Yan
Published: June 2020

Background

Docetaxel (DTX) is a widely used anti-tumour drug, and its dosage is solely determined by body surface area (BSA). Adverse events, such as neutropenia or unsatisfied efficacy, likely occur because of differences in the pharmacokinetics (PK) and pharmacodynamics of patients. Thus, a feasible dosage adjustment method is needed.

Methods

A total of 209 eligible patients who provided consent were enrolled and randomised into two groups to receive the BSA- and PK-guided dosage adjustments of DTX-based chemotherapy (3 weeks per cycle). The AUC of DTX was detected, and the therapeutic window for Chinese patients was determined. The proportion of patients within the therapeutic window was evaluated. Neutropenia was examined in accordance with the toxicity grading standard suggested by the World Health Organisation. Tumour response was assessed in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint was the incidence of neutropenia, and the secondary endpoints were disease control rate (DCR) and 3-year survival rate.

Results

The therapeutic window for Chinese patients was 1.7–2.5 mg·h/L. The proportion of patients within the therapeutic window was 63.89% versus 28.33% (P < 0.0001), and the incidence of neutropenia was 68.33% versus 38.89% (P = 0.001) in the experimental group versus the control group in the sixth cycle, respectively. DCR was 72% versus 85% (P = 0.018) in the control group versus the experimental group. The 3-year survival rate of the PK group was significantly higher than that of the BSA group (P = 0.034).

Conclusions

The PK-guided dosage adjustment of DTX could significantly increase the proportion of patients within the therapeutic window, decrease the incidence of neutropenia and increase the DCR and the 3-year survival rate. The PK-guided dosage adjustment based on the dynamic monitoring of AUC could be a useful method for oncologists to improve individualised treatment options, optimise drug efficacy and reduce drug toxicity.
Misinformation about spinal manipulation and boosting immunity: an analysis of Twitter activity during the COVID-19 crisis
Authors: Kawchuk Greg , Hartvigsen Jan , Harsted Steen , Nim Casper Glissmann , Nyirö Luana
Published: June 2020

Background

Social media has become an increasingly important tool in monitoring the onset and spread of infectious diseases globally as well monitoring the spread of information about those diseases. This includes the spread of misinformation, which has been documented within the context of the emerging COVID-19 crisis. Understanding the creation, spread and uptake of social media misinformation is of critical importance to public safety. In this descriptive study, we detail Twitter activity regarding spinal manipulative therapy (SMT) and claims it increases, or “boosts”, immunity. Spinal manipulation is a common intervention used by many health professions, most commonly by chiropractors. There is no clinical evidence that SMT improves human immunity.

Methods

Social media searching software (Talkwalker Quick Search) was used to describe Twitter activity regarding SMT and improving or boosting immunity. Searches were performed for the 3 months and 12 months before March 31, 2020 using terms related to 1) SMT, 2) the professions that most often provide SMT and 3) immunity. From these searches, we determined the magnitude and time course of Twitter activity then coded this activity into content that promoted or refuted a SMT/immunity link. Content themes, high-influence users and user demographics were then stratified as either promoting or refuting this linkage.

Results

Twitter misinformation regarding a SMT/immunity link increased dramatically during the onset of the COVID crisis. Activity levels (number of tweets) and engagement scores (likes + retweets) were roughly equal between content promoting or refuting a SMT/immunity link, however, the potential reach (audience) of tweets refuting a SMT/immunity link was 3 times higher than those promoting a link. Users with the greatest influence on Twitter, as either promoters or refuters, were individuals, not institutions or organizations. The majority of tweets promoting a SMT/immunity link were generated in the USA while the majority of refuting tweets originated from Canada.

Conclusion

Twitter activity about SMT and immunity increased during the COVID-19 crisis. Results from this work have the potential to help policy makers and others understand the impact of SMT misinformation and devise strategies to mitigate its impact.
EBV-positive intravascular large B-cell lymphoma of the liver: a case report and literature review
Authors: Li Qingjiao , Li Jinghe , Yang Keda , Peng Ying , Xiang Yao , Sun Shuyuan , Zeng Jian , Zhang Xin , Wang Junpu
Published: June 2020

Background

Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare subtype of diffuse large B-cell lymphoma that most commonly involves the central nervous system, skin, and bone marrow. To our knowledge, Epstein-Barr virus (EBV)-positive IVLBCL in the liver has never been reported in the literature.

Case presentation

We report a case of a 65-year-old Chinese man with complaint of fever for 18 days. No obvious abnormality was found by physical examination. Laboratory findings were notable for anemia, thrombocytopenia, and elevated level of serum lactate dehydrogenase. Bone marrow on smear, biopsy, and flow cytometry revealed no lymphoma. Imaging studies showed a slightly lower density lesion in the liver with high fluorodeoxyglucose uptake and hepatosplenomegaly. Percutaneous liver biopsy revealed clustering of large atypical lymphocytes within the hepatic sinusoids. Immunohistochemically, these lymphoma cells were positive for CD20, PAX-5, MUM-1, BCL-6 and CD5, but negative for CD3 and CD10. Besides, Epstein-Barr virus-encoded RNA was detected in tumor cells by in situ hybridization. BCL-2, BCL-6 and MYC genes were intact tested by fluorescence in situ hybridization analysis. The patient was diagnosed as IVLBCL and died after 1 month of hospitalization without receiving immunochemotherapy.

Conclusions

IVLBCL of the liver is a highly rare lymphoma with nonspecific manifestations and dismal prognosis. Full recognition of its clinicopathological features will help to better diagnose this disease.
The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017
Authors: Yi Ming , Li Anping , Zhou Linghui , Chu Qian , Song Yongping , Wu Kongming
Published: June 2020

Background

Acute myeloid leukemia (AML) is a common leukemia subtype and has a poor prognosis. The risk of AML is highly related to age. In the context of population aging, a comprehensive report presenting epidemiological trends of AML is evaluable for policy-marker to allocate healthy resources.

Methods

This study was based on the Global Burden of Disease 2017 database. We analyzed the change trends of incidence rate, death rate, and disability-adjusted life year (DALY) rate by calculating the corresponding estimated annual percentage change (EAPC) values. Besides, we investigated the influence of social development degree on AML’s epidemiological trends and potential risk factors for AML-related mortality.

Results

From 1990 to 2017, the incidence of AML gradually increased in the globe. Males and elder people had a higher possibility to develop AML. Developed countries tended to have higher age-standardized incidence rate and death rate than developing regions. Smoking, high body mass index, occupational exposure to benzene, and formaldehyde were the main risk factors for AML-related mortality. Notably, the contribution ratio of exposure to carcinogens was significantly increased in the low social-demographic index (SDI) region than in the high SDI region.

Conclusion

Generally, the burden of AML became heavier during the past 28 years which might need more health resources to resolve this population aging-associated problem. In the present stage, developed countries with high SDI had the most AML incidences and deaths. At the same time, developing countries with middle- or low-middle SDI also need to take actions to relieve rapidly increased AML burden.
Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations
Authors: Karcher Nicolai , Pasolli Edoardo , Asnicar Francesco , Huang Kun D. , Tett Adrian , Manara Serena , Armanini Federica , Bain Debbie , Duncan Sylvia H. , Louis Petra , Zolfo Moreno , Manghi Paolo , Valles-Colomer Mireia , Raffaetà Roberta , Rota-Stabelli Omar , Collado Maria Carmen , Zeller Georg , Falush Daniel , Maixner Frank , Walker Alan W. , Huttenhower Curtis , Segata Nicola
Published: June 2020

Background

Eubacterium rectaleis one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been carried out.

Results

Here, we leverage metagenomic assembly followed by a reference-based binning strategy to screen over 6500 gut metagenomes spanning geography and lifestyle and reconstruct over 1300E. rectalehigh-quality genomes from metagenomes. We extend previous results of biogeographic stratification, identifying a new subspecies predominantly found in African individuals and showing that closely related non-human primates do not harborE. rectale. Comparison of pairwise genetic and geographic distances between subspecies suggests that isolation by distance and co-dispersal with human populations might have contributed to shaping the contemporary population structure ofE. rectale. We confirm that a relatively recently divergedE. rectalesubspecies specific to Europe consistently lacks motility operons and that it is immotile in vitro, probably due to ancestral genetic loss. The same subspecies exhibits expansion of its carbohydrate metabolism gene repertoire including the acquisition of a genomic island strongly enriched in glycosyltransferase genes involved in exopolysaccharide synthesis.

Conclusions

Our study provides new insights into the population structure and ecology ofE. rectaleand shows that shotgun metagenomes can enable population genomics studies of microbiota members at a resolution and scale previously attainable only by extensive isolate sequencing.
Association between variation of circulating 25-OH vitamin D and methylation of secreted frizzled-related protein 2 in colorectal cancer
Authors: Boughanem Hatim , Cabrera-Mulero Amanda , Hernández-Alonso Pablo , Clemente-Postigo Mercedes , Casanueva Felipe F. , Tinahones Francisco José , Morcillo Sonsoles , Crujeiras Ana B. , Macias-Gonzalez Manuel
Published: June 2020

Backgrounds

Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizzled-related protein (SFRP) family. Indeed, SFRP2 is proposed as a noninvasive biomarker for CRC diagnosis. Vitamin D also antagonizes Wnt signaling in colon cancers cells. Several studies showed that vitamin D was able to alter DNA methylation, although this mechanism is not yet clear. Therefore, the aim of this study was to find an association between circulating 25-OH vitamin D (30th percentile of vitamin D) and the SFRP2 methylation.

Methods

A total of 67 CRC patients were included in the study. These patients were subdivided into two groups based on their 30th percentile vitamin D (20 patients were below, and 47 participants were above the 30th percentile of vitamin D). We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. Finally, we tested the effect of vitamin D on the SFRP2 methylation in human colorectal carcinoma cell lines 116 (HCT116) and studied the association of neoadjuvant therapy under the 30th percentile vitamin D with SFRP2 promoter methylation.

Results

SFRP2 methylation in tumor area was decreased in patients who had higher levels of vitamin D. SFRP2 promoter methylation was positively correlated in tumor area with insulin and homeostasis model assessment of insulin resistance (HOMA-IR) but negatively correlated with HDL-c. SFRP2 methylation was also correlated with T cell lymphoma invasion and metastasis 1 (TIAM1) methylation in tumor area and CCAAT/enhancer-binding protein alpha (C/EBPα) in VAT. Treatment with vitamin D did not affect SFRP2 methylation in HCT116 cell line. Finally, neoadjuvant treatment was correlated with higher circulating 25-OH vitamin D and SFRP2 methylation under linear regression model.

Conclusion

Our results showed that higher circulating vitamin D is associated with low SFRP2 promoter methylation. Therefore, our results could suggest that vitamin D may have an epigenetic effect on DNA methylation. Finally, higher vitamin D could contribute to an improvement response to neoadjuvant treatment.
Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes
Authors: Janickova Lucia , Rechberger Karin Farah , Wey Lucas , Schwaller Beat
Published: June 2020

Background

In fast firing, parvalbumin (PV)-expressing (Pvalb) interneurons, PV acts as an intracellular Ca2+ signal modulator with slow-onset kinetics. In Purkinje cells of PV−/− mice, adaptive/homeostatic mechanisms lead to an increase in mitochondria, organelles equally capable of delayed Ca2+ sequestering/buffering. An inverse regulation of PV and mitochondria likewise operates in cell model systems in vitro including myotubes, epithelial cells, and oligodendrocyte-like cells overexpressing PV. Whether such opposite regulation pertains to all Pvalb neurons is currently unknown. In oligodendrocyte-like cells, PV additionally decreases growth and branching of processes in a cell-autonomous manner.

Methods

The in vivo effects of absence of PV were investigated in inhibitory Pvalb neurons expressing EGFP, present in the somatosensory and medial prefrontal cortex, striatum, thalamic reticular nucleus, hippocampal regions DG, CA3, and CA1 and cerebellum of mice either wild-type or knockout (PV−/−) for the Pvalb gene. Changes in Pvalb neuron morphology and PV concentrations were determined using immunofluorescence, followed by 3D-reconstruction and quantitative image analyses.

Results

PV deficiency led to an increase in mitochondria volume and density in the soma; the magnitude of the effect was positively correlated with the estimated PV concentrations in the various Pvalb neuron subpopulations in wild-type neurons. The increase in dendrite length and branching, as well as thickness of proximal dendrites of selected PV−/− Pvalb neurons is likely the result of the observed increased density and length of mitochondria in these PV−/− Pvalb neuron dendrites. The increased branching and soma size directly linked to the absence of PV is assumed to contribute to the increased volume of the neocortex present in juvenile PV−/− mice. The extended dendritic branching is in line with the hypothesis of local hyperconnectivity in autism spectrum disorder (ASD) and ASD mouse models including PV−/− mice, which display all ASD core symptoms and several comorbidities including cortical macrocephaly at juvenile age.

Conclusion

PV is involved in most proposed mechanisms implicated in ASD etiology: alterations in Ca2+ signaling affecting E/I balance, changes in mitochondria structure/function, and increased dendritic length and branching, possibly resulting in local hyperconnectivity, all in a likely cell autonomous way.
Bulgarian consumers’ objective understanding of front-of-package nutrition labels: a comparative, randomized study
Authors: Andreeva Valentina A. , Egnell Manon , Handjieva-Darlenska Teodora , Talati Zenobia , Touvier Mathilde , Galan Pilar , Hercberg Serge , Pettigrew Simone , Julia Chantal
Published: June 2020

Background

Bulgaria continues to lag behind other EU Member States with respect to chronic disease morbidity and mortality prevention.

Methods

In line with efforts targeting the improvement of dietary practices, this comparative study assessed objective understanding of five different front-of-package labels (FOPL) (Reference Intakes, Multiple Traffic Lights, Warning label, Nutri-Score, and Health Star Rating) in a sample of 1010 Bulgarian adults. Objective understanding was assessed by comparing the results of two nutritional quality ranking tasks (with and without FOPL) in an online randomized experiment featuring three food categories (pizza, cakes, breakfast cereals). Multivariable ordinal logistic regression models within and across food categories were fit.

Results

Compared with the Reference Intakes group, participants randomized to Nutri-Score exhibited the largest improvement in product ranking ability across food categories (OR = 2.33; 95% CI: 1.55–3.51), followed by those randomized to Health Star Rating (OR = 1.99; 95% CI: 1.32–3.00). Nutri-Score also performed best within two (pizza and breakfast cereals) of the three food categories. The Multiple Traffic Lights and Warning label groups did not display any significant improvement in objective understanding either within or across food categories compared with the Reference Intakes group.

Conclusion

Nutri-Score, which is a summary, interpretive, polychromatic FOPL, emerged as the most effective model in the Bulgarian context, with the potential to help consumers better understand the nutritional quality of food. The findings are of particular interest to public health policymakers in the region and across Europe, as the debate about an EU-wide FOPL model continues to gather momentum.

Trial registration

Registration number ACTRN12618001221246. Trial registered at the Australian New Zealand Clinical Trials Registry.