bluuebunny/crossref_metadata_2025 huggingface dataset:
An efficient or methodical review of immunotherapy against breast cancer
Authors: Guanghui Ren , Xiaoyan Hao , Shuyi Yang , Jun Chen , Guobin Qiu
Published: June 2019

Breast cancer (BC) is one of the most widespread malignancies in women worldwide. Breast cancer is mainly classified into a few key molecular subtypes in accordance with hormone and growth factor receptor expression, etc. In spite of numerous advances in the remedy of breast cancer, the development of metastatic disease remains an untreatable and repeated basis of cancer death for women. Preclinical and clinical studies of immunotherapy in cancer remedy have been in progress for the past quite a few decades by an effort to accelerate, augment, and modulate the immune system to spot and devastate cancer cells. Advancement of cancer immunotherapy is rapidly increasing with eminent and most interesting therapy compared to other therapy like targeted therapy, cytotoxic chemotherapy, radiation as well as surgery. Cancer immunotherapy, also known as biological therapy, which denotes the controlling and by means of the patient's own immune system to goal the cancer cells rather than using an extrinsic therapy. In that way, focusing of cancer immunotherapy developing mediators that stimulates or enhances the immune system's recognition and destroying the cancer cells. This review describes a holistic outlook and deeper understanding of the biology of immunotherapy within the system of tumor microenvironment of breast cancer that improve clinical research and constructive impact on the study conclusion.
Magnolol induces apoptosis in osteosarcoma cells via G0/G1 phase arrest and p53‐mediated mitochondrial pathway
Authors: Zhou Siqi , Wen Haiyan , Li Haohuan
Published: June 2019

Osteosarcoma is a highly invasive primary malignancy of bone. Magnolol is biologically active, which shows antitumor effects in a variety of cancer cell lines. However, it has not been elucidated magnolol's effects on human osteosarcoma cells (HOC). This study aimed to determine antitumor activity of magnolol and illustrate the molecular mechanism in HOC. Magnolol showed significant inhibition effect of growth on MG‐63 and 143B cells and induced apoptosis and cell cycle arrest at G0/G1. In osteosarcoma cells, magnolol upregulated expressions of proapoptosis proteins and suppressed expressions of antiapoptosis proteins. Additionally, under the pretreatment of pifithrin‐a (PFT‐a, a p53 inhibitor), the magnolol‐induced apoptosis was significantly reversed. The results above indicated that magnolol induces apoptosis in osteosarcoma cells may via G0/G1 phase arrest and p53‐mediated mitochondrial pathway.
How Brands Acquire Cultural Meaning
Authors: Fournier Susan , Alvarez Claudio
Published: June 2019

This article endeavors to advance research on the cultural resonance of brands by building bridges between branding scholarship in the consumer psychology tradition and interpretive research regarding brands and their meaning makers. We adopt a cognitivist conceptualization of cultural meaning and focus on the application of interpretive insights to well‐established constructs in the consumer psychology of brands: brand associations, product category associations, social identity, and self‐identity. This integrative exercise highlights the value of cultural models in explaining the processes whereby brands acquire meaning, and suggests several themes that are under‐valued when considering this process problem through a psychological lens: the motivational underpinnings of myths and other cultural meaning models, the relative value of shared cultural and brand meanings versus idiosyncratic meanings, the power and primacy of category‐level meaning making over brand‐level meaning making, the complex processes whereby brands gain and lose legitimacy, and the influence of lay theories about brands and branding on how consumers co‐create meaning for brands.
Repair of Central Venous Catheter in a Single‐Center Adult Home Parenteral Nutrition Cohort
Authors: Velapati Saketh R. , Schroeder Sara , Kuchkuntla Aravind R. , Salonen Bradley R. , Bonnes Sara L. , Hurt Ryan T. , Mundi Manpreet S.
Published: June 2019

Background

Patients with chronic intestinal failure who require long‐term parenteral nutrition rely on central venous catheters (CVCs) for access to nutrition and hydration. With prolonged use, complications such as central line–associated bloodstream infection (CLABSI), damage to CVC, and central venous thrombosis (CVT) can threaten the availability of life‐preserving access. Because of this, all efforts should be made to preserve CVCs with techniques such as catheter salvage in case of CLABSI and catheter repair when damaged. The present study was conducted to evaluate the effectiveness and safety of catheter repair in our patient population.

Methods

Retrospective review in 1253 adult patients who received home parenteral nutrition at the Mayo Clinic between September 1, 1997, and April 30, 2018, was conducted to determine the incidence of CLABSI and CVT in patients who underwent CVC repair.

Results

Fifty‐five CVC repairs were performed in 36 patients (n = 23 female) with mean age of 57.05 ± 16.96 years. A total of 14 catheters (25.45%) were complicated with 24 episodes of CLABSI. CLABSI rate before and after repair was 0.23/1000 catheter days and 0.21/1000 catheter days, respectively. Most common indications for eventual catheter replacement were mechanical damage (32%), infection (32%), and switching to alternate mode of nutrition (24%). We had a 100% success rate of catheter repair procedure, and no post‐procedural complications were present.

Conclusion

Catheter repair can increase the catheter survival without increasing the risk of CLABSI, providing not only socioeconomic benefit but also decreasing risk of compromising future vascular access.
Dietitians’ Evaluation of Clearing Luminal Occlusions of Gunk (DECLOG): A Pilot Feasibility Study
Authors: Escuro Arlene A. , Burns Berri , McLaughlin Kathleen , Lopez Rocio , Cresci Gail A.
Published: June 2019

Background

Tube clogging is the most frequent mechanical complication associated with enteral nutrition. The objective of this study was to assess the efficacy of a protocol incorporating prophylactic use of a declogging system with enhanced patient education and monitoring to proactively reduce the incidence of tube occlusions in the home care setting.

Methods

A convenient sample of patients discharged from hospital to home enteral nutrition (HEN) was screened for eligibility and randomized to control group (standard care) or study group (standard care with prophylactic protocol and monitoring). Study patients received 4 enzyme declogging kits before discharge and were instructed to administer them every 7 days for 4 weeks.

Results

Seventeen of 49 (35%) patients reported tube occlusions. The incidence of tube occlusion in the control group was not statistically different than in the study group (29% vs 39%, P = 0.44). There was no difference between the 2 groups for negative tube outcomes, such as tube occlusion (P = 0.44), emergency department visit (P = 0.24), tube replacement (P = 0.99), or hospital readmission (P = 0.33). Continuous feeding method (P = 0.037), small‐bowel feeding tubes (P = 0.016), and tube diameter <14 French (P = 0.069) were associated with tube occlusions.

Conclusion

A prophylactic protocol using an enzyme declogging system did not lessen the likelihood of tube occlusions when compared with standard care. Multiple factors are associated with tube occlusion. More research investigating the use of a declogging system to prevent clogging incidence in patients receiving HEN is warranted.
The ultimate goals of tooth regeneration: Where do we stand?
Authors: Kamate Wasim , Vibhute Nupura , Baad Rajendra , Belgaumi Uzma , Kadashetti Vidya , Bommanvar Sushma
Published: June 2019

The concept of tooth regeneration has fascinated many researchers recently. Several studies have been conducted in an attempt to regenerate either parts of tooth or a whole tooth. Although teeth and its constituent parts have very limited or no capacities of regeneration, several ex vivo and animal studies have exploited the use of stem cells to regenerate parts of a tooth or a whole tooth. This review is an attempt to better understand various aspects of biological regeneration of tooth structures. It gives a conceptual exploration of what we can expect from regeneration of a part of a tooth or a whole tooth and the various factors involved in achieving the ultimate goals of regeneration in which a fully restored and functional tooth is regenerated with the help of regenerative medicine using human stem cells.
Ethyl acetate extract of Nepenthes adrianii x clipeata induces antiproliferation, apoptosis, and DNA damage against oral cancer cells through oxidative stress
Authors: Tang Jen‐Yang , Peng Sheng‐Yao , Cheng Yuan‐Bin , Wang Chun‐Lin , Farooqi Ammad Ahmad , Yu Tzu‐Jung , Hou Ming‐Feng , Wang Sheng‐Chieh , Yen Chia‐Hung , Chan Leong‐Perng , Ou‐Yang Fu , Chang Hsueh‐Wei
Published: June 2019

Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9‐22, OECM‐1, HSC‐3, and SCC9) show IC50 values of cell viability ranging from 8 to 17 μg/mL but the viability of normal oral cells (HGF‐1) remains over 80%. Subsequently, CAL 27 and Ca9‐22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP‐ribose) polymerase (c‐PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS), mitochondrial membrane potential disruption, mitochondrial superoxide, and γH2AX. All these changes of EANA treatments in oral cancer cells were reverted by the ROS scavenger N‐acetylcysteine pretreatment. Therefore, EANA induces preferential killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress.
Health Concerns and Access to Services: Female Sex Workers’ Experiences in Mumbai, India
Authors: Kaloga Marissa , Karandikar Sharvari , Gezinski Lindsay B. , McCloskey Rebecca J.
Published: June 2019

Female sex workers (FSWs) in India experience unmet health‐care needs due to numerous barriers to care. The objectives of this study were to (i) explore the health concerns among FSWs in Kamathipura, a red‐light district of Mumbai, India; and (ii) understand their experiences using health‐related services and resources. This qualitative study used in‐depth, semi‐structured individual interviews with 15 FSWs recruited using snowball sampling. Data analysis consisted of reading transcriptions line by line, identifying themes, and coding categories. A matrix of health concerns and identified resources were created to examine relationships. Participants identified numerous health concerns. Six thematic categories emerged, encompassing all health concern codes: communicable disease, nutrition, substance abuse, reproductive health, mental health, and physical violence. Participants reported varying levels of availability of health services; additionally, their basic health needs exceeded resource availability. FSWs have vital health concerns that go untreated. Current health care and social service funding and interventions are insufficient to meet the needs. Health‐care services must be expanded across all identified health categories and FSWs informed of their existence. Furthermore, prevention and intervention programs, with support from both nonprofits and government, must be prioritized to address the basic food and safety needs of FSWs.
Predictors for Pediatric Blunt Cerebrovascular Injury (BCVI): An International Multicenter Analysis
Authors: Weber Christian D. , Lefering Rolf , Weber Matthias S. , Bier Georg , Knobe Matthias , Pishnamaz Miguel , Kobbe Philipp , Hildebrand Frank ,   TraumaRegister DGU
Published: June 2019

Introduction

Practice guidelines for adult BCVI patients have been implemented recently, but data for this devastating injury pattern in children are still limited. An international multicenter analysis was performed to characterize BCVI in the pediatric population.

Methods

The TraumaRegister DGU®, a prospectively maintained database, was analyzed (01/2002–12/2015). Pediatric patients (0–17 years) with major injuries [Injury Severity Score (ISS) ≥ 9 points] were included. BCVI was divided into carotid artery injury and vertebral artery injury (VAI). Data of demographics, injury, imaging, therapy, and outcome characteristics were analyzed with SPSS (Version 25, IBM Inc., Armonk, NY).

Results

The study cohort included 8128 pediatric trauma patients. We identified 48 BCVIs in 42 children, resulting in an overall prevalence of 0.5%. Carotid injuries were diagnosed more frequently (n = 30; 0.4%) when compared to VAIs (n = 12; 0.1%). The coincidence of head (p = 0.028), facial (p ≤ 0.001), chest (p ≤ 0.001), and spinal injuries (p ≤ 0.001) was higher in BCVI patients. The risk for thromboembolic complications (8.3% vs. 1%, p = 0.026) and in‐hospital mortality (38.1% vs. 7.7%, p ≤ 0.001) was excessive in children with BCVI. We identified various predictors for pediatric BCVI and quantified the cumulative impact of these risk factors.

Conclusion

BCVI is more uncommon in pediatric than in adult trauma patients. Due to the considerable relevance of this injury for both children and adults, special attention should be paid to this entity and associated complications in the early treatment phase after severe pediatric trauma, especially in high‐risk children.
Is postgraduate leadership education a match for the wicked problems of health systems leadership? A critical systematic review
Authors: Onyura Betty , Crann Sara , Tannenbaum David , Whittaker Mary Kay , Murdoch Stuart , Freeman Risa
Published: June 2019

Purpose There have been a growing number of leadership education programs for physicians. However, debates about the value and efficacy of leadership education in medicine persist, and there are calls for systematic and critical perspectives on medical leadership development. Here, we review evidence on postgraduate leadership education and discuss findings in relation to contemporary evidence on leadership education and practice.

Method We searched multiple databases for papers on postgraduate leadership development programs, published in English between 2007 and 2017. We identified 4,691 papers; 31 papers met the full inclusion criteria. Data regarding curricular content and design, learner demographics, instructional methods, and learning outcomes were abstracted and synthesized.

Results There was modest evidence for effectiveness of programs in influencing knowledge and skills gains in select domains. However, the conceptual underpinnings of the ‘leadership’ training delivered were often unclear. Contemporary theory and evidence on leadership practice was not widely incorporated in program design. Programs were almost exclusively uni-professional, focused on discrete skill development, and did not address systems-level leadership issues. Broader leadership capacity building strategies were underutilized. A new wave of longitudinal, integrated clinical and leadership programming is observed.

Conclusions Our findings raise questions about persistent preparation-practice gaps in leadership education in medicine. Leadership education needs to evolve to incorporate broader collective capacity building, as well as evidence-informed strategies for leadership development. Barriers to educational reform need to be identified and addressed as educators work to re-orientate education programs to better prepare budding physician leaders for the challenges of health system leadership.
Glacier sliding, seismicity and sediment entrainment
Authors: Lipovsky Bradley Paul , Meyer Colin R. , Zoet Lucas K. , McCarthy Christine , Hansen Dougal D. , Rempel Alan W. , Gimbert Florent
Published: June 2019

The evolution of glaciers and ice sheets depends on processes in the subglacial environment. Shear seismicity along the ice–bed interface provides a window into these processes. Such seismicity requires a rapid loss of strength that is typically ascribed to rate-weakening friction, i.e., decreasing friction with sliding or sliding rate. Many friction experiments have investigated glacial materials at the temperate conditions typical of fast flowing glacier beds. To our knowledge, however, these studies have all found rate-strengthening friction. Here, we investigate the possibility that rate-weakening rock-on-rock friction between sediments frozen to the bottom of the glacier and the underlying water-saturated sediments or bedrock may be responsible for subglacial shear seismicity along temperate glacier beds. We test this ‘entrainment-seismicity hypothesis’ using targeted laboratory experiments and simple models of glacier sliding, seismicity and sediment entrainment. These models suggest that sediment entrainment may be a necessary but not sufficient condition for the occurrence of basal shear seismicity. We propose that stagnation at the Whillans Ice Stream, West Antarctica may be caused by the growth of a frozen fringe of entrained sediment in the ice stream margins. Our results suggest that basal shear seismicity may indicate geomorphic activity.
Soil and landscape affecting technology transfer targeting subsistence farmers in central Tanzania
Authors: Reinhardt Nadja , Schaffert Angela , Capezzone Filippo , Chilagane Emmanuel , Swai Eliherema , Rweyemamu Cornel Lawrence , Germer Jörn , Asch Folkard , Herrmann Ludger
Published: June 2019

This article deals with technology transfer from science to agriculture with pearl millet (Pennisetum glaucum(L.)R.Br.) in central Tanzania as example. The major question is which validity recommendations from different types of field experiments have and how geo-information (i.e. soil and landscape position) can lead to more site-specific recommendations. Tied ridging and reduced amounts of placed fertilizer during sowing were tested to increase yields on researcher-managed plots on-station, demonstration plots in villages, and farmer-managed plots on-farm. While on-station trials provided potential yield effects, physical distance to the station and differing conditions led to a higher informational value of village plots that mirror the context of local farmers. The treatments often resulted in significant yield increase. Soil and relief information and distance to settlements (i.e. gradient of management intensity) are key factors for data variability in on-farm trials. Unexplained variability is introduced through leaving degrees of freedom with respect to management to the farmer. Apart from soil and physiographic information, the latter should be part of a detailed data collection procedure in agronomic trials in large numbers addressing Sub-Saharan smallholder farming. Balanced data sets with dispersed trials on crucial soil and relief units are essential for future research.
Demographic and Actuarial Aspects of Ageing, With Special Reference to England and Wales
Authors: Benjamin B.
Published: June 2019

The present paper is in two main parts: (1) a general discussion of the population factors which have led to a focusing of attention upon ageing with some reference to recent advances in gerontology and (2) a consideration of the actuarial implications of current gerontological research.
Microbiological quality of milk from farms to milk powder manufacture: an industrial case study
Authors: Paludetti Lizandra F. , Kelly Alan L. , O'Brien Bernadette , Jordan Kieran , Gleeson David
Published: June 2019

The experiments reported in this research paper aimed to track the microbiological load of milk throughout a low-heat skim milk powder (SMP) manufacturing process, from farm bulk tanks to final powder, during mid- and late-lactation (spring and winter, respectively). In the milk powder processing plant studied, low-heat SMP was produced using only the milk supplied by the farms involved in this study. Samples of milk were collected from farm bulk tanks (mid-lactation: 67 farms; late-lactation: 150 farms), collection tankers (CTs), whole milk silo (WMS), skim milk silo (SMS), cream silo (CS) and final SMP. During mid-lactation, the raw milk produced on-farm and transported by the CTs had better microbiological quality than the late-lactation raw milk (e.g., total bacterial count (TBC): 3.60 ± 0.55 and 4.37 ± 0.62 log 10 cfu/ml, respectively). After pasteurisation, reductions in TBC, psychrotrophic (PBC) and proteolytic (PROT) bacterial counts were of lower magnitude in late-lactation than in mid-lactation milk, while thermoduric (LPC—laboratory pasteurisation count) and thermophilic (THERM) bacterial counts were not reduced in both periods. The microbiological quality of the SMP produced was better when using mid-lactation than late-lactation milk (e.g., TBC: 2.36 ± 0.09 and 3.55 ± 0.13 cfu/g, respectively), as mid-lactation raw milk had better quality than late-lactation milk. The bacterial counts of some CTs and of the WMS samples were higher than the upper confidence limit predicted using the bacterial counts measured in the farm milk samples, indicating that the transport conditions or cleaning protocols could have influenced the microbiological load. Therefore, during the different production seasons, appropriate cow management and hygiene practices (on-farm and within the factory) are necessary to control the numbers of different bacterial groups in milk, as those can influence the effectiveness of thermal treatments and consequently affect final product quality.
Ten years of ENT Scotland meetings: an appraisal of the publication rates of trainee-presented scientific papers
Authors: Asimakopoulos P , Charalampidis G , Chakravarthy KM , Mamais C
Published: June 2019

Objective

The ENT Scotland society (formerly known as the Scottish Otolaryngological Society) has two meetings a year and accepts oral presentations from trainees. This study aimed to identify publication rates from these meetings.

Methods

Abstracts of the presentations are published in The Journal of Laryngology and Otology. A structured search on PubMed and Google Scholar was undertaken to identify which presentations from the 2005 to 2014 meetings have been published.

Results

Of the 145 abstracts found, 60.7 per cent were presenting clinical research and 44.1 per cent were related to the head and neck subspecialty. Seventy-three abstracts (50.3 per cent) were associated with publication as a peer-reviewed article; otology papers were more likely to be published than those focusing on other subspecialties (64.3 per cent, p = 0.036). No correlation was found between publication and other factors.

Conclusion

Presentations at the ENT Scotland meetings undergo unbiased peer review and are as likely to be published as those of other conferences.
Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges
Authors: McNulty Helene , Ward Mary , Hoey Leane , Hughes Catherine F. , Pentieva Kristina
Published: June 2019

The functional effects of folate within C1metabolism involve interrelationships with vitamin B12, vitamin B6and riboflavin, and related gene–nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B12status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B12status can be problematic for older people, however, primarily owing to food-bound B12malabsorption which leads to sub-clinical deficiency even with high dietary B12intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.
Are there cognitive benefits of code-switching in bilingual children? A longitudinal study
Authors: Kuzyk Olivia , Friend Margaret , Severdija Vivianne , Zesiger Pascal , Poulin-Dubois Diane
Published: June 2019

The current study explored bilingual parent and child code-switching patterns over time. Concurrent and predictive models of code-switching behaviour on executive function outcomes were also examined in a sample of 29 French–English bilinguals at 36 (Wave 1) and 61 (Wave 2) months of age. We investigated whether code-switching typology in a single-language context predicted executive function performance at each wave independently, and whether growth in code-switching frequency across waves predicted executive function performance at Wave 2. At both waves, parents and children participated in two free play sessions (in English and French), followed by a battery of executive function tasks administered in the dominant language. Results indicate more frequent code-switching from the non-dominant to the dominant language in children, and that children code-switch to fill lexical gaps. Results also suggest that less frequent code-switching in a single-language context is associated with better inhibitory control skills during the preschool period.
Fighting the Tide: Church Schools in South Buckinghamshire, 1902–44
Authors: Masom Grant
Published: June 2019

In 1902 elementary school provision in Oxford diocese – England's largest – reflected the national picture: 72 per cent were church schools, with total rolls of 54 per cent of school-age children. The bitterly contested 1902 Education Act apparently protected the future of church schools, but in practice its provisions severely undermined them, particularly in growing areas of the country. By 1929, Oxford's assistant bishop reported the schools’ situation as ‘critical’. This article examines the impact on the church schools of one rural deanery in South Buckinghamshire, between the 1902 and 1944 Education Acts. Several schools found themselves under threat of closure, while rapid population increase and a rising school leaving age more than quadrupled the number of school-age children in the area. Closer working with the local education authority and other denominations was one option to optimize scarce resources and protect the Church of England's influence on religious education in day schools: but many churchmen fought to keep church schools open at all costs. This strategy met with limited success: by 1939 the proportion of children in church schools had decreased to 10 per cent, with potential consequences for how religion was taught to the other 90 per cent of children.
Psychometric Properties of the French Brief Resilience	Scale
Authors: Jacobs Ingo , Horsch Antje
Published: June 2019

Abstract. The Brief Resilience Scale ( BRS) is a reliable and valid assessment of the self-perceived ability to bounce back or recover quickly from stress. The current study translated and validated the French version of the BRS (BRS-F) in a sample of N = 220 midwives. In a confirmatory factor analysis, the unifactorial model fitted acceptably to the data. High levels of Tucker’s φ implied that the component loadings of the BRS-F and of the original BRS are almost equal. The BRS-F demonstrated good levels of reliability and meaningful correlations with mental health symptoms and burnout. The resilience-mental health difficulties link was fully mediated through emotional exhaustion. Thus, the BRS-F is a psychometrically sound assessment of self-perceived resilience, which is now available to researchers and clinicians in French-speaking contexts. The results also suggest that the BRS-F is relevant for use by healthcare professionals who may benefit from interventions aimed at increasing their resilience.
Incipient Tidal Bar and Sill Formation
Authors: Leuven J. R. F. W. , Kleinhans M. G.
Published: June 2019

Estuaries and rivers show dynamic patterns of bars and channels. Mutually evasive ebb‐ and flood‐dominated tidal channels, that is, parallel tidal channels with net sediment transport in opposing directions, give tidal bars their characteristic shape. Here, we study incipient tidal bars with laboratory scale experiments in a periodically tilting flume. Bar patterns evolved from an initial straight channel in an erodible sand bed. Analysis of time‐lapse imagery and bathymetry shows that alternate bars form within 300 tidal cycles. The bars become discrete, recognizable elements after an initial phase characterized by a rhomboid pattern (short and narrow ridges oblique to the channel). Tidal bars show similarities and contrasts with fluvial bars. In general, morphological shapes are similar, including the presence of alternate bars, midchannel bars, and point bars. Sills are superimposed on incipient tidal bars. Sills are narrow and straight and form by flow divergence and thus sediment convergence between alternate bars. This contrasts with rivers, where sills are remnants of alternate bars. Alternate tidal bars grow further by amalgamation of two opposing U‐shaped lobate bars. The dimensions of incipient tidal bars emerge in the first 500 cycles, after which their length and position determine a large‐scale quasiperiodic variation in the estuary width. The results imply that sills are initiated with the onset of tidal bar formation in straight channels and trigger formation of mutually evasive ebb‐ and flood‐dominated channels, thus explaining their ubiquitous occurrence in tidal systems.
A novel lncRNA n384546 promotes thyroid papillary cancer progression and metastasis by acting as a competing endogenous RNA of miR-145-5p to regulate AKT3
Authors: Feng Jiajia , Zhou Qinyi , Yi Hongliang , Ma Shiyin , Li Dawei , Xu Yanan , Wang Jiadong , Yin Shankai
Published: June 2019

Long noncoding RNAs (lncRNAs) are emerging as important regulators in the development of cancer cells. However, the role and mechanisms of most lncRNAs in papillary thyroid carcinoma (PTC) remain unknown. In this study, we investigated lncRNA expression profiles of PTC using RNA-seq in two groups of PTC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 53 pairs of tissues. We identified a novel lncRNA, n384546, which is highly expressed in PTC tissues and cell lines. n384546 expression was associated with clinicopathological features of PTC patients, such as tumor size, lymph node metastasis, and TNM stage. Functionally, knockdown of n384546 inhibited PTC cell proliferation, invasion, and migration both in vitro and in vivo. In addition, we identified miR-145-5p as a key miRNA target of n384546 using online bioinformatics tools. Anti-miR-145 could partially reverse the effects of n384546 knockdown. Furthermore, we found that n384546 could regulate the expression of AKT3 by sponging miR-145-5p, which was confirmed using an in vitro luciferase assay. In conclusion, we validated n384546 as a novel oncogenic lncRNA in PTC and determined that the n384546/miR-145-5p/AKT3 pathway contributes to PTC progression, which might be used as potential therapeutic targets for PTC patients.
Alternative splicing-derived intersectin1-L and intersectin1-S exert opposite function in glioma progression
Authors: Shao Ying , Chong Wei , Liu Xiaoli , Xu Yun , Zhang Huikun , Xu Qiao , Guo Zhifang , Zhao Yawen , Zhang Ming , Ma Yongjie , Gu Feng
Published: June 2019

Intersectin1 (ITSN1) contains two isoforms: ITSN1-S and ITSN1-L, which is highly regulated by alternative splicing. However, the alteration of alternative splicing and its importance in cancer is still unknown. In this study, our transcriptome analysis by using a large glioma cohort indicated the two isoforms exerted opposite function in glioma progression. Our previous results had shown ITSN1-S could promote glioma development; however, the function of ITSN1-L remained unknown. In this study, we first confirmed that ITSN1-L exerted an inhibitory role in glioma progression both in vivo and in vitro, which was contrary to the function of ITSN1-S. In additional, we also elucidated the mechanisms of ITSN1-L in inhibiting tumor progression. First, we revealed ITSN1-L could interact with α-tubulin to promote HDAC6-dependent deacetylation of ac-tubulin leading to decreased cell motility. Second, ITSN1-L could attenuate cell–substrate adhesion through FAK/integrin β3 pathway. Third, ITSN1-L was able to strengthen cell–cell adhesion by upregulating N-cadherin expression and its re-localization to membrane by ANXA2 and TUBB3/TUBB4. In conclusion, we found for the first time that two isoforms produced by alternative splicing exerted opposite functions in glioma development. Therefore, upregulation of ITSN1-L expression as well as downregulation of ITSN1-S expression probably was a better strategy in glioma treatment. Our present study laid a foundation for the importance of alternative splicing in glioma progression and raised the possibility of controlling glioma development completely at an alternative splicing level to be a more effective strategy.
No trends in spring and autumn phenology during the global warming hiatus
Authors: Wang Xufeng , Xiao Jingfeng , Li Xin , Cheng Guodong , Ma Mingguo , Zhu Gaofeng , Altaf Arain M. , Andrew Black T. , Jassal Rachhpal S.
Published: June 2019

Phenology plays a fundamental role in regulating photosynthesis, evapotranspiration, and surface energy fluxes and is sensitive to climate change. The global mean surface air temperature data indicate a global warming hiatus between 1998 and 2012, while its impacts on global phenology remains unclear. Here we use long-term satellite and FLUXNET records to examine phenology trends in the northern hemisphere before and during the warming hiatus. Our results based on the satellite record show that the phenology change rate slowed down during the warming hiatus. The analysis of the long-term FLUXNET measurements, mainly within the warming hiatus, shows that there were no widespread advancing (or delaying) trends in spring (or autumn) phenology. The lack of widespread phenology trends partly led to the lack of widespread trends in spring and autumn carbon fluxes. Our findings have significant implications for understanding the responses of phenology to climate change and the climate-carbon feedbacks.
A monolithic immersion metalens for imaging solid-state quantum emitters
Authors: Huang Tzu-Yung , Grote Richard R. , Mann Sander A. , Hopper David A. , Exarhos Annemarie L. , Lopez Gerald G. , Klein Amelia R. , Garnett Erik C. , Bassett Lee C.
Published: June 2019

Quantum emitters such as the diamond nitrogen-vacancy (NV) center are the basis for a wide range of quantum technologies. However, refraction and reflections at material interfaces impede photon collection, and the emitters’ atomic scale necessitates the use of free space optical measurement setups that prevent packaging of quantum devices. To overcome these limitations, we design and fabricate a metasurface composed of nanoscale diamond pillars that acts as an immersion lens to collect and collimate the emission of an individual NV center. The metalens exhibits a numerical aperture greater than 1.0, enabling efficient fiber-coupling of quantum emitters. This flexible design will lead to the miniaturization of quantum devices in a wide range of host materials and the development of metasurfaces that shape single-photon emission for coupling to optical cavities or route photons based on their quantum state.
A comprehensive single cell transcriptional landscape of human hematopoietic progenitors
Authors: Pellin Danilo , Loperfido Mariana , Baricordi Cristina , Wolock Samuel L. , Montepeloso Annita , Weinberg Olga K. , Biffi Alessandra , Klein Allon M. , Biasco Luca
Published: June 2019

Hematopoietic Stem/Progenitor cells (HSPCs) are endowed with the role of maintaining a diverse pool of blood cells throughout the human life. Despite recent efforts, the nature of the early cell fate decisions remains contentious. Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured transcriptional landscape of hematopoietic differentiation. Still, this landscape misses important early fate decisions. We here provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands our understanding of the underlying structure of early adult human haematopoiesis. We also show that this map has strong similarities in topology and gene expression to that found in mouse. Finally, we identify the sialomucin CD164, as a reliable marker for the earliest branches of HSPCs specification and we showed how its use can foster the design of alternative transplantation cell products.
Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition
Authors: Pereira Branca I. , Devine Oliver P. , Vukmanovic-Stejic Milica , Chambers Emma S. , Subramanian Priya , Patel Neil , Virasami Alex , Sebire Neil J. , Kinsler Veronica , Valdovinos Alexis , LeSaux Claude Jourdan , Passos João F. , Antoniou Antony , Rustin Malcom H. A. , Campisi Judith , Akbar Arne N.
Published: June 2019

Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with the inhibitory receptor NKG2A expressed by NK and highly differentiated CD8+ T cells to inhibit immune responses against senescent cells. HLA-E expression is induced by senescence-associated secretary phenotype-related pro-inflammatory cytokines, and is regulated by p38 MAP kinase signalling in vitro. Consistently, HLA-E expression is increased on senescent cells in human skin sections from old individuals, when compared with those from young, and in human melanocytic nevi relative to normal skin. Lastly, blocking the interaction between HLA-E and NKG2A boosts immune responses against senescent cells in vitro. We thus propose that increased HLA-E expression contributes to persistence of senescent cells in tissues, thereby suggesting a new strategy for eliminating senescent cells during ageing.
One-pot universal initiation-growth methods from a liquid crystalline block copolymer
Authors: Jin Bixin , Sano Koki , Aya Satoshi , Ishida Yasuhiro , Gianneschi Nathan , Luo Yunjun , Li Xiaoyu
Published: June 2019

The construction of hierarchical nanostructures with precise morphological and dimensional control has been one of the ultimate goals of contemporary materials science and chemistry, and the emulation of tailor-made nanoscale superstructures realized in the nature, using artificial building blocks, poses outstanding challenges. Herein we report a one-pot strategy to precisely synthesize hierarchical nanostructures through an in-situ initiation-growth process from a liquid crystalline block copolymer. The assembly process, analogous to living chain polymerization, can be triggered by small-molecule, macromolecule or even nanoobject initiators to produce various hierarchical superstructures with highly uniform morphologies and finely tunable dimensions. Because of the high degree of controllability and predictability, this assembly strategy opens the avenue to the design and construction of hierarchical structures with broad utility and accessibility.
On-surface synthesis of planar dendrimers via divergent cross-coupling reaction
Authors: Li Deng-Yuan , Li Shi-Wen , Xie Yu-Li , Hua Xin , Long Yi-Tao , Wang An , Liu Pei-Nian
Published: June 2019

Dendrimers are homostructural and highly branched macromolecules with unique dendritic effects and extensive use in multidisciplinary fields. Although thousands of dendrimers have been synthesized in solution, the on-surface synthetic protocol for planar dendrimers has never been explored, limiting the elucidation of the mechanism of dendritic effects at the single-molecule level. Herein, we describe an on-surface synthetic approach to planar dendrimers, in which exogenous palladium is used as a catalyst to address the divergent cross-coupling of aryl bromides with isocyanides. This reaction enables one aryl bromide to react with two isocyanides in sequential steps to generate the divergently grown product composed of a core and two branches with high selectivity and reactivity. Then, a dendron with four branches and dendrimers with eight or twelve branches in the outermost shell are synthesized on Au(111). This work opens the door for the on-surface synthesis of various planar dendrimers and relevant macromolecular systems.
Behavioural correlations of the domestication syndrome are decoupled in modern dog breeds
Authors: Hansen Wheat Christina , Fitzpatrick John L. , Rogell Björn , Temrin Hans
Published: June 2019

Domestication is hypothesized to drive correlated responses in animal morphology, physiology and behaviour, a phenomenon known as the domestication syndrome. However, we currently lack quantitative confirmation that suites of behaviours are correlated during domestication. Here we evaluate the strength and direction of behavioural correlations among key prosocial (sociability, playfulness) and reactive (fearfulness, aggression) behaviours implicated in the domestication syndrome in 76,158 dogs representing 78 registered breeds. Consistent with the domestication syndrome hypothesis, behavioural correlations within prosocial and reactive categories demonstrated the expected direction-specificity across dogs. However, correlational strength varied between dog breeds representing early (ancient) and late (modern) stages of domestication, with ancient breeds exhibiting exaggerated correlations compared to modern breeds across prosocial and reactive behaviours. Our results suggest that suites of correlated behaviours have been temporally decoupled during dog domestication and that recent shifts in selection pressures in modern dog breeds affect the expression of domestication-related behaviours independently.
Epidemiologic evaluation of Nhanes for environmental Factors and periodontal disease
Authors: Emecen-Huja P. , Li H-F. , Ebersole J. L. , Lambert J. , Bush H.
Published: June 2019

Periodontitis is a chronic inflammation that destroys periodontal tissues caused by the accumulation of bacterial biofilms that can be affected by environmental factors. This report describes an association study to evaluate the relationship of environmental factors to the expression of periodontitis using the National Health and Nutrition Examination Study (NHANES) from 1999–2004. A wide range of environmental variables (156) were assessed in patients categorized for periodontitis (n = 8884). Multiple statistical approaches were used to explore this dataset and identify environmental variable patterns that enhanced or lowered the prevalence of periodontitis. Our findings indicate an array of environmental variables were different in periodontitis in smokers, former smokers, or non-smokers, with a subset of specific environmental variables identified in each population subset. Discriminating environmental factors included blood levels of lead, phthalates, selected nutrients, and PCBs. Importantly, these factors were found to be coupled with more classical risk factors (i.e. age, gender, race/ethnicity) to create a model that indicated an increased disease prevalence of 2–4 fold across the sample population. Targeted environmental factors are statistically associated with the prevalence of periodontitis. Existing evidence suggests that these may contribute to altered gene expression and biologic processes that enhance inflammatory tissue destruction.
Safety margins and adaptive capacity of vegetation to climate change
Authors: Gallagher Rachael V. , Allen Stuart , Wright Ian J.
Published: June 2019

Vegetation is composed of many individual species whose climatic tolerances can be integrated into spatial analyses of climate change risk. Here, we quantify climate change risk to vegetation at a continental scale by calculating the safety margins for warming and drying (i.e., tolerance to projected change in temperature and precipitation respectively) across plants sharing 100 km × 100 km grid cells (locations). These safety margins measure how much warmer, or drier, a location could become before its ‘typical’ species exceeds its observed climatic limit. We also analyse the potential adaptive capacity of vegetation to temperature and precipitation change (i.e., likelihood of in situ persistence) using median precipitation and temperature breadth across all species in each location. 47% of vegetation across Australia is potentially at risk from increases in mean annual temperature (MAT) by 2070, with tropical regions most vulnerable. Vegetation at high risk from climate change often also exhibited low adaptive capacity. By contrast, 2% of the continent is at risk from reductions in annual precipitation by 2070. Risk from precipitation change was isolated to the southwest of Western Australia where both the safety margin for drier conditions in the typical species is low, and substantial reductions in MAP are projected.
Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes
Authors: He Funan , Wei Ran , Zhou Zhan , Huang Leihuan , Wang Yinan , Tang Jie , Zou Yangyun , Shi Leming , Gu Xun , Davis Melissa J. , Su Zhixi
Published: June 2019

RNA secondary structure may influence many cellular processes, including RNA processing, stability, localization, and translation. Single-nucleotide variations (SNVs) that alter RNA secondary structure, referred to as riboSNitches, are potentially causative of human diseases, especially in untranslated regions (UTRs) and noncoding RNAs (ncRNAs). The functions of somatic mutations that act as riboSNitches in cancer development remain poorly understood. In this study, we developed a computational pipeline called SNIPER (riboSNitch-enriched or depleted elements in cancer genomes), which employs MeanDiff and EucDiff to detect riboSNitches and then identifies riboSNitch-enriched or riboSNitch-depleted non-coding elements across tumors. SNIPER is available at github: https://github.com/suzhixi/SNIPER/. We found that riboSNitches were more likely to be pathogenic. Moreover, we predicted several UTRs and lncRNAs (long non-coding RNA) that significantly enriched or depleted riboSNitches in cancer genomes, indicative of potential cancer driver or essential noncoding elements. Our study highlights the possibly neglected importance of RNA secondary structure in cancer genomes and provides a new strategy to identify new cancer-associated genes.