bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma deposition—Impact of ions in plasma enhanced chemical vapor deposition, plasma enhanced atomic layer deposition, and applications to area selective deposition
Authors: Vallée Christophe , Bonvalot Marceline , Belahcen Samia , Yeghoyan Taguhi , Jaffal Moustapha , Vallat Rémi , Chaker Ahmad , Lefèvre Gautier , David Sylvain , Bsiesy Ahmad , Possémé Nicolas , Gassilloud Rémy , Granier Agnès
Published: April 2020

In this paper, the emerging role of ionic species in plasma assisted chemical deposition processes is discussed in detail for commemorating the Career of John Coburn, who studied the role of ionic species in plasma etching processes forty years ago. It is shown that, in both plasma enhanced chemical vapor deposition and plasma enhanced atomic layer deposition processes, plasma ions can play a major role in tuning a wide range of physical properties of thin films. In both processes, the possibility of extracting plasma ions with a tunable incident kinetic energy driven on the substrate surface is shown to provide a valuable additional degree of freedom in plasma processing. While a too large incident kinetic energy of plasma ions may have damaging effects linked to surface sputtering and atomic peening, a relatively low energy ion bombardment ensures a substantial improvement of thin film purity and the effective tuning of their microstructural properties. This phenomenon is attributed to the synergetic effect boosting momentum transfer and chemical reactivity among radicals and ionic plasma species, which, in turn, modulates plasma-surface interactions. Taking advantage of these tunable physical properties opens up the way to a large array of pathways for selective deposition processes in both 2D and 3D nanoscale microstructures.
Strategic Social Media Marketing for the Premier Lacrosse League
Authors: Hemme Florian , Morais Dominic G. , Lukow Jennifer
Published: April 2020

Co-founded by brothers Paul and Mike Rabil, the Premier Lacrosse League (PLL) debuted in the U.S. on June 1, 2019 as a professional lacrosse alternative to Major League Lacrosse (MLL). With limited funding available to the league, the Rabils relied heavily on social media tactics to promote their venture. The reader will be tasked to analyze the PLL’s marketing efforts and devise alternative and novel approaches for future years. All information provided in the case is publicly available and references to magazine, newspaper articles, and videos are provided at the end of the case. Names mentioned in the case are the names of real individuals.
Bad Boy for Life: Hip-Hop Music, Race, and Sports
Authors: Smith Earl , Hattery Angela J.
Published: April 2020

P Diddy’sBad Boy for Lifevideo provides a strategic point of departure in the quest for values and community, sui generis, in SportsWorld. This study poses an interruption to the “ideological” articulations of discourse on the relationship between hip-hop music and sports by providing an examination of empirical and scientific data inside of SportsWorld. There is a carefully crafted narrative about the coexistence among Black American athletes, SportsWorld, and hip-hop music. From the beginning of Black athletes’ entry into the White spaces of the so-called level playing field of sports—from National Association of Stock Car Racing to the National Hockey Association to Major League Baseball to National Basketball Association—this integration upsets the norms of both civility and history; because for many in White America, the belief persists that these same athletes were not then and should not be today in those sacred spaces. From Jackie Robinson to the Williams Sisters to Jack Johnson to Tiger Woods to Althea Gibson to Fritz Pollard and, of course, Muhammad Ali—all of these pioneers suffered the indignities of racial discrimination. As Smith argues in his 2014 bookRace, Sport and the American Dream, fast forward, deep inside the second aught of the 21st century, it is often assumed that the addition of hip-hop music to the pregame and half-time entertainment at ballparks, basketball arenas, stadiums, and ice hockey arenas signals a welcoming to the Black Athlete and their fans. Using a Marxian lens, this study argues thatboththese assumptions are no more than the ideology of beliefs that Marx describes as “fantasies and illusions” or more straightforward a “phantasmagoria.” These fantasies and illusions show up as alaterna magicaprojecting images on society and in SportsWorld, where these can be described as commodity fetishism. Through the authors' empirical analysis of data on segregation and integration in SportsWorld, they demonstrate that things are not always as they seem.
“A Breath of Fresh Air”: Media Framing of a Unique National Football League Draft Pick
Authors: Love Adam , Deeb Alexander , Dzikus Lars
Published: April 2020

In the 2016 National Football League (NFL) Draft, Moritz Böhringer became the first international player ever selected without having previously played in North America. The current study examined media coverage of Böhringer during the process of him being identified as an NFL prospect, working out for NFL scouts, being drafted, and trying to make an NFL roster. Ultimately, Böhringer was framed as an international experiment that produced serious interest from NFL teams and created a “feel good” story for fans. The study contributes to the broader understanding of sport, media, race, and nationality, illustrating how Böhringer—despite being a foreign athlete in a quintessentially American sport—was presented as a “breath of fresh air” that provided welcome relief from the “bad apples” in the league.
A highly sensitive and selective nanosensor for near-infrared potassium imaging
Authors: Liu Jianan , Pan Limin , Shang Chunfeng , Lu Bin , Wu Rongjie , Feng Yun , Chen Weiyu , Zhang Rongwei , Bu Jiwen , Xiong Zhiqi , Bu Wenbo , Du Jiulin , Shi Jianlin
Published: April 2020

A highly sensitive and selective near-infrared excited potassium nanosensor has been developed for brain activity monitoring.
Fully stabilized multi-TW optical waveform synthesizer: Toward gigawatt isolated attosecond pulses
Authors: Xue Bing , Tamaru Yuuki , Fu Yuxi , Yuan Hua , Lan Pengfei , Mücke Oliver D. , Suda Akira , Midorikawa Katsumi , Takahashi Eiji J.
Published: April 2020

A 0.24-μJ coherent soft x-ray supercontinuum is created by a fully stabilized 50-mJ three-channel optical waveform synthesizer.
Density waves in shear-thickening suspensions
Authors: Ovarlez Guillaume , Vu Nguyen Le Anh , Smit Wilbert J. , Fall Abdoulaye , Mari Romain , Chatté Guillaume , Colin Annie
Published: April 2020

Flows during discontinuous shear-thickening transition are heterogeneous, unsteady, and loose azimuthal symmetry.
Minibands in twisted bilayer graphene probed by magnetic focusing
Authors: Berdyugin A. I. , Tsim B. , Kumaravadivel P. , Xu S. G. , Ceferino A. , Knothe A. , Kumar R. Krishna , Taniguchi T. , Watanabe K. , Geim A. K. , Grigorieva I. V. , Fal’ko V. I.
Published: April 2020

Detection of magnetic focusing peaks allows probing of minibands in the energy spectrum of twisted bilayer graphene.
Exceptional capacitive deionization rate and capacity by block copolymer–based porous carbon fibers
Authors: Liu Tianyu , Serrano Joel , Elliott John , Yang Xiaozhou , Cathcart William , Wang Zixuan , He Zhen , Liu Guoliang
Published: April 2020

Block copolymer–based porous carbon fibers show ultrahigh capacity and rate for capacitive deionization.
Commensal epitopes drive differentiation of colonic T
regs
Authors: Kuczma Michal P. , Szurek Edyta A. , Cebula Anna , Chassaing Benoit , Jung Yu-Jin , Kang Sang-Moo , Fox James G. , Stecher Bärbel , Ignatowicz Leszek
Published: April 2020

Colonic commensal-derived antigens support expansion and differentiation of immunosupressive CD4 T cells.
Three-dimensional vectorial holography based on machine learning inverse design
Authors: Ren Haoran , Shao Wei , Li Yi , Salim Flora , Gu Min
Published: April 2020

3D vectorial holography reconstructs an arbitrary 3D vectorial field–carrying wavefront using machine learning inverse design.
Nanoparticle elasticity regulates phagocytosis and cancer cell uptake
Authors: Hui Yue , Yi Xin , Wibowo David , Yang Guangze , Middelberg Anton P. J. , Gao Huajian , Zhao Chun-Xia
Published: April 2020

The deformation of soft nanocapsules during cell binding and endocytosis leads to a lower cellular uptake than the stiff ones.
Negative friction coefficient in microscale graphite/mica layered heterojunctions
Authors: Liu Bingtong , Wang Jin , Zhao Shuji , Qu Cangyu , Liu Yuan , Ma Liran , Zhang Zhihong , Liu Kaihui , Zheng Quanshui , Ma Ming
Published: April 2020

Negative friction coefficient attributed to the water layer confined at the interface is observed on microscale.
A novel landscape of nuclear human CDK2 substrates revealed by in situ phosphorylation
Authors: Chi Yong , Carter John H. , Swanger Jherek , Mazin Alexander V. , Moritz Robert L. , Clurman Bruce E.
Published: April 2020

A key cell cycle kinase targets novel landscape of substrates, including proteins that regulate chromatin and gene expression.
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model
Authors: Rockx Barry , Kuiken Thijs , Herfst Sander , Bestebroer Theo , Lamers Mart M. , Oude Munnink Bas B. , de Meulder Dennis , van Amerongen Geert , van den Brand Judith , Okba Nisreen M. A. , Schipper Debby , van Run Peter , Leijten Lonneke , Sikkema Reina , Verschoor Ernst , Verstrepen Babs , Bogers Willy , Langermans Jan , Drosten Christian , Fentener van Vlissingen Martje , Fouchier Ron , de Swart Rik , Koopmans Marion , Haagmans Bart L.
Published: April 2020

Coronavirus in nonhuman primates

We urgently need vaccines and drug treatments for coronavirus disease 2019 (COVID-19). Even under these extreme circumstances, we must have animal models for rigorous testing of new strategies. Rockx
et al.
have undertaken a comparative study of three human coronaviruses in cynomolgus macaques: severe acute respiratory syndrome–coronavirus (SARS-CoV) (2002), Middle East respiratory syndrome (MERS)–CoV (2012), and SARS-CoV-2 (2019), which causes COVID-19 (see the Perspective by Lakdawala and Menachery). The most recent coronavirus has a distinct tropism for the nasal mucosa but is also found in the intestinal tract. Although none of the older macaques showed the severe symptoms that humans do, the lung pathology observed was similar. Like humans, the animals shed virus for prolonged periods from their upper respiratory tracts, and like influenza but unlike the 2002 SARS-CoV, this shedding peaked early in infection. It is this cryptic virus shedding that makes case detection difficult and can jeopardize the effectiveness of isolation.

Science
, this issue p.
1012
; see also p.
942
IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer
Authors: Hubert Margaux , Gobbini Elisa , Couillault Coline , Manh Thien-Phong Vu , Doffin Anne-Claire , Berthet Justine , Rodriguez Céline , Ollion Vincent , Kielbassa Janice , Sajous Christophe , Treilleux Isabelle , Tredan Olivier , Dubois Bertrand , Dalod Marc , Bendriss-Vermare Nathalie , Caux Christophe , Valladeau-Guilemond Jenny
Published: April 2020

cDC1-derived IFN-λ is the predominant IFN in breast tumors, and its production can be induced through TLR3-mediated cDC1 activation.
ScmR, a Global Regulator of Gene Expression, Quorum Sensing, pH Homeostasis, and Virulence in
Burkholderia thailandensis
Authors: Le Guillouzer Servane , Groleau Marie-Christine , Mauffrey Florian , Déziel Eric
Published: April 2020

Coordination of the expression of genes associated with bacterial virulence and environmental adaptation is often dependent on quorum sensing (QS). The QS circuitry of the nonpathogenic bacterium
Burkholderia thailandensis
, widely used as a model system for the study of the human pathogen
Burkholderia pseudomallei
, is complex. We found that the LysR-type transcriptional regulator, ScmR, which is highly conserved and involved in the control of virulence/survival factors in the
Burkholderia
genus, is a global regulator mediating gene expression through the multiple QS systems coexisting in
B. thailandensis
, as well as QS independently. We conclude that ScmR represents a key QS modulatory network element, ensuring tight regulation of the transcription of QS-controlled genes, particularly those required for acclimatization to the environment.
Isotope sclerochronology indicates enhanced seasonal precipitation in northern South America (Colombia) during the Mid-Miocene Climatic Optimum
Authors: Scholz Serena R. , Petersen Sierra V. , Escobar Jaime , Jaramillo Carlos , Hendy Austin J.W. , Allmon Warren D. , Curtis Jason H. , Anderson Brendan M. , Hoyos Natalia , Restrepo Juan C. , Perez Nicolas
Published: April 2020

During the Mid-Miocene Climatic Optimum (MMCO, 14.7–17.3 Ma), global temperatures were warmer than present, and similar to predicted temperatures for the coming century. Limited paleoclimate data exist from the tropics during this period, despite its potential as an analog for future climate conditions. This study presents new subannual stable isotope data (δ18O and δ13C) from a large population of Miocene Turritella gastropods from the Jimol and Castilletes Formations of the Guajira Peninsula, Colombia. Turritellids are aragonitic marine mollusks that live in shallow coastal waters, and their rapid growth rates allow for high-resolution subannual records. We compare these fossils to modern Turritella gastropods from multiple tropical localities to reconstruct subannual climate conditions. The seasonal range in δ18O in the modern shells correlates with the seasonal variance of local precipitation, once temperature seasonality is accounted for. The Miocene fossils show larger (in some cases >2‰) seasonal variation in δ18O than modern Turritella from the same location, suggesting increased seasonality of precipitation in Miocene northern Colombia relative to today. We propose that this increased seasonality of precipitation was due to a more northerly position of the Intertropical Convergence Zone during the mid-Miocene. The resulting wet Miocene paleoenvironment is in stark contrast to semiarid conditions on the Guajira Peninsula today, indicating that this area of tropical South America has undergone a drastic environmental change since the Miocene.
Tidal modulation of river-flood deposits: How low can you go?
Authors: Maselli Vittorio , Normandeau Alexandre , Nones Michael , Tesi Tommaso , Langone Leonardo , Trincardi Fabio , Bohacs Kevin M.
Published: April 2020

Quantification of the interaction between river discharge and tides is vital to characterize fluvio-deltaic systems, to identify diagnostic elements of tidal signatures in the rock record, and to reconstruct paleogeographies. In modern systems, even microtides can significantly influence delta morphodynamics; yet, many fundamental processes, particularly in prodeltaic settings, remain elusive. Here, by combining a unique process-product data set acquired during a flood event of the Po River (Italy) with numerical modeling, we show that tidal signatures are recorded in the open-water prodelta zone of a microtidal system. Based on the analyses of box-cores collected before and after a flood off the main distributary channel, we interpreted storm beds, tide-modulated flood strata of alternating normal and inverse graded beds, and rapid bioturbation. Modeling of the river discharge indicates that, at the peak of the flood, the steepening of the water-surface profile forced by 0.15 m lowering of sea level during low tides generated an 8% increase in river flow velocity. The alternation of profile steepness and associated cyclicity in flow strength during consecutive tidal cycles controlled the sediment load of the plume and, consequently, led to the deposition of tidal-modulated strata. Formation of microtidal signals appears to be enhanced in fluvio-deltaic successions characterized by multiple distributaries and in basins where river floods are out of phase with storm-wave activity. Bioturbation of sediment, which can start during the waning stage of the flow, and erosion by storm waves hamper the preservation of tidal signals, unless rapid burial occurs. The recognition of tidal-modulated strata in river-dominated settings may facilitate the characterization of mudstone reservoirs and reconstruction of paleogeographic conditions during deposition.
Mesalamine-induced eosinophilic pleural effusion
Authors: Al-abcha Abdullah , Raziq Fazal , Kherallah Shouq , Alratroot Ahmad
Published: April 2020

A 45-year-old woman with a medical history of ulcerative colitis (UC) presented with difficulty in breathing. The patient was diagnosed with UC a month prior to presentation and was started on mesalamine suppository. Chest x-ray (CXR) on presentation showed bilateral pleural effusion, which was confirmed on CT angiogram of the chest. Diagnostic and therapeutic thoracentesis was performed and 0.7 L of pleural fluid was removed from the left side. The pleural fluid analysis was consistent with exudative pleural effusion with eosinophilia. Symptomatic improvement was noted after thoracentesis. Mesalamine was stopped and repeat CXR was obtained on the follow-up visit, which showed no pleural effusion. The Naranjo score was calculated to be 7, indicating that the eosinophilic pleural effusion was most probably secondary to adverse reaction from mesalamine.
Crohn’s disease associated adenocarcinoma of ileocaecal region: a miscalculated approach
Authors: Dsouza Royson , Varghese Gigi , Korula Deepa Rebecca , Dutta Amit Kumar
Published: April 2020

Adenocarcinoma of the bowel is a dreadful sequelae of inflammatory bowel disease that can be difficult to diagnose and has been shown to have poor prognosis. The diagnosis is often made on histopathological examination of the resected specimen for what is suspected to be an exacerbation of the underlying intestinal Crohn’s. A 39-year-old woman who was being treated for small bowel Crohn’s disease for 4 years presented with features of intermittent intestinal obstruction that was refractory to medical therapy. A contrast CT of the abdomen was suggestive of ileocaecal Crohn’s disease, and colonoscopy revealed a stricture at proximal transverse colon with multiple superficial ulcers. She underwent a mesentery sparing right hemicolectomy and had an uneventful recovery. The biopsy, however, was reported to be moderately differentiated adenocarcinoma stage T3N0 with a harvest of four pericolic nodes. Adjuvant chemotherapy was advised, which she deferred. Ten months later, she presented to the emergency room with features of intestinal obstruction. Contrast CT of the abdomen showed thickening at the anastomotic site with intestinal obstruction. On exploratory laparotomy, tumour recurrence was noted at the site of the anastomosis and diffuse peritoneal metastasis. A palliative diversion ileostomy was done due to inoperable obstructing disease. She was then given palliative therapy and subsequently succumbed to the illness. The inclusion of mesentery with the resected specimen in Crohn’s disease has been a debate over many years. Since the preoperative diagnosis of carcinoma of the bowel in Crohn’s disease is challenging, all ileocolic resections should be radical as done in oncological resections. This would yield better oncological safety and may improve survival rates.
Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results
Authors: Payne John F. , Wykoff Charles C. , Clark W. Lloyd , Bruce Beau B. , Boyer David S. , Brown David M.
Published: April 2020

Background/aims

To evaluate the long-term effects of treat-and-extend dosing of ranibizumab with and without navigated focal laser for diabetic macular oedema (DME).

Methods

This is a multicentre, randomised clinical trial where 150 eyes were randomised into three cohorts; Monthly (n=30), TReat and EXtend without macular laser photocoagulation (TREX; n=60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n=60). During the first 2 years, eyes either received ranibizumab 0.3 mg every 4 weeks or underwent treat-and-extend ranibizumab with or without angiography-guided laser therapy. In the third year, all eyes were treated as needed with ranibizumab for >5 letters vision loss or if the central retinal thickness (CRT) was >325 µm, and all eyes were eligible to receive focal laser.

Results

109 eyes (73%) completed the 3-year end-point. At week 156, mean best-corrected visual acuity (BCVA) and CRT improved by 6.9, 9.7, 9.5 letters (p=0.60) and 129, 138, 165 µm (p=0.39), in the Monthly, TREX and GILA cohorts, respectively. These improvements were reached prior to week 104 and no significant changes occurred from week 104 to week 156 (BCVA: p=0.34; CRT: p=0.36). The mean number of injections in the third year was 3.0, 3.1, and 2.4 in the Monthly, TREX and GILA cohorts, respectively (p=0.56). 86 eyes (79%) required at least one ranibizumab injection in the third year.

Conclusion

The improvements achieved after 2 years of treat-and-extend ranibizumab for DME were maintained in the third year with a mean of 3 intravitreal injections.

Trial registration number

FDA IND 119146, NCT01934556.
How to manage travel fatigue and jet lag in athletes? A systematic review of interventions
Authors: Janse van Rensburg Dina C(Christa) , Jansen van Rensburg Audrey , Fowler Peter , Fullagar Hugh , Stevens David , Halson Shona , Bender Amy , Vincent Grace , Claassen-Smithers Amanda , Dunican Ian , Roach Gregory Daniel , Sargent Charli , Lastella Michele , Cronje Tanita
Published: April 2020

Objectives

We investigated the management of travel fatigue and jet lag in athlete populations by evaluating studies that have applied non-pharmacological interventions (exercise, sleep, light and nutrition), and pharmacological interventions (melatonin, sedatives, stimulants, melatonin analogues, glucocorticoids and antihistamines) following long-haul transmeridian travel-based, or laboratory-based circadian system phase-shifts.

Design

Systematic review

Eligibility criteria

Randomised controlled trials (RCTs), and non-RCTs including experimental studies and observational studies, exploring interventions to manage travel fatigue and jet lag involving actual travel-based or laboratory-based phase-shifts. Studies included participants who were athletes, except for interventions rendering no athlete studies, then the search was expanded to include studies on healthy populations.

Data sources

Electronic searches in PubMed, MEDLINE, CINAHL, Google Scholar and SPORTDiscus from inception to March 2019. We assessed included articles for risk of bias, methodological quality, level of evidence and quality of evidence.

Results

Twenty-two articles were included: 8 non-RCTs and 14 RCTs. No relevant travel fatigue papers were found. For jet lag, only 12 athlete-specific studies were available (six non-RCTs, six RCTs). In total (athletes and healthy populations), 11 non-pharmacological studies (participants 600; intervention group 290; four non-RCTs, seven RCTs) and 11 pharmacological studies (participants 1202; intervention group 870; four non-RCTs, seven RCTs) were included. For non-pharmacological interventions, seven studies across interventions related to actual travel and four to simulated travel. For pharmacological interventions, eight studies were based on actual travel and three on simulated travel.

Conclusions

We found no literature pertaining to the management of travel fatigue. Evidence for the successful management of jet lag in athletes was of low quality. More field-based studies specifically on athlete populations are required with a multifaceted approach, better design and implementation to draw valid conclusions.

PROSPERO registration number

The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42019126852).
Advancing alcohol research in low-income and middle-income countries: a global alcohol environment framework
Authors: Walls Helen , Cook Sarah , Matzopoulos Richard , London Leslie
Published: April 2020

Alcohol-related harm has gained increased attention in high-income countries (HICs) in recent years which, alongside government regulation, has effected a reduction in alcohol consumption. The alcohol industry has turned its attention to low-income and middle-income country (LMIC) markets as a new source of growth and profit, prompting increased consumption in LMICS. Alcohol use in LMICs is also increasing. There is a need to understand particularly in LMICs the impact of industry strategy in shaping local contexts of alcohol use. We draw on conceptualisations from food systems research, and research on the commercial determinants of health, to develop a new approach for framing alcohol research and discuss implications for alcohol research, particularly in LMICs, focusing on South Africa as an illustrative example. We propose a conceptualisation of the ‘alcohol environment’ as the system of alcohol provision, acquisition and consumption—including, critically, industry advertising and marketing—along with the political, economic and regulatory context of the alcohol industry that mediates people’s alcohol drinking patterns and behaviours. While each country and region is different in terms of its context of alcohol use, we contrast several broadly distinct features of alcohol environments in LMICs and HICs. Improving understanding of the full spectrum of influences on drinking behaviour, particularly in LMICs, is vital to inform the design of interventions and policies to facilitate healthier environments and reduce the harms associated with alcohol consumption. Our framework for undertaking alcohol research may be used to structure mixed methods empirical research examining the role of the alcohol environment particularly in LMICs.
Policy dialogue as a collaborative tool for multistakeholder health governance: a scoping study
Authors: Robert Emilie , Rajan Dheepa , Koch Kira , Muggleworth Weaver Alyssa , Porignon Denis , Ridde Valery
Published: April 2020

Introduction

Health system governance is the cornerstone of performant, equitable and sustainable health systems aiming towards universal health coverage. Global health actors have increasingly been using policy dialogue (PD) as a governance tool to engage with both state and non-state stakeholders. Despite attempts to frame PD practices, it remains a catch-all term for both health systems professionals and researchers.

Method

We conducted a scoping study on PD. We identified 25 articles published in English between 1985 and 2017 and 10 grey literature publications. The analysis was guided by the following questions: (1) How do the authors define PD? (2) What do we learn about PD practices and implementation factors? (3) What are the specificities of PD in low-income and middle-income countries?

Results

The analysis highlighted three definitions of policy dialogue: a knowledge exchange and translation platform, a mode of governance and an instrument for negotiating international development aid. Success factors include the participants’ continued and sustained engagement throughout all the relevant stages, their ability to make a constructive contribution to the discussions while being truly representative of their organisation and their high interest and stake in the subject. Prerequisites to ensuring that participants remained engaged were a clear process, a shared understanding of the goals at all levels of the PD and a PD approach consistent with the PD objective. In the context of development aid, the main challenges lie in the balance of power between stakeholders, the organisational or technical capacity of recipient country stakeholders to drive or contribute effectively to the PD processes and the increasingly technocratic nature of PD.

Conclusion

PD requires a high level of collaborative governance expertise and needs constant, although not necessarily high, financial support. These conditions are crucial to make it a real driver of health system reform in countries’ paths towards universal health coverage.
Obstetrical safety indicators for preventing hospital harms in low risk births: a scoping review protocol
Authors: Conway Aislinn , Reszel Jessica , Walker Mark C , Grimshaw Jeremy M , Dunn Sandra I
Published: April 2020

Introduction

Optimising the safety of obstetric patient care is a primary concern for many hospitals. Performance indicators measuring aspects of patient care processes can lead to improvements in health systems and the prevention of harm to the patient. We present our protocol for a scoping review to identify indicators for obstetric safety in low risk births. We aim to identify indicators addressing preventable hospital harms, to summarise the data and synthesise results.

Methods and analysis

We will use methods described by Arksey and O’Malley and further expanded by Levacet al. We will search electronic databases such as Medline, Embase, CINAHL and the Cochrane Library, and websites from professional bodies and other organisations, using an iterative search strategy.

Two reviewers will independently screen titles and abstracts of search results to determine eligibility for inclusion. If eligibility is not clear, the reviewers will screen the full text version. If reviewers’ decisions regarding eligibility differ, a third reviewer will review the record. Two reviewers will independently extract data from records that meet our inclusion criteria using a standardised data collection form. We will narratively describe quantitative data, such as the frequency with which indicators are identified, and conduct a thematic analysis of the qualitative data. We will compile a comprehensive list of patient safety indicators and organise them according to concepts that best suit the data such as the Donabedian model or the Hospital Harm Framework. We will discuss the implications for future research, clinical practice and policy-making. We will report the conduct of the review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist.

Ethics and dissemination

The sources of information included in this scoping review will be available to the public. Therefore, ethics approval is not warranted. We will disseminate results in a peer-reviewed publication, conference/event presentation(s) and stakeholder communications.
Reducing readmissions and improving patient experience following urological surgery, through early telephone follow-up
Authors: Nettleton Jeremy , Jelski Joseph , Ahmad Adnan
Published: April 2020

Readmission from urological surgery is common, with a readmission rate for day case surgery of 3.7% and 26% for robot-assisted cystectomy. Readmission to secondary care and representation to primary care are both expensive and preventable. This project aimed to reduce both and also enhance the care of patients following urological surgery in a large tertiary referral centre, within the National Health Service. A retrospective telephone follow-up (TFU) survey was set up in the early postoperatively period to measure reattendance and readmission rates and perception of care received. Patients were also asked to suggest how improvement could be made. Quality improvement tools were used to optimise and review the methods and timing of TFU. TFU was initiated as a strategy to enhance care and reduce readmission rates. Phone calls were targeted to occur between 48 and 72 hours following discharge. During the intervention period, 484 phone calls were attempted with 343 being successful. Reattendance rates were reduced by 13% and patient satisfaction improved by 19.6%, following TFU. This intervention also generated additional income for the organisation and enhanced patient satisfaction in the early postoperative period.
COVID-19 and immunomodulation in IBD
Authors: Neurath Markus F
Published: April 2020

The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.
Gamma-glutamyl transferase variability and the risk of hospitalisation for heart failure
Authors: Hong So-hyeon , Lee Ji Sung , Kim Jung A , Lee You-Bin , Roh Eun , Yu Ji Hee , Kim Nam Hoon , Yoo Hye Jin , Seo Ji A , Kim Sin Gon , Kim Nan Hee , Baik Sei Hyun , Choi Kyung Mook
Published: April 2020

Objective

Gamma-glutamyl transferase (GGT) is associated with oxidative stress, inflammation, cardiovascular disease and mortality. Variability in metabolic parameters has recently emerged as an indicator of adverse health outcomes, including heart failure (HF).

Methods

We investigated whether GGT variability was associated with the incidence of hospitalisation for heart failure (HHF) in a Korean population without previous HF, ischaemic heart disease or liver disease. This longitudinal cohort study analysed 119 201 individuals from the Korean National Health Insurance Service-National Health Screening Cohort. GGT variability was calculated as the coefficient of variation (CV), SD and variability independent of the mean (VIM).

Results

During the 8.4 years of follow-up, 1387 cases of HHF (1.16%) developed. In the multivariable-adjusted model, the HR of HHF was 1.22 (95% CI 1.05 to 1.42) in the highest quartile of GGT variability compared with the lowest quartile, as assessed by CV after adjusting for confounding factors, including alcohol consumption and mean GGT levels. Consistent results were obtained using other indices of GGT variability such as SD (HR 1.37, 95% CI 1.16 to 1.62) and VIM (HR 1.29, 95% CI 1.11 to 1.50). In a subgroup analysis stratified by risk factor variables, although a similar relationship was observed, it was more prominent in individuals with dyslipidaemia.

Conclusions

The results of the present study demonstrated that variability in GGT was independently associated with the incidence of HHF. These findings suggest that higher GGT variability may be useful as an indicator of future risk of HF.
Cerebrovascular events after transcatheter mitral valve interventions: a systematic review and meta-analysis
Authors: Châteauneuf Gabriel , Nazif Tamim M , Beaupré Frédéric , Kodali Susheel , Rodés-Cabau Josep , Paradis Jean-Michel
Published: April 2020

Objective

Current guidelines support the use of transcatheter mitral valve interventions to treat some selected high-risk patients with significant mitral valvulopathy. As with any other interventional cardiac procedure, concerns have been raised about cerebrovascular event. The aim of this systematic review and meta-analysis was to determine the incidence of cerebrovascular events following (1) transcatheter mitral valve edge-to-edge repair with mitral valve clip and (2) transcatheter mitral valve replacement (TMVR).

Methods

We conducted a systematic review of studies reporting the cerebrovascular adverse events after transcatheter mitral valve edge-to-edge repair and TMVR procedures. The primary endpoint was the incidence of cerebrovascular events as defined by the Mitral Valve Academic Research Consortium. An event that occurred within 30 days or during index hospitalisation was defined as periprocedural; otherwise it was defined as non-periprocedural. This study was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Aggregated study-level data were pooled using a random effect model. The quality of each study was appraised with the Hawker checklist, a method of systematically reviewing research from different paradigms.

Results

Sixty studies totalling 28 155 patients undergoing edge-to-edge repair with mitral valve clip were included in the analysis. Periprocedural stroke and non-periprocedural stroke rates were 0.9% (95% CI 0.6 to 1.1) and 2.4% (95% CI 1.6 to 3.2), respectively. For TMVR procedures, 26 studies including 1910 patients were analysed. The estimated periprocedural stroke incidence was 1% (95% CI 0.5 to 1.8) compared with 7% (95% CI 0.8 to 18.5) for non-periprocedural stroke.

Conclusions

Transcatheter mitral valve interventions are associated with low rates of cerebrovascular events. The exact mechanisms of these complications are still poorly understood given the relative paucity of good quality data.

Trial registration number

CRD42019117257.
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma
Authors: Liu Sai-Lan , Bian Li-Juan , Liu Ze-Xian , Chen Qiu-Yan , Sun Xue-Song , Sun Rui , Luo Dong-Hua , Li Xiao-Yun , Xiao Bei-Bei , Yan Jin-Jie , Lu Zi-Jian , Yan Shu-Mei , Yuan Li , Tang Lin-Quan , Li Jian-Ming , Mai Hai-Qiang
Published: April 2020

Background

The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).

Methods

Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients.

Results

Eight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed.

Conclusions

The immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.
Decrease in tumor content assessed in biopsies is associated with improved treatment outcome response to pembrolizumab in patients with rare tumors
Authors: Tapia Coya , Aung Phyu P. , Roy-Chowdhuri Sinchita , Xu Mingxuan , Ouyang Fengying , Alshawa Anas , Hajjar Joud , Singh Gopal , Yang Vincent , Castillo Lilibeth , Le Hung , Murthy Ravi , Stephen Bettzy , Hess Kenneth R , Wistuba Ignacio , Naing Aung
Published: April 2020

Background

Decreased tumor content (TC) in resection specimens after neoadjuvant therapy is used to predict prognosis. We investigated whether TC assessed in biopsy specimens or the shift in TC from baseline to on-treatment can be used accordingly to predict response in patients with rare tumors who were treated with pembrolizumab.

Methods

A total of 57 tumors (represented by 173 baseline and 179 on-treatment biopsies) from 57 patients with rare tumors participating in an ongoing phase II clinical trial of pembrolizumab were evaluated. TC was estimated on H&E-stained slides and tumors were dichotomized into low and high TC according to a cut-off of 10%. Necrosis, proliferative fibrosis (PF) and normal tissue were assessed in on-treatment biopsies. TC at baseline and on-treatment, as well as the shift in TC from baseline to on-treatment, was correlated with clinical response defined according to Response Evaluation Criteria in Solid Tumors.

Results

A decrease in TC was seen in 14% (n=8); no change in TC was seen in 75% (n=43); and an increase in TC from baseline to on-treatment was seen in 11% (n=6). Objective response was significantly associated with decrease in TC from baseline to on-treatment (38%, 3/8) compared with no change/increase in TC (6%, 3/49) (p=0.031). Patients with a decrease in TC had a significantly increased time to progression (TTP) (75% probability) compared with patients with an increase (20% probability) or no change in TC (19% probability) (p=0.0042). Low TC was seen in 23% (13/57) of the tumors at baseline and in 26% (15/57) on-treatment. High TC was seen in 77% (44/57) of tumors at baseline and in 74% (42/57) on-treatment. No significant associations with response were seen for necrosis, PF or normal tissue in on-treatment biopsies.

Conclusion

Patients with a decrease in TC from baseline to on-treatment had a significant improvement in objective response and a longer TTP. Our data suggest that the shift in TC might be used to predict response to pembrolizumab in rare tumors. However, further investigations in larger cohorts are needed to determine the clinical value of TC, the shift in TC and the cut-off of 10% assessed in biopsies.

Trial registration number

NCT02721732
Inhibition of TGF-β-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer
Authors: Stüber Tanja , Monjezi Razieh , Wallstabe Lars , Kühnemundt Johanna , Nietzer Sarah Louise , Dandekar Gudrun , Wöckel Achim , Einsele Hermann , Wischhusen Jörg , Hudecek Michael
Published: April 2020

Background

Immunotherapy with chimeric antigen receptor (CAR)-engineered T-cells is effective in some hematologic tumors. In solid tumors, however, sustained antitumor responses after CAR T-cell therapy remain to be demonstrated both in the pre-clinical and clinical setting. A perceived barrier to the efficacy of CAR T-cell therapy in solid tumors is the hostile tumor microenvironment where immunosuppressive soluble factors like transforming growth factor (TGF)-β are thought to inhibit the cellular immune response. Here, we analyzed whether CAR T-cells specific for the receptor tyrosine kinase-like orphan receptor 1 (ROR1) antigen, that is frequently expressed in triple-negative breast cancer (TNBC), are susceptible to inhibition by TGF-β and evaluated TGF-β-receptor signaling blockade as a way of neutralizing the inhibitory effect of this cytokine.

Methods

CD8+and CD4+ROR1-CAR T-cells were prepared from healthy donors and their antitumor function analyzed using the TNBC cell line MDA-MB-231 in vitro and in a microphysiologic 3D tumor model. Analyses were performed in co-culture assays of ROR1-CAR T-cells and MDA-MB-231 cells with addition of exogenous TGF-β.

Results

The data show that exposure to TGF-β engages TGF-β-receptor signaling in CD8+and CD4+ROR1-CAR T-cells as evidenced by phosphorylation of small mothers against decapentaplegic homolog 2. In the presence of TGF-β, the cytolytic activity, cytokine production and proliferation of ROR1-CAR T-cells in co-culture with MDA-MB-231 TNBC cells were markedly impaired, and the viability of ROR1-CAR T-cells reduced. Blockade of TGF-β-receptor signaling with the specific kinase inhibitor SD-208 was able to protect CD8+and CD4+ROR1-CAR T-cells from the inhibitory effect of TGF-β, and sustained their antitumor function in vitro and in the microphysiologic 3D tumor model. Combination treatment with SD-208 also led to increased viability and lower expression of PD-1 on ROR1-CAR T-cells at the end of the antitumor response.

Conclusion

We demonstrate the TGF-β suppresses the antitumor function of ROR1-CAR T-cells against TNBC in preclinical models. Our study supports the continued preclinical development and the clinical evaluation of combination treatments that shield CAR T-cells from TGF-β, as exemplified by the TGF-β-receptor kinase inhibitor SD-208 in this study.
Homozygous variants in SYCP2L cause premature ovarian insufficiency
Authors: He Wen-Bin , Tan Chen , Zhang Ya-Xin , Meng Lan-Lan , Gong Fei , Lu Guang-Xiu , Lin Ge , Du Juan , Tan Yue-Qiu
Published: April 2020

Background

The genetic causes of the majority of cases of female infertility caused by premature ovarian insufficiency (POI) are unknown.

Objective

To identify the genetic causes of POI in 110 patients.

Methods

Whole-exome sequencing was performed on 110 patients with POI, and putative disease-causative variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed for functional characterisation of the identified candidate disease-causative variants.

Results

We identified two homozygous variants (NM_001040274: c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in SYCP2L in two patients, which had co-segregated with POI in these families. Bioinformatic analysis predicted that the two variants are deleterious, and in vitro functional analysis showed that mutant SYCP2L proteins exhibited mislocalisation and loss of function.

Conclusions

SYCP2L is a novel gene found to be responsible for human POI. Our findings provide a potential molecular marker for POI and improve the understanding of the genetic basis of female infertility.
Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lprmice
Authors: Fortner Karen A , Blanco Luz P , Buskiewicz Iwona , Huang Nick , Gibson Pamela C , Cook Deborah L , Pedersen Hege L , Yuen Peter S T , Murphy Michael P , Perl Andras , Kaplan Mariana J , Budd Ralph C
Published: April 2020

Objectives

Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants.

Methods

Lupus-prone MRL-lprmice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function.

Results

MitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody .

Conclusions

These findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus.