bluuebunny/crossref_metadata_2025 huggingface dataset:
A scoping review of Clinical Studies, Hospital Group Reports and National Strategic Documents on vascular access devices in cancer patients
Authors: Clesham Jennifer , Reynolds Helen , Carr Peter J
Published: September 2021

Introduction:

The extent of vascular/venous access device (VAD) research output from the Island of Ireland is unknown. The identification of the papers available is important to create a future research agenda.

Objectives:

The main objective of this study is to answer three questions: What is the number and descriptive quality of reported Vascular Access Device literature from the Island of Ireland? Is the reporting of Catheter Related Infection rates for cancer patients common in Irish Hospital Groups, National Cancer Reports and Publication Outputs? What are the implications for future research in this area?

Methods:

We used a scoping review and searched selected databases, grey literature and hospital regulatory bodies websites following the Joanna Briggs Institute Guidelines 2017. A data charting form was developed based on a template from the Joanna Briggs Institute and this was used to extract data from the included reports.

Results:

A total of 660 reports were screened. Sixty-one full text articles were reviewed from which 20 reports were included for data extraction. Of the reports included the following designs were used: nine retrospective study designs, four guidelines, two prospective study designs, two literature reviews and one of the following; survey, case study and cross sectional analysis designs. We did not identify any randomised controlled trials, systematic reviews, meta-analysis, meta-synthesis and scoping reviews. Five studies included catheter related infection rates. Gaps in the research include the collection of data sets and the need to establish a VAD registry; develop core outcomes for VADs; assessment and evaluation of VAD care bundles among cancer patients; and, the inclusion of public and patient involvement in future VAD research.

Conclusion:

The reporting of VAD outcomes in published literature regarding cancer patients receiving treatment in Ireland is inconsistent and varied with no interventional studies addressing vascular access complications in cancer care.
Antiviral effect of Artemisia aucheri aqueous extract on UL46 and US6 genes of HSV-1
Authors: Zamanian Mahsa , Sharifi Zohreh , Noormohammadi Zahra , Akbarzadeh Tahmineh , Bineshian Farahnaz
Published: September 2021

HSV-1 is associated with oral lesions. Recently, anti-herpetic activity of different plant species has been investigated. In this study, the effects of Artemisia aucheri aqueous extract on the HSV-1 virus-infected Vero cells were assessed. The highest cell viability occurred in plant aqueous extracts was with a concentration of 75 μg/mL, 1–2 h before viral infection. The IC50 of the aqueous extract of 24.7 μg/ml was calculated. Most percentage of infected cell inhibition (89.6%) was with the chloroform fraction in concentration of 75 μg/ml, and the least percentage of infected cell inhibition (21.7%) was in concentration of 12.5 μg/ml with the ethyl acetate fraction in comparison with untreated control. Moreover, Q-PCR results revealed that the expression of genes UL46 and US6 were significantly reduced in the presence of different treatments utilized in the experiment. In conclusion, the present study proposes that aqueous extracts of medicinal plant Artemisia aucheri have anti-viral property and may be considered as a remedy for HSV-1 treatment.
Silencing the single woman: Negotiating the ‘failed’ feminine subject in contemporary UK society
Authors: Gilchrist Kate R
Published: September 2021

Despite a growth in single women in UK society over the past two decades, single femininity continues to be highly stigmatised. Drawing on Judith Butler’s theory of the heterosexual matrix and applying this to qualitative interview data with 25 single women, I argue that single femininity is produced as abject through processes of silencing which render the single female a ‘failed’ subject and reinscribe heteronormative coupled femininity. Yet while deeply painful, such ‘failures’ may also be productive, offering moments where the boundaries of heteronormative feminine subjectivity and hierarchies of intimate life are troubled and transformed. This article complicates understandings of stigma and resistance through a nuanced analysis of processes of abjectification and ambivalence.
Modal analysis and experimental investigation into vibration of the diamond-beaded rope based on lumped mass
Authors: Fu Mengguang , Zhang Peng , Wang Fei
Published: September 2021

The natural vibration characteristics of the diamond-beaded rope (DBR) based on lumped mass are analyzed both theoretically and experimentally. The dynamic model of the DBR is established by means of the multi-body dynamics theory. According to Lagrange’s equations, the control equation of the DBR is derived. It mainly analyzes the influence of the parameters, such as the motion velocity of the DBR, the tension of the DBR, the length of diamond beads, the quality of diamond beads, and their position in the DBR, on the natural vibration characteristics for the DBR are studied. The results show that the natural frequencies and the corresponding vibration shapes of the DBR based on lumped mass change significantly when the variations of the above parameters are considered. In the process of the movement of the DBR, the random impact force of diamond beaded is the key factor that causes the natural frequency of the DBR to fluctuate., In the high-order modal analysis, the natural frequency and vibration mode of the DBR fluctuate more obviously. The relative error of the result between the calculated and the measured is less than 10%, which validates the proposed method.
An analysis on reporting pattern of People’s Daily’s international news coverage: The case of Sino-Japan summit meeting since the normalization of relations between Sino-Japan
Authors: Xinhui Zhang
Published: September 2021

To study the international news reporting patterns of the Chinese media, this research provides a longitudinal analysis of the news coverage of Sino-Japan summit meetings from 1972 to 2019 in the People’s Daily. Based on the framing theory, the results of the analysis show that different aspects of the summit are selected to be covered in the news depending on the Chinese government’s policy towards Japan in different time periods. However, the news coverage itself has maintained a high degree of consistency. Before the period of reform and the opening up of China, there was no mention of the summit meetings’ content; reports only introduced the date, location and attendees. After the reform, information reported about the summit meetings increased and the coverage began including quotations from both the Chinese and Japanese heads of state; at the same time, reports adopted a ‘propagandized’ text editing mode by quoting more from Chinese leaders than Japanese leaders. Furthermore, the People’s Daily framed the Chinese government’s attempts to stabilize and develop Sino-Japanese relations over time.
Journalism as a profession of conditional permeability: A case study of boundaries in a participatory online news setting
Authors: Riedl Martin Johannes
Published: September 2021

Journalistic professionalism serves as a semantic tool for journalists to draw boundaries and to demarcate their profession. This research builds on Andrew Abbott’s book The System of Professions: An Essay on the Division of Expert Labor, and his assessment of journalism as a ‘permeable occupation’. By way of a strategic case study of a German-language news organization, it puts forth the notion of journalism as a profession of conditional permeability in certain participatory online settings. This research traces how journalists at a case organization used professionalism to delineate their own job from two groups of interlopers in online news spaces: Community managers tasked to moderate user comments, as well as audience members who participate by way of commenting on the news. The study draws on a case study of a market leader and early adopter in community management and comment moderation – with evident limitations as far as generalization to other contexts. Journalists used concepts deeply entrenched with journalistic professionalism, such as writing skills, gatekeeping and the application of news judgment to invoke boundaries between professionals and nonprofessionals, but also acknowledged unboundedness within particular subdomains of their work. While journalists asserted control over a journalistic epistemology, practice was partly open for other professionals, such as community managers, but closed for nonprofessionals. Some identified a hierarchy of professions, with community management serving an assistant function to journalism. The concept of conditional permeability accommodates both blurred boundaries towards other professional actors and distinct boundaries towards nonprofessional actors.
Safety performance assessment of a marine dual fuel engine by integrating failure mode, effects and criticality analysis with simulation tools
Authors: Stoumpos Sokratis , Bolbot Victor , Theotokatos Gerasimos , Boulougouris Evangelos
Published: September 2021

Marine Dual Fuel engines have been proved an attractive solution to improve the shipping industry sustainability and environmental footprint. Compared to the conventional diesel engines, the use of additional components to accommodate the natural gas feeding is associated with several safety implications. To ensure the engine safe operation, appropriate engine control and safety systems are of vital importance, whilst potential safety implications due to sensors and actuators faults or failures must be considered. This study aims at investigating the safety issues of a marine dual fuel (DF) engine considering critical operating scenarios, which are identified by employing a Failure Mode, Effects and Criticality Analysis. An existing verified digital twin (DT) of the investigated DF engine, capable of predicting the engine response at steady state and transient conditions with sufficient accuracy is employed to simulate the engine operation for the identified scenarios. The simulated scenarios results analysis is used to support the risk priority number assessment and identify the potential safety implications by considering the manufacturer alarm limits. Appropriate measures are recommended for the investigated DF engine safety performance improvement. This study demonstrates a methodology integrating existing safety methods with state-of-the-art simulation tools for facilitating and enhancing the safety assessment process of marine DF engines considering both steady state conditions and transient operation with main focus on switching operating modes.
Numerical investigation of interaction between propulsion system behaviour and manoeuvrability of a large containership
Authors: Tu Huan , Chen Hui
Published: September 2021

In actual operation process of a ship, the engine-propeller-hull is an integrated system with internal coupling effects, and thus there is a close interaction between the diesel engine propulsion system operation conditions and the ship manoeuvring motions. The propulsion system can experience large power fluctuation during manoeuvring, with considerable torque increase with regard to the stabilized value in straight course. However, the diesel engine propulsion system behaviour and ship manoeuvrability are usually studied separately as they are considered to belong to different disciplines. Thus, it is difficult to reflect the actual operating characteristics of the propulsion system and ship manoeuvring motion under coupled conditions in actual operation. To investigate the interaction between the propulsion system behaviour and the manoeuvrability of a large containership, this paper proposed a multi-disciplinary ship mobility model capable of coupling the marine diesel engine model and the ship manoeuvring model. In the engine model, the mean value modelling approach was adopted to simulate the two-stroke marine diesel engine considering the fact that it can capture the performance of the engine sub-systems including scavenging receiver, exhaust gas receiver, turbocharger, etc. In the manoeuvring model, the MMG-based method was used to simulate the ship manoeuvring motion with three degrees-of-freedom. The engine model and manoeuvring model were coupled through the propeller model that transferring propeller speed and torque between the two models. The coupled model was validated against the engine shop test data and the sea trial results. By applying this coupled model, a series of simulations of turning circle manoeuvres under various scenarios were performed. The simulation results presented the dynamic response of engine internal sub-systems during turning circle manoeuvring, explained the effect of the torque limiter on engine performance and ship manoeuvring motion, and analyse the influence of different propulsion system control strategies on the ship turning circle manoeuvrability. Although the presented case study has been validated on a specific ship, most of the discussed models have a general application.
Move fast and break teachers, or what if Facebook bought Pearson?
Authors: Kupferman David W.
Published: September 2021

This study takes a short trip into the near future to see what happens if Facebook bought the global education corporation Pearson. It takes a prefactual stance, meaning that it is responding to and extrapolating from an event that has not yet happened, but very probably could. The theoretical framework of this piece is futures studies, specifically educational futures, to take contemporary education policy issues and imagine what happens to them when they encounter our present-day anxieties of the future of society. Responding to the call for a creative turn in educational futures, the study uses a narrative approach to considerations of a probable future in which Mark Zuckerberg decides to stop donating hundreds of millions of dollars to various schooling projects and instead purchases Pearson's monopoly in the areas of teacher testing and licensing. In this way, Facebook exerts a level of control over teacher preparation that, while frightening, could very well come to pass. This piece also hopes to contribute to the development of educational dystopia as academic literature.
A research on the mechanism and model of surface micro-damage in grinding hardening
Authors: Shi Xiaoliang , Zhang Xiuming , Xiu Shichao
Published: September 2021

Grinding hardening can obtain hardening effect besides fine machining effect on the surface of workpiece. A certain degree of surface micro-damage will be formed during grinding hardening process which mainly contains micro-crack, melting coating, decarburization, and surface scratch. In order to study the micro-damage of grinding hardening, the paper carries on a grinding hardening experiment and the characteristics of micro-damage are observed. The generation mechanism of micro-crack is revealed. It is formed by the accumulation of dislocation pile-up in the condition of grinding hardening process. When the grinding depth reaches a certain value, the surface micro-crack will be produced obviously and become more serious with the increasing of grinding depth. Other micro-damage containing surface melting coating, decarburization, and surface scratch are also studied and their relevance with micro-crack is revealed. Based on the grinding hardening theory and pile-up dislocation theory, a model for micro-crack of grinding hardening is established. The calculating result of the model accords with the experimental result in general.
Design of a novel inchworm in-pipe robot based on cam-linkage mechanism
Authors: Xie Qizhi , Liu Songyong , Ma Xiliang
Published: September 2021

This paper presents a novel double-direction inchworm in-pipe robot, called the Cam-Linkage Robot (CLR), used to carry sensors and instruments to perform inspection and cleaning jobs inside pipelines. The prototype has been developed to improve the driving ability and reduce the difficulty of control. CLR is suitable for pipe diameters from 360 mm to 400 mm due to its functions of manual adjustment and automatic adaptation. The structure of CLR was presented and some critical design issues on the principle of cam-linkage mechanism were discussed. Based on cam-linkage mechanism, CLR could press the wall actively and creep in two directions via only one motor, so this research has broken the limitation that traditional active wall-press robot needs more than one actuator. The cam pressure angle could be reduced to 0, and the propulsion ability was almost not weakened by the support motion at the stable support stage. Finally, experiments were conducted to validate the locomotion principle and the effectiveness of CLR.
The influence of fracture location and comminution on acute scaphoid fracture displacement: three-dimensional CT analysis
Authors: Bulstra Anne Eva J. , Al-Dirini Rami M. A. , Turow Arthur , Oldhoff Miriam G. E. , Bryant Kimberley , Obdeijn Miryam C. , Doornberg Job N. , Jaarsma Ruurd L. , Bain Gregory I.
Published: September 2021

We aimed to assess the influence of fracture location and comminution on acute scaphoid fracture displacement using three-dimensional CT. CT scans of 51 adults with an acute scaphoid fracture were included. Three-dimensional CT was used to assess fracture location, comminution and displacement. Fracture location was expressed as the height of the cortical breach on the volar and dorsal side of the scaphoid relative to total scaphoid length (%), corresponding to the fracture’s entry and exit point, respectively. We found a near-linear relation between dorsal fracture location and displacement. As dorsal fracture location became more distal, translation (ulnar, proximal, volar) and angulation (flexion, pronation) of the distal fragment relative to the proximal fragment increased. Comminuted fractures had more displacement. Dorsal fracture location predictably dictates the direction of translation and angulation in displaced scaphoid fractures. Surgeon attention to dorsal fracture location can help identify displacement patterns and provide guidance in adequately reducing a displaced scaphoid fracture.

Level of evidence: III
Acne vulgaris
Authors: Pathak Anjali , Dattani Anusha
Published: September 2021

Acne vulgaris (acne) is a multi-factorial chronic inflammatory skin disease that is encountered frequently in general practice, accounting for over 3 500 000 annual consultations in the UK. It has an estimated global prevalence of 9.4%; and is often considered a teenage affliction, impacting virtually all adolescents to some extent. Nevertheless, it is surprisingly common in the adult population, affecting 8% of those aged 25–34 years and 3% of adults aged 35–44 years. This article explores key aspects of diagnosis and management, and considers specific scenarios such as pregnancy and transgender patients as well as the importance of psychosocial support and holistic care.
Comparison of routine blood alcohol tests and ICD-10-AM coding of alcohol involvement for major trauma patients
Authors: Lau Georgina , Gabbe Belinda J , Mitra Biswadev , Dietze Paul M , Braaf Sandra , Beck Ben
Published: September 2021

Background:

Alcohol use is a key preventable risk factor for serious injury. To effectively prevent alcohol-related injuries, we rely on the accurate surveillance of alcohol involvement in injury events. This often involves the use of administrative data, such as International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) coding.

Objective:

To evaluate the completeness and accuracy of using administrative coding for the surveillance of alcohol involvement in major trauma injury events by comparing patient blood alcohol concentration (BAC) with ICD-10-AM coding.

Method:

This retrospective cohort study examined 2918 injury patients aged ≥18 years who presented to a major trauma centre in Victoria, Australia, over a 2-year period, of which 78% ( n = 2286) had BAC data available.

Results:

While 15% of patients had a non-zero BAC, only 4% had an ICD-10-AM code suggesting acute alcohol involvement. The agreement between blood alcohol test results and ICD-10-AM coding of acute alcohol involvement was fair ( κ = 0.33, 95% confidence interval: 0.27–0.38). Of the 341 patients with a non-zero BAC, 82 (24.0%) had ICD-10-AM codes related to acute alcohol involvement. Supplementary factors Y90 Evidence of alcohol involvement determined by blood alcohol level codes, which specifically describe patient BAC, were assigned to just 29% of eligible patients with a non-zero BAC.

Conclusion:

ICD-10-AM coding underestimated the proportion of alcohol-related injuries compared to patient BAC.

Implications:

Given the current role of administrative data in the surveillance of alcohol-related injuries, these findings may have significant implications for the implementation of cost-effective strategies for preventing alcohol-related injuries.
C.A.R.E. in Natural Products Research
Authors: Cordell Geoffrey A.
Published: September 2021

The acronym C.A.R.E. is used to explore some of the parameters in creating research awareness in the contemporary natural product sciences and to encourage graduate students, postdoctoral fellows, and junior faculty to develop good research practices and ethical awareness in developing excellence in their individual and collaborative research programs.
Adventures with Marx
Authors: Herod Andrew
Published: September 2021

An account of my journey from an English schoolboy interested in landscapes to academic geographer, and the role that my engagement with Marx has played in that intellectual odyssey.
Cosplay on Demand? Instagram, OnlyFans, and the Gendered Fantrepreneur
Authors: Rouse Lauren , Salter Anastasia
Published: September 2021

Fan producers engaged in monetization, or what Suzanne Scott has termed “fantrepreneurs,” struggle with legal mechanisms for brand-building given the limitations of both copyright and platform moderation. These challenges have been amplified during the COVID-19 pandemic, which has fundamentally changed the way that cosplayers, or fans who dress up as characters from their favorite television shows or movies, market themselves in an increasingly online space, as opposed to their initial public platforms of conventions. Restricted by digital platforms and their various moderation and monetization methods, cosplayer fantrepreneurs have developed new, multi-platform methods for sustaining their content and community connection. One prominent platform significant to this turn is OnlyFans, which is billed as a “peer-to-peer subscription app,” and allows users to “Sign up and interact with your fans!” Through a sample analysis of 50 cosplayers, this case study considers the approaches of cosplayers on integrating OnlyFans as part of a multiplatform struggle for economic viability. When we contextualize this platform labor in the history of cosplay, we note the hypersexualized labor that has always been central to monetization in this space, and the media franchise exploitation that profits from that labor at the expense of the fan producer, demonstrating the fundamental, gendered exploitation of the trend toward a patronage economy.
Epidemiology of Spine Injuries in National Collegiate Athletic Association Men’s Wrestling Athletes
Authors: Brinkman Joseph C. , Tummala Sailesh V. , McQuivey Kade S. , Hassebrock Jeffrey D. , Pagdilao Christian , Makovicka Justin L. , Chhabra Anikar
Published: September 2021

Background:

Spine injuries are common in collegiate wrestlers and can lead to reinjury, persistent pain, and time lost from participation.

Purpose:

To describe the epidemiology of spine injuries in National Collegiate Athletic Association (NCAA) wrestlers between academic years 2009 to 2010 and 2013 to 2014.

Study Design:

Descriptive epidemiology study.

Methods:

The incidence and characteristics of spine injuries were identified utilizing the NCAA–Injury Surveillance Program database. Spine injuries were assessed for injury type, injury mechanism, time of season, event type, recurrence, participation restriction, and time lost from participation. Rates of injury were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). Injury rate ratios (IRRs) were calculated for event type and time of season, and results with 95% confidence intervals that did not include 1.0 were considered statistically significant.

Results:

There were an estimated 2040 spine injuries reported in the database over the 4-year period, resulting in an injury rate of 0.71 per 1000 AEs.  Spine injuries were over twice as likely to occur in competitions as in practices (IRR, 2.02; 95% confidence interval, 1.10-3.69). More injuries occurred in both the preseason (0.94 per 1000 AEs) and the postseason (1.12 per 1000 AEs) compared with the regular season (0.55 per 1000 AEs). Contact injuries (42%) were the most common mechanism of injury, and brachial plexus injury (20%) was the most common diagnosis. Only 1.3% of injuries required surgery, and athletes most commonly returned to sport within 24 hours (33%) or within 6 days (25%).

Conclusion:

This investigation found an overall injury rate of 0.71 per 1000 AEs in wrestling athletes between academic years 2009 to 2010 and 2013 to 2014. The majority of these injuries were new, and athletes most commonly returned to sport within 24 hours. The injury rate was highest in competition, and both the preseason and the postseason showed a higher injury rate than that in season. Efforts to improve injury prevention and management should be informed by these findings.
Measuring Meaningful Benefit-Risk Tradeoffs to Promote Patient-Focused Drug Development in Prader-Willi Syndrome: A Discrete-Choice Experiment
Authors: Tsai Jui-Hua , Crossnohere Norah L. , Strong Theresa , Bridges John F. P.
Published: September 2021

Background. Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder causing quality of life impairments such as insatiable hunger (hyperphagia) and obesity. We explored caregivers’ willingness to assume treatment risk in exchange for reduced hyperphagia according to a PWS-validated observer-reported outcome measure. Methods. We partnered with PWS patient organizations to develop a discrete-choice experiment exploring caregivers’ benefit-risk tradeoffs for emerging PWS treatments. The treatment benefit was a reduction in hyperphagia (as measured by a 0-, 5-, or 10-point change on the Hyperphagia Questionnaire for Clinical Trials [HQ-CT]). Treatment risks included weight gain (none, 5%, 10%), added risk of skin rash (none, 10%, 20%), and risk of liver damage (none, 1 in 1000, 10 in 1000). Preference models were estimated using mixed logistic regression and maximum acceptable risk. We explored differences in preferences across familial caregivers of patients with and without hyperphagia. Results. Four hundred sixty-eight caregivers completed the online survey. The majority of caregivers reported that patients experienced hyperphagia (68%) and half of patients experienced obesity (52%). Caregivers of patients without hyperphagia were willing to accept greater weight gain (16.4% v. 8.1%, P = 0.004) and a higher risk of skin rash (11.7% v. 6.2% P = 0.008) as compared to caregivers of patients with hyperphagia. Caregivers of patients with hyperphagia would accept a higher risk of liver damage as compared to caregivers of patients without hyperphagia (11.9 out of 1000 v. 6.4 out of 1000, P = 0.04). Conclusions. This research demonstrates that caregivers are willing to accept risk in exchange for a five-point improvement on the HQ-CT, a smaller marginal improvement than had been previously classified as meaningful. Patient experience with hyperphagia is a modifier in how much risk caregivers will accept.
Systemic antiplatelet agents and anticoagulants in eyes with branch retinal vein occlusion
Authors: Singh Pali P. , Borkar Durga S. , Robbins Cason B. , Kim Jane S. , Birnbaum Faith , Gomez-Caraballo Maria , Thomas Akshay S. , Fekrat Sharon
Published: September 2021

Purpose:

The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO).

Methods:

A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded.

Results:

A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents.

Conclusion:

Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit.
A Qualitative Analysis of Unethical Behaviors in Projects: Insight From Moral Psychology
Authors: Sarhadi Mehrdad , Hasanzadeh Sogand
Published: September 2021

Ethical aspects of stakeholder behavior can have a wide range of implications for other areas of project management. This research critically reviewed project ethics under the philosophical paradigm change from modernism to late modernism, which led to a flexible and realizable ethical framework based on Levinasian and Nietzschean moral psychologies. A qualitative approach was adopted through a multiple-case study to confront the theoretical framework with the empirical world, evaluate its authenticity, and obtain a better understanding of its challenges. Research results showed that stakeholders’ unconscious desire for existential meaning can provide considerable potential for dealing with ethical challenges.
Multiparameter phenotyping of platelet reactivity for stratification of human cohorts
Authors: Dunster Joanne L. , Bye Alexander P. , Kriek Neline , Sage Tanya , Mitchell Joanne L. , Kempster Carly , Batista Joana , McKinney Harriet , Thomas Patrick , Jones Chris I. , Downes Kate , Unsworth Amanda J. , Gibbins Jonathan M.
Published: September 2021

Accurate and comprehensive assessment of platelet function across cohorts of donors may be key to understanding the risk of thrombotic events associated with cardiovascular disease, and, hence, to help personalize the application of antiplatelet drugs. However, platelet function tests can be difficult to perform and analyze; they also can be unreliable or uninformative and poorly standardized across studies. The Platelet Phenomic Analysis (PPAnalysis) assay and associated open-source software platform were developed in response to these challenges. PPAnalysis utilizes preprepared freeze-dried microtiter plates to provide a detailed characterization of platelet function. The automated analysis of the high-dimensional data enables the identification of subpopulations of donors with distinct platelet function phenotypes. Using this approach, we identified that the sensitivity of a donor’s platelets to an agonist and their capacity to generate a functional response are distinct independent metrics of platelet reactivity. Hierarchical clustering of these metrics identified 6 subgroups with distinct platelet phenotypes within healthy cohorts, indicating that platelet reactivity does not fit into the traditional simple categories of “high” and “low” responders. These platelet phenotypes were found to exist in 2 independent cohorts of healthy donors and were stable on recall. PPAnalysis is a powerful tool for stratification of cohorts on the basis of platelet reactivity that will enable investigation of the causes and consequences of differences in platelet function and drive progress toward precision medicine.
Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma
Authors: Ferrari Nicola , Ward George , Gewinner Christina , Davis Matthew P. , Jueliger Simone , Saini Harpreet , Munck Joanne , Smyth Tomoko , Ferraldeschi Roberta , Keer Harold , Lyons John , Sims Martin J.
Published: September 2021

Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. Tolinapant has demonstrated evidence of single-agent clinical activity in relapsed/refractory peripheral TCL and cutaneous TCL. To investigate the mechanism of action underlying the single-agent activity observed in the clinic, we have used a comprehensive translational approach integrating in vitro and in vivo models of TCL confirmed by data from human tumor biopsies. Here, we show that tolinapant acts as an efficacious immunomodulatory molecule capable of inducing complete tumor regression in a syngeneic model of TCL exclusively in the presence of an intact immune system. These findings were confirmed in samples from our ongoing clinical study showing that tolinapant treatment can induce changes in gene expression and cytokine profile consistent with immune modulation. Mechanistically, we show that tolinapant can activate both the adaptive and the innate arms of the immune system through the induction of immunogenic forms of cell death. In summary, we describe a novel role for IAP antagonists as immunomodulatory molecules capable of promoting a robust antitumor immune response in TCL.
Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted
Authors: Rubinstein Jeremy D. , Zhu Xiang , Leemhuis Thomas , Pham Giang , Ray Lorraine , Emberesh Sana , Jodele Sonata , Thomas Shawn , Cancelas Jose A. , Bollard Catherine M. , Hanley Patrick J. , Keller Michael D. , Grimley Olivia , Clark Diana , Clark Teri , Lindestam Arlehamn Cecilia S. , Sette Alessandro , Davies Stella M. , Nelson Adam S. , Grimley Michael S. , Lutzko Carolyn
Published: September 2021

Infection with adenoviruses is a common and significant complication in pediatric patients after allogeneic hematopoietic stem cell transplantation. Treatment options with traditional antivirals are limited by poor efficacy and significant toxicities. T-cell reconstitution is critical for the management of adenoviral infections, but it generally takes place months after transplantation. Ex vivo–generated virus-specific T cells (VSTs) are an alternative approach for viral control and can be rapidly generated from either a stem cell donor or a healthy third-party donor. In the context of a single-center phase 1/2 clinical trial, we treated 30 patients with a total of 43 infusions of VSTs for adenoviremia and/or adenoviral disease. Seven patients received donor-derived VSTs, 21 patients received third-party VSTs, and 2 received VSTs from both donor sources. Clinical responses were observed in 81% of patients, with a complete response in 58%. Epitope prediction and potential epitope identification for common HLA molecules helped elucidate HLA restriction in a subset of patients receiving third-party products. Intracellular interferon-γ expression in T cells in response to single peptides and response to cell lines stably transfected with a single HLA molecule demonstrated HLA-restricted CD4+ T-cell response, and these results correlated with clinical outcomes. Taken together, these data suggest that VSTs are a highly safe and effective therapy for the management of adenoviral infection in immunocompromised hosts. The trials were registered at www.clinicaltrials.gov as #NCT02048332 and #NCT02532452.
Characteristics of Upper and Lower Extremity Deep Vein Thrombosis and Predictors of Post-Thrombotic Syndrome in Children
Authors: Avila Laura , Amiri Nour , De Riddhita , Vincelli Jennifer , Pullenayegum Eleanor M , Williams Suzan , Brandao Leonardo R.
Published: September 2021

Background/aims: Our understanding of predictors of post-thrombotic syndrome (PTS) in children is evolving. The present study aimed to investigate differences in patient- and DVT-related characteristics between central venous catheter (CVC) and non-CVC-related thrombosis in children and to study early PTS predictors. Methods: Children aged 0-18 years were recruited ≥6 months after imaging-proven upper (UE) or lower extremity (LE) DVT. PTS was measured using CAPTSure©. Early predictors included age at DVT diagnosis, symptoms, DVT burden, and days on therapeutic anticoagulation within 30 days post-DVT. Analysis of predictors was stratified in CVC and non-CVC-related thrombosis. Generalized estimating equations were used for data analyses. Results: In total, 313 DVT-affected extremities of 256 patients were assessed; 275 (88%) DVT were CVC-related. Patients with non-CVC-related thrombosis were older (median 5.8 years, 25th-75th percentile 4.9-6.4 vs. 3.5 months, 25th-75th percentile 0.7-18.7, p<0.001), and had positive thrombophilia (64% vs 22%, p<0.001) and obesity (30% vs. 13%, p=0.01) more frequently than patients with CVC-related thrombosis. PTS CAPTSure© scores were 9.5 points higher (standard error 3.0, p=0.02) in the non-CVC-related thrombosis stratum. Age at the time of DVT predicted PTS in both strata; DVT burden and time from DVT diagnosis to PTS assessment predicted PTS in CVC-related thrombosis. Conclusions: PTS severity was higher in non-CVC-related than in CVC-related thrombosis. Increasing age at the time of DVT is associated with higher PTS severity. DVT burden and time from DVT diagnosis to PTS assessment are significant PTS predictors in CVC-related thrombosis, indicating that long-term follow up of these children is important.
Treatment of allosensitized patients receiving allogeneic transplantation
Authors: Ciurea Stefan O. , Al Malki Monzr M. , Kongtim Piyanuch , Zou Jun , Aung Fleur M. , Rondon Gabriela , Chen Julianne , Taniguchi Michiko , Otoukesh Salman , Nademanee Auayporn , Forman Stephen J. , Champlin Richard , Gendzekhadze Ketevan , Cao Kai
Published: September 2021

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.
Racial and ethnic enrollment disparities and demographic reporting requirements in acute leukemia clinical trials
Authors: Hantel Andrew , Luskin Marlise R. , Garcia Jacqueline S. , Stock Wendy , DeAngelo Daniel J. , Abel Gregory A.
Published: September 2021

Data regarding racial and ethnic enrollment diversity for acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) clinical trials in the United States are limited, and little is known about the effect of federal reporting requirements instituted in the late 2000s. We examined demographic data reporting and enrollment diversity for ALL and AML trials in the United States from 2002 to 2017, as well as changes in reporting and diversity after reporting requirements were instituted. Of 223 AML trials and 97 ALL trials with results on ClinicalTrials.gov, 68 (30.5%) and 51 (52.6%) reported enrollment by both race and ethnicity. Among trials that reported race and ethnicity (AML, n = 6554; ALL, n = 4149), non-Hispanic (NH)-Black, NH-Native American, NH-Asian, and Hispanic patients had significantly lower enrollment compared with NH-White patients after adjusting for race-ethnic disease incidence (AML odds ratio, 0.68, 0.31, 0.75, and 0.83, respectively; ALL odds ratio, 0.74, 0.27, 0.67, and 0.64; all, P ≤ .01). The proportion of trials reporting race increased significantly after implementation of the reporting requirements (44.2% to 60.2%; P = .02), but race-ethnicity reporting did not (34.8% to 38.6%; P = .57). Reporting proportions according to number of patients enrolled increased significantly after the reporting requirements were instituted (race, 51.7% to 72.7%; race-ethnicity, 39.5% to 45.4%; both, P < .001), and relative enrollment of NH-Black and Hispanic patients decreased (AML odds ratio, 0.79 and 0.77; ALL odds ratio, 0.35 and 0.25; both P ≤ .01). These data suggest that demographic enrollment reporting for acute leukemia trials is suboptimal, changes in diversity after the reporting requirements may be due to additional enrollment disparities that were previously unreported, and enrollment diversification strategies specific to acute leukemia care delivery are needed.
Cancer risk in patients with sleep apnoea following adherent 5-year CPAP therapy
Authors: Justeau Grégoire , Bailly Sebastien , Gervès-Pinquié Chloé , Trzepizur Wojciech , Meslier Nicole , Goupil François , Pigeanne Thierry , Launois Sandrine , Leclair-Visonneau Laurene , Masson Philippe , Bizieux-Thaminy Acya , Racineux Jean-Louis , Gozal David , Gagnadoux Frédéric
Published: September 2021

Background

Increasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA.

Methods

The study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk.

Results

After a median (interquartile range) follow-up of 5.4 (3.1–8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78–1.14).

Conclusions

Adherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated.
Nintedanib in progressive interstitial lung diseases: data from the whole INBUILD trial
Authors: Flaherty Kevin R. , Wells Athol U. , Cottin Vincent , Devaraj Anand , Inoue Yoshikazu , Richeldi Luca , Walsh Simon L.F. , Kolb Martin , Koschel Dirk , Moua Teng , Stowasser Susanne , Goeldner Rainer-Georg , Schlenker-Herceg Rozsa , Brown Kevin K.
Published: September 2021

Background

The primary analysis of the INBUILD trial showed that in subjects with progressive fibrosing interstitial lung diseases (ILDs), nintedanib slowed the decline in forced vital capacity (FVC) over 52 weeks. We report the effects of nintedanib on ILD progression over the whole trial.

Methods

Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice, were randomised to receive nintedanib or placebo. Subjects continued on blinded randomised treatment until all subjects had completed the trial. Over the whole trial, mean±sdexposure to trial medication was 15.6±7.2 and 16.8±5.8 months in the nintedanib and placebo groups, respectively.

Results

In the nintedanib (n=332) and placebo (n=331) groups, respectively, the proportions of subjects who had ILD progression (absolute decline in FVC ≥10% predicted) or died were 40.4% and 54.7% in the overall population (hazard ratio (HR) 0.66, 95% CI 0.53–0.83; p=0.0003) and 43.7% and 55.8% among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT) (HR 0.69, 95% CI 0.53–0.91; p=0.009). In the nintedanib and placebo groups, respectively, the proportions who had an acute exacerbation of ILD or died were 13.9% and 19.6% in the overall population (HR 0.67, 95% CI 0.46–0.98; p=0.04) and 15.0% and 22.8% among subjects with a UIP-like fibrotic pattern on HRCT (HR 0.62, 95% CI 0.39–0.97; p=0.03).

Conclusion

Based on data from the whole INBUILD trial, nintedanib reduced the risk of events indicating ILD progression.