bluuebunny/crossref_metadata_2025_split huggingface dataset:
Friction and Wear of Polyetheretherketone Samples With Different Melt Flow Indices
Authors: Tolochko Oleg V. , Kobykhno Ilya A. , Khashirova Svetlana I. , Zhansitov Azamat A. , Breki Alexander D. , Nosonovsky Michael 
Published: November 2021

Abstract
Polyetheretherketone (PEEK) is a promising polymer material for tribological applications. Friction and wear tests of PEEK samples versus steel with different melt flow indices (MFI) were studied. The results showed dependencies of the friction force on the sliding velocity, either decreasing or increasing depending on whether the normal load exceeds the yield strength of the polymer. The data can be well fitted with the assumption of the two-component friction law involving the Amontons component and an adhesional component. With a decrease in MFI, i.e., with an increase in viscosity of polymer, the adhesive component of friction increases with increasing viscosity while the abrasive wear decreases. At high loads, the plastic displacement increases with an increase in the viscosity and plasticity of the polymer. The wear does not show a clear correlation with the viscosity.
Effects of Thermal Properties of Contact Materials and Slide-Roll Ratio in Elastohydrodynamic Lubrication
Authors: Kaneta Motohiro , Matsuda Kenji , Nishikawa Hiroshi 
Published: November 2021

Abstract
The effects of thermal conductivity, heat capacity, thermal inertia, and slide-roll ratio (SRR) on point elastohydrodynamic lubrication (EHL) are discussed with engineering ceramics and steel by a non-Newtonian thermal EHL analysis. When the thermal conductivities of contacting materials are significantly different, the film thickness is greatly affected by which material has the higher velocity. However, the film thickness is dominated by the heat capacity when the difference in thermal conductivity is not large. In contact of materials with the same mechanical and thermal properties, the film thickness and friction coefficient are influenced by the thermal inertia.
Multicentre prospective observational study of sodium-glucose cotransporter-2 inhibitor-associated postoperative ketoacidosis: the SAPKA study protocol
Authors: Seki Hiroyuki , Kuratani Norifumi , Shiga Toshiya , Iwasaki Yudai , Karita Kanae , Yasuda Kazuki , Yorozu Tomoko 
Published: November 2021

IntroductionSodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycaemic agents that promote urinary glucose excretion in the renal proximal tubule and have cardio-protective and renal-protective properties. However, there are several safety concerns related to increased risks of hypoglycaemic, urinary tract infections and ketoacidosis. Ketoacidosis is a potentially fatal complication that often presents as euglycaemic ketoacidosis during SGLT2 inhibitor treatment. Furthermore, invasive treatment and related surgical stress may increase the risk of ketogenesis. Therefore, this study aims to clarify the incidence of SGLT2 inhibitor-associated postoperative ketoacidosis (SAPKA) among patients who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia.Methods and analysisThis multicentre, prospective, observational study will recruit 750 adult Japanese patients with diabetes who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. Urine samples will be collected on postoperative days 0, 1, 2 and 3. Blood gas analysis will be performed when urine ketone positivity is detected. The incidence of postoperative ketoacidosis will be identified based on urine ketone positivity and a blood pH of ≤7.3. The study will also collect data to identify risk factors for SAPKA.Ethics and disseminationThe study protocol has been approved by the ethics committee of Kyorin University (approval number: 785, 26 October 2020) and local ethical approval will be required at each participating centre. Study findings will be submitted to peer-reviewed journals and abstracts will be submitted to relevant national and international meetings.Trial registration numberUMIN000042795
Comparison of open-skill and closed-skill exercises in improving the response inhibitory ability of the elderly: a protocol for a randomised controlled clinical trial
Authors: Ke Liu , Lanlan Zhang , Jian Zhang , Jianing Wei 
Published: November 2021

IntroductionAs people age, they are more likely to experience a decline in their response inhibition ability, which interferes with daily life. Previous studies have shown that exercise intervention can improve the cognitive ability of the elderly, but research on open-skill and closed-skill exercises to improve the response inhibition in this age group is still limited. This study will explore the advantages of long-term intervention of table tennis (open-skill exercise) compared with fit aerobics (closed-skill exercise) on the response inhibitory ability of the elderly.Methods and analysisA single-blind randomised controlled trial will be conducted. A total of 90 elderly subjects will be recruited and allocated randomly to the following groups: table tennis, fit aerobics and control. The interventions for the table tennis group and the fit aerobics group will be implemented in three 60 min sessions per week for 6 months; the control group will receive no exercise intervention. The primary assessment will be behavioural indicators of response inhibitory ability in the elderly based on the stop signal task. The secondary outcomes will include cognitive ability, mental status and depression in the elderly. Assessments will be conducted at baseline, 3 months, 6 months and 12 months.Ethics and disseminationThis study was approved by the Shanghai University of Sport Research Ethics Committee (102772019RT012) and will provide reference for the advantages of table tennis compared with other types of sports in improving the response inhibitory ability of the elderly. The results of this study will provide a theoretical basis for choosing the best exercise programme to improve the response inhibitory ability of the elderly.Trial registration numberThis study has been registered prospectively in the Chinese Clinical Trial Registry (ChiCTR2100043616, 23 February 2021).
Why does healthcare utilisation differ between socioeconomic groups in OECD countries with universal healthcare coverage? A protocol for a systematic review
Authors: Meulman Iris , Uiters Ellen , Polder Johan , Stadhouders Niek 
Published: November 2021

IntroductionEven in advanced economies with universal healthcare coverage (UHC), a social gradient in healthcare utilisation has been reported. Many individual, community and healthcare system factors have been considered that may be associated with the variation in healthcare utilisation between socioeconomic groups. Nevertheless, relatively little is known about the complex interaction and relative contribution of these factors to socioeconomic differences in healthcare utilisation. In order to improve understanding of why utilisation patterns differ by socioeconomic status (SES), the proposed systematic review will explore the main mechanisms that have been examined in quantitative research.Methods and analysisThe systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines and will be conducted in Embase, PubMed, Scopus, Web of Science, Econlit and PsycInfo. Articles examining factors associated with the differences in primary and specialised healthcare utilisation between socioeconomic groups in Organisation for Economic Co-operation and Development (OECD) countries with UHC will be included. Further restrictions concern specifications of outcome measures, factors of interest, study design, population, language and type of publication. Data will be numerically summarised, narratively synthesised and thematically discussed. The factors will be categorised according to existing frameworks for barriers to healthcare access.Ethics and disseminationNo primary data will be collected. No ethics approval is required. We intend to publish a scientific article in an international peer-reviewed journal.
Prevalence and incidence of dry eye in the USA: a systematic review protocol
Authors: McCann Paul , Abraham Alison G , Gregory Darren G , Hauswirth Scott , Ifantides Cristos , Liu Su-Hsun , Saldanha Ian J , Li Tianjing 
Published: November 2021

IntroductionDry eye is a multifactorial chronic condition characterised by tear film insufficiency and instability, and ocular symptoms including foreign body sensation, itching, irritation, soreness and visual disturbance. The prevalence and incidence of dry eye are major determinants of the magnitude of economic and societal costs of the disease. This protocol proposes a systematic review and meta-analysis of the prevalence and incidence of dry eye in the USA.Methods and analysisWorking with an information specialist, we will develop search strategies for Ovid Medline and Embase for population-based cross-sectional and cohort studies involving US-based populations that report the prevalence and/or incidence of dry eye. We will include studies involving persons of all ages from 1 January 2010 to the current date with no language restrictions. We will also hand-search references of included studies, dry eye epidemiology-related systematic reviews, clinical practice guidelines and literature provided by agencies and organisations. Two investigators will independently screen the titles and abstracts, and then full-text reports to determine eligibility. One investigator will extract study data and perform risk of bias assessments using tools designed specifically for prevalence and incidence studies. A second investigator will verify all extracted study data and risk of bias assessments. We will assess heterogeneity, qualitatively and quantitatively. When appropriate, we will meta-analyse prevalence and incidence estimates.Ethics and disseminationThis review does not require approval by an ethics committee because it will use published studies. We will publish our results in a peer-reviewed journal and present at relevant conferences.PROSPERO registration numberCRD42021256934.
Continuous subcutaneous infusion: is community anticipatory prescribing and administration safe?
Authors: Coyle Séamus , Sinden Rebecca , Wignall-Coyle Jade , Benson Sinead , Powell Paula , Monnery Daniel 
Published: November 2021

ObjectiveThe anticipatory prescribing of pro re nata medications and continuous subcutaneous infusion (CSCI) medication is essential for the timely management of symptomatic patients at the end of life. There is no evidence to support the safety or appropriateness of anticipatory CSCIs. In 2013, in response to safety concerns about end of life prescribing in the community, we designed an educational intervention to improve prescribing practices among non-specialist prescribers in this area.Methods: how the study was performedWe performed a safety-focussed retrospective cohort analysis of end of life community prescriptions of anticipatory CSCIs over a 12-month period, 5 years after creating clinical guidelines and embedding a multiprofessional rolling education programme. Medications prescribed and administered for symptom control at the end of life are compared between specialist and non-specialist prescribers in terms of their adherence to best practice guidance.ResultsMedications prescribed were not universally administered and more commonly not administered without specialist input. Prescriptions of higher doses of opioids and benzodiazepines beyond those recommended by guidance were significantly greater within the cohort of patients receiving specialist oversight. The prescription of a dose range did not result in excessive dose escalation. For patients not receiving specialist palliative care, median morphine and midazolam doses did not escalate at all once a CSCI was commenced. All midazolam administrations were safe.ConclusionsThe practice of anticipatory CSCI prescribing and administration can be safe in the community non-specialist setting when supported by clinical guidelines, specialist advice and ongoing multiprofessional education.
Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study
Authors: Lonardi Sara , Prete Alessandra Anna , Morano Federica , Messina Marco , Formica Vincenzo , Corsi Domenico Cristiano , Orciuolo Corrado , Frassineti Giovanni Luca , Zampino Maria Giulia , Casagrande Mariaelena , Masi Gianluca , Ronzoni Monica , Scartozzi Mario , Buonadonna Angela , Mosconi Stefania , Ratti Margherita , Sartore-Bianchi Andrea , Tamburini Emiliano , Prisciandaro Michele , Bergamo Francesca , Spada Massimiliano , Corallo Salvatore , Vettore Valentina , Loupakis Fotios , Fassan Matteo , Del Bianco Paola , Zagonel Vittorina , Pietrantonio Filippo 
Published: November 2021

BackgroundNo standard therapies beyond first line are established for advanced squamous cell anal carcinoma (aSCAC). Earlier preliminary data suggest activity of epidermal growth factor receptor (EGFR) inhibition and programmed cell death ligand (PD-(L))1 blockade in patients with previously treated disease. Aim of this study was to explore activity and safety of avelumab with/without cetuximab in patients with aSCAC.MethodsIn this open-label, non-comparative, ‘pick the winner’, multicenter randomized phase II trial (NCT03944252), patients with aSCAC progressing after one or more lines of treatment were randomized 1:1 to the anti-PD-L1 agent avelumab alone (arm A) or combined with cetuximab (arm B). Overall response rate (ORR) was the primary endpoint. With one-sided α error set at 0.05 and power of 80%, at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. Secondary endpoints were progression free survival (PFS), overall survival (OS), and safety.ResultsThirty patients per arm were enrolled. Three patients in arm A and five in arm B achieved partial response: primary endpoint was reached in combination arm. ORR was 10% (95% CI 2.1 to 26.5) and 17% (95% CI 5.6 to 34.7) in arms A and B; disease control rate was 50% (95% CI 31.3 to 68.7) in arm A and 57 (95% CI 37.4–74.5) in arm B. At a median follow-up of 26.7 months (IQR 26.5–26.9), median PFS was 2.0 months (95% CI 1.8 to 4.0) in arm A and 3.9 (95% CI 2.1 to 5.6) in arm B. Median OS was 13.9 months (95% CI 7.7 to 19.4) in arm A and 7.8 (95% CI 6.2 to 11.2) in arm B. Acceptable safety profile was observed in both arms.ConclusionsCARACAS study met its primary endpoint in arm B, documenting promising activity of dual EGFR and PD-L1 blockade in aSCAC.
Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer
Authors: Nalawade Saisha A , Shafer Paul , Bajgain Pradip , McKenna Mary K , Ali Arushana , Kelly Lauren , Joubert Jarrett , Gottschalk Stephen , Watanabe Norihiro , Leen Ann , Parihar Robin , Vera Valdes Juan Fernando , Hoyos Valentina 
Published: November 2021

BackgroundSuccessful targeting of solid tumors such as breast cancer (BC) using chimeric antigen receptor (CAR) T cells has proven challenging, largely attributed to the immunosuppressive tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs) inhibit CAR T cell function and persistence within the breast TME. To overcome this challenge, we have developed CAR T cells targeting tumor-associated mucin 1 (MUC1) with a novel chimeric costimulatory receptor that targets tumor necrosis factor–related apoptosis-inducing ligand receptor 2 (TR2) expressed on MDSCs.MethodsThe function of the TR2.41BB costimulatory receptor was assessed by exposing non-transduced (NT) and TR2.41BB transduced T cells to recombinant TR2, after which nuclear translocation of NFκB was measured by ELISA and western blot. The cytolytic activity of CAR.MUC1/TR2.41BB T cells was measured in a 5-hour cytotoxicity assay using MUC1+ tumor cells as targets in the presence or absence of MDSCs. In vivo antitumor activity was assessed using MDSC-enriched tumor-bearing mice treated with CAR T cells with or without TR2.41BB.ResultsNuclear translocation of NFκB in response to recombinant TR2 was detected only in TR2.41BB T cells. The presence of MDSCs diminished the cytotoxic potential of CAR.MUC1 T cells against MUC1+ BC cell lines by 25%. However, TR2.41BB expression on CAR.MUC1 T cells induced MDSC apoptosis, thereby restoring the cytotoxic activity of CAR.MUC1 T cells against MUC1+ BC lines. The presence of MDSCs resulted in an approximately twofold increase in tumor growth due to enhanced angiogenesis and fibroblast accumulation compared with mice with tumor alone. Treatment of these MDSC-enriched tumors with CAR.MUC1.TR2.41BB T cells led to superior tumor cell killing and significant reduction in tumor growth (24.54±8.55 mm3) compared with CAR.MUC1 (469.79±81.46 mm3) or TR2.41BB (434.86±64.25 mm3) T cells alone. CAR.MUC1.TR2.41BB T cells also demonstrated improved T cell proliferation and persistence at the tumor site, thereby preventing metastases. We observed similar results using CAR.HER2.TR2.41BB T cells in a HER2+ BC model.ConclusionsOur findings demonstrate that CAR T cells that coexpress the TR2.4-1BB receptor exhibit superior antitumor potential against breast tumors containing immunosuppressive and tumor promoting MDSCs, resulting in TME remodeling and improved T cell proliferation at the tumor site.
Gamma delta TCR anti-CD3 bispecific molecules (GABs) as novel immunotherapeutic compounds
Authors: van Diest Eline , Hernández López Patricia , Meringa Angelo D , Vyborova Anna , Karaiskaki Froso , Heijhuurs Sabine , Gumathi Bormin Jan , van Dooremalen Sanne , Nicolasen Mara J T , Gatti Lucrezia C D E , Johanna Inez , Straetemans Trudy , Sebestyén Zsolt , Beringer Dennis X , Kuball Jürgen 
Published: November 2021

Backgroundγ9δ2 T cells hold great promise as cancer therapeutics because of their unique capability of reacting to metabolic changes with tumor cells. However, it has proven very difficult to translate this promise into clinical success.MethodsIn order to better utilize the tumor reactivity of γ9δ2T cells and combine this with the great potential of T cell engager molecules, we developed a novel bispecific molecule by linking the extracellular domains of tumor-reactive γ9δ2TCRs to a CD3-binding moiety, creating gamma delta TCR anti-CD3 bispecific molecules (GABs). GABs were tested in vitro and in vivo for ability to redirect T lymphocytes to a variety of tumor cell lines and primary patient material.ResultsGABs utilizing naturally occurring high affinity γ9δ2TCRs efficiently induced αβT cell mediated phosphoantigen-dependent recognition of tumor cells. Reactivity was substantially modulated by variations in the Vδ2 CDR3-region and the BTN2A1-binding HV4-region between CDR2 and CDR3 of the γ-chain was crucial for functionality. GABs redirected αβT cells against a broad range of hematopoietic and solid tumor cell lines and primary acute myeloid leukemia. Furthermore, they enhanced infiltration of immune cells in a 3D bone marrow niche and left healthy tissues intact, while eradicating primary multiple myeloma cells. Lastly, GABs constructed from natural high affinity γ9δ2TCR sequences significantly reduced tumor growth in vivo in a subcutaneous myeloma xenograft model.ConclusionsWe conclude that GABs allow for the introduction of metabolic targeting of cancer cells to the field of T cell engagers.
Clinical and molecular features of 66 patients with musculocontractural Ehlers−Danlos syndrome caused by pathogenic variants inCHST14(mcEDS-CHST14)
Authors: Minatogawa Mari , Unzaki Ai , Morisaki Hiroko , Syx Delfien , Sonoda Tohru , Janecke Andreas R , Slavotinek Anne , Voermans Nicol C , Lacassie Yves , Mendoza-Londono Roberto , Wierenga Klaas J , Jayakar Parul , Gahl William A , Tifft Cynthia J , Figuera Luis E , Hilhorst-Hofstee Yvonne , Maugeri Alessandra , Ishikawa Ken , Kobayashi Tomoko , Aoki Yoko , Ohura Toshihiro , Kawame Hiroshi , Kono Michihiro , Mochida Kosuke , Tokorodani Chiho , Kikkawa Kiyoshi , Morisaki Takayuki , Kobayashi Tetsuyuki , Nakane Takaya , Kubo Akiharu , Ranells Judith D , Migita Ohsuke , Sobey Glenda , Kaur Anupriya , Ishikawa Masumi , Yamaguchi Tomomi , Matsumoto Naomichi , Malfait Fransiska , Miyake Noriko , Kosho Tomoki 
Published: November 2021

BackgroundMusculocontractural Ehlers−Danlos syndrome is caused by biallelic loss-of-function variants inCHST14(mcEDS-CHST14) orDSE(mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated.MethodsWe collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14through international collaborations.ResultsSixty-six patients in 48 families (33 males/females; 0–59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype–phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14than in eight reported patients with mcEDS-DSE.ConclusionThis first international collaborative study of mcEDS-CHST14demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.