bluuebunny/crossref_metadata_2025_split huggingface dataset:
Availability and Quality of Assessment Instruments on Patient-Centredness in the Multimorbid Elderly (AQuA-PCE): a study protocol of a systematic review
Authors: Glattacker Manuela , Kanat Manuela , Schaefer Jonas , Motschall Edith , Kivelitz Laura , Voigt-Radloff Sebastian , Dirmaier Joerg 
Published: February 2020

IntroductionElderly, multimorbid patients are a primary target group for patient-centred care, and fostering patient-centredness (PC) in this group has been associated with different healthcare aims such as safety and quality of healthcare. However, evidence on effects of patient-centred interventions is still limited and mixed. In part, the lack of consistent evidence has its roots in a conceptual uncertainty of the term ‘PC’, which also hampers the development of assessment tools for PC. Consequently, reviews on assessment instruments of PC reveal problems regarding the quality of identified assessment instruments and regarding their comparability. Some of these reviews focus on the elderly. However, while the concept of multimorbidity is partly inherent, this focus is not explicit in any of the reviews.The aim of this systematic review is to identify assessment instruments of PC in the multimorbid elderly, using a subgroup-specific definition of PC (‘subgroup-specific integrative model of PC’) as the conceptual underpinning, and to provide a critical quality appraisal of their psychometric properties.Methods and analysisA comprehensive systematic literature search for assessment tools on PC will be conducted in the MEDLINE, CINAHL, EMBASE, PsycINFO, Web of Science and PSYNDEX electronic databases. The search strategy will be informed by the subgroup-specific integrative model of PC. The electronic literature search will be complemented by a hand-search combining citation tracking, search in project databases, and contacting authors from relevant studies/reviews. The literature search (systematic and hand-search) will cover the period from November, 2018 to December 2019.The retrieval of relevant studies will be conducted via title screening, abstract screening, and full-text eligibility assessment applying defined inclusion criteria. Full texts will be independently assessed by two team members. Data from the included articles will be extracted using a standardised extraction form and evaluated based on the COSMIN methodology for systematic reviews of patient-reported outcome measures, which focuses on the methodological quality of included studies as well as on the measurement properties of the assessment instruments. Data extraction and quality assessment will be conducted by two independent reviewers.Ethics and disseminationThe study has received approval from the Ethics Committee of the University of Freiburg (reference number 587/17). The results of the project will be disseminated via scientific oral presentations at national and international conferences and will be published in scientific journals.Trial registration numbersCRD42018084057; DRKS00013309.
Ultrasound-guided superficial cervical plexus block for analgesia in patients undergoing craniotomy via suboccipital retrosigmoid approach: study protocol of a randomised controlled trial
Authors: Peng Kun , Zeng Min , Dong Jia , Yan Xiang , Wang Dexiang , Li Shu , Peng Yuming 
Published: February 2020

IntroductionScalp nerve block has been proven to be an alternative choice to opioids in multimodal analgesia. However, for the infratentorial space-occupying craniotomy, especially the suboccipital retrosigmoid craniotomy, scalp nerve block is insufficient.Methods and analysisThe study is a prospective, single-centre, randomised, paralleled-group controlled trial. Patients scheduled to receive elective suboccipital retrosigmoid craniotomy will be randomly assigned to the superficial cervical plexus block group or the control group. After anaesthesia induction, superficial cervical plexus nerve block will be performed under the guidance of ultrasound. The primary outcome is the cumulative consumption of sufentanil by the patient-controlled intravenous analgesia pump within 24 hours after surgery. Secondary outcomes include the cumulative consumption of sufentanil at other four time points and numerical rating scale pain severity score.Ethics and disseminationThe protocol (version number: 2.0, 10 April 2019) has been approved by the Ethics Review Committee of China Registered Clinical Trials (Ethics Review No. ChiECRCT-20190047). The findings of this study will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberNCT04036812
Differences in medication beliefs between pregnant women using medication, or not, for chronic diseases: a cross-sectional, multinational, web-based study
Authors: Roldan Munoz Sonia , Lupattelli Angela , de Vries Sieta T , Mol Peter G M , Nordeng Hedvig 
Published: February 2020

ObjectivesTo assess whether medication beliefs differ between women who use or not use medication for their somatic chronic diseases during pregnancy and whether this association varies across diseases.DesignCross-sectional web-based survey.SettingMultinational study in Europe.ParticipantsPregnant women or women with children less than 1 year old from European countries and with asthma, allergy, cardiovascular, rheumatic diseases, diabetes, epilepsy and/or inflammatory bowel diseases (IBD).Primary and secondary outcome measureDifferences in scores of theBeliefs about Medicines Questionnaire(BMQ).ResultsIn total, 1219 women were included (ranging from 736 for allergy to 49 for IBD). Women using medication for their chronic disease (n=770; 63%) had higher scores on the BMQ subscalesnecessity(16.6 vs 12.1, p<0.001) andbenefits(16.2 vs 15.4, p<0.001), and lower values on the subscalesoveruse(12.5 vs 13.1; p=0.005) andharm(9.8 vs 10.7, p<0.001) than women not using medication. No significant differences were shown for theconcernssubscale (12.5 vs 12.3, p=0.484). Beliefs varied somewhat across diseases but in general more positive beliefs among women using medication were shown. Epilepsy was the disease where less differences were observed between women using and not using medication.ConclusionWomen’s beliefs were associated with medication use during pregnancy with only small differences across the diseases. Knowing pregnant women’s beliefs could help identify women who are reluctant to use medication and could guide counselling to support making well-informed treatment decisions.
‘Function First—Be Active, Stay Independent’—promoting physical activity and physical function in people with long-term conditions by primary care: a protocol for a realist synthesis with embedded co-production and co-design
Authors: Law Rebecca-Jane , Williams Lynne , Langley Joseph , Burton Christopher , Hall Beth , Hiscock Julia , Morrison Val , Lemmey Andrew , Partridge Rebecca , Lovell-Smith Candida , Gallanders John , Williams Nefyn 
Published: February 2020

IntroductionPeople with long-term conditions typically have reduced physical functioning, are less physically active and therefore become less able to live independently and do the things they enjoy. However, assessment and promotion of physical function and physical activity is not part of routine management in primary care. This project aims to develop evidence-based recommendations about how primary care can best help people to become more physically active in order to maintain and improve their physical function, thus promoting independence.Methods and analysisThis study takes a realist synthesis approach, following RAMESES guidance, with embedded co-production and co-design. Stage 1 will develop initial programme theories about physical activity and physical function for people with long-term conditions, based on a review of the scientific and grey literature, and two multisector stakeholder workshops using LEGO® SERIOUS PLAY®. Stage 2 will involve focused literature searching, data extraction and synthesis to provide evidence to support or refute the initial programme theories. Searches for evidence will focus on physical activity interventions involving the assessment of physical function which are relevant to primary care. We will describe ‘what works’, ‘for whom’ and ‘in what circumstances’ and develop conjectured programme theories using context, mechanism and outcome configurations. Stage 3 will test and refine these theories through individual stakeholder interviews. The resulting theory-driven recommendations will feed into Stage 4 which will involve three sequential co-design stakeholder workshops in which practical ideas for service innovation in primary care will be developed.Ethics and disseminationHealthcare and Medical Sciences Academic Ethics Committee (Reference 2018-16308) and NHS Wales Research Ethics Committee 5 approval (References 256 729 and 262726) have been obtained. A knowledge mobilisation event will address issues relevant to wider implementation of the intervention and study findings. Findings will be disseminated through peer-reviewed journal publications, conference presentations and formal and informal reports.PROSPERO registration numberCRD42018103027.
PMI’s heated tobacco products marketing claims of reduced risk and reduced exposure may entice youth to try and continue using these products
Authors: McKelvey Karma , Baiocchi Michael , Halpern-Felsher Bonnie 
Published: February 2020

ImportancePhilip Morris International (PMI) is seeking Food and Drug Administration’s (FDA) authorisation to market IQOS as a modified risk tobacco product and to make marketing claims of reduced risk and reduced exposure. Such claims may be misunderstood by youth, thereby increasing their risk for tobacco initiation.ObjectiveTo assess youth (mean age 19.3, SD=1.7) understanding and perceptions of PMI’s proposed consumer marketing claims of reduced risk and reduced exposure, we embedded a randomised controlled experiment into a survey of 450 California youth (April to August 2018). Participants were randomised to see ‘reduced exposure’, ‘reduced risk’ or neither claim. Perceptions of IQOS-related health risks and general harm and understanding of the term ‘switching completely’ as used in PMI’s proposed claims were compared.ResultsMean expectancies to experience specific health risks did not differ by claim exposure. The reduced exposure group’s perceptions of general harm did not differ from those of controls nor from the reduced risk group. The reduced risk group had the largest proportion who perceived IQOS as moderately/less harmful (n=78, 52%); controls the largest proportion perceiving IQOS as quite/extremely harmful (n=91, 63%). While 71% of the sample understood the term ‘switch completely’ correctly as used in the reduced risk (n=194, 71%) and reduced exposure (n=206, 72%) claims, more than 1 in 4 did not.ConclusionsFDA and other regulators must use caution when considering allowing claims of reduced risk or reduced exposure to appear on retail tobacco packaging. Youth misunderstand such claims, and misperceptions of harm are known to lead to tobacco-use initiation.
Higher derivatives driven symmetry breaking in holographic superconductors
Authors: Li Hai-Li , Fu Guoyang , Liu Yan , Wu Jian-Pin , Zhang Xin 
Published: February 2020

AbstractIn this paper, we construct a novel holographic superconductor from higher derivative (HD) gravity involving a coupling between the complex scalar field and the Weyl tensor. This HD coupling term provides a near horizon effective mass squared, which can violates IR Breitenlohner–Freedman (BF) bound by tuning the HD coupling and induces the instability of black brane such that the superconducting phase transition happens. We also study the properties of the condensation and the conductivity in the probe limit. We find that a wider extension of the superconducting energy gap ranging from 4.6 to 10.5 may provide a novel platform to model and interpret the phenomena in the real materials of high temperature superconductor.
Bilateral differences in hamstring coordination in previously injured elite athletes
Authors: Avrillon Simon , Hug François , Guilhem Gaël 
Published: February 2020

Hamstring strain injuries (HSIs) involve tissue disruption and pain, which can trigger long-term adaptations of muscle coordination. However, little is known about the effect of previous HSIs on muscle coordination and in particular, after the completion of rehabilitation and in the absence of symptoms. This study aimed to determine if elite athletes with a prior unilateral HSI have bilateral differences in coordination between the hamstring muscle heads after returning to sport. Seventeen athletes with a unilateral history of biceps femoris (BF) injury participated in the experiment. Surface electromyography was recorded from three hamstring muscles [BF, semimembranosus (SM), and semitendinosus] during submaximal isometric torque-matched tasks at 20% and 50% of maximal voluntary contraction. The product of normalized electromyographic amplitude with functional physiological cross-sectional area (PCSA) and moment arm was considered as an index of individual muscle torque. The contribution of the injured muscle to total knee flexion torque was lower in the injured than the uninjured limb (−5.6 ± 10.2%, P = 0.038). This reduced contribution of BF was compensated by a higher contribution of the SM muscle in the injured limb (+5.6 ± 7.5%, P = 0.007). These changes resulted from a lower contribution of PCSA from the injured muscle (BF) and a larger contribution of activation from an uninjured synergist muscle (SM). In conclusion, bilateral differences in coordination were observed in previously injured athletes despite the completion of rehabilitation. Whether these bilateral differences in hamstring coordination could constitute an intrinsic risk factor that contributes to the high rate of hamstring injury recurrence remains to be investigated. NEW & NOTEWORTHY We used an experimental approach, combining the assessment of muscle activation, physiological cross-sectional area, and moment arm to estimate force-sharing strategies among hamstring muscles during isometric knee flexions. We tested athletes with a history of hamstring injury. We observed a lower contribution of the injured biceps femoris to the total knee flexor torque in the injured limb than in the contralateral limb. This decreased contribution was mainly due to selective atrophy of the injured biceps femoris muscle and was compensated by an increased activation of the semimembranosus muscle.
UBR5 Is Coamplified with MYC in Breast Tumors and Encodes an Ubiquitin Ligase That Limits MYC-Dependent Apoptosis
Authors: Qiao Xi , Liu Ying , Prada Maria Llamazares , Mohan Aravind K. , Gupta Abhishekh , Jaiswal Alok , Sharma Mukund , Merisaari Joni , Haikala Heidi M. , Talvinen Kati , Yetukuri Laxman , Pylvänäinen Joanna W. , Klefström Juha , Kronqvist Pauliina , Meinander Annika , Aittokallio Tero , Hietakangas Ville , Eilers Martin , Westermarck Jukka 
Published: February 2020

Abstract

For maximal oncogenic activity, cellular MYC protein levels need to be tightly controlled so that they do not induce apoptosis. Here, we show how ubiquitin ligase UBR5 functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 ubiquitinates MYC and its effects on MYC protein stability are independent of FBXW7. Silencing of endogenous UBR5 induced MYC protein expression and regulated MYC target genes. Consistent with the tumor suppressor function of UBR5 (HYD) in Drosophila, HYD suppressed dMYC-dependent overgrowth of wing imaginal discs. In contrast, in cancer cells, UBR5 suppressed MYC-dependent priming to therapy-induced apoptosis. Of direct cancer relevance, MYC and UBR5 genes were coamplified in MYC-driven human cancers. Functionally, UBR5 suppressed MYC-mediated apoptosis in p53-mutant breast cancer cells with UBR5/MYC coamplification. Furthermore, single-cell immunofluorescence analysis demonstrated reciprocal expression of UBR5 and MYC in human basal-type breast cancer tissues. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC activity. In MYC-amplified, and p53-mutant breast cancer cells, UBR5 has an important role in suppressing MYC-mediated apoptosis priming and in protection from drug-induced apoptosis.

Significance:
These findings identify UBR5 as a novel MYC regulator, the inactivation of which could be very important for understanding of MYC dysregulation on cancer cells.
Randomized Trial of Intermediate-dose Cytarabine in Induction and Consolidation Therapy in Adults with Acute Myeloid Leukemia
Authors: Wei Hui , Wang Ying , Gale Robert Peter , Lin Dong , Zhou Chunlin , Liu Bingcheng , Qiu Shaowei , Gu Runxia , Li Yan , Zhao Xingli , Wei Shuning , Gong Benfa , Liu Kaiqi , Gong Xiaoyuan , Liu Yuntao , Zhang Guangji , Song Zhen , Wang Yang , Li Wei , Mi Yingchang , Wang Jianxiang 
Published: February 2020

Abstract

Purpose:
Cytarabine, 100–200 mg/mE+2/day, is commonly used in induction therapy of acute myelogenous leukemia (AML). Whether a higher dose of cytarabine would be more effective is unknown. Also, there is controversy whether high-dose cytarabine is better than an intermediate-dose combined with other drugs for post-remission therapy. In this open-label, randomized controlled, parallel group study, roles of intermediate-dose cytarabine were investigated.

Patients and Methods:
Subjects with AML age 15–55 years were randomized to receive daunorubicin, omacetaxine mepesuccinate, and conventional- or intermediate-dose cytarabine. Subjects achieving complete remission were randomized to receive 3 courses of high-dose cytarabine or 2 courses of intermediate-dose cytarabine with daunorubicin in the 1st and mitoxantrone in the 2nd course. The primary endpoint was disease-free survival (DFS).

Results:
591 subjects were randomized to intermediate- (N = 295) or conventional-dose (N = 296) cytarabine group. Three-year DFSs were 67% [95% confidence interval (CI), 61–73] in the intermediate-dose cohort compared with 54% (95% CI, 48–61) in the conventional-dose cohort [Hazard Ratio (HR), 0.67; 95%CI, 0.51–0.89; P = 0.005). Three-year survivals were 68% (95%CI, 63–74) and 59% (95%CI, 53–65; HR, 0.720; 95%CI, 0.56–0.94; P = 0.014). Two courses of intermediate-dose cytarabine with daunorubicin or mitoxantrone resulted in similar DFS and survival as three courses of high-dose cytarabine when used for post-remission therapy.

Conclusions:
Induction therapy with intermediate-dose cytarabine with daunorubicin and omacetaxine mepesuccinate increases DFS and survival in persons with AML ages 15–55 years compared with conventional-dose cytarabine.
See related commentary by Watts and Bradley, p. 3073
Genomic Profiling of Metastatic Uveal Melanoma and Clinical Results of a Phase I Study of the Protein Kinase C Inhibitor AEB071
Authors: Piperno-Neumann Sophie , Larkin James , Carvajal Richard D. , Luke Jason J. , Schwartz Gary K. , Hodi F. Stephen , Sablin Marie-Paule , Shoushtari Alexander N. , Szpakowski Sebastian , Chowdhury Niladri Roy , Brannon A. Rose , Ramkumar Thiruvamoor , de Koning Leanne , Derti Adnan , Emery Caroline , Yerramilli-Rao Padmaja , Kapiteijn Ellen 
Published: February 2020

Abstract

Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed to evaluate the safety and efficacy of the orally available protein kinase C inhibitor, AEB071, in patients with metastatic UM, and to perform genomic profiling of metastatic tumor samples, with the aim to propose combination therapies. Patients with metastatic UM (n = 153) were treated with AEB071 in a phase I, single-arm study. Patients received total daily doses of AEB071 ranging from 450 to 1,400 mg. First-cycle dose-limiting toxicities were observed in 13 patients (13%). These were most commonly gastrointestinal system toxicities and were dose related, occurring at doses ≥700 mg/day. Preliminary clinical activity was observed, with 3% of patients achieving a partial response and 50% with stable disease (median duration 15 weeks). High-depth, targeted next-generation DNA sequencing was performed on 89 metastatic tumor biopsy samples. Mutations previously identified in UM were observed, including mutations in GNAQ, GNA11, BAP1, SF3B1, PLCB4, and amplification of chromosome arm 8q. GNAQ/GNA11 mutations were observed at a similar frequency (93%) as previously reported, confirming a therapeutic window for inhibition of the downstream effector PKC in metastatic UM.
In conclusion, the protein kinase C inhibitor AEB071 was well tolerated, and modest clinical activity was observed in metastatic UM. The genomic findings were consistent with previous reports in primary UM. Together, our data allow envisaging combination therapies of protein kinase C inhibitors with other compounds in metastatic UM.
Oxaliplatin–DNA Adducts as Predictive Biomarkers of FOLFOX Response in Colorectal Cancer: A Potential Treatment Optimization Strategy
Authors: Zimmermann Maike , Li Tao , Semrad Thomas J. , Wu Chun-Yi , Yu Aiming , Cimino George , Malfatti Michael , Haack Kurt , Turteltaub Kenneth W. , Pan Chong-xian , Cho May , Kim Edward J. , Henderson Paul T. 
Published: February 2020

Abstract
FOLFOX is one of the most effective treatments for advanced colorectal cancer. However, cumulative oxaliplatin neurotoxicity often results in halting the therapy. Oxaliplatin functions predominantly via the formation of toxic covalent drug–DNA adducts. We hypothesize that oxaliplatin–DNA adduct levels formed in vivo in peripheral blood mononuclear cells (PBMC) are proportional to tumor shrinkage caused by FOLFOX therapy. We further hypothesize that adducts induced by subtherapeutic “diagnostic microdoses” are proportional to those induced by therapeutic doses and are also predictive of response to FOLFOX therapy. These hypotheses were tested in colorectal cancer cell lines and a pilot clinical study. Four colorectal cancer cell lines were cultured with therapeutically relevant (100 μmol/L) or diagnostic microdose (1 μmol/L) concentrations of [14C]oxaliplatin. The C-14 label enabled quantification of oxaliplatin–DNA adduct level with accelerator mass spectrometry (AMS). Oxaliplatin–DNA adduct formation was correlated with oxaliplatin cytotoxicity for each cell line as measured by the MTT viability assay. Six colorectal cancer patients received by intravenous route a diagnostic microdose containing [14C]oxaliplatin prior to treatment, as well as a second [14C]oxaliplatin dose during FOLFOX chemotherapy, termed a “therapeutic dose.” Oxaliplatin–DNA adduct levels from PBMC correlated significantly to mean tumor volume change of evaluable target lesions (5 of the 6 patients had measurable disease). Oxaliplatin–DNA adduct levels were linearly proportional between microdose and therapeutically relevant concentrations in cell culture experiments and patient samples, as was plasma pharmacokinetics, indicating potential utility of diagnostic microdosing.