bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer
Authors: Wang Jian , Zhang Ruiguang , Lin Zhenyu , Zhang Sheng , Chen Yaobing , Tang Jing , Hong Jiaxin , Zhou Xiaoshu , Zong Yan , Xu Yingzhuo , Meng Rui , Xu Shuangbing , Liu Li , Zhang Tao , Yang Kunyu , Dong Xiaorong , Wu Gang 
Published: July 2020

Abstract
Background
The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC).

Methods
RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. Flow cytometry was performed to detect the status of the immune microenvironment after CDK7 inhibition and antiPD-1 therapy in vivo. CD8 depletion antibodies were used to assess the role of CD8+ T cells in combined CDK7 and PD-1 blockade. The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC.

Results
High CDK7 mRNA and protein levels were identified to be associated with poor prognosis in NSCLC. CDK7 silencing and CDK7 inhibitor THZ1 elicited apoptosis and suppressed tumor growth. Moreover, CDK7 ablation specifically suppressed p38α/MYC-associated genes, and THZ1 inhibited MYC transcriptional activity through downregulating p38α. CDK7 inhibition sensitized NSCLC to p38α inhibitor. Further, THZ1 suppressed PD-L1 expression by inhibiting MYC activity. THZ1 boosted antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with antiPD-1 therapy. The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups.

Conclusion
These data suggest that the combined CDK7 inhibitor THZ1 and antiPD-1 therapy can be an effective treatment in NSCLC.
Platelet count as a biomarker for monitoring treatment response and disease recurrence in recurrent epithelial ovarian cancer
Authors: Hu Qinghong , Hada Abha , Han Liping 
Published: July 2020

Abstract
Objectives
We sought to determine the impact of pretreatment plasma platelet levels, dimerized plasmin fragment (D-dimer) and fibrinogen in recurrent epithelial ovarian cancer (EOC) and the impact of platelet levels on SKOV3 cell lines growth and responsiveness to chemotherapy.

Methods
Under approval of ethical committee, we identified 104 women with recurrent EOC who underwent treatment between January 2010 and February 2015. Reviewing clinical, laboratory, and pathologic records from this retrospective cohort, we analyzed the correlation between pretreatment plasma D-dimer, fibrinogen, platelet levels and clinicopathological parameters, progression free survival (PFS) and overall survival (OS). Inco-culture experiments human ovarian cancer SKOV3 cell lines were used to test the effect of platelet levels on tumor growth and responsiveness to docetaxel.

Results
Of the 104 recurrent EOC, thrombocytosis at diagnosis and the decrease of platelet count by less than 25% after primary therapy were associated with worse median progression free survival (P = 0.003;P = 0.021) and median overall survival (P = 0.009;P = 0.009). Mean platelet levels declined at the end of primary therapy(P < 0.001) and rose at recurrence(P = 0.007). In multivariate analysis, elevated platelet levels at primary therapy and the decrease of platelet count less than 25% after primary therapy were unfavorable prognostic factor for PFS(P = 0.022; P = 0.015) and OS(P = 0.013;P = 0.007) in recurrent EOC, but elevated plasma D-dimer and fibrinogen were not. In SKOV-3 ovarian cancer cell lines, suitable concentration platelet co-culture protected against apoptosis (P < 0.05).

Conclusions
Platelet count during treatment could be used as a biomarker used for monitoring the disease recurrence and predicting treatment response. And platelet with suitable concentration co-culture protected against apoptosis in SKOV3 cell line, which may explain clinical observations.
Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention—MACUSTAR
Authors: Terheyden Jan H. , Holz Frank G. , Schmitz-Valckenberg Steffen , Lüning Anna , Schmid Matthias , Rubin Gary S. , Dunbar Hannah , Tufail Adnan , Crabb David P. , Binns Alison , Sánchez Clara I. , Hoyng Carel , Margaron Philippe , Zakaria Nadia , Durbin Mary , Luhmann Ulrich , Zamiri Parisa , Cunha-Vaz José , Martinho Cecília , Leal Sergio , Finger Robert P. ,   on behalf of the MACUSTAR consortium, Basile P. , Behning C. , Berger M. , Binns A. , Böttger M. , Bouchet C. , Brazier J. E. , Butt T. , Carapezzi C. , Carlton J. , Charil A. , Coimbra R. , Nunes S. , Crabb D. , Cunha-Vaz J. , Dunbar H. , Durbin M. , Finger R. , Holz F. , Hoyng C. , Krätzschmar J. , Leal S. , Luhmann U. , Lüning A. , Margaron Ph. , Martinho C. , Melício B. , Mohand-Saïd S. , Rowen D. , Rubin G. S. , Sahel J. , Sánchez C. I. , Sanches Fernandes D. , Schmid M. , Schmitz-Valckenberg S. , Skelly A. , Stöhr L. , Taylor D. , Terheyden J. , Tufail A. , Vieweg L. , Wintergerst L. , Wojek C. , Zakaria N. , Zamiri P. 
Published: July 2020

AbstractBackgroundThere is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials.MethodsThe protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part’s primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part’s primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities.DiscussionThe MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition.Trial registrationClinicalTrials.govNCT03349801. Registered on 22 November 2017
Conversion among photo-oxidative products of polypropylene in solid, liquid and gaseous states
Authors: Liu Xuan , Yang Rui 
Published: July 2020

AbstractDuring aging of polymers, oxidized species on macromolecular chains in solid state, volatile degradation products in liquid state and gaseous degradation products in gaseous state are often investigated separately. The conversion among these products is not especially concerned and biased results may be obtained based on the products in a single state. In this paper, photo-oxidative products of commercial polypropylene (PP) and unstabilized PP in solid, liquid and gaseous states were investigated by using Fourier transform infrared spectroscopy (FTIR), pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS) and gas chromatography (GC). By comparing the formation profiles, conversion among the photo-oxidative products in three states was traced. During photo-oxidative aging, the main chains of PP were first oxidized to form carbonyl species in solid state, or fractured to form volatile alkenes as liquid. With the proceeding of aging, the oxidized main chains fractured to form small molecules, resulting in the conversion of oxidized species from solid state to liquid and gaseous states. When the aging degree was extremely high, the accumulation of liquid oxidized products was limited due to migration and condensation. Therefore, both the carbonyl index (CI) and the concentrations of volatile oxidized products were increased first and then decreased, while the concentrations of gaseous products kept increasing all along.
Synthesis of cyclophosphamide metabolites by a peroxygenase from Marasmius rotula for toxicological studies on human cancer cells
Authors: Steinbrecht Susanne , Kiebist Jan , König Rosalie , Thiessen Markus , Schmidtke Kai-Uwe , Kammerer Sarah , Küpper Jan-Heiner , Scheibner Katrin 
Published: July 2020

AbstractCyclophosphamide (CPA) represents a widely used anti-cancer prodrug that is converted by liver cytochrome P450 (CYP) enzymes into the primary metabolite 4-hydroxycyclophosphamide (4-OH-CPA), followed by non-enzymatic generation of the bioactive metabolites phosphoramide mustard and acrolein. The use of human drug metabolites as authentic standards to evaluate their toxicity is essential for drug development. However, the chemical synthesis of 4-OH-CPA is complex and leads to only low yields and undesired side products. In past years, fungal unspecific peroxygenases (UPOs) have raised to powerful biocatalysts. They can exert the identical selective oxyfunctionalization of organic compounds and drugs as known for CYP enzymes with hydrogen peroxide being used as sole cosubstrate. Herein, we report the efficient enzymatic hydroxylation of CPA using the unspecific peroxygenase from Marasmius rotula (MroUPO) in a simple reaction design. Depending on the conditions used the primary liver metabolite 4-OH-CPA, its tautomer aldophosphamide (APA) and the overoxidized product 4-ketocyclophosphamide (4-keto-CPA) could be obtained. Using a kinetically controlled approach 4-OH-CPA was isolated with a yield of 32% (purity > 97.6%). Two human cancer cell lines (HepG2 and MCF-7) were treated with purified 4-OH-CPA produced by MroUPO (4-OH-CPAUPO). 4-OH-CPAUPO–induced cytotoxicity as measured by a luminescent cell viability assay and its genotoxicity as measured by γH2AX foci formation was not significantly different to the commercially available standard. The high yield of 4-OH-CPAUPO and its biological activity demonstrate that UPOs can be efficiently used to produce CYP-specific drug metabolites for pharmacological assessment.
Epigenetic regulation of matrix metalloproteinases in inflammatory diseases: a narrative review
Authors: He Jie , Qin Man , Chen Yingyi , Hu Ziqi , Xie Fei , Ye Ling , Hui Tianqian 
Published: July 2020

AbstractWith the acceleration of urbanization and aging and the change of lifestyle, inflammatory diseases have become one of the important threats to the health of the global population. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the metabolism of extracellular matrix (ECM). They play a key role in inflammation-related diseases. Factors such as inflammation, oxidative stress and growth factors stimulate the production of MMPs with subsequent ECM remodeling. Recently, the studies of epigenetic regulation, including the ability to predict disease progression, important pathophysiological deficiencies as well as treatment methods have been extensively discussed. This article reviews the current studies on epigenetic alterations in MMPs during inflammatory response. It is likely to provide new insights into development of efficient medications of epigenetic therapy for inflammatory diseases.
Two-level frame precoding with non-cooperative gateways
Authors: Ramírez Tomás , Mosquera Carlos , López-Valcarce Roberto 
Published: July 2020

AbstractThis paper considers the pre-processing design to mitigate the multibeam interference in the downlink of a high-throughput satellite, with a common precoder for several users sharing the same frame, and limited adaptation capabilities on-board the satellite. Beams are grouped in clusters managed by different non-cooperative gateways. A two-level approach is performed, with an on-board beamforming network complemented by on-ground precoders. The former, designed with the SLNR (signal-to-leakage and noise ratio) criterion, mitigates the inter-cluster interference, whereas the latter fight the intra-cluster multiuser co-channel interference. Judicious user scheduling is also addressed to limit the impact of the multicasting and limited adaptation capabilities. Several two-level precoding designs can be obtained by setting accordingly the degree of cooperation and the frame adaptation, with an overall satisfactory performance with respect to the single-gateway benchmark. In particular, a sector-based solution with non-cooperative gateways presents a good trade-off between gateway autonomy and performance.
A novel authentication scheme based on edge computing for blockchain-based distributed energy trading system
Authors: Ren Yan , Zhao Qiuxia , Guan Haipeng , Lin Zhiqiang 
Published: July 2020

AbstractDistributed energy trading system is a new business model of energy industry. Applying blockchain technology, energy supply contracts can be communicated directly between producers and consumers. However, blockchain is without any identity authentication and legitimate user identities are possibly forged if there is not any user identity authentication procedure in a trading system. In this paper, we design an authentication scheme for blockchain-based energy trading systems by using edge computing, including journalizing processes, registration, and identity authentication. In our scheme, each node has computing power, which can ensure the meter data can be processed locally or on the edge. In addition, the correctness and security analysis of the scheme are also given in this paper. The analysis shows that our scheme is unforgeability and can protect users’ privacy.
Combining abbreviated literature searches with single-reviewer screening: three case studies of rapid reviews
Authors: Affengruber Lisa , Wagner Gernot , Waffenschmidt Siw , Lhachimi Stefan K. , Nussbaumer-Streit Barbara , Thaler Kylie , Griebler Ursula , Klerings Irma , Gartlehner Gerald 
Published: July 2020

Abstract
Background
Decision-makers increasingly request rapid answers to clinical or public health questions. To save time, personnel, and financial resources, rapid reviews streamline the methodological steps of the systematic review process. We aimed to explore the validity of a rapid review approach that combines a substantially abbreviated literature search with a single-reviewer screening of abstracts and full texts using three case studies.

Methods
We used a convenience sample of three ongoing Cochrane reviews as reference standards. Two reviews addressed oncological topics and one addressed a public health topic. For each of the three topics, three reviewers screened the literature independently. Our primary outcome was the change in conclusions between the rapid reviews and the respective Cochrane reviews. In case the rapid approach missed studies, we recalculated the meta-analyses for the main outcomes and asked Cochrane review authors if the new body of evidence would change their original conclusion compared with the reference standards. Additionally, we assessed the sensitivity of the rapid review approach compared with the results of the original Cochrane reviews.

Results
For the two oncological topics (case studies 1 and 2), the three rapid reviews each yielded the same conclusions as the Cochrane reviews. However, the authors would have had less certainty about their conclusion in case study 2. For case study 3, the public health topic, only one of the three rapid reviews led to the same conclusion as the Cochrane review. The other two rapid reviews provided insufficient information for the authors to draw conclusions. Using the rapid review approach, the sensitivity was 100% (3 of 3) for case study 1. For case study 2, the three rapid reviews identified 40% (4 of 10), 50% (5 of 10), and 60% (6 of 10) of the included studies, respectively; for case study 3, the respective numbers were 38% (8 of 21), 43% (9 of 21), and 48% (10 of 21).

Conclusions
Within the limitations of these case studies, a rapid review approach that combines abbreviated literature searches with single-reviewer screening may be feasible for focused clinical questions. For complex public health topics, sensitivity seems to be insufficient.
Standardising care in the ICU: a protocol for a scoping review of tools used to improve care delivery
Authors: Allum Laura , Apps Chloe , Hart Nicholas , Pattison Natalie , Connolly Bronwen , Rose Louise 
Published: July 2020

Abstract
Background
Increasing numbers of critically ill patients experience a prolonged intensive care unit stay contributing to greater physical and psychological morbidity, strain on families and cost to health systems. Quality improvement tools such as checklists concisely articulate best practices with the aim of improving quality and safety; however, these tools have not been designed for the specific needs of patients with prolonged ICU stay.
The primary objective of this review will be to determine the characteristics including format and content of multicomponent tools designed to standardise or improve ICU care. Secondary objectives are to describe the outcomes reported in these tools, the type of patients and settings studied, and to understand how these tools were developed and implemented in clinical practice.

Methods
We will search the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, PsycINFO, Web of Science, OpenGrey, NHS evidence and Trial Registries from January 2000 onwards. We will include primary research studies (e.g. experimental, quasi-experimental, observational and qualitative studies) recruiting more than 10 adult participants admitted to ICUs, high dependency units and weaning centres regardless of length of stay, describing quality improvement tools such as structured care plans or checklists designed to standardize more than one aspect of care delivery. We will extract data on study and patient characteristics, tool design and implementation strategies and measured outcomes. Two reviewers will independently screen citations for eligible studies and perform data extraction. Data will be synthesised with descriptive statistics; we will use a narrative synthesis to describe review findings.

Discussion
The findings will be used to guide development of tools for use with prolonged ICU stay patients. Our group will use experience-based co-design methods to identify the most important actionable processes of care to include in quality improvement tools these patients. Such tools are needed to standardise practice and thereby improve quality of care. Illustrating the development and implementation methods used for such tools will help to guide translation of similar tools into ICU clinical practice and future research.

Systematic review registration
This protocol is registered on the Open Science Framework, https://osf.io/, DOI 10.17605/OSF.IO/Z8MRE
Maternal and perinatal outcomes and pharmacological management of Covid-19 infection in pregnancy: a systematic review protocol
Authors: Thomas Binny , Pallivalapila Abdulrouf , El Kassem Wessam , Tarannum Asma , Al Hail Fatema , Rijims Mohammed , Parappil Hussain , Bayo Arabo Ibrahim , Ahmad Shamsa , Nazar Zachariah , Stewart Derek , Al Hail Moza 
Published: July 2020

AbstractBackgroundOver 4.2 million confirmed cases and more than 285,000 deaths, COVID-19 pandemic continues to harm significant number of people worldwide. Several studies have reported the impact of COVID-19 in general population; however, there is scarcity of information related to pharmacological management and maternal and perinatal outcomes during the pandemic. Altered physiological, anatomical, and immunological response during pregnancy makes it more susceptible to infections. Furthermore, during pregnancy, a woman undergoes multiple interactions with the health care system that increases her chance of getting infected; therefore, managing pregnant population presents a unique challenge.Research questionsThis systematic review seeks to answer the following questions in relation to COVID-19:What are the different clinical characteristics presented in maternal and perinatal population?What are the different maternal and perinatal outcome measures reported?What are the distinct therapeutic interventions reported to treat COVID-19?Is it safe to use “medications” used in the treatment of COVID-19 during antenatal, perinatal, postnatal, and breastfeeding?MethodThe search will follow a comprehensive, sequential three step search strategy. Several databases relevant to COVID-19 and its impact on pregnancy including Medline, CINAHL, and LitCovid will be searched from the inception of the disease until the completion of data collection. The quality of this search strategy will be assessed using Peer Review of Electronic Search Strategies Evidence-Based Checklist (PRESS EBC). An eligibility form will be developed for a transparent screening and inclusion/exclusion of studies. All studies will be sent to RefWorks, and abstraction will be independently performed by two researchers. Risk of bias will be assessed using Cochrane Risk of Bias tool for randomized controlled trials, Newcastle–Ottawa Quality Assessment Scale for non-randomized studies, and for case reports, Murad et al. tool will be used. Decision to conduct meta-analysis will be based on several factors including homogeneity and outcome measures reported; otherwise, a narrative synthesis will be deemed appropriate.DiscussionThis systematic review will summarize the existing data on effect of COVID-19 on maternal and perinatal population. Furthermore, to the best of our knowledge, this is the first systematic review addressing therapeutic management and safety of medicines to treat COVID-19 during pregnancy and breastfeeding.Systematic review registrationThis systematic review has been registered and published with Prospero (CRD42020172773).