bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of care for people with multimorbidity: a focus group study with patients and their relatives
Authors: Pohontsch Nadine Janis , Schulze Josefine , Hoeflich Charlotte , Glassen Katharina , Breckner Amanda , Szecsenyi Joachim , Lühmann Dagmar , Scherer Martin 
Published: June 2021

BackgroundPrevalence of people with multimorbidity rises. Multimorbidity constitutes a challenge to the healthcare system, and treatment of patients with multimorbidity is prone to high-quality variations. Currently, no set of quality indicators (QIs) exists to assess quality of care, let alone incorporating the patient perspective. We therefore aim to identify aspects of quality of care relevant to the patients’ perspective and match them to a literature-based set of QIs.MethodsWe conducted eight focus groups with patients with multimorbidity and three focus groups with patients’ relatives using a semistructured guide. Data were analysed using Kuckartz’s qualitative content analysis. We derived deductive categories from the literature, added inductive categories (new quality aspects) and translated them into QI.ResultsWe created four new QIs based on the quality aspects relevant to patients/relatives. Two QIs (patient education/self-management, regular updates of medication plans) were consented by an expert panel, while two others were not (periodical check-ups, general practitioner-coordinated care). Half of the literature-based QIs, for example, assessment of biopsychosocial support needs, were supported by participants’ accounts, while more technical domains regarding assessment and treatment regimens were not addressed in the focus groups.ConclusionWe show that focus groups with patients and relatives adding relevant aspects in QI development should be incorporated by default in QI development processes and constitute a reasonable addition to traditional QI development. Our QI set constitutes a framework for assessing the quality of care in the German healthcare system. It will facilitate implementation of treatment standards and increase the use of existing guidelines, hereby helping to reduce overuse, underuse and misuse of healthcare resources in the treatment of patients with multimorbidity.Trial registration numberGerman clinical trials registry (DRKS00015718), Pre-Results.
Public acceptance of COVID-19 vaccines: cross-national evidence on levels and individual-level predictors using observational data
Authors: Lindholt Marie Fly , Jørgensen Frederik , Bor Alexander , Petersen Michael Bang 
Published: June 2021

ObjectivesThe management of the COVID-19 pandemic hinges on the approval of safe and effective vaccines but, equally importantly, on high vaccine acceptance among people. To facilitate vaccine acceptance via effective health communication, it is key to understand levels of vaccine scepticism and the demographic, psychological and political predictors. To this end, we examine the levels and predictors of acceptance of an approved COVID-19 vaccine.Design, setting and participantsWe examine the levels and predictors of acceptance of an approved COVID-19 vaccine in large online surveys from eight Western democracies that differ in terms of the severity of the pandemic and their response: Denmark, France, Germany, Hungary, Sweden, Italy, UK and USA (total N=18 231). Survey respondents were quota sampled to match the population margins on age, gender and geographical location for each country. The study was conducted from September 2020 to February 2021, allowing us to assess changes in acceptance and predictors as COVID-19 vaccine programmes were rolled out.Outcome measureThe outcome of the study is self-reported acceptance of a COVID-19 vaccine approved and recommended by health authorities.ResultsThe data reveal large variations in vaccine acceptance that ranges from 83% in Denmark to 47% in France and Hungary. Lack of vaccine acceptance is associated with lack of trust in authorities and scientists, conspiratorial thinking and a lack of concern about COVID-19.ConclusionMost national levels of vaccine acceptance fall below estimates of the required threshold for herd immunity. The results emphasise the long-term importance of building trust in preparations for health emergencies such as the current pandemic. For health communication, the results emphasise the importance of focusing on personal consequences of infections and debunking of myths to guide communication strategies.
Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response
Authors: Diao Pengfei , Jiang Yue , Li Yuanyuan , Wu Xiang , Li Jin , Zhou Chen , Jiang Lei , Zhang Wei , Yan Enshi , Zhang Ping , Ding Xu , Wu Heming , Yuan Hua , Ye Jinhai , Song Xiaomeng , Wan Linzhong , Wu Yunong , Jiang Hongbing , Wang Yanling , Cheng Jie 
Published: June 2021

BackgroundImmune landscape of cancer has been increasingly recognized as a key feature affecting disease progression, prognosis and therapeutic response. Here, we sought to comprehensively characterize the patterns of tumor-infiltrating immune cells (TIIs) in primary oral squamous cell carcinoma (OSCC) and develop immune features-derived models for prognostication and therapeutic prediction.MethodsA total number of 392 patients with OSCC receiving ablative surgery at three independent centers were retrospectively enrolled and defined as training, testing and validation cohorts. Detailed features of 12 types of TIIs at center of tumor and invasive margin were assessed by immunohistochemistry coupled with digital quantification. TIIs abundance in OSCC was also estimated by bioinformatics approaches using multiple publicly available data sets. Prognostic models based on selected immune features were trained via machine learning approach, validated in independent cohorts and evaluated by time-dependent area under the curves and concordance index (C-index). Immune types of OSCC were further identified by consensus clustering and their associations with genetic, molecular features and patient survival were clarified.ResultsPatterns of TIIs infiltration varied among patients and dynamically evolved along with tumor progression. Prognostic models based on selected TIIs were identified as efficient and sensitive biomarkers to stratify patients into subgroups with favorable or inferior survival as well as responders or non-responders to postoperative radiotherapy or immunotherapy. These models outperformed multiple conventional biomarkers and immune-related scores in prognostic prediction. Furthermore, we identified two main immune subtypes of OSCC (immune-hot and immune-cold) which harbored characteristic TIIs infiltrations and genomic and molecular features, and associated with patient survival.ConclusionsOur results delineated immune landscape and subtypes in OSCC, consolidated their clinical values as robust biomarkers to predict patient survival and therapeutic benefits and reinforced key roles of TIIs and tumor-immune interactions underlying oral tumorigenesis, ultimately facilitating development of tailed immunotherapeutic strategies.
Pan-cancer analysis of CD274 (PD-L1) mutations in 314,631 patient samples and subset correlation with PD-L1 protein expression
Authors: Huang Richard S.P. , Decker Brennan , Murugesan Karthikeyan , Hiemenz Matthew , Mata Douglas A. , Li Gerald , Creeden James , Ramkissoon Shakti H. , Ross Jeffrey S. 
Published: June 2021

BackgroundThe effects of non-amplification short variant (SV) mutations in CD274 (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of CD274 mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1.MethodsCGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements. PD-L1 IHC was performed on a subset of cases (n=58,341) using the DAKO 22C3 PD-L1 IHC assay and scored with the tumor proportion score (TPS).ResultsOverall, the prevalence of CD274 SV mutations was low (0.3%, 1081/314,631) with 577 unique variants. The most common CD274 SV mutations were R260H (n=51), R260C (n=18), R125Q (n=12), C272fs*13 (n=11), R86W (n=10), and R113H (n=10). The prevalence of CD274 mutations varied depending on tumor type with diffuse large B-cell lymphoma (1.9%, 19/997), cutaneous squamous cell carcinoma (1.6%, 14/868), endometrial adenocarcinoma (1.0%, 36/3740), unknown primary melanoma (0.9%, 33/3679), and cutaneous melanoma (0.8%, 32/3874) having the highest frequency of mutations. Of the R260H cases concurrently tested with PD-L1 IHC, most (81.8%, 9/11) had no PD-L1 expression, which contrasts to the five E237K cases where most (80%, 4/5) had PD-L1 expression. In addition, we saw a significantly lower level of PD-L1 expression in samples with a clonal truncating variant (nonsense or frameshift indel) when compared with samples with a subclonal truncating variants (mean: TPS=1 vs TPS=38; p<0.001), and also in clonal versus subclonal missense mutations (mean: TPS=11 vs TPS=22, respectively; p=0.049)ConclusionsWe defined the landscape of CD274 mutations in a large cohort of tumor types that can be used as a reference for examining CD274 mutations as potential resistance biomarkers for ICPI. Furthermore, we presented novel data on the correlation of CD274 mutations and PD-L1 protein expression, providing important new information on the potential functionality of these mutations and can serve as a basis for future research.
E-cigarette manufacturers’ compliance with clinical trial reporting expectations: a case series of registered trials by Juul Labs
Authors: DeVito Nicholas J , Drysdale Henry , McKee Martin , Goldacre Ben 
Published: June 2021

BackgroundElectronic cigarettes (e-cigarettes) are a frequently debated topic in public health. It is essential that clinical trials examining e-cigarettes are fully and accurately reported, especially given long-standing concerns about tobacco industry research. We assess the reporting of clinical trials sponsored by Juul Labs, the largest e-cigarette company in the USA, against accepted reporting standards.MethodsWe searched ClinicalTrials.gov for all trials sponsored by Juul Labs and determined those with registry data consistent with coverage by the Food and Drug Administration (FDA) Amendments Act 2007 (FDAAA). For trials with a primary completion date more than 1 year earlier, we searched ClinicalTrials.gov, the academic literature and a Juul-funded research database (JLI Science) for results. For located results, we compared reported outcomes with registered outcomes in line with Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines.ResultsWe located five registered trials sponsored by Juul Labs that appeared covered by the FDAAA 2007 in the public data. All five trials did not have results available on ClinicalTrials.gov. We found one publication and four poster presentations reporting results for four of the five covered trials outside of ClinicalTrials.gov. Of 61 specified outcomes, 28 were CONSORT compliant. Specific outcome reporting issues are detailed.DiscussionOur findings raise substantial concerns regarding these trials. Clinicians, public health professionals, and the public cannot make informed choices about the benefits or hazards of e-cigarettes if the results of clinical trials are not completely and transparently reported. Clarification and potential enforcement of reporting laws may be required.
Flexible ball-milled Bi0.4 Sb1.6 Te3/methyl cellulose thermoelectric films fabricated by screen-printing method
Authors: Li Xiang , Du Yong , Meng Qiufeng 
Published: June 2021

Flexible Bi[Formula: see text]Sb[Formula: see text]Te3 (BST)/methyl cellulose (MC) thermoelectric composite films were prepared by a two-step process: BST powders were successfully prepared via a ball milling method, and then BST/MC composite films with different volume fractions of BST were screen printed on flexible mixed cellulose esters membrane. As the contents of BST powders increased, the electrical conductivity was significantly improved, while the Seebeck coefficient was nearly unchanged, and a room temperature power factor (PF) of 2.32 [Formula: see text]W m[Formula: see text] K[Formula: see text] was achieved when the volume fraction of BST was 80%. After the cold-pressing treatment, both the electrical conductivity and Seebeck coefficient were improved, and a highest PF of 10.07 [Formula: see text]W m[Formula: see text] K[Formula: see text] was obtained at room temperature for the film with 80 vol.% BST, which was [Formula: see text]4.3 times higher than that of the pristine sample (2.32 [Formula: see text]W m[Formula: see text] K[Formula: see text] at room temperature). The tendency of thermoelectric performance varying with BST proportion was explained by the percolation threshold theory. This work shows the great potential of screen-printing technology in flexible and wearable electronics.
14-3-3σFunctions as an Intestinal Tumor Suppressor
Authors: Winter Markus , Rokavec Matjaž , Hermeking Heiko 
Published: June 2021

AbstractAlthough the 14-3-3σ gene was initially identified as a p53 target gene in colorectal cancer cells, its potential role in intestinal tumorigenesis has remained unknown. Here we determined that 14-3-3σ expression is significantly downregulated in primary human colorectal cancer when compared with adjacent normal colonic tissue in patient samples. Downregulation of 14-3-3σ in primary colorectal cancers was significantly associated with p53 mutation, increasing tumor stage, distant metastasis, and poor patient survival. Poor survival was more significantly associated with decreased 14-3-3σ expression in p53 wild-type than in p53-mutant colorectal cancers. 14-3-3σ expression was detected in enterocytes of the transit amplifying zone and gradually increased towards the apical villi in the small intestinal epithelium. In small and large intestinal epithelia and adenomas, 14-3-3σ expression was upregulated in differentiated areas. Deletion of 14-3-3σ in ApcMin mice increased the number and size of adenomas in the small intestine and colon, shortening the median survival by 64 days. 14-3-3σ–deficient adenomas displayed increased proliferation and decreased apoptosis, as well as increased dysplasia. In adenomas, loss of 14-3-3σ promoted acquisition of a mesenchymal-like gene expression signature, which was also found in colorectal cancers from patients with poor relapse-free survival. The transcriptional programs controlled by the 14-3-3σ-interacting factors SNAIL, c-JUN, YAP1, and FOXO1 were activated by deletion of 14-3-3σ, potentially contributing to the enhanced tumor formation and growth. Taken together, these results provide genetic evidence of a tumor-suppressor function of 14-3-3σ in the intestine.Significance:Downregulation of 14-3-3σ in colorectal cancer is associated with metastasis and poor survival of patients, and its inactivation in a murine tumor model drives intestinal tumor formation and epithelial-mesenchymal transition.
NCI Imaging Data Commons
Authors: Fedorov Andrey , Longabaugh William J.R. , Pot David , Clunie David A. , Pieper Steve , Aerts Hugo J.W.L. , Homeyer André , Lewis Rob , Akbarzadeh Afshin , Bontempi Dennis , Clifford William , Herrmann Markus D. , Höfener Henning , Octaviano Igor , Osborne Chad , Paquette Suzanne , Petts James , Punzo Davide , Reyes Madelyn , Schacherer Daniela P. , Tian Mi , White George , Ziegler Erik , Shmulevich Ilya , Pihl Todd , Wagner Ulrike , Farahani Keyvan , Kikinis Ron 
Published: June 2021

AbstractThe National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research.Significance:This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.
HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase
Authors: Ginzel Joshua D. , Acharya Chaitanya R. , Lubkov Veronica , Mori Hidetoshi , Boone Peter G. , Rochelle Lauren K. , Roberts Wendy L. , Everitt Jeffrey I. , Hartman Zachary C. , Crosby Erika J. , Barak Lawrence S. , Caron Marc G. , Chen Jane Q. , Hubbard Neil E. , Cardiff Robert D. , Borowsky Alexander D. , Lyerly H. Kim , Snyder Joshua C. 
Published: June 2021

Abstract

HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (WTHER2), exon-16 null (d16HER2), and N-terminally truncated (p95HER2) HER2 isoforms is used to trace tumorigenesis from initiation to invasion. Tumorigenesis was visualized using whole-gland fluorescent lineage tracing and single-cell molecular pathology. We demonstrate that within weeks of expression, morphologic aberrations were already present and unique to each HER2 isoform. Although WTHER2 cells were abundant throughout the mammary ducts, detectable lesions were exceptionally rare. In contrast, d16HER2 and p95HER2 induced rapid tumor development. d16HER2 incited homogenous and proliferative luminal-like lesions which infrequently progressed to invasive phenotypes whereas p95HER2 lesions were heterogenous and invasive at the smallest detectable stage. Distinct cancer trajectories were observed for d16HER2 and p95HER2 tumors as evidenced by oncogene-dependent changes in epithelial specification and the tumor microenvironment. These data provide direct experimental evidence that intratumor heterogeneity programs begin very early and well in advance of screen or clinically detectable breast cancer.

Implications:
Although all HER2 breast cancers are treated equally, we show a mechanism by which clinically undetected HER2 isoforms program heterogenous cancer phenotypes through biased epithelial specification and adaptations within the tumor microenvironment.
Remote Hemodynamic Monitoring Equally Reduces Heart Failure Hospitalizations in Women and Men in Clinical Practice: A Sex-Specific Analysis of the CardioMEMS Post-Approval Study
Authors: DeFilippis Ersilia M. , Henderson John , Axsom Kelly M. , Costanzo Maria Rosa , Adamson Philip B. , Miller Alan B. , Brett Marie-Elena , Givertz Michael M. 
Published: June 2021

Background:
Response to pharmacological and device-based therapy for heart failure (HF) may vary by sex. We examined sex differences in response to ambulatory hemodynamic monitoring in clinical practice using the CardioMEMS PAS (Post-Approval Study).

Methods:
The CardioMEMS PAS was a prospective, single-arm, multicenter, open-label study of 1200 adults with New York Heart Association class III HF and at least 1 HF hospitalization (HFH) within 12 months who underwent pulmonary artery pressure sensor implantation between 2014 and 2017. Changes in pulmonary artery pressure over time were stratified by ejection fraction <40% and sex. Clinical outcomes including HFH rate at 12 months, 1-year mortality, and quality of life were examined in women and men.

Results:

Four hundred fifty-two women (38% of total) enrolled in the PAS were less likely to be White (78% versus 86%) and more likely to have nonischemic cardiomyopathy (44% versus 34%) and had significantly higher SBP (132 versus 124 mm Hg), mean ejection fraction (44% versus 36%), and pulmonary vascular resistance (3.2 versus 2.6 WU) than men (
P
<0.001 for all). There were similar reductions in pulmonary artery pressure from baseline to 12 months in both men and women for the whole cohort and for subgroups with HF with reduced ejection fraction and HF with preserved ejection fraction. Both sexes experienced significant decreases in HFH over 12 months (men: HR, 0.46 [95% CI, 0.40–0.52]; women: HR, 0.39 [95% CI, 0.33–0.46]). In adjusted models, there were no significant differences in change in HFH between men and women (interaction
P
=0.13) or all-cause mortality at 1 year (adjusted HR, 1.25 [95% CI, 0.88–1.77]).

Conclusions:
Women and men enrolled in the CardioMEMS PAS had similar reductions from baseline in pulmonary artery pressure over 1 year and experienced similar reductions in HFH. Hemodynamic monitoring provides similar benefit with regard to HF events in both women and men.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02279888.
National Tibetan Plateau Data Center: Promoting Earth System Science on the Third Pole
Authors: Pan Xiaoduo , Guo Xuejun , Li Xin , Niu Xiaolei , Yang Xiaojuan , Feng Min , Che Tao , Jin Rui , Ran Youhua , Guo Jianwen , Hu Xiaoli , Wu Adan 
Published: June 2021

AbstractThe Tibetan Plateau, known as the world’s “Third Pole” due to its high altitude, is experiencing rapid, intense climate change, similar to and even far more than that occurring in the Arctic and Antarctic. Scientific data sharing is very important to address the challenges of better understanding the unprecedented changes in the Third Pole and their impacts on the global environment and humans. The National Tibetan Plateau Data Center (TPDC, http://data.tpdc.ac.cn) is one of the first 20 national data centers endorsed by the Ministry of Science and Technology of China in 2019 and features the most complete scientific data for the Tibetan Plateau and surrounding regions, hosting more than 3,500 datasets in diverse disciplines. Fifty datasets featuring high-mountain observations, land surface parameters, near-surface atmospheric forcing, cryospheric variables, and high-profile article-associated data over the Tibetan Plateau, frequently being used to quantify the hydrological cycle and water security, early warning assessments of glacier avalanche disasters, and other geoscience studies on the Tibetan Plateau, are highlighted in this manuscript. The TPDC provides a cloud-based platform with integrated online data acquisition, quality control, analysis, and visualization capability to maximize the efficiency of data sharing. The TPDC shifts from the traditional centralized architecture to a decentralized deployment to effectively connect Third Pole–related data from other domestic and international data sources. As an embryo of data sharing and management over extreme environment in the upcoming “big data” era, the TPDC is dedicated to filling the gaps in data collection, discovery, and consumption in the Third Pole, facilitating scientific activities, particularly those featuring extensive interdisciplinary data use.