bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of knee osteoarthritis care in the Netherlands: a survey on the perspective of people with osteoarthritis
Authors: Oomen J. M. H. , Peters Y. A. S. , van den Ende C. H. , Schers H. J. , Assendelft W. J. J. , Vriezekolk J. E. , Koëter S. 
Published: May 2022

Abstract
Background
Quality indicators (QIs) are used to monitor quality of care and adherence to osteoarthritis (OA) standards of care. Patient reported QIs can identify the most important gaps in quality of care and the most vulnerable patient groups. The aim of this study was to capture the perspective of people with knee OA (KOA) in the Netherlands on the quality of care received, and explore determinants related to lower achievement rates.

Methods
We sent an online survey to all members of The Dutch Knee Panel (n = 622) of the Sint Maartenskliniek Nijmegen, the Netherlands between September and October 2019. The survey consisted of a slightly adapted version of the “OsteoArthritis Quality Indicator” (OA-QI) questionnaire (18 items; yes, no, N/A); a rating of quality of KOA care on a 10-point scale; a question on whether or not one wanted to see change in the care for KOA; and an open-ended question asking recommendations for improvement of OA care. Furthermore, sociodemographic and disease related characteristics were collected. Pass rates for separate QIs and pass rates on patient level were calculated by dividing the number of times the indicator was achieved by the number of eligible persons for that particular indicator.

Results
A total of 434 participants (70%) completed the survey. The mean (SD) pass rate (those answering “Yes”) for separate QIs was 49% (20%); ranging from 15% for receiving referral for weight reduction to 75% for patient education on how to manage knee OA. The mean (SD) pass rate on patient level was 52% (23%). Presence of OA in other joints, comorbidities, and having a knee replacement were associated with higher pass rates. On average, a score of 6.5 (1.6) was given for the quality of care received, and the majority of respondents (59%) wanted change in the care for KOA. Of 231 recommendations made, most often mentioned were the need for tailoring of care (14%), more education (13%), and more empathy and support from healthcare providers (12%).

Conclusion
This study found patients are only moderately satisfied with the OA care received, and showed substantial gaps between perceived quality of care for OA and internationally accepted standards. Future research should focus on the underlying reasons and provide strategies to bridge these gaps.
Diet of Mesozoic toothed birds (Longipterygidae) inferred from quantitative analysis of extant avian diet proxies
Authors: Miller Case Vincent , Pittman Michael , Wang Xiaoli , Zheng Xiaoting , Bright Jen A. 
Published: May 2022

AbstractBackgroundBirds are key indicator species in extant ecosystems, and thus we would expect extinct birds to provide insights into the nature of ancient ecosystems. However, many aspects of extinct bird ecology, particularly their diet, remain obscure. One group of particular interest is the bizarre toothed and long-snouted longipterygid birds. Longipterygidae is the most well-understood family of enantiornithine birds, the dominant birds of the Cretaceous period. However, as with most Mesozoic birds, their diet remains entirely speculative.ResultsTo improve our understanding of longipterygids, we investigated four proxies in extant birds to determine diagnostic traits for birds with a given diet: body mass, claw morphometrics, jaw mechanical advantage, and jaw strength via finite element analysis. Body mass of birds tended to correspond to the size of their main food source, with both carnivores and herbivores splitting into two subsets by mass: invertivores or vertivores for carnivores, and granivores + nectarivores or folivores + frugivores for herbivores. Using claw morphometrics, we successfully distinguished ground birds, non-raptorial perching birds, and raptorial birds from one another. We were unable to replicate past results isolating subtypes of raptorial behaviour. Mechanical advantage was able to distinguish herbivorous diets with particularly high values of functional indices, and so is useful for identifying these specific diets in fossil taxa, but overall did a poor job of reflecting diet. Finite element analysis effectively separated birds with hard and/or tough diets from those eating foods which are neither, though could not distinguish hard and tough diets from one another. We reconstructed each of these proxies in longipterygids as well, and after synthesising the four lines of evidence, we find all members of the family butShengjingornis(whose diet remains inconclusive) most likely to be invertivores or generalist feeders, with raptorial behaviour likely inLongipteryxandRapaxavis.ConclusionsThis study provides a 20% increase in quantitatively supported fossil bird diets, triples the number of diets reconstructed in enantiornithine species, and serves as an important first step in quantitatively investigating the origins of the trophic diversity of living birds. These findings are consistent with past hypotheses that Mesozoic birds occupied low trophic levels.
Structured reporting to improve transparency of analyses in prognostic marker studies
Authors: Sauerbrei Willi , Haeussler Tim , Balmford James , Huebner Marianne 
Published: May 2022

AbstractBackgroundFactors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted.MethodsA systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted.ResultsStructured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance.ConclusionsA substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.
Palbociclib-based high-throughput combination drug screening identifies synergistic therapeutic options in HPV-negative head and neck squamous cell carcinoma
Authors: Gu Ziyue , Shi Chaoji , Li Jiayi , Han Yong , Sun Bao , Zhang Wuchang , Wu Jing , Zhou Guoyu , Ye Weimin , Li Jiang , Zhang Zhiyuan , Zhou Rong 
Published: May 2022

Abstract
Background
Deregulation of cell-cycle pathway is ubiquitously observed in human papillomavirus negative (HPVneg) head and neck squamous cell carcinoma (HNSCC). Despite being an attractive target, CDK4/6 inhibition using palbociclib showed modest or conflicting results as monotherapy or in combination with platinum-based chemotherapy or cetuximab in HPVneg HNSCC. Thus, innovative agents to augment the efficacy of palbociclib in HPVneg HNSCC would be welcomed.

Methods
A collection of 162 FDA-approved and investigational agents was screened in combinatorial matrix format, and top combinations were validated in a broader panel of HPVneg HNSCC cell lines. Transcriptional profiling was conducted to explore the molecular mechanisms of drug synergy. Finally, the most potent palbociclib-based drug combination was evaluated and compared with palbociclib plus cetuximab or cisplatin in a panel of genetically diverse HPVneg HNSCC cell lines and patient-derived xenograft models.

Results
Palbociclib displayed limited efficacy in HPVneg HNSCC as monotherapy. The high-throughput combination drug screening provided a comprehensive palbociclib-based drug-drug interaction dataset, whereas significant synergistic effects were observed when palbociclib was combined with multiple agents, including inhibitors of the PI3K, EGFR, and MEK pathways. PI3K pathway inhibitors significantly reduced cell proliferation and induced cell-cycle arrest in HPVneg HNSCC cell lines when combined with palbociclib, and alpelisib (a PI3Kα inhibitor) was demonstrated to show the most potent synergy with particularly higher efficacy in HNSCCs bearing PIK3CA alterations. Notably, when compared with cisplatin and cetuximab, alpelisib exerted stronger synergism in a broader panel of cell lines. Mechanistically, RRM2-dependent epithelial mesenchymal transition (EMT) induced by palbociclib, was attenuated by alpelisib and cetuximab rather than cisplatin. Subsequently, PDX models with distinct genetic background further validated that palbociclib plus alpelisib had significant synergistic effects in models harboring PIK3CA amplification.

Conclusions
This study provides insights into the systematic combinatory effect associated with CDK4/6 inhibition and supports further initiation of clinical trials using the palbociclib plus alpelisib combination in HPVneg HNSCC with PIK3CA alterations.
Preclinical validation and phase I trial of 4-hydroxysalicylanilide, targeting ribonucleotide reductase mediated dNTP synthesis in multiple myeloma
Authors: Xie Yongsheng , Wang Yingcong , Xu Zhijian , Lu Yumeng , Song Dongliang , Gao Lu , Yu Dandan , Li Bo , Chen Gege , Zhang Hui , Feng Qilin , Zhang Yong , Hu Ke , Huang Cheng , Peng Yu , Wu Xiaosong , Mao Zhiyong , Shao Jimin , Zhu Weiliang , Shi Jumei 
Published: May 2022

Abstract
Background
Aberrant DNA repair pathways contribute to malignant transformation or disease progression and the acquisition of drug resistance in multiple myeloma (MM); therefore, these pathways could be therapeutically exploited. Ribonucleotide reductase (RNR) is the rate-limiting enzyme for the biosynthesis of deoxyribonucleotides (dNTPs), which are essential for DNA replication and DNA damage repair. In this study, we explored the efficacy of the novel RNR inhibitor, 4-hydroxysalicylanilide (HDS), in myeloma cells and xenograft model. In addition, we assessed the clinical activity and safety of HDS in patients with MM.

Methods
We applied bioinformatic, genetic, and pharmacological approaches to demonstrate that HDS was an RNR inhibitor that directly bound to RNR subunit M2 (RRM2). The activity of HDS alone or in synergy with standard treatments was evaluated in vitro and in vivo. We also initiated a phase I clinical trial of single-agent HDS in MM patients (ClinicalTrials.gov: NCT03670173) to assess safety and efficacy.

Results
HDS inhibited the activity of RNR by directly targeting RRM2. HDS decreased the RNR-mediated dNTP synthesis and concomitantly inhibited DNA damage repair, resulting in the accumulation of endogenous unrepaired DNA double-strand breaks (DSBs), thus inhibiting MM cell proliferation and inducing apoptosis. Moreover, HDS overcame the protective effects of IL-6, IGF-1 and bone marrow stromal cells (BMSCs) on MM cells. HDS prolonged survival in a MM xenograft model and induced synergistic anti-myeloma activity in combination with melphalan and bortezomib. HDS also showed a favorable safety profile and demonstrated clinical activity against MM.

Conclusions
Our study provides a rationale for the clinical evaluation of HDS as an anti-myeloma agent, either alone or in combination with standard treatments for MM.
Trial registration: ClinicalTrials.gov, NCT03670173, Registered 12 September 2018.
Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus
Authors: Reijrink M. , van Ark J. , Lexis C. P. H. , Visser L. M. , Lodewijk M. E. , van der Horst I. C. C. , Zeebregts C. J. , van Goor H. , de Jager S. C. A. , Pasterkamp G. , Wolffenbuttel B. H. R. , Hillebrands J. L. 
Published: May 2022

Abstract
Background
Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16−, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD.

Methods
Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers.

Results
Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM.

Conclusions
Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.
Major dietary patterns in relation to chronic low back pain; a cross-sectional study from RaNCD cohort
Authors: Pasdar Yahya , Hamzeh Behrooz , Karimi Sheno , Moradi Shima , Cheshmeh Sahar , Shamsi Mohammad Bagher , Najafi Farid 
Published: May 2022

Abstract
Background
Chronic low back pain (LBP) is the most common musculoskeletal pain that affects a person’s daily activities. This present study aimed at evaluating the relationship between major dietary pattern and Chronic LBP.

Methods
This cross-sectional analysis was examined 7686 Kurdish adults. The RaNCD cohort study physician diagnosed chronic LBP. Dietary patterns were derived using principal component analysis. The three identified dietary patterns derived were named: 1) the vegetarian diet included vegetables, whole grain, legumes, nuts, olive, vegetable oil, fruits, and fruit juice; 2) high protein diet related to higher adherence to red and white meat, legumes, nuts, and egg; and 3) energy-dense diet characterized with higher intake of salt, sweet, dessert, hydrogenated fat, soft drink, refined grain, tea, and coffee. Dietary pattern scores were divided into tertiles. Binary logistic regression in crude, adjusted odds ratios (OR) and 95% confidence intervals (CI) were used to determine this association.

Results
Twenty-two per cent of participants had chronic LBP. Higher adherence to high protein dietary pattern was inversely associated with chronic LBP in crude (OR: 0.79, 95% CI: 0.69–0.9) and adjusted model (for age, sex, smoking, drinking, diabetes, physical activity, body mass index, and waist circumference) (OR: 0.84, 95% CI: 0.72–0.97). In addition, after controlling for the mentioned potential confounders, participants in the highest category of energy dense diet were positively associated with chronic LBP compared with those in the lowest category (OR: 1.13, 95% CI: 1.01–1.32).

Conclusions
Higher adherence to the high protein diet was inversely related to chronic LBP prevalence. In addition, we found that following energy dense diet was positively associated with chronic LBP.
All-in-one approaches for triple-negative breast cancer therapy: metal-phenolic nanoplatform for MR imaging-guided combinational therapy
Authors: Xie Qi , Li Shichao , Feng Xingxing , Shi Jingyu , Li Yang , Yuan Guanjie , Yang Conglian , Shen Yaqi , Kong Li , Zhang Zhiping 
Published: May 2022

AbstractBackgroundConventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects.ResultsHerein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy.ConclusionsA nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.Graphical Abstract
Vision-related quality of life in patients with glaucoma: the role of illness perceptions
Authors: Zhang Qiqi , Zhou Wenzhe , Song Di , Xie Yanqian , Lin Hao , Liang Youping , Ren Yanhan , Liang Yuanbo , Chen Yanyan 
Published: May 2022

Abstract
Purpose
To explore the predictive effects of illness perceptions on vision-related quality of life (VRQoL) in Chinese glaucoma patients.

Methods
In this cross-sectional study, 97 patients with glaucoma completed the brief illness perception questionnaire (BIPQ), the glaucoma quality of life-15 (GQL-15) questionnaire, and a questionnaire regarding sociodemographic and clinical information. A correlation analysis and hierarchical linear regression analysis were performed.

Results
The BIPQ total score was positively correlated with the total score of the GQL-15 questionnaire and the scores of its four dimensions. Chronic comorbidities, the type of glaucoma, the best-corrected visual acuity (BCVA), the mean defect (MD) of visual field in the better eye, and identity in the BIPQ were critical predictors of VRQoL. Illness perceptions independently accounted for 7.8% of the variance in the VRQoL of glaucoma patients.

Conclusions
Patients with stronger illness perceptions and those who perceive themselves as having more glaucoma symptoms are likely to experience worse VRQoL. Illness perceptions in glaucoma patients deserve clinical attention, and further studies are needed to examine whether cognitive interventions targeting illness perceptions can improve VRQoL.
Assessing competence of mid-level providers delivering primary health care in India: a clinical vignette-based study in Chhattisgarh state
Authors: Garg Samir , Tripathi Narayan , Datla Jayathra , Zapata Tomas , Mairembam Dilip S. , Bebarta Kirtti K. , Krishnendhu C. , de Graeve Hilde 
Published: May 2022

Abstract
Background
The global commitment to primary health care (PHC) has been reconfirmed in the declaration of Astana, 2018. India has also seen an upswing in national commitment to implement PHC. Health and wellness centres (HWCs) have been introduced, one at every 5000 population, with the fundamental purpose of bringing a comprehensive range of primary care services closer to where people live. The key addition in each HWC is of a mid-level healthcare provider (MLHP). Nurses were provided a 6-month training to play this role as community health officers (CHOs). But no assessments are available of the clinical competence of this newly inducted cadre for delivering primary care. The current study was aimed at providing an assessment of competence of CHOs in the Indian state of Chhattisgarh.

Methods
The assessment involved a comparison of CHOs with rural medical assistants (RMAs) and medical officers (MO), the two main existing clinical cadres providing primary care in Chhattisgarh. Standardized clinical vignettes were used to measure knowledge and clinical reasoning of providers. Ten ailments were included, based on primary care needs in Chhattisgarh. Each part of clinical vignettes was standardized using expert consultations and standard treatment guidelines. Sample size was adequate to detect 15% difference between scores of different cadres and the assessment covered 132 CHOs, 129 RMAs and 50 MOs.

Results
The overall mean scores of CHOs, RMAs and MOs were 50.1%, 63.1% and 68.1%, respectively. They were statistically different (p < 0.05). The adjusted model also confirmed the above pattern. CHOs performed well in clinical management of non-communicable diseases and malaria. CHOs also scored well in clinical knowledge for diagnosis. Around 80% of prescriptions written by CHOs for hypertension and diabetes were found correct.

Conclusion
The non-physician MLHP cadre of CHOs deployed in rural facilities under the current PHC initiative in India exhibited the potential to manage ambulatory care for illnesses. Continuous training inputs, treatment protocols and medicines are needed to improve performance of MLHPs. Making comprehensive primary care services available close to people is essential to PHC and well-trained mid-level providers will be crucial for making it a reality in developing countries.