bluuebunny/crossref_metadata_2025_split huggingface dataset:
KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
Authors: Joensuu Heikki , Wardelmann Eva , Eriksson Mikael , Reichardt Annette , Hall Kirsten Sundby , Schütte Jochen , Cameron Silke , Hohenberger Peter , Sihto Harri , Jost Philipp J. , Lindner Lars H. , Bauer Sebastian , Nilsson Bengt , Kallio Raija , Pesonen Tommi , Reichardt Peter 
Published: April 2023

Abstract

Purpose:
Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib.

Patients and Methods:
The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses.

Results:
During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15–0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31–0.74; P &lt; 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib.

Conclusions:
Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.
A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer
Authors: Leboulleux Sophie , Do Cao Christine , Zerdoud Slimane , Attard Marie , Bournaud Claire , Lacroix Ludovic , Benisvy Danielle , Taïeb David , Bardet Stéphane , Terroir-Cassou-Mounat Marie , Anizan Nadège , Bouvier-Morel Emilie , Lamartina Livia , Lion Georges , Betrian Sarah , Sajous Christophe , Schiazza Aurélie , Garcia Marie-Eve , Ciappuccini Renaud , Schlumberger Martin , Al Ghuzlan Abir , Godbert Yann , Borget Isabelle 
Published: April 2023

Abstract

Purpose:
To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.

Patients and Methods:
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion &gt; 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.

Results:
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients.

Conclusions:
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.
Predicting article quality scores with machine learning: The U.K. Research Excellence Framework
Authors: Thelwall Mike , Kousha Kayvan , Wilson Paul , Makita Meiko , Abdoli Mahshid , Stuart Emma , Levitt Jonathan , Knoth Petr , Cancellieri Matteo 
Published: April 2023

AbstractNational research evaluation initiatives and incentive schemes choose between simplistic quantitative indicators and time-consuming peer/expert review, sometimes supported by bibliometrics. Here we assess whether machine learning could provide a third alternative, estimating article quality using more multiple bibliometric and metadata inputs. We investigated this using provisional three-level REF2021 peer review scores for 84,966 articles submitted to the U.K. Research Excellence Framework 2021, matching a Scopus record 2014–18 and with a substantial abstract. We found that accuracy is highest in the medical and physical sciences Units of Assessment (UoAs) and economics, reaching 42% above the baseline (72% overall) in the best case. This is based on 1,000 bibliometric inputs and half of the articles used for training in each UoA. Prediction accuracies above the baseline for the social science, mathematics, engineering, arts, and humanities UoAs were much lower or close to zero. The Random Forest Classifier (standard or ordinal) and Extreme Gradient Boosting Classifier algorithms performed best from the 32 tested. Accuracy was lower if UoAs were merged or replaced by Scopus broad categories. We increased accuracy with an active learning strategy and by selecting articles with higher prediction probabilities, but this substantially reduced the number of scores predicted.
The Management of Drinking Water in Trondheim from 950 to 1777 as a Source of Changing Attitudes toward Health
Authors: Swensen Elisabeth Forrestad , van Oosten Roos M.R. , Christophersen Axel 
Published: April 2023

Abstract
This article aims to illuminate how the management of drinking water and public health in Trondheim, Norway changed from 950 to 1777, from a private to public responsibility. A systematic analysis of five excavations in Trondheim shows that during the Middle Ages, only a few citizens had a well or a cistern on their property. This suggests that fetching water from above-ground sources was a regular practice. In the post-medieval period, this changed as the number of wells increased. However, the well water got polluted, and alternative water sources were too far away for the rising population. 18th-century political ideas emphasised how the citizens were now the state’s greatest resource, which prompted new mentalities on how authorities had to take care of the people. In 1777, the public authorities of Trondheim finally established a public water pipe system, ensuring clean water to its citizens.
Northern theories and Southern policies. Why the most influential approaches are insufficient for teaching public policy in Latin America
Authors: Bentancur Nicolás 
Published: April 2023

The main theories of the thriving field of study of public policies have been formulated at institutions of developed countries, mostly by the American academy, based on the particular conditions of policy-making processes of their own country. However, its heuristic premises are considered, initially, as universal and are used extensively in teaching and academic studies around the world. This paper examines the complexities derived from the application of such predominant theoretical approaches to the study and teaching of public policies that are implemented in Latin American countries. Based on an extensive use of specialized literature, 10 public policy variables are identified and organized into two dimensions, one institutional and the other procedural. It is argued that the values of these variables in the countries of this region differ significantly from those observed in the United States, which reveals the explanatory shortcomings of those approaches to account for the particular modalities of public policymaking in these countries.
Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy
Authors: Katsuki Masahito , Shimazu Tomokazu , Kikui Shoji , Danno Daisuke , Miyahara Junichi , Takeshima Ryusaku , Takeshima Eriko , Shimazu Yuki , Nakashima Takahiro , Matsuo Mitsuhiro , Takeshima Takao 
Published: April 2023

Background Misdiagnoses of headache disorders are a serious issue. Therefore, we developed an artificial intelligence-based headache diagnosis model using a large questionnaire database in a specialized headache hospital. Methods Phase 1: We developed an artificial intelligence model based on a retrospective investigation of 4000 patients (2800 training and 1200 test dataset) diagnosed by headache specialists. Phase 2: The model’s efficacy and accuracy were validated. Five non-headache specialists first diagnosed headaches in 50 patients, who were then re-diagnosed using AI. The ground truth was the diagnosis by headache specialists. The diagnostic performance and concordance rates between headache specialists and non-specialists with or without artificial intelligence were evaluated. Results Phase 1: The model’s macro-average accuracy, sensitivity (recall), specificity, precision, and F values were 76.25%, 56.26%, 92.16%, 61.24%, and 56.88%, respectively, for the test dataset. Phase 2: Five non-specialists diagnosed headaches without artificial intelligence with 46% overall accuracy and 0.212 kappa for the ground truth. The statistically improved values with artificial intelligence were 83.20% and 0.678, respectively. Other diagnostic indexes were also improved. Conclusions Artificial intelligence improved the non-specialist diagnostic performance. Given the model’s limitations based on the data from a single center and the low diagnostic accuracy for secondary headaches, further data collection and validation are needed.
Anti-Plasmodial Activity and Mass Spectrometric Profiling of Peptide-enriched Methanol/Water Extract of Leaves from the Himalayan Viola canescens Wall
Authors: Mann Neha , Upadhyay Pooja , Vishnupriya P. , Prabhakar S. , Uniyal P.L. , Lakhanpaul Suman , Sahal Dinkar , Sabareesh V. 
Published: April 2023

Background: Plants belonging to the genus Viola and family Violaceae are well known in Ayurvedic and Unani medicine for their pharmaceutical importance. Viola, commonly known as Banafsha, has been traditionally used as an anti-malarial. The goal of this study was to determine the anti-Plasmodial activity of the cyclotide-rich crude methanol/water extract of leaves from Viola canescens Wall and to analyze its constituents by mass spectrometry (MS). Materials and Methods: Liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) involving quadrupole time-of-flight (Q-ToF) and matrix-assisted laser desorption/ionization (MALDI)-time-of-flight-mass spectrometry (ToF-MS) were applied to investigate the cyclotides rich in methanol/water extract. The intact molecular masses were observed in the range of 2,800–3,400 Daltons, suggesting the presence of peptides. Since various head-to-tail cyclized and intramolecularly disulfide-bonded peptides known as cyclotides have been identified in the Violaceae family, we wanted to verify whether cyclotides are present in our extract. So, the intact masses inferred from the observed spectra were interrogated with Cybase ( www.cybase.org.au ), which is a database on plant cyclotides. Results: We observed promising anti-Plasmodial activity (IC50 44 µg/ml) in the cyclotide-rich methanol/water extract prepared from the leaves of the Himalayan V. canescens Wall. The output obtained from Cybase confirmed the presence of about 20 different cyclotides in our extracts. However, no sequence information could be obtained from Cybase for 14 intact molecular masses, which were inferred from the observed LC-ESI-MS data. Hence, these could correspond to novel peptide/cyclotide sequences, which might be characteristic of Himalayan V. canescens. Conclusion: This is the first report on the anti-Plasmodial activity of the cyclotide-enriched methanol/water crude extract of the leaves of V. canescens.
Integrating digital interventions with clinical practice in youth mental health services
Authors: Cross Shane P , Nicholas Jennifer , Bell Imogen H , Mangelsdorf Shaminka , Valentine Lee , Thompson Andrew , Gleeson John F , Alvarez-Jimenez Mario 
Published: April 2023

Objective Integrating digital technologies with clinical practice promises to improve access and enhance care in the context of high service demand and constrained capacity. Method We outline the emerging research in the integration of digital tools in clinical care, known as blended care, and provide case examples of mental health technology platforms currently in use, summarise findings regarding novel technologies such as virtual reality, and outline real-world implementation challenges and potential solutions. Results Recent evidence shows that blended care approaches are clinically effective and improve service efficiency. Youth-specific technologies such as moderated online social therapy (MOST) are achieving a range of positive clinical and functional outcomes, while emerging technologies like virtual reality have strong evidence in anxiety disorder, and accumulating evidence in psychotic conditions. Implementation science frameworks show promise in helping overcome the common challenges faced in real-world adoption and ongoing use. Conclusion The integrated, blended use of digital mental health technologies with face-to-face clinical care has the potential to improve care quality for young people while helping overcome the growing challenges faced by youth mental health service providers.
Mikenewite, the natural analogue of synthetic α-Mn2+(S4+O3)⋅3H2O, a new sulfite mineral from the Ojuela mine, Mapimí, Mexico
Authors: Yang Hexiong , Jenkins Robert A. , McGlasson James A. , Gibbs Ronald B. , Downs Robert T. 
Published: April 2023

AbstractA new mineral species, mikenewite (IMA2022-102), ideally Mn2+(S4+O3)⋅3H2O, has been discovered from the San Judas Chimney, Ojuela mine, Mapimí, Durango, Mexico. It occurs as spheres of platy crystals. Associated minerals include goethite, cryptomelane, adamite and lotharmeyerite. Mikenewite is yellowish in transmitted light, transparent with a white streak and vitreous lustre. It is brittle and has a Mohs hardness of 2½–3. Cleavage is perfect on {101}. The measured and calculated densities are 2.48(5) and 2.467 g/cm3, respectively. Optically, mikenewite is biaxial (+), with α = 1.606(5), β = 1.614(5), γ = 1.627(1) (white light), 2V(meas.) = 69(3)° and 2V(calc.) = 77°. An electron microprobe analysis yielded an empirical formula (based on 6 O apfu) of (Mn0.86Zn0.12Fe0.04Ca0.02)Σ1.04(S0.98O3)⋅3H2O, which can be simplified to (Mn,Zn,Fe)(SO3)⋅3H2O.Mikenewite is the natural analogue of synthetic α-Mn2+(S4+O3)⋅3H2O, as well as the Mn-analogue of albertiniite, Fe2+(S4+O3)⋅3H2O. It is monoclinic, with space group P21/n and unit-cell parameters a = 6.6390(3), b = 8.8895(4), c = 8.7900(4) Å, β = 96.095(2)°, V = 515.83(4) Å3 and Z = 4. The crystal structure of mikenewite is characterised by each Mn atom coordinated octahedrally by six O atoms, three from different sulfite O atoms and three from H2O molecules. Each S4+O3 group is bonded to three Mn atoms, resulting in a sheet parallel to (101) with the sheet composition of Mn2+(S4+O3)⋅3H2O. Such sheets, stacked along [10$\bar{1}$], are joined together by hydrogen bonds, accounting for the perfect cleavage of the mineral. Mikenewite is dimorphous with orthorhombic Pnma gravegliaite, as albertiniite is with fleisstalite. Its discovery from the Ojuela mine, which is particularly rich in Zn, implies the possibility of finding Zn-bearing sulfites there as well.
Evidence of the anthropogenic origin of the ‘Carmel sapphire’ with enigmatic super-reduced minerals
Authors: Galuskin Evgeny , Galuskina Irina 
Published: April 2023

AbstractCorundum with inclusions of enigmatic super-reduced minerals was found in mineral separates received as a result of alluvial sediment exploration near Mt Carmel, Israel by the Shefa Yamim Company. This corundum, registered as ‘Carmel sapphireTM’, has been an object of numerous publications by W. Griffin's scientific team, in which they propose a questionable hypothesis of sapphire formation at the crust–mantle boundary with the participation of CH4+H2 fluids. Typically the Carmel sapphire is in small fragments of breccia with white cement, which in the opinion of Griffin et al. is a carbonate-cemented volcanic ash. Our investigation of the ‘white breccia’ showed that it consists of unsorted angular fragments of Carmel sapphire from ~1 μm to 7 mm in size cemented by aluminium hydroxides (bauxite) and is a waste product of the fused alumina process, i.e. it has an anthropogenic origin. Phases typical for slags of fused alumina production and metallurgical slags were identified in the ‘white breccia’. Carmel sapphire has numerous microscopic spherical inclusions of Si–Fe alloy indicating that the removal of Si and Fe from the corundum melt occurred at a temperature >2000°С. Osbornite, TiN, from Carmel sapphire has a chemical zonation characteristic of osbornite from fused alumina with enrichment of central zones in carbon. Comparison of the growth heterogeneity of Carmel sapphire and ‘electrocorundum’ indicates that the crystallisation of the corundum melt proceeded in a similar way. Unfortunately, in the case of Carmel sapphire from the Carmel locality, the contamination of geological samples with anthropogenic material has led to popularisation of biased views.
Libbyite, (NH4)2(Na2□)[(UO2)2(SO4)3(H2O)]2⋅7H2O, a new mineral with uranyl–sulfate sheets from the Blue Lizard mine, San Juan County, Utah, USA
Authors: Kampf Anthony R. , Olds Travis A. , Plášil Jakub , Nash Barbara P. , Marty Joe 
Published: April 2023

AbstractThe new mineral libbyite (IMA2022-091), (NH4)2(Na2□)[(UO2)2(SO4)3(H2O)]2⋅7H2O, was found in the Blue Lizard mine, San Juan County, Utah, USA, where it occurs as tightly intergrown aggregates of light green–yellow equant crystals in a secondary assemblage with bobcookite, coquimbite, halotrichite, metavoltine, rhomboclase, römerite, tamarugite, voltaite and zincorietveldite. The streak is very pale green yellow and the fluorescence is strong green under 405 nm ultraviolet light. Crystals are transparent with vitreous lustre. The tenacity is brittle, the Mohs hardness is ~2½, the fracture is curved. The mineral is soluble in H2O and has a calculated density of 3.465 g⋅cm–3. The mineral is optically uniaxial (–) with ω = 1.581(2) and ɛ = 1.540(2). Electron microprobe analyses provided (NH4)1.92K0.08Na2.00U4.00S6.00O41H18.00. Libbyite is tetragonal,P41212,a= 10.7037(11),c= 31.824(2) Å,V= 3646.0(8) Å3andZ= 4. The structural unit is a uranyl–sulfate sheet that has the same topology as the sheets in several synthetic uranyl selenates.
Carbon nanoparticles-Fe(II) complex for efficient theranostics of xenografted colonic tumor
Authors: Xie Ping , Huang Yuanfang , Tang Kexin , Wu Xian , Zeng Cheng , Yang Sheng-Tao , Tang Xiaohai 
Published: April 2023

AbstractBackgroundOverwhelming Fe accumulation in tumor arouses strong oxidative stress. To benefit the cancer patients, Fe(II) delivered by carbon nanoparticles-Fe(II) complex (CNSI-Fe) should be visualized to ensure the successful intratumoral injection and the antitumor mechanisms should be investigated at molecular level.ResultsIntracellular Fe accumulations associating with the uptakes of CNSI-Fe were observed both in vitro and in vivo. The retention of Fe(II) in tumor over 72 h was visualized by magnetic resonance imaging. CNSI-Fe inhibited the tumor growth and expanded the lifespan of colonic tumor-bearing mice. The antitumor activity of CNSI-Fe was attributed to the increases of OH radicals and the oxidative stress in tumor cells, which resulted in cell apoptosis and ferroptosis. The transcriptome analyses confirmed the changes of ferroptosis and inflammation signaling pathways by CNSI-Fe treatment. The low toxicity of CNSI-Fe was indicated by the serum biochemistry, hematology, and histopathology.ConclusionCNSI-Fe induced the efficient apoptosis and ferroptosis of colonic tumor for cancer therapy. Our results would benefit the clinical applications of CNSI-Fe and stimulate great interest in the nanomedicine.
Registered care home managers’ experiences of responding to the national care home visiting guidance in England during the Covid-19 pandemic; a multi-method qualitative study
Authors: Dixon Josie , Lorenz-Dant Klara , Stubbs Edmund , Harrison Dening Karen , Mostaghim Manna , Casson Daniel 
Published: April 2023

Abstract
Background
Visiting restrictions in care homes in England and many comparable countries during the Covid-19 pandemic were extensive and prolonged. We examined how care home managers experienced, understood and responded to the national care home visiting guidance in England in developing their visiting policies.

Methods
A diverse sample of 121 care home managers across England, recruited through varied sources including the NIHR ENRICH network of care homes, completed a 10-item qualitative survey. Follow-up, in-depth qualitative interviews were conducted with a purposive sub-sample of 40 managers. Data were analysed thematically using Framework, a theoretically and methodologically flexible tool for data analysis in multiple researcher teams.

Findings
Some viewed the national guidance positively; as supporting the restrictive measures they felt necessary to protect residents and staff from infection, or as setting a broad policy framework while allowing local discretion. More commonly, however, managers experienced challenges. These included the guidance being issued late; the initial document and frequent, media-led updates not being user-friendly; important gaps, particularly in relation to dementia and the risks and harms associated with restrictions; guidance being unhelpfully open to interpretation while restrictive interpretations by regulators limited apparent scope for discretion; fragmented systems of local governance and poor central-local coordination; inconsistent access and quality of support from local regulators wider sources of information, advice and support that, while often valued, were experienced as uncoordinated, duplicative and sometimes confusing; and insufficient account taken of workforce challenges.

Conclusions
Underlying many of the challenges experienced were structural issues, for which there have been longstanding calls for investment and strategic reform. For increasing sector resilience, these should be urgently addressed. Future guidance would also be significantly strengthened by gathering better data, supporting well-facilitated peer exchange, engaging the sector more fully and dynamically in policy-making and learning from care home managers’ and staff’s experiences, particularly of assessing, managing and mitigating the wider risks and harms associated with visiting restrictions.