bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III Trial of Carboplatin and Paclitaxel Compared With Cisplatin and Paclitaxel in Patients With Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Ozols Robert F. , Bundy Brian N. , Greer Benjamin E. , Fowler Jeffrey M. , Clarke-Pearson Daniel , Burger Robert A. , Mannel Robert S. , DeGeest Koen , Hartenbach Ellen M. , Baergen Rebecca 
Published: August 2023

Purpose: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. Patients and Methods: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). Results: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). Conclusion: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.
Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600–Mutant Pediatric High-Grade Glioma
Authors: Hargrave Darren R. , Terashima Keita , Hara Junichi , Kordes Uwe R. , Upadhyaya Santhosh A. , Sahm Felix , Bouffet Eric , Packer Roger J. , Witt Olaf , Sandalic Larissa , Kieloch Agnieszka , Russo Mark , Cohen Kenneth J. ,   the Investigators involved in the high-grade glioma cohort, Diez Blanca , Cappellano Andrea , Epelman Sidnei , Mancano Bruna , Nysom Karsten , Aerts Isabelle , Bertozzi Anne-Isabelle , Witt Olaf , Kramm Christof , Fleischhack Gudrun , Kordes Uwe , Hernaiz-Driever Pablo , Massimino Maura , Garre Maria Luisa , Locatelli Franco , Terashima Keita , Okada Keiko , Koga Yuki , Van der Lugt Jasper , Maschan Alexey , Lassaletta Alvaro , Holm Stefan , Hargrave Darren , Howell Lisa , Upadhyaya Santhosh , Gauvain Karen , Cohen Kenneth , Baxter Patricia 
Published: August 2023

PURPOSE BRAF V600 mutation is detected in 5%-10% of pediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or in combination with trametinib demonstrated activity in children and adults with relapsed/refractory BRAF V600–mutant HGG. METHODS This phase II study evaluated dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600–mutant pHGG. The primary objective was overall response rate (ORR) by independent review by Response Assessment in Neuro-Oncology criteria. Secondary objectives included ORR by investigator determination, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS A total of 41 pediatric patients with previously treated BRAF V600–mutant HGG were enrolled. At primary analysis, median follow-up was 25.1 months, and 51% of patients remained on treatment. Sixteen of 20 discontinuations were due to progressive disease in this relapsed/refractory pHGG population. Independently assessed ORR was 56% (95% CI, 40 to 72). Median DOR was 22.2 months (95% CI, 7.6 months to not reached [NR]). Fourteen deaths were reported. Median OS was 32.8 months (95% CI, 19.2 months to NR). The most common all-cause adverse events (AEs) were pyrexia (51%), headache (34%), and dry skin (32%). Two patients (5%) had AEs (both rash) leading to discontinuation. CONCLUSION In relapsed/refractory BRAF V600–mutant pHGG, dabrafenib plus trametinib improved ORR versus previous trials of chemotherapy in molecularly unselected patients with pHGG and was associated with durable responses and encouraging survival. These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600–mutant HGG.
Flavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice
Authors: Zhang Lei , Mohankumar Kumaravel , Martin Gregory , Mariyam Fuada , Park Yuri , Han Sang Jun , Safe Stephen 
Published: August 2023

Abstract
Nuclear receptor 4A1 (NR4A1) plays an important role in endometriosis progression; levels of NR4A1 in endometriotic lesions are higher than in normal endometrium, and substituted bis-indole analogs (NR4A1) antagonists suppress endometriosis progression in mice with endometriosis. In addition, the flavonoids kaempferol and quercetin are natural products that directly bind NR4A1 and significantly repress the intrinsic NR4A1-dependent transcriptional activity in human endometriotic epithelial and stromal cells and Ishikawa endometrial cancer cells. NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin suppressed proliferation of human endometriotic epithelial cells and Ishikawa cells by inhibiting epidermal growth factor receptor/c-Myc/survivin-mediated growth-promoting and survival pathways, The mammalian target of rapamycin (mTOR) signaling and αSMA/CTGF/COL1A1/FN-mediated fibrosis signaling but increasing Thioredoxin domain Containing 5/SESN2-mediated oxidative/estrogen receptors stress signaling. In human endometriotic stromal cells, NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin primarily inhibited mTOR signaling by suppressing proliferation of human endometrial stromal cells. In addition, kaempferol and quercetin treatment also effectively suppressed the growth of endometriotic lesions in mice with endometriosis compared with the vehicle without any body weight changes. Therefore, kaempferol and quercetin are NR4A1 antagonists with potential as nutritional therapy for endometriosis.
How venom pore placement may influence puncture performance in snake fangs
Authors: Crofts Stephanie B. , Anderson Philip S. L. 
Published: August 2023

ABSTRACT
When designing experimental studies, it is important to understand the biological context of the question being asked. For example, many biological puncture experiments embed the puncture tool to a standardized depth based on a percentage of the total tool length, to compare the performance between tools. However, this may not always be biologically relevant to the question being asked. To understand how definitions of penetration depth may influence comparative results, we performed puncture experiments on a series of venomous snake fangs using the venom pore location as a functionally relevant depth standard. After exploring variation in pore placement across snake phylogeny, we compared the work expended during puncture experiments across a set of snake fangs using various depth standards: puncture initiation, penetration to a series of depths defined by the venom pore and penetration to 15% of fang length. Contrary to our hypothesis, we found almost no pattern in pore placement between clades, dietary groups or venom toxicity. Rank correlation statistics of our experimental energetics results showed no difference in the broad comparison of fangs when different puncture depth standards were used. However, pairwise comparisons between fangs showed major shifts in significance patterns between the different depth standards used. These results imply that the interpretation of experimental puncture data will heavily depend upon which depth standard is used during the experiments. Our results illustrate the importance of understanding the biological context of the question being addressed when designing comparative experiments.
Clinical impact of 99mTc-HDP SPECT/CT imaging as standard workup for foot and ankle osteoarthritis
Authors: van Hasselt AJ , Pustjens J , de Zwart AD , Dal M , de Vries AJ , van Raaij TM 
Published: August 2023

Objective: The primary aim of this study was to assess to what extent 99mTc-HDP Single photon emission computed tomography/computed tomography (SPECT/CT) will lead to change of diagnosis and treatment, in patients with suspected foot and ankle osteoarthritis (OA). Secondary aim was to assess the intraobserver variability. Methods: Retrospectively 107 patients, with suspected foot and/or ankle OA of which a SPECT/CT was made, were included for analysis. All the clinical and radiological data were randomized and blinded before being scored by one experienced orthopaedic surgeon. Firstly, based on the clinical data and conventional radiographs, a diagnosis and treatment plan was scored. Secondly, the observer accessed the SPECT/CT and could change the diagnosis and treatment plan. Additionally, the intraobserver reliability was determined by data of 18 patients that were added in twofold to the dataset, without awareness of the observer and by calculating the κ values. Results: The diagnosis changed in 53% (57/107) and treatment plans changed in 26% (28/107) of the patients. Intraobserver reliability for the conventional workup was k = 0.54 (moderate strength of agreement), compared to k = 0.66 (substantial strength of agreement) when SPECT/CT data were added. Conclusions: This study describes the influence of SPECT/CT on diagnosis and treatment plans in patients with suspected symptomatic OA. Also, it shows SPECT/CT leads to a higher intraobserver variability. We believe SPECT/CT has a promising role in the workup for foot and ankle OA. Advances in knowledge: In addition to what was found in complex foot and ankle cases, this study shows that in patients with non-complex foot and ankle problems, SPECT/CT has a substantial influence on the diagnosis (and subsequent treatment plan).
Does cone beam CT change the treatment decision for maxillary second and third molars? A prospective study
Authors: Hermann Louise , Nørholt Sven Erik , Wenzel Ann , Taneja Pankaj , Matzen Louise Hauge 
Published: August 2023

Objectives:
To evaluate whether information from CBCT changes the treatment plan for maxillary second and third molars and to examine clinical and radiographic parameters with an impact on treatment decision.

Methods:
This prospective study included 260 maxillary third molars with superimposition onto the second molar in panoramic images (170 patients; mean age 28 years, range 16–63). An initial treatment plan was based on clinical findings and panoramic images. After CBCT, a final treatment plan was decided. Treatment was undertaken based on the final treatment plan. Through logistic regression analyses, impact of clinical and radiographic parameters on change in treatment plan, removal of the third molar vs no treatment, and removal of the second vs third molar were evaluated.

Results:
The treatment plan changed in 82 cases (32%). Sixteen cases (6%) changed from removal of the third molar to removal of the second molar. Regression analyses showed that severe resorption in the second molar was significantly related to a change in treatment plan. Removal of a third molar was decided in 180 cases and regression analyses identified that mesioangulation of the third molar, marginal bone loss, superficial resorption, and age were significantly related to removal of the third molar vs no treatment. Thirty second molars were removed, and regression analyses showed that severe resorption was significantly related to removal of the second molar instead of the third molar.

Conclusions:
Parameters such as resorption evaluated in CBCT can modify the treatment decision, resulting in removal of the second and/or the third molar.
Update on Wilms tumor
Authors: Kister Klaudia , Laskowski Jakub , Bronst Paulina , Mazur Magdalena , Małolepsza Aleksandra , Zach-Źródlak Monika , Czechowska Julia , Rosa Lidia , Rektor Natalia , Szabrańska Anna 
Published: August 2023

Background: Wilms' tumor is the most common childhood renal neoplasm. Among the worst prognosis forms are the bilateral form. The symptom complex is non-specific for malignancy; the first symptoms may include hypertension. Hematuria occurs in 30% of patients. The incidence of distant metastases at the time of diagnosis in children with Wilms' tumor is estimated to be about 20%.The purpose of this article is to present a review of the literature on the standardization of diagnosis, the latest treatment standards and to assess the prognosis of Wilms' Tumor.
Matherial and methods: Using PubMed, SCOPUS and Web of Science databases, the authors reviewed the peer-reviewed international literature from 1980-2023 using the keywords: "Wilms tumor," "renal tumor," "nephroblastoma."
Discussion: Bilateral tumors have the worst prognosis - according to the National Wilms Tumor Study Group, long-term survival is achieved in only 12% to 56% of patients. The prognosis of Wilms' tumor is also dependent on the occurrence of recurrences - local as well as localized outside the renal tissue. A factor directly affecting long-term survival is recurrence, mainly observed within 24 months after the end of therapy. The limitations of conventional therapies, including surgery, chemotherapy and radiotherapy, in preventing recurrence in WT patients and their potential to cause long-term side effects.
Conclusions:
Bilateral Wilms tumor is associated with more aggressive therapy than unilateral disease.In single kidney disease, therapeutic management is aimed at radical removal of all tumor foci, whereas in bilateral tumor, the goal of any management should additionally be to try to preserve the best possible renal function.
Screening in children is important in cancer. General physicians should refer patients for additional imaging studies when there are any diagnostic doubts, as cancer is characterized by a long, asymptomatic development.
The Strategic Role of Supplier Learning
Authors: Gao Long , Nikoofal Mohammad Ebrahim , Zhang Wei 
Published: August 2023

Problem definition: We study a procurement problem, where the supplier holds superior cost information and can learn to improve efficiency over time. Despite its prevalence, the supply chain literature provides limited guidance on how to manage learning suppliers with evolving private information. Methodology/results: We use mechanism design. We show that supplier learning has both efficiency and agency effects, it can induce countervailing incentives, and the agency effect can overwhelm the efficiency effect. As a result, (i) supplier learning can hurt profits, (ii) information asymmetry can improve efficiency, (iii) production distortion can go upward, and (iv) ignoring the agency effect of learning can mislead contract design and inflict severe losses. Managerial implications: Our results suggest that previous studies may have overlooked the downside of learning and overestimated the harm of information asymmetry. Moreover, our results help explain when and why firms should overproduce output and disclose private information voluntarily. By highlighting the strategic role of supplier learning, this study sharpens our understanding of supply chain management. Funding: L. Gao is partly supported by the CoR research grant at University of California, Riverside. W. Zhang is partly supported by the National Natural Science Foundation of China [Grant 71821002]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2021.0285 .
Developing an artificial intelligence diagnostic tool for paediatric distal radius fractures, a proof of concept study
Authors: Aryasomayajula S , Hing CB , Siebachmeyer M , Naeini FB , Ejindu V , Leitch P , Gelfer Y , Zweiri Y 
Published: August 2023

Introduction In the UK, 1 in 50 children sustain a fractured bone yearly, yet studies have shown that 34% of children sustaining an injury do not have a visible fracture on initial radiographs. Wrist fractures are particularly difficult to identify because the growth plate poses diagnostic challenges when interpreting radiographs. Methods We developed Convolutional Neural Network (CNN) image recognition software to detect fractures in radiographs from children. A consecutive data set of 5,000 radiographs of the distal radius in children aged less than 19 years from 2014 to 2019 was used to train the CNN. In addition, transfer learning from a VGG16 CNN pretrained on non-radiological images was applied to improve generalisation of the network and the classification of radiographs. Hyperparameter tuning techniques were used to compare the model with the radiology reports that accompanied the original images to determine diagnostic test accuracy. Results The training set consisted of 2,881 radiographs with a fracture and 1,571 without; 548 radiographs were outliers. With additional augmentation, the final data set consisted of 15,498 images. The data set was randomly split into three subsets: training (70%), validation (10%) and test (20%). After training for 20 epochs, the diagnostic test accuracy was 85%. Discussion A CNN model is feasible in diagnosing paediatric wrist fractures. We demonstrated that this application could be utilised as a tool for improving diagnostic accuracy. Future work would involve developing automated treatment pathways for diagnosis, reducing unnecessary hospital visits and allowing staff redeployment to other areas.
Intellectual and Developmental Disability Research: Success Through Inclusion and Equity
Authors: Belcher Harolyn M.E. , Love Christina E. , Segal Andrew H. , Lopez-Arvizu Carmen 
Published: August 2023

Abstract
“Toward Equity in Research on Intellectual and Developmental Disabilities” (IDD) is a timely and comprehensive article highlighting gaps in the “dominant culture” approach to current research strategies designed to address IDD. Recentering systems involved in the research enterprise are recommended. This commentary provides additional guidance from a social justice, equity, and inclusion lens, including a clinical anthropology approach to research.
Detection of single ions in a nanoparticle coupled to a fiber cavity
Authors: Deshmukh Chetan , Beattie Eduardo , Casabone Bernardo , Grandi Samuele , Serrano Diana , Ferrier Alban , Goldner Philippe , Hunger David , de Riedmatten Hugues 
Published: August 2023

Many quantum information protocols require the storage and manipulation
of information over long times, and its exchange between nodes of a
quantum network across long distances. Implementing these protocols
requires an advanced quantum hardware, featuring, for example, a
register of long-lived and interacting qubits with an efficient
optical interface in the telecommunication band. Here we present the
Purcell-enhanced detection of single solid-state ions in erbium-doped
nanoparticles placed in a fiber cavity, emitting photons at
1536 nm. The open-access design of the cavity allows for
complete tunability in both space and frequency, selecting individual
particles and ions. The ions are confined in a volume two orders of
magnitude smaller than in previous realizations, increasing the
probability of finding ions separated by only a few nanometers, which
could then interact. We report the detection of individual spectral
features presenting saturation of the emission count rate and
linewidth, as expected for two-level systems. We also report an
uncorrected g(2)(0) of 0.24(5) for the emitted field,
confirming the presence of a single emitter. Our fully
fiber-integrated system is an important step towards the realization
of the initially envisioned quantum hardware.
Development and validation of risk prediction model for diabetic neuropathy among diabetes mellitus patients at selected referral hospitals, in Amhara regional state Northwest Ethiopia, 2005–2021
Authors: Gelaw Negalgn Byadgie , Muche Achenef Asmamaw , Alem Adugnaw Zeleke , Gebi Nebiyu Bekele , Chekol Yazachew Moges , Tesfie Tigabu Kidie , Tebeje Tsion Mulat 
Published: August 2023

Background
Diabetic neuropathy is the most common complication in both Type-1 and Type-2 DM patients with more than one half of all patients developing nerve dysfunction in their lifetime. Although, risk prediction model was developed for diabetic neuropathy in developed countries, It is not applicable in clinical practice, due to poor data, methodological problems, inappropriately analyzed and reported. To date, no risk prediction model developed for diabetic neuropathy among DM in Ethiopia, Therefore, this study aimed prediction the risk of diabetic neuropathy among DM patients, used for guiding in clinical decision making for clinicians.

Objective
Development and validation of risk prediction model for diabetic neuropathy among diabetes mellitus patients at selected referral hospitals, in Amhara regional state Northwest Ethiopia, 2005–2021.

Methods
A retrospective follow up study was conducted with a total of 808 DM patients were enrolled from January 1,2005 to December 30,2021 at two selected referral hospitals in Amhara regional state. Multi-stage sampling techniques were used and the data was collected by checklist from medical records by Kobo collect and exported to STATA version-17 for analysis. Lasso method were used to select predictors and entered to multivariable logistic regression with P-value<0.05 was used for nomogram development. Model performance was assessed by AUC and calibration plot. Internal validation was done through bootstrapping method and decision curve analysis was performed to evaluate net benefit of model.

Results
The incidence proportion of diabetic neuropathy among DM patients was 21.29% (95% CI; 18.59, 24.25). In multivariable logistic regression glycemic control, other comorbidities, physical activity, hypertension, alcohol drinking, type of treatment, white blood cells and red blood cells count were statistically significant. Nomogram was developed, has discriminating power AUC; 73.2% (95% CI; 69.0%, 77.3%) and calibration test (P-value = 0.45). It was internally validated by bootstrapping method with discrimination performance 71.7 (95% CI; 67.2%, 75.9%). It had less optimism coefficient (0.015). To make nomogram accessible, mobile based tool were developed. In machine learning, classification and regression tree has discriminating performance of 70.2% (95% CI; 65.8%, 74.6%). The model had high net benefit at different threshold probabilities in both nomogram and classification and regression tree.

Conclusion
The developed nomogram and decision tree, has good level of accuracy and well calibration, easily individualized prediction of diabetic neuropathy. Both models had added net benefit in clinical practice and to be clinically applicable mobile based tool were developed.