bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cytokines IL-3 and GM-CSF regulate the transcriptional activity of retinoic acid receptors in different in vitro models of myeloid differentiation
Authors: Johnson Barton S. , Mueller LeMoyne , Si Jutong , Collins Steven J. 
Published: July 2002

AbstractThe disruption of retinoic acid receptor (RAR) activity that characterizes human acute promyelocytic leukemia (APL) is associated with a block to granulocytic differentiation indicating that RARs are critical regulators of normal myeloid differentiation. Nevertheless, how RAR activity might be regulated in the presumably homogenous concentration of retinoids in blood and bone marrow and how these receptors might interact with specific hematopoietic cytokines to regulate normal myeloid differentiation remain unclear. Here, using several cytokine-dependent in vitro models of myeloid development, it was observed that specific hematopoietic cytokines that normally regulate myeloid lineage commitment and differentiation (interleukin-3 and granulocyte-macrophage colony-stimulating factor) trigger the enhancement of both ligand-dependent and ligand-independent transcriptional activity of both endogenous and exogenous (transiently transfected) RARs. This cytokine-mediated enhancement of RAR activity is not associated with any observed changes in expression of the RARs or their respective coactivators/corepressors. These studies define a previously unknown cytokine-RAR interaction during myelopoiesis and suggest that RAR activation might be a critical downstream event following interleukin-3 and granulocyte-macrophage colony-stimulating factor signaling during myeloid differentiation. This observation of ligand-independent activation of RARs that is mediated by certain cytokines represents a new paradigm with respect to how RAR activity might be modulated during hematopoiesis and also suggests a molecular basis for the differential sensitivity of human acute myelogenous leukemia cells to retinoids.
Delayed discharges from Oxford city hospitals: who and why?
Authors: Carter Nicholas D , Wade Derick T 
Published: July 2002

Objective: To determine the extent and characteristics of discharge delays of younger patients from acute hospital beds in Oxford, England. Design: Three-month prospective analysis of patients deemed to have delayed discharge. Measures: The primary measure was the number of days from the patient being no longer in need of acute medical inpatient care to eventual discharge. Additional assessments included demographic data, primary diagnosis, Motricity Index, Short Orientation-Memory-Concentration Test (SOMC), Barthel Index and contextual data. Setting: The major acute hospitals serving the county of Oxfordshire (560 000 people). Subjects: Fifty patients aged 18–70 years identi”ed by referrals, delayed discharge lists and ward visits whose discharge from hospital had been delayed. Results: The mean (standard deviation, SD) delay period was 36.1 (26.8) days. The mean prevalence and incidence of discharge delays for each three-day period was 19.7 (SD 1.7) and one (SD 1.7) respectively. Most (88%, n = 44) had a primary neurological diagnosis. Twenty-four (48%) patients had Motricity Index scores of less than 50% in one or more limbs and 16 (32%) in two or more limbs. Twenty-six (52%) patients had cognitive impairment (SOMC <18/28). Thirty-nine (78%) patients had a Barthel Index score of less than 15/20 and 24 (48%) of less than 10/20. The period of discharge delay did not correlate with SOMC, Motricity or Barthel Index scores. Only nine had appropriate accommodation available. Conclusion: Patients whose discharge is delayed were common; most had a neurological disability and cognitive impairment; and accommodation was unsuitable or absent for most. Reorganizing services to give patients access to specialized disability services might both improve the care of these patients and increase the ef”ciency of the health service.
Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: A Preliminary Report
Authors: Lee Jung-Hee , Lee Je-Hwan , Ahn Jin-Hee , Bahng Hyeseung , Kim Tae-Won , Kang Yoon-Koo , Lee Kyoo-Hyung , Kim Jin-Cheon , Yu Chang-Sik , Kim Jong-Hoon , Ahn Seung-Do , Kim Woo-Kun , Kim Sang-Hee , Lee Jung-Shin 
Published: July 2002

PURPOSE: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer. PATIENTS AND METHODS: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m2/d and leucovorin 20 mg/m2/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles. RESULTS: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v 70% at 4 years; P = .043). Twenty-three recurrences occurred in arm I and 38 in arm II (P = .047). Overall survival was not significantly different between arms I and II (84% v 82% at 4 years; P = .387). CONCLUSION: Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.
Prognostic Factors for Survival in Adult Patients With Cerebral Low-Grade Glioma
Authors: Pignatti Francesco , van den Bent Martin , Curran Desmond , Debruyne Channa , Sylvester Richard , Therasse Patrick , Áfra Denes , Cornu Philippe , Bolla Michel , Vecht Charles , Karim Abul B.M.F. 
Published: July 2002

PURPOSE: To identify prognostic factors for survival in adult patients with cerebral low-grade glioma (LGG), to derive a prognostic scoring system, and to validate results using an independent data set. PATIENTS AND METHODS: European Organization for Research and Treatment of Cancer (EORTC) trial 22844 and EORTC trial 22845 are the largest phase III trials ever carried out in adult patients with LGG. The trials were designed to investigate the dosage and timing of postoperative radiotherapy in LGG. Cox analysis was performed on 322 patients from EORTC trial 22844 (construction set), and the results were validated on 288 patients from trial 22845 (validation set). Patients with pilocytic astrocytomas were excluded from this prognostic factor analysis. RESULTS: Multivariate analysis on the construction set showed that age ≥ 40 years, astrocytoma histology subtype, largest diameter of the tumor ≥ 6 cm, tumor crossing the midline, and presence of neurologic deficit before surgery were unfavorable prognostic factors for survival. The total number of unfavorable factors present can be used to determine the prognostic score. Presence of up to two of these factors identifies the low-risk group, whereas a higher score identifies high-risk patients. The validity of the multivariate model and of the scoring system was confirmed in the validation set. CONCLUSION: In adult patients with LGG, older age, astrocytoma histology, presence of neurologic deficits before surgery, largest tumor diameter, and tumor crossing the midline were important prognostic factors for survival. These factors can be used to identify low-risk and high-risk patients.
Supported bridge position in one‐stop coronary and craniocervical CT angiography: A randomized clinical trial
Authors: Zhou Heng , Yan Cheng , Ji Min , Shi Zhang , Yang Chun , Zeng Mengsu 
Published: November 2024

AbstractObjectiveThe routine patient arm position differs between coronary CT angiography (CTA) and craniocervical CTA protocols. To investigate the clinical feasibility of supported bridge position (SBP) in combined coronary and craniocervical CTA.MethodsProspective enrollment included patients with suspected coronary artery disease (CAD) or craniocervical artery disease (CCAD) from February 2022 to November 2022. Patients were divided into three groups: coronary or craniocervical CTA according to CAD or CCAD using standard position (group 1), combined CTA with naturally arm‐down position (group 2) and SBP (group 3). Statistical analysis of objective image quality, such as noise and contrast‐to‐noise ratio (CNR), subjective image quality, patient position and radiation dose was performed among the three groups.ResultsTwo hundred and one patients (median age, 67 years; 138 men) were included. In terms of CNR for cardiac segment, group 1 and group 3 had no statistical difference, both significantly higher than group 2 (group 1, 12.56 ± 2.05; group 2, 10.4 ± 2.43; group 3, 11.94 ± 2.22; P < 0.05). Subjective image evaluation revealed no statistically significant differences among the three groups of coronary arteries (P > 0.05). Additionally, the lateral project value of scout images at the heart level indicated a significant difference (119.48 ± 12.19, 182.34 ± 25.09, and 140.58 ± 19.68 of patients, for group 1, group 2, and group 3, respectively, P < 0.05). No statistical differences were observed in between group 1 and group 3 (cardiac scan, 15.77 [15.07–16.37] mGy vs. 14.88 [12.19–18.81] mGy; craniocervical scan, 7.85 [7.69–8.01] mGy vs. 7.88 [7.88–7.89] mGy; all P > 0.05). However, group 2 had a higher dose (19.54 [16.86–22.85] mGy and 10.87 [10.86–10.87] mGy, for cardiac and craniocervical scans, respectively).ConclusionsIn comparison with a naturally arm‐down position, SBP, which aligns the humerus bones with the spinal column, can provide diagnostic image quality at routine dose level of standard position CTA.
Attention 3D UNET for dose distribution prediction of high‐dose‐rate brachytherapy of cervical cancer: Intracavitary applicators
Authors: Gautam Suman , Osman Alexander F. I. , Richeson Dylan , Gholami Somayeh , Manandhar Binod , Alam Sharmin , Song William Y. 
Published: November 2024

AbstractBackgroundFormulating a clinically acceptable plan within the time‐constrained clinical setting of brachytherapy poses challenges to clinicians. Deep learning based dose prediction methods have shown favorable solutions for enhancing efficiency, but development has primarily been on external beam radiation therapy. Thus, there is a need for translation to brachytherapy.PurposeThis study proposes a dose prediction model utilizing an attention‐gating mechanism and a 3D UNET for cervical cancer high‐dose‐rate intracavitary brachytherapy treatment planning with tandem‐and‐ovoid/ring applicators.MethodsA multi‐institutional data set consisting of 77 retrospective clinical brachytherapy plans was utilized in this study. The data were preprocessed and augmented to increase the number of plans to 252. A 3D UNET architecture with attention gates was constructed and trained for mapping the contour information to dose distribution. The trained model was evaluated on a testing data set using various metrics, including dose statistics and dose‐volume indices. We also trained a baseline UNET model for a fair comparison.ResultsThe attention‐gated 3D UNET model exhibited competitive accuracy in predicting dose distributions similar to the ground truth. The average values of the mean absolute errors were 0.46 ± 11.71 Gy (vs. 0.47 ± 9.16 Gy for a baseline UNET) in CTVHR, 0.55 ± 0.67 Gy (vs. 0.70 ± 1.54 Gy for a baseline UNET) in bladder, 0.42 ± 0.46 Gy (vs. 0.49 ± 1.34 Gy for a baseline UNET) in rectum, and 0.31 ± 0.65 Gy (vs. 0.20 ± 3.76 Gy for a baseline UNET) in sigmoid. Our results showed that the mean individual differences in ΔD2cc for bladder, rectum, and sigmoid were 0.38 ± 1.19 (p = 0.50), 0.43 ± 0.71 (p = 0.41), and −0.47 ± 0.79 (p = 0.30) Gy, respectively. Similarly, the mean individual differences in ΔD1cc for bladder, rectum, and sigmoid were 0.09 ± 1.21 (p = 0.36), 0.20 ± 0.95 (p = 0.24), and −0.21 ± 0.59 (p = 0.30) Gy. The mean individual differences for ΔD90, ΔV100%, ΔV150%, and ΔV200% of the CTVHR were −0.45 ± 2.42 (p = 0.26) Gy, 0.55 ± 9.42% (p = 0.78), 0.82 ± 4.21% (p = 0.81), and −0.80 ± 10.48% (p = 0.36), respectively. The model requires less than 5 s to predict a full 3D dose distribution for a new patient plan.ConclusionAttention‐gated 3D UNET revealed a promising capability in predicting voxel‐wise dose distributions compared to 3D UNET. This model could be deployed for clinical use to predict 3D dose distributions for near real‐time decision‐making before planning, quality assurance, and guiding future automated planning, making the current workflow more efficient.
National Institute of Health and Care Excellence Clinical Criteria for the Diagnosis of Knee Osteoarthritis: A Prospective Diagnostic Accuracy Study in Individuals With Type 2 Diabetes
Authors: King Lauren K. , Stanaitis Ian , Hung Vivian , Koppikar Sahil , Waugh Esther J. , Lipscombe Lorraine , Hawker Gillian A. 
Published: November 2024

ObjectiveThe National Institute of Health and Care Excellence (NICE) criteria for osteoarthritis (OA) obviate the need for physical examination or imaging, and their use may improve timely diagnosis of OA. However, they have not been validated.MethodsWithin a larger study of individuals with type 2 diabetes, participants with and without self‐reported knee pain underwent assessment of the NICE criteria for knee OA by questionnaire (index test) and clinical evaluation for established or possible knee OA by a rheumatologist (reference standard). We calculated the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) of the NICE criteria and modified NICE criteria without the stiffness criterion.ResultsOur study included 96 participants: the mean ± SD age was 65.4 ± 8.3 years and 52% were women. Individuals who fulfilled the NICE criteria for knee OA (55.2%) included a spectrum of pain severity on an 11‐point pain numeric rating scale with a median score of 5 (range 1–9). Rheumatologist assessment identified 56 participants (58.3%) with symptomatic knee OA. The sensitivity, specificity, LR+, and LR− of the NICE criteria for symptomatic knee OA were 0.84 (95% confidence interval [CI] 0.74–0.94), 0.85 (95% CI 0.74–0.96), 5.6, and 0.19, respectively. For the modified NICE criteria, these were 0.89 (95% CI 0.82–0.97), 0.85 (95% CI 0.74–0.96), 5.93, and 0.13.ConclusionThe NICE criteria have high sensitivity and specificity for detecting symptomatic knee OA in a population with type 2 diabetes. We found that a modified version, omitting the stiffness criterion, performed similarly. These criteria should be validated in other settings and populations.
Immunosuppressive Drugs in Early Systemic Sclerosis and Prevention of Damage Accrual
Authors: Baron Murray , Nikpour Mandana , Hansen Dylan , Proudman Susanna , Stevens Wendy ,   the Australian Scleroderma Interest Group and the Canadian Scleroderma Research Group, Wang Mianbo 
Published: November 2024

ObjectiveOrgan damage in patients with systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by receiving immunosuppressive drugs (ISs). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC‐DI), has allowed us to investigate whether receiving ISs may reduce global organ damage accrual in patients with early SSc.MethodsThis was a retrospective study of patients with two or less years of disease duration in Canadian and Australian cohorts with SSc. Patients with either limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) were observed separately and divided into groups who were either ever or never exposed to ISs. The SCTC‐DI was the outcome, and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation model.ResultsIn the cohort with lcSSc, there were 210 patients, of whom 34% were exposed to ISs at some time. Exposure to ISs was associated with lower damage scores. In the cohort with dcSSc, there were 192 patients, of whom 76% were exposed to ISs at some time. Exposure to ISs was not associated with damage scores.ConclusionIn this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of receiving ISs on damage accrual in patients with lcSSc. We were unable to determine such an effect in patients with dcSSc, but unknown confounders may have been present, and prospective studies of patients with dcSSc receiving ISs should include the SCTC‐DI to determine the possible effect of ISs on damage accrual.
Oral Glucocorticoids for Skin Fibrosis in Early Diffuse Systemic Sclerosis: A Target Trial Emulation Study From the European Scleroderma Trials and Research Group Database
Authors: Mongin Denis , Matucci‐Cerinic Marco , Walker Ulrich A. , Distler Oliver , Becvar Radim , Siegert Elise , Ananyeva Lidia P. , Smith Vanessa , Alegre‐Sancho Juan Jose , Yavuz Sule , Limonta Massimiliano , Riemekasten Gabriela , Rezus Elena , Vonk Madelon , Truchetet Marie‐Elise , Del Galdo Francesco , Courvoisier Delphine S. , Iudici Michele ,   the EUSTAR Collaborators
Published: November 2024

ObjectiveThe objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc).MethodsWe performed an emulated randomized trial comparing the changes from baseline to 12 ± 3 months of the modified Rodnan skin score (mRSS: primary outcome) in patients with early dcSSc receiving either oral glucocorticoids (≤20 mg/day prednisone equivalent) combined with immunosuppression (treated) or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary end points were the difference occurrence of progressive skin or lung fibrosis and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups.ResultsWe matched 208 patients (mean age 49 years; 33% male; 59% anti‐Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12 ± 3 months was similar in the two groups (decrease of 2.7 [95% confidence interval {95% CI} 1.4–4.0] in treated vs 3.1 [95% CI 1.9–4.4] in control, P = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between‐group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups.ConclusionWe did not find any significant benefit of adding low‐dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.
Evaluating Meaningful Changes in Patient‐Reported Outcome Measurement Information System–Fatigue Scores from Three Phase 3 Clinical Trials of Sarilumab for Patients With Rheumatoid Arthritis
Authors: Bingham Clifton O. , Molina Emily , Praestgaard Amy , Fiore Stefano , Cella David 
Published: November 2024

ObjectiveThe aim of this study was to evaluate changes in fatigue measured by Patient‐Reported Outcome Measurement Information System (PROMIS)‐Fatigue scores in patients with rheumatoid arthritis (RA) who received sarilumab and to assess the proportion of patients achieving clinically meaningful change.MethodsData from three phase 3 randomized controlled trials of patients with RA who received sarilumab—MOBILITY, TARGET, and MONARCH—were evaluated. The 10 RA‐relevant items from the 13‐item Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue were scored in the PROMIS T score metric. Mean changes in 10‐item PROMIS‐Fatigue T score (PROMIS‐Fatigue 10a) were compared, proportions of patients reporting meaningful within‐person change thresholds were assessed, and results were visualized using empirical cumulative distribution function (eCDF) curves.ResultsPatients with RA reported high baseline fatigue. Using PROMIS‐Fatigue 10a, at week 24, patients receiving 150 or 200 mg sarilumab every other week in MOBILITY and TARGET had rapidly and significantly improved mean levels of fatigue compared to those who received placebo. When compared to patients who received adalimumab in MONARCH, patients who received sarilumab had a trend toward increased improvement. eCDF curves showed separation between active treatment versus placebo with both sarilumab doses and across the score range for improvement. Higher proportions of patients reported three‐, five‐, and seven‐point improvements in PROMIS‐Fatigue scores in groups who received active treatment.ConclusionSubstantial proportions of patients with RA who received sarilumab reported meaningful change in fatigue measured by PROMIS‐Fatigue 10a over time. This study demonstrates the ability to convert FACIT‐Fatigue score onto the PROMIS T score metric, the rapid reduction in fatigue with biologic therapies, and the use of novel eCDF curves to show individual patient‐level change.
Advanced 2D Nanomaterials for Phototheranostics of Breast Cancer: A Paradigm Shift
Authors: Parihar Arpana , Gaur Kritika , Sarbadhikary Paromita 
Published: November 2024

AbstractBreast cancer is the leading cause of women's deaths and associated comorbidities. The advanced and targeted strategies against breast cancer have gained considerable attention due to their potential enhanced therapeutic efficacy over conventional therapies. In this context, phototherapies like photodynamic therapy (PDT) and photothermal therapy (PTT) have shown promise as an effective and alternative strategy due to reduced side effects, noninvasiveness, and spatiotemporal specificity. With the advent of nanotechnology, several types of nanomaterials that have shown excellent prospects in increasing the efficacy of photo therapies have been exploited in cancer treatment. In recent years, 2D nanomaterials have stood out promising because of their unique ultrathin planar structure, chemical, physical, tunable characteristics, and corresponding remarkable physiochemical/biological properties. In this review, the potential and the current status of several types of 2D nanomaterials such as graphene‐based nanomaterials, Mxenes, Black phosphorous, and Transition Metal Dichalcogenides for photo/thermo and combination‐based imaging and therapy of breast cancer have been discussed. The current challenges and prospects in terms of translational potential in future clinical oncology are highlighted.