bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prognostic index to predict long‐term mortality in patients with mild to moderate chronic heart failure stabilised on angiotensin converting enzyme inhibitors
Authors: Kearney Mark T. , Nolan James , Lee Amanda J. , Brooksby Paul W. , Prescott Robin , Shah Ajay M. , Zaman Azfar G. , Eckberg Dwain L. , Lindsay H. Stephen , Batin Philip D. , Andrews Richard , Fox Keith A.A. 
Published: June 2003

AbstractBackground:Mortality in patients with mild to moderate chronic heart failure remains high. At present there is no easy way of identifying patients within this population at increased risk of death in the medium to long term.Aims:To develop a prognostic index to identify outpatients with mild to moderate chronic heart failure at increased risk of death.Methods and results:Five hundred and fifty‐three outpatients mean (S.D.) age 63(±10) years with symptoms of chronic heart failure (mean New York Heart Association functional class, 2.3(±0.5)), were recruited between December 1993 and April 1995. By April 2000, 201 patients had died. Using data from non‐invasive measurements of cardiac size, electrical and autonomic function, renal function and plasma biochemistry we identified eight independent predictors of mortality (allP<0.01). To develop a prognostic index, predictors were dichotomised by group median and awarded 0 or 1 point accordingly. Serum sodium≤140 mmol/l (1 point), creatinine≥111 μmol/l (1 point), cardiothoracic ratio≥0.52 (1 point), SDNN≤112 ms (1 point), maximum corrected QT interval≥487 ms (1 point), QRS dispersion≥42.7 ms (1 point), the presence of non‐sustained ventricular tachycardia (1 point) and voltage criteria for left ventricular hypertrophy on 12‐lead ECG (1 point). We calculated risk scores for patients by adding the points of each independent risk factor. In the low‐risk group (0–3 points) mortality at 5 years was 20% and in the high‐risk group (4–8 points) 53%. The area under the receiver–operator characteristic curve using dichotomised variables was 0.74 and for continuous model 0.78.Conclusions:Our prognostic index which uses eight non‐invasive measurements and a straightforward additive points system, has good discrimination and stratifies outpatients with chronic heart failure into high and low risk. This index may be useful in clinical care and risk stratification.
Institutionalisation and schizophrenia in Japan: Social environments and negative symptoms
Authors: Oshima Iwao , Mino Yoshio , Inomata Yoshimasa 
Published: June 2003

BackgroundThe number of psychiatric beds per capita in Japan is the highest in the world, and a replication of earlier British research is needed to identify possible means of improving the mental health system.AimsTo describe the current situation of psychiatric hospitals in Japan and to examine the relationship between negative symptoms of schizophrenia and social environments.MethodIn-patients with schizophrenia were randomly selected from 139 hospitals. Data were obtained for 2758 participants using several scales, including the Manchester Scale and social environment scales.ResultsNegative symptom scales showed a significant correlation with under stimulating social environments in hospitals.ConclusionsThis study confirms the results from the UK and provides evidence for the importance of community-based care and for providing more-stimulating rehabilitation environments.
Newspaper coverage of psychiatry and general medicine: comparing tabloids with broadsheets
Authors: Pieters Guido , De Gucht Véronique , Kajosch Hendrik 
Published: June 2003

Aims and MethodTo study whether psychiatry received differing treatment in newspapers than the other medical specialities, and whether tabloids were more negative in their coverage of general medicine and psychiatry than broadsheets. We conducted a survey of all headlines in all daily newspapers in the Dutch-speaking part of Belgium over a one-month period and judged whether the content was essentially positive, neutral or negative.ResultsThere was no significant difference between articles on general medicine and psychiatry with respect to the tone of the article. Whereas negative articles about medicine focused on both doctor and patient to the same extent, negative articles on psychiatry tended more often to describe the patient. Broadsheets published more negative than positive articles, while tabloids published an equal proportion of negative and positive articles.Clinical ImplicationsThere appears to be no difference in tone with respect to articles on general medicine and psychiatry, respectively. Nevertheless, the fact that negative articles on psychiatry tend to focus more exclusively on the patient points towards continuing stigmatisation of the psychiatric patient. Finally, broadsheets tend to be more negative in covering both general medicine and psychiatry, which contrasts with earlier findings.
Sub-optimal prescribing in an adult community mental health service: prevalence and determinants
Authors: Meagher David , Moran Maria 
Published: June 2003

Aims and MethodTo compare prescribing practice in a community mental health service with evidence-based guidelines and identify factors related to sub-optimal prescribing. All current patients (n=640) were assessed regarding six key aspects of prescribing (polypharmacy, high-dose treatment, use of thioridazine/maintenance benzodiazepine/maintenance hypnotic or routine anticholinergic treatment). The relationship of quality of prescribing practice to demographic, illness and service variables was examined by regression analysis.ResultsFive-hundred and five (79%) patients were receiving psychotropic medication. Of these, 232 (46%) had evidence of sub-optimal prescribing practice. Mean prescribing practice quality score was 0.75 ± 0.99. Maintenance benzodiazepine/ hypnotic (31%) and anticholinergic (30%) use were particularly common. Prescribing practice quality score was higher in those receiving depot antipsychotic treatment (P < 0.01) and in older patients (P < 0.01). Scores were significantly lower in patients whose principal medical contacts were with a consultant rather than a junior doctor (P < 0.001).Clinical ImplicationsPrescribing practices in real-world settings frequently deviate from evidence-based guidelines. The quality of prescribing is related to patient, illness and service variables. In particular, greater contact with consultant staff is linked to better practices. Patients receiving depot antipsychotics are especially liable to less judicious prescribing practice.
Interobserver and Intraobserver Variability in Measurement of Non–Small-Cell Carcinoma Lung Lesions: Implications for Assessment of Tumor Response
Authors: Erasmus Jeremy J. , Gladish Gregory W. , Broemeling Lyle , Sabloff Bradley S. , Truong Mylene T. , Herbst Roy S. , Munden Reginald F. 
Published: June 2003

Purpose: Response of solid malignancies to therapy is usually determined by serial measurements of tumor size. The purpose of our study was to assess the consistency of measurements performed by readers evaluating lung tumors. Materials and Methods: The study group was composed of 33 patients with lung tumors more than 1.5 cm. Bidimensional (BD) and unidimensional (UD) measurements were performed on computed tomography (CT) scans according to the World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST), respectively. Measurements were performed independently by five thoracic radiologists using printed film and were repeated after 5 to 7 days. Inter- and intraobserver measurement variations were estimated through statistical modeling. Results: There were 40 tumors with an average size of 1.8 to 8.0 cm (mean, 4.1 cm). Analysis of variance showed a significant difference (P < .05) among readers and among the measured nodules for UD and BD measurements. Interobserver misclassification rates were more than intraobserver misclassification rates using either progressive disease or response criteria. The probability of misclassifying a tumor with the WHO criteria or RECIST was greatest with interobserver measurements when criteria for progression (43% BD, 30% UD) were used and lowest with intraobserver measurements when criteria for response (2.5% BD, 3.0% UD) were used. In addition, interobserver misclassification rates were more than intraobserver misclassification rates for both regular and irregular tumors. Conclusion: Measurements of lung tumor size on CT scans are often inconsistent and can lead to an incorrect interpretation of tumor response. Consistency can be improved if the same reader performs serial measurements for any one patient.
Effects of Radiotherapy on Cognitive Function in Patients With Low-Grade Glioma Measured by the Folstein Mini-Mental State Examination
Authors: Brown Paul D. , Buckner Jan C. , O’Fallon Judith R. , Iturria Nancy L. , Brown Cerise A. , O’Neill Brian P. , Scheithauer Bernd W. , Dinapoli Robert P. , Arusell Robert M. , Curran Walter J. , Abrams Ross , Shaw Edward G. 
Published: June 2003

Purpose: To assess the neurocognitive effects of cranial radiotherapy on patients with low-grade gliomas, we analyzed cognitive performance data collected in a prospective, intergroup clinical trial. Methods: Patients included 203 adults with supratentorial low-grade gliomas randomly assigned to a lower dose (50.4 Gy in 28 fractions) or a higher dose (64.8 Gy in 36 fractions) of localized radiotherapy. Folstein Mini-Mental State Examination (MMSE) scores and neurologic function scores (NFS) at baseline and key evaluations were analyzed. Median follow-up was 7.4 years in 101 patients still alive. A change of more than three MMSE points was considered clinically significant. Results: In patients without tumor progression, significant deterioration from baseline occurred at years 1, 2, and 5 in 8.2%, 4.6%, and 5.3% of patients, respectively. Most patients with an abnormal baseline MMSE score (< 27) experienced significant increases. Baseline variables such as radiation dose, conformal versus conventional radiotherapy, number of radiation fields, age, sex, tumor size, NFS, seizures, and seizure medications did not predict cognitive function changes. Conclusion: In this population, most low-grade glioma patients maintained a stable neurocognitive status after focal radiotherapy as measured by the MMSE. Patients with an abnormal baseline MMSE were more likely to have an improvement in cognitive abilities than deterioration after receiving radiotherapy. Only a small percentage of patients had cognitive deterioration after radiotherapy. However, more discriminating neurocognitive assessment tools may identify cognitive decline not apparent with the use of the MMSE.
Diet and Breast Cancer: Evidence That Extremes in Diet Are Associated With Poor Survival
Authors: Goodwin Pamela J. , Ennis Marguerite , Pritchard Kathleen I. , Koo Jarley , Trudeau Maureen E. , Hood Nicky 
Published: June 2003

Purpose: Diet has been postulated to influence breast cancer prognosis; however, existing evidence is weak and inconsistent. Previous studies have sought evidence of a linear relationship between diet and breast cancer outcomes. Because of a U-shaped association of body mass index (BMI) with survival in breast cancer, we hypothesized that a nonlinear association also existed for dietary variables. Patients and Methods: Four hundred seventy-seven women with surgically resected T1 to T3, N0/1, M0 breast cancer completed the Block Food Frequency Questionnaire 9.3 ± 4.6 weeks (mean ± standard deviation) after diagnosis, reporting intake over the preceding 12 months. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records. A series of Cox models was performed, modeling the association of dietary factors with breast cancer survival linearly and quadratically, adjusting for total energy intake, tumor- and treatment-related variables, and BMI. Results: Significant nonlinear survival associations were found for protein, oleic acid, cholesterol, polyunsaturated-saturated fat ratio, and for percentage of calories from fat and percentage of calories from carbohydrates in multivariate models. The shape of the survival associations varied across nutrients. Hazard ratios for highest risk quintiles ranged from 2.1 to 6.5. For total fat, adjustment for BMI reduced the multivariate P value obtained from nonlinear Cox models from .05 to .10. No significant linear associations were identified. Conclusion: The association of key dietary variables with breast cancer survival may be U-shaped rather than linear. Our data suggest that midrange intake of most major energy sources is associated with the most favorable outcomes, and extremes are associated with less favorable outcomes.
Phase II Study of the Efficacy and Tolerability of Two Dosing Regimens of the Farnesyl Transferase Inhibitor, R115777, in Advanced Breast Cancer
Authors: Johnston Stephen R.D. , Hickish Tamas , Ellis Paul , Houston Stephen , Kelland Lloyd , Dowsett Mitch , Salter Janine , Michiels Bart , Perez-Ruixo Juan Jose , Palmer Peter , Howes Angela 
Published: June 2003

Purpose: R115777 is an orally active farnesyl transferase inhibitor that specifically blocks farnesylation of proteins involved in growth-factor–dependent cell-signal–transduction pathways. We conducted a phase II study in 76 patients with advanced breast cancer. Patients and Methods: Two cohorts of patients were recruited sequentially. The first cohort (n = 41) received a continuous dosing [CD] regimen of R115777 400 or 300 mg bid. The second cohort (n = 35) received 300 mg bid in a cyclical regimen of 21 days of treatment followed by 7 days of rest (intermittent dosing [ID]). Results: In the CD cohort, four patients (10%) had a partial response (PR) and six patients (15%) had stable disease at ≥ 24 weeks (SD). In the ID cohort, five patients (14%) had a PR and three patients (9%) had prolonged SD. The first six patients in the CD cohort treated at 400 mg bid all developed grade 3 to 4 neutropenia, so the subsequent 35 patients were treated at 300 mg bid. The incidence of hematologic toxicity was significantly lower in the ID than in the CD (300-mg bid) cohort: grade 3 to 4 neutropenia (14% v 43%; P = .016) and grade 3 to 4 thrombocytopenia (3% v 26%; P = .013). One patient in the ID cohort developed grade 2 to 3 neurotoxicity compared with 15 patients in the CD cohort (3% v 37%; P = .0004). Conclusion: The farnesyl transferase inhibitor R115777 has demonstrated clinical activity in patients with metastatic breast cancer, and the ID regimen has a significantly improved therapeutic index compared with the CD regimen.
Phase I Trial of Concurrent Twice-Weekly Recombinant Human Interleukin-12 Plus Low-Dose IL-2 in Patients With Melanoma or Renal Cell Carcinoma
Authors: Gollob Jared A. , Veenstra Korina G. , Parker Robert A. , Mier James W. , McDermott David F. , Clancy Daniel , Tutin Linda , Koon Henry , Atkins Michael B. 
Published: June 2003

Purpose: To maintain interferon gamma (IFNγ) induction by recombinant human interleukin-12 (rhIL-12) and enhance its activity against melanoma and renal cell cancer, a regimen of twice-weekly intravenous (IV) rhIL-12 was modified to include concurrent low-dose subcutaneous (SC) IL-2 in a phase I dose escalation study.Patients and Methods: Patients received 6-week cycles of twice-weekly IV rhIL-12 at doses of 300 to 500 ng/kg. Midway through cycle 1, low-dose SC IL-2 was added. The IL-2 was escalated from 0.5 to 6.0 MU/m2. Grade 3 elevations of hepatic ALT, AST, or alkaline phosphatase were not considered dose-limiting unless values were more than 10 times normal. During cycle 1, patients underwent immune monitoring to assess the effect of IL-2 on lymphocyte activation and cytokine production induced by rhIL-12.Results: Twenty-eight patients were enrolled onto the study. The maximum-tolerated dose (MTD) was 500 ng/kg rhIL-12 plus 3 MU/m2IL-2. Toxicities related to the addition of IL-2 at the MTD included fever or chills, anemia, fatigue, nausea or vomiting, and orthostatic hypotension. At the MTD, IL-2 significantly augmented IFNγ and IFNγ-inducible protein-10 production by rhIL-12 and led to a three-fold expansion of natural killer cells. There was one major clinical response (partial response) as well as two pathologic responses; all occurred in melanoma patients. Stable disease for three to six cycles was only observed at or above the MTD in melanoma and renal cell cancer patients.Conclusion: The addition of concurrent low-dose IL-2 to rhIL-12 is well tolerated, restores and maintains immune activation by rhIL-12, and has clinical activity. This regimen should be further investigated in phase II studies in untreated patients with melanoma or renal cell cancer and in other rhIL-12–responsive malignancies.
Acquisition of Hox codes during gastrulation and axial elongation in the mouse embryo
Authors: Forlani Sylvie , Lawson Kirstie A. , Deschamps Jacqueline 
Published: June 2003

Early sequential expression of mouse Hox genes is essential for their later function. Analysis of the relationship between early Hox gene expression and the laying down of anterior to posterior structures during and after gastrulation is therefore crucial for understanding the ontogenesis of Hox-mediated axial patterning. Using explants from gastrulation stage embryos,we show that the ability to express 3′ and 5′ Hox genes develops sequentially in the primitive streak region, from posterior to anterior as the streak extends, about 12 hours earlier than overt Hox expression. The ability to express autonomously the earliest Hox gene, Hoxb1, is present in the posterior streak region at the onset of gastrulation, but not in the anterior region at this stage. However, the posterior region can induce Hoxb1 expression in these anterior region cells. We conclude that tissues are primed to express Hox genes early in gastrulation, concomitant with primitive streak formation and extension, and that Hox gene inducibility is transferred by cell to cell signalling.Axial structures that will later express Hox genes are generated in the node region in the period that Hox expression domains arrive there and continue to spread rostrally. However, lineage analysis showed that definitive Hox codes are not fixed at the node, but must be acquired later and anterior to the node in the neurectoderm, and independently in the mesoderm. We conclude that the rostral progression of Hox gene expression must be modulated by gene regulatory influences from early on in the posterior streak, until the time cells have acquired their stable positions along the axis well anterior to the node.
Rapid Volumetric Bioprinting of Decellularized Extracellular Matrix Bioinks
Authors: Lian Liming , Xie Maobin , Luo Zeyu , Zhang Zhenrui , Maharjan Sushila , Mu Xuan , Garciamendez‐Mijares Carlos Ezio , Kuang Xiao , Sahoo Jugal Kishore , Tang Guosheng , Li Gang , Wang Di , Guo Jie , González Federico Zertuche , Abril Manjarrez Rivera Victoria , Cai Ling , Mei Xuan , Kaplan David L. , Zhang Yu Shrike 
Published: January 2024

AbstractDecellularized extracellular matrix (dECM)‐based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM‐based materials. In this study, heart‐derived dECM (h‐dECM) and meniscus‐derived dECM (Ms‐dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2‐bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low‐concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte‐laden h‐dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms‐dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.
Multicolor Tunable Upconversion Luminescence via Near‐Infrared Manipulation of Population Pathways of Er3+ Ions Excited‐State Levels for Volumetric Color Displays
Authors: Jia Heng , Li Nan , He Huiyu , Zhang Xucheng , Teng Yingyue , Qin Weiping 
Published: January 2024

AbstractPrecise control over multicolor luminescence of upconversion nanoparticles (UCNPs) is of significant importance for their applications in widespread fields of research. However, realizing the tunable emissions in single UCNPs with a single lanthanide element remains a great challenge. Herein, without multiple lanthanide elements, a new strategy for the regulation of the excited‐state level population pathways of the same lanthanide activator Er3+ ion to obtain multicolor‐tunable upconversion luminescence is proposed through utilizing 980 nm coupled 1973 nm synergistic excitation. Unlike typical single wavelength excitation, the synergistic excitation may affect population pathways of the excited‐state level of Er3+ ion by adjusting excitation wavelength and power density, resulting in a dynamically adjustable change in luminescence color output. Notably, multicolor luminescence involving green, chartreuse, yellow, orange, and red can be tuned dynamically in the NaYF4:Er3+ single UCNPs by using the tunable 980/1973 nm synergistic excitation. This dynamic luminescence color variation from these UCNPs has demonstrated promising potential applications in volumetric color display. The results provide a new approach to achieve multicolor‐tunable upconversion luminescence at single nanoparticles level and open up the possibility of developing true three‐dimensional volumetric color display technologies with resolution at the nanometer range.
A Nucleic Acid‐Based LYTAC Plus Platform to Simultaneously Mediate Disease‐Driven Protein Downregulation
Authors: Huang Yangyang , Zhou Xujiao , Zhang Yirou , Xie Miao , Wang Fujun , Qin Jingcan , Ye Han , Zhang Hong , Zhang Chuan , Hong Jiaxu 
Published: January 2024

AbstractProtein degradation techniques, such as proteolysis‐targeting chimeras (PROTACs) and lysosome‐targeting chimeras (LYTACs), have emerged as promising therapeutic strategies for the treatment of diseases. However, the efficacy of current protein degradation methods still needs to be improved to address the complex mechanisms underlying diseases. Herein, a LYTAC Plus hydrogel engineered is proposed by nucleic acid self‐assembly, which integrates a gene silencing motif into a LYTAC construct to enhance its therapeutic potential. As a proof‐of‐concept study, vascular endothelial growth factor receptor (VEGFR)‐binding peptides and mannose‐6 phosphate (M6P) moieties into a self‐assembled nucleic acid hydrogel are introduced, enabling its LYTAC capability. Small interference RNAs (siRNAs) is then employed that target the angiopoietin‐2 (ANG‐2) gene as cross‐linkers for hydrogel formation, giving the final LYTAC Plus hydrogel gene silencing ability. With dual functionalities, the LYTAC Plus hydrogel demonstrated effectiveness in simultaneously reducing the levels of VEGFR‐2 and ANG‐2 both in vitro and in vivo, as well as in improving therapeutic outcomes in treating neovascular age‐related macular degeneration in a mouse model. As a general material platform, the LYTAC Plus hydrogel may possess great potential for the treatment of various diseases and warrant further investigation.