bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobilization, collection, and processing of peripheral blood stem cells in individuals with sickle cell trait
Authors: Kang Elizabeth M. , Areman Ellen M. , David-Ocampo Virginia , Fitzhugh Courtney , Link Mary E. , Read Elizabeth J. , Leitman Susan F. , Rodgers Griffin P. , Tisdale John F. 
Published: July 2002

Abstract
Mobilized peripheral blood is increasingly used as the source of hematopoietic stem cells for allogeneic transplantation, currently the only curative approach for sickle cell anemia. However, the safety and feasibility of stem cell mobilization in individuals with sickle cell trait (SCT) has not been documented. This study is a prospective controlled trial to evaluate the safety and feasibility of peripheral blood stem cell (PBSC) mobilization in 8 SCT subjects and 8 control subjects matched for age and race. Mobilization with filgrastim 10 μg/kg subcutaneous daily for 5 days was followed by 12-L apheresis on the fifth day. Filgrastim administration was accompanied by similar symptoms in all subjects; no untoward adverse events occurred in either group, including sickle cell crises. CD34+ cell mobilization response was not significantly different between SCT and control subjects. Median CD34+ cell content was also similar in PBSCs collected from SCT versus control subjects, 6.8 versus 3.9 ×106 CD34+ cells/70 kg,P = .165. Red cell depletion from SCT products was not possible by using hydroxyethyl starch sedimentation but was achievable with ammonium chloride lysis. There was no evidence of gelling of SCT products after thaw, and no difference in cell recovery was seen among red cell–depleted versus nondepleted products. Cryopreservation in 5% dimethyl sulfoxide/6% pentastarch was associated with superior cell recovery (both SCT and control subjects) compared with 10% dimethyl sulfoxide (P = .001). The study concluded that filgrastim mobilization, large volume apheresis, processing, and cryopreservation appears to be safe in donors with SCT, allowing PBSC use for transplantation in patients with sickle cell anemia.
Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells
Authors: Wiewrodt Rainer , Thomas Anu P. , Cipelletti Luca , Christofidou-Solomidou Melpo , Weitz David A. , Feinstein Sheldon I. , Schaffer David , Albelda Steven M. , Koval Michael , Muzykantov Vladimir R. 
Published: July 2002

AbstractCell-selective intracellular targeting is a key element of more specific and safe enzyme, toxin, and gene therapies. Endothelium poorly internalizes certain candidate carriers for vascular immunotargeting, such as antibodies to platelet endothelial cell adhesion molecule 1 (PECAM–1). Conjugation of poorly internalizable antibodies with streptavidin (SA) facilitates the intracellular uptake. Although both small and large (100-nm versus 1000-nm diameter) anti-PECAM/SA–beta galactosidase (SA–β-gal) conjugates bound selectively to PECAM-expressing cells, only small conjugates showed intracellular accumulation of active β-gal. To study whether size of the conjugates controls the uptake, a series of anti-PECAM/SA and anti-PECAM/bead conjugates ranging from 80 nm to 5 μm in diameter were produced. Human umbilical vein endothelial cells and PECAM-transfected mesothelioma cells internalized 80- to 350-nm anti-PECAM conjugates, but not conjugates larger than 500 nm. Further, size controls intracellular targeting of active therapeutic cargoes in vitro and in vivo. Small anti-PECAM/DNA conjugates transfected target cells in culture 5-fold more effectively than their large counterpart (350- versus 4200-nm diameter). To evaluate the practical significance of the size-controlled subcellular addressing, we coupled glucose oxidase (GOX) to anti-PECAM and antithrombomodulin. Both types of conjugates had equally high pulmonary uptake after intravenous injection in mice, yet only small (200- to 250-nm), not large (600- to 700-nm), GOX conjugates caused profound oxidative vascular injury in the lungs, presumably owing to intracellular generation of H2O2. Thus, engineering of affinity carriers of specific size permits intracellular delivery of active cargoes to endothelium in vitro and in vivo, a paradigm useful for the targeting of drugs, genes, and toxins.
The Guy's Neurological Disability Scale in patients with multiple sclerosis: a clinical evaluation of its reliability and validity
Authors: Rossier Philippe , Wade Derick T 
Published: July 2002

Objective: To establish reliability and validity of the Guy's Neurological Disability Scale (GNDS) for the assessment of patients with multiple sclerosis (MS) and to investigate whether it can be used by postal questionnaire. Design: An observational study assessing one group of 22 patients using the GNDS face-to-face, repeating the assessment two or three weeks later with other tests; and assessing a second group of 21 patients first using a postal version of the GNDS and then seeing them face-to-face. Setting: Patients in the community attending a day centre or a voluntary support group. Subjects: Patients with multiple sclerosis. Measures: The GNDS was the primary measure, and was compared with the Barthel Index, the Expanded Disability Status Scale (EDSS), the Short Orientation Concentration and Memory Test, the Nine-hole Peg Test, the Rivermead Mobility Index, the Hospital Anxiety and Depression Scale, the Fatigue Severity Scale, visual acuity assessment, swallowing 50 ml of water, and a clinical assessment of dysarthria. Results: The test–retest reliability of the GNDS total score ( r = 0.972) and each of its components ( r varied from 0.685 to 0.987) was good. When compared with the EDSS or the Barthel, the GNDS had good validity (respectively r = 0.636 and r = –0.757). The validity was also measured for the different areas of the GNDS by comparison with corresponding indices or test. The results varied from good to excellent ( r from –0.557 to 0.910). The results were only a little less reliable when a postal questionnaire was used. Conclusion: The GNDS is a valid and reliable tool for the assessment of MS patients. The test–retest correlation varies from good to excellent. It can be used as postal questionnaire even if, as expected, the intervieweradministered method shows slightly better results.
Association between hypermobility and congenital limb defi ciencies
Authors: Hassoon Ali , Kulkarni Jai 
Published: July 2002

Objective: To determine the prevalence of hypermobility in individuals with congenital limb deficiencies and whether congenital limb loss is associated with increased laxity in the remaining joints. Study design: All data were collected during the individuals' visits to the prosthetic clinic. Setting: The subjects were evaluated at the Subregional Disablement Services Centre at University Hospital of South Manchester, UK. Subjects: Forty-five individuals with congenital limb deficiencies were studied (male/female 27: 18; ages 6–31 years). Outcome measure: A modified version of the nine-point Beighton Score for hypermobility was used, using the presently accepted criteria for diagnosing hypermobility. Any individual who scored 3 or more points was considered to have joint hypermobility. Result: Of the 45 individuals with congenital limb deficiencies, 71% had at least one hypermobile joint, whereas 38% had three or more features of hypermobility, with female/male ratio of 2.75: 1. Conclusion: Our results show an increase in joint hypermobility (laxity) in individuals born with congenital limb deficiencies compared with the prevalence of this condition in the general population. As joint hypermobility may predispose individuals to low back pain, joint effusion, recurrent joint dislocation and ligament rupture, it is useful to identify those individuals with hypermobility.
Effects of one-point and four-point canes on balance and weight distribution in patients with hemiparesis
Authors: Laufer Yocheved 
Published: July 2002

Objective: To examine the effects of one-point and four-point canes on postural sway and on the distribution of weight between the lower extremities and the walking aids in hemiparetic patients. Setting: Flieman Geriatric Rehabilitation Hospital, Haifa, Israel. Subjects: Thirty hemiparetic patients following a unilateral stroke, with moderate functional impairment, and 20 age-matched healthy subjects. Intervention: Subjects were tested on two forceplates, which were placed at a 30° angle from each other with the heel end of the plates separated by 3 cm. Each subject was tested under three conditions: with no cane, with a one-point cane, and with a four-point cane. Testing time was 30 seconds, and order of testing was randomized. Outcome measures: Weight borne by the lower extremities and by the walking aids expressed as a percentage of overall body weight, and Sway Index indicating vertical pressure ‘uctuations over both feet. Results: In both subject groups, the one-point cane did not reduce sway signi”cantly in comparison with no cane, while the four-point cane reduced sway signi”cantly in comparison with both no cane and one-point cane. Neither cane type affected weight-bearing on the paretic leg, while signi”cantly reducing weight-bearing on the uninvolved extremity. Mean percentage of body weight on the four-point cane was signi”cantly higher than on the one-point cane Conclusions: A four-point cane increases stability of moderately involved hemiparetic patients during stance more than a one-point cane. The noted shift of weight toward the walking aid does not adversely affect weight-bearing on the paretic limb.
A randomized controlled trial of exercise to improve mobility and function after elective knee arthroplasty. Feasibility, results and methodological difficulties
Authors: Frost H , Lamb S E , Robertson S 
Published: July 2002

Objective: To assess the feasibility of comparing two types of exercise regime aiming to improve mobility and function following knee arthroplasty. Design: A single-blind randomized controlled trial. Subjects: Patients with primary, unilateral knee osteoarthritis undergoing elective knee joint replacement. Intervention: Home-based traditional exercise group (TEG) or home-based functional exercise group (FEG) following discharge from hospital. Outcome measures: These included goniometry; a knee-specific pain score, leg extensor power and a walking test. Patients were followed up at three, six and 12 months after surgery. Results: Forty-seven patients met the study criteria, 24 were randomized to the TEG and 23 to the FEG. There were marked improvements in mobility, leg extensor power and pain in the year after surgery (MANOVA p < 0.001). There were no statistically significant differences between the two exercise groups. Knee flexion decreased during the follow-up period and had not recovered by 12 months. Retention of patients was a problem, with nearly 50% lost to follow-up at 12 months. These patients were assessed as having low motivation during inpatient rehabilitation ( p < 0.05). Conclusions: There were trends in favour of the FEG that were of clinical relevance. A definitive study would need a sample size of at least 100 patients in each arm. It is essential to develop strategies to combat loss to follow-up.
Beyond the 10-m time: A pilot study of timed walks in lower limb amputees
Authors: Hatfield Alison G 
Published: July 2002

Objective: To investigate in a pilot study the use of extended walking times as an objective method of distinguishing differences in outcome in lower limb amputees. Setting: Sixteen lower limb amputees attending the prosthetic clinic. Method: Patients were asked to walk 100 m, turning every 20 m, using their usual walking aids and prostheses at their chosen walking speed. Demographic details and modified Stanmore/Harold Wood mobility grades, walking aids used and discomfort were recorded. Time to walk each 20 m up to 100 m was recorded. Statistical analysis was carried out using the Spearman rank order correlation coefficient. Results: There was a wide age range and differing causes of amputation. Five out of 16 subjects failed to complete 100 m and these had the slowest 20 and 40-m times. The mean time to walk 40 m was 41 seconds for those who were able to complete 100 m and 144 seconds for those who could not complete 100 m. All those with modified Stanmore/Harold Wood mobility grades less than four failed to complete 100 m. There was a high correlation between 20-, 40-, 60-, 80 and 100-m times and mobility grades, which was statistically significant, and between 20-, 40-, 60-, 80 and 100-m times. Conclusion: Forty-metre walking time can differentiate between those of mobility grades 4b–6 and those with lower mobility grades who are unable to walk significantly outside.
Depression after stroke: a review of the evidence base to inform the development of an integrated care pathway. Part 1: Diagnosis, frequency and impact
Authors: Turner-Stokes Lynne , Hassan Nibras 
Published: July 2002

Background: Depression is a common complication of stroke, leading to increased morbidity and mortality. It can impede the process of rehabilitation, and has been associated with poorer outcomes and increased length of stay in hospital. This systematic review was undertaken as a preliminary step to explore the available evidence on which to base an integrated care pathway (ICP) for the management of post-stroke depression (PSD) in a rehabilitation setting. It is divided into two parts. Aims and objectives: In part 1 we review the frequency of depression in stroke and its impact on functional recovery. Also the different methods for diagnosis and measurement. Methods: Data sources comprised a computer-aided search of published studies on depression in stroke and references to literature used in reviews. Main findings: PSD is common and is associated with cognitive, functional and social deficits which potentially limit the outcome from rehabilitation. However, diversity of assessment tools and diagnostic criteria confound assimilation of the available literature. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale and Zung Self-rating Depression Scale were most commonly used and have demonstrable validity in stroke patients but tend to exclude those with aphasia. Instruments developed specifically to include aphasic patients, such as the Stroke Aphasic Depression Scale, are promising but have yet to be fully evaluated. Conclusions: Further work is required to adapt and evaluate instruments to measure depression in the context of stroke. Development of an integrated care pathway may help to establish a more consistent approach to assessment and diagnosis of PSD.
Sensitivity of different ADL measures to apraxia and motor impairments
Authors: Donkervoort Mireille , Dekker Joost , Deelman Betto G 
Published: July 2002

Objective: To determine whether speci”cally designed activities of daily living (ADL) observations can measure disability due to apraxia with more sensitivity than the Barthel ADL Index, a conventional functional scale. Design: Cross-sectional study. Setting: Rehabilitation centres and nursing homes. Subjects: One hundred and six left hemisphere stroke patients with apraxia, hospitalized in rehabilitation centres and nursing homes. Measures: ADL observations, Barthel ADL Index, an apraxia test, Motricity Index, Functional Motor Test. Results: Multivariate analyses showed that the speci”c ADL observations were associated with severity of apraxia (and not with motor impairments). The Barthel ADL Index was associated with motor impairments (and not with severity of apraxia). Conclusion: The assessment of disability in stroke patients with apraxia cannot rely only on the Barthel ADL Index. In addition, the speci”c ADL observation procedure is needed to measure disability due to apraxia.
Estimation of Tax Benefit of US Nonprofit Hospitals
Authors: Plummer Elizabeth , Socal Mariana P. , Bai Ge 
Published: September 2024

ImportanceNonprofit hospitals are under increasing scrutiny to justify the generous tax benefit they receive due to their tax-exempt status. Quantifying the value of the tax benefit they receive at the federal, state, and local levels is critical for designing informed public health policies and ensuring nonprofit hospitals’ taxpayer accountability.ObjectiveTo estimate the financial benefit that nonprofit hospitals derive from their tax-exempt status and assess how the benefit is distributed across state and local communities.Design, Setting, and ParticipantsUsing methodologies and measures consistent with current tax law and practice and data from 2021 Medicare Cost Reports, this study calculated the total financial benefit from nonprofit hospitals’ tax-exempt status for all US nonprofit hospitals with the required Cost Reports data.Main Outcomes and MeasuresNonprofit hospitals’ total tax benefit, which equals the sum of federal and state income tax, sales tax, property tax, the fair market value of charitable contributions from donors, savings from tax exemptions on issued bonds, and federal unemployment tax.ResultsA total of 2927 US nonprofit hospitals received a $37.4 billion total tax benefit in 2021 from federal income tax ($11.5 billion; 31%), sales tax ($9.1 billion; 24%), property tax ($7.8 billion; 21%), state income tax ($3.7 billion; 10%), charitable contributions ($3.2 billion; 8%), bond financing ($2.1 billion; 6%), and federal unemployment tax ($200 million; &amp;lt;1%). Tax benefit varied substantially across states, from $25 098 (Delaware) to $159 464 (Massachusetts) per hospital bed and from $19 (Alabama) to $275 (Massachusetts) per capita. Tax benefit was highly concentrated, with 7% (n = 212) of hospitals accounting for half of the total amount.Conclusion and RelevanceThis study highlights the wide variation of nonprofit hospitals’ tax benefit across states, its high concentration among a small number of hospitals, and the primary role played by state and local taxes. Policy efforts to strengthen nonprofit hospitals’ taxpayer accountability are likely to be more effective when pursued at the local level. The detailed standardized estimation road map can be used by various stakeholders to estimate tax benefit for external valuation and reporting purposes, updated as laws change, and improved upon as better data sources become available.
Determinants of Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma With Nodal Metastases
Authors: Ebrahimi Ardalan , Gupta Ruta , McDowell Lachlan , Magarey Matthew J. R. , Smith Paul N. , Schulte Klaus-Martin , Perriman Diana M. , Veness Michael , Porceddu Sandro , Low Tsu-Hui Hubert , Fowler Allan , Clark Jonathan R. 
Published: September 2024

ImportanceThe eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE).ObjectiveTo identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease.Design, Setting, and ParticipantsThis retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients.ExposureCurative intent surgery ± adjuvant radiotherapy.Main Outcomes and MeasuresDifferences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis.ResultsAmong 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (&amp;gt;3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; &amp;gt;6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors.Conclusions and RelevanceThe study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.
CT45A1‐mediated MLC2 (MYL9) phosphorylation promotes natural killer cell resistance and outer cell fate in a cell‐in‐cell structure, potentiating the progression of microsatellite instability‐high colorectal cancer
Authors: Teng Hao‐Wei , Huang Hsiang‐Yueh , Lin Chun‐Chi , Twu Yuh‐Ching , Yang Wen‐Hao , Lin Wen‐Chun , Lan Hsin‐Yi , Lin Yen‐Yu , Hwang Wei‐Lun 
Published: September 2024

Patients with microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) have high tumor mutation burden and tumor immunogenicity, exhibiting a higher response rate to immunotherapy and better survival. However, a portion of MSI‐H CRC patients still experience adverse disease outcomes. We aimed to identify the tumor‐autonomous regulators determining these heterogeneous clinical outcomes. The Cancer Genome Atlas (TCGA) dataset was used to identify regulators in MSI‐H CRC patients with unfavorable outcomes. Stable CRC tumor clones expressing targeted regulators were established to evaluate migratory and stemness properties, immune cell vulnerability, and cell‐in‐cell (CIC) structure formation. RNA‐sequencing (RNA‐seq) was used to identify enriched biological pathways in stable CRC tumor clones. Clinicopathological characterization of formalin‐fixed paraffin‐embedded (FFPE) MSI‐H CRC specimens was performed to explore the underlying mechanisms involved. We showed that cancer/testis antigen family 45 member A1 (CT45A1) expression was upregulated in MSI‐H CRC patients with poor survival outcomes. CT45A1‐expressing microsatellite stable (MSS) CRC cells showed enhanced migratory ability. However, CT45A1‐expressing MSI‐H CRC cells, but not MSS CRC cells, showed higher resistance to natural killer (NK) cell cytotoxicity and served as outer cells in homotypic CIC structures, preventing exogenous or therapeutic antibody access to inner CRC cells. Inactivating RHO‐ROCK/MLCK‐MLC2 signaling with small‐molecule inhibitors or short‐hairpin RNAs (shRNAs) targeting myosin light chain kinase (MYLK) abolished NK cell resistance and reduced the outer cell fate of CT45A1‐expressing MSI‐H CRC cells. In MSI‐H CRC patients, CT45A1‐positive tumors exhibited increased MLC2 phosphorylation, increased outer cell fate, and decreased survival. We demonstrated that CT45A1 potentiates the advanced progression of MSI‐H CRC, and targeting MLC2 phosphorylation may enhance immunotherapy efficacy in CT45A1‐positive MSI‐H CRC patients.