tbuckley/cabot-search huggingface dataset:
Whole-Body Low-Dose Computed Tomography and Advanced Imaging Techniques for Multiple Myeloma Bone Disease
Authors: Matthew J. Pianko, Evangelos Terpos, G. David Roodman, Chaitanya R. Divgi, Sonja Zweegman, Jens Hillengass, Suzanne Lentzsch
Journal: Clinical Cancer Research (2014)

Detection of lytic bone lesions is crucial in the workup for multiple myeloma and very often dictates the decision to start treatment. Conventional radiography, despite decades of use, is often insufficient for detection of bone disease in multiple myeloma. Modern imaging techniques such as MRI, PET, and CT offer superior detection of myeloma bone disease and extramedullary manifestations of plasma cell dyscrasias. Novel whole-body low-dose computed tomography (WBLDCT) protocols allow for collection of superior image detail of the skeleton at doses of radiation similar to those used for conventional planar radiography. Several studies have shown that WBLDCT has a superior detection rate for lytic bone lesions compared with whole-body X-ray (WBXR), potentially leading to restaging and changes in therapy. MRI and PET provide imaging data important for assessing disease activity and prognostication. Because of several advantages over WBXR, WBLDCT is already the standard imaging technique for use in patients with multiple myeloma in many European institutions. However, the radiographic skeletal survey or WBXR is still the initial study of choice used to screen for myeloma bone disease in many institutions. In this review, we aim to explore the changing landscape of imaging for myeloma bone disease through use of modern imaging techniques.
Abstract 2374: Mir-29/Hsp47 regulate breast cancer progression by modulating the ECM transcription network
Authors: Jieqing Zhu, Gaofeng Xiong, Ren Xu
Journal: Cancer Research (2015)

Abstract The extracellular matrix (ECM), an essential component of tumor microenvironment, play crucial roles in cancer development and progression. Using gene co-expression network analysis, we have identified an ECM transcription network from hundreds of human breast cancer. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. We found that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or non-invasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Co-expression network analysis also showed that levels of microRNA-29b and 29c were inversely correlated with expression of Hsp47 and ECM network genes in human breast cancer tissues. We found that miR-29 repressed expression of Hsp47 along with multiple ECM network genes. Ectopic expression of miR-29b suppressed malignant phenotypes of breast cancer cells in 3D culture. Clinically, increased expression of Hsp47 and reduced levels of miR-29b and 29c were associated with poor survival outcomes in breast cancer patients. Our results show that Hsp47 is regulated by miR-29 during breast cancer development and progression, and that increased Hsp47 expression promotes cancer progression in part by enhancing deposition of ECM proteins. Citation Format: Jieqing Zhu, Gaofeng Xiong, Ren Xu. Mir-29/Hsp47 regulate breast cancer progression by modulating the ECM transcription network. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2374. doi:10.1158/1538-7445.AM2015-2374
Retrograde Cannulation of Cephalic Vein for Hemodialysis
Authors: V. Padmanabha Rao
Journal: JAMA (1970)

An arteriovenous shunt has now been functioning three years with the use of one radial artery and multiple revisions along the cephalic vein. Retrograde cannulation of the cephalic vein has materially added to the survival of this shunt. We describe the technique here in hope that it will be useful to others presented with the same problem.
Estimating Population Cause-Specific Mortality Fractions from in-Hospital Mortality: Validation of a New Method
Authors: Christopher J. L Murray, Alan D Lopez, Jeremy T Barofsky, Chloe Bryson-Cahn, Rafael Lozano
Journal: PLoS Medicine (2007)

Background Cause-of-death data for many developing countries are not available. Information on deaths in hospital by cause is available in many low- and middle-income countries but is not a representative sample of deaths in the population. We propose a method to estimate population cause-specific mortality fractions (CSMFs) using data already collected in many middle-income and some low-income developing nations, yet rarely used: in-hospital death records. Methods and Findings For a given cause of death, a community's hospital deaths are equal to total community deaths multiplied by the proportion of deaths occurring in hospital. If we can estimate the proportion dying in hospital, we can estimate the proportion dying in the population using deaths in hospital. We propose to estimate the proportion of deaths for an age, sex, and cause group that die in hospital from the subset of the population where vital registration systems function or from another population. We evaluated our method using nearly complete vital registration (VR) data from Mexico 1998–2005, which records whether a death occurred in a hospital. In this validation test, we used 45 disease categories. We validated our method in two ways: nationally and between communities. First, we investigated how the method's accuracy changes as we decrease the amount of Mexican VR used to estimate the proportion of each age, sex, and cause group dying in hospital. Decreasing VR data used for this first step from 100% to 9% produces only a 12% maximum relative error between estimated and true CSMFs. Even if Mexico collected full VR information only in its capital city with 9% of its population, our estimation method would produce an average relative error in CSMFs across the 45 causes of just over 10%. Second, we used VR data for the capital zone (Distrito Federal and Estado de Mexico) and estimated CSMFs for the three lowest-development states. Our estimation method gave an average relative error of 20%, 23%, and 31% for Guerrero, Chiapas, and Oaxaca, respectively. Conclusions Where accurate International Classification of Diseases (ICD)-coded cause-of-death data are available for deaths in hospital and for VR covering a subset of the population, we demonstrated that population CSMFs can be estimated with low average error. In addition, we showed in the case of Mexico that this method can substantially reduce error from biased hospital data, even when applied to areas with widely different levels of development. For countries with ICD-coded deaths in hospital, this method potentially allows the use of existing data to inform health policy.
Histopathological Image Analysis: A Review
Authors: M.N. Gurcan, L.E. Boucheron, A. Can, A. Madabhushi, N.M. Rajpoot, B. Yener
Journal: IEEE Reviews in Biomedical Engineering (2009)

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe.
Lack of understanding in fibromyalgia and rheumatoid arthritis: the Illness Invalidation Inventory (3*I)
Authors: M B Kool, H van Middendorp, M A Lumley, Y Schenk, J W G Jacobs, J W J Bijlsma, R Geenen
Journal: Annals of the Rheumatic Diseases (2010)

Background Patients with rheumatic diseases may face ‘discounting’ (denying and patronising) or ‘lack of understanding’ because of having symptoms without external clinical signs, but instruments to assess such invalidation experiences are lacking. Objectives To develop and evaluate the Illness Invalidation Inventory (3*I), to compare invalidation experiences of two groups of patients who differ in visual signs and laboratory findings—rheumatoid arthritis (RA) and fibromyalgia—and to examine the association of invalidation with health status. Methods A questionnaire (eight items with respect to five sources: spouse, family, medical professionals, work environment and social services) was constructed. It was completed by 142 patients with RA and 167 patients with fibromyalgia. Results Principal axis factoring with oblimin rotation yielded two factors with high internal consistency (α&gt;0.70): ‘discounting’ (five items) and ‘lack of understanding’ (three items). Patients with fibromyalgia experienced significantly more discounting and lack of understanding from their family, medical professionals, colleagues and social services than did patients with RA. Both patient groups experienced more invalidation from social services, colleagues and family than from medical professionals and spouses. More discounting and lack of understanding correlated with poorer mental well-being and social functioning in both patient groups. Discounting correlated with more physical disability and pain in patients with RA. Conclusions The 3*I is a brief, reliable instrument for assessing patients' perceptions of invalidation from different sources, which differ between patient groups and are associated with health status. Future validation research should clarify the clinical impact of invalidation on treatment adherence and outcome.
Critical Reviews: How we treat sickle cell patients with leg ulcers
Authors: Caterina P. Minniti, Gregory J. Kato
Journal: American Journal of Hematology (2015)

The past five decades have seen an improvement in the mortality and morbidity of sickle cell disease (SCD) because of prophylaxis against infectious complications, improved and expanded red cell transfusions, implementation of hydroxyurea therapy, and advances in supportive care. Now that the majority of patients in the western hemisphere reaches adulthood, end organ diseases are frequent, which include vasculopathic complications such as chronic leg ulcers. The management of patients with leg ulcers requires the hematologist to lead a team of health care professionals, and investigates the presence of associated, but potentially still occult signs of vasculopathy, such as pulmonary hypertension, renal disease, priapism and retinopathy. These complications may be asynchronous, and long term careful screening is indicated, in order to ensure early diagnosis and intervention. It is crucial to address both the immediate consequences of pain, infection and disability, and long term effects on quality of life, employment and stigma associated with chronic ulceration. Recent insights into their pathophysiology may have practical implications. We propose a holistic approach to the management of patients' physical and emotional problems and mechanisms of ulcers formation and delayed healing. An overview of topical and systemic therapies for chronic ulcers is given, with the understanding that wound care therapy is best left to the wound specialists, medical and surgical, with whom the hematologist must keep an open line of communication. In the absence of evidence-based guidelines, our opinion is based on both a critical review of the literature and our personal clinical and research experience.
Permanent hair removal with a diode-pumped Nd:YAG laser: a pilot study using the direct insertion method
Authors: Ken Hashimoto, Motoichiro Kogure, Timothy L. Irwin, Keiko Tezuka, Toshimitsu Osawa, Kyoichi Kato, Teruko Ebisawa
Journal: Journal of the American Academy of Dermatology (2003)
Recovery of Burkholderia cenocepacia strain PHDC from cystic fibrosis patients in Europe
Authors: T Coenye
Journal: Thorax (2004)

Burkholderia cenocepacia can cause life threatening respiratory tract infections in patients with cystic fibrosis (CF) and has a significant impact on survival. There is extensive evidence for patient to patient spread and nosocomial transmission of this organism, and several widespread B cenocepacia strains have been described including the transatlantic ET12 clone. A study was performed to compare B cenocepacia isolates recovered from CF patients receiving care in several European countries and strains isolated from other clinical samples and the environment, with reference isolates from the epidemic B cenocepacia strain PHDC which has so far only been recovered from CF patients and soil in the USA.A large collection of B cenocepacia isolates, including a large number recovered from CF patients receiving care in several European countries, Canada and the USA, were genotyped by means of randomly amplified polymorphic DNA typing (RAPD) and rep-PCR using the BOX-A1R primer (BOX-PCR).Nineteen Burkholderia cenocepacia isolates cultured from clinical samples in Europe (18 recently recovered from CF patients in France and Italy and one recovered in 1964 from urine in the UK) showed RAPD fingerprinting patterns that were similar to patterns obtained from isolates of B cenocepacia strain PHDC. Subsequent analysis of these isolates using BOX-PCR confirmed that the European isolates and strain PHDC represent the same clone.Strain PHDC represents a second transatlantic B cenocepacia clone capable of colonising patients with CF.
Two- versus 24-hour infusion of cisplatin: pharmacokinetic considerations.
Authors: P A Reece, I Stafford, R L Abbott, C Anderson, J Denham, S Freeman, R G Morris, P G Gill, C L Olweny
Journal: Journal of Clinical Oncology (1989)

The disposition of unchanged cisplatin was compared after two- and 24-hour intravenous (IV) infusion to eight patients with germ cell cancer (dose, 100 mg/m2), 14 patients with head and neck cancer (dose, seven patients 50 mg/m2; seven patients, 100 mg/m2). Patients were randomized to receive either a two- or 24-hour infusion in the first course of treatment and the reverse in the second course. Cisplatin renal clearance, total clearance, and the percentage of the dose excreted unchanged in urine were significantly lower with the longer infusion. Total clearance was 345 +/- 97.0 mL/min/m2 after the two-hour infusion and 268 +/- 70.7 mL/min/m2 after the 24-hour infusion (P less than .0001). Renal clearance was 79.1 +/- 35.3 mL/min/m2 and 34.1 +/- 14.9 mL/min/m2 (P less than .0001). The percentage of the dose excreted unchanged in urine was 22.9 +/- 6.5% and 12.8 +/- 4.0%, respectively (P less than .0001). The ratio of cisplatin renal clearance to creatinine clearance was 1.95 +/- .96 after the two-hour infusion and .90 +/- .40 after the 24-hour infusion (P less than .001). There was only a poor relationship between cisplatin renal clearance and creatinine clearance after a two-hour infusion (r2 = .05, P greater than .1) or 24-hour infusion (r2 = .18, P greater than .05). The severity of emesis was graded on a four-point scale and was significantly less with the 24-hour infusion than with the two-hour infusion (P less than .05). Twenty-four-hour infusion of cisplatin resulted in greater drug retention in patients due to reduced renal clearance, but was also associated with reduced emetic toxicity, probably as a result of lower peak plasma levels.
A heat acclimation protocol for team sports
Authors: C Sunderland, J G Morris, M E Nevill
Journal: British Journal of Sports Medicine (2008)

It is well documented that heat acclimation of six or more sessions of at least 60 min duration prolongs the time to exhaustion during endurance walking, cycling and running in the heat. However, this type of acclimation is not specific to team sport activity and the effect of acclimation on prolonged high-intensity intermittent running has not yet been investigated.To assess the impact of an intermittent acclimation protocol on distance run during team sport activity.The impact of four short heat acclimation sessions (30-45 min of the Loughborough Intermittent Shuttle Test; LIST) on high-intensity intermittent running capacity (LIST) in the heat (30 degrees C, 27% relative humidity (RH)), was examined. Seventeen female well-trained games players were split into three groups: an acclimation group (30 degrees C, 24% RH), a moderate training group (18 degrees C, 41% RH) and a control group who did not complete any training between the main trials (pre-acclimation and post-acclimation). The pre-acclimation (A) and post-acclimation (B) trials were separated by 28 days to control for menstrual phase and verified using hormonal analysis. The four acclimation or moderate training sessions utilising the LIST were completed with one or two rest days interspersed between each session in a 10-day period prior to the post-acclimation trial (B).In the post-acclimation trial distance run was increased by 33% in the acclimation group (A: 7703 (SEM 1401) m vs B: 10215 (SEM 1746) m; interaction group x trial p<0.05), but was unchanged in the moderate and control groups. The acclimation group had a lower rectal temperature (interaction group x trial x time p<0.01) due to a lower rate of rise, and an increase in thermal comfort1 after acclimation (End A: 7 (SEM 2) vs 6 (SEM 2); interaction group x trial p<0.01). There was no difference in serum progesterone, aldosterone or cortisol concentrations following acclimation or between groups.Four 30-45 min sessions of intermittent exercise induced acclimation, and resulted in an improvement in intermittent running exercise capacity in female games players. A lower rectal temperature and a concomitant rise in thermal comfort may be partly responsible for the improvement in exercise capacity.
CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance
Authors: Kang-Seo Park, Mark Raffeld, Yong Wha Moon, Liqiang Xi, Caterina Bianco, Trung Pham, Liam C. Lee, Tetsuya Mitsudomi, Yasushi Yatabe, Isamu Okamoto, Deepa Subramaniam, Tony Mok, Rafael Rosell, Ji Luo, David S. Salomon, Yisong Wang, Giuseppe Giaccone
Journal: Journal of Clinical Investigation (2014)

The majority of non–small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI–sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC.
Impact of Tailored Education on Awareness of Personal Risk for Therapy-Related Complications Among Childhood Cancer Survivors
Authors: Wendy Landier, Yanjun Chen, Golnaz Namdar, Liton Francisco, Karla Wilson, Claudia Herrera, Saro Armenian, Julie A. Wolfson, Can-Lan Sun, F. Lennie Wong, Smita Bhatia
Journal: Journal of Clinical Oncology (2015)

Purpose Survivors of childhood cancer carry a substantial burden of long-term morbidity; personal risk awareness is critical to ensure survivors' engagement in early detection/management of complications. The impact of education provided in survivorship clinics on survivors' understanding of their personal health risks is unclear. Methods Patients diagnosed with cancer at age 21 years or younger and at 2 or more years off therapy completed questionnaires about awareness of personal risk for therapy-related complications at T0 (first survivorship clinic visit) and at T1 to T5 (subsequent visits). After questionnaire completion at each clinic visit, survivors received education tailored to personal risk. Results A total of 369 survivors completed 1,248 visits (median, three visits; range, one to six visits). The median age at cancer diagnosis was 11 years (range, 0 to 21 years); the median age at T0 was 24 years (range, 5 to 57 years); 38% were white; 45% had leukemia; and 34% received hematopoietic cell transplantation. The cohort was at risk for a median of six (range, one to nine) complications. Awareness increased from 38.6% at T0 to 66.3% at T3. Generalized estimating equations (that adjusted for diagnosis, hematopoietic cell transplantation, race/ethnicity, and patient/parent education) showed significant gains in awareness from T0 to T1 (P &lt; .001), T1 to T2 (P = .03), and T2 to T3 (P &lt; .001) but no significant gain thereafter through T5 (P = .7). Predictors of low awareness included education less than a college degree (odds ratio [OR], 1.9; P = .02), longer time from diagnosis (OR, 1.03/year; P = .04), diagnosis of leukemia (OR, 2.1; P = .004), nonwhite race (OR, 2.8; P &lt; .001), and risk for six or fewer complications (OR, 2.1; P = .002). Conclusion Risk-based education in a survivorship clinic significantly increases awareness of personal health risk through three sessions, with saturation thereafter. Vulnerable populations with minimal gain in awareness identified in this study could inform targeted interventions.
Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways
Authors: Vivek Swarup, Daniel Phaneuf, Nicolas Dupré, Susanne Petri, Michael Strong, Jasna Kriz, Jean-Pierre Julien
Journal: The Journal of Experimental Medicine (2011)

TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-κB activation and that NF-κB may constitute a therapeutic target for the disease.