Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival Analysis of Papillary Thyroid Carcinoma in Relation to Stage and Recurrence Risk: A 20-Year Experience in Pakistan

Objective The aim of this study was to evaluate the overall and progression-free survival of papillary thyroid carcinoma (PTC), comparing the American Thyroid Association (ATA) guideline for risk of recurrence with the TNM staging system with dynamic assessment at 2 years. Patients and Methods This study is a retrospective analysis of 689 PTC patients over a 20-year period at a single center. Disease-free survival based on the TNM staging and ATA recurrence risk was calculated using Kaplan-Meier curves. Dynamic response assessment during the first 2 years was compared for both systems. Survival was calculated based on age, baseline resectability, and postthyroidectomy serum tumor marker levels. Results Six hundred eighty-nine (72.2%) of the total thyroid cancer patients had PTC. Four hundred sixty-nine patients were females, and 220 patients were males. The age range was 6 to 87 years. Five hundred thirty-five patients were resectable, and 56 patients were unresectable. One hundred fifty-one patients were excluded due to insufficient information on recurrence risk. By ATA categorization, 39% had low risk, no disease-related mortality; 44% had intermediate risk, 3 died; and 17% had high risk, 32 died. The 5-year disease-free survival was 54%, 26%, and 5% in low-, intermediate-, and high-risk groups, respectively. The log-rank test showed a significant difference in the percent survival (P < 0.01). TNM stage wise, in terms of survival, 1.3% in stage I, 2.2% in stage II, 0% in stage III, and 37.5% in stage IV died. The 20-year disease-free survival showed the following: stage I, 43%; stage II, 28%; stage III, 18%; and stage IV, 2%. There is significant difference in survival rate (P < 0.01). Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, ATA classification (hazards ratio, 2.1; 95% confidence interval, 1.64–2.67; P = 0.001) was better predictive of overall survival versus TNM classification (hazards ratio, 1.3; 95% confidence interval, 1.11–1.43; P = 0.063). Conclusions The ATA risk stratification and continuous reassessment during the first 2 years predicts disease-free survival better than the TNM staging. Age older than 45 years, unresectable disease, and elevated postthyroidectomy thyroglobulin levels dictate a poorer prognosis.
Complete regression of human B‐cell lymphoma xenografts in mice treated with recombinant anti‐CD22 immunotoxin RFB4(dsFv)‐PE38 at doses tolerated by cynomolgus monkeys

RFB4(dsFv)‐PE38 is a recombinant immunotoxin in which the variable light domain (VL) is disulfide bonded via cysteine residues to the variable heavy domain (VH), which in turn is fused to PE38, a mutant form of Pseudomonas exotoxin A. RFB4 binds to CD22, which is a differentiation antigen expressed on the majority of B‐cell leukemias and lymphomas. To examine the potential efficacy of RFB4(dsFv)‐PE38 when administered at a dose schedule appropriate for phase I testing, mice bearing CA46 human CD22+ Burkitt's lymphoma xenografts were treated on alternate days i.v. for 3 doses (QOD ×3). Complete regressions were observed in 80% and 100% of mice treated with 200 and 275 μg/kg QOD ×3, respectively. The higher dose was 27% of the LD50 and 34% of the LD10 in mice. Because RFB4(dsFv)‐PE38 is stable at 37°C, it could also be given by continuous infusion using pumps placed in the peritoneal cavity; complete regressions also resulted from this mode of administration. To study toxicology, a pilot toxicology study of RFB4(dsFv)‐PE38 was undertaken in cynomolgus monkeys, which like humans but unlike mice have CD22, which binds RFB4. Doses of 100 and 500 μg/kg i.v. QOD ×3 were well tolerated, indicating that a dose that cured tumors in mice was tolerated by primates. Based on these preclinical results, RFB4(dsFv)‐PE38 is being developed for the treatment of patients with CD22‐positive leukemias and lymphomas. Int. J. Cancer 81:148–155, 1999. © 1999 Wiley‐Liss, Inc.
Effect of chronic intermittent hypoxia on biological behavior and hypoxia‐associated gene expression in lung cancer cells

Hypoxia plays an important role in the development of solid tumors and is associated with their therapeutic resistance. There exist three major forms of hypoxia: acute, chronic, and intermittent hypoxia. Previous studies have shown that cancer cells could behave in the form of adaptation to hypoxia in tumor growth, which could result in their biological changes and determine their responses to the therapies. To investigate the tumor cells' adaptation to hypoxia, we recreated two models using two lung cancer cell lines in the presence of intermittent hypoxia, which is characterized by changes in oxygen pressure within the disorganized vascular network. We investigated biological behaviors such as cell cycle, proliferation, radiation sensitivity, apoptosis and migration, hypoxia signal pathway in the lung cancer cells treated with chronic intermittent hypoxia, as well as the role of hypoxia inducible factor 1 there, hypoxia‐inducible genes analyzed by real‐time RT‐PCR chip in H446 cells treated with the model. The results indicated the changes of some hypoxia target gene expressions of those induced by hypoxia, some of which were confirmed by real‐time RT‐PCR. The cells mediated by irradiation induced resistance to radiation and apoptosis and increased metastasis in lung cancer cells. It was found that such changes were related to hypoxia inducible factor 1, alpha subunit (HIF‐1α). J. Cell. Biochem. 111: 554–563, 2010. © 2010 Wiley‐Liss, Inc.
Convex optimization of MRI exposure for mitigation of RF-heating from active medical implants

Local RF-heating of elongated medical implants during magnetic resonance imaging (MRI) may pose a significant health risk to patients. The actual patient risk depends on various parameters including RF magnetic field strength and frequency, MR coil design, patient’s anatomy, posture, and imaging position, implant location, RF coupling efficiency of the implant, and the bio-physiological responses associated with the induced local heating. We present three constrained convex optimization strategies that incorporate the implant’s RF-heating characteristics, for the reduction of local heating of medical implants during MRI. The study emphasizes the complementary performances of the different formulations. The analysis demonstrates that RF-induced heating of elongated metallic medical implants can be carefully controlled and balanced against MRI quality. A reduction of heating of up to 25 dB can be achieved at the cost of reduced uniformity in the magnitude of the B1+ ? > field of less than 5%. The current formulations incorporate a priori knowledge of clinically-specific parameters, which is assumed to be available. Before these techniques can be applied practically in the broader clinical context, further investigations are needed to determine whether reduced access to a priori knowledge regarding, e.g. the patient’s anatomy, implant routing, RF-transmitter, and RF-implant coupling, can be accepted within reasonable levels of uncertainty.
Globalised disease control and response distortion: a case study of avian influenza pandemic preparedness in Zambia

The past decade and a half has witnessed an increased and justified interest in global pandemic preparedness, owing to the unprecedented global spread of infectious disease threats, such as Severe Acute Respiratory Syndrome (SARS), H5N1 avian influenza and H1N1 Influenza. The repercussions of human and animal mortalities, and economic losses, have justified the need for globalised disease control responses through global pandemic preparedness. However, the blurring of the distinction between national and global preparedness has implications for the appropriateness of local disease control responses, particularly for poor resource countries reliant on donor aid to support their own preparedness. Examining the case of avian and pandemic preparedness in Zambia, this article explains how international funding led to a distortion of the pandemic response in this developing country. Despite the gains made under the global call for pandemic preparedness, the resulting avian and pandemic influenza response was inappropriate when weighed against Zambia's risk of an H5N1 incursion and the country's wider trade, agricultural and health priorities. We conclude that pandemic preparedness policy processes should take into consideration both the local policy context and realistic risk assessments of the local likelihood and potential impact of disease to ensure both the appropriateness and the sustainability of disease control measures instituted.
Proteasome inhibition causes epithelial–mesenchymal transition upon TM4SF5 expression

Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocarcinoma and causes epithelial–mesenchymal transition (EMT) of hepatocytes. We found that TM4SF5‐expressing cells showed lower mRNA levels but maintained normal protein levels in certain gene cases, indicating that TM4SF5 mediates stabilization of proteins. In this study, we explored whether regulation of proteasome activity and TM4SF5 expression led to EMT. We observed that TM4SF5 expression caused inhibition of proteasome activity and proteasome subunit expression, causing morphological changes and loss of cell–cell contacts. shRNA against TM4SF5 recovered proteasome expression, with leading to blockade of proteasome inactivation and EMT. Altogether, TM4SF5 expression appeared to cause loss of cell–cell adhesions via proteasome suppression and thereby proteasome inhibition, leading to repression of cell–cell adhesion molecules, such as E‐cadherin. J. Cell. Biochem. 112: 782–792, 2011. © 2010 Wiley‐Liss, Inc.
Health disparities of adults with intellectual disabilities: what do we know? What do we do?

BACKGROUND Recent attention to health of people with intellectual disabilities has used a health disparities framework. Building on historical context, the paper summarizes what is known about health disparities from reports and research and provide direction on what to do to reduce these disparities among adults with intellectual disabilities. METHODS The present authors examined literature from 2002 to 2011 on health disparities and people with disabilities looking for broad themes on documenting disparities and on research approaches and methods. RESULTS Multiple countries published reports on health of people with intellectual disabilities. Researchers summarized existing research within a health disparities framework. A number of promising methodologies are identified such as health services research, health indicators, enhanced surveillance and mixed-methods. CONCLUSIONS Strategies to reduce health disparities include use of data to educate decision makers, attention to social determinants and a life-course model and emphasis on leveraging inclusion in mainstream services where possible.
Collaborative regression-based anatomical landmark detection

Anatomical landmark detection plays an important role in medical image analysis, e.g. for registration, segmentation and quantitative analysis. Among the various existing methods for landmark detection, regression-based methods have recently attracted much attention due to their robustness and efficiency. In these methods, landmarks are localised through voting from all image voxels, which is completely different from the classification-based methods that use voxel-wise classification to detect landmarks. Despite their robustness, the accuracy of regression-based landmark detection methods is often limited due to (1) the inclusion of uninformative image voxels in the voting procedure, and (2) the lack of effective ways to incorporate inter-landmark spatial dependency into the detection step. In this paper, we propose a collaborative landmark detection framework to address these limitations. The concept of collaboration is reflected in two aspects. (1) Multi-resolution collaboration. A multi-resolution strategy is proposed to hierarchically localise landmarks by gradually excluding uninformative votes from faraway voxels. Moreover, for informative voxels near the landmark, a spherical sampling strategy is also designed at the training stage to improve their prediction accuracy. (2) Inter-landmark collaboration. A confidence-based landmark detection strategy is proposed to improve the detection accuracy of ‘difficult-to-detect’ landmarks by using spatial guidance from ‘easy-to-detect’ landmarks. To evaluate our method, we conducted experiments extensively on three datasets for detecting prostate landmarks and head & neck landmarks in computed tomography images, and also dental landmarks in cone beam computed tomography images. The results show the effectiveness of our collaborative landmark detection framework in improving landmark detection accuracy, compared to other state-of-the-art methods.
Establishing core mental health workforce attributes for the effective mental health care of people with an intellectual disability and co‐occurring mental ill health

BACKGROUND People with intellectual disability experience high rates of mental ill health but multiple barriers to access to quality mental health care. One significant barrier to access is a generalist mental health workforce that lacks capacity, and consensus on what constitutes core workforce competencies in this area. As such, the first step in developing a comprehensive strategy that addresses these barriers is to define the core mental health workforce attributes. METHODS Thirty-six intellectual disability mental health experts from across Australia participated in a modified online Delphi which aimed to reach consensus on the core attributes required of the generalist mental health workforce. At the end of each Delphi round, descriptive analyses and thematic analyses were completed. RESULTS Consensus was reached among the participants for 102 attributes across 14 clinical domains. The results highlighted specific attributes in all areas of clinical practice, especially for communication (e.g., utilizes assistive communication technology), assessment (e.g., assess contributing factors to behaviours) and intervention (e.g., uses integrative interventions). CONCLUSION A comprehensive strategy is required to facilitate the generalist mental health workforce to obtain these attributes.
Abstract A41: Cancer cells invade or divide, not both

Invasive cancer cells are a critical target for chemotherapy. However most chemotherapeutic agents in clinical use target dividing cancer cells. Cancer cell-cycle kinetics were visualized in Gelfoam histoculture using a fluorescence ubiquitination cell cycle indicator (FUCCI), whereby quiescent cancer cells express mKusabira-Orange fluorescent protein (red) and proliferating cells express mAzami-Green fluorescent protein (green). Real-time imaging demonstrated that cancer cells in G/G1 phase are invasive and disseminate in Gelfoam histoculture. In vivo, FUCCI-expressing cancer cells were in G/G1 phase when they metastasized to the liver. Disseminated cancer cells in the peritoneal cavity were also in G/G1 phase. Most drugs currently in use target cells in S/G 2/M, which may not be capable of invasion. Color-coded cell-cycle imaging in Gelfoam histoculture should provide a novel platform for the rapid screening of candidate therapeutic agents against quiescent invasive cancer cells. Citation Format: Shuya Yano, Sumiyuki Mii, Yasunori Tome, Yukihiko Hiroshima, Fuminari Uehara, Shinji Miwa, Robert M. Hoffman. Cancer cells invade or divide, not both. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A41.
Artifact free reconstruction with the system matrix approach by overscanning the field-free-point trajectory in magnetic particle imaging

Magnetic particle imaging is a tracer-based imaging method that utilizes the non-linear magnetization response of iron-oxide for determining their spatial distribution. The method is based on a sampling scheme where a sensitive spot is moved along a trajectory that captured a predefined field-of-view (FOV). However, particles outside the FOV also contribute to the measurement signal due to their rotation and the non-sharpness of the sensitive spot. In the present work we investigate artifacts that are induced by particles not covered by the FOV and show that the artifacts can be mitigated by using a system matrix that covers not only the region of interest but also a certain area around the FOV. The findings are especially relevant when using a multi-patch acquisition scheme where the boundaries of neighboring patches have to be handled.
A variation-based ring artifact correction method with sparse constraint for flat-detector CT

The reconstructed slice quality of flat-detector computed tomography (CT) is often disturbed by concentric-ring artifacts. Since concentric rings in CT slices appear as straight stripes when transformed into polar coordinates, a variation-based model is proposed to suppress the stripes. The method is motivated by two observations about stripes in polar coordinates: (1) ring artifacts attenuate gradually along the radial direction, leading to a sparse distribution of stripes and (2) stripes greatly distort the image gradient across the stripes, while slightly affecting the image gradient along the stripes. Thus, a ℓ1 ? >-norm-based data fidelity term and a ℓ0 ? >-norm/ℓ1 ? >-norm unidirectional variation-based regularization term are presented to characterize the stripes. The alternating direction method of multipliers is introduced to solve the resulting minimization problem. Moreover, we discuss the interpolation methods used in coordinate transformation and find that the nearest neighbor interpolation is optimal. Experimental results on simulated and real data demonstrate that our method can correct ring artifacts effectively compared with state-of-the-art coordinate transformation-based methods, as well as preserve the structures and details of slices.
A2a adenosine receptor mediates HepG2 cell apoptosis by downregulating Bcl‐XL expression and upregulating bid expression

Extracellular adenosine induced apoptosis in HepG2 cells, a human hepatoma cell line, by tuning apoptosis‐mediator gene transcription. The present study aimed at identifying the responsible adenosine receptor and clarifying the signaling pathway underlying adenosine‐induced HepG2 cell apoptosis. Adenosine and CGS21680, an A2a adenosine receptor agonist, induced HepG2 cell apoptosis, and the effect was inhibited by DMPX, an A2a adenosine receptor antagonist, or by knocking‐down A2a adenosine receptors. Adenosine reduced expression of Bcl‐XL mRNA and protein but otherwise increased expression of the Bid mRNA and protein in HepG2 cells, and those effects were also prevented by knocking‐down A2a adenosine receptors. Adenosine caused disruption of mitochondrial membrane potentials and stimulated cytochrome c efflux from the mitochondria in HepG2 cells. Adenosine activated caspases‐3 and ‐9 in HepG2 cells, which was significantly inhibited by knocking‐down A2a adenosine receptors. The results of the present study indicate that extracellular adenosine downregulates Bcl‐XL expression and upregulates Bid expression, thereby disrupting mitochondrial membrane potentials to allow cytochrome c efflux from the mitochondria, and then causing activation of caspase‐9 and the effector caspase‐3, as mediated via A2a adenosine receptors. J. Cell. Biochem. 113: 1766–1775, 2012. © 2011 Wiley Periodicals, Inc.
Self-calibration of cone-beam CT geometry using 3D–2D image registration

Robotic C-arms are capable of complex orbits that can increase field of view, reduce artifacts, improve image quality, and/or reduce dose; however, it can be challenging to obtain accurate, reproducible geometric calibration required for image reconstruction for such complex orbits. This work presents a method for geometric calibration for an arbitrary source-detector orbit by registering 2D projection data to a previously acquired 3D image. It also yields a method by which calibration of simple circular orbits can be improved. The registration uses a normalized gradient information similarity metric and the covariance matrix adaptation-evolution strategy optimizer for robustness against local minima and changes in image content. The resulting transformation provides a ‘self-calibration’ of system geometry. The algorithm was tested in phantom studies using both a cone-beam CT (CBCT) test-bench and a robotic C-arm (Artis Zeego, Siemens Healthcare) for circular and non-circular orbits. Self-calibration performance was evaluated in terms of the full-width at half-maximum (FWHM) of the point spread function in CBCT reconstructions, the reprojection error (RPE) of steel ball bearings placed on each phantom, and the overall quality and presence of artifacts in CBCT images. In all cases, self-calibration improved the FWHM—e.g. on the CBCT bench, FWHM = 0.86 mm for conventional calibration compared to 0.65 mm for self-calibration (p < 0.001). Similar improvements were measured in RPE—e.g. on the robotic C-arm, RPE = 0.73 mm for conventional calibration compared to 0.55 mm for self-calibration (p < 0.001). Visible improvement was evident in CBCT reconstructions using self-calibration, particularly about high-contrast, high-frequency objects (e.g. temporal bone air cells and a surgical needle). The results indicate that self-calibration can improve even upon systems with presumably accurate geometric calibration and is applicable to situations where conventional calibration is not feasible, such as complex non-circular CBCT orbits and systems with irreproducible source-detector trajectory.