Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of thyroid dysfunction in patients with solid tumors treated with VEGF receptor tyrosine kinase inhibitors: a critical literature review and meta analysis

We performed a systematic review and meta-analysis of thyroid function abnormalities associated with seven vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitors (sorafenib, sunitinib, axitinib, cediranib, pazopanib, regorafenib and vandetanib). Eligible studies included randomized Phase II and III trials of patients with solid tumors on sorafenib OR sunitinib OR axitinib OR cediranib OR pazopanib OR regorafenib OR vandetanib; describing events of hypothyroidism or hyperthyroidism. Our search strategy yielded 195 potentially relevant citations on the seven agents from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible studies, a total of 12 clinical trials were considered eligible for the meta-analysis, including six sunitinib studies, four cediranib studies and two axitinib studies. Patients treated with these agents had a significantly increased risk of all-grade hypothyroidism and the relative risk (RR) of all-grade hypothyroidism was 3.59 (95% CI = 2.40–5.38, p ≤ 0.0001). Exploratory subgroup analysis showed no effect of tumor types or agent used on the RR of hypothyroidism. Our meta-analysis has demonstrated that these three agents are associated with a significantly increased risk of all-grade hypothyroidism; with no difference – on subgroup analysis – between sunitinib and cediranib. Clinicians should be aware of these risks and perform regular thyroid function monitoring.
Changes in daily mood and self-restraint among undercontrolled preadolescents: a time-series analysis of "acting out".

OBJECTIVE Acting out among boys with disruptive behavior disorders was investigated by evaluating how changes in their daily moods predicted changes in their behavior. METHOD During a 6-week period, 20 preadolescent boys enrolled in day treatment programs rated their mood upon arrival at school, and teachers rated their behavior at the end of the day. Time-series and path-analytic methodologies were used to analyze the data. RESULTS The boys did engage in emotional acting out, in that their morning moods predicted their subsequent disruptive behavior, controlling for both individual differences and their behavior the previous day. Boys' mood changes served as a mediator between the intensity of interpersonal conflicts in their lives (with peers and among significant adults) and decrements in their self-restraint. Acting-out behavior was associated with defensive processes, in that boys who reported low subjective distress and whom the teachers rated as high in denial of distress had the strongest links between their moods and behavior. Individual differences in levels of conduct problems, but not hyperactivity, also predicted acting out. CONCLUSION Emotional processes and defensive acting out may often be integral aspects of conduct-disordered behavior.
Uneven Development and Circular Causation

This paper discusses the uneven development and detects the circular causation that occurs in the Kalibata area. Uneven development occurs between the street vendor trade area and Kalibata City trade area. The research method we use are: 1) literature study as a theoretical basis to understand the uneven development theory and the occurrence of circular causation; 2) data collection by conducting interviews, observation, and direct mapping; 3) information processing where we used the data obtained to compare the differences in production processes between two regions. Kalibata City (formal area) and street vendor trade area (informal area) have different potential that generates the difference in the production process. This article found that: 1) street vendor’s consumer facilities is simpler than Kalibata City; 2) street vendor area doesn’t have a legal permit, thus making them susceptible to eviction, 3) street vendor is limited to the area beside the railway, 4) the tools used by the street vendors are less sophisticated than Kalibata City, and; 5) the street vendors have limited skills than the workers in Kalibata City. We also found there are three types of production of street vendors: low, mid, high complexity. Meanwhile, the production process in Kalibata City is ran in a more structured and organized way. These differences trigger the developmental differences between these regions. Circular causation makes it worse. Kalibata City will continue to be able to develop its area, while PKL will be difficult to develop because of its limitations.
The effect of hyperpolarization‐activated cyclic nucleotide‐gated ion channel inhibitors on the vagal control of guinea pig airway smooth muscle tone

Subtypes of the hyperpolarization‐activated cyclic nucleotide‐gated (HCN) family of cation channels are widely expressed on nerves and smooth muscle cells in many organ systems, where they serve to regulate membrane excitability. Here we have assessed whether HCN channel inhibitors alter the function of airway smooth muscle or the neurons that regulate airway smooth muscle tone.
Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study.

OBJECTIVE Few population-based studies have described the epidemiology of subtypes of hyperthyroidism. DESIGN A prospective population-based study, monitoring two well-defined Danish cohorts in Aalborg with moderate iodine deficiency (n=311 102) and Copenhagen with only mild iodine deficiency (n=227 632). METHODS A laboratory monitoring system identified subjects with thyroid function tests suggesting overt hyperthyroidism (low s-TSH combined with high s-thyroxine or s-triiodothyronine). For all subjects, we collected information on medical history, thyroid scintigraphy and thyroid hormone receptor antibody (TRAb) measurement. Information was used to disprove or verify primary overt hyperthyroidism and to subclassify hyperthyroidism into nosological disorders. RESULTS From 1997 to 2000 (2 027 208 person-years of observation), we verified 1682 new cases of overt hyperthyroidism. The overall standardized incidence rate (SIR) per 100 000 person-years was 81.6, and was higher in Aalborg compared with Copenhagen (96.7 vs 60.0, P<0.001), giving an SIR ratio (SIRR (95% confidence interval (CI))) between moderate versus mild iodine-deficient areas of 1.6 (1.4-1.8). Nosological types of hyperthyroidism (percentage/SIRR (95% CI)): multinodular toxic goitre (MNTG) 44.1%/1.9 (1.6-2.2), Graves' disease (GD) 37.6%/1.2 (0.99-1.4), solitary toxic adenoma (STA) 5.7%/2.4 (1.3-3.5), 'mixed type' hyperthyroidism (TRAb-positive, scintigraphicly multinodular) 5.4%/6.0 (3.0-12), subacute thyroiditis 2.3%/0.9 (0.4-1.4), postpartum thyroid dysfunction 2.2%/1.6 (0.8-3.0), amiodarone-associated hyperthyroidism 0.8%/7.1 (1.1-65), hyperthyroidism after thyroid radiation 0.7%/12.3 (0.8-50), lithium-associated hyperthyroidism 0.7%/0.97 (0.4-4.8) and hyperthyroidism caused by various other factors 0.7%. Lifetime risk for overt hyperthyroidism was 10.5%/6.5%/2.4% (females/all/males). CONCLUSION Hyperthyroidism was common in Denmark with MNTG and GD as dominating entities. The higher incidence of hyperthyroidism in the most iodine-deficient region was caused by higher frequency of MNTG, 'mixed-type', STA and amiodarone-associated hyperthyroidism.
Factors affecting capital structure choice: New evidence from Turkish non-financial listed companies

Purpose - Factors affecting capital structure choices of Turkish non-financial listed companies are tested in this study. We investigate the relation between firm leverage and firm level variables, expected inflation and GDP growth rates. Methodology - We used annual data of exchange listed non-financial corporations in addition to expected inflation and GDP growth rates. We applied panel regression models to our panel data set of 292 firms. Findings - We found four factors, i.e. profitability, growth (MVA/BVA), tangibility and industry median leverage are effective in explaining capital structures of Turkish listed firms. While profitability and growth have signs in line with the prediction of the pecking order theory, signs of tangibility and industry median leverage favor the trade off theory. We also divided our sample into clusters based on firm size and 2000 – 2001 financial crisis and repeated the analysis. Conclusion- Results of this analysis suggest that trade off theory explains better the financing behavior of large-sized firms. Pecking order theory seems to better account for financing behaviors of Turkish firms before 2002; and trade off theory seems to explain better their capital structure choices after the 2000 – 2001 financial crisis.
The Legislative Consequences of Congressional Scandals

We explore the consequences of involvement in scandal for members of Congress’ (MCs) success within the House of Representatives. Our analyses target all MCs who served in the 101st to 112th Congresses (1989–2012). Across this time period, we identify 253 discrete member-term observations of professional or personal scandal. Our results demonstrate that scandal stalls the upward trajectory of MCs’ careers in the chamber, affecting their levels of legislative effectiveness, their centrality to the congressional network, and their likelihood of gaining or losing prestigious committee assignments and leadership positions. Importantly, these effects can linger beyond the term following scandal, shaping MCs’ behavior into the future. Our findings demonstrate that in addition to negative electoral repercussions, scandals can have important legislative consequences for members.
Shockwaves Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells Through ATP Release and Activation of P2X7 Receptors

Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5′‐triphosphate (ATP) release‐induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow‐derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c‐fos and c‐jun mRNA was determined with real‐time reverse transcription polymerase chain reaction and Western blotting. P2X7‐siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave‐induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (∼7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c‐fos and c‐jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7‐siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation. STEM Cells 2013;31:1170–1180
QoE-oriented cross-layer downlink scheduling for heterogeneous traffics in LTE networks

With the soaring demands for high speed data communication, as well as transmission of various types of services with different requirements over cellular networks, having a decent radio resource management is considered vital in Long Term Evolution (LTE) system. In particular, satisfying the Quality of Service (QoS) requirements of different applications is one of the key challenges of radio resource management that needs to be dealt by the LTE system. In this paper, we propose a cross-layer design scheme that jointly optimizes three different layers of wireless protocol stack, namely application, Medium Access Control (MAC), and physical layer. The cross-layer optimization framework provides efficient allocation of wireless resources across different types of applications (i.e., real-time and non real-time) run by different users to maximize network resource utilization and user-perceived quality of service, or also known as Quality of Experience (QoE). Here, Mean Opinion Score (MOS) is used as a unified QoE metric that indicates the user-perceived quality for real-time or multimedia services notably video applications. Along with multimedia services, the proposed framework also takes care of non-real-time traffic by ensuring certain level of fairness. Our simulation, applied to scenarios where users simultaneously run different types of applications, confirms that the proposed QoE-oriented cross-layer framework leads to significant improvement in terms of maximizing user-perceived quality as well as maintaining fairness among users.
Human Gut‐Specific Homeostatic Dendritic Cells Are Generated from Blood Precursors by the Gut Microenvironment

Background: Dendritic cells (DC) dictate not only the type of T‐cell immunity, but also homing patterns of T cells in mice. In humans, we characterized normal human gut DC and tested whether gut‐specific homeostatic DC could be generated from blood precursors by factors in the gut microenvironment. Methods: We characterized the phenotype and function of healthy human gut DC compared with blood and skin DC, and studied whether conditioning of blood DC in the presence of colonic biopsy supernatants (Bx‐SN) induced gut‐like phenotype and functions. Results: Blood DC mostly expressed both gut and skin homing markers, indicating potential to migrate to both major immune surface organs, and induced multi‐homing T cells. However, DC within gut or skin did not demonstrate this multi‐homing phenotype, were tissue‐specific, and induced tissue‐specific T cells. Human gut DC were less stimulatory for allogeneic T cells than their dermal and blood counterparts. Human blood DC cultured in vitro lost homing marker expression. Conditioning of human enriched blood DC with colonic Bx‐SN from healthy controls induced a gut‐homing phenotype and a homeostatic profile. Moreover, Bx‐SN‐conditioned DC demonstrated a restricted T‐cell stimulatory capacity and preferentially induced gut‐specific T cells. Retinoic acid and transforming growth factor beta (TGF‐&bgr;) mediated the acquisition of the gut‐homing and homeostatic properties, respectively, induced by colonic Bx‐SN on blood enriched DC. Conclusions: Tissue‐specific factors manipulate immunity via modulating characteristics of DC and may provide tools to generate tissue‐specific immunotherapy. (Inflamm Bowel Dis 2011;)
Statistical confidence for likelihood‐based paternity inference in natural populations

Paternity inference using highly polymorphic codominant markers is becoming common in the study of natural populations. However, multiple males are often found to be genetically compatible with each offspring tested, even when the probability of excluding an unrelated male is high. While various methods exist for evaluating the likelihood of paternity of each nonexcluded male, interpreting these likelihoods has hitherto been difficult, and no method takes account of the incomplete sampling and error‐prone genetic data typical of large‐scale studies of natural systems. We derive likelihood ratios for paternity inference with codominant markers taking account of typing error, and define a statistic Δ for resolving paternity. Using allele frequencies from the study population in question, a simulation program generates criteria for Δ that permit assignment of paternity to the most likely male with a known level of statistical confidence. The simulation takes account of the number of candidate males, the proportion of males that are sampled and gaps and errors in genetic data. We explore the potentially confounding effect of relatives and show that the method is robust to their presence under commonly encountered conditions. The method is demonstrated using genetic data from the intensively studied red deer (Cervus elaphus) population on the island of Rum, Scotland. The Windows‐based computer program, CERVUS , described in this study is available from the authors. CERVUS can be used to calculate allele frequencies, run simulations and perform parentage analysis using data from all types of codominant markers.
Breaking bad news to cancer patients in palliative care: A comparison of national cross-sectional surveys from 2006 and 2012

Abstract Objective: Most cancer patients experience the time when a doctor must “break the bad news” to them, a time when it is necessary for patients to call upon their self-determination to aid in the battle with cancer. The purpose of our study was to clarify the percentage of times doctors deliver bad news to patients at the end of life in each of four different situations, and to define the most common recipients of this bad news. We compare these results for two timepoints: 2006 and 2012. Methods: The study had a national cross-sectional design consisting of self-completed questionnaires sent to all hospitals that provide cancer care. We mailed them to hospital directors in January and February of 2012, requesting a reply. The results of the same survey in 2006 were employed as a point for comparison. Results: A total of 1224 questionnaires were returned during 2012. 1499 responses collected in 2006 were employed as reference data. Some hospital characteristics had changed over that interval; however, the new data obtained were representative for patients being treated in Japanese cancer care hospitals. In hospitals with 300–499, there were significant differences between 2006 and 2012 in the providing information about (“disclosure of cancer diagnosis,” “therapeutic options for treatment,” and “a life-prolonging treatment”). In addition, the likelihood of doctors delivering bad news to patients and family members (as opposed to family members only) at the end of life increased from 2006 to 2012. Significance of Results: Our results suggest that the overall incidence of bad news being disclosed has increased, especially in hub medical institutions for cancer care. Advanced treatment options or domestic legislation may have influenced the frequency or type of bad news.
Development of a patient-specific anatomical foot model from structured light scan data

The use of anatomically accurate finite element (FE) models of the human foot in research studies has increased rapidly in recent years. Uses for FE foot models include advancing knowledge of orthotic design, shoe design, ankle–foot orthoses, pathomechanics, locomotion, plantar pressure, tissue mechanics, plantar fasciitis, joint stress and surgical interventions. Similar applications but for clinical use on a per-patient basis would also be on the rise if it were not for the high costs associated with developing patient-specific anatomical foot models. High costs arise primarily from the expense and challenges of acquiring anatomical data via magnetic resonance imaging (MRI) or computed tomography (CT) and reconstructing the three-dimensional models. The proposed solution morphs detailed anatomy from skin surface geometry and anatomical landmarks of a generic foot model (developed from CT or MRI) to surface geometry and anatomical landmarks acquired from an inexpensive structured light scan of a foot. The method yields a patient-specific anatomical foot model at a fraction of the cost of standard methods. Average error for bone surfaces was 2.53 mm for the six experiments completed. Highest accuracy occurred in the mid-foot and lowest in the forefoot due to the small, irregular bones of the toes. The method must be validated in the intended application to determine if the resulting errors are acceptable.
Orientation of the Foramen Ovale: An Anatomic Study With Neurosurgical Considerations

AbstractUnsuccessful cannulation of the foramen ovale (FO) continues to occur with both fluoroscopic technique and technique using computed tomography paired with navigational technology. Despite advances in stereotactic neurosurgical imaging and technique, anatomic variation of the FO occasionally prevents successful cannulation. Morphometric study of the FO has been limited to length, width, and area parameters; therefore, this report analyzed the orientation of the FO. A total of 139 crania (235 foramina ovalae) were photographed and assessed digitally by ImageJ software (NIH). Foramina were fit with a best fit ellipse. For orientation, the midsagittal plane was located by bisecting the basilar process of the occiput; the coronal plane was identified as perpendicular to the midsagittal plane. The angles between the major axis of the best fit ellipse of the FO and the midsagittal and coronal planes were measured. The angle formed between the major axis of the best fit ellipse of the FO and the coronal plane averaged 35.43° ± 9.74° (mean ± SD) on the left and 36.47° ± 7.60° on the right. The angle formed between the major axis of the best fit ellipse of the FO and the sagittal plane averaged 54.57° ± 9.74° on the left and 53.53° ± 7.60° on the right. No significant difference was found between FO orientation among the sexes. Understanding the orientation of the FO may aid in stereotactic neurosurgical planning and successful cannulation of the FO.
Photo-Induced Precession of Magnetization in (Ga,Mn)As Microbars

Photo-induced precession of magnetization in (Ga,Mn) As microbars has been studied experimentally. It has been found that effective magnetic fields decrease to great extent in the microbars. The damping appears not to be affected severely, at least within the limit of microbars of micrometer size. Our findings indicate that magnetization dynamics can be controlled to some extent by patterning strained epilayers into microstructures.
Clinical relevance of minimal residual disease detection in adult acute myeloid leukemia.

We have used flow cytometry to quantify minimal residual disease (MRD) in 63 patients with acute myeloid leukemia (AML). No significant correlation was found between the level of MRD after induction and disease outcome. After consolidation, a threshold of 3.5 x 10(-4) residual leukemic cells divided the 57 evaluable patients into two distinct groups: the MRDCons(+) and the MRDCons(-) group, with a relapse rate of 81% (22/27) and 27% (8/30), respectively (p = 0.000035). Although not correlated with prognosis, the level of MRD after induction course affected the degree of cytoreduction achieved with consolidation. In fact, the patients who entered a MRDCons(-) status had a median number of leukemic residual cells of 1.8 x 10(-4) after induction; at the same stage, the bone marrow of patients who were in a MRDCons(+) condition harbored a median level of 1.7 x 10(-3) malignant residual cells (p = 0.00073). The MRDCons(+) status also correlated significantly with poor/intermediate risk cytogenetics, MDR1 phenotype, short duration of overall survival, and relapse-free survival (p = 0.024, 0.021, 0.00001, and 0.00001, respectively). In multivariate analysis, the MRDCons(+) status was associated with a high probability of relapse (p < 0.00026) and short duration of relapse free survival (p = 0.008). Stem cell transplantation did not seem to alter the prognostic impact of high levels of MRD after consolidation: within the MRDCons(+) group, the relapse rate after transplant was 78%. Thus, a MRD > or = 3.5 x 10(-4) leukemic cells at the end of consolidation strongly predicts relapse, and is significantly associated with MDR1-positive phenotype and intermediate/unfavorable cytogenetics.