Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Prognostic for Survival in Patients with Malignant Melanoma Spread to the Regional Lymph Nodes

To establish clinical and histologic determinants of survival, records of all UCLA patients with resectable melanoma metastatic to the lymph nodes during the years 1954–1976 were reviewed. These 150 patients were treated first with wide excision, lymphadenectomy, and with radiation/chemotherapy and/or additional surgery only if further recurrences developed. None received adjuvant immunotherapy or chemotherapy. In 97 of 139 patients with identified primary tumors, slides of the primary lesion were reviewed. Putative prognostic factors included age, sex, parity, site of primary tumor, presence of satellitosis, clinical status of nodes, histologic characteristics of primary lesion (Clark's level, thickness of tumor, presence/width of ulceration, and number of mitoses/HPF), time from biopsy of primary tumor to lymphadenectomy, and number of positive nodes. Kaplan-Meier estimates of survival for the entire group at one, two, five, and ten years were 73, 55, 37, and 33%, respectively. Median follow-up period of survivors was four years. Univariate analyses using the log-rank test showed that thickness of the primary lesion (p < 0.001), width of ulceration (p = 0.003), absence of ulceration (p = 0.024), and number of positive nodes (p = 0.033) were prognostic for survival. In multivariate analysis by the Cox procedure, thickness of the primary (p = 0.001) and number of melanoma-containing nodes (p = 0.043) were prognostic for survival. Location of the primary tumor became marginally significant (p = 0.12) in the multivariate model. These findings demonstrate the prognostic importance of characteristics of both the primary lesion and extent of regional dissemination. Future prospective randomized trials for (adjuvant) therapy of Stage II melanoma should be stratified by these variables.
Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson’s disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.
A Review on Sensor Network Issues and Robotics

The interaction of distributed robotics and wireless sensor networks has led to the creation of mobile sensor networks. There has been an increasing interest in building mobile sensor networks and they are the favored class of WSNs in which mobility plays a key role in the execution of an application. More and more researches focus on development of mobile wireless sensor networks (MWSNs) due to its favorable advantages and applications. In WSNs robotics can play a crucial role, and integrating static nodes with mobile robots enhances the capabilities of both types of devices and enables new applications. In this paper we present an overview on mobile sensor networks in robotics and vice versa and robotic sensor network applications.
Overall Graft Loss Versus Death-Censored Graft Loss: Unmasking the Magnitude of Racial Disparities in Outcomes Among US Kidney Transplant Recipients

BackgroundBlack kidney transplant recipients experience disproportionately high rates of graft loss. This disparity has persisted for 40 years, and improvements may be impeded based on the current public reporting of overall graft loss by US regulatory organizations for transplantation. MethodsLongitudinal cohort study of kidney transplant recipients using a data set created by linking Veterans Affairs and US Renal Data System information, including 4918 veterans transplanted between January 2001 and December 2007, with follow-up through December 2010. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). ResultsThree thousand three hundred six non-Hispanic whites (67%) were compared with 1612 non-Hispanic black (33%) recipients with 6.0 ± 2.2 years of follow-up. In the unadjusted analysis, black recipients were significantly more likely to have overall graft loss (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 1.07-1.33), death-censored graft loss (HR, 1.67; 95% CI, 1.45-1.92), and lower mortality (HR, 0.83; 95% CI, 0.72-0.96). In fully adjusted models, only death-censored graft loss remained significant (HR, 1.38; 95% CI, 1.12-1.71; overall graft loss [HR, 1.08; 95% CI, 0.91-1.28]; mortality [HR, 0.84; 95% CI, 0.67-1.06]). A composite definition of graft loss reduced the magnitude of disparities in blacks by 22%. ConclusionsNon-Hispanic black kidney transplant recipients experience a substantial disparity in graft loss, but not mortality. This study of US data provides evidence to suggest that researchers should focus on using death-censored graft loss as the primary outcome of interest to facilitate a better understanding of racial disparities in kidney transplantation.
Genomic Epidemiology of a Dengue Virus Epidemic in Urban Singapore

ABSTRACT Dengue is one of the most important emerging diseases of humans, with no preventative vaccines or antiviral cures available at present. Although one-third of the world's population live at risk of infection, little is known about the pattern and dynamics of dengue virus (DENV) within outbreak situations. By exploiting genomic data from an intensively studied major outbreak, we are able to describe the molecular epidemiology of DENV at a uniquely fine-scaled temporal and spatial resolution. Two DENV serotypes (DENV-1 and DENV-3), and multiple component genotypes, spread concurrently and with similar epidemiological and evolutionary profiles during the initial outbreak phase of a major dengue epidemic that took place in Singapore during 2005. Although DENV-1 and DENV-3 differed in viremia and clinical outcome, there was no evidence for adaptive evolution before, during, or after the outbreak, indicating that ecological or immunological rather than virological factors were the key determinants of epidemic dynamics.
Teratogenic effects of lead acetate on kidney.

BACKGROUND Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both men and women. Conflicting reports have appeared on lead induced nephrotoxicity in experimental studies in the past. There is hardly any work on its teratogenic effects on kidney. Present study was therefore designed to investigate the effects of lead acetate on developing kidney. METHODS Twelve mice were used as experimental model and were divided into two groups of six animals each; group A served as control group and B was used as an experimental group. Lead acetate (10 mg/kg) dissolved in 0.02 ml of distilled water was administered as a single daily dose orally to group B whereas weight related amount of distilled water was given to group A for the entire period of experiment. On 18th day of gestation foetuses were dissected free of uterine wall under the dissecting microscope and were sacrificed; kidneys were removed and fixed in 10% formalin, dehydrated in ascending grades of alcohol, cleared in xylene and infiltrated with filtered paraffin. The paraffin blocks were made and five micron thin sections were obtained using a rotary microtome. The sections were stained with Hematoxylin and eosin and, PAS; these were examined under light microscope. RESULTS Significant decrease in cortical thickness was observed which varied from 578.61 +/- 1.4 microm in group A to 515.6 +/- 5 microm in group B (p < 0.001). Diameter of renal corpuscles varied from 57.7 +/- 0.07 microm in group A to 50.5 +/- 0.07 microm in group B (p < 0.001). Moderate cortical tubular atrophy showing thickening of endothelial basement membrane in glomeruli, desquamated epithelium with degenerated nuclei in proximal and distal tubules were observed in group B in contrast to group A. CONCLUSION The results of the investigation indicated that lead acetate administration to the dams produced deleterious effects on the developing kidney in mice.
CXCL12/CXCR4 Protein Signaling Axis Induces Sonic Hedgehog Expression in Pancreatic Cancer Cells via Extracellular Regulated Kinase- and Akt Kinase-mediated Activation of Nuclear Factor κB

Background: CXCL12/CXCR4 and hedgehog pathways, predominantly acting in paracrine fashion, play important roles in pancreatic cancer pathobiology. Results: CXCL12/CXCR4 signaling regulates the expression of hedgehog ligand, the sonic hedgehog, in pancreatic cancer cells. Conclusion: Our findings indicate a novel molecular link between CXCL12/CXCR4 and hedgehog pathways. Significance: Our data provide a molecular basis for an active bidirectional tumor-stromal interaction in pancreatic cancer. Recent evidence suggests a major role of tumor-stromal interactions in pancreatic cancer pathobiology. The chemokine CXCL12 (stromal cell-derived factor 1 (SDF-1)), abundantly produced by stromal cells, promotes progression, metastasis, and chemoresistance of pancreatic cancer cells. On the other hand, pancreatic tumor cell-derived sonic hedgehog (SHH) acts predominantly on stromal cells to induce desmoplasia and, thus, has a paracrine effect on tumorigenesis and therapeutic outcome. In this study, we examined the association between these two proteins of pathological significance in pancreatic cancer. Our data demonstrate that CXCL12 leads to a dose- and time-dependent up-regulation of SHH in pancreatic cancer cells. CXCL12-induced SHH up-regulation is specifically mediated through the receptor CXCR4 and is dependent on the activation of downstream Akt and ERK signaling pathways. Both Akt and ERK cooperatively promote nuclear accumulation of NF-κB by inducing the phosphorylation and destabilization of its inhibitory protein, IκB-α. Using dominant negative IκB-α, a SHH promoter (deletion mutant) reporter, and chromatin immunoprecipitation assays, we demonstrate that CXCL12 exposure enhances direct binding of NF-κB to the SHH promoter and that suppression of NF-κB activation abrogates CXCL12-induced SHH expression. Finally, our data demonstrate a strong correlative expression of CXCR4 and SHH in human pancreatic cancer tissues, whereas their expression is not observed in the normal pancreas. Altogether, our data reveal a novel mechanism underlying aberrant SHH expression in pancreatic cancer and identify a molecular link facilitating bidirectional tumor-stromal interactions.
Merkel cell carcinoma: a primer for the radiologist.

OBJECTIVE Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor. The purpose of this review is to provide a comprehensive description of the staging, workup, treatment, and follow-up of MCC. CONCLUSION Sentinel lymph node mapping and PET/CT are the cornerstones of staging of MCC. MCC is a radiosensitive tumor, and hence radiotherapy plays a major role in its management. Close follow-up with PET/CT helps in detecting recurrences of MCC.
Effects of inhaled nitric oxide on oxygenation and haemodynamic performance during one-lung ventilation in pigs

Abstract Objective: To study the effects of 20 ppm inhaled nitric oxide (iNO) on haemodynamics and systemic oxygenation during one-lung ventilation (OLV) in vivo. Design: Prospective animal study with a cross-over design. Setting: Animal laboratory of a university hospital. Subjects: Eight female pigs. Outcome measures: The pigs were anaesthetized, tracheally intubated, and mechanically ventilated. Following placement of femoral arterial and pulmonary artery catheters, a left-sided double-lumen tube (DLT) was placed via tracheotomy After DLT placement, in each animal OLV was performed during intravenous anaesthesia in a cross-over design with and without iNO (20ppm) in 100% oxygen. After haemodynamic stabilization, haemodynamic measurements and blood gas analyses were made, in addition we measured differential lung perfusion with colored microspheres in three animals. Results and Conclusions: iNO did not improve oxygenation nor did iNO reduce pulmonary arterial pressure in our animal model. Mixed venous PvO2 and cardiac output were comparable during the study periods.
Dietary fructose in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults and children. A number of genetic and environmental factors are known to predispose individuals to NAFLD. Certain dietary sugars, particularly fructose, are suspected to contribute to the development of NAFLD and its progression. The increasing quantity of fructose in the diet comes from sugar additives (most commonly sucrose and high fructose corn syrup) in beverages and processed foods. Substantial links have been demonstrated between increased fructose consumption and obesity, dyslipidemia, and insulin resistance. Growing evidence suggests that fructose contributes to the development and severity of NAFLD. In human studies, fructose is associated with increasing hepatic fat, inflammation, and possibly fibrosis. Whether fructose alone can cause NAFLD or if it serves only as a contributor when consumed excessively in the setting of insulin resistance, positive energy balance, and sedentary lifestyle is unknown. Sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added (fructose‐containing) sugars. (HEPATOLOGY 2013;57:2525–2531)
Information and communication technology (ICT) use in child and family nursing: What do we know and where to now?

Abstract Whilst the use of information and communication technology (ICT) in acute care services has been well documented, less is known about the impact of computerising community-based primary care such as child and family health nursing services. This self-complete survey of 606 nurses working in the Victorian Maternal and Child Health (MCH) service (response rate 60%) found that the predominately older workforce were confident with the use of ICT. This contrasts with findings from the acute sector where older nurses had lower ICT confidence. The survey revealed a variation in ICT support and a lack of data collection system compatibility. Professional education resources were not able to be effectively used in all locally supplied computers. Although MCH nurses have adapted well to computerisation, there is room for improvement. Appropriate resourcing, education and infrastructure support are areas that need to be addressed and would benefit from an overarching body responsible for development and quality assurance.
Can We? Administrative Limits Revisited

The idea of administrative limits—in the sense of constraints or bounds on what can be achieved by the activity of administration in general and public administration in particular—is important for a proper understanding of twenty-first-century public administration. What are the effective limits of taxable capacity in the modern state, as debt-ridden governments seek to reduce debt levels and budget deficits after the financial crashes and economic recession of the late 2000s? What are the limits of safety and security that can be realistically achieved by administrative structures and procedures in a so-called risk society? What are the limits to the achievement of ambitious social engineering to improve the human lot by conventional organizations and bureaucracies? Such issues are not new. Questions of this kind have long been asked by scholars in the intersecting fields of public administration, policy studies, and political science. Nonetheless, the author argues, they address issues that are of continuing, central importance to government and society in today’s world.
Plantar Sole Unweighting Alters the Sensory Transmission to the Cortical Areas

It is well established that somatosensory inputs to the cortex undergo an early and a later stage of processing. The later has been shown to be enhanced when the earlier transmission decreased. In this framework, mechanical factors such as the mechanical stress to which sensors are subjected when wearing a loaded vest are associated with a decrease in sensory transmission. This decrease is in turn associated with an increase in the late sensory processes originating from cortical areas. We hypothesized that unweighting the plantar sole should lead to a facilitation of the sensory transmission. To test this hypothesis, we recorded cortical somatosensory evoked potentials (SEPs) of individuals following cutaneous stimulation (by mean of an electrical stimulation of the foot sole) in different conditions of unweighting when standing still with eyes closed. To this end, the effective bodyweight (BW) was reduced from 100% BW to 40% BW. Contrary to what was expected, we found an attenuation of sensory information when the BW was unweighted to 41% which was not compensated by an increase of the late SEP component. Overall these results suggested that the attenuation of sensory transmission observed in 40 BW condition was not solely due to the absence of forces acting on the sole of the feet but rather to the current relevance of the afferent signals related to the balance constraints of the task.
HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1α) in regulating pro-inflammatory cytokines (PICs) pathway in the rat hippocampus after cardiac arrest (CA) induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR). Those PICs include interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1α and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1β, IL-6 and TNF-α were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1α and the time courses for HIF-1α and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1α by systemic administration of ML228, HIF-1α activator, significantly attenuated the amplified IL-6/IL-6R and TNF-α /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1β and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1β, IL-6 and TNF-α and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1α plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1α improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that HIF-1α plays an important role in regulating PIC signal pathways and Caspase-3. The subsequent induction of HIF-1α and its target signals is likely a part of the intrinsic neuroprotective effects aimed at attenuating damage as a result of global cerebral ischemia. Thus, targeting one or more of these signaling molecules has clinical implications for treatment and improvement of CA-evoked global cerebral ischemia often observed in clinics.
Positional Cloning of the Human Quantitative Trait Locus Underlying Taste Sensitivity to Phenylthiocarbamide

The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibrium between single-nucleotide polymorphism (SNP) markers and PTC taste sensitivity in unrelated subjects. This region contains a single gene that encodes a member of the TAS2R bitter taste receptor family. We identified three coding SNPs giving rise to five haplotypes in this gene worldwide. These haplotypes completely explain the bimodal distribution of PTC taste sensitivity, thus accounting for the inheritance of the classically defined taste insensitivity and for 55 to 85% of the variance in PTC sensitivity. Distinct phenotypes were associated with specific haplotypes, which demonstrates that this gene has a direct influence on PTC taste sensitivity and that sequence variants at different sites interact with each other within the encoded gene product.