Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles of reactive oxygen species in the fate of stem cells.

SIGNIFICANCE Stem cells are characterized by the properties of self-renewal and the ability to differentiate into multiple cell types, and thus maintain tissue homeostasis. Reactive oxygen species (ROS) are a natural byproduct of aerobic metabolism and have roles in cell signaling. Regulation of ROS has a vital role in maintaining "stemness" and differentiation of the stem cells, as well as in progression of stem-cell-associated diseases. RECENT ADVANCES As of late, much research has been done on the adverse effects of ROS in stem cells. However, recently it has become apparent that in some cases redox status of the stem cell does have a role in maintaining its identity as such. Both pluripotent and multipotent stem cell types have been reported to possess enzymatic and nonenzymatic mechanisms for detoxification of ROS and to correct oxidative damage to the genome as well as the proteome. CRITICAL ISSUES Although context dependent and somewhat varied among different stem cell types, the correlation seems to exist between antioxidant defense level and stem cell fate change (i.e., proliferation, differentiation, and death). Changes in stem cell redox regulation may affect the pathogenesis of various human diseases. FUTURE DIRECTIONS Dissecting the defined roles of ROS in distinct stem cell types will greatly enhance their basic and translational applications. Here, we discuss the various roles of ROS in adult, embryonic, and induced pluripotent stem cells.
Spread of Diadema Mass Mortality Through the Caribbean

Populations of the ecologically important sea urchin Diadema antillarum suffered severe mass mortalities throughout the Caribbean. This mortality was first observed at Panama in January 1983; by January 1984 it had spread to the rest of the Caribbean and to Bermuda. The sequence of mortality events in most areas is consistent with the hypothesis that the causative agent was dispersed by major surface currents over large distances. However, some of the late die-offs in the southeastern Caribbean do not fit this pattern. Several lines of indirect evidence suggest that the phenomenon is due to a water-borne pathogen. If so, this is the most extensive epidemic documented for a marine invertebrate.
A sharp programmable passive filter based on filtering by Aliasing

This paper presents the 1st integrated circuit demonstration of Filtering by Aliasing (FA). FA is a recent technique that uses linear periodically time varying (LPTV) analog circuitry prior to a sampler to provide a desired CT-to-DT transfer function. Such LPTV signal processing offers far superior programmability and performance relative to LTI design. The presented IC applies FA to a single-pole passive RC filter. The resistor, realized as a switched resistor ladder, is continuously varied using on-chip digital control while the output is sampled at a baseband rate. Measured CT-to-DT responses show tunable-bandwidth filter roll-off better than 60 dB/dec, stop-band suppression up to 60 dB, tunable carrier up to 800 MHz, up to 31 dBm out-of-band IIP3, and harmonic rejection.
Structure–function relationship depends on glaucoma severity

Background/aims: To determine the structure–function relationship throughout the different stages of glaucoma. Methods: Subjects: 228 controls and 1007 suspected, early, moderate, or advanced glaucomas. In controls, Pearson coefficient of variation (PCV) of standard automated perimetry mean sensitivity (SAP-MS) and global mean retinal nerve fibre layer thickness (RNFL, Heidelberg Retina Tomograph) were calculated. Piecewise linear regression was used to evaluate if the data were related better to two separate regression lines in all population. Results: PCV for SAP-MS and RNFL was 6.19% and 29.27%, respectively. For SAP-MS >22.42 dB (piecewise linear regression-obtained breakpoint, p<0.05), the logarithmic and linear relationships between SAP-MS and mean RNFL thickness were not different (r = 0.182, r = 0.185 respectively; p = 0.950). For SAP-MS <22.42 dB, the logarithmic and linear relationships between SAP-MS and mean RNFL thickness were not different (r = 0.353, r = 0.344 respectively; p = 0.884). Conclusion: The logarithmic and linear relationships between SAP-MS and mean RNFL thickness did not differ when individuals were stratified using the piecewise linear regression-obtained cut-off point. The curvilinear relationship between the morphological and perimetric results may be due to the wide variability in normal morphology and limitations in the dynamic range of the morphological tests in cases with moderate and severe defects.
Joint model for a diagnostic test without a gold standard in the presence of a dependent terminal event

Breast cancer patients after breast conservation therapy often develop ipsilateral breast tumor relapse (IBTR), whose classification (true local recurrence versus new ipsilateral primary tumor) is subject to error, and there is no available gold standard. Some patients may die because of breast cancer before IBTR develops. Because this terminal event may be related to the individual patient's unobserved disease status and time to IBTR, the terminal mechanism is non‐ignorable. This article presents a joint analysis framework to model the binomial regression with misclassified binary outcome and the correlated time to IBTR, subject to a dependent terminal event and in the absence of a gold standard. Shared random effects are used to link together two survival times. The proposed approach is evaluated by a simulation study and is applied to a breast cancer data set consisting of 4477 breast cancer patients. The proposed joint model can be conveniently fit using adaptive Gaussian quadrature tools implemented in SAS 9.3 (SAS Institute Inc., Cary, NC, USA) procedure NLMIXED. Copyright © 2014 John Wiley & Sons, Ltd.
Retrospective histopathological analysis of various neoplasms of different parts of the gastrointestinal tract seen at the Kathmandu University Teaching Hospital (KUTH), Dhulikhel, Nepal.

OBJECTIVE To find out the spectrum of various histopathologic types of primary neoplasms of different parts of the gastrointestinal tract (oesophagus, stomach, small intestine, colorectum, anal canal) seen at the Kathmandu University Teaching Hospital (KUTH), Dhulikhel as there exists a worldwide wide variation in the distribution of various neoplasms of different parts of the gastrointestinal tract, which appears largely due to exogenous factors rather than due to inherent differences between populations. MATERIALS AND METHODS This was a retrospective study. It was carried out at Kathmandu University Teaching Hospital (KUTH), Dhulikhel, Kavre, Nepal. All neoplasms of the gastrointestinal tract seen at the KUTH during the period 1st January 2004 to 31st December 2004 were included in this study and examined by light microscope (LM). RESULTS A total number of 18 cases of neoplasms of the gastrointestinal tract were seen. Out of these, 3 (16.7%) were of the oesophagus (all squamous cell carcinoma), 10 (55.5%) were of the stomach (six intestinal type and four diffuse type), 2 (11.1%) were of the small intestine (one was lymphoma of the mucosa associated lymphoid tissue--MALTOMA and other was a malignant gastrointestinal stromal tumour--GIST), 3 (16.7%) were of the colorectum (all adenocarcinoma), and none was of the anal canal. CONCLUSION Relatively large number of cases of the carcinoma of the stomach were found in our this small series of the cases of the gastrointestinal tract in comparison to the Western countries.
Endocrine and neurogenic regulation of the orphan nuclear receptors Nur77 and Nurr-1 in the adrenal glands

nurr77 and nurr-1 are growth factor-inducible members of the steroid/thyroid hormone receptor gene superfamily. In order to gain insight into the potential roles of nur77 in the living organism, we used pharmacologic treatments to examine the expression of nur77 in the mouse adrenal gland. We found that nur77 and nurr-1 are induced in the adrenal gland upon treatment with pentylene tetrazole (Ptz; Metrazole). This induction is separable into distinct endocrine and neurogenic mechanisms. In situ hybridization analysis demonstrates that nur77 expression upon Ptz treatment in the adrenal cortex is localized primarily to the inner cortical region, the zona fasciculata-reticularis, with minimal induction in the zona glomerulosa. This induction is inhibitable by pretreatment with dexamethasone, indicating involvement of the hypothalamic-pituitary-adrenal axis in the activation of adrenal cortical expression. When mice were injected with adrenocorticotrophic hormone (ACTH), nur77 expression in the adrenal gland spanned all cortical layers including the zona glomerulosa, but medullary expression was not induced. Ptz also induces expression of both nur77 and nurr-1 in the adrenal medulla. Medullary induction is likely to have a neurogenic origin, as nur77 expression was not inhibitable by dexamethasone pretreatment and induction was seen after treatment with the cholinergic neurotransmitter nicotine. nur77 is also inducible by ACTH, forskolin, and the second messenger analog dibutyryl cyclic AMP in the ACTH-responsive adrenal cortical cell line Y-1. Significantly, Nur77 isolated from ACTH-stimulated Y-1 cells bound to its response element whereas Nur77 present in unstimulated cells did not. Moreover, Nur77 in ACTH-treated Y-1 cells was hypophosphorylated at serine 354 compared with that in untreated cells. These results, taken together with the previous observation that dephosphorylation of serine 354 affects DNA binding affinity in vitro, show for the first time that phosphorylation of Nur77 at serine 354 is under hormonal regulation, modulating its DNA binding affinity. Thus, ACTH regulates Nur77 in two ways: activation of its gene and posttranslational modification. A promoter analysis of nur77 induction in Y-1 cells indicates that the regulatory elements mediating ACTH induction differ from those required for induction in the adrenal medullary tumor cell line PC12 and in 3T3 fibroblasts.
The validity and reliability of a novel indoor player tracking system for use within wheelchair court sports

Abstract The aim of the current study was to investigate the validity and reliability of a radio frequency-based system for accurately tracking athlete movement within wheelchair court sports. Four wheelchair-specific tests were devised to assess the system during (i) static measurements; (ii) incremental fixed speeds; (iii) peak speeds; and (iv) multidirectional movements. During each test, three sampling frequencies (4, 8 and 16 Hz) were compared to a criterion method for distance, mean and peak speeds. Absolute static error remained between 0.19 and 0.32 m across the session. Distance values (test (ii)) showed greatest relative error in 4 Hz tags (1.3%), with significantly lower errors seen in higher frequency tags (<1.0%). Relative peak speed errors of <2.0% (test (iii)) were revealed across all sampling frequencies in relation to the criterion (4.00 ± 0.09 m · sˉ1). Results showed 8 and 16 Hz sampling frequencies displayed the closest-to-criterion values, whilst intra-tag reliability never exceeded 2.0% coefficient of variation (% CV) during peak speed detection. Minimal relative distance errors (<0.2%) were also seen across sampling frequencies (test (iv)). To conclude, the indoor tracking system is deemed an acceptable tool for tracking wheelchair court match play using a tag frequency of 8 or 16 Hz.
A relational understanding of sibling experiences of children with rare life-limiting conditions

Mucopolysaccharidoses (MPS) and Batten disease are rare life-limiting conditions (LLCs) characterised by progressive and permanent physical and cognitive decline. The impact of such conditions on families, and notably on siblings, has not yet been described or documented. This paper presents data from a UK-wide study that sought to understand the family experience of supporting a child with the rare degenerative LLCs of MPS and Batten disease. The aim of this paper is to report sibling experiences related to these rare degenerative and progressive conditions, in order to inform the future development of supportive interventions. Eight siblings of children with MPS (n = 7) and Batten Disease (n = 1) participated in semi-structured qualitative interviews. A card sort technique was utilised to support and engage the children. Siblings are clearly impacted emotionally, pragmatically and relationally by the ill health of another child in the family. The data indicate four key themes which demonstrate impacts on siblings: perceptions of the condition and its symptoms, impact on daily life, emotional consequences and ways of coping. Siblings often had considerable knowledge of the condition and took on important roles in symptom management. However, these experiences were in the context of managing relationships within the family (often protecting parents from an awareness of how much they knew) and relationships at school (including distraction from learning and being bullied by peers). The data highlight how sibling experiences are generated through a combination of negative disability discourses and support through peers and family members. The data indicate how these features shift as a consequence of witnessing the advancement of their brother’s or sister’s condition and the emotional sequelae of disease progression. Exploration of siblings’ experiences of living with such rare progressive and degenerative LLCs suggest the focus of interventions to support this group should address their emotional health and ways to overcome isolation and build connections with other siblings who share their unique experiences. Critically, the data suggest that sibling support should be cognisant of the trajectory of the illness as well as the family, school and peer relational contexts that siblings inhabit.
Is malignant nodule topography an additional risk factor for metastatic disease in low-risk differentiated thyroid cancer?

BACKGROUND Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. In recent decades, the incidence has been increasing, largely due to increased detection of patients with low-risk or very low-risk DTC. According to European Thyroid Association and American Thyroid Association guidelines, radioiodine (RAI) thyroid remnant ablation is not indicated in very low-risk patients, while its role is still debated in low-risk patients. Accordingly, risk stratification of DTC patients is pivotal when deciding for or against RAI ablation. Presently, risk stratification is based on pTNM staging integrated with clinical parameters. The aim of our study was to evaluate the relationship between location of malignant thyroid nodules within the thyroid gland and the presence of loco-regional and/or distant metastases in patients with pT1a-pT1b DTCs. METHODS We reviewed the records of 246 patients (214 women, 32 men; female-to-male ratio 6.7:1) affected by unifocal DTC ≤ 2 cm, who had undergone RAI thyroid remnant ablation (activity ranged 555-4588 MBq) after levothyroxine withdrawal or after recombinant human TSH (rhTSH) stimulation. The majority of the patients (91.5%) were affected by papillary thyroid carcinoma. RESULTS Metastases were discovered by posttreatment whole-body scintigraphy in 29 out of 246 (11.8%) patients. In patients with metastases, malignant thyroid nodules were located in the right lobe (14/123, 11.4%), left lobe (7/95, 7.4%), and isthmus (8/27, 29.6%). The prevalence of metastases was significantly higher in patients with DTC located in the isthmus, compared to other sites (χ(2) = 9.6, p = 0.002). CONCLUSIONS Our data show for the first time that a location of a thyroid cancer in the isthmus is an additional risk factor for RAI avid metastatic disease in pT1a-pT1b DTC patients, regardless of the presence or absence of other risk factors.
Mixed Duopoly with a Partial‐Delegated‐Public Firm

We compare the welfare results of mixed duopoly model where a firm can be private, public or partial&#8208;delegated&#8208;public. We consider two types of partial&#8208;delegated&#8208;public firms. In partial&#8208;delegated&#8208;public with location delegation, the firm chooses location to maximize its profit while the social planner chooses price to maximize social surplus. Partial&#8208;delegated&#8208;public firm with price delegation is the opposite where the firm chooses price to maximize its profit. We find significant differences in equilibrium outcomes both between the two types of partial&#8208;delegated&#8208;public firms, and between the partial&#8208;delegated&#8208;public firms and the purely private/public firms. While equilibrium prices in the partial&#8208;delegated&#8208;public firm cases lie in between those in the pure cases (purely private or purely public), the private firm's profit may be higher when its rival is a partial&#8208;delegated&#8208;public firm rather than a purely private/public firm. We also find a &#8216;trade&#8208;off&#8217; within the two partial&#8208;delegated&#8208;public firm cases: social surplus is higher under location delegation, but consumer surplus and profit of the partial&#8208;delegated&#8208;public firm are higher under price delegation.
The influence of newborn early literacy intervention programs in three canadian provinces

Low levels of literacy in early childhood can have lasting effects on children’s educational and intellectual development. Many countries have implemented newborn literacy programs designed to teach parents pre-literacy promoting activities to share with their children. We conducted 2 quasi-experimental studies using 1) a pre-test/post-test design and 2) a non-equivalent control group design to examine the effect of newborn literacy programs on parents’ self-reported literacy intentions/behaviors, values toward literacy, and parent-child interactions. Parents were recruited from 3 provinces, 2 with newborn literacy programs (intervention) and 1 without (control). Parents in the intervention group completed prenatal and postnatal (after participation in program) questionnaires. Parents in the control group completed 1 questionnaire. Questionnaires were designed to capture parents’ literacy intentions (prenatal), behaviors (postnatal), values, and parent-child interactions (postnatal). A total of 98 parents were included in study one and 174 were included in study two. Parents’ self-reported prenatal intentions and values were higher than their postnatal behaviors and values. Parents in the intervention group exhibited higher literacy behaviors and values and greater enjoyment reading to their children than parents in the control group, though they also reported reading to their children less frequently. Parents in the intervention group had significantly higher Positive Interactive scores than controls. Overall, we found participation in newborn literacy programs positively impacted parenting behaviors and attitudes. Lower postnatal within-group scores (intentions and values versus behaviors and values) may have been the result of participants’ high expectations. Given our findings, we recommend that these programs continue.
Efficacy of Bicarbonate in Decreasing Pain on Intradermal Injection of Local Anesthetics: A Meta-Analysis

Objective: Intradermal injection of local anesthetic often results in pain on injection due in part to the acidic pH of commercially prepared solutions, which are optimized to prolong shelf life. Although there are other possible explanations (eg, noxious properties of local anesthetics, pressure effect of infiltration), the etiology is most likely multifactorial. Although addition of bicarbonate to local anesthetics may decrease pain on intradermal injection, the extent of this analgesic effect is uncertain. We performed a meta-analysis of available trials investigating pain during intradermal injection of buffered local anesthetic preparations. Methods: We searched the National Library of Medicine's PubMed database for all relevant articles published on the topic through November 2006. Inclusion criteria included double-blind, randomized controlled trials and use of a visual analog scale to measure pain on infiltration of local anesthetic buffered with sodium bicarbonate compared with that of unbuffered local anesthetic. Meta-analysis was performed using the Review Manager 4.2. 7 (The Cochrane Collaboration, 2004). A random-effects model was used. Results: Our search resulted in 86 abstracts, of which 12 articles met all inclusion criteria. Overall, there were 609 observations for buffered local anesthetic and 615 for unbuffered local anesthetic. Use of buffered local anesthetic resulted in a statistically lower weighted mean difference in visual analog scale of −1.17 (95% confidence interval, −1.68 to −0.67) compared with unbuffered local anesthetic. Conclusions: Our systematic review suggests that the use of buffered local anesthetics seems to be associated with a statistical decrease in pain of infiltration when compared with unbuffered local anesthetic.
‘Eppur si move’: The Association Between Electrophysiological and Psychophysical Signatures of Perceived Movement Illusions

ABSTRACT Vibration applied to muscle tendons induces an illusory perception of movement by activating spindle receptors and Ia afferent fibers. While neural structures supporting such illusions are quite defined, functional and psychophysical correlates of their perception have not been deeply investigated. The authors aimed at exploring subjective perception of illusory movements thanks to a repeated-stimulation multimodal approach. The integrated analysis of electroencephalography, source data (standardized low-resolution brain electromagnetic tomography–sLORETA), and psychophysical evaluation pointed at the activation of a frontoparietal sensorimotor network, with prefrontal-medial regions mainly involved in supporting the awareness for illusory movements. Further, illusions showed consistency in terms of presence, vividness, and duration. Finally, superior parietal structures seemed to play an important role in self-attribution of agency and ownership during such experiences.
Circulating tumor DNA profiling reveals clonal evolution and real‐time disease progression in advanced hepatocellular carcinoma

Circulating tumor DNA (ctDNA) provides a potential non‐invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis. Further analysis was conducted on the 4th HCC case with multiple lesion samples and sequential plasma samples. We identified 160 subclonal SNVs in tumor tissues as well as matched peritumor tissues with PBMC as control. 96.9% of this patient's tissue mutations could be also detected in plasma samples. These subclonal SNVs were grouped into 9 clusters according to their trends of cellular prevalence shift in tumor tissues. Two clusters constituted of tumor stem somatic mutations showed circulating levels relating with cancer progression. Analysis of tumor somatic mutations revealed that circulating level of such tumor stem somatic mutations could reflect tumor burden and even predict prognosis earlier than traditional strategies. Furthermore, HCK (p.V174M), identified as a recurrent/metastatic related mutation site, could promote migration and invasion of HCC cells. Taken together, study of mutation profiles in biopsy and plasma samples in HCC patients showed that ctDNA could overcome tumor heterogeneity and real‐time track the therapeutic responses in the longitudinal monitoring.