Miracle-dz/UniFAR-FTUs huggingface dataset:
Erythropoietin has an anti‐myeloma effect – a hypothesis based on a clinical observation supported by animal studies

Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end‐stage renal failure and cancer‐related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was <6 months. All six patients were treated with rHuEpo for their anemia, either without any chemotherapy or very mild chemotherapy for a short time. Yet, surprisingly they lived for 45–133 months totally from MM diagnosis and 38–94 months with rHuEpo (with a good quality of life). In fact, one patient, is still alive and well, more than 8 yr after chemotherapy was discontinued because of a resistant aggressive disease. The course in these six MM patients led us to hypothesize that Epo might have an antineoplastic or antimyeloma effect. We proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with MOPC‐315 myeloma cells. We then presented evidence that the mechanism is a new immune‐mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Fututre trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.
A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients.

We evaluated whether the combination of triptorelin, a LHRH analog (LHRH-A), with dexamethasone and lanreotide, a somatostatin analog, can produce objective clinical responses in metastatic androgen ablation-refractory prostate cancer (stage D3) patients who have relapsed, after combined androgen blockade (LHRH-A plus antiandrogen) and antiandrogen withdrawal. Eleven stage D3 patients with diffuse bony metastases, who had progressed despite initial responses (lasting <12 months) to combined androgen blockade therapy and subsequently failed antiandrogen withdrawal, received oral dexamethasone (4 mg daily for the first month, tapered down to 2 mg after the first month and 1 mg after the second month, and continued on 1 mg thereafter) and lanreotide (30 mg im every 14 d) in combination with triptorelin (3.75 mg im every 28 d). Serum prostate-specific antigen, alkaline phosphatase, performance status, and bone pain were assessed monthly during therapy. Fasting blood glucose was measured biweekly, and serum IGF-I, T, and dehydroepiandrosterone sulfate levels were assessed at baseline, at response to the combination therapy, and at relapse from it. Ten of 11 stage D3 patients [90.9% of patients; 95% confidence interval (CI), 58.7-99.8%] had durable objective clinical responses (including > or = 50% prostate-specific antigen decline in 8 patients, 72.7%; 95% CI, 39-94%). All patients reported significant and durable improvement of bone pain (for a median duration of 13 months; 95% CI, 12-14 months; range, 6-22 months) and performance status (median duration, 19 months; 95% CI, 13-25 months; range, 7-22 months) without major treatment-related side effects. The median progression-free survival was 7 months (95% CI, 4-10 months; range, 3-17 months), and the median overall survival was 18 months (95% CI, 16-20 months; range, 7-22 months). Five of six total deaths occurred secondary to disease progression. We observed a statistically significant (P = 0.018) reduction in serum IGF-I levels at response to the combination therapy (60% reduction of baseline IGF-I levels). Dehydroepiandrosterone sulfate levels, although already significantly suppressed at baseline, had an additional significant reduction (P < 0.02) at response to therapy. T levels remained suppressed within castration levels (<3 nmol/liter, at baseline and throughout therapy, including relapse). The combination therapy of LHRH-A with dexamethasone plus somatostatin analog produces objective clinical responses and symptomatic improvement in androgen ablation (LHRH-A) refractory prostate cancer patients.
Serum Lipids in the GENECARD Study of Coronary Artery Disease Identify Quantitative Trait Loci and Phenotypic Subsets on Chromosomes 3q and 5q

Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease‐related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results.
Molecular cloning and transfection studies of M6b‐2, a novel splice variant of a member of the PLP‐DM20/M6 gene family

The present study documents the nucleic acid and deduced amino acid sequence of M6b‐2, a novel splice variant of the M6b gene, which belongs to the PLP‐DM20/M6 gene family. M6b‐2 differs from the previously published M6b by a novel 40‐amino acid insertion which is characterised by a high proline content, two casein kinase, and one tyrosine kinase consensus sequences. M6b‐2 mRNA is enriched in perinatal central nervous system (CNS), and although it declines during development, it does persist into adulthood. Transient transfection studies coupled to secondary structure and hydrophobicity analysis suggest that the novel polypeptide in M6b‐2 lies at the cytoplasmic face of the plasma membrane. It is therefore possible that the function(s) of M6b‐2 may be regulated intracellularly by phosphorylation during CNS development. J. Neurosci. Res. 52:633–640, 1998. © 1998 Wiley‐Liss, Inc.
Good teacher education – an exploratory study

Good or effective education of prospective teachers in traditional higher education settings seemingly differ from educating them in Open Distance Learning (ODL). The literature was reviewed with reference to ‘good teacher education’ in traditional higher education and that in ODL contexts. Content analysis was done with the responses to two open-ended questions, e-mailed to staff members of the Department of Teacher Education in the College of Education at an ODL institution, namely ‘What is good teacher education? ’ and ‘What is good teacher education in ODL? ’ Since the researcher is part of the College of Education, she made use of convenience sampling. In comparing literature with the empirical findings it seems that good teacher education contains many of the same elements in ODL and traditional higher education settings. The context in ODL teacher education is different, but all student teachers need particular generic skills and competences. Interactive digital communication technologies are, however, more extensively used in ODL. Recommendations on how teacher education in both settings can be improved are made.
New members of the chemokine receptor gene family

Chemokines are relatively small peptides with potent chemoattractant and activation activities for leukocytes. Several chemokine receptors have been cloned and characterized and all are members of the G protein‐coupled receptor superfamily. Using degenerate oligonucleotides and polymerase chain reaction, we have identified seven novel receptors with significant homology to chemokine receptors. Two of these sequences are presented here for the first time. We have shown, with gene mapping studies, that receptors with the highest sequence similarity are closely linked on human chromosomes. This close genetic association suggests a functional relationship as well.
Me, My Girls, and the Ideal Hotel: Segmenting Motivations of the Girlfriend Getaway Market Using Fuzzy C-Medoids for Fuzzy Data

Segmenting the motivation of travelers using the push and pull framework remains ubiquitous in tourism. This study segments the girlfriend getaway (GGA) market on motivation (push) and accommodation (pull) attributes and identifies relationships between these factors. Using a relatively novel clustering algorithm, the Fuzzy C-Medoids clustering for fuzzy data (FCM-FD), on a sample of 749 women travelers, three segments (Socializers, Enjoyers, and Rejoicers) are uncovered. The results of a multinomial fractional model show relationships between the clusters of motivation and accommodation attributes as well as sociodemographic characteristics. The research highlights the importance of using a gendered perspective in applying well established motivation models such as the push and pull framework. The findings have implications for both destination and accommodation management.
Toward Practical Self-Supervised Monocular Indoor Depth Estimation

The majority of self-supervised monocular depth estimation methods focus on driving scenarios. We show that such methods generalize poorly to unseen complex indoor scenes, where objects are cluttered and arbitrarily arranged in the near ﬁeld. To obtain more robustness, we propose a structure distillation approach to learn knacks from a pre-trained depth estimator that produces structured but metric-agnostic depth due to its in-the-wild mixed-dataset training. By combining distillation with the self-supervised branch that learns metrics from left-right consistency, we attain structured and metric depth for generic indoor scenes and make inferences in real-time. To facilitate learning and evaluation, we collect SimSIN, a dataset from simulation with thousands of environments, and UniSIN, a dataset that contains about 500 real scan sequences of generic indoor environments. We experiment in both sim-to-real and real-to-real settings, and show improvements both qualitatively and quantitatively, as well as in downstream applications using our depth maps. This work provides a full study, covering methods, data, and applications. We believe the work
Exome Sequencing Reveals the Likely Involvement of SOX10 in Uveal Melanoma

Purpose To identify the spectrum of somatic mutations in an Asian Indian patient with uveal melanoma (UM) without metastasis using exome sequencing. Case Report A 49-year-old man from India was diagnosed as having cilio-choroidal (uveal) melanoma (UM), without metastasis, in his right eye with the help of magnetic resonance imaging. This was later confirmed by histopathological evaluation. Two individuals from India with non-neoplastic blind eyes were recruited as controls. The affected eyes from the UM patient and the two control individuals were enucleated, and uveal tissues were collected. DNA was extracted from uveal tissue, and the matched blood sample from each of the three individuals was followed by exome sequencing. Statistical and bioinformatic analyses were done to identify somatic mutations and their putative associations with UM. Thirty-one somatic mutations (25 amino acid altering) in protein-coding (exonic) regions were detected in the UM patient. Of the amino acid–altering somatic mutations, 16 mutations were predicted to be candidate mutations relevant to UM. Somatic mutations, putatively causal for UM, were identified in GNAQ, SF3B1, and SOX10. Conclusions Somatic mutations in GNAQ and SF3B1 genes were probable drivers of UM in the Indian patient; these were also reported earlier in some White patients. In addition, a frameshift deletion of 20 base pairs has been identified in SOX10 in the UM patient. Somatic mutations in SOX10, a transcription factor, which acts upstream of microphthalmia-associated transcription factor and synergizes with microphthalmia-associated transcription factor, was identified in some melanoma cell lines. The transcription factor SOX10 was found to have an essential role in melanocyte development and pigmentation. Our finding of the frameshift deletion (p.H387fs) in exon 4 of SOX10 in UM provides an important insight and complements earlier findings of mutations in GNAQ and SF3B1 on the genomic basis of UM.
A 64-channel readout ASIC for nanowire biosensor array with electrical calibration scheme

A 1.8-mW, 18.5-mm2 64-channel current readout ASIC was implemented in 0.18-µm CMOS together with a new calibration scheme for silicon nanowire biosensor arrays. The ASIC consists of 64 channels of dedicated readout and conditioning circuits which incorporate correlated double sampling scheme to reduce the effect of 1/f noise and offset from the analog front-end. The ASIC provides a 10-bit digital output with a sampling rate of 300 S/s whilst achieving a minimum resolution of 7 pArms. A new electrical calibration method was introduced to mitigate the issue of large variations in the nano-scale sensor device parameters and optimize the sensor sensitivity. The experimental results show that the proposed calibration technique improved the sensitivity by 2 to 10 times and reduced the variation between dataset by 9 times.
Metabolic Fate of Peroxynitrite in Aqueous Solution

Peroxynitrite, the reaction product of nitric oxide (NO) and superoxide (O2) is assumed to decompose upon protonation in a first order process via intramolecular rearrangement to NO3−. The present study was carried out to elucidate the origin of NO2− found in decomposed peroxynitrite solutions. As revealed by stopped-flow spectroscopy, the decay of peroxynitrite followed first-order kinetics and exhibited a pKa of 6.8 ± 0.1. The reaction of peroxynitrite with NO was considered as one possible source of NO2−, but the calculated second order rate constant of 9.1 × 104 M−1 s−1 is probably too small to explain NO2− formation under physiological conditions. Moreover, pure peroxynitrite decomposed to NO2− without apparent release of NO. Determination of NO2− and NO3− in solutions of decomposed peroxynitrite showed that the relative amount of NO2− increased with increasing pH, with NO2− accounting for about 30% of decomposition products at pH 7.5 and NO3− being the sole metabolite at pH 3.0. Formation of NO2− was accompanied by release of stoichiometric amounts of O2 (0.495 mol/mol of NO2−). The two reactions yielding NO2− and NO3− showed distinct temperature dependences from which a difference in Eact of 26.2 ± 0.9 kJ mol−1 was calculated. The present results demonstrate that peroxynitrite decomposes with significant rates to NO2− plus O2 at physiological pH. Through formation of biologically active intermediates, this novel pathway of peroxynitrite decomposition may contribute to the physiology and/or cytotoxicity of NO and superoxide.
Slack-performance relationship before, during and after a financial crisis: empirical evidence from European manufacturing firms

This thesis studied the slack - performance relationship under different external environments by taking advantage of the financial crisis of 2008-09, which provides a natural experiment opportunity for the study. Besides the management of slack, adaptation profiles are also examined by building the two-stage adaptation process model in concordance with different period of financial crisis. Based on empirical analysis and theoretical research, this thesis finds that slack management impacts the firms' performance as well as firms' adaptation to respond to financial crisis. Another novelty of this thesis is to examine ambidexterity in detail by employing constructs of alignment and adaptability from the perspective of organizational slack. Thesis tries to evidence that European manufacturing firms have various adaptation processes, profiles and risk-taking behaviors with varying performance implications based on their slack management in response to financial crisis. To that end, this study investigates empirically, publicly-held 671 western European manufacturing firms, by comparatively examining their organizational slack management and performance characteristics before, during and after the recent financial crisis period 2007-8 . This research employs longitudinal panel data. The data was drawn from Thomson one banker database for the period of2004-2013.
Nutrient intakes by young children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet. The STRIP Baby Project. Special Turku Coronary Risk Factor Intervention Project for Babies.

OBJECTIVE To evaluate the impact of individualized and repeatedly given dietary counseling on fat intake and nutrient intake of children aged 8 months to 4 years. DESIGN Prospective randomized clinical trial. PARTICIPANTS Children (N = 1062) from 1054 families were randomized to an intervention (n = 540) or a control (n = 522) group when each child participant was 6 months old. INTERVENTIONS The children in the intervention group were counseled to reduce their intake of saturated fat and cholesterol but to ensure their adequate energy intake. Dietary issues were discussed with the families of the children in the control group only briefly according to the current practice of well-baby clinics. MAIN OUTCOME MEASURES Food consumption was evaluated by using 3- and 4-day food records that were kept at 5- to 12-month intervals, and nutrient intakes were analyzed with a Micro Nutrica computer program (Social Insurance Institution, Turku, Finland). RESULTS The intake of fat (29% of the energy intake) and cholesterol (70 mg) showed no differences between the groups of children at 8 months of age. The fat intake in the children in the intervention group was then continuously 2% of the energy intake below that of the children in the control group (P < .001). After the age of 13 months, the cholesterol intake of the children in the control group exceeded that of the children in the intervention group by 20 mg (P < .001). The children in the intervention group consumed 3% (of the energy intake) less saturated (P < .001) and 1% (of the energy intake) more polyunsaturated fats (P < .001) than did the children in the control group at age 13 months and older. The carbohydrate intake was slightly higher in the children in the intervention group than in the children in the control group. Intakes of vitamins, minerals, and trace elements showed no differences between the 2 groups. CONCLUSIONS The intakes of fat by the children in the intervention and control groups were markedly below values that were recommended for the first 2 years of life. Despite the low intake of fat, the intake of other nutrients fulfilled current recommendations, except for vitamin D and iron. Individualized dietary counseling that led to clear changes in the type of fat intake had a minimal effect on vitamin or mineral intakes.
Modification of human glioma locomotion in vitro by cytokines EGF, bFGF, PDGFbb, NGF, and TNF alpha.

Cytokines exert receptor-mediated control over glia. Up-regulation of receptor expression of cytokine production corresponds with the acquisition of a neoplastic phenotype. A modified radial dish assay was used to determine whether in vitro locomotion of glioma cells is modified by the epidermal growth factor, the basic fibroblast growth factor, the bb dimer of platelet-derived growth factor, the nerve growth factor, or the tumor necrosis factor alpha. Human glioma cells were plated in the center of a petri dish with one of these cytokines in 0.5 ml agar (50 ng/ml if the cytokine was distributed evenly throughout the dish) at one edge, and 0.5 ml plain agar at the opposite edge. After 24 hours, a central zone of cells was established; the agar was gelatinized. Feeding medium was added to the dish, and slow elution from the agar established a cytokine gradient. Cell counts were performed daily over 6 to 10 days at predetermined distances on both sides of the central zone to assess directional cellular movement with respect to the cytokine gradient and the plain agar. The epidermal growth factor caused continuous chemoattraction, whereas the tumor necrosis factor alpha caused slight chemorepulsion for 24 to 48 hours, followed by strong chemoattraction. The bb dimer of platelet-derived growth factor, the basic fibroblast growth factor, and the nerve growth factor all maintained chemorepulsion over the entire 6 to 10 days. Therefore, the cytokines did affect glioma cell motility in vitro, and the modified radial dish assay used in this study provided a useful in vitro model for assessing the impact of the cytokines on glioma cell locomotion. (ABSTRACT TRUNCATED AT 250 WORDS)
Cure frailty models for survival data: Application to recurrences for breast cancer and to hospital readmissions for colorectal cancer

Owing to the natural evolution of a disease, several events often arise after a first treatment for the same subject. For example, patients with a primary invasive breast cancer and treated with breast conserving surgery may experience breast cancer recurrences, metastases or death. A certain proportion of subjects in the population who are not expected to experience the events of interest are considered to be ‘cured’ or non-susceptible. To model correlated failure time data incorporating a surviving fraction, we compare several forms of cure rate frailty models. In the first model already proposed non-susceptible patients are those who are not expected to experience the event of interest over a sufficiently long period of time. The other proposed models account for the possibility of cure after each event. We illustrate the cure frailty models with two data sets. First to analyse time-dependent prognostic factors associated with breast cancer recurrences, metastases, new primary malignancy and death. Second to analyse successive rehospitalizations of patients diagnosed with colorectal cancer. Estimates were obtained by maximization of likelihood using SAS proc NLMIXED for a piecewise constant hazards model. As opposed to the simple frailty model, the proposed methods demonstrate great potential in modelling multivariate survival data with long-term survivors (‘cured’ individuals).
Identification of a combined biomarker for malignant transformation in oral submucous fibrosis

Background Oral submucous fibrosis (OSF) is a chronic progressive disease of the oral cavity that is considered a common potentially malignant disorder in South Asia. Areca nut chewing is the main etiological factor, but its carcinogenic mechanism has yet to be proven. The purpose of this study was to identify the useful biomarkers in predicting high‐risk patients with OSF. Methods Thirty‐six cases of OSF and six cases of normal oral mucosa (NOM) were used for this study. Immunohistochemical staining was performed for Ki67, cyclin D1, p16, p53, β‐catenin, c‐Jun, c‐Met, and insulin‐like growth factor II mRNA‐binding protein 3 (IMP3). The expression patterns of NOM served as guidelines for the scoring system. Results The expression of Ki67, cyclin D1, c‐Met, IMP3, and β‐catenin showed a significant difference between OSF and NOM samples. The combined biomarkers of Ki67 and p16 showed significantly different expression between the transformation and non‐transformation groups. With discriminant analysis, we proposed a noble formula and cutoff value for predicting high‐risk patients with OSF. Conclusion The notable biomarkers in our present study were Ki67 and p16 showing significantly different expression levels between the transformation and non‐transformation groups. With the identification of high‐risk patients with OSF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSF.