Miracle-dz/UniFAR-FTUs huggingface dataset:
Preferential star strand biogenesis of pre‐miR‐24‐2 targets PKC‐alpha and suppresses cell survival in MCF‐7 breast cancer cells

microRNAs (miRNA) are regulators of cellular pathways and alterations of normal miRNA expression levels have been shown to increase tumorigenesis. miR‐24 has been demonstrated as having both tumor suppressive and oncogenic properties depending on cell context. Here, we demonstrate a possible role for pre‐miR‐24‐2 as a tumor suppressor in the MCF‐7 breast cancer cell line through the preferential processing of mature miR‐24‐2* over miR‐24. Specifically, we show that the ectopic expression of miR‐24‐2* in MCF‐7 breast cancer cells results in a suppression of cellular survival both in vivo and in vitro. Notably, the overexpression of miR‐24‐2* results in a dampening of cell survival through the targeted suppression of PKCα. In addition, a similar biological change is observed in vivo where MCF‐7 cells overexpressing pre‐miR‐24‐2 have decreased tumorigenicity and tumor incidence. Taken together our data demonstrate that when overexpressed biogenesis of the pre‐miR‐24‐2 favors miR‐24‐2* in the MCF‐7 breast cancer cell line and suggests a tumor suppressive role for miR‐24‐2* observed through the inhibition of PKCα‐mediated cellular survival. © 2013 Wiley Periodicals, Inc.
Modeling Semicontinuous Longitudinal Expenditures: A Practical Guide.

OBJECTIVE To compare different strategies for analyzing longitudinal expenditure data that have a point mass at $0. We provide guidance on parameter interpretation, research questions, and model selection. DATA SOURCES, STUDY DESIGN, AND DATA COLLECTION One-part models, uncorrelated two-part models, correlated conditional two-part (CTP) models, and correlated marginalized two-part (MTP) models have been proposed for longitudinal expenditures that often exhibit a large proportion of zeros and a distribution of continuous, highly right-skewed positive values. Guidance on implementing and interpreting each of these model is illustrated with an example of longitudinal (2000-2003) specialty care expenditures of veterans with hypertension, drawn from Veterans Administration data. PRINCIPAL FINDINGS The four strategies answer different research questions, are appropriate for different structures of data, and provide different results. If there is a point mass at $0, then the MTP model may be most useful if the primary interest is in mean expenditures of the entire population. A CTP model may be most useful if the primary interest is in the level of expenditures conditional on them being incurred. CONCLUSIONS Researchers should consider which modeling strategy for longitudinal expenditure outcomes is both consistent with research aims and appropriate for the data at hand.
Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without pre‐operative blood transfusion

Pre‐operative red blood cell (RBC) transfusions are often recommended for patients with sickle cell disease (SCD) who require elective surgery under general anesthesia. However, definitive randomized studies demonstrating the benefit of transfusions in this setting have not been conducted. In particular, the merits of transfusion prior to minor or low‐risk surgical procedures in children with SCD have not been demonstrated.
Prospective Study of Sentinel Lymph Node Biopsy Without Further Pelvic Lymphadenectomy in Patients With Sentinel Lymph Node–Negative Cervical Cancer

Objective The aim of the present study was to evaluate the incidence of lymphedema and cancer recurrence rate in patients with cervical cancer who undergo sentinel lymph node (SLN) biopsy alone in the absence of SLN metastases. Patients and Methods The study included 35 consecutive patients with cervical cancer scheduled for radical hysterectomy at Tohoku University Hospital between May 2006 and July 2009. All patients had International Federation of Gynecology and Obstetrics stages IA1 to IIA1 disease. Patients in whom SLNs were detected unilaterally or not detected and/or whose lymph nodes were diagnosed intraoperatively as positive metastasis underwent systemic pelvic lymphadenectomy. Patients who were found negative for SLN metastasis did not undergo further pelvic lymphadenectomy. Results The mean number of detected SLNs was 4.1 (range, 1–11). True lymph node metastasis could be detected in 11 (31%) of the 35 cases. Intraoperative frozen section identified correctly in 8 of 11 metastatic patients. Twenty-three patients underwent SLN biopsy alone without systematic pelvic lymphadenectomy. None of the 23 patients diagnosed with negative SLNs have experienced a lymph node recurrence in the pelvic cavity. New symptomatic lower extremity lymphedema was identified in 2 (8.7%) of the 23 patients who underwent SLN biopsy alone and in 5 (42%) of 12 patients who underwent systematic lymphadenectomy. Conclusion Radical hysterectomy with SLN biopsy alone seems to be a safe and effective strategy for detection of lymph node metastasis and for reducing the number of patients with lower extremity lymphedema, but a more convenient and sensitive procedure for intraoperative diagnosis needs to be established.
Changes in metabolism affect expression of ABC transporters through ERK5 and depending on p53 status

Changes in metabolism require the efflux and influx of a diverse variety of metabolites. The ABC superfamily of transporters regulates the exchange of hundreds of substrates through the impermeable cell membrane. We show here that a metabolic switch to oxidative phosphorylation (OXPHOS), either by treating cells with dichloroacetate (DCA) or by changing the available substrates, reduced expression of ABCB1, ABCC1, ABCC5 and ABCG2 in wild-type p53-expressing cells. This metabolic change reduced histone changes associated to active promoters. Notably, DCA also inhibited expression of these genes in two animal models in vivo. In contrast, OXPHOS increased the expression of the same transporters in mutated (mut) or null p53-expressing cells. ABC transporters control the export of drugs from cancer cells and render tumors resistant to chemotherapy, playing an important role in multiple drug resistance (MDR). Wtp53 cells forced to perform OXPHOS showed impaired drug clearance. In contrast mutp53 cells increased drug clearance when performing OXPHOS. ABC transporter promoters contain binding sites for the transcription factors MEF2, NRF1 and NRF2 that are targets of the MAPK ERK5. OXPHOS induced expression of the MAPK ERK5. Decreasing ERK5 levels in wtp53 cells increased ABC expression whereas it inhibited expression in mutp53 cells. Our results showed that the ERK5/MEF2 pathway controlled ABC expression depending on p53 status.
Observer ratings of health and sickness: can other people tell us anything about our health that we don't already know?

After administering interviews covering health conditions, physical limitations, optimism, and affect to 851 older adults, interviewers rated the health and sickness of the interviewees. Observers' ratings of health and sickness were more highly correlated with the severity of participants' self-reported health conditions than were participants' self-ratings of health. This finding is likely attributable to participants' self-ratings of health being more highly correlated with their optimism and positive affect than the observers' ratings. Participants rated as sicker and less healthy at baseline were at a 3 times greater risk for mortality over 114 months. This association was independent of participants' self-rated health as well as demographics, self-reported health conditions, years of smoking, physical limitations, body mass index, optimism, and affect.
Identification of a Novel Domain of Ras and Rap1 That Directs Their Differential Subcellular Localizations*

The small GTPase Ha-Ras and Rap1A exhibit high mutual sequence homology and share various target proteins. However, they exert distinct biological functions and exhibit differential subcellular localizations; Rap1A is predominantly localized in the perinuclear region including the Golgi apparatus and endosomes, whereas Ha-Ras is predominantly localized in the plasma membrane. Here, we have identified a small region in Rap1A that is crucial for its perinuclear localization. Analysis of a series of Ha-Ras-Rap1A chimeras shows that Ha-Ras carrying a replacement of amino acids 46-101 with that of Rap1 exhibits the perinuclear localization. Subsequent mutational studies indicate that Rap1A-type substitutions within five amino acids at positions 85-89 of Ha-Ras, such as NNTKS85-89TAQST, NN85-86TA, and TKS87-89QST, are sufficient to induce the perinuclear localization of Ha-Ras. In contrast, substitutions of residues surrounding this region, such as FAI82-84YSI and FEDI90-93FNDL, have no effect on the plasma membrane localization of Ha-Ras. A chimeric construct consisting of amino acids 1-134 of Rap1A and 134-189 of Ha-Ras, which harbors both the palmitoylation and farnesylation sites of Ha-Ras, exhibits the perinuclear localization like Rap1A. Introduction of a Ha-Ras-type substitution into amino acids 85-89 (TAQST85-89NNTKS) of this chimeric construct causes alteration of its predominant subcellular localization site from the perinuclear region to the plasma membrane. These results indicate that a previously uncharacterized domain spanning amino acids 85-89 of Rap1A plays a pivotal role in its perinuclear localization. Moreover, this domain acts dominantly over COOH-terminal lipid modification of Ha-Ras, which has been considered to be essential and sufficient for the plasma membrane localization.
How does EuroSCORE II perform in UK cardiac surgery; an analysis of 23 740 patients from the Society for Cardiothoracic Surgery in Great Britain and Ireland National Database

Objective The original EuroSCORE models are poorly calibrated for predicting mortality in contemporary cardiac surgery. EuroSCORE II has been proposed as a new risk model. The objective of this study was to assess the performance of EuroSCORE II in UK cardiac surgery. Design A cross-sectional analysis of prospectively collected multi-centre clinical audit data, from the Society for Cardiothoracic Surgery in Great Britain and Ireland Database. Setting All NHS hospitals, and some UK private hospitals performing adult cardiac surgery. Patients 23 740 procedures at 41 hospitals between July 2010 and March 2011. Main outcome measures The main outcome measure was in-hospital mortality. Model calibration (Hosmer–Lemeshow test, calibration plot) and discrimination (area under receiver operating characteristic curve) were assessed in the overall cohort and clinically defined sub-groups. Results The mean age at procedure was 67.1 years (SD 11.8) and 27.7% were women. The overall mortality was 3.1% with a EuroSCORE II predicted mortality of 3.4%. Calibration was good overall but the model failed the Hosmer–Lemeshow test (p=0.003) mainly due to over-prediction in the highest and lowest-risk patients. Calibration was poor for isolated coronary artery bypass graft surgery (Hosmer–Lemeshow, p<0.001). The model had good discrimination overall (area under receiver operating characteristic curve 0.808, 95% CI 0.793 to 0.824) and in all clinical sub-groups analysed. Conclusions EuroSCORE II performs well overall in the UK and is an acceptable contemporary generic cardiac surgery risk model. However, the model is poorly calibrated for isolated coronary artery bypass graft surgery and in both the highest and lowest risk patients. Regular revalidation of EuroSCORE II will be needed to identify calibration drift or clinical inconsistencies, which commonly emerge in clinical prediction models.
Realized Volatility Forecasting of Agricultural Commodity Futures Using Long Memory and Regime Switching

We investigate the dynamic properties of the realized volatility of five agricultural commodity futures by employing the high-frequency data from Chinese markets and find that the realized volatility exhibits both long memory and regime switching. To capture these properties simultaneously, we utilize a Markov switching autoregressive fractionally integrated moving average (MS-ARFIMA) model to forecast the realized volatility by combining the long memory process with regime switching component, and compare its forecast performances with the competing models at various horizons. The full-sample estimation results show that the dynamics of the realized volatility of agricultural commodity futures are characterized by two levels of long memory: one associated with the low-volatility regime and the other with the high-volatility regime, and the probability to stay in the low-volatility regime is higher than that in the high-volatility regime. The out-of-sample volatility forecast results show that the combination of long memory with switching regimes improves the performance of realized volatility forecast, and the proposed model represents a superior out-of-sample realized volatility forecast to the competing models. Copyright © 2016 John Wiley & Sons, Ltd.
PR‐Set7‐mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression

Increasing evidence indicates that the post‐translational modifications of the histone proteins play critical roles in all eukaryotic DNA‐templated processes. To gain further biological insights into two of these modifications, the mono‐ and trimethylation of histone H4 lysine 20 (H4K20me1 and H4K20me3), ChIP‐chip experiments were performed to identify the precise genomic regions on human chromosomes 21 and 22 occupied by these two modifications. Detailed analysis revealed that H4K20me1 was preferentially enriched within specific genes; most significantly between the first ∼5% and 20% of gene bodies. In contrast, H4K20me3 was preferentially targeted to repetitive elements. Among genes enriched in H4K20me3, the modification was typically targeted to a small region ∼1 kb upstream of transcription start. Our collective findings strongly suggest that H4K20me1 and H4K20me3 are both physically and functionally distinct. We next sought to determine the role of H4K20me1 in transcription since this has been controversial. Following the reduction of PR‐Set7/Set8/KMT5a and H4K20me1 in cells by RNAi, all H4K20me1‐associated genes analyzed displayed an ∼2‐fold increase in gene expression; H4K20me3‐associated genes displayed no changes. Similar results were obtained using a catalytically dead dominant negative PR‐Set7 indicating that H4K20me1, itself, is essential for the selective transcriptional repression of H4K20me1‐associated genes. Furthermore, we determined that the H4K20me1‐associated DNA sequences were sufficient to nucleate H4K20me1 and induce repression in vivo. Our findings reveal the molecular mechanisms of a mammalian transcriptional repressive pathway whereby the DNA sequences within specific gene bodies are sufficient to nucleate the monomethylation of H4K20 which, in turn, reduces gene expression by half. J. Cell. Biochem. 110: 609–619, 2010. © 2010 Wiley‐Liss, Inc.
Influenza in the United Kingdom 1977–1981

Summary The laboratory surveillance of influenza in the UK has continued to demonstrate the regularity of influenza outbreaks each winter even in the absence of increase in the other indices which reflect the morbidity and mortality associated with influenza. The period of five years from 1976 to 1981 has seen the appearance of a second sub-type of influenza A with the return of the historic H1N1 virus; and the continued circulation of H3N2 concurrently with H1N1 virus. Variants of both these influenza A viruses have been demonstrated as well as further changes in the strains of influenza B virus isolated during this time.
Gendered poverty in peasant households: A case study of northern Mozambique

This dissertation examines the nature and consequences of gendered time poverty in northern Mozambique. Evidence from sub-Saharan Africa indicates that women are more likely to be time poor than men as they bear the double burden of productive and reproductive work in the household. This gender division of labor, dictated by social norms, constrains women’s freedom, agency, and well-being. Based on fieldwork in the Nampula province of Mozambique in 2013 this dissertation examines gender differences in time poverty through both Foster-Greer-Thorbecke (FGT) set of indexes and a measure of work intensity. The analysis shows that women are both more time poor compared to men and they are more likely to experience high levels of work intensity. The investigation of the determinants of time poverty shows that women’s access to economic resources, notably education and assets including land, has no bearing on women’s time poverty, and gender is the main determinant of time poverty. Given women’s critical role in food production and provisioning, the dissertation examines the consequences of unequal gender roles and time poverty of women for household food security and nutrition outcomes. Analysis focuses on the likely adverse effects of unforeseen events, such as illness in the family, on food security of smallholder farming households. The theoretical model and simulations of the model show that an unexpected crisis increases the demand for labor provided by the woman to which most women respond by reducing their work hours on the farm and by reducing their leisure time. The latter outcome results in deterioration of the woman’s labor productivity. Overall, the household suffers a loss in farm production, which is the main source of household’s food consumption. The dissertation contributes both new evidence on gendered time poverty and its consequences and a gendered model of the agricultural household that integrates role of social norms. The findings suggest that the efforts to increase agricultural productivity need not focus exclusively on agricultural aspects. The policy emphasis on reduction of women’s unpaid workload in the short run along with a target to create redistribution of reproductive work in the long run would yield considerable benefits for agricultural sector.
Comparative Review of the Treatment Methodologies of Carotid Stenosis

Abstract The treatment of carotid stenosis entails three methodologies, namely, medical management, carotid angioplasty and stenting (CAS), as well as carotid endarterectomy (CEA). The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) have shown that symptomatic carotid stenosis greater than 70% is best treated with CEA. In asymptomatic patients with carotid stenosis greater than 60%, CEA was more beneficial than treatment with aspirin alone according to the Asymptomatic Carotid Atherosclerosis (ACAS) and Asymptomatic Carotid Stenosis Trial (ACST) trials. When CAS is compared with CEA, the CREST resulted in similar rates of ipsilateral stroke and death rates regardless of symptoms. However, CAS not only increased adverse effects in women, it also amplified stroke rates and death in elderly patients compared with CEA. CAS can maximize its utility in treating focal restenosis after CEA and patients with overwhelming cardiac risk or prior neck irradiation. When performing CEA, using a patch was equated to a more durable result than primary closure, whereas eversion technique is a new methodology deserving a spotlight. Comparing the three major treatment strategies of carotid stenosis has intrinsic drawbacks, as most trials are outdated and they vary in their premises, definitions, and study designs. With the newly codified best medical management including antiplatelet therapies with aspirin and clopidogrel, statin, antihypertensive agents, strict diabetes control, smoking cessation, and life style change, the current trials may demonstrate that asymptomatic carotid stenosis is best treated with best medical therapy. The ongoing trials will illuminate and reshape the treatment paradigm for symptomatic and asymptomatic carotid stenosis.
Babesia bovis Merozoite Surface Antigen 1 and Rhoptry-Associated Protein 1 Are Expressed in Sporozoites, and Specific Antibodies Inhibit Sporozoite Attachment to Erythrocytes

ABSTRACT We examined Babesia bovis sporozoites for the expression of two molecules, merozoite surface antigen 1 (MSA-1) and rhoptry-associated protein 1 (RAP-1), that are postulated to be involved in the invasion of host erythrocytes. Both MSA-1 and RAP-1 were transcribed and expressed in infectious sporozoites. Importantly, monospecific MSA-1 and RAP-1 antisera each inhibited sporozoite invasion of erythrocytes in vitro. This is the first identification of antigens expressed in Babesia sp. sporozoites and establishes that, at least in part, sporozoites and merozoites share common targets of antibody mediated inhibition of erythrocyte invasion.
Preventing community-wide transmission of Cryptosporidium: a proactive public health response to a swimming pool-associated outbreak – Auglaize County, Ohio, USA

SUMMARY The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4–∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.
The physiological and morphological phenotype of a yeast mutant resistant to the quaternary ammonium salt N-(dodecyloxycarboxymethyl)-N,N,N-trimethyl ammonium chloride

We investigated the action of the quaternary ammonium salt (QAS) called IM (N-(dodecyloxycarboxymethyl)-N,N,N-trimethyl ammonium chloride) on Saccharomyces cerevisiae yeast cells. Changes in the yeast cell ultrastructure were confirmed by electron microscopy. We treated resistant mutant cells with QAS, and confirmed destruction of the mutant cytoplasm, an increase in the thickness of the cell wall, separation of the cell wall from the cytoplasm, and the accumulation of numerous lipid droplets. We also observed a relatively high production of lipids in the cells of the parental wild-type strain Σ1278b and in its IM-resistant (IMR) mutant in the presence of the QAS. The IMR mutant showed increased sensitivity to CaCl2 and SDS, and resistance to ethidium bromide, chloramphenicol, erythromycin and osmotic shock. It also tolerated growth at low pH. We suggest that the resistance to IM could be connected with the level of permeability of the cell membrane because the IMR mutant was sensitive to this compound in vivo in the presence of SDS and guanidine hydrochloride, which cause increased permeability of the cell plasma membrane.