Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential impact of circulating tumor cells on disease recurrence and survivals in patients with head and neck squamous cell carcinomas: An updated meta-analysis

Purpose The prognostic impact of circulating tumor cells (CTC) on disease recurrence, progression and survivals in patients with head and neck squamous cell carcinoma (HNSCC) has not been adequately described. The objective of this study was to determine the impacts of the presence of CTC on loco-regional recurrence and survival of HNSCC patients by conducting a systematic review and meta-analysis. Methods A comprehensive search for articles published between 1990 and 2016 was conducted and data from these studies were extracted, using the MEDLINE, Cochrane Library, and EMBASE databases. The main outcomes were overall survival (OS) and recurrence-free survival (RFS) of HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. The quality of the studies, heterogeneity and publication bias were assessed with the appropriate statistical methods. Results Six eligible studies with 429 patients were identified. The presence of CTC was significantly associated shorter RFS (HR = 4.88 [95%CI: 1.93–12.35], P < 0.001). However, it could not predict patients’ OS (HR = 1.92 [95%CI: 0.93–3.96], P = 0.078). The following analyses using univariable values of each study also made the similar results (HR = 1.70 [95%CI: 0.83–3.45] for OS, HR = 3.79 [95%CI: 2.02–7.13] for RFS). Heterogeneity and publication bias were not significant, except one enrolled study. Conclusions The presence of CTC is not a significant prognostic indicator for OS of patients with HNSCC, although it could reflect the outcomes of loco-regional disease.
How well do activity monitors estimate energy expenditure? A systematic review and meta-analysis of the validity of current technologies

Objective To determine the accuracy of wrist and arm-worn activity monitors’ estimates of energy expenditure (EE). Data sources SportDISCUS (EBSCOHost), PubMed, MEDLINE (Ovid), PsycINFO (EBSCOHost), Embase (Ovid) and CINAHL (EBSCOHost). Design A random effects meta-analysis was performed to evaluate the difference in EE estimates between activity monitors and criterion measurements. Moderator analyses were conducted to determine the benefit of additional sensors and to compare the accuracy of devices used for research purposes with commercially available devices. Eligibility criteria We included studies validating EE estimates from wrist-worn or arm-worn activity monitors against criterion measures (indirect calorimetry, room calorimeters and doubly labelled water) in healthy adult populations. Results 60 studies (104 effect sizes) were included in the meta-analysis. Devices showed variable accuracy depending on activity type. Large and significant heterogeneity was observed for many devices (I2 >75%). Combining heart rate or heat sensing technology with accelerometry decreased the error in most activity types. Research-grade devices were statistically more accurate for comparisons of total EE but less accurate than commercial devices during ambulatory activity and sedentary tasks. Conclusions EE estimates from wrist and arm-worn devices differ in accuracy depending on activity type. Addition of physiological sensors improves estimates of EE, and research-grade devices are superior for total EE. These data highlight the need to improve estimates of EE from wearable devices, and one way this can be achieved is with the addition of heart rate to accelerometry. PROSPEROregistration number CRD42018085016.
The molecular structure of Schistosoma mansoni PNP isoform 2 provides insights into the nucleoside selectivity of PNPs

Purine nucleoside phosphorylases (PNPs) play an important role in the blood fluke parasite Schistosoma mansoni as a key enzyme of the purine salvage pathway. Here we present the structural and kinetic characterization of a new PNP isoform from S. mansoni, named as SmPNP2. Screening of different ligands using a thermofluorescence approach indicated cytidine and cytosine as potential ligands. The binding of cytosine was confirmed by isothermal titration calorimetry, with a KD of 27 μM, and kinetic parameters for cytidine catalysis were obtained by ITC resulting in a KM of 76.3 μM. SmPNP2 also displays catalytic activity against inosine and adenosine, making it the first described PNP with robust catalytic activity towards both pyrimidines and purines. Crystallographic structures of SmPNP2 with different ligands were obtained and comparison of these structures with the previously described S. mansoni PNP (SmPNP1) provided clues for the unique capability of SmPNP2 to bind pyrimidines. When compared with the structure of SmPNP1, substitutions in the vicinity of SmPNP2 active site alter the architecture of the nucleoside base binding site allowing an alternative binding mode for nucleosides, with a 180° rotation from the canonical binding mode. The remarkable plasticity of this binding site deepens the understanding of the correlation between structure and nucleotide selectivity, offering new ways to analyses PNP activity. Author Summary Schistosoma mansoni is a human parasite dependent on purine salvage for purine bases supply. Purine nucleoside phosphorylase (PNP) is a key enzyme in this pathway. It carries two PNP isoforms, one previously characterized (SmPNP1) and one unknown (SmPNP2). Here we present the crystallographic structure of SmPNP2 and its complex with cytosine, cytidine, ribose-l-phosphate, adenine, hypoxanthine, and tubercidin. Cytidine and cytosine were identified as ligands of SmPNP2 using a thermofluorescence approach. Binding of cytosine was proven by Isothermal Titration Calorimetry (ITC) and cytidine, inosine, and adenosine kinetic parameters were also obtained. Purine bases showed different binding in the active site, rotated 180° from the canonical binding mode. It’s the first report showing a Low Molecular Mass PNP capable of catalyzing both types of nucleotide bases. The SmPNP2 odd behavior sheds a new light on the Schistosoma mansoni’s life cycle metabolic adaptation.
Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

OBJECTIVE: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer. METHODS: In the present study, 200 individuals were separated into three groups: (i) 72 women constituting the control group who were selected according to rigorous and well-established criteria; (ii) 56 patients with benign breast tumors; and (iii) 72 patients with malignant breast cancers of different clinical stages. The miR-195 and let-7a expression levels in serum were evaluated by real-time PCR. The results were assessed alone and in combination, and the analysis included an estimation of sensitivity and specificity in ROC curves. RESULTS: Compared with the benign and control groups, both microRNAs were downregulated in the malignant breast cancer patient group. Compared with the malignant group, the combination of both biomarkers in the control and benign groups showed good sensitivity and specificity in the serum with AUCs of 0.75 and 0.72, respectively. The biomarker combination for the control group versus the malignant group exhibited a better sensitivity and specificity than for the benign group versus the malignant group. CONCLUSION: These findings support the evidence that the analysis of miR-195 and let-7a can be used as a non-invasive biomarker for breast cancer detection.
Cord Blood Erythropoietin and Hepcidin Reflect Lower Newborn Iron Stores due to Maternal Obesity during Pregnancy

Abstract Objective Obesity during pregnancy impedes fetal iron endowment. In adults, both iron depletion and hypoxia stimulate erythropoietin (Epo) production, while hepcidin, the primary iron regulator, is inhibited by Epo and stimulated by obesity. To understand this relationship in fetuses, we investigated obesity, inflammation, and fetal iron status on fetal Epo and hepcidin levels. Study Design Epo, hepcidin, C-reactive protein (CRP), and ferritin levels were measured in 201 newborns of 35 to 40 weeks' gestation with historical risk factors for a low fetal iron endowment, including half with maternal obesity. Results Epo was unrelated to fetal size, but Epo was directly related to maternal body mass index (BMI; kg/m2) (p < 0.03) and CRP (p < 0.0005) at delivery. Epo levels were twice as likely to be elevated (≥50 IU/L) while comparing the lowest quartile of ferritin with the upper three quartiles (p < 0.01). Hepcidin was directly related to ferritin (p < 0.001) and indirectly related to maternal BMI (p < 0.015), but BMI became nonsignificant when undergoing multivariate analysis. Hepcidin was unrelated to Epo. Conclusion Although some of the fetal responses involving Epo were similar to adults, we did not find a hepcidin–Epo relationship like that of adults, where fetal liver is the site of both hepcidin and Epo production.
The amorphous nature of agile: no one size fits all

Purpose This paper aims to investigate the extent to which newly agile organizations followed 2001’s Agile Manifesto, especially in terms of the 12 principles of the agile approach, as included in the Manifesto. Design/methodology/approach The authors conducted in-depth case studies of groups in three large business organizations that had recently adopted agile. Two researchers spent one day at each site, attending daily standups and conducting interviews with managers, developers and customers. Findings Across the three organizations, developers were faithful to two agile principles: the primacy of delivering valuable software continually and regular reflections on the process with an eye toward improvement. The developers were uniformly unfaithful to the principle that requires face-to-face communication. Each organization varied in their adherence to the remaining nine principles. Obstacles to faithful adoption included the experience of the organization with agile, the extent to which the industry was regulated and the extent to which developers and customers were physically dispersed. Originality/value While past research on agile development is extensive, this paper examines perspectives on the method and its adoption through the lens of the original Agile Manifesto and its 12 principles. The principles were grouped into three broader categories – software delivery, people and process – to provide additional insights and to sharpen the analysis.
Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models

The plasma membrane is a highly complex multicomponent system that is central to the functioning of cells. Cholesterol, a key lipid component of the plasma membrane, promotes the formation of nanodomains. These nanodomains are often correlated across the two membrane leaflets, but the underlying physical mechanism remains unclear. Using coarse-grained molecular dynamics simulations, we investigate the influence of cholesterol flip-flop on membrane properties, in particular, the interleaflet coupling of cholesterol-enriched domains. We show that the cholesterol density correlation between the leaflets of an average mammalian plasma membrane is significantly reduced by suppressing interleaflet cholesterol population. Our results suggest an amplifying role of cholesterol in signal transduction across the leaflets.
Knowledge, stigma, health seeking behaviour and its determinants among patients with post kalaazar dermal leishmaniasis, Bihar, India

Background Lesishmaniasis is a neglected tropical disease endemic in Bihar, India. Inappropriate health seeking behaviour of post kala-azar dermal leishmaniasis (PKDL) patients may increase the disease duration, severity and transmissibility. Simultaneously, lack of knowledge and perceived stigma may also increase the length of delay in receiving treatment. This ultimately effects the kala-azar elimination program. Methods A cross sectional study was conducted in 120 confirmed PKDL patients, aged 18 years and older. Data related to knowledge and health seeking behaviour was collected by a pre-tested questionnaire. EMIC stigma scale was used for assessing the perceived stigma. Patients were personally interviewed after taking informed consent. Data analysis was done by using SPSS 16 software. Results The time between appearance of symptoms and first medical consultation (patient delay) ranged from 15 days to 5475 days (15 years) with a median of 285 days. The time between first medical consultations to onset of specific treatment (system delay) ranged from 2 to 5475 days with a median of 365 days. Many patients approached first to quacks (8.4%), homeopathic and ayurvedic practitioners (25.8%) upon recognition of symptoms. Majority of the patients (68.3%) had poor knowledge about PKDL and its vector. Type of skin lesions and gender had significant association with patient delay and system delay respectively (p<0.05). Distance to primary health centre (PHC) had significant association with patients delay as well as system delay (p<0.05). Patients with younger age, unmarried and polymorphic lesions had higher stigma (p<0.05). Patients with PKDL feel stigmatized in different areas. Conclusion PKDL treatment delays were unacceptably high and patients had poor knowledge compounded with feelings of stigmatization. To reduce the delay, a system may be evolved to establish some sort of public-private collaboration, besides awareness programs should be tailored, and implemented for improving the patient education regarding the disease and its linkage with VL.
Disproportionate feedback interactions govern cell-type specific proliferation in mammalian cells

In mammalian cells, the critical decision to maintain quiescence over proliferation commitment in and around the G1-S transition depends on more than one intertwined feedback interaction, and is highly cell-type dependent. However, the precise role played by these individual feedback regulations, in order to generate such diverse nature of proliferation commitment, is still poorly understood. Herein, we propose a generic mathematical model of G1-S transition in mammalian cells that not only reconciles distinct single cell experimental observations in a cell-type specific manner, but also makes experimentally testable non-intuitive predictions. Intriguingly, The model analysis reveals that the feedback motifs responsible for the G1-S transition act in a disparate fashion to organize the cell-type specific proliferation response in different mammalian cells. The proposed model, in principle, can be effectively tuned to explore proliferation dynamics in a cell-type specific way to gain crucial insights about novel therapeutic intervention to prevent unwanted cellular proliferation.
Bridging Cancer Biology with the Clinic: Comprehending and Exploiting IDH Gene Mutations in Gliomas

Isocitrate dehydrogenases 1 and 2 (IDH1/2) are enzymes that play a major role in the Krebs cycle. Mutations in these enzymes are found in the majority of lower gliomas and secondary glioblastomas, but also in myeloid malignancies and other cancers. IDH1 and IDH2 mutations are restricted to specific arginine residues in the active site of the enzymes and are gain-of-function, i.e. they confer a neomorphic enzyme activity resulting in the accumulation of D-2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite causing profound metabolic dysregulation which, among others, results in methylator phenotypes and in defects in homologous recombination repair. In this review, we summarize current knowledge regarding the function of normal and mutated IDH, explain the possible mechanisms through which these mutations might drive malignant transformation of progenitor cells in the central nervous system, and provide a comprehensive review of potential treatment strategies for IDH-mutated malignancies, focusing on gliomas.
‘There is still so much inside’: The impact of personalised reminiscence, facilitated by a tablet device, on people living with mild to moderate dementia and their family carers

The aim of this qualitative study was to explore the impact of a home-based, personalised reminiscence programme facilitated through an iPad app on people living with dementia and their family carers. Semi-structured interviews were used to collect data from 15 people living with dementia and 17 family carers from a region of the United Kingdom. The interviews were recorded, transcribed and analysed using thematic analysis. Six key themes emerged related to usability (‘It’s part of my life now’); revisiting the past (‘Memories that are important to me’); home use (‘It was homely’); impact on the person living with dementia (‘It helped me find myself again’); gains and abilities (‘There is still so much inside’) and impact on relationships (‘It’s become very close’). These themes highlighted the impact of the reminiscence experience at an individual and relationship level for people living with dementia and their carers. The reminiscence experience also appeared to facilitate the development of new insights among participants that emphasised abilities and gains rather than disabilities and losses. The significance of personal memories was a core theme although this was not without its challenges, particularly if memories were distressing. The reminiscence experience was differentiated by individual roles. Carers tended to become more relationship-focused, whereas people living with dementia highlighted the significance of learning new skills. The study concluded that individual specific reminiscence supported by an iPad app can have a positive impact on people living with dementia and their carers at an individual and relationship level.
Monovalent cation transporters at the plasma membrane in yeasts

Maintenance of proper intracellular concentrations of monovalent cations, mainly sodium and potassium, is a requirement for survival of any cell. In the budding yeast Saccharomyces cerevisiae, monovalent cation homeostasis is determined by the active extrusion of protons through the Pma1 H+‐ATPase (reviewed in another chapter of this issue), the influx and efflux of these cations through the plasma membrane transporters (reviewed in this chapter), and the sequestration of toxic cations into the vacuoles. Here, we will describe the structure, function, and regulation of the plasma membrane transporters Trk1, Trk2, Tok1, Nha1, and Ena1, which play a key role in maintaining physiological intracellular concentrations of Na+, K+, and H+, both under normal growth conditions and in response to stress.
Ensemble statistics accessed through proxies: Range heuristic and dependence on low-level properties in variability discrimination

People can quickly and accurately compute not only the mean size of a set of items but also the size variability of the items. However, it remains unknown how these statistics are estimated. Here we show that neither parallel access to all items nor random subsampling of just a few items is sufficient to explain participants' estimations of size variability. In three experiments, we had participants compare two arrays of circles with different variability in their sizes. In the first two experiments, we manipulated the congruency of the range and variance of the arrays. The arrays with congruent range and variability information were judged more accurately, indicating the use of range as a proxy for variability. Experiments 2B and 3 showed that people also are not invariant to low- or mid-level visual information in the arrays, as comparing arrays with different low-level characteristics (filled vs. outlined circles) led to systematic biases. Together, these experiments indicate that range and low- or mid-level properties are both utilized as proxies for variability discrimination, and people are flexible in adopting these strategies. These strategies are at odds with the claim of parallel extraction of ensemble statistics per se and random subsampling strategies previously proposed in the literature.
The activation of spatial antecedents from overt pronouns in american sign language

Abstract Two experiments are presented which investigate the processing of pronominal reference in American Sign Language (ASL). Pronominal reference in ASL involves the association of nominals with loci in signing space, and pronouns are directed towards these spatial loci. Deaf subjects viewed videotaped ASL sentences with and without pronouns and responded to probe signs presented either immediately after the pronoun or after a 1000-msec delay. In both experiments, we found evidence for referent activation by an overt pronoun: responses to referent probes were faster when a pronoun was present in the sentence. Experiment 1 indicated that pronoun activation was not immediate, and there was no strong evidence for the inhibition of non-referents. Experiment 2 was designed to investigate whether the pronoun also activated a representation of the spatial locus associated with the referent. If the pronoun activates a spatial representation, we predicted that spatially incongruent probes would produce a great.
Task Scheduling in Real Time Systems with Energy Harvesting and Energy Minimization

Energy is a major concern in battery operated real time devices (e.g. sensor nodes situated in remote areas) as battery life is solely responsible for the functioning of such devices. For such systems to work continuously and successively a regular source of energy is required. The lifetime of such systems can be increased by reducing the energy consumption and increasing energy production. Dynamic Voltage Scaling (DVS) scheduling algorithms is an existing approach for minimizing energy consumption. Energy harvesting is used for energy production (as a source of energy) and Earliest Deadline First (EDF) is an existing traditional approach for task scheduling in real time systems. In this paper, we propose a real time task scheduling algorithm using both DVS and EDF with energy harvesting. The proposed approach is designed to reduce energy consumption and enhanced the system lifetime. Our experimental results show that the proposed approach increases the task feasibility and reduces the energy consumption to increase the system lifetime.