Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx

Given the crucial role of Mouse double minute 4 (MDM4) oncoprotein in p53 pathway, single nucleotide polymorphisms (SNPs) could serve as such biomarkers for prediction of SCCOP recurrence. Thus, we investigated associations between three tagging putatively functional variants of MDM4, two in the 3′ untranslated region of 3′ UTR [rs11801299 (NC_000001.10:g.204529084G>A) and rs10900598(NC_000001.10:g.204525568G>T)] and one in intron 1 [rs1380576(NC_000001.10:g.204488278G>C)], and recurrence risk of SCCOP in 1,008 incident patients. A log‐rank test and multivariable Cox models were used to assess associations. Patients with MDM4‐rs10900598 GT/TT had a worse disease‐free survival (DFS) compared with corresponding GG genotype, while those with rs11801299 AG/AA genotypes had a lower recurrence risk than the cases with rs11801299 GG genotype (both log‐rank, P < 0.001). Multivariable analysis showed that significantly different recurrence risk were found among patients with MDM4‐rs10900598 GT/TT and rs11801299 AG/AA variant genotypes (HR, 2.0, 95% CI, 1.4‐2.9 and HR, 0.4, 95% CI, 0.3‐0.6, respectively) compared with their corresponding common homozygous genotypes. Furthermore, after combining the risk genotypes of the three SNPs, patients among low‐risk group had a significantly lower risk of SCCOP recurrence than those in high‐risk group (HR, 0.2, 95% CI, 0.1‐0.3). The risk for both individual SNPs or combined risk genotypes was restricted to HPV‐positive SCCOP patients. Our findings suggest that the MDM4 polymorphisms may, individually or in combination, confer an independent risk of SCCOP recurrence, particularly in HPV‐positive SCCOP patients. However, larger studies are needed to validate our findings.
An acetylatable lysine controls CRP function in E. coli

Transcriptional regulation is the key to ensuring that proteins are expressed at the proper time and the proper amount. In Escherichia coli, the transcription factor cAMP receptor protein (CRP) is responsible for much of this regulation. Questions remain, however, regarding the regulation of CRP activity itself. Here, we demonstrate that a lysine (K100) on the surface of CRP has a dual function: to promote CRP activity at Class II promoters, and to ensure proper CRP steady state levels. Both functions require the lysine's positive charge; intriguingly, the positive charge of K100 can be neutralized by acetylation using the central metabolite acetyl phosphate as the acetyl donor. We propose that CRP K100 acetylation could be a mechanism by which the cell downwardly tunes CRP‐dependent Class II promoter activity, whilst elevating CRP steady state levels, thus indirectly increasing Class I promoter activity. This mechanism would operate under conditions that favor acetate fermentation, such as during growth on glucose as the sole carbon source or when carbon flux exceeds the capacity of the central metabolic pathways.
Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study.

BACKGROUND There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). OBJECTIVE Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. METHODS We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. RESULTS NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. CONCLUSION This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.
Changing Indications in Penetrating Keratoplasty: A Systematic Review of 34 Years of Global Reporting

Background Penetrating keratoplasty (PK) ranks among the oldest and most common kinds of human tissue transplantation. Based on the hypothesis that reported indications for PK significantly vary between global regions and over time, the present systematic review aimed to provide a thorough overview of global PK indications as reported in peer-reviewed manuscripts. Methods A literature search of PubMed and MEDLINE was conducted to retrieve articles published from January 1980 to May 2014. Indications for PK within 7 global regions were compared using a modified classification system for PK indications and analyzed via multivariate regression. Results A total of 141 publications from 37 countries were included, recording 180 865 PK cases. Postcataract surgery edema was the predominant indication in North America (28.0%) and ranked second in Europe (20.6%), Australia (21.1%), the Middle East (13.6%), Asia (15.5%), and South America (18.6%). Keratoconus was the leading indication in Europe (24.2%), Australia (33.2%), the Middle East (32.8%), Africa (32.4%), and South America (22.8%). It ranked third in North America (14.2%). Keratitis was the primary indication in Asia (32.3%). Fuchs endothelial corneal dystrophy was the fourth most common indication in North America (12.9%) and Europe (10.2%) and fifth in South America (3.8%). Multivariate analysis supported these results and revealed individual regional changes over time. Conclusions Systematic analysis reveals characteristic chronological and regional differences in reported global PK indications. Leading reported indications for PK between 1980 and 2014 were keratoconus (Europe, Australia, the Middle East, Africa, and South America), pseudophakic bullous keratopathy/aphakic bullous keratopathy (North America), and keratitis (Asia).
Acute Effects of Ballistic vs Passive Static Stretching Involved in A Pre-Match Warm-Up Regarding Vertical Jump and Linear Sprint Performance in Soccer Players.

The purpose of this study was to compare the effects of introducing passive static and ballistic stretching in a standard soccer match warm-up. The variables addressed were the Counter Movement Jump (CMJ), Abalakov jump and the 40 m linear sprint. The sample was composed of 33 male subjects, divided in two age groups. U16 and adult players formed the groups, in order to cross check if there were differences between them. Each group was further subdivided into two groups regarding the type of stretching carried out during the stretching phase. Prior to the warm-up, the tests previously described were assessed. In the experimental phase, standard stretching was carried out consisting of: an initial phase in which players had to execute continuous running; a general phase in which players had to make articulate moves; a technical phase, in which players had to execute exercises with the ball; a 5 vs. 5 small sided game was carried out during the tactical phase; and, in the final phase, activation exercises and sprints were carried out by the players. Eventually, the same variables were assessed again once the warm-up was finished. There were no statistically significant differences between the two types of stretching included in the pre-match warm-up. It can be concluded that ballistic and passive static stretching (<10s) did not cause, under these circumstances, any effect in the assessed variables related to soccer performance (linear sprint, CMJ and Abalakov). This has to be considered by coaches when devising soccer related warm-ups.
Obesity and p16INK4A Downregulation Activate Breast Adipocytes and Promote Their Protumorigenicity

ABSTRACT Obesity is increasingly recognized as a risk factor for breast cancer development. However, the molecular basis of obesity-related breast carcinogenesis remains elusive. In this study, we have shown that obesity reduces the level of the tumor suppressor p16INK4A protein in breast adipocytes, which showed active features and strong procarcinogenic potential both in vitro and in orthotopic tumor xenografts compared to mature adipocytes from lean women. Furthermore, obesity triggered epithelial-to-mesenchymal transition (EMT) in breast ductal epithelial cells. Interestingly, specific downregulation of p16INK4A increased the expression/secretion levels of various adipokines, including leptin, and activated breast adipocytes from lean women. Consequently, like breast adipocytes from obese women, p16-deficient adipocytes induced EMT in normal primary breast luminal cells in a leptin-dependent manner and enhanced tumor growth. Additionally, we have shown that p16INK4A negatively controls leptin at the mRNA level through microRNAs 141 and 146b-5p (miR-141 and miR-146b-5p), which bind the leptin mRNA at a specific sequence in the 3′ untranslated region (UTR). These results show that obesity activates breast stromal adipocytes through p16 downregulation, which upregulates leptin and promotes procarcinogenic processes.
Dissection of the experimental outcome of split-protocol

The split-protocol theory was developed for load balancing and quicker data communication. Split-protocol computing paradigm uses web services on geographically distributed web servers on the cloud. A system of large split-servers that form the cloud to handle computing and storage task that would otherwise create a massive CPU utilisation if we work with the traditional individual server. In an earlier paper, we established that the application split-protocol produces higher performance compared to traditional clusters. Based on the necessity, diverse types of split configurations are applied for higher throughput, better response and connection time. The experiential throughput enhancement was within the range 6.5%-25% over non-split systems. This paper examines empirical results split systems to understanding its behaviour compared with non-split systems. Split-protocol was implemented on private cloud for internal data servers of the organisation, not made available to the general public. The split concept emerged from the HTTP/TCP/IP network protocol implementation. The split-system model with given sets of constraints can produce better throughput than conventional equivalent server systems. In this paper, we have presented the analytical model to support a high performance of split-protocol implementation. We have also mathematically evaluated the inherent reliability characteristics of the split-system.
Neuronal Responses across Cortical Field A1 in Plasticity Induced by Peripheral Auditory Organ Damage

The adult auditory cortex is capable of a plastic reorganization of its tonotopic map after damage to restricted parts of the cochlear sensory epithelium. We examine the precise conditions of cochlear damage required to demonstrate such plasticity in the primary auditory cortex (A1) of the cat and the changes observed in neuronal responses in the A1 which has reorganized in plasticity of the tonotopic map. From these data we attempt to predict the conditions required for similar plasticity to occur in humans after coachlear damage.
A neural network based place recognition technique for a crowded indoor environment

Place recognition in a crowded and cluttered environment is a challenging task due to its dynamic characteristics such as moving obstacles, varying lighting conditions and occlusions. This work presents a robust place recognition technique that could be applied into a similar environment, by combining well known Bag of Words technique with a feedforward neural network. The feedforward neural network we use have three layers with a single hidden layer and it relies on rectifier and softmax activation functions. We employ cross entropy function to model the cost of our neural network and utilize Adam algorithm for minimizing this cost at the training phase. The output layer with softmax activation in the neural network, produces a vector of probabilities which represent the likelihood of test image being captured from a given region. These values are further improved by incorporating a transition matrix which is based on the building layout. We have evaluated our neural network based place recognition technique with data collected from a crowded indoor shopping mall and promising results have been observed by this approach. We also have analyzed the behavior of neural network for changes in hyper-parameters and presented the results.
Orientation and mobility aids for individuals with blindness: Verbal description vs. audio-tactile map

ABSTRACT Individuals with visual impairment face significant challenges traveling in the physical environment. Independent movement is directly connected to the quality of someone’s life, and thus, orientation and mobility issues are always listed among the top priorities of research in the field. The aim of the present research was to examine the level of accuracy of the cognitive map developed through the use of a verbal description versus the cognitive map developed using an audio-tactile map. A comparison of the effectiveness of the two mobility aids in detecting specific points of interest in the physical environment was an objective of the research. The procedure involved the study of a map using the two mobility aids, and an assessment through the transfer to the corresponding physical environment. The results suggest that an individual with visual impairment can acquire and use a functional cognitive map through the use of an audio-tactile map, while relying on a verbal description entails greater difficulty in detecting specific points of interest when he/she comes into the physical environment.
TBF and SFQ performance analysis using AODV UU on wireless ad-hoc network implementation

Several traffic control algorithms on Queueing Discipline (qdisc) has been proposed to improve the ability qdisc in the variety of network applications. This paper has implemented two methods of queueing discipline, which are classless queueing Token Bucket Filter (TBF) and Stochastic Fair Queueing (SFQ). These qdisc were implemented by using Ad hoc On-Demand Distance Vector (AODV) protocol in several static-mobile and hop scenario over wireless ad-hoc network. In addition, we also examined the effect of tuning the parameters of each qdisc to the performance of TBF and SFQ, which perturb and quantum for SFQ, rate and burst for TBF. Based on the gained insight, both TBF and SFQ have better performance in static scenario. Tuning parameters on the value and specific scenario is quite influential in SFQ and TBF performance.
Highlights of the ESPEN-ESPGHAN-ECFS Guidelines on Nutrition Care for Infants and Children With Cystic Fibrosis

From the Department o University Medical C enterology and Nutri Children’s Hospital Z Ca’ Granda, Ospedal Studi di Milano, Milan Ghent University Ho Unit, St James’ Univ Hygiene, Faculty of P University of Varna, Gastroenterology, He Center, Princess Eliz University Childre Germany, the yyDepa Institute, Novum, Stoc The Leeds Children’s and Clinical Nutrition Nice Sophia-Antipolis Address correspondence MBBS, Department o University Medical (e-mail: michaelwil@ The authors have no con Copyright # 2016 by E Hepatology, and Nut Gastroenterology, He DOI: 10.1097/MPG.0000
Mdm2 Splice isoforms regulate the p53/Mdm2/Mdm4 regulatory circuit via RING domain-mediated ubiquitination of p53 and Mdm4

ABSTRACT p53 is regulated by heterodimer E3 ligase Mdm2-Mdm4 via RING domain interaction. Mdm2 transcripts undergo alternative splicing, and Mdm2 splice isoforms are increased in cancer and induced by DNA damage. Although 2 major Mdm2 splice isoforms that do not bind to p53 were reported to impact the p53 pathway, the underlying biochemical mechanisms were not understood. Here, we show that these Mdm2 splice isoforms ubiquitinate Mdm2 and Mdm4 in vivo and regulate the activity of Mdm2-Mdm4 E3 complex in cells. The Mdm2 isoforms are capable of promoting p53 ubiquitination in the absence of Mdm2 or Mdm4. The 2 isoforms stimulate Mdm2 or Mdm4 activity for p53 ubiquitination in vivo and promote degradation of p53 and Mdm4 in cells. However, the Mdm2 isoforms have opposing effects on the steady-state p53 levels depending on the stoichiometric ratios of Mdm2, Mdm4 and the isoforms, causing either decreased or increased p53 levels in cells. Our data indicate that the Mdm2 splice isoforms can act as independent E3 ligases for p53 when Mdm2 and Mdm4 are absent, form potent heterodimer E3 ligases with either Mdm2 or Mdm4 for targeting p53 degradation, or act as inhibitory regulators of Mdm2-Mdm4 E3 ligase activity by downregulating Mdm4. These findings suggest that Mdm2 splice isoforms may play critical roles in the regulatory loop of p53/Mdm2-Mdm4 via a RING domain-mediated biochemical mechanism.
UNderstanding uptake of Immunisations in TravellIng aNd Gypsy communities (UNITING): protocol for an exploratory, qualitative study

Introduction Gypsies, Travellers and Roma (referred to here as Travellers) experience significantly poorer health and have shorter life expectancy than the general population. They are also less likely to access health services including immunisation. To improve immunisation rates, we need to understand what helps and hinders individuals in these communities in taking up immunisations. This study has two aims: (1) Investigate the barriers and facilitators to acceptability and uptake of immunisations among six Traveller communities in the UK; (2) Identify potential interventions to increase uptake in these Traveller communities. Methods and analysis A three-phase qualitative study with six Traveller communities. PHASE 1: In each community, we will explore up to 45 Travellers’ views about the influences on their immunisation behaviours and ideas for improving uptake in their community. PHASE 2: In each community, we will investigate 6–8 service providers’ perspectives on barriers and facilitators to childhood and adult immunisations for Traveller communities with whom they work, and ideas to improve uptake. Interview data will be analysed using the Framework approach. PHASE 3: The findings will be discussed and interventions prioritised in six workshops, each with 10–12 phase 1 and 3–4 phase 2 participants. Ethics and dissemination This research received approval from NRES Committee Yorkshire and The Humber-Leeds East (Ref. 13/YH/02). It will produce (1) findings on the barriers and facilitators to uptake of immunisations in six Traveller communities; (2) a prioritised list of potentially feasible and acceptable interventions for increasing uptake in these communities; and (3) methodological development in undertaking research with diverse Traveller communities. The study has the potential to inform new ways of delivering services to ensure high immunisation uptake. Findings will be disseminated to participants, relevant UK organisations with responsibility for the implementation of immunisation policy and Traveller health/welfare; and submitted for publication in academic journals. Trial registration number ISRCTN20019630.
Effects of exercise on fetal-placental growth and uteroplacental blood flow in the rat.

The effects of daily maternal exercise on fetal-placental growth and development and the associated changes in uteroplacental blood flow were studied in pregnant rats. Pregnant females were exercised for 1 h (0% grade at 28 m/min) daily between either days 1 and 12, 1 and 18, 1 and 22, 12 and 18, or 12 and 22 of gestation and compared with nonexercised controls. Exercise between days 1 and 12 of pregnancy had no effect on fetal-placental parameters (i.e., fetal weight or gestation length) relative to controls. In contrast, exercise between days 1 and 22 and 12 and 22 resulted in a lower number of live pups born, an increase in gestational length, and an increased birth weight of the live pups relative to controls. Exercise between days 1 and 18 or 12 and 18 induced a significant (p less than or equal to 0.05) suppression of uteroplacental blood flow, the number of viable fetuses, and placental weights as compared with controls. Daily exercise had no effect on ovarian function as indicated by the comparable serum progesterone levels in all groups. These data indicate that an exercised-induced depression of uteroplacental blood flow is related to impaired fetal-placental growth and development during pregnancy in the rat.
Nicotinic acetylcholine receptors regulate vestibular afferent gain and activation timing

Little is known about the function of the cholinergic efferents innervating peripheral vestibular hair cells. We measured vestibular sensory evoked potentials (VsEPs) in α9 knockout (KO) mice, α10 KO mice, α7 KO mice, α9/10 and α7/9 double KO mice, and wild‐type (WT) controls. We also studied the morphology and ultrastructure of efferent terminals on vestibular hair cells in α9, α10, and α9/10 KOs. Both type I and type ll vestibular hair cells express the α9 and α10 subunits. The efferent boutons on vestibular cells in α9, α10, and α9/10 KOs appeared normal, but a quantitative analysis was not performed. Mean VsEP thresholds were significantly elevated in α9 and α9/10 KO animals. Some α9 and α9/10 KO animals, however, had normal or near‐normal thresholds, whereas others were greatly affected. Despite individual variability in threshold responses, latencies were consistently shortened. The double α7/9 KO resulted in decreased variance by normalizing waveforms and latencies. The phenotypes of the α7 and α10 single KOs were identical. Both α7 and α10 KO mice evidenced normal thresholds, decreased activation latencies, and larger amplitudes compared with WT mice. The data suggest a complex interaction of nicotinic acetylcholine receptors (nAChRs) in regulating vestibular afferent gain and activation timing. Although the α9/10 heteromeric nAChR is an important component of vestibular efferent activity, other peripheral or central nAChRs involving the α7 subunit or α10 subunit and α9 homomeric receptors are also important. J. Comp. Neurol. 525:1216–1233, 2017. © 2016 Wiley Periodicals, Inc.
Neuropsychology and cognitive neuroscience in the fMRI era: A recapitulation of localizationist and connectionist views.

OBJECTIVE We highlight the past 25 years of cognitive neuroscience and neuropsychology, focusing on the impact to the field of the introduction in 1992 of functional MRI (fMRI). METHOD We reviewed the past 25 years of literature in cognitive neuroscience and neuropsychology, focusing on the relation and interplay of fMRI studies and studies utilizing the "lesion method" in human participants with focal brain damage. RESULTS Our review highlights the state of localist/connectionist research debates in cognitive neuroscience and neuropsychology circa 1992, and details how the introduction of fMRI into the field at that time catalyzed a new wave of efforts to map complex human behavior to specific brain regions. This, in turn, eventually evolved into many studies that focused on networks and connections between brain areas, culminating in recent years with large-scale investigations such as the Human Connectome Project. CONCLUSIONS We argue that throughout the past 25 years, neuropsychology-and more precisely, the "lesion method" in humans-has continued to play a critical role in arbitrating conclusions and theories derived from inferred patterns of local brain activity or wide-spread connectivity from functional imaging approaches. We conclude by highlighting the future for neuropsychology in the context of an increasingly complex methodological armamentarium. (PsycINFO Database Record