Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab1 interacts with GOLPH3 and controls Golgi structure and contractile ring constriction during cytokinesis in Drosophila melanogaster

Cytokinesis requires a tight coordination between actomyosin ring constriction and new membrane addition along the ingressing cleavage furrow. However, the molecular mechanisms underlying vesicle trafficking to the equatorial site and how this process is coupled with the dynamics of the contractile apparatus are poorly defined. Here we provide evidence for the requirement of Rab1 during cleavage furrow ingression in cytokinesis. We demonstrate that the gene omelette (omt) encodes the Drosophila orthologue of human Rab1 and is required for successful cytokinesis in both mitotic and meiotic dividing cells of Drosophila melanogaster. We show that Rab1 protein colocalizes with the conserved oligomeric Golgi (COG) complex Cog7 subunit and the phosphatidylinositol 4-phosphate effector GOLPH3 at the Golgi stacks. Analysis by transmission electron microscopy and 3D-SIM super-resolution microscopy reveals loss of normal Golgi architecture in omt mutant spermatocytes indicating a role for Rab1 in Golgi formation. In dividing cells, Rab1 enables stabilization and contraction of actomyosin rings. We further demonstrate that GTP-bound Rab1 directly interacts with GOLPH3 and controls its localization at the Golgi and at the cleavage site. We propose that Rab1, by associating with GOLPH3, controls membrane trafficking and contractile ring constriction during cytokinesis.
Survival differences among the oldest old in Sardinia: who, what, where, and why?

A study of centenarians in Sardinia detected the existence of an area where the number of centenarians is higher than elsewhere, in particularly for men. There is a widespread opinion that the existence of a greater or a lesser number of centenarians largely depends on mortality features between 80 and 100 years. This study aims to cast light on our knowledge of elderly mortality differentials, total and by cause of death, in Sardinia, and attempts to verify this hypothesis. To do so, an analysis is conducted of age and sex mortality trends over time at province and municipality level. Results fully confirm the underlying hypothesis.
A Practitioner’s Guide to Cluster-Robust Inference

We consider statistical inference for regression when data are grouped into clusters, with regression model errors independent across clusters but correlated within clusters. Examples include data on individuals with clustering on village or region or other category such as industry, and state-year differences-in-differences studies with clustering on state. In such settings, default standard errors can greatly overstate estimator precision. Instead, if the number of clusters is large, statistical inference after OLS should be based on cluster-robust standard errors. We outline the basic method as well as many complications that can arise in practice. These include cluster-specific fixed effects, few clusters, multiway clustering, and estimators other than OLS.
Mitogen-Activated Protein Kinase-Interacting Kinase Regulates mTOR/AKT Signaling and Controls the Serine/Arginine-Rich Protein Kinase-Responsive Type 1 Internal Ribosome Entry Site-Mediated Translation and Viral Oncolysis

ABSTRACT Translation machinery is a major recipient of the principal mitogenic signaling networks involving Raf-ERK1/2 and phosphoinositol 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR). Picornavirus internal ribosomal entry site (IRES)-mediated translation and cytopathogenic effects are susceptible to the status of such signaling cascades in host cells. We determined that tumor-specific cytotoxicity of the poliovirus/rhinovirus chimera PVSRIPO is facilitated by Raf-ERK1/2 signals to the mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) and its effects on the partitioning/activity of the Ser/Arg (SR)-rich protein kinase (SRPK) (M. C. Brown, J. D. Bryant, E. Y. Dobrikova, M. Shveygert, S. S. Bradrick, V. Chandramohan, D. D. Bigner, and M, Gromeier, J. Virol. 22:13135–13148, 2014, doi:http://dx.doi.org/10.1128/JVI.01883-14). Here, we show that MNK regulates SRPK via mTOR and AKT. Our investigations revealed a MNK-controlled mechanism acting on mTORC2-AKT. The resulting suppression of AKT signaling attenuates SRPK activity to enhance picornavirus type 1 IRES translation and favor PVSRIPO tumor cell toxicity and killing. IMPORTANCE Oncolytic immunotherapy with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES, is demonstrating early promise in clinical trials with intratumoral infusion in recurrent glioblastoma (GBM). Our investigations demonstrate that the core mechanistic principle of PVSRIPO, tumor-selective translation and cytotoxicity, relies on constitutive ERK1/2-MNK signals that counteract the deleterious effects of runaway AKT-SRPK activity in malignancy.
A Systematic Review of Crisis Interventions Used in the Emergency Department: Recommendations for Pediatric Care and Research

Objective: In this systematic review, we evaluated the effectiveness of emergency department (ED)-based management interventions for mental health presentations with an aim to provide recommendations for pediatric care. Methods: A search of electronic databases, references, key journals, and conference proceedings was conducted, and primary authors were contacted. Experimental and observational studies that evaluated ED crisis care with pediatric and adult patients were included. Adult-based studies were evaluated for potential translation to pediatric investigation. Pharmacological-based studies were excluded. Inclusion screening, study selection, and methodological quality were assessed by 2 independent reviewers. One reviewer extracted the data, and a second checked for completeness and accuracy. Presentation of study outcomes included odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CI). Meta-analysis was deferred due to clinical heterogeneity in intervention, patient population, and outcome. Results: Twelve observational studies were included in the review with pediatric (n = 3), and adult or unknown (n = 9) aged participants. Pediatric studies supported the use of specialized care models to reduce hospitalization (OR, 0.45; 95% CI, 0.33-0.60), return ED visits (OR, 0.60; 95% CI, 0.28-1.25), and length of ED stay (MD, −43.1 minutes; 95% CI, −63.088 to −23.11 minutes). In an adult study, reduced hospitalization was reported in a comparison of a crisis intervention team to standard care (OR, 0.59; 95% CI, 0.43-0.82). Five adult-based studies assessed triage scales; however, little overlap in the scales investigated, and the outcomes measured limited comparability and generalizability for pediatrics. In a comparison of a mental health scale to a national standard, a study demonstrated reduced ED wait (MD, −7.7 minutes; 95% CI, −12.82 to −2.58 minutes) and transit (MD, −17.5 minutes; 95% CI, −33.00 to −1.20 minutes) times. Several studies reported a shift in triage scores of psychiatric patients dependent on the scale or nurse training (psychiatric vs emergency), but linkage to system- or patient-based outcomes was not made, limiting clinical interpretation. Conclusions: Pediatric studies have demonstrated that the use of specialized care models for mental health care can reduce hospitalization, return ED visits, and length of ED stay. Evaluation of these models using more rigorous study designs and the inclusion of patient-based outcomes will improve this evidence base. Adult-based studies provided recommendations for pediatric research including a focus on triage and restraint use.
Human Brain Basis of Musical Rhythm Perception: Common and Distinct Neural Substrates for Meter, Tempo, and Pattern

Rhythm as the time structure of music is composed of distinct temporal components such as pattern, meter, and tempo. Each feature requires different computational processes: meter involves representing repeating cycles of strong and weak beats; pattern involves representing intervals at each local time point which vary in length across segments and are linked hierarchically; and tempo requires representing frequency rates of underlying pulse structures. We explored whether distinct rhythmic elements engage different neural mechanisms by recording brain activity of adult musicians and non-musicians with positron emission tomography (PET) as they made covert same-different discriminations of (a) pairs of rhythmic, monotonic tone sequences representing changes in pattern, tempo, and meter, and (b) pairs of isochronous melodies. Common to pattern, meter, and tempo tasks were focal activities in right, or bilateral, areas of frontal, cingulate, parietal, prefrontal, temporal, and cerebellar cortices. Meter processing alone activated areas in right prefrontal and inferior frontal cortex associated with more cognitive and abstract representations. Pattern processing alone recruited right cortical areas involved in different kinds of auditory processing. Tempo processing alone engaged mechanisms subserving somatosensory and premotor information (e.g., posterior insula, postcentral gyrus). Melody produced activity different from the rhythm conditions (e.g., right anterior insula and various cerebellar areas). These exploratory findings suggest the outlines of some distinct neural components underlying the components of rhythmic structure.
Visual prognostic value of optical coherence tomography and photopic negative response in chiasmal compression.

PURPOSE To investigate the potential of the optical coherence tomography (OCT) measurement of retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) area and photopic negative response (PhNR) for predicting postoperative visual outcome in chiasmal compression, prospectively. METHODS Eighteen eyes of 18 patients undergoing chiasmal decompression surgery were prospectively assessed before, and 3 months after surgery with standard automated perimetry (SAP), OCT, and PhNR. Preoperative measurements were compared with 20 eyes of 20 age-matched controls. Spearman's correlation and regression analyses were conducted to evaluate the relationship between preoperative RNFL thickness, GCC area, PhNR/b-wave amplitude ratio, postoperative mean deviation (MD) and temporal visual field sensitivity (1/Lambert). RESULTS Preoperative measurements of RNFL thickness, GCC area, and PhNR/b-wave amplitude ratio were reduced significantly in patients compared with normal controls. Preoperative RNFL thickness of the temporal quadrant, GCC area, and PhNR/b-wave amplitude ratio were correlated significantly with postoperative MD and temporal visual field sensitivity (1/Lambert). CONCLUSIONS An eye with the more demonstrable structural deterioration, as shown by reduced RNFL thickness and GCC area, and retinal ganglion cell dysfunction as shown by decreased PhNR/b-wave amplitude ratio was associated with the worse visual fields outcome. RNFL thickness and GCC area measurements using OCT and PhNR/b-wave amplitude ratio could be a useful prognostic indicator in the preoperative assessment of chiasmal compression.
Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide

Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and related Actinomycetes convert their MDP to an N-glycolylated form through the action of N-acetyl muramic acid hydroxylase (NamH). We used a combination of bacterial genetics and synthetic chemistry to investigate whether N-glycolylation of MDP alters NOD2-mediated immunity. Upon infecting macrophages with 12 bacteria, tumor necrosis factor (TNF) α secretion was NOD2 dependent only with mycobacteria and other Actinomycetes (Nocardia and Rhodococcus). Disruption of namH in Mycobacterium smegmatis obrogated NOD2-mediated TNF secretion, which could be restored upon gene complementation. In mouse macrophages, N-glycolyl MDP was more potent than N-acetyl MDP at activating RIP2, nuclear factor κB, c-Jun N-terminal kinase, and proinflammatory cytokine secretion. In mice challenged intraperitoneally with live or killed mycobacteria, NOD2-dependent immune responses depended on the presence of bacterial namH. Finally, N-glycolyl MDP was more efficacious than N-acetyl MDP at inducing ovalbumin-specific T cell immunity in a model of adjuvancy. Our findings indicate that N-glycolyl MDP has a greater NOD2-stimulating activity than N-acetyl MDP, consistent with the historical observation attributing exceptional immunogenic activity to the mycobacterial cell wall.
Association of P2Y12 Gene Promoter DNA Methylation with the Risk of Clopidogrel Resistance in Coronary Artery Disease Patients

Background. Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR). Methods. The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR. Result. Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, P = 0.009; CpG2, P = 0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients (P = 0.026) and in subgroup of Albumin < 35 (P = 0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR. Conclusions. The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR.
Factors influencing caries experience among adults with physical and intellectual disabilities.

BACKGROUND There is limited and inconsistent evidence on the influence of residential setting on caries experience of adults with physical and intellectual disabilities (PID), described here as care-recipients. OBJECTIVE To examine caries experience and associated factors among adults with PID. METHODS Mailed questionnaire survey (2005-2006) of carers of adults with PID (18-44 years) in South Australia from family homes, community housing, and institutions, and oral examinations of care-recipients recording decayed (D), missing (M) and filled (F) teeth (DMFT). RESULTS Carers completed questionnaires for 485 care-recipients, 267 of whom were examined (completion rate=55.1%). The prevalence of decay (D>0) was 16.9% and 76.3% had caries experience (DMFT>0). In unadjusted analysis, care-recipients at institutions had a significantly higher mean DMFT than other settings. After adjusting for carer and care-recipient characteristics, there was no difference in any of the DMFT components among residential settings. However, there were statistically significant associations (OR+/-95% CI excluding unity) between decayed teeth and moderate and high intake of sweet drinks and frequency of dental visits. Higher odds of missing teeth were associated with type of disability, general anaesthetic requirement for dental treatment and low and high carer-contact. Higher odds of filled teeth were associated with age, no oral hygiene assistance (OHA) and high carer-contact. Higher odds of caries experience were associated with age and no OHA. CONCLUSIONS Residential setting was not associated with caries experience. Modifiable risk factors were diet, frequency of dental visits, no OHA and carer-contact hours.
Orthographic word knowledge growth in school-age children.

PURPOSE Natural reading experiences provide an opportunity for the development of orthographic word knowledge as well as other forms of partial word knowledge. The purpose of this study was to compare the orthographic word knowledge growth of school-age children with relatively low language skills (LL group) to that of age- and gender-matched peers with high language skills (HL group). METHOD Thirty-two children, 16 per group, read stories containing rare words 3 times, 2-3 days apart. Posttesting, completed at the end of each session, required participants to indicate recognition of the rare words encountered in the stories while not indicating recognition of orthographically similar nonwords. RESULTS Over time, both groups showed significant growth in recognition of the orthographic forms of the rare words. However, the groups differed in the extent to which they indicated that the orthographically similar nonwords were words, with the LL group indicating that significantly more of the nonwords were words. CONCLUSION Results provide some preliminary evidence that children with relatively weaker language skills are able to develop orthographic knowledge of unfamiliar words through reading experiences, but their orthographic representations may not be as well defined as those of children with stronger language skills.
A Step towards the Detection of Semantic Variants of Terms in Technical Documents

This paper reports the results of a preliminary experiment on the detection of semantic variants of terms in a French technical document. The general goal of our work is to help the structuration of terminologies. Two kinds of semantic variants can be found in traditional terminologies: strict synonymy links and fuzzier relations like see-also. We have designed three rules which exploit general dictionary information to infer synonymy relations between complex candidate terms. The results have been examined by a human terminologist. The expert has judged that half of the overall pairs of terms are relevant for the semantic variation. He validated an important part of the detected links as synonymy. Moreover, it appeared that numerous errors are due to few mis-interpreted links: they could be eliminated by few exception rules.
Vital Signs: Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016

Background In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. Methods This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. Results During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus–associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%–7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%–14%]). Birth defects were reported in 15% (95% CI = 8%–26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). Conclusions and Implications for Public Health Practice These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.
Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir

ABSTRACT In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUCss] and 37% for peak plasma concentration at steady state [Cmax,ss]) and increased by indinavir (33% for AUCss). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUCss orCmax,ss. Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.
Phosphating of Calcium Carbonate for Obtaining Hydroxyapatite from the Ostrich Egg Shell

The Hydroxyapatite (HA), the major component of the inorganic portion of bones, may be obtained from different sources for use as biomaterial in the reconstruction of critical bone defects. Among these resources, the eggshell appears as a promising alternative since it is a waste material which may be reused as a source of calcium carbonate after adequate treatment, giving rise to mineral hydroxyapatite. After morphological and physicochemical adjustments allowing its standardization and utilization, hydroxyapatite (HA) may turn into a potentially useful biomaterial for different experimental purposes. This paper aims to present a viable method for obtaining a hydroxyapatite from Ostrich eggshell by wet precipitation process. This phosphating technique with emphasis on the issue of sustainable reuse of disposable materials allows the production of a synthetic crystalline material with characteristics similar to those of bone and tooth. The structural characterization was performed by X-Ray diffraction and scanning electron microscopy with field emission gun and energy dispersive X-ray in the Military Institute of Engineering.