Miracle-dz/UniFAR-FTUs huggingface dataset:
Ten-year results of the MILD trial demonstrate the safety and efficacy of biennial lung cancer screening.

Background— The Multicentric Italian Lung Detection (MILD) trial demonstrated that prolonged low-dose computed tomography (LDCT) screening could achieve a 39% reduction in lung cancer (LC) mortality. We have here evaluated the long-term results of annual vs. biennial LDCT, and the impact of screening intensity on overall and LC specific mortality at 10 years. Patients and methods— Between 2005 and 2018, the MILD trial prospectively randomized the 2,376 screening arm participants to annual (n=1190) or biennial (n=1186) LDCT, for a median screening period of 6.2 years and 23,083 person-years of follow-up. The primary outcomes were 10-year overall and LC specific mortality, and the secondary endpoints were the frequency of advanced stage and interval LCs. Results— The biennial LDCT arm showed a similar overall mortality (HR 0.80, 95% CI 0.57-1.12) and LC specific mortality at 10 years (HR 1.10, 95% CI 0.59-2.05), as compared with annual LDCT arm. Biennial screening saved 44% of follow-up LDCTs in subjects with negative baseline LDCT, and 38% of LDCTs in all participants, with no increase in the Conclusions— The MILD trial provides original evidence that prolonged screening beyond five years with biennial LDCT can achieve a LC mortality reduction comparable to annual LDCT, in subjects with a negative baseline examination.
Hospitalization Rates and Causes Among Persons With HIV in the United States and Canada, 2005–2015

Background. To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. clinical cohorts, followed count HIV every and categorized ICD codes of primary diagnoses using modified Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL. person-years), the from to cells/ all-cause hospitalization decreased from 22.3 person-years decreased for almost all diagnostic categories. rates decreased for and conditions, increased for non-AIDS–defining infection, were stable for most other categories. hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.
dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors

receptor periaqueductal dorsal horn (PAG/RVM/SDH) pathway is one of the most important neural pathways involved in descending pain modulation It been demonstrated that specific activation of the vesicular glutamate transporter 2–immunoreactive (VGLUT2-ir) neurons in the The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABA A receptor (GABA A R) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors. for immunofluorescence analysis and analysis of Western blot data. The comparison of electrophysiology data was made using a 2-way repeated-measures ANOVA with Bonferroni’s post hoc test or Student’s t test. Statistical analyses were performed using GraphPad Prism, version 6.0e (GraphPad Software). Normality and equal variance tests were performed for all statistical analyses. A P value of 0.05 or less was considered statistically significant.
Administrative Profiles Unit and Multi-Sessions Management Scheme for IPBrick Private Cloud

IPBrick solution for the Private Cloud has some limitations which can be challenged in future by its competitors in the market. The administrative access to the web interface of an IPBrick server is restricted to one user who manages everything by using a given set of features and services. The existing solution also does not support Multi-Sessions Management due to which multiple update operations can't be applied on the database simultaneously and if it is attempted then it can have adverse affects on the consistency of data stored in the Database. The aim of this thesis is to develop features like Administrative Profiles and Multi-Sessions Management for the betterment of IPBrick Solution.
RR Lyrae Stars and Anomalous Cepheids in the Draco Dwarf Spheroidal Galaxy

We present new results on RR Lyrae stars and anomalous Cepheids in the Draco dwarf spheroidal galaxy. We have increased the number of double-mode RR Lyrae stars and found three new anomalous Cepheids. With period-magnitude and period-amplitude diagrams, we discuss the Oosterhoff classification of Draco. Contradictory results were found in that Draco appears to contain both Oosterhoff I and II type RR Lyrae populations.
Analysis of FcERI-Mediated Mast Cell Stimulation by Surface-Carried Antigens

Clustering of the type I receptor for IgE (FcaRI) on mast cells initiates a cascade of biochemical processes that result in secretion of inflammatory mediators. To determine the FcsRI proximity, cluster size, and mobility requirements for initiating the FcaRI cascade, a novel experimental protocol has been developed in which mast cells are reacted with glass surfaces carrying different densities of both antigen and bound IgE, and the cell's secretory response to these stimuli is measured. The results have been analyzed in terms of a model based on the following assumptions: 1) the glass surface antigen distribution and consequently that of the bound IgE are random; 2) FcsRl binding to these surface-bound IgEs immobilizes the former and saturates the latter; 3) the cell surface is formally divided into small elements, which function as a secretory stimulus unit when occupied by two or more immobilized IgE-FcsRI complexes; 4) alternatively, similar stimulatory units can be formed by binding of surface-carried IgE dimers to two FcsRI. This model yielded a satisfactory and self-consistent fitting of all of the different experimental data sets. Hence the present results establish the essential role of FcsRI immobilization for initiating its signaling cascade. Moreover, it provides independent support for the notion that as few as two FcsRls immobilized at van der Waals contact constitute an "elementary stimulatory unit" leading to mast cell (RBL-2H3 line) secretory response.
ROUS-WHIPPLE AWARD LECTURE How Endothelial Cells Regulate Transmigration of Leukocytes in the In ﬂ ammatory Response

Leukocytes attach to vascular endothelial cells at the site of in ﬂ ammation via a series of intercellular adhesive interactions. In a separate step in leukocyte extravasation, transendothelial migration is regu-latedby moleculesthat play no role in the preceding stepsof tethering, rolling,adhesion,and locomotion. Transendothelial migration itself can be dissected into a series of distinct interactions regulated sequentially by molecules concentrated at the endothelial cell border; these include platelet/endothelial cell adhesion molecule, poliovirus receptor (CD155), and CD99. These molecules are components of the lateral border recycling compartment (LBRC), a perijunctional network of interconnected tubulovesicular membrane that traf ﬁ cs to surround the leukocyte as it passes across the endothelial cell. This targeted recycling of LBRC requires kinesin to move the membrane along microtubules, and interfering with LBRC traf ﬁ ckingblockstransmigrationofneutrophils,monocytes,andlymphocytes.TheLBRCisalsorecruitedto mediatetranscellularmigrationwhen thatoccurs. Movement of the LBRC is coordinatedwith eventson the luminalsurface,suchasclusteringofintercellularadhesionmolecule1andvascularcelladhesionmolecule 1 under the migrating leukocyte, as well as movement of vascular endothelial cadherin and its associated catenins out of the junction at the site of transendothelial migration. How these events are coordinated is not known, but their regulation shares common signaling pathways that may serve to connect these steps.
Using nanomaterial to enhance the performance of medium-voltage insulators and streetlights considering environmental impacts

Nanoparticles are small objects that their size, in at least one dimension, is between 1 and 100 nm. Nanomaterials characteristics are completely different from larger particles. Therefore, Nanotechnology can be used to enhance the properties of many products. Although it is possible to use nanotechnology to improve the performance and life cycle of various electric components, Alborz Electric Power Distribution Company efforts have been focused on using TiO2 nanoparticles in street lamps as well as medium-voltage silicon rubber insulators. The properties of titanium dioxide nanoparticle are presented. Then the applications of this nanomaterial in insulators and lamps were explained. Finally, the possible impacts of using it on environment were discussed.
Fast Exocytosis with Few Ca 2 (cid:1) Channels in Insulin-Secreting Mouse Pancreatic B Cells

The association of L-type Ca 2 (cid:1) channels to the secretory granules and its functional significance to secretion was investigated in mouse pancreatic B cells. Nonstationary fluctuation analysis showed that the B cell is equipped with (cid:2) 500 (cid:1) 1 C L-type Ca 2 (cid:1) channels, corresponding to a Ca 2 (cid:1) channel density of 0.9 channels per (cid:2) m 2 . Analysis of the kinetics of exocytosis during voltage-clamp depolarizations revealed an early component that reached a peak rate of 1.1 pFs (cid:3) 1 ( (cid:4) 650 granules/s) 25 ms after onset of the pulse and is completed within (cid:5) 100 ms. This component represents a subset of (cid:4) 60 granules situated in the immediate vicinity of the L-type Ca 2 (cid:1) channels, corresponding to (cid:5) 10% of the readily releasable pool of granules. Experiments involving photorelease of caged Ca 2 (cid:1) revealed that the rate of exocytosis was half-maximal at a cytoplasmic Ca 2 (cid:1) concentration of 17 (cid:2) M, and concentrations (cid:6) 25 (cid:2) M are required to attain the rate of exocytosis observed during voltage-clamp depolarizations. The rapid component of exocytosis was not affected by inclusion of millimolar concentrations of the Ca 2 (cid:1) buffer EGTA but abolished by addition of exogenous L C753–893 , the 140 amino acids of the cytoplasmic loop connecting the 2 nd and 3 rd transmembrane region of the (cid:1) 1 C L-type Ca 2 (cid:1) channel, which has been proposed to tether the Ca 2 (cid:1) channels to the secretory granules. In keeping with the idea that secretion is determined by Ca 2 (cid:1) influx through individual Ca 2 (cid:1) channels, exocytosis triggered by brief (15 ms) depolarizations was enhanced 2.5-fold by the Ca 2 (cid:1) channel agonist BayK8644 and 3.5-fold by elevating extracellular Ca 2 (cid:1) from 2.6 to 10 mM. Recordings of single Ca 2 (cid:1) channel activity revealed that patches predominantly contained no channels or many active channels. We propose that several Ca 2 (cid:1) channels associate with a single granule thus forming a functional unit. This arrangement is important in a cell with few Ca 2 (cid:1) channels as it ensures maximum usage of the Ca 2 (cid:1) entering the cell while minimizing the influence of stochastic variations of the Ca 2 (cid:1) channel activity.
Lack of effect of chronic calcium antagonist treatment on ,-and 2-adrenoceptors in right atria from patients with or without heart failure

We studied the effects of chronic calcium antagonist (calcium entry blocker, CEB; nifedipine, verapamil, diltiazem) treatment on 13-adrenoceptor density (assessed by (-)-[1251I]-iodocyanopindolol [ICYP] binding) and subtype distribution in right atria from 65 patients without apparent heart failure undergoing elective coronary artery bypass grafting (CAD-patients) and from 13 patients with moderate heart failure (NYHA class III to class III-IV) undergoing mitral valve replacement (MVD-patients). ,-adrenoceptor ,-adrenoceptor density or P2-adrenoceptor ratio. 12-adrenoceptor ratio, however, was not changed (67:33%). Chronic CEB-treatment of MVD-patients did not prevent the decrease in atrial 13-adrenoceptors. We conclude that chronic CEB-treatment does not affect human right atrial 1B-adrenoceptor density, either in patients without apparent heart failure or in patients with moderate heart failure. In addition, the increase in atrial 13l-adrenoceptors caused by chronic l31-adrenoceptor antagonist treatment seems not to be affected by simultaneous CEB-treatment.
Standardisation, Multi-Measure, Data Quality and Trending: A Qualitative Study on Multidisciplinary Perspectives to Improve ICU Early Mobility Monitoring

Objective: To explore multi-clinician perspectives on ICU early mobility, monitoring, and to assess the perceived value of technology-generated mobility metrics to provide user feedback to inform research, practice improvement, and technology development. Methods: We performed a qualitative descriptive study. Three focus groups were conducted with critical care clinicians, including nurses (n=10), physical therapists (n=8) and physicians (n=8) at an academic medical centre that implemented an ICU early mobility programme in 2012. Qualitative thematic analysis was used to code transcripts and identify overarching themes. Findings: Along with reaffirming the value of performing ICU early mobility interventions, four themes for improving mobility monitoring emerged, including the need for: 1) standardised indicators for documenting mobility; 2) inclusion of both quantitative and qualitative metrics to measure mobility; 3) a balance between quantity and quality of data; and 4) trending mobility metrics over time. Conclusion: ICU mobility monitoring should be standardised, and data generated should be high quality, capable of supporting trend analysis, and meaningful. By improving measurement and monitoring of ICU mobility, future researchers can examine the arc of activity that patients in the ICU undergo and develop models to understand factors that influence successful implementation. This qualitative descriptive study explored clinician perspectives on ICU EM, monitoring EM, and technology-generated mobility metrics to inform research, and technology development. The study was conducted at a 2018. Our ICU EM programme, began 2012, involves daily Focus groups explored
REVIEW Elucidating the Metabolic Regulation of Liver Regeneration

The regenerative capability of liver is well known, and the mechanisms that regulate liver regeneration are extensively studied. Such analyses have de ﬁ ned general principles that govern the hepatic regenerative response and implicated speci ﬁ c extracellular and intracellular signals as regulated during and essential for normal liver regeneration. Nevertheless, the most proximal events that stimulate liver regeneration and the distal signals that terminate this process remain incompletely understood. Recent data suggest that the metabolic response to hepatic insuf ﬁ ciency might be the proximal signal that initiates regenerative hepatocellular proliferation. This review provides an overview of the data in support of a metabolic model of liver regeneration and re ﬂ ects on the clinical implications and areas for further study suggested by these ﬁ ndings. (Am J Pathol 2014, 184: 309 e 321; http://dx.doi.org/ 10.1016/j.ajpath.2013.04.034)
Screening Exon 16 and 17 of the Amyloid Precursor Protein Gene in Sporadic Early-Onset Alzheimer’s Disease (sEOAD)

Early-onset Alzheimer’s disease (EOAD) can be familial (FAD) or sporadic (sEOAD); both have a disease onset ≤ 65 years of age. 451 sEOAD samples were screened for known causative mutations in exon 16 and 17 of the Amyloid Precursor Protein gene (APP). Four samples were shown to be heterozygous for one of three known causative mutations: p.A713T, p.V717I and p.V717G, this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a non-significantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6 bp deletion on splicing, COS-7 and BE(2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harbouring the deletion found no evidence of transcripts with exon 17 removed.
Impact of Sound Exposure and Aging on Brain-Derived Neurotrophic Factor and TrkB Receptors Levels in Dorsal Cochlear Nucleus 80 Days Following Sound Exposure

Recent studies suggested that acute sound exposure resulting in a temporary threshold shift in young adult animals within a series of maladaptive plasticity changes in central auditory structures. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in post-trauma peripheral hair cell and spiral ganglion cell survival and has been shown to modulate synaptic strength in cochlear nucleus following sound exposure. The present study evaluated levels of BDNF and its receptor (tyrosine kinase B, [TrkB]) in the dorsal cochlear nucleus (DCN) following a unilateral moderate sound exposure in young (7–8 months) and aged (28–29 months) Fischer Brown Norway (FBN) rats. Eighty days post-exposure, ABR thresholds for young exposed rats approached control values while aged exposed rats showed residual permanent threshold shifts relative to aged controls. BDNF protein levels were significantly up-regulated by 9% in young exposed fusiform cells ipsilateral to the exposure. BDNF levels in aged sound-exposed fusiform cells increased 31% ipsilateral to the exposure. Protein levels of the BDNF receptor, TrkB, were also significantly increased in aged but not in young sound-exposed DCN fusiform cells. The present findings suggest a relationship between the up-regulation of BDNF/TrkB and the increase in spontaneous and driven activity previously observed for aged and sound-exposed fusiform cells. This might be due to a selective maladaptive compensatory down-regulation of glycinergic inhibition in DCN fusiform cells. suggest that sound exposure and aging result in increased neuronal activity in the auditory brainstem BDNF signaling in BDNF protein in findings are Future studies investigate the role of BDNF and TrkB receptors in the context of the compensatory activity-dependant down-regulation of inhibitory neurotransmitter function following sound exposure and in aging at higher levels of the auditory
Splitting p 63

Different syndromes can result from mutations in a single gene. Quite often, these represent variations in severity, as do the FGFR3 mutations, which cause hypochondroplasia, achondroplasia, and thanatophoric dysplasia. More-divergent phenotypes may reflect the difference between gain-of-function and loss-of-function mutations, as occurs with dominant brachydactyly type B and recessive Robinow syndrome, which are caused by different mutations of the ROR2 gene. Other examples of allelic heterogeneity reflect a selective disruption of some but not all the gene’s functions, as in the contrast, because of an FGFR2 mutation, between Apert and Crouzon syndromes. For some genes there are multiple phenotypes associated with mutations, but a clear genotype-phenotype correlation is lacking. A striking example of such allelic heterogeneity are the GLI3 morphopathies: Greig syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly type A/B. We here review the spectrum of p63 mutations that have been found to underlie five human malformation syndromes: ectrodactyly–ectodermal dysplasia–clefting (EEC) syndrome (MIM 604292), ankyloblepharon–ectodermal dysplasia– clefting (AEC) syndrome (MIM 106260), limb-mammary syndrome (LMS [MIM 603543]), acro-dermato-unguallacrimal-tooth (ADULT) syndrome (MIM 103285), and nonsyndromic split-hand/split-foot malformation (SHFM). The localization and functional effects of the mutations that underlie these syndromes establish a striking genotype-phenotype correlation. Functional analysis of these mutations has provided valuable new insights
Efficacy and Safety of a Naphthoquine-Azithromycin Coformulation for Malaria Prophylaxis in Southeast Asia: A Phase 3, Double-blind, Randomized, Placebo-controlled Trial

Background. A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand. Methods. We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5–65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections. Results. Of the 531 subjects completing the trial, there were 46 and 3 blood smear–positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%–95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%–95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale . The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group ( P > .05). Conclusions. Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population.