A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: The iESRD study

Background: Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown. Results: Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ TEMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate. Conclusions: Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe

Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2-and 3-jet events in pp collisions at root s=13TeV

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Delta phi(12), is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 35.9 fb(-1) are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with themeasurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 degrees <Delta phi(12) <180 degrees. The 2- and 3-jet measurements are not simultaneously described by any of models.Peer reviewe

Combination Treatment of Intense Pulsed Light Therapy and Meibomian Gland Expression for Evaporative Dry Eye

Dry eye disease (DED) is most commonly caused by evaporative subtypes and mainly induced by meibomian gland dysfunction (MGD). Intense pulsed light (IPL) combined with meibomian gland expression (MGX) is a noninvasive treatment for improvement of ocular discomfort symptoms and MGD. In this prospective study between November 2020 and May 2022, the patients with MGD and abnormal meibomian expressibility that met the criteria of both ocular surface disease index (OSDI) &ge; 13 scores and standardized patient evaluation of eye dryness (SPEED) &ge; 8 scores were enrolled in Kaohsiung Veteran General Hospital. Three separate treatment sessions of IPL therapy combined with MGX were administered to the lower lids, with an interval of 28 days. Further tear film assessment included lipid layer thickness (LLT), tear meniscus height (TMH), noninvasive tear break-up time (NIBUT), and meibomian gland loss (MGL) either before or after first and third IPL therapy combined with MGX. In addition, lissamine green staining and pain scores were also recorded. We totally enrolled 37 patients of 74 eyes. Men accounted for 18.92% (7/37). The mean age was 54.51 &plusmn; 11.72 years. The mean OSDI scores were 58.12 &plusmn; 22, while the SPEED scores were 17.03 &plusmn; 5.98. The mean Schirmer&rsquo;s test was 3.66 &plusmn; 2.43 mm. After three sessions of IPL treatment with MGX, the OSDI, SPEED, LLT, TMH, MGL, MGXS, and pain scores were significantly improved. For the MGX scores (MGXS) &le; 20 group, lissamine green scores showed nearly significant improvements. For the MGXS &gt; 20 group, TMH revealed statistical improvement. Noninvasive IPL therapy with MGX statistically improved not only dry eye symptoms, but also tear film assessments, including LLT, TMH, and MGL

RcsB regulation of the YfdX-mediated acid stress response in Klebsiella pneumoniae CG43S3.

In Klebsiella pneumoniae CG43S3, deletion of the response regulator gene rcsB reduced the capsular polysaccharide amount and survival on exposure to acid stress. A comparison of the pH 4.4-induced proteomes between CG43S3 and CG43S3ΔrcsB revealed numerous differentially expressed proteins and one of them, YfdX, which has recently been reported as a periplasmic protein, was absent in CG43S3ΔrcsB. Acid survival analysis was then conducted to determine its role in the acid stress response. Deletion of yfdX increased the sensitivity of K. pneumoniae CG43S3 to a pH of 2.5, and transforming the mutant with a plasmid carrying yfdX restored the acid resistance (AR) levels. In addition, the effect of yfdX deletion was cross-complemented by the expression of the periplasmic chaperone HdeA. Furthermore, the purified recombinant protein YfdX reduced the acid-induced protein aggregation, suggesting that YfdX as well as HdeA functions as a chaperone. The following promoter activity measurement revealed that rcsB deletion reduced the expression of yfdX after the bacteria were subjected to pH 4.4 adaptation. Western blot analysis also revealed that YfdX production was inhibited by rcsB deletion and only the plasmid expressing RcsB or the nonphosphorylated form of RcsB, RcsBD56A, could restore the YfdX production, and the RcsB-mediated complementation was no longer observed when the sensor kinase RcsD gene was deleted. In conclusion, this is the first study demonstrating that YfdX may be involved in the acid stress response as a periplasmic chaperone and that RcsB positively regulates the acid stress response partly through activation of yfdX expression. Moreover, the phosphorylation status of RcsB may affect the YfdX expression under acidic conditions

Atropine use may lead to post-operative respiratory acidosis in neonates receiving ductal ligation: A retrospective cohort study

Background: Patent ductus arteriosus (PDA) is one of the most common cardiac conditions in preterm infants. Closure of the PDA in symptomatic patients can be achieved medically or surgically. Atropine is commonly administered in general anesthesia as a premedication in this age group but with limited evidence addressing the effect of its use. Our study examined the association of the use of atropine as a premedication in PDA ligation and the risk of post-operative respiratory complications. Methods: This retrospective cohort study included 150 newborns who have failed medical treatment for PDA and received PDA ligation during 2008–2012 in a single tertiary medical center. Ninety-two of them (61.3%) received atropine as premedication for general anesthesia while 58 (38.7%) did not. Post-operative respiratory condition, the need of cardiopulmonary resuscitation and the presence of bradycardia were measured. Results: Patients with atropine use were associated with increased odds of respiratory acidosis in both univariate analysis (22.9% vs 7.3%; OR = 3.785, 95% CI = 1.211–11.826, p = 0.022) and multivariate analysis (OR = 4.030, 95% CI = 1.230–13.202, p = 0.021), with an even higher odds of respiratory acidosis in patients receiving both atropine and ketamine. Conclusion: The use of atropine as premedication in general anesthesia for neonatal PDA ligation is associated with higher risk of respiratory acidosis, which worsens with the combined use of ketamine. Key Words: respiratory acidosis, atropine, patent ductus arteriosus, ketamin