bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane-dependent relief of translation elongation arrest on pseudouridine- and N1-methyl-pseudouridine-modified mRNAs
Authors: Svitkin Yuri V , Gingras Anne-Claude , Sonenberg Nahum 
Published: December 2021

Abstract
Expression of therapeutically important proteins has benefited dramatically from the advent of chemically modified mRNAs that feature decreased lability and immunogenicity. This had a momentous effect on the rapid development of COVID-19 mRNA vaccines. Incorporation of the naturally occurring pseudouridine (Ψ) or N1-methyl-pseudouridine (N1mΨ) into in vitro transcribed mRNAs prevents the activation of unwanted immune responses by blocking eIF2α phosphorylation, which inhibits translation. Here, we report that Ψs in luciferase (Luc) mRNA exacerbate translation pausing in nuclease-untreated rabbit reticulocyte lysate (uRRL) and promote the formation of high-order-ribosome structures. The major deceleration of elongation occurs at the Ψ-rich nucleotides 1294–1326 of Ψ-Luc mRNA and results in premature termination of translation. The impairment of translation is mainly due to the shortage of membranous components. Supplementing uRRL with canine microsomal membranes (CMMs) relaxes the impediments to ribosome movement, resolves collided ribosomes, and greatly enhances full-size luciferase production. CMMs also strongly stimulated an extremely inefficient translation of N1mΨ-Luc mRNA in uRRL. Evidence is presented that translational pausing can promote membrane recruitment of polysomes with nascent polypeptides that lack a signal sequence. Our results highlight an underappreciated role of membrane binding to polysomes in the prevention of ribosome collision and premature release of nascent polypeptides.
Manipulating spatial alignment of donor and acceptor in host–guest MOF for TADF
Authors: Liu Xiao-Ting , Hua Weijie , Nie Hong-Xiang , Chen Mingxing , Chang Ze , Bu Xian-He 
Published: December 2021

Abstract
Thermally activated delayed fluorescence (TADF) was achieved when electron-rich triphenylene (Tpl) donors were confined to a cage-based porous metal-organic framework (MOF) host (NKU-111) composed of electron-deficient 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (Tpt) acceptor as the ligand. The spatially separated donor and acceptor molecules in a face-to-face stacking pattern generated strong through-space charge transfer (CT) interactions with a small energy splitting between the singlet and triplet excited states (∼0.1 eV), which enabled TADF. The resulting Tpl@NKU-111 exhibited an uncommon enhanced emission intensity as the temperature increased. Extensive steady-state and time-resolved spectroscopic measurements and first-principles simulations revealed the chemical and electronic structure of this compound in both the ground and low-lying excited states. A double-channel (T1, T2) intersystem crossing mechanism with S1 was found and explained as single-directional CT from the degenerate HOMO−1/HOMO of the guest donor to the LUMO+1 of one of the nearest acceptors. The rigid skeleton of the compound and effective through-space CT enhanced the photoluminescence quantum yield (PLQY). A maximum PLQY of 57.36% was achieved by optimizing the Tpl loading ratio in the host framework. These results indicate the potential of the MOFs for the targeted construction and optimization of TADF materials.
Fossil Felidae (Carnivora: Mammalia) from the Yuanmou hominid site, southern China (Late Miocene) and its significance in the living environment of the fossil ape
Authors: Jiangzuo Qigao , Li Shijie , Fu Jiao , Wang Shiqi , Ji Xueping , Duan Mei , Che Decai 
Published: December 2021

Abstract
The Yuanmou hominid site is a rare Late Miocene fossil locality in southern China, where thousands of fossil specimens of the ape Lufengpithecus hudiensis have been found. These have been well studied, but the taxonomy of other mammalian groups is not fully understood. This is especially the case for large predator Felidae, which play a key role in the palaeo-environment in which these fossil apes lived. Here we study the systematics of fossil Felidae from Yuanmou, which is composed of four species of machairodonts: Amphimachairodus cf. horribilis, Longchuansmilus xingyongi gen. & sp. nov., aff. Yoshi sp., Machairodontinae gen. & sp. indet. and one species of feline, Felinae gen. & sp. indet. Longchuansmilus xingyongi is a member of Machairodontini, related to Lokotunjailurus and possibly two derived species of Paramachaerodus, i.e. P. orientalis and P. maximiliani. The high diversity of machairodonts suggests a unique palaeo-environment of the Yuanmou Basin during the Late Miocene, different from northern Eurasia or modern south-eastern Asia. An analysis of body size and intraguild competition suggests that aff. Yoshi sp. and Machairodontinae gen. & sp. indet. are probably regular predators of the fossil great ape, which may have pushed the high evolutionary rate of the fossil ape.
Preoperative evaluation in thoracic surgery: limits of the patient's functional operability and consequence for perioperative anaesthesiologic management
Authors: Starke Henning , von Dossow Vera , Karsten Jan 
Published: December 2021

Purpose of review
Preoperative evaluation of older and more morbid patients in thoracic surgery is getting more advanced. In this context, early risk stratification has a crucial role for adequate informed decision-making, and thus for generating favourable effects of clinical outcome.

Recent findings
Recent findings confirm that many risk factors impair mortality and morbidity beyond classical medical findings like results of lung function tests and values of the revised cardiac risk index. Especially results from holistic views on patients’ functional status like frailty assessments are linked with long-term survival after lung resection.

Summary
A comprehensive risk stratification by anaesthesiologists generates valuable guidance for the best strategy of clinical treatment. This includes preoperative, peri-operative and postoperative interventions, provided by interdisciplinary healthcare providers, resulting in an Early Risk Stratification and Strategy (’ERSAS’) pathway.
The Nurse Practitioner as Both Servant Leader and Clinical Leader
Authors: Maglione Joyce L. 
Published: December 2021

ABSTRACT:
Servant leadership prioritizes the needs of others. This leadership approach developed by Robert Greenleaf emphasizes a service-oriented holistic model of leadership. The characteristics of servant leadership within the context of a primary healthcare setting with the nurse practitioner as both servant-leader and clinical leader are examined in this article.
Outcome of bystander cardiopulmonary resuscitation after out-of-hospital cardiac arrest in Beijing
Authors: Shi Xian , Wu Yang , Li Haibin , Ma Shengkui , Li Dou , Gao Ding , Cui Hao , Yu Changxiao , Yang Song , Tang Ziren , Shao Fei 
Published: December 2021

Abstract

Aim:
We aimed to investigate the association between bystander cardiopulmonary resuscitation (CPR) and survival of patients with out-of-hospital cardiac arrests (OHCA) in Beijing.

Methods:
This observational study analyzed adult patients with OHCA treated by the Beijing emergency medical service (EMS) from January 2013 to December 2017. Data were collected in a Utstein style with a 1-year follow-up and a primary outcome of survival to hospital discharge. Secondary outcomes were return of spontaneous circulation (ROSC), survival to admission, favorable neurological outcome at hospital discharge, and survival and favorable neurological outcomes of up to 1 year.

Results:
A total of 5016 patients with OHCA from Beijing's urban area were recorded by EMS, wherein 765 patients (15.25%) underwent bystander CPR. The data were propensity score-matched forage, sex, location, witness, aetiology, initial rhythm, and call to EMS arrival to compare the difference between the occurrence and nonoccurrence of bystander CPR. The survival upon the discharge of patients who experienced bystander CPR was superior to that of patients who did not receive bystander CPR (3.7% vs 1.2%, respectively; P
< 0.001). Moreover, patients with OHCA resuscitated with bystander CPR achieved better outcomes of ROSC, survival to admission, favorable neurological outcome at hospital discharge, survival and favorable neurological outcome after 1 year compared with those who were not resuscitated with bystander CPR.

Conclusion:
Survival and neurological outcome of patients who underwent bystander CPR was better than those who underwent nonbystander CPR in Beijing. However, the rate of bystander CPR was low.
Neurocardiovascular coupling in congenital diaphragmatic hernia patients undergoing different types of surgical treatment
Authors: Hendrikx Dries , Costerus Sophie A. , Zahn Katrin , Perez-Ortiz Alba , Dorado Alexander Caicedo , Van Huffel Sabine , de Graaff Jurgen , Wijnen René , Wessel Lucas , Tibboel Dick , Naulaers Gunnar 
Published: December 2021

BACKGROUND
The effect of peri-operative management on the neonatal brain is largely unknown. Triggers for perioperative brain injury might be revealed by studying changes in neonatal physiology peri-operatively.

OBJECTIVE
To study neonatal pathophysiology and cerebral blood flow regulation peri-operatively using the neuro-cardiovascular graph.

DESIGN
Observational, prospective cohort study on perioperative neuromonitoring. Neonates were included between July 2018 and April 2020.

SETTING
Multicentre study in two high-volume tertiary university hospitals.

PATIENTS
Neonates with congenital diaphragmatic hernia were eligible if they received surgical treatment within the first 28 days of life. Exclusion criteria were major cardiac or chromosomal anomalies, or syndromes associated with altered cerebral perfusion or major neurodevelopmental impairment. The neonates were stratified into different groups by type of peri-operative management.

INTERVENTION
Each patient was monitored using near-infrared spectroscopy and EEG in addition to the routine peri-operative monitoring. Neurocardiovascular graphs were computed off-line.

MAIN OUTCOME MEASURES
The primary endpoint was the difference in neurocardiovascular graph connectivity in the groups over time.

RESULTS
Thirty-six patients were included. The intraoperative graph connectivity decreased in all patients operated upon in the operation room (OR) with sevoflurane-based anaesthesia (P < 0.001) but remained stable in all patients operated upon in the neonatal intensive care unit (NICU) with midazolam-based anaesthesia. Thoracoscopic surgery in the OR was associated with the largest median connectivity reduction (0.33 to 0.12, P < 0.001) and a loss of baroreflex and neurovascular coupling. During open surgery in the OR, all regulation mechanisms remained intact. Open surgery in the NICU was associated with the highest neurovascular coupling values.

CONCLUSION
Neurocardiovascular graphs provided more insight into the effect of the peri-operative management on the pathophysiology of neonates undergoing surgery. The neonate's clinical condition as well as the surgical and the anaesthesiological approach affected the neonatal physiology and CBF regulation mechanisms at different levels.

TRIAL REGISTRATION
NL6972, URL: https://www.trialre-gister.nl/trial/6972.
Drug–Drug Interactions Between Mycophenolic Acid and Proton Pump Inhibitors: A Systematic Review and Meta-Analysis
Authors: Sakuludomkan Wannachai , Na Takuathung Mingkwan , Dukaew Nahathai , Koonrungsesomboon Nut 
Published: December 2021

Purpose:
The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA).

Methods:
PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C0), maximum concentration (Cmax), time to maximum concentration (Tmax), the dose-adjusted area under the concentration–time curve from time 0–12 hours (AUC0–12 h/D), and half-life (t1/2)], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model.

Results:
Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C0 [mean difference (MD) = −0.62 mg/L; P = 0.003] lower C
max (MD = −4.71 mg/L; P = 0.01), and longer Tmax (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC0–12 h/D, t1/2, or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium.

Conclusions:
Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.
Has the Time Come for Systematic Therapeutic Drug Monitoring of First-Line and WHO Group A Antituberculosis Drugs?
Authors: Lemaitre Florian 
Published: December 2021

Abstract:
Tuberculosis (TB) is a major global health issue, with approximately 10 million people being infected each year, and is the leading cause of mortality from infectious disease, with 1.5 million deaths a year. Optimal TB treatment requires a combination of drugs for an adequate treatment duration owing to persistent organisms, hardly accessible infection sites, and a high risk of resistance selection. Long-term therapy increases the risk of patients' loss of adherence, adverse drug reactions, and drug–drug interactions, potentially leading to treatment failure. The high interpatient variability of TB drug exposure is another point eliciting interest in therapeutic drug monitoring (TDM) to optimize treatment. Studies reporting clinically relevant exposure thresholds, which might be proposed as targets toward treatment personalization, are discussed. Practical TDM strategies have also been reported to circumvent issues related to delayed drug absorption and the need for multiple samples when evaluating the area under the curve of drug concentrations. The need for treatment individualization is further emphasized because of the development of multidrug-resistant TB or extensively drug-resistant TB. Finally, the willingness to shorten the treatment duration while maintaining success is also a driver for ensuring adequate exposure to TB drugs with TDM. The aim of the present review was to underline the role of TDM in drug-susceptible TB and World Health Organization group A TB drugs.
Early versus Delayed Implant Exchange after Periprosthetic Breast Infection: A Single Center Study
Authors: Falola Reuben A. , Shin Hope D. , Monsivais Sharon E. , Czerwinski Wendy L. 
Published: December 2021

Background:
Breast implant infections are challenging problems for both plastic surgeons and patients. They may require readmissions, re-operations, and have the potential to compromise the final result. Our goal was to determine whether early operative intervention (return to the operating room <72 h after diagnosis of infection) or intravenous antibiotics with later operative intervention increased long-term retention of a prosthesis.

Methods:
A retrospective review was conducted of patients who were hospitalized or underwent reoperation for an infection from 2006 through 2016. The length of hospitalization, length of IV antibiotic use, and retention of the breast prosthesis at 3-months after reoperation were recorded for each patient.

Results:
A total of 43 patients were included in our study. Of these, 33 patients underwent early intervention, and 10 patients underwent delayed intervention. The average length of stay was significantly shorter in the early versus delayed return to OR group (4.1 versus 6.4 days; P = 0.008). The average duration of antibiotics was shorter in the early intervention group than the delayed group (5.1 versus 6.4 days; P = 0.28). At 3-months postoperatively, a greater proportion of patients in the early intervention group compared with the delayed group retained their breast prostheses (87.5% versus 60%; P = 0.25).

Conclusions:
The results of this study demonstrate that breast implants may be salvaged after early (<72 hours) or delayed (>72 hours) operative intervention; however, early intervention is associated with a significantly shorter length of stay, and trends toward a shorter antibiotic course and higher rate of implant retention at 3 months.
Analysis of Corneal Scheimpflug Densitometry and Ocular Wavefront Aberrations Post Descemet Stripping Automated Endothelial Keratoplasty
Authors: Arora Ritu , Gupta Palak , Sahu Jigyasa , Jain Parul , Vishwanath Shweta , Shroff Rushad 
Published: December 2021

Purpose:
To assess the role of corneal densitometry and wavefront aberrations post Descemet stripping automated endothelial keratoplasty (DSAEK) and their correlation with visual acuity.

Methods:
Twenty-seven eyes of 25 patients with nonresolving corneal edema for more than 3 months as a result of Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, or secondary endothelial dysfunction were enrolled in a prospective interventional study and underwent DSAEK. Postoperative evaluation for corneal aberrations, including Higher order aberrations (HOAs) and corneal densitometry (CD), was performed using anterior-segment optical coherence tomography (Avanti RTvue XR; Optovue) and Scheimpflug imaging (Pentacam, Oculus Optikgeräte GmbH, Wetzlar, Germany) at 6 months. A correlation analysis of corneal aberrations, including HOAs and CD, with postoperative best-corrected visual acuity at 6 months was performed.

Results:
Mean best-corrected visual acuity (BCVA) improved from 1.67±0.53 log of minimum angle of resolution (logMAR) to 0.2±0.22 logMAR post DSAEK at 6 months (P≤0.0001). At 6 months, mean root-mean-square (RMS) total corneal aberrations (includes HOA and low-order aberration [LOA]), RMS total HOA, and RMS LOA of the central 6-mm zone were 4.99±2.64, 1.80±0.9, and 4.55±2.64, respectively. The mean corneal densitometry from anterior, central, and posterior zones were 39.12±12.77, 23.9±7.2, and 13.54±2.04 gray scale units, respectively. Total anterior aberrations (r=0.051; P=0.006), anterior LOA (r=0.049; P=0.009), total corneal aberrations (r=0.051; P=0.001), total HOAs (r=0.095; P=0.057) and LOAs (r=0.050; P=0.002), and total CD from 0 to 2 mm (r=0.010; P=0.038) and 2 to 6 mm (r=0.014; P=0.018) showed a significant inverse correlation with postoperative BCVA.

Conclusion:
There was an inverse relationship between post DSAEK BCVA and total corneal HOAs and full-thickness densitometry at 6 months. Scheimpflug imaging with added tools for corneal aberration and densitometry analysis gives further insight into the suboptimal vision achieved despite transparent corneas post DSAEK.
Association of Metabolic Syndrome With Glaucoma and Ocular Hypertension in a Midwest United States Population
Authors: Wu Kristi Y. , Hodge David O. , White Launia J. , McDonald Jacinta , Roddy Gavin W. 
Published: December 2021

Précis:
For patients with glaucoma, metabolic syndrome was associated with higher intraocular pressure and greater central corneal thickness. Patients with metabolic syndrome were more likely to have ocular hypertension.

Purpose:
The purpose of this study was to determine whether glaucomatous optic neuropathy, also known as glaucoma, and ocular hypertension are more likely to occur in patients with metabolic syndrome.

Patients and Methods:
Patients in Olmsted County, MN, were identified as having metabolic syndrome based on diagnosis codes, laboratory values, and/or medication use to meet 3 or more of the 5 standard criteria for diagnosing metabolic syndrome: systemic hypertension, hyperglycemia, hypertriglyceridemia, reduced high-density lipoprotein cholesterol, and central adiposity defined by increased body mass index. Patients with glaucoma, including primary open angle, low tension, pigment dispersion, and pseudoexfoliation, were identified using diagnostic codes. The charts of patients with glaucoma were individually reviewed to collect visual acuity, intraocular pressure, cup to disc ratio, central corneal thickness, visual field mean deviation, retinal nerve fiber layer thickness, and treatment of intraocular pressure. Patients with ocular hypertension were separately identified and similarly evaluated.

Results:
For patients with glaucoma, those with metabolic syndrome had higher intraocular pressure and greater central corneal thickness compared with those without metabolic syndrome. After adjustment for central corneal thickness, there was no longer a significant difference in intraocular pressure between groups. Metabolic syndrome was also associated with the diagnosis of ocular hypertension, and although central corneal thickness trended higher in patients with metabolic syndrome, it did not attain statistical significance.

Conclusion:
In Olmsted County, though metabolic syndrome was associated with ocular hypertension and higher intraocular pressure in patients with glaucoma, the results were likely related to a thicker central corneal in this patient population.
Management of stable coronary artery disease and atrial fibrillation with anti-thrombotic therapy
Authors: Malladi Srikanth , Hamid Kewan , Pendyala Nitin Chandra , Veerapaneni Vijaysai , Deliwala Smit , Dubre Donald , Elian Samir A. , Singh Adiraj 
Published: December 2021

Abstract

Introduction:
Long term management of patients with stable coronary artery disease of >1 year after myocardial infarction (MI) or percutaneous coronary intervention and atrial fibrillation is unclear. Current guidelines recommend using oral anti-coagulation (OAC) alone although the recommendation is weak and there is low quality evidence. Two new randomized control trials (RCTs) were published recently. We conducted an updated meta-analysis to evaluate the effect of these studies on patient outcomes

Objective:
To conduct a systematic review and meta-analysis of published RCTs and observational studies to compare OAC alone versus OAC plus single anti-platelet therapy.

Methods:
Electronic searches were conducted using appropriate terms from 3 databases. Relevant studies included. Data extracted and analysis were performed using STATA.

Measurements:
Summary statistics were pooled and measured for primary and secondary outcomes of both treatment arms.

Main results:
Eight studies involving 10,120 patients were included for the analysis. Five thousand two hundred thirty-seven patients were on combination therapy while 4883 were on OAC alone. There was no statistically significant difference in the primary outcome of major adverse cardiac events (hazard ratio [HR] 1.067; 95% confidence interval [CI] 0.912–1.249; P value .417). There was no statistically significant difference even in the measured secondary outcomes namely all cause mortality (HR 1.048; 95% CI 0.830–1.323; P value .695), cardiovascular mortality (HR 0.863; 95% CI 0.593–1.254; P value .439). However, we found statistically significant difference between the 2 groups in the incidence of MI with higher incidence in mono therapy group (HR 1.229; 95% CI 1.011–1.495; P value .039) and higher incidence of major bleeding in the combination therapy group in the subgroup analysis (HR 0.649; 95% CI 0.464–0.907; P value .011).

Conclusion:
We found no reduction of major adverse cardiac event between combination therapy and mono therapy. Although mono therapy showed increased risk of major bleeding overall, subgroup analysis of the RCTs showed increased risk of major bleeding in the combination therapy group. MI was higher in the mono therapy group compared to the combination therapy group, however this outcome was not reproducible in the subgroup analysis of the RCTs.