bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Syncytial Virus Prefusion F Vaccine in Adults With Concomitant Inactivated Influenza Vaccine
Authors: Falsey Ann R , Walsh Edward E , Scott Daniel A , Gurtman Alejandra , Zareba Agnieszka , Jansen Kathrin U , Gruber William C , Dormitzer Philip R , Swanson Kena A , Jiang Qin , Gomme Emily , Cooper David , Schmoele-Thoma Beate
Published: December 2021

Background

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults and adults with comorbidities. An effective vaccine is needed. An investigational bivalent prefusion F vaccine (RSVpreF) was assessed in healthy adults.

Methods

This phase 1/2 study randomized adults 18–85 years old to receive placebo or 60, 120, or 240 µg RSVpreF (with or without aluminum hydroxide) alone or concomitantly with seasonal inactivated influenza vaccine (SIIV). Safety and immunogenicity were assessed.

Results

In older adults, reactogenicity events were predominantly mild or moderate among RSVpreF recipients; adverse events through 1 month postvaccination were similar across formulations. Coadministration with SIIV did not appear to affect safety among younger or older adults. All RSVpreF formulations with or without concomitant SIIV elicited robust RSV serum-neutralizing responses in adults aged 50–85 years 1 month postvaccination. Neutralizing titers 1 and 12 months postvaccination were 6.9–14.9 and 2.9–4.5 times, respectively, those before vaccination. SIIV immune responses trended lower when coadministered with RSVpreF.

Conclusions

RSVpreF formulations administered alone or with SIIV were well tolerated and highly immunogenic in older adults, supporting the potential for RSVpreF to protect older adults from RSV disease.

Clinical Trials Registration

NCT03529773.
Transmission barrier of the blaKPC plasmid mediated by type I restriction-modification systems in Escherichia coli
Authors: Li Dan , Li Pei , Peng Mingjia , Zhao Xiaoyu , Jiang Xiaoying , Wang Dongliang , Yuan Yuan , Guo Qinglan , Wang Minghua , Xu Xiaogang , Wang Minggui
Published: December 2021

Background

Transportation of carbapenem-resistant plasmids contributes to carbapenem resistance in Gram-negative bacteria. KPC enzymes are the most clinically important enzymes among carbapenem-resistant Klebsiella pneumoniae, whereas the rate of blaKPC in Escherichia coli is low. The CRISPR-Cas system and restriction-modification system (R-M system) in bacteria defend against invading genomes. Currently, the role of the immune systems in the low rate of KPC-producing E. coli remains unclear.

Objectives

We investigated the relationship between immune systems and the low detection rate of blaKPC in E. coli.

Methods

We searched for blaKPC among 1039 E. coli whole genomes available in GenBank using nucleotide BLAST. CRISPR-Cas systems and the R-M system were detected in all strains having the ST as blaKPC-positive strains. Nucleotide BLAST was used to search for protospacers on blaKPC plasmids. A conjugation assay was performed to determine whether the R-M system influences the acquisition of blaKPC plasmids by E. coli.

Results

ST131 was the dominant ST of KPC-producing E. coli and IncN was the main plasmid type (12/32). CRISPR-Cas systems were frequently present in E. coli carrying blaKPC. Furthermore, CRISPR-Cas systems in E. coli didn’t target plasmids with blaKPC. Type I R-M systems were rare in KPC-producing E. coli, but significantly over-represented in KPC-negative strains. E. coli DH5α with hsdR deletion accepted blaKPC-carrying plasmids, whereas those with hsdR complementation impeded blaKPC-carrying plasmid conjugation.

Conclusions

Horizontal transmission of blaKPC occurs among E. coli. The type I R-M system is associated with the defence against blaKPC plasmid transport into E. coli.
Logic of informal provability with truth values
Authors: Pawlowski Pawel , Urbaniak Rafal
Published: December 2021

Classical logic of formal provability includes Löb’s theorem, but not reflection. In contrast, intuitions about the inferential behavior of informal provability (in informal mathematics) seem to invalidate Löb’s theorem and validate reflection (after all, the intuition is, whatever mathematicians prove holds!). We employ a non-deterministic many-valued semantics and develop a modal logic T-BAT of an informal provability operator, which indeed does validate reflection and invalidates Löb’s theorem. We study its properties and its relation to known provability-related paradoxical arguments. We also argue that T-BAT is a fairly sensible candidate for a formal logic of informal provability.
Effect of carrier material on the thermodynamic properties and recrystallization kinetics of andrographolide-solid dispersion
Authors: Zhao Guowei , Zhang Junfang , Cai Ping , Ou Liquan , Liang Xinli , Dong Wei , Liao Zhenggen
Published: December 2021

Objectives

This work investigated the effect of the lipophilic long carbon chain of carrier material on the thermodynamic properties and the recrystallization kinetics of solid dispersion (SD).

Methods

The thermodynamic properties and recrystallization kinetic parameters of amorphous andrographolide (AG)-PEG8000 laurate (SM12)-SD, AG-PEG8000 palmitate (SM16)-SD and AG-PEG8000 behenate (SM22)-SD were determined and calculated by differential scanning calorimetry combining AGV equation and Avrami equation.

Key findings

From AG-SM12-SD to AG-SM22-SD with the increase of the carbon chain length of carrier material, the glass transition temperature, the maximum relaxation enthalpy and the mean relaxation time of SD increased at first and then decreased; the isothermal crystallization rate constants at different temperatures and non-isothermal crystallization rate constants at different heating rates of SD showed a trend of decreasing at first and then increasing.

Conclusions

Increasing the carbon chain length of polyethylene glycol fatty acid ester can improve the space-limiting effect of the carrier material on the AG molecule, but the carbon chain length of carrier was not the longer the better. SM16 had the appropriate spatial scale, which better limited the molecular mobility of AG in SD, so AG-SM16-SD has better thermodynamic stability and recrystallization kinetic stability.
Natural variation in stomatal dynamics drives divergence in heat stress tolerance and contributes to seasonal intrinsic water-use efficiency in Vitis vinifera (subsp. sativa and sylvestris)
Authors: Faralli Michele , Bontempo Luana , Bianchedi Pier Luigi , Moser Claudio , Bertamini Massimo , Lawson Tracy , Camin Federica , Stefanini Marco , Varotto Claudio
Published: December 2021

Stomata control CO2 uptake for photosynthesis and water loss through transpiration, thus playing a key role in leaf thermoregulation, water-use efficiency (iWUE), and plant productivity. In this work, we investigated the relationship between several leaf traits and hypothesized that stomatal behavior to fast (i.e. minutes) environmental changes co-determines, along with steady-state traits, the physiological response of grapevine to the surrounding fluctuating environment over the growing season. No relationship between iWUE, heat stress tolerance, and stomatal traits was observed in field-grown grapevine, suggesting that other physiological mechanisms are involved in determining leaf evaporative cooling capacity and the seasonal ratio of CO2 uptake (A) to stomatal conductance (gs). Indeed, cultivars that in the field had an unexpected combination of high iWUE but low sensitivity to thermal stress displayed a quick stomatal closure to light, but a sluggish closure to increased vapor pressure deficit (VPD) levels. This strategy, aiming both at conserving water under a high to low light transition and in prioritizing evaporative cooling under a low to high VPD transition, was mainly observed in the cultivars Regina and Syrah. Moreover, cultivars with different known responses to soil moisture deficit or high air VPD (isohydric versus anisohydric) had opposite behavior under fluctuating environments, with the isohydric cultivar showing slow stomatal closure to reduced light intensity but quick temporal responses to VPD manipulation. We propose that stomatal behavior to fast environmental fluctuations can play a critical role in leaf thermoregulation and water conservation under natural field conditions in grapevine.
The effects of lensing by local structures on the dipole of radio source counts
Authors: Murray Calum
Published: December 2021

Our peculiar motion in a homogeneous and isotropic universe imprints a dipole in the cosmic microwave background (CMB) temperature field and similarly imprints a dipole in the distribution of extragalactic radio sources on the sky. Each of these effects have been measured; however, each of these measurements give different results for the velocity of our motion through the Universe: the radio dipole measurements finds the speed of our motion to be around three times larger than that of the CMB. Here we show the effects of the previously unconstrained lensing dipole, whereby necessarily local structures (required for large angular lensing scales) will distort the distribution of radio sources on the sky. We find that the inclusion of these effects does not reduce the tension between the CMB and radio source dipole measurements; however, without their inclusion future extragalactic number counts could lead to incorrect inferences of our peculiar motion. In addition we can constrain the size of the lensing dipole to be κ < 3 · 10−2 at the 2σ level.
A selection function toolbox for subsets of astronomical catalogues
Authors: Boubert Douglas , Everall Andrew
Published: December 2021

Large catalogues are ubiquitous throughout astronomy, but most scientific analyses are carried out on smaller samples selected from these catalogues by chosen cuts on catalogued quantities. The selection function of that scientific sample – the probability that a star in the catalogue will satisfy these cuts and so make it into the sample – is thus unique to each scientific analysis. We have created a general framework that can flexibly estimate the selection function of a sample drawn from a catalogue in terms of position, magnitude and colour. Our method is unique in using the binomial likelihood and accounting for correlations in the selection function across position, magnitude, and colour using Gaussian processes and spherical harmonics. We have created a new open-source python package selectionfunctiontoolbox that implements this framework and used it to make three different estimates of the APOGEE DR16 red giant sample selection function, as a subset of 2MASS, with each estimate using an increasing amount of technical knowledge of the APOGEE targeting. In a companion paper, we applied our methodology to derive estimates of the astrometric and spectroscopic selection functions of Gaia EDR3. Our framework will make it trivial for astrophysicists to estimate the selection function that they should be using with the custom sample of stars that they have chosen to answer their scientific question.
How cosmological merger histories shape the diversity of stellar haloes
Authors: Rey Martin P , Starkenburg Tjitske K
Published: December 2021

We introduce and apply a new approach to probe the response of galactic stellar haloes to the interplay between cosmological merger histories and galaxy formation physics. We perform dark matter-only, zoomed simulations of two Milky Way-mass hosts and make targeted, controlled changes to their cosmological histories using the genetic modification technique. Populating each history’s stellar halo with a semi-empirical, particle tagging approach then enables a controlled study, with all instances converging to the same large-scale structure, dynamical and stellar mass at z = 0 as their reference. These related merger scenarios alone generate an extended spread in stellar halo mass fractions (1.5 dex) comparable to the observed population, with the largest scatter achieved by growing late (z ≤ 1) major mergers that spread out existing stars to create massive, in-situ dominated stellar haloes. Increasing a last major merger at z ∼ 2 brings more accreted stars into the inner regions, resulting in smaller scatter in the outskirts which are predominantly built by subsequent minor events. Exploiting the flexibility of our semi-empirical approach, we show that the diversity of stellar halo masses across scenarios is reduced by allowing shallower slopes in the stellar mass–halo mass relation for dwarf galaxies, while it remains conserved when central stars are born with hotter kinematics across cosmic time. The merger-dependent diversity of stellar haloes thus responds distinctly to assumptions in modelling the central and dwarf galaxies respectively, opening exciting prospects to constrain star formation and feedback at different galactic mass-scales with the coming generation of deep, photometric observatories.
Tracing the Origin and Evolutionary Fate of Recent Gene Retrocopies in Natural Populations of the House Mouse
Authors: Zhang Wenyu , Tautz Diethard
Published: December 2021

Although the contribution of retrogenes to the evolution of genes and genomes has long been recognized, the evolutionary patterns of very recently derived retrocopies that are still polymorphic within natural populations have not been much studied so far. We use here a set of 2,025 such retrocopies in nine house mouse populations from three subspecies (Mus musculus domesticus, M. m. musculus, and M. m. castaneus) to trace their origin and evolutionary fate. We find that ancient house-keeping genes are significantly more likely to generate retrocopies than younger genes and that the propensity to generate a retrocopy depends on its level of expression in the germline. Although most retrocopies are detrimental and quickly purged, we focus here on the subset that appears to be neutral or even adaptive. We show that retrocopies from X-chromosomal parental genes have a higher likelihood to reach elevated frequencies in the populations, confirming the notion of adaptive effects for “out-of-X” retrogenes. Also, retrocopies in intergenic regions are more likely to reach higher population frequencies than those in introns of genes, implying a more detrimental effect when they land within transcribed regions. For a small subset of retrocopies, we find signatures of positive selection, indicating they were involved in a recent adaptation process. We show that the population-specific distribution pattern of retrocopies is phylogenetically informative and can be used to infer population history with a better resolution than with SNP markers.
Coronaviral RNA-methyltransferases: function, structure and inhibition
Authors: Nencka Radim , Silhan Jan , Klima Martin , Otava Tomas , Kocek Hugo , Krafcikova Petra , Boura Evzen
Published: December 2021

Coronaviral methyltransferases (MTases), nsp10/16 and nsp14, catalyze the last two steps of viral RNA-cap creation that takes place in cytoplasm. This cap is essential for the stability of viral RNA and, most importantly, for the evasion of innate immune system. Non-capped RNA is recognized by innate immunity which leads to its degradation and the activation of antiviral immunity. As a result, both coronaviral MTases are in the center of scientific scrutiny. Recently, X-ray and cryo-EM structures of both enzymes were solved even in complex with other parts of the viral replication complex. High-throughput screening as well as structure-guided inhibitor design have led to the discovery of their potent inhibitors. Here, we critically summarize the tremendous advancement of the coronaviral MTase field since the beginning of COVID pandemic.
Inference with Many Weak Instruments
Authors: Mikusheva Anna , Sun Liyang
Published: December 2021

We develop a concept of weak identification in linear instrumental variable models in which the number of instruments can grow at the same rate or slower than the sample size. We propose a jackknifed version of the classical weak identification-robust Anderson–Rubin (AR) test statistic. Large-sample inference based on the jackknifed AR is valid under heteroscedasticity and weak identification. The feasible version of this statistic uses a novel variance estimator. The test has uniformly correct size and good power properties. We also develop a pre-test for weak identification that is related to the size property of a Wald test based on the Jackknife Instrumental Variable Estimator. This new pre-test is valid under heteroscedasticity and with many instruments.
European bio-naïve spondyloarthritis patients initiating TNF inhibitor: time trends in baseline characteristics, treatment retention and response
Authors: Christiansen Sara Nysom , Ørnbjerg Lykke Midtbøll , Rasmussen Simon Horskjær , Loft Anne Gitte , Askling Johan , Iannone Florenzo , Zavada Jakub , Michelsen Brigitte , Nissen Michael , Onen Fatos , Santos Maria Jose , Pombo-Suarez Manuel , Relas Heikki , Macfarlane Gary J , Tomsic Matija , Codreanu Catalin , Gudbjornsson Bjorn , Van der Horst-Bruinsma Irene , Di Giuseppe Daniela , Glintborg Bente , Gremese Elisa , Pavelka Karel , Kristianslund Eirik Klami , Ciurea Adrian , Akkoc Nurullah , Barcelos Anabela , Sánchez-Piedra Carlos , Peltomaa Ritva , Jones Gareth T , Rotar Ziga , Ionescu Ruxandra , Grondal Gerdur , Van de Sande Marleen G H , Laas Karin , Østergaard Mikkel , Hetland Merete L
Published: December 2021

Objectives

To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment.

Methods

Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999–2008), B (2009–2014) and C (2015–2018). Retention, remission and response rates were assessed at 6, 12 and 24 months.

Results

In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months.

Conclusion

Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.
Features of non-Hodgkin’s lymphoma diagnosed in minor salivary gland biopsies from primary Sjögren’s syndrome patients
Authors: Parreau Simon , Nocturne Gaétane , Mariette Xavier , Burroni Barbara , Lazure Thierry , Besson Florent L , Régent Alexis , Mouthon Luc , Terrier Benjamin , Seror Raphaele , Le Guern Véronique
Published: December 2021

Objective

To evaluate the contribution of minor salivary gland biopsy (mSGB) histology in diagnosing primary SS (pSS)-associated non-Hodgkin B-cell lymphoma (NHL).

Methods

pSS patients with mSGB at NHL diagnosis were included.

Results

Among the 24 patients (92.3% female, mean age 61.3 years) with an mSGB at NHL diagnosis, 13 (54.2%) had mSGB histology–revealed NHL (mSGB+); it was the only site enabling NHL diagnosis in 10/13 (76.9%) patients. Mucosa-associated lymphoid tissue (MALT) lymphoma was found in 23/24 (95.8%) patients; 100% of mSGB+ identified MALT lymphomas. pSS and lymphoma characteristics were comparable for mSGB+ and mSGB− patients. Eight (61.5%) of the 13 mSGB+ patients and all 11 mSGB− patients were treated for lymphoma. Between diagnosis and 1 year of follow-up, the ESSDAI without the NHL item remained stable (7.4 vs 5.0; P = 0.33) for the five untreated patients, while it decreased significantly for the 19 treated patients (15.8 vs 5.1; P = 0.004).

Conclusion

For pSS patients with suspected NHL, mSGB histology enabled NHL diagnosis in half of them, MALT was found in 95.8% and all mSGB+ were MALT lymphomas, thereby avoiding more invasive biopsy. Our results suggest that mSGB should be obtained at pSS diagnosis and repeated during follow-up when NHL is suspected.
INDOOR RADON CONCENTRATION AND EXCESS LIFETIME CANCER RISK
Authors: Otansev Pelin , Bingöldağ Nesli
Published: December 2021

In this study, the indoor radon ( 222Rn) levels in summer and winter seasons were measured by using a total of 537 CR-39 detectors. The arithmetic mean values (ranges) of radon activity concentrations (RACs) in summer and winter seasons were found to be 71 Bq m −3 (27–313 Bq m−3) and 241 (89–1047 Bq m−3), respectively. In 20 houses, the RAC was higher than 400-Bq m−3 critical value declared by the Turkish Atomic Energy Authority (TAEK). The mean radon concentrations in summer and winter seasons were below the critical value declared by TAEK. According to normality test, the radon distributions in summer and winter seasons were determined as log-normal. The annual mean effective dose equivalent and the mean excess lifetime cancer risk were calculated as 8 mSv y−1 and 26 × 10−3.
The Frequency and Topology of Pseudoorthologs
Authors: Smith Megan L , Hahn Matthew W
Published: December 2021

Phylogenetics has long relied on the use of orthologs, or genes related through speciation events, to infer species relationships. However, identifying orthologs is difficult because gene duplication can obscure relationships among genes. Researchers have been particularly concerned with the insidious effects of pseudoorthologs—duplicated genes that are mistaken for orthologs because they are present in a single copy in each sampled species. Because gene tree topologies of pseudoorthologs may differ from the species tree topology, they have often been invoked as the cause of counterintuitive results in phylogenetics. Despite these perceived problems, no previous work has calculated the probabilities of pseudoortholog topologies or has been able to circumscribe the regions of parameter space in which pseudoorthologs are most likely to occur. Here, we introduce a model for calculating the probabilities and branch lengths of orthologs and pseudoorthologs, including concordant and discordant pseudoortholog topologies, on a rooted three-taxon species tree. We show that the probability of orthologs is high relative to the probability of pseudoorthologs across reasonable regions of parameter space. Furthermore, the probabilities of the two discordant topologies are equal and never exceed that of the concordant topology, generally being much lower. We describe the species tree topologies most prone to generating pseudoorthologs, finding that they are likely to present problems to phylogenetic inference irrespective of the presence of pseudoorthologs. Overall, our results suggest that pseudoorthologs are unlikely to mislead inferences of species relationships under the biological scenarios considered here.[Birth–death model; orthologs; paralogs; phylogenetics.]
Potassium deficiency inhibits leaf growth and promotes leaf necrotic spots in Neolamarckia cadamba (Roxb.) Bosser
Authors: Liu Yi , Lu Lu , Zhang Yuanyuan , Yin Qi , Yi Na , Qaseem Mirza Faisal , Li Huiling , Wu Ai-Min
Published: December 2021

Leaves, being a key plant organ involved in photosynthesis, play an important role in plant growth and development. Although there have been a few studies on the effects of potassium (K+) deficiency on the leaves of woody plants, knowledge about mechanism of necrotic spot formation on leaves during K+ deficiency is scarce. We used a hydroponics setup to understand the effects of K+ deficiency on Neolamarckia cadamba (Roxb.) Bosser. K+ deficiency resulted in smaller leaves and necrotic spots on the older leaves, whereas regulatory modules of the differentially expressed genes (DEGs) involved in cell proliferation, cell cycle and cell expansion were downregulated. K+ deficiency increased the activity of reactive oxygen species scavenging enzymes such as superoxide dismutase, ascorbate peroxidases and malondialdehyde, and expression of DEGs related to these was also upregulated. Strong diaminobenzidine staining was observed on the older leaves showing accumulation of H2O2 during K+ deficiency treatment. In addition, putrescine and ethylene synthesis genes were upregulated. Fifteen DEGs in response to ethylene signaling, including ETR1, ETR2, EBF1, ERF1 and ERF2, were upregulated in the third week. The leaf growth changes caused by K+ deficiency in N. cadamba were well demonstrated by our findings.
Establishing Clinical Cut-points on the Pediatric PROMIS-Pain Interference Scale in Youth With Abdominal Pain
Authors: Gamwell Kaitlyn L. , Mara Constance A. , Hommel Kevin A. , Kashikar-Zuck Susmita , Cunningham Natoshia R.
Published: December 2021

Objective:

Abdominal pain is a common presenting complaint in youth seeking medical care and can be debilitating. Therefore, it is important to understand the impact of pain on functioning using a clinically sensitive approach. The National Institutes of Health has established a common core of psychometrically precise measures through the Patient-Reported Outcomes Measurement Information System (PROMIS) initiative. The Pediatric PROMIS-Pain Interference (PPPI) scale was developed to measure pain-related interference, drawing from existing legacy measures. However, its clinical validity has not been thoroughly established in clinical populations. The current study sought to develop clinical cut-points and investigate the validity of the PPPI in a large sample (N=5281) of youth presenting to gastroenterological care with abdominal pain symptoms.

Materials and Methods:

Convergent validity of the PPPI was investigated. Quartile and tertile groupings of the PPPI were calculated and compared with cut-points derived from healthy populations and mixed convenience samples on clinical outcomes via multivariate analyses of variance.

Results:

There was good evidence of convergent validity. The tertile solution was superior in classifying different levels of pain-related outcomes as compared with other cut-points. The tertile solution suggested the following PPPI groupings: minimal (≤51), moderate (52 to 59), and severe (≥60).

Discussion:

Results suggest the PPPI is a valid measure with clinically meaningful cut-points to assess pain-related interference in youth with abdominal pain.
Impact of Transversus Abdominis Plane Block With Bupivacaine or Ropivacaine Versus Intrathecal Morphine on Opioid-related Side Effects After Cesarean Delivery
Authors: Huang Jia-Yu , Wang Li-Zhong , Chang Xiang-Yang , Xia Feng
Published: December 2021

Objectives:

Intrathecal morphine (ITM) is frequently associated with side effects such as postoperative nausea and vomiting (PONV) and pruritus. The aim of this meta-analysis was to compare the impact of transversus abdominis plane (TAP) block versus ITM on side effects following cesarean delivery.

Materials and Methods:

PubMed, Embase, Web of Science, and CENTRAL were searched for randomized controlled trials that compared TAP with ITM for cesarean delivery. The primary outcomes were opioid-related side effects. The secondary outcomes included pain scores, opioid consumption, patient satisfaction, and time to the first analgesia request.

Results:

Seven studies involving 660 patients were included. TAP blocks were performed with bupivacaine or ropivacaine. There was less PONV with TAP versus ITM (risk ratio [RR]=0.45, 95% confidence interval [CI]: 0.33-0.63,P<0.001;I2=0%), but no significant difference in pruritus (RR=0.76, 95% CI: 0.49-1.18,P=0.22;I2=78%) and sedation (RR=0.44, 95% CI: 0.19-1.00,P=0.05;I2=0%). TAP had a greater morphine consumption in 24 hours (mean difference: 5.80 mg; 95% CI: 1.38-10.22 mg,P=0.01;I2=89%) and higher pain score at rest at 6 hours (mean difference: 0.70, 95% CI: 0.39-1.02,P<0.001;I2=56%), but similar pain at rest at 24 hours and on movement compared with ITM. No differences were found in time to first analgesia and patient satisfaction.

Discussion:

Compared with ITM, TAP block is associated with less PONV but inferior early analgesia after cesarean delivery. However, the heterogeneity among the studies highlights the need for more well-designed studies to obtain more robust conclusions.
Pitch Accuracy of Vocal Singing in Deaf Children With Bimodal Hearing and Bilateral Cochlear Implants
Authors: Xu Li , Yang Jing , Hahn Emily , Uchanski Rosalie , Davidson Lisa
Published: December 2021

Objectives:

The purpose of the present study was to investigate the pitch accuracy of vocal singing in children with severe to profound hearing loss who use bilateral cochlear implants (CIs) or bimodal devices [CI at one ear and hearing aid (HA) at the other] in comparison to similarly-aged children with normal-hearing (NH).

Design:

The participants included four groups: (1) 26 children with NH, (2) 13 children with bimodal devices, (3) 31 children with bilateral CIs that were implanted sequentially, and (4) 10 children with bilateral CIs that were implanted simultaneously. All participants were aged between 7 and 11 years old. Each participant was recorded singing a self-chosen song that was familiar to him or her. The fundamental frequencies (F0) of individual sung notes were extracted and normalized to facilitate cross-subject comparisons. Pitch accuracy was quantified using four pitch-based metrics calculated with reference to the target music notes: mean note deviation, contour direction, mean interval deviation, and F0 variance ratio. A one-way ANOVA was used to compare listener-group difference on each pitch metric. A principal component analysis showed that the mean note deviation best accounted for pitch accuracy in vocal singing. A regression analysis examined potential predictors of CI children’s singing proficiency using mean note deviation as the dependent variable and demographic and audiological factors as independent variables.

Results:

The results revealed significantly poorer performance on all four pitch-based metrics in the three groups of children with CIs in comparison to children with NH. No significant differences were found among the three CI groups. Among the children with CIs, variability in the vocal singing proficiency was large. Within the group of 13 bimodal users, the mean note deviation was significantly correlated with their unaided pure-tone average thresholds (r = 0.582, p = 0.037). The regression analysis for all children with CIs, however, revealed no significant demographic or audiological predictor for their vocal singing performance.

Conclusion:

Vocal singing performance in children with bilateral CIs or bimodal devices is not significantly different from each other on a group level. Compared to children with NH, the pediatric bimodal and bilateral CI users, in general, demonstrated significant deficits in vocal singing ability. Demographic and audiological factors, known from previous studies to be associated with good speech and language development in prelingually-deafened children with CIs, were not associated with singing accuracy for these children.
Defining Incidence of Acute Compartment Syndrome in the Research Setting: A Proposed Method From the PACS Study
Authors: Leroux Andrew , Frey Katherine P. , Crainiceanu Ciprian M. , Obremskey William T. , Stinner Daniel J. , Bosse Michael J. , Karunakar Madhav A. , O'Toole Robert V. , Carroll Eben A. , Hak David J. , Hayda Roman , Alkhoury Dana , Schmidt Andrew H.
Published: December 2021

Objective:

To compare the retrospective decision of an expert panel who assessed likelihood of acute compartment syndrome (ACS) in a patient with a high-risk tibia fracture with decision to perform fasciotomy.

Design:

Prospective observational study.

Setting:

Seven Level 1 trauma centers.

Patients/Participants:

One hundred eighty-two adults with severe tibia fractures.

Main Outcome Measurements:

Diagnostic performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver–operator curve) of an expert panel's assessment of likelihood ACS compared with fasciotomy as the reference diagnostic standard.

Secondary Outcomes:

The interrater reliability of the expert panel as measured by the Krippendorff alpha. Expert panel consensus was determined using the percent of panelists in the majority group of low (expert panel likelihood of ≤0.3), uncertain (0.3–0.7), or high (>0.7) likelihood of ACS.

Results:

Comparing fasciotomy (the diagnostic standard) and the expert panel's assessment as the diagnostic classification (test), the expert panel's determination of uncertain or high likelihood of ACS (threshold >0.3) had a sensitivity of 0.90 (0.70, 0.99), specificity of 0.95 (0.90, 0.98), PPV of 0.70 (0.50, 0.86), and NPV of 0.99 (0.95, 1.00). When a threshold of >0.7 was set as a positive diagnosis, the expert panel assessment had a sensitivity of 0.67 (0.43, 0.85), specificity of 0.98 (0.95, 1.00), PPV of 0.82 (0.57, 0.96), and NPV of 0.96 (0.91, 0.98).

Conclusion:

In our study, the retrospective assessment of an expert panel of the likelihood of ACS has good specificity and excellent NPV for fasciotomy, but only low-to-moderate sensitivity and PPV. The discordance between the expert panel–assessed likelihood of ACS and the decision to perform fasciotomy suggests that concern regarding potential diagnostic bias in studies of ACS is warranted.

Level of Evidence:

Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.
Patient-Specific Precision Injury Signatures to Optimize Orthopaedic Interventions in Multiply Injured Patients (PRECISE STUDY)
Authors: McKinley Todd O. , Gaski Greg E. , Billiar Timothy R. , Vodovotz Yoram , Brown Krista M. , Elster Eric A. , Constantine Greg M. , Schobel Seth A. , Robertson Henry T. , Meagher Ashley D. , Firoozabadi Reza , Gary Joshua L. , O'Toole Robert V. , Aneja Arun , Trochez Karen M. , Kempton Laurence B. , Steenburg Scott D. , Collins Susan C. , Frey Katherine P. , Castillo Renan C. ,   on behalf of METRC
Published: December 2021

Optimal timing and procedure selection that define staged treatment strategies can affect outcomes dramatically and remain an area of major debate in the treatment of multiply injured orthopaedic trauma patients. Decisions regarding timing and choice of orthopaedic procedure(s) are currently based on the physiologic condition of the patient, resource availability, and the expected magnitude of the intervention. Surgical decision-making algorithms rarely rely on precision-type data that account for demographics, magnitude of injury, and the physiologic/immunologic response to injury on a patient-specific basis. This study is a multicenter prospective investigation that will work toward developing a precision medicine approach to managing multiply injured patients by incorporating patient-specific indices that quantify (1) mechanical tissue damage volume; (2) cumulative hypoperfusion; (3) immunologic response; and (4) demographics. These indices will formulate a precision injury signature, unique to each patient, which will be explored for correspondence to outcomes and response to surgical interventions. The impact of the timing and magnitude of initial and staged surgical interventions on patient-specific physiologic and immunologic responses will be evaluated and described. The primary goal of the study will be the development of data-driven models that will inform clinical decision-making tools that can be used to predict outcomes and guide intervention decisions.
Streamlining Trauma Research Evaluation With Advanced Measurement (STREAM) Study: Implementation of the PROMIS Toolbox Within an Orthopaedic Trauma Clinical Trials Consortium
Authors: Carlini Anthony R. , Collins Susan C. , Staguhn Elena D. , Frey Katherine P. , O'Toole Robert V. , Archer Kristin R. , Obremskey William T. , Agel Julie , Kleweno Conor P. , Morshed Saam , Weaver Michael J. , Higgins Thomas F. , Bosse Michael J. , Levy Joseph F. , Wu Albert W. , Castillo Renan C. ,   on behalf of METRC
Published: December 2021

The Patient-Reported Outcomes Measurement Information System (PROMIS) has developed item banks, short forms, and computer-adaptive tests (CATs) to help standardize measurement for important patient-reported outcome domains. These tools have the potential to revolutionize outcome measurement in clinical research through greater assessment precision while reducing response burden. Perceived implementation challenges include the need for CAT software, mobile technology, and Internet access. Here, we present preliminary results examining the feasibility of using PROMIS tools within a large, multicenter clinical trials consortium. The assessment of 10 PROMIS domains was incorporated into the longitudinal data collection of 6 ongoing orthopaedic trauma clinical trials for participants being evaluated at 3, 6, and 12 months after an orthopaedic injury. Twelve-month assessments included both CAT assessments and completion of full item banks for a subset of domains. Data were collected for 1000 trauma patients at 43 trauma centers using a custom-built application which included an interface with our primary data capture system. Paper short forms were available as backup instruments and used infrequently. Six- and 12-month study assessments were conducted for 83% and 77% of patients, respectively. It was feasible to use PROMIS tools in a large multicenter, trauma orthopaedics research setting. The ability to efficiently assess a wide spectrum of domains is critically important to the successful completion of future large-scale trials.

Level of Evidence:

Prognostic Level II.
Characteristics of Children With Culture Negative Acute Hematogenous Musculoskeletal Infections
Authors: Searns Justin B. , DeVine Mackenzie N. , MacBrayne Christine E. , Williams Manon C. , Pearce Kelly , Donaldson Nathan , Parker Sarah K.
Published: December 2021

Background:

Identifying the causative pathogen for acute hematogenous musculoskeletal infections (MSKIs) allows for directed antimicrobial therapy and diagnostic confidence. However, 20% to 50% of children with acute MSKIs remain culture negative. The objective of this study was to compare characteristics of culture negative MSKI patients to those where a pathogen is identified.

Methods:

Electronic medical records of children admitted between July 2014 to September 2018 to a single quaternary care pediatric hospital with acute MSKIs were retrospectively reviewed. Clinical and demographic characteristics were compared between culture positive and culture negative MSKIs.

Results:

A total of 170 patients were included of whom 43 (25%) were culture negative. All culture negative patients had at least 1 culture type obtained, and the majority (84%) had both blood and source cultures performed. When compared with patients with a causative pathogen identified, culture negative patients were younger (2.3 vs. 9.8 y), smaller (13.5 vs. 31.6 kg), less likely to be febrile on arrival (56% vs. 77%), less likely to have an abscess on imaging (23% vs. 48%), and were more likely to have uncomplicated septic arthritis (35% vs. 8%). No critically ill patient was culture negative. Seven culture negative patients had additional Kingella kingae testing performed, none of which were positive.

Conclusions:

Despite targeted and standardized efforts to identify causative bacteria, 25% of children with acute MSKIs never have a pathogen identified. Culture negative patients are younger, less febrile, are less likely to have an abscess, and more likely to have isolated septic arthritis.

Level of Evidence:

This is a retrospective cohort study interested in identifying patient characteristics that predict rate of culture positivity for acute MSKIs. This study meets criteria for Level II evidence.
Acute kidney injury following adult lung transplantation
Authors: Jing Lei , Chen Wenhui , Zhao Li , Guo Lijuan , Liang Chaoyang , Chen Jingyu , Wang Chen
Published: December 2021

Background:

Acute kidney injury (AKI) is a common and serious complication following lung transplantation (LTx), and it is associated with high mortality and morbidity. This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.

Methods:

This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019. The outcomes were AKI incidence, risk factors, mortality, and kidney recovery. Multivariate analysis was performed to identify independent risk factors. Survival analysis was presented using the Kaplan–Meier curves.

Results:

AKI occurred in 137 of the 191 patients (71.7%), with transient AKI in 43 (22.5%) and persistent AKI in 94 (49.2%). AKI stage 1 occurred in 27/191 (14.1%), stage 2 in 46/191 (24.1%), and stage 3 in 64/191 (33.5%) of the AKI patients. Renal replacement therapy (RRT) was administered to 35/191 (18.3%) of the patients. Male sex, older age, mechanical ventilation (MV), severe hypotension, septic shock, multiple organ dysfunction (MODS), prolonged extracorporeal membrane oxygenation (ECMO), reintubation, and nephrotoxic agents were associated with AKI (P < 0.050). Persistent AKI was independently associated with pre-operative pulmonary hypertension, severe hypotension, post-operative MODS, and nephrotoxic agents. Severe hypotension, septic shock, MODS, reintubation, prolonged MV, and ECMO during or after LTx were related to severe AKI (stage 3) (P < 0.050). Patients with persistent and severe AKI had a significantly longer duration of MV, longer duration in the intensive care unit (ICU), worse downstream kidney function, and reduced survival (P < 0.050).

Conclusions:

AKI is common after LTx, but the pathogenic mechanism of AKI is complicated, and prerenal causes are important. Persistent and severe AKI were associated with poor short- and long-term kidney function and reduced survival in LTx patients.
Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial
Authors: Liu Yongjun , Yu Xiangyou , Zhu Duming , Zeng Jun , Lin Qinhan , Zang Bin , Chen Chuanxi , Liu Ning , Liu Xiao , Gao Wei , Guan Xiangdong
Published: December 2021

Background:

Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.

Methods:

In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1–0.2 mg/kg for 0.5–5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg−1·h−1, which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg−1·h−1, whereas for propofol the loading infusion dose was 0.5–1.0 mg/kg for 0.5–5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg−1·h−1, which could be adjusted to 0.30–4.00 mg·kg−1·h−1 to achieve −2 to +1 Richmond Agitation-Sedation Scale sedation within 6–24 h of drug administration.

Results:

Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar.

Conclusions:

ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.

Trial registration:

ClinicalTrials.gov, NCT04147416.
Phacoemulsification in patients with corneal opacities using slit illumination of the surgical microscope
Authors: Rateb Mahmoud Fathy , Hussien Mohamed Shehata , Tohamy Dalia , Kedwany Salma Mohamed
Published: December 2021

Performing phacoemulsification in eyes with corneal opacities is challenging even with expert surgeons. Several techniques have been described to improve intraoperative visualization through opacified corneas. This retrospective interventional case series included 10 eyes of 10 patients with coexisting senile cataract and corneal opacity who underwent phacoemulsification with intraocular lens (IOL) implantation under slit illumination of the surgical microscope. Uneventful phacoemulsification with IOL implantation was achieved in all eyes without intraoperative complications. Slit illumination reduced the light scattering and reflection from the corneal opacity, enhanced the red reflex, and improved depth perception simultaneously in different steps of phacoemulsification. Phacoemulsification was safely performed in eyes with corneal opacity under slit illumination of the surgical microscope. It can be considered as a viable option for improving intraoperative visualization in patients with corneal opacities without additional instrumentation.
A global study of pain prevalence across 52 countries: examining the role of country-level contextual factors
Authors: Zimmer Zachary , Fraser Kathryn , Grol-Prokopczyk Hanna , Zajacova Anna
Published: December 2021

There is wide variation in population-level pain prevalence estimates in studies of survey data around the world. The role of country-level social, economic, and political contextual factors in explaining this variation has not been adequately examined. We estimated the prevalence of unspecified pain in adults aged 25+ years across 52 countries using data from the World Health Survey 2002 to 2004. Combining data sources and estimating multilevel regressions, we compared country-level pain prevalence and explored which country-level contextual factors explain cross-country variations in prevalence, accounting for individual-level demographic factors. The overall weighted age- and sex-standardized prevalence of pain across countries was estimated to be 27.5%, with significant variation across countries (ranging from 9.9% to 50.3%). Women, older persons, and rural residents were significantly more likely to report pain. Five country-level variables had robust and significant associations with pain prevalence: the Gini Index, population density, the Gender Inequality Index, life expectancy, and global region. The model including Gender Inequality Index explained the most cross-country variance. However, even when accounting for country-level variables, some variation in pain prevalence remains, suggesting a complex interaction between personal, local, economic, and political impacts, as well as inherent differences in language, interpretations of health, and other difficult to assess cultural idiosyncrasies. The results give new insight into the high prevalence of pain around the world and its demonstrated association with macrofactors, particularly income and gender inequalities, providing justification for regarding pain as a global health priority.