bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-degenerate-pump four-wave mixing kinetic inductance travelling-wave parametric amplifiers
Authors: Longden J C , Tan B-K
Published: January 2024

Kinetic inductance travelling-wave parametric amplifiers (KITWPAs) have been demonstrated to achieve high gain over broad bandwidths whilst achieving near quantum-limited noise performance, properties which are extremely important for many ultra-sensitive experiments. In early KITWPA designs, the requirement for phase-matching lead to the creation of a large zero-gain gap in the centre of the gain profile where the peak gain is, which also slightly narrows down the operational bandwidth of the device. This has been mitigated in more recent designs by introducing a DC bias to the KITWPA device, which allows the gap to be tuned away from the amplification band. However, the added DC biasing requires a more complicated experimental setup and potentially leads to unwanted heat leak in the cryogenic environment. Additionally, operation with a DC bias also become challenging at higher frequencies beyond the microwave regime. In this paper, we present the concept of a KITWPA operating in a non-degenerate-pump four-wave mixing (NP-4WM) regime, whereby the injection of two pump tones along with a weak signal results in a broad, flat gain profile that removes the zero-gain gap as well as eliminates the need for a DC bias and the complexities associated with it. We demonstrate how a NP-4WM KITWPA is feasible to achieve broadband amplification at a range of frequencies, first in the microwave range where most KITWPAs reported to-date have been successfully experimentally characterised. We then extend the designs to several millimetre (mm) bands to illustrate how we can use this technique to design a broadband front-end pre-amplifier that covers several Atacama Large Millimetre/sub-millimetre Array (ALMA) Bands.
Apparent Treatment-Resistant Hypertension in the First Year Associated With Cardiovascular Mortality in Peritoneal Dialysis Patients
Authors: Zhu Qingyao , Huo Zhihao , Zeng Fang , Gong Nirong , Ye Peiyi , Pan Jianyi , Kong Yaozhong , Dou Xianrui , Wang Di , Huang Shuting , Yang Cong , Liu Dehui , Zhang Guangqing , Ai Jun
Published: January 2024

BACKGROUND

Few reports have focused on the association between apparent treatment-resistant hypertension (aTRH) and cardiovascular (CV) mortality in peritoneal dialysis (PD) population, thus we conducted this retrospective cohort to explore it.

METHODS

This was a retrospective cohort study conducted from January 2011 to January 2020 with PD patients in 4 Chinese dialysis centers. aTRH was defined according to the American College of Cardiology and American Heart Association guidelines. aTRH duration was calculated as the total number of months when patients met the diagnostic criteria in the first PD year. The primary outcome was CV mortality, and the secondary outcomes were CV events, all-cause mortality, combined endpoint (all-cause mortality and transferred to hemodialysis [HD]), and PD withdrawal (all-cause mortality, transferred to HD, and kidney transplantation). Cox proportional hazards models were used to assess the association.

RESULTS

A total of 1,422 patients were finally included in the analysis. During a median follow-up period of 26 months, 83 (5.8%) PD patients incurred CV mortality. The prevalence of aTRH was 24.1%, 19.9%, and 24.6% at 0, 3, and 12 months after PD initiation, respectively. Overall, aTRH duration in the first PD year positively associated with CV mortality (per 3 months increment, adjusted hazards ratio [HR], 1.29; 95% confidence interval 1.10, 1.53; P = 0.002). After categorized, those with aTRH duration more than 6 months presented the highest adjusted HR of 2.92. Similar results were found for secondary outcomes, except for the CV event.

CONCLUSIONS

Longer aTRH duration in the first PD year is associated with higher CV mortality and worse long-term clinical outcomes. Larger studies are warranted to confirm these findings.

CLINICAL TRIALS REGISTRATION

There is no clinical trial registration for this retrospective study.
Implementation of vancomycin AUC/MIC dosing vs traditional trough dosing and incidence of acute kidney injury at a rural community hospital
Authors: McClure Shannon , McElroy Laura , Gugkaeva Zina
Published: January 2024

Purpose

Vancomycin treats methicillin-resistant Staphylococcus aureus infections in hospitalized patients, yet nephrotoxicity is a major risk. Dosing based on the ratio of vancomycin 24-hour area under the curve to minimum inhibitory concentration (AUC/MIC) is preferred over a trough-only vancomycin dosing approach to minimize the risk of acute kidney injury (AKI). This study compares the safety of AUC/MIC-guided and trough-only vancomycin dosing at a 255-bed hospital.

Methods

A retrospective cohort study of adult patients with stable renal function who received at least 3 days of intravenous vancomycin via either AUC/MIC or trough-only dosing was conducted. The primary outcome was AKI occurrence during treatment. Secondary outcomes included the frequencies of therapeutic, subtherapeutic, and supratherapeutic vancomycin troughs. Relative risk calculations were performed for all outcomes.

Results

600 patients from the trough-only group and 561 patients from the AUC/MIC group were included. 121 patients from the trough-only group and 87 patients from the AUC/MIC group experienced AKI during treatment (relative risk [RR], 0.769; 95% CI, 0.599-0.988; P = 0.0397). Compared with the trough-only group, the AUC/MIC group was significantly less likely to have supratherapeutic troughs (RR, 0.703; 95% CI, 0.611-0.809; P < 0.0001) and significantly more likely to have therapeutic troughs (RR, 1.14; 95% CI, 1.069-1.211; P < 0.0001), with no significant between-group difference in subtherapeutic troughs (RR, 1.03; 95% CI, 0.854-1.25; P = 0.74).

Conclusion

AUC/MIC dosing was associated with significantly lower risk of AKI, a lower risk of supratherapeutic trough levels, and a higher risk of therapeutic trough levels, with no significant difference in subtherapeutic troughs when compared to trough-only dosing. Limitations of this study included its retrospective nature and reliance on manual chart review.
Investigating Equivalence of In-Person and Telehealth-Based Neuropsychological Assessment Performance for Individuals Being Investigated for Younger Onset Dementia
Authors: Brown Aimee D , Kelso Wendy , Eratne Dhamidhu , Loi Samantha M , Farrand Sarah , Summerell Patrick , Neath Joanna , Walterfang Mark , Velakoulis Dennis , Stolwyk Renerus J
Published: January 2024

Objective

Given the rapid shift to in-home teleneuropsychology models, more research is needed to investigate the equivalence of non-facilitator models of teleneuropsychology delivery for people with younger onset dementia (YOD). This study aimed to determine whether equivalent performances were observed on neuropsychological measures administered in-person and via teleneuropsychology in a sample of people being investigated for YOD.

Method

Using a randomized counterbalanced cross-over design, 43 participants (Mage = 60.26, SDage = 7.19) with a possible or probable YOD diagnosis completed 14 neuropsychological tests in-person and via teleneuropsychology, with a 2-week interval. Repeated measures t-tests, intraclass correlation coefficients (ICC), and Bland Altman analyses were used to investigate equivalence across the administration conditions.

Results

No statistical differences were found between in-person and teleneuropsychology conditions, except for the Hospital Anxiety and Depression Scale Anxiety subtest. Small to negligible effect sizes were observed (ranging from .01 to .20). ICC estimates ranged from .71 to .97 across the neuropsychological measures. Bland Altman analyses revealed that the Wechsler Adult Intelligence Scale—Fourth Edition Block Design subtest had slightly better overall performance in the in-person condition and participants reported higher levels of anxiety symptoms during the teleneuropsychology condition; however, average anxiety symptoms remained within the clinically normal range. Participants reported a high level of acceptability for teleneuropsychology assessments.

Conclusions

These results suggest that performances are comparable between in-person and teleneuropsychology assessment modalities. Our findings support teleneuropsychology as a feasible alternative to in-person neuropsychological services for people under investigation of YOD, who face significant barriers in accessing timely diagnoses and treatment options.
Using normative modeling to assess pharmacological treatment effect on brain state in patients with schizophrenia
Authors: Lin Xiao , Huo Yanxi , Wang Qiandong , Liu Guozhong , Shi Jie , Fan Yong , Lu Lin , Jing Rixing , Li Peng
Published: January 2024

Quantifying individual differences in neuroimaging metrics is attracting interest in clinical studies with mental disorders. Schizophrenia is diagnosed exclusively based on symptoms, and the biological heterogeneity makes it difficult to accurately assess pharmacological treatment effects on the brain state. Using the Cambridge Centre for Ageing and Neuroscience data set, we built normative models of brain states and mapped the deviations of the brain characteristics of each patient, to test whether deviations were related to symptoms, and further investigated the pharmacological treatment effect on deviation distributions. Specifically, we found that the patients can be divided into 2 groups: the normalized group had a normalization trend and milder symptoms at baseline, and the other group showed a more severe deviation trend. The baseline severity of the depression as well as the overall symptoms could predict the deviation of the static characteristics for the dorsal and ventral attention networks after treatment. In contrast, the positive symptoms could predict the deviations of the dynamic fluctuations for the default mode and dorsal attention networks after treatment. This work evaluates the effect of pharmacological treatment on static and dynamic brain states using an individualized approach, which may assist in understanding the heterogeneity of the illness pathology as well as the treatment response.
European Society of Cardiology quality indicators for the care and outcomes of adults undergoing transcatheter aortic valve implantation
Authors: Ali Noman , Aktaa Suleman , Younsi Tanina , Beska Ben , Batra Gorav , Blackman Daniel J , James Stefan , Ludman Peter , Mamas Mamas A , Abdel-Wahab Mohamed , Borregaard Britt , Iung Bernard , Joner Michael , Kunadian Vijay , Modine Thomas , Neylon Antoinette , Petronio Anna S , Pibarot Philippe , Popescu Bogdan A , Sabaté Manel , Stortecky Stefan , Teles Rui C , Treede Hendrik , Gale Chris P
Published: January 2024

Aims

To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing transcatheter aortic valve implantation (TAVI).

Methods and results

We followed the European Society of Cardiology (ESC) methodology for the development of QIs. Key domains were identified by constructing a conceptual framework for the delivery of TAVI care. A list of candidate QIs was developed by conducting a systematic review of the literature. A modified Delphi method was then used to select the final set of QIs. Finally, we mapped the QIs to the EuroHeart (European Unified Registries on Heart Care Evaluation and Randomized Trials) data standards for TAVI to ascertain the extent to which the EuroHeart TAVI registry captures information to calculate the QIs. We formed an international group of experts in quality improvement and TAVI, including representatives from the European Association of Percutaneous Cardiovascular Interventions, the European Association of Cardiovascular Imaging, and the Association of Cardiovascular Nursing and Allied Professions. In total, 27 QIs were selected across 8 domains of TAVI care, comprising 22 main (81%) and 5 secondary (19%) QIs. Of these, 19/27 (70%) are now being utilized in the EuroHeart TAVI registry.

Conclusion

We present the 2023 ESC QIs for TAVI, developed using a standard methodology and in collaboration with ESC Associations. The EuroHeart TAVI registry allows calculation of the majority of the QIs, which may be used for benchmarking care and quality improvement initiatives.
Diversifying in the mountains: spatiotemporal diversification of frogs in the Western Ghats biodiversity hotspot
Authors: Cyriac Vivek Philip , Mohan Ashwini Venkatanarayana , Dinesh K P , Torsekar Varun , Jayarajan Aditi , Swamy Priyanka , Vijayakumar S P , Shanker Kartik
Published: January 2024

Mountain ranges are hotspots of biodiversity. However, the mechanisms that generate biodiversity patterns in different mountainous regions and taxa are not apparent. The Western Ghats (WG) escarpment in India is a globally recognized biodiversity hotspot with high species richness and endemism. Most studies have either invoked paleoclimatic conditions or climatic stability in the southern WG refugium to explain this high diversity and endemism. However, the factors driving macroevolutionary change remain unexplored for most taxa. Here, we generated the most comprehensive dated phylogeny to date for ranoid frogs in the WG and tested the role of paleoclimatic events or climatic stability in influencing frog diversification. We found that the diversity of different ranoid frog clades in the WG either accumulated at a constant rate through time or underwent a decrease in speciation rates around 3–2.5 Ma during the Pleistocene glaciation cycles. We also find no significant difference in diversification rate estimates across elevational gradients and the three broad biogeographic zones in the WG (northern, central, and southern WG). However, time-for-speciation explained regional species richness within clades, wherein older lineages have more extant species diversity. Overall, we find that global paleoclimatic events have had little impact on WG frog diversification throughout most of its early history until the Quaternary and that the WG may have been climatically stable allowing lineages to accumulate and persist over evolutionary time.
Diving-wave time-lapse delay for CO2 thin layer detection
Authors: Martinez Ricardo , Vinje Vetle , Stovas Alexey , Mispel Joachim , Ringrose Philip , Duffaut Kenneth , Landrø Martin
Published: January 2024

We have derived an analytical approximate expression to estimate the delay in diving seismic waves due to thin layers of CO2. The expression is valid for high frequencies and can be used to estimate the delay in diving waves at seismic frequencies for large separations between the source and receiver (offset). The approximation may be used to assess CO2 detection limits using diving waves and to support survey planning for CO2 monitoring and full-waveform inversion (FWI) cycle skipping analysis. In this study, we analyse the diving-wave response to a thin layer of CO2 for band-limited data using acoustic finite-difference modelling, and compare the results against the analytical calculations. We find that the responses are offset-dependent and related to double- and single-leg interactions between the diving waves and the CO2. To test the methods, we created a synthetic representation of the 2010 subsurface conditions for the top CO2 layer at the Sleipner storage complex in the North Sea, by combining base and monitor post-stack seismic data with field velocity trends. Using the acoustic finite-difference method, we model pre-stack data that captures the complexity of field data and demonstrate the use of the diving-wave delay for CO2 migration monitoring and CO2 thin layer detection.
Solving nonlinear ODEs with the ultraspherical spectral method
Authors: Qin Ouyuan , Xu Kuan
Published: January 2024

We extend the ultraspherical spectral method to solving nonlinear ordinary differential equation (ODE) boundary value problems. Naive ultraspherical Newton implementations usually form dense linear systems explicitly and solve these systems exactly by direct methods, thus suffering from the bottlenecks in both computational complexity and storage demands. Instead, we propose to use the inexact Newton–GMRES framework for which a cheap but effective preconditioner can be constructed and a fast Jacobian-vector multiplication can be effected, thanks to the structured operators of the ultraspherical spectral method. The proposed inexact Newton–GMRES–ultraspherical framework outperforms the naive implementations in both speed and storage, particularly for large-scale problems or problems whose linearization has solution-dependent variable coefficients in higher-order terms. Additional acceleration can be gained when the method is implemented with mixed precision arithmetic.
Reduction in use of MRI and arthroscopy among patients with degenerative knee disease in independent treatment centers versus general hospitals: a time series analysis
Authors: Kuhrij Laurien S , Marang-van de Mheen Perla J , van Lier Lisanne , Alimahomed Razia , Nelissen Rob G H H , van Bodegom-Vos Leti
Published: January 2024

The use of MRI and arthroscopy are considered low-value care in most patients with degenerative knee disease. To reduce these modalities, there have been multiple efforts to increase awareness. Reductions have been shown for general hospitals (GH), but it is unclear whether this may be partly explained by a shift of patients receiving these modalities in independent treatment centers (ITCs). The aims of this study were to assess (i) whether the trend in use of MRI and arthroscopy in patients with degenerative knee disease differs between ITCs and GH, and (ii) whether the Dutch efforts to raise awareness on these recommendations were associated with a change in the trend for both types of providers. All patients insured by a Dutch healthcare insurer aged ≥50 years with a degenerative knee disease who were treated in a GH or ITC between July 2014 and December 2019 were included. Linear regression was used with the quarterly percentage of patients receiving an MRI or knee arthroscopy weighted by center volume, as the primary outcome. Interrupted time-series analysis was used to evaluate the effect of the Dutch efforts to raise awareness. A total of 14 702 patients included were treated in 90 GHs (n = 13 303, 90.5%) and 29 ITCs (n = 1399, 9.5%). Across the study period, ITCs on an average had a 16% higher MRI use (P < .001) and 9% higher arthroscopy use (P = .003). MRI use did not change in both provider types, but arthroscopy use significantly decreased and became stronger in ITCs (P = .01). The Dutch efforts to increase awareness did not significantly influence either MRI or arthroscopy use in ITCs (P = .55 and P = .84) and GHs (P = .13 and P = .70). MRI and arthroscopy uses were higher in ITCs than GHs. MRI use did not change significantly among patients ≥ 50 years with degenerative knee disease in both provider types between 2014 and 2019. MRI- and arthroscopy use decreased with ITCs on average having higher rates for both modalities, but also showing a stronger decrease in arthroscopy use. The Dutch efforts to increase awareness did not accelerate the already declining trend in the Netherlands.
Direct observations of microbial community succession on sinking marine particles
Authors: Stephens Brandon M , Durkin Colleen A , Sharpe Garrett , Nguyen Trang T H , Albers Justine , Estapa Margaret L , Steinberg Deborah K , Levine Naomi M , Gifford Scott M , Carlson Craig A , Boyd Philip W , Santoro Alyson E
Published: January 2024

Microbial community dynamics on sinking particles control the amount of carbon that reaches the deep ocean and the length of time that carbon is stored, with potentially profound impacts on Earth’s climate. A mechanistic understanding of the controls on sinking particle distributions has been hindered by limited depth- and time-resolved sampling and methods that cannot distinguish individual particles. Here, we analyze microbial communities on nearly 400 individual sinking particles in conjunction with more conventional composite particle samples to determine how particle colonization and community assembly might control carbon sequestration in the deep ocean. We observed community succession with corresponding changes in microbial metabolic potential on the larger sinking particles transporting a significant fraction of carbon to the deep sea. Microbial community richness decreased as particles aged and sank; however, richness increased with particle size and the attenuation of carbon export. This suggests that the theory of island biogeography applies to sinking marine particles. Changes in POC flux attenuation with time and microbial community composition with depth were reproduced in a mechanistic ecosystem model that reflected a range of POC labilities and microbial growth rates. Our results highlight microbial community dynamics and processes on individual sinking particles, the isolation of which is necessary to improve mechanistic models of ocean carbon uptake.
Early-career general practitioners’ antibiotic prescribing for acute infections: a systematic review
Authors: Baillie Emma J , Merlo Greg , Van Driel Mieke L , Magin Parker J , Hall Lisa
Published: January 2024

Background

Antimicrobial resistance is a worldwide threat, exacerbated by inappropriate prescribing. Most antibiotic prescribing occurs in primary care. Early-career GPs are important for the future of antibiotic prescribing and curbing antimicrobial resistance.

Objectives

To determine antibiotic prescribing patterns by early-career GPs for common acute infections.

Methods

A systematic literature search was conducted using PubMed, Embase and Scopus. Two authors independently screened abstracts and full texts for inclusion. Primary outcomes were antibiotic prescribing rates for common acute infections by GPs with experience of 10 years or less. Secondary outcomes were any associations between working experience and antibiotic prescribing.

Results

Of 1483 records retrieved, we identified 41 relevant studies. Early-career GPs were less likely to prescribe antibiotics compared with their more experienced colleagues (OR range 0.23–0.67). Their antibiotic prescribing rates for ‘any respiratory condition’ ranged from 14.6% to 52%, and for upper respiratory tract infections from 13.5% to 33%. Prescribing for acute bronchitis varied by country, from 15.9% in Sweden to 26% in the USA and 63%–73% in Australia. Condition-specific data for all other included acute infections, such as sinusitis and acute otitis media, were limited to the Australian context.

Conclusions

Early-career GPs prescribe fewer antibiotics than later-career GPs. However, there are still significant improvements to be made for common acute conditions, as their prescribing is higher than recommended benchmarks. Addressing antimicrobial resistance requires an ongoing worldwide effort and early-career GPs should be the target for long-term change.
Efficient selection of gravitationally lensed OH megamasers with MeerKAT and the Square Kilometre Array
Authors: Button Charissa B , Deane Roger P
Published: January 2024

There has been a recent resurgence in hydroxyl (OH) megamaser research driven by Square Kilometre Array (SKA) precursor/pathfinder telescopes. This will continue in the lead-up to the SKA mid-frequency array, which will greatly expand our view of OH megamasers and their cosmic evolution over ≳80 per cent of the age of the Universe. This is expected to yield large scientific returns as OH megamasers trace galaxy mergers, extreme star formation, high molecular gas densities, and potentially binary/dual supermassive black hole systems. In this paper, we predict the distortion to the OH luminosity function that a magnification bias will inflict, and in turn, predict the distortion on the OH megamaser number counts as a function of redshift. We identify spectral flux density thresholds that will enable efficient lensed OH megamaser selection in large spectral line surveys with MeerKAT and SKA. The surface density of lensed galaxies that could be discovered in this way is a strong function of the redshift evolution of the OH megamaser luminosity function, with predictions as high as ∼1 lensed OH source per square degree at high redshifts (z ≳ 1) for anticipated SKA spectral line survey designs. This could enable efficient selection of some of the most highly obscured galaxies in the Universe. This high-redshift selection efficiency, in combination with the large survey speed of the SKA at ≲1 GHz frequencies and the high magnifications possible with compact OH emission regions (μOH ≫ 10), will enable a transformational view of OH in the Universe.
A new precise determination of the primordial abundance of deuterium: measurement in the metal-poor sub-DLA system at z = 3.42 towards quasar J 1332+0052
Authors: Kislitsyn P A , Balashev S A , Murphy M T , Ledoux C , Noterdaeme P , Ivanchik A V
Published: January 2024

The theory of Big Bang nucleosynthesis, coupled with an estimate of the primordial deuterium abundance (D/H)pr, offers insights into the baryon density of the Universe. Independently, the baryon density can be constrained during a different cosmological era through the analysis of cosmic microwave background anisotropy. The comparison of these estimates serves as a rigorous test for the self-consistency of the standard cosmological model and stands as a potent tool in the quest for new physics beyond the standard model of particle physics. For a meaningful comparison, a clear understanding of the various systematic errors affecting deuterium measurements is crucial. Given the limited number of D/H measurements, each new estimate carries significant weight. This study presents the detection of D i absorption lines in a metal-poor sub-Damped Lyman-α system ($\rm [O/H]=-1.71\pm 0.02$, log N(H i) = 19.304 ± 0.004) at zabs = 3.42 towards the quasar SDSS J133254.51+005250.6. Through simultaneous fitting of H i and D i Lyman-series lines, as well as low-ionization metal lines, observed at high spectral resolution and high signal-to-noise using VLT/UVES and Keck/HIRES, we derive log (D i/H i) = −4.622 ± 0.014, accounting for statistical and systematic uncertainties of 0.008dex and 0.012 dex, respectively. Thanks to negligible ionization corrections and minimal deuterium astration at low metallicity, this D/H ratio provides a robust measurement of the primordial deuterium abundance, consistent and competitive with previous works. Incorporating all prior measurements, the best estimate of the primordial deuterium abundance is constrained as: (D/H)pr = (2.533 ± 0.024) × 10−5. This represents a 5 per cent improvement in precision over previous studies and reveals a moderate tension with the expectation from the standard model (≈2.2σ). This discrepancy underscores the importance of further measurements in the pursuit of new physics.
Reverse V-shaped osteotomy for ankylosing rocker-bottom foot deformity in patients with rheumatoid arthritis: A report of three cases
Authors: Noguchi Takaaki , Hirao Makoto , Ebina Kosuke , Etani Yuki , Okamura Gensuke , Tsuboi Hideki , Goshima Atsushi , Okada Seiji , Hashimoto Jun
Published: January 2024

This study evaluated a reverse V-shaped osteotomy for ankylosing rocker-bottom foot deformity in patients with rheumatoid arthritis. Three feet were presented in this study: rheumatoid rocker-bottom deformities with painful and/or infectious bony prominence towards the bottom of the foot, treated with a reverse V-shaped osteotomy in the mid-hindfoot. In all three cases, significant correction was achieved with restoration of the medial longitudinal arch, and improvement in clinical scores was confirmed. Reverse V-shaped osteotomy has the potential to be a useful and definitive procedure for ankylosing rocker-bottom deformity in patients with rheumatoid arthritis.
Cell-cell communication and initial population composition shape the structure of potato spindle tuber viroid quasispecies
Authors: Wu Jian , Bisaro David M
Published: January 2024

RNA viruses and viroids replicate with high mutation rates, forming quasispecies, population of variants centered around dominant sequences. The mechanisms governing quasispecies remain unclear. Plasmodesmata regulate viroid movement and were hypothesized to impact viroid quasispecies. Here, we sequenced the progeny of potato spindle tuber viroid intermediate (PSTVd-I) strain from mature guard cells lacking plasmodesmal connections and from in vitro-cultivated mesophyll cell protoplasts from systemic leaves of early-infected tomato (Solanum lycopersicum) plants. Remarkably, more variants accumulated in guard cells compared to whole leaves. Similarly, after extended cell culture, we observed more variants in cultivated mesophyll protoplasts. Coinfection and single-cell sequencing experiments demonstrated that the same plant cell can be infected multiple times by the same or different PSTVd sequences. To study the impact of initial population composition on PSTVd-I quasispecies, we conducted coinfections with PSTVd-I and variants. Two inoculum ratios (10:1 or 1:10) established quasispecies with or without PSTVd-I as the master sequence. In the absence of the master sequence, the percentage of novel variants initially increased. Moreover, a 1:1 PSTVd-I/variant RNA ratio resulted in PSTVd-I dominating (>50%), while the variants reached 20%. After PSTVd-I-only infection, the variants reached around 10%, while after variant-only infection, the variants were significantly more than 10%. These results emphasize the role of cell-to-cell communication and initial population composition in shaping PSTVd quasispecies.
Signaling-biophysical modeling unravels mechanistic control of red blood cell phagocytosis by macrophages in sickle cell disease
Authors: Zhang Yu , Qiang Yuhao , Li He , Li Guansheng , Lu Lu , Dao Ming , Karniadakis George E , Popel Aleksander S , Zhao Chen
Published: January 2024

Red blood cell (RBC) aging manifests through progressive changes in cell morphology, rigidity, and expression of membrane proteins. To maintain the quality of circulating blood, splenic macrophages detect the biochemical signals and biophysical changes of RBCs and selectively clear them through erythrophagocytosis. In sickle cell disease (SCD), RBCs display alterations affecting their interaction with macrophages, leading to aberrant phagocytosis that may cause life-threatening spleen sequestration crises. To illuminate the mechanistic control of RBC engulfment by macrophages in SCD, we integrate a system biology model of RBC-macrophage signaling interactions with a biophysical model of macrophage engulfment, as well as in vitro phagocytosis experiments using the spleen-on-a-chip technology. Our modeling framework accurately predicts the phagocytosis dynamics of RBCs under different disease conditions, reveals patterns distinguishing normal and sickle RBCs, and identifies molecular targets including Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) and cluster of differentiation 47 (CD47)/signal regulatory protein α (SIRPα) as therapeutic targets to facilitate the controlled clearance of sickle RBCs in the spleen.
How Much Are Government Jobs in Developing Countries Worth?
Authors: Mangal Kunal
Published: January 2024

Government jobs in developing countries are valuable not just because they pay relatively higher wages, but also because they provide many valuable amenities. How does the value of these amenities compare with the nominal wage itself? The observed search behavior of candidates preparing for competitive exams for government jobs is used to infer a lower bound on the total value of a government job, including amenities. Based on a sample of 147 candidates preparing for civil service exams in Pune, India, the amenity value of a government job is estimated to comprise at least two-thirds of total compensation. The high amenity value is not driven by misinformed beliefs about the nominal wage, nor by a high value placed on the process of studying itself. Insights from focus group discussions help explain which government job amenities are most valued in this setting.
Immediate Weightbearing through Walker or Crutches After Surgical Fixation of Clavicle Fractures in Patients with Lower Extremity Fractures: A Retrospective Cohort Study
Authors: Frane Nicholas , Watzig Benjamin , Vohra Arjun , Deeyor Sorka , Hui Clayton , McKee Michael , Dehghan Niloofar
Published: January 2024

Objectives:

To assess the safety of immediate upper extremity weightbearing as tolerated (WBAT) rehabilitation protocol after clavicle fracture open reduction internal fixation (ORIF).

Methods:

Design:

Retrospective Cohort Study

Setting:

Three Level-One trauma centers

Patients Selection Criteria:

Patients greater than 18 years of age who had ORIF of mid-shaft clavicle fractures and lower extremity fractures who were allowed immediate WBAT on their affected upper extremity through use of a walker or crutches were included. All clavicles were fixed with either precontoured clavicular plates or locking compression plates. Included patients were, and clinical/radiographic follow-up until fracture union, nonunion, or construct failure.

Outcome Measures and Comparisons:

WBAT patients were matched in a one-to-one fashion to a cohort with isolated clavicle fractures who were treated non-weightbearing (NWB) postoperatively on their affected upper extremity. Matching was done based on age, sex, and temporality of fixation. After matching, treatment and control groups were compared to determine differences in possible confounding variables that could influence the primary outcome including patient demographics, fracture classification, cortices of fixation, and construct type. All patients were assessed to verify conformity with weight bearing recommendation. Primary outcome was early hardware failure with or without revision surgery. Secondary outcomes included post operative infections, and union of fracture.

Result

s:

39 patients were included in the WBAT cohort, there were no significant differences with the matched NWB cohort based on patient demographics, . Both the WBAT and NWB cohorts both had 2.5% chance of acute hardware failure (HWF) that required surgical intervention (p=1.0). Additionally, there was no difference in overall HWF (p=0.49). All patients despite weight bearing status including those that required revision ORIF for acute HWF had union of their fracture (p=1.0).

Conclusions:

Our data would support that immediate weightbearing after clavicle fracture fixation in patients with concomitant lower extremity trauma does not lead to an increase in hardware failure or impact ultimate union. This challenges the dogma of prolonged postoperative weightbearing restrictions and allow for earlier rehabilitation.
Incidence of Tether Breakage in Anterior Vertebral Body Tethering
Authors: Cahill Patrick J. , Miyanji Firoz , Lullo Brett R. , Samdani Amer F. , Lonner Baron S. , Pahys Joshua M. , Hwang Steven W. , Haber Lawrence L. , Alanay Ahmet , Shah Suken A. , Parent Stefan , Blakemore Laurel C. , Hoernschemeyer Daniel G. , Neal Kevin M. ,   Harms Study Group, Newton Peter O.
Published: January 2024

Background:

Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT. The incidence of tether breakage in TAVBT is hypothesized to be high and increase with time postoperatively.

Methods:

All patients with right-sided, thoracic curves who underwent TAVBT with at least 2 and up to 3 years of radiographic follow-up were included. Tether breakage between 2 vertebrae was defined a priori as any increase in adjacent screw angle >5 degrees from the minimum over the follow-up period. The presence and timing of tether breakage were noted for each patient. A Kaplan-Meier survival analysis was performed to calculate expected tether breakage up to 36 months. χ2 analysis was performed to examine the relationship between tether breakage and reoperations. Independent t test was used to compare the average final Cobb angle between cohorts.

Results:

In total, 208 patients from 10 centers were included in our review. Radiographically identified tether breakage occurred in 75 patients (36%). The initial break occurred at or beyond 24 months in 66 patients (88%). Kaplan-Meier survival analysis estimated the cumulative rate of expected tether breakage to be 19% at 24 months, increasing to 50% at 36 months. Twenty-one patients (28%) with a radiographically identified tether breakage went on to require reoperation, with 9 patients (12%) requiring conversion to posterior spinal fusion. Patients with a radiographically identified tether breakage went on to require conversion to posterior spinal fusion more often than those patients without identified tether breakage (12% vs. 2%; P=0.004). The average major coronal curve angle at final follow-up was significantly larger for patients with radiographically identified tether breakage than for those without tether breakage (31 deg±12 deg vs. 26 deg±12 deg; P=0.002).

Conclusions:

The incidence of tether breakage in TAVBT is high, and it is expected to occur in 50% of patients by 36 months postoperatively.

Level of Evidence:

Level IV
Predictive Modeling of COVID-19 Intensive Care Unit Patient Flows and Nursing Complexity
Authors: Simoncini Elsa , Jarry Angélique , Moussion Aurélie , Marcheschi Aude , Giordanino Pascale , Lusenti Chantal , Bruder Nicolas , Velly Lionel , Boussen Salah ,   on behalf of the GRAM+ (Groupe de Recherche en Réanimation et Anesthésie de Marseille Pluridisciplinaire)
Published: January 2024

This study aimed to develop a Monte Carlo simulation model to forecast the number of ICU beds needed for COVID-19 patients and the subsequent nursing complexity in a French teaching hospital during the first and second pandemic outbreaks. The model used patient data from March 2020 to September 2021, including age, sex, ICU length of stay, and number of patients on mechanical ventilation or extracorporeal membrane oxygenation. Nursing complexity was assessed using a simple scale with three levels based on patient status. The simulation was performed 1000 times to generate a scenario, and the mean outcome was compared with the observed outcome. The model also allowed for a 7-day forecast of ICU occupancy. The simulation output had a good fit with the actual data, with an R
2 of 0.998 and a root mean square error of 0.22. The study demonstrated the usefulness of the Monte Carlo simulation model for predicting the demand for ICU beds and could help optimize resource allocation during a pandemic. The model's extrinsic validity was confirmed using open data from the French Public Health Authority. This study provides a valuable tool for healthcare systems to anticipate and manage surges in ICU demand during pandemics.
Effects of Adjuvant Chemotherapy on Early-onset Stage II Colon Cancer at Different Tumor Sites
Authors: Tan Chang , Wang Qianqian , Yao Shukun
Published: January 2024

Objectives:

Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC.

Methods:

Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used.

Results:

Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P=0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P=0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P=0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P=0.02).

Conclusions:

The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.
Ear Keloid as an Unusual Complication of Prolonged Mask Use during the COVID-19 Pandemic
Authors: Lumintang Loelita Marcelia , Dohi Teruyuki , Ogawa Rei
Published: January 2024

The recent COVID-19 pandemic required many people to wear ear-loop face masks (ELFMs) for protracted periods, and ear injuries have been reported. Here, we report a rare case of a keloid on the right posterior ear that appeared to arise from prolonged ELFM use. A 76-year-old Japanese man presented with a 7.3 × 2.2 × 1.4-cm keloid running from the medial retroauricular sulcus to the posterior lobule. The lack of keloid history suggested the absence of genetic risk factors. The patient reported extensive mask-wearing habits that were augmented by the pandemic. The keloid developed from an ear injury. Although it healed well, it started thickening 2 months later. Because local mechanical forces (eg, pressure/friction) can promote keloid growth, the ELFM may have provoked the keloid. The patient disclosed a history of uncontrolled hypertension and diabetes mellitus, which associate with severe keloids. The whole keloid was removed via total excision, and the defect was closed primarily and subjected to 15Gy/2Fr radiotherapy. The patient was advised to use a different mask type. Twelve months later, the scar had healed without complications or recurrence and with good cosmetic outcomes. Thus, ELFMs can promote retroauricular keloid formation, possibly by imposing local pressure/friction. ELFMs may also raise local skin temperatures and humidity, thereby fostering infection, which can trigger keloids. Hypertension/diabetes may further elevate the risk of EFLM-induced keloid. Thus, an auricular keloid is an unusual complication of prolonged ELFM use. Combination therapy can have excellent outcomes. Patients with keloid risk factors should be advised to use face masks without ear loops.
Second-stage Scrotoplasty with Autologous Tissue Augmentation after Metoidioplasty
Authors: Everett Ross G. , Butler Christi , Dy Geolani W. , Dugi Daniel D.
Published: January 2024

We present our technique for second-stage scrotoplasty with autologous tissue augmentation following gender-affirming metoidioplasty. This technique augments the scrotum while removing the upper labia majora and making the penis more visible and accessible. This procedure avoids the need for testicular prostheses and their potential for discomfort, displacement, extrusion, or infection. Our preliminary results show that the complication rate is low.
Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease
Authors: Ratner Jessica A. , Blaney Hanna , Rastegar Darius A.
Published: January 2024

Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying alcohol use disorder (AUD). Alcohol withdrawal syndrome (AWS) can be dangerous, is a common barrier to AUD recovery, and may complicate inpatient admissions for liver-related complications. Hepatologists can address these comorbid conditions by learning to accurately stage alcohol-associated liver disease, identify AUD using standardized screening tools (eg, Alcohol Use Disorder Identification Test), and assess risk for and symptoms of AWS. Depending on the severity, alcohol withdrawal often merits admission to a monitored setting, where symptom-triggered administration of benzodiazepines based on standardized scoring protocols is often the most effective approach to management. For patients with severe liver disease, selection of benzodiazepines with less dependence on hepatic metabolism (eg, lorazepam) is advisable. Severe alcohol withdrawal often requires a “front-loaded” approach with higher dosing, as well as intensive monitoring. Distinguishing between alcohol withdrawal delirium and hepatic encephalopathy is important, though it can be difficult, and can be guided by differentiating clinical characteristics, including time to onset and activity level. There is little data on the use of adjuvant medications, including anticonvulsants, dexmedetomidine, or propofol, in this patient population. Beyond the treatment of AWS, inpatient admission and outpatient hepatology visits offer opportunities to engage in planning for ongoing management of AUD, including initiation of medications for AUD and referral to additional recovery supports. Hepatologists trained to identify AUD, alcohol-associated liver disease, and risk for AWS can proactively address these issues, ensuring that patients’ AWS is managed safely and effectively and supporting planning for long-term recovery.
Comparison Between 24-2 ZEST and 24-2 ZEST FAST Strategies in Glaucoma and Ocular Hypertension Using a Fundus Perimeter
Authors: Romano Dario , Oddone Francesco , Montesano Giovanni , Fogagnolo Paolo , Colizzi Benedetta , Tanga Lucia , Giammaria Sara , Rui Chiara , Rossetti Luca M.
Published: January 2024

Précis:

Using a Compass (CMP) (CMP, Centervue, Padova, Italy) fundus perimeter, Zippy Estimation by Sequential Testing (ZEST) FAST strategy showed a significant reduction in examination time compared with ZEST, with good agreement in the quantification of perimetric damage.

Purpose:

The aim of this study was to compare the test duration of ZEST strategy with ZEST FAST and to evaluate the test-retest variability of ZEST FAST strategy on patients with glaucoma and ocular hypertension.

Patients and Methods:

This was a multicenter retrospective study. We analyzed 1 eye of 60 subjects: 30 glaucoma patients and 30 patients with ocular hypertension. For each eye we analyzed, 3 visual field examinations were performed with Compass 24-2 grid: 1 test performed with ZEST strategy and 2 tests performed with ZEST FAST. Mean examination time and mean sensitivity between the 2 strategies were computed. ZEST FAST test-retest variability was examined.

Results:

In the ocular hypertension cohort, test time was 223±29 seconds with ZEST FAST and 362±48 seconds with ZEST (38% reduction, P<0.001). In glaucoma patients, it was respectively 265±62 and 386±78 seconds (31% reduction using ZEST FAST, P<0.001). The difference in mean sensitivity between the 2 strategies was −0.24±1.30 dB for ocular hypertension and −0.14±1.08 dB for glaucoma. The mean difference in mean sensitivity between the first and the second test with ZEST FAST strategy was 0.2±0.8 dB for patients with ocular hypertension and 0.24±0.96 dB for glaucoma patients.

Conclusions:

ZEST FAST thresholding provides similar results to ZEST with a significantly reduced examination time.
Curricula Mapping of Physician Associate/Physician Assistant-Comparable Professions Worldwide Using the Learning Opportunities, Objectives, and Outcomes Platform
Authors: Smalley Scott , Bruza-Augatis Mirela , Colletti Thomas , Heistermann Peter , Mahmud Alias , Song David , Juarez Laura , Tshotetsi Lumbani , Fahringer David , Smith Jami , Ahlers Olaf , Showstark Mary
Published: January 2024

Given the international growth of physician associate/physician assistant (PA) and PA-comparable professions, it is crucial to understand the educational curricula of PA/PA-comparable professions worldwide. This article provides an overview of the process and development of the PA/PA-comparable curricula mapping design applying an international framework. It uses an innovative web-based tool, the Learning Opportunities, Objectives, and Outcomes Platform (LOOOP), to map and evaluate course content, teaching strategies, assessment formats, and learning outcomes. It highlights the project's rationale, challenges, and future implications.