bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-designing marine science for the ocean we want
Authors: Pendleton Linwood H , Alexandroff Stella J , Clausen Alison , Schmidt Jörn O , Browman Howard I
Published: February 2023

The United Nations Decade of Ocean Science for Sustainable Development requires that all of the Actions it endorses have concrete plans to involve stakeholders in the co-creation of ocean science. As a result, we have a unique opportunity to test different approaches to stakeholder engagement to see what works and what does not. Here, we feature short essays in the “Food for Thought” series in which leaders from Decade-endorsed Actions describe how they plan to incorporate stakeholders in the co-design, co-production, and co-delivery of ocean science and how they will measure whether these approaches were successful. We also invited submissions to the journal’s “Stories from the Front Lines” series, in which authors were asked to share unvarnished accounts of the lessons learned from previous efforts to co-design ocean science. We hope that these initial articles will be the beginning of an ongoing series in which new Decade Actions will also document their plans to implement, monitor, and measure the success or failure of these approaches.
Health Risk, Insurance, and Optimal Progressive Income Taxation
Authors: Jung Juergen , Tran Chung
Published: February 2023

We study the optimal progressivity of personal income taxes in a general equilibrium overlapping generations model where individuals are exposed to idiosyncratic shocks to labor productivity and health status over the lifecycle. Our results—based on a calibration to the US economy—indicate that both, the presence of health risk and the available insurance institutions, have a strong effect on the optimal level of tax progressivity. Given the fragmented and non-universal health insurance system in the US, a welfare maximizing income tax system is substantially more progressive than the current US income tax. The higher progressivity provides additional redistribution and social insurance, especially for unhealthy low income individuals who have limited access to health insurance. When exposure to health risk is removed or reduced by introducing more comprehensive health insurance systems, we observe large decreases in the optimal level of income tax progressivity, and the optimal tax system resembles findings from the previous literature. These findings highlight the importance of accounting for the unique characteristics of health risk and the design of the health insurance system when characterizing optimal income taxes.
3D acoustoelastic FD modeling of elastic wave propagation in prestressed solid media
Authors: Yang Haidi , Fu Li-Yun , Li Hongyang , Du Qizhen , Zheng Haochen
Published: February 2023

Seismic exploration of deep oil/gas reservoirs involves the propagation of seismic waves in high-pressure media. Traditional elastic wave equations are not suitable for describing such media. The theory of acoustoelasticity establishes the dynamic equation of wave propagating in prestressed media through constitutive relation using third-order elastic constants. Many studies have been carried out on numerical simulations for acoustoelastic waves, but are mainly limited to 2D cases. A standard staggered-grid (SSG) finite-difference (FD) approach and the perfectly matched layer (PML) absorbing boundary are combined to solve 3D first-order velocity-stress equations of acoustoelasticity to simulate wave propagating in 3D prestressed solid medium. Our numerical results are partially validated by plane-wave analytical solution through the comparison of calculated and theoretical P-/S-wave velocities as a function of confining prestress. We perform numerical simulations of acoustoelastic waves under confining, uniaxial and pure-shear prestressed conditions. The results show the stress-induced velocity anisotropy in acoustoelastic media, which is closely related to the direction of prestresses. Comparisons to seismic simulations based on the theory of elasticity illustrate the limitation of conventional elastic simulations for prestressed media. Numerical simulations prove the significant effect of prestressed conditions on seismic responses.
The Transformation of International Organizations—Specialization, New Initiatives, and Working Methods—Some Observations on the Work of UNCITRAL Working Group III
Authors: Giorgetti Chiara
Published: February 2023

International organizations are essential actors in the international legal system and play key roles in all aspects of international law, from its creation to its enforcement and implementation. As their work becomes progressively more significant and specialized, international organizations have also embarked on many new initiatives and have adopted new working methods. An interesting example of this development is the effort of United Nations Commission on International Trade Law (UNCITRAL) Working Group III (WGIII) to reform Investor–State Dispute Settlement (ISDS), a unique international dispute settlement mechanism that permits a foreign investor to bring a claim against a State on issues related to international investment law. At a time of declining international codification, UNCITRAL WGIII’s plan to reform ISDS stands out as remarkably ambitious. It is also responsive to identified vacuums and needs and is likely to lead, at least partially, to a degree of reform of ISDS. In this short contribution, I first introduce the codification of international economic law issues as distinct from other kinds of codification. I then introduce UNCITRAL and explore the work of UNCITRAL WGIII more specifically. In particular, I explain and assess the ISDS reform process as an example of an ongoing transformation of the work of international organizations and a new initiative on which they embarked using a specific methodology of selecting issues, developing draft texts, and serving as a place for drafting negotiations.
TCF-1 negatively regulates the suppressive ability of canonical and noncanonical Tregs
Authors: Mammadli Mahinbanu , Suo Liye , Sen Jyoti Misra , Karimi Mobin
Published: February 2023

Regulatory T cells are suppressive immune cells used in various clinical and therapeutic applications. Canonical regulatory T cells express CD4, FOXP3, and CD25, which are considered definitive markers of their regulatory T-cell status when expressed together. However, a subset of noncanonical regulatory T cells expressing only CD4 and FOXP3 have recently been described in some infection contexts.

Using a unique mouse model for the first time demonstrated that the TCF-1 regulation of regulatory T-cell suppressive function is not limited to the thymus during development. Our data showed that TCF-1 also regulated regulatory T cells’ suppressive ability in secondary organs and graft-vs-host disease target organs as well as upregulating noncanonical regulatory T cells. Our data demonstrated that TCF-1 regulates the suppressive function of regulatory T cells through critical molecules like GITR and PD-1, specifically by means of noncanonical regulatory T cells. Our in vitro approaches show that TCF-1 regulates the regulatory T-cell effector-phenotype and the molecules critical for regulatory T-cell migration to the site of inflammation.

Using in vivo models, we show that both canonical and noncanonical regulatory T cells from TCF-1 cKO mice have a superior suppressive function, as shown by their ability to control conventional T-cell proliferation, avert acute graft-vs-host disease, and limit tissue damage. Thus, for the first time, we provide evidence that TCF-1 negatively regulates the suppressive ability of canonical and noncanonical regulatory T cells. These findings provide evidence that TCF-1 is a novel target for developing strategies to treat alloimmune disorders.
Racial disparities in diagnostic evaluation of uterine cancer among Medicaid beneficiaries
Authors: Xu Xiao , Chen Ling , Nunez-Smith Marcella , Clark Mitchell , Wright Jason D
Published: February 2023

Background

To inform reasons contributing to Black-White disparity in early diagnosis of uterine cancer, we compared the quality of diagnostic evaluation received by Black vs White patients with abnormal uterine bleeding (AUB) ultimately diagnosed with uterine cancer.

Methods

Using 2008-2019 MarketScan Multi-State Medicaid Database, we identified Black (n = 858) and White (n = 1749) patients with uterine cancer presenting with AUB. Quality of diagnostic evaluation was measured by delayed diagnosis (>1 year after AUB reporting), not receiving guideline-recommended diagnostic procedures, delayed time to first diagnostic procedure (>2 months after AUB reporting), number of diagnostic procedures received, and number of evaluation and management visits for AUB. The association between race and quality indicators was examined by multivariable regressions adjusting for patient characteristics.

Results

Black patients were more likely than White patients to experience delayed diagnosis (11.3% vs 8.3%, P = .01; adjusted odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.27 to 2.29) or to not receive guideline-recommended diagnostic procedures (10.1% vs 5.0%, P < .001; adjusted OR = 1.94, 95% CI = 1.40 to 2.68). Even when they did receive recommended diagnostic procedures, Black patients were more likely than White patients to experience delay in time to the first diagnostic procedure (adjusted OR = 1.46, 95% CI = 1.09 to 1.97). In addition, Black patients underwent more evaluation and management visits for AUB before getting diagnosed compared with White patients (adjusted mean ratio = 1.13, 95% CI = 1.04 to 1.23).

Conclusions

Black and White patients with uterine cancer differed in the quality of diagnostic evaluation received. Improving equity in this area may help reduce Black-White disparity in stage at diagnosis.
Associations between antidiabetic medication use and breast cancer survival outcomes among medicare beneficiaries
Authors: Fahim Shahariar Mohammed , Qian Jingjing , Hsu Chiu-Hsieh , Zeng Peng , Lin Fang-Ju , McDaniel Cassidi C , Chou Chiahung
Published: February 2023

Objective

This study examined the associations between mortality (all-cause and breast cancer-specific) and different antidiabetic medication use before breast cancer diagnosis.

Methods

This study used a longitudinal, retrospective cohort design. Linked Surveillance, Epidemiology and End Results (SEER)-Medicare databases from 2007 to 2013 were used to identify female beneficiaries who had continuous Medicare enrollment, a new breast cancer diagnosis between 2008 and 2013, and exposure to the antidiabetic medication. Different classes of antidiabetic medications from one year before their breast cancer diagnosis were considered as users while all other non-users were excluded. Both all-cause mortality and breast cancer-specific mortality were treated as outcomes. Cox proportional hazards models for all-cause mortality and sub-distribution hazards models for breast cancer-specific mortality were employed to estimate both unadjusted and adjusted hazard ratios and 95% confidence intervals (CI) for risks of survival outcomes, controlling for severity of diabetes and other covariates.

Key findings

A total of 1715 women with breast cancer used antidiabetic medications one year before their breast cancer diagnosis. Compared to metformin, women using insulin, sulfonylurea and combination treatments before their breast cancer diagnosis had a higher risk for all-cause mortality (adjusted Hazard Ratio, aHR: 1.64, 95% CI 1.29, 2.07; aHR: 1.35, 95% CI 1.04, 1.75 and aHR: 1.44, 95% CI 1.14, 1.83, respectively). Women with advanced-stage breast cancer and higher levels of diabetes severity were more likely to get all-cause mortality (all P < 0.05). Women with combination treatments had a statistically higher risk of breast cancer-specific mortality (aHR: 1.52, 95% CI 1.05, 2.19) than metformin users.

Conclusions

Among women with breast cancer, mortality risk is associated with pre-diagnosis exposure to different types of antidiabetic medications.
Presbyters as Priests and Clerics: Terminology in the Letters of Innocent I
Authors: Dunn Geoffrey D
Published: February 2023

In the letters of Innocent I (402–17), presbyters are both priests (sacerdotes) and clerics (clerici), but usually only one of these dimensions is mentioned at a time. Presbyters shared priesthood with bishops, but only with regard to certain functions and responsibilities, like presiding over some of the sacraments. At other times it was their subservience to their bishops that saw them identified as clerics. An accurate picture comes from reading Innocent’s letters in their totality, rather than from any particular passage in isolation. The elasticity of terms is a reflection of a theology of ministry still in the early stages of its development. This is seen particularly in relation to marriage as an eligibility criterion and sexual continence and children as a cause for dismissal; these were priestly requirements that Innocent applied to everyone in official positions of authority and service, whether presbyters or not. This realization contributes to a better understanding of presbyters in late antiquity.
H i filaments as potential compass needles? Comparing the magnetic field structure of the Small Magellanic Cloud to the orientation of GASKAP-H i filaments
Authors: Ma Y K , McClure-Griffiths N M , Clark S E , Gibson S J , van Loon J Th , Soler J D , Putman M E , Dickey J M , Lee M -Y , Jameson K E , Uscanga L , Dempsey J , Dénes H , Lynn C , Pingel N M
Published: February 2023

High-spatial-resolution H i observations have led to the realization that the nearby (within few hundreds of parsecs) Galactic atomic filamentary structures are aligned with the ambient magnetic field. Enabled by the high-quality data from the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope for the Galactic ASKAP H i survey, we investigate the potential magnetic alignment of the $\gtrsim\!{10}\, {\rm pc}$-scale H i filaments in the Small Magellanic Cloud (SMC). Using the Rolling Hough Transform technique that automatically identifies filamentary structures, combined with our newly devised ray-tracing algorithm that compares the H i and starlight polarization data, we find that the H i filaments in the north-eastern end of the SMC main body (‘Bar’ region) and the transition area between the main body and the tidal feature (‘Wing’ region) appear preferentially aligned with the magnetic field traced by starlight polarization. Meanwhile, the remaining SMC volume lacks starlight polarization data of sufficient quality to draw any conclusions. This suggests for the first time that filamentary H i structures can be magnetically aligned across a large spatial volume ($\gtrsim\!{\rm kpc}$) outside of the Milky Way. In addition, we generate maps of the preferred orientation of H i filaments throughout the entire SMC, revealing the highly complex gaseous structures of the galaxy likely shaped by a combination of the intrinsic internal gas dynamics, tidal interactions, and star-formation feedback processes. These maps can further be compared with future measurements of the magnetic structures in other regions of the SMC.
Indirect measurements of gas velocities in galaxy clusters: effects of ellipticity and cluster dynamic state
Authors: Zhuravleva Irina , Chen Mandy C , Churazov Eugene , Schekochihin Alexander A , Zhang Congyao , Nagai Daisuke
Published: February 2023

While awaiting direct velocity measurements of gas motions in the hot intracluster medium, we rely on indirect probes, including gas perturbations in galaxy clusters. Using a sample of ∼80 clusters in different dynamic states from Omega500 cosmological simulations, we examine scaling relations between the fluctuation amplitudes of gas density, δρ/ρ, pressure, δP/P, X-ray surface brightness, Sunyaev–Zel’dovich (SZ) y-parameter, and the characteristic Mach number of gas motions, M1d. In relaxed clusters, accounting for halo ellipticities reduces δρ/ρ or δP/P by a factor of up to 2 within r500c. We confirm a strong linear correlation between δρ/ρ (or δP/P) and M1d in relaxed clusters, with the proportionality coefficient η ≈ 1. For unrelaxed clusters, the correlation is less strong and has a larger η ≈ 1.3 ± 0.5 (1.5 ± 0.5) for δρ/ρ (δP/P). Examination of the M1d − δρ/ρ relation shows that it is almost linear for relaxed clusters, while for the unrelaxed ones, it is closer to $\delta \rho /\rho \propto M_{\rm 1d}^2$. In agreement with previous studies, we observe a strong correlation of M1d with radius. Correcting for these correlations leaves a residual scatter in M1d of ∼4(7) per cent for relaxed (perturbed) clusters. Hydrostatic mass bias correlates with M1d as strongly as with δρ/ρ in relaxed clusters. The residual scatters after correcting for derived trends is ∼6−7 per cent. These predictions can be verified with existing X-ray and SZ observations of galaxy clusters combined with forthcoming velocity measurements with X-ray microcalorimeters.
Similar properties between gamma-ray emission of 3C 454.3 and solar GeV flares
Authors: Peng Fang-Kun , Hou Shu-Jin , Zhang Hai-Ming , Xue Rui , Shu Xin-Wen
Published: February 2023

Based on the survey data observed by Fermi-Large Area Telescope (LAT), we elaborate the statistical characteristics of gamma-ray flares from 3C 454.3 and solar GeV flares among flare parameters, such as isotropic energy (Eγ), peak luminosity (LP), and duration time (TDuration). We find two significant correlations as: $T_{\rm Duration} \propto E_{\gamma }^{0.31\pm 0.03}$ and $L_{\rm P} \propto E_{\gamma }^{0.61\pm 0.03}$ for 3C 454.3. The exponents are in a better agreement those of the Sun from the first Fermi-LAT solar flare catalogue, namely $T_{\rm Duration,\odot } \propto E_{\gamma ,\odot }^{0.38\pm 0.08}$ and $L_{\rm P,\odot } \propto E_{\gamma ,\odot }^{0.81\pm 0.08}$. The relationship of TDuration–Eγ and LP–Eγ could be interpreted naturally as due to magnetic dissipation through reconnection. On top of that the frequency distributions of isotropic energy, peak luminosity, and duration time of gamma-ray emission of 3C 454.3 show power-law forms, and the waiting time distribution can be described by a non-stationary Poisson process. These distribution behaviours are comparable to those of the Sun, Sagittarius A*, and M87, and follow the prediction of a self-organized criticality model. All statistical properties suggest that similar to the physical process accounting for solar GeV flares and X-ray flares in supermassive black hole systems, magnetic reconnection cloud govern the energy-release, and particle acceleration process for gamma-ray flares of 3C 454.3.
Axisymmetric viscous overstability in fully self-gravitating systems. Conditions for the onset of overstable oscillations
Authors: Mondino-Llermanos Annabella E , Salo Heikki
Published: February 2023

We examine the onset of viscous overstability in dense self-gravitating particle rings. This oscillatory instability offers a plausible explanation for the periodic radial density variations seen at several locations of Saturn’s B and inner-A ring. So far, the theoretical understanding of overstable ring systems relies mainly on analytical results based on approximate treatments of ring self-gravity which omit the emergence of self-gravity wakes (small-scale gravitational instabilities). Therefore, the interplay between the two mechanisms, self-gravity and overstability, is still not well understood. Here, we address numerically the factors that determine the onset of overstability in self-gravitating rings. We confirm that weak self-gravity promotes overstability whereas strong self-gravity, with prominent wake structure, weakens the overstable pattern. This strong gravity regime corresponds to optical depths beyond a threshold value. In systems where overstable oscillations and wakes co-exist, we detect a strong anticorrelation between the strength of wakes and overstable oscillations. It is this interaction that eventually leads to the suppression of overstability, with strong transient wake structure preventing the phase synchronization between density and velocity oscillations required to maintain a coherent overstable pattern. Finally, we derive a composite criterion for the onset of overstability valid even in the regime of strong gravity wakes, framed in terms of collective properties of the system: the central-plane filling factor and the ratio of gravitational and collisional viscosities. In the limit where gravity wakes are omitted, our new criterion agrees with that found by the kinetic theory analysis of linear stability.
Genomic Basis of Adaptation to a Novel Precipitation Regime
Authors: Elfarargi Ahmed F , Gilbault Elodie , Döring Nina , Neto Célia , Fulgione Andrea , Weber Andreas P M , Loudet Olivier , Hancock Angela M
Published: February 2023

Energy production and metabolism are intimately linked to ecological and environmental constraints across the tree of life. In plants, which depend on sunlight to produce energy, the link between primary metabolism and the environment is especially strong. By governing CO2 uptake for photosynthesis and transpiration, leaf pores, or stomata, couple energy metabolism to the environment and determine productivity and water-use efficiency (WUE). Although evolution is known to tune physiological traits to the local environment, we lack knowledge of the specific links between molecular and evolutionary mechanisms that shape this process in nature. Here, we investigate the evolution of stomatal conductance and WUE in an Arabidopsis population that colonized an island with a montane cloud scrubland ecosystem characterized by seasonal drought and fog-based precipitation. We find that stomatal conductance increases and WUE decreases in the colonizing population relative to its closest outgroup population from temperate North Africa. Genome-wide association mapping reveals a polygenic basis of trait variation, with a substantial contribution from a nonsynonymous single-nucleotide polymorphism in MAP KINASE 12 (MPK12 G53R), which explains 35% of the phenotypic variance in WUE in the island population. We reconstruct the spatially explicit evolutionary history of MPK12 53R on the island and find that this allele increased in frequency in the population due to positive selection as Arabidopsis expanded into the harsher regions of the island. Overall, these findings show how adaptation shaped quantitative eco-physiological traits in a new precipitation regime defined by low rainfall and high humidity.
Influence of CYP2A6 Genetic Variation, Nicotine Dependence Severity, and Treatment on Smoking Cessation Success
Authors: Chenoweth Meghan J , Lerman Caryn , Knight Jo , Tyndale Rachel F
Published: February 2023

Introduction

Genetic variation in Cytochrome P450 2A6 (CYP2A6), the major nicotine metabolizing enzyme, is associated with nicotine dependence and smoking cessation. Nicotine dependence severity also predicts smoking cessation. Our goals were to determine how CYP2A6 variation and nicotine dependence alter smoking cessation, and whether dependence could refine CYP2A6-based treatment recommendations.

Aims and Methods

Adult smokers treated for 12 weeks with placebo, nicotine patch, or varenicline (NCT01314001) were grouped as CYP2A6 normal (n = 567) or slow (n = 432) nicotine metabolizers based on a CYP2A6 weighted genetic risk score. Fagerström test for nicotine dependence scores were measured at baseline and biochemically verified smoking cessation was assessed at end of treatment.

Results

Dependence neither mediated nor moderated an association between CYP2A6 variation and smoking cessation overall, within any treatment arm, or after stratifying by ancestry (n = 591 European, n = 408 African ancestry) or sex (n = 444 women, n = 555 men). In within-treatment analyses, the mediation effect odds ratio (OR) ranged from 0.95 to 1.00 and the bias-corrected 95% confidence interval contained 1. Moderation (i.e. interaction) effect ORs ranged from 0.88 to 1.61 (p = .397–.828). For CYP2A6 normal metabolizers, quit rates on varenicline were similar for those with high (41.1%) and low (43.4%) dependence, while quit rates were lower for those with high versus low dependence on both patch (16.5 vs. 29.7%) and placebo (8.9 vs. 18.5%). CYP2A6 slow metabolizers with high versus low dependence had lower quit rates in all three treatment arms.

Conclusions

Although nicotine dependence severity neither mediated nor moderated CYP2A6 associations with smoking cessation, incorporating information on dependence may optimize the choice of smoking cessation treatment aid in CYP2A6 normal and slow metabolizers.

Implications

Variation in CYP2A6 and nicotine dependence severity alter smoking cessation success. Our findings suggest that while nicotine dependence severity is unlikely to mediate or moderate CYP2A6 associations with cessation, incorporating patient information on both CYP2A6 and nicotine dependence severity may lead to improved smoking cessation strategies.
Zeatin: The 60th anniversary of its identification
Authors: Jameson Paula Elizabeth
Published: February 2023

While various labs had shown cell division-inducing activity in a variety of plant extracts for over a decade, the identification of zeatin (Z) in 1964, the first known naturally occurring cytokinin, belongs to Letham and co-workers. Using extracts from maize (Zea mays), they were the first to obtain crystals of pure Z and in sufficient quantity for structural determination by MS, NMR, chromatography, and mixed melting-point analysis. This group also crystallized Z-9-riboside (ZR) from coconut (Cocos nucifera) milk. However, their chemical contributions go well beyond the identification of Z and ZR and include two unambiguous syntheses of trans-Z (to establish stereochemistry), the synthesis of 3H-cytokinins that facilitated metabolic studies, and the synthesis of deuterated internal standards for accurate mass spectral quantification. Letham and associates also unequivocally identified Z nucleotide, the 7-and 9-glucoside conjugates of Z, and the O-glucosides of Z, ZR, dihydro Z (DHZ) and DHZR as endogenous compounds and as metabolites of exogenous Z. Their contributions to the role of cytokinins in plant physiology and development were also substantial, especially the role of cytokinins moving in the xylem. These biological advances are described and briefly related to the genetic/molecular biological contributions of others that established that plants have an absolute requirement for cytokinin.
OPTIMISING THE PARAMETERS OF COCHLEAR IMPLANT IMAGING WITH CONE-BEAM COMPUTED TOMOGRAPHY
Authors: Söderqvist Samuel , Sivonen Ville , Aarnisalo Antti , Karppi Harri , Sinkkonen Saku T , Koivisto Juha
Published: February 2023

With computed tomography (CT), the delicate structures of the inner ear may be hard to visualise, which a cochlear implant (CI) electrode array can further complicate. The usefulness of a novel cone-beam CT device in CI recipient’s inner ear imaging was evaluated and the exposure parameters were optimised to attain adequate clinical image quality at the lowest effective dose (ED). Six temporal bones were implanted with a Cochlear Slim Straight electrode array and imaged with six different imaging protocols. Contrast-to-noise ratio was calculated for each imaging protocol, and three observers evaluated independently the image quality of each imaging protocol and temporal bone. The overall image quality of the inner ear structures did not differ between the imaging protocols and the most relevant inner ear structures of CI recipient’s inner ear can be visualised with a low ED. To visualise the most delicate structures in the inner ear, imaging protocols with higher radiation exposure may be required.
Integration of serum metabolomics and network pharmacology reveals the immunoenhancing mechanisms of Qishenbuqi capsules
Authors: Zhao Ziyu , Fan Yuhui , Cui Yutao , Yang Lan , Wu Yanfei , Yuan Yuan , Zhang Ping , Zhao Ruping , Ji Jianjun , Xu Sheng , Qin Xuemei , Liu Xiao-jie
Published: February 2023

Introduction

Qishenbuqi capsule (QSBQC), a listed Chinese patent prescription, comprises of 4 herbs. Clinically, it has been shown to improve immune functions.

Methods

Subjects with Qi deficiency and non-Qi deficiency were recruited, who then took QSBQC for 4 weeks. Traditional Chinese medicine (TCM) syndrome scores and the levels of white blood cells, CD3+ T cells (CD3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), and CD4+/CD8+ were determined. Serum metabolomics was used to explore the metabolic mechanisms of QSBQC on improving immunity. Meanwhile, the potential active ingredients, targets, and pathways of QSBQC on enhancing immunity were screened by network pharmacology.

Results

QSBQC significantly improved TCM syndrome scores and increased the number of CD8+ T cells of both Qi deficiency and non-Qi deficiency subjects. Serum metabolomics revealed that QSBQC regulated 18 differential metabolites and 8 metabolic pathways of Qi deficiency, and 12 differential metabolites and 7 metabolic pathways of non-Qi deficiency subjects. The “herbs-compounds-pathways” diagram showed that PQ-2, cimifugin, and divaricatol were the main active components. Pathways in cancer and arginine and proline metabolism could be the most important pathways.

Conclusion

Our research revealed the immunoenhancing mechanisms of QSBQC and improved the combination of TCM theory and modern western medicine theory.
Femoral Deformity in Tibia Vara and Its Response to Growth Modulation
Authors: Walker Janet L. , Dueber David M. , Scott Allison C. , Stephenson Lindsay P. , Lerman Joel A. , Nossov Sarah B. , Franklin Corinna C. , Powell Kenneth P. , Westberry David E. , Ackman Jeffery D.
Published: February 2023

Background:

While tibia vara is a disorder of the proximal tibial physis, femoral deformity frequently contributes to the overall limb malalignment. Our purpose was to determine how femoral varus deformity in tibia vara responds to growth modulation, with/without lateral tension band plating (LTBP) to the femur.

Methods:

One-hundred twenty-seven limbs undergoing LTBP for tibia vara were reviewed. All had tibial LTBP and 35 limbs also had femoral LTBP for varus. Radiographs were measured for correction of the mechanical lateral distal femoral angle (mLDFA) and mechanical axis deviation (MAD). Preoperative-femoral varus was defined with an age-adjusted guide: mLDFA >95 degrees for 2 to below 4 years and mLDFA >90 degrees for 4 to 18 years. The 35 limbs having femoral LTBP were compared with 50 limbs with femoral varus and no femoral LTBP. In addition, 42 limbs that did not have preoperative-femoral varus were followed. Patients with early-onset (below 7 y) tibia vara were compared with those with late-onset (≥8 y). Outcome success was based on published age-adjusted mLDFA and MAD norms.

Results:

Following femoral LTBP, the mean mLDFA decreased from 98.0 to 87.1 degrees. All femurs had some improvement, with 28/35 femurs (80%) achieving complete correction. One limb, with late follow-up, overcorrected, requiring reverse (medial) femoral tension band plating.

For the 50 limbs with femoral varus and only tibial LTBP, 16/22 limbs (73%) with early-onset and 11/28 limbs (39%) with late-onset completely corrected their femoral deformities. If the limb had preoperative-femoral varus, femoral LTBP statistically correlated with successful mLDFA correction and improvement of MAD, only in the late-onset group.

Forty-two limbs, without preoperative-femoral varus, had no change in their mean mLDFA of 87 degrees. However, 4 femurs (10%) ended with posttreatment varus.

Conclusions:

Femoral LTBP is effective in correcting femoral varus deformity in the tibia vara. For femoral varus associated with late-onset tibia vara, femoral LTBP should be considered. Those that had femoral LTBP had statistically more successful femoral and overall limb varus correction. However, in early-onset tibia vara, with associated femoral varus, observation is warranted because 73% of femurs are corrected without femoral intervention. This study was underpowered to show additional improvement with femoral LTBP in the early-onset group. Even limbs with normal femoral alignment, should be observed closely for the development of femoral varus, during tibial LTBP treatment for tibia vara.

Level of Evidence:

Level III.
Sulfur dioxide reduction at coal-fired power plants in North Carolina and associations with preterm birth among surrounding residents
Authors: Wilkie Adrien A. , Richardson David B. , Luben Thomas J. , Serre Marc L. , Woods Courtney G. , Daniels Julie L.
Published: February 2023

Background:

Coal-fired power plants (CFPP) are major contributors of air pollution, including the majority of anthropogenic sulfur dioxide (SO2) emissions, which have been associated with preterm birth (PTB). To address a 2002 North Carolina (NC) policy, 14 of the largest NC CFPPs either installed desulfurization equipment (scrubbers) or retired coal units, resulting in substantial reductions of SO2 air emissions. We investigated whether SO2 air emission reduction strategies at CFPPs in NC were associated with changes in prevalence of PTB in nearby communities.

Methods:

We used US EPA Air Markets Program Data to track SO2 emissions and determine the implementation dates of intervention at CFPPs and geocoded 2003–2015 NC singleton live births. We conducted a difference-in-difference analysis to estimate change in PTB associated with change in SO2 reduction strategies for populations living 0–<4 and 4–<10 miles from CFPPs pre- and postintervention, with a comparison of those living 10–<15 miles from CFPPs.

Results:

With the spatial-temporal exposure restrictions applied, 42,231 and 41,218 births were within 15 miles of CFPP-scrubbers and CFPP-retired groups, respectively. For residents within 4–<10 miles from a CFPP, we estimated that the absolute prevalence of PTB decreased by −1.5% [95% confidence interval (CI): −2.6, −0.4] associated with scrubber installation and −0.5% (95% CI: −1.6, 0.6) associated with the retirement of coal units at CFPPs. Our findings were imprecise and generally null-to-positive among those living within 0–<4 miles regardless of the intervention type.

Conclusions:

Results suggest a reduction of PTB among residents 4–<10 miles of the CFPPs that installed scrubbers.
The impact of genetics on the long QT syndrome: myth or reality?
Authors: Schwartz Peter J. , Sala Luca
Published: February 2023

Purpose of review

To summarize and critically assess the contribution of genetics to the Long QT Syndrome (LQTS), with specific reference to the unraveling of its underlying mechanisms and to its impact on clinical practice.

Recent findings

The evolution towards our current approach to therapy for LQTS patients is examined in terms of risk stratification, gene-specific management, and assessment of the clinical impact that genetic modifiers may have in modulating the natural history of the patients. Glimpses are provided on the newest multidisciplinary approaches to study disease mechanisms, test new candidate drugs and identify precision treatments.

It is undeniable that genetics has revolutionized our mechanistic understanding of cardiac channelopathies. Its impact has been enormous but, curiously, the way LQTS patients are being treated today is largely the same that was used in the pregenetic era, even though management has been refined and gene-specific differences allow a more individually tailored antiarrhythmic protection. The synergy of genetic findings with modern in vitro and in silico tools may expand precision treatments; however, they will need to prove more effective than the current therapeutic approaches and equally safe.
Cervical Collars and Dysphagia Among Geriatric TBIs and Cervical Spine Injuries: A Retrospective Cohort Study
Authors: Jarvis Stephanie , Sater Alexandre , Gordon Jeffrey , Nguyen Allan , Banton Kaysie , Bar-Or David
Published: February 2023

Introduction:

Dysphagia, a complication of traumatic brain injuries (TBIs), can lead to death. Cervical collar (c-collar) restriction may increase the risk for dysphagia. The objective was to determine how c-collars affect dysphagia rates.

Methods:

This retrospective cohort study included geriatric TBIs or cervical spine injuries (January 2016 to December 2018) at a Level 1 trauma center. Outcomes (dysphagia, aspiration, and respiratory failure) were compared by c-collar placement.

Results:

There were 684 patients: 21.5% had a c-collar and 78.5% did not. Demographics, injury severity score, and Glasgow Coma Scale were comparable. Dysphagia (53.7% vs. 39.3%, p = .002) and respiratory failure (17.0% vs. 6.9%, p = .0002) were more common among patients with c-collars. Aspiration rates (p = .11) were similar. After adjustment, patients with a c-collar had a significantly higher odds of dysphagia and respiratory failure. Among patients who did not receive swallow therapy, aspiration (p = .02) and respiratory failure (p < .0001) were more common for those with c-collars.

Conclusions:

C-collar placement increased the risk for dysphagia and respiratory failure. There was evidence that swallow therapy may modify the effect of c-collar placement. For patients who did not receive swallow therapy, aspiration was more common among those with a c-collar. Dysphagia screening among patients with a c-collar may improve patient quality.
Patient Acceptance of Novel Therapeutic Options for Sensorineural Hearing Loss—A Pilot Study
Authors: Lembacher Matthias J. , Arnoldner Christoph , Landegger Lukas D.
Published: February 2023

Objectives

Numerous preclinical experiments over the past years have shown the potential of novel therapeutic approaches for sensorineural hearing loss (SNHL) that are now awaiting clinical translation. In this pilot study, we aimed to evaluate the patient acceptance of these future innovative therapies in individuals with SNHL.

Study Design

Cross-sectional exploratory pilot study.

Setting

Tertiary care academic hospital.

Patients

In total, 72 individuals (43 female and 29 male, 59 affected subjects and 13 parents) with different types of SNHL were surveyed between May 2020 and November 2020.

Intervention

The interest/willingness to consider new therapeutic options (viral vectors, stem cells, CRISPR/Cas) for themselves or their children was assessed with the help of a questionnaire, and the answers were matched with a quality-of-life score and sociodemographic as well as clinical characteristics.

Main Outcome Measure

Acceptance of new therapeutic strategies for SNHL in a representative population.

Results

Even with the currently associated treatment uncertainties, 48 patients (66.7%) suffering from SNHL stated that new therapies could be a potential future option for them. Half of these (24 individuals; 33.3%) expressed high acceptance toward the novel strategies. Subjects with a positive attitude toward new therapies in general and viral vectors specifically were significantly older.

Conclusion

With two-thirds of patients affected by SNHL expressing acceptance toward novel therapies, this pilot study highlights the importance of investigating such attitudes and motivates further translational research to offer additional treatment strategies to this patient population.
Differential Expression of Na/K-ATPase in the Human Saccule of Patients With and Without Otologic Disease
Authors: Avillion Michael P. , Lopez Ivan A. , Matsui Hirooki , Ishiyama Gail , Ishiyama Akira
Published: February 2023

Hypothesis

Na+, K+-ATPase (Na/K-ATPase) α1 subunit expression in the saccule of patients diagnosed with otologic disease is different compared with normal controls.

Background

We have recently characterized changes in the expression of Na/K-ATPase α1 subunit in the normal and pathological cochlea; however, no studies have determined the distribution Na/K-ATPase α1 subunit in the human saccule. The present study uses archival temporal bones to study the expression Na/K-ATPase α1 subunit in the human saccule.

Methods

Archival celloidin formalin fixed 20-micron thick sections of the vestibule from patients diagnosed with Menière's disease (n = 5), otosclerosis (n = 5), sensorineural hearing loss, and normal hearing and balance (n = 5) were analyzed. Sections containing the saccular macula were immunoreacted with mouse monoclonal antibodies against Na/K-ATPase α1 subunit. Micrographs were acquired using a high-resolution digital camera coupled to a light inverted microscope.

Results

In the normal human saccule vestibular sensory epithelium, Na/K-ATPase α1 immunoreactivity (IR) was present in nerve fibers and calyces that surround type I vestibular hair cells and nerve terminals. The transition epithelium cells were also Na/K-ATPase α1 immunoreactive. Comparison between normal and pathological specimens showed that there was a significant reduction of Na/K-ATPase α1 IR in the saccule vestibular sensory epithelium from patients with Menière’s disease, otosclerosis, and sensorineural hearing loss.

Conclusions

The decrease of Na/K-ATPase-IR α1 in the saccule vestibular sensory epithelium from patients with otopathologies suggests its critical role in inner ear homeostasis and pathology.
Inflammatory and Nested Testicular Sex Cord Tumor
Authors: Acosta Andres M. , Bridge Julia A. , Dal Cin Paola S. , Sholl Lynette M. , Cornejo Kristine M. , Fletcher Christopher D.M. , Ulbright Thomas M.
Published: February 2023

A subset of malignant testicular sex cord tumors (TSCTs), heretofore interpreted as Sertoli cell tumors, not otherwise specified, exhibits distinctive morphologic features that partially overlap with those of seminoma. In this study, we evaluated the clinicopathologic and molecular characteristics of 13 such tumors. The patients were 20 to 73 years old (median, 36 y), and all with available data presented with testicular masses (median size, 3 cm), with 2 having synchronous retroperitoneal metastases. All 11 patients with available follow-up developed metastases to retroperitoneal lymph nodes, nonretroperitoneal lymph nodes, bone, contralateral testis, and/or lung. Microscopically, the tumors showed solid nests and sheets of epithelioid cells with granular, eosinophilic to clear/vacuolated cytoplasm, admixed in most (12/13) cases with variable proportions of lymphocytes, plasma cells, eosinophils, and neutrophils. Additional features included intracytoplasmic hyaline inclusions and a prominent collagenous, sometimes hyalinized stroma. Mitotic activity was relatively low (median, 1 mitosis/10 HPF), but tumor necrosis was frequent (11/13). Local invasion of adjacent structures and lymphovascular invasion were noted in some tumors (4/9 cases with available data for each feature). All were α-inhibin-positive and lacked nuclear reactivity for β-catenin. In addition, all tested cases were positive for epithelial membrane antigen (9/9) and steroidogenic factor-1 (8/8), and 8/10 expressed CD30. Two “index” cases were initially analyzed using a DNA sequencing panel, which identified EWSR1::ATF1 fusions in both. Subsequently, EWSR1::ATF1 fusions were demonstrated in 8 of the remaining 11 cases using fluorescence in situ hybridization or DNA sequencing. One of the 3 cases that were negative for EWSR1::ATF1 harbored ATF1 amplification. This study, therefore, shows that a group of malignant TSCTs resembling seminoma is characterized by α-inhibin and steroidogenic factor-1 positivity, no expression of nuclear β-catenin, frequent CD30 positivity and recurrent EWSR1::ATF1 fusions. We have descriptively termed these neoplasms “inflammatory and nested TSCT.” Importantly, inflammatory and nested TSCTs show significant differences in morphology, immunoprofile, molecular biology, and, likely, clinical behavior from Sertoli cell tumors, not otherwise specified and should be classified separately.
Implementation of a Risk-Stratified Anticoagulation Protocol Increases Success of Lower Extremity Free Tissue Transfer in the Setting of Thrombophilia
Authors: Deldar Romina , Gupta Nisha , Bovill John D. , Zolper Elizabeth G. , Kim Kevin G. , Fan Kenneth L. , Evans Karen K.
Published: February 2023

Introduction:

Optimal perioperative thromboprophylaxis is crucial to avoid flap thrombosis and to achieve high rates of microsurgical success. At our institution, implementation of a risk-stratified anticoagulation (AC) protocol preliminarily showed a reduction in postoperative thrombotic events and flap loss. We present an updated analysis of surgical outcomes using risk-stratified AC in thrombophilic patients who underwent free tissue transfer (FTT) reconstruction for non-traumatic lower extremity (LE) wounds.

Methods:

We retrospectively reviewed patients who underwent FTT to the LE from 2012 to 2021. Our risk-stratification AC protocol was implemented in July 2015. Low-risk and moderate-risk patients received subcutaneous heparin (SQH). High-risk patients received heparin infusion titrated to a goal PTT of 50-70 seconds. Prior to July 2015, non-stratified patients were treated with either SQH or low-dose heparin infusion (500 U/hour). Patients were divided into two cohorts (non-stratified and risk-stratified) based on date of FTT reconstruction. Primary outcomes included rates of postoperative complications, flap salvage, and flap success.

Results:

Two-hundred nineteen hypercoagulable patients who underwent FTT to LE were treated with non-stratified (n=26) or risk-stratified (n=193) thromboprophylaxis. Overall flap success rate was 96.8% (n=212). Flap loss was lower among risk-stratified patients (1.6% vs. 15.4%, p=0.004), which paralleled a significant reduction in postoperative thrombotic events (2.6% vs. 15.4%, p=0.013). Flap salvage was accomplished more often in the risk-stratified cohort (80% vs. 0%, p=0.048). Intraoperative anastomotic revision (OR: 6.10; p=0.035) and non-risk stratification (OR: 9.50; p=0.006) were independently associated with flap failure.

Conclusion:

Hypercoagulability can significantly impact microsurgical outcomes. Implementation of a risk-stratified AC protocol can significantly improve flap outcomes.
Investigation of Hospital Pricing Information for Plastic Surgery Procedures Reveals Widespread Violation of CMS’s Price Transparency Act
Authors: Askinas Carly , Shih Sabrina , Puyana Salomon , Chaffin Abigail E. , Jansen David A.
Published: February 2023

Background:

Price transparency allows patients to estimate surgical procedure costs, which can affect where they elect to receive care and should theoretically force hospitals to set lower and more uniform prices. To elucidate the traditionally opaque nature of healthcare pricing, the Centers for Medicare and Medicaid Services (CMS) has mandated that hospitals publicly release their pricing information. We sought to investigate the utility of price transparency for plastic surgery patients, who are uniquely situated to benefit due to the dominance of elective procedures.

Methods:

This study included 54 randomly chosen public and private hospitals. Pricing information for 15 common plastic surgery-related procedures was compiled from their websites.

Results: One year after this ruling went into effect, only 13% of hospitals were fully compliant with CMS requirements for reporting standard charges. The most commonly reported plastic surgery procedures were adjacent tissue transfers (CPT 14000, 14001, 14301, 14302), with an average of 32.4% of hospitals listing pricing data. The 25.9% of hospitals reporting the immediate insertion of breast implants (CPT 19340) pricing presented a wide range of gross prices from $2,346.09 to $29,969.35. Free and pedicled flaps (CPT 19364, 19361, 19367, 19368, 19369) were less commonly reported than autologous tissue transfer or non-flap breast procedures (p=0.00).

Conclusions:

A comparative analysis of published prices provides a starting point for surgeons to recommend facilities to patients based on price. However, significant variability was observed in data presentation, reported procedures, and listed prices. These inconsistencies in reporting and unrealistic ranges in price render the comparison of plastic surgery prices between hospitals impractical.