bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory response by 48 h after admission and mortality in patients with acute myocardial infarction complicated by cardiogenic shock
Authors: Kunkel Joakim Bo , Josiassen Jakob , Helgestad Ole Kristian Lerche , Schmidt Henrik , Holmvang Lene , Jensen Lisette Okkels , Thøgersen Michael , Fosbøl Emil , Ravn Hanne Berg , Møller Jacob Eifer , Hassager Christian
Published: March 2023

Aims

Cardiogenic shock (CS) is known to induce an inflammatory response. The prognostic utility of this remains unclear. To investigate the association between C-reactive protein (CRP) levels and leucocyte count and mortality in patients with acute myocardial infarction complicated by CS (AMICS).

Methods and results

Consecutive patients (N = 1716) admitted between 2010 and 2017 with an individually validated diagnosis of AMICS were included. The analysis was restricted to patients alive at 48 h after first medical contact and a valid CRP and leucocyte measurement at 48 ± 12 h from the first medical contact. A combined inflammatory score for each patient was computed by summing the CRP and leucocyte count z-scores to normalize the response on a standard deviation scale. Associations with mortality were analysed using a multivariable Cox proportional hazards model stratified by inflammatory response quartiles: Of the 1716 patients in the cohort, 1111 (64.7%) fulfilled inclusion criteria. The median CRP level at 48 h was 145 mg/dL [interquartile range (IQR) 96–211]. The median leucocyte count was 12.6 × 10−9/L (IQR 10.1–16.4). Patients with the highest inflammatory response (Q4) had lower median left ventricular ejection fractions and higher lactate levels at the time of diagnosis. The 30-day all-cause mortality rates were 46% in Q4 and 21% in Q1 (P < 0.001). In multivariable models, the inflammatory response remained associated with mortality [hazard ratio (HR)Q4 2.32, 95% confidence interval (CI) 1.59–3.39, P < 0.001]. The finding was also significant in AMICS patients presenting with out-of-hospital cardiac arrest following multivariable adjustment (HRQ4 3.37, 95% CI 2.02–4.64, P < 0.001).

Conclusion

Cardiogenic shock induces an acute inflammatory response, the severity of which is associated with mortality.
Breast arterial calcification is associated with incident atrial fibrillation among older but not younger post-menopausal women
Authors: Iribarren Carlos , Chandra Malini , Parikh Rishi V , Sanchez Gabriela , Sam Danny L , Azamian Farima Faith , Cho Hyo-Min , Ding Huanjun , Molloi Sabee , Go Alan S
Published: March 2023

Aims

The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women.

Methods and results

We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing. Among 4908 women, 354 incident cases of AF (7%) were ascertained after a mean (standard deviation) of 7 (2) years of follow-up. In Cox regression adjusting for a propensity score for BAC, BAC presence vs. absence was not significantly associated with AF [hazard ratio (HR) = 1.12; 95% confidence interval (CI), 0.89–1.42; P = 0.34]. However, a significant (a priori hypothesized) age by BAC interaction was found (P = 0.02) such that BAC presence was not associated with incident AF in women aged 60–69 years (HR = 0.83; 95% CI, 0.63–1.15; P = 0.26) but was significantly associated with incident AF in women aged 70–79 years (HR = 1.75; 95% CI, 1.21–2.53; P = 0.003). No evidence of dose–response relationship between BAC gradation and AF was noted in the entire cohort or in age groups separately.

Conclusion

Our results demonstrate, for the first time, an independent association between BAC and AF in women over age 70 years.
Clinical utility of the 4S-AF scheme in predicting progression of atrial fibrillation: data from the RACE V study
Authors: Artola Arita Vicente , Van De Lande Martijn E , Khalilian Ekrami Neda , Nguyen Bao-Oanh , Van Melle Joost M , Geelhoed Bastiaan , De With Ruben R , Weberndörfer Vanessa , Erküner Ömer , Hillege Hans , Linz Dominik , Ten Cate Hugo , Spronk Henri M H , Koldenhof Tim , Tieleman Robert G , Schotten Ulrich , Crijns Harry J G M , Van Gelder Isabelle C , Rienstra Michiel
Published: March 2023

Aims

The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF.

Methods and results

We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 [interquartile range (IQR) 58–71] years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA2DS2-VASc (the CHA2DS2–VASc score assesses thromboembolic risk. C, congestive heart failure/left ventricular dysfunction; H, hypertension; A2, age ≥ 75 years; D, diabetes mellitus; S2, stroke/transient ischaemic attack/systemic embolism; V, vascular disease; A, age 65–74 years; Sc, sex category (female sex)) score was 2 (IQR 2–3), and median follow-up was 2.1 (1.5–2.6) years. The average score of the 4S-AF scheme was 4.6 ± 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression [odds ratio (OR) 1.1 95% CI 0.88–1.41, C-statistic 0.53]. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severity, only including stroke risk, severity of AF burden and substrate of AF) scheme, predicted the risk of progression (OR 1.59 95% CI 1.15–2.27, C-statistic 0.62) even after adjusting for sex and age.

Conclusions

In self-terminating AF patients, the 4S-AF scheme does not predict AF progression. The 3S-AF scheme, excluding the symptom domain, may be a more appropriate score to predict AF progression.

Trial registration numbers

Clinicaltrials.gov NCT02726698 for RACE V
Visualization and mapping of the right phrenic nerve by intracardiac echocardiography during atrial fibrillation ablation
Authors: Liu Xinmeng , Lin Rong , Peng Xiaodong , Wang Xuesi , Li Yukun , Liu Xiaoxia , Wang Wei , Yu Ronghui , Bai Rong , Ma Changsheng , Ruan Yanfei , Liu Nian
Published: March 2023

Objective

This study aimed to evaluate the feasibility of real-time visualization and mapping of the right phrenic nerve (RPN) by using intracardiac echocardiography (ICE) during atrial fibrillation (AF) ablation.

Background

RPN injury is a complication associated with the ablation of AF. Multiple approaches are currently being used to prevent and detect RPN injuries. However, none of these approaches can directly visualize the RPN in real-time during the ablation procedure.

Methods and results

The RPN was detected using ICE. The RPN and its adjacent structures were analysed. The relationship between the RPN’s distance from the superior vena cava (SVC) and its pacing capture threshold was quantified. The safety of SVC isolation guided by the ICE-visualized RPN was evaluated. Thirty-eight people were enrolled in this study. The RPN was visualized by ICE in 92% of patients. It ran through the space between the SVC and the mediastinal pleura and had a ‘straw’-like appearance upon ICE imaging. The course of the RPN was close to the SVC (minimum 1.0 ± 0.4 mm) and the right superior pulmonary vein (minimum 14.1 ± 7.3 mm). There was a positive linear correlation between the RPN’s capture threshold and its distance from the SVC (Spearman’s correlation coefficient = 0.728, < 0.001). SVC isolation was guided by the RPN; none of the patients developed an RPN injury.

Conclusions

RPN can be visualized by ICE in most patients, thus providing a novel approach for the real-time detection of RPN during AF ablation.
Reducing last-minute cancellations of elective urological surgery—effectiveness of specialist nurse preoperative assessment
Authors: Spazzapan Martina , Javier Pinky , Abu-Ghanem Yasmin , Dryhurst David , Faure Walker Nicholas , Lunawat Rahul , Nkwam Nkwam , Tasleem Ali
Published: March 2023

Last-minute cancellations in urological surgery are a global issue, resulting in the wastage of resources and delays to patient care. In addition to non-cessation of anticoagulants and inadequately treated medical comorbidities, untreated urinary tract infections are a significant cause of last-minute cancellations. This study aimed to ascertain whether the introduction of a specialist nurse clinic resulted in a reduction of last-minute cancellations of elective urological surgery as part of our elective recovery plan following the Coronavirus disease 2019, the contagious disease caused by severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 pandemic. A specialist urology nurse-led clinic was introduced to review urine culture results preoperatively. Specialist nurses contacted patients with positive urine cultures and their general practitioners by telephone and email to ensure a minimum of 2 days of ‘lead-in’ antibiotics were given prior to surgery. Patients unfit for surgery were postponed and optimized, and vacant slots were backfilled. A new guideline was created to improve the timing and structure of the generic preassessment. Between 1 January 2021 and 30 June 2021, a mean of 40 cases was booked each month, with average cancellations rates of 9.57/40 (23.92%). After implementing changes on 1 July 2021, cancellations fell to 4/124 (3%) for the month. On re-audit, there was a sustained and statistically significant reduction in cancellation rates: between 1 July 2021 and 31 December 2021 cancellations averaged 4.2/97.5 (4.3%, P < .001). Two to nine (2%–16%) patients were started on antibiotics each month, while another zero to two (0%–2%) were contacted for other reasons. The implementation of a specialist urology nurse-led preassessment clinic resulted in a sustained reduction in cancellations of last-minute elective urological procedures.
SystematicIn VitroMetabolic Profiling of the OXIZID Synthetic Cannabinoids BZO-4en-POXIZID, BZO-POXIZID, 5F-BZO-POXIZID, BZO-HEXOXIZID and BZO-CHMOXIZID
Authors: Watanabe Shimpei , Baginski Steven , Iwai Takahiro , Matsushita Ritsuko , Takatsu Masahisa , Nakanishi Toshio , Lindbom Karin , Mckenzie Craig , Vikingsson Svante , Kronstrand Robert , Gréen Henrik , Seto Yasuo
Published: March 2023

A new class of synthetic cannabinoids termed OXIZIDs has recently emerged on the recreational drug market. In order to continue the detection of new drugs in biological specimens, the identification of metabolites is essential. The aim of this study was to elucidate the metabolites of BZO-4en-POXIZID produced in human liver microsomes (HLMs) and human hepatocyte incubations and to compare the results with closely related analogs using the same experimental setup. Each drug was incubated for 1 h in HLM and BZO-4en-POXIZID was also incubated in human hepatocytes for up to 3 h. Subsequently, the incubates were analyzed by liquid chromatography–high-resolution mass spectrometry. BZO-4en-POXIZID metabolites were obtained in the incubation with HLMs and human hepatocytes, via the metabolic pathways of dihydrodiol formation, hydroxylation, reduction of the alkene bond and glucuronidation. The major metabolic pathway was found to be dihydrodiol formation at the pentenyl tail moiety. BZO-POXIZID, 5 F-BZO-POXIZID, BZO-HEXOXIZID and BZO-CHMOXIZID underwent similar metabolism to those reported in the literature, via the metabolic pathways of N-dealkylation, hydroxylation, ketone formation and oxidative defluorination (to alcohol or carboxylic acid). The results suggest that OXIZIDs are mainly metabolized at the N-alkyl moiety and the major metabolic pathways are hydroxylation when the N-alkyl moiety is a simple hydrocarbon, whereas functional-group-specific pathways (dihydrodiol formation and oxidative defluorination) are preferred when the moiety contains specific functional groups (alkene or fluoro), as has been observed for other synthetic cannabinoids. The major metabolites generated via these major metabolic pathways should serve as useful analytical targets for urine analysis. Furthermore, the higher abundance of glucuronidated metabolite suggests that enzymatic hydrolysis of glucuronides may be necessary for urine analysis to increase phase I metabolite concentration and improve detection.
Treatment of Severe Road Rash with ReCell® Autologous Skin Cell Suspension
Authors: Grossman Holly , Pang Alan , Griswold John
Published: March 2023

Road rash injuries are often variable in severity, with injuries ranging from simple scrapes to full-thickness burns. Autologous skin cell suspension devices, such as ReCell®, have shown increased promise by creating results comparable to the current standard of care, split-thickness skin grafting with significantly less donor skin required. We present a case of a 29-year-old male with significant road rash after a motorcycle accident at highway speeds, who was successfully treated solely with ReCell application. After surgery, he reported decreased pain with wound care and showed overall wound improvement with no changes in range of motion at 2-week follow-up. This case demonstrates the potential of ReCell as an independent treatment modality for pain and skin injury secondary to severe road rash.
Introduction to the legal mobilization special focus
Authors: Handmaker Jeff
Published: March 2023

For many of us who study, or practice legal mobilization, the image of a duck-rabbit can be regarded as a metaphor of the very different world views and vocabularies that legal scholars and legal practitioners as well as social scientists and social activists use in explaining and practising law-based advocacy. Conventional, siloed approaches by academics and practitioners alike are common, though hardly desirable. We feel that rather than ask which vocabulary is more important, it is imperative to focus on the process of how people can understand each other, irrespective of the language and terms they are using. Moreover, we are curious why it is important to make such distinctions in conceptualizing and analysing the context of law-based advocacy and the many forms that legal mobilization adopts.
Effects of epigenetic therapy on natural killer cell function and development in hematologic malignancy
Authors: Lordo Matthew R , Stiff Andrew R , Oakes Christopher C , Mundy-Bosse Bethany L
Published: March 2023

Epigenetic therapy is an emerging field in the treatment of human cancer, including hematologic malignancies. This class of therapeutic agents approved by the US Food and Drug Administration for cancer treatment includes DNA hypomethylating agents, histone deacetylase inhibitors, IDH1/2 inhibitors, EZH2 inhibitors, and numerous preclinical targets/agents. Most studies measuring the biological effects of epigenetic therapy focus their attention on either their direct cytotoxic effects on malignant cells or their effects on modifying tumor cell antigen expression, exposing them to immune surveillance mechanisms. However, a growing body of evidence suggests that epigenetic therapy also has effects on the development and function of the immune system, including natural killer cells, which can alter their response to cancer cells. In this review, we summarize the body of literature studying the effects of different classes of epigenetic therapy on the development and/or function of natural killer cells.
Local and large-scale effects on the astrophysics of void galaxies
Authors: Rodríguez-Medrano Agustín M , Paz Dante J , Stasyszyn Federico A , Rodríguez Facundo , Ruiz Andrés N , Merchán Manuel
Published: March 2023

Galaxies in cosmic voids have been reported with properties related to a delayed evolution compared to the rest of the Universe. These characteristics reflect the interaction of galaxies with the environment. However, it is not clear the degree of influence of the large-scale structure on the properties of void galaxies or if these are only influenced by the low local density around them typical of these regions. In this article, we identified cosmic voids in the SDSS-DR16 and studied the g–r colour, star formation rate, and concentration of galaxies. We identified galaxy groups to characterize the local environment and studied the properties of galaxies as a function of total and stellar masses, separately analysing those in voids and the general sample. Our results show that galaxies that inhabit haloes of a given mass (below ${\sim}10^{13.5}{\rm M}_{\odot }$), are bluer, have a higher star formation rate and are less concentrated when the host halo is inside voids compared to other regions. For larger halo masses, the trend disappears. We also analyse whether the properties of galaxies are sensitive to the type of voids that inhabit. This is done by separating voids embedded in overdense regions (S-type) from those that asymptotically converge to the average density of the Universe (R-type). We found that galaxies in R-type voids are bluer, with higher SFR and less concentration than in S-type voids. Our results indicate some degree of correlation of galaxy properties with the large-scale environment provided by voids, suggesting possible second-order mechanisms in galaxy evolution.
Exploring the influence of different velocity fields on Wolf–Rayet star spectra
Authors: Lefever R R , Sander A A C , Shenar T , Poniatowski L G , Dsilva K , Todt H
Published: March 2023

Given their strong stellar winds, Wolf–Rayet (WR) stars exhibit emission line spectra that are predominantly formed in expanding atmospheric layers. The description of the wind velocity field $\upsilon (r)$ is therefore a crucial ingredient in the spectral analysis of WR stars, possibly influencing the determination of stellar parameters. In view of this, we perform a systematic study by simulating a sequence of WR-star spectra for different temperatures and mass-loss rates using β-type laws with 0.5 ≤ β ≤ 20. We quantify the impact of varying $\upsilon (r)$ by analysing diagnostic lines and spectral classifications of emergent model spectra computed with the Potsdam Wolf–Rayet (PoWR) code. We additionally cross-check these models with hydrodynamically consistent – hydro – model atmospheres. Our analysis confirms that the choice of the β exponent has a strong impact on WR-star spectra, affecting line widths, line strengths, and line profiles. In some parameter regimes, the entire range of WR subtypes could be covered. Comparison with observed WR stars and hydro models revealed that values of β ≳ 8 are unlikely to be realized in nature, but a range of β values needs to be considered in spectral analysis. UV spectroscopy is crucial here to avoid an underestimation of the terminal velocity $\upsilon _\infty$. Neither single- nor double-β descriptions yield an acceptable approximation of the inner wind when compared to hydro models. Instead, we find temperature shifts to lower T2/3 when employing a hydro model. Additionally, there are further hints that round-lined profiles seen in several early WN stars are an effect from non-β velocity laws.
The stellar population responsible for a kiloparsec-size superbubble seen in the JWST ‘phantom’ images of NGC 628
Authors: Mayya Y D , Alzate J A , Lomelí-Núez L , Zaragoza-Cardiel J , Gómez-González V M A , Silich S , Fernández-Arenas D , Vega O , Ovando P A , Rodríguez L H , Rosa-González D , Luna A , Zamora-Avilés M , Rosales-Ortega F
Published: March 2023

We here study the multiband properties of a kiloparsec-size superbubble in the late-type spiral galaxy NGC 628. The superbubble is the largest of many holes seen in the early release images using James Webb Space Telescope (JWST)/MIRI filters that trace the polycyclic aromatic hydrocarbon (PAH) emissions. The superbubble is located in the interarm region ∼3 kpc from the Galactic Centre in the south-east direction. The shell surrounding the superbubble is detected in H i, CO, and H α with an expansion velocity of 12 km s−1 and contains as much as 2 × 107 M⊙ of mass in gas that is mostly in molecular form. We find a clear excess of blue, bright stars inside the bubble as compared to the surrounding disc on the Hubble Space Telescope/Advanced Camera for Surveys images. These excess blue, bright stars are part of a stellar population of 105 M⊙ mass that is formed over the last 50 Myr in different star formation episodes, as determined from an analysis of colour–magnitude diagrams using a Bayesian technique. The mechanical power injected by the massive stars of these populations is sufficient to provide the energy necessary for the expansion of the shell gas. Slow and steady, rather than violent, injection of energy is probably the reason for the maintenance of the shell structure over the kiloparsec scale. The expanding shell is currently the site for triggered star formation as inferred from the JWST 21 µm (F2100W filter) and the H α images.
A possible signature of the influence of tidal perturbations in dwarf galaxy scaling relations
Authors: Watkins A E , Salo H , Kaviraj S , Collins C A , Knapen J H , Venhola A , Román J
Published: March 2023

Dwarf galaxies are excellent cosmological probes, because their shallow potential wells make them very sensitive to the key processes that drive galaxy evolution, including baryonic feedback, tidal interactions, and ram pressure stripping. However, some of the key parameters of dwarf galaxies, which help trace the effects of these processes, are still debated, including the relationship between their sizes and masses. We re-examine the Fornax Cluster dwarf population from the point of view of isomass-radius–stellar mass relations (IRSMRs) using the Fornax Deep Survey Dwarf galaxy Catalogue, with the centrally located (among dwarfs) $3.63 \mathcal {M}_{\odot }$ pc−2 isodensity radius defining our fiducial relation. This relation is a powerful diagnostic tool for identifying dwarfs with unusual structure, as dwarf galaxies’ remarkable monotonicity in light profile shapes, as a function of stellar mass, reduces the relation’s scatter tremendously. By examining how different dwarf properties (colour, 10th nearest neighbour distance, etc.) correlate with distance from our fiducial relation, we find a significant population of structural outliers with comparatively lower central mass surface density and larger half-light-radii, residing in locally denser regions in the cluster, albeit with similar red colours. We propose that these faint, extended outliers likely formed through tidal disturbances, which make the dwarfs more diffuse, but with little mass-loss. Comparing these outliers with ultra-diffuse galaxies (UDGs), we find that the term UDG lacks discriminatory power; UDGs in the Fornax Cluster lie both on and off of IRSMRs defined at small radii, while IRSMR outliers with masses below $\sim 10^{7.5} \mathcal {M}_{\odot }$ are excluded from the UDG classification due to their small effective radii.
The effects of Galactic model uncertainties on LISA observations of double neutron stars
Authors: Storck Anatole , Church Ross P
Published: March 2023

Observations of binaries containing pairs of neutron stars using the upcoming space-based gravitational wave observatory, LISA, have the potential to improve our understanding of neutron star physics and binary evolution. In this work, we assess the effect of changing the model of the Milky Way’s kinematics and star formation history on predictions of the population of double neutron stars that will be detected and resolved by LISA. We conclude that the spatial distribution of these binaries is insensitive to the choice of Galactic models, compared to the stochastic variation induced by the small sample size. In particular, the time-consuming computation of the binaries’ Galactic orbits is not necessary. The distributions of eccentricity and gravitational-wave frequency are, however, affected by the choice of star formation history. Binaries with eccentricities e  > 0.1, which can be measured by LISA observations, are mostly younger than $100\, {\rm Myr}$. We caution that comparisons between different predictions for LISA observations need to use consistent star formation histories, and that the Galactic star formation history should be taken into account in the analysis of the observations themselves. The lack of strong dependence on Galactic models means that LISA detection of double neutron star binaries may provide a relatively clean probe of massive binary star evolution.
Noise reduction in single-shot images using an auto-encoder
Authors: Bartlett Oliver J , Benoit David M , Pimbblet Kevin A , Simmons Brooke , Hunt Laura
Published: March 2023

We present an application of auto-encoders to the problem of noise reduction in single-shot astronomical images and explore its suitability for upcoming large-scale surveys. Auto-encoders are a machine learning model that summarizes an input to identify its key features, and then from this knowledge predicts a representation of a different input. The broad aim of our auto-encoder model is to retain morphological information (e.g. non-parametric morphological information) from the survey data while simultaneously reducing the noise contained in the image. We implement an auto-encoder with convolutional and max pooling layers. We test our implementation on images from the Panoramic Survey Telescope and Rapid Response System that contain varying levels of noise and report how successful our auto-encoder is by considering mean squared error, structural similarity index, the second-order moment of the brightest 20 per cent of the galaxy’s flux M20, and the Gini coefficient, while noting how the results vary between original images, stacked images, and noise-reduced images. We show that we are able to reduce noise, over many different targets of observations, while retaining the galaxy’s morphology, with metric evaluation on a target-by-target analysis. We establish that this process manages to achieve a positive result in a matter of minutes, and by only using one single-shot image compared to multiple survey images found in other noise reduction techniques.
PHOSPHATE STARVATION RESPONSE1 (PHR1) interacts with JASMONATE ZIM-DOMAIN (JAZ) and MYC2 to modulate phosphate deficiency-induced jasmonate signaling in Arabidopsis
Authors: He Kunrong , Du Jiancan , Han Xiao , Li Huiqiong , Kui Mengyi , Zhang Juping , Huang Zhichong , Fu Qiantang , Jiang Yanjuan , Hu Yanru
Published: March 2023

Phosphorus (P) is a macronutrient necessary for plant growth and development. Inorganic phosphate (Pi) deficiency modulates the signaling pathway of the phytohormone jasmonate in Arabidopsis thaliana, but the underlying molecular mechanism currently remains elusive. Here, we confirmed that jasmonate signaling was enhanced under low Pi conditions, and the CORONATINE INSENSITIVE1 (COI1)-mediated pathway is critical for this process. A mechanistic investigation revealed that several JASMONATE ZIM-DOMAIN (JAZ) repressors physically interacted with the Pi signaling-related core transcription factors PHOSPHATE STARVATION RESPONSE1 (PHR1), PHR1-LIKE2 (PHL2), and PHL3. Phenotypic analyses showed that PHR1 and its homologs positively regulated jasmonate-induced anthocyanin accumulation and root growth inhibition. PHR1 stimulated the expression of several jasmonate-responsive genes, whereas JAZ proteins interfered with its transcriptional function. Furthermore, PHR1 physically associated with the basic helix–loop–helix (bHLH) transcription factors MYC2, MYC3, and MYC4. Genetic analyses and biochemical assays indicated that PHR1 and MYC2 synergistically increased the transcription of downstream jasmonate-responsive genes and enhanced the responses to jasmonate. Collectively, our study reveals the crucial regulatory roles of PHR1 in modulating jasmonate responses and provides a mechanistic understanding of how PHR1 functions together with JAZ and MYC2 to maintain the appropriate level of jasmonate signaling under conditions of Pi deficiency.
Complex systems of secrecy: the offshore networks of oligarchs
Authors: Chang Ho-Chun Herbert , Harrington Brooke , Fu Feng , Rockmore Daniel N
Published: March 2023

Following the invasion of Ukraine, the USA, UK, and EU governments–among others–sanctioned oligarchs close to Putin. This approach has come under scrutiny, as evidence has emerged of the oligarchs’ successful evasion of these punishments. To address this problem, we analyze the role of an overlooked but highly influential group: the secretive professional intermediaries who create and administer the oligarchs’ offshore financial empires. Drawing on the Offshore Leaks Database provided by the International Consortium of Investigative Journalists (ICIJ), we examine the ties linking offshore expert advisors (lawyers, accountants, and other wealth management professionals) to ultra-high-net-worth individuals from four countries: Russia, China, the USA, and Hong Kong. We find that resulting nation-level “oligarch networks” share a scale-free structure characterized by a heterogeneity of heavy-tailed degree distributions of wealth managers; however, network topologies diverge across clients from democratic versus autocratic regimes. While generally robust, scale-free networks are fragile when targeted by attacks on highly connected nodes. Our “knock-out” experiments pinpoint this vulnerability to the small group of wealth managers themselves, suggesting that sanctioning these professional intermediaries may be more effective and efficient in disrupting dark finance flows than sanctions on their wealthy clients. This vulnerability is especially pronounced amongst Russian oligarchs, who concentrate their offshore business in a handful of boutique wealth management firms. The distinctive patterns we identify suggest a new approach to sanctions, focused on expert intermediaries to disrupt the finances and alliances of their wealthy clients. More generally, our research contributes to the larger body of work on complexity science and the structures of secrecy.
THE THERMOLUMINESCENCE (TL) DOSE RESPONSE OF COMPOSITE PEAK 5 IN LIF:MG,TI (TLD-100): DEPENDENCE ON THE ORDER OF KINETICS
Authors: Nemirovsky Dimitry , Oster Leonid , Reshes Galina , Biderman Shlomo , Bokobza Yogev , Sterenberg Matan , Eliyahu Ilan , Shapiro Alexander , Herman Benny , Horowitz Yigal
Published: March 2023

A seeming contradiction in the prediction of the spatially correlated trapping center/luminescent center model applied to LiF:Mg,Ti has been the linear/supralinear behavior of the dose response of glow peak 5a. In the TC/LC model, the localised electron–hole recombination, giving rise to glow peak 5a, is expected to result in an extended region of linear dose response. Deconvolution of the glow curves based on first order kinetic peak shapes results, however, in a dose response of peak 5a, which closely resembles the linear/supralinear dose response of peak 5. It is demonstrated herein that when general-order kinetics peak shapes are used for peak 5a, the analysis can result in a linear dose response of glow peak 5a up to dose levels as high as 30 Gy, well beyond the 1-Gy onset of supralinearity of peak 5. The extended linearity suggests a resolution of the contradiction.
No Increased Detection of Nucleic Acids of CNS-related Viruses in the Brains of Patients with Schizophrenia, Bipolar Disorder, and Autism Spectrum Disorder
Authors: Min Shishi , Gandal Michael J , Kopp Richard F , Liu Chunyu , Chen Chao
Published: March 2023

Background and Hypothesis

Viral infections are increasingly recognized in the etiology of psychiatric disorders based on epidemiological and serological studies. Few studies have analyzed viruses directly within the brain and no comprehensive investigation of viral infection within diseased brains has been completed. This study aims to determine whether viral infection in brain tissues is a risk factor for 3 major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder.

Study Design

This study directly evaluated the presence of viral DNA or RNA in 1569 brains of patients and controls using whole-genome sequencing and RNA sequencing data with 4 independent cohorts. The PathSeq tool was used to identify known human viruses in the genome and transcriptome of patients and controls.

Study Results

A variety of DNA and RNA viruses related to the central nervous system were detected in the brains of patients with major psychiatric disorders, including viruses belonging to Herpesviridae, Polyomaviridae, Retroviridae, Flaviviridae, Parvoviridae, and Adenoviridae. However, no consistent significant differences were found between patients and controls in terms of types and amount of virus detected at both DNA and RNA levels.

Conclusions

The findings of this study do not suggest an association between viral infection in postmortem brains and major psychiatric disorders.
The case for tracing forward not backward through an overdraft
Authors: Wilde David
Published: March 2023

This article suggests that there is a respectable argument—contrary to generally held views—that equity can often trace through an overdrawn bank account, on general principle. But the direction of that tracing would be forward (as normal with tracing); not backward (the unconventional direction usually associated with potential tracing through overdrafts).
Maternal intermittent fasting deteriorates offspring metabolism via suppression of hepatic mTORC1 signaling
Authors: Yin Wenzhen , Sun Lijun , Liang Yuan , Luo Chao , Feng Tiange , Zhang Yunhua , Zhang Weizhen , Yin Yue
Published: March 2023

The metabolic benefits of intermittent fasting (IF) have been well recognized. However, limited studies have examined the relationship between long‐term maternal IF before pregnancy and offspring health. In this study, a C57BL/6J mouse model of long‐term IF before pregnancy was established: 4‐week‐old female mice were subjected to alternate‐day fasting for 12 weeks and resumed normal diet after mating. Female mice in the control group were fed ad libitum. Offspring mice were weaned at 6 weeks of age and fed a normal chow diet or a 60% high‐fat diet. The effects of long‐term pre‐pregnancy IF on offspring metabolism and its underlying mechanism were examined. We found that neonatal IF offspring weighted significantly less relevant to control mice. This difference gradually disappeared as a result of catch‐up growth. In the IF offspring, adipose tissue mass was significantly increased. This alteration was associated with a considerable deterioration in glucose tolerance. No significant difference in food intake was observed. Further, lipid deposition as well as triglyceride contents in the liver were greatly increased. Maternal IF significantly decreased levels of DNA methyltransferase in the liver of offspring. DNA methylation modifications of molecules associated with the mTORC1 signaling pathway were significantly altered, leading to the significant inhibition of mTORC1 signaling. Overexpression of S6K1 activated hepatic mTORC1 signaling and reversed the metabolic dysfunction in IF offspring. In conclusion, long‐term pre‐pregnancy IF increases hepatic steatosis and adiposity, as well as impairs glucose metabolism in adult offspring. This occurs through DNA methylation‐dependent suppression of hepatic mTORC1 signaling activity.
Aspartate and Acetate Fuel Gastrointestinal Stromal Tumors Beyond the Warburg Effect
Authors: Lai Ying-Chieh , Lin Gigin , Ho Kung-Chu , Lu Kuan-Ying , Tsai Cheng-Kun , Hung Cheng-Yu , Yeh Ta-Sen
Published: March 2023

Background:

Metabolic reprogramming is closely linked to the tumorigenesis and drug resistance of gastrointestinal stromal tumors (GISTs). Mapping the metabolic orbit of GISTs is a prerequisite if intervention against the metabolic vulnerability of refractory GISTs is desirable.

Methods:

A total of 43 patients with treatment-naïve GISTs who had undergone surgical resections were enrolled, on whom a metabolomics profile detected from surgical specimens was constructed based on the 1H-nuclear magnetic resonance (NMR) platform. The mRNA and protein levels of GLUT1, HK2, ACSS2, and FASN were assayed. Dual-tracer 18F-FDG/11C-acetate PET imaging was introduced before surgery in 15 patients.

Results:

1H-NMR-based metabolomics revealed that GISTs were characterized by upregulation of glutamate, ascorbate, aspartate and glycine and downregulation of choline, creatine, glucose and glycerol. Bioinformatics analysis showed that the TCA cycle and alanine, aspartate, and glutamate metabolism were the two leading pathways. High- and nonhigh-risk (including intermediate-, low-, and very low-risk) GISTs preferentially displayed upregulation of HK2 and ACSS2, respectively, echoed by in vivo imaging that high- and nonhigh-risk GISTs preferentially exhibited higher uptake of 18F-FDG and 11C-acetate, respectively, while 18F-FDG and 11C-acetate were complementary to each other. Nuclear ACSS2 was exclusively identified in high-risk GISTs.

Conclusion:

We describe a metabolic landscape of GISTs that read aspartate as a de facto “oncometabolite,” which was replenished via the TCA cycle and alanine, aspartate, and glutamate metabolism. Glycolysis and ACSS2-mediated acetate metabolism competed and complemented fatty acid synthesis, although glycolysis remained an aggressive phenotype.
Development of the Illinois Surgical Quality Improvement Collaborative (ISQIC)
Authors: Bilimoria Karl Y. , McGee Michael F. , Williams Mark V. , Johnson Julie K. , Halverson Amy L. , O’Leary Kevin J. , Farrell Paula , Thomas Juliana , Love Remi , Kreutzer Lindsey , Dahlke Allison R. , D’Orazio Brianna , Reinhart Steven , Dienes Katelyn , Schumacher Mark , Shan Ying , Quinn Christopher , Prachand Vivek N. , Sullivan Susan , Cradock Kimberly A. , Boyd Kelsi , Hopkinson William , Fairman Colleen , Odell David , Stulberg Jonah J. , Barnard Cindy , Holl Jane , Merkow Ryan P. , Yang Anthony D. ,   on behalf of the Illinois Surgical Quality Improvement Collaborative
Published: March 2023

Introduction:

In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the first 3 years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research.

Methods:

ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the perioperative microsystem. The components were developed from available evidence, a detailed needs assessment of the hospitals, reviewing experiences from prior surgical and nonsurgical QI Collaboratives, and interviews with QI experts. The components comprise 5 domains: guided implementation (eg, mentors, coaches, statewide QI projects), education (eg, process improvement [PI] curriculum), hospital- and surgeon-level comparative performance reports (eg, process, outcomes, costs), networking (eg, forums to share QI experiences and best practices), and funding (eg, for the overall program, pilot grants, and bonus payments for improvement).

Results:

Through implementation of the 21 novel ISQIC components, hospitals were equipped to use their data to successfully implement QI initiatives and improve care. Formal (QI/PI) training, mentoring, and coaching were undertaken by the hospitals as they worked to implement solutions. Hospitals received funding for the program and were able to work together on statewide quality initiatives. Lessons learned at 1 hospital were shared with all participating hospitals through conferences, webinars, and toolkits to facilitate learning from each other with a common goal of making care better and safer for the surgical patient in Illinois. Over the first 3 years, surgical outcomes improved in Illinois.

Discussion:

The first 3 years of ISQIC improved care for surgical patients across Illinois and allowed hospitals to see the value of participating in a surgical QI learning collaborative without having to make the initial financial investment themselves. Given the strong support and buy-in from the hospitals, ISQIC has continued beyond the initial 3 years and continues to support QI across Illinois hospitals.
Surgeon Accuracy in Prediction of Stability of Posterior Wall Acetabular Fractures. A Survey of Orthopaedic Trauma Surgeons
Authors: Vatti Lohith , Schoenfeldt Theodore , Eikani Carlo , Dickens Brooke , Cohen Joseph , Dillman Daryl
Published: March 2023

Objectives:

This study aims to investigate surgeon accuracy in prediction of the stability of posterior wall acetabular fractures by comparing “examination under anesthesia” findings to submitted estimations on the basis of radiograph and computed tomography (CT) imaging across a range of experience in orthopaedic surgeons and trainees.

Methods:

Records of patients who underwent examination under anesthesia after presenting with posterior wall acetabular fractures at 2 different institutions were pooled for data collection, totaling 50 cases. Radiographs, CT images, and information regarding the presence of a hip dislocation requiring procedural reduction were provided to participants for review. A survey was generated for submission of impressions of stability for each individual case and disseminated among orthopaedic trainees and surgeons in practice.

Results:

The submissions of 11 respondents were analyzed. Mean accuracy was calculated to be 0.70 (SD = 0.07). Sensitivity and specificity of respondents were 0.68 (SD = 0.11) and 0.71 (SD = 0.12), respectively. Positive predictive value and negative predictive value for respondents were 0.56 (SD = 0.09) and 0.82 (SD = 0.04), respectively. There was poor correlation of accuracy with years of experience with R2 calculated to be 0.0004 and poor agreement between observers with Kappa measurement of interobserver reliability of 0.46.

Conclusions:

Our study suggests that surgeons are unable to consistently differentiate between stable and unstable patterns on the basis of assessments based on x-ray and CT. Years of experience in training or practice was not found to be associated with improved accuracy of stability prediction.
Grading Systems of Lumbar Facet Joint Inflammatory Changes on Magnetic Resonance Imaging
Authors: Acosta José I. , Mandell Jacob C. , Ermann Joerg , Isaac Zacharia , Zampini Jay M. , DeFilipp Miriam , Gottreich Julia R. , Andrew Michael , Katz Jeffrey N.
Published: March 2023

Study Design.

A scoping review.

Objective.

We aimed to identify and characterize grading systems of the inflammatory features of the lumbar facet joints (FJs) noted on magnetic resonance imaging and summarize their reliability.

Summary of Background Data.

Chronic low back pain is one of the most common causes of disability worldwide and is frequently accompanied by FJ osteoarthritis. Inflammatory changes in the lumbar FJs are commonly noted in imaging studies of patients with FJ osteoarthritis and low back pain. Several grading systems for these inflammatory changes have been developed. However, these grading system’s features and reliability have yet to be reviewed.

Materials and Methods.

We performed a literature search of studies reporting grading systems for FJ inflammatory changes published in English or Spanish between 1985 and 2022. We collected data on reported interreader reliability measures of each grading system. Finally, we compared the features of inflammation described by each system.

Results.

Six studies met the inclusion criteria and were used in our analysis. Features commonly graded in these systems are the hyperintensity signal noted within the FJ, bone marrow edema, and the extent of the soft-tissue edema surrounding the FJs. We found that the interreader reliability measures ranged from 0.56 to 0.96.

Conclusions.

Only 6 studies have reported methods for documenting inflammation in the FJs. Studies varied in the precise tissues and phenomena included in the grading systems. However, the systems were generally reliable. Future studies should document the reliability of these methods when independent investigators are not involved in developing the classification schemes. Further work might combine one or more of these measures to establish a standard and reliable grading system for inflammatory changes in the FJs, including signal intensity within the joint, bone marrow edema, and soft-tissue inflammation.
The Microbiome of Complicated Diverticulitis: An Imbalance of Sulfur-Metabolizing Bacteria
Authors: Portolese Austin C. , McMullen Brittney N. , Baker Samantha K. , Chen See Jeremy R. , Yochum Gregory S. , Koltun Walter A. , Lamendella Regina , Jeganathan Nimalan A.
Published: March 2023

BACKGROUND:

The progression to acute diverticulitis from the relatively benign condition of colonic diverticulosis is not well characterized. A smaller subset may even develop complicated (perforated) diverticulitis resulting in sepsis and/or death. Characterizing the differences between recurrent, uncomplicated diverticulitis and the more virulent, complicated diverticulitis is necessary to guide clinical decision making. Alterations to the microbiome offer a possible explanation for local inflammation and the pathophysiology of diverticular disease.

OBJECTIVE:

To characterize the mucosal-associated microbiome in patients with recurrent uncomplicated diverticulitis and complicated (perforated) diverticulitis.

DESIGN:

Microbial DNA was extracted from full-thickness surgical specimens for 16S rRNA gene sequencing, targeting the V4 hypervariable region. Sequences were analyzed and a quantitative characterization based on taxonomic classification was performed.

SETTING:

A tertiary care academic medical center.

PATIENTS:

This study compared 48 patients with recurrent, uncomplicated diverticulitis and 35 patients with radiographically-confirmed perforated (complicated) diverticulitis. Tissues were harvested from surgical resection specimens to include both diseased regions as well as non-diseased (adjacent normal) regions.

MAIN OUTCOME MEASURES:

We assessed differences in relative abundance and taxonomic classification of mucosal-associated microbes in surgical resection specimens from diverticular disease.

RESULTS:

When analyzing the tissue of diverticular resection specimens, the complicated diseased segments demonstrated an increased abundance of sulfur-reducing and sulfur-oxidizing bacteria when compared to non-diseased, adjacent normal regions. When comparing diseased segments, tissues of complicated patients had a marked increase in sulfur-reducing microbes.

LIMITATIONS:

We characterized the mucosal-associated microbiome present at the time of surgical resection, limiting conclusions on its role in pathophysiology. Furthermore, antibiotic usage and bowel preparation prior to surgery may result in perturbations to microbial flora.

CONCLUSIONS:

The microbiome of complicated diverticulitis is marked by a localized imbalance of sulfur-metabolizing microbes. The abundance of sulfur-reducing microbes may lead to an excess of hydrogen sulfide and subsequent inflammation.