bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive pressure-volume loops provide incremental value to age, sex, and infarct size for predicting adverse cardiac remodelling after ST-elevation myocardial infarction
Authors: Lav Theodor , Engstrøm Thomas , Kyhl Kasper , Nordlund David , Lønborg Jacob , Engblom Henrik , Erlinge David , Arheden Håkan
Published: January 2025

Aims

This study aimed to assess the predictive value of non-invasive pressure–volume (PV) loop variables by cardiovascular magnetic resonance (CMR) for determining development of adverse remodelling 3 months after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).

Methods and results

In total, 181 STEMI patients examined with CMR during the index admission (baseline) after primary PCI and at 3-month follow-up in The Third DANish Study of Optimal Acute Treatment of Patients with STEMI (DANAMI-3) study were retrospectively analysed. A time-varying elastance model for generating PV loops from CMR volumetry and brachial blood pressure was used to calculate contractility, arterial elastance, stroke work, potential energy, efficiency, external power, ventriculoarterial coupling, and energy per ejected volume. Adverse remodelling was seen in 28 patients (15%), defined as a concomitant increase in end-diastolic and end-systolic volume of ≥12% from baseline to follow-up. PV loop variables measured at baseline showed predictive value for adverse remodelling, independent of age, sex, and infarct size (IS) by a logistic regression analysis: contractility [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.8–12.4] and efficiency (OR 1.05, 95% CI 1.00–1.11). Furthermore, females showed a higher increase in contractility between the timepoints (ΔContractility = 0.4 ± 0.4 mmHg/mL vs. 0.1 ± 0.4 mmHg/mL, P < 0.0001). A higher energy expenditure was seen at baseline in left arterial descending artery infarctions compared to left circumflex artery and right coronary artery infarctions.

Conclusion

Non-invasive PV loop variables by CMR have incremental predictive value to age, sex, and IS for determining development of adverse cardiac remodelling in STEMI patients treated with primary PCI. Furthermore, the PV loop variables show significant differences in post-infarct cardiovascular adaptation between sexes and culprit vessels.
Bariatric surgery and cardiovascular outcomes in patients with obesity, metabolic dysfunction-associated steatotic liver disease, and coronary artery disease: a population-based matched cohort study
Authors: Krishnan Arunkumar , Sims Omar T , Teran Daniel , Woreta Tinsay A , Hutson William R , Alqahtani Saleh A
Published: January 2025

Aims

Bariatric surgery (BS) is a potential treatment option for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity. These patients are also at substantial risk of developing cardiovascular events and associated mortality. We aimed to assess whether BS could reduce major adverse cardiovascular events (MACE) and mortality and improve long-term survival.

Methods and results

Using the TriNetX data, adult patients (>18 years) with a diagnosis of MASLD, obesity (i.e. body mass index ≥35 kg/m2), and pre-existing coronary artery disease (CAD) between 1 January 2005 and 31 December 2022 were included. Patients with a BS were compared with those with no history of BS. Primary outcomes were the incidence of MACE, heart failure, cerebrovascular events, and coronary artery procedures or surgeries at years 1, 3, 5, 7, and 10. The secondary outcome was all-cause mortality at years 1, 3, 5, 7, and 10. We performed 1:1 propensity score matching (PSM), sensitivity analysis, and survival analysis. After PSM, both groups had a total of 1038 patients. At year 1, BS patients had a significantly lower incidence of MACE [hazard ratio (HR) = 0.56; 95% confidence interval (CI), 0.39–0.80], cerebrovascular disease (HR = 0.62; 95% CI, 0.46–0.82), and coronary artery procedures and surgeries (HR = 0.65; 95% CI, 0.42–0.98). Similarly, at years 3, 5, 7, and 10, BS patients had a significantly lower incidence of MACE, heart failure, cerebrovascular disease, and coronary artery procedures and surgeries. BS patients had significantly lower 3-, 5-, 7-, and 10-year all-cause mortality. Sensitivity analysis confirmed these findings.

Conclusions

BS in patients with MASLD, obesity, and pre-existing CAD can considerably reduce the risk of recurring cardiovascular events and markedly improve survival immediately within the first year of BS and can persist long-term, even a decade after BS.
Impact of atrial fibrillation diagnosis-to-ablation time on 24-month efficacy and safety outcomes in the Cryo Global Registry
Authors: Lawin Dennis , Stellbrink Christoph , Chun Kyoung-Ryul Julian , Li Cheng-Hung , van Bragt Kelly A , Kueffer Fred , Selma Jada M , Oh Il-Young , Herzet Jean Manuel , Nitta Junichi , Chang Ting Yung , Lawrenz Thorsten
Published: January 2025

Aims

Early rhythm control therapy in atrial fibrillation (AF) results in higher freedom from atrial arrhythmia (AA) recurrence and improved cardiovascular outcomes. The optimal timing of cryoballoon ablation (CBA) is unknown.

Methods and results

We evaluated AA recurrence and procedure-related complications of early vs. late CBA (≤12 vs. >12 months from diagnosis) in patients enrolled in the prospective Cryo Global Registry (121 centres in 37 countries, NCT02752737). A total of 3447 subjects were followed through 12 months and 1220 through 24 months. In summary, 1573 patients (46%) had early ablation at a median (IQR) of 0.3 (0.1–0.6) years from AF diagnosis (age 62 ± 12 years., 35.8% female, 71.4% paroxysmal), and 1874 (54%) had late ablation at a median of 3.4 (1.9–6.7) years after diagnosis (age 61 ± 11 years, 36.2% female, 75.0% paroxysmal). Early ablation patients were less hypertensive (53.5% vs. 57.9%, P = 0.01) and less symptomatic (1.5 ± 1.1 vs. 1.8 ± 1.1 symptoms/patient, P < 0.01) and had smaller left atrial diameters (41 ± 7 mm vs. 42 ± 7 mm, P < 0.01). Freedom from AA recurrence was 81.5% (95% CI: 78.7–83.9%) in the early vs. 71.7% (95% CI: 68.9–74.3%) in the late ablation group at 24 months (P < 0.01). The risk of cardioversion was 41% lower in the early ablation group [HRAdj: 0.59 (0.42–0.83), P < 0.01]. Serious procedure-related adverse events occurred in 2.4 and 3.5% of patients in the early and late ablation groups (P = 0.045), respectively.

Conclusion

CBA within 12 months from AF diagnosis resulted in higher freedom from AA recurrence and is associated with fewer safety events in a real-world evaluation.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT02752737
Digest: Evolution of redirected help in a viscous population
Authors: Rai Shriza , Mishra Geetanjali
Published: January 2025

When broods fail, parents may assist neighbors’ offspring, a behavior called redirected helping that is observed in many species. Flatrès and Wild used inclusive fitness models to study this behavior (Selective advantage of redirected helping in a viscous population. Evolution, 2024, qpae175. https://doi.org/10.1093/evolut/qpae175). They showed that redirected helping can evolve in viscous populations, where individuals stay near their birthplace, increasing relatedness and competition among neighbors, especially when helping costs are low. Life-history traits like survival, dispersal, and brood-failure rates shape this behavior. Interestingly, survival benefits from helping can outweigh reproductive gains, challenging assumptions and providing fresh insights into cooperative breeding dynamics.
The Chromosome-level Genome of the Ctenophore Mnemiopsis leidyi A. Agassiz, 1865 Reveals a Unique Immune Gene Repertoire
Authors: Koutsouveli Vasiliki , Torres-Oliva Montserrat , Bayer Till , Fuß Janina , Grossschmidt Nora , Marulanda-Gomez Angela M , Jensen Nadin , Gill Diana , Schmitz Ruth A , Pita Lucía , Reusch Thorsten B H
Published: January 2025

Ctenophora are basal marine metazoans, the sister group of all other animals. Mnemiopsis leidyi is one of the most successful invasive species worldwide with intense ecological and evolutionary research interest. Here, we generated a chromosome-level genome assembly of M. leidyi with a focus on its immune gene repertoire. The genome was 247.97 Mb, with N50 16.84 Mb, and 84.7% completeness. Its karyotype was 13 chromosomes. In this genome and that of two other ctenophores, Bolinopsis microptera and Hormiphora californensis, we detected a high number of protein domains related to potential immune receptors. Among those, proteins containing Toll/interleukin-1 (TIR2) domain, NACHT domain, Scavenger Receptor Cystein-Rich (SRCR) domain, or C-type Lectin domain (CTLD) were abundant and presented unique domain architectures in M. leidyi. M. leidyi seems to lack bona fide Toll-like Receptors, but it does possess a repertoire of 15 TIR2 domain-containing genes. Besides, we detected a bona fide NOD-like receptor and 38 NACHT domain-containing genes. In order to verify the function of those domain-containing genes, we exposed M. leidyi to the pathogen Vibrio coralliilyticus. Among the differentially expressed genes, we identified potential immune receptors, including four TIR2 domain-containing genes, all of which were upregulated in response to pathogen exposure. To conclude, many common immune receptor domains, highly conserved across metazoans, are already present in Ctenophora. These domains have large expansions and unique architectures in M. leidyi, findings consistent with the basal evolutionary position of this group, but still might have conserved functions in immunity and host–microbe interaction.
Protein Quality Control is a Master Modulator of Molecular Evolution in Bacteria
Authors: Diaz Arenas Carolina , Alvarez Maristella , Wilson Robert H , Shakhnovich Eugene I , Ogbunugafor C Brandon
Published: January 2025

The bacterial protein quality control (PQC) network comprises a set of genes that promote proteostasis (proteome homeostasis) through proper protein folding and function via chaperones, proteases, and protein translational machinery. It participates in vital cellular processes and influences organismal development and evolution. In this review, we examine the mechanistic bases for how the bacterial PQC network influences molecular evolution. We discuss the relevance of PQC components to contemporary issues in evolutionary biology including epistasis, evolvability, and the navigability of protein space. We examine other areas where proteostasis affects aspects of evolution and physiology, including host-parasite interactions. More generally, we demonstrate that the study of bacterial systems can aid in broader efforts to understand the relationship between genotype and phenotype across the biosphere.
Modelling of seismic wave propagation in moving fluids and stationary elastic solids
Authors: Chen Liang , Huang Jianping
Published: January 2025

Forward modelling is crucial for seismic data processing, which is the core of reverse time migration and full-waveform inversion. Numerical simulation based on conventional elastic wave equations in stationary solids neglects the fluidity of fluids (e.g. sea water), making it difficult to simulate the propagation of seismic waves in moving fluids accurately. To solve the problem, we start with classical equations of fluid mechanics and derive a new set of elastic wave equations that can be used to simultaneously model wave propagation both in moving fluids and stationary solids. For high-precision numerical simulations, a staggered-grid finite-difference scheme is used to solve the proposed equations. Numerical tests on a homogeneous uniformly moving model demonstrate that the dynamic and kinematic characteristics (e.g. wavelength and amplitude) of elastic waves in moving fluids are quite different from those in stationary medium. Forward modelling for a two-layer model that has a flowing water layer and a stationary rock layer is used to study the reflection and transmission patterns of elastic waves in the solid–fluid interface. With the help of the superposition principle of vectors and Snell's law, the transmission angles can be easily calculated. A further test for a more complex stratified model indicates that the energy and traveltime differences of reflected waves are expected to be evidence for the identification of moving fluids. Numerical experiments on the Marmousi II model demonstrate that the relative wavefield error is positively correlated with the maximum moving velocity and the wavelet dominant frequency.
Understanding health care price variation: evidence from Transparency-in-Coverage data
Authors: Whaley Christopher , Radhakrishnan Nandita , Richards Michael , Simon Kosali , Chartock Benjamin
Published: January 2025

Competition in health care markets should lead to lower prices and less dispersion, with consumer choice as the driving mechanism. Several studies document price variation, suggesting room for improvement; however, they relied on selected data from insurers who provide access to data, limiting generalizability. We document the nature of price variation in the private US market across geography, payer, and provider by leveraging a new dataset, implementing a descriptive analysis using the most comprehensive data available: Transparency-in-Coverage. We measured health care prices in 3 ways: percentile distribution prices for common services, state-level and insurer-level facility fee price indices, and regression-adjusted mean inpatient and outpatient prices. Variation is large: the mean facility fee for a foot X-ray, for example, is $86 at Anthem and $190 at UnitedHealth. Pricing does not appear to be uniform; there is just 22% correlation between an insurer's inpatient price and outpatient facility price. And there is little difference in ordering of high-price states depending on alternative measures, such as relative to Medicare. Results suggest greater consideration of policies to address high and variable prices for US health care.
Early clinical experience using tecovirimat during the 2022 mpox epidemic in Toronto underscores ongoing clinical equipoise and the need for randomized trials
Authors: Khera Shreya S , Mishra Sharmistha , Pico Espinosa Oscar Javier , Gough Kevin , Tan Charlie , Walmsley Sharon , Zhabokritsky Alice , Sharma Malika , Chan Adrienne K , Leis Jerome A , Oo Myo Minn , Tan Darrell H S
Published: January 2025

Background

Tecovirimat is an antiviral drug that was used compassionately for treating mpox in high-income settings during the 2022 global outbreak. Randomized controlled trials of its efficacy have not yet been completed.

Objectives

To describe medication adherence, tolerability and clinical outcomes of adults receiving open-label tecovirimat for mpox infection.

Methods

We conducted a prospective observational study and a retrospective case series of adults with mpox cared for at three academic hospitals in Toronto, Canada, between May and August 2022. We present a descriptive analysis of those prescribed oral tecovirimat 600 mg twice daily for 14 days for the management of severe manifestations.

Results

Of 69 consenting participants, all were cisgender men, of whom 60 (87%) identified as gay, and 6 (9%) as bisexual. Nearly half (46%) were living with HIV, with a median (IQR) CD4 count of 468 (328–678) cells/mm3, among whom plasma HIV RNA was <20 copies/mL in 29 (91%) participants. One-third (33%) of participants received tecovirimat during the course of their illness. All participants experienced a decline in number of symptoms over time, but three treated participants initially experienced worsening symptoms despite therapy. Self-reported adherence to tecovirimat was excellent and tolerability was good.

Conclusions

Our experience prescribing tecovirimat for mpox suggests it is safe and well tolerated, but the evolution of symptoms in some tecovirimat-treated patients underscores the ongoing uncertainty regarding its efficacy. In the context of considerable community demand for the drug, efforts should be made to connect mpox patients to rigorous randomized controlled trials, given this ongoing clinical equipoise.
A novel approach to managing gingival recession in protruded roots: a case report
Authors: Lahham Cezar , Kharroubi Rand , AbuQubi Basem , Shatara Aram , Lahham Elias Edward
Published: January 2025

This case report presents an innovative approach to managing severe isolated gingival recession associated with root protrusion beyond bone boundaries in a 28-year-old female patient. The patient, who had a history of orthodontic treatment for a 5-year-period, displayed significant gingival recession at the lower right central incisor. Conventional orthodontic repositioning was declined by the patient, leading to the adoption of an alternative treatment strategy. A combination of odontoplasty to trim the protruding root (~1 mm) and a connective tissue graft was employed. The procedure involved meticulous flap creation, root surface biomodification, and precise graft placement to achieve optimal functional and esthetic outcomes. Follow-up over 3 months revealed increased keratinized tissue thickness and complete root coverage, with high patient satisfaction. This novel technique demonstrates the potential to address complex recession cases effectively, preserving root structure and enhancing graft vascularization. Further research is warranted to validate these findings across broader clinical scenarios.
A reference framework for extremely metal-poor OB star studies: calibrations for stellar parameters and intrinsic colours
Authors: Lorenzo M , Garcia M , Castro N , Najarro F , Cerviño M , Herrero A , Simón-Díaz S
Published: January 2025

We provide the first reference framework for extremely metal-poor (XMP) OB-type stars. We parsed a grid of 0.10 $Z_{\odot }$fastwind models, covering the parameter space of O stars and early-B supergiants, through contemporary spectral classification criteria to deliver a calibration of key stellar properties as a function of spectral type, and tabulated colours for the most common photometric systems. By using an extensive grid of models, we account for the different combinations of stellar parameters that result in the same spectral morphology and provide a range of parameters and colours compatible with each spectral subtype and luminosity class. We supply updated photometric criteria to optimize candidate selection of OB stars in XMP environments. We find 0.10 $Z_{\odot }$OB stars are 1–6 kK hotter and produce higher ionizing fluxes than their Galactic analogues. In addition, we find a bimodal distribution of the He ii-ionizing flux with spectral type; because of its known dependence on effective temperature and the wind, log $q_{\mathrm{He II}}$ for individual XMP late-O type stars could be underestimated by up to 4 orders of magnitude by other calibrations, some of them used by population synthesis codes. Finally, we used our calibrated colours to map the extinction of the 0.10 $Z_{\odot }$ galaxy Sextans A finding that reddening is non-negligible and uneven.
Strange quark matter as dark matter: 40 yr later, a reappraisal
Authors: Clemente Francesco Di , Casolino Marco , Drago Alessandro , Lattanzi Massimiliano , Ratti Claudia
Published: January 2025

Forty years ago Witten suggested that dark matter could be composed of macroscopic clusters of strange quark matter. This idea was very popular for several years, but it dropped out of fashion once lattice quantum chromodynamics calculations indicated that the confinement/deconfinement transition, at small baryonic chemical potential, is not first order, which seemed to be a crucial requirement in order to produce large clusters of quarks. Here, we revisit the conditions under which strangelets can be produced in the Early Universe. We discuss the impact of an instability in the hadronic phase separating a low density, positive-strange-charge phase from a high-density phase with a negative strange charge. This second phase can rapidly stabilize by forming colour-superconducting gaps. The strangelets then undergo partial evaporation. In this way, we obtain distributions of their sizes in agreement with the observational constraints and we discuss the many astrophysical and cosmological implications of these objects. Finally, we examine the most promising techniques to detect this type of strangelets. We also show that strangelets can exist with masses $\lesssim $1017 g, while primordial black holes are ruled out in that mass range, allowing us to distinguish between these two dark matter candidates.
Internal dynamics of multiple populations in 28 Galactic globular clusters: a wide-field study with Gaia and the Hubble Space Telescope
Authors: Cordoni G , Casagrande L , Milone A P , Dondoglio E , Mastrobuono-Battisti A , Jang S , Marino A F , Lagioia E P , Legnardi M V , Ziliotto T , Muratore F , Mehta V , Lacchin E , Tailo M
Published: January 2025

We present a detailed analysis of the internal dynamics of multiple stellar populations (MPs) in 28 Galactic globular clusters (GCs) across a wide field of view, extending from the innermost regions to the clusters’ outskirts. Using astrophotometric catalogues from ground-based observations, Gaia and the Hubble Space Telescope (HST), we identify first- (1P) and second-population (2P) stars, and study the internal dynamics of MPs using high-precision Gaia DR3 and HST proper motions. Our results reveal that while the 1P transitions from isotropy to slight tangential anisotropy towards the outer regions, 2P stars become increasingly radially anisotropic beyond the half-light radius. We also explore the connection between the dynamics of MPs and the clusters’ structural and dynamical properties, finding statistically significant differences in the anisotropy profiles of dynamically young and non-relaxed clusters, particularly beyond the 1–2 half-light radii. In these regions, 1P stars transition from isotropic to slightly tangentially anisotropic motion, while 2P stars become more radially anisotropic. In contrast, dynamically older clusters, with mixed MPs, exhibit weaker relative differences. Furthermore, clusters with orbits closer to the Galactic Centre exhibit larger dynamical differences between 1P and 2P stars than those with larger peri-Galactic radii. These findings are consistent with a scenario where 2P stars form in a more centrally concentrated environment, where the interaction with the Milky Way tidal field plays a crucial role in the dynamical evolution of MPs, especially of 1P.
Connection between steep radio spectral slopes and dust extinction in QSOs: evidence for outflow-driven shocks in dusty QSOs
Authors: Fawcett V A , Harrison C M , Alexander D M , Morabito L K , Kharb P , Rosario D J , Baghel Janhavi , Ghosh Salmoli , Sasikumar Silpa , Petley J , Sargent C , Calistro Rivera G
Published: January 2025

Recent studies have found a striking positive correlation between the amount of dust obscuration and enhanced radio emission in quasi-stellar objects (QSOs). However, what causes this connection remains unclear. In this paper we analyse uGMRT Band-3 (400 MHz) and Band-4 (650 MHz) data of a sample of 38 1.0 < z < 1.5 QSOs with existing high-resolution $0{_{.}^{\prime\prime}} 2$ e-MERLIN 1.4 GHz imaging. In combination with archival radio data, we have constructed sensitive 4–5 band radio spectral energy distributions (SEDs) across 0.144–3 GHz to further characterize the radio emission in dusty QSOs. We find that the dusty QSOs [those with $E(B-V)$ > 0.1 mag] are more likely to exhibit steep spectral slopes ($\alpha$ < $-0.5$; S $\propto$ $\nu ^{\alpha }$) than the non-dusty QSOs [$E(B-V)$ < 0.1 mag], with fractions of 46$\pm$12 and 12$\pm$4 per cent, respectively. A higher fraction of the non-dusty QSOs have peaked radio SEDs (48$\pm$9 per cent) compared to the dusty QSOs (23$\pm$8 per cent). We discuss the origin of the radio emission, finding that the majority of the peaked, predominantly non-dusty, QSOs have consistent sizes and luminosities with compact jetted radio galaxies. However, the connection between steepness and dust obscuration implies an outflow-driven shock origin for the enhanced radio more commonly found in dusty QSOs. These results add to the emerging picture whereby dusty QSOs are in an earlier blow-out phase, with shocks that heat and destroy the surrounding dust, eventually revealing a typical non-dusty QSO.
Evidence that pre-processing in filaments drives the anisotropic quenching of satellite galaxies in massive clusters
Authors: Stephenson H M O , Stott J P , Butler J , Webster M , Head J
Published: January 2025

We use a sample of 11 $z\approx 0.2\!-\!0.5$ ($z_{\text{med.}} = 0.36$) galaxy clusters from the Cluster Lensing And Supernovae survey with Hubble to analyse the angular dependence of satellite galaxy colour $(B-R)$ and passive galaxy fraction ($f_{\text{pass.}}$) with respect to the major axis of the brightest cluster galaxy (BCG). This phenomenon has been dubbed as ‘anisotropic quenching’, ‘angular conformity’ or ‘angular segregation’, and it describes how satellite galaxies along the major axis of the BCG are more likely to be quenched than those along the minor axis. A highly significant anisotropic quenching signal is found for satellites, with a peak in $(B-R)$ and $f_{\text{pass.}}$ along the major axis. We are the first to measure anisotropic quenching out to cluster-centric radii of $3R_{200}$ ($R_{200\text{, med.}} \approx 933$$\mathrm{k}\text{pc}$). We find that the signal is significant out to at least $2.5R_{200}$, and the amplitude of the signal peaks at $\approx 1.25R_{200}$. This is the first time a radial peak of the anisotropic quenching signal has been measured directly. We suggest that this peak could be caused by a build-up of backsplash galaxies at this radius. Finally, we find that $f_{\text{pass.}}$ is significantly higher along the major axis for fixed values of local surface density. The density drops less rapidly along the major axis and so satellites spend more time being pre-processed here compared to the minor axis. We therefore conclude that pre-processing in large-scale structure, and not active galactic nuclei outflows, is the cause of the anisotropic quenching signal in massive galaxy clusters, however, this may not be the cause in lower mass haloes.
Allostery and Evolution: A Molecular Journey Through the Structural and Dynamical Landscape of an Enzyme Super Family
Authors: Coquille Sandrine , Pereira Caroline Simões , Roche Jennifer , Santoni Gianluca , Engilberge Sylvain , Brochier-Armanet Céline , Girard Eric , Sterpone Fabio , Madern Dominique
Published: January 2025

Allosteric regulation is a powerful mechanism for controlling the efficiency of enzymes. Deciphering the evolutionary mechanisms by which allosteric properties have been acquired in enzymes is of fundamental importance. We used the malate (MalDH) and lactate deydrogenases (LDHs) superfamily as model to elucidate this phenomenon. By introducing a few of mutations associated to the emergence of allosteric LDHs into the non-allosteric MalDH from Methanopyrus kandleri, we have gradually shifted its enzymatic profile toward that typical of allosteric LDHs. We first investigated the process triggering homotropic activation. The structures of the resulting mutants show the typical compact organization of the R-active state of LDHs, but a distorted (T-like) catalytic site demonstrating that they corresponds to hybrid states. Molecular dynamics simulations and free energy calculations confirmed the capability of these mutants to sample the T-inactive state. By adding a final single mutation to fine-tune the flexibility of the catalytic site, we obtained an enzyme with both sigmoid (homotropic) and hyperbolic (heterotropic) substrate activation profiles. Its structure shows a typical extended T-state as in LDHs, whereas its catalytic state has as a restored configuration favorable for catalysis. Free energy calculations indicate that the T and R catalytic site configurations are in an equilibrium that depends on solvent conditions. We observed long-range communication between monomers as required for allosteric activation. Our work links the evolution of allosteric regulation in the LDH/MDH superfamily to the ensemble model of allostery at molecular level, and highlights the important role of the underlying protein dynamics.
Temporal merging into pitch with click train in the macaque auditory cortex
Authors: Song Peirun , Xu Haoxuan , Ye Hangting , Du Xinyu , Zhai Yuying , Bao Xuehui , Huang Qianyue , mehmood Ishrat , Tanigawa Hisashi , Niu Wanqiu , Tu Zhiyi , Chen Pei , Zhang Tingting , Zhao Xuan , Yu Xiongjie
Published: January 2025

Temporal integration stands as a cornerstone of auditory perception, yet its underlying neural mechanisms have remained relatively elusive. The intricate process by which discrete auditory stimuli integrate into cohesive perception is defined as “temporal merging” in this study. We use a paradigm, the transitional click train, to probe the intricacies of temporal merging within the auditory cortex. The protocol underscores a robust change response in an adapted auditory cortex upon introducing a perceptual switch between distinct pitches. Our findings delineate four pivotal determinants that modulate this change response: train duration, Inter-Click Interval (ICI) length, ICI contrast, and train regularity. Comparative analyses between the Auditory Cortex (AC) and the Medial Geniculate Body (MGB) underscore a cortical origin for this temporal merging, diverging from traditional thalamic inputs. Furthermore, the change response's clinical potential is explored, demonstrating its promise as a biomarker in anesthesia monitoring and psychiatric conditions. Collectively, this research elucidates the neuronal underpinnings of temporal integration in auditory perception, provides initial evidence for the neuronal mechanisms underlying pitch perception with click trains, and introduces a potent paradigm with vast clinical implications.
Lymph node silicosis and recurrent tuberculosis in a short service goldminer
Authors: Knight D , Murray J , Roberts R , Ehrlich R
Published: January 2025

Silica exposure and silicosis are strongly associated with pulmonary tuberculosis (TB), with ex-miners from the South African gold mines carrying a large burden of both diseases. We present a case of lymph node silicosis and recurrent TB complicated by cavitation with aspergilloma requiring right upper lobectomy, in a 38-year-old ex-goldminer with only 19 months of silica exposure. While silicosis was detected histologically in the lymph nodes, radiological findings and histopathological lung parenchyma lesions were consistent with inactive TB. A worker’s compensation claim for silicotuberculosis was unsuccessful. The findings highlight the need to take into account the contribution of subradiological silicosis and/or a low silica exposure threshold to increased TB risk, and the persistence of such TB risk following exit from exposure. The case also demonstrates the need to differentiate between the radiological and pathological features of silicosis and TB, and the possible mechanistic role of lymph node silicosis in increasing TB risk. These considerations have relevance to the surveillance of silica-exposed workers in high TB settings and the potential to reduce TB risk through silica dust control.
Liver transplantation for colorectal cancer with liver metastases
Authors: Ueberroth Benjamin E , Kriss Michael , Burton James R , Messersmith Wells A
Published: January 2025

Over the last decade, multiple clinical trials have demonstrated a survival benefit for liver transplantation in colorectal cancer with liver metastases. Additionally, advances in donor organ preservation have expanded organ availability affording the opportunity to expand indications for liver transplantation, such as colorectal cancer with unresectable liver metastases. Current data support comparable overall survival (OS) for liver transplantation for colorectal cancer with liver metastases compared with general liver transplantation recipients. Supported by this data, in the United States, allocation policy is changing to include deceased donor livers for patients with unresectable colorectal cancer liver metastases. Available studies to date demonstrate improved outcomes with primary tumor R0 resection, 6-12 months of pretransplantation chemotherapy, and careful radiologic restaging (including positron emission tomography/computed tomography) to confirm lack of extrahepatic disease. A response to pretransplantation chemotherapy is a key predictor of long-term outcomes and progression during chemotherapy appears to be a contraindication to proceeding to transplant. A carcinoembryonic antigen level ≤80 µg/L and largest liver tumor dimension <5.5 cm are both associated with improved progression-free and OS in the available literature. Liver transplantation for colorectal cancer with unresectable liver metastases is associated with longer progression-free and OS compared with chemotherapy alone. Patient selection based on imaging, laboratory, and clinical findings is critical to identify patients most likely to benefit. Liver transplantation should be considered at all centers with an active transplant program to improve outcomes for patients with advanced colorectal cancer.
Select updates from ASCO and ESMO 2024 for gastrointestinal cancer care
Authors: Jang Tim , Kim George P , George Thomas J
Published: January 2025

Background

Gastrointestinal (GI) malignancies remain the culprit behind a substantial portion of cancer-related mortality worldwide, and outcomes for patients with advanced or metastatic GI cancers remain poor despite continued efforts to improve care. In 2024, the ongoing clinical trials to optimize and improve GI cancer care showcased progress in molecular diagnostics, systemic therapies, and localized treatment approaches, providing hope for continued progress toward improved patient outcomes.

Materials and Methods

This review summarizes selected updates in GI cancer care from the 2024 ASCO and ESMO Annual Meetings, including both positive and negative trials that, while not universally practice-changing, contribute to shaping GI cancer care, clinical management, or address key questions in the field. The selected trials cover early detection and diagnostic advances, perioperative management, metastatic disease management, and immune checkpoint inhibitor (ICI)’s emerging role in GI cancer.

Results

Various clinical trials in perioperative management and their results continue to reshape or strengthen the current treatment paradigms. The use of ICIs for microsatellite instability-high colorectal cancer (CRC) presented a notable advancement with the potential to improve patient outcomes. Localized treatments such as thermal ablation appear to benefit some patients with CRC and liver metastases.

Conclusions

The collection of trial results presented at the 2024 ASCO and ESMO Annual Meetings denote the ongoing efforts of the medical and scientific community for optimizing GI cancer care. The ongoing efforts of the GI cancer research and patient community provide hope for continued progress toward improved patient outcomes and new standards of care.
From disorganized data to emergent dynamic models: Questionnaires to partial differential equations
Authors: Sroczynski David W , Kemeth Felix P , Georgiou Anastasia S , Coifman Ronald R , Kevrekidis Ioannis G
Published: January 2025

Starting with sets of disorganized observations of spatially varying and temporally evolving systems, obtained at different (also disorganized) sets of parameters, we demonstrate the data-driven derivation of parameter dependent, evolutionary partial differential equation (PDE) models capable of generating the data. This tensor type of data is reminiscent of shuffled (multidimensional) puzzle tiles. The independent variables for the evolution equations (their “space” and “time”) as well as their effective parameters are all emergent, i.e. determined in a data-driven way from our disorganized observations of behavior in them. We use a diffusion map based questionnaire approach to build a smooth parametrization of our emergent space/time/parameter space for the data. This approach iteratively processes the data by successively observing them on the “space,” the “time” and the “parameter” axes of a tensor. Once the data become organized, we use machine learning (here, neural networks) to approximate the operators governing the evolution equations in this emergent space. Our illustrative examples are based (i) on a simple advection–diffusion model; (ii) on a previously developed vertex-plus-signaling model of Drosophila embryonic development; and (iii) on two complex dynamic network models (one neuronal and one coupled oscillator model) for which no obvious smooth embedding geometry is known a priori. This allows us to discuss features of the process like symmetry breaking, translational invariance, and autonomousness of the emergent PDE model, as well as its interpretability.
Using contribution mapping to evaluate the research impact of Universities of Applied Sciences
Authors: Coombs Sarah K , Meister-Broekema Peter , Meijer Ingeborg
Published: January 2025

Research conducted by Universities of Applied Sciences (UASs) is frequently driven by professional practice where researchers are challenged with finding solutions to real-life problems. These real-life solutions are significantly enhanced by the participation of stakeholders. Through this inclusion and the resulting interactions, activities, and knowledge transfer, between the stakeholder and research(ers), impacts occur at a micro level. Micro impacts are the normal impacts that occur during the research process through interactions between researchers and stakeholders, that facilitate an unexpected and unplanned effect, be it positive or negative (Lykke et al. 2023, Mapping Research Activities and Societal Impact by Taxonomy of Indicators: Uniformity and Diversity across Academic Fields, Journal of Documentation, 79: 1049–70). Contribution analysis has been recognized as a viable method for evaluating micro impacts. One recognized contribution analysis framework is Kok and Schuit’s (2012, Contribution Mapping: A Method for Mapping the Contribution of Research to Enhance Its Impact, Health Research Policy and Systems, 10: 21) Contribution Mapping. It is also one of the frameworks acknowledged as conforming to several of the recommendations for evaluating UAS research impact. However, to do justice to the nature of Practice Oriented research, a new framework is needed. The purpose of this article is to test how Contribution Mapping works in real-life to answer the question: What can we learn from Contribution Mapping as an impact evaluation tool for a future UAS specific research impact evaluation framework? This article will examine the specificity of UAS research, the relevance of Contribution Mapping for evaluating UAS research, and the theoretical and practical implications of Contribution Mapping. Through inductive analysis conducted on information gleaned from interviews and focus groups, observations, challenges, and limitations are identified, and modifications suggested to take into consideration for a new framework.
Off-label use of biologics in urticarial vasculitis: a European retrospective cohort study
Authors: Maisonobe Lucas , Korganow Anne-Sophie , Berti Alvise , Deroux Alban , Dupin Nicolas , Aractingi Selim , Emmi Giacomo , Vandergheynst Frederic , Fabre Marc , Kluger Nicolas , Roux Marielle , Abisror Noémie , Benyamine Audrey , Cassone Giulia , Chasset François , Doutre Marie-Sylvie , Foucher Aurélie , Freguin Caroline , Gobert Delphine , Gombeir Yannick , Hernandez-Rodriguez José , Legouellec Noémie , Pinault Anne-Lise , Titeca Dimitri , Jachiet Marie , Terrier Benjamin
Published: January 2025

Objectives

Urticarial vasculitis (UV) is characterized by atypical urticarial lesions and leukocytoclastic vasculitis, sometimes with extracutaneous manifestations. First-line treatment is based on colchicine, hydroxychloroquine, dapsone or low-dose glucocorticoids. In refractory forms, the use of biologics has been anecdotally described as potentially effective. We aimed to describe the efficacy and safety of biologics in patients with UV.

Methods

We conducted a retrospective European multicentre study including patients with hypocomplementemic or normocomplementemic UV who received at least one biologic, including anti-CD20, anti-IgE and/or IL1-targeted therapy, from 2008 to 2021. We analyzed clinical and biological characteristics as well as efficacy and safety of the biologics.

Results

Forty-one patients receiving 52 therapeutic sequences were analyzed, including rituximab in 23, IL1-targeted therapy in 16 and anti-IgE in 13 cases. UV was hypocomplementemic in 24 (59%) cases. Biologics were used in median in 5th line of treatment, in combination with glucocorticoids in 75%. After a median follow-up of 25 (IQR 12–43) months, the cutaneous response was complete in 40%, partial in 37% and inadequate in 23%. Glucocorticoid discontinuation was achieved in 34% of patients. Serious adverse events, mainly infectious, were observed in 7 (17%) patients.

Conclusion

Biologics are an effective and rather well-tolerated treatment option for UV that are refractory to conventional therapies.
Machine Learning-based Cluster Analysis Identifies Three Unique Phenotypes of Patients With Adult Spinal Deformity With Distinct Clinical Profiles and Long-term Recovery Trajectory
Authors: Cui Peng , Wang Peng , Wang Shuaikang , Han Di , Huang Qingyang , Wang Wei , Chen Xiaolong , Lu Shibao
Published: January 2025

Study design:

A retrospective review of a prospective adult spinal deformity data.

Objective:

To identify distinct patient clinical profiles and recovery trajectories in patients with adult spinal deformity (ASD).

Summary of Background Data:

Patients with ASD exhibit a diverse array of symptoms and significant heterogeneity in clinical presentations, posing challenges to precise clinical decision-making. Accurate patient selection may provide further insight to personalized management strategies.

Methods:

Latent profile analysis (LPA) was performed to determine possible patient phenotype. Goodness-of-fit indices were used to determine the optimal cluster profiles. Outcome differences were evaluated using Analysis of Variance (ANOVA) and subsequent post hoc Tukey’s test, while significant predictors of group membership were identified through multinomial logistic regression.

Results:

A total of 204 ASD patients (mean age of 60.3 ± 11.8 years, comprising 62.3% females) with complete 1-year and 2-year follow-up outcome were included. LPA identified three phenotypes: 51 patients in phenotype 1, 73 patients in phenotype 2 and 80 patients in phenotype 3, respectively. Each phenotype exhibited a unique symptom profile and distinct functional recovery trajectories. Patients in phenotype 3, although demonstrated the worst Scoliosis Research Society-22 questionnaire (SRS-22r) domains at baseline, patients in this cluster exhibited the most substantial Δchange in SRS-22r domains except for self-image at both 1-year and 2-year follow-up. Remarkably, a relative large proportion of patients (58.8%) who were dissatisfied at 1-year follow-up transited to satisfied at 2-year follow-up. Advanced age, longer symptom duration, severe preoperative pelvic incidence-lumbar lordosis (PI-LL) mismatch, higher preoperative sagittal vertical axis (SVA), fusion extending to sacrum/pelvis and grade ≥ 3 osteotomy predicted membership in the phenotype 3.

Conclusions:

LPA enabled the delineation of three distinct phenotypes among ASD patients, each characterized by unique clinical profiles and distinct long-term recovery trajectories. By pinpointing the crucial variables that uniquely distinguish and predict membership in different phenotypes, the study provides valuable guidance for patient stratification.
Efficacy and safety of Matricaria chamomilla intervention in managing menopausal symptoms: a triple-blind clinical trial
Authors: Mohsenzadeh-Ledari Farideh , Agajani Delavar Mouloud , Moghadamnia Ali Akbar , Khafri Soraya , Bekhradi Reza , Behmanesh Fereshteh , Yazdani Shahla
Published: January 2025

Objective

Menopausal symptoms can significantly impact women's quality of life. Herbal interventions like Matricaria chamomilla (chamomile) have been suggested as potential remedies. However, their efficacy and safety remain underexplored.

Methods

This triple-blind clinical trial enrolled 80 postmenopausal women meeting specific criteria. Inclusion criteria included participants in early or late perimenopause, defined by a symptom score >15, FSH levels >40, or 2 years since menopause, with no significant comorbidities. Participants were randomly assigned to intervention and placebo groups. In a triple-blind clinical trial with 80 postmenopausal women (aged 47‐62) from Babol City Health Center, participants were randomly assigned to receive either chamomile (100 mg capsules with 1.2% apigenin, four times daily) or a placebo over 12 weeks. Symptoms of menopause were assessed using the Australian Menopause Association's Scorecard Symptom Questionnaire. Over 12 weeks, they received either chamomile or placebo capsules, with side effect assessments every 4 weeks.

Results

Notable differences were found between the intervention and control groups in the overall scores on the symptom scorecard from baseline to 12 weeks' postintervention (−10.36; 95% confidence interval [CI], −13.84 to −6.92; P < 0.001). Specific subscores also improved in the intervention group: vasomotor (−2.25; 95% CI, −3.09 to −1.42; P < 0.001), psychological (−3.74; 95% CI, −5.29 to −2.20; P < 0.001), locomotor (−2.70; 95% CI, −3.63 to −1.77; P < 0.001), and urological (−1.89; 95% CI, −2.77 to −1.00; P < 0.001). Both groups showed significant changes in total symptom scores over time (P < 0.001). Two participants experienced side effects, including mouth sores, skin spots, and itching, in the chamomile group, which led to their dropping out of the study.

Conclusions

Chamomile intervention shows promise in alleviating menopausal symptoms, but its use warrants caution due to associated side effects. Further research is necessary to optimize dosage and mitigate adverse reactions for safer and more effective management of menopausal symptoms.
Words to Avoid During Wide-awake Local Anesthesia No Tourniquet Surgery to Enhance Patient Experience
Authors: Brutus Jean Paul , Barone Natasha , Stolberg Kira , Russell Patricia , Lalonde Donald H.
Published: January 2025

In the evolving landscape of ambulatory surgery, wide-awake local anesthesia no tourniquet (WALANT) surgery has emerged as a preferred approach due to its efficacy, cost-effectiveness, and patient satisfaction. This paradigm shift places the patient at the center of intraoperative communication, requiring a significant change in the dialogue within the operating room (OR). Traditional conversations, which often exclude the unconscious patient, must evolve to accommodate and prioritize the psychological comfort of the conscious patient. This article examines the impact of language, tone, and conversation content on the patient experience during WALANT. We propose a communication framework that emphasizes empathy, reassurance, and patient inclusion to reduce anxiety and increase patient compliance. By analyzing common OR dialogues and their potential impact on awake patients, we identify specific phrases and words that may exacerbate patient stress or discomfort. Alternatives are suggested to foster a more positive and inclusive environment. Our recommendations are based on extensive clinical experience and supported by relevant literature, highlighting the critical role of mindful communication in improving clinical outcomes and patient satisfaction in WALANT.