bluuebunny/crossref_metadata_2025 huggingface dataset:
A fast neural emulator for interstellar chemistry
Authors: Ramos A Asensio , Plaza C Westendorp , Navarro-Almaida D , Rivière-Marichalar P , Wakelam V , Fuente A
Published: June 2024

Astrochemical models are important tools to interpret observations of molecular and atomic species in different environments. However, these models are time-consuming, precluding a thorough exploration of the parameter space, leading to uncertainties and biased results. Using neural networks to simulate the behaviour of astrochemical models is a way to circumvent this problem, providing fast calculations that are based on real astrochemical models. In this paper, we present a fast neural emulator of the astrochemical code Nautilus based on conditional neural fields. The resulting model produces the abundance of 192 species for arbitrary times between 1 and 107 yr. Uncertainties well below 0.2 dex are found for all species, while the computing time is of the order of 104 smaller than Nautilus. This will open up the possibility of performing much more complex forward models to better understand the physical properties of the interstellar medium. As an example of the power of these models, we ran a feature importance analysis on the electron abundance predicted by Nautilus. We found that the electron density is coupled to the initial sulphur abundance in a low-density gas. Increasing the initial sulphur abundance from a depleted scenario to the cosmic abundance leads to an enhancement of an order of magnitude of the electron density. This enhancement can potentially influence the dynamics of the gas in star formation sites.
Galaxy Spectra neural Network (GaSNet). II. Using deep learning for spectral classification and redshift predictions
Authors: Zhong Fucheng , Napolitano Nicola R , Heneka Caroline , Li Rui , Bauer Franz Erik , Bouche Nicolas , Comparat Johan , Kim Young-Lo , Krogager Jens-Kristian , Longhetti Marcella , Loveday Jonathan , Roukema Boudewijn F , Rouse Benedict L , Salvato Mara , Tortora Crescenzo , Assef Roberto J , Cassarà Letizia P , Costantin Luca , Croom Scott M , Davies Luke J M , Fritz Alexander , Guiglion Guillaume , Humphrey Andrew , Pompei Emanuela , Ricci Claudio , Sifón Cristóbal , Tempel Elmo , Zafar Tayyaba
Published: June 2024

The size and complexity reached by the large sky spectroscopic surveys require efficient, accurate, and flexible automated tools for data analysis and science exploitation. We present the Galaxy Spectra Network/GaSNet-II, a supervised multinetwork deep learning tool for spectra classification and redshift prediction. GaSNet-II can be trained to identify a customized number of classes and optimize the redshift predictions. Redshift errors are determined via an ensemble/pseudo-Monte Carlo test obtained by randomizing the weights of the network-of-networks structure. As a demonstration of the capability of GaSNet-II, we use 260k Sloan Digital Sky Survey spectra from Data Release 16, separated into 13 classes including 140k galactic, and 120k extragalactic objects. GaSNet-II achieves 92.4 per cent average classification accuracy over the 13 classes and mean redshift errors of approximately 0.23 per cent for galaxies and 2.1 per cent for quasars. We further train/test the pipeline on a sample of 200k 4MOST (4-metre Multi-Object Spectroscopic Telescope) mock spectra and 21k publicly released DESI (Dark Energy Spectroscopic Instrument) spectra. On 4MOST mock data, we reach 93.4 per cent accuracy in 10-class classification and mean redshift error of 0.55 per cent for galaxies and 0.3 per cent for active galactic nuclei. On DESI data, we reach 96 per cent accuracy in (star/galaxy/quasar only) classification and mean redshift error of 2.8 per cent for galaxies and 4.8 per cent for quasars, despite the small sample size available. GaSNet-II can process ∼40k spectra in less than one minute, on a normal Desktop GPU. This makes the pipeline particularly suitable for real-time analyses and feedback loops for optimization of Stage-IV survey observations.
Revealing asymmetry on mid-plane of protoplanetary disc through modelling of axisymmetric emission: methodology
Authors: Aizawa Masataka , Muto Takayuki , Momose Munetake
Published: June 2024

This study proposes an analytical framework for deriving the surface brightness profile and geometry of a geometrically thin axisymmetric disc from interferometric observation of continuum emission. Such precise modelling facilitates the exploration of faint non-axisymmetric structures, such as spirals and circumplanetary discs. As a demonstration, we simulate interferometric observations of geometrically thin axisymmetric discs. The proposed method can reasonably recover the injected axisymmetric structures, whereas Gaussian fitting of the same data yielded larger errors in disc orientation estimation. To further test the applicability of the method, it was applied to the mock data for $m=1,2$ spirals and a point source, which are embedded in a bright axisymmetric structure. The injected non-axisymmetric structures were reasonably recovered except for the innermost parts, and the disc geometric parameter estimations were better than Gasussian fitting. The method was then applied to the real data of Elias 20 and AS 209, and it adequately subtracted the axisymmetric component, notably in Elias 20, where substantial residuals remained without our method. We also applied our method to continuum data of PDS 70 to demonstrate the effectiveness of the method. We successfully recovered emission from PDS 70 c consistently with previous studies, and also tentatively discovered new substructures. The current formulation can be applied to any data for disc continuum emission, and aids in the search of spirals and circumplanetary discs, whose detection is still limited.
What determines the boundaries of H2O maser emission in an X-ray illuminated gas disc?
Authors: Kuo C Y , Gao F , Braatz J A , Pesce D W , Humphreys E M L , Reid M J , Impellizzeri C M V , Henkel C , Wagner J , Wu C E
Published: June 2024

High precision mapping of H$_{2}$O megamaser emission from active galaxies has revealed more than a dozen Keplerian H$_{2}$O maser discs, which enable a $\sim$4 per cent uncertainty estimate of the Hubble constant as well as providing accurate masses for the central black holes. These discs often have well-defined inner and outer boundaries of maser emission on sub-parsec scales. In order to better understand the physical conditions that determine the inner and outer radii of a maser disc, we examine the distributions of gas density and X-ray heating rate in a warped molecular disc described by a power-law surface density profile. For a suitable choice of the disc mass, we find that the outer radius $R_{\rm out}$ of the maser disc predicted from our model can match the observed value, with $R_{\rm out}$ mainly determined by the maximum heating rate or the minimum density for efficient maser action, depending on the combination of the Eddington ratio, black hole mass, and disc mass. Our analysis also indicates that the inner radius for maser action is comparable to the dust sublimation radius, suggesting that dust may play a role in determining the inner radius of a maser disc. Finally, our model predicts that H$_{2}$O gigamaser discs could exist at the centres of high-z quasars, with disc sizes of $\gtrsim 10-30$ pc.
Metal factories in the early Universe
Authors: Eales Stephen , Gomez Haley , Dunne Loretta , Dye Simon , Smith Matthew W L
Published: June 2024

We have estimated the mass of metals in the molecular gas in 13 dusty star-forming galaxies at $z \sim 4$ in which the gas, based on previous observations, lies in a cold rotating disc. We estimated the metal masses using either the submillimetre line or continuum emission from three tracers of the overall metal content – carbon atoms, carbon monoxide molecules, and dust grains – using the first simultaneous calibration of all three tracers. We obtain very similar mass estimates from the different tracers, which are similar to the entire metal content of a present-day massive early-type galaxy. We used the dynamical masses of these galaxies to estimate an upper limit on the mass of the molecular gas in each galaxy, allowing us to estimate a lower limit on the metal abundance of the gas, finding values for many of the galaxies well above the solar value. We show that the high metal masses and metal abundances are what is expected shortly after the formation of a galaxy for a top-heavy IMF. We suggest a scenario for galaxy evolution in which massive galaxies reach a high metal abundance during their formation phase, which is then gradually reduced by dry mergers with lower mass galaxies. We show that the metals in the outflows from high-redshift dusty star-forming galaxies can quantitatively explain the long-standing puzzle that such a large fraction of the metals in galaxy clusters ($\simeq$0.75) is in the intracluster gas rather than in the galaxies themselves.
CANUCS: UV and ionizing properties of dwarf star-forming galaxies at z ~ 5–7
Authors: Harshan Anishya , Bradač Maruša , Abraham Roberto , Asada Yoshihisa , Brammer Gabriel , Desprez Guillaume , Iyer Karthiek , Martis Nicholas S , Matharu Jasleen , Mowla Lamiya , Muzzin Adam , Noirot Gaël , Rihtaršič Gregor , Sarrouh Ghassan T E , Sawicki Marcin , Strait Victoria , Willott Chris J
Published: June 2024

The epoch of reionization (EoR) progressed through the emission of ionizing photons from galaxies to their local intergalactic medium. In this work, we characterize the dwarf star-forming galaxies as candidates for the source of ionizing photons that drove EoR. We investigate the ionizing properties and star formation histories of star-forming dwarf galaxies at the last stages of EoR at $4.8\lt z \lt 7$ using observations from the CAnadian NIRISS Unbiased Cluster Survey (CANUCS). The magnification due to gravitational lensing allows us to probe large dynamic ranges in stellar mass ($2\times 10^{6}\le {M}_*/{\rm M}_\odot \le 5\times 10^{9}$) and ultraviolet (UV) magnitudes ($-22.68\le M_{\rm UV}\le =-15.95$). We find a median UV slope $\beta _{1500}\,$ of $-2. 56\pm 0.23$ and the production efficiency of ionizing photons $\log$$\xi _{\rm {ion}}\,$$=25.39\pm 0.6$ for the full sample ($4.8\lt z \lt 7$) with a median stellar mass of $6.3\pm 0.5\times 10^{7} \, {\rm M}_\odot$. We find both $\beta _{1500}\,$ and $\xi _{\rm {ion}}\,$ are marginally correlated with the stellar mass of the galaxy, indicating a possible greater contribution of dwarf galaxies to the reionization of the Universe. We find that on average, galaxies in our sample are experiencing a recent rise/burst of star formation which translates to a higher scatter in $\xi _{\rm {ion}}\,$ and a large scatter in H$\alpha$ equivalent widths (EWs). Finally, we investigate the trends of H$\alpha$ and [O iii] + H$\beta$ EWs with UV magnitude and find $M_{\rm UV}$ is correlated between H$\alpha$ but not with [O iii] + H$\beta$ EWs indicating low metallicities and recent burst in the UV faint galaxies.
PHACTboost: A Phylogeny-Aware Pathogenicity Predictor for Missense Mutations via Boosting
Authors: Dereli Onur , Kuru Nurdan , Akkoyun Emrah , Bircan Aylin , Tastan Oznur , Adebali Ogün
Published: June 2024

Most algorithms that are used to predict the effects of variants rely on evolutionary conservation. However, a majority of such techniques compute evolutionary conservation by solely using the alignment of multiple sequences while overlooking the evolutionary context of substitution events. We had introduced PHACT, a scoring-based pathogenicity predictor for missense mutations that can leverage phylogenetic trees, in our previous study. By building on this foundation, we now propose PHACTboost, a gradient boosting tree–based classifier that combines PHACT scores with information from multiple sequence alignments, phylogenetic trees, and ancestral reconstruction. By learning from data, PHACTboost outperforms PHACT. Furthermore, the results of comprehensive experiments on carefully constructed sets of variants demonstrated that PHACTboost can outperform 40 prevalent pathogenicity predictors reported in the dbNSFP, including conventional tools, metapredictors, and deep learning–based approaches as well as more recent tools such as AlphaMissense, EVE, and CPT-1. The superiority of PHACTboost over these methods was particularly evident in case of hard variants for which different pathogenicity predictors offered conflicting results. We provide predictions of 215 million amino acid alterations over 20,191 proteins. PHACTboost is available at https://github.com/CompGenomeLab/PHACTboost. PHACTboost can improve our understanding of genetic diseases and facilitate more accurate diagnoses.
Soma-germline communication drives sex maintenance in the Drosophila testis
Authors: Zhang Rui , Shi Peiyu , Xu Shuyang , Ming Zhe , Liu Zicong , He Yuanyuan , Dai Junbiao , Matunis Erika , Xu Jin , Ma Qing
Published: June 2024

In adult gonads, disruption of somatic sexual identity leads to defective gametogenesis and infertility. However, the underlying mechanisms by which somatic signals regulate germline cells to achieve proper gametogenesis remain unclear. In our previous study, we introduced the chinmoSex Transformation (chinmoST) mutant Drosophila testis phenotype as a valuable model for investigating the mechanisms underlying sex maintenance. In chinmoST testes, depletion of the Janus Kinase-Signal Transducer and Activator of Transcription downstream effector Chinmo from somatic cyst stem cells (CySCs) feminizes somatic cyst cells and arrests germline differentiation. Here, we use single-cell RNA sequencing to uncover chinmoST-specific cell populations and their transcriptomic changes during sex transformation. Comparative analysis of intercellular communication networks between wild-type and chinmoST testes revealed disruptions in several soma-germline signaling pathways in chinmoST testes. Notably, the insulin signaling pathway exhibited significant enhancement in germline stem cells (GSCs). Chinmo cleavage under targets and tagmentation (CUT&Tag) assay revealed that Chinmo directly regulates two male sex determination factors, doublesex (dsx) and fruitless (fru), as well as Ecdysone-inducible gene L2 (ImpL2), a negative regulator of the insulin signaling pathway. Further genetic manipulations confirmed that the impaired gametogenesis observed in chinmoST testes was partly contributed by dysregulation of the insulin signaling pathway. In summary, our study demonstrates that somatic sex maintenance promotes normal spermatogenesis through Chinmo-mediated conserved sex determination and the insulin signaling pathway. Our work offers new insights into the complex mechanisms of somatic stem cell sex maintenance and soma-germline communication at the single-cell level. Additionally, our discoveries highlight the potential significance of stem cell sex instability as a novel mechanism contributing to testicular tumorigenesis.
The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection
Authors: Lee Chan Mi , Choi Yunsang , Choi Seong Jin , Moon Song Mi , Kim Eu Suk , Kim Hong Bin , Ham Sin Young , Park Jeong Su , Yeom Jinki , Song Kyoung-Ho
Published: June 2024

Background

Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM.

Methods

Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5–30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model.

Results

Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA– isolates showed higher virulence than non-ST191, bfmS–, and bauA+ isolates, respectively.

Conclusions

ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.
Predictors of response to immunotherapy in colorectal cancer
Authors: González-Montero Jaime , Rojas Carlos I , Burotto Mauricio
Published: June 2024

Colorectal cancer (CRC) is a major cause of cancer-related deaths globally. While treatment advancements have improved survival rates, primarily through targeted therapies based on KRAS, NRAS, and BRAF mutations, personalized treatment strategies for CRC remain limited. Immunotherapy, mainly immune checkpoint blockade, has shown efficacy in various cancers but is effective in only a small subset of patients with CRC with deficient mismatch repair (dMMR) proteins or high microsatellite instability (MSI). Recent research has challenged the notion that CRC is immunologically inert, revealing subsets with high immunogenicity and diverse lymphocytic infiltration. Identifying precise biomarkers beyond dMMR and MSI is crucial to expanding immunotherapy benefits. Hence, exploration has extended to various biomarker sources, such as the tumor microenvironment, genomic markers, and gut microbiota. Recent studies have introduced a novel classification system, consensus molecular subtypes, that aids in identifying patients with CRC with an immunogenic profile. These findings underscore the necessity of moving beyond single biomarkers and toward a comprehensive understanding of the immunological landscape in CRC, facilitating the development of more effective, personalized therapies.
Charting the evolutionary path of the SUMO modification system in plants reveals molecular hardwiring of development to stress adaptation
Authors: Ghosh Srayan , Mellado Sanchez Macarena , Sue-Ob Kawinnat , Roy Dipan , Jones Andrew , Blazquez Miguel A , Sadanandom Ari
Published: June 2024

SUMO modification is part of the spectrum of Ubiquitin-like (UBL) systems that give rise to proteoform complexity through post-translational modifications (PTMs). Proteoforms are essential modifiers of cell signaling for plant adaptation to changing environments. Exploration of the evolutionary emergence of Ubiquitin-like (UBL) systems unveils their origin from prokaryotes, where it is linked to the mechanisms that enable sulfur uptake into biomolecules. We explore the emergence of the SUMO machinery across the plant lineage from single-cell to land plants. We reveal the evolutionary point at which plants acquired the ability to form SUMO chains through the emergence of SUMO E4 ligases, hinting at its role in facilitating multicellularity. Additionally, we explore the possible mechanism for the neofunctionalization of SUMO proteases through the fusion of conserved catalytic domains with divergent sequences. We highlight the pivotal role of SUMO proteases in plant development and adaptation, offering new insights into target specificity mechanisms of SUMO modification during plant evolution. Correlating the emergence of adaptive traits in the plant lineage with established experimental evidence for SUMO in developmental processes, we propose that SUMO modification has evolved to link developmental processes to adaptive functions in land plants.
The Arabidopsis ARID–HMG DNA-BINDING PROTEIN 15 modulates jasmonic acid signaling by regulating MYC2 during pollen development
Authors: Sachdev Sonal , Biswas Ruby , Roy Adrita , Nandi Ayantika , Roy Vishal , Basu Sabini , Chaudhuri Shubho
Published: June 2024

The intricate process of male gametophyte development in flowering plants is regulated by jasmonic acid (JA) signaling. JA signaling initiates with the activation of the basic helix–loop–helix transcription factor (TF), MYC2, leading to the expression of numerous JA-responsive genes during stamen development and pollen maturation. However, the regulation of JA signaling during different stages of male gametophyte development remains less understood. This study focuses on the characterization of the plant ARID–HMG DNA-BINDING PROTEIN 15 (AtHMGB15) and its role in pollen development in Arabidopsis (Arabidopsis thaliana). Phenotypic characterization of a T-DNA insertion line (athmgb15-4) revealed delayed bolting, shorter siliques, and reduced seed set in mutant plants compared to the wild type. Additionally, AtHMGB15 deletion resulted in defective pollen morphology, delayed pollen germination, aberrant pollen tube growth, and a higher percentage of nonviable pollen grains. Molecular analysis indicated the downregulation of JA biosynthesis and signaling genes in the athmgb15-4 mutant. Quantitative analysis demonstrated that JA and its derivatives were ∼10-fold lower in athmgb15-4 flowers. Exogenous application of methyl jasmonate could restore pollen morphology and germination, suggesting that the low JA content in athmgb15-4 impaired JA signaling during pollen development. Furthermore, our study revealed that AtHMGB15 physically interacts with MYC2 to form a transcription activation complex. This complex promotes the transcription of key JA signaling genes, the R2R3-MYB TFs MYB21 and MYB24, during stamen and pollen development. Collectively, our findings highlight the role of AtHMGB15 as a positive regulator of the JA pathway, controlling the spatiotemporal expression of key regulators involved in Arabidopsis stamen and pollen development.
Reverse social contagion as a mechanism for regulating mass behaviors in highly integrated social systems
Authors: Porfiri Maurizio , De Lellis Pietro , Aung Eighdi , Meneses Santiago , Abaid Nicole , Waters Jane S , Garnier Simon
Published: June 2024

Mass behavior is the rapid adoption of similar conduct by all group members, with potentially catastrophic outcomes such as mass panic. Yet, these negative consequences are rare in integrated social systems such as social insect colonies, thanks to mechanisms of social regulation. Here, we test the hypothesis that behavioral deactivation between active individuals is a powerful social regulator that reduces energetic spending in groups. Borrowing from scaling theories for human settlements and using behavioral data on harvester ants, we derive ties between the hypermetric scaling of the interaction network and the hypometric scaling of activity levels, both relative to the colony size. We use elements of economics theory and metabolic measurements collected with the behavioral data to link activity and metabolic scalings with group size. Our results support the idea that metabolic scaling across social systems is the product of different balances between their social regulation mechanisms.
Prevalence of tight glycemic control based on frailty status and associated factors in community-dwelling older adults
Authors: Tan Li Feng , Merchant Reshma Aziz
Published: June 2024

Background

Tight control of type 2 diabetes (T2DM) in frail older adults has shown to be associated with adverse outcomes. The objective of this study is to determine the prevalence of tight glycemic control based on underlying frailty status and its association with functional and cognitive measures in community-dwelling older adults.

Methodology

Ancillary study of the Singapore Population Health Studies on older adults aged ≥65 years with T2DM. Tight glycemic control cut-offs were based on the 2019 Endocrine Society guideline using HbA1c target range based on a patient’s overall health status measured by the FRAIL scale. Data on basic demographics, frailty, cognitive, and functional statuses were collected. Multivariable regression was used to assess potential factors associated with tight glycemic control.

Results

Of 172 community-dwelling older adults with diabetes mellitus and HbA1c done, frail (65%) and pre-frail (64.4%) participants were more likely to have tight glycemic control than robust participants (31.6%, P < 0.001). In multi-variate analysis, frailty (OR 6.43, 95% CI 1.08–38.1, P = 0.041), better cognition (OR 1.15, 95% CI 1.02–1.32, P = 0.028), and multi-morbidity (OR 7.36, 95% CI 1.07–50.4, P = 0.042) were found to be significantly associated with increased odds of tight glycemic control.

Conclusion

Tight glycemic control was highly prevalent in frail and pre-frail older adults, especially in those with multi-morbidity and better cognition. Future prospective longitudinal studies are required to evaluate effectiveness of frailty screening in making treatment decisions and long-term outcomes.

Key messages What is already known on this topic:  There is growing recognition that glycemic targets should be adjusted based on health or frailty status. However, there is no consensus on how health status or frailty should be defined when determining glycemic control targets. What this study adds:  Our study found that tight glycemic control was highly prevalent in frail and pre-frail older adults. Our findings highlight the importance of assessing for tight glycemic control based on frailty status and further work is needed to aid implementation of screening and intervention policies to avoid the attendant harms of tight glycemic control.
Design and performance of double-layered artificial chordae
Authors: Zhang Tingchao , Dou Yichen , Li Yang , Luo Rifang , Yang Li , Zhang Weiwei , Wang Yunbing , Zhang Xingdong
Published: June 2024

Surgical repair with artificial chordae replacement has emerged as a standard treatment for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) sutures are commonly employed as artificial chordae; however, they have certain limitations, such as potential long-term rupture and undesired material/tissue response. This study introduces a novel approach to artificial chordae design, termed the New Artificial Chordae (NAC), which incorporates a double-layered structure. The NAC comprises a multi-strand braided core composed of ultra-high molecular weight polyethylene (UHMWPE) fibers as the inner core, and an outer tube made of hydrophobic porous ePTFE. Compared to traditional ePTFE sutures, NAC exhibits increased flexibility, enhanced tensile strength, longer elongation and improved fatigue resistance. Moreover, NAC exhibits a more hydrophobic surface, which contributes to enhanced hemocompatibility. The study also includes in vivo investigations conducted on animal models to evaluate the biocompatibility and functional efficacy of the artificial chordae. These experiments demonstrate the enhanced durability and biocompatibility of the NAC, characterized by improved mechanical strength, minimal tissue response and reduced thrombus formation. These findings suggest the potential application of NAC as a prosthetic chordae replacement, offering promising prospects to address the limitations associated with current artificial chordae materials and providing novel ideas and approaches for the development of sustainable and biocompatible regenerative biomaterials.
Phylo2Vec: A Vector Representation for Binary Trees
Authors: Penn Matthew J , Scheidwasser Neil , Khurana Mark P , Duchêne David A , Donnelly Christl A , Bhatt Samir
Published: June 2024

Binary phylogenetic trees inferred from biological data are central to understanding the shared history among evolutionary units. However, inferring the placement of latent nodes in a tree is computationally expensive. State-of-the-art methods rely on carefully designed heuristics for tree search, using different data structures for easy manipulation (e.g., classes in object-oriented programming languages) and readable representation of trees (e.g., Newick-format strings). Here, we present Phylo2Vec, a parsimonious encoding for phylogenetic trees that serves as a unified approach for both manipulating and representing phylogenetic trees. Phylo2Vec maps any binary tree with n leaves to a unique integer vector of length n-1. The advantages of Phylo2Vec are 4-fold: (i) fast tree sampling, (ii) compressed tree representation compared to a Newick string, (iii) quick and unambiguous verification if 2 binary trees are identical topologically, and (iv) systematic ability to traverse tree space in very large or small jumps. As a proof of concept, we use Phylo2Vec for ML inference on 5 real-world datasets and show that a simple hill-climbing-based optimization scheme can efficiently traverse the vastness of tree space from a random to an optimal tree.
LeverAge: A European network to leverage the multi-age workforce
Authors: Marcus Justin , Scheibe Susanne , Kooij Dorien , Truxillo Donald M , Zaniboni Sara , Abuladze Liili , Al Mursi Noura , Bamberger Peter A , Balytska Mariia , Betanzos Norma D , Perek-Białas Jolanta , Boehm Stephan Alexander , Burmeister Anne , Cabib Ignacio , Caon Maurizio , Deller Jürgen , Derous Eva , Drury Lisbeth , Eppler-Hattab Raphael , Fasbender Ulrike , Fülöp Marta , Furunes Trude , Gerpott Fabiola H , Goštautaitė Bernadeta , Halvorsen Cal J , Hernaus Tomislav , Inceoglu Ilke , Iskifoglu Mustafa , Ivanoska Kalina Sotiroska , Kanfer Ruth , Kenig Nikolina , Kiran Sibel , Klimek Sabina , Kunze Florian , Mertan Emete Biran , Varianou-Mikellidou Cleo , Moasa Horia , Ng Yin Lu , Parker Sharon K , Reh Susan , Resuli Vebina , Schmeink Martina , Silberg Slavka , Sousa Inês C , Steiner Dirk D , Stukalina Yulia , Tomas Jasmina , Topa Gabriela , Turek Konrad , Vignoli Michela , von Bonsdorff Monika , Wang Dahua , Wang Mo , Yeung Dannii Yuen-lan , Yildirim Kemal , Zhang Xin , Žnidaršič Jana
Published: June 2024

Bringing together 150+ scholars and practitioners from 50+ countries, and funded by the European Commission, COST Action LeverAge (https://www.cost.eu/actions/CA22120/) is the first network-building project of its kind in the work and organizational psychology and human resource management (WOP/HRM) aspects of work and aging. Focused on the aging workforce, the Action aims to foster interdisciplinary and multinational scientific excellence and the translation of science to practical and societal impact across 4 years. Based on a research synthesis, we identify five broad research directions for work and aging science including work and organizational practices for a multi-age workforce, successful aging at work, the integration of age-diverse workers and knowledge transfer, aging and technology at work, and career development in later life and retirement. We provide key research questions to guide scientific inquiry along these five research directions alongside best practice recommendations to expand scholarly impact in WOP/HRM.
Do Resident Unions Improve Graduate Medical Education Training? Benefits and Potential Pitfalls
Authors: Julian Katherine A. , Baron Robert B.
Published: June 2024

The last 10 years have seen an increase in union representation for residents and fellows across the United States. It is estimated that 15% of residents and fellows are represented by unions. With increasing numbers of U.S. residents and fellows in graduate medical education (GME) programs being represented by unions, the authors contend that it is worthwhile to consider the benefits and potential drawbacks of resident unions and how GME and health system leaders can best work to ensure that the educational needs of residents continue to be emphasized in an era of resident unionization. Union bargaining can be a method to secure salary increases and other benefits for residents. Unionization can also provide a mechanism for more rapidly addressing worker protection issues and allows residents to advocate on behalf of patients. Residents participating as union leaders may develop important leadership and negotiation skills as well as gain beneficial knowledge about health system structure, financing, and priorities. However, with all the possible benefits that may come with resident unionization, there are also potential pitfalls. The collective bargaining process may create an adversarial relationship between program and institution leaders and trainees. Additionally, while residents are considered employees and able to collectively bargain, the National Labor Relations Board has also acknowledged that residents are “students learning their chosen medical craft.” Program and institution leaders have an obligation to prioritize resident education and adhere to accreditation requirements even when these requirements conflict with union demands. Furthermore, because of the obligation to protect the public, program leaders should maintain control of resident academic due process issues. Program and institutional leaders must continue to prioritize resident education. Furthermore, GME leaders have a joint responsibility to create clinical learning environments that are conducive to quality patient care and promote resident learning and well-being.
First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma
Authors: Luan Tao , Lin Xinqing , Xie Xiaohong , Yang Gang , Wang Shuaiying , Hao Jianqing , Zhou Chengzhi
Published: June 2024

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced nonsmall cell lung cancer (NSCLC). In the 2023 National Comprehensive Cancer Network guidelines for NSCLC, antibody-drug conjugate trastuzumab emtansine is recommended for the treatment of HER2-mutant lung cancer. However, this medication is currently not approved in certain regions.So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients. In our study of a patient with HER2 exon 20 insertion lung adenocarcinoma who had previously failed multiple epidermal growth factor receptor (EGFR)-TKI treatments, we discovered that sunvozertinib could stabilize the patient’s condition, achieving a progression-free survival of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20 insertion patients who have failed TKI therapy.
Characteristics of Patients Hospitalized in Rural and Urban ICUs From 2010 to 2019
Authors: Harlan Emily A. , Ghous Muhammad , Moscovice Ira S. , Valley Thomas S.
Published: June 2024

OBJECTIVES:

Rural hospitals are threatened by workforce shortages and financial strain. To optimize regional critical care delivery, it is essential to understand what types of patients receive intensive care in rural and urban hospitals.

DESIGN:

A retrospective cohort study.

SETTING AND PATIENTS:

All fee-for-service Medicare beneficiaries in the United States who were 65 years old or older hospitalized in an ICU between 2010 and 2019 were included. Rural and urban hospitals were classified according to the 2013 National Center For Health Statistics Urban-Rural Classification Scheme for Counties. Patient comorbidities, primary diagnoses, organ dysfunction, and procedures were measured using the International Classification of Diseases, 9th and 10th revisions diagnosis and procedure codes. Standardized differences were used to compare rural and urban patient admission characteristics.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

There were 12,224,097 ICU admissions between 2010 and 2019, and 1,488,347 admissions (12.2%) were to rural hospitals. The most common diagnoses in rural hospitals were cardiac (30.3%), infectious (24.6%), and respiratory (10.9%). Patients in rural ICUs had similar organ dysfunction compared with urban hospitals (mean organ failures in rural ICUs 0.5, sd 0.8; mean organ failures in urban ICUs 0.6, sd 0.9, absolute standardized mean difference 0.096). Organ dysfunction among rural ICU admissions increased over time (0.4 mean organ failures in 2010 to 0.7 in 2019, p < 0.001).

CONCLUSIONS:

Rural hospitals care for an increasingly complex critically ill patient population with similar organ dysfunction as urban hospitals. There is a pressing need to develop policies at federal and regional healthcare system levels to support the continued provision of high-quality ICU care within rural hospitals.
Paired Treatment Using Radiofrequency Microneedling and 755-nm Picosecond Laser With Fractionated Lens Array for Facial Rejuvenation
Authors: Tao Joy , Hashemi David A. , Bajaj Shirin , Wang Jordan V. , Geronemus Roy G.
Published: June 2024

BACKGROUND

Patients frequently complain about fine lines, wrinkles, dyschromia, and photoaging, for which lasers and energy-based devices can treat each of these. Pairing various devices in a single treatment session can be safe and effective, but different technologies, mechanisms, histologies, parameters, and techniques must be considered.

OBJECTIVE

To examine the utility of a paired treatment regimen using radiofrequency microneedling and 755-nm picosecond laser with fractionated lens array to improve the clinical appearance of facial wrinkles and photoaging.

MATERIALS AND METHODS

A prospective clinical study investigated this paired treatment regimen using 4 monthly sessions.

RESULTS

Twenty-five subjects were enrolled, while 18 subjects completed 3-month follow-up. The mean age was 54 years, and 92% were women. Fitzpatrick Skin Types I to IV were represented. Assessments compared baseline with the 3-month follow-up. Two of 3 blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 94.4% of cases. For physician Global Aesthetic Improvement Scale, 100% of subjects had clinical improvement. Overall, 88.9% of subjects were considered to be satisfied with their treatment. No serious or unanticipated adverse events occurred.

CONCLUSION

Paired treatment using radiofrequency microneedling and 755-nm picosecond laser with fractionated lens array can safely and effectively improve facial wrinkles and photoaging.
Contact Lens–Assisted DMEK for Corneal Decompensation With an Anterior Chamber Intraocular Lens: A Novel Technique
Authors: Tan Reginald Robert G.
Published: June 2024

Purpose:

To describe a novel technique in which a contact lens was used to facilitate Descemet membrane endothelial keratoplasty (DMEK) in an eye with an anterior chamber intraocular lens (ACIOL).

Methods:

A 71-year-old man with a long-standing ACIOL developed bullous keratopathy. As the patient was at high risk of complications due to multiple ocular comorbidities, DMEK was performed with the ACIOL left in the anterior chamber. An inserted cosmetic contact lens was used as a platform for the graft unfolding.

Results:

Partial graft detachment on the third postoperative day required rebubbling. This successfully cleared up the cornea after a few weeks. At the one-month follow-up, the uncorrected distance visual acuity improved to 20/50, with an endothelial cell loss of 35.2%. Steroid-induced ocular hypertension necessitated a trabeculectomy by the fifth postoperative month. At the sixth follow-up month, endothelial cell loss was 64%.

Conclusions:

Contact lens–assisted DMEK is a safe procedure for eyes with an ACIOL. However, good foresight is needed regarding whether the ACIOL should be kept or exchanged.
Flavonoids as dual-action agents for anticancer and anti-tooth caries: a molecular docking and dynamics simulation on MMP2 inhibition
Authors: Yarmohammadi Ebrahim , Naimiyan Atiyeh , Taherkhani Amir
Published: June 2024

Objective:

Cancer pathogenesis is linked to matrix metalloproteinase-2 (MMP2). Numerous studies have indicated an elevated expression of MMP2 in the tissue microenvironment of different cancers, including breast, oral, prostate, ovarian, colorectal, bladder, lung, and hepatocellular carcinoma. The significant role of MMP2 in the degradation of organic compounds in dentin, causing dental caries, has been indicated by accumulating evidence. This study explored the possibility of using flavonoids as natural compounds capable of inhibiting MMP2 to meet the need for new and potent MMP2 inhibitors.

Methods:

The AutoDock software evaluated the binding energies between selected flavonoids and the MMP2 catalytic domain and ranked the ligands based on their inhibition constant (Ki) values and Gibbs free binding energy scores. The Discovery Studio Visualizer tool demonstrated how the highest-ranked flavonoids interact with the MMP2. Molecular dynamics was conducted for the most potent MMP2 inhibitor in a 100 ns computer simulation.

Results:

Kaempferol 3-rutinoside-7-sophoroside demonstrated an inhibitory effect against MMP2 with a Ki value and ΔGbinding score of 209.92 fM and −17.30 kcal/mol, respectively. This flavonoid was able to restrict MMP2 activity within a femtomolar range. This study identified eight flavonoids with Ki values in the picomolar range. According to the study, the docked pose of kaempferol 3-rutinoside-7-sophoroside within the MMP2 catalytic domain reached stability after a simulation of ~60 nanoseconds.

Conclusion:

Inhibition of MMP2 by flavonoids, notably kaempferol derivatives, might be an effective therapeutic strategy for cancer treatment.
Extraosseous osteosarcoma of the larynx: an unusual tumor managed with radical surgery – case report
Authors: Martín Pérez Jesús A. , Gurrola Machuca Hector , Domínguez Páez Casandra , Cortázar Sánchez Carlos A. , Nagore Ancona Jesús F. , Ramírez Gómez Julio I. , Navarrete Tolentino Juan C. , Hernández Hernández Regina C. , Burgos Morales Itzel
Published: June 2024

Introduction and importance:

Extraosseous osteosarcoma (EOO) is a malignant tumor that arises in soft tissue without affecting bone or periosteum but produces osteoid, osseous, or chondroid material. It is a very rare malignancy that accounts for approximately less than 1% of all tissue sarcomas and ~2–4% of all osteosarcomas. EOO in the head and neck region is extremely rare; however, in the larynx, it is exceptional, with only one case reported worldwide in the literature to date.

Case presentation:

A 72-year-old male with no personal history of interest in the current condition presented with dysphonia, hoarseness, and dyspnea for 6 months. A flexible nasofibrolaryngoscopy (FNFL) and computed tomography (CT) scan exhibited a glottic tumor with a lumen obstruction of 90%. An endoscopic resection was performed, reporting an EOO, osteoblastic, and ulcerated type. During follow-up, tumoral persistence was detected, leading to the decision to perform a definitive radical treatment with a total laryngectomy.

Clinical discussion:

Its presentation in the head and neck region is exceptional, with only a few isolated cases reported in the literature. Available data on treatment recommendations have emphasized the importance of timely surgical intervention with adjuvant radiation therapy if necessary for the head and neck.

Conclusion:

Extraosseous osteoblastoma of the larynx is an extremely rare and infrequent disease. Correct diagnosis and oncological surgical management of this disease are essential for optimal and even curative treatment of the patient.
Reduced Cochlear MRI Signal and Hearing Outcomes in Conservatively Managed Vestibular Schwannoma Patients
Authors: Jones Arthur , Saputra Lydia , Matthews Timothy
Published: June 2024

Objective

This study aimed to determine if hypointense cochlear magnetic resonance imaging (MRI) constructive interference in steady-state (CISS) signal correlates with hearing outcomes in conservatively managed vestibular schwannoma (VS) patients.

Study Design

Retrospective review of 657 cases from 1992 to 2020.

Setting

Tertiary academic referral center.

Patients

A retrospective review was performed to identify conservatively managed VS patients with appropriate baseline MRI, audiology, and at least 12-month audiological follow-up. Patients were excluded if they progressed to surgery or radiotherapy in less than 12 months, bilateral tumors, or surgery on the contralateral ear.

Intervention

Conservatively managed patients with CISS imaging studies and audiology testing.

Main Outcome Measure(s)

Primary outcome measure change in pure-tone average (PTA) and word recognition score (WRS). Secondary outcome measures tumor size, presence of lateral fluid cap, or cystic changes.

Results

A total of 92 individuals (47% male, 58 ± 11.6 yr) met the inclusion criteria, with 36 (39%) of patients demonstrating abnormal cochlear CISS signal. At baseline, abnormal cochlear CISS signal was associated with higher intracanalicular (IC) length (7.9 versus 6.6 mm,p= 0.0177) and lower WRS (55.7 versus 78.8 dBHL,p= 0.0054). During follow-up, individuals with abnormal cochlear CISS signal had significantly higher PTA (62.4 versus 46.4 dBHL,p= 0.0010). After adjusting for baseline covariates, abnormal cochlear CISS signal was consistently associated with a greater increase in PTA of 8.3 dBHL (95% confidence interval, 2.9–13.7;p= 0.0032) from baseline when compared with the normal group.

Conclusions

Abnormal cochlear signal on MRI CISS sequences is associated with poorer hearing outcomes in conservatively managed VS patients.
Clinical Applications for Spread of Excitation Functions Obtained Via Electrically Evoked Compound Action Potentials (eCAP)
Authors: Berg Katelyn A. , DeFreese Andrea J. , Sisler-Dinwiddie Allyson L. , Labadie Robert F. , Tawfik Kareem O. , Gifford René H.
Published: June 2024

Objectives

To assess the clinical utility of spread of excitation (SOE) functions obtained via electrically evoked compound action potentials (eCAP) to 1) identify electrode array tip fold-over, 2) predict electrode placement factors confirmed via postoperative computed tomography (CT) imaging, and 3) predict postoperative speech recognition through the first year post-activation in a large clinical sample.

Study Design

Retrospective case review

Setting

Cochlear implant (CI) program at a tertiary medical center

Patients

Two hundred seventy-two ears (238 patients) with Cochlear Ltd. CIs (mean age = 46 yr, range = 9 mo–93 yr, 50% female) implanted between August 2014 and December 2022 were included.

Main Outcome Measures

eCAP SOE widths (mm) (probe electrodes 5, 11, and 17), incidence of electrode tip fold-over, CT imaging data (electrode-to-modiolus distance, angular insertion depth, scalar location), and speech recognition outcomes (consonant–nucleus–consonant [CNC], AzBio quiet, and +5 dB SNR) through the first year after CI activation.

Results

1) eCAP SOE demonstrated a sensitivity of 85.7% for identifying tip fold-over instances that were confirmed by CT imaging. In the current dataset, the tip fold-over incidence rate was 3.1% (7 patients), with all instances involving a precurved electrode array. 2) There was a significant positive relationship between eCAP SOE and mean electrode-to-modiolus distance for precurved arrays, and a significant positive relationship between eCAP SOE and angular insertion depth for straight arrays. No relationships between eCAP SOE and scalar location or cochlea diameter were found in this sample. 3) There were no significant relationships between eCAP SOE and speech recognition outcomes for any measure or time point, except for a weak negative correlation between average eCAP SOE widths and CNC word scores at 6 months post-activation for precurved arrays.

Conclusions

In the absence of intraoperative CT or fluoroscopic imaging, eCAP SOE is a reasonable alternative method for identifying electrode array tip fold-over and should be routinely measured intraoperatively, especially for precurved electrode arrays with a sheath.