bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma
Authors: Paajanen Juuso , Richards William G. , Xie Yue , Mazzola Emanuele , Sidopoulos Kristina , Kuckelman John , Gill Ritu R. , Bueno Raphael 
Published: January 2025

Objective:
We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS).

Summary Background Data:
Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery.

Methods:
All patients who underwent PD between 1998 and 2022 were identified. Patients with diffuse PM who achieved macroscopic complete resection and had sufficient information on tumor relapse were included. Postoperative scans were reviewed to determine the timing and sites of the first recurrence.

Results:
A total of 436 patients had tumor recurrence during follow-up. Local recurrences occurred most frequently (N=370, 85%) and represented the only recurrence site in 29% (N=129) of cases. Patients with sarcomatoid tumors relapsed earlier than other subtypes (P=0.003) with more frequent distant spread compared to other subtypes (P<0.001). Multivariable analysis revealed that age (P=0.015), preoperative tumor volume (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), and TNM stage IV (P=0.003) were associated with DFI. Similarly, age (P=0.042), performance status (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), TNM stages III and IV (P=0.003 and 0.010 respectively), type of surgery (P=0.019), and number of recurrent lesions (P=0.024) were associated with PRS. Recurrence surgery (HR 0.46, 95% CI 0.29–0.74) and chemotherapy (HR 0.69, 95% CI 0.54–0.92) were independently associated with PRS in patients with distant with or without local recurrences.

Conclusions:
PM is frequently associated with local recurrence. Repeat surgical resection is feasible and can achieve good local control in selected cases.
Perspectives, Experiences, and Opportunities of Academic Surgeons in the Era of Healthcare Corporatization
Authors: Sakowitz Sara , Bakhtiyar Syed Shahyan , Sienna Nicholas S. , Mallick Saad , Ali Konmal , Benharash Peyman , Jolly Richard , Donahue Timothy R. 
Published: January 2025

Objective:
To characterize contemporary surgeons’ viewpoints and perspectives on the academic mission during healthcare corporatization.

Summary Background Data:
Academic surgery, traditionally driven by the tripartite missions of excellence in clinical care, scientific research, and education, faces increasing challenges from a corporatized healthcare environment. While previous studies have addressed the financial aspects of corporatization, a comprehensive evaluation of academic surgeons’ attitudes and experiences remains lacking.

Methods:
An online survey was distributed to a national sample of academic surgical department chairs and program directors assessing their views, perspectives, and experiences with healthcare corporatization. We also analyzed trends in National Institutes of Health (NIH) funding and abstract submissions to the Academic Surgical Congress.

Results:
Of 105 respondents, 72.9% believe corporatization negatively impacts academic surgery. Among program directors, 79.1% feel corporatization prioritizes clinical productivity over research and teaching. Similarly, 82.8% of department chairs report their faculty often must prioritize clinical duties over other academic responsibilities.
Qualitative analysis reveals that surgeons perceive corporatization as a significant barrier to achieving their goals. Many feel that profit has become “king,” reducing their roles to “cogs in a wheel.”
While overall NIH funding increased, the proportion awarded to surgical departments remained largely unchanged from 2006 to 2023 (2.7% vs. 2.8%, P=0.94). Additionally, the proportion of basic science abstracts submitted to the Academic Surgical Congress declined by 37.9%.

Conclusions:
Corporatization has had a profound impact on surgeons’ perceptions of their roles, responsibilities, and autonomy. Surgical departments must take intentional steps to preserve the multidimensional mission of the academic surgeon.
Description of Veillonella absiana sp. nov., isolated from pig faeces
Authors: Bai Lu , Paek Jayoung , Shin Yeseul , Kim Hongik , Kim Si Hyun , Shin Jeong Hwan , Kook Joong-Ki , Chang Young-Hyo 
Published: January 2025

Two Gram-stain-negative cocci anaerobes were isolated from pig faeces and designated as strains YH-vei2232T and YH-vei2233. Phylogenetic analysis using 16S rRNA gene sequences revealed that the isolates were most closely related to Veillonella rogosae KCTC 5967T, with 97.0% similarity. Analysis of housekeeping gene sequences (rpoB) revealed the strain formed a sub-cluster within the genus Veillonella. The average nucleotide identities between the two isolates and the most closely related strains within genus Veillonella were <75.0%. The major fatty acids were Summed Feature 8 and C16 : 1
ω9c. The cell wall peptidoglycan contained meso-diaminopimelic acid. The major metabolic end products of isolates were propionic and acetic acids. The genomic DNA G+C contents of both strains were 40.1 mol%. The chemotaxonomic, phenotypic and phylogenetic properties of YH-vei2232T (=KCTC 25748T=NBRC 116427T) and YH-vei2233 (=KCTC 25749=NBRC 116428) suggest that they represent a novel species of the genus Veillonella, for which the name Veillonella absiana sp. nov. is proposed.
Super-compensator alleles rescue diverse deleterious substitutions and buffer the effects of mutations
Authors: Jiang Wenhong , Yin Hengchuang , Khan Saad S. , Yiparemu  
Published: January 2025

AbstractUnderstanding loss-of-function mutations and their potential compensatory mechanisms is crucial for elucidating the complexities of gene expression. Here, we investigate whether additional mutations can rescue non-functional alleles and their evolutionary significance. To achieve this, we conducted an extensive analysis of 372,867 amino acid sequence variants of the imidazole glycerol-phosphate dehydratase (IGPD, PDB: 6ezm) protein, which is over 1000 times greater than previously examined. We discovered that one or more additional substitutions located in loop and interface regions could easily restore function for each of the 10,019 of 31,701 (31.6%) non-functional missense allele. We further identified a small set of super-compensatory substitutions that can increase the function of many diverse alleles and flatten the fitness landscape, that is, buffer the fitness effects of both beneficial and deleterious substitutions. We also found that the protein structures of rescuable variants are more stable than those of non-rescuable variants. This suggests that restoring the stability of protein structures is a key part of compensation. These findings offer new insights into the understanding of protein function loss and its adaptive compensatory evolution.
Building an atlas of mechanobiology: high-throughput contractility screen of 2418 kinase inhibitors in five primary human cell types reveals selective divergent responses among related cell types
Authors: Shpak Anton , Wan Jeremy , Huang Ricky , Cortes Enrico , Wang Yao , Damoiseaux Robert , Pushkarsky Ivan 
Published: January 2025

AbstractCellular mechanical forces play crucial roles in both normal physiology and disease, yet drug discovery efforts targeting mechanobiology have been limited in part by assumptions about the conservation of contractile pathways across cell types. Here, we present the first high-throughput contractility screen of an annotated kinase inhibitor library, evaluating 2,418 compounds across five primary human cell types using the FLECS (Fluorescent Elastomer Contractility Sensors) platform. Quantification of contractile responses revealed selective divergent responses among related cell types. Clustering analysis identified distinct mechanobiological profiles and novel pathway associations that challenge the assumption that contractile pathways are too highly conserved for selective targeting. This systematic approach supports wider adoption of mechanical phenotypic screening as a viable strategy for discovering cell-type specific contractile pathway modulators for a broad range of mechanically-driven disease indications.
Whole-genome duplication increases genetic diversity and load in outcrossingArabidopsis
Authors: Vlček Jakub , Hämälä Tuomas , Cobo Cristina Vives , Curran Emma , Šrámková Gabriela , Slotte Tanja , Schmickl Roswitha , Yant Levi , Kolář Filip 
Published: January 2025

AbstractGenetic variation underpins evolutionary change, but accumulation of slightly deleterious mutations also increases mutation load. There are multiple factors affecting the extent of load such as population size and breeding system, yet other potential determinants remain unexplored. A common macromutation, whole-genome duplication (WGD) occurs broadly across Eukaryotes, yet we lack a clear understanding of how WGD impacts neutral and selective processes within a population. Using forward simulations and empirical analysis of 632 short- and 16 long-read sequenced individuals ofArabidopsis arenosa(23 diploid and 42 natural autotetraploid populations), we test for the effects of WGD on genome-wide diversity and mutation load. Our simulations show how genetic variation gradually rises in autotetraploids due to increase of mutational target size. Moreover, mutation load increases due to relaxed purifying selection when deleterious mutations are masked by additional chromosome copies. Empirical data confirm these patterns, showing significant increase in nucleotide diversity, ratios of non-synonymous to synonymous SNPs, and number of indels and large structural variants inA. arenosaautotetraploids. However, a rather modest increase in load proxies together with a broad distribution and niche of autotetraploids suggests load accumulation has not (yet) limited their successful expansion. Overall, we demonstrate a complex interplay between neutral processes and purifying selection in shaping genetic variation following WGD and highlight ploidy as an important determinant of genetic diversity and mutation load in natural populations.
SFCalculator: connecting deep generative models and crystallography
Authors: Li Minhuan , Dalton Kevin , Hekstra Doeke 
Published: January 2025

AbstractProteins drive biochemical transformations by transitioning through distinct conformational states. Understanding these states is essential for modulating protein function. Although X-ray crystallography has enabled revolutionary advances in protein structure prediction by machine learning, this connection was made at the level of atomic models, not the underlying data. This lack of connection to crystallographic data limits the potential for further advances in both the accuracy of protein structure prediction and the application of machine learning to experimental structure determination. Here, we present SFCalculator, a differentiable pipeline that generates crystallographic observables from atomistic molecular structures with bulk solvent correction, bridging crystallographic data and neural network-based molecular modeling. We validate SFCalculator against conventional methods and demonstrate its utility by establishing three important proof-of-concept applications. First, SFCalculator enables accurate placement of molecular models relative to crystal lattices (known as phasing). Second, SFCalculator enables the search of the latent space of generative models for conformations that fit crystallographic data and are, therefore, also implicitly constrained by the information encoded by the model. Finally, SFCalculator enables the use of crystallographic data during training of generative models, enabling these models to generate an ensemble of conformations consistent with crystallographic data. SFCalculator, therefore, enables a new generation of analytical paradigms integrating crystallographic data and machine learning.
Metabolic implications for dual substrate growth in “CandidatusAccumulibacter”
Authors: Páez-Watson Timothy , Jansens Casper , van Loosdrecht Mark C.M. , Roy Samarpita 
Published: January 2025

ABSTRACTThis study explores the metabolic implications of dual substrate uptake in“Candidatus Accumulibacter”, focusing on the co-consumption of volatile fatty acids and amino acids under conditions typical of enhanced biological phosphorus removal (EBPR) systems. Combining batch tests from highly enriched “Ca.Accumulibacter” cultures with conditional flux balance analysis (cFBA) predictions, we demonstrated that co-consumption of acetate and aspartate leads to synergistic metabolic interactions, lowering ATP loss compared to individual substrate consumption. The metabolic synergy arises from the complementary roles of acetate and aspartate uptake: acetate uptake provides acetyl-CoA to support aspartate metabolism, while aspartate conversion generates NADH, reducing the need for glycogen degradation during acetate uptake. We termed this type of metabolic interaction as reciprocal synergy. We further expanded our predictions to uncover three types of interactions between catabolic pathways when substrates are co-consumed by “Ca.Accumulibacter”: (i) neutral, (ii) one-way synergistic and (iii) reciprocal synergistic interactions. Our results highlight the importance of network topology in determining metabolic interactions and optimizing resource use. These findings provide new insights into the metabolism “Ca.Accumulibacter” and suggest strategies for improving EBPR performance in wastewater treatment plants, where the influent typically contains a mixture of organic carbon compounds.SynopsisThis research demonstrates how dual substrate uptake by “Ca.Accumulibacter” enhances metabolic efficiency in EBPR by reducing global ATP losses through optimization of storage polymer usage.
Transmission Dynamics of Eastern Equine Encephalitis Infection Rates: The Role of Avian Host Stage and Differential Mosquito Exposure
Authors: Ounsinegad Aurod , Mitchell Christopher , Komar Nicholas 
Published: January 2025

ABSTRACTThe Eastern equine encephalitis virus (EEEV) is a neurological mosquito-borne disease that spans the northeastern coast of the United States and Canada. Prior studies have focused on how mosquitoes prefer to take blood meals from hatch-year avian hosts rather than adult avian hosts to determine the rate at which the virus is spread between the Black-Tailed Mosquito (Culiseta melanura) and select avian species. In these studies, it was found that mosquito blood meal preference correlated well with avian brooding seasons for certain avian species such as the European Starling (Sturnus vulgaris) and the American Robin (Turdus migratorius). In this study, a host stage-structured model is developed where the avian host group is split into two categories: adult avians and hatch-year avians. The system of ordinary differential equations (ODEs) used to create this model are analyzed to better understand the transmission dynamics of EEEV between the two host classes. The extent to which fluctuations occurred in transmission rates according to host/vector abundances, mosquito biting rate, and host stage was explored. By utilizing the model, it was found that when hatch-year avians are more exposed to the virus, a cyclic outbreak can be observed. Since hatch-year avians lack defensive mechanisms, unlike their adult counterpart, they are more readily exposed to the mosquito vector.Author SummaryIn this study, researchers developed a host stage-structured model to investigate how Eastern equine encephalitis virus (EEEV) transmission dynamics vary between adult and hatch-year avian hosts along the northeastern coast of North America. Previous research established that the primary vector, Black-Tailed Mosquito (Culiseta melanura), preferentially feeds on hatch-year (hatchling and fledgling) avians rather than adults, with blood meal patterns aligning with breeding seasons of species like European Starlings and American Robins. The authors constructed a system of ordinary differential equations to analyze transmission patterns between these two distinct host classes. Their model revealed that higher virus exposure in hatch-year avians, which lack the defensive capabilities of adults, can trigger cyclic disease outbreaks. Key factors examined included host/vector populations, mosquito biting rates, and host life stage. The findings suggest that the increased vulnerability of hatch-year avians to mosquito feeding can be one of the factors that significantly influences EEEV transmission dynamics in the region.
Developmentally cascading structures do not lose evolutionary potential, but compound developmental instability in rat molars
Authors: Vitek Natasha S. , Saks Ella , Dong Amy , Burroughs Robert W. , Ward Devin L , Pomeroy Emma , Martin-Gronert Malgorzata , Ozanne Susan E. 
Published: January 2025

AbstractIncreasing variability down serially segmented structures, such as mammalian molar teeth and vertebrate limb segments, is a much-replicated pattern. The same phenotypic pattern has conflicting interpretations at different evolutionary scales. Macroevolutionary patterns are thought to reflect greater evolutionary potential in later-forming segments, but microevolutionary patterns are thought to reflect less evolutionary potential and greater phenotypic plasticity. We address this conflict by recalculating evolutionary potential (evolvability) from published mammalian molar data and directly measuring phenotypic plasticity from a controlled feeding experiment. Effects on lengths and widths are discordant in a way that suggests general growth pathways have a role in phenotypically plastic dental responses to nutrition. Effects on successive trait means do not necessarily increase downstream, contrary to long-standing hypotheses. We confirm prior findings of increasing non-inherited variance downstream, showing decoupling between effects on trait mean and variance. These patterns can be explained by a cascading model of tooth development compounding the effect of anatomically hyper-local developmental instability as an influence separate from general environmental effects on the developing embryo. When evaluated in terms of evolvability, not heritability, later-developing molars are equally or more evolvable than earlier-developing molars, aligning their microevolutionary potential with macroevolutionary patterns in other serially segmented structures.
Performance of o1 pro and GPT-4 in self-assessment questions for nephrology board renewal
Authors: Noda Ryunosuke , Yuasa Chiaki , Kitano Fumiya , Ichikawa Daisuke , Shibagaki Yugo 
Published: January 2025

ABSTRACTBackgroundLarge language models (LLMs) are increasingly evaluated in medical education and clinical decision support, but their performance in highly specialized fields, such as nephrology, is not well established. We compared two advanced LLMs, GPT-4 and the newly released o1 pro, on comprehensive nephrology board renewal examinations.MethodsWe administered 209 Japanese Self-Assessment Questions for Nephrology Board Renewal from 2014–2023 to o1 pro and GPT-4 using ChatGPT pro. Each question, including images, was presented in separate chat sessions to prevent contextual carryover. Questions were classified by taxonomy (recall/interpretation/problem-solving), question type (general/clinical), image inclusion, and nephrology subspecialty. We calculated the proportion of correct answers and compared performances using chi-square or Fisher’s exact tests.ResultsOverall, o1 pro scored 81.3% (170/209), significantly higher than GPT-4’s 51.2% (107/209; p<0.001). o1 pro exceeded the 60% passing criterion every year, while GPT-4 achieved this in only two out of the ten years. Across taxonomy levels, question types, and the presence of images, o1 pro consistently outperformed GPT-4 (p<0.05 for multiple comparisons). Performance differences were also significant in several nephrology subspecialties, such as chronic kidney disease, confirming o1 pro’s broad superiority.Conclusiono1 pro substantially outperformed GPT-4 in a comprehensive nephrology board renewal examination, demonstrating advanced reasoning and integration of specialized knowledge. These findings highlight the potential of next-generation LLMs as valuable tools in specialty medical education and possibly clinical support in nephrology, warranting further and careful validation.
Age-associated B-cells are expanded in early arthritis linked to atherosclerosis and immune circuits - a potential role as a biomarker for risk stratification
Authors: Miranda-Prieto Daniel , Alperi-López Mercedes , Pérez-Álvarez Ángel I. , Alonso-Castro Sara , Suárez Ana , Rodríguez-Carrio Javier 
Published: January 2025

ABSTRACTObjectiveimmune dysregulation may play a role in cardiovascular (CV) risk excess in rheumatoid arthritis (RA). However, exact mediators are unknown. Age-associated B cells (ABCs) have emerged as multi-faceted pro-inflammatory mediators, also in the atherosclerosis microenvironment, but their role in autoimmunity is ill-defined. Our aim was to evaluate ABCs levels in the earliest stages of inflammatory arthritis and their potential role as biomarkers of atherosclerosis.MethodsABCs were quantified by flow cytometry in 58 early RA patients, 11 individuals with clinical-suspect arthralgia (CSA) and 33 healthy controls (HC). Atherosclerosis occurrence was measured by Doppler-ultrasound. Cytokines were measured by multiplex immunoassays. Cardiometabolic-related proteins were evaluated using high-throughput targeted proteomics.ResultsCirculating ABCs were increased in RA patients compared with HC within the CD19+ and PBMCs pools (p=0.013 and p<0.001, respectively). Numerically higher ABCs levels were found in CSA. ABCs frequency was unrelated to disease features and traditional CV risk factors but negatively associated with good therapeutic outcomes upon csDMARD at 6 and 12 months. ABCs frequency was positively correlated with proinflammatory cytokines (IFNg, TNF, IL-6 and IL-21) and proteomic signatures related to B- and T-cell responses as well as cellular pathways linked to atherosclerosis.ABCs were independently associated with atherosclerosis occurrence and extent in RA patients. Furthermore, adding ABCs levels significantly improved risk stratification over conventional instruments.ConclusionsABCs expansion is an early event along arthritis course, linked to therapeutic outcomes, inflammatory milieu and atherosclerosis burden. ABCs may be a missing link between humoral responses and atherosclerosis in autoimmunity.