bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Value of Magnetic Resonance Imaging in Assessing Immediate Efficacy After Microwave Ablation of Lung Malignancies
Authors: Zhu Fandong , Yang Chen , Wang Jianyun , Zhou Tong , Li Qianling , Wang Subo , Zhao Zhenhua 
Published: July 2024

Purpose:
To investigate the imaging performance and parametric analysis of magnetic resonance imaging (MRI) immediately after microwave ablation (MWA) of lung malignancies.

Materials and Methods:
We retrospectively analyzed the MRI performance immediately after MWA of 34 cases of lung malignancies. The ablation zone parameters of lung malignancies were measured, including the long diameter (L), short diameter (S), and safety margin of the ablation zone on plain computed tomography (CT), T1-weighted imaging (T1WI), and T2-weighted imaging (T2WI) after MWA. The study calculated the tumor volume (V0), the ablation zone volume (V1), and the ratio of V0 to V1 (V%). Statistical differences between the parameters were analyzed.

Results:
The ablation area of the lesion exhibited central low signal and peripheral high signal on T2WI, central high signal and peripheral equal or high signal on T1WI, and circumferential enhancement in the periphery. The safety margin measured on T2WI was greater than that measured on plain CT and T1WI. On plain CT, the L, S, and V1 were smaller in the effective treatment group than in the ineffective treatment group (P<0.05). On T1WI, the V% and safety margin were greater in the effective treatment group than in the ineffective treatment group (P=0.009 and P=0.016, respectively).

Conclusions:
MRI may be a new, valuable method to assess immediate efficacy after MWA for lung malignancies using the ablation zone parameters V% on T1WI and safety margin on T2WI.
Early Use of Aspirin for Coronary Allograft Prophylaxis in Heart Transplant Recipients
Authors: Kessler Iglesias Cassia , Bloom Jason E. , Xiao Xiaoman , Moskovitch Jeremy , Eckford Hunter , Offen Sophie , Kotlyar Eugene , Keogh Anne , Jabbour Andrew , Bergin Peter , Leet Angeline , Hare James L. , Taylor Andrew J. , Hayward Christopher S. , Jansz Paul , Kaye David M. , Macdonald Peter S. , Muthiah Kavitha 
Published: July 2024

Background.
Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting.

Methods.
This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up.

Results.
There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P = 0.08).

Conclusions.
In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials.
Body Size Remains the Major Source of Sex Disparity Despite Updated Liver Transplant Allocation Policies
Authors: Tanaka Tomohiro , Ross-Driscoll Katherine , Pancholia Smita , Axelrod David 
Published: July 2024

Background.
Efforts to address US liver transplant (LT) access inequities continue, yet disparities linked to candidate traits persist.

Methods.
Analyzing national registry data pre- and post-Acuity Circle (AC) policy, our study assessed the impact of low body surface area (BSA) on LT waitlist mortality. The outcomes of LT candidates listed in the pre-AC era (n = 39 227) and post-AC (n = 38 443) were compared for patients with low BSA (22.9% pre-AC and 23.3% post-AC).

Results.
Fine-Gray competing risk models highlighted that candidates with low BSA had a lower likelihood of LT both pre-AC (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.92-0.95) and post-AC (HR 0.96; 95% CI, 0.94-0.98), with minimal improvement in waitlist mortality/dropout risk from pre-AC (HR 1.15; 95% CI, 1.09-1.21) to post-AC (HR 1.13; 95% CI, 1.06-1.19). Findings were mostly reaffirmed by Cox regression models incorporating the trajectory of Model for End-stage Liver Disease (MELD) scores as time-dependent covariates. Regions 3, 5, and 7 showed notable LT waitlist disparities among low BSA patients post-AC policy. Causal mediation analysis revealed that low BSA and the difference between MELD-sodium and MELD 3.0 (MELD_D, as a proxy for the potential impact of the introduction of MELD 3.0) largely explained the sex disparity in AC allocation (percent mediated 90.4).

Conclusions.
LT waitlist disparities for female candidates persist, largely mediated by small body size. Although MELD 3.0 may reduce some disparities, further body size adjustments for in allocation models are justified.
Comparison of Climate Impact, Clinical Outcomes, and Cost-Efficiency of Pediatric Transumbilical Laparoscopic-Assisted Appendectomy vs Standard 3-Port Laparoscopic Appendectomy
Authors: Fitzpatrick Colleen M , Meinrenken Christoph J , Eimicke William B 
Published: July 2024

BACKGROUND:
Healthcare is responsible for 8.5% of US greenhouse gas emissions. This impact must be mitigated while maintaining clinical excellence. This study compares clinical outcomes, cost-efficiency, and climate impact of transumbilical laparoscopic-assisted appendectomy (TULAA) vs 3-port laparoscopic appendectomy (LA).

STUDY DESIGN:
IRB approval was obtained. Appendectomies performed between January 1, 2020, and December 31, 2022, at a tertiary children’s hospital were reviewed. Data abstracted included clinical characteristics, operative approach and findings, supplies and equipment used, and complication. For analysis, TULAA was combined with cases converted to LA (TULAA+C). To determine a surgical site infection increase of ≤2.5%, a minimum sample size of 479 patients per group was needed to achieve a power of 80%. A composite supply list for each approach was determined by averaging supplies from cases reviewed. The composite was used to calculate cost-efficiency and climate impact. Life cycle assessment was used to determine the carbon footprint (according to International Organization for Standardization standard 14067) of supplies and equipment.

RESULTS:
Analysis was performed on 1,611 appendectomies: 497 LA and 1,114 TULAA+C (932 TULAA and 182 converted). Except for BMI, there were no clinically significant differences between groups. Surgical site infection did not increase with TULAA+C (15, 1.3%) vs LA (6, 1.2%), p = 0.81. TULAA+C ($369.21 per case) was more cost-efficient than LA ($879.30 per case) and TULAA+C (24.8 kilograms of carbon dioxide equivalents) produced fewer emissions than LA (27.4 kilograms of carbon dioxide equivalents).

CONCLUSIONS:
Although patient safety and excellent clinical outcomes must remain the top priority in healthcare, the current environmental crisis demands consideration of climate impact. When clinical noninferiority can be demonstrated, treatment options with fewer greenhouse gas emissions should be chosen.
Human Brain Ancestral Barcodes
Authors: Shibata Darryl 
Published: July 2024

AbstractDynamic CpG methylation “barcodes” were read from 15,000 to 21,000 single cells from three human male brains. To overcome sparse sequencing coverage, the barcode had ∼31,000 rapidly fluctuating X-chromosome CpG sites (fCpGs), with at least 500 covered sites per cell and at least 30 common sites between cell pairs (average of ∼48). Barcodes appear to start methylated and record mitotic ages because excitatory neurons and glial cells that emerge later in development were less methylated. Barcodes are different between most cells, with average pairwise differences (PWDs) of ∼0.5 between cells. About 10 cell pairs per million were more closely related with PWDs < 0.05. Barcodes appear to record ancestry and reconstruct trees where more related cells had similar phenotypes, albeit some pairs had phenotypic differences. Inhibitory neurons showed more evidence of tangential migration than excitatory neurons, with related cells in different cortical regions. fCpG barcodes become polymorphic during development and can distinguish between thousands of human cells.
Analysis of Ground Reaction Force Impulses During Uneven Walking for Young and Older Adults
Authors: Hosseini Yazdi Seyed Saleh 
Published: July 2024

AbstractHumans navigate various terrains by exerting forces to direct the Center of Mass (COM) and maintain balance. During walking, humans transition from one stance leg to the next by exerting impulses during the step-to-step transition. Studying these transition impulses may provide insight into how humans traverse uneven terrains. When walking speed increased (constant terrain amplitude), the average braking and propulsive impulses (posterior/anterior) increased comparably (−0.0270 m · s−1· g−1v−1versus 0.0252 m s−1· g−1v−1). In the vertical direction, while the collision impulse remained constant, the push-off impulse declined by -0.0535 m · s−1· g−1· v−1. The interaction of age and speed also increased the collision impulse (0.0202 m · s−1· g−1· v−1). With the rise of terrain amplitude (constant speed), the braking and propulsive impulses rose by -0.0607 m · s−1· g−1· m−1and 0.0701 m · s−1· g−1· m−1, respectively. Thus, we could infer that the propulsive impulse also contributed to the gait mechanical energy. While the collision impulse increased with terrain amplitude (0.1775 m · s−1· g−1· m−1) and the interaction of age and terrain amplitude (0.1058 m · s−1· g−1· m−1), the push-off impulse declined (−0.2700 m · s−1· g−1· m−1and -0.1473 m · s−1· g−1· m−1). We also observed the push-off as a fraction of the total vertical impulse declined. Therefore, we detected a mechanical energy deficit in the step-to-step transition that must have been compensated for during the mid-flight phase. Considering the portion of push-off occurring after the subsequent heel-strike as delayed push-off, while it increased with walking speed, it declined with terrain amplitude. Thus, during uneven walking, the push-off exertion must have been interrupted, indicating the demand for further mechanical energy infusion after the transition.
An Adipo-Pulmonary Axis Mediated by FABP4 Hormone Defines a Therapeutic Target Against Obesity-Induced Airway Disease
Authors: Burak M. Furkan , Tuncman Gurol , Ayci Ayse Nur , Chetal Kashish , Seropian Grace Yankun Lee , Inouye Karen , Lai Zon Weng , Dagtekin Nurdan , Sadreyev Ruslan I. , Israel Elliot , Hotamışlıgil Gökhan S 
Published: July 2024

AbstractObesity-related airway disease is a clinical condition without a clear description and effective treatment. Here, we define this pathology and its unique properties, which differ from classic asthma phenotypes, and identify a novel adipo-pulmonary axis mediated by FABP4 hormone as a critical mediator of obesity-induced airway disease. Through detailed analysis of murine models and human samples, we elucidate the dysregulated lipid metabolism and immunometabolic responses within obese lungs, particularly highlighting the stress response activation and downregulation of surfactant-related genes, notably SftpC. We demonstrate that FABP4 deficiency mitigates these alterations, demonstrating a key role in obesity-induced airway disease pathogenesis. Importantly, we identify adipose tissue as the source of FABP4 hormone in the bronchoalveolar space and describe strong regulation in the context of human obesity, particularly among women. Finally, our exploration of antibody-mediated targeting of circulating FABP4 unveils a novel therapeutic avenue, addressing a pressing unmet need in managing obesity-related airway disease. These findings not only define the presence of a critical adipo-pulmonary endocrine link but also present FABP4 as a therapeutic target for managing this unique airway disease that we refer to as fatty lung disease associated with obesity.Graphical AbstractOne Sentence SummaryInvestigating FABP4’s pivotal role in obesity-driven airway disease, this study unveils an adipo-pulmonary axis with potential therapeutic implications.
Growth of soil ammonia-oxidizing archaea on air-exposed solid surface
Authors: Abiola Christiana , Gwak Joo-Han , Lee Ui-Ju , Awala Samuel Imisi , Jung Man-Young , Park Woojun , Rhee Sung-Keun 
Published: July 2024

AbstractSoil microorganisms often thrive as microcolonies or biofilms within pores of soil aggregates exposed to the soil atmosphere. However, previous studies on the physiology of soil ammonia-oxidizing microorganisms (AOM), which play a critical role in the nitrogen cycle, were primarily conducted using freely suspended AOM cells (planktonic cells) in liquid media. In this study, we examined the growth of two representative soil ammonia-oxidizing archaea (AOA),Nitrososphaera viennensisEN76 and “Nitrosotenuis chungbukensis” MY2, and an ammonia-oxidizing bacterium,Nitrosomonas europaeaATCC 19718 on polycarbonate membrane filters floated on liquid media to observe their adaptation to air-exposed solid surfaces. Interestingly, ammonia oxidation activities ofN. viennensisEN76 and “N. chungbukensis” MY2 were significantly repressed on floating filters compared to the freely suspended cells in liquid media. Conversely, the ammonia oxidation activity ofN. europaeaATCC 19718 was comparable on floating filters and liquid media.N. viennensisEN76 andN. europaeaATCC 19718 developed microcolonies on floating filters. Transcriptome analysis ofN. viennensisEN76 floating filter-grown cells revealed upregulation of unique sets of genes for cell wall and extracellular polymeric substance biosynthesis, H2O2-induced oxidative stress defense, and ammonia oxidation, including ammonia monooxygenase subunit C (amoC3) and the multicopper oxidases. These genes may play a pivotal role in adapting AOA to air-exposed solid surfaces. Furthermore, the floating filter technique resulted in the enrichment of distinct soil AOA communities dominated by the “Ca. Nitrosocosmicus” clade. Overall, this study sheds light on distinct adaptive mechanisms governing AOA growth on air-exposed solid surfaces.
Mechanism of host cell invasion byLeishmaniathrough KMP-11 mediated cholesterol-transport and membrane phase transition
Authors: Sannigrahi Achinta , Ghosh Souradeepa , Pradhan Supratim , Jana Pulak , Jawed Junaid Jibran , Majumdar Subrata , Roy Syamal , Karmakar Sanat , Mukherjee Budhaditya , Chattopadhyay Krishnananda 
Published: July 2024

AbstractThe first step of successful infection by any intracellular pathogen relies on its ability to invade its host cell membrane. However, the detailed structural and molecular understanding underlying lipid membrane modification during pathogenic invasion remains unclear. In this study, we show that a specificLeishmania donovani(LD) protein, KMP-11, forms oligomers that bridge LD and host macrophage (MΦ) membranes. This KMP-11 induced interaction between LD and MΦ depends on the variations in cholesterol (CHOL) and ergosterol (ERG) contents in their respective membranes. These variations are crucial for the subsequent steps of invasion, including (a) the initial attachment, (b) CHOL transport from MΦ to LD, and (c) detachment of LD from the initial point of contact through a liquid ordered (Lo) to liquid disordered (Ld) membrane-phase transition. To validate the importance of KMP-11, we generated KMP-11 depleted LD, which failed to attach and invade host MΦ. Through tryptophan-scanning mutagenesis and synthesized peptides, we developed a generalized mathematical model, which demonstrates that the hydrophobic moment and the symmetry sequence code at the membrane interacting protein domain are key factors in facilitating the membrane phase transition and, consequently, the host cell infection process by Leishmania parasites.
Stratifying variant deleteriousness and trait-modulating effect under human recent adaptation
Authors: Fan Xutong , Huang Dandan , Dong Xinran , Yi Xianfu , Wang Jianhua , Zhang Shijie , Dong Xiaobao , Gu Xiaoqiong , Li Miaoxin , Sham Pak Chung , Zhou Wenhao , Li Mulin Jun 
Published: July 2024

AbstractDespite advances in annotating and interpreting human genetic variants, existing methods to distinguish deleterious/pathogenic from neutral variants still inadequately capture the nuanced impact of genetic variants on fitness and disease susceptibility. In this study, we introduced a new deep learning framework, the FIND model, by stratifying genetic variants into refined categories based on selection pressures and derived allele frequency. FIND demonstrated superior performance over existing genome-wide methods, delivering enhanced resolution in differentiating trait-modulating alleles from those that are pathogenic or neutral. Access to base-wise informative annotations has unveiled novel features that significantly enhance the model interpretability, and FIND has adeptly delineated evolutionary trends in human accelerated regions. Furthermore, applying FIND to the interpretation of clinical variants demonstrates its substantial potential in reclassifying variants of unknown significance. This work advances our understanding of the genetic underpinnings of human adaptation and disease, providing a new tool to explore the complexities of genetic contributions to health.
Deep Learning-Driven Discovery of FDA-Approved BCL2 Inhibitors: In Silico Analysis Using a Deep Generative Model NeuralPlexer for Drug Repurposing in Cancer Treatment
Authors: Sayyah Ehsan , Tunç Hüseyin , Durdağı Serdar 
Published: July 2024

ABSTRACTFinding strong inhibitors of the BCL2 target, which is essential for controlling apoptosis and ensuring the survival of cancer cells, has prompted research into FDA-approved drugs. This study uses an advanced deep generative model called NeuralPlexer to produce protein-ligand complex conformations one-by-one and performin silicoanalysis. This is the first time in the literature using NeuralPlexer in virtual screening, as we comprehensively evaluate the conformations of an FDA-approved drug library to ascertain their potential efficacy in suppressing BCL2 by utilizing NeuralPlexer’s capabilities. Obtained results were re-confirmed by physics-based molecular simulations and neural relational inference (NRI) analysis. Our study reveals several intriguing candidates such as Lathyrol and Fadrozole with potent inhibitory interactions with the BCL2 target, offering important new information for repurposing currently available drugs in cancer treatment. This work highlights the promise of deep learning technology in pharmaceutical research by integrating NeuralPlexer into the process of drug development, while also improving the accuracy of predictions made about protein-ligand interactions.
Modeling the effect of daytime duration on the biosynthesis of terpenoid precursors
Authors: Basallo Oriol , Lucido Abel , Sorribas Albert , Marin-Sanguino Alberto , Vilaprinyo Ester , Martinez Emilce , Eleiwa Abderrahmane , Alves Rui 
Published: July 2024

AbstractTerpenoids are valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. Circadian regulation affects MVA and MEP pathway activity at three levels: substrate availability, gene expression of pathway enzymes, and utilization of IPP and DMAPP for synthesizing complex terpenoids. There is a gap in understanding the interplay between the circadian rhythm and the dynamics and regulation of the two pathways. In this paper we create a mathematical model of the MVA and MEP pathways in plants that incorporates the effects of circadian rhythms. We then used the model to investigate how annual and latitudinal variations in circadian rhythm affect IPP and DMAPP biosynthesis. We found that, despite significant fluctuations in daylight hours, the amplitude of oscillations in IPP and DMAPP concentrations remains stable, highlighting the robustness of the system. We also examined the impact of removing circadian regulation from different parts of the model on its dynamic behavior. We found that regulation of pathway substrate availability alone results in higher sensitivity to daylight changes, while gene expression regulation alone leads to less robust IPP/DMAPP concentration oscillations. Our results suggest that the combined circadian regulation of substrate availability, gene expression, and product utilization, along with MVA- and MEP-specific regulatory loops, create an optimal operating regime. This regime maintains pathway flux closely coupled to demand and stable across a wide range of daylight hours, balancing the dynamic behavior of the pathways and ensuring robustness in response to cellular demand for IPP/DMAPP.
Mistargeted retinal axons induce a synaptically independent subcircuit in the visual thalamus of albino mice
Authors: McCracken Sean , McCoy Liam , Hu Ziyi , Hodges Julie , Valkova Katia , Williams Philip R. , Morgan Josh 
Published: July 2024

ABSTRACTIn albino mice and EphB1 knock out mice, mistargeted retinal ganglion cell (RGC) axons form dense islands of axon terminals in the dorsal lateral geniculate nuclei (dLGN). The formation of these islands of retinal input depends on developmental patterns of spontaneous retinal activity. We reconstructed the microcircuitry of the activity dependent islands and found that the boundaries of the island represent a remarkably strong segregation within retinogeniculate connectivity. We conclude that, when sets of retinal input are established in the wrong part of the dLGN, the developing circuitry responds by forming a synaptically isolated subcircuit within the otherwise fully connected network. The fact that there is a developmental starting condition that can induce a synaptically segregated microcircuit has important implications for our understanding of the organization of visual circuits and for our understanding of the implementation of activity dependent development.