bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic alterations associated with resistance and circulating tumor DNA dynamics for early detection of progression on CDK4/6 inhibitor in advanced breast cancer
Authors: Kindt Charlotte K. , Alves Carla L. , Ehmsen Sidse , Kragh Amalie , Reinert Thomas , Vogsen Marianne , Kodahl Annette R. , Rønlev Jeanette D. , Ardik Dilan , Sørensen Anna L. , Evald Kirstine , Clemmensen Mia L. , Staaf Johan , Ditzel Henrik J. 
Published: August 2024

AbstractCombined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improves outcome for patients with estrogen receptor‐positive (ER+) metastatic breast cancer, but drug resistance and thus disease progression inevitably occur. Herein, we aimed to identify genomic alterations associated with combined CDK4/6i and endocrine therapy resistance, and follow the levels of specific mutations in longitudinal circulating tumor DNA (ctDNA) for early detection of progression. From a cohort of 86 patients with ER+ metastatic breast cancer we performed whole exome sequencing or targeted sequencing of paired tumor (N = 8) or blood samples (N = 5) obtained before initiation of combined CDK4/6i and endocrine therapy and at disease progression. Mutations in oncogenic genes at progression were rare, while amplifications of growth‐regulating genes were more frequent. The most frequently acquired alterations observed were PIK3CA and TP53 mutations and PDK1 amplification. Longitudinal ctDNA dynamics of mutant PIK3CA or private mutations revealed increased mutation levels at progression in 8 of 10 patients (80%). Impressively, rising levels of PIK3CA‐mutated ctDNA were detected 4–17 months before imaging. Our data add to the growing evidence supporting longitudinal ctDNA analysis for real‐time monitoring of CDK4/6i response and early detection of progression in advanced breast cancer. Further, our analysis suggests that amplification of growth‐related genes may contribute to combined CDK4/6i and endocrine therapy resistance.
S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella‐based tumor therapy and host defense
Authors: Guo Yanxia , Sun Yujie , Li Zhongying , Zuo Chaohui , Liu Xiaoqing , Chen Yu , Xun Zhen , Liu Jinling , Mei Yang , Min Jung‐Joon , Wen Min , Zheng Jin Hai , Tan Wenzhi 
Published: August 2024

AbstractBacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor‐specific targeting, and deep‐tissue penetration. However, the specific molecular mechanisms of bacteria‐mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella‐mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF‐α, and IL‐1β, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella‐mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella‐mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.
Risk assessment of 2β,3β‐19α‐trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth
Authors: Oshiiwa Bruna , da Silva Aline Pereira , Alves Greice Rafaele , Filho Valdir Cechinel , Niero Rivaldo , O'Neill de Mascarenhas Gaivão Isabel , de Oliveira Liana Martins , de Lima Luan Vitor Alves , Mantovani Mário Sérgio , Maistro Edson Luis 
Published: August 2024

AbstractRubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β‐19α‐trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT‐qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M‐TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.
A multiscale modeling to determine in vitro mechanical responses of different cells at the cell‐substrate interface under fluid perfusion
Authors: Gupta Abhisek , Barui Ananya , Banerjee Rupak K. , Das Apurba , Chowdhury Amit Roy 
Published: August 2024

AbstractInvestigating the influence of different cellular mechanical and physical properties on cells in vitro is important for assessing cellular activities like differentiation, proliferation, and migration. Evaluating the mechanical response of the cells lodged on a scaffold due to variations in substrate roughness, substrate elasticity, fluid flow, and the shapes of the cells is the main goal of the study. In this comprehensive analysis, a combination of the fluid structure interaction method and the submodeled finite element technique was employed to anticipate the mechanical responses across various cells at the interface between cells and the substrate. Fluid inlet velocity, substrate roughness, and substrate material were varied in this analysis. Different cell shapes were considered along with various components such as cell membrane, cytoplasm, nucleus, and cytoskeletons. This analysis shows the effect of these individual parameters on the elastic strain and strain energy density of cells at the cell‐substrate interface. The results highlight that substrate roughness has a more significant impact on the mechanical response of cells at the interface than substrate elasticity. However, effect of the substrate elasticity becomes crucial for extremely soft substrate materials. The results of this research can be applied to identify the optimal parameters for fluid flow and create a suitable condition for cell culture.
Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism
Authors: Fann Yu‐Ning , Teo Wan‐Huai , Lee Hsin‐Chen , Liao Chen‐Chung , Tsay Yeou‐Guang , Huang Tung‐Fu , Lo Jeng‐Fan 
Published: August 2024

AbstractBackgroundSarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co‐chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular Dnaja3 haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both in vitro and in vivo.MethodsWe generated mouse strain with Dnaja3 heterozygosity (HSA‐Dnaja3f/+) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and HSA‐Dnaja3f/+ mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and HSA‐Dnaja3f/+ mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short‐term and long‐term GMI treatment were administrated intraperitoneally to the HSA‐Dnaja3f/+ young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, respectively.ResultsMuscular Dnaja3 heterozygosity resulted in impaired locomotor activity (P < 0.05), reduced muscular cross‐sectional area (P < 0.0001), and up‐regulation of lipogenesis (ACC2) and pro‐inflammation (STAT3) in skeletal muscles (P < 0.05). Primary myoblasts from the HSA‐Dnaja3f/+ mice displayed impaired mitochondrial respiration (P < 0.01) and imbalanced mitochondrial ROS levels. A systemic proteomic analysis of the purified mitochondria from the primary myoblasts was conducted to show the abnormalities in mitochondrial function and fatty acid metabolism (P < 0.0001). At age of 13 to 14 months, the HSA‐Dnaja3f/+ mice displayed increased body fat mass (P < 0.001), reduced fat‐free mass (P < 0.01), and impaired glucose and insulin tolerance (P < 0.01). The short‐term GMI treatment improved locomotor activity (P < 0.01) and down‐regulated the protein levels of STAT3 (P < 0.05), ACC2, and mitochondrial respiratory complex III (UQCRC2) (P < 0.01) via DNAJA3 activation. The long‐term GMI treatment ameliorated fat mass accumulation, glucose intolerance, and systemic inflammation (AST) (P < 0.05) in skeletal muscle, while enhancing thermogenesis (UCP1) (P < 0.01) in eWAT. GMI treatment promoted myogenesis, enhanced oxygen consumption, and ameliorated STAT3 (P < 0.01) through DNAJA3 activation (P < 0.05) in vitro.ConclusionsMuscular Dnaja3 haploinsufficiency dysregulates mitochondrial function and lipid metabolism then leads to sarcopenic obesity. GMI emerges as a therapeutic regimen for sarcopenic obesity treatment through DNAJA3 activation.
The effect of conjoint behavioral consultation on achieving communication skills in children with autism spectrum disorder
Authors: Aykut Pelin , Kahveci Gul 
Published: August 2024

AbstractThis study, uniquely designed with tact and mand‐modeling procedures presented through the Conjoint Behavioral Consultation (CBC) method, aims to evaluate the effects on the communication skills of preschool children with autism spectrum disorder (ASD) and the impact on disruptive behaviors (tantrums) at home. A pilot study with the families of three participants informed the adaptations for the main study, which was implemented with the families of nine participants. The research was conducted using an Embedded Mixed Methods Design, a distinctive approach that allowed for a comprehensive understanding of the outcomes. The primary research design was a single‐subject research model with multiple probes across participants' designs, ensuring a thorough and individualized assessment. The study was carried out in both home and clinical settings, involving the participation of special education teachers and families. The findings indicate that the tact and mand‐modeling procedures presented through the CBC method significantly improved the children's communication skills and led to substantial reductions in tantrum behaviors. All families indicated that the dependent variables held significant social importance. Significant enhancements were noted in the children's communication skills and social engagements after the intervention. The CBC intervention was determined to be feasible and feasible for families, with no additional expenses accrued. The long‐term suitability and usefulness of the product in many environments increased its societal acceptance. This study revealed that the CBC approach had a favorable and reliable effect on academic and behavioral advancement.
State‐of‐the‐Art Quantification of Liver Iron With MRI—Vendor Implementation and Available Tools
Authors: Tipirneni‐Sajja Aaryani , Shrestha Utsav , Esparza Juan , Morin Cara E. , Kannengiesser Stephan , Roberts Nathan T. , Peeters Johannes M. , Sharma Samir D. , Hu Houchun H. 
Published: August 2024

The role of MRI to estimate liver iron concentration (LIC) for identifying patients with iron overload and guiding the titration of chelation therapy is increasingly established for routine clinical practice. However, the existence of multiple MRI‐based LIC quantification techniques limits standardization and widespread clinical adoption. In this article, we review the existing and widely accepted MRI‐based LIC estimation methods at 1.5 T and 3 T: signal intensity ratio (SIR) and relaxometry (R2 and R2*) and discuss the basic principles, acquisition and analysis protocols, and MRI‐LIC calibrations for each technique. Further, we provide an up‐to‐date information on MRI vendor implementations and available offline commercial and free software for each MRI‐based LIC quantification approach. We also briefly review the emerging and advanced MRI techniques for LIC estimation and their current limitations for clinical use. Lastly, we discuss the implications of MRI‐based LIC measurements on clinical use and decision‐making in the management of patients with iron overload. Some of the key highlights from this review are as follows: 1) Both R2 and R2* can estimate accurate and reproducible LIC, when validated acquisition parameters and analysis protocols are applied, 2) Although the Ferriscan R2 method has been widely used, recent consensus and guidelines endorse R2*‐MRI as the most accurate and reproducible method for LIC estimation, 3) Ongoing efforts aim to establish R2*‐MRI as the standard approach for quantifying LIC, and 4) Emerging R2*‐MRI techniques employ radial sampling strategies and offer improved motion compensation and broader dynamic range for LIC estimation.Evidence Level1Technical EfficacyStage 2
Deciphering the spatial fingerprint of drought propagation through precipitation, vegetation and groundwater
Authors: Bilal Syed Bakhtawar , Gupta Vivek 
Published: August 2024

AbstractDroughts, depending on their nature, have had devastating consequences, including crop destruction, famine and millions of deaths, particularly in countries like India that heavily rely on rainfall for agriculture. The present study aims to quantify the linkage between meteorological, agricultural and hydrological drought at a high spatial resolution across India. These connections were established by developing various drought propagation metrics followed by subsequent correlation analysis, lag analysis and clustering. Standard Precipitation Index (SPI), Deviation in NDVI (Dev‐NDVI) and GRACE Drought Severity Index (GRACE‐DSI) were used to represent meteorological, agricultural and hydrological droughts. Run theory with thresholds of −1, −0.5 and −0.05 were used to delineate the drought events for meteorological, hydrological and agricultural droughts, respectively. Furthermore, multivariate K‐means clustering based on factors such as drought duration, latitude, longitude, severity, propagation and recovery speeds was done to create spatial clusters having similar drought characteristics. Correlation analysis showed the highest average correlations at a lag of around 7–8 months between meteorological and hydrological drought, a lag of 1–2 months in case of meteorological and agricultural drought and a lag of 3–4 months between agricultural and hydrological drought. The analysis of drought duration indicated that, on average, meteorological drought in India lasted for 2.34 months, while agricultural drought lasted for 3 months, reflecting a 26.5% increase, whereas hydrological drought lasted for 5.22 months, indicating a notable 123% increase. This increase in average drought duration as it propagates from meteorological to agricultural to hydrological drought can be attributed to the lengthening property of drought propagation. Clustering analysis reveals presence of five homogeneous drought clusters. Additionally, cluster analysis reveals that for meteorological and agricultural droughts arid regions showed the highest severity whereas for hydrological droughts north Indian states including Punjab and Haryana showed the highest severity.
Endoscopic cystostomy and biliary sphincterotomy for choledochoceles: A pediatric case series
Authors: Saad Michelle , Abu‐El‐Haija Maisam , Lin Tom K. , Towbin Alexander J. , Trout Andrew T. , Bernieh Anas , Tiao Greg , Vitale David S. 
Published: August 2024

AbstractManagement of choledochoceles (type III choledochal cysts) in children varies. We highlight the potential role of endoscopic management of choledochoceles with cystostomy and biliary sphincterotomy through a series of three successfully treated pediatric patients aged 12–13 at our tertiary center. Patients presented with symptoms including abdominal pain and pancreatitis. Choledochoceles were identified by preprocedure imaging on magnetic resonance imaging, with sizes ranging between 7 and 15 mm in maximal diameter. Histology revealed two choledochoceles lined by biliary epithelium and one by intestinal epithelium. Clinical improvement was sustained at a 2‐year follow‐up, with radiographic resolution on repeat imaging and normal tumor markers. We conclude that endoscopic management of choledochoceles with cystostomy and biliary sphincterotomy is a therapeutic option in children and can lead to sustained resolution of associated symptoms. While there is some lifetime risk of malignancy with choledochal cysts, malignancy in choledochoceles is rare.
Recordings of Superior Laryngeal Nerve Sensory Nerve Action Potentials in a Rat Model
Authors: Jaleel Zaroug , Aboueisha Mohamed A , Adcock Kelson , Cvancara David J. , Martinez Vicente , Kinney Greg , Perkel David J. , Bhatt Neel K. 
Published: August 2024

ObjectiveSuperior laryngeal nerve (SLN) function is critical to laryngeal sensation. Sensory dysfunction in the larynx, mediated through the internal branch of the superior laryngeal nerve (iSLN), is thought to occur with aging and neurodegenerative disease. However, objective analysis of iSLN neurophysiology is difficult due to its anatomic location and small diameter. This study measures sensory nerve action potentials (SNAP) from the iSLN in a rat model.MethodsSNAP data were obtained from two adult rat strains (Sprague–Dawley, SD and Fischer 344 × Brown Norway F1 Hybrid rats, FBN). Evoked responses were obtained by stimulating the main trunk of the SLN and recording the response using a 160‐μm cuff electrode placed around the iSLN. SNAP were averaged from 10 stimulations. Laryngeal adductor reflex (LAR) threshold measurements were obtained with stimulation of the iSLN and direct laryngoscopy. The sections of the iSLN were obtained for histologic analysis.ResultsSLN‐evoked responses were successfully obtained in 18 hemi‐laryngeal preparations (SD n = 13 and FBN n = 5) with corresponding LAR threshold measurements. Mean(±SD) SNAP latency, total duration, amplitude, negative durations, and intensity were 2.28 ms (±0.56), 2.13 ms (±0.70), 879 μV (±535), and 0.69 mA (±0.25), respectively. SLN stimulation threshold to elicit an LAR was of 0.84 mA (±0.31).ConclusionIt is feasible to record evoked SLN responses in two adult rat strains. This work may lead to a tractable animal model for objective measurements of SLN neurophysiology with various disease states.Level of EvidenceNA Laryngoscope, 134:5028–5033, 2024
Percutaneous Tracheostomy Via Grigg's Technique in Children: Does Age and Size Matter?
Authors: Sozduyar Sumeyye , Ergun Ergun , Khalilova Pari , Gollu Gulnur , Ates Ufuk , Can Ozlem S. , Kendirli Tanil , Yagmurlu Aydin , Cakmak Murat , Kologlu Meltem 
Published: August 2024

ObjectivesPercutaneous tracheostomy is rarely performed in children, especially in infants. In the present study, we aimed to evaluate the complications and outcomes of PT via the Griggs technique according to the age and size of pediatric patients.MethodsThis study included 110 PICU patients who underwent PT using the Griggs technique between 2012 and 2020. The patients were divided into six groups according to their age, demographic data, primary disease, mean duration of intubation before PT, mean duration of PICU and hospitalization after PT, complications, and decannulation outcomes were compared between these groups.ResultsThe mean age and mean weight of the patients were 43.6 ± 58.9 months (1 month–207 months) and 14.6 ± 14.9 kg (2.6–65 kg), respectively. Mean intubation times before the procedures were 64.6 ± 40 days and 38.6 ± 37.9. Thirty‐seven (33.6%) infants were under 6 months of age(Group 1). There were no intraoperative complications. Tracheostomy site stenosis was significantly greater in Group 1 than in the other age groups (p = 0.032). Granuloma formation and dermatitis incidence were similar in all age groups.ConclusionPT is a safe and feasible procedure even in small infants. The accidental decannulation risk is lower than standard tracheostomy. Interacting with rigid bronchoscopy guidance is essential to perform a safer procedure. The first tracheostomy change after PT in small infants under 6 months of age, the possibility of tracheostomy site (stoma) stenosis should be considered.Level of EvidenceLevel III Laryngoscope, 2024
Long‐range transport of littoral methane explains the metalimnetic methane peak in a large lake
Authors: Khatun Santona , Berg Jasmine S. , Jézéquel Didier , Moiron Marthe , Escoffier Nicolas , Schubert Carsten J , Bouffard Damien , Perga Marie‐Elodie 
Published: August 2024

AbstractIn large and stratified lakes, substantial methane stocks are often observed within the metalimnion. The origin of the methane (CH4) accumulated in the metalimnion during stratification, which can sustain significant emissions during convective mixing, is still widely debated. While commonly attributed to the transport of methane produced anaerobically ex situ, recent evidence suggests that oxic in situ methane production could also contribute to metalimnetic methane peaks. Here, we assessed the origin, that is, pelagic CH4 production or transport of sublittoral CH4 through the interflow, of metalimnetic methane in Lake Geneva, the largest lake in Western Europe. Microbial diversity data do not support the hypothesis of oxic methane production in the metalimnion. In contrast, both spatial and temporal surveys of methane show that maxima occur at depths and sites most affected by the Rhône River inflow. Methane δ13C values point to an anaerobic sublittoral methane source, within a biogeochemical hotspot close to the river delta region, and an efficient transport across several kilometers in a vertically well‐constrained metalimnion. Our current findings emphasize the indirect role of river interflows for the long‐range transport of CH4 produced in sediment biogeochemical hotspots, even for large lakes where sublittoral habitats represent a fairly limited fraction of the lake volume.