bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexistence of a novel SV2B-ALK, EML4-ALK double-fusion in a lung poorly differentiated adenocarcinoma patient and response to alectinib: a case report and literature review
Authors: Chen Huang , Zhang Menglan , Bai Liyan , Niu Yun , Wang Xiaowei , Jiang Ruiying , Wang Ye , Feng Qianqian , Wang Bei , Dai Tingli , Yuan Mingming , Chen Rongrong , Qi Yujuan , Zhong Dingrong 
Published: December 2024

BackgroundAnaplastic lymphoma kinase (ALK) rearrangement, the most common oncogenic rearrangement in lung adenocarcinoma, occurs in approximately 5% of non-small cell lung cancer (NSCLC) patients. EML4 gene is the most common partner of ALK rearrangement, and distinct EML4-ALK fusions differ in their responsiveness to ALK tyrosine kinase inhibitors. However, the concurrence of two ALK rearrangements in one patient and whose response to ALK-TKIs have rarely been reported so far.Case presentationA 47-year-old Chinese male was diagnosed with stage IV lung adenocarcinoma with multiple intracranial metastases and adrenal metastasis. After progression of two lines of chemotherapy combined with local radiotherapy regimens, his tumor tissue sample was sent to perform the DNA-based next-generation sequencing of 116 genes. Surprisingly, EML4-ALK (E13:A20) fusion and a novel SV2B-ALK (S6:A20) fusion were concurrently identified, which was confirmed using immunohistochemistry and fluorescence in-situ hybridization. Given the superior efficacy of alectinib, the patient received alectinib in the third-line setting with the progression-free survival over 14 months up to now. Moreover, through comprehensive review of previous literatures, a total of 22 patients with multiple ALK fusions and their response to ALK-TKIs were summarized.ConclusionThis is the first report of a NSCLC patient with a novel SV2B-ALK, EML4-ALK double-fusion benefiting from alectinib. Alectinib may be an effective therapeutic option for both primary and metastatic lesions including brain metastases in the late-line setting in NSCLC patients with double-ALK fusion.
Nutraceuticals silybin B, resveratrol, and epigallocatechin-3 gallate-bind to cardiac muscle troponin to restore the loss of lusitropy caused by cardiomyopathy mutations in vitro, in vivo, and in silico
Authors: Yang Zeyu , Sheehan Alice M. , Messer Andrew E. , Tsui Sharmane , Sparrow Alexander , Redwood Charles , Kren Vladimir , Gould Ian R. , Marston Steven B. 
Published: December 2024

IntroductionAdrenergic activation of protein kinase A (PKA) in cardiac muscle targets the sarcolemma, sarcoplasmic reticulum, and contractile apparatus to increase contractile force and heart rate. In the thin filaments of the contractile apparatus, cardiac troponin I (cTnI) Ser22 and Ser23 in the cardiac-specific N-terminal peptide (NcTnI: residues 1 to 32) are the targets for PKA phosphorylation. Phosphorylation causes a 2-3 fold decrease of affinity of cTn for Ca2+ associated with a higher rate of Ca2+ dissociation from cTnC leading to a faster relaxation rate of the cardiac muscle (lusitropy). Cardiomyopathy-linked mutations primarily affect Ca2+ regulation or the PKA-dependent modulatory system, such that Ca2+-sensitivity becomes independent of phosphorylation level (uncoupling) and this could be sufficient to induce cardiomyopathy. A drug that could restore the phosphorylation-dependent modulation of Ca2+-sensitivity could have potential for treatment of these pathologies. We have found that a number of small molecules, including silybin B, resveratrol and EGCG, can restore coupling in single filament assays.MethodsWe did molecular dynamics simulations (5x1500ns for each condition) of the unphosphorylated and phosphorylated cardiac troponin core with the G159D DCM mutation in the presence of the 5 ligands and analysed the effects on several dynamic parameters. We also studied the effect of the ligands on the contractility of cardiac muscle myocytes with ACTC E99K and TNNT2 R92Q mutations in response to dobutamine.ResultsSilybin B, EGCG and resveratrol restored the phosphorylation-induced change in molecular dynamics to wild-type values, whilst silybin A, an inactive isomer of silybin B, and Epicatechin gallate, an EGCG analogue that does not recouple, did not. We analysed the atomic-level changes induced by ligand binding to explain recoupling. Mutations ACTC E99K and TNNT2 R92Q blunt the increased relaxation speed response to β1 adrenergic stimulation of cardiac myocytes and we found that resveratrol, EGCG and silybin B could restore the β1 adrenergic response, whereas silybin A did not.DiscussionThe uncoupling phenomenon caused by cardiomyopathy-related mutations and the ability of small molecules to restore coupling in vitro and lusitropy in myocytes is observed at the cellular, molecular and atomistic levels therefore, restoring lusitropy is a suitable target for treatment. Further research on compounds that restore lusitropy is thus indicated as treatments for genetic cardiomyopathies. Further molecular dynamics simulations could define the specific properties needed for recoupling and allow for the prediction and design of potential new drugs.
Critical review of aging clocks and factors that may influence the pace of aging
Authors: Min Mildred , Egli Caitlin , Dulai Ajay S. , Sivamani Raja K. 
Published: December 2024

Background and objectivesAging clocks are computational models designed to measure biological age and aging rate based on age-related markers including epigenetic, proteomic, and immunomic changes, gut and skin microbiota, among others. In this narrative review, we aim to discuss the currently available aging clocks, ranging from epigenetic aging clocks to visual skin aging clocks.MethodsWe performed a literature search on PubMed/MEDLINE databases with keywords including: “aging clock,” “aging,” “biological age,” “chronological age,” “epigenetic,” “proteomic,” “microbiome,” “telomere,” “metabolic,” “inflammation,” “glycomic,” “lifestyle,” “nutrition,” “diet,” “exercise,” “psychosocial,” and “technology.”ResultsNotably, several CpG regions, plasma proteins, inflammatory and immune biomarkers, microbiome shifts, neuroimaging changes, and visual skin aging parameters demonstrated roles in aging and aging clock predictions. Further analysis on the most predictive CpGs and biomarkers is warranted. Limitations of aging clocks include technical noise which may be corrected with additional statistical techniques, and the diversity and applicability of samples utilized.ConclusionAging clocks have significant therapeutic potential to better understand aging and the influence of chronic inflammation and diseases in an expanding older population.
Assuring assistance to healthcare and medicine: Internet of Things, Artificial Intelligence, and Artificial Intelligence of Things
Authors: Belbase Poshan , Bhusal Rajan , Ghimire Sapana Sharma , Sharma Shreesti , Banskota Bibek 
Published: December 2024

IntroductionThe convergence of healthcare with the Internet of Things (IoT) and Artificial Intelligence (AI) is reshaping medical practice with promising enhanced data-driven insights, automated decision-making, and remote patient monitoring. It has the transformative potential of these technologies to revolutionize diagnosis, treatment, and patient care.PurposeThis study aims to explore the integration of IoT and AI in healthcare, outlining their applications, benefits, challenges, and potential risks. By synthesizing existing literature, this study aims to provide insights into the current landscape of AI, IoT, and AIoT in healthcare, identify areas for future research and development, and establish a framework for the effective use of AI in health.MethodA comprehensive literature review included indexed databases such as PubMed/Medline, Scopus, and Google Scholar. Key search terms related to IoT, AI, healthcare, and medicine were employed to identify relevant studies. Papers were screened based on their relevance to the specified themes, and eventually, a selected number of papers were methodically chosen for this review.ResultsThe integration of IoT and AI in healthcare offers significant advancements, including remote patient monitoring, personalized medicine, and operational efficiency. Wearable sensors, cloud-based data storage, and AI-driven algorithms enable real-time data collection, disease diagnosis, and treatment planning. However, challenges such as data privacy, algorithmic bias, and regulatory compliance must be addressed to ensure responsible deployment of these technologies.ConclusionIntegrating IoT and AI in healthcare holds immense promise for improving patient outcomes and optimizing healthcare delivery. Despite challenges such as data privacy concerns and algorithmic biases, the transformative potential of these technologies cannot be overstated. Clear governance frameworks, transparent AI decision-making processes, and ethical considerations are essential to mitigate risks and harness the full benefits of IoT and AI in healthcare.
Vaccine sero-monitoring and sero-surveillance of Peste des petits ruminants in small ruminants in West Gojjam zone, Amhara region, Ethiopia
Authors: Mandefro Mesafint , Ibrahim Saddam Mohammed , Sibhatu Demeke , Kassa Nebiyou , Emiyu Kemal , Debebe Kebede , Dessalegn Bereket , Birhan Mastewal , Bitew Molalegne 
Published: December 2024

BackgroundPeste des petits ruminants (PPR) is an acute or subacute, highly contagious, and economically important, transboundary disease of small ruminants caused by Peste des petits ruminants virus (PPRV).ObjectivesThe objective of this study was to determine the seroconversion rate in PPR vaccinated flock of sheep (Sekela district) and the seroprevalence of PPRV in unvaccinated flocks of sheep and goats (Yilmanadensa district).MethodsA cross-sectional study was conducted from January to March 2022 in two selected districts of West Gojjam zone, Ethiopia. Multistage cluster sampling was used to select sampling units by successively selecting districts, kebeles, and villages purposively based on their accessibility and vaccination status. Individual animals were selected haphazardly mimicking simple random sampling. Accordingly, a total of 660 blood samples were collected. Out of this, 300 sheep were vaccinated 4 months prior to sampling using the Nigerian 75/1 strain-based freeze-dried live attenuated PPR vaccine and 360 small ruminants (288 sheep and 72 goats) were unvaccinated and assayed for anti-PPRV antibodies using commercial c-ELISA.ResultsThe post-vaccination herd immunity was 76.66% (95% CI: 71.46–81.34), which is slightly lower than the threshold herd immunity recommended by the PPR global control and eradication strategy, which is set to be 80%, to efficiently break the epidemiological cycle of the virus. Seroprevalence of PPRV in unvaccinated sheep and goats was 3.61% (95% CI: 1.94–6.1), indicating the possible circulation of PPRV in the area. Although small ruminants develop solid immunity following natural infection in endemic countries, the infection of naïve animals allows continuous circulation of the virus.ConclusionsIn light of the accumulating evidence of low post-vaccination herd immunity in small ruminants in Ethiopia, the undergoing PPR vaccination strategy needs to be reevaluated to achieve the desired herd immunity at any time ultimately aiding the eradication goal by 2030.
Effects of corn oil ingestion on the intestinal mucosa of normal dogs
Authors: An Su-Jin , Kim Young Joo , Hong Il-Hwa , Jung Dong-In 
Published: December 2024

IntroductionWe assessed corn oil’s oral effectiveness in detecting small bowel changes in healthy dogs through ultrasonography, endoscopy, and histopathology. We hypothesize that corn oil ingestion will not significantly increase the visibility of lymphatics and lacteals in healthy dogs.MethodsFive healthy male beagles were studied under institutional guidelines. The small intestine’s mucosal changes were observed post corn oil consumption (0.5 mL/kg) at various time intervals using ultrasonography, endoscopy, and histopathology. Ultrasonography was employed in real-time, and mucosal echogenicity scores were assigned at multiple time points. Endoscopic and capsule endoscopic examinations were conducted weekly at different intervals post oil consumption, with biopsy samples taken from the duodenal and ileal mucosa for histopathological evaluations.ResultsUltrasonographic evaluations showed no pathological conditions in any dog. While conventional endoscopic evaluations reflected normal variation, capsule endoscopy revealed significant duodenal and jejunal mucosal changes 3 h post-ingestion, but not in the ileum. Histopathological evaluation indicated a transient rise in the dilation of ileum villi 3 h post-ingestion, reducing by 12 h.ConclusionIn conclusion, this study demonstrated that the observed physiological changes in the small intestinal mucosa, including lymphatic dilation, hyperechoic speckles, and stripes, were within the normal range after oil ingestion in healthy Beagle dogs.
The effects of camel milk in systemic inflammation and oxidative stress of cigarette smoke-induced chronic obstructive pulmonary disease model in rat
Authors: Behrouz Sepide , Mohammadi Mahla , Sarir Hadi , Boskabady Mohammad Hossein 
Published: December 2024

BackgroundThe effects of camel milk in inflammation and systemic oxidative stress of cigarette smoke (CS)-induced chronic obstructive pulmonary disease (COPD) associated with small airway inflammation in rats were investigated.Methods35 male Wistar rats were randomly divided into five groups: (a) control, (b) CS-exposed rats, c and (d) CS-exposed rats treated with the 4 and 8 mL/kg camel milk, and (e) CS-exposed rats treated with 1 mg/kg dexamethasone.ResultsTotal and differential WBC counts, serum level of TNF-α and malondialdehyde (MDA) level in serum and homogenized tissues of the heart, kidney, liver, and testicle were significantly increased, but catalase (CAT), superoxide dismutase (SOD) and thiol levels were significantly decreased in CS-exposed rats (p &lt; 0.01 to p &lt; 0.001). Treatment with dexamethasone and both doses of camel milk improved all measured variables compared to the COPD group (p &lt; 0.05 to p &lt; 0.001). The improvements of most variables in the treated group with high dose of camel milk were higher than the effect of dexamethasone (p &lt; 0.05 to p &lt; 0.001). These findings suggest that camel milk has a therapeutic potential for treating systemic oxidative stress and inflammatory induced by CS.ConclusionTherefore, camel milk might be effective in attenuating the effects of CS-induced systemic inflammation and oxidative stress.
Hydroxyproline in Urine Microvesicles as a Biomarker of Fibrosis in the Renal Transplant Patient
Authors: Torres Sánchez María José , Ruiz Fuentes María Carmen , Clavero García Elena , Rísquez Chica Noelia , Espinoza Muñoz Karla , Espigares Huete María José , Caba Molina Mercedes , Osuna Antonio , Wangensteen Rosemary 
Published: December 2024

Background/Objectives: Interstitial fibrosis/tubular atrophy in kidney transplantation is an unspecific lesion induced by immune and non-immune factors, which determines the progression of chronic kidney disease. Hydroxyproline is an imino acid that is part of the molecule of collagen. The aim of this study was to assess hydroxyproline in urine microvesicles as a marker of fibrosis in the renal transplant patient. Patients and Methods: An observational cross-sectional study was conducted on 46 renal transplant patients who had undergone renal biopsy with diagnostic intention, as well as 19 healthy controls. Clinical, histological, and laboratory variables were collected at the time of marker determination and renal function was analyzed 2 years later. Hydroxyproline was measured in urine microvesicles. Results: Renal transplant patients showed a higher microvesicular concentration of hydroxyproline compared to the control group, with the following medians (interquartile range (IQR)): 28.024 (5.53) ng/mL vs. 2.51 (1.16) ng/mL, p < 0.001. In the transplanted patients, patients in whom biopsy showed some score of total cortical parenchymal inflammation (ti) displayed a significantly higher concentration of hydroxyproline in urine microvesicles than those patients who did not score for cortical parenchymal inflammation (29.91 ± 2.797 ng/mL vs. 22.72 ± 8.697 ng/mL, p = 0.034). No significant correlation was observed between urinary markers and serum creatinine, calcium, and parathyroid hormone (PTH). Conclusions: The concentration of hydroxyproline in urinary microvesicles increased in renal transplant patients relative to healthy controls. Hydroxyproline in urinary microvesicles is a marker of chronic renal inflammation in transplanted patients, and further studies are required to confirm this finding in other pathologies, as well as the association with fibrosis and the evolution of renal function.
Genome-Wide Identification, Functional Characterization, and Stress-Responsive Expression Profiling of Subtilase (SBT) Gene Family in Peanut (Arachis hypogaea L.)
Authors: Li Shipeng , Fu Huiwen , Sharif Yasir , Abdullaziz Sheidu , Wang Lihui , Zhang Yongli , Zhuang Yuhui 
Published: December 2024

Subtilases (SBTs), known as serine proteases or phytoproteases in plants, are crucial enzymes involved in plant development, growth, and signaling pathways. Despite their recognized importance in other plant species, information regarding their functional roles in cultivated peanut (Arachis hypogea L.) remains sparse. We identified 122 AhSBT genes in the STQ peanut genome, classifying them into six subgroups based on phylogenetic analysis. Detailed structural and motif analyses revealed the presence of conserved domains, highlighting the evolutionary conservation of AhSBTs. The collinearity results indicate that the A. hypogea SBT gene family has 17, 5, and 1 homologous gene pairs with Glycine max, Arabidopsis thaliana, and Zea mays, respectively. Furthermore, the prediction of cis-elements in promoters indicates that they are mainly associated with hormones and abiotic stress. GO and KEGG analyses showed that many AhSBTs are important in stress response. Based on transcriptome datasets, some genes, such as AhSBT2, AhSBT18, AhSBT19, AhSBT60, AhSBT102, AhSBT5, AhSBT111, and AhSBT113, showed remarkably higher expression in diverse tissues/organs, i.e., embryo, root, and leaf, potentially implicating them in seed development. Likewise, only a few genes, including AhSBT1, AhSBT39, AhSBT53, AhSBT92, and AhSBT115, were upregulated under abiotic stress (drought and cold) and phytohormone (ethylene, abscisic acid, paclobutrazol, brassinolide, and salicylic acid) treatments. Upon inoculation with Ralstonia solanacearum, the expression levels of AhSBT39, AhSBT50, AhSBT92, and AhSBT115 were upregulated in disease-resistant and downregulated in disease-susceptible varieties. qRT-PCR-based expression profiling presented the parallel expression trends as generated from transcriptome datasets. The comprehensive dataset generated in the study provides valuable insights into understanding the functional roles of AhSBTs, paving the way for potential applications in crop improvement. These findings deepen our understanding of peanut molecular biology and offer new strategies for enhancing stress tolerance and other agronomically important traits.
Centella asiatica Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis
Authors: Kundu Payel , Yasuhara Kanon , Brandes Mikah S. , Zweig Jonathan A. , Neff Cody J. , Holden Sarah , Kessler Kat , Matsumoto Steven , Offner Halina , Waslo Carin S. , Vandenbark Arthur , Soumyanath Amala , Sherman Larry S. , Raber Jacob , Gray Nora E. , Spain Rebecca I. 
Published: December 2024

Background/Objectives: Centella asiatica (L.) Urban (family Apiaceae) (C. asiatica) is a traditional botanical medicine used in aging and dementia. Water extracts of C. asiatica (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from C. asiatica. To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. Results: At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. Conclusions: In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS.
Investigations on the Performance of a 5 mm CdTe Timepix3 Detector for Compton Imaging Applications
Authors: Useche Parra Juan S. , Roque Gerardo , Schütz Michael K. , Fiederle Michael , Procz Simon 
Published: December 2024

Nuclear power plant decommissioning requires the rapid and accurate classification of radioactive waste in narrow spaces and under time constraints. Photon-counting detector technology offers an effective solution for the quick classification and detection of radioactive hotspots in a decommissioning environment. This paper characterizes a 5 mm CdTe Timepix3 detector and evaluates its feasibility as a single-layer Compton camera. The sensor’s electron mobility–lifetime product and resistivity are studied across bias voltages ranging from −100 V to −3000 V, obtaining values of μeτe = (1.2 ± 0.1) × 10−3 cm2V−1, and two linear regions with resistivities of ρI=(5.8±0.2) GΩ cm and ρII=(4.1±0.1) GΩ cm. Additionally, two calibration methodologies are assessed to determine the most suitable for Compton applications, achieving an energy resolution of 16.3 keV for the 137Cs photopeak. The electron’s drift time in the sensor is estimated to be (122.3 ± 7.4) ns using cosmic muons. Finally, a Compton reconstruction of two simultaneous point-like sources is performed, demonstrating the detector’s capability to accurately locate radiation hotspots with a ∼51 cm resolution.