bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling genetic links between gut microbiota and asthma: a Mendelian randomization
Authors: Zheng XuWen , Chen MaoBing , Zhuang Yi , Zhao Liang , Qian YongJun , Shi ChengCheng 
Published: September 2024

BackgroundMultiple studies suggest a potential connection between the gut microbiome and asthma. Our objective is to use advanced genetic and metagenomic techniques to elucidate the causal relationships and underlying mechanisms between gut microbiota and asthma.MethodsThe study utilized comprehensive Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) analyses to examine the relationship between 119 gut microbiota genera and asthma, using publicly accessible genome-wide association studies (GWAS). The meta-analysis synthesized summary effect estimates obtained from LDSC, forward MR, and reverse MR. The MiBioGen collaboration, involving 18,340 individuals, identified genetic variations associated with gut bacteria. Asthma data were collected from the UK Biobank, FinnGen, and GERA, encompassing a total of 82,060 cases and 641,049 controls.ResultsLDSC analysis revealed significant negative genetic correlations between asthma and RuminococcaceaeUCG004 (Rg = −0.55, p = 7.66 × 10−5) and Subdoligranulum (Rg = −0.35, p = 3.61 × 10−4). Forward MR analysis suggested associations between Butyricicoccus (OR = 0.92, p = 0.01), Turicibacter (OR = 0.95, p = 0.025), Butyrivibrio (OR = 0.98, p = 0.047), and reduced asthma risk. Conversely, Coprococcus2 (OR = 1.10, p = 0.035) and Roseburia (OR = 1.07, p = 0.039) were associated with increased risk. Reverse MR analysis indicated significant associations between genetically predicted asthma and Eubacteriumxylanophilumgroup (Beta = −0.08, p = 9.25 × 10−7), LachnospiraceaeNK4A136group (Beta = −0.05, p = 1.26 × 10−4), and Eisenbergiella (Beta = 0.06, p = 0.015, Rg_P = 0.043).ConclusionThe findings underscore significant genetic correlations and causal relationships between specific gut microbiota and asthma. These insights highlight the potential of gut microbiota as both markers and modulators of asthma risk, offering new avenues for targeted therapeutic strategies.
Photobiomodulation regulates astrocyte activity and ameliorates scopolamine-induced cognitive behavioral decline
Authors: Park Ji On , Hong Namgue , Lee Min Young , Ahn Jin-Chul 
Published: September 2024

IntroductionThe pathophysiological mechanism of Alzheimer’s disease (AD) has not been clearly identified, and effective treatment methods have not yet been established. Scopolamine causes cholinergic dysfunction in the brain, including the accumulation of amyloid-beta plaques, thereby increasing oxidative stress and neuroinflammation, mimicking AD. Glial cells such as astrocytes have recently been identified as possible biomarkers for AD. Photobiomodulation (PBM) elicits a beneficial biological response in cells and tissues. PBM effects on the central nervous system (CNS) have been widely researched, including effects on astrocyte activity.MethodsIn the present study, PBM was performed using light at the near-infrared wavelength of 825 nm. The Morris water maze and Y-maze tests were employed to evaluate cognitive function decline in a scopolamine-induced memory dysfunction model and its improvement with PBM. In addition, alteration of the mitogen-activated protein kinase (MAPK) pathway and immunofluorescence expression levels of active astrocytes were observed in the hippocampus, which is one of the areas affected by AD, to evaluate the mechanism of action of PBM.ResultsA reduction in the neuronal cell death in the hippocampus caused by scopolamine was observed with PBM. Moreover, alteration of a MAPK pathway-related marker and changes in glial fibrillary acidic protein (an active astrocyte marker) expression were observed in the PBM-treated group. Finally, significant correlations between functional and histological results were found, validating the results.DiscussionThese findings indicate the possibility of behavioral and histological improvement due to PBM in scopolamine-induced CNS alteration, which mimics AD. This improvement could be related to neuroinflammatory modulation and altered astrocyte activity.
Determinants of infarct progression and perfusion core growth in transferred LVO patients from remote regions
Authors: Valente Michael , Bivard Andrew , Yan Bernard , Davis Stephen M. , Campbell Bruce C. V. , Mitchell Peter J. , Ma Henry , Parsons Mark W. 
Published: September 2024

IntroductionRepeat imaging when regional and remote stroke patients arrive at a comprehensive stroke center (CSC) can delay endovascular thrombectomy (EVT). We examined which clinical and imaging parameters predict infarct progression and perfusion core growth during transport.MethodsWe included patients recruited from 2017 to 2023 in a prospective database who were transferred from remote sites with large vessel occlusion, had CT perfusion imaging at the primary stroke center (PSC), and had repeat CT on arrival at the CSC demonstrating persistent occlusion. The key imaging characteristics were perfusion core change (rCBF &lt; 30%) and ASPECTS change. Multiple and ordinal logistic regression analyses were used to assess the relationship between background clinical and imaging variables and the CT-perfusion core and ASPECTS on arrival. DEFUSE 3 criteria (ASPECTS ≥ 6, perfusion core &lt; 70 mL) were used to define “favorable imaging.”ResultsIn 90 patients with CT perfusion at both PSC and CSC and persistent occlusion, the median time from onset to PSC presentation was 279 min (IQR 143–702). The median time from PSC presentation to CSC arrival was 243.5 min (IQR 186–335), and the median distance traveled was 186.5 km (IQR 101–258). Lower baseline ASPECTS (per point) was associated with a 7 mL increase (95%CI 2–11 mL) in perfusion core between scans (p = 0.004). The time from onset, the time between PSC and CSC, and the distance traveled were not significantly associated with either ASPECTS or perfusion core growth during transport. In total, 11 out of 78 patients (14%) had deterioration of initially favorable imaging profiles during transport.ConclusionPerfusion core growth during transport was uncommon and most strongly associated with lower ASPECTS at the PSC. Initially, favorable PSC imaging May predict whether repeat imaging is necessary at the CSC.
Effect of glymphatic system function on cognitive function in patients with chronic kidney disease
Authors: Ko Junghae , Park Bong Soo , Heo Chang Min , Yi Jiyae , Lee Dong Ah , Park Kang Min 
Published: September 2024

ObjectivesStudies have recently shown an alteration of the structural connectivity and a dysfunctional glymphatic system in patients with chronic kidney disease (CKD). In this study, we aimed to investigate the effects of the structural connectivity and glymphatic system on the cognitive function of patients with CKD.MethodsWe prospectively enrolled patients with CKD and healthy controls. The CKD group was divided into two regarding their cognitive function. All patients received brain magnetic resonance imaging, including diffusion tensor imaging (DTI). We calculated the measures of structural connectivity and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, a neuroimaging marker of the glymphatic system function, and compared the indices between groups.ResultsThe mean clustering coefficient, local efficiency, and small-worldness index in patients with CKD were lower than those in healthy controls (0.125 ± 0.056 vs. 0.167 ± 0.082, p = 0.008; 1.191 ± 0.183 vs. 1.525 ± 0.651, p = 0.002; 0.090 ± 0.043 vs. 0.143 ± 0.102, p = 0.003; respectively). The DTI-ALPS index was lower in patients with CKD than in healthy controls (1.436 vs. 1.632, p &lt; 0.001). Additionally, the DTI-ALPS index differed significantly between CKD patients with and without cognitive impairment. Notably, this index was lower in patients with CKD and cognitive impairment than in patients without cognitive impairment (1.338 vs. 1.494, p = 0.031). However, there were no differences of the structural connectivity between CKD patients with and without cognitive impairment.ConclusionWe found lower DTI-ALPS index in patients with CKD, which could be related with glymphatic system dysfunction. Moreover, those with cognitive impairment in the CKD group had a lower index than those without, indicating a link between the glymphatic system function and cognitive function.
Causal relationship between genetic-predicted uric acid and cervical cancer risk: evidence for nutritional intervention on cervical cancer prevention
Authors: Cao Chunge , Cai Dajun , Liu Hao , Zhang Xia , Cai Lina , Sun Caiping , Wang Huifang , Zhao Hu , Yue Chaoyan 
Published: September 2024

IntroductionThe relationship between serum uric acid (SUA) and cervical cancer is inconclusive. This study aims to investigate the causal relationship between SUA levels and cervical cancer incidence, and to evaluate the potential role of nutritional interventions in cervical cancer prevention.MethodsWe conducted a two-sample bidirectional Mendelian randomization (MR) analysis using genetic instruments from publicly available genome-wide association studies (GWASs) of individuals of predominantly European ancestry. Methods such as inversevariance weighted, weighted-median, weighted model, and MR-Egger were applied. Sensitivity tests, including leave-one-out, MR-PRESSO, and Cochran’s Q test, assessed heterogeneity and pleiotropy.ResultsOur findings revealed that a high SUA concentration significantly increased the risk of malignant cervical cancer: a 1 mg/mL increase in SUA was associated with a 71% higher risk (OR = 1.71, 95% CI = 1.10–2.67; p = 0.018). Stratification by histological type showed a significant causal effect on cervical adenocarcinoma risk (OR = 2.56, 95% CI = 1.14–5.73; p = 0.023). However, no clear evidence was found for a causal effect of cervical cancer on SUA levels.ConclusionThis study identified a causal relationship between elevated SUA levels and the risk of malignant cervical cancer, particularly cervical adenocarcinoma. These findings provide novel insights into the mechanisms of cervical carcinogenesis and suggest that managing SUA levels could be a potential strategy for cervical cancer prevention through dietary management.
Consumption of edible oil blended with flax, coconut, sunflower, and olive oil can significantly improve the negative health consequences of high-fat/high-cholesterol diet in Sprague Dawley rats
Authors: Rabail Roshina , Altemimi Ammar B. , Maerescu Cristina Maria , Socol Claudia Terezia , Criste Florin Leontin , Khalid Abdur Rauf , Mahwish  , Hussain Shahzad , Liu Zhi-Wei , Aadil Rana Muhammad 
Published: September 2024

BackgroundIncreasing cardiac, hepatic, and metabolic diseases have raised the need to modify our contemporary lifestyles toward balancing and diversifying the nutrients in our daily diet. Objective: Dietary fats should be modified to healthier versions by blending different vegetable oils. Therefore, in this study, an oil blend with health-protective and promoting fatty acid combinations was investigated to bring down the progression of cardiac and other metabolic diseases.MethodologyA bio-efficacy trial was performed to investigate the therapeutic potential of an oil blend in 30 hyperlipidemic rats. Five rats were allocated to each group (coconut, flaxseed, olive, sunflower, and blended oil) for 42 days and were compared with the initial values of hyperlipidemic rats. Methodological investigations were performed for the body weight, naso-anal length, various obesity indices, visceral fat accumulation, blood and serum, cardiovascular risk indices, and echocardiograph.ResultsBlended oil consumption indicated significant reductions of 53.12% in body fat content (3.98 ± 0.96), 6.82% in Lee index (289.60 ± 8.27), 16.84% in BMI (0.15 ± 0.003), 57.37% in total cholesterol (52.00 ± 9.03), 68.57% in triacylglycerides (99.00 ± 9.19), 61.16% in atherogenic index (0.88 ± 0.12), and 58.72% in coronary risk index (2.88 ± 0.12), when compared with the initial values.ConclusionBlended oil consumption has significantly reduced various obesity indices, improved lipid profile, and provided significant protection against cardiovascular risk indices. Moreover, the results of blended oil indicated significant health protective ameliorations in electrocardiographs. Its regular consumption could help to reduce the onset of obesity and metabolic diseases.
Malignant granular cell tumor of chest wall: a case report
Authors: Flauto Fabiano , Servetto Alberto , Bianco Roberto , Formisano Luigi 
Published: September 2024

BackgroundGranular Cell Tumors (GCTs), also known as Abrikossoff tumors, are rare neoplasms that typically originate from Schwann cells. These tumors most commonly occur in the head and neck region, particularly the tongue. While GCTs are generally benign, less than 2% of cases exhibit aggressive biological features such as rapid growth, high recurrence rates, and metastasis. In this report, we present a rare case of a Malignant Granular Cell Tumor (MGCT) of the chest wall, which posed significant challenges in both characterization and management.Case PresentationA fifty-year-old man underwent an ultrasound examination for a nodular mass on his right chest wall. The ultrasound revealed a firm, hard mass measuring 2 cm x 2 cm with an uncertain diagnosis. A fine-needle aspiration biopsy (FNAB) guided by ultrasound was performed, resulting in a diagnosis of Abrikossoff tumor. The patient subsequently underwent radical excision of the mass, which confirmed the initial diagnosis. Nine months after surgery, a new mass with similar characteristics was detected during a physical examination. The patient underwent a second surgery, but this time the histopathological examination was negative for neoplastic cells. However, another mass appeared at the same site as the previous surgical excision. A CT scan and MRI of the right chest wall confirmed the presence of a 2 cm x 2 cm nodular mass. The patient then underwent a deeper excision. Histomorphological and immunohistochemical assessments confirmed the recurrence of MGCT.ConclusionThis case highlights the malignant potential of GCTs. The numerous local recurrences necessitated three surgeries and additional procedures. The aggressive nature of this pathology underscores the complexity of managing these tumors, which are poorly understood and lack proven post-operative strategies for controlling local and distant disease.
Cue-based feeding in the NICU—a pathway to earlier oral feeding of preterm infants
Authors: Ofek Shlomai Noa , Mordechai Chen , Morag Iris , Bdolach Abram Tali , Eventov Friedman Smadar 
Published: September 2024

AimTo compare volume-driven and cue-based feeding of low birth weight preterm infants, regarding short-term outcomes, including transition to oral feeds, weight gain, and length of stay.MethodsThis was a retrospective cohort study. Feeding and weight gain outcomes were compared between infants fed by volume-driven and cue-based feeds. The groups were subdivided by birth weight categories.ResultsThe study group included 240 low birth weight preterm infants born before 34 weeks of gestation, 120 infants fed by volume-driven feeding were compared to 120 infants fed by cue-based feeding. The groups were sub-analyzed by birth weight categories: &lt;1,500 g and 1,500–2,500 g. Study groups were comparable regarding baseline characteristics and neonatal morbidities. Infants fed by cue-based feeding were more likely to achieve full oral feeding faster and at an earlier gestational age. Infants with a birth weight &lt;1,500 g were less likely to experience adverse respiratory episodes during cue-based feeding. Although the rate of weight gain was reduced in cue-based feeding in the heavier infant group, discharge weight, breastfeeding rates, and length of stay were comparable between the groups.ConclusionsCue-based feeding results in faster transition to full oral feeding in very low birth weight preterm infants and at an earlier gestational age.
Adverse event profile differences between pralsetinib and selpercatinib: a real-world study based on the FDA adverse events reporting system
Authors: Jie Qiong , Li Yuanyuan , Jing Li , Chen Jinjin , Li Yang 
Published: September 2024

AimsThe objective of this study is to compare the adverse events (AEs) associated with pralsetinib and selpercatinib.MethodsTo evaluate the imbalance of AEs linked to pralsetinib and selpercatinib in real-world data, the reporting odds ratio (ROR) was utilized to detect potential signals of AEs. Stratified analysis was conducted to examine the differences in AEs occurring among different genders and age groups taking pralsetinib and selpercatinib.ResultsFAERS received 891 reports for pralsetinib and 569 reports for selpercatinib. Our analysis confirmed expected AEs like hypertension, fatigue, and elevated transaminase levels. Unexpected AEs such as rhabdomyolysis, myocardial injury and cognitive disorder were associated with pralsetinib, while selpercatinib was linked with pulmonary embolism, deep vein thrombosis, and pericardial effusion. The risk of AEs such as decreased platelet count, anemia, decreased white blood cell count, pneumonitis, asthenia, and edema caused by pralsetinib is significantly higher than that of selpercatinib. In contrast, the risk of AEs such as ascites, elevated alanine aminotransferase, and elevated aspartate aminotransferase caused by selpercatinib is significantly higher than that of pralsetinib. Women treated with pralsetinib experience higher rates of hypertension, pulmonary embolism, and blurred vision than men, who are more susceptible to rhabdomyolysis. Adults between 18 and 65 years are more likely to experience taste disorder, edema, and pulmonary embolism than individuals older than 65, who are particularly vulnerable to hypertension. For patients treated with selpercatinib, males demonstrate a significantly higher incidence of QT prolongation, urinary tract infection, and dysphagia. Individuals aged 18 to 65 are more likely to experience pyrexia and pleural effusion than those older than 65, who are more prone to hypersensitivity.ConclusionIn the clinical administration of pralsetinib and selpercatinib, it is crucial to monitor the effects of gender and age on AEs and to be vigilant for unlisted AEs.
A validated UPLC-MS/MS method for quantification of pyrotinib and population pharmacokinetic study of pyrotinib in HER2-positive breast cancer patients
Authors: Zhu Yunfang , Xu Yuxiang , Zhao Haopeng , Qie Hongxin , Gao Xiaonan , Gao Jinglin , Feng Zhangying , Bai Jing , Feng Rui , Wang Mingxia 
Published: September 2024

ObjectivePyrotinb has been approved for the treatment of HER2-positive advanced or metastatic breast cancer in China. However, the plasma concentration of pyrotinb in different patients varies greatly, and in the course of treatment, if patients have intolerable adverse reactions, the drug dosage will be reduced or even stopped. This study set out to establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the determination of pyrotinb in human plasma, analyze the population pharmacokinetics (PPK) of pyrotinib and assess the influence of patient variables on PK of pyrotinib in patients with HER2 positive breast cancer.MethodAn UPLC-MS/MS method was developed to measure pyrotinib in human plasma. Utilizing a gradient elution procedure and a Kinetex C18 column (2.1 mm × 100 mm, 1.7 μm), sample separation was accomplished in 5.5 min. Pyrotinb extraction via protein precipitation was used as a sample pre-treatment technique. In total, 50 patients provided 158 plasma samples, which were identified and used in the PPK investigation. The non-linear mixed-effects modeling (NONMEM) approach was used to assess the plasma concentrations and covariates information. For the final PPK model evaluation, external evaluation, non-parametric bootstrap, visual predictive check (VPC), and goodness-of-fit (GOF) were used.ResultsThe UPLC-MS/MS method for determining plasma concentration of pyrotinib in patients had good selectivity and linearity in the range of 1–1,000 ng/mL. Pyrotinib concentration profile in HER2-positive breast cancer patients was well described by a single-compartment PPK model with first-order absorption and elimination. The formulas for the final estimated values of overall parameters of CL/F and Vd/F and Ka are respectively: CL/FL/h=88.8×eTP/67.2×0.376, V/FL=3940, KAh−1=0.357FIXED. No dosage adjustment was advised, despite the possibility that the total protein levels could have a substantial impact on the apparent distribution volume of pyrotinib with limited magnitude.ConclusionIn this study, an UPLC-MS/MS method was established to determine the concentration of pyrotinib in human plasma. A population pharmacokinetic model of pyrotinib in HER2 positive breast cancer patients suggested that low serum total protein reduced the clearance rate of pyrotinib in patients. Clinical medical staff should pay attention to the liver function of patients with abnormal serum total protein and be alert to the occurrence of adverse drug reactions.
A quantitative systems pharmacology (QSP) platform for preclinical to clinical translation of in-vivo CRISPR-Cas therapy
Authors: Desai Devam A. , Schmidt Stephan , Cristofoletti Rodrigo 
Published: September 2024

Background: In-vivo CRISPR Cas genome editing is a complex therapy involving lipid nanoparticle (LNP), messenger RNA (mRNA), and single guide RNA (sgRNA). This novel modality requires prior modeling to predict dose-exposure-response relationships due to limited information on sgRNA and mRNA biodistribution. This work presents a QSP model to characterize, predict, and translate the Pharmacokinetics/Pharmacodynamics (PK/PD) of CRISPR therapies from preclinical species (mouse, non-human primate (NHP)) to humans using two case studies: transthyretin amyloidosis and LDL-cholesterol reduction.Methods: PK/PD data were sourced from literature. The QSP model incorporates mechanisms post-IV injection: 1) LNP binding to opsonins in liver vasculature; 2) Phagocytosis into the Mononuclear Phagocytotic System (MPS); 3) LNP internalization via endocytosis and LDL receptor-mediated endocytosis in the liver; 4) Cellular internalization and transgene product release; 5) mRNA and sgRNA disposition via exocytosis and clathrin-mediated endocytosis; 6) Renal elimination of LNP and sgRNA; 7) Exonuclease degradation of sgRNA and mRNA; 8) mRNA translation into Cas9 and RNP complex formation for gene editing. Monte-Carlo simulations were performed for 1000 subjects and showed a reduction in serum TTR.Results: The rate of internalization in interstitial layer was 0.039 1/h in NHP and 0.007 1/h in humans. The rate of exocytosis was 6.84 1/h in mouse, 2690 1/h in NHP, and 775 1/h in humans. Pharmacodynamics were modeled using an indirect response model, estimating first-order degradation rate (0.493 1/d) and TTR reduction parameters in NHP.Discussion: The QSP model effectively characterized biodistribution and dose-exposure relationships, aiding the development of these novel therapies. The utility of platform QSP model can be paramount in facilitating the discovery and development of these novel agents.