bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin‐dependent kinase 4/6 inhibitors and cardiotoxic events in breast cancer: A pharmacovigilance study based on the FAERS database
Authors: Li Ting , Zhang Miaomiao , Zhang Tian , Li Shaoqiang , Kou Chen , Zhao Ming , Huang Jing , Cao Weihang , Jin Pengfei 
Published: November 2024

AbstractRecent trials have highlighted the cardiotoxicity of ribociclib, a CDK4/6 inhibitor, particularly its association with QT prolongation. However, studies on the link between CDK4/6 inhibitors and cardiotoxic events show inconsistent results, and the factors influencing these events and related drug interactions remain underexplored. To address these uncertainties, our study utilizes the FDA adverse event reporting system database (Q1 2015 to Q1 2024) to examine the cardiotoxic events of CDK4/6 inhibitors in breast cancer patients. We employed a comprehensive analytical framework, applying disproportionality methods including Bayesian confidence propagation neural network, proportional reporting ratio, and reporting odds ratio. Our findings highlight significant variability in cardiotoxic events among different CDK4/6 inhibitors, with ribociclib (IC: 0.26, 95%CI: 0.18–0.34) exhibiting pronounced cardiotoxicity. Notably, ribociclib was associated with serious cardiotoxic events such as torsade de pointes/QT prolongation (IC: 2.11, 95% CI: 1.90–2.29) and conduction defects (IC: 2.07, 95% CI: 1.87–2.23). For the first time, palbociclib has been identified with positive signals for cardiotoxic events at the preferred terms level, including pulmonary oedema, increased blood pressure, myocardial infarction, and cardiac flutter. Moreover, multivariable logistic regression and Bayesian network analyses reveal that age, geographic location, and the number of concomitant medications significantly influence cardiotoxic events. Our study also highlights significant drug interactions that increase the probability of specific cardiotoxic outcomes, notably with drugs like sertraline, lansoprazole, capecitabine, and torasemide. These findings highlight the need for personalized treatment plans to mitigate cardiotoxic events and improve patient safety.
Postprandial Sleep in Short‐Sleeping Mexican Cavefish
Authors: Gallman Kathryn , Rastogi Aakriti , North Owen , O'Gorman Morgan , Hutton Pierce , Lloyd Evan , Warren Wesley C. , Kowalko Johanna E. , Duboue Erik R. , Rohner Nicolas , Keene Alex C. 
Published: November 2024

ABSTRACTInteractions between sleep and feeding behaviors are critical for adaptive fitness. Diverse species suppress sleep when food is scarce to increase the time spent foraging. Postprandial sleep, an increase in sleep time following a feeding event, has been documented in vertebrate and invertebrate animals. While interactions between sleep and feeding appear to be highly conserved, the evolution of postprandial sleep in response to changes in food availability remains poorly understood. Multiple populations of the Mexican cavefish, Astyanax mexicanus, have independently evolved sleep loss and increased food consumption compared to surface‐dwelling fish of the same species, providing the opportunity to investigate the evolution of interactions between sleep and feeding. Here, we investigate the effects of feeding on sleep in larval and adult surface fish, and in two parallelly evolved cave populations of A. mexicanus. Larval surface and cave populations of A. mexicanus increase sleep immediately following a meal, providing the first evidence of postprandial sleep in a fish model. The amount of sleep was not correlated to meal size and occurred independently of feeding time. In contrast to larvae, postprandial sleep was not detected in adult surface or cavefish, which can survive for months without food. Together, these findings reveal that postprandial sleep is present in multiple short‐sleeping populations of cavefish, suggesting sleep‐feeding interactions are retained despite the evolution of sleep loss. These findings raise the possibility that postprandial sleep is critical for energy conservation and survival in larvae that are highly sensitive to food deprivation.
Association between serum alder‐specific immunoglobulin E positivity and seasonal onset of eosinophilic esophagitis
Authors: Watanabe Akihiro , Tanaka Fumio , Sawada Akinari , Nishida Yu , Maruyama Hirotsugu , Ominami Masaki , Otani Koji , Fukunaga Shusei , Hosomi Shuhei , Fujiwara Yasuhiro 
Published: November 2024

AbstractBackground and AimPollen exposure may induce seasonal onset of eosinophilic esophagitis. However, whether serum pollen‐specific immunoglobulin E positivity can predict such seasonal eosinophilic esophagitis onset remains unclear. Here, we aimed to evaluate the association between pollen‐specific immunoglobulin E positivity and the seasonal onset of eosinophilic esophagitis during the pollen dispersal period.MethodsWe seasonally classified eosinophilic esophagitis patients and compared their clinical and endoscopic findings. Seasonal trends with respect to the positivity rate of serum pollen‐specific immunoglobulin E were examined. Pollens such as alder, cedar, cypress, birch, orchard grass, timothy, ragweed, and mugwort were evaluated. We classified patients into two groups: tested positive or negative for each pollen‐specific immunoglobulin E. We then evaluated whether the positivity of each pollen‐specific immunoglobulin E was associated with the seasonal onset of eosinophilic esophagitis during the pollen dispersal period.ResultsWe included 122 patients diagnosed with eosinophilic esophagitis between 2010 and 2019. Among them, 31 (25.4%), 42 (34.4%), 29 (23.8%), and 20 (16.4%) patients were diagnosed during spring, summer, fall, and winter, respectively. No significant differences were observed in clinical and endoscopic findings across seasons. No significant seasonal trends were observed in the positivity rate of each pollen‐specific immunoglobulin E. The positivity rate of alder‐specific immunoglobulin E was significantly associated with the seasonal onset of eosinophilic esophagitis (P < 0.01). However, the positivity rates of other pollen‐specific immunoglobulin E were not associated with the seasonal onset of eosinophilic esophagitis.ConclusionsSerum alder‐specific immunoglobulin E positivity was associated with the seasonal onset of eosinophilic esophagitis.
Association between microenvironment‐related genes and prognosis of primary central nervous system lymphoma
Authors: Hattori Keiichiro , Makishima Kenichi , Suma Sakurako , Abe Yoshiaki , Suehara Yasuhito , Sakamoto Tatsuhiro , Kurita Naoki , Ishii Ryota , Matsuoka Ryota , Matsuda Masahide , Tsurubuchi Takao , Nishikawa Ryo , Tanaka Shota , Mukasa Akitake , Narita Yoshitaka , Ichimura Koichi , Nagane Motoo , Takano Shingo , Mathis Bryan J. , Ishikawa Eiichi , Matsubara Daisuke , Chiba Shigeru , Sakata‐Yanagimoto Mamiko 
Published: November 2024

AbstractBackgroundPrimary central nervous system lymphoma (PCNSL) is a rare lymphoid malignancy. Systemic profiling of the PCNSL tumor microenvironment (TME) was previously conducted through gene expression analysis. We investigated the prognostic impact of TME on survival to establish novel prognostic biomarkers in PCNSL patients.MethodsWe analyzed expression levels of 770 neuroinflammation‐related (NFR) genes via NanoString nCounter technology in tumor samples from 30 PCNSL patients. Genes related to the “recurrence group (RG)” or “non‐recurrence group (NRG)” were identified and validated using whole transcriptomic analysis of an independent PCNSL cohort (n = 30).ResultsForty‐five of 770 NFR genes were highly expressed in the RG (3‐year overall survival (OS, 22.2%), compared with the NRG group (3‐year OS 66.7%). Signatures related to glial cells were enriched in the RG‐associated gene set. Multivariate analysis revealed that high expressions of TUBB4A (p = 0.028, HR: 3.88), S100B (p = 0.046, HR: 3.093), and SLC6A1 (p = 0.034, HR: 3.765) were significantly related to death. Expression levels of these three genes were also significantly associated with poor OS in the validation cohort. Immunohistochemical staining against TUBB4A, S100B, and proteins specific to glial cells (GFAP, OLIG2, and CD68) revealed significantly higher positivity in RG glial cells.ConclusionThese data suggest that TME‐related genes play a crucial role in the pathogenesis of PCNSL, complementing the well‐known involvement of the NF‐kB signaling pathway. TME targeting, especially glial cell‐specific proteins, may thus open new and complementary avenues of therapy for all stages of PCNSL.
Atrial arrhythmias with mediastinal lymphadenopathy presentation of isolated atrial myocarditis
Authors: Kumar Sharath , Yalagudri Sachin , Saggu Daljeet , Mansoor M. , Tourani Vijaya K. , Narasimhan Calambur 
Published: November 2024

AbstractObjectivesWe present a case series of patients with granulomatous myocarditis presenting as atrial arrhythmias accompanied by lymphadenopathy.BackgroundAtrial myocarditis (AM) may be the cause of atrial fibrillation (AF) in patients without risk factors.MethodsPatients with atrial fibrillation without risk factors underwent 18F‐Fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET). We performed biopsy of lymph nodes or myocardium in patients with atrial uptake of 18F‐FDG‐PET.ResultsAM was observed in 15 patients. The median age of the patients was 42 years and left ventricular ejection fraction (LVEF) at presentation was 45%. All patients had AF, atrial flutter was noted in 4 patients (26.7%) and 2 patients (13.3%) had atrioventricular nodal reentrant tachycardia (AVNRT). 18F‐FDG‐PET uptake was noted in the atria in all patients and in the ventricles in 3 patients (20%). Cardiac sarcoidosis was the diagnosis in 12 patients (80%) while 3 patients (20%) had tuberculosis. The median CHA2DS2 VASc score was 1. Four patients (26.7%) presented with ischemic stroke. All patients were treated with disease‐specific therapy in addition to antiarrhythmic medications. Over a median follow up of 26 months, a significant improvement in clinical status commensurate with a decline in atrial uptake was noted. A non‐significant improvement in LVEF to 56% with disease‐specific therapy was observed. (p = 0.09).ConclusionAtrial fibrillation with granulomatous lymphadenopathy may be a presenting feature of AM. The risk of stroke is high in these individuals. AM should be suspected in young individuals presenting with atrial fibrillation and stroke without conventional risk factors.
Regulation of MareA Gene on Monascus Growth and Metabolism Under Different Nitrogen Sources
Authors: Li Zhuolan , Zhang Sicheng , Guo Shixin , Li Ailing , Wang Yurong 
Published: November 2024

ABSTRACTMonascus is a widely used natural microorganism in our country, which can produce useful secondary metabolites. Studies have shown that the nitrogen source directly affects the growth, reproduction, and secondary metabolites of Monascus. As a global transcriptional regulator of nitrogen metabolism, MareA gene is involved in the regulation of secondary metabolism. In this study, we found the MareA gene that is highly homologous to the AreA gene sequence, and used MareA to obtain ΔMareA and OE‐MareA. Three strains were cultured with glutamine, urea, NaNO3, and (NH4)2SO4 nitrogen sources. The Monascus pigments and related genes were analyzed by solid‐state fermentation under different nitrogen sources. The results showed that the pigment production of the ΔMareA decreased, but the OE‐MareA did the opposite. The secondary metabolites of the three strains were analyzed by HPLC and expression level of pigment biosytnthesis gene was determined by RT‐qPCR. The relative expression levels of four key Monascus pigment genes in ΔMareA were significantly upregulated in mppE gene, but downregulated in MpPKS5, mppG, and mppD genes. Monascus pigment genes were increased in OE‐MareA. In terms of growth regulation, the expression of VosA and LaeA genes was significantly reduced in ΔMareA, while OE‐MareA significantly promoted the expression of GprD genes. The pigment production and gene expression in ΔMareA were significantly lower than that of C100, while the opposite was true of OE‐MareA when NaNO3 was added to the culture medium. In conclusion, MareA gene had different regulatory effects on Monascus growth and pigments metabolism under different nitrogen sources.
Upadacitinib is associated with clinical response and steroid‐free remission for children and adolescents with inflammatory bowel disease
Authors: Runde Joseph , Ryan Kelsey , Hirst Joseph , Lebowitz Jonathan , Chen Wenya , Brown Jeffrey , Strople Jennifer 
Published: November 2024

AbstractObjectiveUpadacitinib, an oral Janus kinase inhibitor (JAKi), is approved for inflammatory bowel disease (IBD) in adults. As on‐label use will face significant delay in pediatrics, a real‐world understanding of safety and efficacy in children is critical.MethodsThis is a single‐center retrospective cohort of pediatric subjects (ages 9–20 years) with a diagnosis of IBD initiated on upadacitinib. The primary outcome was clinical response following induction (decrease of ≥20 points in the Pediatric Ulcerative Colitis Activity Index [PUCAI] or ≥12.5 points for the Pediatric Crohn's Disease Activity Index [PCDAI]). Secondary outcomes included steroid‐free clinical remission (SF‐CR) following induction and at Week 24 (PUCAI or PCDAI ≤10), post‐induction mucosal response and remission (Mayo for ulcerative colitis [UC]/IBD‐unclassified [IBD‐U] and simple‐endoscopic scoring for CD), and improvement in calprotectin and C‐reactive protein (CRP) post‐induction. Monitoring for adverse events was recorded.ResultsTwenty subjects (40% female with a median age of 16.3 years; 3 CD, 13 UC, 4 IBD‐U) were initiated on upadacitinib. Clinical response at Week 8 (UC/IBD‐U) and Week 12 (CD), was achieved in 90% (18/20). SF‐CR was seen in 75% (16/20) following induction and maintained in 65% (11/17) reaching Week 24 of therapy. In subjects with UC/IBD‐U (17), PUCAI was significantly improved at Weeks 8 and 24. Calprotectin post‐induction showed a significant downtrend, whereas CRP did not. Endoscopic response was noted in seven of the eight cases, with three achieving endoscopic remission. One patient underwent subtotal colectomy after 2 weeks of upadacitinib induction. Another patient stopped therapy following the creation of a diverting ileostomy secondary to rectal perforation experienced following manual dilation of a rectal stricture. No new safety signals were reported.ConclusionTherapeutic options for children with IBD remain limited. In cases refractory to approved agents, our experience suggests that upadacitinib is effective with no new safety signals in a small subset of patients with IBD (ages 9–20 years) treated at a children's hospital.
Sequential fermentation of Ginkgo biloba seeds by Bacillus subtilis natto and Lactobacillus plantarum enhanced nutrition, flavor and lipid‐lowering activity
Authors: Bai Yun , Fang Xianying , Jiang Yunpeng , Xu Jiahui , Wu Lulu , Li Qi , Cao Fuliang , Zhao Linguo 
Published: November 2024

AbstractBACKGROUNDGinkgo biloba seeds (GBS) are rich in flavonoids, proteins and reducing sugar, and have been consumed as food and medicinal nuts for thousands of years. However, the presence of ginkgotoxins and their poor palatability limit people's consumption of them.RESULTSThis study used solid‐state fermentation with Bacillus subtilis natto and Lactobacillus plantarum to enhance the safety and benefits of GBS. Optimized fermentation conditions increased the content of beneficial components like total flavonoids, soluble protein and reducing sugar while eliminating unpleasant odors (isoamyl aldehyde and hexanal) and reducing the toxin 4′‐O‐methylpyridoxine by 91.17%. Fermentation of GBS powder can significantly enhance its anti‐inflammatory and antioxidant activities in vitro (P < 0.001). Furthermore, it exhibits a dose‐dependent effect within a certain concentration range. Mixed fermentation (FBnLp) was evaluated for its effects on obesity and metabolic syndrome in mice fed a high‐fat diet. FBnLp significantly reduced body and liver weight gain, prevented dyslipidemia and decreased inflammatory and oxidative stress compared to unfermented GBS. Histological analysis showed that FBnLp improved liver health by reducing fat accumulation and preventing non‐alcoholic fatty liver disease. Meanwhile, it was found that feeding FBnLp increased the expression of CPT‐1α, which regulates energy expenditure and fat breakdown, and downregulated the expression of SREBP‐1c, FAS and ACC, which regulate fat synthesis.CONCLUSIONThis research provides new insights and technological support for the application and development of FBnLp as a functional product, addressing key issues in its use and industry growth. © 2024 Society of Chemical Industry.
Preclinical development and characterisation of PP353, a formulation of linezolid for intradiscal administration
Authors: Hagger Graham , Guest Sarah , Birchall Stephen , Bradley Alys , Brindley Charlie , Corbett David , Cummings Paul J. , Freire Cristina , Harris James , Wise Andrew , Wood Melanie , Czaplewski Lloyd G. 
Published: November 2024

AbstractIntroductionBacterial infection of the intervertebral disc can lead to vertebral endplate edema known as Modic changes, with associated chronic low back pain. Oral antimicrobial therapy has shown efficacy but relies on prolonged dosing and may not be optimal in terms of patient outcome, side effects, or antibiotic stewardship. There is no antibiotic formulation approved for intradiscal administration. Here, we describe the development and preclinical characterization of a formulation of linezolid, a suspension of 50 mg/mL micronized powder, for intradiscal administration.MethodsMicronization, particle size analysis, Franz cell diffusion assays, ex vivo bioassay, and estimates of gelling temperature were used to optimize the composition and properties of the formulation. Performance of the formulation was assessed using sheep to characterize the pharmacokinetics and a model of intradiscal infection was developed to demonstrate efficacy. Suitability for human administration was demonstrated in a Good Laboratory Practice (GLP) local tolerance study.ResultsMicronized linezolid, formulated as a powder suspension using a vehicle containing poloxamer 407 and iohexol, provided a temperature‐dependent radio‐opaque gel that was suitable for image‐guided percutaneous intradiscal administration. Efficacy in a sheep model of intradiscal Staphylococcus aureus infection was demonstrated. The formulation provides a high level of sheep disc tissue exposure, with Cmax of 6500 μg/g and limited systemic exposure, with a plasma Cmax of 0.04 μg/mL per 0.1 mL dose (5 mg of linezolid). Deconvolution of plasma linezolid pharmacokinetics correlated with linezolid remaining in the disc over time. Observations from a GLP local tolerance study with the linezolid formulation were of a minor nature and related to the intradiscal administration procedure.ConclusionsLinezolid can be formulated for image‐guided percutaneous intradiscal administration. The formulation is now in a Phase 1b clinical trial to evaluate safety, pharmacokinetics, and efficacy in patients with CLBP and suspected bacterial infection.
Cognitive‐Affective‐Behavioral Themes in Post‐Purchase Attitudes Toward Virtual Tourism Experiences: A Mixed‐Method Approach
Authors: Baruah Angana , Chatterjee Devlina 
Published: November 2024

ABSTRACTVirtual tourism experiences (VTEs) have grown rapidly after COVID and are expected to grow further. Customer attitudes toward VTEs are therefore of interest. Attitude, in general, is known to have three components: cognitive, affective, and behavioral. Thematic details of attitudes toward VTEs have not yet been explored, motivating the current study. We use a mixed‐method approach to explore latent themes within online reviews for VTEs. Latent Dirichlet allocation, used for topic modeling, is applied to 58,675 reviews from Airbnb online experiences. Next, we analyze 70 online reviews from Viator using thematic analysis. The primary themes that emerge are host appreciation, recommendation, hedonic experience, interactive aspects, social connections, and culture and learning. We discuss in detail how these themes relate to the tri‐component model of attitude. Our study of post‐purchase consumer attitudes provides new insights into the design, delivery, and marketing of VTEs which has academic as well as managerial implications.
Undergoing cartilage procedures before total knee arthroplasty is not associated with worse postoperative functional outcomes, readmission rates or complication rates
Authors: Khan Irfan A. , Cozzarelli Nicholas F. , Hohmann Alexandra L. , Siddiqui Hassan , Tjoumakaris Fotios P. , Freedman Kevin B. , Fillingham Yale A. 
Published: November 2024

AbstractPurposePatients undergoing total knee arthroplasty (TKA) with prior knee cartilage surgery have unclear outcomes in the literature. This study compared outcomes after TKA in patients with or without prior knee cartilage surgery, and we hypothesized there would be equivocal outcomes between groups.MethodsA retrospective matched case–control study was conducted on patients from our institution who underwent ipsilateral cartilage procedure(s) and TKA (cases) or TKA alone (controls) from 2000 to 2022. Cartilage procedures included Autologous Chondrocyte Implantation (ACI), Osteochondral Allograft (OCA) and Microfracture (MFx). Matching was performed in 1:3 (case:control) ratio for age, sex, body mass index, Charlson Comorbidity Index, pre‐TKA Kellgren–Lawrence osteoarthritis grade and follow‐up for knee injury and osteoarthritis outcome score for joint replacement (KOOS‐JR). Mann–Whitney U and χ2 analyses were conducted, with significance being a p < 0.05. A priori power analysis required 29 patients per cohort to reach a clinically detectable difference of 11 for KOOS‐JR.ResultsForty‐three cases (one ACI, eight OCA and 34 MFx) and 129 controls were included after matching, with no significant demographic differences. Cases underwent TKA after cartilage surgery at a mean of 4.6 years. No significant differences existed between cases and controls for the preoperative KOOS‐JR (45.2 vs. 47.8; p = 0.353), postoperative KOOS‐JR (69.8 vs. 69.9; p = 0.974) or Delta KOOS‐JR (30.4 vs. 26.0; p = 0.387). No significant differences existed for 90‐day readmission rates (4.7% vs. 2.3%; p = 0.600) or revision TKA rates (11.6% vs. 5.4%; p = 0.177).ConclusionPatients with and without prior cartilage surgery experience similar functional outcomes, readmission rates and revision rates after TKA on the same knee. Patients who are candidates for TKA with a history of cartilage surgery may be counselled that their surgical history on that knee does not convey the risk of worse functional outcomes.Level of EvidenceLevel III case–control study.