bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy
Authors: Carbone Maria Luigia , Capone Alessia , Guercio Marika , Reddel Sofia , Silvestris Domenico Alessandro , Lulli Daniela , Ramondino Carmela , Peluso Daniele , Quintarelli Concetta , Volpe Elisabetta , Failla Cristina Maria 
Published: August 2023

IntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor.
The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers
Authors: Biatta Chiara M. , Paudice Michele , Greppi Marco , Parrella Veronica , Parodi Alessia , De Luca Giuseppa , Cerruti Gianna Maria , Mammoliti Serafina , Caroti Cinzia , Menichini Paola , Fronza Gilberto , Pesce Silvia , Marcenaro Emanuela , Vellone Valerio G. 
Published: August 2023

Backgroundwe evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups.Methodspatients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS).Results34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16].Conclusionimmunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup.
Development and external validation of a mixed-effects deep learning model to diagnose COVID-19 from CT imaging
Authors: Bridge Joshua , Meng Yanda , Zhu Wenyue , Fitzmaurice Thomas , McCann Caroline , Addison Cliff , Wang Manhui , Merritt Cristin , Franks Stu , Mackey Maria , Messenger Steve , Sun Renrong , Zhao Yitian , Zheng Yalin 
Published: August 2023

BackgroundThe automatic analysis of medical images has the potential improve diagnostic accuracy while reducing the strain on clinicians. Current methods analyzing 3D-like imaging data, such as computerized tomography imaging, often treat each image slice as individual slices. This may not be able to appropriately model the relationship between slices.MethodsOur proposed method utilizes a mixed-effects model within the deep learning framework to model the relationship between slices. We externally validated this method on a data set taken from a different country and compared our results against other proposed methods. We evaluated the discrimination, calibration, and clinical usefulness of our model using a range of measures. Finally, we carried out a sensitivity analysis to demonstrate our methods robustness to noise and missing data.ResultsIn the external geographic validation set our model showed excellent performance with an AUROC of 0.930 (95%CI: 0.914, 0.947), with a sensitivity and specificity, PPV, and NPV of 0.778 (0.720, 0.828), 0.882 (0.853, 0.908), 0.744 (0.686, 0.797), and 0.900 (0.872, 0.924) at the 0.5 probability cut-off point. Our model also maintained good calibration in the external validation dataset, while other methods showed poor calibration.ConclusionDeep learning can reduce stress on healthcare systems by automatically screening CT imaging for COVID-19. Our method showed improved generalizability in external validation compared to previous published methods. However, deep learning models must be robustly assessed using various performance measures and externally validated in each setting. In addition, best practice guidelines for developing and reporting predictive models are vital for the safe adoption of such models.
Mendelian randomization analysis revealed a gut microbiota–mammary axis in breast cancer
Authors: Zhang Shuwan , Zhang Wenchuan , Ren Haiyue , Xue Rui , Wang Zitong , Wang Zhe , Lv Qingjie 
Published: August 2023

BackgroundObservational epidemiological studies suggested an association between the gut microbiota and breast cancer, but it remains unclear whether the gut microbiota causally influences the risk of breast cancer. We employed two-sample Mendelian randomization (MR) analysis to investigate this association.MethodsWe used summary statistics of the gut microbiome from a genome-wide association study (GWAS) of 18,340 individuals in the MiBioGen study. GWAS summary statistics for overall breast cancer risk and hormone receptor subtype-specific analyses were obtained from the UK Biobank and FinnGen databases, totaling 400,000 individuals. The inverse variance-weighted (IVW) MR method was used to examine the causal relationship between the gut microbiome and breast cancer and its subtypes. Sensitivity analyses were conducted using maximum likelihood, MR-Egger, and MR pleiotropic residual sums and outliers methods.ResultsThe IVW estimates indicated that an increased abundance of Genus_Sellimonas is causally associated with an increased risk of ER+ breast cancer [odds ratio (OR) = 1.09, p = 1.72E−04, false discovery rate (FDR) = 0.02], whereas an increased abundance of Genus_Adlercreutzia was protective against ER+ breast cancer (OR = 0.88, p = 6.62E−04, FDR = 0.04). For Her2+ breast cancer, an increased abundance of Genus_Ruminococcus2 was associated with a decreased risk (OR = 0.77, p = 4.91E−04, FDR = 0.04), whereas an increased abundance of Genus_Erysipelatoclostridium was associated with an increased risk (OR = 1.25, p = 6.58E−04, FDR = 0.04). No evidence of heterogeneity or horizontal pleiotropy was found.ConclusionOur study revealed a gut microbiota–mammary axis, providing important data supporting the potential use of the gut microbiome as a candidate target for breast cancer prevention, diagnosis, and treatment.
Effects of adult education on cognitive function and risk of dementia in older adults: a longitudinal analysis
Authors: Takeuchi Hikaru , Kawashima Ryuta 
Published: August 2023

IntroductionMid/late-life cognitive activities are associated with a lower rate of subsequent cognitive decline and lower subsequent dementia risk over time.MethodsIn this study, we investigated the association between adult education class participation and subsequent cognitive decline and dementia risk over time after adjusting for baseline cognitive function and genetic risk of dementia, correcting for several potential confounding variables, using a large prospective cohort data of participants from the UK Biobank study followed from 2006 to 2010.ResultsThe results revealed that participation in adult education classes at baseline was associated with greater subsequent retention of fluid intelligence score. Cox proportional hazard models revealed that subjects who participated in adult education classes showed a significantly lower risk of incident dementia 5 years after baseline compared with those that did not at baseline.DiscussionIn this study, we show that participation in adult education classes preceded greater retention of subsequent fluid intelligence and a lower risk of developing dementia after 5 years: this association did not change after adjusting for cognitive function at baseline or genetic predisposition to dementia. Accordingly, participation in such classes could reduce the risk of developing dementia.
The role of electrocochleography and the caloric test in predicting short-term recurrence of benign paroxysmal positional vertigo
Authors: Zhang Yanmei , Wang Yueqi , Zhen Zhen , Zhang Junbo , Zeng Zhengang , Zhong Zhen , Wang Quangui 
Published: August 2023

ObjectiveThe study aimed to assess the value of physiological tests for evaluating inner ear function in predicting the short-term recurrence of benign paroxysmal positional vertigo (BPPV).Materials and methodsThe clinical information of all idiopathic BPPV patients who were treated in our clinic between February 2021 and December 2022 were reviewed. All patients included in the study had completed audiology examinations including pure tone audiometry, electrocochleography (EcochG), auditory brainstem response, and vestibular function examination such as the vestibular caloric test. The relationships between the results of the above tests and short-term recurrent BPPV were analyzed.ResultsA total of 96 patients with unilateral idiopathic BPPV were included for analysis. The numbers of non-recurrent patients and recurrent patients were 57 (59.4%) and 39 (40.6%), respectively. Only the results of EcochG and the caloric test showed significant differences between non-recurrent and recurrent patients (both P &lt; 0.05). The results of these two tests were also found to be independently predictive of short-term recurrence (both P &lt; 0.05). The non-recurrence rate for patients with normal results in both tests reached up to 78.3%, which was significantly higher than that for patients with abnormal results in both tests, 28.6% (P &lt; 0.05).ConclusionEndolymphatic hydrops and canal paresis were independent risk factors for short-term recurrent BPPV. Additional treatments should be considered to reduce the recurrence rate, including dehydration treatment and vestibular rehabilitation.
Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane
Authors: Xu Hongliang , Lv Hanyu , Chen Xin , Lian Yajun , Xing Guolan , Wang Yingzi , Hu Ruimin 
Published: August 2023

IntroductionWilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition.MethodsA total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated.ResultsWe identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G&gt;T (R778L, 39.06%, exon 8), followed by c.2621C&gt;T (A874V, 10.94%, exon 11) and c.3316G&gt;A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study.DiscussionOur work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD.
Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation
Authors: Janilkarn-Urena Isis , Idrissova Alina , Zhang Mindy , VanDreal Masha , Sanghavi Neysa , Skinner Samantha G. , Cheng Sydney , Zhang Zeyu , Watanabe Junji , Asatryan Liana , Cadenas Enrique , Davies Daryl L. 
Published: August 2023

IntroductionExcessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin (DHM) is a bioactive polyphenol and flavonoid that has traditionally been used in Chinese herbal medicine for its robust antioxidant and anti-inflammatory properties. It is derived from many plants, including Hovenia dulcis and is found as the active ingredient in a variety of popular hangover remedies. Investigations utilizing DHM have demonstrated its ability to alleviate ethanol-induced disruptions in mitochondrial and lipid metabolism, while demonstrating hepatoprotective activity.MethodsFemale c57BL/6J mice (n = 12/group) were treated using the Lieber DeCarli forced-drinking and ethanol (EtOH) containing liquid diet, for 5 weeks. Mice were randomly divided into three groups: (1) No-EtOH, (2) EtOH [5% (v/v)], and (3) EtOH [5% (v/v)] + DHM (6 mg/mL). Mice were exposed to ethanol for 2 weeks to ensure the development of ALD pathology prior to receiving dihydromyricetin supplementation. Statistical analysis included one-way ANOVA along with Bonferroni multiple comparison tests, where p ≤ 0.05 was considered statistically significant.ResultsDihydromyricetin administration significantly improved aminotransferase levels (AST/ALT) and reduced levels of circulating lipids including LDL/VLDL, total cholesterol (free cholesterol), and triglycerides. DHM demonstrated enhanced lipid clearance by way of increased lipophagy activity, shown as the increased interaction and colocalization of p62/SQSTM-1, LC3B, and PLIN-1 proteins. DHM-fed mice had increased hepatocyte-to-hepatocyte lipid droplet (LD) heterogeneity, suggesting increased neutralization and sequestration of free lipids into LDs. DHM administration significantly reduced prominent pro-inflammatory cytokines commonly associated with ALD pathology such as TNF-α, IL-6, and IL-17.DiscussionDihydromyricetin is commercially available as a dietary supplement. The results of this proof-of-concept study demonstrate its potential utility and functionality as a cost-effective and safe candidate to combat inflammation and the progression of ALD pathology.
Bioanalytical method validation and application to a phase 1, double-blind, randomized pharmacokinetic trial of a standardized Centella asiatica (L.) Urban water extract product in healthy older adults
Authors: Wright Kirsten M. , Bollen Melissa , David Jason , Mepham Bridgette , Alcázar Magaña Armando , McClure Christine , Maier Claudia S. , Quinn Joseph F. , Soumyanath Amala 
Published: August 2023

Introduction:Centella asiatica is an herbaceous plant reputed in Eastern medicine to improve memory. Preclinical studies have shown that C. asiatica aqueous extract (CAW) improves neuronal health, reduces oxidative stress, and positively impacts learning and cognition. This study aimed to develop and validate bioanalytical methods for detecting known bioactive compounds from C. asiatica in human biological matrices and apply them to a human pharmacokinetic trial in healthy older adults.Methods: High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used for detecting triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. Validation parameters including linearity, precision, accuracy, recovery and thermal stability were evaluated. The method was applied to a Phase I, randomized, double-blind, crossover trial of two doses (2 or 4 g) of a standardized C. asiatica water extract product (CAP) in eight healthy older adults. Pharmacokinetic parameters were measured over a 12-h post administration period and acute safety was assessed.Results: The method satisfied US Food &amp; Drug Administration criteria for linearity and recovery of the analytes of interest in human plasma and urine. The method also satisfied criteria for precision and accuracy at medium and high concentrations. Single administration of 2 and 4 g of CAP was well tolerated and safe in healthy older adults. The parent triterpene glycosides, asiaticoside and madecassoside, were not detected in plasma and in minimal amounts in urinary excretion analyses, while the aglycones, asiatic acid and madecassic acid, showed readily detectable pharmacokinetic profiles. Similarly, the di-caffeoylquinic acids and mono-caffeoylquinic acids were detected in low quantities, while their putative metabolites showed readily detectable pharmacokinetic profiles and urinary excretion.Discussion: This method was able to identify and calculate the concentration of triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. The oral absorption of these key compounds from CAP, and its acute safety in healthy older adults, support the use of this C. asiatica product in future clinical trials.
Multisystem inflammatory syndrome drug treatment in countries with different income profiles: a scoping review
Authors: Nagem Lopes Luis Phillipe , da Cunha Lidiane Gomes , Silva Alice Ramos Oliveira , Land Marcelo Gerardin Poirot , Fonseca Adriana Rodrigues , Lopes Luciane Cruz , Lima Elisangela Costa 
Published: August 2023

Objective: The purpose of this study was to map and describe the studies that have investigated therapeutic alternatives for the management of paediatric multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Considering the origin of the studies performed (low-, middle- and high-income countries), a systematic scoping review was conducted with primary studies that reported the use of medications for the treatment of patients with MIS-C.Sources: The searches were performed in MEDLINE, Embase, Lilacs, Epistemonikos, CINAHL, and CENTRAL, in the grey literature (theses and dissertations from CAPES, ProQuest, and PROSPERO) and in clinical trial databases until May 2022. The selection and extraction of studies were performed independently by two reviewers.Summary of the findings: A total of 173 studies were included, most of which were published as case reports or series. No randomized controlled clinical trials (RCTs) were identified. The investigated drugs were immunoglobulins, glucocorticoids, monoclonal antibodies, anticoagulants, and antiplatelet agents.Conclusion: The dosages, when reported, were heterogeneous among the studies. The ethnicity and comorbidity of the participants were poorly reported. Monoclonal antibodies, drugs with higher costs, were mostly described in studies of high-income countries.
Impact of continuous pharmaceutical care led by clinical pharmacists during transitions of care on medication adherence and clinical outcomes for patients with coronary heart disease: a prospective cohort study
Authors: Gao Lingyan , Han Yalei , Jia Zhankun , Wang Pengfei , Zhang Meijing , Ma Teng , Yan Suying , Liu Hua 
Published: August 2023

Objectives: The study aimed to explore the impact of a continuous pharmaceutical care (CPC) program during care transitions on medication adherence and clinical outcomes for patients with coronary heart disease (CHD).Methods: A prospective cohort study was conducted from April 2020 to February 2021. Patients diagnosed with CHD were selected and divided into intervention (CPC) and usual care (UC) groups by nurses at equal intervals based on admission time. The intervention group received CPC services provided by clinical pharmacists (including medication reconciliation, disease education, medication guidance, lifestyle counseling, and follow-up services) and usual care. The UC group received only routine medical care. The study compared medication adherence, clinical indicators (low-density lipoprotein cholesterol [LDL-C], blood pressure [BP], glycated hemoglobin [HbA1c] control rates), the incidence of adverse drug reactions (ADRs), and readmission rates (overall, major adverse cardiovascular events [MACEs]-related, and CHD risk factors-related) at admission and 1, 3, and 6 months after discharge between the two groups.Results: A total of 228 patients with CHD completed the study, including 113 patients in the CPC group and 115 patients in the UC group. There were no significant differences (p &gt; 0.05) in both groups in demographic and clinical characteristics at baseline. A total of 101 drug-related problems were identified in the CPC group (an average of 0.89 per person). The CPC group showed significantly higher medication adherence at 1, 3, and 6 months after discharge than the UC group (p &lt; 0.05). At 3 and 6 months after discharge, the intervention group had significantly higher control rates of LDL-C (61.11% vs. 44.64% at 3 months, 78.18% vs. 51.43% at 6 months), and BP (91.15% vs. 77.39% at 3 months, 88.50% vs. 77.19% at 6 months). The CPC group had higher HbA1c control rates (53.85% vs. 34.21% at 3 months, 54.05% vs. 38.46% at 6 months) than the UC group. However, the differences were not statistically significant. The incidence of ADRs 6 months after discharge was significantly lower in the CPC group than in the UC group (5.13% vs. 12.17%, p &lt; 0.05). The CPC group had a lower overall readmission rate (13.27% vs. 20.00%), MACE-related readmission rate (5.31% vs. 12.17%), and readmission rate related to CHD risk factors (0.88% vs. 2.61%) 6 months after discharge compared to the UC group. However, these differences were not statistically significant (p &gt; 0.05).Conclusion: CPC led by clinical pharmacists during care transitions effectively improved medication adherence, safety, and risk factor control in patients with CHD.