bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of high-dose steroids versus low-dose steroids in the treatment of immune checkpoint inhibitor-associated myocarditis: a case series and systematic review
Authors: Man Xiuyue , Wang Hong , Chen Chen , Cong Xiaofeng , Sun Lemeng , Sun Xueru , Chen Chen , Zhang Jing , Yang Lei 
Published: February 2025

BackgroundImmune checkpoint inhibitor-associated myocarditis (ICI-M) is a rare yet potentially fatal complication of immunotherapy, with no standardized treatment protocol due to limited data. The use of varying steroid doses has resulted in inconsistent outcomes.MethodsWe retrospectively identified patients diagnosed with ICI-M at our institution between January 2020 and February 2024. Additionally, we conducted a comprehensive literature review using PubMed, Embase, and the Cochrane Library to facilitate a comparative analysis of clinical responses. The primary aim was to compare clinical outcomes and therapeutic responses between patients treated with high-dose versus low-dose methylprednisolone.ResultsPatients receiving an initial high-dose intravenous methylprednisolone (1 g/day) exhibited a more rapid reduction in myocardial injury markers, including troponin I/T (cTnI/T), creatine kinase (CK), and N-terminal pro b-type natriuretic peptide (NT-proBNP), compared to those receiving lower doses. This group also demonstrated lower incidences of biomarker rebound and maintained lower levels over time. Additionally, the clinical treatment process was more straightforward in the high-dose group, with treatment efficacy surpassing that observed in patients who received an initial methylprednisolone (mPSL) dose of less than 1 g/day. Regarding prognosis, the incidence of major adverse cardiovascular events (MACE) and cardiovascular mortality was significantly lower in the high-dose group compared to the low-dose group.ConclusionsIn patients with immune checkpoint inhibitor-associated myocarditis, the prompt administration of high-dose corticosteroid pulse therapy (1 g/day) is strongly associated with improved clinical outcomes. This intervention rapidly lowers myocardial injury biomarkers (cTnI/T, CK, NT-proBNP) while minimizing the risk of biomarker rebound, thus optimizing clinical management. Notably, it significantly reduces the incidence of major adverse cardiovascular events (MACE), thereby enhancing patient prognosis. The duration of therapy should be tailored based on clinical response. In cases of steroid resistance, combination therapies may provide additional benefit.
Advanced disease and CD8+ TEMRA cells predict severe infections in multiple myeloma
Authors: Tranter Eva , Busch David , Heck Clarissa , Blau Igor Wolfgang , Nogai Axel , Schiele Phillip , Meisel Christian , Bullinger Lars , Frentsch Marco , Na Il-Kang 
Published: February 2025

IntroductionInfections are a major cause of early morbidity and mortality in patients with multiple myeloma (MM) who are characterized by immunodeficiency secondary to disease. However, prospectively collected data on infection risk in this population are scarce. We aimed at identifying parameters in monoclonal gammopathy of undetermined significance (MGUS) and newly diagnosed MM (NDMM) patients with predictive power for early severe infections (SI).MethodsWe conducted a prospective study with newly diagnosed MGUS and NDMM patients. Besides clinical and laboratory data, immune parameters were collected at initial diagnosis before therapy initiation. Primary endpoint was the occurrence of SI within 12 months after diagnosis.Results45% of patients developed infection, 26% with SI. Four main risk factors for SI were identified: ECOG ≥ 2 (p &lt; 0.001), ISS stage II/III (p = 0.002), therapeutic intervention (p &lt; 0.001), and elevated CD8+ TEMRA cells (p = 0.027). A risk score was compiled, enabling the stratification of patients with low or high risk for SI with a sensitivity of 92.9% and a specificity of 80%.ConclusionWe developed a straightforward risk score that considers the relevance of T cell fitness in MGUS and NDMM patients and can help physicians to identify patients at risk of infection, thus enabling the implementation of timely and individualized prevention strategies.
Anticholinergic burden and behavioral and psychological symptoms in older patients with cognitive impairment
Authors: Pistorio Sabrina , Scotto di Tella Gianluca , Canzanella Vittoria , Merenda Raffaella , Cuomo Gianluigi , Iacotucci Paola , Carnovale Vincenzo , Bencivenga Leonardo , Vargas Maria , Manes Annalaura , Cataldi Mauro , Rengo Giuseppe , Zanetti Michela , Femminella Grazia Daniela 
Published: February 2025

BackgroundDrugs with anticholinergic properties are frequently prescribed to patients with cognitive impairment. The cholinergic system plays an important role in learning processes, memory, and emotions regulation. The aim of this research is to report use of anticholinergic drugs in a clinical population and to investigate the correlation between the use of anticholinergic drugs and the risk of presenting with more severe behavioral and psychological symptoms (BPSD).MethodPatients with a diagnosis of subjective cognitive impairment, mild cognitive impairment (MCI) or dementia were recruited. Screening tests for cognitive impairment (MMSE) and functional status (ADL, IADL) were performed. BPSD were evaluated with the Neuropsychiatric Inventory (NPI). The anticholinergic burden was calculated using the ACB calculator. We compared patients at low risk of anticholinergic adverse effects (ACB &lt; 3) versus patients at high risk (ACB ≥ 3). Chi-square test and Mann–Whitney test were used to compare the two groups. A multiple linear regression was performed to identify factors associated with higher NPI score and a logistic regression model was built to identify drug classes associated with ACB ≥ 3.ResultA total of 173 patients (mean age 74 ± 7, 74 men) were included in the study; 132 patients with ACB &lt; 3 (low risk) versus 41 patients with ACB ≥3 (high risk) were compared. No statistically significant differences were found between the two groups in terms of demographics (age, sex) and anamnestic variables (education, marital status, family history of dementia, hypertension, diabetes, smoking, dyslipidemia, atrial fibrillation, coronary heart disease and use of alcohol). Significantly higher NPI scores were found in patients with ACB ≥ 3 (mean scores 47.3 ± 34.8 versus 25.5 ± 24.6, p &lt; 0.001). Patients with ACB ≥ 3 showed lower MMSE (18.5 ± 8.6 versus 22.4 ± 7, p = 0.004) and more IADLs lost. In the multivariate regression analysis, after adjusting for age, sex, polypharmacy and IADLs lost, only the MMSE and the ACB scores were independent predictors of the NPI score. Being on antipsychotics, antidepressants and antidiabetic drugs was associated with increased risk of higher anticholinergic burden.ConclusionIn conclusion, the anticholinergic burden might play a significant role as a risk factor for developing more severe BPSD in patients with cognitive decline, independently from their degree of cognitive impairment.
MAEMC-NET: a hybrid self-supervised learning method for predicting the malignancy of solitary pulmonary nodules from CT images
Authors: Zhao Tianhu , Yue Yong , Sun Hang , Li Jingxu , Wen Yanhua , Yao Yudong , Qian Wei , Guan Yubao , Qi Shouliang 
Published: February 2025

IntroductionPulmonary granulomatous nodules (PGN) often exhibit similar CT morphological features to solid lung adenocarcinomas (SLA), making preoperative differentiation challenging. This study aims to address this diagnostic challenge by developing a novel deep learning model.MethodsThis study proposes MAEMC-NET, a model integrating generative (Masked AutoEncoder) and contrastive (Momentum Contrast) self-supervised learning to learn CT image representations of intra- and inter-solitary nodules. A generative self-supervised task of reconstructing masked axial CT patches containing lesions was designed to learn intra- and inter-slice image representations. Contrastive momentum is used to link the encoder in axial-CT-patch path with the momentum encoder in coronal-CT-patch path. A total of 494 patients from two centers were included.ResultsMAEMC-NET achieved an area under curve (95% Confidence Interval) of 0.962 (0.934–0.973). These results not only significantly surpass the joint diagnosis by two experienced chest radiologists (77.3% accuracy) but also outperform the current state-of-the-art methods. The model performs best on medical images with a 50% mask ratio, showing a 1.4% increase in accuracy compared to the optimal 75% mask ratio on natural images.DiscussionThe proposed MAEMC-NET effectively distinguishes between benign and malignant solitary pulmonary nodules and holds significant potential to assist radiologists in improving the diagnostic accuracy of PGN and SLA.
The gastric microbiome altered by A4GNT deficiency in mice
Authors: Gong Dawei , Gao Yuqiang , Shi Rui , Xu Xiaona , Yu Mengchao , Zhang Shumin , Wang Lili , Dong Quanjiang 
Published: February 2025

BackgroundSelective antimicrobial effects have been found for α1,4-linked N-acetylglucosamine residues at the terminus of O-glycans attached to a core protein of gastric gland mucin. A4gnt encodes α1,4-N-acetylglucosaminyl transferase, which is responsible for the biosynthesis of α1,4-linked N-acetylglucosamine. The impact of A4GNT on the establishment and homeostasis of the gastric microbiome remains to be clarified. The aim of this study was to characterize the gastric microbiome in mice deficient for the production of α1,4-linked N-acetylglucosamine.MethodsThe gastric microbiome within A4gnt−/− mice and wild-type mice was analyzed using high-throughput sequencing of bacterial 16S rRNA.ResultsIn A4gnt−/− mice, which spontaneously develop gastric cancer, the community structure of the gastric microbiome was altered. The relative abundance of mutagenic Desulfovibrio and proinflammatory Prevotellamassilia in these mice was significantly increased, especially 4 weeks after birth. The co-occurrence network appeared to be much more complex. Functional prediction demonstrated considerable decreases in the relative frequencies of functions associated with polysaccharide metabolism and transportation.ConclusionThe distinct profile in A4gnt−/− mice demonstrated a vital role of A4GNT in the establishment of the gastric microbiome. A dysbiotic gastric microbiome may contribute to the spontaneous development of gastric cancer in mice.
Olfaction-based learned preference assessment without the use of motivational fear or motivational weight loss
Authors: Moss Sara E. , McCurdy Ekaterina S. , Thomas Natalya N. , Gulick Danielle , Poff Angela M. , D'Agostino Dominic P. 
Published: February 2025

IntroductionReliable assessments of learning ability in preclinical models are essential for studying neurodegenerative, developmental, and inflammatory disorders. However, many inbred strains of mice present background pathologies that interfere with traditional learning tests. The C57BL/6 J mouse, a widely used laboratory strain, sporadically develops auditory and visual impairments that complicate interpretation. In this study, we establish an olfaction-based learned preference protocol designed to evaluate learning ability independent of fear responses, motivational weight loss, or visual cues in C57BL/6 J mice.Methods and resultsLeveraging the species’ natural preference for sweet flavors, we tested different sweeteners and confirmed their passive preference for sucrose was more robust than for saccharin or sucralose. We then trained mice to associate either lemon or rose scents with a sucrose paste reward, and tested whether they demonstrated a learned preference for the sucrose-associated scent over the neutral scent. Mice developed an appetitive olfactory preference for sucrose as a reward, in the absence of motivational weight loss, as measured by time spent exploring a three-chamber association box with access to both scents. We assessed whether this protocol discriminated learning deficit induced by lipopolysaccharide (LPS) administration.ConclusionWe conclude that this protocol is a viable tool for assessing learning abilities in preclinical models with auditory or visual deficits, motor impairments, or an inability to tolerate motivational weight loss.
Profiling gene alterations in striatonigral neurons associated with incubation of methamphetamine craving by cholera toxin subunit B-based fluorescence-activated cell sorting
Authors: Altshuler Rachel D. , Burke Megan A. M. , Garcia Kristine T. , Class Kenneth , Cimbro Raffaello , Li Xuan 
Published: February 2025

IntroductionIn both rats and humans, methamphetamine (Meth) seeking progressively increases during abstinence, a behavioral phenomenon termed “incubation of Meth craving”. We previously demonstrated a critical role of dorsal striatum (DS) in this incubation in rats. However, circuit-specific molecular mechanisms in DS underlying this incubation are largely unknown. Here we combined a newly developed fluorescence-activated sorting (FACS) protocol with fluorescence-conjugated cholera toxin subunit B-647 (CTb-647, a retrograde tracer) to examine gene alterations in the direct-pathway (striatonigral) medium spiny neurons (MSNs) associated with incubation of Meth craving.MethodsWe injected CTb-647 bilaterally into substantia nigra before or after training rats to self-administer Meth or saline (control condition) for 10 days (6 h/d). On abstinence day 1 or day 28, we collected the DS tissue from both groups for subsequent FACS and examined gene expressions in CTb-positive (striatonigral MSNs) and CTb-negative (primarily non-striatonigral MSNs). Finally, we examined gene expressions in DS homogenates, to demonstrate cell-type specificity of gene alterations observed on abstinence day 28.ResultsOn abstinence day 1, we found mRNA expression of Gabrb3 decreased only in CTb-positive (but not CTb-negative) neurons of Meth rats compared with saline rats, while mRNA expression of Usp7 decreased in all sorted DS neurons. On abstinence day 28, we found increased mRNA expression for Grm3, Opcml, and Usp9x in all sorted DS neurons, but not DS homogenate.DiscussionTogether, these data demonstrated that incubation of Meth craving was associated with time-dependent, circuit-specific, and cell type-specific gene alterations in DS involved in glutamatergic, GABAergic, opioidergic, and protein degradation signaling.
Study on the correlation between carotid plaque calcification types and acute ischemic stroke
Authors: Chu Tianyu , Guo Zhongping , Zhang Yonggang , Liu Ying , Gu Yan 
Published: February 2025

IntroductionComputed tomography angiography (CTA) was used to explore the correlation between the calcification types of carotid plaques and ipsilateral acute ischemic stroke. This could provide new insights into the clinical evaluation and treatment of ischemic stroke.MethodsThis study obtained information on patients undergoing head and neck CTA examinations at the First People's Hospital of Lianyungang between September 2022 and August 2023 to investigate the clinical differences in baseline data between the acute ischemic stroke and control groups. Patients meeting the inclusion and exclusion criteria were classified into 1 to 6 groups according to their plaque calcification characteristics. The correlation between calcified plaque type and ipsilateral acute ischemic anterior circulation stroke was analyzed using paired sample chi-square and Spearman correlation tests.ResultsBased on the inclusion and exclusion criteria, this study included 589 patients with plaques at the bifurcation of the carotid arteries. In both the acute ischemic stroke and control groups, sex, smoking, alcohol consumption, systolic blood pressure, blood sugar, cholesterol, high-density lipoprotein, and homocysteine levels were statistically significant (p &lt; 0.05). During the Spearman correlation analysis between calcification type and acute stroke (1,178 carotid arteries), different calcification types of plaques were linked with ipsilateral acute anterior circulation stroke with statistically significant differences (p &lt; 0.001). Finally, the chi-squared test of the paired samples showed that the grade of plaque calcification is often higher on the side of acute infarction than on the side without acute infarction, and the difference is statistically significant (p &lt; 0.001).DiscussionCarotid plaque calcification is associated with acute ischemic stroke. Our findings provide novel insights into the study of calcification in carotid atherosclerotic plaques and additional radiological evidence to clinically assess the risk of ischemic stroke.
Bedside cerebral microvascular imaging of patients with disorders of consciousness: a feasibility study
Authors: Ge Qianqian , Huang Lijie , Fu Qiang , Han Shuai , Wang Rui , He Jianghong , Li Changhui , Luo Jianwen , Xu Long 
Published: February 2025

BackgroundEfficient bedside neurofunctional monitoring is crucial for managing disorders of consciousness (DoC). Ultrafast Power Doppler Imaging (uPDI) outperforms traditional Ultrasound in bedside for assessing the microcirculatory system. However, intracranial blood flow imaging traditionally faces limitations due to the skull’s impedance. This constraint is circumvented in common post-craniectomy DoC patients, who present a unique observational window for uPDI.MethodsWe conducted uPDI scans on five DoC patients of different ages and consciousness levels who had undergone decompressive craniectomy. We compared the imaging results from uPDI with traditional PDI and identified the physiological and pathological conditions with uPDI.ResultsDetailed microvascular images of both cortical and subcortical areas were obtained using uPDI through the craniectomy window. Notably, uPDI demonstrates high sensitivity and imaging depth, revealing microvessels as small as 320 μm in diameter at 4 cm depth, and detecting blood flow signals up to 6 cm beneath the scalp.ConclusionThrough the decompressive cranial windows of DoC patients, we obtained cerebral microvascular images with significantly higher sensitivity without the need for contrast agents.SignificanceOur research provides a novel bedside cerebral microcirculation imaging method for patients with DoC, offering convenient neurofunctional assessment to improve the clinical management of DoC patients.
Relationship of METS-IR with cardiometabolic multimorbidity in China: a nationwide longitudinal cohort study
Authors: Zhou Chunyan , Zhang Yanyu , Liu Xiaoyi , He Chenyu , Li Shiyang 
Published: February 2025

BackgroundCardiometabolic multimorbidity (CMM) has emerged as a global health challenge with a high mortality risk. This study aimed to explore the association between the metabolic score for insulin resistance (METS-IR) and the incidence of CMM.MethodsThis study included 6,977 individuals in the CHARLS database. We used multiple cox proportional hazards regression and restricted cubic splines (RCS) analysis to evaluate the association between METS-IR and CMM. Subgroup analyses and interaction tests were also performed.ResultsDuring a median 109 (108–109) months of follow-up, 745 (10.7%) participants were diagnosed with new-onset CMM. The incidences of CMM among participants in quartiles (Q) 1–4 of METS-IR were 4.99, 7.51, 10.67, and 19.54%, respectively. METS-IR was significantly higher in individuals with CMM compared to those without CMM (p &lt; 0.001). After multivariate adjustment, a higher METS-IR was significantly associated with an increased risk of CMM. Compared to participants in Q1 of METS-IR, the hazard ratios (HRs) (95% confidence intervals [CIs]) using cox proportional hazards regression analysis for those in Q2–4 were 1.52 (1.15–2.00), 2.02 (1.56–2.63), and 3.61 (2.80–4.64), respectively. RCS analysis revealed a significant nonlinear association between METS-IR and CMM (nonlinear p &lt; 0.05). The association between METS-IR and the incidence of CMM was present in almost all the subgroups. Furthermore, the predictive ability of METS-IR for CMM was 0.669, which surpassed that of both the triglyceride to high-density lipoprotein cholesterol ratio and the triglyceride glucose index.ConclusionA higher METS-IR was closely associated with an increased risk of CMM. Further studies on METS-IR could be beneficial for preventing and treating CMM.
Serum alpha-1 acid glycoprotein and gallstone risk in US adult women: a cross-sectional analysis of the NHANES
Authors: Li Xiaocheng , He Peiling 
Published: February 2025

BackgroundGallstone disease, a common biliary disorder, is linked to inflammation and immune responses. However, the association between serum alpha-1 acid glycoprotein (AGP), a key inflammatory marker, and gallstone risk remains underexplored.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 and 2021–2023 cycles were analyzed. Gallstone disease was determined by self-reported physician diagnosis. Serum AGP levels were measured using a high-sensitivity turbidimetric immunoassay. Weighted logistic regression, subgroup analyses, smoothed curve analysis, and multiple imputation were used to examine the relationship between AGP and gallstone risk.ResultsThis cross-sectional analysis included 1,903 adult women in the U.S. aged 20–49. After adjusting for all covariates, serum AGP levels were positively associated with gallstone risk (OR: 3.07; 95% CI: 1.16, 8.11; p = 0.036). Compared to the first tertile (T1), the third AGP tertile (T3) had an OR of 1.87 (95% CI: 1.11, 3.14; p = 0.030). Smoothed curve analysis indicated a positive relationship between AGP and gallstone risk. Subgroup analyses consistently demonstrated this positive association across various demographic and clinical categories, with significant interactions observed for the ratio of family income to poverty. Sensitivity analyses using multiple imputation further supported the conclusion that AGP was associated with increased gallstone risk.ConclusionAGP is significantly associated with an increased risk of gallstones in U.S. adult women, suggesting its potential as a biomarker for risk stratification. Further research is needed to elucidate the underlying mechanisms and potential causal relationships.