bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a beta-lactam graded challenge process for inpatients with self-reported penicillin allergies at an academic medical center
Authors: Sunagawa Shawnalyn W. , Bergman Scott J. , Kreikemeier Emily , Watkins Andrew B. , Alexander Bryan T. , Miller Molly M. , Schroeder Danny , Stohs Erica J. , Van Schooneveld Trevor C. , May Sara M. 
Published: July 2023

BackgroundThe Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available.MethodsFollowing multi-disciplinary review, an order set for beta-lactam graded challenges (GC) was implemented in 2018. This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents. Inpatient orders for GC from 3/2018–6/2022 were retrospectively reviewed to evaluate ordering characteristics, outcomes of the challenge, and whether documentation of the allergy history was updated. All beta-lactam challenges administered to inpatients were included, and descriptive statistics were performed.ResultsOverall, 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams. Ceftriaxone accounted for the most challenges (43%). All oral challenges were recommended by an Infectious Diseases consult service, as were a majority of IV challenges (60%). Less than one in five were administered in an ICU (19%). Almost all (n = 150, 96%) were tolerated without any adverse event. There was one reaction (1%) of hives and six (4%) involving a rash, none of which had persistent effects. Allergy information was updated in the electronic health record after 92% of the challenges.ConclusionBoth intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process.
Evaluation of raw and processed Phellodendri Chinensis Cortex using the quality marker analysis strategy by UHPLC-Q-Orbitrap MS and multivariate statistical analysis
Authors: Wang Wang , Shi Xuqin , Zhu Guoxue 
Published: July 2023

Introduction: Phellodendri Chinensis Cortex is a necessary part of healthcare for its significant clinical efficacy. Raw and processed Phellodendri Chinensis Cortex is both documented in the Chinese Pharmacopoeia (2015). After processing, the therapeutic effects are believed to differ according to traditional Chinese medicine theories. However, the chemical mechanism responsible for this processing, according to traditional Chinese medicine theories, is still not clear.Methods: In this study, the therapeutic effects of various ions were examined based on traditional Chinese medicine theories by ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) coupled with multivariate statistical analysis, such as principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), to comprehensively compare the differences between raw and processed Phellodendri Chinensis Cortex for the first time.Results: A total of 48 compounds were screened, out and 10 of them simultaneously transformed with significant variation in processed products compared with raw materials. It was illustrated that the contents of berberine, palmatine, jatrorrhizine, magnoflorine, menisperine, phellodendrine, tetrahydrojatrorrhizine, and tetrahydropalmatine decreased, while the compounds of berberrubine and fernloylquinic acid methyl ester newly appeared in processed herbs. This is likely to be related to the conversion of ingredients during processing.Discussion: Altogether, the fact that quality markers have been successfully identified to differentiate processed Phellodendri Chinensis Cortex from raw materials suggests that this approach could be used for the investigation of chemical transformation mechanisms involved in the processing of herbal medicine.
Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study
Authors: Reis Bárbara Carvalho Santos Dos , Soares Faccion Roberta , de Carvalho Flavia Amendola Anisio , Moore Daniella Campelo Batalha Cox , Zuma Maria Celia Chaves , Plaça Desirée Rodrigues , Salerno Filgueiras Igor , Leandro Mathias Fonseca Dennyson , Cabral-Marques Otavio , Bonomo Adriana Cesar , Savino Wilson , Freitas Flávia Cristina de Paula , Faoro Helisson , Passetti Fabio , Robaina Jaqueline Rodrigues , de Oliveira Felipe Rezende Caino , Novaes Bellinat Ana Paula , Zeitel Raquel de Seixas , Salú Margarida dos Santos , de Oliveira Mariana Barros Genuíno , Rodrigues-Santos Gustavo , Prata-Barbosa Arnaldo , Vasconcelos Zilton Farias Meira de 
Published: July 2023

IntroductionDespite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin.MethodsTo further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. ResultsAnalyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C.DiscussionThese data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.
Causal relationship between osteoarthritis with atrial fibrillation and coronary atherosclerosis: a bidirectional Mendelian randomization study of European ancestry
Authors: Yin Meng , Xu Wenchang , Pang Jixiang , Xie Siwen , Xiang Mengting , Shi Bin , Fan Hua , Yu Gongchang 
Published: July 2023

BackgroundOsteoarthritis (OA) is a degenerative disease with high prevalence. Some observational studies have shown that patients with osteoarthritis often have co-existing cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary atherosclerosis (CA). However, there is still a lack of stronger evidence confirming the association between osteoarthritis and cardiovascular disease. In this study, we used a bidirectional two-sample Mendelian randomization study to investigate the relationship between OA with AF and CA.MethodsOA data from the UK Biobank and arcOGEN (Arthritis Research UK Osteoarthritis Genetics, a study that aimed to find genetic determinants of osteoarthritis and elucidate the genetic architecture of the disease) integration were selected for the study (n = 417,596), AF data were obtained from six studies (n = 1,030,836), and coronary atherosclerosis data were derived from the FinnGen (n = 218,792). MR analysis was performed primarily using the Inverse variance weighted (IVW) method, with MR Egger, weighted median, simple mode, weighted mode as supplements, sensitivity analysis was performed using Cochran Q statistic, and leave-one-out analysis.ResultsWe found that OA and AF were positively associated [IVW: OR (95% CI): 1.11 (1.04, 1.19), P = 0.002], while OA and CA were negatively associated [IVW: OR (95% CI): 0.88 (0.79, 0.98), P = 0.02]. In the reverse MR analysis, no effect of AF on OA was found [IVW: OR (95% CI): 1.00 (0.97, 1.03), P = 0.84], meanwhile, CA and OA were found to be associated negatively [IVW: OR (95% CI): 0.95 (0.92, 0.99), P = 0.01]. No violations of MR assumptions were found in the sensitivity analysis.ConclusionThis research confirms that OA is a risk factor for AF, and there is a mutual protective factor between OA and CA. However, further studies are still necessary to elucidate the underlying mechanisms.
Machine learning-based detection of cardiovascular disease using ECG signals: performance vs. complexity
Authors: Pham Huy , Egorov Konstantin , Kazakov Alexey , Budennyy Semen 
Published: July 2023

IntroductionCardiovascular disease remains a significant problem in modern society. Among non-invasive techniques, the electrocardiogram (ECG) is one of the most reliable methods for detecting cardiac abnormalities. However, ECG interpretation requires expert knowledge and it is time-consuming. Developing a novel method to detect the disease early improves the quality and efficiency of medical care.MethodsThe paper presents various modern approaches for classifying cardiac diseases from ECG recordings. The first approach suggests the Poincaré representation of ECG signal and deep-learning-based image classifiers. Additionally, the raw signals were processed with the one-dimensional convolutional model while the XGBoost model was facilitated to predict based on the time-series features.ResultsThe Poincaré-based methods showed decent performance in predicting AF (atrial fibrillation) but not other types of arrhythmia. XGBoost model gave an acceptable performance in long-term data but had a long inference time due to highly-consuming calculations within the pre-processing phase. Finally, the 1D convolutional model, specifically the 1D ResNet, showed the best results in both studied CinC 2017 and CinC 2020 datasets, reaching the F1 score of 85% and 71%, respectively, and they were superior to the first-ranking solution of each challenge. The 1D models also presented high specificity. Additionally, our paper investigated efficiency metrics including power consumption and equivalent CO2 emissions, with one-dimensional models like 1D CNN and 1D ResNet being the most energy efficient. Model interpretation analysis showed that the DenseNet detected AF using heart rate variability while the 1D ResNet assessed the AF patterns in raw ECG signals.DiscussionDespite the under-performed results, the Poincaré diagrams are still worth studying further because of the accessibility and inexpensive procedure. In the 1D convolutional models, the residual connections are useful to keep the model simple but not decrease the performance. Our approach in power measurement and model interpretation helped understand the numerical complexity and mechanism behind the model decision.
Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas
Authors: Wang Kai , Gui Lin , Lu Haizhen , He Xiaohui , Li Dezhi , Liu Chang , Liu Shaoyan , Wang Xiaolei 
Published: July 2023

BackgroundThis study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs).MethodsIn this prospective, single-arm, single-centre clinical trial, patients meeting the inclusion criteria were treated with preoperative neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m2 cisplatin and 175 mg/m2 paclitaxel. This was followed by surgery and postoperative adjuvant therapy. The primary endpoint was the postoperative pathological complete response (pCR) rate. All statistical analyses were performed using SPSS 26.ResultsA total of 22 patients were enrolled. The location of primary lesion showed: hypopharynx were 15 (68.2%), oropharynx were 6 (27.3%) and oral cavity was 1 (4.5%). The postoperative pCR rate, was 36.4% (8/22), and there was no delay to surgery due to adverse drug reactions. The rate of laryngeal function preservation was 90.9% (20/22). Delayed wound healing was the main surgical complication, with an incidence of 22.7% (5/22). The median follow-up time was 9.5 months, and only 1 patient (4.55%) suffered a regional recurrence.ConclusionPreoperative treatment with pembrolizumab and chemotherapy in resectable LA-HNSCC has a high pCR rate with no significant impact on surgical safety. This treatment was found to increase the rate of laryngeal function preservation. However, the effects of neoadjuvant immunotherapy on long-term prognosis in LA-HNSCCs require further study.
Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients
Authors: An Zesheng , Figueroa-Parra Gabriel , Zhou Xian , Li Yanfeng , Jaquith Jane , McCarthy-Fruin Kathleen , Sletten Jennifer , Warrington Kenneth J. , Weyand Cornelia , Crowson Cynthia S. , Chumsri Saranya , Knutson Keith L. , Sanchez-Rodriguez Alain , Thanarajasingam Uma , Duarte-García Alí , Zeng Hu 
Published: July 2023

IntroductionThe longitudinal responses towards multiple doses of COVID-19 mRNA vaccines in patients with systemic autoimmune diseases remain incompletely understood. While observational studies suggested the safety of COVID-19 mRNA vaccines in rheumatic disease patients, laboratory evidence is lacking.MethodsHere we evaluated seroreactivity, clinical manifestions, and multiple disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases.ResultsMost patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Patients with systemic lupus erythematosus (SLE) or psoriatic arthritis (PsA) remained without significant flares post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I interferon (IFN) signature genes were highly variable but did not show consistent or significant increases. Frequency of double negative 2 (DN2) B cells remained largely stable.DiscussionOur data provide experimental evidences indicating the efficacy and safety of repeated COVID-19 mRNA vaccination in rheumatic disease patients.
Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis
Authors: Koudriavtseva Tatiana , Lorenzano Svetlana , Cellerino Maria , Truglio Mauro , Fiorelli Marco , Lapucci Caterina , D’Agosto Giovanna , Conti Laura , Stefanile Annunziata , Zannino Silvana , Filippi Maria Maddalena , Cortese Antonio , Piantadosi Carlo , Maschio Marta , Maialetti Andrea , Galiè Edvina , Salvetti Marco , Inglese Matilde 
Published: July 2023

ObjectivesRecent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities.MethodsWe compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (n=30; 23F/7M, 40 ± 8.14 years) or a relapse (n=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (n=30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis.ResultsCompared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3.ConclusionTissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis.Clinical trial registrationClinicalTrials.gov, identifier NCT04380220.
Diversity, metabolome profiling and bioactivities of benthic filamentous cyanobacteria isolated from coastal mangroves of Mayotte
Authors: Wang Huibin , Halary Sébastien , Duval Charlotte , Bernard Cécile , Troussellier Marc , Beniddir Mehdi A. , Brunel Jean-Michel , Castaldi Andrea , Caudal Flore , Golléty Claire , Martin Coralie , Bourguet-Kondracki Marie-Lise , Duperron Sébastien 
Published: July 2023

IntroductionCyanobacteria are important members of the dense biofilms that colonize available substrates in mangrove habitats worldwide. However, their taxonomic diversity and biological activities have received little attention.MethodsThe occurrence of cyanobacteria is evaluated in 27 biofilms collected from mangroves in Mayotte. Filamentous cyanobacterial strains were isolated and characterized using 16S rRNA comparative gene sequence analysis. LC-MS/MS experiments were performed on the crude extracts of the faster-growing strains, and construction of their molecular network showed a conspectus of their chemical diversity. Biological activities of the strain extracts were then evaluated using standard assays.Results and discussionIsolation procedures yielded 43 strains representing 22 species-level taxa, of which only three could be assigned to existing species. Some of these strains were among the most abundant cyanobacteria present in biofilms. PCR assays did not support the production of the major cyanotoxins. Analysis of metabolites from 23 strains using both in silico tools ISDB- DNP (In silico Data Base–Dictionary of Natural Products) and MolDiscovery, revealed occurrence of godavarin K, a limonoid natural product previously isolated from the seeds of an Indian mangrove tree. This annotation was further confirmed by the marine database MarinLit, suggesting that cyanobacteria might be an alternative source of godavarin K and its four isomers. While no significant antimicrobial and cytotoxic activities were observed, some strains exhibited anthelmintic and antibiofilm activities that warrant further investigation and may be relevant to biofilm ecology. Mangrove biofilms thus appear to be an untapped reservoir of novel culturable cyanobacterial lineages, with bioactivities relevant to their biofilm lifestyle, which may be of interest for bioinspiration.
Comparative study of 18F-DCFPyL PET/CT and 99mTc-MDP SPECT/CT bone imaging for the detection of bone metastases in prostate cancer
Authors: Hu Xiongjian , Cao Yiming , Ji Bin , Zhao Min , Wen Qiang , Chen Bin 
Published: July 2023

PurposeThis study aimed to compare the diagnostic efficiency of 18F-DCFPyL PET/CT imaging and 99mTc-MDP SPECT/CT bone imaging for the detection of bone metastases in prostate cancer.MethodsA retrospective analysis was conducted on 31 patients with confirmed prostate cancer between September 2020 and September 2022 at China-Japan Union Hospital of Jilin University. All patients underwent 18F-DCFPyL PET/CT and 99mTc-MDP SPECT/CT bone imaging. The gold standard was the pathology or Best Valuable Comparator (BVC) result based on clinical follow-up. Diagnostic performance indicators, including sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV), were analyzed at both the patient and lesion levels. The paired sample chi-square test was used to compare the two imaging methods. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated for each method. The AUC values were compared using the Z-test, and a p-value &lt; 0.05 was considered statistically significant.ResultsOf the 31 prostate cancer patients, 18 were diagnosed with bone metastases, with a total of 84 bone metastatic lesions. At the patient level, 18F-DCFPyL PET/CT imaging showed superior diagnostic performance compared to 99mTc-MDP SPECT/CT bone imaging in all indicators: sensitivity (100% vs. 77.8%, p &lt; 0.01), specificity (92.3% vs. 69.2%, p &lt; 0.05), accuracy (96.8% vs. 74.2%, p &lt; 0.01), PPV (94.7% vs. 77.8%, p &lt; 0.01), and NPV (100% vs. 69.2%, p &lt; 0.01). The AUC values for 18F-DCFPyL PET/CT imaging and 99mTc-MDP SPECT/CT bone imaging were 0.962 and 0.735 (Z = 2.168, p &lt; 0.05). At the lesion level, 18F-DCFPyL PET/CT imaging showed superior diagnostic performance compared to 99mTc-MDP SPECT/CT bone imaging in all indicators: sensitivity (97.6% vs. 72.6%, p &lt; 0.01), specificity (95.7% vs. 73.9%, p &lt; 0.01), accuracy (97.2% vs. 72.9%, p &lt; 0.01), PPV (98.8% vs. 91.0%, p &lt; 0.01), and NPV (91.7% vs. 42.5%, p &lt; 0.01). The AUC values for 18F-DCFPyL PET/CT imaging and 99mTc-MDP SPECT/CT bone imaging were 0.966 and 0.733 (Z = 3.541, p &lt; 0.001).ConclusionCompared with 99mTc-MDP SPECT/CT bone imaging, 18F-DCFPyL PET/CT imaging demonstrated higher diagnostic efficiency for bone metastases in prostate cancer, and it can more accurately determine the presence of bone metastases. It is an important supplement to imaging examination for prostate cancer patients and has great potential and broad application prospects.
The decoupling between hemodynamic parameters and neural activity implies a complex origin of spontaneous brain oscillations
Authors: Li Ming , He Lihua , Zhang Zhuo , Li Zhen , Zhu Xuan , Jiao Chong , Hu Dewen 
Published: July 2023

IntroductionSpontaneous low-frequency oscillations play a key role in brain activity. However, the underlying mechanism and origin of low-frequency oscillations remain under debate.MethodsOptical imaging and an electrophysiological recording system were combined to investigate spontaneous oscillations in the hemodynamic parameters and neuronal activity of awake and anesthetized mice after Nω-nitro-L-arginine methyl ester (L-NAME) administration.ResultsThe spectrum of local field potential (LFP) signals was significantly changed by L-NAME, which was further corroborated by the increase in energy and spatial synchronization. The important finding was that L-NAME triggered regular oscillations in both LFP signals and hemodynamic signals. Notably, the frequency peak of hemodynamic signals can be different from that of LFP oscillations in awake mice.DiscussionA model of the neurovascular system was proposed to interpret this mismatch of peak frequencies, supporting the view that spontaneous low-frequency oscillations arise from multiple sources.