bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nrf2 orchestrates transition from acute to chronic otitis media through inflammatory macrophages
Authors: Fan Wenyan , Xu Hongming , Shen Chenling , Fang Jia , Li Xiaoyan 
Published: April 2023

IntroductionAcute and chronic otitis media (AOM and COM) are common middle ear infections that can lead to hearing loss and other complications. Recent research has shown that both macrophages and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway are involved in the immune response to and the resolution of otitis media. However, the specific effects of Nrf2 on macrophages in the transition of AOM to COM are not well understood, and a practical approach to prevent this transition by targeting Nrf2/macrophages has not been established.MethodsIn an AOM mouse model using lipopolysaccharide (LPS) injection into the middle ear, middle ear effusion (OME)-macrophages were isolated and analyzed for Nrf2 expression. M2-like polarization of macrophages was induced by Nrf2 activation and its effects on inflammatory resolution were studied by examining inflammatory neutrophils and macrophages, proinflammatory cytokines, and oxidative levels. The survival of human middle ear epithelial cells (HMMECs) co-cultured with Nrf2-modified macrophages was also evaluated. Furthermore, restoration of Nrf2 in macrophages with adeno-associated virus (AAV) vectors was performed to determine the effect on the transition of AOM to COM in experimental mice.ResultsReduced Nrf2 in OME-macrophages during the recovery phase was associated with uncured AOM or its development into COM, demonstrated by persistent increases in inflammatory neutrophils and macrophages, proinflammatory cytokines, and oxidative levels. Nrf2 activation induced M2-like polarization of macrophages, which improved the survival of co-cultured HMMECs treated with LPS in vitro. Restoration of Nrf2 in OME-derived low-Nrf2-expressing macrophages with AAV vectors significantly inhibited the transition of AOM to COM in experimental mice.DiscussionNrf2 in macrophages plays a critical role in the immune response to and resolution of otitis media Restoration of Nrf2 expression in OME-macrophages could be a promising therapeutic approach to prevent the development of COM in AOM patients.
Focused ultrasound for the remote modulation of nitric oxide release from injectable PEG-fibrinogen hydrogels for tendon repair
Authors: Meyers Kaylee M. , Simon Alex , Khan Zerin M. , Rajachar Rupak M. , Vlaisavljevich Eli 
Published: April 2023

Introduction: Tendon disorders such as tendinosis, the degradation of collagen in tendon, or tendonitis, inflammation of tendon tissue, contribute to 30% of musculoskeletal complaints. To address the limitations of currently available treatments for tendon repair, an injectable polyethylene glycol (PEG)-fibrinogen hydrogel encompassing nitric oxide (NO) releasing µ-particles was generated. The release of nitric oxide, a therapeutic molecule that modulates many wound healing processes, from the hydrogel can be modified with thermal and mechanical stimulus. To achieve remote control over NO release from hydrogels after deployment, focused ultrasound (FUS) was explored as it provides highly controlled thermal and mechanical stimulus non-invasively.Methods: In this work, the ability of FUS to remotely elicit on-demand NO generation from acoustically active composite hydrogels via thermal and/or mechanical stimulus was explored. Specifically, the temperature and time-dependent release of NO was simulated and characterized when applying FUS to composite hydrogels.Results: Results from acoustic simulations as well as thermocouple heating studies indicated that high spatial and temporal control over hydrogel warming could be achieved non-invasively with a 3.5 MHz FUS transducer. FUS was also able to remotely control NO release from hydrogels with various thermal magnitudes and durations. Additionally, no apparent changes in the mechanical properties of hydrogels were observed with FUS treatment.Discussion: Utilizing FUS thermal and mechanical stimulus provides a potential method of remotely controlling NO release from hydrogels at a wound site to aid in tendon repair.
Improved social functioning and role functioning in rheumatic patients using a non-verbal communication tool: Results from a randomized, double-blind, controlled pilot-study
Authors: Karnik Julia , Riedl David , Schirmer Michael 
Published: April 2023

IntroductionPain is a leading symptom in patients with rheumatic diseases, limiting not only physical functioning but also social well-being. This study studied the practicability of colored wristbands as non-verbal communication tools and the effects of these tools on social and role functioning in rheumatic patients.MethodsThis prospective, double-blind, randomized controlled pilot study recruited 110 patients. Practicability of colored silicon wristbands as non-verbal communication tools was assessed by questionnaires. The control group received written information on the rheumatic diseases and their management in general. Social functioning and role functioning were assessed using two subscales from the EORTC QLQ-C30.ResultsA significant overall improvement of social functioning (p = 0.005) and role functioning (p = 0.001) with medium to large effect size were reported by patients both in the intervention and the control group. Post hoc analyses revealed a significant change in the mean social functioning (p = 0.007) and role functioning scores with medium effect size, while no such effect was found in the control group for neither variable (p = 0.006 and p = 0.06–0.21, respectively). 42.9% of the patients will continue to use a non-verbal communication tool in the future. Practicability of the wristbands was limited by small size of the wristbands in 17.6% and uncomfortable wearing of the wristbands and skin irritation each in 4.4% of the patients.DiscussionThis study shows first promising results for the use of a non-verbal communication tool in about 50.0% of the patients with rheumatic diseases, to improve their social functioning and role functioning.
Antidepressants amitriptyline, fluoxetine, and traditional Chinese medicine Xiaoyaosan caused alterations in gut DNA virome composition and function in rats exposed chronic unpredictable mild stress
Authors: Li Jialin , Qu Wan , Hu Chengcheng , Liu Zongbao , Yan He 
Published: April 2023

BackgroundIn clinical practice, antidepressant drugs are widely used to treat depression. Previous studies have attention to the impact of antidepressants on the bacterial microbiome, while the role of these drugs in the gut virome is still unclear.MethodsIn this study, we estimated the effects of antidepressant amitriptyline (Ami), fluoxetine (Flu), and traditional Chinese medicine Xiaoyaosan (XYS) administration on gut viral composition and function in a chronic unpredictable mild stress (CUMS)-induced depression rat model based on shotgun metagenomic sequencing.ResultsThe results showed that treatment with Ami, Flu, and XYS significantly changed the gut viral composition compared with the CUMS-induced rats. At the family level, the abundance of f_unclassified_Caudovirales in CUMS rats was remarkably lower than in the HC rats, nevertheless, XYS significantly recovered the abundance of Caudovirales. Meanwhile, the abundance of Podoviridae was expanded in CUMS rats compared with the HC rats, and the profile was then significantly reduced after XYS treatment. Furthermore, both antidepressants and XYS increased the abundance of Siphoviridae compared with the CUMS rats, but only Ami treatments had significant differences. Subsequent function annotation further implied that Ami, Flu, and XYS showed to involve an alteration of the diverse viral functions, such as carbohydrate metabolism, xenobiotics biodegradation and metabolism, community-prokaryotes, translation, and neurodegenerative disease. Additionally, the co-occurrence network displayed that there are complex interactions between viral operational taxonomic units (vOTUs) represented by temperate phages and the majority of bacterial genera in the intestine ecosystem.ConclusionOur study proved for the first time that depression is characterized by massive alterations and functional distortion of the gut viruses, and after oral administration of Ami, Flu, and XYS could affect disordered gut virome, which could be a novel target in depression.
Identification of microbial community in the urban environment: The concordance between conventional culture and nanopore 16S rRNA sequencing
Authors: Lee Annie Wing-Tung , Chan Chloe Toi-Mei , Wong Lily Lok-Yee , Yip Cheuk-Yi , Lui Wing-Tung , Cheng Kai-Chun , Leung Jake Siu-Lun , Lee Lam-Kwong , Wong Ivan Tak-Fai , Ng Timothy Ting-Leung , Lao Hiu-Yin , Siu Gilman Kit-Hang 
Published: April 2023

IntroductionMicrobes in the built environment have been implicated as a source of infectious diseases. Bacterial culture is the standard method for assessing the risk of exposure to pathogens in urban environments, but this method only accounts for &lt;1% of the diversity of bacteria. Recently, full-length 16S rRNA gene analysis using nanopore sequencing has been applied for microbial evaluations, resulting in a rise in the development of long-read taxonomic tools for species-level classification. Regarding their comparative performance, there is, however, a lack of information.MethodsHere, we aim to analyze the concordance of the microbial community in the urban environment inferred by multiple taxonomic classifiers, including ARGpore2, Emu, Kraken2/Bracken and NanoCLUST, using our 16S-nanopore dataset generated by MegaBLAST, as well as assess their abilities to identify culturable species based on the conventional culture results.ResultsAccording to our results, NanoCLUST was preferred for 16S microbial profiling because it had a high concordance of dominant species and a similar microbial profile to MegaBLAST, whereas Kraken2/Bracken, which had similar clustering results as NanoCLUST, was also desirable. Second, for culturable species identification, Emu with the highest accuracy (81.2%) and F1 score (29%) for the detection of culturable species was suggested.DiscussionIn addition to generating datasets in complex communities for future benchmarking studies, our comprehensive evaluation of the taxonomic classifiers offers recommendations for ongoing microbial community research, particularly for complex communities using nanopore 16S rRNA sequencing.
Machine learning algorithms assist early evaluation of enteral nutrition in ICU patients
Authors: Wang Ya-Xi , Li Xun-Liang , Zhang Ling-Hui , Li Hai-Na , Liu Xiao-Min , Song Wen , Pang Xu-Feng 
Published: April 2023

BackgroundThis study applied machine learning (ML) algorithms to construct a model for predicting EN initiation for patients in the intensive care unit (ICU) and identifying populations in need of EN at an early stage.MethodsThis study collected patient information from the Medical Information Mart for Intensive Care IV database. All patients enrolled were split randomly into a training set and a validation set. Six ML models were established to evaluate the initiation of EN, and the best model was determined according to the area under curve (AUC) and accuracy. The best model was interpreted using the Local Interpretable Model-Agnostic Explanations (LIME) algorithm and SHapley Additive exPlanation (SHAP) values.ResultsA total of 53,150 patients participated in the study. They were divided into a training set (42,520, 80%) and a validation set (10,630, 20%). In the validation set, XGBoost had the optimal prediction performance with an AUC of 0.895. The SHAP values revealed that sepsis, sequential organ failure assessment score, and acute kidney injury were the three most important factors affecting EN initiation. The individualized forecasts were displayed using the LIME algorithm.ConclusionThe XGBoost model was established and validated for early prediction of EN initiation in ICU patients.
Evaluating dried salted cod amino acid signature for nutritional quality assessment and discriminant analysis
Authors: Quaresma M. A. G. , Pereira G. , Nunes M. L. , Sponda C. , Jardim A. , Gonçalves H. , Santos C. , Roseiro L. C. 
Published: April 2023

AimThus, the aim of this study was to answer three scientific questions: (1) Are the protein content and amino acid profile of dried salted cod influenced by species (Gadus morhua and Gadus macrocephalus)? (2) Are the protein content and amino acid profile of dried salted cod influenced by the geographical area of capture (Iceland and Norway)? and (3) Does the amino acid profile have the potential to be used as a discriminator of species and geographical areas of capture?MethodsA total of 45 dried salted cods (2–3 kg of dry weight; n = 15 samples/origin) were used in this study. The Atlantic cod was fished in the Atlantic northeast (FAO 27 area) within the Exclusive Economic zones (EEZ) of Norway (n = 15) and Iceland (n = 15), while the Pacific cod was caught in the Pacific northeast (FAO 67 area) within the Alaska EEZ (n = 15). Total protein content was determined by the Kjeldahl method, in accordance with the AOAC procedures. The amino acid profile was analyzed by HPLC with fluorescence detection (at excitation and emission wavelengths of 338 and 425 nm, respectively).ResultsThe Atlantic cod presented higher contents of total protein (33.90 versus 33.10 g/100 g of cod edible portion; p = 0.017) and total amino acid contents (32.52 versus 32.04 g/100 g of cod edible portion; p = 0.015) but displayed lower percentage of indispensable amino acids (32.16 versus 32.83 g/100 g of protein; p &lt; 0.001) than Pacific cod. Among the Atlantic cod harvesting locations, the Norwegian cod displayed higher total amino acid contents (96.91 versus 96.81 g/100 g of protein; p = 0.012) and higher percentage of indispensable amino acids (35.38 versus 28.94 g/100 g of protein; p = 0.042) than the Icelandic counterpart. A correct classification of 100% was obtained for the Pacific and Icelandic cod varieties, but the classification accuracy in the Norwegian cod was of just 86.67%, since 2 samples out of 15 were incorrectly classified as Icelandic.ConclusionThe comparison of cod species showed that the Atlantic cod had a significantly lower EAAI than the Pacific cod (p &lt; 0.001; 88.23 versus 88.61). On the other hand, the comparison of the two origins in the Atlantic cod, showed that Norwegian cod displayed a significantly higher EAAI than the Icelandic cod (99.15 versus 77.32). The assessment of the EAAI allows the classification of the protein’s nutritional quality, allowing us to classify both cod species as a good protein source to human diet. However, within the Atlantic cod, the Norwegian cod’s protein is classified as high quality, while the Icelandic cod attain the classification of useful quality. Regarding the amino acid profile discriminatory potential to classify cod samples. The results show that the AA profile has 100% accuracy in the separation of cod species, but was not globally efficient in the differentiation of the Norwegian from the Icelandic cod.
Emerging trends of BCG immunotherapy for bladder cancer in last decade: a bibliometric and visualization analysis
Authors: Chen Xingfeng , He Fang , Zhang Wenjin , Fu Yao , Cao Zhiqin 
Published: April 2023

BackgroundOne of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) following transurethral resection.MethodsWe searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of co-occurrence, co-polymerization and visualization.ResultsA total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years.ConclusionThe results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy.
Different risk and prognostic factors for liver metastasis of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population
Authors: Zhang Ningning , Xiang Yimei , Shao Qing , Wu Jing , Liu Yumin , Long Hua , Tao Dan , Zeng Xiaohua 
Published: April 2023

PurposeThe present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.Materials and methodsPatients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan–Meier method.ResultsIn total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P &lt; 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively.ConclusionsDe novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.
Therapeutic mammoplasty: a “wise” oncoplastic choice—lessons from the largest single-center cohort from Asia
Authors: Koppiker Chaitanyanand , Joshi Sneha , Mishra Rupa , Kelkar Devaki A. , Chigurupati Pragnya , Joshi Anjali , John Jisha , Kadu Shweta , Bagdia Amitkumar , Thakkar Deepti , Deshmukh Chetan , Allampati Harikiran , Sharan Gautam , Dhar Upendra , Nare Smeeta , Nagarkar Sanket , Busheri Laleh , Varghese Beenu , Pai Mugdha 
Published: April 2023

IntroductionThe majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM.MethodsAll patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures.ResultsThe median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1–pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains.ConclusionWe conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.