bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulated microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia
Authors: Miao Lu‐Wei , Liu Tian‐Zhen , Sun Yue‐Hong , Cai Nan , Xuan Ying‐Ying , Wei Zhenlong , Cui Bing‐Bing , Jing Lin‐Lin , Ma Hui‐Ping , Xian Cory J. , Wang Ju‐Fang , Gao Yu‐Hai , Chen Ke‐Ming 
Published: October 2023

AbstractOxidative stress has been considered to be closely related to spaceflight‐induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity‐induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca2+ overload, and the latter was found to be caused by increased activity of Ca2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A‐elicited Ca2+ influx. Supplementation of HC‐067047, a specific antagonist of TRPV4, attenuated microgravity‐induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity‐induced shortening of primary cilia led to increased TRPV4 levels and Ca2+ influx. When primary cilia were protected by miR‐129‐3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity‐induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity‐induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca2+ overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts.
Comparative Efficacy and Safety of Antidepressants for Patients with Chronic Back Pain: A Network Meta‐Analysis
Authors: Ma Tao , Qi Hongyu , Mao Yuanrong , Wang Ya , Duan Baolin , Ma Ke 
Published: October 2023

AbstractVarious antidepressants have introduced in clinical practice for pain management, but it is important to understand how to properly use them. We therefore performed a systematic review and network meta‐analysis to compare and rank the efficacy and safety of antidepressants for patients with chronic back pain. We identified eligible randomized controlled trials (RCTs) that investigated the efficacy and safety of antidepressants for chronic back pain from PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov, searching from inception to May 2023. Six categories of antidepressants for the treatment of chronic back pain were included, and the surface under the cumulative ranking probabilities was applied to rank the treatment strategies. Overall, we selected 19 RCTs recruiting 2903 patients for the meta‐analysis. Tricyclic antidepressants presented the best relative effects for relief in pain score (surface under the cumulative ranking, 84.4%). The results of pairwise comparison analyses found the use of serotonin–noradrenaline reuptake inhibitors (SNRIs) significantly reduced pain score and low disability score compared with placebo, irrespective of treatment duration. Noradrenaline–dopamine reuptake inhibitors (relative risk [RR], 2.80; 95% confidence interval [CI], 1.30‐6.03; P = .008) and SNRIs (RR, 1.17; 95% CI, 1.07‐1.27; P < .001) significantly increased the risk of adverse events. SNRIs were associated with an increased risk of withdrawal due to adverse events (RR, 2.37; 95% CI, 1.64‐3.43; P < .001). This study found that antidepressants are more efficacious than placebos for treating chronic back pain, and tricyclic antidepressants are the most likely medications that lead to pain relief.
Engineered small extracellular vesicle‑mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy
Authors: Kang Ji‐Young , Mun Dasom , Chun Yumin , Park Da‐Seul , Kim Hyoeun , Yun Nuri , Joung Boyoung 
Published: October 2023

AbstractSmall‐interfering RNA (siRNA) therapy is considered a powerful therapeutic strategy for treating cardiac hypertrophy, an important risk factor for subsequent cardiac morbidity and mortality. However, the lack of safe and efficient in vivo delivery of siRNAs is a major challenge for broadening its clinical applications. Small extracellular vesicles (sEVs) are a promising delivery system for siRNAs but have limited cell/tissue‐specific targeting ability. In this study, a new generation of heart‐targeting sEVs (CEVs) has been developed by conjugating cardiac‐targeting peptide (CTP) to human peripheral blood‐derived sEVs (PB‐EVs), using a simple, rapid and scalable method based on bio‐orthogonal copper‐free click chemistry. The experimental results show that CEVs have typical sEVs properties and excellent heart‐targeting ability. Furthermore, to treat cardiac hypertrophy, CEVs are loaded with NADPH Oxidase 4 (NOX4) siRNA (siNOX4). Consequently, CEVs@siNOX4 treatment enhances the in vitro anti‐hypertrophic effects by CEVs with siRNA protection and heart‐targeting ability. In addition, the intravenous injection of CEVs@siNOX4 into angiotensin II (Ang II)‐treated mice significantly improves cardiac function and reduces fibrosis and cardiomyocyte cross‐sectional area, with limited side effects. In conclusion, the utilization of CEVs represents an efficient strategy for heart‐targeted delivery of therapeutic siRNAs and holds great promise for the treatment of cardiac hypertrophy.
Network pharmacology prediction and molecular docking analysis reveal the mechanism of modified Bushen Yiqi formulas on chronic obstructive pulmonary disease
Authors: Choi Wenglam , Wu Yueren , Li Yifan , Dong Jingcheng 
Published: October 2023

AbstractBackgroundThe present study aimed to explore the mechanism of the modified Bushen Yiqi formula (MBYF) in the treatment of chronic obstructive pulmonary disease (COPD) based on network pharmacology and molecular docking.MethodsFirst, the active ingredients and corresponding targets in MBYF were mined through the Traditional Chinese Medicine Systems Pharmacology database. Subsequently, Online Mendelian Inheritance in Man, DrugBank, and GeneCard were used to screen COPD‐related targets. Cytoscape was used to construct a network of candidate components of MBYF in COPD treatment. The overlapping targets of COPD and MBYF were used to treat COPD, and then CytoHubba and CytoNAC plug‐ins in Cytoscape were used for topology analysis to build the core network. In addition, core targets were used for Gene Ontology analysis and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes. Finally, AutoDock Vina software was used to conduct a molecular docking study on the core active ingredients and core targets to verify the above network pharmacological analysis.ResultsSeventy‐nine active components of MBYF were screened and 261 corresponding targets were found. At the same time, 1307 related targets corresponding to COPD were screened and 111 overlapping targets were matched. By bioinformatics analysis, 10 core targets were identified, and subsequently, enrichment analysis revealed 385 BP, two CC, eight MF and 78 related signaling pathways. The binding of the core active components in MBYF to the core target was further verified by molecular docking, and all showed good binding.ConclusionsThe active components of MBYF, such as quercetin, kaempferol, luteolin, and baicalein, may be the material basis for the treatment of chronic obstructive pulmonary disease. They affect the expression of inflammatory cells and inflammatory factors, protein phosphorylation, and smooth muscle hyperplasia through tumor necrosis factor, interleukin‐17, mitogen‐activated protein kinase, nuclear factor‐kappa B and other signaling pathways.
Counterexamples to Gerbner's conjecture on stability of maximal F‐free graphs
Authors: Wang Jian , Wang Shipeng , Yang Weihua 
Published: October 2023

AbstractLet and let be an ‐chromatic graph with a color‐critical edge, that is, there exists such that has chromatic number . Gerbner recently conjectured that every ‐vertex maximal ‐free graph with at least edges contains an induced complete ‐partite graph on vertices. Let be a graph obtained from copies of by sharing a common edge. In this paper, we show that for all if is an ‐vertex maximal ‐free graph with at least edges, then contains an induced complete bipartite graph on vertices. We also construct graphs to show that the magnitude in is best possible, which disproves Gerbner's conjecture for .
Automation and artificial intelligence in radiation therapy treatment planning
Authors: Jones Scott , Thompson Kenton , Porter Brian , Shepherd Meegan , Sapkaroski Daniel , Grimshaw Alexandra , Hargrave Catriona 
Published: October 2023

AbstractAutomation and artificial intelligence (AI) is already possible for many radiation therapy planning and treatment processes with the aim of improving workflows and increasing efficiency in radiation oncology departments. Currently, AI technology is advancing at an exponential rate, as are its applications in radiation oncology. This commentary highlights the way AI has begun to impact radiation therapy treatment planning and looks ahead to potential future developments in this space. Historically, radiation therapist's (RT's) role has evolved alongside the adoption of new technology. In Australia, RTs have key clinical roles in both planning and treatment delivery and have been integral in the implementation of automated solutions for both areas. They will need to continue to be informed, to adapt and to transform with AI technologies implemented into clinical practice in radiation oncology departments. RTs will play an important role in how AI‐based automation is implemented into practice in Australia, ensuring its application can truly enable personalised and higher‐quality treatment for patients. To inform and optimise utilisation of AI, research should not only focus on clinical outcomes but also AI's impact on professional roles, responsibilities and service delivery. Increased efficiencies in the radiation therapy workflow and workforce need to maintain safe improvements in practice and should not come at the cost of creativity, innovation, oversight and safety.
Ultrasensitive PCR system for HBV DNA detection: Risk stratification for occult hepatitis B virus infection in English blood donors
Authors: Fu Michael X. , Simmonds Peter , Andreani Julien , Baklan Hatice , Webster Mhairi , Asadi Romisa , Golubchik Tanya , Breuer Judith , Ijaz Samreen , Ushiro‐Lumb Ines , Brailsford Su , Irving William L. , Andersson Monique , Harvala Heli 
Published: October 2023

AbstractOccult hepatitis B (HBV) infection (OBI), characterized by low viral loads, accounts for much of the risk of HBV transfusion‐transmitted infection. With anticore antibodies (anti‐HBc) screening introduced in England, the imperative to identify OBI donors has increased. We aimed to develop an ultra‐sensitive PCR system and investigate risk factors for HBV DNA presence in blood donations. Seven extraction methods and three PCR assays were compared. The optimal system was sought to determine HBV DNA presence in anti‐HBc‐positive donations. Predictors of DNA positivity were subsequently investigated. Extraction from 5 mL of plasma increased sample representation and resulted in HBV DNA detection in low viral load samples (~0.5 IU/mL). Screening of 487 763 donations in 2022 identified two OBI donors and 2042 anti‐HBc‐positive donors, 412 of the latter with anti‐HBs < 100 mIU/mL. Testing of 134 anti‐HBc‐positive donations utilizing the 5 mL extraction method identified two further HBV DNA‐positive donations. Higher anti‐HBc titer and anti‐HBs negativity were significant predictors of DNA detectability in anti‐HBc‐positive donations. An ultrasensitive PCR assay identified potentially infectious donations increasing HBV DNA detection in anti‐HBc‐positive donors from 0.5% to 1.9%. Anti‐HBc titers may further complement the risk stratification for DNA positivity in anti‐HBc screening and minimize unnecessary donor deferral.
Prediction of symptomatic anastomotic leak after rectal cancer surgery: A machine learning approach
Authors: Shen Yu , Huang Li‐Bin , Lu Anqing , Yang Tinghan , Chen Hai‐Ning , Wang Ziqiang 
Published: October 2023

AbstractIntroductionAnastomotic leakage (AL) remains the most dreaded and unpredictable major complication after low anterior resection for mid‐low rectal cancer. The aim of this study is to identify patients with high risk for AL based on the machine learning method.MethodsPatients with mid‐low rectal cancer undergoing low anterior resection were enrolled from West China Hospital between January 2008 and October 2019 and were split by time into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) method and stepwise method were applied for variable selection and predictive model building in the training cohort. The area under the receiver operating characteristic curve (AUC) and calibration curves were used to evaluate the performance of the models.ResultsThe rate of AL was 5.8% (38/652) and 7.2% (15/208) in the training cohort and validation cohort, respectively. The LASSO‐logistic model selected almost the same variables (hypertension, operating time, cT4, tumor location, intraoperative blood loss) compared to the stepwise logistic model except for tumor size (the LASSO‐logistic model) and American Society of Anesthesiologists score (the stepwise logistic model). The predictive performance of the LASSO‐logistics model was better than the stepwise‐logistics model (AUC: 0.790 vs. 0.759). Calibration curves showed mean absolute error of 0.006 and 0.013 for the LASSO‐logistics model and stepwise‐logistics model, respectively.ConclusionOur study developed a feasible predictive model with a machine‐learning algorithm to classify patients with a high risk of AL, which would assist surgical decision‐making and reduce unnecessary stoma diversion. The involved machine learning algorithms provide clinicians with an innovative alternative to enhance clinical management.
Impact of Medicaid expansion on the multimodal treatment of biliary tract cancer
Authors: Ortiz Rueda Belisario , Endo Yutaka , Tsilimigras Diamantis I. , Araujo Lima Henrique , Munir Muhammad Musaab , Woldesenbet Selamawit , Dillhoff Mary , Ejaz Aslam , Cloyd Jordan , Pawlik Timothy M. 
Published: October 2023

AbstractIntroductionThe impact of Medicaid expansion (ME) on the treatment of patients with cancer remains controversial, especially individuals requiring complex multidisciplinary care. We sought to evaluate the impact of Medicaid expansion (ME) on receipt of multimodal care, including surgical resection, for Stage I–III biliary tract cancer (BTC).MethodsPatients diagnosed with BTC between 40 and 65 years of age were identified from the National Cancer Database and divided into pre‐ (2008–2012) and post‐ (2015–2018) ME cohorts. Difference‐in‐difference (DID) analysis was used to determine the impact of ME on the utilization of surgery and multimodal chemotherapy and/or radiotherapy treatment for BTC.ResultsAmong 12,415 patients with BTC (extrahepatic, n = 5622, 45.3%; intrahepatic, n = 4352, 35.1%; gallbladder, n = 1944, 15.7%; overlapping, n = 497, 4.0%), 5835 (47.0%) and 6580 (53.0%) patients were diagnosed before versus after ME, respectively. Overall utilization of surgery (OR 1.13, 95% CI 1.02–1.26) and multimodality therapy (OR 1.13, 95% CI 1.01–1.27) increased in states that adopted ME. Utilization of surgery among uninsured/Medicaid patients in ME states increased relative to patients living in non‐ME states (∆+10.1%, p = 0.01). Similarly, the use of multimodal treatment increased among uninsured/Medicaid patients living in ME versus non‐ME states (∆+6.4%, p = 0.04); in contrast, there were no difference among patients with other insurance statuses (overall: ∆+1.5%, private: ∆−2.0%, other: ∆+3.9%, all p > 0.5). Uninsured/Medicaid patients with BTC who lived in a ME state had a lower risk of long‐term death in the post‐ME era (HR 0.81, 95% CI 0.67–0.98; p = 0.03).ConclusionsImplementation of ME positively impacted survival among patients who underwent surgical and multimodal treatment for Stage I–III BTC.
Music literacy training in dermatology: A mixed methods cohort study of postgraduate education
Authors: Matthews Raymond , Wray Alexander , Peilober‐Richardson Francesca , Young Helen S. 
Published: October 2023

AbstractBackgroundWe have previously pioneered arts‐based training to enhance clinical skills in senior and resident dermatologists. However, the utility of music to support the development of dermatological skills such as listening, observation, description and communication is unexplored.ObjectivesWe hypothesised that music literacy training (MLT) would enhance the clinical dermatology skills of newly qualified doctors and could be effectively delivered in a single‐session virtual format.MethodsOur training comprised a 2.5‐h course held in October 2021 on the virtual meeting platform Zoom. The course was led by a music educator and included sessions which placed particular emphasis on listening to music, discriminating auditory cues to interpret imagery and meaning, and describe this to others. Participants explored concepts such as pitch, melody, pace, rhythm, dynamics and timbre by working collaboratively, independently and in small break‐out groups. All participants documented their learning journey through pre‐ and post‐course reflective essays and the training was evaluated by a pre‐ and post‐course dermatology clinical assessment.ResultsMusic served as a catalyst for reflection and discussion, supporting significant improvement key clinical skills such as listening, clinical observation and description in newly qualified doctors. Participants reported increased confidence communicating with others and found the course structure enjoyable and fun.ConclusionsCombined qualitative and quantitative evidence highlights the benefit of MLT in developing key clinical skills in newly qualified doctors which is effective when delivered in a single‐session, virtual format.
Tackling steroid phobia: Insights from behavioural economics and psychological approaches
Authors: Nakashima Chisa , Ohtake Fumio , Otsuka Atushi 
Published: October 2023

AbstractSteroid phobia, characterized by an irrational fear or avoidance of topical corticosteroids, poses a significant challenge to the effective treatment of various skin conditions, including atopic dermatitis (AD) and psoriasis. This issue has its roots in the introduction of topical corticosteroids in the 1950s and has been perpetuated by concerns regarding adverse effects and misinformation. International Dermatological Societies including the Japanese Dermatological Association have endeavored to address this problem by providing information and guidance to physicians and patients, resulting in a better understanding of appropriate steroid use and risk management. Despite these efforts, steroid phobia has not been fully resolved in the world, including in Japan.To shed light on potential solutions, this review explores the field of behavioral economics, which offers insights into human decision‐making processes and cognitive biases. Richard Thaler's concept of nudges emerges as a promising strategy for influencing patients' decision‐making regarding steroid treatments. However, the effectiveness of nudges may vary depending on the strength of an individual's concerns and fears. In cases where patients exhibit strong resistance to steroid use, alternative psychological techniques that establish trust and facilitate clear communication may be more beneficial.This review emphasizes the necessity of adopting a multifaceted approach that integrates principles from behavioral economics and employs complementary psychological strategies to address steroid phobia and enhance treatment adherence in affected patient populations. By combining these approaches, healthcare professionals can tackle the complex nature of steroid phobia and promote better treatment outcomes for patients with skin conditions.
Association of ethnicity and time to surgery among patients with chronic rhinosinusitis
Authors: Tam Benjamin , Collet Casey , Le Jessica , Badash Ido , Garcia Erick , Wrobel Bozena , Rice Dale , Hur Kevin 
Published: October 2023

AbstractObjectivesDetermine factors associated with delayed endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS).MethodsThis is a retrospective cohort study conducted at a tertiary care academic center. Patients were included in the study if they were at least 18 years old and underwent surgery for CRS. Electronic medical records were retrospectively reviewed to collect demographic and clinical data. Patients with CRS secondary to another pathology such as malignancy were excluded. Multiple linear regression was performed to determine factors associated with the number of days between a patient's preoperative consultation and the date of surgery.ResultsA total of 103 patients with a mean age of 46.6 ± 16.8 years were included in the analysis; 51.5% of patients were females, 46.6% identified as White, and 29.1% identified as Hispanic. The majority of patients (67.0%) had preferred provider organization health insurance; 43.7% of patients had nasal polyps, 70.9% had a deviated nasal septum, and the mean preoperative Sinonasal Outcomes Test‐22 (SNOT‐22) score was 41.0 ± 23.8. The mean time to surgery after the final preoperative visit was 71.7 days ± 65.6 days. Hispanic ethnicity was associated with increased time to surgery (p < .05) when controlling for other variables. No other variables were associated with time to surgery on multivariate analysis.ConclusionHispanic ethnicity may be an independent predictor of increased time to sinus surgery independent of disease severity and other demographic variables.Level of Evidence2b