bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Nonlinear Dynamic Behaviors of Vertical Rotor System Supported by Aerostatic Bearings
Authors: Qiu Shun , Ke Changlei , Li Kongrong , Zhang Xiaohua , Peng Nan , Liu Liqiang 
Published: October 2024

Abstract
A common issue associated with gas bearing–rotor systems is the tendency to generate self-excited vibrations, leading to instability. To address this problem, the fluid–structure coupling model of an aerostatic bearing–rotor system is established in this paper. Then, a hybrid method combining the finite difference method (FDM) and direct integration method is employed to solve the bearing lubrication equation and rotor motion equation simultaneously. Furthermore, based on the orbits of rotor center, frequency spectrum diagrams, Poincaré maps, waterfall diagrams, and bifurcation diagrams, the effects of rotational speed, rotor mass, orifice diameter, and nominal clearance on the nonlinear dynamic behaviors of the bearing–rotor system are investigated. The results indicate that the system exhibits rich nonlinear behaviors with increasing rotational speed and rotor mass, including the occurrence of typical half-speed whirl. However, the nonlinear vibrations of the system can be restricted by selecting appropriate bearing structural parameters, providing theoretical guidance for the design of aerostatic bearing–rotor systems.
Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study
Authors: Imamura Keiko , Izumi Yuishin , Egawa Naohiro , Ayaki Takashi , Nagai Makiko , Nishiyama Kazutoshi , Watanabe Yasuhiro , Murakami Takenobu , Hanajima Ritsuko , Kataoka Hiroshi , Kiriyama Takao , Nanaura Hitoki , Sugie Kazuma , Hirayama Takehisa , Kano Osamu , Nakamori Masahiro , Maruyama Hirofumi , Haji Shotaro , Fujita Koji , Atsuta Naoki , Tatebe Harutsugu , Tokuda Takahiko , Takahashi Naoto , Morinaga Akiko , Tabuchi Riko , Oe Motoki , Kobayashi Mihoko , Lobello Kasia , Morita Satoshi , Sobue Gen , Takahashi Ryosuke , Inoue Haruhisa 
Published: October 2024

IntroductionAmyotrophic lateral sclerosis (ALS) is a progressive, severe neurodegenerative disease caused by motor neuron death. Development of a medicine for ALS is urgently needed, and induced pluripotent cell-based drug repurposing identified a Src/c-Abl inhibitor, bosutinib, as a candidate for molecular targeted therapy of ALS. A phase 1 study confirmed the safety and tolerability of bosutinib in a 12-week treatment of ALS patients. The objectives of this study are to evaluate the efficacy and longer-term safety of bosutinib in ALS patients.Methods and analysisAn open-label, multicentre phase 2 study was designed. The study consisted of a 12-week observation period, a 1-week transitional period, a 24-week study treatment period and a 4-week follow-up period. Following the transitional period, patients whose total Revised ALS Functional Rating Scale (ALSFRS-R) score declined by 1 to 4 points during the 12-week observation period were to receive bosutinib for 24 weeks. In this study, 25 ALS patients will be enrolled; patients will be randomly assigned to the following groups: 12 patients in the 200 mg quaque die (QD) group and 13 patients in the 300 mg QD group of bosutinib. The safety and exploratory efficacy of bosutinib in ALS patients for 24 weeks will be assessed. Efficacy using the ALSFRS-R score will be compared with the external published data from an edaravone study (MCI186-19) and registry data from a multicentre ALS cohort study, the Japanese Consortium for Amyotrophic Lateral Sclerosis Research.Ethics and disseminationThis study was approved by the ethics committees of Kyoto University, Tokushima University, Kitasato University, Tottori University, Nara Medical University School of Medicine, Toho University and Hiroshima University. The findings will be disseminated in peer-reviewed journals and at scientific conferences.Trial Registration numberjRCT2051220002; Pre-results,NCT04744532; Pre-results
Patient delay, diagnosis delay, and treatment outcomes among migrant patients with tuberculosis in Shanghai, China, 2018-2020: a mixed-methods study
Authors: Jia Yufei , Jiang Weixi , Xiao Xiao , Lou Zhexun , Tang Shenglan , Chen Jing , Long Qian 
Published: October 2024

ObjectivesThis study aimed to examine patient delay, diagnosis delay and treatment performance among patients with tuberculosis (TB) in Shanghai, China in 2018–2020 focusing on disparities between migrant and local patients with TB.DesignMixed-method study.Setting and participantsQuantitative data were collected from the TB information management system in Shanghai; 17 533 bacteriologically confirmed and clinically diagnosed patients with pulmonary TB registered in 2018–2020 were included. Qualitative interviews were conducted with TB administrators (n=3) and community healthcare providers (two groups, n=10 in total) from Shanghai.Main outcome measuresPatient delay, diagnosis delay and treatment completion were examined by resident type using descriptive analysis and logistic regressions. Qualitative interviews were conducted to understand factors associated with the disparities.ResultsFrom 2018 to 2020, migrant patients with TB accounted for 44.40% of total cases. There was no significant difference in patient delay between migrant and local patients (18.47 days on average). 22.12% of migrants and 16.52% of locals experienced diagnosis delays exceeding 14 days, respectively. After adjusting for all variables, migrant patients (OR 1.30, 95% CI 1.18 to 1.44) and initial care seeking at general hospitals (OR 3.76, 95% CI 3.45 to 4.09) were associated with a higher probability of diagnosis delay. 93.9% of migrant patients and 89.4% of the local patients had a successful TB treatment without statistically significant difference after adjusting for all variables. Qualitative interviews revealed a standard approach to managing patients with TB in Shanghai no matter their resident type. Young migrant patients who were able to maintain their jobs in Shanghai often had better treatment adherence. Despite patients’ COVID-19 fear and limited care access in 2020, TB treatment minimally affected for both due to community-based case management.ConclusionsMigrant patients were more likely to experience diagnosis delay. It should improve awareness and knowledge of TB among healthcare professionals at general hospitals to mitigate the risk of diagnosis delay.
Multiarm, non-randomised, single-centre feasibility study—investigation of the differential biology between benign and malignant renal masses using advanced magnetic resonance imaging techniques (IBM-Renal): protocol
Authors: Horvat-Menih Ines , McLean Mary A , Zamora-Morales Maria Jesus , Wylot Marta , Kaggie Joshua , Khan Alixander S , Gill Andrew B , Duarte Joao , Locke Matthew J , Mendichovszky Iosif , Li Hao , Priest Andrew N , Warren Anne Y , Welsh Sarah J , Jones James O , Armitage James N , Mitchell Thomas J , Stewart Grant D , Gallagher Ferdia A 
Published: October 2024

IntroductionLocalised renal masses are an increasing burden on healthcare due to the rising number of cases. However, conventional imaging cannot reliably distinguish between benign and malignant renal masses, and renal mass biopsies are unable to characterise the entirety of the tumour due to sampling error, which may lead to delayed treatment or overtreatment. There is an unmet clinical need to develop novel imaging techniques to characterise renal masses more accurately. Renal tumours demonstrate characteristic metabolic reprogramming, and novel MRI methods have the potential to detect these metabolic perturbations, which may therefore aid accurate characterisation. Here, we present our study protocol for the investigation of the differential biology of benign and malignant renal masses using advanced MRI techniques (IBM-Renal).Methods and analysisIBM-Renal is a multiarm, single-centre, non-randomised, feasibility study with the aim to provide preliminary evidence for the potential role of the novel MRI techniques to phenotype localised renal lesions. 30 patients with localised renal masses will be recruited to three imaging arms, with 10 patients in each: (1) hyperpolarised [1-13C]-pyruvate MRI, (2) deuterium metabolic imaging (DMI) and (3) sodium MRI. The diagnosis will be made on samples acquired at biopsy or at surgery. The primary objective is the technical development of the novel MRI techniques, with the ultimate aim to understand whether these can identify differences between benign and malignant tumours, while the secondary objectives aim to assess how complementary the techniques are, and if they provide additional information. The exploratory objective is to link imaging findings with clinical data and molecular analyses for the biological validation of the novel MRI techniques.Ethics and disseminationThis study was ethically approved (UK REC HRA: 22/EE/0136; current protocol version 2.1 dated 11 August 2022). The plans for dissemination include presentations at conferences, publications in scientific journals, a doctoral thesis and patient and public involvement.Trial registration numberNCT06016075.
Development and validation of a clinical diagnostic model for myocardial ischaemia in borderline coronary lesions based on optical pumped magnetometer magnetocardiography: a prospective observational cohort study
Authors: Yang Shuwen , Feng Lanxin , Zhang Mingduo , Zhang Min , Ma Zhao , Zhang Huan , Zhang YaZhe , Liu Linqi , Zhou Shu , Zhao Xin , Yang Xue Yao , He Jiqiang , Ren Yanlong , Luo Yawei , Xu Feng , Tu Chenchen , Song Xiantao , Zhang Hong-Jia 
Published: October 2024

ObjectivesTo develop and validate a clinical diagnostic model based on optical pumped magnetometer magnetocardiography (OPM-MCG) for the detection of myocardial ischaemia in patients with borderline coronary lesions prior to invasive coronary angiography (ICA).DesignProspective observational cohort study.SettingSingle centre of the China National Clinical Research Centre for Cardiovascular Disease (NCCMRC).ParticipantsAdults with borderline coronary lesions on ICA (n=141).InterventionsUnderwent OPM-MCG before ICA and fractional flow reserve measurement.ResultsFive parameters were included in the final diagnostic model: MAgmax-TT, δDtsum-PN, δAgsum-C, δArsum-N and δArmin-N. 1000 bootstrap replications showed that the area under the receiver operating characteristic curve and 95% CI of the diagnostic model were 0.864 (0.803–0.925), with a sensitivity of 79.4%, specificity of 80.8%, positive predictive value of 79.4% and negative predictive value of 80.8%. Decision curve analysis showed a net benefit from the predictive model when the threshold probability of an ischaemic patient was >12%, suggesting the potential utility of the model in the real world.ConclusionsA nomogram based on five OPM-MCG parameters was developed to assess myocardial ischaemia in patients with borderline coronary lesions and has the potential to reduce the need for unnecessary ICA.Trial registration numberChina Clinical Trial Registry (ChiCTR2300072382).
Food insecurity and other barriers to adherence to a gluten-free diet in individuals with coeliac disease and non-coeliac gluten sensitivity in the Netherlands: a mixed-methods study
Authors: Smeets Sharine M , Kiefte-de Jong Jessica C , van der Velde Laura A 
Published: October 2024

ObjectivesTo determine the prevalence of food insecurity among individuals with coeliac disease (CeD) and non-coeliac gluten sensitivity (NCGS) in the Netherlands and explore its association with diet quality and other barriers to adherence to a gluten-free diet.DesignMixed-method design comprising a survey and semistructured interviews.SettingAn online survey was distributed through social media accounts and the newsletter of the Dutch Association for Celiac Disease. Community-dwelling patients were surveyed and interviewed between June and November 2023.Participants and outcome measuresIn total 548 adults with CeD and NCGS in the Netherlands who adhered to a gluten-free diet completed the survey including questions related to demographics, household food insecurity, financial stress and diet quality. Regression analyses were conducted to assess associations between food insecurity and diet quality, and between food insecurity and perceived difficulty of gluten-free eating and cooking. Additionally, semistructured interviews with eight food insecure adults with CeD were conducted.ResultsThe prevalence of food insecurity was 23.2%, with 10.4% reporting very low food security. Very low food insecurity was associated with poorer diet quality (β=−5.5; 95% CI=−9.2 to –1.9; p=0.003). Food insecurity was associated with heightened perceived barriers across multiple themes. In age, income and education adjusted models, compared with food secure participants, low food secure participants were more likely to experience difficulty regarding skills (OR=2.5; 95% CI=1.5 to 4.3; p≤0.001), social circumstances (OR=2.6; 95% CI=1.1 to 6.4; p=0.038), resources (OR=2.5; 95% CI=1.5 to 4.4; p=0.001) and naturally gluten-free products (OR=1.8; 95% CI=1.0 to 3.1; p=0.045) in gluten-free eating and cooking. Participants with very low food security were more likely to experience difficulty regarding skills (OR=4.4; 95% CI=2.4 to 8.1; p≤0.001) and resources (OR=4.2; 95% CI=2.3 to 7.8; p<0.001) in gluten-free eating and cooking. The qualitative analysis provided a deeper understanding of these challenges, including employed strategies to manage costs and insights into the mental burden associated with adhering to a gluten-free diet.ConclusionThese findings indicate that food insecurity is prevalent among Dutch people with CeD and NCGS, with potential impact on diet quality and adherence to a gluten-free diet. It further provided insight into perceived barriers to adhering to a gluten-free diet among this target population. These challenges should be taken into account by clinicians and policy makers.
Direct oral anticoagulant approvals by four major regulatory agencies: a cross-sectional analysis of premarket and postmarket evidence
Authors: Mooghali Maryam , Zhou Tianna , Ross Joseph S 
Published: October 2024

ObjectivesTo compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies.DesignCross-sectional.SettingEuropean Medicines Association (EMA), US Food and Drug Administration (FDA), Health Canada and Australian Therapeutic Goods Administration (TGA).ParticipantsApixaban, dabigatran, edoxaban and rivaroxaban marketing authorisations.Outcome measuresConcordance among regulatory agencies with respect to (1) premarket evidence used to establish efficacy and safety and (2) postmarket safety boxed warnings and postmarketing study requirements.ResultsApixaban, dabigatran and rivaroxaban were approved by each of the four regulatory agencies; edoxaban was only not approved by TGA. For premarket efficacy evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for three (75%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for four (100%) drugs and number of phase 2 trials for three (75%) drugs. For the premarket safety evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for two (50%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for three (75%) drugs and number of phase 2 trials for zero (0%) drugs. For postmarket safety information, FDA was the only agency that issued boxed warnings (for three (75%) drugs). Additionally, EMA and TGA required postmarketing studies (for four (100%) and two (50%) drugs, respectively), while FDA and Health Canada did not have any postmarketing requirements.ConclusionsThere was a high degree of concordance in the phase 3 trial premarket evidence used to establish efficacy and safety of direct oral anticoagulant approvals across four major regulatory agencies, but discordance in the phase 2 trial premarket evidence used, as well as in postmarket safety boxed warnings and postmarketing study requirements. These discrepancies highlight opportunities for further harmonisation in the evaluation and regulation of medical products globally.
Effectiveness of the etonogestrel subdermal implant in users with overweight and obesity: a systematic literature review
Authors: Goto Daisuke , Grunden John W , Klinghardt Moritz , Patel Vanessa Perez , von Stockum Sophia , Barnett Clare , Bitzer Johannes 
Published: October 2024

BackgroundThe etonogestrel (ENG) subdermal implant is considered a well-tolerated and effective contraception option to avoid unintended pregnancies. However, it is unclear whether being affected by overweight or obesity diminishes the effectiveness of the implant.ObjectivesTo systematically assess the published evidence on implant contraceptive effectiveness in women with overweight or obesity, and in women who underwent bariatric surgery.Search strategyA systematic search of MEDLINE and Embase for publications reporting implant effectiveness since 2011.Selection criteriaPrimary publications of randomised and non-randomised trials, observational studies and case reports were included.Data collection and analysisTwo independent reviewers identified the Pearl Index, qualitative descriptions of contraceptive failure, implant exposure and potential bias, and assessed overall quality of evidence.Main resultsWe found 12 publications meeting our criteria, consisting of nine observational studies and three case reports. Excluding case reports, the publications reported Pearl Indices from 0.0/100 women-years (WY) to 0.23/100WY for women with overweight and obesity, respectively. No studies met the eligibility criteria for the post-bariatric surgery population.ConclusionsObserved implant effectiveness in women with overweight and obesity falls within the range of published data across all weight groups (0.0–1.4/100 WY) and does not suggest a reduced effectiveness associated with higher body mass index. Large, well-controlled studies designed to specifically assess the effectiveness of the ENG implant with respect to user weight, particularly in women following bariatric surgery, are warranted.
Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma
Authors: Ku Keun Bon , Kim Chae Won , Kim Yumin , Kang Byeong Hoon , La Jeongwoo , Kang In , Park Won Hyung , Ahn Stephen , Lee Sung Ki , Lee Heung Kyu 
Published: October 2024

BackgroundCertain cancers present challenges for treatment because they are resistant to immune checkpoint blockade (ICB), attributed to low tumor mutational burden and the absence of T cell-inflamed features. Among these, glioblastoma (GBM) is notoriously resistant to ICB. To overcome this resistance, the identification of T cells with heightened stemness marked by T-cell factor 1 (TCF1) expression has gained attention. Several studies have explored ways to preserve stem-like T cells and prevent terminal exhaustion. In this study, we investigate a target that triggers stem-like properties in CD8 T cells to enhance the response to ICB in a murine GBM model.MethodsUsingFcgr2b−/−mice and a murine GL261 GBM model, we confirmed the efficacy of anti-programmed cell death protein-1 (PD-1) immunotherapy, observing improved survival. Analysis of immune cells using fluorescence-activated cell sorting and single-cell RNA sequencing delineated distinct subsets of tumor-infiltrating CD8 T cells inFcgr2b−/−mice. The crucial role of the stem-like feature in the response to anti-PD-1 treatment for reinvigorating CD8 T cells was analyzed. Adoptive transfer of OT-I cells into OVA-expressing GL261 models and CD8 T cell depletion inFcgr2b−/−mice confirmed the significance ofFcgr2b−/−CD8 T cells in enhancing the antitumor response. Last, S1P1inhibitor treatment confirmed that the main source of tumor antigen-specificFcgr2b−/−CD8 T cells is the tumor-draining lymph nodes (TdLNs).ResultsIn a murine GBM model, anti-PD-1 monotherapy and single-Fc fragment of IgG receptor IIb (FcγRIIB) deletion exhibit limited efficacy. However, their combination substantially improves survival by enhancing cytotoxicity and proliferative capacity in tumor-infiltratingFcgr2b−/−CD8 T cells. The improved response to anti-PD-1 treatment is associated with the tumor-specific memory T cells (Ttsms) exhibiting high stemness characteristics within the tumor microenvironment (TME). Ttsms in the TdLN thrives in a protective environment, maintaining stem-like characteristics and serving as a secure source for tumor infiltration. This underscores the significance of FcγRIIB ablation in triggering Ttsms and enhancing ICB therapy against GBM.ConclusionsDeletion of FcγRIIB on CD8 T cells leads to the generation of a Ttsms, which is localized in TdLN and protected from the immunosuppressive TME. Incorporating these highly stemness-equipped Ttsms enhances the response to anti-PD-1 therapy in immune-suppressed brain tumors.
Accurate prenatal diagnosis of facioscapulohumeral muscular dystrophy 1 using nanopore sequencing
Authors: Wang Yanan , Zhao Zhenhua , Meng Fei , Kong Xiangdong 
Published: October 2024

BackgroundFacioscapulohumeral muscular dystrophy 1 (FSHD1) is an autosomal dominant muscular disorder mainly caused by the contraction and hypomethylation of the D4Z4 repeat array in chromosome 4q35. Prenatal diagnosis of FSHD1 is challenging due to the highly repetitive and long genomic structure. In this study, a pregnant woman diagnosed with FSHD1 using optical genome mapping sought assistance for a healthy offspring.MethodsAt the 17th week of gestation, she underwent amniocentesis, and genomic DNA (gDNA) was extracted from amniocytes. Whole-genome sequencing of the gDNA was performed using the nanopore MinION platform.ResultsDespite a sequencing depth of only 7.3×, bioinformatic analyses revealed that the fetus inherited four D4Z4 repeat units with the permissive 4qA from the mother and the eight D4Z4 repeat units with the non-permissive 4qB from the father. To validate the results, SNP-based linkage analyses were conducted with gDNA from the proband, the proband’s father and proband’s amniocytes. Results indicated that the fetus inherited the maternal pathogenic haplotype based on 144 informative SNPs. Linkage analysis was consistent with the nanopore sequencing.ConclusionNanopore sequencing proves to be an accurate and direct method for genetic testing of monogenic diseases at the single-nucleotide level. This study represents the first application of nanopore sequencing in the prenatal diagnosis of FSHD1, providing a significant advantage for patients with de novo mutations.