bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty-Aware, Structure-Preserving Machine Learning Approach for Domain Shift Detection From Nonlinear Dynamic Responses of Structural Systems
Authors: Najera-Flores David A. , Jacobs Justin , Dane Quinn D. , Garland Anthony , Todd Michael D. 
Published: July 2024

Abstract
Complex structural systems deployed for aerospace, civil, or mechanical applications must operate reliably under varying operational conditions. Structural health monitoring (SHM) systems help ensure the reliability of these systems by providing continuous monitoring of the state of the structure. SHM relies on synthesizing measured data with a predictive model to make informed decisions about structural states. However, these models—which may be thought of as a form of a digital twin—need to be updated continuously as structural changes (e.g., due to damage) arise. We propose an uncertainty-aware machine learning model that enforces distance preservation of the original input state space and then encodes a distance-aware mechanism via a Gaussian process (GP) kernel. The proposed approach leverages the spectral-normalized neural GP algorithm to combine the flexibility of neural networks with the advantages of GP, subjected to structure-preserving constraints, to produce an uncertainty-aware model. This model is used to detect domain shift due to structural changes that cannot be observed directly because they may be spatially isolated (e.g., inside a joint or localized damage). This work leverages detection theory to detect domain shift systematically given statistical features of the prediction variance produced by the model. The proposed approach is demonstrated on a nonlinear structure being subjected to damage conditions. It is shown that the proposed approach is able to rely on distances of the transformed input state space to predict increased variance in shifted domains while being robust to normative changes.
A Simple Point-of-Care Device for Temperature Control of Multiple Reactions During Recombinase Polymerase Amplification
Authors: Schultz Aubrey L. , Servoss Shannon L. , Beitle Robert 
Published: July 2024

Abstract
For individuals with infectious diseases, early and accurate diagnosis is critical. A rapid diagnosis allows for prompt and effective treatment and increases the chance of a full recovery without complications. Additionally, when containing a wide-scale infectious disease outbreak, circumstances are significantly improved by the ability to test the populace frequently, swiftly, and affordably. Regarding specificity and sensitivity, nucleic acid amplification tests (NAAT) are one of the best options for diagnosing infectious diseases. Historically, polymerase chain reaction (PCR) has been used, but complex thermocycling and complicated PCR protocols have often limited PCR to clinical settings. Due to increased simplicity, the isothermal NAAT recombinase polymerase amplification (RPA) has the potential to deliver reliable Point-of-Care (POC) diagnostics in low-resource settings. When designing POC devices for isothermal NAATs, creating isothermal temperature conditions is perhaps the most significant challenge. This work presents a flexible and robust device capable of incubating 3 RPA reactions for simultaneous amplification in conditions conducive to POC testing. The device costs ∼$60 USD to construct and is easy to assemble. A battery-powered polyimide thin-film resistive heater provides energy, and the device only requires power for a fraction of the total incubation time. The device uses a phase change material (PCM) to regulate temperature to avoid the complexity of a microcontroller. RPA reactions were successfully incubated for 30 min using the device.
Prediction for Global Whipping Responses of a Large Cruise Ship Under Unprecedented Sea Conditions Using an LSTM-Based Encoder–Decoder Model
Authors: Liu Ruixiang , Li Hui , Ong Muk Chen , Zou Jian 
Published: July 2024

Abstract
Global whipping responses contribute to a significant increase in vertical bending moments (VBM), making their accurate prediction crucial for ship safety. In this study, a long short-term memory (LSTM)-based encoder–decoder model is established to predict the whipping responses under varying sea states. The model is trained on a comprehensive dataset, which includes motion data and VBM history of a cruise ship under various sea conditions. This dataset is established via numerical simulation, ensuring a wide range of scenarios for the model to learn from. The efficacy of the LSTM encoder–decoder model in capturing global whipping responses is initially verified under a single sea condition case. This step confirms the model's ability to accurately predict vertical bending moments under known conditions. Subsequently, the model's performance under unprecedented sea conditions is examined. Given that the distribution of training data significantly influences the model's performance and the data from diverse sea conditions typically exhibit distinct data distribution, a mixed data training strategy is employed during the training process in this scenario. The results indicate that the LSTM encoder–decoder model effectively captures whipping responses. Furthermore, the mixed data training strategy significantly improves the model's prediction accuracy for global whipping responses under unprecedented sea conditions.
Mar1, a high mobility group box protein, regulates
n
-alkane adsorption and cell morphology of the dimorphic yeast
Yarrowia lipolytica
Authors: Kimura-Ishimaru Chiaki , Liang Simiao , Matsuse Katsuro , Iwama Ryo , Sato Kenta , Watanabe Natsuhito , Tezaki Satoshi , Horiuchi Hiroyuki , Fukuda Ryouichi 
Published: July 2024

ABSTRACT

The dimorphic yeast
Yarrowia lipolytica
possesses an excellent ability to utilize
n
-alkane as a sole carbon and energy source. Although there are detailed studies on the enzymes that catalyze the reactions in the metabolic processes of
n
-alkane in
Y. lipolytica
, the molecular mechanism underlying the incorporation of
n
-alkane into the cells remains to be elucidated. Because
Y. lipolytica
adsorbs
n
-alkane, we postulated that
Y. lipolytica
incorporates
n
-alkane through direct interaction with it. We isolated and characterized mutants defective in adsorption to
n
-hexadecane. One of the mutants harbored a nonsense mutation in
MAR1
(
M
orphology and
n
-alkane
A
dsorption
R
egulator 1) encoding a protein containing a high mobility group box. The deletion mutant of
MAR1
exhibited defects in adsorption to
n
-hexadecane and filamentous growth on solid media, whereas the strain that overexpressed
MAR1
exhibited hyperfilamentous growth. Fluorescence microscopic observations suggested that Mar1 localizes in the nucleus. RNA-sequencing analysis revealed the alteration of the transcript levels of several genes, including those encoding transcription factors and cell surface proteins, by the deletion of
MAR1
. These findings suggest that
MAR1
is involved in the transcriptional regulation of the genes required for
n
-alkane adsorption and cell morphology transition.

IMPORTANCE

Yarrowia lipolytica
, a dimorphic yeast capable of assimilating
n
-alkane as a carbon and energy source, has been extensively studied as a promising host for bioconversion of
n
-alkane into useful chemicals and bioremediation of soil and water contaminated by petroleum. While the metabolic pathway of
n
-alkane in this yeast and the enzymes involved in this pathway have been well characterized, the molecular mechanism to incorporate
n
-alkane into the cells is yet to be fully understood. Due to the ability of
Y. lipolytica
to adsorb
n
-alkane, it has been hypothesized that
Y. lipolytica
incorporates
n
-alkane through direct interaction with it. In this study, we identified a gene,
MAR1
, which plays a crucial role in the transcriptional regulation of the genes necessary for the adsorption to
n
-alkane and the transition of the cell morphology in
Y. lipolytica
. Our findings provide valuable insights that could lead to advanced applications of
Y. lipolytica
in
n
-alkane bioconversion and bioremediation.
Characteristics of myopic maculopathy in Chinese children and adolescents with high myopia
Authors: Jiang Feng , Xiao Ou , Guo Xinxing , Yin Qiuxia , Luo Lixia , He Mingguang , Li Zhixi 
Published: July 2024

Aims
To investigate the characteristics of myopic maculopathy among highly myopic Chinese children and adolescents and explore its associated risk factors.

Methods
Children and adolescents aged 7–17 years with spherical equivalent (SE) ≤ −6.00 dioptres (D) were recruited. Myopic maculopathy was categorised based on the International Meta-Analysis of Pathological Myopia Classification. The extent of diffuse choroidal atrophy (DCA) was classified using Early Treatment Diabetic Retinopathy Study grid (ETDRS). The area of DCA was categorised into three classes relative to optic disk area (DA): A1 (≤1 DA), A2 (1 to ≤5 DA) and A3 (5 to ≤10 DA). Logistic regression was used to identify risk factors associated with myopic maculopathy.

Results
Of the 425 participants aged 13.66±2.67 years, the proportions of tessellated fundus and DCA were 11.76% and 12.24%, and no more severe fundus lesions or ‘plus’ lesions. The proportion of DCA was 27.03% in children under 11, significantly higher than the 9.12% observed in those aged 11 and older (p<0.001). The percentages of DCA involving the outer, middle and central circles of the ETDRS grid were 42.31%, 55.77% and 1.92%. Myopic maculopathy was significantly associated with younger age (p<0.001), longer axial length (AL; p<0.001) and larger β-zone peripapillary atrophy (β-PPA; p=0.012).

Conclusion
In highly myopic children and adolescents, myopic maculopathy predominantly manifested as DCA (12.24%), with no cases of worse myopic maculopathy or ‘plus’ lesions. Younger age, longer AL and larger β-PPA were risk factors for myopic maculopathy.
How can healthcare organisations improve the social determinants of health for their local communities? Findings from realist-informed case studies among secondary healthcare organisations in England
Authors: Gkiouleka Anna , Munford Luke , Khavandi Sam , Watkinson Ruth , Ford John 
Published: July 2024

ObjectivesIncreasingly, healthcare and public health strategists invite us to look at healthcare organisations as not just care providers but as anchor institutions (ie, large community-rooted organisations with significant impact in the local economy, social fabric and overall community well-being). In response, this study explores the mechanisms through which healthcare organisations can impact social determinants of health and communities in their local areas.DesignWe conducted case studies with interviews and synthesised the findings using a realist approach to produce a set of explanations (programme theory) of how healthcare organisations can have a positive impact on the overall well-being of local communities by operating as anchor institutions.SettingSecondary healthcare organisations in England, including mental health and community services.ParticipantsStaff from case study sites which were directly employed or actively engaged in the organisation’s anchor institution strategy. Data collection took place from early June to the end of August 2023.ResultsWe found four building blocks for effective anchor activity including employment, spending, estates and sustainability. Healthcare organisations—as anchor institutions—can improve the social determinants of health for their local communities through enabling accessible paths for local community recruitment and career progression; empowering local businesses to join supply chains boosting income and wealth; transforming organisational spaces into community assets; and supporting local innovation and technology to achieve their sustainability goals. These blocks need to be integrated across organisations on the basis of a population health approach promoted by supportive leadership, and in collaboration with a diverse range of local partners.ConclusionsHealthcare organisations have the potential for a positive impact on the overall well-being of local communities. Policymakers should support healthcare organisations to leverage employment, spending, estates and sustainability to help address the unequal distribution of the social determinants of health.
Effect of modified opioid sparing anaesthesia on postoperative quality of recovery in patients undergoing laparoscopic bariatric surgery: protocol for a monocentre, double-blind randomised controlled trial – the MOSA study
Authors: Li Shikuo , Li Honghao , Zhang Ruqiang , Zhang Furong , Yin Jianwei , He Liang 
Published: July 2024

IntroductionObesity patients undergoing laparoscopic bariatric surgery (LBS) are frequently encountered perioperative adverse events related to opioids-based anaesthesia (OBA) or opioids-free anaesthesia (OFA). While modified opioid-sparing anaesthesia (MOSA) has been shown to lower the occurrence of adverse events related to OBA and OFA. This study is to assess the efficacy of MOSA in enhancing the recovery quality among individuals undergoing LBS.Methods and analysisA single-centre, prospective, double-blind, randomised controlled trial is conducted at a tertiary hospital. A total of 74 eligible participants undergoing elective LBS will be recruited and randomly allocated. Patients in the MOSA group will receive a combination of low-dose opioids, minimal dexmedetomidine, esketamine and lidocaine, while in the OBA group will receive standard general anaesthesia with opioids. Patients in both groups will receive standard perioperative care. The primary outcome is the quality of recovery-15 score assessed at 24 hours after surgery. Secondary outcomes include pain levels, anxiety and depression assessments, gastrointestinal function recovery, perioperative complication rates, opioid consumption and length of hospital stay.Ethics and disseminationEthical approval has been provided by the Ethical Committee of Yan’an Hospital of Kunming City (approval No. 2023-240-01). Eligible patients will provide written informed consent to the investigator. The outcomes of this trial will be disseminated in a peer-reviewed scholarly journal.Trial registration numberThe study protocol is registered athttps://www.chictr.org.cn/on 19 December 2023. (identifier: ChiCTR2300078806). The trial was conducted using V.1.0.
FXa-mediated PAR-2 promotes the efficacy of immunotherapy for hepatocellular carcinoma through immune escape and anoikis resistance by inducing PD-L1 transcription
Authors: Li Xuemei , Gao Lei , Wang Bofang , Hu Jike , Yu Yang , Gu Baohong , Xiang Lin , Li Xiaomei , Li Haiyuan , Zhang Tao , Wang Yunpeng , Ma Chenhui , Dong Jiahong , Lu Jianrong , Lucas Alexandra , Chen Hao 
Published: July 2024

BackgroundThe high metastasis rate is one of the main reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC). Coagulation factor Xa (FXa) and its receptor proteinase-activated receptor-2 (PAR-2) proven to promote tumor metastasis in other forms of cancer. Here, we explore the role and mechanism of FXa in the regulation of resistance of anoikis and immune escape of HCC.MethodsIn vitro and in vivo experiments were conducted to explore the role of FXa in HCC metastasis and its potential mechanism. The effects of FXa inhibitor rivaroxaban on HCC immunotherapy were evaluated using intrahepatic metastasis animal models and clinical trial (No. ChiCTR20000040540). We investigated the potential of FXa inhibition as a treatment for HCC.ResultsFXa was highly expressed in HCC and promoted metastasis by activating PAR-2. Mechanistically, FXa-activated PAR-2 endows HCC cells with the ability of anoikis resistance to survive in the circulating blood by inhibiting the extrinsic apoptosis pathway. Furthermore, suspension stimulation-induced phosphorylation of STAT2, which promotes programmed death-ligand 1 (PD-L1) transcription and inhibits the antitumor effects of immune cells by inhibiting the infiltration of CD8+T cells in tumors and the levels of secreted cytokines. In vivo inhibition of FXa with rivaroxaban reduced HCC metastasis by decreasing PD-L1 expression and exhausting tumor-infiltrating lymphocytes. Notably, the combination of rivaroxaban and anti-programmed death-1 monoclonal antibody (anti-PD-1) programmed Death-1 monoclonal antibody (anti-PD-1) induced synergistic antitumor effects in animal models. Most importantly, rivaroxaban improved the objective response rate of patients with HCC to immune checkpoint inhibitors and prolonged overall survival time.ConclusionsFXa-activated PAR-2 promotes anoikis resistance and immune escape in HCC, suggesting the potential for combining coagulation inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance the therapeutic efficacy of HCC.
Assessment of the role of high-density lipoproteins and their immunomodulatory activity in systemic lupus erythematosus immunopathology
Authors: Pérez-Ocampo Julián , Vergara-Serpa Oscar , Velásquez-Franco Carlos Jaime , Taborda Natalia A , Yassin Lina M , Hernandez Juan C 
Published: July 2024

ObjectiveTo explore the potential associations between high-density lipoprotein (HDL) levels and inflammasome components in the context of systemic lupus erythematosus (SLE).MethodsA cross-sectional study was conducted. A group of 50 patients with SLE and 50 healthy controls matched by sex and similar age ranges were enrolled. Serum HDL cholesterol (HDL-C) and C reactive protein (CRP) levels were quantified. Serum cytokine levels, including IL-1β and IL-6, were determined by ELISA. The gene expression of inflammasome-related genes in peripheral blood mononuclear cells was measured by quantitative real-time PCR.ResultsHDL-C levels were lower in the patients with SLE (p<0.05), and on segregation according to disease activity, those with active SLE had the lowest HDL-C levels. Patients with SLE presented higher concentrations of the serum inflammatory cytokines IL-1β and IL-6 (p<0.0001) but similar levels of CRP to those in controls. A similar scenario was observed for the gene expression of inflammasome components, where all the evaluated markers were significantly upregulated in the SLE population. These results revealed significant negative correlations between HDL levels and disease activity, serum IL-6 and IL-1β levels and the mRNA expression of NLRP3, IL-1β and IL-18. In addition, significant positive correlations were found between disease activity and serum IL-1β and between disease activity and the mRNA expression of IL-18, and interestingly, significant positive correlations were also observed between active SLE and serum IL-1β and the mRNA expression of NLRP3.ConclusionOur results suggest that HDL is essential for SLE beyond atherosclerosis and is related to inflammation regulation, possibly mediated by inflammasome immunomodulation.
Pain intensity and opioid consumption after temporary and permanent peripheral nerve stimulation: a 2-year multicenter analysis
Authors: West Tyler , Hussain Nasir , Bhatia Anuj , ElSaban Mariam , Kilgore Anthony E , Palettas Marilly , Abdel-Rasoul Mahmoud , Javed Saba , D'Souza Ryan S 
Published: July 2024

ObjectivePeripheral nerve stimulation (PNS) is an emerging neuromodulation modality, yet there remains limited data highlighting its long-term effectiveness. The objective of this study was to report real-world data on pain intensity and opioid consumption after temporary and permanent PNS for chronic pain up to 24 months postimplantation.MethodsA retrospective study was conducted on all patients who received PNS implants at a multi-centered enterprise between January 1, 2014 and February 24, 2022. The two co-primary outcomes were: (1) change in pain intensity (11-point Numerical Rating Scale) from baseline to 12 months postimplant; and (2) comparison of the change in pain intensity between temporary and permanent PNS cohorts 12 months postimplant.Results126 patients were included in this analysis. Pain intensity significantly decreased 12 months postimplant in the overall cohort (mean difference (MD) −3.0 (95% CI −3.5 to −2.4), p<0.0001). No significant difference in this reduction was identified between temporary and permanent PNS cohorts (MD 0.0 (95% CI −1.1 to 1.0), p=1.00) 12 months postimplantation. Pain intensity significantly decreased in the overall, temporary, and permanent cohorts at all secondary time points (3, 6, and 24 months). No change in daily opioid consumption was observed at 6 and 12 months postimplant in the overall cohort.ConclusionThis study found that both temporary and permanent PNS may be effective for reducing pain intensity in patients with chronic pain up to 24 months postimplantation, although no changes in opioid consumption were observed. The decrease in pain intensity was comparable between patients receiving temporary versus permanent implants, highlighting that temporary PNS may achieve long-lasting clinical benefits. However, given the substantial loss to follow-up, further large-scale studies are needed to solidify conclusions about the efficacy of PNS.
Efficacy and safety of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biological treatments: results through 5 years from the SELECT-BEYOND study
Authors: Fleischmann Roy , Meerwein Sebastian , Charles-Schoeman Christina , Combe Bernard , Hall Stephen , Khan Nasser , Carter Kyle M , Camp Heidi S , Rubbert-Roth Andrea 
Published: July 2024

ObjectiveTo evaluate the efficacy and safety of upadacitinib over 5 years among patients with rheumatoid arthritis (RA) in a long-term extension (LTE) of the SELECT-BEYOND phase 3 trial.MethodsPatients refractory to ≥1 biological disease-modifying antirheumatic drug (DMARD) received upadacitinib 15 mg or 30 mg once daily or placebo, in combination with background conventional synthetic DMARD(s). At week 12, patients randomised to placebo were switched to upadacitinib 15 mg or 30 mg. All patients who completed the week 24 visit could enter the LTE for up to 5 years. Efficacy was analysed as observed and by non-responder imputation through week 260. Treatment-emergent adverse events per 100 patient-years were summarised over 5 years.ResultsOf the 498 patients randomised, 418 (84%) completed week 24 and entered the LTE. Of those who remained in the trial (n=80, upadacitinib 15 mg; n=81, upadacitinib 30 mg), 36%/36% and 81%/77% randomised to upadacitinib 15/30 mg were in Clinical Disease Activity Index (CDAI) remission or low disease activity at week 260, respectively (as observed). Approximately 47% of all patients who began in high disease activity demonstrated a CDAI improvement >12 at week 260 with upadacitinib 15/30 mg. Functional and pain-related outcomes also showed comparable improvements with both doses. Numerically higher rates of anaemia, herpes zoster and creatine phosphokinase elevation were observed with upadacitinib 30 mg vs 15 mg. No new safety issues were identified.ConclusionsUpadacitinib 15/30 mg continued to be effective in treating clinical and functional outcomes in patients with RA. The safety profile observed over 5 years was consistent with earlier study-specific and integrated assessments of upadacitinib treatment.