bluuebunny/crossref_metadata_2025_split huggingface dataset:
An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body 68Ga- DOTATATE PET/CT
Authors: Haque Fahmida , Carrasquillo Jorge A. , Turkbey Evrim B. , Mena Esther , Lindenberg Liza , Eclarinal Philip C. , Nilubol Naris , Choyke Peter L. , Floudas Charalampos S. , Lin Frank I. , Turkbey Baris , Harmon Stephanie A. 
Published: November 2024

Abstract
Background
Somatostatin receptor (SSR) targeting radiotracer 68Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 68Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model’s detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted.

Results
The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on 68Ga- DOTATATE PET scans.

Conclusions
The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up.
https://www.clinicaltrials.gov/study/NCT03206060, https://www.clinicaltrials.gov/study/NCT04086485, https://www.clinicaltrials.gov/study/NCT05012098.
The long non-coding RNA lncRNA-DRNR enhances infectious bronchitis virus replication by targeting chicken JMJD6 and modulating interferon-stimulated genes expression via the JAK-STAT signalling pathway
Authors: Yan Wenjun , Fu Xue , Li Hao , Wang Kailu , Song Cailiang , Hou Chengyao , Lei Cangwei , Wang Hongning , Yang Xin 
Published: November 2024

AbstractInfectious bronchitis virus (IBV) is the causative agent of infectious bronchitis (IB), a severe disease that primarily affects young chickens and poses a significant challenge to the global poultry industry. Understanding the complex interaction between the virus and its host is vital for developing innovative antiviral strategies. Long non-coding RNA (lncRNA) plays a crucial role in regulating host antiviral immune responses. Our previous studies have shown that IBV infection disrupts the stability of lncRNA in host cells, indicating a potential regulatory role for lncRNA in IBV pathogenesis. It is still not clear how lncRNA precisely modulates IBV replication. In this study, we observed down-regulation ofMSTRG.26120.58 (named lncRNA-DRNR) expression in various chicken cell lines upon IBV infection. We demonstrated that silencing lncRNA-DRNR using siRNA enhances intracellular replication of IBV. Through exploring genes encoding proteins upstream and downstream of lncRNA-DRNR within a 100 kb range, we identified chJMJD6 (chicken JMJD6) as a potential target gene negatively regulated by lncRNA-DRNR expression levels. Furthermore, chJMJD6 inhibits STAT1 methylation, thereby affecting the induction of interferon-stimulated genes (ISGs) through the activation of the IFN-β-mediated JAK-STAT signalling pathway, ultimately promoting the intracellular replication of IBV. In summary, our findings reveal the critical role played by lncRNA-DRNR during IBV infection, providing novel insights into mechanisms underlying coronavirus-induced disruption in lncRNA stability.
Scaling up production of cephalosporin C by Acremonium chrysogenum W42-I in a fermenter using submerged fermentation
Authors: Ibrahim Asmaa A. , El-Housseiny Ghadir S. , Aboshanab Khaled M. , Stratmann Ansgar , Yassien Mahmoud A. , Hassouna Nadia A. 
Published: November 2024

AbstractCephalosporins presently stand as the most extensively utilized antibiotic in clinical settings. Acremonium (A.) chrysogenum is the main strain used in the manufacturing of cephalosporin C (CPC), which offers distinct advantages, including a wide-ranging antibacterial spectrum and powerful antibacterial efficacy. Our study aimed to determine the optimal conditions for scaling up the production of CPC from A. chrysogenum W42-I starting with the optimized conditions on the shake flask level obtained from our previous study and utilizing the optimized media (CPC2). The results indicated that an inoculum size equivalent to 1% v/v, aeration at 1 vvm, and an agitation rate of 400 rpm, with controlled pH at 4, were the most favorable conditions for the CPC production using a laboratory fermentor (14 L). The concentration of generated CPC was assessed using two standard curves obtained from agar well diffusion and high-performance liquid chromatography (HPLC). These optimized conditions resulted in a production of 399.52 µg/mL showing a significant increase of approximately 3.4 folds when compared to the unoptimized fermentation run. In conclusion, our findings demonstrated a more favorable time course for CPC production in the fermentor compared to that in the shake flask. Notably, there was a two-fold increase in production within the first three days. Fortunately, the fermentor achieved a noteworthy increase in output, generating 1.598 gm of the CPC within 4 L.
Motivations of Israeli physicians to return, or not, to Israel after their fellowship abroad
Authors: Seluk Lior , Weltsch Daniel , Segal Gadi , Gilboa Mayan 
Published: November 2024

Abstract
Background
Emigration of healthcare professionals, particularly physicians, is an unresolved “pandemic”, influenced by various factors. In high-income countries, the training phase (fellowship) abroad is critical for career development, yet it poses challenges for the retention of these professionals upon their completion of training. This study aimed to identify the determinants influencing Israeli physicians' decisions to return to their home country after completing fellowship training abroad.

Methods
This cross-sectional study conducted in early 2024, surveyed Israeli physicians with post-graduate training who pursued a fellowship abroad between 2013 and 2024. An anonymous survey included questions on demographics, training experience, and professional challenges. Analytical methods included descriptive statistics and regression analysis to explore factors associated with the decision to return.

Results
Of the 323 individuals surveyed, 297 met the inclusion criteria. Among them, 141 (47.5%) have returned to Israel, while 156 (52.5%) currently reside abroad, 48 (31%) of them have completed their fellowship. Respondents identified several challenges, beginning with a complex application process prior to fellowship (47% stated this as a major challenge), substantial financial burdens averaging 35,546 USD in direct out-of-pocket expenses during, and job uncertainty, with only 55% having secured positions upon return. Of the 156 Israeli fellows still abroad, 107 (69%) reported medium to low confidence in returning. Factors associated with a higher likelihood of confidence in returning to Israel included a secured job position upon return (OR 8.6, 95% CI 3.1–28.9) and having an opportunity for a position that would utilize the skills gained during the fellowship (OR 3.5, 95% CI 1.3–10.2).

Conclusion
The decision to return to Israel after a fellowship abroad is influenced by a mix of professional, personal, and geopolitical factors. To counteract the critical issue of brain drain, it is essential to enhance occupational certainty for returning physicians. These findings highlight the urgent need for healthcare policies that provide robust support for returning professionals and address their specific challenges.
Multi-channel neural audio decorrelation using generative adversarial networks
Authors: Anemüller Carlotta , Thiergart Oliver , Habets Emanuël A. P. 
Published: November 2024

AbstractThe degree of correlation between the sounds received by the ears significantly influences the spatial perception of a sound image. Audio signal decorrelation is, therefore, a commonly used tool in various spatial audio rendering applications. In this paper, we propose a multi-channel extension of a previously proposed decorrelation method based on generative adversarial networks. A separate generator network is employed for each output channel. All generator networks are optimized jointly to obtain a multi-channel output signal with the desired properties. The training objective includes a number of individual loss terms to control both the input-output and the inter-channel correlation as well as the quality of the individual output channels. The proposed approach is trained on music signals and evaluated both objectively and through formal listening tests. Thereby, a comparison with two classical signal processing-based multi-channel decorrelators is performed. Additionally, the influence of the number of output channels, the individual loss term weightings, and the employed training data on the proposed method’s performance is investigated.
Multi-scale Information Aggregation for Spoofing Detection
Authors: Li Changtao , Wan Yi , Yang Feiran , Yang Jun 
Published: November 2024

AbstractSynthesis artifacts that span scales from small to large are important cues for spoofing detection. However, few spoofing detection models leverage artifacts across different scales together. In this paper, we propose a spoofing detection system built on SincNet and Deep Layer Aggregation (DLA), which leverages speech representations at different levels to distinguish synthetic speech. DLA is totally convolutional with an iterative tree-like structure. The unique topology of DLA makes possible compounding of speech features from convolution layers at different depths, and therefore the local and the global speech representations can be incorporated simultaneously. Moreover, SincNet is employed as the frontend feature extractor to circumvent manual feature extraction and selection. SincNet can learn fine-grained features directly from the input speech waveform, thus making the proposed spoofing detection system end-to-end. The proposed system outperforms the baselines when tested on ASVspoof LA and DF datasets. Notably, our single model surpasses all competing systems in ASVspoof DF competition with an equal error rate (EER) of 13.99%, which demonstrates the importance of multi-scale information aggregation for synthetic speech detection.
Non-linear connection between the triglyceride–glucose index and prediabetes risk among Chinese adults: a secondary retrospective cohort study
Authors: Cao Changchun , Han Yong , Deng Huanhua , Zhang Xiaohua , Hu Haofei , Zha Fubing , Wang Yulong 
Published: November 2024

Abstract
Background
The triglyceride–glucose (TyG) index has garnered recognition as a surrogate marker for insulin resistance, a pivotal factor in the pathogenesis of various metabolic disorders. Despite its emerging role, the empirical evidence delineating its association with prediabetes mellitus (Pre-DM) remains scant. This research aims to clarify the link between the TyG index and the likelihood of Pre-DM development within a Chinese demographic.

Methods
This investigation was structured as a retrospective cohort analysis, encompassing a sample of 179,177 Chinese adults. These individuals underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. To ascertain the relationship between the TyG index and the incidence of Pre-DM, this study employed Cox regression analysis complemented by sensitivity and subgroup assessments. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore the existence of any non-linear connection within this association.

Results
Upon adjusting for a comprehensive array of confounding variables, a statistically significant positive correlation between the TyG index and the risk of Pre-DM was identified (HR: 1.60, 95%CI 1.56–1.65, P < 0.001). The analysis illuminated a non-linear relationship, with an inflection point at a TyG index value of 8.78. For TyG index values below and above this inflection point, the HR was calculated to be 1.94 (95%CI 1.86–2.03) and 1.26 (95%CI 1.20–1.33), respectively. Sensitivity analyses further fortified the reliability of these findings.

Conclusions
This comprehensive examination delineated a significantly positive, non-linear correlation between the TyG index and the risk of Pre-DM within a Chinese population. Individuals with TyG index values below 8.78 have a significantly increased risk of developing prediabetes. These findings underscore the TyG index’s potential efficacy as a predictive tool for assessing Pre-DM risk in clinical practice.
Optimized Machine Learning Algorithms for Predicting the Punching Shear Resistance of Flat Slabs with Transverse Reinforcement
Authors: Yan Hua-Jun , Xie Nan 
Published: November 2024

AbstractIn the calculation of reinforced concrete (RC) flat slabs with transverse reinforcement, punching shear resistance is one of the most critical factors. It is true that design provisions may be implemented, but they often result in significant biases and deviations from expectations. This study aims to present an optimized machine learning (ML) algorithm for estimating the punching shear resistance. Four machine learning (ML) algorithms (SVR, DT, RF, and XGBoost) with Bayesian optimization (BO) are presented in this paper to provide accurate predictions for flat slabs. The adoptability and optimization of the models are achieved through the analysis of a database of 337 test specimens with nine design parameters. Machine learning (ML) techniques are used to estimate punching shear resistance, which is compared with design provisions and equations relating to critical shear crack theory (CSCT). According to this study, Bayesian optimization is still capable of improving the performance of conventional machine learning algorithms, while the XGBoost-based model offers advanced capabilities. Predictions based on BO-XGBoost are in good agreement with actual values (MAE, RMSE, and R2 are 0.09 MN, 0.14 MN, and 0.92, respectively) in test set. Following a detailed explanation using Shapley additive explanation (SHAP), a high-performance ML approach is used to investigate the predictive results. With the proposed optimized algorithms, it is possible to determine the punching shear resistance of flat slabs with transverse reinforcement during the preliminary stages of the construction.
Out-of-pocket payment and catastrophic health expenditure of tuberculosis patients in accessing care at public-private mix clinics in Myanmar, 2022
Authors: Khaing Myat Noe Thiri , U Nandi , Maw Luu , Arkar Htet , Naing Saw Pa Pa , Thet May Me 
Published: November 2024

Abstract
Background
The financial burden of tuberculosis (TB) can hinder patients and their families, creating obstacles throughout the care cascade, despite TB prevention and control being provided free of charge. In Myanmar, patients can visit private providers operating under public-private mix (PPM) schemes, where TB services (diagnosis and treatment) are typically offered at no cost. The study focused on quantifying the financial burden faced by TB patients seeking care from Myanmar's PPM providers.

Methods
This cross-sectional telephone survey included 695 adults seeking TB treatment [drug-susceptible TB (DS-TB) and retreatment TB] from various private providers in four states and regions with high TB burden in Myanmar. Telephone interviews were conducted in May and June 2022. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2022 and estimated throughout pre- and post-TB treatment episodes. The TB-affected households were defined as experiencing catastrophic health expenditure if their expenditure due to TB exceeded 20% of their capacity to pay, as recommended by the World Health Organization. All cost data were collected in Myanmar Kyats (MMK) and converted to USD (1 USD = 1850 MMK as of July 20, 2022). Logistic regression analysis was done to identify the determinants of catastrophic health expenditure.

Results
The findings showed patients made a median of 7 times for clinic visits throughout their treatment, with the median total cost for the entire TB treatment being 53.4 US dollars (USD), including direct medical and testing costs (11.9 USD) and direct non-medical patient expenditure (11.6 USD). Pre-treatment costs were higher compared to post-treatment costs (the intensive phase and continuation phase). During the intensive phase, TB care cost was nearly free, but during the continuation phase, it was a median of 2.6 USD. About 34.5% of patients experienced catastrophic health expenditure due to TB treatment, with expenses exceeding 20% of their capacity to pay. Multivariate regression analysis revealed that patients with a history of hospitalization (aOR = 14.84; P < 0.01), seeking care from regions other than Yangon (aOR = 2.6; P < 0.01), and using coping strategies (aOR = 12.53; P < 0.01), were more likely to face catastrophic financial burdens. Higher monthly household income (over 162 USD) was associated with a decreased risk of incurring catastrophic health expenditure (aOR = 0.38; P < 0.01).

Conclusions
TB patients and their households in Myanmar faced risk of catastrophic costs, even when treated in the private sector with free diagnostic charges and anti-TB medicine. The study highlighted the need for additional strategies or policies to make TB care affordable and mitigate the financial burden of TB-affected households.

Graphical Abstract
Clinical characteristics and short-term outcomes of patients with critical acute pulmonary embolism requiring extracorporeal membrane oxygenation: from the COMMAND VTE Registry-2
Authors: Takabayashi Kensuke , Yamashita Yugo , Morimoto Takeshi , Chatani Ryuki , Kaneda Kazuhisa , Nishimoto Yuji , Ikeda Nobutaka , Kobayashi Yohei , Ikeda Satoshi , Kim Kitae , Inoko Moriaki , Takase Toru , Tsuji Shuhei , Oi Maki , Takada Takuma , Otsui Kazunori , Sakamoto Jiro , Ogihara Yoshito , Inoue Takeshi , Usami Shunsuke , Chen Po-Min , Togi Kiyonori , Koitabashi Norimichi , Hiramori Seiichi , Doi Kosuke , Mabuchi Hiroshi , Tsuyuki Yoshiaki , Murata Koichiro , Nakai Hisato , Sueta Daisuke , Shioyama Wataru , Dohke Tomohiro , Nishikawa Ryusuke , Ono Koh , Kimura Takeshi ,   On behalf of the COMMAND VTE Registry-2 Investigators
Published: November 2024

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database.

Methods
We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO.

Results
Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only.

Conclusions
The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials.
Increasing carotenoid production in Xanthophyllomyces dendrorhous/Phaffia rhodozyma: SREBP pathway activation and promoter engineering
Authors: Durán Alejandro , Venegas Maximiliano , Barahona Salvador , Sepúlveda Dionisia , Baeza Marcelo , Cifuentes Víctor , Alcaíno Jennifer 
Published: November 2024

AbstractThe yeast Xanthophyllomyces dendrorhous synthesizes astaxanthin, a high-value carotenoid with biotechnological relevance in the nutraceutical and aquaculture industries. However, enhancing carotenoid production through strain engineering remains an ongoing challenge. Recent studies have demonstrated that carotenogenesis in X. dendrorhous is regulated by the SREBP pathway, which includes the transcription factor Sre1, particularly in the mevalonate pathway that also produces precursors used for ergosterol synthesis. In this study, we explored a novel approach to enhance carotenoid synthesis by replacing the native crtE promoter, which drives geranylgeranyl pyrophosphate synthesis (the step where carotenogenesis diverges from ergosterol biosynthesis), with the promoter of the HMGS gene, which encodes 3-hydroxy-3-methylglutaryl-CoA synthase from the mevalonate pathway. The impact of this substitution was evaluated in two mutant strains that already overproduce carotenoids due to the presence of an active Sre1 transcription factor: CBS.cyp61-, which does not produce ergosterol and strain CBS.SRE1N.FLAG, which constitutively expresses the active form of Sre1. Wild-type strain CBS6938 was used as a control. Our results showed that this modification increased the crtE transcript levels more than threefold and fourfold in CBS.cyp61−.pHMGS/crtE and CBS.SRE1N.FLAG.pHMGS/crtE, respectively, resulting in 1.43-fold and 1.22-fold increases in carotenoid production. In contrast, this modification did not produce significant changes in the wild-type strain, which lacks the active Sre1 transcription factor under the same culture conditions. This study highlights the potential of promoter substitution strategies involving genes regulated by Sre1 to enhance carotenoid production, specifically in strains where the SREBP pathway is activated, offering a promising avenue for strain improvement in industrial applications.