bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust bioprocess design and evaluation of commercial media for the serial expansion of human induced pluripotent stem cell aggregate cultures in vertical-wheel bioreactors
Authors: Borys Breanna S. , Dang Tiffany , Worden Hannah , Larijani Leila , Corpuz Jessica M. , Abraham Brett D. , Gysel Emilie J. , Malinovska Julia , Krawetz Roman , Revay Tamas , Argiropoulos Bob , Rancourt Derrick E. , Kallos Michael S. , Jung Sunghoon 
Published: July 2024

Abstract
Background
While pluripotent stem cell (PSC) therapies move toward clinical and commercial applications at a rapid rate, manufacturing reproducibility and robustness are notable bottlenecks in regulatory approval. Therapeutic applications of PSCs require large cell quantities to be generated under highly robust, well-defined, and economically viable conditions. Small-scale and short-term process optimization, however, is often performed in a linear fashion that does not account for time needed to verify the bioprocess protocols and analysis methods used. Design of a reproducible and robust bioprocess should be dynamic and include a continuous effort to understand how the process will respond over time and to different stresses before transitioning into large-scale production where stresses will be amplified.

Methods
This study utilizes a baseline protocol, developed for the short-term culture of PSC aggregates in Vertical-Wheel® bioreactors, to evaluate key process attributes through long-term (serial passage) suspension culture. This was done to access overall process robustness when performed with various commercially available media and cell lines. Process output variables including growth kinetics, aggregate morphology, harvest efficiency, genomic stability, and functional pluripotency were assessed through short and long-term culture.

Results
The robust nature of the expansion protocol was demonstrated over a six-day culture period where spherical aggregate formation and expansion were observed with high-fold expansions for all five commercial media tested. Profound differences in cell growth and quality were revealed only through long-term serial expansion and in-vessel dissociation operations. Some commercial media formulations tested demonstrated maintenance of cell growth rates, aggregate morphology, and high harvest recovery efficiencies through three bioreactor serial passages using multiple PSC lines. Exceptional bioprocess robustness was even demonstrated with sustained growth and quality maintenance over 10 serial bioreactor passages. However, some commercial media tested proved less equipped for serial passage cultures in bioreactors as cultures led to cell lysis during dissociation, reduction in growth rates, and a loss of aggregate morphology.

Conclusions
This study demonstrates the importance of systematic selection and testing of bioprocess input variables, with multiple bioprocess output variables through serial passages to create a truly reproducible and robust protocol for clinical and commercial PSC production using scalable bioreactor systems.
Targeting TXNIP in endothelial progenitors mitigates IL-8-induced neutrophil recruitment under metabolic stress
Authors: Jolibois Julia , Domingues Alison , El Hamaoui Divina , Awaida Raphaël , Berger-de-Gaillardo Mathilde , Guérin Daniel , Smadja David M , Marquet-DeRougé Perrine , Margaill Isabelle , Rossi Elisa , Nivet-Antoine Valérie 
Published: July 2024

Abstract
Background
This study explores the potential role of Thioredoxin-interacting protein (TXNIP) silencing in endothelial colony-forming cells (ECFCs) within the scope of age-related comorbidities and impaired vascular repair. We aim to elucidate the effects of TXNIP silencing on vasculogenic properties, paracrine secretion, and neutrophil recruitment under conditions of metabolic stress.

Methods
ECFCs, isolated from human blood cord, were transfected with TXNIP siRNA and exposed to a high glucose and β-hydroxybutyrate (BHB) medium to simulate metabolic stress. We evaluated the effects of TXNIP silencing on ECFCs’ functional and secretory responses under these conditions. Assessments included analyses of gene and protein expression profiles, vasculogenic properties, cytokine secretion and neutrophil recruitment both in vitro and in vivo. The in vivo effects were examined using a murine model of hindlimb ischemia to observe the physiological relevance of TXNIP modulation under metabolic disorders.

Results
TXNIP silencing did not mitigate the adverse effects on cell recruitment, vasculogenic properties, or senescence induced by metabolic stress in ECFCs. However, it significantly reduced IL-8 secretion and consequent neutrophil recruitment under these conditions. In a mouse model of hindlimb ischemia, endothelial deletion of TXNIP reduced MIP-2 secretion and prevented increased neutrophil recruitment induced by age-related comorbidities.

Conclusions
Our findings suggest that targeting TXNIP in ECFCs may alleviate ischemic complications exacerbated by metabolic stress, offering potential clinical benefits for patients suffering from age-related comorbidities.
Efficiency evaluation of 28 health systems by MCDA and DEA
Authors: Dlouhý Martin , Havlík Pavel 
Published: July 2024

Abstract
Background
Policymakers, who are constantly discussing growing health expenditures, should know whether the health system is efficient. We can provide them with such information through international health system efficiency evaluations. The main objectives of this study are: (a) to evaluate the efficiency of health systems in 28 developed countries by multiple-criteria decision analysis (MCDA) and data envelopment analysis (DEA) and (b) to identify reasonable benchmark countries for the Czech Republic, for which we collect information on the relative importance of health system inputs and outputs.

Methods
We used MCDA and DEA to evaluate the efficiency of the health systems of 28 developed countries. The models included four health system inputs (health expenditure as a relative share of GDP, the number of physicians, nurses, and hospital beds) and three health system outputs (life expectancy at birth, healthy life expectancy, and infant mortality rate). The sample covers 27 OECD countries and Russia, which is also included in the OECD database. To determine the input and output weights, we used a questionnaire sent to health policy experts in the Czech Republic.

Results
We obtained subjective information on the relative importance of the health system inputs and outputs from 27 Czech health policy experts. We evaluated health system efficiency using four MCDA and two DEA models. According to the MCDA models, Turkey, Poland, and Israel were found to have efficient health systems. The Czech Republic ranked 16th, 19th, 15th, and 17th. The benchmark countries for the Czech Republic’s health system were Israel, Estonia, Luxembourg, Italy, the UK, Spain, Slovenia, and Canada. The DEA model with the constant returns to scale identified four technically efficient health systems: Turkey, the UK, Canada, and Sweden. The Czech Republic was found to be one of the worst-performing health systems. The DEA model with the variable returns to scale identified 15 technically efficient health systems. We found that efficiency results are quite robust. With two exceptions, the Spearman rank correlations between each pair of models were statistically significant at the 0.05 level.

Conclusions
During the model formulation, we investigated the pitfalls of efficiency measurement in health care and used several practical solutions. We consider MCDA and DEA, above all, as exploratory methods, not methods providing definitive answers.
Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum β-lactamase-producing Enterobacterales rectal carriage
Authors: Bay Pierre , Fihman Vincent , Woerther Paul-Louis , Peiffer Bastien , Gendreau Ségolène , Arrestier Romain , Labedade Pascale , Moncomble Elsa , Gaillet Antoine , Carteaux Guillaume , de Prost Nicolas , Mekontso Dessap Armand , Razazi Keyvan 
Published: July 2024

Abstract
Background
Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene.

Methods
This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP.

Results
Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01).

Conclusion
mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.
Development of a propionate metabolism-related gene-based molecular subtypes and scoring system for predicting prognosis in bladder cancer
Authors: Zheng Fuchun , Wang Zhipeng , Li Sheng , Xiong Situ , Yuan Yuyang , Zeng Jin , Tan Yifan , Liu Xiaoqiang , Xu Songhui , Fu Bin 
Published: July 2024

Abstract
Purpose
Bladder cancer (BLCA) is a prevalent malignancy. Dysregulated propionate metabolism, a key cancer factor, suggests a potential target for treating metastatic cancer. However, a complete understanding of the link between propionate metabolism-related genes (PMRGs) and bladder cancer is lacking.

Methods
From the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we gathered BLCA patient data, which was classified into distinct subgroups using non-negative matrix factorization (NMF). Survival and pathway analyses were conducted between these clusters. The PMRGs model, created through univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, was assessed for prognostic significance using Kaplan–Meier and receiver operating characteristic (ROC) curves. A comprehensive evaluation included clinical, tumor microenvironment (TME), drug sensitivity, and immunotherapy analyses. Finally, the expression of HSD17B1 essential genes was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR), with further validation through Transwell, wound healing, colony-formation, and EDU assays.

Results
We discovered two distinct subcategories (CA and CB) within BLCA using NMF analysis, with CA demonstrating significantly better overall survival compared to CB. Additionally, six PMRGs emerged as critical factors associated with propionate metabolism and prognosis. Kaplan–Meier analysis revealed that high-risk PMRGs were correlated with a poorer prognosis in BLCA patients. Moreover, significant differences were observed between the two groups in terms of infiltrated immune cells, immune checkpoint expression, TME scores, and drug sensitivity. Notably, we found that suppressing HSD17B1 gene expression inhibited the invasion of bladder cancer cells.

Conclusion
Our study proposes molecular subtypes and a PMRG-based score as promising prognostic indicators in BLCA. Additionally, cellular experiments underscore the pivotal role of HSD17B1 in bladder cancer metastasis and invasion, suggesting its potential as a novel therapeutic target.
Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn’s disease and chronic fatigue syndrome
Authors: Bourgonje Arno R. , Hörstke Nicolai V. , Fehringer Michaela , Innocenti Gabriel , Vogl Thomas 
Published: July 2024

Abstract
Background
Elevated systemic antibody responses against gut microbiota flagellins are observed in both Crohn’s disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting potential serological biomarkers for diagnosis. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) “stimulator” and (2) “silent” flagellins, which bind TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 (involving a C-terminal domain); (3) “evader” flagellins of pathogens, which entirely circumvent TLR5 activation via mutations in the N-terminal TLR5 binding motif.

Results
Here, we show that both CD and ME/CFS patients exhibit elevated antibody responses against distinct regions of flagellins compared to healthy individuals. N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling “stimulator” and “silent” flagellins more than evaders. However, C-terminal antibody-bound flagellins showed a higher resemblance to the stimulator than to silent flagellins in CD, which was not observed in ME/CFS.

Conclusions
These findings suggest that antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Blocking this interaction could lead commensal bacteria to be recognized as pathogenic evaders, potentially contributing to dysregulation in both diseases. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between the diseases. Overall, these results highlight the diagnostic potential of these antibody responses and lay a foundation for deeper mechanistic studies of flagellin/TLR5 interactions and their impact on innate/adaptive immunity balance.

Graphical Abstract
Blood and urine biomarkers of disease progression in IgA nephropathy
Authors: Duan Zhi-Yu , Zhang Chun , Chen Xiang-Mei , Cai Guang-Yan 
Published: July 2024

AbstractThe prognosis of patients with IgA nephropathy (IgAN) is variable but overall not good. Almost all patients with IgAN are at risk of developing end-stage renal disease within their expected lifetime. The models presently available for prediction of the risk of progression of IgAN, including the International IgA Nephropathy Prediction Tool, consist of traditional clinical, pathological, and therapeutic indicators. Finding biomarkers to improve the existing risk prediction models or replace pathological indicators is important for clinical practice. Many studies have attempted to identify biomarkers for prediction of progression of IgAN, such as galactose-deficient IgA1, complement, a spectrum of protein biomarkers, non-coding RNA, and shedding cells. This article reviews the biomarkers of progression of IgAN identified in recent years, with a focus on those with clinical value, in particular the combination of multiple biomarkers into a biomarker spectrum. Future research should focus on establishing a model based primarily on biomarkers that can predict progression of IgAN and testing it in various patient cohorts.
Spatio-temporal evolution of water engineering facilities and social influences on the Grand Canal during the Ming and Qing dynasties
Authors: Cheng Wang , Lifeng Tan , Guanhua Wang , Liang Li , Xin Qiu , Yiwen Zhang 
Published: July 2024

Abstract
This research explores the spatial distribution patterns of water engineering facilities along the Grand Canal during the Ming and Qing dynasties. It employs the entropy method to assess the social development status of prefectures during these periods and uses the Tobit model to examine the primary indicators influencing the distribution of water engineering facilities. The results show that the spatial distribution pattern of water engineering facilities was characterized by aggregation during the Ming and Qing dynasties. In contrast, the Qing dynasty’s distribution was more dispersed, with a shift in the construction focus of water engineering facilities towards the south. The spatial distribution pattern of water engineering facilities in the Ming Dynasty centered around the hotspot areas of Shuntian Prefecture, Yanzhou Prefecture, and Yangzhou Prefecture. During continuous improvements, these facilities exhibited a multi-point-regional aggregation phenomenon.The influence of commercial development indicator on the spatial distribution of water engineering facilities is positively correlated in both the Ming and Qing dynasties. However, the impacts of the indicator on different types of water engineering facilities vary between the two dynasties. During the Ming Dynasty, the indicators of transportation accessibility and cultural prosperity facilitated the construction of regional water engineering facilities, whereas in the Qing Dynasty, they significantly influenced several types of water engineering facilities. During the Ming and Qing Dynasties, neither the agricultural development indicator nor the population size indicator significantly affected the distribution of water engineering facilities. However, there was a negative correlation between the population size indicator and the distribution of water distribution facilities in the Ming Dynasty. This study enhances the importance of environmental protection in historical societies and provides a valuable reference for other international studies of linear cultural and material heritage.
A “set” of ancient bronze bells excavated in Changsha, Hunan Province, China
Authors: Li Kin Sum , Liu Yu , Ma Guancong , Liu Kwong Ip , Ng Michael Kwok-Po , Liu Haiwang , Wilson Keith , Chen Xueqing , Lee Kin San , Fang Qin , Poon Johnny M. , Qin Xu , Chun Tsz Hin , Jiang Haoran 
Published: July 2024

Abstract
This article explores the criteria used to ascertain whether or not, and how, ancient Chinese bronze bells might form sets of musical instruments, thus clarifying their original intended use by ancient musicians. The focus is on ten bells unearthed from Changsha city in Hunan province in China, which date to the twelfth century BCE. A range of diverse relationships between these bells provide valuable insights that can be explored. Debate is ongoing among music historians regarding the nature of the bells. Some argue that the ten bells do not constitute a set of musical instruments because their designs and acoustic properties lack sufficient similarity and correlation. Conversely, another group of historians suggests that nine of the ten bells could indeed be seen as a set, but with the tenth bell being an outlier due to its distinct design. The third group of historians contends that the ten bells should be considered a musical set because of their organized sequence of consecutive semi-tones, while the design differences of the bells are less significant and can be overlooked if we focus on their musical functions. In this study, we scrutinize the assumptions made by these music historians, including their definitions of design similarity and the sequence of progressive pitches. Further previously overlooked criteria, such as the geographical proximity of these ten bells and others found in neighboring areas, and the incremental changes in the bell sizes, are also considered. Through the use of these criteria we aim to explore a wide range of relationships between ancient Chinese bells and to reassess what other new evidence the bells may offer to the study of ancient Chinese musical concepts. The concept of the chromatic scale discovered by ancient Chinese musicians was embodied on the casting of bronze bells.
Gca-pvt-net: group convolutional attention and PVT dual-branch network for oracle bone drill chisel segmentation
Authors: Liu Guoqi , Yang Yiping , Li Xueshan , Liu Dong , Ru Linyuan , Han Yanbiao 
Published: July 2024

Abstract
Oracle bones (Obs) are a significant carrier of the shang dynasty civilization, primarily consisting of tortoise shells and animal bones, through the study of which we can gain a deeper understanding of the political, economic, religious, and cultural aspects of the shang dynasty. The oracle bone drill chisel (Obdc) is considered an essential non-textual material. The segmentation of Obdc assists archaeologists determine the approximate age of the Obs, which possesses considerable research value. However, the breakage of thousands of years of underground buried Obs, the blurring of the edges of the area burned by the Obdc, the different shapes, and the inconsistent number have brought challenges to the accurate segmentation of the Obdc. In this article, we propose a group convolutional attention and pvt dual-branch network (GCA-PVT-Net) for Obdc segmentation. To our knowledge, this paper is the first to research the automatic segmentation of Obdc. It is a hybrid Convolutional neural network (CNN) and Transformer framework. The work offers the following contributions: (1) The Obdc images are labeled based on the delineation criteria of different drill chisel (DC) shapes to create the Obdc dataset. (2) A convolutional attention module (CAM) is proposed as both an encoder and decoder. The feature extraction process, which effectively integrates global and local information, ensures better modeling of long-term correlations in images while preserving details. (3) A channel feature aggregation module (CFAM) is designed to enhance the effective integration of channel features, enabling feature fusion across various branches and at different levels. (4) The edge deep supervision strategy is applied to smooth the jagged edge of the predicted images at the decoder’s end. Extensive experiments on the Obdc dataset show that GCA-PVT-Net outperforms other state-of-the-art (SOTA) methods. The comparative experimental results show that the edge accuracy and segmentation accuracy of the model reach the top 1.