bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer
Authors: Hung Hao-Chien , Fan Ming-Huei , Wang Daniel , Miao Carol H. , Su Pong , Liu Chao-Lien 
Published: September 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year survival rate of 6% following a diagnosis, and novel therapeutic modalities are needed. Protease-activated receptor 1 (PAR1) is abundantly overexpressed by both tumor cells and multiple stroma cell subsets in the tumor microenvironment (TME), thereby offering a suitable immunotherapy target.

Methods
A chimeric antigen receptor (CAR) strategy was applied to target PAR1 using a human anti-PAR1 scFv antibody fused to the transmembrane region with two co-stimulatory intracellular signaling domains of cluster of differentiation 28 (CD28) and CD137 (4-1BB), added to CD3ζ in tandem.

Results
The engineered PAR1CAR-T cells eliminated PAR1 overexpression and transforming growth factor (TGF)-β-mediated PAR1-upregulated cancer cells by approximately 80% in vitro. The adoptive transfer of PAR1CAR-T cells was persistently enhanced and induced the specific regression of established MIA PaCa-2 cancer cells by > 80% in xenograft models. Accordingly, proinflammatory cytokines/chemokines increased in CAR-T-cell-treated mouse sera, whereas Ki67 expression in tumors decreased. Furthermore, the targeted elimination of PAR1-expressing tumors reduced matrix metalloproteinase 1 (MMP1) levels, suggesting that the blocking of the PAR1/MMP1 pathway constitutes a new therapeutic option for PDAC treatment.

Conclusions
Third-generation PAR1CAR-T cells have antitumor activity in the TME, providing innovative CAR-T-cell immunotherapy against PDAC.
BMI-based obesity classification misses children and adolescents with raised cardiometabolic risk due to increased adiposity
Authors: Zapata J. Karina , Azcona-Sanjulian M. Cristina , Catalán Victoria , Ramírez Beatriz , Silva Camilo , Rodríguez Amaia , Escalada Javier , Frühbeck Gema , Gómez-Ambrosi Javier 
Published: September 2023

Abstract
Objective
To assess how inaccurately the body mass index (BMI) is used to diagnose obesity compared to body fat percentage (BF%) measurement and to compare the cardiometabolic risk in children and adolescents with or without obesity according to BMI but with a similar BF%.

Methods
A retrospective cross-sectional investigation was conducted including 553 (378 females/175 males) white children and adolescents aged 6–17 years, 197 with normal weight (NW), 144 with overweight (OW) and 212 with obesity (OB) according to BMI. In addition to BMI, BF% measured by air displacement plethysmography, as well as markers of cardiometabolic risk had been determined in the existing cohort.

Results
We found that 7% of subjects considered as NW and 62% of children and adolescents classified as OW according to BMI presented a BF% within the obesity range. Children and adolescents without obesity by the BMI criterion but with obesity by BF% exhibited higher blood pressure and C-reactive protein (CRP) in boys, and higher blood pressure, glucose, uric acid, CRP and white blood cells count, as well as reduced HDL-cholesterol, in girls, similar to those with obesity by BMI and BF%. Importantly, both groups of subjects with obesity by BF% showed a similarly altered glucose homeostasis after an OGTT as compared to their NW counterparts.

Conclusions
Results from the present study suggest increased cardiometabolic risk factors in children and adolescents without obesity according to BMI but with obesity based on BF%. Being aware of the difficulty in determining body composition in everyday clinical practice, our data show that its inclusion could yield clinically useful information both for the diagnosis and treatment of overweight and obesity.
Optimization of polyhydroxyalkanoate production in Halomonas sp. YLGW01 using mixed volatile fatty acids: a study on mixture analysis and fed-batch strategy
Authors: Park Yerin , Jeon Jong-Min , Park Jea-Kyung , Yang Yung-Hun , Choi Shin Sik , Yoon Jeong-Jun 
Published: September 2023

AbstractPolyhydroxyalkanoate (PHA) is one of the most promising materials for replacing petroleum-based plastics, and it can be produced from various renewable biomass sources. In this study, PHA production was conducted using Halomonas sp. YLGW01 utilizing mixed volatile fatty acids (VFAs) as carbon sources. The ratio and concentration of carbon and nitrogen sources were optimized through mixture analysis and organic nitrogen source screening, respectively. It was found that the highest cell dry weight (CDW) of 3.15 g/L and PHA production of 1.63 g/L were achieved when the ratio of acetate to lactate in the mixed VFAs was 0.45:0.55. Furthermore, supplementation of organic nitrogen sources such as soytone resulted in a ninefold increase in CDW (reaching 2.32 g/L) and a 22-fold increase in PHA production (reaching 1.60 g/L) compared to using inorganic nitrogen sources. Subsequently, DO-stat, VFAs consumption rate stat, and pH–stat fed-batch methods were applied to investigate and evaluate PHA productivity. The results showed that when pH–stat-based VFAs feeding was employed, a CDW of 7 g/L and PHA production of 5.1 g/L were achieved within 68 h, with a PHA content of 73%. Overall, the pH–stat fed-batch strategy proved to be effective in enhancing PHA production by Halomonas sp. YLGW01 utilizing VFAs.
Description of the design of a mixed-methods study to assess the burden and determinants of malaria transmission for tailoring of interventions (microstratification) in Ibadan and Kano metropolis
Authors: Ozodiegwu Ifeoma D. , Ogunwale Akintayo O. , Surakat Olabanji , Akinyemi Joshua O. , Bamgboye Eniola A. , Fagbamigbe Adeniyi F. , Bello Musa Muhammad , Adamu Al-Mukhtar Y. , Uhomobhi Perpetua , Ademu Cyril , Okoronkwo Chukwu , Adeleke Monsuru , Ajayi IkeOluwapo O. 
Published: September 2023

Abstract
Background
Rapid urbanization in Nigerian cities may lead to localized variations in malaria transmission, particularly with a higher burden in informal settlements and slums. However, there is a lack of available data to quantify the variations in transmission risk at the city level and inform the selection of appropriate interventions. To bridge this gap, field studies will be undertaken in Ibadan and Kano, two major Nigerian cities. These studies will involve a blend of cross-sectional and longitudinal epidemiological research, coupled with longitudinal entomological studies. The primary objective is to gain insights into the variation of malaria risk at the smallest administrative units, known as wards, within these cities.

Methods/results
The findings will contribute to the tailoring of interventions as part of Nigeria’s National Malaria Strategic Plan. The study design incorporates a combination of model-based clustering and on-site visits for ground-truthing, enabling the identification of environmental archetypes at the ward-level to establish the study’s framework. Furthermore, community participatory approaches will be utilized to refine study instruments and sampling strategies. The data gathered through cross-sectional and longitudinal studies will contribute to an enhanced understanding of malaria risk in the metropolises of Kano and Ibadan.

Conclusions
This paper outlines pioneering field study methods aimed at collecting data to inform the tailoring of malaria interventions in urban settings. The integration of multiple study types will provide valuable data for mapping malaria risk and comprehending the underlying determinants. Given the importance of location-specific data for microstratification, this study presents a systematic process and provides adaptable tools that can be employed in cities with limited data availability.
Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells
Authors: Khera Neha , Rajkumar Asvika Soodhalaagunta , Abdulkader M Alkurdi Khlood , Liu Zhiao , Ma Hong , Waseem Ahmad , Teh Muy-Teck 
Published: September 2023

AbstractMultidrug resistance renders treatment failure in a large proportion of head and neck squamous cell carcinoma (HNSCC) patients that require multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. Through transcriptome datamining, 28 genes were subjected to pharmacological and siRNA rescue functional assays on 12 strains of chemoresistant cell lines each against cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX) and docetaxel (DTX). Ten multidrug chemoresistance genes (TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1 and BIRC5) were identified. Of these, four genes (TOP2A, DNMT1, INHBA and NEK2) were upregulated in an HNSCC patient cohort (n = 221). Silencing NEK2 abrogated chemoresistance in all drug-resistant cell strains. INHBA and TOP2A were found to confer chemoresistance in majority of the drug-resistant cell strains whereas DNMT1 showed heterogeneous results. Pan-cancer Kaplan-Meier survival analysis on 21 human cancer types revealed significant prognostic values for INHBA and NEK2 in at least 16 cancer types. Drug library screens identified two compounds (Sirodesmin A and Carfilzomib) targeting both INHBA and NEK2 and re-sensitised cisplatin-resistant cells. We have provided the first evidence for NEK2 and INHBA in conferring chemoresistance in HNSCC cells and siRNA gene silencing of either gene abrogated multidrug chemoresistance. The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalised biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumour types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signalling mechanisms in tumour chemoresistance.
Selenium-integrated conjugated oligomer nanoparticles with high photothermal conversion efficiency for NIR-II imaging-guided cancer phototheranostics in vivo
Authors: Yang Lele , Gao Yijian , Wei Jinchao , Cheng Zehua , Wu Sijia , Zou Liang , Li Shengliang , Li Peng 
Published: September 2023

AbstractSecond near-infrared (NIR-II) fluorescence imaging in the range of 1000–1700 nm has great prospects for in vivo imaging and theranostics monitoring. At present, few NIR-II probes with theranostics properties have been developed, especially the high-performance organic theranostics material remains underexploited. Herein, we demonstrate a selenium (Se)-tailoring method to develop high-efficient NIR-II imaging-guided material for in vivo cancer phototheranostics. Via Se-tailoring strategy, conjugated oligomer TPSe-based nanoparticles (TPSe NPs) achieve bright NIR-II emission up to 1400 nm and exhibit a relatively high photothermal conversion efficiency of 60% with good stability. Moreover, the TPSe NPs demonstrate their photothermal ablation of cancer cells in vitro and tumor in vivo with the guidance of NIR-II imaging. It is worth noting that the TPSe NPs have good biocompatibility without obvious side effects. Thus, this work provides new insight into the development of NIR-II theranostics agents.
Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex
Authors: Zhang Yini , Tang Jianan , Wang Xuemei , Sun Yisi , Yang Tianying , Shen Xiaorong , Yang Xinyue , Shi Huijuan , Sun Xiaoxi , Xin Aijie 
Published: September 2023

Abstract
Background
Actin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms.

Methods
Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a.

Results
The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice.

Conclusions
Loss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.
Regulation of anoikis by extrinsic death receptor pathways
Authors: Han Ying-Hao , Wang Yuan , Lee Seung-Jae , Jin Mei-Hua , Sun Hu-Nan , Kwon Taeho 
Published: September 2023

AbstractMetastatic cancer cells can develop anoikis resistance in the absence of substrate attachment and survive to fight tumors. Anoikis is mediated by endogenous mitochondria-dependent and exogenous death receptor pathways, and studies have shown that caspase-8-dependent external pathways appear to be more important than the activity of the intrinsic pathways. This paper reviews the regulation of anoikis by external pathways mediated by death receptors. Different death receptors bind to different ligands to activate downstream caspases. The possible mechanisms of Fas-associated death domain (FADD) recruitment by Fas and TNF receptor 1 associated-death domain (TRADD) recruitment by tumor necrosis factor receptor 1 (TNFR1), and DR4- and DR5-associated FADD to induce downstream caspase activation and regulate anoikis were reviewed. This review highlights the possible mechanism of the death receptor pathway mediation of anoikis and provides new insights and research directions for studying tumor metastasis mechanisms.
STING signaling activation modulates macrophage polarization via CCL2 in radiation-induced lung injury
Authors: Ni Jianjiao , Guo Tiantian , Zhou Yue , Jiang Shanshan , Zhang Long , Zhu Zhengfei 
Published: September 2023

Abstract
Background
Radiation-induced lung injury (RILI) is a prevalent complication of thoracic radiotherapy in cancer patients. A comprehensive understanding of the underlying mechanisms of RILI is essential for the development of effective prevention and treatment strategies.

Methods
To investigate RILI, we utilized a mouse model that received 12.5 Gy whole-thoracic irradiation. The evaluation of RILI was performed using a combination of quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), histology, western blot, immunohistochemistry, RNA sequencing, and flow cytometry. Additionally, we established a co-culture system consisting of macrophages, lung epithelial cells, and fibroblasts for in vitro studies. In this system, lung epithelial cells were irradiated with a dose of 4 Gy, and we employed STING knockout macrophages. Translational examinations were conducted to explore the relationship between STING expression in pre-radiotherapy lung tissues, dynamic changes in circulating CCL2, and the development of RILI.

Results
Our findings revealed significant activation of the cGAS-STING pathway and M1 polarization of macrophages in the lungs of irradiated mice. In vitro studies demonstrated that the deficiency of cGAS-STING signaling led to impaired macrophage polarization and RILI. Through RNA sequencing, cytokine profiling, and rescue experiments using a CCL2 inhibitor called Bindarit, we identified the involvement of CCL2 in the regulation of macrophage polarization and the development of RILI. Moreover, translational investigations using patient samples collected before and after thoracic radiotherapy provided additional evidence supporting the association between cGAS-STING signaling activity, CCL2 upregulation, and the development of radiation pneumonitis.

Conclusions
The cGAS-STING signaling pathway plays a crucial role in regulating the recruitment and polarization of macrophages, partly through CCL2, during the pathogenesis of RILI.
Suboptimal birth spacing practice and its predictors among reproductive-age women in Sub-Saharan African countries: a multilevel mixed-effects modeling with robust Poisson regression
Authors: Mare Kusse Urmale , Sabo Kebede Gemeda , Mohammed Ahmed Adem , Leyto Simeon Meskele , Mulaw Getahun Fentaw , Tebeje Tsion Mulat , Aychiluhm Setognal Birara , Ebrahim Oumer Abdulkadir , Wuneh Abel Gebre , Seifu Beminate Lemma 
Published: September 2023

Abstract
Background
Despite the availability of exempted family planning services, a significant proportion of women in African countries continue to experience inadequately spaced pregnancies. To the authors’ knowledge, evidence of suboptimal birth intervals at the SSA level is lacking and previous studies have been limited to specific geographic area. Therefore, this analysis was aimed to estimate the pooled prevalence of suboptimal birth spacing and its predictors among childbearing women in SSA.

Methods
Pooled DHS data from 35 SSA countries were used and a weighted sample of 221,098 reproductive-age women was considered in the analysis. The survey across all countries employed a cross-sectional study design and collected data on basic sociodemographic characteristics and different health indicators. Forest plot was used to present the overall and country-level prevalence of suboptimal birth spacing. Multilevel mixed-effects models with robust Poisson regression were fitted to identify the predictors of suboptimal birth spacing. Akaike’s and Bayesian information criteria and deviance were used to compare the models. In a multivariable regression model, a p-value less than 0.05 and an adjusted prevalence ratio with the corresponding 95% CI were used to assess the statistical significance of the explanatory variables.

Results
The pooled prevalence of suboptimal birth spacing among women in SSA was 43.91% (43.71%-44.11%), with South Africa having the lowest prevalence (23.25%) and Chad having the highest (59.28%). It was also found that 14 of the 35 countries had a prevalence above the average for SSA. Rural residence [APR (95% CI) = 1.10 (1.12–1.15)], non-exposure to media [APR (95% CI) = 1.08 (1.07–1.11)], younger maternal age [APR (95% CI) = 2.05 (2.01–2.09)], non-use of contraception [APR (95% CI) = 1.18 (1.16–1.20)], unmet need for family planning [APR (95% CI) = 1.04 (1.03–1.06)], higher birth order [APR (95% CI) = 1.31 (1.28–1.34)], and desire to have at least six children [APR (95% CI) = 1.14 (1.13–1.16)] were the predictors of suboptimal birth spacing practice.

Conclusion
More than four out of ten reproductive-age women in SSA countries gave birth to a subsequent child earlier than the recommended birth spacing, with considerable variations across the countries. Thus, interventions designed at enhancing optimal birth spacing should pay particular attention to young and socioeconomically disadvantaged women and those residing in rural regions. Strengthening community health programs and improving accessibility and availabilities of fertility control methods that ultimately impacts optimal reproductive behaviors is crucial to address contraceptive utilization and unmet need.
Establishment of an NPK nutrient monitor system in yield-graded cotton petioles under drip irrigation
Authors: Dong Zhiqiang , Liu Yang , Li Minghua , Ci Baoxia , Feng Xiaokang , Wen Shuai , Lu Xi , He Zheng , Ma Fuyu 
Published: September 2023

Abstract
Background
The determination of nutrient content in the petiole is one of the important methods for achieving cotton fertilization management. The establishment of a monitoring system for the nutrient content of cotton petioles during important growth periods under drip irrigation is of great significance for achieving precise fertilization and environmental protection.

Methods
A total of 100 cotton fields with an annual yield of 4500–7500 kg/ha were selected among the main cotton-growing areas of Northern Xinjiang. The nitrate nitrogen (NO3−–N), inorganic phosphorus (PO43−–P) and inorganic potassium (K+–K) content and yield of cotton petioles were recorded. Based on a yield of 6000 kg/ha as the dividing line, a two-level and yield-graded monitoring system for NO3−–N, PO43−–P and K+–K in cotton petioles during important growth periods was established, and predictive yield models for NO3−–N, PO43−–P and K+–K in petioles during important growth periods were established.

Results
The results showed found that the yields of the 100 cotton fields surveyed were normally distributed. Therefore, two yield grades were classified using 6000 kg/ha as a criterion. Under different yield-graded, the NO3−–N, PO43−–P and K+–K content of petiole at important growth stages was significantly positively correlated with yield. Further, the variation range of NO3−–N, PO43−–P and K+–K content in petioles could be used as a standard for yield-graded. In addition, a yield prediction model for the NO3−–N, PO43−–P and K+–K content of petioles was developed. The SSO-BP validation model performed the best (R2 = 0.96, RMSE = 0.06 t/ha, MAE = 0.05 t/ha) in the full bud stage, which was 12.9% higher than the BP validation model. However, the RMSE and MAE were decreased by 86.7% and 88.1%, respectively.

Conclusion
The establishment of NPK nutrition monitor system of cotton petioles under drip irrigation based on yield-graded provides an important basis for nutrition monitor of cotton petiole under drip irrigation in Xinjiang. It also provides a new method for cotton yield prediction.