bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAFs-derived SCUBE1 promotes malignancy and stemness through the Shh/Gli1 pathway in hepatocellular carcinoma
Authors: Zhao Jungang , Li Rizhao , Li Jiacheng , Chen Ziyan , Lin Zixia , Zhang Baofu , Deng Liming , Chen Gang , Wang Yi 
Published: November 2022

Abstract
Background
The tumour microenvironment and cirrhotic liver are excellent sources of cancer-associated fibroblasts (CAFs), which participate in carcinogenesis. Thus, it is important to clarify the crosstalk between CAFs and HCC cells and the related mechanism in regulating carcinogenesis.

Methods
Human hepatocellular carcinoma (HCC) tissues and matched adjacent normal tissues were obtained from HCC patients. Immunohistochemistry, Western blotting (WB) and RT–qPCR were performed to detect the expression of SCUBE1. The roles of SCUBE1 in inducing stemness features in HCC cells were explored and investigated in vitro and in vivo. Student’s t tests or Mann–Whitney U tests were used to compare continuous variables, while chi-square tests or Fisher’s exact tests were used to compare categorical variables between two groups.

Results
SCUBE1 was confirmed to be highly expressed in CAFs in HCC and had a strong connection with stemness and a poor prognosis. In addition, CAFs were found to secrete SCUBE1 to enhance the malignancy of HCC cells and increase the proportion of CD133-positive cells. Silencing SCUBE1 expression had the opposite effect. The Shh pathway was activated by SCUBE1 stimulation. Inhibition of cyclopamine partially reversed the stimulating effect of SCUBE1 both in vivo and in vitro. Moreover, based on the RT–qPCR, ELISA and WB results, a high SCUBE1 expression level was found in HCC tissue and serum.

Conclusion
This study revealed that CAFs-derived SCUBE1 can enhance the malignancy and stemness of HCC cells through the Shh pathway. This study aims to provide new perspectives for future HCC studies and provide new strategies for HCC treatment.
Genome-wide profiling of retroviral DNA integration and its effect on clinical pre-infusion CAR T-cell products
Authors: Shao Lipei , Shi Rongye , Zhao Yingdong , Liu Hui , Lu Alexander , Ma Jinxia , Cai Yihua , Fuksenko Tatyana , Pelayo Alejandra , Shah Nirali N. , Kochenderfer James N. , Norberg Scott M. , Hinrichs Christian , Highfill Steven L. , Somerville Robert P , Panch Sandhya R. , Jin Ping , Stroncek David F. 
Published: November 2022

Abstract
Background
Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are the most commonly used vectors in the manufacturing process. However, the integration pattern of these viral vectors and subsequent effect on CAR T-cell products is still unclear.

Methods
We used a modified viral integration sites analysis (VISA) pipeline to evaluate viral integration events around the whole genome in pre-infusion CAR T-cell products. We compared the differences of integration pattern between lentiviral and γ-retroviral products. We also explored whether the integration sites correlated with clinical outcomes.

Results
We found that γ-retroviral vectors were more likely to insert than lentiviral vectors into promoter, untranslated, and exon regions, while lentiviral vector integration sites were more likely to occur in intron and intergenic regions. Some integration events affected gene expression at the transcriptional and post-transcriptional level. Moreover, γ-retroviral vectors showed a stronger impact on the host transcriptome. Analysis of individuals with different clinical outcomes revealed genes with differential enrichment of integration events. These genes may affect biological functions by interrupting amino acid sequences and generating abnormal proteins, instead of by affecting mRNA expression. These results suggest that vector integration is associated with CAR T-cell efficacy and clinical responses.

Conclusion
We found differences in integration patterns, insertion hotspots and effects on gene expression vary between lentiviral and γ-retroviral vectors used in CAR T-cell products and established a foundation upon which we can conduct further analyses.
Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing
Authors: Hiramuki Yosuke , Kure Yuriko , Saito Yoshihiko , Ogawa Megumu , Ishikawa Keiko , Mori-Yoshimura Madoka , Oya Yasushi , Takahashi Yuji , Kim Dae-Seong , Arai Noriko , Mori Chiaki , Matsumura Tsuyoshi , Hamano Tadanori , Nakamura Kenichiro , Ikezoe Koji , Hayashi Shinichiro , Goto Yuichi , Noguchi Satoru , Nishino Ichizo 
Published: November 2022

Abstract
Background
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by asymmetric muscle wasting and weakness. FSHD can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1, DNMT3B, or LRIF1. Genetic diagnosis of FSHD is challenging because of the complex procedures required.

Methods
We applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients.

Results
We found significant hypomethylation of contracted 4q-D4Z4 repeats in FSHD1, and both 4q- and 10q-D4Z4 repeats in FSHD2. We also found that the hypomethylation in the contracted D4Z4 in FSHD1 is moderately correlated with patient phenotypes.

Conclusions
Our method contributes to the development for the diagnosis of FSHD using Nanopore long-read sequencing. This finding might give insight into the mechanisms by which repeat contraction causes disease pathogenesis.
Beneficial effect of time-restricted eating on blood pressure: a systematic meta-analysis and meta-regression analysis
Authors: Wang Weihao , Wei Ran , Pan Qi , Guo Lixin 
Published: November 2022

AbstractBackgroundAs a cardiometabolic disease, hypertension has shown an obvious upward trend, becoming a global epidemic chronic disease. Lifestyle intervention is a fundamental method for lowering blood pressure. This systematic review and meta-analysis aimed to evaluate the effects of time-restricted eating (TRE) on blood pressure.MethodsStudies were retrieved from the PubMed, Embase, Cochrane Library, and Web of Science databases to evaluate the effects of TRE on blood pressure. The time frame of search was from the start of database construction until July 14, 2022.There were no language restrictions. Meta-analysis and meta-regression were performed using Stata version 16. The weighted mean difference with 95% CI was used to assess the effect of TRE on blood pressure, heart rate, weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. The main ending of this article were blood pressure and heart rate, while the secondary ending were weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides.ResultsTen randomized controlled trials involving 694 patients were identified. TRE significantly reduced systolic blood pressure (SBP) (mean difference = −4.15; 95% CI: −6.73, −2.30;P< 0.0001), but had no significant effect on diastolic blood pressure (DBP) (mean difference = −2.06; 95% CI: −4.16, 0.02;P= 0.053) and no beneficial effect on heart rate (mean difference = 0.36; 95% CI: −2.83, 3.54;P= 0.0825). TRE promoted weight loss (mean difference = −1.63; 95% CI: −2.61, −0.64;P= 0.001) and decreased blood glucose levels (mean difference = −2.80; 95% CI: −4.64, −0.96;P= 0.003), but had no significant effect on total cholesterol (mean difference = 0.03, 95% CI: −10.01, 10.08;P= 0.995), HDL-C (mean difference = 0.85, 95% CI: −1.80, 3.49;P= 0.531), LDL-C (mean difference = −0.86, 95% CI: −6.47, 4.76;P= 0.764), or triglycerides (mean difference = −3.524, 95% CI: −9.49, 2.45;P= 0.248). In a separate meta-regression analysis, the degree of SBP change was related to weight loss (P= 0.044) but not to glucose improvement (P= 0.867).ConclusionsThe present meta-analysis suggests that TRE significantly reduced SBP, while no effect of reducing DBP was seen. The observed lower blood pressure may be attributed to significant weight loss. The effects of TRE on heart rate and blood lipid levels were not apparent.
Curcumin improves insulin sensitivity in high-fat diet-fed mice through gut microbiota
Authors: Zhong Yue , Xiao Yang , Gao Jing , Zheng Zhaozheng , Zhang Ziheng , Yao Lu , Li Dongmin 
Published: November 2022

Abstract
Background
Insulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice.

Methods
Glucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100 mg kg−1 d−1, p.o.) or vehicle for 4 weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4 weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA).

Results
Curcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota.

Conclusions
The effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.
Successful breastfeeding following a level II NICU stay in Qatar – a longitudinal study
Authors: Viswanathan Brijroy , El Bedaywi Rajai , Tomerak Ahmed , Abedin Sarfrazul , Chandra Prem 
Published: November 2022

Abstract
Background
Exclusive breastfeeding is an essential need for mothers and newborn babies, but cultural practices and employment demands significantly influence feeding practices. The association between neonatal intensive care unit (NICU) admission and breastfeeding outcomes are variable. Data for Qatar and Middle East, in particular, are limited. Hence, this study aims to estimate the rate of breastfeeding at the time of NICU discharge and the rate of successful breastfeeding after NICU discharge in Qatar during well-baby follow-ups.

Methods
This quantitative longitudinal study was conducted over 18 months from January 2019 and included neonates born in Al Wakra Hospital admitted to the NICU. Demographic data, feeding during NICU stay and at discharge were obtained from lactation charts. Data regarding feeding practices after discharge were obtained through a questionnaire administered at 4 weeks and 8 weeks in well-baby clinics. Descriptive statistics and logistic regression analyses were performed to determine the rates of breastfeeding and the association between the various factors.

Results
Of the 678 participants screened, 364 were eligible for analysis. The rates of exclusive breastfeeding were 20% (73/364), 54% (197/364) and 42% (153/364) at discharge, 4 weeks and 8 weeks, respectively. Any breastfeeding was 64% (233/364), 40% (146/364) and 43% (157/364) at discharge, 4 weeks and 8 weeks, respectively. Logistic regression analysis showed that neonates who had NICU stays longer than 4 days had a higher rate of exclusive breastfeeding at discharge (adjusted odds ratio 3.000; 95% CI 1.25, 7.198) but had a reduced rate of breastfeeding and higher rate of formula feeding during follow-ups. Although breastfeeding rates were better in preterm infants at NICU discharge, regression analysis showed that none of the other factors, including gestation and maternal education had a significant association with the rate of exclusive breastfeeding at the time of discharge or during follow-ups.

Conclusions
The overall breastfeeding rates from this level II NICU in Qatar are better than previously available data. Studies with extended follow-up and assessment of intervention methods should be planned to improve and sustain the practice of exclusive breastfeeding.
Combining novel feature selection strategy and hyperspectral vegetation indices to predict crop yield
Authors: Fei Shuaipeng , Li Lei , Han Zhiguo , Chen Zhen , Xiao Yonggui 
Published: November 2022

Abstract
Background
Wheat is an important food crop globally, and timely prediction of wheat yield in breeding efforts can improve selection efficiency. Traditional yield prediction method based on secondary traits is time-consuming, costly, and destructive. It is urgent to develop innovative methods to improve selection efficiency and accelerate genetic gains in the breeding cycle.

Results
Crop yield prediction using remote sensing has gained popularity in recent years. This paper proposed a novel ensemble feature selection (EFS) method to improve yield prediction from hyperspectral data. For this, 207 wheat cultivars and breeding lines were grown under full and limited irrigation treatments respectively, and their canopy hyperspectral reflectance was measured at the flowering, early grain filling (EGF), mid grain filling (MGF), and late grain filling (LGF) stages. Then, 115 vegetation indices were extracted from the hyperspectral reflectance and combined with four feature selection methods, i.e., mean decrease impurity (MDI), Boruta, FeaLect, and RReliefF to train deep neural network (DNN) models for yield prediction. Next, a learning framework was developed by combining the predicted values of the selected and the full features using multiple linear regression (MLR). The results show that the selected features contributed to higher yield prediction accuracy than the full features, and the MDI method performed well across growth stages, with a mean R2 ranging from 0.634 to 0.666 (mean RMSE = 0.926–0.967 t ha−1). Also, the proposed EFS method outperformed all the individual feature selection methods across growth stages, with a mean R2 ranging from 0.648 to 0.679 (mean RMSE = 0.911–0.950 t ha−1).

Conclusions
The proposed EFS method can improve grain yield prediction from hyperspectral data and can be used to assist wheat breeders in earlier decision-making.
The tibetan medicine Zuozhu-Daxi can prevent Helicobacter pylori induced-gastric mucosa inflammation by inhibiting lipid metabolism
Authors: Shi Yanyan , Ning Jing , Norbu Kelsang , Hou Xingzi , Zheng Huiling , Zhang Hejun , Yu Wei , Zhou Feng , Li Yuan , Ding Shigang , Zhang Qingying 
Published: November 2022

AbstractBackgroundTibetan medicine has been used in clinical practice for more than 3800 years. Zuozhu-Daxi (ZZDX), a classic traditional Tibetan medicine, has been proved to be effective in the treatment of digestive diseases, such as chronic gastritis, gastric ulcer, etc.Helicobacter pylori(H. pylori), one of the most common pathogenic microbes, is regarded as the most common cause of gastritis. Researching on the effects of ZZDX onH. pylori-induced gastric mucosa inflammation could provide more evidences onH. pyloritreatment and promote the development of Tibetan medicine. This study aimed to explore whether ZZDX could rescueH. pylori-induced gastric mucosa inflammation and its mechanism.MethodsMale C57BL/6 mice were infected withH. pylori, and orally treated with ZZDX to rescue gastric mucosa inflammation induced byH. pyloriinfection. Pathology of gastric mucosa inflammation was evaluated under microscopy by hematoxylin–eosin (HE) staining. The infection status ofH. pyloriwas evaluated by immunohistochemical (IHC) staining. The reactive oxygen species (ROS) level in serum was evaluated using a detection kit. IL-1α, IL-6, and PGE2 expression levels in serum were measured using ELISA. IL-1α, IL-8, TNF-α, and NOD1 expression levels in gastric tissues were measured using real-time PCR. RNA sequencing and gene certification of interest were performed to explore the mechanisms in vivo and in vitro.ResultsThe results showed that ZZDX could significantly inhibitH. pylori-induced gastric mucosa inflammation using HE staining. IL-1α, IL-6, and PGE2 expression levels in serum were significantly decreased after treatment with ZZDX. ZZDX treatment significantly decreased the mRNA expression of IL-8 induced byH. pyloriinfection in gastric tissues.Elovl4, Acot1andScd1might be involved in the mechanisms of ZZDX treatment. However, theH. pyloriinfection status in the gastric mucosa was not reduced after ZZDX treatment.ConclusionsZZDX reversed gastric mucosal injury and alleviated gastric mucosa inflammation induced byH. pyloriinfection.
Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency
Authors: Kubaski Francyne , Burlina Alberto , Pereira Danilo , Silva Camilo , Herbst Zackary M. , Trapp Franciele B. , Michelin-Tirelli Kristiane , Lopes Franciele F. , Burin Maira G. , Brusius-Facchin Ana Carolina , Netto Alice B. O. , Poletto Edina , Bernardes Tamires M. , Carvalho Gerson S. , Sorte Ney B. , Ferreira Fernanda N. , Perin Nilza , Clivati Marta R. , de Santana Marnie T. S. , Lobos Sandra F. G. , Leão Emilia K. E. A. , Coutinho Marcelo P. , Pinos Paola V. , Santos Maria L. S. F. , Penatti Debora A. , Lourenço Charles M. , Polo Giulia , Giugliani Roberto 
Published: November 2022

Abstract
Background
Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Results
DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns.

Conclusions
The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Authors: Raulin Ana-Caroline , Doss Sydney V. , Trottier Zachary A. , Ikezu Tadafumi C. , Bu Guojun , Liu Chia-Chen 
Published: November 2022

AbstractAlzheimer’s disease (AD) is the most common cause of dementia worldwide, and its prevalence is rapidly increasing due to extended lifespans. Among the increasing number of genetic risk factors identified, the apolipoprotein E (APOE) gene remains the strongest and most prevalent, impacting more than half of all AD cases. While the ε4 allele of theAPOEgene significantly increases AD risk, the ε2 allele is protective relative to the common ε3 allele. These gene alleles encode three apoE protein isoforms that differ at two amino acid positions. The primary physiological function of apoE is to mediate lipid transport in the brain and periphery; however, additional functions of apoE in diverse biological functions have been recognized. Pathogenically, apoE seeds amyloid-β (Aβ) plaques in the brain with apoE4 driving earlier and more abundant amyloids. ApoE isoforms also have differential effects on multiple Aβ-related or Aβ-independent pathways. The complexity of apoE biology and pathobiology presents challenges to designing effective apoE-targeted therapeutic strategies. This review examines the key pathobiological pathways of apoE and related targeting strategies with a specific focus on the latest technological advances and tools.
Characteristics and costs of electric scooter injuries in Helsinki: a retrospective cohort study
Authors: Vasara Henri , Toppari Linda , Harjola Veli-Pekka , Virtanen Kaisa , Castrén Maaret , Kobylin Arja 
Published: November 2022

Abstract
Background and purpose
The incidence of electric scooter (e-scooter) injuries has increased drastically in numerous countries after widespread availability of shared e-scooters. The economic impact on society from a broader perspective has not been studied. We aimed to estimate the incidence of e-scooter injuries, describe the injury patterns, and estimate the costs of e-scooter injuries.

Patients and methods:
We performed a retrospective cohort study including all e-scooter-related injuries presented in the three adult emergency departments in Helsinki in 2021. We collected the patient data from the university hospital information system. Injury severity was evaluated based on the Abbreviated Injury Score. The cost of the hospital treatment was analyzed based on our hospital district’s service price listing. In addition, we recorded the total amount of sick leave days and estimated their economic impact.

Results
In total, 446 e-scooter injuries were identified and taken into the analysis (434 affecting riders and 12 non-riders). The median age of the patients was 26 (IQR 22–33), and 59% were male. 257 (58%) of the of the injuries were minor, whereas 155 (35%) were moderate, 30 (7%) serious, 3 (0.7%) severe, and one (0.2%) critical. Furthermore, 220 (49%) of the patients sustained head injuries. A major spike in accident incidence was seen during the weekend (Friday to Sunday) nights, accompanied by a proportional increase in patients with alcohol intoxication. Including both the costs of the hospital care and absence from work, the approximated total cost of e-scooter injuries was 1.7 million euros, with a median cost of a single accident being 1148 euros (IQR 399–4263 €).

Interpretation:
Considerable number of the injuries are moderate, severe, or worse. Comprehensive preventive measures must be conducted to decrease the incidence of e-scooter injuries. The use of helmets should be strongly encouraged to prevent severe head injuries. The nighttime bans during weekends and speed limits on e-scooters appear to be justifiable.