bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring Infant Caregivers' Provision of Modified Formulas: Potential Demographic Differences and Reasons for Provisions
Authors: Gershman Haley , Romo-Palafox Maria J. , Rajeh Tassneem , Fleming-Milici Frances , Harris Jennifer L. 
Published: May 2022

BackgroundFormula brands have modified the ingredients in standard infant formulas and extensively market modified formulas, claiming benefits for infants that are not supported by scientific evidence. This exploratory study examined the proportion of infant caregivers who reported serving modified formula, demographic differences, and reasons for providing them.MethodsThis is a cross-sectional online survey of US caregivers of infants (6–11 months) who provided formula in the past month (N = 436). Participants reported the type of formula served most often and agreement with potential reasons for provision. Logistic regression assessed the odds of serving modified formula by demographic characteristics. MANOVA examined differences in agreement with purchase reasons between caregivers by the type of formula provided.ResultsApproximately one-half (47%) of participants reported serving modified formula most often; sensitive and organic/non-GMO were the most common types provided. Caregivers in the middle-income group were most likely to serve modified formulas, but the provision did not differ by other demographic characteristics. Agreement with reasons for providing was highest for “pediatricians recommend” and “benefits my child” (M = 4.2 out of 5). Agreement with “my pediatrician prescribed” and “natural ingredients” was significantly higher for modified vs. standard formula providers.ConclusionWidespread provision of modified formula by infant caregivers raises concerns due to its higher cost and the lack of scientific evidence supporting benefits for babies. These findings suggest that regulations limiting unsubstantiated formula claims and restrictions on misleading marketing to consumers are necessary. Additional research is needed to understand pediatricians' perceptions of modified formulas and reasons for recommending them to patients.
Application of Green Technologies in Design-Based Extraction of Celastrus paniculatus (Jyotishmati) Seeds, SEM, GC-MS Analysis, and Evaluation for Memory Enhancing Potential
Authors: Arya Ashwani , Kaushik Deepak , Almeer Rafa , Bungau Simona G. , Sayed Amany A. , Abdel-Daim Mohamed M. , Bhatia Saurabh , Mittal Vineet 
Published: May 2022

BackgroundThe Celastrus paniculatus (CP), commonly known as Jyotishmati, is considered as “elixir of life” by Indian people for the prevention or management of many ailments. The seed powder and its extract have widely used commercially for the preparation of various Ayurvedic formulations for the improvement of memory. CP seeds were generally extracted by conventional extraction methods (CEMs) which are assumed to impact environment burden and also produce low extract yield. Green extraction with possible improvement in extract yield has always been the need of hour for selected medicinal plant.ObjectiveIn the present research, we aimed to optimize the different extraction factors in microwave and ultrasound-based extraction. The various extracts obtained in conventional and green methods are also evaluated for the possible improvement in memory enhancing potential.Materials and MethodsThe selected medicinal herb was extracted by CEM (maceration and percolation). In green methods such microwave-assisted extraction (MAE) and ultrasound assisted-extraction (UAE), various parameters were optimized using Box-Behnken design coupled with response surface methodology. The scanning electron microscopy (SEM) and gas chromatography–mass spectroscopy (GC-MS) analyses were also done to confirm the possible improvement in concentration of plant actives. The Swiss albino mice were used to evaluate memory enhancing potential of different extracts.ResultsAt the optimized conditions MAE and UAE the extraction yield, total phenolic content (TPC) and Total flavonoid content (TFC) are significantly improved. The GC-MS analysis further confirms the improvement in concentration of certain fatty acid esters, pilocarpine, and steroidal compounds in optimized extracts. The optimized extracts also exhibited the significant improvement in behavioral parameters, oxidative stress-induced parameters, and acetylcholinesterase inhibitory potential.Discussion and ConclusionFrom the results, we can say that the application of green technologies in design-based extraction of selected herb not only significantly reduces the extraction time but also improves the extract yield and concentration of plant actives. In nutshell, it can be concluded that the green approaches for extraction of seeds of Celastrus paniculatus could be scale up at a commercial level to meet the rising demand for herbal extract.
Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function
Authors: Li Xiaogang , Li Ruixuan , You Nana , Zhao Xiexiong , Li Jiaying , Jiang Weihong 
Published: May 2022

BackgroundWe aimed to investigate the effect and mechanism of butyric acid on rat myocardial fibrosis (MF).Methods16S rRNA sequencing was used to analyze the gut microbiota characteristics of the Sham group and MF group. HPLC was applied to measure butyric acid in the feces and serum. In vitro, rat macrophages RMa-bm were stimulated with LPS and IL-4, respectively, and then butyrate was added to study the influences of butyrate on M1/M2 polarization and mitochondrial function of rat macrophages. The rat macrophages and rat myocardial fibroblasts were co-cultured to explore the effect of butyrate on rat myocardial fibroblasts. In addition, MF rats were fed with butyric acid diet.ResultsCompared with the Sham group, collagen deposition in the MF group was increased, and fibrosis was serious. The abundance of Desulfovibrionaceae and Helicobacteraceae in the MF group was increased compared with the Sham group. Gut epithelial cells were destroyed in the MF group compared with the Sham group. Compared with the Sham group, LPS content in the MF group was increased and butyric acid was decreased. Butyrate inhibited M1 and promoted M2. Furthermore, butyrate may promote mitochondrial function recovery by regulating M1/M2 polarization of macrophages. After adding butyrate, cell proliferation ability was decreased, and aging and apoptosis were increased, which indicated that butyrate inhibited rat myocardial fibroblasts activity. Moreover, butyric acid could protect mitochondria and improve the symptoms of rats with MF.ConclusionsButyric acid ameliorated MF by regulating M1/M2 polarization of macrophages and promoting recovery of mitochondrial function.
The Application and Value of 3T Magnetic Resonance Imaging in the Display of Pulmonary Nodules
Authors: Feng Hui , Shi Gaofeng , Liu Hui , Xu Qian , Wang Lijia , Zhang Ning 
Published: May 2022

ObjectiveThe aim of this study was to evaluate the sensitivity and accuracy of multi-sequence 3T magnetic resonance imaging (MRI) in the detection of different types of pulmonary nodules.MethodsA total of 68 patients with pulmonary nodules identified using computed tomography (CT) subsequently underwent MRI. Using CT images with a slice thickness of 1 mm as the gold standard, the sensitivity of three MRI sequences in detecting different types of pulmonary nodules was calculated, and the image quality was also evaluated. Nodule types included solid nodules, ground glass nodules (GGN), and part-solid nodules (PSN). Statistical analyses of data were conducted using the software SPSS 21.0. The intra-class correlation coefficient was calculated in order to compare the consistency of nodule size in both MRI and CT.ResultsCT detected 188 pulmonary nodules in 68 patients, including 87 solid nodules and 101 sub-solid nodules, the latter comprising 46 PSNs and 55 GGNs. The average nodule diameter was approximately 7.7 mm. The sensitivity of MRI in detecting nodules ≥ 6 mm in diameter and those of &gt; 8 mm in diameter was 92% and 100%, respectively, and the sequence with the highest detection rate was T2-BLADE. In relation to solid nodules, the sequence with the highest detection rate was T1 Star-VIBE, while the T2-BLADE sequence demonstrated the highest detection rate of sub-solid nodules. The image quality of the T1 Star-VIBE sequence was better than that of both the T2-HASTE and the T2-BLADE sequences. The consistency of CT and MRI sequences for nodule size was high with a consistency coefficient of 0.94–0.98.ConclusionThe detection rate of MRI for nodules with a diameter of &gt; 8 mm was 100%. The T2-BLADE sequence had the highest detection sensitivity. The sequence with the best image quality was the T1 Star-VIBE.
Molecular Landscape and Prognostic Biomarker Analysis of Advanced Pancreatic Cancer and Predictors of Treatment Efficacy of AG Chemotherapy
Authors: Du Juan , Qiu Xin , Lu Changchang , Zhu Yahui , Kong Weiwei , Xu Mian , Zhang Xin , Tang Min , Chen Jun , Li Qi , Li Aimei , He Jian , Gu Qing , Wang Lei , Qiu Yudong , Liu Baorui 
Published: May 2022

PurposeAlthough mutational analysis of pancreatic cancer has provided valuable clinical information, it has not significantly changed treatment prospects. The purpose of this study is to further investigate molecular alterations in locally advanced pancreatic cancer and identify predictors of the efficacy of nab-paclitaxel plus gemcitabine (AG) chemotherapy.Experimental designTumor samples from 118 pancreatic cancer patients who received AG chemotherapy as first-line treatment were sequenced and genomic profile was generated. Molecular alterations and the involved signaling pathways were analyzed. Genes with a significant difference in mutation frequency between primary and metastatic tumors were identified, and prognostic-related mutant genes were screened using SPSS version 22.0.ResultsThe most common altered genes in the patients were KRAS (94.9%), TP53 (81.4%), CDKN2A (36.4%), and SMAD4 (22.9%). The mutational frequencies of CDKN2B (14.8% vs. 0%, p = 0.001), FAT3 (7.4% vs. 0%, p = 0.041), MTAP (13% vs. 1.6%, p = 0.023), and SMAD4 (31.4% vs. 15.6%, p = 0.049) in metastatic tumors were significantly higher than that in primary tumors. TP35 and KRAS mutations were significantly correlated with objective response rate, while EPHA7, RNF43, and HMGA2 mutations were significantly correlated with disease control rate. Additionally, patients with TGFR2B, FGF23, EPHA7, SMARCA4, CARD11, ADGRA2, CCNE1, and ACVR2A alterations had a worse overall survival. Further, EPHA7, CARD11, NOTCH1, GATA6, ACVR2A, and HMGA2 mutations indicated undesirable progression-free survival.ConclusionsCDKN2B, FAT3, MTAP, and SMAD4 may be biomarkers that distinguish primary tumors from metastases. EPHA7 mutation may serve as a prognostic biomarker to predict the treatment efficacy of AG chemotherapy in locally advanced pancreatic cancer.
Assessment of Statistical Process Control Based DVH Action Levels for Systematic Multi-Leaf Collimator Errors in Cervical Cancer RapidArc Plans
Authors: Zhang Hanyin , Lu Wenli , Cui Haixia , Li Ying , Yi Xin 
Published: May 2022

BackgroundIn the patient-specific quality assurance (QA), DVH is a critical clinically relevant parameter that is finally used to determine the safety and effectiveness of radiotherapy. However, a consensus on DVH-based action levels has not been reached yet. The aim of this study is to explore reasonable DVH-based action levels and optimal DVH metrics in detecting systematic MLC errors for cervical cancer RapidArc plans.MethodsIn this study, a total of 148 cervical cancer RapidArc plans were selected and measured with COMPASS 3D dosimetry system. Firstly, the patient-specific QA results of 110 RapidArc plans were retrospectively reviewed. Then, DVH-based action limits (AL) and tolerance limits (TL) were obtained by statistical process control. Secondly, systematic MLC errors were introduced in 20 RapidArc plans, generating 380 modified plans. Then, the dose difference (%DE) in DVH metrics between modified plans and original plans was extracted from measurement results. After that, the linear regression model was used to investigate the detection limits of DVH-based action levels between %DE and systematic MLC errors. Finally, a total of 180 test plans (including 162 error-introduced plans and 18 original plans) were prepared for validation. The error detection rate of DVH-based action levels was compared in different DVH metrics of 180 test plans.ResultsA linear correlation was found between systematic MLC errors and %DE in all DVH metrics. Based on linear regression model, the systematic MLC errors between -0.94 mm and 0.88 mm could be caught by the TL of PTV95 ([-1.54%, 1.51%]), and the systematic MLC errors between -1.00 mm and 0.80 mm could also be caught by the TL of PTVmean ([-2.06%, 0.38%]). In the validation, for original plans, PTV95 showed the minimum error detection rate of 5.56%. For error-introduced plans with systematic MLC errors more than 1mm, PTVmean showed the maximum error detection rate of 88.89%, and then was followed by PTV95 (86.67%). All the TL of DVH metrics showed a poor error detection rate in identifying error-induced plans with systematic MLC errors less than 1mm.ConclusionIn 3D quality assurance of cervical cancer RapidArc plans, process-based tolerance limits showed greater advantages in distinguishing plans introduced with systematic MLC errors more than 1mm, and reasonable DVH-based action levels can be acquired through statistical process control. During DVH-based verification, main focus should be on the DVH metrics of target volume. OARs in low-dose regions were found to have a relatively higher dose sensitivity to smaller systematic MLC errors, but may be accompanied with higher false error detection rate.
Anlotinib Downregulates RGC32 Which Provoked by Bevacizumab
Authors: Liu Zhujun , Qin Tingting , Yuan Xiaohan , Yang Jie , Shi Wei , Zhang Xiaoling , Jia Yanan , Liu Shaochuan , Wang Jing , Li Kai 
Published: May 2022

BackgroundBevacizumab is the representative drug in antiangiogenic therapy for lung cancer. However, it induced resistance in some neoplasm. Anlotinib, a novel multi-target tyrosine kinase inhibitor which has an inhibitory action on both angiogenesis and malignancy, is possible to reverse the resistance.MethodsTranswell migration and invasion experiments of bevacizumab with or without anlotinib were conducted to verify the activated/inhibited ability of lung adenocarcinoma cells. We sequenced A549 cells with enhanced migration and invasion abilities after bevacizumab treatment, screened out the differentially expressed gene and further confirmed by western blot and q-PCR assays. We also investigated immunohistochemical staining of tumor tissue in mice and human lung adenocarcinoma.ResultsBevacizumab facilitated migration and invasion of lung adenocarcinoma cells. Differentially expressed gene RGC32 was screened out. Bevacizumab upregulated the expression of RGC32, N-cadherin, and MMP2 through ERK-MAPK and PI3K-AKT pathways. Anlotinib downregulated their expression and reversed the effect of bevacizumab on A549 cells. In vivo experiments confirmed that higher-dose bevacizumab facilitated metastasis in tumor-bearing nude mice and upregulated the expression of RGC32, N-cadherin, and MMP2, whereas anlotinib abrogated its effect. Expression of both RGC32 and N-cadherin positively correlated with lymph node metastasis and stage in lung adenocarcinoma was found. Survival analysis revealed that higher expressions of RGC32 and N-cadherin were associated with poor progression-free survival and overall survival.ConclusionsBevacizumab may promote invasion and metastasis of lung adenocarcinoma cells by upregulating RGC32 through ERK-MAPK and PI3K-AKT pathways to promote epithelial–mesenchymal transition, whereas anlotinib reverses the effect. RGC32 and N-cadherin are independent prognostic factors in lung adenocarcinoma.
Identification of Novel Immune Ferropotosis-Related Genes Associated With Clinical and Prognostic Features in Gastric Cancer
Authors: Xiao Chen , Dong Tao , Yang Linhui , Jin Liangzi , Lin Weiguo , Zhang Faqin , Han Yuanyuan , Huang Zhijian 
Published: May 2022

BackgroundGastric cancer (GC) is the fifth commonest cancer and the third commonest reason of death causing by cancer worldwide. Currently, tumor immunology and ferropotosis develop rapidly that has made gastric cancer be treated in new directions. So, finding the potential targets and prognostic biomarkers for immunotherapy combined with ferropotosis is urgent.MethodsBy mining TCGA, immune-related genes, ferropotosis-related genes and immune-ferropotosis-related differentially expressed genes (IFR-DEGs) were identified. The independent prognostic value of IFR-DEGs was determined by differential expression analysis, prognostic analysis, and univariate and lasso regression analysis. Then, based on the prognostic risk model, the correlation between IFR-DEGs and immune scores, immune checkpoints were evaluated. Besides, we predicted the response of high and low risk groups to drugs.ResultsA 15-gene prognostic feature was constructed. The high-risk group had a poorer prognosis than the low-risk group. High-risk group had higher level of Treg immune cell infiltration compared with that in the low-risk group, and the tumor purity, immune checkpoint PD-1 and CTLA4, and immunity in the high-risk group were higher than those in the low-risk group. These results indicate that immune ferropotosis-related genes migh be potential predictors of STAD’s response to ICI immunotherapy biomarkers. In addition, the response of small molecule drugs such as Nilotini, Sunitinib, Imatinib, etc. for high and low risk groups was predicted.ConclusionIFRSig can be regarded as an independent prognostic feature and may estimate OS and clinical treatment response in patients with STAD. IFRSig also has important correlation with immune microenvironment. A new understanding of the immune-ferropotosis-related genes during the occurrence and development of STAD is provided in this study.
Effect of Training Healthcare Providers in Helping Babies Breathe Program on Neonatal Mortality Rates
Authors: Mayer Maria M. , Xhinti Nomvuyo , Mashao Lolly , Mlisana Zolile , Bobotyana Luzuko , Lowman Casey , Patterson Janna , Perlman Jeffrey M. , Velaphi Sithembiso 
Published: May 2022

BackgroundTraining in the Helping Babies Breathe (HBB) Program has been associated with a reduction in early neonatal mortality rate (ENMR), the neonatal mortality rate (NMR), and fresh stillbirth rate (FSBR) in low- and middle-income countries (LMICs). This program was implemented in five different healthcare facilities in the Oliver Reginald Tambo (ORT) District, South Africa from September 2015 to December 2020.ObjectiveTo determine and compare the FSBR, ENMR, and NMR between 2015 before initiation of the program (baseline) and subsequent years up to 2020 following the implementation of facility-based training of HBB in five hospitals in ORT District.MethodsRecords of perinatal statistics from January 2015 to December 2020 were reviewed to calculate FSBR, ENMR, and NMR. Data were collected from the five healthcare facilities which included two district hospitals (Hospital A&amp;B), two regional hospitals (Hospital C&amp;D), and one tertiary hospital (Hospital E). Comparisons were made between pre- (2015) and post- (2016–2020) HBB implementation periods. Differences in changes over time were also assessed using linear regression analysis.ResultsThere were 19,275 births in 2015, increasing to 22,192 in 2020 with the majority (55.3%) of births occurring in regional hospitals. There were significant reductions in ENMR (OR−0.78, 95% CI 0.70–0.87) and NMR (OR−0.81, 95% CI 0.73–0.90), but not in FSBR, in the five hospitals combined when comparing the two time periods. Significant reduction was also noted in trends over time in ENMR (r2 = 0.45, p = 0.001) and NMR (r2 = 0.23, p = 0.026), but not in FSBR (r2 = 0.0, p = 0.984) with all hospitals combined. In looking at individual hospitals, Hospital A (r2 = 0.61, p &lt; 0.001) and Hospital E (r2 = 0.19, p = 0.048) showed a significant reduction in ENMR over time, but there were no significant changes in all mortality rates for Hospitals B, C, and D, and for the district or regional hospitals combined.ConclusionThere was an overall reduction of 22% and 19% in ENMR and NMR, respectively, from pre- to post-HBB implementation periods, although there were variations from year to year over the 5-year period and, across hospitals. These differences suggest that there were other factors that affected the perinatal/neonatal outcomes in the hospital sites in addition to the implementation of training in HBB.
Hepatotoxicity of the Major Anthraquinones Derived From Polygoni Multiflori Radix Based on Bile Acid Homeostasis
Authors: Kang Li , Li Dan , Jiang Xin , Zhang Yao , Pan Minhong , Hu Yixin , Si Luqin , Zhang Yongjun , Huang Jiangeng 
Published: May 2022

Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.