bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific effects of maternal dietary carbohydrate quality on fetal development and offspring metabolic phenotype in mice
Authors: Campbell G. Jean , Lucic Fisher Sophie G. , Brandon Amanda E. , Senior Alistair M. , Bell-Anderson Kim S. 
Published: July 2022

ObjectivesIn utero glycemia is an important determinant of fetal growth. Women with gestational diabetes are more likely to deliver large-for-gestational age babies that are at increased risk for obesity. The maternal nutritional state modulates the development of offspring biological systems during the critical periods of gestation and lactation. Carbohydrate typically contributes most of the dietary energy, however, there are very few mechanistic studies investigating the effects of maternal dietary carbohydrate quality on fetal and offspring outcomes. Therefore, we sought to investigate the direct effects of maternal carbohydrate quality on sex-specific offspring metabolic programming.MethodsFemale C57BL/6 mice were fed one of five isocaloric diets: four high-sugar diets based on glucose, sucrose, isomaltulose or fructose (all containing 60% energy as carbohydrate), or a standard, minimally processed, chow diet, and were mated with chow-fed males. Half of the dams were sacrificed for fetus dissection and placental collection, with the remaining giving live birth. All dams were metabolically profiled before and during pregnancy, and pups were similarly profiled at 12 weeks of age.ResultsOverall, glucose-fed dams were heavier and fatter than chow or isomaltulose-fed dams. Female fetuses from glucose and isomaltulose-fed mothers weighed less and had smaller livers, than those from chow-fed mothers, with isomaltulose-fed female fetuses also having decreased placental mass. In contrast, male fetuses responded differently to the maternal diets, with heart mass being significantly increased when their mothers were fed fructose-containing diets, that is, sucrose, isomaltulose and fructose. High-sugar fed female offspring weighed the same, but were significantly fatter, than chow-fed offspring at 12 weeks of age, while glucose and isomaltulose-fed male pups displayed a similar phenotype to their mothers’.ConclusionWhile both glucose and isomaltulose diets constrained fetal growth in females, only placentas from isomaltulose-fed dams were significantly smaller than those from chow-fed mothers, suggesting the mechanisms through which fetal growth is reduced may be different. Female fetuses of isomaltulose-fed mothers were also lighter than sucrose-fed fetuses suggesting the glycemic index, or rate of glucose digestion and absorption, may be an important factor in determining nutrient availability to the growing fetus.
Intrauterine Growth Restriction Induces Adulthood Chronic Metabolic Disorder in Cardiac and Skeletal Muscles
Authors: Li Ping , He Lewei , Lan Yue , Fang Jie , Fan Zhenxin , Li Yifei 
Published: July 2022

ObjectiveAlthough population-based studies of intrauterine growth restriction (IUGR) demonstrated a series of postnatal complications, several studies identified that IUGR could definitely cause dysfunction of metabolism of cardiac and skeletal muscles in the perinatal period and early life. However, it is still unknown if such metabolic alternation would remain for long term or not, and whether normal protein diet administration postnatally would protect the IUGR offsprings from a “catch-up growth” and be able to reverse the premature metabolic remodeling.Materials and MethodsWe established an IUGR rat model with pregnant rats and a low-protein diet, and the developmental phenotypes had been carefully recorded. The cardiac and skeletal muscles had been collected to undergo RNA-seq.ResultsAccording to a series of comparisons of transcriptomes among various developmental processes, programmed metabolic dysfunction and chronic inflammation activity had been identified by transcriptome sequencing in IUGR offsprings, even such rats presented a normal developmental curve or body weight after normal postnatal diet feeding.ConclusionThe data revealed that IUGR had a significant adverse impact on long-term cardiovascular function in rats, even they exhibit good nutritional status. So that, the fetal stage adverse events would encode the lifelong disease risk, which could hide in young age. This study remaindered that the research on long-term molecular changes is important, and only nutrition improvement would not totally reverse the damage of IUGR.
Evaluation of the association between haemoglobin levels and preterm birth at Khartoum, Sudan: A hospital-based study
Authors: Elmugabil Abdelmageed , Alhabrdi Nadiah M. , Rayis Duria A. , Al-Wutayd Osama , Adam Ishag 
Published: July 2022

ObjectiveThe objective of this study was to determine the association between haemoglobin level and PB.MethodsA cross-sectional study was conducted in Khartoum, Sudan. Questionnaires on demographics and medical and obstetric factors were completed. A logistic regression analysis was performed.ResultsOf the 1,716 pregnant women, approximately two-thirds (65.7%) had anaemia (haemoglobin &lt; 11 g/dl) and six (0.3%) had severe anaemia (haemoglobin &lt; 8 g/dl). Of the 1,716 women, 283 (16.5%) had a PB. In multivariable logistic regression, parity (AOR = 1.15, 95% CI = 1.09–1.21, P &lt; 0.001) was positively associated with PB. Compared to those with haemoglobin levels of 10–10.9 g/dl, pregnant women with haemoglobin levels of 8–8.9 (AOR = 0.41, 95% CI = 0.22–0.77), 9–9.9 (AOR = 0.59, 95% CI = 0.38–0.91), and 11–11.9 g/dl (AOR = 0.53, 95% CI = 0.36–0.77) were at a lower risk of PB. Women with haemoglobin levels of 12–13 g/dl were at a higher risk of PB (AOR = 1.62, 95% CI = 1.06–2.45). There was no significant association between women with haemoglobin levels &lt; 8 g/dl and &gt; 13 g/dl and PB.ConclusionThis study showed different levels of association between haemoglobin levels and PB.
Effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus: A randomized clinical trial
Authors: Khorshidi Masoud , Sayyari Aliakbar , Aryaeian Naheed , Olang Beheshteh , Alaei Mohammadreza , Khalili Mitra , Hosseini Amirhossein , Salehi Masoud 
Published: July 2022

BackgroundVascular dysfunction is a major complication of diabetes mellitus that leads to cardiovascular disease (CVD). This study aimed to examine the effects of omega-3 consumption on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus (T1DM).MethodsIn this randomized, double-blind, placebo-controlled clinical trial, 51 adolescents (10–18 years) with T1DM completed the study. Patients received 600 mg/day [containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA)] of omega-3 or placebo for 12 weeks. Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), serum insulin (SI), urine albumin-creatinine ratio (uACR), blood pressure, and anthropometric indices were assessed at the baseline and after the intervention.ResultsFollowing supplementation, omega-3 significantly increased FMD (3.1 ± 4.2 vs. −0.6 ± 4%, p = 0.006) and decreased TG (−7.4 ± 10.7 vs. −0.1 ± 13.1 mg/dl, p = 0.022) in comparison with the placebo group. However, no significant difference was observed regarding CIMT (-0.005 ± 0.036 vs. 0.003 ± 0.021 mm, p = 0.33). Although hs-CRP was significantly decreased within the omega-3 group (p = 0.031); however, no significant change was observed compared to placebo group (p = 0.221). Omega-3 supplementation had no significant effect on other variables.ConclusionGiven the elevation in FMD and reduction in TG, omega-3 supplementation can improve vascular function and may reduce the risk of cardiovascular disease in adolescents with T1DM patients.
The In-Vitro Antitumor Effects of AST-3424 Monotherapy and Combination Therapy With Oxaliplatin or 5-Fluorouracil in Primary Liver Cancer
Authors: Zhang Yu , Qin Shukui , Chao Jiaojiao , Luo Yan , Sun Yandi , Duan Jianxin 
Published: July 2022

BackgroundPrimary liver cancer (PLC) is a common and highly lethal malignancy in the world. Approximately 85% of PLC is hepatocellular carcinoma (HCC), and this study mainly focuses on HCC. The onset of liver cancer is insidious and often complicated with basic liver disease. Meanwhile, its clinical symptoms are atypical, and the degree of malignancy is high. What is worse is that its treatment is difficult, and the prognosis is poor. All these factors make its mortality close to its incidence. AST-3424 is a prodrug of a potent nitrogen mustard, which targets the tumor by its specific and selective mode of activation and results in the concentration of the drug in the tumor and plays a higher intensity of antitumor effect with reduced side effects. The purpose of this study was to explore the in-vitro antitumor activity and mechanism of AST-3424 monotherapy and combination therapy with oxaliplatin (OXA) or 5-fluorouracil (5-Fu). Moreover, it can provide an experimental basis for further studies.MethodsTumor growth of HCC cells was examined by using the Cell Counting Kit-8 (CCK-8), flow cytometry, and clone formation assays. Tumor migration of HCC cells was examined by using the Transwell assay. The in-vitro antitumor activity of AST-3424 monotherapy and combination therapy with OXA and 5-Fu was quantified by growth and metastasis inhibition rate. The underlying molecular mechanism was investigated by using Western blotting.ResultsThe inhibiting effects of AST-3424 were significant in both HepG2 cells and PLC/PRF/5 cells. Moreover, HepG2 cells showed higher sensitivity to AST-3424. With increasing AST-3424 concentration, AKR1C3 protein expression level was downregulated significantly. The inhibition of AST-3424 was significantly higher than OXA, 5-Fu, Sor (sorafenib), and Apa (apatinib) in both HCC cells. AST-3424 monotherapy and combination therapy with OXA or 5-Fu all strongly inhibited the proliferation of HCC cells, blocked HCC cells in the S phase, promoted apoptosis induction, and suppressed the migration of HCC cells. Among them, the antitumor effect of AST-3424 in combination with OXA was obviously enhanced. Western blotting analysis demonstrated the regulation of P21, Bax, Caspase3, PARP, MMP-2, MMP-9, and p-Smad proteins in the presence of AST-3424 monotherapy and combination therapy with OXA or 5-Fu, indicating that its antitumor mechanisms may be associated with the regulation of the TGF-β signaling cascade.ConclusionThe in-vitro studies revealed that AST-3424 in combination with both OXA and 5-Fu showed an increased antitumor effect, and the combination with OXA resulted in a synergistic effect. Together with the in-vitro results, additional in-vitro and in-vivo studies are warranted to further certify its antitumor effects and explore more potential antitumor mechanisms.
Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database
Authors: Jiao Dechuang , Ma Youzhao , Zhu Jiujun , Dai Hao , Yang Yue , Zhao Yajie , Guo Xuhui , Liu Zhenzhen 
Published: July 2022

ObjectiveThis study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010–2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan–Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer–specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses.ResultsAmong the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, P &lt; 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753–0.797, P &lt; 0.001) and OS (HR = 0.667, 95% CI = 0.653–0.681, P &lt; 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age &lt; 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age &lt;35 years.ConclusionsIn conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age &lt;35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.
Long-Term Disease Control After locoregional Pelvic Chemoradiation in Patients with Advanced Anal Squamous Cell Carcinoma
Authors: Grave Athénaïs , Blanc Julie , De Bari Berardino , Pernot Mandy , Boulbair Fatiha , Noirclerc Monique , Vienot Angélique , Kim Stefano , Borg Christophe , Boustani Jihane 
Published: July 2022

IntroductionThe incidence of metastatic squamous cell carcinoma of the anus (SCCA) is increasing. Even if systemic docetaxel, cisplatin, and 5-Fluorouracil (DCF) provide a high rate of long-term remission, the role of pelvic chemoradiation (CRT) is unknown in this setting. We reported the safety and efficacy of local CRT in patients with synchronous metastatic SCCA who achieved objective response after upfront DCF.MethodsPatients included in Epitopes HPV01 or Epitopes HPV02 or SCARCE trials and treated with DCF followed by pelvic CRT were included. Concurrent chemotherapy was based on mitomycin (MMC) (10 mg/m² for two cycles) and fluoropyrimidine (capecitabine 825 mg/m² twice a day at each RT treatment day or two cycles of intra-venous 5FU 1000 mg/m² from day 1 to day 4). Primary endpoints were safety, local complete response rate, and local progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and metastasis-free survival (MFS).ResultsFrom 2013 to 2018, 16 patients received DCF followed by a complementary pelvic CRT for advanced SCCA. Median follow-up was 42 months [range, 11-71]. All patients received the complete radiation dose. Compliance to concurrent CT was poor. Overall, 13/15 of the patients (87%) had at least one grade 1-2 acute toxicity and 11/15 of the patients (73%) had at least one grade 3-4 toxicity. There was no treatment-related death. The most frequent grade 3-4 adverse effects were neutropenia (36%), dermatitis (40%), and anitis (47%). Eleven patients (73%) had at least one chronic grade 1 or 2 toxicity. One patient had a grade 4 chronic rectitis (7%). Complete local response rate was 81% at first evaluation and 62.5% at the end of the follow-up. Median local PFS was not reached and the 3-year local PFS was 77% (95%CI 76.8-77).ConclusionsIn patients with metastatic SCCA who had a significant objective response after upfront DCF, local CRT was feasible with high complete local response rate. The good local control rate, despite interruptions due to toxicities and low CT compliance, underline the role of pelvic RT. The high rate of toxicity prompts the need to adapt CRT regimen in the metastatic setting.
Clinical M2 Macrophage-Related Genes Can Serve as a Reliable Predictor of Lung Adenocarcinoma
Authors: Xu Chaojie , Song Lishan , Yang Yubin , Liu Yi , Pei Dongchen , Liu Jiabang , Guo Jianhua , Liu Nan , Li Xiaoyong , Liu Yuchen , Li Xuesong , Yao Lin , Kang Zhengjun 
Published: July 2022

BackgroundNumerous studies have found that infiltrating M2 macrophages play an important role in the tumor progression of lung adenocarcinoma (LUAD). However, the roles of M2 macrophage infiltration and M2 macrophage-related genes in immunotherapy and clinical outcomes remain obscure.MethodsSample information was extracted from TCGA and GEO databases. The TIME landscape was revealed using the CIBERSORT algorithm. Weighted gene co-expression network analysis (WGCNA) was used to find M2 macrophage-related gene modules. Through univariate Cox regression, lasso regression analysis, and multivariate Cox regression, the genes strongly associated with the prognosis of LUAD were screened out. Risk score (RS) was calculated, and all samples were divided into high-risk group (HRG) and low-risk group (LRG) according to the median RS. External validation of RS was performed using GSE68571 data information. Prognostic nomogram based on risk signatures and other clinical information were constructed and validated with calibration curves. Potential associations of tumor mutational burden (TMB) and risk signatures were analyzed. Finally, the potential association of risk signatures with chemotherapy efficacy was investigated using the pRRophetic algorithm.ResultsBased on 504 samples extracted from TCGA database, 183 core genes were identified using WGCNA. Through a series of screening, two M2 macrophage-related genes (GRIA1 and CLEC3B) strongly correlated with LUAD prognosis were finally selected. RS was calculated, and prognostic risk nomogram including gender, age, T, N, M stage, clinical stage, and RS were constructed. The calibration curve shows that our constructed model has good performance. HRG patients were suitable for new ICI immunotherapy, while LRG was more suitable for CTLA4-immunosuppressive therapy alone. The half-maximal inhibitory concentrations (IC50) of the four chemotherapeutic drugs (metformin, cisplatin, paclitaxel, and gemcitabine) showed significant differences in HRG/LRG.ConclusionsIn conclusion, a comprehensive analysis of the role of M2 macrophages in tumor progression will help predict prognosis and facilitate the advancement of therapeutic techniques.
Efficacy of stereotactic body radiation therapy for locoregional recurrent pancreatic cancer after radical resection
Authors: Ji Xiaoqin , Zhou Bin , Ding Wei , Wang Jiasheng , Jiang Wanrong , Li Yikun , Hu Jun , Sun Xiangdong 
Published: July 2022

ObjectiveThis study aimed to analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for locoregional recurrent pancreatic cancer after radical resection.MethodsPatients with locoregional recurrent pancreatic cancer after surgery treated with SBRT in our institution were retrospectively investigated from January 2010 to January 2020. Absolute neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS) and cumulative incidences of local failure (LF) and metastatic failure (MF).ResultsA total of 22 patients received SBRT with a median prescribed dose of 40 Gy (range of 30-50 Gy)/4 to 7 fractions. The median OS of all patients was 13.6 months (95% CI, 9.6-17.5 months). 0-1 performance status (HR 12.10, 95% CI 2.04-71.81, P=0.006) and ≤2.1 pre-SBRT NLR (HR 4.05, 95% CI 1.21-13.59, P=0.023) were significant predictors of higher OS on multivariable analysis. The median progression-free survival (PFS) of the cohort was 7.5 months (95% CI, 6.5-8.5 months). The median time to LF and MF were 15.6 months and 6.4 months, respectively. The rate of MF as a first event was higher than that of first event LF. Pain relief was observed in all patients (100%) 6 weeks after SBRT. In terms of acute toxicity, grade 1 including fatigue (6, 27.3%), anorexia (6, 27.3%), nausea (4, 18.2%) and leukopenia (4, 18.2%) was often observed. No acute toxicity of grade 4 or 5 was observed. In terms of late toxicity, no treatment-related toxicity was found during follow-up.ConclusionThis study showed that SBRT can significantly reduce pain, effectively control local tumor progression, and have acceptable toxicity for patients with locoregional recurrence after radical resection of primary pancreatic cancer. Good performance status and lower pre-SBRT NLR were associated with improved overall survival.
Application of artificial intelligence to pancreatic adenocarcinoma
Authors: Chen Xi , Fu Ruibiao , Shao Qian , Chen Yan , Ye Qinghuang , Li Sheng , He Xiongxiong , Zhu Jinhui 
Published: July 2022

Background and ObjectivesPancreatic cancer (PC) is one of the deadliest cancers worldwide although substantial advancement has been made in its comprehensive treatment. The development of artificial intelligence (AI) technology has allowed its clinical applications to expand remarkably in recent years. Diverse methods and algorithms are employed by AI to extrapolate new data from clinical records to aid in the treatment of PC. In this review, we will summarize AI’s use in several aspects of PC diagnosis and therapy, as well as its limits and potential future research avenues.MethodsWe examine the most recent research on the use of AI in PC. The articles are categorized and examined according to the medical task of their algorithm. Two search engines, PubMed and Google Scholar, were used to screen the articles.ResultsOverall, 66 papers published in 2001 and after were selected. Of the four medical tasks (risk assessment, diagnosis, treatment, and prognosis prediction), diagnosis was the most frequently researched, and retrospective single-center studies were the most prevalent. We found that the different medical tasks and algorithms included in the reviewed studies caused the performance of their models to vary greatly. Deep learning algorithms, on the other hand, produced excellent results in all of the subdivisions studied.ConclusionsAI is a promising tool for helping PC patients and may contribute to improved patient outcomes. The integration of humans and AI in clinical medicine is still in its infancy and requires the in-depth cooperation of multidisciplinary personnel.