bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastasis Patterns and Prognosis of Elderly Patients With Esophageal Adenocarcinoma in Stage IVB: A Population-Based Study
Authors: Qiu Guanghao , Zhang Hanlu , Wang Fuqiang , Zheng Yu , Wang Zihao , Wang Yun 
Published: May 2021

BackgroundEsophageal adenocarcinoma (EAC) is the most common kind of esophageal cancer. Age at diagnosis of advanced EAC is greater. Studies about practice patterns for elderly EAC patients with distant metastasis (DM) in stage IVB are limited. This retrospective, population-based study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) to evaluate 855 elderly EAC patients with DM in stage IVB from 2010 to 2015.Methods855 elderly EAC patients with DM in stage IVB between 2010 and 2015 were included in this study. Univariate and multivariate Cox-regression and Kaplan-Meier analyses were used to assess prognosis. These patients were classified to bone-only, brain-only, lung-only, liver-only, and multiple (patients with two or more organs in metastasis)-site group according to the site of metastasis. Overall survival (OS), cancer-specific survival (CSS), median survival time (MST), and survival rate (SR) were evaluated to analyze the survival outcomes.ResultsThe most common metastasis site was the liver among the single-organ metastasis population, followed by lung, bone, and brain. Compared with the bone-only group, the multiple-site group was associated with worst OS (HR: 1.037, 95% CI: 0.811–1.327, p = 0.770) and CSS (HR: 1.052, 95% CI: 0.816–1.357, p = 0.695). The multiple-site group also had the lowest MST in the population (MST: 2 months in OS and 3 months in CSS) and SR (6-month SR: 27.1% in OS, 29.9% in CSS, 1-year SR: 10.7% in OS, 12.0% in CSS, 3-year SR: 2.5% in OS, 2.8% in CSS). Compared to untreated patients (N) in the total population, other patients who were treated with surgery (S), radiotherapy (R), and chemotherapy (C) are beneficial for the prognosis (OS and CSS: p &lt; 0.001).ConclusionThis population-based study was conducted to ascertain metastasis patterns and survival outcomes of EAC patients with DM in stage IVB. Elderly patients with multiple-site metastasis exhibited the worst OS and CSS among all the populations, and patients with bone-only metastasis had the worst OS and CSS among single-organ metastasis populations. Active treatment is beneficial for elderly EAC patients with DM in stage IVB, especially chemotherapy. This study also shows that more than one third of the patients had not received any therapy.
A Prognostic DNA Damage Repair Genes Signature and Its Impact on Immune Cell Infiltration in Glioma
Authors: Wang Guohui , Zhou Huandi , Tian Lei , Yan Tianfang , Han Xuetao , Chen Pengyu , Li Haonan , Wang Wenyan , Xiao Zhiqing , Hou Liubing , Xue Xiaoying 
Published: May 2021

ObjectiveGlioma is the most frequent type of malignant cerebral tumors. DNA damage repair genes (DDRGs) play a crucial role in the development of cancer. In this study, we constructed a DDRGs signature and investigated the potential mechanisms involved in this disease.MethodsRNA sequence data, microarray data, and corresponding clinical information of gliomas were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO). Subsequently, we identified candidate genes by differential analysis and Cox regression analysis. The least absolute shrinkage and selection operator Cox regression model was utilized to construct a DDRGs signature using TCGA training dataset. According to this signature, patients with glioma were divided into low- and high-risk groups. The predictive ability of the signature was validated by prognostic analysis, receiver operating characteristic curves, principal component analysis, and stratification analysis in TCGA testing and CGGA verification datasets. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the immune microenvironment of glioma. Moreover, we conducted GSEA to determine the functions and pathways in the low- and high-risk groups. Finally, a nomogram was constructed by combining the signature and other clinical features.ResultsA total of 1,431 samples of glioma (592 from TCGA, 686 from the CGGA, and 153 from the GEO) and 23 samples of normal brain tissue from the GEO were analyzed in this study. There were 51 prognostic differentially expressed DDRGs. Additionally, five DDRGs (CDK4、HMGB2、WEE1、SMC3 and GADD45G) were selected to construct a DDRGs signature for glioma, stratifying patients into low- and high-risk groups. The survival analysis showed that the DDRGs signature could differentiate the outcome of the low- and high-risk groups, showing that high-risk gliomas were associated with shorter overall survival. The immune microenvironment analysis revealed that more immunosuppressive cells, such as tumor associated macrophages and regulatory T cells, were recruited in the high-risk group. GSEA also showed that high-risk glioma was correlated with the immune and extracellular matrix pathways.ConclusionThe five DDRGs signature and its impact on the infiltration of immunosuppressive cells could precisely predict the prognosis and provide guidance on the treatment of glioma.
Primary Care Case Management of Febrile Children: Insights From the ePOCT Routine Care Cohort in Dar es Salaam, Tanzania
Authors: van de Maat Josephine , De Santis Olga , Luwanda Lameck , Tan Rainer , Keitel Kristina 
Published: May 2021

Aim: To provide insight in the primary health care (PHC) case management of febrile children under-five in Dar es Salaam, and to identify areas for improving quality of care.Methods: We used data from the routine care arm of the ePOCT trial, including children aged 2–59 months who presented with an acute febrile illness to two health centers in Dar es Salaam (2014–2016). The presenting complaint, anthropometrics, vital signs, test results, final diagnosis, and treatment were prospectively collected in all children. We used descriptive statistics to analyze the frequencies of diagnoses, adherence to diagnostics, and prescribed treatments.Results: We included 547 children (47% male, median age 14 months). Most diagnoses were viral: upper respiratory tract infection (60%) and/or gastro-enteritis (18%). Vital signs and anthropometric measurements taken by research staff and urinary testing failed to influence treatment decisions. In total, 518/547 (95%) children received antibiotics, while 119/547 (22%) had an indication for antibiotics based on local guidelines. Antibiotic dosing was frequently out of range. Non-recommended treatments were common (29%), most often cough syrup and vitamins.Conclusion: Our study points to challenges in using diagnostic test results, concerns regarding quality of antibiotic prescriptions, and frequent use of non-evidence-based complementary medicines in PHC in Tanzania. Larger studies on diagnostic and treatments processes in PHC in Tanzania are needed to inform effective solutions to support PHC workers in case management of children.
Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice
Authors: Lai Jianfei , Qian Qianyu , Ding Qinchao , Zhou Li , Fu Ai , Du Zhongyan , Wang Cui , Song Zhenyuan , Li Songtao , Dou Xiaobing 
Published: May 2021

Background: Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure.Purpose: The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning.Methods: Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated.Resluts: Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1.Conclusion: Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.
The Ethyl Acetate Extract From Celastrus orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB
Authors: Tao Lide , Yin Zixin , Ni Tengyang , Chu Zewen , Hao Shihua , Wang Zeyu , Sunagawa Masataka , Wang Haibo , Liu Yanqing 
Published: May 2021

Objective: To investigate the effect of ethyl acetate extract from Celastrus orbiculatus (COE) on gastric cancer cell apoptosis and reveal its underlying molecular mechanism. In addition, it was aimed to stablish a theoretical basis for the clinical application of Celastrus orbiculatus in the gastric cancer treatment.Material and Methods: Western blot and RT-qPCR were used to detect mRNA and protein expression of PHB in gastric cancer and adjacent tissues. MTT method was used to detect the COE effect on the proliferation of AGS cells and to determine the 50% inhibitory concentration COE on these cells. COE effect on AGS apoptosis was evaluated by flow cytometry. Changes in apoptosis-related proteins expression in AGS cells were detected by western blot and changes in mitochondrial membrane potential were detected by JC-1 fluorescence staining. PHB expression was knocked down in AGS cells by lentiviral-mediated RNA interference. The COE antitumor effect was assessed in vivo using a subcutaneous transplantation tumor model in nude mice and in vivo fluorescence tracing technique in small animals.Results: The clinical samples analysis results showed that the PHB expression in gastric cancer samples was significantly higher than in corresponding adjacent tissues. MTT results showed that the AGS cell proliferation was significantly inhibited. RT-qPCR and western blot results showed that COE can significantly inhibit the PHB mRNA and protein expression, respectively. Flow cytometry analysis showed that COE was able to significantly promote AGS cell apoptosis. Western blot results also indicated that apoptosis-related protein expression changed significantly; BCL-2 expression significantly reduced while the Caspase-3 and Bax expression significantly increased after COE treatment. JC-1 fluorescence staining results showed that COE changed the mitochondrial membrane potential and activated the mitochondrial apoptosis pathway. Furthermore, in vivo experiments results demonstrated that the growth of subcutaneous transplanted tumor was significantly inhibited by the PHB knockdown and by the COE intragastric administration.Conclusion: COE can significantly promote apoptosis of human gastric cancer cells, which can be achieved by inhibiting PHB expression, thus altering the structure and function of mitochondria and activating the mitochondria apoptosis pathway. The antitumor effect of COE has also been proved in vivo.
Pharmacokinetics of Intraperitoneal Vancomycin and Amikacin in Automated Peritoneal Dialysis Patients With Peritonitis
Authors: Falbo dos Reis Pâmela , Barretti Pasqual , Marinho Laudilene , Balbi Andre Luís , Awdishu Linda , Ponce Daniela 
Published: May 2021

Objective: The study aimed to evaluate the vancomycin and amikacin concentrations in serum and dialysate for automatic peritoneal dialysis (APD) patients.Methods: A total of 558 serum and dialysate samples of 12 episodes of gram-positive and 18 episodes of gram-negative peritonitis were included to investigate the relationship between vancomycin and amikacin concentrations in serum and dialysate on the first and third days of treatment. Samples were analysed 30, 120 min, and 48 h after intraperitoneal administration of vancomycin in peritonitis caused by gram-positive agents and 30, 120 min, and 24 h after intraperitoneal administration of amikacin in peritonitis caused by gram-negative agents. Vancomycin was administered every 72 h and amikacin once a day. The target therapeutic concentration of amikacin was 25–35 mg/l at the peak moment and 4–8 mg/l at the trough moment; and after 48 h for vancomycin, 15–20 mg/l at the trough moment.Results: For peritonitis caused by gram-negative agents, at the peak moment, therapeutic levels of amikacin were reached in dialysate in 80.7% of patients with evolution to cure and in 50% of patients evaluated as non-cure (p = 0.05). At the trough moment, only 38% were in therapeutic concentrations in the dialysate in the cure group and 42.8% in the non-cure group (p = 1). Peak plasma concentrations were subtherapeutic in 98.4% of the samples in the cure group and in 100% of the non-cure group. At the trough moment, therapeutic concentrations were present in 74.4% of the cure group and 71.4% of the non-cure group (p = 1). Regarding vancomycin and among gram-positive agents, therapeutic levels were reached at the peak moment in 94% of the cure group and 6% of the non-cure group (p = 0.007). After 48 h, 56.8% of the cure group had a therapeutic serum concentration whereas for the non-cure group it was only 33.3% (p = 0.39).Conclusion: Despite a small sample size, we demonstrated peak dialysate amikacin level and peak serum vancomycin level correlates well with Gram-negative and Gram positve peritonitis cure, respectively. It is suggested to study the antibiotics pharmacodynamics for a better understanding of therapeutic success in a larger sample.
Pharmacological Screening of Viola odorata L. for Memory-Enhancing Effect via Modulation of Oxidative Stress and Inflammatory Biomarkers
Authors: Saleem Uzma , Hira Sundas , Anwar Fareeha , Shah Muhammad Ajmal , Bashir Samia , Baty Roua S. , Badr Reem H. , Blundell Renald , Batiha Gaber El-Saber , Ahmad Bashir 
Published: May 2021

Purpose: Alzheimer disease (AD) is a progressive neurodegenerative disorder that is caused by neuroinflammation and oxidative stress. The present study aimed to characterize and then investigate the memory-enhancing potential of Viola odorata methanolic extract in lipopolysaccharide (LPS)–treated mice.Methods:V. odorata characterization was done by using the GCMS technique. Neuroinflammation was induced by the intracerebroventricular administration of LPS at a dose of 12 µg. Animals were divided randomly into six groups (n = 10). Group I was normal control, which was given vehicle. Group II was disease control, which received LPS (12 µg) via the intracerebroventricular route. Group III was standard, which was administered with donepezil (3 µg) orally for 21 days. Groups IV–VI were the treatment groups, which were administered with the extract at 100, 200, and 400 mg/kg dose levels orally respectively for 21 days. Groups III–VI received LPS (12 µg) on the first day along with their treatments. During the treatment, the animals were assessed for memory retention by employing different behavioral paradigms namely elevated plus maze, passive avoidance, foot shock and open field. Various mediators [endogenous antioxidants, neurotransmitters, and acetylcholinesterase (AChE)] involved in the pathogenesis of AD were quantified by using the UV spectrophotometric method.Results: Extract-treated groups showed a remarkable improvement in cognitive impairment in all behavioral paradigms. Oxidative stress biomarkers, that is, superoxide dismutase, catalase, and glutathione were raised dose-dependently in the treatment groups with a dose-dependent decrease in the malonaldehyde and AChE levels in the brains of the treated animals. The treatment groups showed decreased levels of inflammatory biomarkers, that is, tumor necrosis factor–alpha, nuclear factor kappa light-chain enhancer of activated β-cells, and cyclo-oxygenase, which supports the therapeutic effectiveness of the treatment.Conclusion: Based on behavioral, oxidative stress biomarker, and neuroinflammatory data, it is concluded that V. odorata possesses memory-enhancing activity and may prove a beneficial role in the management of AD.
Multimodal Analgesia With Long-Acting Dinalbuphine Sebacate Plus Transversus Abdominis Plane Block for Perioperative Pain Management in Bariatric Surgery: A Case Report
Authors: Liu Shih-Yuan , Ho Yi-Hong , Wong Chih-Shung 
Published: May 2021

Laparoscopic bariatric surgery is increasingly performed in morbidly obese patients. However, post-surgical pain is common and is usually managed with classical opioids such as morphine and fentanyl. Further, morbidly obese patients are predisposed to opioid-related side effects, especially post-operative nausea and vomiting (PONV), and respiratory depression. Obstructive sleep apnea in morbidly obese patients even predisposes them to respiratory depression. Thus, reducing opioid consumption is important. Multimodal analgesia (MMA) provides optimal perioperative analgesia while minimizing opioid consumption. Studies have shown that MMA strategy can provide sufficient pain relief in bariatric surgery with enhanced recovery. There are very few reports on the use of dinalbuphine sebacate (DS), a newly introduced non-controlled opioid medication with long-lasting analgesic effects. DS has a different mechanism of action from that of morphine or fentanyl and is non-addictive, with minimal side effects. It has been successfully used in laparoscopic cholecystectomy in our previous study. We present a case of a new MMA protocol with DS on a 46-year-old morbidly obese female patient who underwent laparoscopic sleeve gastrectomy. The MMA protocol included ultrasound-guided intramuscular DS injection plus transversus abdominis plane (TAP) block and other analgesics; it achieved good perioperative analgesia with opioid-sparing effect and enhanced patient’s recovery with no pain in the following 4 months.
Linear Behavior of the Phase Lifetime in Frequency-Domain Fluorescence Lifetime Imaging of FRET Constructs
Authors: Sumetsky Daniel , Jiang James Y. , Ayad Marina A. , Mahon Timothy , Menaesse Audrey , Cararo-Lopes Marina M. , Patel Mihir V. , Firestein Bonnie L. , Boustany Nada N. 
Published: May 2021

We utilize a cost-effective frequency-domain fluorescence lifetime imaging microscope to measure the phase lifetime of mTFP1 in mTFP1-mVenus fluorescence resonance energy transfer (FRET) constructs relevant to the VinTS molecular tension probe. Our data were collected at 15 modulation frequencies ω/2π selected between 14 and 70 MHz. The lifetime of mTFP1 was τD = 3.11 ± 0.02 ns in the absence of acceptor. For modulation frequencies, ω, such that (ω · τD) &lt; 1.1, the phase lifetime of mTFP1in the presence of acceptor (mVenus), τϕDA, was directly related to the amplitude-weighted lifetime τaveDA inferred from the known FRET efficiency (EFRETtrue) of the constructs. A linear fit to a plot of (ω·τϕDA) vs. (ω·τaveDA) yielded a slope of 0.79 ± 0.05 and intercept of 0.095 ± 0.029 (R2 = 0.952). Thus, our results suggest that a linear relationship exists between the apparent EFRETapp based on the measured phase lifetime and EFRETtrue for frequencies such that (ω · τD) &lt; 1.1. We had previously reported a similar relationship between EFRETapp and EFRETtrue at 42 MHz. Our current results provide additional evidence in support of this observation, but further investigation is still required to fully characterize these results. A direct relationship between τϕDAand τaveDA has the potential to simplify significantly data acquisition and interpretation in fluorescence lifetime measurements of FRET constructs.
Association of Self-Compassion With Suicidal Thoughts and Behaviors and Non-suicidal Self Injury: A Meta-Analysis
Authors: Suh Hanna , Jeong Jisun 
Published: May 2021

Objectives: Self-compassion functions as a psychological buffer in the face of negative life experiences. Considering that suicidal thoughts and behaviors (STBs) and non-suicidal self-injury (NSSI) are often accompanied by intense negative feelings about the self (e.g., self-loathing, self-isolation), self-compassion may have the potential to alleviate these negative attitudes and feelings toward oneself. This meta-analysis investigated the associations of self-compassion with STBs and NSSI.Methods: A literature search finalized in August 2020 identified 18 eligible studies (13 STB effect sizes and seven NSSI effect sizes), including 8,058 participants. Two studies were longitudinal studies, and the remainder were cross-sectional studies. A random-effects meta-analysis was conducted using CMA 3.0. Subgroup analyses, meta-regression, and publication bias analyses were conducted to probe potential sources of heterogeneity.Results: With regard to STBs, a moderate effect size was found for self-compassion (r = −0.34, k = 13). Positively worded subscales exhibited statistically significant effect sizes: self-kindness (r = −0.21, k = 4), common humanity (r = −0.20, k = 4), and mindfulness (r = −0.15, k = 4). For NSSI, a small effect size was found for self-compassion (r = −0.29, k = 7). There was a large heterogeneity (I2 = 80.92% for STBs, I2 = 86.25% for NSSI), and publication bias was minimal. Subgroup analysis results showed that sample characteristic was a moderator, such that a larger effect size was witnessed in clinical patients than sexually/racially marginalized individuals, college students, and healthy-functioning community adolescents.Conclusions: Self-compassion was negatively associated with STBs and NSSI, and the effect size of self-compassion was larger for STBs than NSSI. More evidence is necessary to gauge a clinically significant protective role that self-compassion may play by soliciting results from future longitudinal studies or intervention studies.