bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung Stereotactic Body Radiotherapy (SBRT) Using Spot-Scanning Proton Arc (SPArc) Therapy: A Feasibility Study
Authors: Liu Gang , Zhao Lewei , Qin An , Grills Inga , Deraniyagala Rohan , Stevens Craig , Zhang Sheng , Yan Di , Li Xiaoqiang , Ding Xuanfeng 
Published: April 2021

PurposeWe developed a 4D interplay effect model to quantitatively evaluate breathing-induced interplay effects and assess the feasibility of utilizing spot-scanning proton arc (SPArc) therapy for hypo-fractionated lung stereotactic body radiotherapy (SBRT). The model was then validated by retrospective application to clinical cases.Materials and MethodsA digital lung 4DCT phantoms was used to mimic targets in diameter of 3cm with breathing motion amplitudes: 5, 10, 15, and 20 mm, respectively. Two planning groups based on robust optimization were generated: (1) Two-field Intensity Modulated Proton Therapy (IMPT) plans and (2) SPArc plans via a partial arc. 5,000 cGy relative biological effectiveness (RBE) was prescribed to the internal target volume (ITV) in five fractions. To quantitatively assess the breathing induced interplay effect, the 4D dynamic dose was calculated by synchronizing the breathing pattern with the simulated proton machine delivery sequence, including IMPT, Volumetric repainting (IMPTvolumetric), iso-layered repainting (IMPTlayer) and SPArc. Ten lung patients’ 4DCT previously treated with VMAT SBRT, were used to validate the digital lung tumor model. Normal tissue complicated probability (NTCP) of chestwall toxicity was calculated.ResultTarget dose were degraded as the tumor motion amplitude increased. The 4D interplay effect phantom model indicated that motion mitigation effectiveness using SPArc was about five times of IMPTvolumetric or IMPTlayer using maximum MU/spot as 0.5 MU at 20 mm motion amplitude. The retrospective study showed that SPArc has an advantage in normal tissue sparing. The probability of chestwall’s toxicity were significantly improved from 40.2 ± 29.0% (VMAT) (p = 0.01) and 16.3 ± 12.0% (IMPT) (p = 0.01) to 10.1 ± 5.4% (SPArc). SPArc could play a significant role in the interplay effect mitigation with breathing-induced motion more than 20 mm, where the target D99 of 4D dynamic dose for patient #10 was improved from 4,514 ± 138 cGy [RBE] (IMPT) vs. 4,755 ± 129 cGy [RBE] (SPArc) (p = 0.01).ConclusionSPArc effectively mitigated the interplay effect for proton lung SBRT compared to IMPT with repainting and was associated with normal tissue sparing. This technology may make delivery of proton SBRT more technically feasible and less complex with fewer concerns over underdosing the target compared to other proton therapy techniques.
Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells
Authors: Tucci Jonathan , Chen Ting , Margulis Katherine , Orgel Etan , Paszkiewicz Rebecca L. , Cohen Michael D. , Oberley Matthew J. , Wahhab Rachel , Jones Anthony E. , Divakaruni Ajit S. , Hsu Cheng-Chih , Noll Sarah E. , Sheng Xia , Zare Richard N. , Mittelman Steven D. 
Published: April 2021

BackgroundThere is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells.MethodsWe cultured 3T3-L1 adipocytes, and tested whether ALL cells or ALL-released cytokines induced FFA release. We investigated whether ALL cells took up these FFA, and using fluorescent tagged BODIPY-FFA and lipidomics, evaluated which lipid moieties were being transferred from adipocytes to ALL. We evaluated the effects of adipocyte-derived lipids on ALL cell metabolism using a Seahorse XF analyzer and expression of enzymes important for lipid metabolism, and tested whether these lipids could protect ALL cells from chemotherapy. Finally, we evaluated a panel of lipid synthesis and metabolism inhibitors to determine which were affected by the presence of adipocytes.ResultsAdipocytes release free fatty acids (FFA) when in the presence of ALL cells. These FFA are taken up by the ALL cells and incorporated into triglycerides and phospholipids. Some of these lipids are stored in lipid droplets, which can be utilized in states of fuel deprivation. Adipocytes preferentially release monounsaturated FFA, and this can be attenuated by inhibiting the desaturating enzyme steroyl-CoA decarboxylase-1 (SCD1). Adipocyte-derived FFA can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of pharmacological acetyl-CoA carboxylase (ACC) inhibition. Further, adipocytes alter ALL cell metabolism, shifting them from glucose to FFA oxidation. Interestingly, the unsaturated fatty acid, oleic acid, protects ALL cells from modest concentrations of chemotherapy, such as those that might be present in the ALL microenvironment. In addition, targeting lipid synthesis and metabolism can potentially reverse adipocyte protection of ALL cells.ConclusionThese findings uncover a previously unidentified interaction between ALL cells and adipocytes, leading to transfer of FFA for use as a metabolic fuel and macromolecule building block. This interaction may contribute to ALL resistance to chemotherapy, and could potentially be targeted to improve ALL treatment outcome.
An Immune-Related lncRNA Expression Profile to Improve Prognosis Prediction for Lung Adenocarcinoma: From Bioinformatics to Clinical Word
Authors: Zhang Boxiang , Wang Rui , Li Kai , Peng Ziyang , Liu Dapeng , Zhang Yunfeng , Zhou Liuzhi 
Published: April 2021

BackgroundLung cancer is still the top-ranked cancer-related deaths all over the world. Now immunotherapy has emerged as a promising option for treating lung cancer. Recent evidence indicated that lncRNAs were also key regulators in immune system. We aimed to develop a novel prognostic signature based on the comprehensive analysis of immune-related lncRNAs to predict survival outcome of LUAD patients.MethodsThe gene expression profiles of 491 LUAD patients were downloaded from TCGA. 1047 immune-related lncRNAs were obtained through Pearson correlation analysis of immune genes and lncRNAs using statistical software R language. Univariate and multivariate Cox regression analysis were performed to determine the optimal immune-related lncRNAs prognostic signature (ITGCB-DT, ABALON, TMPO-AS1 and VIM-AS1). Finally, we validated the immune-related lncRNAs prognostic signature in The First Affiliated Hospital of Xi’an Jiaotong University cancer center cohort.ResultsA four immune-related lncRNAs prognostic signature was constructed to predict the survival outcome of LUAD patients. Statistical significance were found that the LUAD patients in high-risk group suffered shorter overall survival than those in low-risk group (P &lt;0.001). ROC curve analysis shown that the four immune-related lncRNAs prognostic signature had the best predictive effect compared with age, gender, AJCC-stage, T stage, N stage, M stage (AUC = 0.756). More importantly, clinical cohort studies proved that the signature could predict the overall survival of LUAD patients with an AUC = 0.714.ConclusionsIn summary, we demonstrated that the novel immune-related lncRNAs signature had the ability to predict the prognosis of LUAD patients, which might serve as potential prognostic biomarkers and guide the individualized treatment strategies for LUAD patients.
Cardiovascular Pharmacological Support Among Preterm Infants in Chinese Referral Center Neonatal Intensive Care Units
Authors: Luo Ningxin , Jiang Siyuan , McNamara Patrick J. , Li Xiaoying , Guo Yan , Wang Yang , Han Junyan , Deng Yingping , Yang Yi , Lee Shoo K. , Cao Yun 
Published: April 2021

Objective: To describe cardiovascular pharmacological support in infants born at &lt;34 weeks' gestation within the first postnatal week in Chinese neonatal intensive care units (NICUs).Design: A secondary analysis of data from a multicenter randomized controlled study (REIN-EPIQ). A questionnaire regarding cardiovascular support practices was also completed by all participating NICUs.Setting: Twenty-five tertiary hospitals from 19 provinces in China.Patients: All infants born at &lt;34 weeks' gestation and admitted to participating NICUs within the first postnatal week from May 2015 to April 2018 were included. Infants who were discharged against medical advice were excluded.Measures and Main Results: Among the 26,212 preterm infants &lt;34 weeks, 16.1% received cardiovascular pharmacological support. The use rates increased with decreasing gestational age and birth weight, with 32.5% among infants &lt;28 weeks and 35.9% among infants &lt;1,000 g. Cardiovascular pharmacological support was independently associated with higher risks of death (aOR 2.8; 95% CI 2.4–3.3), severe intraventricular hemorrhage (IVH) (aOR 2.1; 95% CI 1.8–2.5) and bronchopulmonary dysplasia (BPD) (aOR 2.2; 95% CI 2.0–2.5). Overall 63.1% courses of cardiovascular pharmacological support were &gt;3 days. Prolonged cardiovascular pharmacological support (&gt;3 days) was independently associated with lower rates of survival without morbidity in very-low-birth-weight infants, compared with infants with shorter durations. Dopamine was the most commonly used cardiovascular agent. The cardiovascular pharmacological support rates varied from 1.9 to 65.8% among the participating NICUs.Conclusions: The rate of cardiovascular pharmacological support within the first postnatal week was high with prolonged durations in Chinese NICUs. Marked variation in cardiovascular support existed among participating NICUs. Cardiovascular pharmacological support during the early postnatal period, especially prolonged, may be associated with adverse neonatal outcomes.Clinical Trial Registration: The original trial was registered as “Reduction of Infection in Neonatal Intensive Care Units using the Evidence-based Practice for Improving Quality” (ID: NCT02600195) on clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02600195?term=NCT02600195&amp;draw=2&amp;rank=1.
Fecal and Duodenal Microbiota in Pediatric Celiac Disease
Authors: Abdukhakimova Diyora , Dossybayeva Kuanysh , Poddighe Dimitri 
Published: April 2021

Background and Objective: The gut microbiota plays a role in regulating the host immunity. Therefore, alterations in gut microbiota (or dysbiosis) have been investigated in several gastrointestinal diseases, including Celiac Disease (CD). The aim of this study is to summarize the main characteristics of the gut microbiota in pediatric CD.Methods: We performed a systematic review to retrieve the available studies investigating the gut microbiota in pediatric CD patients and controls. In detail, after the screening of &gt;2,200 titles from the medical literature, 397 articles were assessed for eligibility based on the abstracts: of those, 114 full-text original articles were considered as eligible according to the aim of this systematic review.Results: The final search output consisted of 18 articles describing the gut microbiota of CD children and including one or more control groups. Eleven pediatric studies provided information on the duodenal microbiota and as many investigated the fecal microbiota; three articles analyzed the microbiota on both fecal and duodenal samples from the same cohorts of patients.Conclusion: Due to the heterogeneity of the experimental procedures and study design, it is not possible to evidence any specific celiac signature in the fecal and/or duodenal microbiota of CD children. However, some specific components of the fecal microbiota and, in detail, Bifidobacterium spp. (e.g., Bifidobacterium longum) may deserve additional research efforts, in order to understand their potential value as both probiotic therapy and diagnostic/prognostic biomarker.
Prevalence of and Trends in the Co-Existence of Obesogenic Behaviors in Adolescents From 15 Countries
Authors: Fan Hui , Zhang Xingyu 
Published: April 2021

Background:The global epidemic of pediatric obesity is well-known, but data on co-existence of obesogenic behaviors are limited. We aim to report the prevalence of and trends in the co-existence of obesogenic behaviors in adolescents from 15 countries.Methods:This study was based on the Global School-based Student Health Survey 2003–2017 and included 121,963 adolescents aged 12–15 years from 15 countries where at least 2 cross-sectional surveys were conducted. We used sampling weights and calculated the country-level prevalence of and trends in the co-existence of obesogenic behaviors (low fruit and vegetable intake, anxiety-induced insomnia, no physical activity, and sedentary behavior) during survey years. Pooled prevalence and trend estimates were calculated with random-effects models.Results:Pooled prevalence of exposure ≥ 1, ≥2, and ≥3 obesogenic behaviors was 88.2, 44.9, and 9.8% in the first survey and 88.4, 46.4, and 10.2% in the last survey, respectively. Plateauing, increasing, and decreasing trends in the co-existence of obesogenic behaviors were observed in different countries. Specifically, we identified a plateauing pooled trend in the exposure ≥ 1, ≥2, and ≥3 obesogenic behaviors [odds ratios (95% confidence intervals): 1.03 (0.93, 1.14), 1.05 (0.97, 1.13), and 1.06 (0.95, 1.18), respectively].Conclusion:Trends in the prevalence of the co-existence of obesogenic behaviors varied significantly across different countries, but the prevalence remained high in most countries. These findings suggest the need for behavioral interventions to mitigate obesogenic behaviors in adolescents for overweight and obesity prevention.
No Efficacy of the Combination of Lopinavir/Ritonavir Plus Hydroxychloroquine Versus Standard of Care in Patients Hospitalized With COVID-19: A Non-Randomized Comparison
Authors: Gagliardini Roberta , Cozzi-Lepri Alessandro , Mariano Andrea , Taglietti Fabrizio , Vergori Alessandra , Abdeddaim Amina , Di Gennaro Francesco , Mazzotta Valentina , Amendola Alessandra , D’Offizi Giampiero , Palmieri Fabrizio , Marchioni Luisa , Piselli Pierluca , Agrati Chiara , Nicastri Emanuele , Capobianchi Maria Rosaria , Petrosillo Nicola , Ippolito Giuseppe , Vaia Francesco , Girardi Enrico , Antinori Andrea 
Published: April 2021

Objectives: No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC).Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included.Primary endpoint: time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used.Results: A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51–76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups.Conclusion: In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.
Efficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and Design
Authors: Feng Luda , Han Fang , Zhou Li , Wu Shengxian , Du Yawei , Zhang Dandan , Zhang Chi , Gao Ying 
Published: April 2021

Background: Although revascularization treatment is recommended as the first-line therapy for patients with non-minor acute ischemic stroke (AIS), it only benefits a minority of patients. Previous studies have reported the positive effects of Panax notoginseng saponins (PNS) (Xueshuantong lyophilized powder) on AIS, however, there have been no rigorous trials. This study aims to assess the efficacy and safety of PNS therapy for patients with AIS.Methods: The Evaluation of Xueshuantong in Patients with acutE ischemiC sTroke (EXPECT) trial is a multicenter, randomized, placebo-controlled, double-blind study aiming to enroll 480 patients in China. Eligible patients with AIS within 72 h of symptom onset will randomly receive either PNS or PNS placebo for 10 days and subsequently be followed up to 90 days. The primary outcome will be a change in the National Institute of Health Stroke Scale (NIHSS) score from baseline to 10 post-randomization days. The secondary outcomes include early neurological improvement (proportion of patients with NIHSS score 0–1), and Patient-Reported Outcomes Scale for Stroke score at 10 post-randomization days, the proportion of patients with life independence (modified Rankin Scale score of 0–1), the proportion of patients with a favorable outcome (Barthel Index ≥90), and Stroke-Specific Quality of Life score at 90 days. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of PNS.Conclusions: To our knowledge, this study is the first double-blind trial to assess the efficacy and safety of PNS in patients with AIS. Findings of the EXPECT trial will be valuable in improving evidence regarding the clinical application of PNS therapy in patients with AIS ineligible for revascularization treatment in the reperfusion era.
Inhibition of Small-Conductance, Ca2+-Activated K+ Current by Ondansetron
Authors: Guo Shuai , Chen Zhenhui , Chen Peng-Sheng , Rubart Michael 
Published: April 2021

Background:Small-conductance Ca2+-activated K+channels (SK channels) have been proposed as antiarrhythmic targets for the treatment of atrial fibrillation. We previously demonstrated that the 5-HT3receptor antagonist ondansetron inhibits heterologously expressed, human SK2 (hSK2) currents as well as native cardiac SK currents in a physiological extra-/intracellular [K+] gradient at therapeutic (i.e., sub-micromolar) concentrations. A recent study, using symmetrical [K+] conditions, challenged this result. The goal of the present study was to revisit the inhibitory effect of ondansetron on hSK2-mediated currents in symmetrical [K+] conditions.Experimental Approach:The whole-cell patch clamp technique was used to investigate the effects of ondansetron and apamin on hSK2-mediated currents expressed in HEK 293 cells. Currents were measured in symmetrical [K+] conditions in the presence of 100 nM [Ca2+]o.Results:Expression of hSK2 produced inwardly rectifying whole-cell currents in the presence of 400 nM free cytosolic Ca2+. Ondansetron inhibited whole-cell hSK2 currents withIC50values of 154 and 113 nM at −80 and 40 mV, respectively. Macroscopic current inhibited by ondansetron and current inhibited by apamin exhibited inwardly rectifying current-voltage relationships with similar reversal potentials (apamin, ∼5 mV and ondansetron, ∼2 mV). Ondansetron (1 μM) in the continuing presence of apamin (100 nM) had no effect on hSK2-mediated whole-cell currents. Wild-type HEK 293 cells did not express ondansetron- or apamin-sensitive currents.Conclusion:Ondansetron in sub-micromolar concentrations inhibits hSK2 currents even under altered ionic conditions.
Usability and User Experience of Cognitive Intervention Technologies for Elderly People With MCI or Dementia: A Systematic Review
Authors: Contreras-Somoza Leslie María , Irazoki Eider , Toribio-Guzmán José Miguel , de la Torre-Díez Isabel , Diaz-Baquero Angie Alejandra , Parra-Vidales Esther , Perea-Bartolomé María Victoria , Franco-Martín Manuel Ángel 
Published: April 2021

IntroductionIncorporating technology in cognitive interventions represents an innovation, making them more accessible, flexible, and cost-effective. This will not be feasible without adequate user-technology fit. Bearing in mind the importance of developing cognitive interventions whose technology is appropriate for elderly people with cognitive impairment, the objective of this systematic review was to find evidence about usability and user experience (UX) measurements and features of stimulation, training, and cognitive rehabilitation technologies for older adults with mild cognitive impairment (MCI) or dementia.MethodThe Medline, PubMed, Scopus, ScienceDirect, and PsycINFO databases were searched for literature published in the last 10 years (2009–2019), and three researchers independently reviewed potentially eligible studies, following specific inclusion criteria. A systematic review of the studies was conducted, presenting a qualitative synthesis of usability and UX measures with their outcomes, study characteristics and features of the cognitive intervention technologies.ResultsTen studies were selected: five were cognitive stimulation and five were cognitive training. Most of them (60%) were computer-based programs with a serious game format. Efficiency and effectiveness were the most frequent measurements used for collecting objective usability data, showing that elderly people with cognitive impairment require more time (45%) and help (40%) but can complete tasks (60%). Regarding UX or subjective usability data, questionnaires and scales were the most used methods, reporting positive experience despite certain difficulties with the interface in five studies.ConclusionMeasuring usability and UX in cognitive intervention technologies for older adults with MCI or dementia provides an integrated view that can contribute to their development according to the needs and characteristics of the target population. More research is required to include this population group in usability and UX studies, as well as standardized tools and consensus on the relationship of these terms to guarantee the future effectiveness of cognitive intervention technologies.Review registrationThis review was registered in the PROSPERO (CRD42020158147) International Register of Systematic Review Protocols.