bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study
Authors: Ko Heejoo , Chang Jee Suk , Moon Jin Young , Lee Won Hee , Shah Chirag , Shim Jin Sup (Andy) , Han Min Cheol , Baek Jong Geol , Park Ryeong Hwang , Kim Yong Bae , Kim Jin Sung 
Published: April 2021

PurposeHow modern cardiac sparing techniques and beam delivery systems using advanced x-ray and proton beam therapy (PBT) can reduce incidental radiation exposure doses to cardiac and pulmonary organs individually or in any combination is poorly investigated.MethodsAmong 15 patients with left-sided breast cancer, partial wide tangential 3D-conformal radiotherapy (3DCRT) delivered in conventional fractionation (CF) or hypofractionated (HF) schedules; PBT delivered in a CF schedule; and volumetric modulated arc therapy (VMAT) delivered in an HF schedule, each under continuous positive airway pressure (CPAP) and free-breathing (FB) conditions, were examined. Target volume coverage and doses to organs-at-risk (OARs) were calculated for each technique. Outcomes were compared with one-way analysis of variance and the Bonferroni test, with p-values &lt;0.05 considered significant.ResultsTarget volume coverage was within acceptable levels in all interventions, except for the internal mammary lymph node D95 (99% in PBT, 90% in VMAT-CPAP, 84% in VMAT-FB, and 74% in 3DCRT). The mean heart dose (MHD) was the lowest in PBT (&lt;1 Gy) and VMAT-CPAP (2.2 Gy) and the highest in 3DCRT with CF/FB (7.8 Gy), respectively. The mean lung dose (MLD) was the highest in 3DCRT-CF-FB (20 Gy) and the lowest in both VMAT-HF-CPAP and PBT (approximately 5–6 Gy). VMAT-HF-CPAP and PBT delivered a comparable maximum dose to the left ascending artery (7.2 and 6.13 Gy, respectively).ConclusionsBoth proton and VMAT in combination with CPAP can minimize the radiation exposure to heart and lung with optimal target coverage in regional RT for left-sided breast cancer. The clinical relevance of these differences is yet to be elucidated. Continued efforts are needed to minimize radiation exposures during RT treatment to maximize its therapeutic index.
Sensitivity of the Molecular Test in Saliva for Detection of COVID-19 in Pediatric Patients With Concurrent Conditions
Authors: Ana Laura Guzmán-Ortiz , Abraham Josué Nevárez-Ramírez , Briceida López-Martínez , Israel Parra-Ortega , Tania Angeles-Floriano , Nancy Martínez-Rodríguez , Lourdes Jamaica-Balderas , Daniela De la Rosa-Zamboni , Fernando Ortega-Riosvelasco , Carlos Mauricio Jaramillo-Esparza , Sergio René Bonilla-Pellegrini , Irineo Reyna-Trinidad , Horacio Márquez-González , Oscar Medina-Contreras , Héctor Quezada 
Published: April 2021

Background: The reference standard for the molecular diagnostic testing for COVID-19 is the use of nasopharyngeal or combined nasopharyngeal and oropharyngeal (NP/OP) swabs. Saliva has been proposed as a minimally invasive specimen whose collection reduces the risks for health care personnel.Objective: To assess the suitability of saliva for COVID-19 diagnosis as a replacement of the reference standard NP/OP swab in the setting of a tertiary care pediatric unit.Study design: A paired study based in the prospective cohort design in patients suspected of having COVID-19.Methods: RT-PCR was used to detect SARS-CoV-2 in paired samples of saliva and NP/OP swab collected from May through August 2020 from 156 pediatric participants, of whom 128 has at least one comorbidity and 91 showed clinical symptoms related to SARS-CoV-2 infection. Additionally, we studied a group of 326 members of the hospital staff, of whom 271 had symptoms related to SARS-CoV-2 infection.Results: In the group of pediatric participants the sensitivity of the diagnostic test in saliva was 82.3% (95% CI 56.6–96.2) and the specificity 95.6% (95% CI 90.8–98.4). The prevalence of COVID-19 was 10.9% (17/156). In 6 of the 23 participants who tested positive for SARS-CoV-2 in at least one specimen type, the virus was detected in saliva but not in NP/OP swab, while in 3 participants the NP/OP swab was positive and saliva negative. In the group of adults, the sensitivity of the test in saliva was 77.8% (95% CI 67.2–86.3) and prevalence 24.8% (81/326). Discordant results between the two types of specimens showed a significant association with low viral load in the pharynx of adults but not of pediatric participants.Interpretation: In the context of a pediatric tertiary care hospital, the sensibility of the test in saliva is not high enough to replace the use of NP/OP swab for COVID-19 diagnosis. Neither NP/OP swab nor saliva could detect all the participants infected with SARS-CoV-2.
The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited
Authors: Ji Bin , Wen Zina , Ni Chaobo , Zhu Qiqi , Wang Yiyan , Li Xiaoheng , Zhong Ying , Ge Ren-Shan 
Published: April 2021

Background: Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. Here, we reported the effects of gestational exposure to DIHP on testis development in male rats.Methods: Pregnant Sprague-Dawley rats were orally fed with vehicle (corn oil, control) or DIHP (10, 100, 500, and 1,000 mg/kg) from gestational day (GD) 12–21. At GD21, serum testosterone levels, the number and distribution of fetal Leydig cells, and testicular mRNA and protein levels, the incidence of multinucleated gonocytes, and focal testicular hypoplasia in the neonatal testis were measured.Results: DIHP increased the fetal Leydig cell cluster size and decreased the fetal Leydig cell size with LOAEL of 10 mg/kg. DIHP did not affect the fetal Leydig cell number. DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP dose-dependently increased the percentage of multinucleated gonocytes with the low observed adverse-effect level (LOAEL) of 100 mg/kg. DIHP induced focal testicular hypoplasia.Conclusion: Gestational exposure to DIHP causes testis dysgenesis in rats.
Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
Authors: Xue Chenyang , Chen Wei , Yuan Aiwu , Chen Cheng , Li Shuaihu , Chen Kai , Zhao Yang , Xiao Tian , Shao Genze , Zou Yongdong , Zheng Duo 
Published: April 2021

Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth in vivo. The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was −17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC.
Phytoconstituents, In Vitro Anti-Infective Activity of Buddleja indica Lam., and In Silico Evaluation of its SARS-CoV-2 Inhibitory Potential
Authors: Youssef Fadia S. , Altyar Ahmed E. , Omar Abdelsattar M. , Ashour Mohamed L. 
Published: April 2021

Phytochemical investigation of Buddleja indica Lam. leaves methanol extract (BIT) resulted in the isolation of six known compounds for the first time from the plant, namely, p-hydroxybenzoic acid 1), caffeic acid 2), quercetin 3-O-β-D glucoside-7-O-α-L-rhamnoside 3), kaempferol 3-O-β-D glucoside-7-O-α-L-rhamnoside 4), quercetin 7-O-β-D glucoside 5) and kaempferol 6). BIT extract showed potent antibacterial activity with MIC values ranging between 0.48 and 1.95 μg/ml with Bacillus subtilis was the most susceptible to the BIT effect. It showed a notable antimycobacterial and anti-Helicobacter pylori activity with MIC values of 100 and 80 μg/ml, respectively. Vesicular stomatitis virus (VSV) was more sensitive to the antiviral activity of BIT comparable to herpes simplex virus type 1 (HSV-1), showing 48.38 and 41.85% inhibition of the viral replication at a dose of 50 μg/ml for VSV and HSV-1, respectively. In silico molecular docking of the isolated compounds revealed that caffeic acid 2) showed the highest fitting within the active sites of DNA-gyrase, topoisomerase IV, and SARS-CoV-2 MPro. Quercetin 7-O-β-D glucoside 5) revealed the best fitting in dihydrofolate reductase active site with ∆ G value equals −36.53 Kcal/mol. Kaempferol 6) exhibited the highest fitting towards β-lactamase, SARS-CoV-2PLpro, and SARS-CoV-2 3CLpro active sites. Thus, B. indica Lam. can be considered as a future source of cheap, substantially safe, and credible antibacterial, antifungal, and antiviral candidate of natural origin that could effectively participate in solving the problem of COVID-19 pandemic. These findings provide a scientific consolidation for the ethnomedicinal uses of Buddleja indica Lam. as a topical antiseptic.
The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense
Authors: Lohakul Jinapath , Chaiprasongsuk Anyamanee , Jeayeng Saowanee , Saelim Malinee , Muanjumpon Phetthinee , Thanachaiphiwat Saowalak , Tripatara Pinpat , Soontrapa Kittipong , Lumlerdkij Natchagorn , Akarasereenont Pravit , Panich Uraiwan 
Published: April 2021

Polyherbal formulation combining multiple herbs is suggested to achieve enhanced therapeutic effects and reduce toxicity. Harak herbal formula (HRF) extracts were proposed to regulate skin responses to UVR through their ability to suppress UVA-induced matrix metalloproteinase-1 (MMP-1) and pigmentation via promoting antioxidant defenses in in vitro models. Therefore, natural products targeting Nrf2 (nuclear factor erythroid 2-related factor 2)-regulated antioxidant response might represent promising anti-photoaging candidates. Hesperetin (HSP) was suggested as a putative bioactive compound of the HRF, as previously shown by its chemical profiling using the liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). In this study, we explored the anti-photoaging effects of HRF extracts and HSP on normal human dermal fibroblasts (NHDFs) and mouse skin exposed to UVA irradiation. Pretreatment of NHDFs with HRF extracts and HSP protected against UVA (8 J/cm2)-mediated cytotoxicity and reactive oxygen species (ROS) formation. The HRF and HSP pretreatment also attenuated the UVA-induced MMP-1 activity and collagen depletion concomitant with an upregulation of Nrf2 activity and its downstream genes (GST and NQO-1). Moreover, our findings provided the in vivo relevance to the in vitro anti-photoaging effects of HRF as topical application of the extracts (10, 30 and 100 mg/cm2) and HSP (0.3, 1, and 3 mg/cm2) 1 h before UVA exposure 3 times per week for 2 weeks (a total dose of 60 J/cm2) mitigated MMP-1 upregulation, collagen loss in correlation with enhanced Nrf2 nuclear accumulation and its target protein GST and NQO-1 as well as reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) in irradiated mouse skin. Thus, our findings revealed that HRF extracts and HSP attenuated UVA-induced photoaging via upregulating Nrf2, together with their abilities to reduce ROS formation and oxidative damage. Our study concluded that the HRF and its bioactive ingredient HSP may represent potential candidates for preventing UVA-induced photoaging via restoration of redox balance.
Limited Sampling Strategy for Estimation of Mycophenolic Acid Exposure in Adult Chinese Heart Transplant Recipients
Authors: Xiang Hongping , Zhou Hong , Zhang Jing , Sun Yongfeng , Wang Yirong , Han Yong , Cai Jie 
Published: April 2021

Background: With the increasing use of mycophenolic acid (MPA) formulations in organ transplantation, the need for personalized immunosuppressive therapy has become well recognized based on therapeutic drug monitoring (TDM) for avoidance of drug-related toxicity while maintaining efficacy. Few studies have assessed area under the 12 h concentration-time curve of MPA (MPA-AUC0–12h) in heart transplant recipients who received mycophenolate mofetil (MMF) dispersible tablets (MMFdt). The aim of the study was to investigate the pharmacokinetics (PK) of MMFdt combined with tacrolimus and further to develop a practical method for estimation of MPA-AUC0–12h using a limited sampling strategy (LSS).Methods: A prospective study in a single center was performed in patients who continuously administrated with MMFdt or MMF capsule (MMFc) for at least 7 days after cardiac transplantation from 2018 to 2020. A total of 48 Chinese adult heart transplant recipients were enrolled. Blood samples were collected before and 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after MMF administration. The validated high-performance liquid chromatography combined with tandem mass spectrometry method was used to measure MPA concentrations. Non-compartmental pharmacokinetic (PK) analysis was applied to calculate the data obtained from individual recipients by WinNonlin. LSS models were developed for MPA-AUC0–12h prediction with multivariate stepwise regression analysis.Results: A large inter-individual variability was observed in AUC0–12h, Tmax, Cmax, MRT0–12h, t1/2 and CL/F after multiple dosing of MMFdt. However, no significant differences were observed between main PK parameters of MMFdt and MMFc. The best estimation of MPA-AUC0–12h was achieved with four points: MPA-AUC0–12h = 8.424 + 0.781 × C0.5 + 1.263 × C2 + 1.660 × C4 + 3.022 × C6 (R2 = 0.844). The mean prediction error (MPE) and mean absolute prediction error (MAPE) of MPA-AUC0–12h were 2.09 ± 14.05% and 11.17 ± 8.52%, respectively. Both internal and external validations showed good applicability for four-point LSS equation.Conclusion: The results provide strong evidence for the use of LSS model other than a single time-point concentration of MPA when performing TDM. A four-point LSS equation using the concentrations at 0.5, 2, 4, 6 h is recommended to estimate MPA-AUC0–12h during early period after transplantation in Chinese adult heart transplant recipients receiving MMFdt or MMFc. However, proper internal and external validations with more patients should be conducted in the future.
Serum Creatinine as a Potential Biomarker of Skeletal Muscle Atrophy in Non-small Cell Lung Cancer Patients
Authors: das Neves Willian , Alves Christiano R. R. , de Souza Borges Ana Paula , de Castro Gilberto 
Published: April 2021

Objectives: Identifying simple biomarkers to determine muscle atrophy in non-small-cell lung cancer (NSCLC) patients remains a critical research gap. Since creatinine is mainly a product from intramuscular creatine metabolism, we tested the hypothesis that low serum creatinine levels would be associated to skeletal muscle atrophy in NSCLC patients.Materials and Methods: This is a prospective cohort study including 106 treatment-naive patients with histologically confirmed stage IV NSCLC. All patients performed routine serum creatinine laboratory tests. We divided patients into two groups based on low (&lt;0.7 mg/dL for male and &lt;0.5 mg/dL for female) or normal creatinine levels. We compared body mass index (BMI), psoas muscle cross-sectional area, adipose tissue area and complete blood counts between groups.Results: Male and female NSCLC patients with low serum creatinine levels had low muscle cross-sectional area as compared to patients with normal serum creatinine levels. Male NSCLC patients with low serum creatinine also displayed reduced BMI, reduced adipose tissue area, and elevated systemic inflammation compared to NSCLC patients with normal serum creatinine levels. There were no significant differences between female groups for BMI, adipose tissue area and inflammatory markers.Conclusions: Serum creatinine is a potential prognostic biomarker of skeletal muscle atrophy in NSCLC patients. Since serum creatinine is a simple and accessible measurement, we suggest that it should be monitored in longitudinal follow-up of NSCLC patients as a biomarker of muscle atrophy.
Relationship Between Cognitive Fusion, Experiential Avoidance, and Obsessive–Compulsive Symptoms in Patients With Obsessive–Compulsive Disorder
Authors: Xiong Ai , Lai Xiong , Wu Siliang , Yuan Xin , Tang Jun , Chen Jinyuan , Liu Yang , Hu Maorong 
Published: April 2021

Objective: This study aimed to explore the relationship among cognitive fusion, experiential avoidance, and obsessive–compulsive symptoms in patients with obsessive–compulsive disorder (OCD).Methods: A total of 118 outpatient and inpatient patients with OCD and 109 healthy participants, gender- and age-matched, were selected using cognitive fusion questionnaire (CFQ), acceptance and action questionnaire−2nd edition (AAQ-II), Yale–Brown scale for obsessive–compulsive symptoms, Hamilton anxiety scale, and Hamilton depression scale for questionnaire testing and data analysis.Results: The levels of cognitive fusion and experiential avoidance in the OCD group were significantly higher than those in the healthy control group (P &lt; 0.05). Regression analysis results showed that, in predicting the total score of obsessive–compulsive symptoms, AAQ-II (β = 0.233, P &lt; 0.05) and CFQ (β = 0.262, P &lt; 0.01) entered the equation, which explained 17.1% variance. In predicting anxiety, only AAQ-II (β = 0.222, P &lt; 0.05) entered the equation, which explained 13% variance. In the prediction of depression, AAQ-II (β = 0.412, P &lt; 0.001) entered the equation, which explained 17.7% variance.Conclusion: Cognitive fusion and experiential avoidance may be important factors for the maintenance of OCD, and experiential avoidance can positively predict the anxiety and depression of OCD patients.
The Long-Term Public Health Impact of a Community-Based Participatory Research Project for Health Promotion Among Socially Disadvantaged Women—A Case Study Protocol
Authors: Abu-Omar Karim , Ziemainz Heiko , Loss Julika , Laxy Michael , Holle Rolf , Thiel Ansgar , Herbert-Maul Annika , Linder Stephanie , Till Maike , Sauter Alexandra 
Published: April 2021

Introduction: Community-based participatory research (CBPR) is considered to be of high potential for health promotion among socially disadvantaged groups. However, the long-term implementation and transfer of these approaches remain challenging, and the public health impact they achieve is difficult to study. This also pertains to the potential health effects and cost-effectiveness of CBPR. This study protocol describes the follow-up case study (NU-BIG) after 15 years of the BIG project (“movement as investment in health”), a project to promote physical activity among socially disadvantaged women. Through a participatory approach, BIG empowers the addressed women to plan and implement low-threshold physical activity offers. Since the project started in 2005, it was transferred to 17 communities in Germany.Materials and Analysis: NU-BIG intends to examine the long-term effects, including economic aspects, of the BIG project on individual and structural levels at all project sites, as well as its long-term implementation and transfer. NU-BIG is a cross-sectional and longitudinal study using a mixed method approach. For the longitudinal section, we re-analyze existing data from former BIG evaluations. For cross-sectional data collection, we use questionnaires and conduct qualitative interviews and focus groups. Women who take part in BIG program offers are part of the research team and will use the photo-voice approach to report on the effects of BIG. The study population consists of about 800 women who participate in BIG project offers and 50 persons involved in the implementation of the BIG project at local sites.Discussion: The expected results from NU-BIG are highly relevant for studying the long-term public health impact of CBPR. In particular, this project intends to answer questions on how the transfer of such projects can succeed and which factors determine if a CBPR project can be sustained at the community level. Eventually, these results can contribute to the further development of participatory approaches to provide effective health promotion among socially disadvantaged groups.Conclusion: Although CBPR is seen of having the potential to reduce health disparities, there is still a lack of research on its long-term effects and public health impact. NU-BIG aims at generating knowledge about the economic effects, reach, efficacy, adoption, implementation, and maintenance of a CBPR project. The expected results could be of high interest for BIG and other CBPR-projects.
A Follow-Up Investigation of Mental Health Among Discharged COVID-19 Patients in Wuhan, China
Authors: Li Li , Wu Michael Shengtao , Tao Junxiu , Wang Weijun , He Jing , Liu Ru , Guo Juan , Chen Yun , Li Kejian , Li Shilong , Qi Bo , Han Buxin 
Published: April 2021

Objective: To understand the mental health status and its risk factors among discharged COVID-19 patients during the first month of centralized quarantine and the subsequent home isolation.Methods: The scales of the Insomnia Severity Index (ISI), General Anxiety Disorder (GAD-7), and Patient Health Questionnaire (PHQ-9) were used to measure the symptoms of insomnia, anxiety, and depression in 782 COVID-19 patients during the first month of centralized quarantine (March 16 to 26, 2020) and then during home isolation (April 3 to 10, 2020).Results: During the centralized quarantine, the prevalence rates of insomnia, anxiety, and depressive symptoms were 44.37, 31.59, and 27.62%, respectively, and those during the home isolation decreased significantly at 27.11, 17.26, and 16.11%, respectively. In both waves, women showed a higher prevalence of symptoms of poor mental health compared to men, and middle-aged (40–59 years old) and elderly (≥60 years old) showed a higher risk of symptoms of poor mental health compared to the younger. In addition, the severity of COVID-19 revealed no significant relationship to symptoms of poor mental health, whereas, the interaction analysis revealed that those with other underlying diseases showed more symptoms of poor mental health during the centralized quarantine and a greater decrease during the follow-up home isolation.Conclusion: The discharged COVID-19 patients suffered from mental health problems such as, insomnia, depression, and anxiety, and this was especially so for women, the middle-aged and elderly, and those with underlying diseases, but along with the rehabilitation and the environmental change from centralized quarantine to home isolation, all the mental symptoms were significantly alleviated. Based on a follow-up investigation, the current results provide critical evidence for mental health and early rehabilitation upon the discharged COVID-19 patients.