bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-HT1B receptor agonist attenuates cocaine self-administration after protracted abstinence and relapse in rats
Authors: Scott Samantha N , Garcia Raul , Powell Gregory L , Doyle Sophia M , Ruscitti Brielle , Le Tien , Esquer Aracely , Blattner Kevin M , Blass Benjamin E , Neisewander Janet L 
Published: May 2021

Background: The 5-HT1B receptor (5-HT1BR) agonist, CP94253, enhances cocaine intake during maintenance of self-administration (SA) but attenuates intake after 21 days of forced abstinence in male rats. Aims: We examined whether CP94253 attenuates cocaine intake in female rats after a period of abstinence, and if these attenuating effects persist or revert to enhancing cocaine intake during resumption (i.e. relapse) of daily cocaine SA. Methods: Male and female rats trained to lever press on a fixed ratio 5 schedule of cocaine reinforcement underwent ⩾21 days of forced abstinence. They were then tested for the effects of CP94253 (5.6 mg/kg, SC) or vehicle on cocaine SA. During the test session, rats had 1-h access to the training dose of cocaine (0.75 mg/kg, IV) followed by 1-h access to a lower cocaine dose (0.075 mg/kg, IV). Rats then resumed cocaine SA for 15 days to mimic relapse and were retested as done previously. Subsequently, rats underwent abstinence again (21–60 days) and were tested for CP94253 effects on locomotion and cue reactivity (i.e. responding for light/tone cues previously paired with cocaine infusions). Results: Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA and decreased cue reactivity while having no effect on locomotion. Conclusions: CP94253 decreases cocaine intake and cocaine seeking in both males and females even after resumption of cocaine SA. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting, and therefore, 5-HT1BR agonists may have clinical efficacy as anti-relapse medications for cocaine use disorders.
Program Evaluation of Population- and System-Level Policies: Evidence for Decision Making
Authors: Walker Simon , Fox Aimee , Altunkaya James , Colbourn Tim , Drummond Mike , Griffin Susan , Gutacker Nils , Revill Paul , Sculpher Mark 
Published: May 2021

Background Policy evaluations often focus on ex post estimation of causal effects on short-term surrogate outcomes. The value of such information is limited for decision making, as the failure to reflect policy-relevant outcomes and disregard for opportunity costs prohibits the assessment of value for money. Further, these evaluations do not always consider all relevant evidence, other courses of action, or decision uncertainty. Methods In this article, we explore how policy evaluation could better meet the needs of decision making. We begin by defining the evidence required to inform decision making. We then conduct a literature review of challenges in evaluating policies. Finally, we highlight potential methods available to help address these challenges. Results The evidence required to inform decision making includes the impacts on the policy-relevant outcomes, the costs and associated opportunity costs, and the consequences of uncertainty. Challenges in evaluating health policies are described using 8 categories: 1) valuation space; 2) comparators; 3) time of evaluation; 4) mechanisms of action; 5) effects; 6) resources, constraints, and opportunity costs; 7) fidelity, adaptation, and level of implementation; and 8) generalizability and external validity. Methods from a broad set of disciplines are available to improve policy evaluation, relating to causal inference, decision-analytic modeling, theory of change, realist evaluation, and structured expert elicitation. Limitations The targeted review may not identify all possible challenges, and the methods covered are not exhaustive. Conclusions Evaluations should provide appropriate evidence to inform decision making. There are challenges in evaluating policies, but methods from multiple disciplines are available to address these challenges. Implications Evaluators need to carefully consider the decision being informed, the necessary evidence to inform it, and the appropriate methods. [Box: see text]
The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer
Authors: Zang Mingcui , Guo Xun , Chen Manqiu 
Published: May 2021

Objective MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). Methods The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3ʹ untranslated region (3ʹ UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. Results Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3ʹ UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. Conclusions miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.
Factors affecting the accuracy and reliability of the measurement of anti-Müllerian hormone concentration in the clinic
Authors: Fu Yun-Xing , Wang Hui , Hu Ting , Wang Fei-Miao , Hu Rong 
Published: May 2021

Objective We aimed to identify the factors that influence serum anti-Müllerian hormone (AMH) concentration measurements. Methods We collected serum samples between May and September 2018 and compared the effect on AMH concentration measured by ELISA of conditions including venepuncture, storage time, storage temperature, locations of the reaction microplate, and the use of the oral contraceptive pill and gonadotrophin-releasing hormone (GnRH). Results AMH concentration was not affected by food intake but was affected by haemolysis. It was also much higher in samples on the edge of the ELISA microtitre plate. AMH concentration increased after incubation at room temperature for 1 day, 4°C for 3 days, −20°C for 1 month and −40°C for 4 months, but no change occurred during storage at −80°C for 9 months. AMH concentration was high in patients following GnRH agonist treatment but was not affected by oral contraceptives. Conclusions No fasting is required prior to AMH measurement. Placement of serum samples on the edge of microtitre plates affects the results of the AMH ELISA. If serum samples cannot be assayed immediately, it is best to store them at −80°C. Basal AMH concentration cannot be used as a measure of ovarian reserve after GnRH agonist treatment.
Possible involvement of the Hedgehog and PDPK1–Akt pathways in the growth and migration of small-cell lung cancer
Authors: Tang Naiwang , Hu Bin , Zhang Yin , Chen Zhiwei , Yu Ronghuan 
Published: May 2021

Background Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC. Methods The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells. Results PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression. Conclusions The interaction between the PDPK1–Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.
Ultraviolet light-emitting diode irradiation induces reactive oxygen species production and mitochondrial membrane potential reduction in HL-60 cells
Authors: Xie Dong , Li Yun-Long , Wang Gui-Fen , Jiang Jian , Sun Li-Rong 
Published: May 2021

Objective Ultraviolet light-emitting diode (UV LED) irradiation at 280 nm has been confirmed to induce apoptosis in cultured HL-60 cells, but the underlying mechanisms remain unclear. This study aimed to investigate the effects of 280 nm UV LED irradiation on reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) in HL-60 cells. Methods HL-60 cells were irradiated with 0, 8, 15, or 30 J/m2 of 280 nm UV LED and incubated for 2 hours. The intracellular ROS levels were assessed using the fluorescent probe 2ʹ-7ʹ-dichlorodihydrofluorescein diacetate (DCFH-DA) and a fluorescence plate reader. MMP was determined by flow cytometry using 5,5ʹ,6,6ʹ-tetrachloro-1,1ʹ,3,3ʹ-tetraethylbenzimidazol-carbocyanine iodide (JC-1) staining. The apoptosis-related proteins Bax and Bcl-2 were evaluated by western blot. Results UV LED irradiation at 280 nm induced a dose-dependent increase in ROS production and loss of MMP, and it activated apoptosis at irradiation doses of 8 to 30 J/m2. These results were consistent with a previous apoptosis study from the authors’ group. Conclusion Enhanced ROS production and mitochondrial depolarization are two distinct but interacting events, and both are involved in UV LED-induced apoptosis in HL-60 cells.
Efficacy of perioperative intravenous dexmedetomidine administration for the prevention of postoperative sore throat: a meta-analysis
Authors: Liu Yuanhui , Ai Dongmei , Wang Xiaobin 
Published: May 2021

Objective Postoperative sore throat (POST) is an undesirable intubation-related complication after surgery. Several studies have investigated the efficacy of perioperative intravenous dexmedetomidine administration for the prevention of POST, but the results have been inconsistent. We aimed to summarize all existing evidence and draw a more precise conclusion to guide future clinical work. Methods PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure databases were comprehensively searched for all randomized controlled trials published before 1 February 2021 that investigated the efficacy of dexmedetomidine for the prevention of POST. Results Nine studies involving 400 patients were included in our meta-analysis. Compared with the control groups (i.e., saline and anesthetic drugs), perioperative intravenous use of dexmedetomidine significantly reduced the incidence of POST [risk ratio (RR): 0.56; 95% confidence interval (CI): 0.40–0.77; I2 = 0%) and coughing on the tube during extubation (RR: 0.58; 95% CI: 0.41–0.82; I2 = 0%). Additionally, patients in the dexmedetomidine group were more likely to develop bradycardia (RR: 2.46; 95% CI: 1.28–4.71; I2 = 0%) and hypotension (RR: 3.26; 95% CI: 1.14–9.33; I2 = 0%) during the administration of dexmedetomidine than those in the control group. Conclusion Perioperative intravenous administration of dexmedetomidine has a positive effect on the prevention of POST.
Association of BCL2 polymorphisms and the IL19 single nucleotide polymorphism rs2243188 with systemic lupus erythematosus
Authors: Wang Weijie , Wang Xinchang , Yang Kepeng , Fan Yongsheng 
Published: May 2021

Objective Abnormal B cell lymphoma-2 (Bcl-2) and interleukin-19 (IL-19) expression is closely related to systemic lupus erythematosus (SLE) pathogenesis. We aimed to determine whether BCL2 polymorphisms and a single nucleotide polymorphism (SNP) of IL19 are significantly associated with SLE susceptibility and if this is affected by synergism between IL19 and BCL2 genotypes. Methods This observational cohort study randomly enrolled 150 patients with SLE and 150 healthy controls. Major BCL2 and IL19 allele and genotype distributions were examined in the two groups. The IL19 SNP rs2243188 was determined using the TaqMan-MGB probe method. The synergistic effect between BCL2 and IL19 and clinical symptoms of SLE was also analyzed. Results The distribution of major BCL2 genotypes and common BCL2 alleles, especially for genotypes 191, 193, and 197, differed significantly between patients and controls. A significant difference in the dominant genetic model was also observed between groups, but not in the recessive model. The risk of disease in individuals who carried both 195-bp BCL2 and 138-bp IL19 susceptibility alleles was higher than in those carrying either allele alone. Conclusions This preliminary study suggested that BCL2 polymorphisms and the IL19 SNP rs2243188 are closely related to the pathogenesis of SLE.
Study of Gene Expression of Programmed Cell Death Ligand 1 (PD-L1) in Breast Cancer Patients
Authors: Gadelrab H , Mokhtar M , Morsy H , Elnaggar M 
Published: May 2021

Introduction: Breast cancer is the most frequently occurring cancer among females and the second most common cancer overall. Programmed Cell Death Ligand 1 (PD-L1) plays an important role in blocking ‘cancer-immunity cycle’ and is considered as a major inhibitory pathway. The aim of the present study was to clarify the alterations of expression of PD-L1 in peripheral blood mononuclear cytes (PBMCs) of female breast cancer patients and analyze its association with clinico-pathological criteria as well as therapeutic response. Materials and Methods: The study was conducted on 45 female breast cancer patients and 45 female controls. Blood samples were collected followed by PBMCs isolation, total RNA extraction, reverse transcription and finally, quantitative polymerase chain reaction (qPCR) using SYBR Green DNA binding dye. Expression levels of PD-L1 were calculated and then compared with clinicopathological parameters of the patients in addition to initial therapeutic response. Results: A significant difference was detected for PD-L1 expression levels in breast cancer patients compared to controls. A significant association with age, metastatic breast cancer, estrogen receptor (ER) negative status as well as high concentrations of cancer antigen 15-3 (CA15-3) was detected. On the other hand, no significant association was recognized with tumor size, lymph nodal status, histopathological type, grade, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER-2) status, triple negative, among de novo and recurrent metastatic patients and for the number of metastatic sites as well as the therapeutic response. Conclusions: This study paves the way of the use of PD-L1 as a noninvasive prognostic and diagnostic biomarker for poor prognosis of breast cancer.
Immunohistochemical Expression of CD68 in Triple Negative Invasive Ductal Carcinoma of the Breast and its Correlation with Clinicopathological Parameters
Authors: Khalaf AA , Fadaly GA , El-Sarha AI , El-Karmouty AF 
Published: May 2021

Introduction: Triple negative breast cancer (TNBC) is an aggressive form of breast cancer associated with a poor prognosis. No targeted treatment is available for this subtype. Tumor microenvironment (TME) has been increasingly considered a diagnostic and a prognostic biomarker and a therapeutic target for breast cancer. Tumor associated macrophages (TAM) are a pivotal member of TME and have been proposed as potential targets of therapy. Material and Methods: The immunohistochemical expression of CD68+ve TAM was studied in both tumor stroma (TS) and tumor nest (TN) in 50 cases of triple negative invasive ductal carcinoma as well as in 10 control cases of benign breast lesions. Results: The cases were divided into high or low density groups according to the median. The median in CD68+ve TAM in TS was (61.88), while in CD68+ve TAM in TN was (49.88). The expression of CD68+ve TAM in TS was low in 22 cases and high in 28 cases, while its expression in TN was low in 35 cases and high in 15 cases. There was no statistical association between high CD68+ve TAM in TN and different clinicopathological parameters, meanwhile a statistically significant association was found between high CD68 +ve TAM in TS and tumor grade, lymph/vascular invasion and lymph node metastasis. Conclusions: High expression of TAM in TS, but not in TN, is of clinical significance in patients with TNBC and highlights the importance of analyzing the localization rather than merely the presence of TAM as a marker for prognosis and a potential target for future treatment of triple negative breast cancer.
Hippocampal Dosimetric Evaluation in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Intensity Modulated Radiotherapy
Authors: Al Daly Moustafa , Makady Nafie F. 
Published: May 2021

Introduction: Treatment of locally advanced nasopharyngeal (Npx) cancer usually requires the inclusion of the sphenoid body or higher in intermediate risk CTV dose regions. This makes the avoidance of intracranial OAR such as temporal lobes, optic apparatus and cochlea challenging. There are different accumulating data confirming the impact of hippocampus (HC) irradiation on neurocognitive functions after whole brain radiotherapy & Npx cases were specifically addressed in several publications. The specified dose constrain in RTOG 0933 was Dmax <9 Gy. Our aim is to retrospectively evaluate the doses delivered to the HC in patients with locally advanced Npx carcinoma. Methods: Our study included twelve patients with locally advanced nasopharyngeal carcinoma (Stage III-IVA) previously treated at NEMROCK by either IMRT or VMAT. The HC was retrospectively delineated without being accounted for in the inverse treatment planning. Bilateral HC were delineated as a single OAR, and a margin of 3 mm was added to create the HC zone. We evaluated the doses delivered to the hippocampus by conducting a dosiemtric analysis on the treatment plan already used. Results: DVH Analysis: The mean volumes (std) for PTV70 primary, PTV70 LN and PTV59.4 were 83.62 cm3 (±33.51), 119.5 cm3 (±122.66) and 1017.58 cm3 (±140.28) respectively. The mean HC volume (std) was 4.17 cm3 (±1.66). The mean HC Dmin, Dmean, Dmedian and Dmax were 6.57 Gy, 25.05 Gy, 24.18 Gy and 52.95 Gy respectively. The mean HC V5, V10, V20, V40, V50 and V60 were 92.83%, 78.95%, 55.91%, 20.37%, 9.9% and 3.38% respectively. There was no difference between IMRT and VMAT in terms of HC volumetric and dosimetric parameters. Conclusion: In locally advanced Npx carcinoma, HC is exposed to significant doses, particularly with T4 disease (intracranial extension). In view of the low radiation tolerance of HC and its close proximity to CTV54-60 Gy in Npx cases, HC contouring and avoidance should be considered.
Out Come of Wide Local Excision with and without Corticosteroid Therapy in Management of Idiopathic Granulomatous Mastitis
Authors: Maher R Amira , Osman Ahmed Gamal Eldin , Fahmy K , M Shinamwi , Al Atarash Osama 
Published: May 2021

Introduction: Idiopathic granulomatous mastitis is a rare benign breast disease. Initial reports from hospitals in Egypt from Departments of Pathology at Cancer Institutes of Cairo, Tanta and Mansoura Universities; indicate that the disease is not as rare as that in the developed countries. It often mimics breast carcinoma both clinically and radiologically. Histological examination is the gold standard for diagnosis. Management of Idiopathic granulomatous mastitis is still debatable. In our study, we aimed to evaluate the addition of corticosteroid therapy to surgical excision in management of idiopathic granulomatous mastitis. Patients and Methods: This is a comparative study was conducted at Ain-Shams University Hospital’s breast clinic on patients with idiopathic granulomatous mastitis from to August 2015 till September 2018. Thirty patients were divided into 2 groups. Group (A) includes patients who underwent surgical management only. Group (B) includes patients who received corticosteroid therapy according to the severity of the cases then surgical Excision was done for the residual lesion. Follow up of all cases up to 1-2 years was done to document the recurrence rate and compare the cosmetic outcome of both groups. Informed consent was obtained from all patients included in the study. Results: The mean age of the affected women was 38.80 and 33.13 in group (A) and group (B), respectively and it wasn’t statistically different (p value = 0.099). The most common presenting symptom was a palpable mass in the breast (66.7% and 93.3%) in group (A) and group (B) respectively. Recurrence rate was higher in group (A) (40%) with no recurrence documented in group (B) however 2 cases were omitted from the study due to steroid noncompliance and complications. Cosmetic outcome was excellent in 76.9% of group (B) and good in 53.3% of group (A). Conclusion: Systemic steroid therapy with surgical resection is the recommended as first-line treatment strategy for IGM as it shows less recurrence rate and surgical scarring. Increased awareness of IGM will increase their understanding and improve their management.