bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED: Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma
Authors: Firouzi Amoodizaj Fatemeh , Baghaeifar Sevda , Taheri Elham , Farhoudi Sefidan Jadid Mahdieh , Safi Maryam , Seyyed Sani Nasrin , Hajazimian Saba , Isazadeh Alireza , Shanehbandi Dariush 
Published: March 2020

AbstractGastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer‐related death worldwide. The doxorubicin hydrochloride is one of the important chemotherapeutic anticancer agents, with a limited therapeutic efficacy for treatment of GC. Therefore, taking advantage of synergistic effects by strategies like combination therapy seems appropriate and promising in treatment of GC. The aim of this study was to investigate a novel method to enhance the therapeutic efficacy of doxorubicin (as a chemotherapeutic agent) by co‐administration of curcumin (as a bioactive herbal compound) in GC treatment. In the present study, the effects of curcumin, doxorubicin, and their combinations (Dox‐Cur) were evaluated on the viability, morphological features, tumor spheroid formation, migration, invasion, and apoptosis of gastric adenocarcinoma cell line (AGS). Moreover, expression levels of BAX, BCL‐2, and CASP9 genes were assessed among AGS cells treated with curcumin, doxorubicin, and Dox‐Cur. The obtained results showed that all of curcumin, doxorubicin, and Dox‐Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration‐ and time‐dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox‐Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox‐Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy.
Preparative separation of chlorogenic acid from Eucommia ulmoides extract via fractional extraction
Authors: Wang Wanru , Liu Fusong , Dai Guilin , Zhang Panliang , Tang Kewen 
Published: March 2020

AbstractBACKGROUNDChlorogenic acid is an important bioactive substance with wide pharmacological effects mostly related to scavenging free radicals and as an anti‐virus. This article reports on the continuous separation of chlorogenic acid from Eucommia ulmoides crude extract using multistage centrifugal fractional extraction.RESULTSAn efficient extraction system was constructed. A quantitative mathematical model was established to simulate and optimize the fractional extraction process, and the optimum process conditions were obtained. Residual rate was successfully introduced as the purity reference to optimize the separation of chlorogenic acid. Chlorogenic acid was continuously obtained from Eucommia ulmoides extract by fractional extraction in a cascade of ten stages with high purity of 97.2% and yield of 81.4%.CONCLUSIONFractional extraction is an efficient and likely unique technology to continuously and selectively separate target substance from complex natural extract. It has the advantages of large output and low cost, and is more suitable for industrial‐scale production. © 2020 Society of Chemical Industry
Carbon mineralization, biological indicators, and phytotoxicity to assess the impact of urban sewage sludge on two light‐textured soils in a microcosm
Authors: Hechmi Sarra , Hamdi Helmi , Mokni‐Tlili Sonia , Zoghlami Inès Rahma , Khelil Mohamed Naceur , Benzarti Saoussen , Hassen Abdennaceur , Jedidi Naceur 
Published: March 2020

AbstractThe agricultural reuse of urban sewage sludge (USS) modifies soil properties depending on sludge quality, management, and pedo‐environmental conditions. The aim of this microcosm study was to assess C mineralization and subsequent changes in soil properties after USS addition to two typical Mediterranean soils: sandy (Soil S) and sandy loam (Soil A) at equivalent field rates of 40 t ha−1 (USS‐40) and 120 t ha−1 (USS‐120). Outcomes proved the biodegradability of USS through immediate CO2 release inside incubation bottles in a dose‐dependent manner. Accordingly, the highest rates of daily C emission were recorded with USS‐120 (3.7 and 3.9 mg kg−1 d−1 for Soils S and A, respectively) after 84 d of incubation at 25 °C. The addition of USS also improved soil fertility by enhancing soil macronutrients, microbial proliferation, and protease activity. Protease showed significant correlation with N, total organic C, and heterotrophic bacteria, reflecting the biostimulation and bioaugmentation effects of sludge. Soil indices like C/N/P stoichiometry and metabolic quotient (qCO2) varied mostly with mineralization rates of C and P in both soils. Despite a significant increase of soil salinity and total heavy metal content (lead, nickel, zinc, and copper) with USS dose, wheat germination was not affected by these changes. Both experimental soils showed intrinsic (Soil A) and incubation‐induced (Soil S) phytotoxicities that were alleviated by USS addition. This was likely due to the enhancement of biodegradation and/or retention of phytotoxicants originating from previous land uses. Urban sewage sludge amendments could have applications in soil remediation by reducing the negative effects of allelopathic and/or anthropogenic phytoinhibitors.
Prognostic impact of the number of metastatic lymph nodes in distal bile duct cancer: An analysis of Japanese registration cases by the study group for biliary surgery of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery
Authors: Ishihara Shin , Horiguchi Akihiko , Endo Itaru , Wakaki Toshifumi , Hirano Satoshi , Yamaue Hiroki , Yamamoto Masakazu 
Published: March 2020

AbstractBackgroundLymph node metastasis is an important prognostic factor for distal bile duct cancer. The number of lymph node metastases was adopted for nodal classification. However, different cutoff values have been proposed, ranging from two to five.MethodsA total of 1748 cases who underwent curative surgery with pancreatoduodenectomy for distal bile duct cancer registered in the nationwide biliary tract cancer registry in Japan from 2008 to 2013 were included. Univariate Cox regression was performed to assess the effect of prognostic lymph node metastasis counts on mortality and to determine cutoff values.ResultsThe overall survival rate after resection was 47.4% at 5 years. Univariate and multivariate analysis found prognostic factors to include lymph node metastasis. The cutoff point was set to two lymph node metastases using the Cox model. There were significant differences in pairwise comparisons between three groups by the number of metastatic lymph node (P < .001 for 0 vs 1‐2 and P = .003 for 1–2 vs ≥3).ConclusionOur data suggest lymph node classification as N0 (patients without lymph node metastases), N1 (metastasis in 1–2 regional lymph nodes), and N2 (metastases in ≥3 regional lymph nodes).
Facile one‐pot, three‐component synthesis of novel bis(heterocycles) incorporating thieno[2,3‐b]thiophenes via Michael addition reaction
Authors: Eid Elshimaa M. , Hassaneen Huwaida M. E. , Abdelhamid Ismail A. , Elwahy Ahmed H. M. 
Published: March 2020

AbstractA synthesis of novel series of bis(2‐amino‐3‐cyano‐4H‐chromene), bis(2‐amino‐3‐cyanopyrano[3,2‐c]chromene), bis(6‐amino‐5‐cyano‐1,4‐dihydropyrano[2,3‐c]pyrazole), and bis(2,7‐diamino‐3,4,6‐tricyanopyrazolo[1,5‐a]pyridine) derivatives linked to thieno[2,3‐b]thiophene core via ether or ester linkages was reported. The formation of the target compounds presumably proceeds through a three component reaction of the appropriate bis(aldehyde) with 2 M of each of malononitrile and the corresponding active methylene compounds namely; dimedone, 4‐hydroxycoumarine, 5‐methyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one, or cyanomethylpyrazole in dioxane at reflux in the presence of piperdine as a basic catalyst. The chemical structures of the new compounds were elucidated by several spectral tools.
Cytomegalovirus, Epstein‐Barr virus, and human herpesvirus‐6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome
Authors: Shikova Evelina , Reshkova Valentina , Kumanova Аntoniya , Raleva Sevdalina , Alexandrova Dora , Capo Natasa , Murovska Modra , on behalf of the European Network on ME/CFS (EUROMENE)  
Published: March 2020

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem chronic disease. The etiology and pathogenesis of ME/CFS are unknown. Infections of cytomegalovirus (CMV), Epstein‐Barr virus (EBV), and human herpesvirus‐6 (HHV‐6) are suspected as etiological agents for ME/CFS. This study aims to estimate prevalence and type (active/latent) of EBV, CMV, and HHV‐6 infections in Bulgarian ME/CFS patients. In the study were included 58 patients with ME/CFS and 50 healthy controls. Virus‐specific antibodies were detected by enzyme‐linked immunosorbent assay and viral genomic sequences in peripheral blood mononuclear cell (PBMCs) and plasma samples by nested polymerase chain reaction (PCR). We did not observe any significant differences in virus‐specific immunoglobulin G and immunoglobulin M positivity rates between patients with ME/CFS and control group. In ME/CFS plasma samples, EBV DNA was found in 24.1%, CMV DNA in 3.4%, and HHV‐6 DNA in 1.7% of samples. EBV DNA was detected in 4%, and CMV and HHV‐6 DNA were not found in plasma samples of controls. The frequency of viral genome detection in PBMCs of patients and controls was 74% vs 78% for CMV, 81% vs 84% for EBV, and 82.8% vs 82% for HHV‐6. The difference in frequency of EBV active infection in ME/CFS and control group was statistically significant (P = .0027). No ME/CFS and control individuals with active CMV and HHV‐6 infection were observed. In conclusion, this study using both serological and PCR‐based techniques for distinguishing between active and latent infection showed high rate of active EBV infection among patients with ME/CFS indicating that at least in a subset of cases, EBV is important factor for the development of disease.
Circadian rhythms in the mouse reproductive axis during the estrous cycle and pregnancy
Authors: Yaw Alexandra M. , Duong Thu V. , Nguyen Duong , Hoffmann Hanne M. 
Published: March 2020

AbstractMolecular and behavioral timekeeping is regulated by the circadian system which includes the brain's suprachiasmatic nucleus (SCN) that translates environmental light information into neuronal and endocrine signals aligning peripheral tissue rhythms to the time of day. Despite the critical role of circadian rhythms in fertility, it remains unexplored how circadian rhythms change within reproductive tissues during pregnancy. To determine how estrous cycle and pregnancy impact phase relationships of reproductive tissues, we used PER2::Luciferase (PER2::LUC) circadian reporter mice and determined the time of day of PER2::LUC peak (phase) in the SCN, pituitary, uterus, and ovary. The relationships between reproductive tissue PER2::LUC phases changed throughout the estrous cycle and late pregnancy and were accompanied by changes to PER2::LUC period in the SCN, uterus, and ovary. To determine if the phase relationship adaptations were driven by sex steroids, we asked if progesterone, a hormone involved in estrous cyclicity and pregnancy, could regulate Per2‐luciferase expression. Using an in vitro transfection assay, we found that progesterone increased Per2‐luciferase expression in immortalized SCN (SCN2.2) and arcuate nucleus (KTAR) cells. In addition, progesterone shortened PER2::LUC period in ex vivo uterine tissue recordings collected during pregnancy. As progesterone dramatically increases during pregnancy, we evaluated wheel‐running patterns in PER2::LUC mice. We confirmed that activity levels decrease during pregnancy and found that activity onset was delayed. Although SCN, but not arcuate nucleus, PER2::LUC period changed during late pregnancy, onset of locomotor activity did not correlate with SCN or arcuate nucleus PER2::LUC period.
Rare variants and biological pathways identified in treatment‐refractory depression
Authors: McClain Lora Lee , Shaw Patricia , Sabol Roisin , Chedia Anna Maria , Segretti Anna Maria , Rengasamy Manivel , Finegold David N. , Pan Lisa , Peters David Gerard 
Published: March 2020

AbstractIndividuals diagnosed with major depressive disorder not responding to at least two adequate treatments are defined as treatment‐refractory major depressive disorder (TR‐MDD). Some TR‐MDD patients have altered metabolic phenotypes that may be pharmacologically reversed. The characterization of these phenotypes and their underlying etiologies is paramount, particularly their genetic components. In this study, TR‐MDD patients (n = 124) were recruited and metabolites were quantified in their cerebrospinal fluid (CSF) and peripheral blood. Three sub‐categories of deficiencies were examined, namely 5‐methyltetrahydrofolte (in CSF; n = 13), tetrahydrobiopterin (in CSF; n = 11), and abnormal acylcarnitine profiles (in peripheral blood; n = 8). Whole exome sequencing was performed on genomic DNA from the entire TR‐MDD cohort and exonic variant allele frequencies for cases were compared to a control cohort (1:5 matching on ancestry). Low frequency, damaging alleles were identified and used for in silico pathway analyses. Three association signals for TR‐MDD approached genome‐wide significance on chromosomes 22, 7, and 3. Three risk‐associated variants from a prior depression study were replicated. Relevant biological pathways were identified that contained an enrichment of rare, damaging variants in central nervous system (CNS)‐specific pathways, including neurotransmitter receptors, potassium channels, and synapse transmission. Some TR‐MDD patients had rare variants in genes that were previously associated with other psychiatric disorders, psychiatric endophenotypes, CNS structural defects, and CNS‐related cellular and molecular functions. Exome analysis of metabolically phenotyped TR‐MDD patients has identified potentially functional gene pathways and low frequency, deleterious gene variants for further investigation. Further studies in larger cohorts of biochemically phenotyped TR‐MDD patients are desirable to extend and confirm these findings.
A newly isolated Streptomyces rimosus strain capable of degrading deltamethrin as a pesticide in agricultural soil
Authors: Khajezadeh Masoud , Abbaszadeh‐Goudarzi Kazem , Pourghadamyari Hossein , Kafilzadeh Farshid 
Published: March 2020

AbstractChemical pesticides or insecticides with complex structures are highly abundant in the biosphere and have inevitable side effects on farmland, natural resources, and human health. Deltamethrin is the most popular and widely used pesticide that disrupts the cellular calcium channels. In the present study, isolated strains of bacteria were examined to determine the ones that were capable of degrading deltamethrin. Different species of bacteria were evaluated in terms of the capability to degrade deltamethrin. It is important to note that Streptomyces rimosus was able to degrade up to 200 mg/L deltamethrin concentration and could be grown in mineral salt medium agar containing deltamethrin to be used as a source of carbon and energy. The results demonstrated that there is a diversity of deltamethrin‐degrading bacteria in agricultural soil ecosystems. The application of these bacteria, especially S. rimosus, might be used as a bioremediation technique to decrease pesticide contamination of the ecosystem.
Comparison between two rabbit models of posttraumatic osteoarthritis: A longitudinal tear in the medial meniscus and anterior cruciate ligament transection
Authors: Huang Kai , Cai Hai‐li , Zhang Peng‐li , Wu Li‐dong 
Published: March 2020

AbstractAnimal osteoarthritis (OA) models have been developed to understand OA progression and evaluate new OA therapies. However, individual variations in joint lesions remain a critical problem in most current OA models. We established a novel rabbit model by creating a longitudinal tear in the medial meniscus body that was reproducible and similar to posttraumatic biomechanical disturbances in human OA. New Zealand rabbits underwent surgery and were assessed for 9 weeks. The rabbits were randomized into the sham control, medial meniscal tear (MMT), and anterior cruciate ligament transection (ACLT) groups. The animals were sacrificed at 4, 6, and 9 weeks posttreatment. The knee joints were harvested for histological and gene expression assessments. Both the MMT and ACLT procedures led to time‐dependent degenerative changes in the femoral condyle cartilage. At each time point, the MMT group cartilage showed more severe degenerative changes than did the ACLT group cartilage. Consistently, inflammatory cytokine and catabolic gene expression were significantly higher, and anabolic gene expression was significantly lower in the MMT group than in the ACLT group. MMT treatment caused more severe structural damage to the cartilage and higher catabolic gene expression levels than the ACLT model at each time point. The MMT model may be highly beneficial in investigating posttraumatic OA (PTOA) development, especially PTOA from a meniscal injury. The MMT model replicated key features of human PTOA, including meniscal lesions, inflammatory responses, and the progression to osteoarthritic cartilage degeneration, thereby providing an exciting new avenue for translating promising treatments to clinical practice.
Addition of [18F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross‐Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma
Authors: John Binu V. , Aubuchon Sean , Dahman Bassam , Konjeti Venkata Rajesh , Heuman Douglas , Hubert Jennifer , Thomas Smitha , Deng Yangyang , Solomon Cynthia , Sundaram Latha Thankam , Love Eleanor , Singal Amit G. , Tatum James L. 
Published: March 2020

In this work, we characterize the value of positron emission tomography (PET) with computed tomography (CT) in combination with cross‐sectional imaging for staging and prognostication of hepatocellular carcinoma (HCC) patients. In this retrospective cohort study, HCC patients underwent PET‐CT after initial staging with contrast‐enhanced CT or magnetic resonance imaging (MRI). The benefit of PET‐CT was measured by the identification of new HCC lesions, and potential harm was quantified by the number of false positives and subsequent diagnostic evaluation. We used multivariate Cox regression analysis to evaluate the association between the highest grade on PET‐CT with the risk of extrahepatic metastasis, progression‐free, and overall survival. Among 148 patients, PET‐CT detected additional extrahepatic metastasis in 11.9% of treatment‐naïve and 13.8% of treatment‐experienced patients. PET‐CT changed the Barcelona Clinic Liver Cancer (BCLC) staging in 5.9% of treatment‐naïve and 18.8% of treatment‐experienced patients compared with CT/MRI alone, changing HCC management in 9.9% and 21.3% of patients, respectively. Of the patients, 5% (n = 8) experienced severe physical harm requiring additional procedures to evaluate extrahepatic findings. High tumor grade on PET‐CT was independently associated with a higher likelihood of extrahepatic metastasis (hazard ratio [HR], 17.1; 95% confidence interval [CI], 3.6‐81.5) and worse overall survival (HR, 2.4; 95% CI, 1.4‐4.3). Treatment‐experienced patients (versus treatment‐naïve patients; HR, 9.7; 95% CI, 1.9‐49.4) and BCLC stage A (HR, 8.2; 95% CI, 1.5‐45.9; P < 0.01) and BCLC stage B (HR, 20.6; 95% CI, 1.5‐282.2; P < 0.05) were more likely to have an upstaging with PET‐CT compared with BCLC stage C (reference). PET‐CT provides prognostic information and improves tumor staging beyond CT/MRI alone, with subsequent changes in management for patients with HCC.
Composition, diversity, and activity of aerobic ammonia‐oxidizing Bacteria and Archaea in the intertidal sands of a grand strand South Carolina beach
Authors: Taylor Harrison B. , Kurtz Harry D. 
Published: March 2020

AbstractAerobic ammonia oxidation to nitrite has been established as an important ecosystem process in regulating the level of nitrogen in marine ecosystems. This process is carried out by ammonia‐oxidizing bacteria (AOB) within the classes Betaproteobacteria and Gammaproteobacteria and ammonia‐oxidizing Archaea (AOA) from the phylum Thaumarchaeota, and the latter of which has been established as more prevalent in marine systems. This study investigated the presence, abundance, and activity of these groups of microbes at a beach near Springmaid Pier in Myrtle Beach, South Carolina, through the implementation of next generation sequencing, quantitative PCR (qPCR), and microcosm experiments to monitor activity. Sequencing analysis revealed a diverse community of ammonia‐oxidizing microbes dominated by AOA classified within the family Nitrosopumilaceae, and qPCR revealed the abundance of AOA amoA genes over AOB by at least an order of magnitude in most samples. Microcosm studies indicate that the rates of potential ammonia oxidation in these communities satisfy Michaelis–Menten substrate kinetics and this process is more active at temperatures corresponding to summer months than winter. Potential rates in AOA medium were higher than that of AOB medium, indicating a potentially greater contribution of AOA to this process in this environment. In conclusion, this study provides further evidence of the dominance of AOA in these environments compared with AOB and highlights the overall efficiency of this process at turning over excess ammonium that may be present in these environments.
Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
Authors: Xu T. , Liu T. , Li G. , Dugal C. , Aydemir N. A. , Liu Y. , Roeske J. C. 
Published: March 2020

PurposeTo predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro‐level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha‐immuno‐conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly nonuniform and unsteady distributions of irradiation sources. Since the micro‐level distribution of emitters cannot be measured and obtained in patients with current technology, a modeling toolset to give more insight of the internal dose could be an alternative.MethodsA multi‐physics model based on a Monte Carlo microdosimetry technique and computational fluid dynamics (CFD) modeling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time‐dependent absorbed dose to the target.ResultsThe conceptual model is capable of handling complex nonuniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios.ConclusionModeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future.