bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous totally robotic rectal resection and partial nephrectomy: case report and review of literature
Authors: Cochetti G. , Tiezzi A. , Spizzirri A. , Giuliani D. , Rossi de Vermandois J. A. , Maiolino G. , Coccetta M. , Napolitano V. , Pennetti Pennella F. , Francesconi S. , Mearini E.
Published: May 2020

Introduction

The incidence of synchronous RCC and colorectal cancer is heterogeneous ranging from 0.03 to 4.85%. Instead, only one case of huge colon carcinoma and renal angiomyolipoma was reported. The treatment of synchronous kidney and colorectal neoplasm is, preferably, synchronous resection. Currently, laparoscopic approach has shown to be feasible and safe, and it has become the gold standard of synchronous resection due to advantages of minimally invasive surgery. We presented a case synchronous renal neoplasm and colorectal cancer undergone simultaneous totally robotic renal enucleation and rectal resection with primary intracorporeal anastomosis. As our knowledge, this is the first case in literature of simultaneous robotic surgery for renal and colorectal tumor.

Case presentation

A 53-year-old woman was affected by recto-sigmoid junction cancer and a solid 5 cm left renal mass. We performed a simultaneous robotic low anterior rectal resection and renal enucleation. Total operative time was 260 min with robotic time of 220 min; estimated blood loss was 150 ml; time to flatus was 72 h, and oral diet was administered 4 days after surgery. The patient was discharged on the eighth post-operative day without peri- and post-operative complication. The definitive histological examination showed a neuroendocrine tumor pT2N1 G2, with negative circumferential and distal resection margins. Renal tumor was angiomyolipoma. At 23 months follow-up, the patient is recurrence free.

Discussion and conclusion

As our knowledge, we described the first case in literature of simultaneous robotic anterior rectal resection and partial nephrectomy for treatment of colorectal tumor and renal mass. Robotic rectal resection with intracorporeal anastomosis surgery seems to be feasible and safe even when it is associated with simultaneous partial nephrectomy. Many features of robotic technology could be useful in combined surgery. This strategy is recommended only when patients’ medical conditions allow for longer anesthesia exposure. The advantages are to avoid a delay treatment of second tumor, to reduce the time to start the post-operative adjuvant chemotherapy, to avoid a second anesthetic procedure, and to reduce the patient discomfort. However, further studies are needed to evaluate robotic approach as standard surgical strategy for simultaneous treatment of colorectal and renal neoplasm.
The economic benefits of increasing breastfeeding rates in Spain
Authors: Quesada Juan Antonio , Méndez Ildefonso , Martín-Gil Rocío
Published: May 2020

Background

Interventions aimed at promoting breastfeeding rates are among the most effective possible health policies available, with an estimated return of US$35 per dollar invested. Indeed, some authors found that a 10% increase in exclusive breastfeeding rates in the first two years of life led to a reduction in treatment costs of US$312 million in the US, US$7.8 million in the UK, US$30 million in China, and US$1.8 million in Brazil. Among high-income countries, Spain stands out for its low breastfeeding rate.

Methods

We calculated the savings that the Spanish National Health System would have benefited from had breastfeeding rates been higher in Spain, both from the time of hospital discharge and at 6 months postpartum. We followed the methods used in similar studies carried out in the US, Italy, Australia, the Netherlands, and the UK, to conservatively estimate these potential savings by considering only the lower thresholds in all our estimates. Here we approximated the benefits of having increased exclusive breastfeeding rates based on the lower incidence of infantile pathologies among exclusively breastfed infants. Robust evidence indicates that among breastfed infants there is a lower prevalence of otitis media, gastroenteritis, respiratory infections, and necrotising enterocolitis. We obtained the estimated monetary cost of these diseases by combining their prevalences with data about their economic costs for diagnosis-related groups.

Results

The estimated effects we calculated imply that the Spanish National Health System could have saved more than €5.6 million for every percentage point increase in exclusive breastfeeding rates in Spain during 2014.

Conclusions

Breastfeeding is essential both for the health of mothers and the health and development of newborns but is rarely considered as an economic issue and remains economically invisible. In addition to the improved wellbeing of mothers and their infants, breastfeeding can positively impact society as a whole and should therefore be better defined in public policies. Thus, strategies aimed at increasing exclusive breastfeeding rates would likely contribute to lowering the fiscal burden of the Spanish National Health System. Moreover, the magnitude of these potential benefits suggests that such policies would likely be socially cost–effective.
Primary undifferentiated spindle cell sarcoma obstructing the right ventricular outflow tract
Authors: Kwon Jintae , Kwon Kyewon
Published: May 2020

Background

Primary undifferentiated spindle cell sarcoma in the right ventricle is an extremely rare tumor. Radical surgical excision is the optimal treatment for long-term survival due to poor response to chemotherapy or radiotherapy at an advanced stage.

Case presentation

A 42-year-old man with no previous medical history presented with mild dyspnea on exertion and abdominal distension that lasted a week. Computed tomography (CT) revealed a huge homogeneous mass completely obstructing the right ventricle and extending into the pulmonary trunk. However, he suddenly collapsed the next day while on his way to an echocardiography. An extracorporeal membrane oxygenation (ECMO) device was inserted percutaneously and ECMO support was urgently initiated. Based on consideration of right ventricular outflow tract (RVOT) obstruction in the initial CT scan, we decided to remove the mass from the right ventricle immediately. The main mass was resected to relieve the RVOT obstruction, and after the operation, the ECMO was removed from the operation room. However, the patient failed to regain consciousness and electroencephalography (EEG) and subsequent magnetic resonance imaging (MRI) indicated severe hypoxic brain damage. We assume CPR was unsuccessful because the mass completely blocked the RVOT. Pathology revealed the mass was an undifferentiated spindle cell sarcoma.

Conclusions

We present the case of a 42-year-old male with cardiac arrest due to right ventricular outflow tract obstruction by a tumor of the right ventricle. Surgical resection was performed and in histopathology it was proved to be an undifferentiated spindle cell sarcoma.
Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers
Authors: Mittica Gloria , Goia Margherita , Gambino Angela , Scotto Giulia , Fonte Mattia , Senetta Rebecca , Aglietta Massimo , Borella Fulvio , Sapino Anna , Katsaros Dionyssios , Maggiorotto Furio , Ghisoni Eleonora , Giannone Gaia , Tuninetti Valentina , Genta Sofia , Eusebi Chiara , Momi Marina , Cassoni Paola , Valabrega Giorgio
Published: May 2020

Background

Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm a predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival.

Results

We collected an additional 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous (p <  0.001) and as discrete variable (10% cut-off: p <  0.003; Immunoreactive score: p <  0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the combined dataset, combining data of new validation cohort with the previously published cohort, showed that AR <  10% significantly correlates with worse outcomes (p = 0.005 for Progression Free Survival (PFS) and p = 0.002 for brain PFS (bPFS) respectively).

Comparison of AR expression between primary tissue and paired brain metastases in the combined dataset did not show any statistically significant difference.

Conclusions

We confirmed AR loss as predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients’ prognosis.
MicroRNA-145-5p regulates the proliferation of epithelial ovarian cancer cells via targeting SMAD4
Authors: Zhou Jie , Zhang Xiyi , Li Weiling , Chen Yuanyuan
Published: May 2020

Background

Epithelial ovarian cancer (EOC) is one of the most prevalent malignancies affecting females worldwide; however, its etiology mechanism remains unclear. In various malignancies, miR-145-5p is a widely accepted and versatile miRNA. Therefore, our research focused on exploring the activity and etiology of miR-145-5p in the modulation of metastasis, migration, and proliferation of EOC cells. The direct reactions between the 3′UTRs of SMAD4 mRNA and miR-145-5p were verified using dual luciferase reporter test. SKOV-3 cells were subsequently transfected using miR-145-5p mimics. Cell migration, death, and proliferation were evaluated using MTT, flow cytometry, and Transwell test. In addition, SMAD4 transcription and translation were evaluated using qRT-PCR and Western blot.

Results

We found that miR-145-5p expression was repressed prevalently in EOC tissues, apart from SMAD4 upregulation. Excessive miR-145-5p expression remarkably reinforced EOC cell death and repressed EOC cell proliferation. Furthermore, upregulated miR-145-5p expression noticeably repressed migration via MMP-2 and MMP-9 downregulation. Moreover, SMAD4 was downregulated via miR-145-5p transfection. The dual luciferase test revealed that miR-145-5p directly targeted SMAD4.

Conclusions

Our research suggests that miR-145-5p serves as a malignancy repressor and exerts an essential impact on inhibiting malignancy generation and reinforcing EOC death via targeting SMAD4. MiR-145-5p application could serve as a promising strategy to treat EOC.
Correction to: Comparative effectiveness of post-discharge strategies for hospitalized smokers: Study protocol for the Helping HAND 4 randomized controlled trial
Authors: Rigotti Nancy A. , Schnitzer Kristina , Davis Esa M. , Regan Susan , Chang Yuchiao , Kelley Jennifer H. K. , Notier Anna E. , Gilliam Karen , Douaihy Antoine , Levy Douglas E. , Singer Daniel E. , Tindle Hilary A.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Implementation of an intervention to improve the adoption of asthma self-management practices in Peru: Asthma Implementation Research (AIRE) randomized trial study protocol
Authors: Romani Elisa D. , Siddharthan Trishul , Lovatón Nair , Alvítez-Luna Carol C. , Flores-Flores Oscar , Pollard Suzanne L.
Published: May 2020

Introduction

Asthma is the most common chronic disease among children worldwide, with 80% of asthma-related deaths occurring in low- and middle-income countries (LMICs). While evidence-based guidelines exist for asthma treatment and management, adoption of guideline-based practices is low in high-income country and LMIC settings alike. While asthma prevalence among children and adolescents in Lima, Peru is in the range of 13%–19.6%, our data suggest that < 5% of children in low-resource communities are currently taking guideline-based therapies. There is an urgent need for effective, locally tailored solutions to address the asthma treatment gap in low-income communities in Peru.

Methods

This study aims to develop and test a locally adapted intervention package to improve adoption of self-management practices and utilization of preventive health services for asthma among children in Lima Norte. The intervention package was designed using a systematic, theory-based framework (Capability, Opportunity, Motivation – Behavior Framework) and is rooted in a multi-phased formative research approach. The main study design is an individually randomized implementation-effectiveness hybrid trial enrolling 110 children aged 5–17 years with asthma and their caregivers. Families allocated to the treatment group receive the supported self-management intervention package, while families allocated to the control group receive the standard of care plus asthma education. We will follow participants monthly for six months and evaluate asthma control (Asthma Control Test), healthcare utilization, and medication adherence (Adherence to Refills and Medications Scale). Disease-specific quality of life for children (Pediatric Asthma Quality of Life Questionnaire) and caregivers (Pediatric Asthma Caregiver’s Quality of Life Questionnaire) will be evaluated at baseline, 3 months, and 6 months. We will also evaluate acceptability, feasibility, and fidelity of the intervention using mixed methods approaches.

Discussion

The long-term goal of this study is to disseminate locally appropriate asthma management strategies in LMIC settings. This study will contribute to the body of knowledge surrounding approaches for developing and evaluating intervention strategies for asthma using systematic, theory-based approaches grounded in local context. Such strategies have the potential to inform the development and adaptation of appropriate and scalable solutions for asthma management in LMIC settings.

Trial registration

ClinicalTrials.gov, NCT03986177. Registered on 14 June 2019.
The impact of sex and gender on immunotherapy outcomes
Authors: Klein Sabra L. , Morgan Rosemary
Published: May 2020

Immunotherapies are often used for the treatment, remission, and possible cure of autoimmune diseases, infectious diseases, and cancers. Empirical evidence illustrates that females and males differ in outcomes following the use of biologics for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA), infectious diseases, e.g., influenza, and solid tumor cancers. Females tend to experience more adverse reactions than males following the use of a class of biologics referred to as immunotherapies. For immunotherapies aimed at stimulating an immune response, e.g., influenza vaccines, females develop greater responses and may experience greater efficacy than males. In contrast, for immunotherapies that repress an immune response, e.g., tumor necrosis factor (TNF) inhibitors for RA or checkpoint inhibitors for melanoma, the efficacy is reportedly greater for males than females. Despite these differences, discrepancies in reporting differences between females and males exist, with females have been historically excluded from biomedical and clinical studies. There is a critical need for research that addresses the biological (i.e., sex) as well as sociocultural (i.e., gender) causes of male-female disparities in immunotherapy responses, toxicities, and outcomes. One-size-fits-all approaches to immunotherapies will not work, and sex/gender may contribute to variable treatment success, including adherence, in clinical settings.
Correction to: Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy‑associated cardiomyopathy
Authors: Wang Yi , Guo Zhiheng , Gao Yongmei , Liang Ping , Shan Yanhong , He Jin
Published: May 2020

Following publication of the original article [1], the authors identified an error in Figs. 1b, 5b.
Direct activation of tRNA methyltransferase-like 1 (Mettl1) gene by thyroid hormone receptor implicates a role in adult intestinal stem cell development and proliferation during Xenopus tropicalis metamorphosis
Authors: Na Wonho , Fu Liezhen , Luu Nga , Shi Yun-Bo
Published: May 2020

Background

Thyroid hormone (T3) plays an important role in vertebrate development. Compared to the postembryonic development of uterus-enclosed mammalian embryos, T3-dependent amphibian metamorphosis is advantageous for studying the function of T3 and T3 receptors (TRs) during vertebrate development. The effects of T3 on the metamorphosis of anurans such as Xenopus tropicalis is known to be mediated by TRs. Many putative TR target genes have been identified previously. Among them is the tRNA methyltransferase Mettl1.

Results

We studied the regulation of Mettl1 gene by T3 during intestinal metamorphosis, a process involves near complete degeneration of the larval epithelial cells via apoptosis and de novo formation of adult epithelial stem cells and their subsequent proliferation and differentiation. We observed that Mettl1 was activated by T3 in the intestine during both natural and T3-induced metamorphosis and that its mRNA level peaks at the climax of intestinal remodeling. We further showed that Mettl1 promoter could be activated by liganded TR via a T3 response element upstream of the transcription start site in vivo. More importantly, we found that TR binding to the TRE region correlated with the increase in the level of H3K79 methylation, a transcription activation histone mark, and the recruitment of RNA polymerase II by T3 during metamorphosis.

Conclusions

Our findings suggest that Mettl1 is activated by liganded TR directly at the transcriptional level via the TRE in the promoter region in the intestine during metamorphosis. Mettl1 in turn regulate target tRNAs to affect translation, thus facilitating stem cell formation and/or proliferation during intestinal remodeling.
RETRACTED ARTICLE: Research on the construction and simulation of PO-Dijkstra algorithm model in parallel network of multicore platform
Authors: Zhang Bo , Hu De Ji
Published: May 2020

The development of multicore hardware has provided many new development opportunities for many application software algorithms. Especially, the algorithm with large calculation volume has gained a lot of room for improvement. Through the research and analysis, this paper has presented a parallel PO-Dijkstra algorithm for multicore platform which has split and parallelized the classical Dijkstra algorithm by the multi-threaded programming tool OpenMP. Experiments have shown that the speed of PO-Dijkstra algorithm has been significantly improved. According to the number of nodes, the completion time can be increased by 20–40%. Based on the improved heterogeneous dual-core simulator, the Dijkstra algorithm in Mi Bench is divided into tasks. For the G.72 encoding process, the number of running cycles using “by function” is 34% less than using “divided by data,” while the power consumption is only 83% of the latter in the same situation. Using “divide by data” will reduce the cost and management difficulty of real-time temperature. Using “divide by function” is a good choice for streaming media data. For the Dijkstra algorithm, the data is data without correlation, so using a simpler partitioning method according to the data partitioning can achieve good results. Through the simulation results and the analysis of the results of real-time power consumption, we conclude that for data such as strong data correlation of streaming media types, using “divide by function” will have better performance results; for data types where data correlation is not very strong, the effect of using “divide by data” is even better.
RETRACTED ARTICLE: Parameter estimation of network signal normal distribution applied to carbonization depth in wireless networks
Authors: Cai Min , Yang Jun
Published: May 2020

For the average state of the normal distribution parameter estimation, regular normal distribution parameter gives an estimation, but the carbonation depth of influence factors is more of a parameter estimation, shooting low deficiencies; therefore, putting forward application in the carbonation depth of the normal distribution parameter is estimated. A normal distribution parameter estimation model is constructed, and a normal distribution parameter estimation model framework is constructed by using the least squares method to determine the expression of normal distribution parameters. Based on the linear deviation calculation of normal distribution parameters and the determination of the maximum similar value of parameters, the parameter estimation is realized by using the Bayesian function of carbonization depth. The parameter estimation of network signal based on carbonization depth is proposed. Parameter estimation can play an important role in the intelligent analysis of big data, and it is also an important basic guarantee for machine learning algorithms. Using the integrity test results and error rate test result, variable parameters calculated from measured parameters, substitution shooting parameters calculation formula of parameter estimation is put forward by the conventional parameter estimation methods, which shot up to 22.12%, is suitable for the carbonation depth of the normal distribution parameter estimation.
Anti-inflammatory effect of hispidin on LPS induced macrophage inflammation through MAPK and JAK1/STAT3 signaling pathways
Authors: Han Ying-Hao , Chen Dong-Qin , Jin Mei-Hua , Jin Ying-Hua , Li Jing , Shen Gui-Nan , Li Wei-Long , Gong Yi-Xi , Mao Ying-Ying , Xie Dan-Ping , Lee Dong-Seok , Yu Li-Yun , Kim Sun-Uk , Kim Ji-Su , Kwon Taeho , Cui Yu-Dong , Sun Hu-Nan
Published: May 2020

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.
What is the significance of the traditional pinching mode of holding chopsticks?
Authors: Shimomura Yoshihiro , Ohsawa Takeaki , Shimura Megumi , Xia Yali , Iwanaga Koichi , Katsuura Tetsuo
Published: May 2020

Background

The purpose of this study was to clarify the influence of manipulation mode of chopsticks on the learning process, using assessment of task performance and electromyography, and to understand the significance of the traditional manipulation mode from the viewpoint of physiological anthropology. Previous studies have described two modes of manipulating chopsticks, the traditional pincers-pinching mode and the scissors-pinching mode.

Methods

We conducted experiments with two conditions of holding chopsticks: scissors mode and pincers mode. Eight subjects participated and were assigned to these modes, and they learned handling tasks in their assigned mode for 5 days with the non-dominant hand. We measured task execution times and conducted electromyography of the following muscles: first dorsalis interosseus, flexor pollicis brevis, flexor digiti minimi brevis, flexor digitorum superficialis, and extensor digitorum.

Results

The training effects were found in each mode. The pincers mode showed significantly shorter task performance times than did scissors mode. On electromyography, significant increases in activity of flexor digiti minimi brevis and tended an increase in flexor digitorum superficialis and a decrease in extensor digitorum occurred in pincers mode but not in scissors mode.

Conclusions

The traditional mode of holding chopsticks was associated with not only high task performance but also an advantage in terms of learning motor control.
Early recovery following new onset anosmia during the COVID-19 pandemic – an observational cohort study
Authors: Hopkins Claire , Surda Pavol , Whitehead Emily , Kumar B. Nirmal
Published: May 2020

Background

A rapidly evolving evidence suggests that smell and taste disturbance are common symptoms in COVID-19 infection. As yet there are no reports on duration and recovery rates. We set out to characterise patients reporting new onset smell and taste disturbance during the COVID-19 pandemic and report on early recovery rates.

Methods

Online Survey of patients reporting self-diagnosed new onset smell and taste disturbance during the COVID-19 pandemic, with 1 week follow-up.

Results

Three hundred eighty-two patents completed bot an initial and follow-up survey. 86.4% reported complete anosmia and a further 11.5% a very severe loss of smell at the time of completing the first survey. At follow-up 1 week later, there is already significant improvement in self-rating of severity of olfactory loss. 80.1% report lower severity scores at follow-up, 17.6% are unchanged and 1.9% are worse. 11.5% already report compete resolution at follow up, while 17.3% report persistent complete loss of smell, with reported duration being 1 to over 4 weeks. This is reflected in the overall cumulative improvement rate of 79% patients overall in the interval between surveys.

Conclusions

A review of the growing evidence base supports the likelihood that out cohort have suffered olfactory loss as part of COVID-19 infection. While early recovery rates are encouraging, long term rates will need to be further investigated and there may be an increase in patients with persistent post-viral loss as a result of the pandemic. We further call for loss of sense of smell to be formerly recognised as a marker of COVID-19 infection.
Differential gene methylation and expression of HOX transcription factor family in orbitofacial neurofibroma
Authors: Arnold Antje , Imada Eddie Luidy , Zhang M. Lisa , Edward Deepak P. , Marchionni Luigi , Rodriguez Fausto J.
Published: May 2020

Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. In orbitofacial neurofibromatosis type 1, NFs may cause progressive, disfiguring tumors of the lid, brow, temple, face and orbit. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We used Illumina Methylation EPIC BeadChip to study DNA methylation differences between orbitofacial NFs (N = 20) and NFs at other sites (N = 4). Global methylation differences were detected between the two groups and the top differentially methylated genes were part of the HOX (Homebox) family of transcription factors (HOXC8, HOXC4, HOXC6, HOXA6 and HOXD4), which were hypomethylated in orbitofacial NFs compared to the non-orbital NFs. Conversely, LTF (lactoferrin) was relatively hypermethylated in orbitofacial NF compared to non-orbitofacial NF. HOXC8 protein levels were higher in orbitofacial plexiform NFs (p = 0.04). We found no significant differences in the expression of HOXC4, HOXA6, or HOXD4 between the two groups. HOXC8 mRNA levels were also higher in orbitofacial NFs and HOXC8 overexpression in a non-neoplastic human Schwann cell line resulted in increased growth. In summary, we identified gene methylation and expression differences between orbitofacial NF and NFs occurring at other locations. Further investigation may be warranted, given that the HOX family of genes play an important role during development, are dysregulated in a variety of cancers, and may provide novel insights into therapeutic approaches.
miR-185-5p response to usnic acid suppresses proliferation and regulating apoptosis in breast cancer cell by targeting Bcl2
Authors: Değerli Elif , Torun Vildan , Cansaran-Duman Demet
Published: May 2020

Background

Breast cancer is the most common cancer types among women. Recent researches have focused on determining the efficiency of alternative molecules and miRNAs in breast cancer treatment. The aim of this study was to determine the effect of usnic acid response-miR-185-5p on proliferation in the breast cancer cell and to determine its relationship with apoptosis pathway.

Methods

The cell proliferation and cell apoptosis rate were significantly increased following the ectopic expression of miR-185-5p in BT-474 cells. Furthermore, the results of cell cycle assay performed by flow cytometry revealed that the transfection with miR-185-5p induced G1/S phase arrest. The apoptosis-related genes expression analysis was performed by qRT-PCR and the direct target of miR-185-5p in BT-474 cells was identified by western blot and luciferase reporter assay.

Results

Our data showed that miR-185-5p can cause significant changes in apoptosis-related genes expression levels, suggesting that cell proliferation was suppressed by miR-185-5p via inducing apoptosis in breast cancer cells. According to western blot results, miR-185-5p lead to decrease BCL2 protein level in BT-474 cells and direct target of miR-185-5p was identified as BCL by luciferase reporter assay.

Conclusion

This study revealed that miR-185-5p may be an effective agent in the treatment of breast cancer.
Simultaneous determination of itraconazole and its CYP3A4-mediated metabolites including N-desalkyl itraconazole in human plasma using liquid chromatography-tandem mass spectrometry and its clinical application
Authors: Imoto Yumi , Mino Yasuaki , Naito Takafumi , Ono Takaaki , Kawakami Junichi
Published: May 2020

Background

Itraconazole (ITZ), a triazole antifungal agent, is metabolized to hydroxy-ITZ (OH-ITZ), keto-ITZ (KT-ITZ), and N-desalkyl ITZ (ND-ITZ) by cytochrome P450 3A4. The pharmacokinetics of ND-ITZ remain largely unknown due to the lack of an accurate and reliable determination method. This study aimed to develop a simultaneous determination method for ITZ and its three major metabolites including ND-ITZ in human plasma using isocratic liquid chromatography coupled to tandem mass spectrometry and then apply the method in a clinical setting.

Methods

Plasma specimens were pretreated by protein precipitation with acetonitrile. The supernatant was separated on a 3-μm particle octadecyl silane column (75 × 2.0 mm I.D.) in an isocratic elution of acetonitrile and 5 mM ammonium acetate (pH 6.0) (57:43, v/v). The method was applied to 10 patients treated with oral ITZ.

Results

The calibration curves of ITZ, OH-ITZ, KT-ITZ, and ND-ITZ were linear over the concentration ranges of 15–1500, 15–1500, 1–100, and 1–100 ng/mL, respectively. The pretreatment recoveries and matrix factors were 90.1–102.2% and 99.1–102.7%. Their intra- and inter-assay accuracies and imprecisions were 94.1–106.7% and 0.3–4.4%. The plasma concentrations of ITZ, OH-ITZ, KT-ITZ, and ND-ITZ 12 h after dosing ranged from 32.5–1127.1, 19.0–1166.7, 1.1–5.4, and 3.5–28.3 ng/mL, respectively, in immunocompromised patients.

Conclusions

This study developed a simultaneous determination method for concentrations of ITZ and its three metabolites including ND-ITZ in a clinical setting.
Acute and residual concentration-dependent toxicities of some selected insecticides to adult Bactrocera invadens Drew, Tsuruta and White (Diptera: Tephritidae)
Authors: Abdullahi G. , Obeng-Ofori D. , Afreh-Nuamah K. , Billah M. K.
Published: May 2020

Background

The high yield loss reported from the infestations of fruits byBactrocera invadensDrew, Tsuruta and White in West Africa can impact negatively on the growth of horticulture in the region. Similarly, the shortage of insecticides specifically registered for the control of this pest in Ghana makes decision by farmers on which insecticide to use against this pest uncertain and risky.

Results

The result for the acute lethal toxicity shows that the lethal concentration (LC) values of the tested insecticides are 0.59 (diazinon (Diazol)), 0.81 (chlorpyrifos (Pyrinex)), 1.21 (cypermethrin+dimethoate (Cydim super)), and 3.12 (deltamethrin (Deltapaz)) ml L−1of water. The result for the residual toxicities of three concentrations for each of the tested insecticides shows that the lethal times LT (LT50and90) for the adultB. invadensdiffered significantly for all the ages of the residues. Some insecticides exhibited low lethal time even on panels that are up to 6 days old after treatment.

Conclusion

We concluded that the acute lethal toxicity of the insecticides from most-to-least toxic are diazinon (Diazol) > chlorpyrifos (Pyrinex) > cypermethrin + dimethoate (Cydim super) > deltamethrin (Deltapaz). The residual toxicity of the label rates of all the insecticides are equal to those of the higher doses but better than those of the least doses. The implication of these findings for the management ofB. invadenshas been discussed.
Tamoxifen stimulates gonad development and somatic growth in the tadpoles of Indian skipper frog, Euphlyctis cyanophlyctis
Authors: Phuge Samadhan
Published: May 2020

Background

Endocrine disruptors are one of the major threats to aquatic animals affecting their development and physiology. Amphibians are very sensitive to aquatic contaminants as their skin is semi-permeable. Several contaminants easily enter into their body, act as endocrine disruptors, and interfere in sexual development and metamorphosis. Endocrine disruptors have diverse effects in different species mainly due to the variations in developmental patterns. In the present study, I evaluated the endocrine disrupting potential of tamoxifen (anti-estrogen) in the tadpoles of Indian skipper frog Euphlyctis cyanophlyctis with undifferentiated type of gonad differentiation (testis differentiates through an ovarian phase).

Methods

I exposed the tadpoles to four concentrations of tamoxifen (25, 50, 100, and 200 μg/l) during larval development (Gosner stages 25–42) and studied their metamorphosis, somatic and sexual development.

Results

Tamoxifen does not influence gonad differentiation and sex ratio (proportion of males and females). However, all the concentrations of tamoxifen stimulated gonad development resulted in testis maturation in males and increased oocytes size in females. Tamoxifen treatments delayed metamorphosis and stimulated somatic growth.

Conclusion

These results suggest that tamoxifen does not act as an anti-estrogen in E. cyanophlyctis while stimulate sexual development in both males and females through unknown mechanism. These results are useful to understand the mechanism of action of tamoxifen in lower vertebrates and develop E. cyanophlyctis as an indigenous amphibian model for endocrine disruption studies.
Isolation and characterization of the local entomopathogenic bacterium, Bacillus thuringiensis isolates from different Egyptian soils
Authors: Abo-Bakr Aya , Fahmy Eman Mahmoud , Badawy Fatma , Abd El-latif Ashraf Oukasha , Moussa Saad
Published: May 2020

The local entomopathogenic bacterium, Bacillus thuringiensis (Bt) was isolated and characterized from 16 soil samples collected from different governorates in Egypt. Among 56 bacterial colonies obtained, only 16 colonies were characterized by traits of Bacillus. All the 16 isolates were toxic to the neonates of the cotton leaf worm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae). Damietta and El-Sharkyia bacterial isolates showed appreciable mortality rates (100 and 96.6%), respectively, which were higher than that caused by the standard isolates of Bt entomocidus (that produce Cry1 C toxin) for which they were selected for further characterization. Scanning electron microscope of Damietta bacterial isolate showed the presence of a bipyramidal crystal protein; consistent with the presence of Cry1 toxin class, however, El-Sharkyia bacterial isolate produced spherical-shaped crystals consistent of Cry2 toxin class. Electrophoretic patterns of different isolates and standards revealed different molecular weight bands, ranged from 195 to 8KDa. Damietta and El-Sharkyia bacterial isolates produced major protein bands with molecular weights of 130 KDa, which was also present in Bt entomocidus. Both isolates also shared protein bands with Bt entomocidus with molecular weights of 80, 70, 65, 51, and 22 KDa. The 16S rRNA sequences of both isolates were submitted to the NCBI Gene Bank database, with accession numbers of LC070660 for Damietta isolate and LC070661 for El-Sharkiya isolate. The existence of different Cry genes in the 2 isolates was studied by PCR, using general primers of 5 Cry genes. Cry1 gene was detected in both isolates; however, Cry 2 gene was detected only in Damietta isolate.
How to study ethnic food: senses, power, and intercultural studies
Authors: Karaosmanoğlu Defne
Published: May 2020

This article gives a broad review of the literature focusing on food, senses, and intercultural relations. Integrating cultural studies literature and concepts into ethnic food studies, it tries to understand the ways in which ethnic food becomes an agent of social change and helps to build, promote, and improve intercultural relations. More specifically, this article tries to explore the ways in which ethnic food could be used as a pedagogical tool in intercultural relations. The following questions are explored in anthropology and cultural studies literature: To what extent can ethnic food bring a feeling of connection with other cultures? To what extent can it bring an understanding of others? What kind of a role do the senses of taste and smell play in this process? At least three steps are proposed in the study of ethnic food and intercultural relations: Integrating sensory studies into food studies, applying self-reflexive ethnographic methodologies which are based on experience and emotion, and finally exploring the relationship between food and power, and food and agency.
Diagnostic utility of strain and shear wave ultrasound elastography in differentiation of benign and malignant solid breast lesions
Authors: Ahmed Ahmed Tohamy
Published: May 2020

Background

The purpose of our study was to assess diagnostic performance and comparison of strain and shear wave ultrasound elastography for differentiation of benign and malignant breast lesions compared to histopathological diagnosis as a reference standard. Our single center study involved 100 female patients with 132 solid breast masses. All patients underwent supervision of medical history, clinical examination, conventional B-mode ultrasound which was evaluated according to the BIRADS (Breast Imaging Reporting and Data System), and strain and shear wave ultrasound elastography. Strain ratio for strain elastography, mean elasticity value, and stiff ratio for shear wave elastography were calculated. All breast lesions were biopsied. Comparison of the elastography results with the histopathological diagnoses was done.

Results

There was no statistically significant difference as regard the AUCs for calculated values of strain and shear wave ultrasound elastography (strain ratio, 0.916; mean elasticity, 0.884; and stiff ratio, 0.872; P > 0.05). The AUCs for the combined use of B-mode US and elastography techniques were improved as the following: B-mode + strain, 0.920; B-mode + shear wave 0.952 with a significant P value < 0.001. Higher diagnostic accuracy was noted with the combination of strain and shear wave elastography than each single elastographic modality (P = 0.02).

Conclusions

Ultrasound elastography of breast masses is a non-invasive procedure with high sensitivity. Strain and shear wave elastography had almost similar diagnostic performance and displayed higher diagnostic performance if combined with B-mode ultrasound which helps in decreasing the number of unneeded breast biopsies.
Exploring barriers and facilitators to integrated hypertension-HIV management in Ugandan HIV clinics using the Consolidated Framework for Implementation Research (CFIR)
Authors: Muddu Martin , Tusubira Andrew K. , Nakirya Brenda , Nalwoga Rita , Semitala Fred C. , Akiteng Ann R. , Schwartz Jeremy I. , Ssinabulya Isaac
Published: May 2020

Background

Persons living with HIV (PLHIV) receiving antiretroviral therapy have increased risk of cardiovascular disease (CVD). Integration of services for hypertension (HTN), the primary CVD risk factor, into HIV clinics is recommended in Uganda. Our prior work demonstrated multiple gaps in implementation of integrated HTN care along the HIV treatment cascade. In this study, we sought to explore barriers to and facilitators of integrating HTN screening and treatment into HIV clinics in Eastern Uganda.

Methods

We conducted a qualitative study at three HIV clinics with low, intermediate, and high HTN care cascade performance, which we classified based on our prior work. Guided by the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured interviews and focus group discussions with health services managers, healthcare providers, and hypertensive PLHIV (n = 83). Interviews were transcribed verbatim. Three qualitative researchers used the deductive (CFIR-driven) method to develop relevant codes and themes. Ratings were performed to determine valence and strengths of each CFIR construct regarding influencing HTN/HIV integration.

Results

Barriers to HTN/HIV integration arose from six CFIR constructs: organizational incentives and rewards, available resources, access to knowledge and information, knowledge and beliefs about the intervention, self-efficacy, and planning. The barriers include lack of functional BP machines, inadequate supply of anti-hypertensive medicines, additional workload to providers for HTN services, PLHIV’s inadequate knowledge about HTN care, sub-optimal knowledge, skills and self-efficacy of healthcare providers to screen and treat HTN, and inadequate planning for integrated HTN/HIV services.

Relative advantage of offering HTN and HIV services in a one-stop centre, simplicity (non-complex nature) of HTN/HIV integrated care, adaptability, and compatibility of HTN care with existing HIV services are the facilitators for HTN/HIV integration. The remaining CFIR constructs were non-significant regarding influencing HTN/HIV integration.

Conclusion

Using the CFIR, we have shown that while there are modifiable barriers to HTN/HIV integration, HTN/HIV integration is of interest to patients, healthcare providers, and managers. Improving access to HTN care among PLHIV will require overcoming barriers and capitalizing on facilitators using a health system strengthening approach. These findings are a springboard for designing contextually appropriate interventions for HTN/HIV integration in low- and middle-income countries.
PARP Inhibitors for Ovarian Cancer: Current Indications, Future Combinations, and Novel Assets in Development to Target DNA Damage Repair
Authors: Konstantinopoulos Panagiotis A. , Lheureux Stephanie , Moore Kathleen N.
Published: May 2020

PARP inhibitors (PARPIs) have revolutionized the treatment of epithelial ovarian cancer, first for BRCA-associated cancer, and, recently, for all epithelial cancers of serous or high-grade endometrioid subtypes in the front line. Although there is hope that PARPIs will help prevent recurrences when used following frontline maintenance, cancer will still recur in most women, and the need for active combination strategies as well as continued development of novel assets, either as monotherapy or in combination, will be urgently needed. This review article discusses the current indications for PARPIs in both frontline and recurrent settings, current research in combination approaches, and finally, ongoing research on novel methods to target DNA damage response in an effort to exploit the common susceptibility to DNA damage repair in epithelial ovarian cancer and improve outcomes for patients.
A novel and cost-effective ex vivo orthotopic model for the study of human breast cancer in mouse mammary gland organ culture
Authors: Gupta Akash , Gupta Geetanjali , Mehta Rajeshwari R. , Ivancic David Z. , Walker Rashidra R. , Patel Jankiben R. , Gallegos Karen M. , Davidson A. Michael , Khan Seema A. , Mehta Rajendra G. , Tilghman Syreeta L.
Published: May 2020

Mouse Mammary Organ Culture (MMOC) is used to evaluate the efficacy of chemopreventive agents against the development of carcinogen-induced preneoplastic lesions and is highly correlative to in vivo carcinogenesis models. Here, we developed a new ex vivo MMOC model, by introducing human breast cancer cells into the mouse mammary gland. This novel model, termed human Breast Cancer in MMOC (BCa-MMOC), mimics in vivo orthotopic breast cancer mouse models. To develop this model, estradiol- and progesterone- sensitized female mice were injected with letrozole sensitive- and resistant T47D breast cancer cells in the mammary glands and then sacrificed. The glands were cultured in vitro with hormone-supplemented media. On day 25, the glands were fixed and processed by histopathology and immunohistochemistry to evaluate for the presence of T47D cells, growth pattern, cancer markers, and estradiol responsiveness. Histopathological analyses demonstrated an identical pattern of growth between the breast cancer cells injected ex vivo and in vivo. Interestingly, clusters of cancer cells in the mammary gland stroma appeared similar to those observed in human breast tumors. The injected T47D cells survived and proliferated for 15 days maintaining expression of ER, PR, EGFR, and aromatase. The aromatase-overexpressing T47D grown in the BCa-MMOC sufficiently metabolized estrogen, resulting in enhanced cell proliferation, induction of estrogen target genes (i.e. ER and PR-B), and showed typical changes to estrogenic milieu. In summary, here we show a novel, inexpensive ex vivo model, to potentially study the effects of therapeutic agents on cancer cells grown in an orthotopic micromilieu.
A collection of genetic mouse lines and related tools for inducible and reversible intersectional misexpression
Authors: Ahmadzadeh Elham , Bayin N. Sumru , Qu Xinli , Singh Aditi , Madisen Linda , Stephen Daniel , Zeng Hongkui , Joyner Alexandra L. , Rosello-Diez Alberto
Published: May 2020

Thanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches utilizing two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach utilizes available lines expressing tTA/rTA to control timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf) and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.