bluuebunny/crossref_metadata_2025 huggingface dataset:
An agent-based model of prostate Cancer bone metastasis progression and response to Radium223
Authors: Casarin Stefano , Dondossola Eleonora
Published: June 2020

Background

Bone metastasis is the most frequent complication in prostate cancer patients and associated outcome remains fatal. Radium223 (Rad223), a bone targeting radioisotope improves overall survival in patients (3.6 months vs. placebo). However, clinical response is often followed by relapse and disease progression, and associated mechanisms of efficacy and resistance are poorly understood.

Research efforts to overcome this gap require a substantial investment of time and resources. Computational models, integrated with experimental data, can overcome this limitation and drive research in a more effective fashion.

Methods

Accordingly, we developed a predictive agent-based model of prostate cancer bone metastasis progression and response to Rad223 as an agile platform to maximize its efficacy. The driving coefficients were calibrated on ad hoc experimental observations retrieved from intravital microscopy and the outcome further validated, in vivo.

Results

In this work we offered a detailed description of our data-integrated computational infrastructure, tested its accuracy and robustness, quantified the uncertainty of its driving coefficients, and showed the role of tumor size and distance from bone on Rad223 efficacy. In silico tumor growth, which is strongly driven by its mitotic character as identified by sensitivity analysis, matched in vivo trend with 98.3% confidence. Tumor size determined efficacy of Rad223, with larger lesions insensitive to therapy, while medium- and micro-sized tumors displayed up to 5.02 and 152.28-fold size decrease compared to control-treated tumors, respectively. Eradication events occurred in 65 ± 2% of cases in micro-tumors only. In addition, Rad223 lost any therapeutic effect, also on micro-tumors, for distances bigger than 400 μm from the bone interface.

Conclusions

This model has the potential to be further developed to test additional bone targeting agents such as other radiopharmaceuticals or bisphosphonates.
MAGE-A4, NY-ESO-1 and SAGE mRNA expression rates and co-expression relationships in solid tumours
Authors: Ishihara Mikiya , Kageyama Shinichi , Miyahara Yoshihiro , Ishikawa Takeshi , Ueda Shugo , Soga Norihito , Naota Hiroaki , Mukai Katsumi , Harada Naozumi , Ikeda Hiroaki , Shiku Hiroshi
Published: June 2020

Background

Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE).

Methods

MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Informed consent was obtained from individuals prior to study enrolment.

Results

In total, 585 samples in 21 tumour types were evaluated between June 2009 and March 2018. The positive expression rates of these CT antigens were as follows: MAGE-A4, 34.6% (range, 30.7–38.7); NY-ESO-1, 21.0% (range, 17.2–25.1); and SAGE, 21.8% (range, 18.5–25.4). The MAGE-A4 antigen was expressed in 54.9% of oesophageal cancers, 37.5% of head and neck cancers, 35.0% of gastric cancers and 34.2% of ovarian cancers; the NY-ESO-1 antigen was expressed in 28.6% of lung cancers, 25.3% of oesophageal cancers and 22.6% of ovarian cancers; and the SAGE antigen was expressed in 35.3% of prostate cancers, 32.9% of oesophageal cancers and 26.3% of ovarian cancers. The most common tumour type in this study was oesophageal cancer. MAGE-A4, NY-ESO-1 and SAGE antigen expression were assessed in 214 oesophageal cancer samples, among which 24 (11.2%) were triple-positive, 58 (27.1%) were positive for any two, 59 (27.6%) were positive for any one, and 73 (34.1%) were triple negative.

Conclusions

Oesophageal cancer exhibited a relatively high rate of CT antigen mRNA expression positivity.
Nomograms that predict the survival of patients with adenocarcinoma in villous adenoma of the colorectum: a SEER-based study
Authors: Tang Chao-Tao , Zeng Ling , Yang Jing , Zeng Chunyan , Chen Youxiang
Published: June 2020

Background

Considering that the knowledge of adenocarcinoma in villous adenoma of the colorectum is limited to several case reports, we designed a study to investigate independent prognostic factors and developed nomograms for predicting the survival of patients.

Methods

Univariate and multivariate Cox regression analyses were used to evaluate prognostic factors. A nomogram predicting cancer-specific survival (CSS) was performed; internally and externally validated; evaluated by receiver operating characteristic (ROC) curve, C-index, and decision curve analyses; and compared to the 7th TNM stage.

Results

Patients with adenocarcinoma in villous adenoma of the colorectum had a 1-year overall survival (OS) rate of 88.3% (95% CI: 87.1–89.5%), a 3-year OS rate of 75.1% (95% CI: 73.3–77%) and a 5-year OS rate of 64.5% (95% CI: 62–67.1%). Nomograms for 1-, 3- and 5-year CSS predictions were constructed and performed better with a higher C-index than the 7th TNM staging (internal: 0.716 vs 0.663; P < 0.001; external: 0.713 vs 0.647; P < 0.001). Additionally, the nomogram showed good agreement between internal and external validation. According to DCA analysis, compared to the 7th TNM stage, the nomogram showed a greater benefit across the period of follow-up regardless of the internal cohort or external cohort.

Conclusion

Age, race, T stage, pathologic grade, N stage, tumor size and M stage were prognostic factors for both OS and CSS. The constructed nomograms were more effective and accurate for predicting the 1-, 3- and 5-year CSS of patients with adenocarcinoma in villous adenoma than 7th TNM staging.
Genotype–phenotype correlation in two Polish neonates with alveolar capillary dysplasia
Authors: Kozłowska Zuzanna , Owsiańska Zuzanna , Wroblewska Joanna P. , Kałużna Apolonia , Marszałek Andrzej , Singh Yogen , Mroziński Bartłomiej , Liu Qian , Karolak Justyna A. , Stankiewicz Paweł , Deutsch Gail , Szymankiewicz-Bręborowicz Marta , Szczapa Tomasz
Published: June 2020

Background

Alveolar capillary dysplasia (ACD) is a rare cause of severe pulmonary hypertension and respiratory failure in neonates. The onset of ACD is usually preceded by a short asymptomatic period. The condition is refractory to all available therapies as it irreversibly affects development of the capillary bed in the lungs. The diagnosis of ACD is based on histopathological evaluation of lung biopsy or autopsy tissue or genetic testing ofFOXF1on chromosome 16q24.1. Here, we describe the first two Polish patients with ACD confirmed by histopathological and genetic examination.

Case presentation

The patients were term neonates with high Apgar scores in the first minutes of life. They both were diagnosed prenatally with heart defects. Additionally, the first patient presented with omphalocele. The neonate slightly deteriorated around 12thhour of life, but underwent surgical repair of omphalocele followed by mechanical ventilation. Due to further deterioration, therapy included inhaled nitric oxide (iNO), inotropes and surfactant administration. The second patient was treated with prostaglandin E1 since birth due to suspicion of aortic coarctation (CoA). After ruling out CoA in the 3rdday of life, infusion of prostaglandin E1 was discountinued and immediately patient’s condition worsened. Subsequent treatment included re-administration of prostaglandin E1, iNO and mechanical ventilation. Both patients presented with transient improvement after application of iNO, but died despite maximized therapy. They were histopathologically diagnosed post-mortem with ACD. Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involvingFOXF1and an ~ 0.7 Mb in size involvingFOXF1enhancer and leavingFOXF1intact.

Conclusions

Both patients presented with a distinct course of ACD, extra-pulmonary manifestations and response to medications. Surgery and ceasing of prostaglandin E1 infusion should be considered as potential causes of this variability. We further highlight the necessity of thorough genetic testing and histopathological examination and propose immunostaining for CD31 and CD34 to facilitate the diagnostic process for better management of infants with ACD.
Unknown HIV status and the TB/HIV collaborative control program in Ethiopia: systematic review and meta-analysis
Authors: Arega Balew , Minda Abraham , Mengistu Getachew , Endale Mulugeta , Agunie Asnake
Published: June 2020

Background

Ethiopia has shown significant efforts to address the burden of TB/HIV comorbidity through the TB/HIV collaborative program. However, these diseases are still the highest cause of death in the country. Therefore, this systematic review and meta-analysis evaluated this program by investigating the overall proportion of unknown HIV status among TB patients using published studies in Ethiopia.

Methods

We conducted a systematic review and meta-analysis of published studies in Ethiopia. We identified the original studies using the databases MEDLINE/PubMed, and Google Scholar. The heterogeneity across studies was assessed using Cochran’s Q test and I 2 statistics. The Begg’s rank correlation and the Egger weighted regression tests were assessed for the publication bias. We estimated the pooled proportion of unknown HIV status among TB patients using the random-effects model.

Results

Overall, we included 47 studies with 347,896 TB patients eligible for HIV test. The pooled proportion of unknown HIV status among TB patients was 27%(95% CI; 21–34%) and with a substantial heterogeneity (I2 = 99.9%). In the subgroup analysis, the pooled proportion of unknown HIV status was 39% (95% CI; 25–54%) among children and 20% (95% CI; 11–30%) among adults. In the region based analysis, the highest pooled proportion of unknown HIV status was in Gambella, 38% (95% CI; 16–60%) followed by Addis Ababa, 34%(95% CI; 12–55%), Amhara,30%(95% CI; 21–40%),and Oromia, 23%(95% CI; 9–38%). Regarding the study facilities, the pooled proportion of unknown HIV status was 33% (95% CI; 23–43%) in the health centers and 26%(95% CI; 17–35%) in the hospitals. We could not identify the high heterogeneity observed in this review and readers should interpret the results of the pooled proportion analysis with caution.

Conclusion

In Ethiopia, about one-third of tuberculosis patients had unknown HIV status. This showed a gap to achieve the currently implemented 90–90-90 HIV/AIDS strategic plan in Ethiopia, by 2020. Therefore, Ethiopia should strengthen TB/HIV collaborative activities to mitigate the double burden of diseases.
Behavioral barriers to the use of modern methods of contraception among unmarried youth and adolescents in eastern Senegal: a qualitative study
Authors: Cohen Nicki , Mendy Finou Thérèse , Wesson Jennifer , Protti Amanda , Cissé Carol , Gueye Elhadji Babacar , Trupe Lydia , Floreak Rosii , Guichon Dana , Lorenzana Karina , Buttenheim Alison
Published: June 2020

Background

Many unmarried young people in low- and middle-income countries (LMIC) want to avoid pregnancy but do not use modern methods of contraception—as a result, half of teen births in these countries are unintended. Researchers have identified numerous barriers that prevent youth from using contraception. However, much of the research in West Africa is narrowly focused on married women, and relatively little research has been done to understand the needs, preferences, barriers, and solution set for sexually active unmarried young people who would like to avoid pregnancy. The purpose of this study was to gain insight into the behavioral barriers that prevent unmarried young people in eastern Senegal from using modern methods of contraception.

Methods

This qualitative study conducted in 2017 in the Tambacounda and Kedougou regions in Senegal explores attitudes and beliefs relating to sex and contraception among unmarried young women and men through 48 in-depth individual interviews with young people aged 15–24 and parents of youth and 5 sex-segregated focus groups with 6–9 young people per group. The research team conducted a thematic content analysis and synthesized the findings by major theme following the behavioral diagnosis methodology.

Results

Drawing insights from behavioral science, the analysis yields five key findings: (1) unmarried young people avoid making a decision about contraception because thinking about contraceptive use provokes uncomfortable associations with a negative identity (i.e., being sexually active before marriage); (2) unmarried young people see modern methods as inappropriate for people like them; (3) unmarried young people are overconfident in their ability to prevent pregnancy through traditional and folk methods; (4) unmarried young people overestimate the social and health risks of modern contraceptive methods; and (5) unmarried young people fail to plan ahead and are not prepared to use modern contraceptive methods before every sexual encounter.

Conclusions

Interventions aimed at increasing uptake of contraceptives among unmarried young people in eastern Senegal must address several significant behavioral barriers in addition to structural, informational, and socio-cultural barriers in order to be successful.
Association between osteoarthritis and unmet medical needs in Korea: limitations in activities as a mediator
Authors: Jo Hooin , Kim Eun-san , Jung Boyoung , Sung Soo-Hyun , Ha In-Hyuk
Published: June 2020

Background

The role of limitations in activities in relation to unmet needs is not clarified. This study aimed to analyze the effects of osteoarthritis on unmet medical needs and the mediating effects of limitations in activities.

Methods

A total number of 10,129 population aged ≥50 years were included using data from the Korean National Health and Nutrition Examination Survey from January 2010 to December 2013. Osteoarthritis was defined as Kellgren-Lawrence grade ≥ 2 in the knee, hip, and lumbar spine joints with pain reported to have lasted for ≥3 months. Limitations in activities were defined as currently experiencing restricted daily and social activities. Unmet medical needs were analyzed after they were further divided into availability, accessibility, and acceptability. Causal mediation analysis was employed to analyze mediating effects.

Results

The osteoarthritis group had a higher odds ratio (OR: 1.65; 95% confidence interval [CI], 1.56–1.75) for the total effects of osteoarthritis on unmet medical needs than the non-osteoarthritis group. Furthermore, the OR for the indirect effects mediated by limitations in activities was higher in the osteoarthritis group (OR: 1.07; 95% CI, 1.05–1.08), indicating that 13.2% of the total effect was mediated. When the analysis was further classified according to cause, the mediating effect of limitations in activities was the strongest at 23.9% for unmet medical needs due to lack of transportation accessibility.

Conclusions

Osteoarthritis exerts significant effects on the experience of unmet medical needs, and limitations in activities mediate such experiences of unmet medical needs in osteoarthritis patients.
Comparison of radiological and clinical outcomes, complications, and implant removals in anatomically pre-contoured clavicle plates versus reconstruction plates – a propensity score matched retrospective cohort study of 106 patients
Authors: Fang Christian X. , Liu Ruiping , Yee Dennis K. H. , Chau Jackie , Lau Tak-Wing , Chan Rebecca , Woo Siu-Bon , Wong Tak-Man , Fang Evan , Leung Frankie
Published: June 2020

Background

Plate fixation is frequently used to treat displaced midshaft clavicular fractures, however the ideal plate choice remains subject to discussion; reconstruction locking compression plates (RLCPs) are cheaper and can be easily contoured, whereas anatomically pre-contoured locking compression plates (ALCPs) are thought to provide better stability and therefore lower rates of mechanical failure.

To compare the incidence of mechanical failures, functional and radiological outcomes in patients with midshaft clavicular fractures treated with ALCPs versus RLCPs.

Methods

A propensity score matched retrospective cohort study was conducted across two centers. One hundred and six consecutively recruited patients with displaced midshaft clavicular fractures, who were treated with plate fixation and had a minimum follow-up of 6 months, were matched on gender, age, fracture grading, energy of injury, and fracture location. The resulting groups included 53 ALCP-treated fractures and 53 matched controls treated with RLCPs.

Results

During a mean follow-up of 20.5 months, there were no implant deformities in the ALCP group whereas the RLCP group had 6 patients (11.3%, p = 0.012) with implant deformities (5 occurrences of plate bending with fracture union, and 1 plate breakage with nonunion). Despite the higher rate of plate deformities in the RLCP group, there were no statistically significant differences in number of patients recovering full shoulder range of motion (ALCP 90.6%, RLCP 88.7%, p = 0.751), incidence of rest pain (ALCP 13.2%, RLCP 9.4%, p = 0.542), or implant removals (ALCP 49.1%, RLCP 56.6%, p = 0.439).

Conclusion

ALCPs may be superior to RLCPs in terms of implant stability but appear to produce similar clinical results.
Cerebrospinal fluid-cutaneous fistula associated with post-traumatic Charcot spinal arthropathy: a case report and review of literature
Authors: Ryu Ji Hyun , Lee Jun-Seok , Lim Chang-Rack , Cho Wan Jae , Kim Ki-Won
Published: June 2020

Background

Charcot spinal arthropathy, also known as Charcot spine and neuropathic spinal arthropathy, is a progressive and destructive condition that affects an intervertebral disc and the adjacent vertebral bodies following loss of spinal joint innervation. We report the first case of Charcot spinal arthropathy (CSA) associated with cerebrospinal fluid (CSF)-cutaneous fistula.

Case presentation

A 54-year-old male who underwent T10-L2 posterior instrumented spinal fusion seven years prior for treatment of T11 burst fracture and accompanying T11 complete paraplegia visited our department complaining of leakage of clear fluid at his lower back. The patient had also undergone various types of skin graft and myocutaneous flap surgeries for treatment of repetitive pressure sores around his lumbosacral area. The patient presented with persistent CSF leakage from a cutaneous fistula (CSF-cutaneous fistula) formed in a lumbosacral pressure sore. The CSF-cutaneous fistula arose from the L5 post-traumatic CSA. Surgery was planned for management of CSF-cutaneous fistula and post-traumatic L5 CSA. We successfully treated the CSF-cutaneous fistula with ligation and transection of the dural sac and cauda equina at the L2-L3 level. In addition, the post-traumatic L5 CSA was successfully treated with a posterior four-rod spinopelvic fixation from T9 to ilium and S2 foramina. After surgery, the CSF leakage stopped and no other adverse neurological changes were found. The four-rod spinopelvic construct was well maintained five years later.

Conclusions

CSA associated with CSF-cutaneous fistula is a very rare disorder. Only surgical treatment for both CSA and CSF-cutaneous fistula with ligation and transection of the dural sac and posterior four-rod spinopelvic fixation can bring satisfactory results.
Anti-rheumatic treatment and prosthetic joint infection: an observational study in 494 elective hip and knee arthroplasties
Authors: Borgas Ylva , Gülfe Anders , Kindt Mikael , Stefánsdóttir Anna
Published: June 2020

Background

Surgical site infections are more frequent among patients with rheumatic disease. To what extent this is related to immunosuppressive antirheumatic drugs is unclear, as is the value of discontinuing medication perioperatively. The aim of study was to assess the rate of surgical site infections after knee and hip replacement in patients with inflammatory joint disease, with an emphasis on periprosthetic joint infection, and to investigate the influence of treatment with disease-modifying antirheumatic drugs (DMARDs) in this regard.

Methods

Data were collected from 494 primary elective hip (51.4%) and knee arthroplasties, along with demographic and medication data. The primary outcome was surgical site infection during the first year after surgery.

Results

In 78% (n = 385) of the cases the patient used 1 to 3 disease-modifying antirheumatic drugs perioperatively. Thirty-two percent (n = 157) of patients used a TNF-alpha inhibitor. The rate of surgical site infection was 3.8% (n = 19). The rate of periprosthetic joint infection was 1.4% (n = 7), all of which occurred after knee arthroplasty. Periprosthetic joint infection occurred in only 1 patient medicating perioperatively with a TNF-alpha inhibitor.

Conclusion

Surgical site infections were not associated with ongoing medication with disease-modifying antirheumatic drugs. Due to the low event rate this should be interpreted with caution, but our center will maintain its routine of continuing treatment with TNF-alpha inhibitors perioperatively.
Orthotopic liver transplantation for Management of a Giant Liver Hemangioma: a case report and review of literature
Authors: Eghlimi Hesameddin , Arasteh Peyman , Azade Nazanin
Published: June 2020

Background

Hepatic hemangioma (HH) is the most common benign tumor of the liver. In special conditions such as rapidly growing tumors, persistent pain, hemorrhage and when pressure effect on adjacent organs exist treatment is indicated. Surgical management is the most common treatment for HH.

Case presentation

A 38-year-old male patient was diagnosed with HH for 7 years. The initial presentation of the mass was progressive abdominal distention causing early satiety, gastro-esophageal reflux disease, vomiting, dysphagia and weight loss. Later, the patient developed bilateral lower extremity edema. Imaging with computed tomography (CT scan) showed a large mass measuring 32.4*26*3.1 cm which was considered unresectable. The patient underwent a deceased donor liver transplantation. The excised mass was 9 kg. After nine days of hospitalization the patient was discharged in good condition. Three months later, the patient was admitted due to fever and cytomegalovirus infection for which he received intravenous ganciclovir and was discharged. In the latest follow-up the patient had no liver or kidney dysfunction eight months after the transplantation.

Conclusion

With appropriate patient selection, liver transplantation can be considered as a treatment option for patients with huge HHs which are life-threatening and surgically unresectable.
Recurrent broad ligament leiomyosarcoma with pancreatic and thigh metastasis: a case report
Authors: Tian Xuan , Yan Xin , Wu Jun , Song Hongli , Shen Zhongyang
Published: June 2020

Background

Leiomyosarcoma (LMS) is an uncommon mesenchymal neoplasm, which infrequently metastasizes to pancreas and thigh. Clinical presentation and imaging findings of metastatic broad ligament LMS are often nonspecific. Complete excision plays an important role in treatment of patients with localized LMS.

Case presentation

Here, we report a case of a 33-year-old woman with recurrent broad ligament LMS metastasizing to pancreas and thigh. Previously, she was diagnosed with broad ligament LMS and underwent hysterectomy, bilateral salpingo-oophorectomy. The disease-free interval was 2.5 years until metastases were found. Computerized tomography (CT) of abdomen and thighs, magnetic resonance imaging (MRI) of thighs and whole-body 18-fluorodeoxyglucose positron emission tomography - computed tomography (PET-CT) performed, revealed pancreatic and thigh metastasis. Ultrasonography-guided biopsy and histological examinations confirmed LMS at both the sites. Pancreatic metastasis was completely resected first. Then the patient underwent surgical resection of thigh metastasis when both chemotherapy and radiotherapy failed. She recovered well and remained free of disease recurrence in the 2 years follow-up.

Conclusions

Though imaging lacks specificity, it is a valuable asset in assessing the burden of disease and characterizing lesions while histological examination with immunohistochemistry is helpful for the diagnosis of LMS. Complete surgical resection of all metastatic sites where-ever feasible should be strongly considered in a treated case of broad ligament LMS with a durable disease-free interval.
Functional expression of a novel methanol-stable esterase from Geobacillus subterraneus DSM13552 for biocatalytic synthesis of cinnamyl acetate in a solvent-free system
Authors: Cai Xianghai , Lin Lin , Shen Yaling , Wei Wei , Wei Dong-zhi
Published: June 2020

Background

Esterases are widely distributed in nature and have important applications in medical, industrial and physiological. Recently, the increased demand for flavor esters has prompted the search of catalysts like lipases and esterases. Esterases from thermophiles also show thermal stability at elevated temperatures and have become enzymes of special interest in biotechnological applications. Although most of esterases catalyzed reactions are carried out in toxic and inflammable organic solvents, the solvent-free system owning many advantages such as low cost and easy downstream processing.

Results

The gene estGSU753 from Geobacillus subterraneus DSM13552 was cloned, sequenced and overexpressed into Escherichia coli BL21 (DE3). The novel gene has an open reading frame of 753 bp and encodes 250-amino-acid esterase (EstGSU753). The sequence analysis showed that the protein contains a catalytic triad formed by Ser97, Asp196 and His226, and the Ser of the active site is located in the conserved motif Gly95-X-Ser97-X-Gly99 included in most esterases and lipases. The protein catalyzed the hydrolysis of pNP-esters of different acyl chain lengths, and the enzyme specific activity was 70 U/mg with the optimum substrate pNP-caprylate. The optimum pH and temperature of the recombinant enzyme were 8.0 and 60 °C respectively. The resulting EstGSU753 showed remarkable stability against methanol. After the incubation at 50% methanol for 9 days, EstGSU753 retained 50% of its original activity. Even incubation at 90% methanol for 35 h, EstGSU753 retained 50% of its original activity. Also, the preliminary study of the transesterification shows the potential value in synthesis of short-chain flavor esters in a solvent-free system, and more than 99% conversion was obtained in 6 h (substrate: cinnamyl alcohol, 1.0 M).

Conclusions

This is the first report of esterase gene cloning from Geobacillus subterraneus with detailed enzymatic properties. This methanol-stable esterase showed potential value in industrial applications especially in the perfume industry.
Eucalyptus essential oils inhibit the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through reducing MAPK and NF-κB pathways
Authors: Ho Chen-Lung , Li Lan-Hui , Weng Yueh-Chun , Hua Kuo-Feng , Ju Tz-Chuen
Published: June 2020

Background

Eucalyptusessential oils have been used in traditional medicine for centuries. It was reported thatEucalyptusleaves possess antioxidant and antimicrobial effects. Here, we investigated the anti-inflammatory activity of the essential oils extracted from the leaves of four differentEucalyptusspecies in RAW264.7 macrophages.

Methods

Lipopolysaccharide (LPS)-activated RAW264.7 macrophages were used to evaluate the anti-inflammatory activity of the leaf essential oils ofEucalyptus. The cell survival was quantified by an Alamar Blue assay. Nitric oxide (NO) production was assessed by Griess reaction. TNF-α and IL-6 production were measured by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-κB (NF-κB) transcriptional activity was measured by NF-κB reporter assay. Intracellular protein expression levels were determined by Western blot. The expression levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and NF-κB pathway were measured by western blot in LPS-activated RAW 264.7 macrophage.

Results

The essential oils extracted fromEucalyptus citriodoraleaf exert the best NO inhibitory activity in LPS-activated RAW264.7 macrophages. The essential oils were fractionated into fractions A-H, and fraction F has been demonstrated to inhibit the expression levels of TNF-α, IL-6, NO, iNOS and COX-2 in LPS-activated RAW264.7 macrophages. Mechanistic analysis revealed that fraction F reduced the phosphorylation levels of ERK1/2, p38, PKC-α, PKC-ε and PKC-δ, and inhibited the NF-κB transcriptional activity. The chemical composition of Fraction F was determined by GC-MS.

Conclusions

The discoveries made herein could help develop innovative nonsteroidal anti-inflammatory drugs with minimal side effects and strong efficacy. Clinical trials on theseEucalyptusleaf essential oils will help customize and optimize their therapeutic administration.
Sexual harassment against female nurses: a systematic review
Authors: Kahsay Woldegebriel Gebregziabher , Negarandeh Reza , Dehghan Nayeri Nahid , Hasanpour Marzieh
Published: June 2020

Background

Sexual harassment is complex and has occupational hazards in nursing. Nurses experienced it than other employees. Female nurses are with the highest rate in the profession. Our aim was to determine the prevalence of sexual harassment against female nurses, the types, perpetrators, and health consequences of the harassment.

Method

We undertook a systematic review to synthesize quantitative research studies found in Pubmed, Scopus, ProQuest, Web of Science and Google Scholar databases. The studies included were observational, on sexual harassment against female nurse, full text, and published in peer-reviewed English journals up to August 2018. Two independent reviewers searched the articles and extracted data from the articles. The quality of the articles was evaluated using the Modified Newcastle Ottawa Scale for Cross-Sectional Studies Quality Assessment Tool. A descriptive analysis was done to determine the rate of items from the percentages or proportions of the studies.

Result

The prevalence of sexual harassment against female nurses was 43.15%. It ranged 10 to 87.30%. The 35% of the female nurses were verbally, 32.6% non-verbally, 31% physically and 40.8% were being harassed psychologically. The 46.59% of them were harassed by patients, 41.10% by physicians, 27.74% by patients’ family, 20% by nurses and 17.8% were by other coworker perpetrators. The 44.6% of them were developed mental problems, 30.19% physical health problems, 61.26% emotional, 51.79% had psychological disturbance and 16.02% with social health problems.

Conclusion

The prevalence of sexual harassment against female nurses is high. Female nurses are being sexually harassed by patients, patient families, physicians, nurses, and other coworkers. The harassment is affecting mental, physical, emotional, social and psychological health of female nurses. It is recommended policymakers to develop guidelines on work ethics, legality and counseling programs. Nursing associations to initiate development of workplace safety policy. A safe and secure working environment is needed in the nursing practice and nursing curriculum in prevention strategy. Research is needed on factors associated with sexual harassment. Since only female nurses were the participants, it could not be representative of all nurses. There was no fund of this review.
Defining and assessing context in healthcare implementation studies: a systematic review
Authors: Rogers L. , De Brún A. , McAuliffe E.
Published: June 2020

Background

The implementation of evidence-based healthcare interventions is challenging, with a 17-year gap identified between the generation of evidence and its implementation in routine practice. Although contextual factors such as culture and leadership are strong influences for successful implementation, context remains poorly understood, with a lack of consensus regarding how it should be defined and captured within research. This study addresses this issue by providing insight into how context is defined and assessed within healthcare implementation science literature and develops a definition to enable effective measurement of context.

Methods

Medline, PsychInfo, CINAHL and EMBASE were searched. Articles were included if studies were empirical and evaluated context during the implementation of a healthcare initiative. These English language articles were published in the previous 10 years and included a definition and assessment of context. Results were synthesised using a narrative approach.

Results

Three thousand and twenty-one search records were obtained of which 64 met the eligibility criteria and were included in the review. Studies used a variety of definitions in terms of the level of detail and explanation provided. Some listed contextual factors (n = 19) while others documented sub-elements of a framework that included context (n = 19). The remaining studies provide a rich definition of general context (n = 11) or aspects of context (n = 15). The Alberta Context Tool was the most frequently used quantitative measure (n = 4), while qualitative papers used a range of frameworks to evaluate context. Mixed methods studies used diverse approaches; some used frameworks to inform the methods chosen while others used quantitative measures to inform qualitative data collection. Most studies (n = 50) applied the chosen measure to all aspects of study design with a majority analysing context at an individual level (n = 29).

Conclusions

This review highlighted inconsistencies in defining and measuring context which emphasised the need to develop an operational definition. By providing this consensus, improvements in implementation processes may result, as a common understanding will help researchers to appropriately account for context in research.
Study protocol for the implementation and evaluation of the Self-harm Assessment and Management for General Hospitals programme in Ireland (SAMAGH)
Authors: Arensman Ella , Troya M. Isabela , Nicholson Sarah , Sadath Anvar , Cully Grace , Ramos Costa Ana Paula , Benson Ruth , Corcoran Paul , Griffin Eve , Williamson Eileen , Eustace Joe , Shiely Frances , Browne John , Rigby Jan , Jeffers Anne , Cassidy Eugene
Published: June 2020

Background

Previous self-harm is one of the strongest predictors of future self-harm and suicide. Increased risk of repeated self-harm and suicide exists amongst patients presenting to hospital with high-risk self-harm and major self-harm repeaters. However, so far evidence-based training in the management of self-harm for mental health professionals is limited. Within this context, we aim to develop, implement and evaluate a training programme, SAMAGH, Self-harm Assessment and Management Programme for General Hospitals in Ireland. SAMAGH aims to (a) reduce hospital-based self-harm repetition rates and (b) increase rates of mental health assessments being conducted with self-harm patients. We also aim to evaluate the training on self-harm knowledge, attitudes, and skills related outcomes of healthcare professionals involved in the training.

Methods/design

The study will be conducted in three phases. First, the SAMAGH Training Programme has been developed, which comprises two parts: 1) E-learning Programme and 2) Simulation Training. Second, SAMAGH will be delivered to healthcare professionals from general hospitals in Ireland. Third, an outcome and process evaluation will be conducted using a pre-post design. The outcome evaluation will be conducted using aggregated data from the National Self-Harm Registry Ireland (NSHRI) on self-harm repetition rates from all 27 public hospitals in Ireland. Aggregated data based on the 3-year average (2016, 2017, 2018) self-harm repetition rates prior to the implementation of the SAMAGH will be used as baseline data, and NSHRI data from 6 and 12 months after the implementation of SAMAGH will be used as follow-up. For the process evaluation, questionnaires and focus groups will be administered and conducted with healthcare professionals who completed the training.

Discussion

This study will contribute to the evidence base regarding the effectiveness of an evidence informed training programme that aims to reduce repeated hospital self-harm presentations and to improve compliance with self-harm assessment and management. This study is also expected to contribute to self-harm and suicide training with the possibility of being translated to other settings. Its feasibility will be evaluated through a process evaluation.
Patient-relevant outcomes: what are we talking about? A scoping review to improve conceptual clarity
Authors: Kersting Christine , Kneer Malte , Barzel Anne
Published: June 2020

Background

With respect to patient-centered care, measuring care effects based on patient-relevant outcomes is becoming increasingly important. There is some uncertainty about what outcomes are particularly relevant to patients and who determines their relevance. To determine this, we conducted a scoping review of the international literature with the aim to improve the conceptual clarity regarding (1) the terminology used for supposedly patient-relevant outcomes, (2) the variety of outcomes considered patient-relevant, and (3) justifications for the choice of these specific outcomes.

Methods

We conducted a systematic search in Embase, PubMed (including Medline), Cochrane Central, Scopus, and Google Scholar with a special focus on article titles. Search terms included patient-relevant, patient-important, patient-preferred, and outcome(s), endpoint(s), parameter(s), indicator(s). We limited the search period from January 2000 to July 2019. Full-text articles reporting outcomes that were described as patient-relevant met the inclusion criteria. Two researchers independently analyzed all eligible articles applying quantitative and structuring content analysis.

Results

We identified 155 articles, 44 of which met the inclusion criteria. A content analysis revealed 35 different terms used with regard to patient-relevant outcomes. However, authors predominantly referred to patient-important outcomes (23 articles, 52.3%) and patient-relevant outcomes (17 articles, 38.6%). A structuring content analysis of all extracted outcomes revealed a total of 281 codes, pooled in 32 inductive categories. Among these, the following categories dominated: symptoms, adverse events/complications, survival/mortality, pain. In just 16 of the articles (36.4%), authors provided justifications for the choice of the outcome being based either on patient and/or expert opinions. In another 13 articles (29.5%), no justification was provided.

Conclusion

This scoping review on patient-relevant outcomes was driven by the questions (1) what outcomes are particularly relevant to patients, and (2) who determines their relevance. We found a wide range of supposedly patient-relevant outcomes, with only one third of articles involving patients in the justification of the outcome selection. In view of this conceptual uncertainty it appears difficult to determine or even to compare a particular patient benefit of interventions. A set of generic outcomes relevant to patients would be helpful to contribute to a consistent understanding of patient relevance.
Cytotoxicity study of the interleukin-12-expressing recombinant Newcastle disease virus strain, rAF-IL12, towards CT26 colon cancer cells in vitro and in vivo
Authors: Najmuddin Syed Umar Faruq Syed , Amin Zahiah Mohamed , Tan Sheau Wei , Yeap Swee Keong , Kalyanasundram Jeevanathan , Ani Muhamad Alhapis Che , Veerakumarasivam Abhimanyu , Chan Soon Choy , Chia Suet Lin , Yusoff Khatijah , Alitheen Noorjahan Banu
Published: June 2020

Background

Oncolytic viruses have emerged as an alternative therapeutic modality for cancer as they can replicate specifically in tumour cells and induce toxic effects leading to apoptosis. Despite the great potentials and promising results shown in multiple studies, it appears that their efficacy is still moderate and deemed as not sufficient in clinical studies. In addressing this issue, genetic/molecular engineering approach has paved its way to improve the therapeutic efficacy as observed in the case of herpes simplex virus (HSV) expressing granulocyte–macrophage colony-stimulating factor (GM-CSF). This study aimed to explore the cytotoxicity effects of recombinant NDV strain AF2240-i expressing interleukin-12 (rAF-IL12) against CT26 colon cancer cells.

Methods

The cytotoxicity effect of rAF-IL12 against CT26 colon cancer cell line was determined by MTT assay. Based on the IC50 value from the anti-proliferative assay, further downward assays such as Annexin V FITC and cell cycle progression were carried out and measured by flow cytometry. Then, the in vivo study was conducted where the rAF-IL12 viral injections were given at the intra-tumoral site of the CT26 tumour-burden mice. At the end of the experiment, serum biochemical, T cell immunophenotyping, serum cytokine, histopathology of tumour and organ section, TUNEL assay, and Nanostring gene expression analysis were performed.

Results

The rAF-IL12 induced apoptosis of CT26 colon cancer cells in vitro as revealed in the Annexin V FITC analysis and also arrested the cancer cells progression at G1 phase of the cell cycle analysis. On the other hand, the rAF-IL12 significantly (p < 0.05) inhibited the growth of CT26 tumour in Balb/c mice and had regulated the immune system by increasing the level of CD4 + , CD8 + , IL-2, IL-12, and IFN-γ. Furthermore, the expression level of apoptosis-related genes (bax and p53) was up-regulated as a result of the rAF-IL12 treatment. Additionally, the rAF-IL12 had also down-regulated the expression level of KRAS, BRAF, MAPK1, Notch1, CCL2, and VEGF oncogenes. Besides, rAF-IL12 intra-tumoral delivery was considered safe and not hazardous to the host as evidenced in pathophysiology of the normal tissues and organs of the mice as well as from the serum biochemistry profile of liver and kidney.

Conclusions

These results indicated that rAF-IL12 had better anti-tumoral and cytotoxicity effects compared to its parental wild-type, AF2240-i in combatting the CT26 colon cancer model.
Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation
Authors: Xie Mengyan , Yu Tao , Jing Xinming , Ma Ling , Fan Yu , Yang Fengming , Ma Pei , Jiang Huning , Wu Xi , Shu Yongqian , Xu Tongpeng
Published: June 2020

Background

Circular RNAs (circRNAs) play important regulatory roles in the development of various cancers. However, biological functions and the underlying molecular mechanism of circRNAs in gastric cancer (GC) remain obscure.

Methods

Differentially expressed circRNAs were identified by RNA sequencing. The biological functions of circSHKBP1 in GC were investigated by a series of in vitro and in vivo experiments. The expression of circSHKBP1 was evaluated using quantitative real-time PCR and RNA in situ hybridization, and the molecular mechanism of circSHKBP1 was demonstrated by western blot, RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Lastly, mouse xenograft and bioluminescence imaging were used to exam the clinical relevance of circSHKBP1 in vivo.

Results

Increased expression of circSHKBP1(hsa_circ_0000936) was revealed in GC tissues and serum and was related to advanced TNM stage and poor survival. The level of exosomal circSHKBP1 significantly decreased after gastrectomy. Overexpression of circSHKBP1 promoted GC cell proliferation, migration, invasion and angiogenesis in vitro and in vivo, while suppression of circSHKBP1 plays the opposite role. Exosomes with upregulated circSHKBP1 promoted cocultured cells growth. Mechanistically, circSHKBP1 sponged miR-582-3p to increase HUR expression, enhancing VEGF mRNA stability. Moreover, circSHKBP1 directly bound to HSP90 and obstructed the interaction of STUB1 with HSP90, inhibiting the ubiquitination of HSP90, resulting in accelerated GC development in vitro and in vivo.

Conclusion

Our findings demonstrate that exosomal circSHKBP1 regulates the miR-582-3p/HUR/VEGF pathway, suppresses HSP90 degradation, and promotes GC progression. circSHKBP1 is a promising circulating biomarker for GC diagnosis and prognosis and an exceptional candidate for further therapeutic exploration.
Factors associated with quality of life among chronic kidney disease patients in Nepal: a cross-sectional study
Authors: Mahato Shambhu Kumar Saxena , Apidechkul Tawatchai , Sriwongpan Pamornsri , Hada Rajani , Sharma Guna Nidhi , Nayak Shravan Kumar , Mahato Ram Kumar
Published: June 2020

Background

Chronic kidney disease (CKD) leads to decreased quality of life (QOL) by increasing the risk of death during the progression of its pathogenesis. However, many factors can be improved to support QOL. This study aimed to assess QOL among CKD patients in Nepal and to determine the factors associated with their QOL.

Method

A cross-sectional study was used for data collection. CKD cases receiving medical attention in the Bir Hospital in Mahaboudh, Kathmandu; Tribhuvan University Teaching Hospital in Maharajgunj, Kathmandu; Sumeru Hospital in Dhapakhel, Lalitpur; and Shahid Dharma Bhakta National Transplant Centre in Bhaktapur between August and October 2019 were invited to participate in the study. A validated questionnaire and the kidney disease quality of life short form (KDQOL-SF™ 1.3) were used to assess QOL. A questionnaire was completed by the researcher in face-to-face interviews. Logistic regression was used to detect the associations between variables at the significance level of α = 0.05.

Results

A total of 440 participants were recruited into the study: 56.59% were males, 74.32% were aged between 31 and 70 years, 25.68% were illiterate, and 82.95% were unemployed. The prevalence of good QOL among CKD in the domains of the physical component summary (PCS), mental component summary (MCS), and kidney disease component summary (KDCS) with and without hemodialysis were 53.64, 22.05, 21.28, and 13.19%, respectively. After controlling for all potential confounding factors, eight variables were found to be associated with good QOL in the domain of PCS: age, education, stage of CKD, hemodialysis, transporting oneself to a hospital, health insurance, medical expenses, and perceived lack of difficulty in handling medical expenses. Six variables were associated with good QOL in the domain of MCS after controlling for all potential confounding factors: residence, stage of CKD, transporting oneself to a hospital, health insurance, medical expenses, and perceived lack of difficulty in handling medical expenses.

Conclusions

Public health interventions should be developed and implemented to improve QOL among CKD patients in Nepal by focusing on older female patients who have low education, live in rural areas and no health insurance.