bluuebunny/crossref_metadata_2025 huggingface dataset:
A Moderated Mediation Model of Entrepreneurial Self-Efficacy, Institutional Environment, and Entrepreneurial Orientation for SME Development
Authors: Alarjani Fahad Nasser F. , Anwar Bilal , Danial Aslam Hassan , Iqbal Shahid , Ayub Arslan
Published: July 2020

A vital component for sustainable economic development is the entrepreneurship regardless of the social, geopolitical, and economic situations. However, it is an intimidating challenge to develop and maintain productive small and medium enterprises (SMEs). This article investigates the role of entrepreneurial self-efficacy (ESE) and institutional environment in entrepreneurial orientation and the development of a successful entrepreneurship-based SME. It integrates the institutional climate, self-efficacy, and theory of planned behavior to address the abovementioned challenge in the context of the Kingdom of Saudi Arabia. This study adopts an instrument to collect data from Saudi SME owners and employs SPSS Amos to analyze the proposed moderated mediation model. The outcomes of this study identify the contribution of ESE and institutional environment in the productiveness of an effective entrepreneurship-based SME.
The impact of COVID-19 pandemic on orthopaedic specialty in Malaysia: A cross-sectional survey
Authors: Teo Seow Hui , Abd Rahim Mohd Rashdan , Nizlan Nasir M
Published: July 2020

Purpose:

This study aims to investigate further how the coronavirus disease 2019 (COVID-19) pandemic is affecting orthopaedic surgeon in Malaysia in terms of exposure, general perceptions of risk, and the impact on their current and future practice.

Methods:

Orthopaedic surgeons nationwide were invited through email and text messages to answer an online self-administered questionnaire collecting demographic information, COVID-19 exposure experience, perception of risk, and impact on orthopaedic practice.

Results:

Of the respondents, 4.7% and 14.0% were involved in frontline treatment for COVID-19 patients with non-orthopaedic and orthopaedic problem, respectively. Respondents working in Ministry of Health had highest percentage of involvement as frontliner, 7.8% (8/103) and 20.4% (21/103) for non-orthopaedic and orthopaedic related COVID-19 treatment, respectively (not significant). Their main concern was an infection of family members (125/235, 53.2%). Majority of respondents were still working (223/235, 94.9%), running outpatient clinics (168/223, 75.3%), and continued with their semi-emergency (190/223, 85.2%) and emergency surgeries (213/223, 95.5%). Of the surgeons, 11.2% (25/223) did not screen their patients for COVID-19 prior to elective surgeries, 30.9% (69/223) did not have any training on proper handling of personal protective equipment (PPE), 84.8% (189/223) make decision to manage more conservatively due to COVID-19 and 61.9% (138/223) had their income affected. Of the surgeons, 19.3% (43/223) started using telehealth facilities.

Conclusion:

Direct exposure to treatment of COVID-19 patients among the respondent is low and the main concern was infecting their family member. There are still several surgeons who did not conduct preoperative COVID-19 screening and practice without proper PPE training.
Effect of Sex on Anterior Cruciate Ligament Injury–Related Biomechanics During the Cutting Maneuver in Preadolescent Athletes
Authors: Petrovic Milos , Sigurðsson Haraldur B. , Sigurðsson Hjálmar J. , Sveinsson Thorarinn , Briem Kristín
Published: July 2020

Background:

There are 2 movement patterns associated with an anterior cruciate ligament (ACL) injury: dynamic valgus and stiff landing. Although sex-dependent differences have been identified for adults, less is known for preadolescent athletes regarding movement patterns known to load the ACL.

Hypothesis:

We hypothesized that girls would demonstrate greater vertical ground reaction forces and knee valgus angles. We further hypothesized that the exercise intervention would affect girls more than boys and that this would primarily be demonstrated in less sagittal plane excursions, increased vertical ground reaction forces and knee valgus moments for girls than for boys.

Study Design:

Controlled laboratory study.

Methods:

Male and female soccer and handball players (n = 288; age range, 9-12 years) were recruited. A motion capture system synchronized to a force platform was used to record 5 trials of a cutting maneuver before and after a 5-minute fatigue intervention. Linear mixed models were constructed, and analysis of variance was used to analyze differences in outcomes associated with the sex of the athletes.

Results:

Boys showed greater peak knee valgus moment (0.26 vs 0.22 N·m/kg, respectively; P = .048), peak knee internal rotation moment (–0.13 vs –0.10 N·m/kg, respectively; P = .021), knee rotation excursion (–7.9° vs –6.9°, respectively; P = .014), and knee extension excursion (2.7° vs 1.4°, respectively; P < .001) compared with that in girls. A significant sex × fatigue intervention interaction ( F = 7.6; P = .006) was found, which was caused by a greater increase in first peak vertical ground-reaction force (vGRF) from before to after the fatigue intervention for girls (15.3 to 16.0 N/kg) compared with boys (16.4 to 16.5 N/kg).

Conclusion:

Differences detected for biomechanical factors during the cutting maneuver do not point to a greater ACL injury risk for prepubescent or early pubescent girls than for boys. Nonetheless, girls go on to develop more detrimental movement patterns in adolescence than those in boys in terms of biomechanical risk factors.

Clinical Relevance:

Early adolescence is a good target age to learn and develop muscular control; balance, strength; flexibility; and jumping, running, and landing control. This time of physical and athletic growth may therefore be an appropriate period to influence biomechanical factors and thereby task execution and the injury risk.
Preclerkship Point-of-Care Ultrasound: Image Acquisition and Clinical Transferability
Authors: Khoury Michel , Fotsing Salomon , Jalali Alireza , Chagnon Nicolas , Malherbe Stéphanie , Youssef Nermine
Published: July 2020

Introduction:

The integration of point-of-care ultrasound (POCUS) in preclerkship medical education is currently popular and based on the notion that POCUS may improve diagnostic and procedural skills in medical students. However, empirical evidence demonstrating that POCUS can enhance clinical skills in preclerkship students has been lacking. We sought to evaluate anatomical sonographic knowledge and ultrasound generation capabilities associated with the implementation of a 3-h echocardiography training camp led by 2 emergency physicians and using a flipped classroom design.

Methods:

Preclerkship students from the University of Ottawa (n = 32) were recruited to participate. A flipped classroom model was adopted, providing students with a 3-chaptered peer-designed, expert validated ultrasound manual before the workshop, to maximize scanning times (2 h of reading). A pretest Likert-type design was used to assess student perception of the ultrasound tool. Similarly, a pretest/post-test model was used to assess sonographic anatomical identification. In addition, a subsequent Objective Structured Clinical Examination (OSCE) test was done 3 weeks after the hands-on session, to evaluate image generation (4 cardiac views: parasternal long, parasternal short, subxiphoid, and apical 4 chambers), understanding of knobology and structural labeling.

Results:

For the sonographic anatomy, there was a statistically significant increase ( P < .001) between pretest (average = 12.12) and post-test (average = 18.85). The OSCE, which also ascertained knowledge retention, found that 81% of students were able to generate all 4 cardiac views perfectly, 6% were able to obtain 3 views, 10% obtained 2 views and 3% successfully generated a single view. The most challenging scan to generate was the apical 4-chamber view.

Conclusion:

The positive outcomes stemming from this study reinforces the notion that formal curricular integration of POCUS at the preclerkship level has tangible benefits for medical students.
‘Perfectly individualized and constantly visible’? Lateral tightness in a prison holding men convicted of sex offences
Authors: Ievins Alice
Published: July 2020

Late-modern penal power has been described as ‘tight’. Through the increasing use of indeterminate sentences and psychological assessment, and the growing insistence that prisoners engage in self-government, the prison monitors and seeks to change those it holds. This tight and disciplinarian power is often described as contributing to the increasing fragmentation and atomisation of the prisoner community. However, this article, which is based on research conducted in a English medium-security prison for men convicted of sex offences, argues that tightness can operate through the prisoner community, in a process which it terms ‘lateral regulation’. It shows that prisoners spend a lot of time observing, categorising and policing their peers, in ways which replicate and often uphold the more formal systems of power. However, the relationship between these two systems of power is complex, and prisoners’ collective self-regulation can conflict with and challenge the demands of the penal institution, in a way which reveals some of the weaknesses in the institution’s disciplinary gaze, and indicates the normative motivations underlying this regulation.
An Artistic Virtue? Student Perceptions of Humility in Music Participation
Authors: Coppola William J.
Published: July 2020

Humility is considered to be an important social virtue, particularly in interpersonal contexts. Given the highly social nature of music participation, researchers have begun exploring the potential role that humility might play in music education. The purpose of this study was to examine how middle school, high school, and undergraduate band students ( N = 116) perceived the virtue of humility, including whether they viewed it to be a social strength among various types of musicians. Results indicated that students viewed humility to be a positive quality and a social strength for different types of musicians (i.e., band directors, section leaders, famous musicians). However, middle schoolers struggled to articulate a meaning of humility consistent with accepted definitions put forth by social scientists. Based on these findings, I offer recommendations for music educators to model and promote humility as a positive and necessary virtue in their ensembles and classrooms.
Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes
Authors: Matsushita Junya , Suzuki Takehiro , Okamura Kazuyuki , Ichihara Gaku , Nohara Keiko
Published: July 2020

Background

Various treatments for hepatocellular carcinoma (HCC) are utilized in clinical practice; however, the prognosis is still poor on account of high recurrence rates. DNA methylation levels of CpG islands around promoters (promoter CpGis) inversely regulate gene expression and closely involved in carcinogenesis. As a new strategy, several chemicals globally inhibiting DNA methylation have been developed aiming at reducing DNA methylation levels and maintaining the expression of tumor suppressor genes. On the other hand, since these drugs nonspecifically modify DNA methylation, they can cause serious adverse effects. In order to ameliorate the methods by targeting specific CpGs, information of cancer-related genes that are regulated by DNA methylation is required.

Methods

We searched candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and which are involved in HCC cases. To do so, we first identified genes whose expression were changed in HCC by comparing gene expressions of 371 HCC tissues and 41 non-tumor tissues using the Cancer Genome Atlas (TCGA) database. The genes were further selected for poor prognosis by log-rank test of Kaplan-Meier plot and for cancer relevance by Pubmed search. Expression profiles of upregulated genes in HCC tissues were assessed by Gene Ontology (GO) analysis. Finally, using DNA methylation data of TCGA database, we selected genes whose promoter DNA methylation levels were inversely correlated with gene expression.

Results

We found 115 genes which were significantly up- or downregulated in HCC tissues and were associated with poor prognosis and cancer relevance. The upregulated genes were significantly enriched in cell division, cell cycle, and cell proliferation. Among the upregulated genes in HCC, we identified hypomethylation of CpGis around promoters of FANCB, KIF15, KIF4A, ERCC6L, and UBE2C. In addition, TCGA data showed that the tumor suppressor gene P16 is unexpectedly overexpressed in many types of cancers.

Conclusions

We identified five candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and associate with cancer cases and poor prognosis in HCC. Modification of site-specific DNA methylation of these genes enables a different approach for HCC treatment with higher selectivity and lower adverse effects.
CDSnake: Snakemake pipeline for retrieval of annotated OTUs from paired-end reads using CD-HIT utilities
Authors: Kondratenko Yulia , Korobeynikov Anton , Lapidus Alla
Published: July 2020

Background

Illumina paired-end reads are often used for 16S analysis in metagenomic studies. Since DNA fragment size is usually smaller than the sum of lengths of paired reads, reads can be merged for downstream analysis. In spite of development of several tools for merging of paired-end reads, poor quality at the 3′ ends within the overlapping region prevents the accurate combining of significant portion of read pairs. Recently CD-HIT-OTU-Miseq was presented as a new approach for 16S analysis using the paired-end reads, it completely avoids the reads merging process due to separate clustering of paired reads. CD-HIT-OTU-Miseq is a set of tools which are supposed to be successively launched by auxiliary shell scripts. This launch mode is not suitable for processing of big amounts of data generated in modern omics experiments. To solve this issue we created CDSnake – Snakemake pipeline utilizing CD-HIT tools for easier consecutive launch of CD-HIT-OTU-Miseq tools for complete processing of paired end reads in metagenomic studies. Usage of pipeline make 16S analysis easier due to one-command launch and helps to yield reproducible results.

Results

We benchmarked our pipeline against two commonly used pipelines for OTU retrieval, incorporated into popular workflow for microbiome analysis, QIIME2 - DADA2 and deblur. Three mock datasets having highly overlapping paired-end 2 × 250 bp reads were used for benchmarking - Balanced, HMP, and Extreme. CDSnake outputted less OTUs than DADA2 and deblur. However, on Balanced and HMP datasets number of OTUs outputted by CDSnake was closer to real number of strains which were used for mock community generation, than those outputted by DADA2 and deblur. Though generally slower than other pipelines, CDSnake outputted higher total counts, preserving more information from raw data. Inheriting this properties from original CD-HIT-OTU-MiSeq utilities, CDSnake made their usage handier due to simple scalability, easier automated runs and other Snakemake benefits.

Conclusions

We developed Snakemake pipeline for OTU-MiSeq utilities, which simplified and automated data analysis. Benchmarking showed that this approach is capable to outperform popular tools in certain conditions.
Extending rnaSPAdes functionality for hybrid transcriptome assembly
Authors: Prjibelski Andrey D. , Puglia Giuseppe D. , Antipov Dmitry , Bushmanova Elena , Giordano Daniela , Mikheenko Alla , Vitale Domenico , Lapidus Alla
Published: July 2020

Background

De novo RNA-Seq assembly is a powerful method for analysing transcriptomes when the reference genome is not available or poorly annotated. However, due to the short length of Illumina reads it is usually impossible to reconstruct complete sequences of complex genes and alternative isoforms. Recently emerged possibility to generate long RNA reads, such as PacBio and Oxford Nanopores, may dramatically improve the assembly quality, and thus the consecutive analysis. While reference-based tools for analysing long RNA reads were recently developed, there is no established pipeline for de novo assembly of such data.

Results

In this work we present a novel method that allows to perform high-quality de novo transcriptome assemblies by combining accuracy and reliability of short reads with exon structure information carried out from long error-prone reads. The algorithm is designed by incorporating existing hybridSPAdes approach into rnaSPAdes pipeline and adapting it for transcriptomic data.

Conclusion

To evaluate the benefit of using long RNA reads we selected several datasets containing both Illumina and Iso-seq or Oxford Nanopore Technologies (ONT) reads. Using an existing quality assessment software, we show that hybrid assemblies performed with rnaSPAdes contain more full-length genes and alternative isoforms comparing to the case when only short-read data is used.
An integrative network-driven pipeline for systematic identification of lncRNA-associated regulatory network motifs in metastatic melanoma
Authors: Singh Nivedita , Eberhardt Martin , Wolkenhauer Olaf , Vera Julio , Gupta Shailendra K.
Published: July 2020

Background

Melanoma phenotype and the dynamics underlying its progression are determined by a complex interplay between different types of regulatory molecules. In particular, transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) interact in layers that coalesce into large molecular interaction networks. Our goal here is to study molecules associated with the cross-talk between various network layers, and their impact on tumor progression.

Results

To elucidate their contribution to disease, we developed an integrative computational pipeline to construct and analyze a melanoma network focusing on lncRNAs, their miRNA and protein targets, miRNA target genes, and TFs regulating miRNAs. In the network, we identified three-node regulatory loops each composed of lncRNA, miRNA, and TF. To prioritize these motifs for their role in melanoma progression, we integrated patient-derived RNAseq dataset from TCGA (SKCM) melanoma cohort, using a weighted multi-objective function. We investigated the expression profile of the top-ranked motifs and used them to classify patients into metastatic and non-metastatic phenotypes.

Conclusions

The results of this study showed that network motif UCA1/AKT1/hsa-miR-125b-1 has the highest prediction accuracy (ACC = 0.88) for discriminating metastatic and non-metastatic melanoma phenotypes. The observation is also confirmed by the progression-free survival analysis where the patient group characterized by the metastatic-type expression profile of the motif suffers a significant reduction in survival. The finding suggests a prognostic value of network motifs for the classification and treatment of melanoma.
Exogenous 2-(3,4-Dichlorophenoxy) triethylamine alleviates salinity stress in maize by enhancing photosynthetic capacity, improving water status and maintaining K+/Na+ homeostasis
Authors: Li Lijie , Gu Wanrong , Zhang Liguo , Li Congfeng , Chen Xichang , Qian Chunrong , Wang Zhenhua , Li Wenhua , Zuo Shiyu , Wei Shi
Published: July 2020

Background

Soil salinity restricts plant growth and productivity. 2-(3,4-dichlorophenoxy) triethylamine (DCPTA) can alleviate salinity stress in plants. However, the mechanism of DCPTA-mediated salinity tolerance has not been fully clarified. We aimed to investigate its role in enhancing photosynthetic capacity, improving water status, maintaining K+/Na+ homeostasis and alleviating salinity stress in maize (Zea mays L.).

Results

In present study, maize seedlings were grown in nutrient solutions with a combination of NaCl (0, 150 mM) and DCPTA (0, 20, 100, and 400 μM). And photosynthesis, water status, ion homeostasis and the expression of genes involved in ion uptake and transport were evaluated in the maize seedlings. The results demonstrated that DCPTA alleviated the growth inhibition of maize seedlings exposed to salinity stress by increasing the net photosynthetic rate (Pn) and the quantum efficiency of photosystem II (PSII) photochemistry. DCPTA improved the root hydraulic conductivity, which help maintained the water status. A relatively high K+ concentration but a relatively low Na+ concentration and the Na+/K+ ratio were observed in the presence of DCPTA under salinity stress. Additionally, DCPTA altered the expression of four genes (ZmSOS1, ZmHKT1, ZmNHX1 and ZmSKOR) that encode membrane transport proteins responsible for K+/Na+ homeostasis.

Conclusions

DCPTA improved the salinity tolerance of maize may be associated with enhanced photosynthetic capacity, maintenance of water status and altered expression of genes involved in ion uptake and transport.
Integrated metabolomic and transcriptomic analysis of the anthocyanin regulatory networks in Salvia miltiorrhiza Bge. flowers
Authors: Jiang Tao , Zhang Meidi , Wen Chunxiu , Xie Xiaoliang , Tian Wei , Wen Saiqun , Lu Ruike , Liu Lingdi
Published: July 2020

Background

The objectives of this study were to reveal the anthocyanin biosynthesis metabolic pathway in white and purple flowers of Salvia miltiorrhiza using metabolomics and transcriptomics, to identify different anthocyanin metabolites, and to analyze the differentially expressed genes involved in anthocyanin biosynthesis.

Results

We analyzed the metabolomics and transcriptomics data of S. miltiorrhiza flowers. A total of 1994 differentially expressed genes and 84 flavonoid metabolites were identified between the white and purple flowers of S. miltiorrhiza. Integrated analysis of transcriptomics and metabolomics showed that cyanidin 3,5-O-diglucoside, malvidin 3,5-diglucoside, and cyanidin 3-O-galactoside were mainly responsible for the purple flower color of S. miltiorrhiza. A total of 100 unigenes encoding 10 enzymes were identified as candidate genes involved in anthocyanin biosynthesis in S. miltiorrhiza flowers. Low expression of the ANS gene decreased the anthocyanin content but enhanced the accumulation of flavonoids in S. miltiorrhiza flowers.

Conclusions

Our results provide valuable information on the anthocyanin metabolites and the candidate genes involved in the anthocyanin biosynthesis pathways in S. miltiorrhiza.
Misdiagnosis of peripheral abscess caused by duodenal foreign body: a case report and literature review
Authors: Wang Zhihui , Du Zhiqiang , Zhou Xiangrong , Chen Tianming , Li Chunyan
Published: July 2020

Background

The induction of chronic inflammation, perforation, and abscess by foreign bodies (FBs) in adults is uncommon. We present a delayed diagnosis case for a patient who had a fishbone stuck in the duodenal bulb, resulting in chronic abdominal pain for nearly 3 months. We present the diagnosis and treatment procedures for chronic patients, which differ from those for acute and emergency FB ingestion, and also summarize the characteristics of such patients through a systematic literature review.

Case presentation

A 68-year-old woman was brought to our hospital with repeated right upper abdominal pain lasting for 3 months and aggravation for 9 h. Computed tomography (CT) showed a streaky high-density shadow (approximately 3 cm in length) on the posterior wall of the gastric antrum extending outside the wall. Endoscopic ultrasonography showed hyperechoic space with a cross-section of approximately 0.1 × 0.1 cm in the deep submucosal layer of the local stomach, accompanied by an acoustic shadow in the rear. The possibility of a fishbone as well as perforation was considered and the object was removed using FB forceps. Fasting as well as acid inhibition and anti-infection medication were prescribed for the patient. She eventually recovered and was discharged from the hospital.

Conclusion

Endoscopic intervention can be recommended as the first option for patients with gastrointestinal FBs.
Noninfectious mixed cryoglobulinaemic glomerulonephritis and monoclonal gammopathy of undetermined significance: a coincidental association?
Authors: Flavell Adam L. , Fullinfaw Robert O. , Smith Edward R. , Holt Stephen G. , Finlay Moira J. , Barbour Thomas D.
Published: July 2020

Background

Cryoglobulins are cold-precipitable immunoglobulins that may cause systemic vasculitis including cryoglobulinaemic glomerulonephritis (CGN). Type 1 cryoglobulins consist of isolated monoclonal immunoglobulin (mIg), whereas mixed cryoglobulins are typically immune complexes comprising either monoclonal (type 2) or polyclonal (type 3) Ig with rheumatoid activity against polyclonal IgG. Only CGN related to type 1 cryoglobulins has been clearly associated with monoclonal gammopathy of undetermined significance (MGUS) using the conventional serum-, urine- or tissue-based methods of paraprotein detection.

Case presentation

We present four patients with noninfectious mixed (type 2 or 3) CGN and MGUS. Two patients had type 2 cryoglobulinaemia, one had type 3 cryoglobulinaemia, and one lacked definitive typing of the serum cryoprecipitate. The serum monoclonal band was IgM-κ in all four cases. Treatments included corticosteroids, cyclophosphamide, plasma exchange, and rituximab. At median 3.5 years’ follow-up, no patient had developed a haematological malignancy or advanced chronic kidney disease. Other potential causes of mixed cryoglobulinaemia were also present in our cohort, notably primary Sjögren’s syndrome in three cases.

Conclusion

Our study raises questions regarding the current designation of type 2 CGN as a monoclonal gammopathy of renal significance, and the role of clonally directed therapies for noninfectious mixed CGN outside the setting of haematological malignancy.
An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report
Authors: Galante J. R. , Daruwalla C. P. , Roberts I. S. D. , Haynes R. , Storey B. C. , Bottomley M. J.
Published: July 2020

Background

A number of disease processes can culminate in rapidly progressive glomerulonephritis, including pauci-immune focal segmental necrotising glomerulonephritis, usually seen with positive serum antineutrophil cytoplasmic antibodies (ANCA). Propylthiouracil (PTU) has been associated with drug-induced ANCA-associated vasculitis (AAV), with antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) present individually and together having been recognised. ‘Double-positive’ vasculitis with ANCA and anti-glomerular basement membrane (GBM) antibodies has also been reported in association with PTU treatment. We present a case of PTU-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate.

Case presentation

A 51-year-old man presented 2 weeks after re-commencing propylthiouracil (PTU) treatment for Graves’ disease, with a severe acute kidney injury and haemato-proteinuria. He demonstrated positive titres for autoantibodies to PR3 (76.9 IU/mL), MPO (28.8 IU/mL) and GBM (94 IU/mL). Renal biopsy demonstrated numerous glomerular crescents, widespread IgG4-positive lymphoplasmacytic infiltrate and mesangial positivity for IgA. PTU was stopped and he was treated with steroids, plasma exchange and cyclophosphamide with sustained improvement in his renal function.

Conclusions

This case of drug-induced AAV presented a unique and intriguing collection of serological and histological features. We propose that the PTU-induced AAV resulted in epiphenomena of anti-GBM antibody production and an IgG4-cell-rich tubulointerstitial infiltrate. It is uncertain whether the mesangial IgA deposition preceded or resulted from the AAV.
A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway
Authors: Al-Khayal Khayal , Vaali-Mohammed Mansoor-Ali , Elwatidy Mohammed , Bin Traiki Thamer , Al-Obeed Omar , Azam Mohammad , Khan Zahid , Abdulla Maha , Ahmad Rehan
Published: July 2020

Background

Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer.

Methods

Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/− 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA.

Results

In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells.

Conclusion

Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.
Protocol of the QUATTRO-II study: a multicenter randomized phase II study comparing CAPOXIRI plus bevacizumab with FOLFOXIRI plus bevacizumab as a first-line treatment in patients with metastatic colorectal cancer
Authors: Miyo Masaaki , Kato Takeshi , Yoshino Takayuki , Yamanaka Takeharu , Bando Hideaki , Satake Hironaga , Yamazaki Kentaro , Taniguchi Hiroya , Oki Eiji , Kotaka Masahito , Oba Koji , Miyata Yoshinori , Muro Kei , Komatsu Yoshito , Baba Hideo , Tsuji Akihito
Published: July 2020

Background

First-line treatment with FOLFOXIRI plus bevacizumab (BEV) is highly effective and regarded as one of the standards-of-care for patients with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea as side effects. AXEPT, an Asian phase III study, showed that modified CAPIRI+BEV [capecitabine (CAP: 1600 mg/m2), irinotecan (IRI: 200 mg/m2), and BEV (7.5 mg/m2)] was non-inferior to FOLFIRI+BEV as a second-line therapy for mCRC patients and was associated with a lower incidence of hematologic toxicities. Thus, a reduced dose of the CAP and IRI regimen in combination with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) may be more feasible than FOLFOXIRI+BEV, without compromising efficacy.

Methods

QUATTRO-II is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses of OX and IRI will be investigated as a safety lead-in. In Step 2, patients will be randomized to the recommended dose of either CAPOXIRI+BEV or FOLFOXIRI+BEV. Induction triplet chemotherapy plus BEV treatments will be administered for up to 4 months followed by fluoropyrimidine plus BEV maintenance. The primary endpoint is progression-free survival (PFS). The similarity in PFS between the two arms will be evaluated by observing whether the point estimate of hazard ratio (HR) for PFS falls between 0.80 and 1.25. Ensuring a 70% probability that the observed HR will be “0.8 < HR < 1.25” under the assumption of the true HR of 1.0, and 100 patients will be evaluated during the 3-year study period. Secondary endpoints include overall survival, overall response rate, safety, and patient reported outcome (PRO) (FACT/GOG-Ntx4).

Discussion

Considering the lower incidence of hematologic toxicities with modified CAPIRI+BEV than with FOLFIRI+BEV, CAPOXIRI+BEV may be a promising treatment option if sufficient efficacy and lower hematologic toxicities are indicated in this study. Additionally, a lower incidence of peripheral sensory neuropathy (PSN) reported following CAPEOX treatment compared to that after FOLFOX in ACHIEVE, an adjuvant phase III trial, suggest that CAPOXIRI+BEV can mitigate OX-induced PSN.

Trial registration

Clinicaltrials.gov NCT04097444. Registered September 20, 2019, https://clinicaltrials.gov/ct2/show/study/NCT04097444/ Japan Registry of Clinical Trials jRCTs041190072. Registered October 9, 2019.
Determinants of caregiver burden of persons with disabilities in a rural district in Egypt
Authors: Ghazawy Eman Ramadan , Mohammed Eman Sameh , Mahfouz Eman Mohamed , Abdelrehim Marwa Gamal
Published: July 2020

Background

Family caregivers are critical partners in the plan of care of people with disabilities. The study aims to demonstrate the factor structure and internal consistency of the Caregiver Burden Inventory (CBI) among the studied caregivers of disabled persons and to determine the effects of patients’ and caregivers’ characteristics on the burden and its dimensions.

Methods

A cross-sectional study among 260 family caregivers of disabled patients was carried out in a randomly chosen rural area, Minia, Egypt, 2019. Exploratory factor analysis (EFA) was conducted to determine the factorial validity of the CBI. Multiple linear regression was used to identify the significant factors affecting the burden.

Results

Factor analysis resulted in a five-factor solution using 20 items (four for each dimension) accounting for 72.7% of the total variance. The CBI and its dimensions showed high internal consistency (Cronbach’s alpha value > 0.70). Education of caregiver, family income, mental impairments, and mixed disabilities were significant predictors of total CBI burden.

Conclusions

CBI is an effective multidimensional measure of the caregiver burden of disabled subjects. Caregivers experienced a distinct level of burden that is determined by caregiver and care recipient characteristics. Therefore, support and individualized counseling services should be optimized.
Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: study protocol of a randomised controlled multicentre trial (BIOPEX-2 study)
Authors: Sharabiany Sarah , Blok Robin D. , Lapid Oren , Hompes Roel , Bemelman Wilhelmus A. , Alberts Victor P. , Lamme Bas , Wijsman Jan H. , Tuynman Jurriaan B. , Aalbers Arend G. J. , Beets Geerard L. , Fabry Hans F. J. , Cherepanin Ivan M. , Polat Fatih , Burger Jacobus W. A. , Rutten Harm J. T. , Bosker Robert J. I. , Talsma Koen , Rothbarth Joost , Verhoef Cees , van de Ven Anthony W. H. , van der Bilt Jarmila D. W. , de Graaf Eelco J. R. , Doornebosch Pascal G. , Leijtens Jeroen W. A. , Heemskerk Jeroen , Singh Baljit , Chaudhri Sanjay , Gerhards Michael F. , Karsten Tom M. , de Wilt Johannes H. W. , Bremers Andre J. A. , Vuylsteke Ronald J. C. L. M. , Heuff Gijsbert , van Geloven Anna A. W. , Tanis Pieter J. , Musters Gijsbert D.
Published: July 2020

Background

Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer.

Methods

Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function.

Discussion

The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place.

Trial registration

The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019.
Application of flexible fiberoptic bronchoscopy in the removal of adult airway foreign bodies
Authors: Ma Weijun , Hu Juan , Yang Miaoli , Yang Yeye , Xu Min
Published: July 2020

Background

Flexible fiberoptic bronchoscopy is a rapid, cost effective and safe procedure.

Aim

To analyze demographic information and endoscopic findings in adult patients with airway foreign body aspiration and its removal.

Methods

Fifty-seven adults (40 males, 17 females; average age 40 years old) with airway foreign body aspiration were analyzed. Cough (37, 65%) was the most common clinical presentation. The most common foreign body was bone followed by dental prosthesis and food debris.

Results

In the current study, 42 out of the 57 (74%) airway foreign bodies were successfully removed under flexible fiberoptic bronchoscopy. However, it was failed in 15 patients and thus, rigid bronchoscopy was used to remove foreign bodies successfully in 13 of the 15 patients. Thoracotomy was performed for the 2 patients whose foreign body removal was unsuccessful even with rigid bronchoscopy.

Conclusion

The findings of the current study revealed that flexible fiberoptic bronchoscopy is a safe and effective procedure for the removal of adult airway foreign bodies in the majority of cases. Rigid bronchoscopy can be a backup procedure in case flexible bronchoscopy is failed.
Attenuation of intestinal inflammation in IL-10 deficient mice by a plasmid carrying Lactococcus lactis strain
Authors: Zurita-Turk Meritxell , Mendes Souza Bianca , Prósperi de Castro Camila , Bastos Pereira Vanessa , Pecini da Cunha Vanessa , Melo Preisser Tatiane , Caetano de Faria Ana Maria , Carmona Cara Machado Denise , Miyoshi Anderson
Published: July 2020

Background

Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract (GIT) and to date, no efficient treatments exist. Interleukin-10 (IL-10), one of the most important anti-inflammatory cytokines of the immune response, has been under study due to its potential for IBD therapy; however, systemic treatments lead to undesirable side effects and oral administration is limited due to its quick degradation. To avoid these bottlenecks, we previously engineered an invasiveLactococcus lactis(L. lactis) strain capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 ofMus musculus(pValac:il-10) that diminished inflammation in two induced mouse models of intestinal inflammation. Thus, the aim of this study was to analyze its therapeutic effect in the IL-10-deficient mouse model (IL-10−/−) that spontaneously and gradually develops an inflammation that modifies the immune system and resembles Crohn’s disease (CD) in humans, and evaluate if it would also diminish and/or prevent the onset of this disease.

Results

Oral administration ofL. lactisMG1363 FnBPA+ (pValac:il-10) to IL-10−/−mice not only led to IL-10 production by these, but consequently also diminished the severe development of the disease, with animals showing lower macroscopic scores and histological damages, increased IL-10 levels and tendency to lower pro-inflammatory cytokine levels.

Conclusions

The results of this study, together with the previously published ones using this DNA delivery-based strategy, show that it is capable of creating and maintaining an anti-inflammatory environment in the GIT and thus effectively diminish the onset of inflammation in various mouse models.
Using qualitative evaluation components to help understand context: case study of a family planning intervention with female community health volunteers (FCHVs) in Nepal
Authors: Marston Cicely , Arjyal Abriti , Maskey Smriti , Regmi Shophika , Baral Sushil
Published: July 2020

Background

Evaluations of health interventions are increasingly concerned with measuring or accounting for ‘context’. How to do this is still subject to debate and testing, and is particularly important in the case of family planning where outcomes will inevitably be influenced by contextual factors as well as any intervention effects. We conducted an evaluation of an intervention where female community health volunteers (FCHVs) in Nepal were trained to provide better interpersonal communication on family planning. We included a context-orientated qualitative component to the evaluation. Here, we discuss the evaluation findings, specifically focusing on what was added by attending to the context. We explore and illustrate important dimensions of context that may also be relevant in future evaluation work.

Methods

The evaluation used a mixed methods approach, with a qualitative component which included in-depth interviews with women of reproductive age, FCHVs, and family planning service providers. We conducted iterative, thematic analysis.

Results

The life-history fertility and contraception narratives generated from the in-depth interviews contextualised the intervention, yielding nuanced data on contraceptive choices, needs, and areas for future action. For instance, it highlighted how women generally knew about effective contraceptive methods and were willing to use them: information was not a major barrier. Barriers instead included reports of providers refusing service when women were not in the fifth day of their menstrual cycle when this was unnecessary. Privacy and secrecy were important to some women, and risked being undermined by information sharing between FCHVs and health services. The qualitative component also revealed unanticipated positive effects of our own evaluation strategies: using referral slips seemed to make it easier for women to access contraception.

Conclusions

Life history narratives collected via in-depth interviews helped us understand pathways from intervention to effect from the user point of view without narrowly focusing only on the intervention, highlighting possible areas for action that would otherwise have been missed. By attending to context in a nuanced way in evaluations, we can build a body of evidence that not only informs future interventions within that context, but also builds better knowledge of contextual factors likely to be important elsewhere.
Common mental disorders and its associated factors and mental health care services for Ethiopian labour migrants returned from Middle East countries in Addis Ababa, Ethiopia
Authors: Tilahun Melkie , Workicho Abdulhalik , Angaw Dessie Abebaw
Published: July 2020

Background

The migration of young Ethiopian men and women to the Middle East countries was mainly for economic reasons. The migration was largely irregular that posed a wide range of unfavorable life conditions for some of the migrants. The overall objective is to assess common mental disorders and its associated factors for Ethiopian migrants returned from the Middle East countries and to describe mental health care services targeting these migrants.

Methods

The study employed a mixed-methods approach. For the quantitative part, a systematic random sampling technique was used to select a sample of 517 returnees. An interviewer-administered questionnaire based on Self Report Questionnaire-20 was used to collect data from respondents. The qualitative study employed a phenomenological study design to describe mental health care services. Key informant interviews and non-participant observation techniques were used to collect qualitative data.

Results

The prevalence of common mental disorder among Ethiopian migrants returned from the Middle East countries was found to be 29.2%. education (AOR=2.90 95%CI: 1.21, 6.94), physical abuse (AOR=12.17 95%CI: 5.87, 25.22), not getting salary properly and timely (AOR=3.35 95%CI: 1.47, 7.63), history of mental illness in the family (AOR=6.75 95%CI: 1.03, 43.95), detention (AOR=4.74 95%CI: 2.60, 8.62), guilty feeling for not fulfilling goal (AOR=9.58 95%CI: 4.43, 20.71), and denial of access to health care (AOR=3.20 95%CI:1.53, 6.67) were significantly associated with a common mental disorder. Shelter based and hospital-based mental health care services were rendered for a few return migrants with mental disorders. The services were primarily targeted, female return migrants.

Conclusion

The prevalence of common mental disorder was high among migrants returned from the Middle East countries. Despite the high burden of mental distress, only a small proportion of return migrants with mental illness is getting mental health care services.