bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective cross-sectional observational study on the epidemiological profile of dengue cases in Pernambuco state, Brazil, between 2015 and 2017
Authors: do Nascimento Iasmyn Dayanne Santos , Pastor André Filipe , Lopes Thaísa Regina Rocha , Farias Pablo Cantalice Santos , Gonçales Juliana Prado , do Carmo Rodrigo Feliciano , Durães-Carvalho Ricardo , da Silva Caroline Simões , Silva Júnior José Valter Joaquim
Published: June 2020

Background

The spread of Dengue virus (DENV) infections, as well as their signs and symptoms, are the result of a complex interaction between several factors. In Brazil, especially in the Northeastern, dengue is an important public health problem. Here, we report an epidemiological analysis of dengue cases in Pernambuco state, Northeastern Brazil, during 2015–2017.

Methods

This work is a retrospective cross-sectional observational study on the epidemiological profile of all dengue cases confirmed and reported to the Health Secretary of Pernambuco between 2015 and 2017. These data cover all municipalities of Pernambuco, except Fernando de Noronha. DENV-positive individuals were classified according to the dengue type (without and with warning signs, or severe dengue), age, gender, ethnicity and intermediate geographic region of residence (Recife, Caruaru, Serra Talhada or Petrolina). The distribution of cases over the years was assessed by χ2 test. Temperature and rainfall data were evaluated by Unpaired t-test. p-value < 0.05 and CI 95% were considered in all analyses.

Results

Most dengue cases was without warning signs. The most observed characteristics in the less severe dengue phenotypes were: female, mulatto ethnicity and age between 20 and 39 years old; this profile was more clearly observed in 2015. In 2016 and 2017, however, the numbers of dengue without and with warning signs were more evenly distributed and the difference in cases within groups decreased significantly. Regarding severe dengue, mulattoes were the most affected, but it is possible to note a trend towards a more uniform distribution between the genders and ages. Recife was the region with the highest numbers of both total cases and incidence rates and the highest rainfall levels. Overall, over the years, there has been a decrease in dengue cases in all regions of Pernambuco.

Conclusions

We identified the epidemiological profile of dengue in Pernambuco, Brazil, reporting the gender, age, ethnicity and regions most affected by different dengue types. In addition, we observed that these cases were probably more influenced by rainfall than by temperature. Finally, we believe that this epidemiological knowledge is important to direct public health policies to the reality of each population.
The impact of cardiopulmonary resuscitation (CPR) training on schoolchildren and their CPR knowledge, attitudes toward CPR, and willingness to help others and to perform CPR: mixed methods research design
Authors: Pivač Sanela , Gradišek Primož , Skela-Savič Brigita
Published: June 2020

Background

The benefits of cardiopulmonary resuscitation training for schoolchildren are well known, but the appropriate age for introducing training is still being discussed. This is a very important issue, since out-of-hospital cardiac arrest is a major public health concern. The objective of this study was to investigate the effects of implemented cardiopulmonary resuscitation training on the knowledge of schoolchildren in the last three grades of Slovenian elementary schools and theirs willingness, attitudes, and intentions toward helping others and performing cardiopulmonary resuscitation. The experience of training instructors was also explored.

Methods

A mixed methods research design was employed, using a Separate Pre-Post Samples Design and focus groups. Research was conducted in 15 Slovenian public elementary schools offering cardiopulmonary resuscitation training. Focus groups included training instructors and developers. Data was collected with a structured questionnaire from April to June 2018 and analyzed using univariate and bivariate analyses. The three focus groups were convened in September and October 2018. Content analysis of the discussion transcriptions was conducted. The sample included 764 schoolchildren aged 12.5–14.5 years before cardiopulmonary resuscitation training and 566 schoolchildren after training. Three non-homogeneous focus groups included eight cardiopulmonary resuscitation instructors.

Results

Significant progress in cardiopulmonary resuscitation knowledge was noted after training implementation, with the greatest progress seen in the youngest age group (mean age 12.5). The greatest increase after training was seen for the variables Attitude toward helping others (p = 0.001) and Self-confidence (p = 0.001). Analysis of the focus groups yielded two themes: (a) the effects of cardiopulmonary resuscitation training on schoolchildren, and (b) the systemic responsibility of the school system and professional bodies.

Conclusions

Significant progress in schoolchildren’s cardiopulmonary resuscitation knowledge after training was established. Early introduction of training is recommended. Cardiopulmonary resuscitation knowledge raises awareness of the responsibility to help others and increases self-confidence to provide bystander cardiopulmonary resuscitation. It can be concluded that early cardiopulmonary resuscitation training for children is crucial. It should be a mandatory part of school curricula in those countries where cardiopulmonary resuscitation is not yet mandatory.
Efficacy of nano-carbonate apatite dentifrice in relief from dentine hypersensitivity following non-surgical periodontal therapy: a randomized controlled trial
Authors: Ding Pei-Hui , Dai Anna , Hu Hua-Jiao , Huang Jia-Ping , Liu Jia-Mei , Chen Li-Li
Published: June 2020

Background

Dentine hypersensitivity (DH) could occur or intensify after non-surgical periodontal therapy because of the exposure of dentine tubules, but currently no gold standard exists to treat DH. It has been demonstrated that nano-sized particles presented potential for dentine tubules blocking and remineralization. This randomized controlled trial aimed to investigate the efficacy of dentifrice containing nano-carbonate apatite (n-CAP) in reducing dentine hypersensitivity (DH) after non-surgical periodontal therapy.

Methods

48 periodontitis patients with DH were included in this clinical trial. After non-surgical periodontal therapy, patients included were randomized to test and control group and the respective dentifrices were applied at chairside, after which they were instructed to brush teeth with the allocated dentifrices twice a day at home. Periodontal parameters were recorded at baseline and the last follow-up. DH was measured by air-blast test and recorded by visual analogue scale (VAS) and Schiff sensitivity scale at baseline, after polishing (0 week) and 2/4/6 weeks.

Results

45 participants completed the follow-up. Periodontal parameters were improved and comparable between groups. Significant reduction in DH was observed in both groups at all time-points compared to baseline in terms of VAS and Schiff score. The test group achieved significantly greater relief from hypersensitivity compared with the control group after 4-week at-home use (for change of VAS, test group: 2.27 ± 2.47 versus control group: 1.68 ± 2.24, p = 0.036; for change of Schiff, test group: 0.94 ± 0.92 versus control group: 0.61 ± 0.83, p < 0.001). The 6-week results showed borderline significance between groups in terms of change of Schiff (p = 0.027) and no significance in terms of change of VAS (p = 0.256).

Conclusions

Home-use of n-CAP based dentifrice had some benefit on alleviation of DH following non-surgical periodontal therapy after 4 weeks compared to the control product.

Trial registration

Chinese Clinical Trials Registry (No. ChiCTR-IPR-17011678, http://www.chictr.org.cn/, registered 16 June, 2017).
Clinical aspects and the quality of life among women with endometriosis and infertility: a cross-sectional study
Authors: Pessoa de Farias Rodrigues Marina , Lima Vilarino Fabia , de Souza Barbeiro Munhoz Alessandra , da Silva Paiva Laércio , de Alcantara Sousa Luiz Vinicius , Zaia Victor , Parente Barbosa Caio
Published: June 2020

Background

The quality of life (QoL) of patients with endometriosis and infertility was assessed in different stages and correlated with the clinical features of the cases.

Methods

The present study was a cross-sectional study; 106 women were included, divided in two endometriosis groups (Grade I/II, 26 women, and Grade II/IV, 74 women). All participants attended the Endometriosis and Infertility Outpatient Clinic of the Instituto Ideia Fértil de Saúde Reprodutiva, Faculdade de Medicina do ABC, São Paulo, Brazil, were and responded to the Short Form (SF) Health Survey-36. Convenience sampling was used due to the authors’ access to the study population; however, the sample number was calculated to be sufficient for 95% power in both groups.

Results

Homogeneity was observed between Grade I/II and Grade III/IV staging, with similar mean ages (35.27, ±3.64 years and 34.04, ±3.39 years, respectively, p = 0.133); types of infertility (p = 0.535); infertility time (p = 0.654); degrees of pain (p = 0.849); and symptoms common to endometriosis, namely, dysmenorrhea (p = 0.841), dyspareunia (0.466), chronic pelvic pain (p = 0.295), and intestinal (p = 0.573) or urinary (p = 0.809) diseases. Comparisons of median scores in the QoL domains demonstrated that the distributions of QoL and clinical symptoms were significantly related between the types of dyspareunia and the following domains: physical functioning (p = 0.017), role- emotional (p = 0.013), and general health (p = 0.001). Regarding pain outside of menstruation, there was significance in the pain domain (p = 0.017), and degree of pain was significance in physical functioning (p = 0.005) and role-physical (p = 0.011) domains.

Conclusions

The present study pointed out that it is not the stage of endometriosis that interferes in the quality of life of women with endometriosis and infertility but rather the clinical manifestations, such as dyspareunia and pain. Thus, we can conclude that the patient’s perception of the disease should be considered in health care and that the losses are independent of the degree of endometriosis in this population with the aggravating factor of infertility.
Evaluation of the effect of items’ format and type on psychometric properties of sixth year pharmacy students clinical clerkship assessment items
Authors: AlKhatib Hatim S. , Brazeau Gayle , Akour Amal , Almuhaissen Suha A.
Published: June 2020

Background

Examinations are the traditional assessment tools. In addition to measurement of learning, exams are used to guide the improvement of academic programs. The current study attempted to evaluate the quality of assessment items of sixth year clinical clerkships examinations as a function of assessment items format and type/structure and to assess the effect of the number of response choices on the characteristics of MCQs as assessment items.

Methods

A total of 173 assessment items used in the examinations of sixth year clinical clerkships of a PharmD program were included. Items were classified as case based or noncase based and as MCQs or open-ended. The psychometric characteristics of the items were studied as a function of the Bloom’s levels addressed, item format, and number of choices in MCQs.

Results

Items addressing analysis skills were more difficult. No differences were found between case based and noncase based items in terms of their difficulty, with a slightly better discrimination in the latter.Open-ended items were easier, yet more discriminative. MCQs with higher number of options were easier. Open-ended questions were significantly more discriminative in comparison to MCQs as case based items while they were more discriminative as noncase based items.

Conclusion

Item formats, structure, and number of options in MCQs significantly affected the psychometric properties of the studied items. Noncase based items and open-ended items were easier and more discriminative than case based items and MCQs, respectively. Examination items should be prepared considering the above characteristics to improve their psychometric properties and maximize their usefulness.
A qualitative study on aspects of consent for genomic research in communities with low literacy
Authors: Bukini Daima , Mbekenga Columba , Nkya Siana , Purvis Lisa , McCurdy Sheryl , Parker Michael , Makani Julie
Published: June 2020

Background

Low literacy of study participants in Sub - Saharan Africa has been associated with poor comprehension during the consenting process in research participation. The concerns in comprehension are far greater when consenting to participate in genomic studies due to the complexity of the science involved. While efforts are made to explore possibilities of applying genomic technologies in diseases prevalent in Sub Saharan Africa, we ought to develop methods to improve participants’ comprehension for genomic studies. The purpose of this study was to understand different approaches that can be used to seek consent from individuals with low literacy in Sub-Saharan African countries in genomic research to improve comprehension.

Methods

Using qualitative study design, we conducted focus-group discussions, in-depth interviews and participant observations as data collection methods. This study was embedded in a hospital based genomic study on Sickle Cell Disease at Muhimbili National Hospital in Tanzania. Thematic content analysis was used to analyse the transcripts and field notes.

Results

Findings from this study show that literacy level has little influence on understanding the research details. According to the participants of this study, the methods used to provide information, the language, and time spent with the study participants were the key factors influencing understanding. The availability of group sessions held before individual consent to allow for a detailed questions and answers format was agreed to be the best method to facilitate the comprehension.

Conclusion

The quality of the consenting process of participants will be influence by a number of factors. The type of research consented for, where the research will be implemented and who are the potential study participants are amongst the factors that need to be assessed during the consenting. Measures to improve participants’ comprehension need to be developed when consenting participants with low literacy level in genomic studies.
High flow nasal therapy during early pulmonary rehabilitation in patients with acute severe exacerbation of COPD: beneficial or illusory?
Authors: Prieur Guillaume , Combret Yann , Medrinal Clement
Published: June 2020

In study “Effect of high-flow nasal therapy during early pulmonary rehabilitation in patients with severe AECOPD: a randomized controlled study” by Tung et al., authors concluded HFNT utilization led to enhanced exercise tolerance and a reduction of systemic inflammation. Nevertheless, some points requires additional discussion, the conclusion of the trial seems overstated. The baseline differences between groups induces substantial modifications in the conclusions of this trial. HFNT does not seem to add any benefit on exercise tolerance or systemic inflammation, nor on pulmonary function. The only difference that remained significant in homogenous statistical significance is dyspnea on the mMRC scale but clinical significance is highly questionable.
Gluten hydrolyzing activity of Bacillus spp isolated from sourdough
Authors: Rashmi Bennur Somashekharaiah , Gayathri Devaraja , Vasudha Mahanthesh , Prashantkumar Chakra Siddappa , Swamy Chidanandamurthy Thippeswamy , Sunil Kumar S. , Somaraja Palegar Krishnappa , Prakash Patil
Published: June 2020

Background

Celiac disease is an intestinal chronic disorder with multifactorial etiology resulting in small intestinal mucosal injuries and malabsorption. In genetically predisposed individuals with HLA DQ2/DQ8 molecules, the gluten domains rich in glutamine and proline present gluten domains to gluten reactive CD4+ T cells causing injury to the intestine. In the present experimental design, the indigenous bacteria from wheat samples were studied for their gluten hydrolyzing functionality.

Results

Proteolytic activity of Bacillus spp. was confirmed spectrophotometrically and studied extensively on gliadin-derived synthetic enzymatic substrates, natural gliadin mixture, and synthetic highly immunogenic 33-mer peptide. The degradation of 33-mer peptide and the cleavage specificities of the selected isolates were analyzed by tandem mass spectrometry. The gluten content of the sourdough fermented by the chosen bacterial isolates was determined by R5 antibody based competitive ELISA. All the tested isolates efficiently hydrolyzed Z-YPQ-pNA, Z-QQP-pNA, Z-PPF-pNA, and Z-PFP-pNA and also cleaved 33-mer immunogenic peptide extensively. The gluten content of wheat sourdough was found to be below 110 mg/kg.

Conclusion

It has been inferred that four Bacillus spp especially GS 188 could be useful in developing gluten-reduced wheat food product for celiac disease prone individuals.
The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers
Authors: Chen Jing , Zhao Xu , Yuan Yuan , Jing Jing-Jing
Published: June 2020

Background

Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers.

Methods

Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene–gene interaction network was performed by GeneMANIA and the protein–protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tract cancers were further analyzed.

Results

Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were differentially expressed in digestive tract cancers. For esophageal carcinoma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC.

Conclusions

Members of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated in both STAD and CRC, and thus could be used as a diagnostic biomarker. Differential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verification experiment.
Myocarditis successfully diagnosed and controlled with speckle tracking echocardiography
Authors: Uziębło-Życzkowska Beata , Mielniczuk Marta , Ryczek Robert , Krzesiński Paweł
Published: June 2020

Background

Speckle tracking echocardiography (STE) is an objective, well-validated and reproducible technique of assessing left ventricular longitudinal deformation; it also offers a more sensitive assessment of myocardial contractility than widely used visual estimation. Evaluating global longitudinal strain may help identify patients with subclinical left ventricular systolic dysfunction.

Case presentation

We report the case of a 28-year-old man with myocarditis, which successfully diagnosed and followed-up with the novel echocardiography method using speckle tracking imaging. The patient was referred to our hospital with an initial diagnosis of ST-segment elevation myocardial infarction. Transthoracic echocardiography did not show any contractility abnormalities. Hence, in the course of further diagnostics, left ventricular function was assessed by STE. Depressed global longitudinal strain was noted within several segments of the left ventricle. Then, cardiac magnetic resonance imaging was performed to confirm the diagnosis of myocarditis.

Conclusions

STE seems to be competitive in relation to cardiac magnetic resonance imaging in the diagnosis of some diseases, such as myocarditis.
Correction to: Gender inequality in the health workforce in the midst of achieving universal health coverage in Mexico
Authors: Montañez-Hernández Julio César , Alcalde-Rabanal Jacqueline Elizabeth , Nigenda-López Gustavo Humberto , Aristizábal-Hoyos Gladis Patricia , Dini Lorena
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Human induced pluripotent stem cell line banking for the production of rare blood type erythrocytes
Authors: Park Yu Jin , Jeon Su-Hee , Kim Hyun-Kyung , Suh Eun Jung , Choi Seung Jun , Kim Sinyoung , Kim Hyun Ok
Published: June 2020

Background

The in vitro production of mature human red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has been the focus of research to meet the high demand for blood transfusions. However, limitations like high costs and technological requirements restrict the use of RBCs produced by iPSC differentiation to specific circumstances, such as for patients with rare blood types or alloimmunized patients. In this study, we developed a detailed protocol for the generation of iPSC lines derived from peripheral blood of donors with O D-positive blood and rare blood types (D–and Jr(a-)) and subsequent erythroid differentiation.

Methods

Mononuclear cells separated from the peripheral blood of O D-positive and rare blood type donors were cultured to produce and expand erythroid progenitors and reprogrammed into iPSCs. A 31-day serum-free, xeno-free erythroid differentiation protocol was used to generate reticulocytes. The stability of iPSC lines was confirmed with chromosomal analysis and RT-PCR. Morphology and cell counts were determined by microscopy observations and flow cytometry.

Results

Cells from all donors were successfully used to generate iPSC lines, which were differentiated into erythroid precursors without any apparent chromosomal mutations. This differentiation protocol resulted in moderate erythrocyte yield per iPSC.

Conclusions

It has previously only been hypothesized that erythroid differentiation from iPSCs could be used to produce RBCs for transfusion to patients with rare blood types or who have been alloimmunized. Our results demonstrate the feasibility of producing autologous iPSC-differentiated RBCs for clinical transfusions in patients without alternative options.
Myelination- and immune-mediated MR-based brain network correlates
Authors: Cerina Manuela , Muthuraman Muthuraman , Gallus Marco , Koirala Nabin , Dik Andre , Wachsmuth Lydia , Hundehege Petra , Schiffler Patrick , Tenberge Jan-Gerd , Fleischer Vinzenz , Gonzalez-Escamilla Gabriel , Narayanan Venu , Krämer Julia , Faber Cornelius , Budde Thomas , Groppa Sergiu , Meuth Sven G.
Published: June 2020

Background

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear.

Methods

In order to determine the MRI-derived correlates of myelin dynamics and to test if brain network characteristics derived from diffusion tensor imaging reflect microstructural tissue reorganization, we took advantage of the cuprizone model of general demyelination in mice and performed longitudinal histological and imaging analyses with behavioral tests. By introducing cuprizone into the diet, we induced targeted and consistent demyelination of oligodendrocytes, over a period of 5 weeks. Subsequent myelin synthesis was enabled by reintroduction of normal food.

Results

Using specific immune-histological markers, we demonstrated that 2 weeks of cuprizone diet induced a 52% reduction of myelin content in the corpus callosum (CC) and a 35% reduction in the neocortex. An extended cuprizone diet increased myelin loss in the CC, while remyelination commenced in the neocortex. These histologically determined dynamics were reflected by MRI measurements from diffusion tensor imaging. Demyelination was associated with decreased fractional anisotropy (FA) values and increased modularity and clustering at the network level. MRI-derived modularization of the brain network and FA reduction in key anatomical regions, including the hippocampus, thalamus, and analyzed cortical areas, were closely related to impaired memory function and anxiety-like behavior.

Conclusion

Network-specific remyelination, shown by histology and MRI metrics, determined amelioration of functional performance and neuropsychiatric symptoms. Taken together, we illustrate the histological basis for the MRI-driven network responses to demyelination, where increased modularity leads to evolving damage and abnormal behavior in MS. Quantitative information about in vivo myelination processes is mirrored by diffusion-based imaging of microstructural integrity and network characteristics.
Influenza a virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1
Authors: Du Yinping , Yang Fan , Wang Qiuxia , Xu Nuo , Xie Yizhang , Chen Sujuan , Qin Tao , Peng Daxin
Published: June 2020

Background

Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood.

Methods

In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection.

Results

The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1.

Conclusion

Collectively, our findings suggest that IAV infection induces SOCS1 expression to promote JAK1 degradation, which in turn inhibits host innate immune responses.
Reliability of ITV approach to varying treatment fraction time: a retrospective analysis based on 2D cine MR images
Authors: Cusumano Davide , Dhont Jennifer , Boldrini Luca , Chiloiro Giuditta , Romano Angela , Votta Claudio , Longo Silvia , Placidi Lorenzo , Azario Luigi , De Spirito Marco , Verellen Dirk , Valentini Vincenzo
Published: June 2020

Background

Internal Target Volume (ITV) is one of the most common strategies to passively manage tumour motion in Radiotherapy (RT).

The reliability of this approach is based on the assumption that the tumour motion estimated during pre-treatment 4D Computed Tomography (CT) acquisition is representative of the motion during the whole RT treatment. With the introduction of Magnetic Resonance-guided RT (MRgRT), it has become possible to monitor tumour motion during the treatment and verify this assumption.

Aim of this study was to investigate the reliability of the ITV approach with respect to the treatment fraction time (TFT) in abdominal and thoracic lesions.

Methods

A total of 12 thoracic and 15 abdominal lesions was analysed. Before treatment, a 10-phase 4DCT was acquired and ITV margins were estimated considering the envelope of the lesion contoured on the different 4DCT phases.

All patients underwent MRgRT treatment in free-breathing, monitoring the tumour position on a sagittal plane with 4 frames per second (sec). ITV margins were projected on the tumour trajectory and the percentage of treatment time in which the tumour was inside the ITV (%TT) was measured to varying of TFT.

The ITV approach was considered moderately reliable when %TT ≥ 90% and strongly reliable when %TT ≥ 95%. Additional ITV margins required to achieve %TT ≥ 95% were also calculated.

Results

In the analysed cohort of patients, ITV strategy can be considered strongly reliable only for lung lesions with TFT ≤ 7 min (min). The ITV strategy can be considered only moderately reliable for abdominal lesions, and additional margins are required to obtain %TT ≥ 95%.

Considering a TFT ≤ 4 min, additional margins of 2 mm in cranio-caudal (CC) and 1 mm in antero-posterior (AP) are suggested for pancreatic lesions, 3 mm in CC and 2 mm in AP for renal and liver ones.

Conclusions

On the basis of the analysed cases, the ITV approach appears to be reliable in the thorax, while it results more challenging in the abdomen, due to the higher uncertainty in ITV definition and to the observed larger intra and inter-fraction motion variability. The addition of extra margins based on the TFT may represent a valid tool to compensate such limitations.
Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking
Authors: Ruan Xiaofeng , Du Peng , Zhao Kang , Huang Jucun , Xia Hongmei , Dai Dan , Huang Shu , Cui Xiang , Liu Liming , Zhang Jianjun
Published: June 2020

Background

At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application.

Methods

First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein–protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects.

Results

First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine–cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels.

Conclusions

DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.
SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins
Authors: Chen Fan , Keleş Sündüz
Published: June 2020

Advances in high-throughput profiling of RNA-binding proteins (RBPs) have resulted inCLIP-seq datasets coupled with transcriptome profiling by RNA-seq. However, analysis methods that integrate both types of data are lacking. We describe SURF, Statistical Utility for RBP Functions, for integrative analysis of large collections of CLIP-seq and RNA-seq data. We demonstrate SURF’s ability to accurately detect differential alternative transcriptional regulation events and associate them to local protein-RNA interactions. We apply SURF to ENCODE RBP compendium and carry out downstream analysis with additional reference datasets. The results of this application are browsable athttp://www.statlab.wisc.edu/shiny/surf/.
Corneal cross-linking versus standard care in children with keratoconus – a randomised, multicentre, observer-masked trial of efficacy and safety (KERALINK): a statistical analysis plan
Authors: Chowdhury Kashfia , Doré Caroline J. , Bunce Catey , Larkin Daniel F. P.
Published: June 2020

Background

The KERALINK trial tests the hypothesis that corneal cross-linking (CXL) treatment reduces the progression of keratoconus in comparison to standard care in patients aged 10–16 years. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written before the end of the patient follow-up, while the outcome of the trial is still unknown.

Design and methods

KERALINK is a randomised controlled, observer-masked, multicentre trial in progressive keratoconus comparing epithelium-off CXL with standard care, including spectacles or contact lenses as necessary for best-corrected acuity. Keratoconus is a disorder of the shape of the cornea in which the normally round dome-shaped clear front window of the eye (cornea) thins progressively leading to a cone-like bulge. This impairs the ability of the eye to focus properly, causing reduced vision which requires spectacle or contact lens wear or, in a minority of patients, eventually corneal replacement by a transplant for best vision. The primary outcome measure is the between-group difference in K2 at 18 months adjusted for K2 at baseline examination. K2 is the value of the steepest corneal meridian as measured on Pentacam topography. Secondary outcomes are keratoconus progression, time to keratoconus progression, visual acuity, refraction, apical corneal thickness and adverse events. Patient-reported effects will be explored by questionnaires. We describe in detail the statistical aspects of KERALINK: the outcome measures, the sample size calculation, general analysis principles, the planned descriptive statistics and statistical models, and planned subgroup and sensitivity analyses.

Discussion

The KERALINK statistical analysis will provide comprehensive and precise information on the relative effectiveness of the two treatments. The plan will be implemented in May 2020 when follow-up for the trial is completed.

Trial registration

EudraCT, 2016-001460-11. Registered on 19 May 2016.
Pan-American Trypanosoma (Megatrypanum) trinaperronei n. sp. in the white-tailed deer Odocoileus virginianus Zimmermann and its deer ked Lipoptena mazamae Rondani, 1878: morphological, developmental and phylogeographical characterisation
Authors: Garcia Herakles A. , Blanco Pilar A. , Rodrigues Adriana C. , Rodrigues Carla M. F. , Takata Carmen S. A. , Campaner Marta , Camargo Erney P. , Teixeira Marta M. G.
Published: June 2020

Background

The subgenus Megatrypanum Hoare, 1964 of Trypanosoma Gruby, 1843 comprises trypanosomes of cervids and bovids from around the world. Here, the white-tailed deer Odocoileus virginianus (Zimmermann) and its ectoparasite, the deer ked Lipoptena mazamae Rondani, 1878 (hippoboscid fly), were surveyed for trypanosomes in Venezuela.

Results

Haemoculturing unveiled 20% infected WTD, while 47% (7/15) of blood samples and 38% (11/29) of ked guts tested positive for the Megatrypanum-specific TthCATL-PCR. CATL and SSU rRNA sequences uncovered a single species of trypanosome. Phylogeny based on SSU rRNA and gGAPDH sequences tightly cluster WTD trypanosomes from Venezuela and the USA, which were strongly supported as geographical variants of the herein described Trypanosoma (Megatrypanum) trinaperronei n. sp. In our analyses, the new species was closest to Trypanosoma sp. D30 from fallow deer (Germany), both nested into TthII alongside other trypanosomes from cervids (North American elk and European fallow, red and sika deer), and bovids (cattle, antelopes and sheep). Insights into the life-cycle of T. trinaperronei n. sp. were obtained from early haemocultures of deer blood and co-culture with mammalian and insect cells showing flagellates resembling Megatrypanum trypanosomes previously reported in deer blood, and deer ked guts. For the first time, a trypanosome from a cervid was cultured and phylogenetically and morphologically (light and electron microscopy) characterised.

Conclusions

In the analyses based on SSU rRNA, gGAPDH, CATL and ITS rDNA sequences, neither cervids nor bovids trypanosomes were monophyletic but intertwined within TthI and TthII major phylogenetic lineages. One host species can harbour more than one species/genotype of trypanosome, but each trypanosome species/genotype was found in a single host species or in phylogenetically closely related hosts. Molecular evidence that L. mazamae may transmit T. trinaperronei n. sp. suggests important evolutionary constraints making tight the tripartite T. trinaperronei-WTD-deer ked association. In a plausible evolutionary scenario, T. trinaperronei n. sp. entered South America with North American white-tailed deer at the Pliocene-Pleistocene boundary following the closure of the Panama Isthmus.
Generation of myogenic progenitor cell-derived smooth muscle cells for sphincter regeneration
Authors: Thurner Marco , Deutsch Martin , Janke Katrin , Messner Franka , Kreutzer Christina , Beyl Stanislav , Couillard-Després Sébastien , Hering Steffen , Troppmair Jakob , Marksteiner Rainer
Published: June 2020

Background

Degeneration of smooth muscles in sphincters can cause debilitating diseases such as fecal incontinence. Skeletal muscle-derived cells have been effectively used in clinics for the regeneration of the skeletal muscle sphincters, such as the external anal or urinary sphincter. However, little is known about the in vitro smooth muscle differentiation potential and in vivo regenerative potential of skeletal muscle-derived cells.

Methods

Myogenic progenitor cells (MPC) were isolated from the skeletal muscle and analyzed by flow cytometry and in vitro differentiation assays. The differentiation of MPC to smooth muscle cells (MPC-SMC) was evaluated by immunofluorescence, flow cytometry, patch-clamp, collagen contraction, and microarray gene expression analysis. In vivo engraftment of MPC-SMC was monitored by transplanting reporter protein-expressing cells into the pyloric sphincter of immunodeficient mice.

Results

MPC derived from human skeletal muscle expressed mesenchymal surface markers and exhibit skeletal myogenic differentiation potential in vitro. In contrast, they lack hematopoietic surface marker, as well as adipogenic, osteogenic, and chondrogenic differentiation potential in vitro.Cultivation of MPC in smooth muscle differentiation medium significantly increases the fraction of alpha smooth muscle actin (aSMA) and smoothelin-positive cells, while leaving the number of desmin-positive cells unchanged. Smooth muscle-differentiated MPC (MPC-SMC) exhibit increased expression of smooth muscle-related genes, significantly enhanced numbers of CD146- and CD49a-positive cells, and in vitro contractility and express functional Cavand Kvchannels. MPC to MPC-SMC differentiation was also accompanied by a reduction in their skeletal muscle differentiation potential. Upon removal of the smooth muscle differentiation medium, a major fraction of MPC-SMC remained positive for aSMA, suggesting the definitive acquisition of their phenotype. Transplantation of murine MPC-SMC into the mouse pyloric sphincter revealed engraftment of MPC-SMC based on aSMA protein expression within the host smooth muscle tissue.

Conclusions

Our work confirms the ability of MPC to give rise to smooth muscle cells (MPC-SMC) with a well-defined and stable phenotype. Moreover, the engraftment of in vitro-differentiated murine MPC-SMC into the pyloric sphincter in vivo underscores the potential of this cell population as a novel cell therapeutic treatment for smooth muscle regeneration of sphincters.
One molecular fingerprint to rule them all: drugs, biomolecules, and the metabolome
Authors: Capecchi Alice , Probst Daniel , Reymond Jean-Louis
Published: June 2020

Background

Molecular fingerprints are essential cheminformatics tools for virtual screening and mapping chemical space. Among the different types of fingerprints, substructure fingerprints perform best for small molecules such as drugs, while atom-pair fingerprints are preferable for large molecules such as peptides. However, no available fingerprint achieves good performance on both classes of molecules.

Results

Here we set out to design a new fingerprint suitable for both small and large molecules by combining substructure and atom-pair concepts. Our quest resulted in a new fingerprint called MinHashed atom-pair fingerprint up to a diameter of four bonds (MAP4). In this fingerprint the circular substructures with radii of r = 1 and r = 2 bonds around each atom in an atom-pair are written as two pairs of SMILES, each pair being combined with the topological distance separating the two central atoms. These so-called atom-pair molecular shingles are hashed, and the resulting set of hashes is MinHashed to form the MAP4 fingerprint. MAP4 significantly outperforms all other fingerprints on an extended benchmark that combines the Riniker and Landrum small molecule benchmark with a peptide benchmark recovering BLAST analogs from either scrambled or point mutation analogs. MAP4 furthermore produces well-organized chemical space tree-maps (TMAPs) for databases as diverse as DrugBank, ChEMBL, SwissProt and the Human Metabolome Database (HMBD), and differentiates between all metabolites in HMBD, over 70% of which are indistinguishable from their nearest neighbor using substructure fingerprints.

Conclusion

MAP4 is a new molecular fingerprint suitable for drugs, biomolecules, and the metabolome and can be adopted as a universal fingerprint to describe and search chemical space. The source code is available at https://github.com/reymond-group/map4 and interactive MAP4 similarity search tools and TMAPs for various databases are accessible at http://map-search.gdb.tools/ and http://tm.gdb.tools/map4/.
A comparison of nasogastric tube insertion by SORT maneuver (sniffing position, NGT orientation, contralateral rotation, and twisting movement) versus neck flexion lateral pressure in critically ill patients admitted to ICU: a prospective randomized clinical trial
Authors: Sanaie Sarvin , Mirzalou Negin , Shadvar Kamran , Golzari Samad E. J. , Soleimanpour Hassan , Shamekh Ali , Bettampadi Deepti , Safiri Saeid , Mahmoodpoor Ata
Published: June 2020

Background

Although many techniques have been introduced to facilitate nasogastric tube (NGT) insertion using anatomic landmarks and a group of devices, there is a lack of general consensus regarding a standard method. The current study purposed to investigate if SORT maneuver (sniffing position, NGT orientation, contralateral rotation, and twisting movement) increases the success rate of NGT correct placement versus neck flexion lateral pressure (NFLP) method.

Methods

A randomized controlled trial study was conducted in two university affiliated intensive care units (tertiary referral center). Three hundred and ninety-six critically ill patients older than 18 years of age were randomly divided into SORT (n = 200) and NFLP (n = 196) groups. The technique was classified as “failed” after the third unsuccessful attempt. Patient characteristics, success rate for the first attempt, time required for the successful first attempt and overall successful insertion time, various complications including kinking, coiling and bleeding and ease of insertion were noted as main outcomes measured.

Results

Ease of insertion was significantly better in the SORT group compared to the NFLP group (P < 0.001). The number of failed attempts was significantly higher in the NFLP group (7.5%) vs the SORT group (3.0%) (P = 0.046). The pattern of complications was not different between two study groups (P = 0.242). The odds of stage II (odds ratio (OR) = 49.9; 95% confidence interval (CI) 25.2 to 98.6), stage III (OR = 67.1; 95% CI 14.9 to 302.8)) and stage IV (OR = 11.8; 95% CI 3.4 to 41.2) ease of insertion were much higher in NFLP compared to SORT group, after adjusting for age and body mass index (BMI). The odds of failure was not significantly different in NFLP group compared to SORT group (OR = 2.3; 95% CI 0.85 to 6.3), after adjusting for age and BMI.

Conclusions

SORT technique may be considered as a promising method for successful NGT insertions in critically ill patients. However, more trials are needed to confirm the results of this study. The decision must account for individual patient and clinical factors and the operator’s experience and preference.

Trial registration: The study was registered at government registry of clinical trials in Iran (http://www.IRCT.ir) (number: IRCT20091012002582N18, 13 March 2018)