bluuebunny/crossref_metadata_2025 huggingface dataset:
Perception, attitude, practice and barriers towards medical research among undergraduate students
Authors: El Achi Dina , Al Hakim Lara , Makki Maha , Mokaddem Mona , Khalil Pamela Abi , Kaafarani Bilal R. , Tamim Hani
Published: June 2020

Background

Early exposure to medical research, specifically at the undergraduate level, contributes in building a solid medical education for students. In 2014, the Medical Research Volunteer Program (MRVP) was established at the American University of Beirut (AUB). This program provides undergraduate students with the opportunity to be involved in ongoing medical research projects, on a voluntary basis. Little is known about undergraduates’ outlook on medical research and the challenges they face. The aim of this study was to assess, among AUB undergraduate students, the perception, attitude, practice and barriers towards medical research, as well as to identify factors affecting them, such as background characteristics and research involvement.

Methods

A cross sectional study was carried out at AUB, where undergraduate students enrolled in specific chosen classes were surveyed in spring 2019 via paper based questionnaires. Close-ended questions assessed students’ attitude, perception, practice and barriers towards medical research using a 5-point likert scale. Moreover, demographic characteristics and research involvement information were collected.

Results

Five hundred and twenty three students were surveyed. About half of the students were premedical students (51.5%), and only 43.6% of them were aware of the medical research program at their university. The average attitude, perception, practice and barriers scores were found to be 3.58, 4.35, 3.58 and 2.60, respectively (on a scale from 1 to 5). Students found the lack of mentoring and guidance to be the main barrier in conducting medical research.

Conclusion

Our findings reveal that students express interest towards medical research and recognize its importance. A medical research program at the undergraduate level is indispensable in guiding students in their future career endeavors. Therefore, research programs should be constantly monitored to assure a research-oriented environment within institutions.
Comparing video-based versions of Halsted’s ‘see one, do one’ and Peyton’s ‘4-step approach’ for teaching surgical skills: a randomized controlled trial
Authors: Seifert Lukas B. , Schnurr Benedikt , Stefanescu Maria-Christina , Sader Robert , Ruesseler Miriam , Sterz Jasmina
Published: June 2020

Background

Teaching complex motor skills at a high level remains a challenge in medical education. Established methods often involve large amounts of teaching time and material. The implementation of standardized videos in those methods might help save resources. In this study, video-based versions of Peyton’s ‘4-step Approach’ and Halsted’s ‘See One, Do One’ are compared. We hypothesized that the video-based ‘4-step Approach’ would be more effective in learning procedural skills than the ‘See One, Do One Approach’.

Methods

One-hundred-two naïve students were trained to perform a structured facial examination and a Bellocq’s tamponade with either Halsted’s (n = 57) or Peyton’s (n = 45) method within a curricular course. Steps 1 (Halsted) and 1–3 (Peyton) were replaced by standardized teaching videos. The performance was measured directly (T1) and 8 weeks (T2) after the intervention by blinded examiners using structured checklists. An item-analysis was also carried out.

Results

At T1, performance scores significantly differed in favor of the video-based ‘4-step Approach’ (p < 0.01) for both skills. No differences were found at T2 (p < 0.362). The item-analysis revealed that Peyton’s method was significantly more effective in the complex subparts of both skills.

Conclusions

The modified video-based version of Peyton’s ‘4-step Approach’ is the preferred method for teaching especially complex motor skills in a large curricular scale. Furthermore, an effective way to utilize Peyton’s method in a group setting could be demonstrated. Further studies have to investigate the long-term learning retention of this method in a formative setting.
The cost-effectiveness of food consistency modification with xanthan gum-based Nutilis Clear® in patients with post-stroke dysphagia in Poland
Authors: Pelczarska Aleksandra , Jakubczyk Michał , Niewada Maciej
Published: June 2020

Background

Dysphagia is a well-known stroke complication characterised by difficulty in swallowing. It may affect the majority of stroke patients and increases mortality and morbidity, due to aspiration pneumonia and malnutrition. Food thickening may help patients to feed themselves, and its effectiveness was demonstrated. However, the cost-effectiveness studies are lacking. We evaluate the cost-utility of xanthan gum-based consistency modification therapy (Nutilis Clear®) in adult post-stroke patients from the public payer perspective in Poland.

Methods

Routine clinical practice was used as a comparator, as no alternative specific treatment for dysphagia is available. To verify the robustness of the results against the modelling approach, we built two models: a static (a fixed simple-equations model, 8-week time horizon of dysphagia) and a dynamic one (Markov model, with a possible dysphagia resolution over a 1-year horizon). In both models, the treatment costs, health state utilities, and clinical events (i.e. aspiration, aspiration pneumonia, death) were included. Parameters were estimated jointly for both models, except for the duration of dysphagia and the risk of aspiration pneumonia (specific to the time horizon). We only assumed Nutilis Clear® to prevent aspirations, without affecting dysphagia duration.

Results

The average cost of one quality-adjusted life year (i.e. the incremental cost-utility ratios, ICURs) amounted to 21,387 PLN (€1 ≈ 4.5 PLN), and 20,977 PLN in static and dynamic model, respectively; far below the cost-effectiveness threshold in Poland (147,024 PLN). The one-way, scenario, and probabilistic sensitivity analysis confirmed these findings.

Conclusions

Nutilis Clear® is highly cost-effective in Poland from the public payer perspective. Our approach can be used in other countries to study the cost-effectiveness of food thickening in stroke patients.
MicroRNAs signatures, bioinformatics analysis of miRNAs, miRNA mimics and antagonists, and miRNA therapeutics in osteosarcoma
Authors: Otoukesh Babak , Abbasi Mehdi , Gorgani Habib-o-Lah , Farahini Hossein , Moghtadaei Mehdi , Boddouhi Bahram , Kaghazian Peyman , Hosseinzadeh Shayan , Alaee Atefe
Published: June 2020

MicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.
Relationship between different particle size fractions and all-cause and cause-specific emergency ambulance dispatches
Authors: Wang Xiaojie , Tian Junzhang , Li Ziyi , Lai Jun , Huang Xin , He Yongcong , Ye Zebing , Li Guowei
Published: June 2020

Background

Evidence on the relationship between different particle size fractions and emergency ambulance dispatches (EAD) remains limited and sparse.

Methods

We collected daily data of EAD, ambient air pollution and meteorological data from 2014 to 2018 in Guangzhou, China. We used a generalized additive model with covariate adjustments to estimate the associations between different particle size fractions and EAD related to all-cause, cardiovascular diseases, and respiratory diseases. Several subgroup and sensitivity analyses were also performed.

Results

Significant associations were observed between PM2.5, PM2.5–10, PM10 and EADs. A 10 μg/m3 increase of PM2.5, PM2.5–10, and PM10 was associated with an increase of 0.98% (95% CI: 0.67, 1.28%), 2.06% (95% CI: 1.44, 2.68%), and 0.75% (95%CI: 0.53, 0.96%) in all-cause EAD, with an increase of 0.69% (95% CI: 0.00, 1.39%), 2.04% (95% CI: 0.64, 3.45%), and 0.60% (95%CI: 0.11,1.10%) in cardiovascular-related EAD, and an increase of 1.14% (95% CI: 0.25, 2.04%), 2.52% (95% CI: 0.72, 4.35%), and 0.89% (95%CI: 0.25,1.52%) in respiratory-related EAD at lag03, respectively. The results were robust in subgroup and sensitivity analyses.

Conclusions

This study revealed that PM2.5, PM2.5–10 and PM10 were significantly related with risks of all-cause and cause-specific EAD. More evidence of high quality may be needed to further support our results in this ecological study.
Impacts of ambient air pollution on glucose metabolism in Korean adults: a Korea National Health and Nutrition Examination Survey study
Authors: Hwang Myung-Jae , Kim Jong-Hun , Koo Youn-Seo , Yun Hui-Young , Cheong Hae-Kwan
Published: June 2020

Background

Exposure to air pollution was reported to affect glucose metabolism, increasing the risk of diabetes mellitus. We conducted an epidemiological study on glucose metabolism and air pollution by exploring the levels of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) with changes in ambient air quality, depending on the characteristics of the susceptible population.

Methods

We carried out a cross-sectional analysis of a nationally representative sample of 10,014 adults (4267 in male and 5747 in female) from the Korea National Health and Nutrition Examination Survey in 2012 and 2013 along with data from the Korean Air Quality Forecasting System. The analysis was performed using a generalized linear model stratified by sex, age, and presence of diabetes. We assessed the changes in FBG and HbA1c associated with exposures to particulate matter (PM10), fine particulate matter (PM2.5), and nitrogen dioxide (NO2) after controlling for confounders.

Results

There were 1110 participants with diabetes (557 in male and 553 in female). Overall, the FBG level increased by 7.83 mg/dL (95% confidence interval [CI]: 2.80–12.87) per interquartile range (IQR) increment of NO2, 5.32 mg/dL (95% CI: 1.22–9.41) per IQR increment of PM10 at a moving average of 0–6 days, and 4.69 mg/dL (95% CI: 0.48–8.91) per IQR increment of PM2.5 at a moving average of 0–5 days. HbA1c increased by 0.57% (95% CI: 0.04–1.09) per IQR increment of PM10 at a moving average of 0–60 days and 0.34% (95% CI: 0.04–0.63) per IQR increment of PM2.5 at a moving average of 0–75 days. The change in FBG and HbA1c increased more in the diabetic group, especially in males aged 65 years or more. There was a strong association between elevation in diabetes-related parameters and exposure to air pollution.

Conclusions

Our study provides scientific evidence supporting that short- and mid-term exposure to air pollution is associated with changes in biological markers related to diabetes. This finding suggests that the impact of air pollution should be reflected in chronic disease management when establishing local health care policies.
Occupational pesticide exposure and the risk of death in patients with Parkinson’s disease: an observational study in southern Brazil
Authors: Schneider Medeiros Márcio , P. Reddy Sumanth , P. Socal Mariana , Schumacher-Schuh Artur Francisco , Mello Rieder Carlos Roberto
Published: June 2020

Background

Multiple studies have suggested that various pesticides are associated with a higher risk of developing Parkinson’s disease (PD) and may influence the progression of the disease. However, the evidence regarding the impact of pesticide exposure on mortality among patients with PD is equivocal. This study examines whether pesticide exposure influences the risk of mortality among patients with PD in Southern Brazil.

Methods

A total of 150 patients with idiopathic PD were enrolled from 2008 to 2013 and followed until 2019. In addition to undergoing a detailed neurologic evaluation, patients completed surveys regarding socioeconomic status and environmental exposures.

Results

Twenty patients (13.3%) reported a history of occupational pesticide exposure with a median duration of exposure of 10 years (mean = 13.1, SD = 11.2). Patients with a history of occupational pesticide exposure had higher UPDRS-III scores, though there were no significant differences in regards to age, sex, disease duration, Charlson Comorbidity Index, and age at symptom onset. Patients with occupational pesticide exposure were more than twice as likely to die than their unexposed PD counterparts (HR = 2.32, 95% CI [1.15, 4.66],p = 0.018). Occupational pesticide exposure was also a significant predictor of death in a cox-proportional hazards model which included smoking and caffeine intake history (HR = 2.23, 95% CI [1.09, 4.59],p = 0.03)) and another which included several measures of socioeconomic status (HR = 3.91, 95% CI [1.32, 11.58],p = 0.01).

Conclusion

In this prospective cohort study, we found an increased all-cause mortality risk in PD patients with occupational exposure to pesticides. More studies are needed to further analyze this topic with longer follow-up periods, more detailed exposure information, and more specific causes of mortality.
Low-kilovolt x-ray intraoperative radiotherapy for pT3 locally advanced colon cancer: a single-institution retrospective analysis
Authors: Ma Li , Qiang Junhao , Yin Heliang , Lin Lin , Jiao Yan , Ma Changying , Li Xinwei , Dong Li , Cui Jinglin , Wei Dongmei , Sharma Ankur M. , Schwartz David L. , Gu Weikuan , Chen Hong
Published: June 2020

Background

Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT.

Methods

We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS.

Results

The median follow-up of patients was 20.5 months (range, 6.1–38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively.

Conclusion

Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.
Identification of a novel IL-5 signaling pathway in chronic pancreatitis and crosstalk with pancreatic tumor cells
Authors: Gitto Sarah B. , Beardsley Jordan M. , Nakkina Sai Preethi , Oyer Jeremiah L. , Cline Kathryn A. , Litherland Sally A. , Copik Alicja J. , Khaled Amr S. , Fanaian Na’im , Arnoletti J. Pablo , Altomare Deborah A.
Published: June 2020

Background

While inflammation is associated with pancreatic cancer, the underlying mechanisms leading to cancer initiation are still being delineated. Eosinophils may promote or inhibit tumor growth, although the specific role in pancreatic cancer has yet to be determined. Eosinophil-supporting cytokine interleukin-5 and receptor are likely to have a role, but the significance in the pancreatic cancer microenvironment is unknown.

Methods

Genetically engineered Akt1Myr/KRasG12D and KRasG12D mice were used to model changes induced by chronic inflammation. Tissue samples were collected to analyze the tumor microenvironment and infiltration of immune cells, whereas serum was collected to analyze cytokine and amylase activity in the inflammatory model. The expression of IL-5R and the effects of IL-5 were analyzed in human and murine tumor cells.

Results

Compound Akt1Myr/KRasG12D mice, compared to single KRasG12D or Akt1Myr mice, exhibited increased tissue damage after repeat inductions of inflammation, and had accelerated tumor development and metastasis. M2 macrophages and newly identified eosinophils co-localized with fibrotic regions rather than infiltrating into tumors, consistent with immune cell privilege. The majority of eosinophils found in the pancreas of Akt1Myr/KRasG12D mice with chronic inflammation lacked the cytotoxic NKG2D marker. IL-5 expression was upregulated in pancreatic cells in response to inflammation, and then diminished in advanced lesions. Although not previously described in pancreatic tumors, IL-5Rα was increased during mouse pancreatic tumor progression and expressed in human pancreatic ductal adenocarcinomas (7 of 7 by immunohistochemistry). IL-5 stimulated tumor cell migration and activation through STAT5 signaling, thereby suggesting an unreported tumor-promoting role for IL-5Rα in pancreatic cancer.

Conclusions

Chronic inflammation induces increased pancreatic cancer progression and immune cells such as eosinophils are attracted to areas of fibrosis. Results suggest that IL-5 in the pancreatic compartment stimulates increased IL-5Rα on ductal tumor cells to increase pancreatic tumor motility. Collectively, IL-5/IL-5Rα signaling in the mouse and human pancreatic tumors microenvironment is a novel mechanism to facilitate tumor progression.
Evaluation of T-activated proteins as recall antigens to monitor Epstein–Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting
Authors: Körber Nina , Behrends Uta , Protzer Ulrike , Bauer Tanja
Published: June 2020

Background

Pools of overlapping synthetic peptides are routinely used for ex vivo monitoring of antigen-specific T-cell responses. However, it is rather unlikely that these peptides match those resulting from naturally processed antigens. T-activated proteins have been described as immunogenic and more natural stimulants, since they have to pass through antigen processing and comprise activation of all clinically relevant effector cell populations.

Methods

We performed comparative analysis of numbers and cytokine expression pattern of CD4 and CD8 T cells after stimulation with recombinant, urea-formulated T-activated EBV-BZLF1, -EBNA3A, and HCMV-IE1, and -pp65 proteins or corresponding overlapping peptide pools. Freshly isolated and cryopreserved PBMC of 30 EBV- and 19 HCMV-seropositive and seven EBV- and HCMV-seronegative subjects were stimulated ex vivo and analysed for IFN-γ, TNF and IL-2 production by flow cytometry-based intracellular cytokine staining.

Results

T-activated proteins showed a high specificity of 100% (EBV-BZLF1, HCMV-IE1, and -pp65) and 86% (EBV-EBNA3A), and a high T-cell stimulatory capacity of 73–95% and 67–95% using freshly isolated and cryopreserved PBMC, respectively. The overall CD4 T-cell response rates in both cohorts were comparable after stimulation with either T-activated protein or peptide pools with the exception of lower numbers of CD8 T cells detected after stimulation with T-activated EBV-EBNA3A- (p = 0.038) and HCMV-pp65- (p = 0.0006). Overall, the number of detectable antigen-specific T cells varied strongly between individuals. Cytokine expression patterns in response to T-activated protein and peptide pool-based stimulation were similar for CD4, but significantly different for CD8 T-cell responses.

Conclusion

EBV and HCMV-derived T-activated proteins represent innovative, highly specific recall antigens suitable for use in immunological endpoint assays to evaluate success or failure in immunotherapy clinical trials (e.g. to assess the risk of EBV and/or HCMV reactivation after allogenic hematopoietic stem cell transplantation). T-activated proteins could be of particular importance, if an impaired antigen processing (e.g. in a post-transplant setting) must be taken into account.
Clinical significance of circulating tumor cells and metabolic signatures in lung cancer after surgical removal
Authors: Yang Dawei , Yang Xiaofang , Li Yang , Zhao Peige , Fu Rao , Ren Tianying , Hu Ping , Wu Yaping , Yang Hongjun , Guo Na
Published: June 2020

Background

Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain.

Methods

Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes.

Results

LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC before surgery. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 147 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA (LC patients after surgery) and LB (LC patients before surgery) groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC.

Conclusions

These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.
Examining working mothers’ experience of exclusive breastfeeding in Ghana
Authors: Abekah-Nkrumah Gordon , Antwi Maame Yaa , Nkrumah Jacqueline , Gbagbo Fred Yao
Published: June 2020

Background

Although substantial evidence exists on factors that influence exclusive breastfeeding, there is a general lack of qualitative studies that examine how specific workplace factors constrain or promote exclusive breastfeeding among working mothers. The current study therefore examines working mothers’ experience of exclusive breastfeeding, laying emphasis on the influence of workplace factors on working mothers’ decision to exclusively breastfeed their babies.

Methods

The study uses a qualitative research approach and a three-stage purposive sampling procedure to select 20 mothers from 10 organizations in five industries for in-depth interviews on their exclusive breastfeeding experience. Data collected from the interviews were analysed using content analysis, with two major themes emerging for discussion.

Results

The results suggest that two major factors influence exclusive breastfeeding among working mothers: practice of exclusive breast feeding (knowledge and understanding of exclusive breastfeeding, and experience in exclusive breastfeeding) and workplace factors (length of maternity leave, closing time, absence of maternity policy in organizations, inadequate institutional support and family work-life balance).

Conclusion

The results of the study suggest that workplace factors play an equally crucial role in the decision by mothers to exclusively breastfeed their babies. Thus, in the special case of working mothers where breastfeeding prevalence is low, the findings of this study can be crucial in evolving appropriate policies to support working mothers in their effort to exclusively breastfeed their babies.
Radioprotective efficacy of plastic polymer against the toxicogenomic effects of radiopharmaceutical 18F-FDG on human lymphocytes
Authors: Lopes Nilson Benedito , Almeida Igor Vivian , Lopes Pedro Henrique Silvestre , Vicentini Veronica Elisa Pimenta
Published: June 2020

Background

Healthcare workers occupationally exposed to 18F-FDG cannot wear protective equipment, such as lead aprons, since the interaction between high energy radiation (511 keV) and metal increases the dose of radiation absorption. The objective of this study was to evaluate the shielding efficacy of a plastic polymer against the toxicogenomic effects of ionizing radiation in human lymphocytes, using cytokinesis-block micronucleus assays.

Methods

Human peripheral blood lymphocytes were isolated from three subjects and cultured under standard conditions. The cultures were exposed to 300 mCi of 18F-FDG at a distance of 10 cm for 10 min, in the absence of shielding or with lead, polymer, and lead + polymer shields.

Results

Lead shielding was found to increase the number of counts detected by Geiger-Müller radiation monitors as a consequence of the photoelectron effect. Conversely, the lead + polymer shield reduced the number of counts. The lead, polymer, and lead + polymer shields significantly reduced the frequency of micronuclei, nucleoplasmic bridges, and nuclear buds induced by ionizing radiation. Regarding cytotoxicity, only the lead + polymer shield re-established the cell cycle at the level observed for the negative control.

Conclusions

Lead aprons that are internally coated with polymer increased the radiological protection of individuals occupationally exposed to 18F-FDG PET/CT, especially during examinations.
Effect of symmetrical restoration for the migration of uncemented total hip arthroplasty: a randomized RSA study with 75 patients and 5-year follow-up
Authors: Kiernan Sverrir , Geijer Mats , Sundberg Martin , Flivik Gunnar
Published: June 2020

Background

Inferior placement of a femoral stem is predictive for early loosening and failure, but does restoration of the original hip anatomy benefit the function and survival of a total hip replacement?

Methods

Seventy-five patients with primary unilateral hip osteoarthritis operated with an uncemented anatomical stem were randomized for either standard or modular stems. We used 50 ABG II stems with modular necks and 25 standard stems (control group). We measured the symmetry in hip anatomy between healthy and operated side. The anatomical restoration variables were anteversion, global offset, and femoral offset/acetabular offset (FO/AO) quota. We performed measurements using a CT-based 3D templating and measuring software. Migratory behavior of the stems was then measured postoperatively with repeated radiostereometry (RSA) examinations over 5 years.

Results

Both stem types showed an early (within 3 months) good stabilization after an initial slight rotation into retroversion and subsidence. There were no significant differences in RSA migration between modular and standard stems. Postoperative anteversion and FO/AO quota had no impact on stem migration. The standard stem tended to result in insufficient global offset (GO), whereas the modular stem did not.

Conclusions

The modular stem gave good symmetrical anatomical restoration and, like the standard version, a benign migratory behavior. Anteversion, GO, and FO/AO quota had no significant impact on stem migration. It therefore seems to be of no importance whether we choose a modular or a standard stem with regard to postoperative stem migration for this stem type. We overestimated the effect anatomical parameters have on stem movement; hence, we believe the study to be underpowered.

Trial registration

ClinicalTrials.gov identifier: NCT01512550. Registered 19 January 2012—retrospectively registered,
Identification of therapeutic targets from genetic association studies using hierarchical component analysis
Authors: Lee Hao-Chih , Ichikawa Osamu , Glicksberg Benjamin S. , Divaraniya Aparna A. , Becker Christine E. , Agarwal Pankaj , Dudley Joel T.
Published: June 2020

Background

Mapping disease-associated genetic variants to complex disease pathophysiology is a major challenge in translating findings from genome-wide association studies into novel therapeutic opportunities. The difficulty lies in our limited understanding of how phenotypic traits arise from non-coding genetic variants in highly organized biological systems with heterogeneous gene expression across cells and tissues.

Results

We present a novel strategy, called GWAS component analysis, for transferring disease associations from single-nucleotide polymorphisms to co-expression modules by stacking models trained using reference genome and tissue-specific gene expression data. Application of this method to genome-wide association studies of blood cell counts confirmed that it could detect gene sets enriched in expected cell types. In addition, coupling of our method with Bayesian networks enables GWAS components to be used to discover drug targets.

Conclusions

We tested genome-wide associations of four disease phenotypes, including age-related macular degeneration, Crohn’s disease, ulcerative colitis and rheumatoid arthritis, and demonstrated the proposed method could select more functional genes than S-PrediXcan, the previous single-step model for predicting gene-level associations from SNP-level associations.
Receptor protein tyrosine phosphatase delta is not essential for synapse maintenance or transmission at hippocampal synapses
Authors: Han Kyung Ah , Lee Hee-Yoon , Lim Dongseok , Shin Jungsu , Yoon Taek Han , Liu Xinran , Um Ji Won , Choi Se-Young , Ko Jaewon
Published: June 2020

Members of the leukocyte common antigen-related receptor protein tyrosine phosphatase (LAR-RPTP) family, comprising PTPσ, PTPδ and LAR, are key hubs for presynaptic assembly and differentiation in vertebrate neurons. However, roles of individual LAR-RPTP members have not been investigated using member-specific conditional knockout mice. Here, we show that loss of PTPδ had no overt effect on synapse development in mouse cultured hippocampal neurons. Moreover, loss of PTPδ in presynaptic CA1 hippocampal neurons did not influence neurotransmitter release in subicular pyramidal neurons, suggesting that PTPδ is not critical for presynaptic function in vivo. Our results demonstrate that PTPδ is not essential for synapse maintenance or transmission, at least in the mouse hippocampus, and underscore the importance of using sophisticated genetic approaches to confirm the roles of synaptic proteins.
The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia
Authors: Wang Wen-Tao , Chen Tian-Qi , Zeng Zhan-Cheng , Pan Qi , Huang Wei , Han Cai , Fang Ke , Sun Lin-Yu , Yang Qian-Qian , Wang Dan , Luo Xue-Qun , Sun Yu-Meng , Chen Yue-Qin
Published: June 2020

Background

Mixed-lineage leukemia (MLL) gene rearrangements trigger aberrant epigenetic modification and gene expression in hematopoietic stem and progenitor cells, which generates one of the most aggressive subtypes of leukemia with an apex self-renewal. It remains a challenge to directly inhibit rearranged MLL itself because of its multiple fusion partners and the poorly annotated downstream genes of MLL fusion proteins; therefore, novel therapeutic targets are urgently needed.

Methods

qRT-PCR, receiver operating characteristic (ROC), and leukemia-free survival analysis were used to validate LAMP5-AS1 (LAMP5 antisense 1) expression and evaluate its clinical value. We performed in vitro and in vivo experiments to investigate the functional relevance of LAMP5-AS1 in MLL leukemia progression and leukemia cell stemness. RNA electrophoretic mobility shift assays (EMSA), histone methyltransferase assay, RNA pull-down assay, and RNA fluorescence in situ hybridization (FISH) were used to validate the relationship between LAMP5-AS1 and the methyltransferase activity of DOT1L. The downstream ectopic target genes of LAMP5-AS1/DOT1L were validated by the chromatin immunoprecipitation (ChIP) and western blot.

Results

We discovered that a long noncoding RNA (lncRNA) LAMP5-AS1 can promote higher degrees of H3K79 methylation, followed by upregulated expression of the self-renewal genes in the HOXA cluster, which are responsible for leukemia stemness in context of MLL rearrangements. We found that LAMP5-AS1 is specifically overexpressed in MLL leukemia patients (n = 58) than that in the MLL-wt leukemia (n = 163) (p < 0.001), and the patients with a higher expression level of LAMP5-AS1 exhibited a reduced 5-year leukemia-free survival (p < 0.01). LAMP5-AS1 suppression significantly reduced colony formation and increased differentiation of primary MLL leukemia CD34+ cells. Mechanistically, LAMP5-AS1 facilitated the methyltransferase activity of DOT1L by directly binding its Lys-rich region of catalytic domain, thus promoting the global patterns of H3K79 dimethylation and trimethylation in cells. These observations supported that LAMP5-AS1 upregulated H3K79me2/me3 and the transcription of DOT1L ectopic target genes.

Conclusions

This is the first study that a lncRNA regulates the self-renewal program and differentiation block in MLL leukemia cells by facilitating the methyltransferase activity of DOT1L and global H3K79 methylation, showing its potential as a therapeutic target for MLL leukemia.
Hsa_circ_0003998 promotes epithelial to mesenchymal transition of hepatocellular carcinoma by sponging miR-143-3p and PCBP1
Authors: Song Li-na , Qiao Guang-lei , Yu Jian , Yang Chun-mei , Chen Ying , Deng Zhou-feng , Song Li-hua , Ma Li-jun , Yan Hong-li
Published: June 2020

Background

Circular RNAs (circRNAs) play a critical regulatory role in cancer progression. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) metastasis remain mostly unknown.

Methods

Has_circ_0003998 (circ0003998) was identified by RNAs sequencing in HCC patients with /without portal vein tumor thrombus (PVTT) metastasis. The expression level of circ0003998 was further detected by in situ hybridization on tissues microarray (ISH-TMA) and qRT-PCR in 25 HCC patients with PVTT metastasis. Moreover, the 25 HCC patients with PVTT metastasis and 50 HCC patients without PVTT metastasis were recruited together to analyze the correlation between circ0003998 expression and HCC clinical characteristics. Transwell, migration and CCK8 assays, as well as nude mice model of lung or liver metastasis were used to evaluate the role of circ0003998 in epithelial to mesenchymal transition (EMT) in HCC. The regulatory mechanisms of circ0003998 in miR-143-3p and PCBP1 were determined by dual-luciferase reporter assay, nuclear-cytoplasmic fractionation, fluorescent in situ hybridization, RNA pull- down, microRNA sequence, western blot and RNA immunoprecipitation.

Results

Compared with adjacent normal liver tissues (ANL), circ0003998 expression was significantly upregulated in PVTT tissues and HCC tissues, and its expression correlates with the aggressive characteristics of HCC patients. Further assays suggested that circ0003998 promoted EMT of HCC both in vitro and in vivo. Mechanistically, our data indicated that circ0003998 may act as a ceRNA (competing endogenous RNA) of microRNA-143-3p to relieve the repressive effect on EMT-related stimulator, FOSL2; meanwhile, circ0003998 could bind with PCBP1-poly(rC) binding protein 1 (PCBP1) to increase the expression level of EMT-related genes, CD44v6.

Conclusion

Circ0003998 promotes EMT of HCC by circ0003998/miR-143-3p/FOSL2 axis and circ0003998 /PCBP1/CD44v6 axis.
Long non-coding RNA THOR promotes ovarian Cancer cells progression via IL-6/STAT3 pathway
Authors: Ge Jing , Han Tao , Shan Lili , Na Jing , Li Ya , Wang Jun
Published: June 2020

Background

Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear.

Methods

RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts.

Results

In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression.

Conclusion

Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.
Pure dysgerminoma of the ovary: CT and MRI features with pathological correlation in 13 tumors
Authors: Zhao Shuhui , Sun Fan , Bao Lei , Chu Caiting , Li Haiming , Yin Qiufeng , Guan Wenbin , Wang Dengbin
Published: June 2020

Background

To investigate the spectrum of CT and MRI findings of dysgerminoma of the ovary.

Methods

CT and MRI imaging of 12 patients with 13 histologically proven dysgerminomas of the ovary were retrospectively reviewed. Patients, ages ranged from 6 ~ 27 years (mean, 17.2 years). Two observers evaluated the following CT and MRI features of the tumor by consensus: (i) location, shape, and size; (ii) attenuation, T2 signal intensity, and ADC value; (iii) patterns of contrast enhancement; (iv) presence of fibrovascular septa; (v) presence of necrosis, hemorrhage, and calcification; (vi) presence of “ovarian vascular pedicle” sign. We also noted the extent or stage of the tumors.

Results

75% lesions arised in the right ovary. Bilateral ovaries were involved in one case. Tumors displayed as a purely or predominantly solid mass (mean size, 17.0 ± 7.8 cm). Ten tumors were shaped multilobulated. The mean ADC value of lesions was 0.830 ± 0.154 × 10− 3 mm2/s. Characteristic fibrovascular septa were observed in all lesions. Among them, classic septa were present in 69% lesions. They were thin, hypointense on T2WI with a linear intense enhancement indicating the blood vessels in septa. Due to the stromal edema, fibrovascular septa may become thick even amorphous in shape, hyperintense on T2WI and even low attenuation on CT with a slight enhancement except for a bright blood vessel on the edge. Massive necrosis was observed only in one lesion. Calcification was present in 3 of the 5 tumors on CT. “Ovarian vascular pedicle” sign was present in 12 lesions. Lymphadenopathy, retroperitoneal spread, and distant metastases combined with an implantation in Douglas’ cul-de-sac were present in one patient respectively.

Conclusion

On CT and MR images, ovarian dysgerminoma often appears as a large solid mass. The edematous condition of characteristic fibrovascular septa can be well displayed by imaging which then can guide the radiologists to make an accurate diagnosis. Calcifications often occur in the tumor. Nonspecific low ADC value and “ovarian vascular pedicle” sign may narrow the differential diagnosis.
Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: a narrative literature review
Authors: Andreozzi F. , Candido R. , Corrao S. , Fornengo R. , Giancaterini A. , Ponzani P. , Ponziani M. C. , Tuccinardi F. , Mannino D.
Published: June 2020

Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care.
Immunohistochemical expression of Cyclin D1 among Sudanese patients diagnosed with benign and malignant prostatic lesions
Authors: Ahmed Eiman Siddig , Elnour Lubna S. , Hassan Rowa , Siddig Emmanuel E. , Chacko Mintu Elsa , Ali Eman T. , Mohamed Mona A. , Munir Abdalla , Muneer Mohamed S. , Mohamed Nouh S. , Edris Ali M. M.
Published: June 2020

Objectives

Prostate cancer (PC) is common cancer worldwide. Several markers have been developed to differentiate between benign prostatic hyperplasia (BPH) from PC. A descriptive retrospective hospital-based study aimed at determining the expression of Cyclin D1 in BPH and PC. The study took place at different histopathology laboratories in Khartoum state, Sudan, from December 2016 to January 2019. Formalin-fixed paraffin-embedded blocks were sectioned and fixed in 3-aminopropyltriethoxysilane coated slides incubated into primary antibody for Cyclin D1. The assessment of immunoreactivity of Cyclin D1 of each section was done using the Gleason scoring system.

Results

A total of 153 males’ prostate sections included in this study, of them, 120 (78.4%) were PC, and 33 (21.6%) were BPH. Their age ranged from 45 to 88 years, mean age was 66.19 ± 8.599. 142 (92.8%) did not have a family history of PC, while 11 (7.2%) patients reported having a family history. The Gleason scoring showed a total of 81 (52.9%) patients with high-grade and 39 (25.5%) with low-grade. 118 (97.5%) patients had PC showed positive results for Cyclin D1, while BPH was 3 (2.5%). P value < 0.001. Cyclin D1 staining was associated with high-grade Gleason score and perineural invasion, P value 0.001.
A rare case of anaphylaxis to Indian jujube (Ziziphus Mauritiana Lam)
Authors: Aberumand Babak , Borici-Mazi Rozita
Published: June 2020

Background

Indian jujube (Ziziphus Mauritiana Lam) is a sweet fruit from a tree native to tropical and subtropical regions of Asia and India. A few case reports have implicated Indian jujube to cause latex-fruit syndrome. We present the first case of an anaphylactic reaction to this fruit in a patient with no latex allergy.

Case presentation

A 55-year-old male was referred to the Outpatient Allergy Clinic at Queen’s University for evaluation of anaphylaxis caused by ingestion of Indian jujube. He presented to the Emergency Department (ED) with scalp pruritus, dyspnea and generalized urticaria, which occurred two hours after he had consumed a homemade candied fruit cocktail consisting of Indian jujube, water, Thai and Indian sweetener. In the ED, he was treated with epinephrine, intravenous diphenhydramine and steroids. He did not have any previous history of environmental or food allergies but had consumed this fruit frequently since childhood. In clinic, he underwent skin-prick testing with a saline slurry of candied jujube, which resulted in a positive wheal and flare response with appropriate controls. On subsequent visit, skin-prick tests were performed with saline slurries of the Thai and Indian sweetener used to make the cocktail. Both tests were negative when applied to a healthy volunteer. Skin-prick testing to latex allergen and latex specific IgE were both negative. He was diagnosed with an IgE-mediated anaphylactic reaction to the Indian jujube fruit. He was advised to avoid consumption of Indian jujubes and carry an epinephrine autoinjector.

Conclusions

Anaphylaxis secondary to Indian jujube ingestion is an extremely rare phenomenon in patients without a latex allergy. A possible allergy to Indian jujube should be taken into consideration when working up anaphylaxis, especially in patient of Asian and Indian descent who have ceased regular consumption of the fruit.
Atypical case of hantavirus infection in Sri Lanka mimicking leptospirosis: a case report
Authors: Dalugama Chamara , Nanayakkara Madushi , Rathnayaka Nimanthi , Medagama Arjuna
Published: June 2020

Background

Hantavirus infection is an emerging zoonotic infection which has two characteristic patterns of presentation: hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. The clinical presentation of hantavirus infection closely mimics leptospirosis.

Case presentation

This case report describes a previously apparently well 36-year-old Sri Lankan Sinhalese man who presented with an acute febrile illness with myalgia, with liver involvement in the form of transaminitis, cardiac involvement in the form of myocarditis, acute kidney injury, and pulmonary involvement. He was initially managed as severe leptospirosis with multiorgan dysfunction with antibiotics, steroids, and N-acetyl cysteine. A diagnosis of acute hantavirus infection was made subsequently. He made an uneventful recovery.

Conclusion

Hantavirus infections need to considered in the differential diagnosis of patients presenting with acute febrile illness with multiorgan involvement. Larger studies are needed to evaluate the seroprevalence of hantavirus in Sri Lanka because it could be an emerging serious public health problem.
Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate
Authors: Ahirrao Vinod K. , Jadhav Rajiv A. , Rane Vipul P. , Bhamare Harshal R. , Yeole Ravindra D.
Published: June 2020

Alalevonadifloxacin mesylate (ALA), pro-drug of levonadifloxacin is a new antibiotic approved in India to treat infections caused by Gram-positive bacteria. Alkyl mesylates (AMs) are known genotoxic impurities (GTI’s) formed in drug substances isolated as mesylate salts. Time-dependent selected reaction monitoring (t-SRM)-based gas chromatography tandem mass spectrometry (GC-MS/MS) method has been developed for trace estimation of AMs, namely, methyl methane sulfonate (MMS), ethyl methane sulfonate (EMS) and isopropyl methane sulfonate (IMS) in ALA. Liquid-liquid extraction (LLE) procedure using dichloromethane (DCM) as an extracting solvent was employed to extract AMs from the drug substance. Automatic selective reaction monitoring (auto-SRM) tool was applied to identify the most intense SRM pair of the ions to achieve the highest sensitivity. The method was validated in terms of specificity, linearity, sensitivity, precision, and accuracy. The limit of quantitation (LOQ) for the MMS, EMS and IMS were 5, 10, and 20 ng/g of ALA, respectively. For all analytes, the correlation coefficient (R) were greater than 0.9975 in the concentration range of 3.0–260 ng/mL. Mean recovery of all analytes was in the range of 91.77 to 97.65%.