bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive investigation of early kidney damage in streptozotocin-induced diabetic rats by intravoxel incoherent motion diffusion-weighted (IVIM) MRI
Authors: Feng You-Zhen , Chen Xiao-Qiao , Cheng Zhong-Yuan , Lin Qi-Ting , Chen Ping-Kang , Si-Tu Ding-Kun , Cao Rui , Qian Long , Heng Baoli , Cai Xiang-Ran
Published: September 2021

Background

The current study investigated the performance of intravoxel incoherent motion diffusion (IVIM) technology in monitoring early renal injury in streptozotocin rats.

Methods

Forty-eight Sprague-Dawley (SD) rats were divided into a control group and a diabetic mellitus (DM) group. Six rats in each group were randomly selected for MR scans at four different time points (0, 4, 8, and 12 weeks). The IVIM-derived parameters (D, D*, f and ADC values) of the renal cortex (CO), outer and inner stripe of the outer medulla (OS, IS), and internal medulla (IM) were acquired. Changes in each IVIM-derived parameter over time were analyzed, and differences between the two groups at each point were assessed. The associations between the IVIM parameters and IV collagen expression, urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) were investigated.

Results

The D and D* values of CO and the ADC values of CO, OS, IS and IM displayed significantly different trends between the two groups over time (P<0.05). In addition, significant correlations were discovered between the D* value of CO and UV and BUN (r=0.527, P=0.033; r=0.617, P=0.005), between the ADC value of IM and BUN (r=0.557, P=0.019) and between the f value of IM and BUN (r=0.527, P=0.033). No correlation was found between IVIM parameters and IV collagen expression and Scr.

Conclusions

IVIM is a potential sensitive and noninvasive technology for the simultaneous assessment of early renal cortical and medullary injuries induced by diabetes.
EMMPRIN expression is associated with metastatic progression in osteosarcoma
Authors: Kim Han-Soo , Kim Ha Jeong , Lee Mi Ra , Han Ilkyu
Published: September 2021

Background

Extracellular matrix metalloproteinase inducer (EMMPRIN), a cell-surface glycoprotein, is overexpressed in several cancer types. EMMPRIN induces a metastatic phenotype by triggering the production of matrix metalloproteinase proteins (MMPs) such as MMP1 and MMP2, and vascular endothelial growth factor (VEGF) in cancer cells and the surrounding stromal cells. The purpose of this study was to investigate the expression and role of EMMPRIN in osteosarcoma.

Methods

The level of EMMPRIN expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) in 6 tumor-derived osteosarcoma cell lines and compared with that in normal osteoblasts. To study the prognostic significance of EMMPRIN expression, immunohistochemistry was carried out in prechemotherapy biopsies of 54 patients. siRNA knockdown of EMMPRIN in SaOS-2 cells was conducted to explore the role of EMMPRIN. To study the role of EMMPRIN in tumor-stromal interaction in MMP production and invasion, co-culture of SaOS-2 cells with osteoblasts and fibroblasts was performed. Osteosarcoma 143B cells were injected into the tail vein of BALB/c mice and lung metastasis was analyzed.

Results

EMMRIN mRNA expression was significantly higher in 5 of 6 (83%) tumor-derived cells than in MG63 cells. 90% of specimens (50/54) stained positive for EMMPRIN by immunohistochemistry, and higher expression of EMMPRIN was associated with shorter metastasis-free survival (p = 0.023). Co-culture of SaOS-2 with osteoblasts resulted in increased production of pro-MMP2 and VEGF expression, which was inhibited by EMMPRIN-targeting siRNA. siRNA knockdown of EMMPRIN resulted in decreased invasion. EMMPRIN shRNA-transfected 143B cells showed decreased lung metastasis in vivo.

Conclusions

Our data suggest that EMMPRIN acts as a mediator of osteosarcoma metastasis by regulating MMP and VEGF production in cancer cells as well as stromal cells. EMMPRIN could serve as a therapeutic target in osteosarcoma.
Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus minimally invasive esophagectomy for resectable esophageal adenocarcinoma, a randomized controlled trial (ROBOT-2 trial)
Authors: Tagkalos E. , van der Sluis P. C. , Berlth F. , Poplawski A. , Hadzijusufovic E. , Lang H. , van Berge Henegouwen M. I. , Gisbertz S. S. , Müller-Stich B. P. , Ruurda J. P. , Schiesser M. , Schneider P. M. , van Hillegersberg R. , Grimminger P. P.
Published: September 2021

Background

For patients with esophageal adenocarcinoma or cancer of the gastroesophageal junction, radical esophagectomy with 2-field lymphadenectomy is the cornerstone of the multimodality treatment with curative intent. Both conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE) were shown to be superior compared to open transthoracic esophagectomy considering postoperative complications. However, no randomized comparison exists between MIE and RAMIE in the Western World for patients with esophageal adenocarcinoma.

Methods

This is an investigator-initiated and investigator-driven multicenter randomized controlled parallel-group superiority trial. All adult patients (age ≥ 18 and ≤ 90 years) with histologically proven, surgically resectable (cT1-4a, N0–3, M0) esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 218) with resectable esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction are randomized to either RAMIE (n = 109) or MIE (n = 109). The primary outcome of this study is the total number of resected abdominal and mediastinal lymph nodes specified per lymph node station.

Conclusion

This is the first randomized controlled trial designed to compare RAMIE to MIE as surgical treatment for resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. The hypothesis of the proposed study is that RAMIE will result in a higher abdominal and mediastinal lymph node yield specified per station compared to conventional MIE.

Short-term results and the primary endpoint (total number of resected abdominal and mediastinal lymph nodes per lymph node station) will be analyzed and published after discharge of the last randomized patient within this trial.

Trial registration

ClinicalTrials.gov Identifier: NCT04306458. Registered 13th March 2020, https://clinicaltrials.gov/ct2/show/NCT04306458; Date of first enrolment 18.01.2021; Target sample size 218; Recruitment status: Recruiting; Protocol version 2; Issue date 10.03.2020; Rev. 02.02.2021; Authors ET, PCvdS, PPG.
The role of weight- and appearance-related discrimination on eating disorder symptoms among adolescents and emerging adults
Authors: Cohrdes Caroline , Santos-Hövener Claudia , Kajikhina Katja , Hölling Heike
Published: September 2021

Background

Eating disorder symptoms (EDs) have been discussed as a prominent problem among late adolescent girls with serious health risks and long-term consequences. However, there is a lack of population-based evidence on EDs comprising the age range from early adolescence to emerging adulthood as well as considering both females and males equally. Additionally, the differential role of a comprehensive set of several relevant risk factors and particularly weight- and appearance-related discrimination warrants further attention. Thus, we aimed to contribute to a better understanding of sex- and age-related differences in associations between discrimination experience and other relevant personal risk factors (body image, social media use, self-efficacy, social support) with EDs. Furthermore, we were interested in the exploration of underlying mechanisms enhancing the risk of EDs by taking discrimination experience into account.

Methods

Based on a logistic regression model, we investigated associations between weight- and appearance-related discrimination and EDs while controlling for other relevant personal risk factors in a subsample of N = 8504 adolescents and emerging adults (54.4% female, mean age = 20.71 years, SD = 4.32 years) drawn from a German representative health survey (KiGGS Wave 2). In a second step, we investigated the mediating role of discrimination experience between the other risk factors and EDs with the help of a path model.

Results

While controlling for other relevant personal risk factors, weight- and appearance-related discrimination was significantly related to EDs. Whereas the risk of EDs was significantly enhanced in males and emerging adults frequently experiencing weight-related discrimination, adolescents showed a higher risk of EDs when experiencing appearance-related discrimination. Moreover, discrimination experience partly explained the associations between body image dissatisfaction, low self-efficacy, high media use and ED symptoms.

Conclusions

The results highlight weight- and appearance-related discrimination as one central factor to be considered in the pathogeneses of EDs and underpin the need for discrimination prevention as well as the promotion of adaptive coping with discrimination experience to reduce the risk of developing ED symptoms. Males and emerging adults need particular attention when facing weight-related discrimination whereas risk constellations and EDs particularly affecting females need further investigation.
Comparison of influenza surveillance systems in Australia, China, Malaysia and expert recommendations for influenza control
Authors: El Guerche-Séblain Clotilde , Rigoine De Fougerolles Thierry , Sampson Kim , Jennings Lance , Van Buynder Paul , Shu Yuelong , Sekawi Zamberi , Yee-Sin Leo , Walls Tony , Vitoux Olivier , Yin J. Kevin , Wong Ada , Schellevis Francois , Vanhems Philippe
Published: September 2021

Background

The Western Pacific Region (WPR) is exposed each year to seasonal influenza and is often the source of new influenza virus variants and novel pathogen emergence. National influenza surveillance systems play a critical role in detecting emerging viruses, monitoring influenza epidemics, improving public disease awareness and promoting pandemic preparedness, but vary widely across WPR countries. The aim of this study is to improve existing influenza surveillance systems by systematically comparing selected WPR influenza surveillance systems.

Methods

Three national influenza surveillance systems with different levels of development (Australia, China and Malaysia) were compared and their adherence to World Health Organization (WHO) guidance was evaluated using a structured framework previously tested in several European countries consisting of seven surveillance sub-systems, 19 comparable outcomes and five evaluation criteria. Based on the results, experts from the Asia-Pacific Alliance for the Control of Influenza (APACI) issued recommendations for the improvement of existing surveillance systems.

Results

Australia demonstrated the broadest scope of influenza surveillance followed by China and Malaysia. In Australia, surveillance tools covered all sub-systems. In China, surveillance did not cover non-medically attended respiratory events, primary care consultations, and excess mortality modelling. In Malaysia, surveillance consisted of primary care and hospital sentinel schemes. There were disparities between the countries across the 5 evaluation criteria, particularly regarding data granularity from health authorities, information on data representativeness, and data communication, especially the absence of publicly available influenza epidemiological reports in Malaysia. This dual approach describing the scope of surveillance and evaluating the adherence to WHO guidance enabled APACI experts to make a number of recommendations for each country that included but were not limited to introducing new surveillance tools, broadening the use of specific existing surveillance tools, collecting and sharing data on virus characteristics, developing immunization status registries, and improving public health communication.

Conclusions

Influenza monitoring in Australia, China, and Malaysia could benefit from the expansion of existing surveillance sentinel schemes, the broadened use of laboratory confirmation and the introduction of excess-mortality modelling. The results from the evaluation can be used as a basis to support expert recommendations and to enhance influenza surveillance capabilities.
Tolerability of MenACWY-TT vaccination in adolescents in the Netherlands; a cross-sectional study
Authors: Kemmeren J. M. , van Balveren L. , Kant A. , de Melker H.
Published: September 2021

Background

In 2018, meningococcal ACWY-TT vaccine (MenACWY-TT) was offered to adolescents in the Netherlands within the National Immunization Programme at 14 years of age. A questionnaire study assessed the tolerability of this vaccine.

Methods

Five thousand adolescents were invited to participate and to fill in two questionnaires about systemic events in the week before vaccination and local reactions and systemic events in the week after vaccination. Frequencies of local and systemic adverse events in the week after vaccination were calculated. Association between the occurrence of systemic symptoms in the week before and after the vaccination was tested by using generalized mixed models (GLMM).

Results

Of all adolescents, 139 returned one or both questionnaires. Any local reaction within 7 days after vaccination was reported by 55.6% of the adolescents. Pain (50%) and reduced use of the injected arm (21.3%) were most often reported. Any systemic event was reported by 67.6% of the participants, with myalgia as the most often reported event (37.0%). Compared with the week before vaccination, there were no increased odds of experiencing systemic symptoms in the week after vaccination (OR 0.95; 95%CI 0.40–2.27).

Conclusions

After vaccination with MenACWY-TT vaccine, most adolescents reported one or more adverse events, which were mostly mild and transient. Systemic symptoms were not reported more often in the week after compared to the week before vaccination. Unfortunately, due to a low response rate we were not able to detect the absolute elevated risks the sample size calculation was based on. However, despite limited data, our results are in line with results from prelicensure data, and indicate that MenACWY-TT vaccination is well tolerated in adolescents.
Is there a difference in body size dissatisfaction between the patients with obesity seeking and not seeking treatment for obesity?
Authors: Gruszka Wojciech , Owczarek Aleksander J. , Glinianowicz Mateusz , Bąk-Sosnowska Monika , Chudek Jerzy , Olszanecka-Glinianowicz Magdalena
Published: September 2021

Background

Various factors motivate people to undertake treatment for obesity. Among others they include health benefits, willingness to please others, and dissatisfaction with one’s appearance. The present study aimed to assess body size dissatisfaction in patients with obesity seeking and not seeking treatment for obesity.

Methods

Two-hundred-sixteen adult subjects (154 women, 62 men) including 80 people with BMI ≥ 30 kg/m2 starting treatment for obesity (BMI 35.7 ± 5.3 kg/m2) and 136 volunteers with obesity (BMI 34.7 ± 4.3 kg/m2) not seeking treatment for obesity, were enrolled. Body size satisfaction was assessed using the Figure Rating Scale adapted by Stunkard.

Results

Patients with obesity starting obesity treatment had more often a high level of body size dissatisfaction than volunteers with obesity not seeking the treatment (p <  0.001). There was a significant difference in the distribution of body size dissatisfaction in women (p <  0.05), but not in men (p = 0.47).

Conclusion

Patients with obesity, especially women, seeking obesity treatment more often represent a high level of body size dissatisfaction than volunteers with obesity not seeking treatment for obesity. This implies the need for public health campaigns to address negative attitudes or misconceptions about obesity and its treatment. Placing more attention and emphasis on body size dissatisfaction in more vulnerable women with obesity may help to define personal motivations and goals, strengthen the doctor-patient relationship and better adapt therapeutic strategies.
Association of Environmental tobacco smoke exposure with depression among non-smoking adults
Authors: Okekunle Akinkunmi Paul , Asowata Jeffery Osahon , Lee Jung Eun , Akpa Onoja Matthew
Published: September 2021

Background

Depression is a psychological dysfunction that impairs health and quality of life. However, whether environmental tobacco smoke exposure (ETSE) is associated with depression is poorly understood. This study was designed to evaluate the association of ETSE with depression among non-smoking adults in the United States.

Method

Using the 2015–2016 United States National Health and Nutrition Examination Survey (NHANES), we identified 2623 adults (females – 64.2%, males – 35.8%) who had never smoked and applied multivariable adjusted-logistic regression to determine the adjusted odds ratio (aOR) and 95% confidence interval (CI) at P < 0.05 for the association of ETSE with depression adjusting for relevant confounders.

Results

Mean age of respondents was 46.5 ± 17.9 years, 23.5% reported ETSE, and 4.7% reported depression. Also, aORs for the association of ETSE with depression were 1.992 (1.987, 1.997) among females and 0.674 (0.670, 0.677) among males. When we examined the association by age groups, the aORs were 1.792 (1.787, 1.796) among young adults (< 60 years) and 1.146 (1.140, 1.152) among older adults (≥60 years).

Conclusions

We found that ETSE was associated with higher odds of depression among females but not among males.
Study protocol for Healthy Conversations @ Playgroup: a multi-site cluster randomized controlled trial of an intervention to promote healthy lifestyle behaviours in young children attending community playgroups
Authors: Trost Stewart G. , Byrne Rebecca , Williams Kate E. , Johnson Brittany J. , Bird Anna , Simon Kate , Chai Li Kheng , Terranova Caroline O. , Christian Hayley E. , Golley Rebecca K.
Published: September 2021

Background

Early childhood is a critical window for preventing obesity and chronic disease. Yet, 1 in 4 Australian children aged 5 years and under are affected by overweight or obesity; and significant proportions of children under 5 years fail to meet guidelines for diet quality, physical activity (PA), screen time, and sleep. Consequently, effective interventions to promote healthy lifestyle behaviors and prevent obesity during early childhood are needed. Community playgroups provide an opportunity for parents, carers, and children to meet in a safe and relaxed environment to play and share information. The structure, low cost and reach of playgroups provide a unique platform to engage parents in a scalable program to promote healthful lifestyle behaviors and prevent childhood obesity. However, the evidence base for the effectiveness of health promotion programs delivered in community playgroup settings is limited and lacking credible evidence from rigorously conducted randomized controlled trials.

Methods

The Healthy Conversations @ Playgroup randomized controlled trial (RCT) aims to address the underlying behavioral risk factors for obesity by helping parents take effective steps to improve their child’s dietary, PA, screen time, and sleep behaviors. The intervention program comprises 10 “healthy conversations” led by a trained peer facilitator, designed to increase parents’ behavioral capability and self-efficacy to implement autonomy-supportive parenting practices. The program will be delivered biweekly during regularly scheduled playgroup sessions over 10-weeks. Effectiveness will be tested in a 2-arm cluster RCT involving 60 community playgroups in three states across Australia. After baseline assessments, participating playgroups will be randomly allocated to either intervention or wait-list control conditions. Primary outcomes (vegetable intake, discretionary foods, daily PA, screen time, sleep duration, and body mass index [BMI] z-score) will be assessed at baseline, immediately post-intervention (10-weeks; T2) and 6-months post-intervention (T3). Outcomes will be assessed for differential change at T2 and T3.

Discussion

The Healthy Conversations @ Playgroup trial will rigorously evaluate a novel peer-led intervention program to promote healthful lifestyle behaviors and prevent obesity in children and families attending community playgroups. If effective, the program could be immediately scaled-up and delivered in community playgroups across Australia.

Trial registration

Trial registered 22nd January 2021 with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000055808).
Population preferences and attitudes towards COVID-19 vaccination: a cross-sectional study from Pakistan
Authors: Tahir Muhammad Junaid , Saqlain Muhammad , Tariq Waleed , Waheed Summaiya , Tan Steven H. S. , Nasir Sarim Irhas , Ullah Irfan , Ahmed Ali
Published: September 2021

Background

While vaccine development is itself a challenge; ensuring optimal vaccine uptake at population level can present an even more significant challenge. Therefore, this study aimed to assess the Pakistani population’s attitude and preferences towards the Coronavirus disease 2019 (COVID-19) vaccine.

Method

A cross-sectional study was carried out through an online self-administered questionnaire from 27 September 2020 to 11 October 2020. A total of 883 people responded to the survey. The questionnaire included the participants’ socio-demographic variables, attitudes, beliefs towards the COVID-19 vaccine and acceptance and rejection of vaccination, and reasons for them. Logistic regression analysis was used to analyze the predictors for vaccine acceptance and willingness to pay for the vaccine.

Results

A majority (70.8%) of respondents will accept the COVID-19vaccine if available, and 66.8% showed a positive attitude towards vaccination. Monthly family income, education level, self-diagnosis of COVID-19 or a friend, family member, or colleague are significant factors influencing the acceptance of COVID-19 vaccination. The dogma of being naturally immune to COVID-19 was a key reason for the refusal of the vaccine. Less than half (48%) of those who refuse will vaccinate themselves if government officials have made it compulsory. A third (33.9%) of participants were willing to pay up to (7 USD) 1000 Pkr (Pakistani Rupees) for the vaccine.

Conclusion

The population’s positive attitude should be improved by increasing awareness and eradicating false myths about vaccines through large-scale campaigns.
Seven-year follow-up of a patient with hereditary gingival fibromatosis treated with a multidisciplinary approach: case report
Authors: Li Ning , Wang Wenfang , Sun Yuanyuan , Wang Hongning , Wang Tiejun
Published: September 2021

Background

Hereditary gingival fibromatosis (HGF) is rare in clinical practice, and the long-term results of the combined orthodontic-periodontal treatment of HGF are rarely reported.

Case presentation

This study reports for the first time the results of seven years of follow-up in a seven-year-old girl with HGF. The diagnosis was confirmed by clinical signs, family history and histopathological examination. First, periodontal scaling and oral hygiene reinforcement were performed regularly in the mixed dentition stage. Next, gingivoplasty was performed on the permanent dentition. Two months after the surgery, treatment with fixed orthodontic appliances was conducted. The teeth were polished on a monthly basis, and oral hygiene was reinforced to control gingival enlargement. Gingival hypertrophy recurred slightly, and gingivectomies were performed in the months following the start of orthodontic treatment. Follow-up was performed for 24 months with orthodontic retention, and gingival enlargement remained stable after the combined treatment.

Conclusions

The risk of gingival hyperplasia recurrence during and after orthodontic treatment is high, but satisfying long-term outcomes can be achieved with gingivectomy, malocclusion correction, and regular follow-up maintenance.
Comparison of conventional and wide field direct ophthalmoscopy on medical students’ self-confidence for fundus examination: a 1-year follow-up
Authors: Ayub Gabriel , Souza Rafael Boava , de Albuquerque Andrelisa Marina , de Vasconcellos José Paulo Cabral
Published: September 2021

Background

Fundus examination is an easy, quick and effective way to diagnose sight- and life-threatening diseases. However, medical students and physicians report lack of proficiency and self-confidence in perform fundoscopy. The aim of this study was to compare students’ self-confidence in fundus examination, using two different direct ophthalmoscopes, 1 month and 1 year after practical training.

Methods

In this prospective cohort, medical students (MS) of the same class were divided in small groups for PanOptic (PO) or conventional (CO) direct ophthalmoscope training. The intervention group encompassed MS of the 4th -year (class of 2019), and the control group encompassed MS of year behind (class of 2020). A questionnaire to measure self-confidence in fundoscopy technique assessing optic nerve, cup-to-disc ratio and macula was translated and validated to Portuguese, and applied 1-month and 1-year after practical training.

Results

One-hundred and sixty-seven MS were enrolled (35 PO group, 38 CO group, and 94 control group). PO group had a significantly higher overall self-confidence comparing either control or CO groups, respectively (3.57 ± 0.65 vs. 2.97 ± 1.03 vs. 2.46 ± 0.87, p < 0.01) as well as in evaluate cup-to-disc ratio (3.09 ± 0.75 vs. 2.32 ± 0.87 vs. 1.46 ± 0.81, p < 0.01), optic disc margins (3.26 ± 0.85 vs. 2.71 ± 0.96 vs. 2.01 ± 0.97, p < 0.01) and macula (3.43 ± 1.12 vs. 2.89 ± 1.08 vs. 2.02 ± 0.89, p < 0.01) 1-month after practical training. One-year after intervention, CO group showed a significantly higher score compared to PO group in overall self-confidence (3.31 ± 0.69 vs. 3.18 ± 0.73, p = 0.03) and in optic disc margins assessing (3.16 ± 0.85 vs. 2.95 ± 0.78, p = 0.03), but not significant in the evaluation of cup-to-disc ratio (2.78 ± 0.97 vs. 2.68 ± 0.94, p = 0.08), and macula (3.34 ± 0.79 vs. 3.27 ± 0.98, p = 0.07).

Conclusions

Students were more confident in use PO as an instrument to perform direct ophthalmoscopy immediately after practical training, but confidence level of CO was higher compared to PO one year after practical training. These findings would help medical schools decide which ophthalmoscope to choose to teach fundus examination.
Conducting online OSCEs aided by a novel time management web-based system
Authors: Shaban Sami , Tariq Irfan , Elzubeir Margaret , Alsuwaidi Ahmed R , Basheer Alsajir , Magzoub Mohi
Published: September 2021

Background

Objective Structured Clinical Examinations (OSCEs) are an essential part of the assessment process for medical students. They have traditionally been face-to-face assessments, however, due to the COVID-19 pandemic, medical schools have been forced to attempt to carry them out remotely. OSCEs are difficult to carry out online due to rotation management aspects which make it difficult to synchronize movement of students from one station to another.

Methods

The authors have developed a dynamic OSCE time management website which aids in solving the movement synchronization issue. This secure website enables participants to view the list of stations they are allowed to enter, and the start and end time of each station. OSCE administrators can control time of entry and monitor progress of the OSCE remotely.

Results

The authors have used the system to conduct several exams successfully, showing the feasibility and cost effectiveness of this method, as well as user acceptance and satisfaction. In contrast to traditional OSCEs, students are set up in individual virtual rooms for the whole exam while examiners, simulated patients and proctors rotate between them.

Conclusions

This online OSCE implementation shows feasibility, cost effectiveness and acceptance of this method. The authors found that student outcomes are comparable to traditional OSCEs conducted in the past. There was no significant difference in student marks in one exam compared to last year, while marks were slightly higher in two exams, potentially due to lack of physical exam stations. An unresolved drawback is the inability to assess physical exam stations online, although having students verbally describe what they would do in physical exam situations may be a partial solution.
TV medical dramas: health sciences students’ viewing habits and potential for teaching issues related to bioethics and professionalism
Authors: Cambra-Badii Irene , Moyano Elisabet , Ortega Irene , Baños Josep-E , Sentí Mariano
Published: September 2021

Background

Medical dramas have been popular since their inception, especially among medical students. We hypothesized that the recent increase in the availability of TV medical series through online streaming platforms has probably changed health science students’ viewing habits as well as the representation of bioethical conflicts and health professionals.

Methods

We invited undergraduate students of medicine, nursing, and human biology to complete a self-administered questionnaire about their viewing habits and perceptions of the depictions of bioethical issues and professionalism in TV medical series.

Results

Of the 355 respondents, 98.6 % had watched TV in the last year, 93.5 % watched TV series, and 49.6 % watched medical dramas more than once a week. The most-viewed medical dramas were The Good Doctor, House MD, and Grey’s Anatomy. The most-remembered bioethical topics were medical errors, inappropriate professional behaviors, and death. Most students considered that ideals of professionalism were depicted positively and professionals were portrayed as intelligent, professionally qualified, and competent.

Conclusions

Medical dramas are very popular with health science students and are potentially useful as teaching tools for discussing issues related to bioethics and professionalism.
Evidence-based practice in primary healthcare from the managerial point of view – a national survey
Authors: Abelsson Tobias , Morténius Helena , Karlsson Ann-Kristin , Bergman Stefan , Baigi Amir
Published: September 2021

Background

The vast availability of and demand for evidence in modern primary healthcare force clinical decisions to be made based on condensed evidence in the form of policies and guidelines. Primary healthcare managers play a key role in implementing these governing documents. Thus, the aim of this article is to investigate the use and availability of evidence-based practice resources from the perspective of first-line primary healthcare managers.

Methods

The study is based on a national survey of primary healthcare managers, consisting of 186 respondents, recruited nationally from Sweden. The data was analysed using empirically constructed concepts and validated using factor analysis. A chi-square test was utilized to determine the statistical significance of comparisons. Associations between variables were calculated using Spearman’s correlation coefficients. All tests were two-sided, and the significance level was set to 0.05.

Results

A majority (97 %) of managers stated that guidelines and policy documents impacted primary healthcare; 84 % of managers observed a direct effect on daily practices. Most of the managers (70 %) stated that some adaptation was needed when new evidence was introduced. The managers emphasized the importance of keeping themselves updated and open to new information about work routines (96 %).

Conclusions

The study illustrates a nearly unanimous response about the influence of clinical evidence on daily practice. The emphasis on the importance of all staff members keeping their professional knowledge up to date is viewed as a direct result of this effect on daily practice. An information-dense organization such as a primary healthcare organization would have much to gain from increased cooperation with regional information resources such as clinical libraries.
Horizontal gene transfer-mediated bacterial strain variation affects host fitness in Drosophila
Authors: Wang Yun , Baumdicker Franz , Schweiger Paul , Kuenzel Sven , Staubach Fabian
Published: September 2021

Background

How microbes affect host fitness and environmental adaptation has become a fundamental research question in evolutionary biology. To better understand the role of microbial genomic variation for host fitness, we tested for associations of bacterial genomic variation andDrosophila melanogasteroffspring number in a microbial Genome Wide Association Study (GWAS).

Results

We performed a microbial GWAS, leveraging strain variation in the genusGluconobacter, a genus of bacteria that are commonly associated withDrosophilaunder natural conditions. We pinpoint the thiamine biosynthesis pathway (TBP) as contributing to differences in fitness conferred to the fly host. While an effect of thiamine on fly development has been described, we show that strain variation in TBP between bacterial isolates from wild-caughtD. melanogastercontributes to variation in offspring production by the host. By tracing the evolutionary history of TBP genes inGluconobacter, we find that TBP genes were most likely lost and reacquired by horizontal gene transfer (HGT).

Conclusion

Our study emphasizes the importance of strain variation and highlights that HGT can add to microbiome flexibility and potentially to host adaptation.
Clinical and functional characterization of a novel STUB1 frameshift mutation in autosomal dominant spinocerebellar ataxia type 48 (SCA48)
Authors: Chen Huan-Yun , Hsu Chia-Lang , Lin Han-Yi , Lin Yung-Feng , Tsai Shih-Feng , Ho Yu-Jung , Li Ye-Ru , Tsai Jin-Wu , Teng Shu-Chun , Lin Chin-Hsien
Published: September 2021

Background

Heterozygous pathogenic variants in STUB1 are implicated in autosomal dominant spinocerebellar ataxia type 48 (SCA48), which is a rare familial ataxia disorder. We investigated the clinical, genetic and functional characteristics of STUB1 mutations identified from a Taiwanese ataxia cohort.

Methods

We performed whole genome sequencing in a genetically undiagnosed family with an autosomal dominant ataxia syndrome. Further Sanger sequencing of all exons and intron–exon boundary junctions of STUB1 in 249 unrelated patients with cerebellar ataxia was performed. The pathogenicity of the identified novel STUB1 variant was investigated.

Results

We identified a novel heterozygous frameshift variant, c.832del (p.Glu278fs), in STUB1 in two patients from the same family. This rare mutation is located in the U-box of the carboxyl terminus of the Hsc70-interacting protein (CHIP) protein, which is encoded by STUB1. Further in vitro experiments demonstrated that this novel heterozygous STUB1 frameshift variant impairs the CHIP protein’s activity and its interaction with the E2 ubiquitin ligase, UbE2D1, leading to neuronal accumulation of tau and α-synuclein, caspase-3 activation, and promoting cellular apoptosis through a dominant-negative pathogenic effect. The in vivo study revealed the influence of the CHIP expression level on the differentiation and migration of cerebellar granule neuron progenitors during cerebellar development.

Conclusions

Our findings provide clinical, genetic, and a mechanistic insight linking the novel heterozygous STUB1 frameshift mutation at the highly conserved U-box domain of CHIP as the cause of autosomal dominant SCA48. Our results further stress the importance of CHIP activity in neuronal protein homeostasis and cerebellar functions.
Blood leukocyte count as a systemic inflammatory biomarker associated with a more rapid spirometric decline in a large cohort of iron and steel industry workers
Authors: Kong Nan , Chen Guoshun , Wang Haitao , Li Jianyu , Yin Shuzhen , Cao Xue , Wang Tao , Li Xin , Li Yanan , Zhang Huanling , Yu Shanfa , Tang Jinglong , Sood Akshay , Zheng Yuxin , Leng Shuguang
Published: September 2021

Objective

Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers.

Methods

We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses.

Results

The average annual change of lung function was − 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and − 34.36 ml/year in forced vital capacity (FVC) in males, and − 39.06 ml/year in FEV1 and − 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC.

Conclusions

Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.
Metabolic engineering of Deinococcus radiodurans for pinene production from glycerol
Authors: Helalat Seyed Hossein , Jers Carsten , Bebahani Mandana , Mohabatkar Hassan , Mijakovic Ivan
Published: September 2021

Background

The objective of this work was to engineer Deinococcus radiodurans R1 as a microbial cell factory for the production of pinene, a monoterpene molecule prominently used for the production of fragrances, pharmaceutical products, and jet engine biofuels. Our objective was to produce pinene from glycerol, an abundant by-product of various industries.

Results

To enable pinene production in D. radiodurans, we expressed the pinene synthase from Abies grandis, the geranyl pyrophosphate (GPP) synthase from Escherichia coli, and overexpressed the native 1-deoxy-d-xylulose 5-phosphate synthase. Further, we disrupted the deinoxanthin pathway competing for the substrate GPP by either inactivating the gene dr0862, encoding phytoene synthase, or substituting the native GPP synthase with that of E. coli. These manipulations resulted in a D. radiodurans strain capable of producing 3.2 ± 0.2 mg/L pinene in a minimal medium supplemented with glycerol, with a yield of 0.13 ± 0.04 mg/g glycerol in shake flask cultures. Additionally, our results indicated a higher tolerance of D. radiodurans towards pinene as compared to E. coli.

Conclusions

In this study, we successfully engineered the extremophile bacterium D. radiodurans to produce pinene. This is the first study demonstrating the use of D. radiodurans as a cell factory for the production of terpenoid molecules. Besides, its high resistance to pinene makes D. radiodurans a suitable host for further engineering efforts to increase pinene titer as well as a candidate for the production of the other terpenoid molecules.
Influence of B. subtilis 3NA mutations in spo0A and abrB on surfactin production in B. subtilis 168
Authors: Klausmann Peter , Lilge Lars , Aschern Moritz , Hennemann Katja , Henkel Marius , Hausmann Rudolf , Morabbi Heravi Kambiz
Published: September 2021

Background

Bacillus subtilis is a well-established host for a variety of bioproduction processes, with much interest focused on the production of biosurfactants such as the cyclic lipopeptide surfactin. Surfactin production is tightly intertwined with quorum sensing and regulatory cell differentiation processes. As previous studies have shown, a non-sporulating B. subtilis strain 3NA encoding a functional sfp locus but mutations in the spo0A and abrB loci, called JABs32, exhibits noticeably increased surfactin production capabilities. In this work, the impacts of introducing JABs32 mutations in the genes spo0A, abrB and abh from 3NA into strain KM1016, a surfactin-forming derivative of B. subtilis 168, was investigated. This study aims to show these mutations are responsible for the surfactin producing performance of strain JABs32 in fed-batch bioreactor cultivations.

Results

Single and double mutant strains of B. subtilis KM1016 were constructed encoding gene deletions of spo0A, abrB and homologous abh. Furthermore, an elongated abrB version, called abrB*, as described for JABs32 was integrated. Single and combinatory mutant strains were analysed in respect of growth behaviour, native PsrfA promoter expression and surfactin production. Deletion of spo0A led to increased growth rates with lowered surfactin titers, while deletion or elongation of abrB resulted in lowered growth rates and high surfactin yields, compared to KM1016. The double mutant strains B. subtilis KM1036 and KM1020 encoding Δspo0A abrB* and Δspo0A ΔabrB were compared to reference strain JABs32, with KM1036 exhibiting similar production parameters and impeded cell growth and surfactin production for KM1020. Bioreactor fed-batch cultivations comparing a Δspo0A abrB* mutant of KM1016, KM681, with JABs32 showed a decrease of 32% in surfactin concentration.

Conclusions

The genetic differences of B. subtilis KM1016 and JABs32 give rise to new and improved fermentation methods through high cell density processes. Deletion of the spo0A locus was shown to be the reason for higher biomass concentrations. Only in combination with an elongation of abrB was this strain able to reach high surfactin titers of 18.27 g L−1 in fed-batch cultivations. This work shows, that a B. subtilis strain can be turned into a high cell density surfactin production strain by introduction of two mutations.
Regulating the T7 RNA polymerase expression in E. coli BL21 (DE3) to provide more host options for recombinant protein production
Authors: Du Fei , Liu Yun-Qi , Xu Ying-Shuang , Li Zi-Jia , Wang Yu-Zhou , Zhang Zi-Xu , Sun Xiao-Man
Published: September 2021

Escherichia coli is the most widely used bacterium in prokaryotic expression system for the production of recombinant proteins. In BL21 (DE3), the gene encoding the T7 RNA polymerase (T7 RNAP) is under control of the strong lacUV5 promoter (PlacUV5), which is leakier and more active than wild-type lac promoter (PlacWT) under certain growth conditions. These characteristics are not advantageous for the production of those recombinant proteins with toxic or growth-burdened. On the one hand, leakage expression of T7 RNAP leads to rapid production of target proteins under non-inducing period, which sucks resources away from cellular growth. Moreover, in non-inducing or inducing period, high expression of T7 RNAP production leads to the high-production of hard-to-express proteins, which may all lead to loss of the expression plasmid or the occurrence of mutations in the expressed gene. Therefore, more BL21 (DE3)-derived variant strains with rigorous expression and different expression level of T7 RNAP should be developed. Hence, we replaced PlacUV5 with other inducible promoters respectively, including arabinose promoter (ParaBAD), rhamnose promoter (PrhaBAD), tetracycline promoter (Ptet), in order to optimize the production of recombinant protein by regulating the transcription level and the leakage level of T7 RNAP. Compared with BL21 (DE3), the constructed engineered strains had higher sensitivity to inducers, among which rhamnose and tetracycline promoters had the lowest leakage ability. In the production of glucose dehydrogenase (GDH), a protein that causes host autolysis, the engineered strain BL21 (DE3::ara) exhibited higher biomass, cell survival rate and foreign protein expression level than that of BL21 (DE3). In addition, these engineered strains had been successfully applied to improve the production of membrane proteins, including E. coli cytosine transporter protein (CodB), the E. coli membrane protein insertase/foldase (YidC), and the E. coli F-ATPase subunit b (Ecb). The engineered strains constructed in this paper provided more host choices for the production of recombinant proteins.
Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition
Authors: Elango Ramesh , Vishnubalaji Radhakrishnan , Shaath Hibah , Alajez Nehad M.
Published: September 2021

Background

DNA methylation plays a crucial role in multiple cellular processes such as gene regulation, chromatin stability, and genetic imprinting. In mammals, DNA methylation is achieved by DNA methyltransferases (DNMTs). A number of studies have associated alterations in DNMT activity to tumorigenesis; however, the exact role of DNMTs in shaping the genome in triple negative breast cancer (TNBC) is still being unraveled.

Methods

In the current study, we employed two DNMT inhibitors (Decitabine and 5-Azacytidine), two TNBC models (MDA-MB-231 and BT-549) and whole transcriptome RNA-Seq and characterized the transcriptional alterations associated with DNMT inhibition. Colony forming unit (CFU), flow cytometry, and fluorescent microscopy were used to assess cell proliferation, cell cycle distribution, and cell death, respectively. Ingenuity pathway analysis (IPA) was used for network and pathway analyses.

Results

Remarkably, DNMT inhibition induced the expression of genes involved in endoplasmic reticulum response to stress, response to unfolder protein, as well as cobalamin metabolic processes. In contrast, suppression of cellular processes related to cell cycle and mitosis were hallmarks of DNMT inhibition. Concordantly, DNMT inhibition led to significant inhibition of TNBC cell proliferation, G2-M cell cycle arrest and induction of cell death. Mechanistically, DNMT inhibition activated TP53, NUPR1, and NFkB (complex) networks, while RARA, RABL6, ESR1, FOXM1, and ERBB2 networks were suppressed. Our data also identified the long noncoding RNA (lncRNA) transcriptional portrait associated with DNMT inhibition and identified 25 commonly upregulated and 60 commonly downregulated lncRNAs in response to Decitabine and 5-Azacytidinec treatment in both TNBC models. TPT1-AS1 was the most highly induced (6.3 FC), while MALAT1 was the most highly suppressed (− 7.0 FC) lncRNA in response to DNMT inhibition.

Conclusions

Taken together, our data provides a comprehensive view of transcriptome alterations in the coding and noncoding transcriptome in TNBC in response to DNMT inhibition.