bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of internet platforms for oral health information and associated factors among adolescents from Jakarta: a cross sectional study
Authors: Maharani Diah Ayu , El Tantawi Maha , Yoseph Marsha Griselda , Rahardjo Anton
Published: January 2021

Background

The growth of the internet has increased its use to obtain health information including oral health information (OHI). This study assessed Indonesian adolescents’ use of different internet platforms to obtain OHI and factors associated with this use.

Methods

A cross-sectional study surveyed middle school students in five regions in Jakarta in 2019. Participants completed a questionnaire that assessed demographics, oral health practices (toothbrushing and dental visits), the presence of dental pain, using internet platform to obtain OHI and type of information searched for. Multinomial logistic regression was used to assess the association between using the internet for OHI (Google, Social Media (SM), both or none) and the independent factors: demographics, oral health practice, dental pain and whether participants search for causes, symptoms, prevention or treatment of oral diseases (ODs).

Results

Most of the 521 participants were female (55.7%) with mean age = 13.4 years. Almost all of them (93.7%) searched the internet for OHI through Google (40.7%) or Google with SM (36.1%). Searching for OHI over SM was significantly associated with toothbrushing (OR = 4.12, 95% CI = 1.43, 11.89) and less dental visits (OR = 0.16, 95% CI = 0.05, 0.60). Searching Google for OHI was significantly associated with looking for information about causes (OR = 3.69, 95% CI = 1.33, 10.26) and treatment (OR = 6.17, 95% CI = 2.23, 17.03) of ODs.

Conclusions

Most adolescents used Google to seek OHI. Oral health practices and types of OHI searched for differed by internet platform. Dental health professionals should consider using internet-based interventions to promote oral health to this age group.
Rationale and design of the validation of bladder health instrument for evaluation in women (VIEW) protocol
Authors:   for the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium, Lukacz Emily S. , Constantine Melissa L. , Kane Low Lisa , Lowder Jerry L. , Markland Alayne D. , Mueller Elizabeth R. , Newman Diane K. , Rickey Leslie M. , Rockwood Todd , Rudser Kyle
Published: January 2021

Background

Bladder health is an understudied state and difficult to measure due to lack of valid and reliable instruments. While condition specific questionnaires assess presence, severity and degree of bother from lower urinary tract symptoms, the absence of symptoms is insufficient to assume bladder health. This study describes the methodology used to validate a novel bladder health instrument to measure the spectrum of bladder health from very healthy to very unhealthy in population based and clinical research.

Methods

Three samples of women are being recruited: a sample from a nationally representative general population and two locally recruited clinical center samples—women with a targeted range of symptom severity and type, and a postpartum group. The general population sample includes 694 women, 18 years or older, randomly selected from a US Postal delivery sequence file. Participants are randomly assigned to electronic or paper versions of the bladder health instrument along with a battery of criterion questionnaires and a demographic survey; followed by a retest or a two-day voiding symptom diary. A total of 354 women around 7 clinical centers are being recruited across a spectrum of self-reported symptoms and randomized to mode of completion. They complete the two-day voiding symptom diary as well as a one-day frequency volume diary prior to an in-person evaluation with a standardized cough stress test, non-invasive urine flowmetry, chemical urine analysis and post void residual measurement. Independent judge ratings of bladder health are obtained by interview with a qualified health care provider. A total of 154 postpartum women recruited around 6 of the centers are completing similar assessments within 6–12 weeks postpartum. Dimensional validity will be evaluated using factor analysis and principal components analysis with varimax rotation, and internal consistency with Cronbach’s alpha. Criterion validity will be assessed using multitrait-multimethod matrix including correlations across multiple data sources and multiple types of measures.

Discussion

We aim to validate a bladder health instrument to measure the degree of bladder health within the general population and among women (including postpartum) recruited from local clinical centers.

Trial registration NCT04016298 Posted July 11, 2019 (https://www.clinicaltrials.gov/ct2/show/NCT04016298?cond=bladder+health&draw=2&rank=1).
Real-world characteristics of women with endometriosis-related pain entering a multidisciplinary endometriosis program
Authors: Agarwal Sanjay K. , Antunez-Flores Oscar , Foster Warren G. , Hermes Ashwaq , Golshan Shahrokh , Soliman Ahmed M. , Arnold Amanda , Luna Rebecca
Published: January 2021

Background

Women with endometriosis are commonly treated by their sole provider. In this single-provider model of care, women frequently report long diagnostic delays, unresolved pelvic pain, multiple laparoscopic surgeries, sequential consultations with numerous providers, and an overall dissatisfaction with care. The emergence of multidisciplinary endometriosis centers aims to reduce diagnostic delays, improve pain management, and promote patient satisfaction; however, baseline data at the time of presentation to a multidisciplinary center are lacking.

Methods

A real-world, retrospective, single-site, cross-sectional study of women with surgically confirmed and/or clinically diagnosed endometriosis generated baseline data for a planned longitudinal assessment of multidisciplinary care of endometriosis. The primary objective was to determine the proportion of patients experiencing mild, moderate, or severe pain for dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia at entry into a multidisciplinary endometriosis clinic. Also explored were relationships between pain scores and clinical endpoints obtained from electronic medical records.

Results

More than half (59%) of the study participants (n = 638) reported experiencing pelvic pain for ≥ 5 years. Pain intensity was highest for patients reporting dysmenorrhea, followed by NMPP, and dyspareunia. Significant correlations were observed between total pelvic pain and patient age (r = –0.22, p < 0.001, n = 506) and number of previous healthcare providers (r = 0.16, p = 0.006, n = 292); number of previous providers and duration of pain (r = 0.21, p = < 0.0001, n = 279); and duration of pain and years since diagnosis (r = 0.60, p < 0.001, n = 302). Mean pain scores differed significantly by age group for dysmenorrhea (p < 0.001), NMPP (p = 0.005), and total pelvic pain (p < 0.001), but not for dyspareunia (p = 0.06), with the highest mean pain scores reported among those < 30 years of age.

Conclusion

These real-world data indicate that in the single-provider model of care, unresolved pelvic pain is common among women with endometriosis. Alternative care models, including a multidisciplinary approach, need to be evaluated for improvements in clinical outcomes. These data also highlight the importance of addressing NMPP, which may be particularly troublesome for patients.
Understanding the key processes of excellence as a prerequisite to establishing academic centres of excellence in Africa
Authors: Fekadu Abebaw , Oppenheim Claire , Manyazewal Tsegahun , Nislow Corey , Woldeamanuel Yimtubezinash , Hailu Asrat , Belete Anteneh , Wondimagegn Dawit , Hanlon Charlotte , Gebremariam Tsige , Collins Asha , Larson Christopher J. , Gebreyes Wondwossen , Aklilu Eleni , Muula Adamson S. , Mugus Sabina , Caffrey Conor R. , Giday Mirutse , Yimer Getnet , Davey Gail , Medhin Girmay , Makonnen Eyasu
Published: January 2021

Background

Africa’s economic transformation relies on a radical transformation of its higher education institutions. The establishment of regional higher education Centres of Excellence (CoE) across Africa through a World Bank support aims to stimulate the needed transformation in education and research. However,excellenceis a vague, and often indiscriminately used concept in academic circles. More importantly, the manner in which aspiring institutions can achieve academic excellence is described inadequately. The main objective of this paper is to describe the core processes of excellence as a prerequisite to establishing academic CoE in Africa.

Methods

The paper relies on our collaborative discussions and real-world insight into the pursuit of academic excellence, a narrative review using Pubmed search for a contextual understanding of CoEs in Africa supplemented by a Google search for definitions of CoEs in academic contexts.

Results

We identified three key, synergistic processes of excellence central to institutionalizing academic CoEs: participatory leadership, knowledge management, and inter-disciplinary collaboration. (1) Participatory leadership encourages innovations to originate from the different parts of the organization, and facilitates ownership as well as a culture of excellence. (2) Centers of Excellence arefuture-orientedin that they are constantly seeking to achieve best practices, informed by the most up-to-date and cutting-edge research and information available. As such, the process by which centres facilitate the flow of knowledge within and outside the organization, or knowledge management, is critical to their success. (3) Such centres also rely on expertise from different disciplines and ‘engaged’ scholarship. This multidisciplinarity leads to improved research productivity and enhances the production of problem-solving innovations.

Conclusion

Participatory leadership, knowledge management, and inter-disciplinary collaborations are prerequisites to establishing academic CoEs in Africa. Future studies need to extend our findings to understand the processes key to productivity, competitiveness, institutionalization, and sustainability of academic CoEs in Africa.
Evaluating pharmacy students’ knowledge and skills in reproductive, maternal, new-born and child health care at a South African university
Authors: Egieyeh Elizabeth , van Huyssteen Mea , Coetzee Renier , Bheekie Angeni
Published: January 2021

Background

Maternal and child mortality is a global concern and one of South Africa’s quadruple burdens of disease. As easily accessible frontline healthcare workers, pharmacists play an important role in the continuum of maternal and child health (MCH) care according to recommendations by international health regulatory bodies. Pharmacy schools are obliged to train pharmacy students to meet the priority health needs of the population so that graduates are ‘fit for purpose’. The baseline study aimed to evaluate the knowledge and skills of 2017 final year pharmacy students who were exposed to a fragmented MCH care curriculum at a university in South Africa to inform curriculum review.

Methods

A descriptive, quantitative, non-randomized study was conducted among final year pharmacy students using a self-administered structured questionnaire. The questionnaire was designed in sections to assess participants’ knowledge of reproductive and sexual health (RSH), maternal and antenatal care (MAC), neonatal and child care (NCC) and skills related to infant growth assessment procedures. Data was analysed descriptively using frequencies and percentages. A score of 50% in each section of the questionnaire indicated a pass. Participants assessed their exposure to MCH topics in the curriculum.

Results

Of the 89 available students, 61% consented to participate in the study. The average scores attained for each section were; 62.4% for RSH, 54.5% for MAC, 50.4% for NCC and 25.3% for infant growth assessment. The pass rate was 78% for RSH, 56% for MAC, 57% for NCC, and 19% for infant growth assessment. About 13% of the participants passed all the knowledge and the skills sections. Age, gender, being a parent or doing locums did not have any influence on participants’ performance. Participants reported that they had more on-campus curriculum content exposure to RSH compared to other MCH care topics.

Conclusion

Final year pharmacy students showed adequate knowledge of RSH with adequate curriculum exposure. Average knowledge of MAC, NCC and poor skills in infant growth assessment which corresponded to curriculum exposure was observed. The results suggest the need for improvement in the current curriculum in the affected areas to adequately equip students to render desirable services.
Applying probability calibration to ensemble methods to predict 2-year mortality in patients with DLBCL
Authors: Fan Shuanglong , Zhao Zhiqiang , Yu Hongmei , Wang Lei , Zheng Chuchu , Huang Xueqian , Yang Zhenhuan , Xing Meng , Lu Qing , Luo Yanhong
Published: January 2021

Background

Under the influences of chemotherapy regimens, clinical staging, immunologic expressions and other factors, the survival rates of patients with diffuse large B-cell lymphoma (DLBCL) are different. The accurate prediction of mortality hazards is key to precision medicine, which can help clinicians make optimal therapeutic decisions to extend the survival times of individual patients with DLBCL. Thus, we have developed a predictive model to predict the mortality hazard of DLBCL patients within 2 years of treatment.

Methods

We evaluated 406 patients with DLBCL and collected 17 variables from each patient. The predictive variables were selected by the Cox model, the logistic model and the random forest algorithm. Five classifiers were chosen as the base models for ensemble learning: the naïve Bayes, logistic regression, random forest, support vector machine and feedforward neural network models. We first calibrated the biased outputs from the five base models by using probability calibration methods (including shape-restricted polynomial regression, Platt scaling and isotonic regression). Then, we aggregated the outputs from the various base models to predict the 2-year mortality of DLBCL patients by using three strategies (stacking, simple averaging and weighted averaging). Finally, we assessed model performance over 300 hold-out tests.

Results

Gender, stage, IPI, KPS and rituximab were significant factors for predicting the deaths of DLBCL patients within 2 years of treatment. The stacking model that first calibrated the base model by shape-restricted polynomial regression performed best (AUC = 0.820, ECE = 8.983, MCE = 21.265) in all methods. In contrast, the performance of the stacking model without undergoing probability calibration is inferior (AUC = 0.806, ECE = 9.866, MCE = 24.850). In the simple averaging model and weighted averaging model, the prediction error of the ensemble model also decreased with probability calibration.

Conclusions

Among all the methods compared, the proposed model has the lowest prediction error when predicting the 2-year mortality of DLBCL patients. These promising results may indicate that our modeling strategy of applying probability calibration to ensemble learning is successful.
Clinical learning environment of nursing and midwifery students in Ghana
Authors: Ziba Florence Assibi , Yakong Vida Nyagre , Ali Zakari
Published: January 2021

Background

Data on student experience of the clinical learning environment in Ghana are scarce. We therefore aimed to assess students’ evaluation of the clinical learning environment and the factors that influence their learning experience.

Methods

This was a cross-sectional survey of 225 undergraduate nursing and midwifery students. We used the Clinical Learning Environment and Supervision + Nurse Teacher (CLES +T) evaluation scale to assess students’ experience of their clinical placement. The association between student demographic characteristics and clinical placement experience was determined using t-test or ANOVA.

Results

Most of the sampled students were Nurses (67%) and in the third year of training (81%). More students received supervision from a nurse (57%) during clinical placement and team supervision (67%) was the most common during clinical placement. Nursing students were more likely to rate their clinical experience better than midwifery students (p=0.002). Students who had increased contact with private supervisors were also more likely to rate their experience higher (p=0.002). Clinical experience was also rated higher by students who received successful supervision compared to those who had unsuccessful or team supervision (p=0.001).

Conclusion

Team supervision is high in health facilities where students undertake clinical placement in Ghana. Frequent contact with private supervisor and successful supervision are associated with better rating of clinical experience among Ghanaian undergraduate nursing and midwifery students.
Evidence-based smoking cessation treatment: a comparison by healthcare system
Authors: Lewis Jennifer A. , Senft Nicole , Chen Heidi , Weaver Kathryn E. , Spalluto Lucy B. , Sandler Kim L. , Horn Leora , Massion Pierre P. , Dittus Robert S. , Roumie Christianne L. , Tindle Hilary A.
Published: January 2021

Background

A systems-level approach to smoking cessation treatment may optimize healthcare provider adherence to guidelines. Institutions such as the Veterans Health Administration (VHA) are unique in their systematic approach, but comparisons of provider behavior in different healthcare systems are limited.

Methods

We surveyed general medicine providers and specialists in a large academic health center (AHC) and its affiliated VHA in the Mid-South in 2017 to determine the cross-sectional association of healthcare system in which the provider practiced (exposure: AHC versus VHA) with self-reported provision of evidence-based smoking cessation treatment (delivery of counseling plus smoking cessation medication or referral) at least once in the past 12 months (composite outcome). Multivariable logistic regression with adjustment for specialty was performed in 2017–2019.

Results

Of 625 healthcare providers surveyed, 407 (65%) responded, and 366 (59%) were analyzed. Most respondents practiced at the AHC (273[75%] vs VHA 93[25%]) and were general internists (215[59%]); pulmonologists (39[11%]); hematologists/oncologists (69[19%]); and gynecologists (43[12%]). Most respondents (328[90%]) reported the primary outcome. The adjusted odds of evidence-based smoking cessation treatment were higher among VHA vs. AHC healthcare providers (aOR = 4.3; 95% CI 1.3–14.4;p = .02). Health systems differed by provision of individual treatment components, including smoking cessation medication use (98% VHA vs. 90% AHC,p = 0.02) and referral to smoking cessation services (91% VHA vs. 65% AHCp = 0.001).

Conclusions

VHA healthcare providers were significantly more likely to provide evidence-based smoking cessation treatment compared to AHC healthcare providers. Healthcare systems’ prioritization of and investment in smoking cessation treatment is critical to improving providers’ adherence to guidelines.
Patients and relatives as auditors of safe practices in oncology and hematology day hospitals
Authors: Rodrigo Rincón Isabel , Irigoyen Aristorena Isabel , Tirapu León Belén , Zaballos Barcala Nicolás , Sarobe Carricas Maite , Lobo Palanco Joaquín , Antelo Caamaño María Luisa , Martin Vizcaíno Marta Patricia , Burnett Susan
Published: January 2021

Background

When there is a gap in professionals’ adherence to safe practices during cancer treatment, the consequences can be serious. Identifying these gaps in order to enable improvements in patient safety can be a challenge. This study aimed to assess if cancer patients and their relatives can be given the skills to audit reliably four safe practices, and to explore whether they are willing to play this new role.

Methods

We recruited 136 participants in 2018, from the oncology and haematology day hospital of a tertiary hospital in Spain. Patient identification, hand hygiene, blood or chemotherapy identification, and side effects related to transfusion and chemotherapy, were the safe practices selected for evaluation.

The study comprised two parts: an interventional educational program and a cross-sectional design to collect data and assess to what degree participants are able and willing to be auditors depending on their characteristics using multivariate logistic regression models. A participant’s auditing skill were assessed pre and post the educational intervention.

Results

The model was seeking predictors of being a good auditor. 63 participants (46.3%) were classified as good auditors after the training. To have younger age, higher educational level and to have had an experience of an adverse event were associated with a higher probability of being a good auditor. Additionally, 106 (77.9%) participants said that they would like to audit anonymously the professionals’ compliance of at least three of four safe practices. The willingness to audit safe practices differed depending on the safe practice but these differences did not reach statistical significance.

Conclusions

The data gathered by patients and relatives acting as auditors can provide healthcare organizations with valuable information about safety and quality of care that is not accessible otherwise. This new role provides an innovative way to engage patients and their families’ in healthcare safety where other methods have not had success. The paper sets out the methods that healthcare organizations need to undertake to enrol and train patients and relatives in an auditor role.
To do or not to do – a survey study on factors associated with participating in the Danish screening program for colorectal cancer
Authors: Nielsen Jesper Bo , Berg-Beckhoff Gabriele , Leppin Anja
Published: January 2021

Background

Screening programs for colorectal cancer (CRC) exist in many countries, and with varying participation rates. The present study aimed at identifying socio-demographic factors for accepting a cost-free screening offer for CRC in Denmark, and to study if more people would accept the screening offer if the present fecal test was replaced by a blood test.

Methods

We used a cross-sectional survey design based on a representative group of 6807 Danish citizens aged 50–80 years returning a fully answered web-based questionnaire with socio-demographic data added from national registries. Data were analyzed in STATA and based on bivariate analyses followed by regression models.

Results

Danes in general have a high level of lifetime participation (+ 80%) in the national CRC screening program. The results of the stepwise logistic regression model to predict CRC screening participation demonstrated that female gender, higher age, higher income, and moderate alcohol intake were positively associated with screening participation, whereas a negative association was observed for higher educational attainment, obesity, being a smoker, and higher willingness to take health risks. Of the 1026 respondents not accepting the screening offer, 61% were willing to reconsider their initial negative response if the fecal sampling procedure were replaced by blood sampling.

Conclusion

The CRC screening program intends to include the entire population within a certain at-risk age group. However, individual factors (e.g. sex, age obesity, smoking, risk aversity) appear to significantly affect willingness to participate in the screening program. From a preventive perspective, our findings indicate the need for a more targeted approach trying to reach these groups.
Influence of participation in a quality improvement collaborative on staff perceptions of organizational sustainability
Authors: Ford James H. , Gilson Aaron
Published: January 2021

Background

Sustainability capacity (SC), which is an organization’s ability to implement and maintain change, is influenced by internal attributes, environmental contextual influencers, and intervention attributes. Temporal changes in staff SC perceptions, as well as the influence of quality improvement collaborative (QIC) participation, has generally not been explored. This project addresses this gap, measuring staff SC perceptions at four time points (baseline and every 9 months) for clinics participating in an intervention – the Network for the Improvement of Addiction Treatment QIC initiative (called NIATx200).

Methods

A mixed linear model repeated measures analysis was applied to matched staff members (n = 908, representing 2329 total cases) across the evaluation timeframe. Three separate statistical models assessed potential predictors of SC perceptions: Time (Models I-III); NIATx200 intervention, staff job function, and tenure (Models II &III); and NIATx200 participation hours and four organizational variables (Model III).

Results

For Model I, staff perceptions of total SC increased throughout most of the study (t1,4 = − 6.74, p < .0001; t2,4 = − 3.100, p < .036; t3,4 = − 0.23, p = ns). Model II did not change Model I’s overall Time effect, but combined NIATx200 services (t = − 2.23, p = .026), staff job function (t = − 3.27, p = .001), and organizational administrators (t = − 3.50, p = .001) were also significantly associated with greater perceptions of total SC. Inclusion of additional variables in Model III demonstrated the importance of a higher participation level (t = − 3.09, p < .002) and being in a free-standing clinic (t = − 2.06, p < .04) on staff perceptions of total SC.

Conclusion

Although staff exposure to sustainability principals was minimal in NIATx200, staff perceptions about their organization’s SC significantly differed over time. However, an organization’s participation level in a QIC became the principal predictor of staff SC perceptions, regardless of other factors’ influence. Given these findings, it is possible to develop and introduce specific sustainability content within the structure of a QIC to assess the impact on staff SC perceptions over time and the sustainment of organizational change.

Trial registration

ClinicalTrials.gov, NCT00934141. Registered July 6, 2009. Retrospectively registered.
Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes
Authors: Wakasugi Satomi , Mita Tomoya , Katakami Naoto , Okada Yosuke , Yoshii Hidenori , Osonoi Takeshi , Kuribayashi Nobuichi , Taneda Yoshinobu , Kojima Yuichi , Gosho Masahiko , Shimomura Iichiro , Watada Hirotaka
Published: January 2021

Background

Previous studies have suggested that high mean glucose levels and glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear.

Methods

This exploratory cross-sectional study used baseline data from an ongoing prospective, multicenter, observational study with 5 years of follow-up. Study participants included 445 outpatients with type 2 diabetes and no history of apparent cardiovascular disease who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were analyzed using multivariate regression models.

Results

In a linear regression model, all CGM-derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM-derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥ 1800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c.

Conclusions

Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.
The additive effects of kidney dysfunction on left ventricular function and strain in type 2 diabetes mellitus patients verified by cardiac magnetic resonance imaging
Authors: Zhang Yi , Wang Jin , Ren Yan , Yan Wei-feng , Jiang Li , Li Yuan , Yang Zhi-gang
Published: January 2021

Background

Patients with type 2 diabetes mellitus (T2DM) are susceptible to coexisted with chronic kidney disease (CKD), which may increase cardiovascular mortality in these patients. The present study aimed to verify whether CKD aggravates the deterioration of left ventricular (LV) myocardial strain in T2DM patients and to explore the risk factors associated with LV strain.

Materials and methods

In total, 105 T2DM patients and 52 healthy individuals were included and underwent cardiac magnetic resonance examination. Patients were divided into the following two groups: T2DM with CKD (n = 33) and T2DM without CKD (n = 72). The baseline clinical and biochemical indices were obtained from hospital records before the cardiac magnetic resonance scan. Cine sequences, including long-axis views (2-chamber and 4-chamber) and short-axis views, were acquired. LV function and global strain parameters were measured based on cine sequences and compared among three groups. Pearson’s analysis was performed to investigate the correlation between LV strain parameters and clinical indices. Multiple linear regression analysis was used to identify the independent indicators of LV strain.

Results

Compared with normal controls, T2DM patients without CKD had a significantly decreased magnitude of peak strain (PS; radial), peak systolic strain rate (radial), and peak diastolic strain rate (radial and circumferential) (all P < 0.05). Furthermore, T2DM patients with CKD displayed markedly lower magnitudes of PS (radial, circumferential, and longitudinal) and peak diastolic strain rate (circumferential and longitudinal) than both normal controls and T2DM patients without CKD (all P < 0.05). The eGFR was positively associated with the magnitude of PS (R = radial, 0.392; circumferential, 0.436; longitudinal, 0.556), while uric acid was negatively associated with the magnitude of PS (R = radial, − 0.361; circumferential, − 0.391; longitudinal, − 0.460) (all P < 0.001). Multivariable linear regression indicated that the magnitude of PS was independently associated with eGFR (β = radial, 0.314; circumferential, 0.292; longitudinal, 0.500) and uric acid (β = radial, − 0.239; circumferential, − 0.211; longitudinal, − 0.238) (all P < 0.05).

Conclusions

Kidney dysfunction may aggravate the deterioration of LV strain in T2DM patients. LV strain is positively associated with the estimated glomerular filtration rate and negatively associated with uric acid, which may be independent risk factors for predicting reduction of LV strain.
Relationship between insulin resistance, coronary plaque, and clinical outcomes in patients with acute coronary syndromes: an analysis from the PROSPECT study
Authors: Farhan Serdar , Redfors Björn , Maehara Akiko , McAndrew Thomas , Ben-Yehuda Ori , De Bruyne Bernard , Mehran Roxana , Vogel Birgit , Giustino Gennaro , Serruys Patrick W. , Mintz Gary S. , Stone Gregg W.
Published: January 2021

Background

We investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study.

Methods

Patients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2 < HOMA-IR < 5), or diabetic-IR (DIR; HOMA-IR ≥ 5). Coronary plaque characteristics were investigated by intravascular ultrasound. The primary endpoint was major adverse cardiac events (MACE); a composite of cardiac death, cardiac arrest, myocardial infarction, and rehospitalization for unstable/progressive angina.

Results

Among non-diabetic patients, 109 patients (21.5%) were categorized as LIR, and 65 patients (12.8%) as DIR. Patients with DIR or DM had significantly higher rates of echolucent plaque compared with LIR and IS. In addition, DIR and DM were independently associated with increased risk of MACE compared with IS (adjusted hazard ratio [aHR] 2.29, 95% confidence interval [CI] 1.22–4.29, p = 0.01 and aHR 2.12, 95% CI 1.19–3.75, p = 0.009, respectively).

Conclusions

IR is common among patients with ACS. DM and advanced but not early stages of IR are independently associated with increased risk of adverse cardiovascular events.

Trial Registration ClinicalTrials.gov Identifier: NCT00180466.
Improved production of germacrene A, a direct precursor of ß-elemene, in engineered Saccharomyces cerevisiae by expressing a cyanobacterial germacrene A synthase
Authors: Zhang Weixin , Guo Junqi , Wang Zheng , Li Yanwei , Meng Xiangfeng , Shen Yu , Liu Weifeng
Published: January 2021

Background

The sesquiterpene germacrene A is a direct precursor of ß-elemene that is a major component of the Chinese medicinal herb Curcuma wenyujin with prominent antitumor activity. The microbial platform for germacrene A production was previously established in Saccharomyces cerevisiae using the germacrene A synthase (LTC2) of Lactuca sativa.

Results

We evaluated the performance of LTC2 (LsGAS) as well as nine other identified or putative germacrene A synthases from different sources for the production of germacrene A. AvGAS, a synthase of Anabaena variabilis, was found to be the most efficient in germacrene A production in yeast. AvGAS expression alone in S. cerevisiae CEN.PK2-1D already resulted in a substantial production of germacrene A while LTC2 expression did not. Further metabolic engineering the yeast using known strategies including overexpression of tHMGR1 and repression of squalene synthesis pathway led to an 11-fold increase in germacrene A production. Site-directed mutagenesis of AvGAS revealed that while changes of several residues located within the active site cavity severely compromised germacrene A production, substitution of Phe23 located on the lateral surface with tryptophan or valine led to a 35.2% and 21.8% increase in germacrene A production, respectively. Finally, the highest production titer of germacrene A reached 309.8 mg/L in shake-flask batch culture.

Conclusions

Our study highlights the potential of applying bacterial sesquiterpene synthases with improved performance by mutagenesis engineering in producing germacrene A.
Effective production of human growth factors in Escherichia coli by fusing with small protein 6HFh8
Authors: Kim Young Su , Lee Hye-Jeong , Han Man-ho , Yoon Nam-kyung , Kim Yeu-chun , Ahn Jungoh
Published: January 2021

Background

Growth factors (GFs) are signaling proteins that affect cellular processes such as growth, proliferation, and differentiation. GFs are used as cosmeceuticals, exerting anti-wrinkle, anti-aging, and whitening effects, and also as pharmaceuticals to treat wounds, growth failure, and oral mucositis. However, in mammalian and bacterial cells, low productivity and expression in inclusion bodies, respectively, of GFs does not satisfy the consumer demand. Here, we aimed to develop a bacterial expression system that produces high yields of soluble GFs that can be purified in their native forms.

Results

We present Fh8, an 8-kDa peptide from Fasciola hepatica with an N-terminal hexa-histidine (6HFh8), as a fusion partner for enhanced human GF production in recombinant Escherichia coli. The fusion partner harboring a tobacco etch virus (TEV) protease cleavage site was fused to the N-terminus of 10 human GFs: acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), epidermal growth factor (EGF), human growth hormone (hGH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor 165 (VEGF165), keratinocyte growth factor 1 (KGF-1), placental growth factor (PGF), stem cell factor (SCF), and tissue inhibitor of metalloproteinase 1 (TIMP-1). The fusion proteins were expressed in E. coli under the control of T7 promoter at three temperatures (25 °C, 30 °C, and 37 °C). All individual fusion proteins, except for SCF and TIMP-1, were successfully overexpressed in cytoplasmic soluble form at more than one temperature. Further, the original aFGF, IGF-1, EGF, and VEGF165 proteins were cleaved from the fusion partner by TEV protease. Five-liter fed-batch fermentation approaches for the 6HFh8-aFGF (lacking disulfide bonds) and 6HFh8-VEGF165 (a cysteine-rich protein) were devised to obtain the target protein at concentrations of 9.7 g/l and 3.4 g/l, respectively. The two GFs were successfully highly purified (> 99% purity). Furthermore, they exerted similar cell proliferative effects as those of their commercial equivalents.

Conclusions

We demonstrated that 6HFh8-GF fusion proteins could be overexpressed on a g/l scale in the cytoplasm of E. coli, with the GFs subsequently highly purified and maintaining their biological activity. Hence, the small protein 6HFh8 can be used for efficient mass-production of various GFs.
CircNEIL3 promotes cervical cancer cell proliferation by adsorbing miR-137 and upregulating KLF12
Authors: Chen Yuan , Geng Yiting , Huang Junchao , Xi Dan , Xu Guoping , Gu Wendong , Shao Yingjie
Published: January 2021

Background

CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear.

Methods

This study collected GSE113696 data from the GEO database to search for differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to detect the expression level of circNEIL3 in cervical cancer cells and tissues. Then, functional experiments in vitro and in vivo were performed to evaluate the effects of circNEIL3 in cervical cancer.

Results

CircNEIL3 was highly expressed in cervical cancer. In vivo and in vitro experiments verified that circNEIL3 enhanced the proliferation capacity of cervical cancer cells. RNA immunoprecipitation, luciferase reporter assay, pull-down assay, and fluorescent in situ hybridization confirmed the interaction between circNEIL3 and miR-137 in cervical cancer. A luciferase reporter assay showed that circNEIL3 adsorbed miR-137 and upregulated KLF12 to regulate the proliferation of cervical cancer cells.

Conclusions

CircNEIL3 is an oncogene in cervical cancer and might serve as a ceRNA that competitively binds to miR-137, thereby indirectly upregulating the expression of KLF12 and promoting the proliferation of cervical cancer cells.
Catastrophic health expenditure among single empty-nest elderly with multimorbidity in rural Shandong, China: the effect of co-occurrence of frailty
Authors: Jing Zhengyue , Li Jie , Fu Pei Pei , Wang Yi , Yuan Yemin , Zhao Dan , Hao Wenting , Yu Caiting , Zhou Chengchao
Published: January 2021

Background

Previous studies have indicated that older adults with multimorbidity had higher risk of incurring catastrophic health expenditure (CHE). However, the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity remains unclear. This study aims to explore the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity, and whether this effect is moderated by economic status.

Methods

A cross-sectional household survey of the older adults in 2019 in Shandong province, China. A total of 606 single empty-nest elderly aged 60 years or older were included in this study. CHE was defined as the out-of-pocket payments for health care that equals or exceeds 40% of the household’ s capacity to pay. Logistic regression models are employed to examine the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity. The interaction term is introduced to explore the economic status difference in this effect.

Results

The CHE incidence for single empty-nest elderly with multimorbidity alone is 64.2%, and the co-occurrence of frailty results in an increase by almost 1.3 times (84.0%) in CHE incidence among single empty-nest elderly with multimorbidity. The co-occurrence of frailty increases the risk of incurring CHE among the single empty-nest elderly with multimorbidity, with the odds of incurring CHE increased by 3.19 times (OR = 3.19; P = 0.005). Furthermore, the interaction analysis shows that the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity still exist in lower economic status groups (OR = 4.64; P = 0.027), but not in higher economic status (OR = 2.76; P = 0.062).

Conclusions

This study demonstrates that there is a positive effect of co-occurrence of frailty on the CHE among the single empty-nest elderly with multimorbidity, and this effect varies by economic status. The health policy-makers should reorganize the healthcare system to make it pro-poor, so as to meet the multiple medical demand and reduce the potential economic burden and inequalities of older adults.
Exploring equity and inclusion in Malawi’s National Disability Mainstreaming Strategy and Implementation Plan
Authors: Ebuenyi Ikenna D. , Smith Emma M. , Munthali Alister , Msowoya Steven W. , Kafumba Juba , Jamali Monica Z. , MacLachlan Malcolm
Published: January 2021

Background

Equity and inclusion are important principles in policy development and implementation. The aim of this study is to explore the extent to which equity and inclusion were considered in the development of Malawi’s National Disability Mainstreaming Strategy and Implementation Plan.

Methods

We applied an analytical methodology to review the Malawi’s National Disability Mainstreaming Strategy and Implementation Plan using the EquIPP (Equity and Inclusion in Policy Processes) tool. The EquIPP tool assesses 17 Key Actions to explore the extent of equity and inclusion.

Results

The development of the Malawi National Disability Mainstreaming Strategy and Implementation Plan was informed by a desire to promote the rights, opportunities and wellbeing of persons with disability in Malawi. The majority (58%) of the Key Actions received a rating of three, indicating evidence of clear, but incomplete or only partial engagement of persons with disabilities in the policy process. Three (18%) of the Key Actions received a rating of four indicating that all reasonable steps to engage in the policy development process were observed. Four (23%) of the Key Actions received a score five indicating a reference to Key Action in the core documents in the policy development process.

Conclusions

The development of disability policies and associated implementation strategies requires equitable and inclusive processes that consider input from all stakeholders especially those whose wellbeing depend on such policies. It is pivotal for government and organisations in the process of policy or strategy development and implementation, to involve stakeholders in a virtuous process of co-production – co-implementation – co-evaluation, which may strengthen both the sense of inclusion and the effectiveness of the policy life-cycle.
Metabolomic signatures of the long-term exposure to air pollution and temperature
Authors: Nassan Feiby L. , Kelly Rachel S. , Kosheleva Anna , Koutrakis Petros , Vokonas Pantel S. , Lasky-Su Jessica A. , Schwartz Joel D.
Published: January 2021

Background

Long-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood.

Objectives

We aimed to determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature.

Methods

We quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM2.5, NO2, O3, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures.

Results

Men (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m2. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM2.5, 15 metabolites with NO2, and 6 metabolites with temperature) while no metabolites were associated with O3. One out of five ICA factors (factor 2) was significantly associated with PM2.5. We identified eight perturbed metabolic pathways with long-term exposure to PM2.5and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair.

Conclusions

Using a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM2.5, NO2and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.
Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA
Authors: Zhang Long , Mu Chaofeng , Zhang Tinghong , Yang Dejun , Wang Chenou , Chen Qiong , Tang Lin , Fan Luhui , Liu Cong , Shen Jianliang , Li Huaqiong
Published: January 2021

Background

To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery.

Results

Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo.

Conclusions

The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.