bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the effects of text messaging and mobile social networking on physical activity and anthropometric indices of middle-aged women: a randomized controlled trial
Authors: Ansari Kousar , Afshari Poorandokht , Abedi Parvin , Haghighizadeh Mohammadhossein
Published: January 2022

Background

Physical inactivity is a global health problem which is more prevalent among women. Among different age groups, middle-aged women are more vulnerable to physical inactivity as one of consequences of menopause. This study aimed to compare the effect of text messaging and that of mobile social networking on the improvement of physical activity and anthropometric indices of middle-aged women in Iran.

Methods

This was a randomized controlled trial in which 110 overweight or obese women who were physically inactive were recruited and allocated into two groups of text messaging (n = 55) or mobile social networking (n = 55). Women in both groups received information regarding the necessity, benefits, and barriers of physical activity and how to overcome these barriers for 12 weeks. The International Physical Activity Questionnaire (IPAQ), and a demographic questionnaire were used to collect data. Anthropometric indices including weight, height, waist circumference, hip circumference, waist/hip ratio, and body fat percentage were measured at baseline, as well as 4, 8, and 12 weeks after intervention. Data were analyzed using independent t-test, Chi-square, and repeated measure test.

Results

In the mobile social networking group, most women had moderate physical activity after 12 weeks (P < 0.05). The mean physical activity and energy expenditure were significantly higher in the mobile social group than those in the text messaging. In the 12th week of intervention, there was a significant reduction in the weight and BMI of the participants in the mobile social networking group compared to the text messaging group (P < 0.05). The waist and hip circumferences of women in the mobile social networking group reduced significantly after 12 weeks of intervention in comparison to the text messaging group (P = 0.001). The two groups did not show any significant difference regarding waist/hip ratio. While the body fat percentage was reduced in the mobile social networking group in the 4th, 8th, and 12th week of intervention, the differences between the two groups was not significant.

Conclusion

Both text messaging and mobile social networking were effective in promoting physical activity and reducing anthropometric indices except for waist/hip ratio and body fat percentages, but the effect of mobile social networking was more pronounced. Thus, mobile social networking is recommended for promoting physical activity among middle-aged women.
Challenges of and possible solutions for living with endometriosis: a qualitative study
Authors: Márki Gabriella , Vásárhelyi Dorottya , Rigó Adrien , Kaló Zsuzsa , Ács Nándor , Bokor Attila
Published: January 2022

Background

Endometriosis as a chronic gynecological disease has several negative effects on women’s life, thereby placing a huge burden on the patients and the health system. The negative impact of living with endometriosis (impaired quality of life, diverse medical experiences) is detailed in the literature, however, we know less about patients’ self-management, social support, the meaning of life with a chronic disease, and the needs of patients. To implement a proper multidisciplinary approach in practice, we need to have a comprehensive view of the complexity of endometriosis patients’ life and disease history.

Methods

Four focus group discussions were conducted between October 2014 and November 2015 by a team consisting of medical and psychological specialists. 21 women (age: 31.57; SD = 4.45) with surgical and histological confirmation of endometriosis were included in the study. Discussions were audiotaped and transcribed verbatim, and a 62,051-word corpus was analyzed using content analysis.

Results

Four main themes emerged from the analysis: (1) the impact of endometriosis on quality of life, (2) medical experiences, (3) complementary and alternative treatments, and (4) different coping strategies in disease management. All themes were interrelated and highly affected by a lack of information and uncertainty caused by endometriosis. A supporting doctor-patient relationship, active coping, and social support were identified as advantages over difficulties. Finding the positive meaning of life after accepting endometriosis increased the possibility of posttraumatic growth. Furthermore, women’s needs were identified at all levels of the ecological approach to health promotion.

Conclusions

Our results highlight the need for multidisciplinary healthcare programs and interventions to find solutions to the difficulties of women with endometriosis. To achieve this goal, a collaboration of professionals, psychologists, and support organizations is needed in the near future.
Retrieval practice and spaced learning: preventing loss of knowledge in Dutch medical sciences students in an ecologically valid setting
Authors: Donker Stijn C. M. , Vorstenbosch Marc A. T. M. , Gerhardus Martin J. T. , Thijssen Dick H. J.
Published: January 2022

Introduction

Knowledge, once acquired, degrades over time. Exams that contain questions related to previously acquired knowledge (‘retrieval practice questions’) may promote retrieval practice and spaced learning, and subsequently prevent knowledge loss. To investigate this hypothesis, we compare the score of retrieval practice questions to regular questions in exams of a two-year (bio)medical study program.

Methods

The two-year “Mechanisms of Health and Disease”-program for biomedical sciences and medical students in Nijmegen (the Netherlands) contains 14 spaced exams of 80 questions each. The percentages of correct-, false-, and non-answers were compared between regular questions and retrieval practice questions. Using Pearson correlations between question scores and exam scores (RiT-values), the impact of retrieval practice questions on the internal consistency of exams was determined. Mixed model analyses determined changes in outcomes across time.

Results

Analysis of 2006 regular questions and 1728 retrieval practice questions revealed a significantly higher percentage of correct and false answers, and a significantly lower percentage of non-answers, in retrieval practice questions versus regular questions (all P < 0.05). Scores did not change across time. RiT-values were slightly lower in retrieval practice questions, with a small inverse trend across time.

Conclusion

Our data indicate preservation of knowledge, possibly related to retrieval practice and/or spaced learning. Although the RiT-values of retrieval practice questions were slightly lower than those of regular questions, the discriminative capacity was well within acceptable range. These data highlight the potency of retrieval practice questions to prevent knowledge decrement, without altering exam quality.
Symbiotic relationships through longitudinal integrated clerkships in general practice
Authors: O’Regan Andrew , O’Doherty Jane , Green James , Hyde Sarah
Published: January 2022

Background

Longitudinal integrated clerkships (LICs) are an innovation in medical education that are often successfully implemented in general practice contexts. The aim of this study was to explore the experiences and perspectives of general practitioner (GP)-tutors on the impact of LICs on their practices, patients and the wider community.

Methods

GPs affiliated with the University of Limerick School of Medicine- LIC were invited to participate in in-depth interviews. Semi-structured interviews were conducted in person and over the phone and were based on a topic guide. The guide and approach to analysis were informed by symbiosis in medical education as a conceptual lens. Data were recorded, transcribed and analysed using an inductive thematic approach.

Results

Twenty-two GPs participated. Two main themes were identified from interviews: ‘roles and relationships’ and ‘patient-centred physicians’. Five subthemes were identified which were: ‘GP-role model’, ‘community of learning’, and ‘mentorship’, ‘student doctors’ and ‘serving the community’.

Conclusion

LICs have the potential to develop more patient-centred future doctors, who have a greater understanding of how medicine is practised in the community. The LIC model appears to have a positive impact on all stakeholders but their success hinges on having adequate support for GPs and resourcing for the practices.
Perceptions of oncology as a career choice among the early career doctors in Pakistan
Authors: Aemaz Ur Rehman Muhammad , Farooq Hareem , Ebaad Ur Rehman Muhammad , Ali Muhammad Mohsin , Zafar Amjad , Khokhar Muhammad Abbas
Published: January 2022

Background

Lack of oncologists is a growing global concern. With the rise in cancer burden across the world, the supply–demand mismatch of the oncology workforce is projected to increase. Furthermore, oncology is a low-ranked field of choice among medical students, and without understanding the perceptions and concerns of early-career doctors regarding oncology, any investments made in cancer care will be futile. This study aims to determine the opinions of young doctors and the factors most affecting their preferences in order to devise focused strategies to attract more doctors into oncology.

Methods

A cross-sectional study was conducted on 300 early-career doctors across various public and private hospitals in Pakistan, from March to November 2019. A close-ended, self-administered questionnaire was used to assess their opinions in terms of the workplace environment, scope, and the emotional and financial aspects of oncology. Data was analyzed using SPSS version 23 and the influence (positive or negative) of the perceptions on the choice of oncology as a career was determined by binary logistic regression analysis.

Results

Almost three-quarters of the participants did not want a career in oncology. The top positive perceptions about oncology in descending order were: progressive field, gender-neutral, stable working hours, financially healthy, and work-family balance. Top negative perceptions were: lack of oncologic facilities in hospitals, radiation exposure, need for private practice, poor patient prognosis, high patient load, and depressing environment. Participants who attended private medical school (p < 0.10), planned to live abroad (p < 0.10), had an oncologist (p < 0.05), cancer survivor or death due to cancer in the family (p < 0.05), were more likely to adopt oncology as a career. Those who believed that poor patient prognosis can have an impact on career choice were less likely to prefer oncology (p < 0.05).

Conclusion

Despite the rising cancer burden, early career doctors are reluctant to join oncology. Curricular, infrastructural and policy changes are needed at the level of medical school, oncology training and practice to recruit more young doctors and minimize the existing paucity of the oncologic workforce.
Findings and lessons learnt implementing a cardiovascular disease quality improvement program in Australian primary care: a mixed method evaluation
Authors: Hespe C. M. , Giskes K. , Harris M. F. , Peiris D.
Published: January 2022

Background

There are discrepancies between evidence-based guidelines for screening and management of cardiovascular disease (CVD) and implementation in Australian general practice. Quality-improvement (QI) initiatives aim to reduce these gaps. This study evaluated a QI program (QPulse) that focussed on CVD assessment and management.

Methods

This mixed-methods study explored the implementation of guidelines and adoption of a QI program with a CVD risk-reduction intervention in 34 general practices. CVD screening and management were measured pre- and post-intervention. Qualitative analyses examined participants’ Plan-Do-Study-Act (PDSA) goals and in-depth interviews with practice stakeholders focussed on barriers and enablers to the program and were analysed thematically using Normalisation Process Theory (NPT).

Results

Pre- and post-intervention data were available from 15 practices (n = 19,562 and n = 20,249, respectively) and in-depth interviews from seven practices. At baseline, 45.0% of patients had their BMI measured and 15.6% had their waist circumference recorded in the past 2 years and blood pressure, lipids and smoking status were measured in 72.5, 61.5 and 65.3% of patients, respectively. Most high-risk patients (57.5%) were not prescribed risk-reducing medications. After the intervention there were no changes in the documentation and prevalence of risk factors, attainment of BP and lipid targets or prescription of CVD risk-reducing medications. However, there was variation in performance across practices with some showing isolated improvements, such as recording waist circumference (0.7-32.2% pre-intervention to 18.5-69.8% post-intervention), BMI and smoking assessment. Challenges to the program included: lack of time, need for technical support, a perceived lack of value for quality improvement work, difficulty disseminating knowledge across the practice team, tensions between the team and clinical staff and a part-time workforce.

Conclusion

The barriers associated with this QI program was considerable in Australian GP practices. Findings highlighted they were not able to effectively operationalise the intervention due to numerous factors, ranging from lack of internal capacity and leadership to competing demands and insufficient external support.

Trial registration

Australian New Zealand Clinical Trials Reference Number (ACTRN12615000108516), registered 06/02/2015.
Introducing a MAP for adherence care in the paediatric cystic fibrosis clinic: a multiple methods implementation study
Authors: Richards Bianca , Osborne Sonya R. , Simons Megan
Published: January 2022

Background

People with cystic fibrosis are required to adhere to a burdensome daily treatment regimen. Comprehensive adherence protocols can support more consistent use of adherence interventions and improve treatment adherence rates. This study aimed to explore the feasibility, acceptability, and appropriateness of implementing an adherence protocol into the outpatient cystic fibrosis clinic of a tertiary, paediatric hospital.

Methods

This implementation study employed a pre-post observation design, using multiple methods. Focus groups and semi-structured interviews were conducted pre-implementation to understand clinician and consumer perspectives on adherence care. A multicomponent adherence protocol (including multidisciplinary written treatment plans, digital mental health screening and customised communication tools) was then implemented as standard care for a three-month implementation phase. Quantitative data was collected throughout using purpose-designed audit tools and surveys. The Replicating Effective Practice (REP) Framework guided the implementation process. Analysis was informed by The Consolidated Framework for Implementation Research (CFIR) to identify factors that support or challenge the integration of adherence protocols into standard care.

Results

Thirteen clinicians, eight parents and two adolescents participated in focus groups or interviews that informed development of the tailored multicomponent adherence protocol for implementation. Medical chart audits demonstrated that the protocol was used with 44–57% of eligible consumers three months after introduction. Eighteen clinicians and five consumers participated in post-implementation phase questionnaires. The protocol was considered acceptable and appropriate to clinicians and consumers. Changes in clinicians’ practice behaviour were short-lived peaks in response to targeted intervention strategies throughout the implementation phase, such as audit and feedback.

Conclusions

An adherence protocol is not an “off the shelf” solution to the adherence challenge in a hospital outpatient setting. Despite the tailored adherence protocol being considered appropriate and acceptable to clinicians and consumers, low fidelity indicates limited feasibility in the outpatient clinic setting, where multi-disciplinary members are all considered responsible for adherence care interventions. Key implementation factors and strategies to consider prior to introducing an adherence protocol are described.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12619001730190 (Retrospectively registered).
Psychometric properties of the Persian version of Depression Anxiety Stress Scale-21 Items (DASS-21) in a sample of health professionals: a cross-sectional study
Authors: Kakemam Edris , Navvabi Elahe , Albelbeisi Ahmed Hassan , Saeedikia Faeze , Rouhi Amin , Majidi Soheila
Published: January 2022

Background

Although the Depression Anxiety Stress Scale-21 Items (DASS-21) has been used in different countries and translated into different languages, the Persian version of this scale has not been validated for healthcare professions in Iran. Therefore, the purpose of this study was to examine the psychometric properties of the Persian version of DASS-21 for nurses.

Methods

This cross-sectional study was conducted among 1135 nurses working in public hospitals, who were selected through convenience sampling. DASS-21, which consists of 21 items and three dimensions (depression, anxiety, and stress), has been translated into Persian, and there is an online version available. A confirmatory factor analysis (CFA) was performed to examine the factor structure of this scale. Cronbach’s alpha coefficient was also measured to establish internal consistency. Besides, the intraclass correlation coefficient (ICC) was calculated to assess the test-retest reliability.

Results

The Cronbach’s alpha coefficient was acceptable for anxiety (0.79), stress (0.91), and depression (0.93). An acceptable test-retest reliability (0.740-0.881, P < 0.01) was also reported for DASS-21 and its three dimensions. The results of CFA showed acceptable model fit (χ2/(df) = 1457/(186), P < 0.001), root mean square error of approximation (RMSEA = 0.078), Tucker-Lewis index (TLI = 0.906), comparative fit index (CFI = 0.917), and standardized root mean square residual (SRMR = 0.047). Fifty-seven nurses were included in the test-retest. The ICCs for all dimensions ranged from 0.75 to 0.86, indicating the acceptable test-retest reliability of the scale.

Conclusion

The Persian version of DASS-21 showed good psychometric characteristics, and it was confirmed as a valid and reliable tool for evaluating depression, anxiety, and stress among Iranian nurses. However, further validation studies of the Persian DSASS-21 are needed among other healthcare professionals, including physicians, midwives, and allied health professionals.
Identification of heart failure with preserved ejection fraction helps risk stratification for hypertrophic cardiomyopathy
Authors: Liu Jie , Wang Dong , Ruan Jieyun , Wu Guixin , Xu Lianjun , Jiang Wen , Wang Jizheng , Sun Xiaolu , Kang Lianming , Song Lei
Published: January 2022

Background

Heart failure with preserved ejection fraction (HFpEF) is the dominant form of heart failure (HF). We here aimed to investigate the characteristics and prognosis of HFpEF in patients with hypertrophic cardiomyopathy (HCM).

Methods

This was a prospective cohort study and patients with HCM with available NT-proBNP results were enrolled. Patients were categorized into HFpEF [defined as LVEF ≥50%, with symptoms or signs of HF, and N-terminal pro-brain natriuretic peptide ≥800 pg/mL according to American Heart Association (AHA) criteria] and without heart failure (non-HF). The outcomes of interest were all-cause death, cardiovascular death, and sudden cardiac death (SCD).

Results

Of 1178 included patients with HCM, 513 (43.5%) were identified as having HFpEF according to AHA criteria. Compared with non-HF patients, patients with HFpEF had significantly larger maximal wall thickness (P < 0.001), higher maximal left ventricular outflow tract gradient (P < 0.001), higher proportion of atrial fibrillation (P < 0.001), higher incidence of all-cause death (log-rank test, P = 0.002), and cardiovascular death (log-rank test, P = 0.005). Multivariable Cox analysis showed that patients with HFpEF had a nearly two-fold higher risk of all-cause death (adjusted HR = 1.80, 95% CI 1.11–2.90; P = 0.017) and cardiovascular death (adjusted HR =1.82, 95% CI 1.05–3.18; P = 0.033) than non-HF patients.

Conclusions

Patients with HCM have a high prevalence of HFpEF and those with HFpEF present greater disease severity and higher mortality than non-HF patients, and thus may require an appropriate and more aggressive treatment for HF management. Identification of patients with HFpEF using AHA criteria can provide guidance on patient risk stratification for patients with HCM.
The effect of oral diabetes medications on glycated haemoglobin (HbA1c) in Asians in primary care: a retrospective cohort real-world data study
Authors: Fang Hao Sen Andrew , Gao Qiao , Tan Wei Ying , Lee Mong Li , Hsu Wynne , Tan Ngiap Chuan
Published: January 2022

Background

Clinical trials have demonstrated that initiating oral anti-diabetic drugs (OADs) significantly reduce glycated hemoglobin (HbA1c) levels. However, variability in lifestyle modifications and OAD adherence impact on their actual effect on glycemic control. Furthermore, evidence on dose adjustments and discontinuation of OAD on HbA1c is lacking. This study aims to use real-world data to determine the effect of OAD initiation, up-titration, down-titration, and discontinuation on HbA1c levels, among Asian patients managed in primary care.

Methods

A retrospective cohort study over a 5-year period, from Jan 2015 to Dec 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of type 2 diabetes mellitus (T2DM) managed by a network of primary care clinics in Singapore. Nine OADs from five different classes (biguanides, sulphonyurea, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 [SGLT-2] inhibitors, and alpha-glucosidase inhibitors) were evaluated. Patients were grouped into “No OAD”, “Non-titrators,” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the various OAD titrations were identified. Subsequently, a descriptive analysis of HbA1c values before and after each titration was performed to compute a mean difference for each unique titration identified.

Results

Among the cohort of 57,910 patients, 43,338 of them had at least one OAD titration, with a total of 76,990 pairs of HbA1c values associated with an OAD titration. There were a total of 206 unique OAD titrations. Overall, initiation of OADs resulted in a reduction of HbA1c by 3 to 12 mmol/mol (0.3 to 1.1%), respectively. These results were slightly lower than those reported in clinical trials of 6 to 14 mmol/mol (0.5 to 1.25%). The change of HbA1c levels due to up-titration, down-titration, and discontinuation were −1 to −8 mmol/mol (−0.1 to −0.7%), +1 to 7 mmol/mol (+0.1 to +0.6%), and +2 to 11 mmol/mol (+0.2 to +1.0%), respectively. The HbA1c lowering effect of initiating newer OADs, namely DPP-4 inhibitors and SGLT-2 inhibitors was 8 to 11 mmol/mol (0.7 to 0.9%) and 7 to 11 mmol/mol (0.6 to 1.0%), respectively.

Conclusion

The real-world data on Asians with T2DM in this study show that the magnitudes of OAD initiation and dose titration are marginally lower than the results from clinical trials. During shared decision-making in selecting treatment options, the results enable physicians to communicate realistic expectation of the effect of oral medications on the glycemic control of their patients in primary care.
Epidemiology and control of SARS-CoV-2 epidemics in partially vaccinated populations: a modeling study applied to France
Authors: Bosetti Paolo , Tran Kiem Cécile , Andronico Alessio , Colizza Vittoria , Yazdanpanah Yazdan , Fontanet Arnaud , Benamouzig Daniel , Cauchemez Simon
Published: January 2022

Background

Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics.

Methods

We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively.

Results

In our baseline scenario characterized by basic reproduction number R0=5 and a vaccine coverage of 70–80–90% among 12–17, 18–59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0–17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective.

Conclusions

With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology.
Identification of a novel HOOK3-FGFR1 fusion gene involved in activation of the NF-kappaB pathway
Authors: Zhang Xuehong , Wang Furong , Yan Fanzhi , Huang Dan , Wang Haina , Gao Beibei , Gao Yuan , Hou Zhijie , Lou Jiacheng , Li Weiling , Yan Jinsong
Published: January 2022

Background

Rearrangements involving the fibroblast growth factor receptor 1 (FGFR1) gene result in 8p11 myeloproliferative syndrome (EMS), which is a rare and aggressive hematological malignancy that is often initially diagnosed as myelodysplastic syndrome (MDS). Clinical outcomes are typically poor due to relative resistance to tyrosine kinase inhibitors (TKIs) and rapid transformation to acute leukemia. Deciphering the transcriptomic signature of FGFR1 fusions may open new treatment strategies for FGFR1 rearrangement patients.

Methods

DNA sequencing (DNA-seq) was performed for 20 MDS patients and whole exome sequencing (WES) was performed for one HOOK3-FGFR1 fusion positive patient. RNA sequencing (RNA-seq) was performed for 20 MDS patients and 8 healthy donors. Fusion genes were detected using the STAR-Fusion tool. Fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), and Sanger sequencing were used to confirm the HOOK3-FGFR1 fusion gene. The phosphorylation antibody array was performed to validate the activation of nuclear factor-kappaB (NF-kappaB) signaling.

Results

We identified frequently recurrent mutations of ASXL1 and U2AF1 in the MDS cohort, which is consistent with previous reports. We also identified a novel in-frame HOOK3-FGFR1 fusion gene in one MDS case with abnormal monoclonal B-cell lymphocytosis and ring chromosome 8. FISH analysis detected the FGFR1 break-apart signal in myeloid blasts only. qRT-PCR and Sanger sequencing confirmed the HOOK3-FGFR1 fusion transcript with breakpoints located at the 11th exon of HOOK3 and 10th exon of FGFR1, and Western blot detected the chimeric HOOK3-FGFR1 fusion protein that is presumed to retain the entire tyrosine kinase domain of FGFR1. The transcriptional feature of HOOK3-FGFR1 fusion was characterized by the significant enrichment of the NF-kappaB pathway by comparing the expression profiling of FGFR1 fusion positive MDS with 8 healthy donors and FGFR1 fusion negative MDS patients. Further validation by phosphorylation antibody array also showed NF-kappaB activation, as evidenced by increased phosphorylation of p65 (Ser 536) and of IKBalpha (Ser 32).

Conclusions

The HOOK3-FGFR1 fusion gene may contribute to the pathogenesis of MDS and activate the NF-kappaB pathway. These findings highlight a potential novel approach for combination therapy for FGFR1 rearrangement patients.
The crosstalk between reactive oxygen species and noncoding RNAs: from cancer code to drug role
Authors: Zuo Jing , Zhang Zhe , Li Maomao , Yang Yun , Zheng Bohao , Wang Ping , Huang Canhua , Zhou Shengtao
Published: January 2022

Oxidative stress (OS), characterized by the excessive accumulation of reactive oxygen species (ROS), is an emerging hallmark of cancer. Tumorigenesis and development driven by ROS require an aberrant redox homeostasis, that activates onco-signaling and avoids ROS-induced programmed death by orchestrating antioxidant systems. These processes are revealed to closely associate with noncoding RNAs (ncRNAs). On the basis of the available evidence, ncRNAs have been widely identified as multifarious modulators with the involvement of several key redox sensing pathways, such as NF-κB and Nrf2 signaling, therefore potentially becoming effective targets for cancer therapy. Furthermore, the vast majority of ncRNAs with property of easy detected in fluid samples (e.g., blood and urine) facilitate clinicians to monitor redox homeostasis, indicating a novel method for cancer diagnosis. Herein, focusing on carcinoma initiation, metastasis and chemoradiotherapy resistance, we aimed to discuss the ncRNAs-ROS network involved in cancer progression, and the potential clinical application as biomarkers and therapeutic targets.
Analysis of plasma proteins using 2D gels and novel fluorescent probes: in search of blood based biomarkers for Alzheimer’s disease
Authors: Laffoon Scott B. , Doecke James D. , Roberts Anne M. , Vance Jennifer A. , Reeves Benjamin D. , Pertile Kelly K. , Rumble Rebecca L. , Fowler Chris J. , Trounson Brett , Ames David , Martins Ralph , Bush Ashley I. , Masters Colin L. , Grieco Paul A. , Dratz Edward A. , Roberts Blaine R.
Published: January 2022

Background

The Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer’s disease.

Methods

The concentration of proteins in plasma covers a vast range of 12 orders of magnitude. Therefore, to search for medium to low abundant biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL.

Results

We report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent on APOE ε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a preliminary validation study, on unique individual samples compared to the discovery cohort, using a targeted LC-MS/MS assay on a subset of discovered biomarkers. We found that targets that displayed a high degree of isoform specific changes in the 2D gels were not changed in the targeted MS assay which reports on the total level of the biomarker.

Conclusions

This demonstrates that further development of mass spectrometry assays is needed to capture the isoform complexity that exists in theses biological samples. However, this study indicates that a peripheral protein signature has potential to aid in the characterization of AD.
Interplay between nitric oxide and gonadotrophin-releasing hormone in the neuromodulation of the corpus luteum during late pregnancy in the rat
Authors: Vallcaneras Sandra , Morales Laura , Delsouc María Belén , Ramirez Darío , Filippa Verónica , Fernández Marina , Telleria Carlos M. , Casais Marilina
Published: January 2022

Background

Nitric oxide and GnRH are biological factors that participate in the regulation of reproductive functions. To our knowledge, there are no studies that link NO and GnRH in the sympathetic ganglia. Thus, the aim of the present work was to investigate the influence of NO on GnRH release from the coeliac ganglion and its effect on luteal regression at the end of pregnancy in the rat.

Methods

The ex vivo system composed by the coeliac ganglion, the superior ovarian nerve, and the ovary of rats on day 21 of pregnancy was incubated for 180 min with the addition, into the ganglionic compartment, of L-NG-nitro arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. The control group consisted in untreated organ systems.

Results

The addition of L-NAME in the coeliac ganglion compartment decreased NO as well as GnRH release from the coeliac ganglion. In the ovarian compartment, and with respect to the control group, we observed a reduced release of GnRH, NO, and noradrenaline, but an increased production of progesterone, estradiol, and expression of their limiting biosynthetic enzymes, 3β-HSD and P450 aromatase, respectively. The inhibition of NO production by L-NAME in the coeliac ganglion compartment also reduced luteal apoptosis, lipid peroxidation, and nitrotyrosine, whereas it increased the total antioxidant capacity within the corpora lutea.

Conclusion

Collectively, the results indicate that NO production by the coeliac ganglion modulates the physiology of the ovary and luteal regression during late pregnancy in rats.
‘Finishing the race’ – a cohort study of weight and blood glucose change among the first 36,000 patients in a large-scale diabetes prevention programme
Authors: Marsden Antonia M. , Bower Peter , Howarth Elizabeth , Soiland-Reyes Claudia , Sutton Matt , Cotterill Sarah
Published: January 2022

Background

The NHS Diabetes Prevention Programme for England, “Healthier You”, encourages behaviour change regarding healthy eating and physical exercise among people identified to be at high risk of developing type 2 diabetes. The aim of this research was to examine change, and factors associated with change, in measures of HbA1c and weight in participants and completers of the programme between 2016 and 2019.

Methods

Participant-level data collected by programme service providers on referrals prior to March 2018 was analysed. Changes from baseline to both 6 months and completion in HbA1c and weight were examined using mixed effects linear regression, adjusting for patient characteristics, service provider and site.

Results

Completers had average improvements in HbA1c of 2.1 mmol/mol [95% CI: − 2.2, − 2.0] (0.19% [95% CI: − 0.20, − 0.18]) and reductions of 3.6 kg [95% CI: − 3.6, − 3.5] in weight, in absolute terms. Variation across the four providers was observed at both time points: two providers had significantly smaller average reductions in HbA1c and one provider had a significantly smaller average reduction in weight compared to the other providers. At both time points, ex- or current smokers had smaller reductions in HbA1c than non-smokers and those from minority ethnic groups lost less weight than White participants. For both outcomes, associations with other factors were small or null and variation across sites remained after adjustment for provider and case mix.

Conclusions

Participants who completed the programme, on average, experienced improvements in weight and HbA1c. There was substantial variation in HbA1c change and smaller variation in weight loss between providers and across different sites. Aside from an association between HbA1c change and smoking, and between weight loss and ethnicity, results were broadly similar regardless of patient characteristics.
Bone marrow stromal antigen 2 (BST-2) genetic variants influence expression levels and disease outcome in HIV-1 chronically infected patients
Authors: Mlimi Hlelolwenkosi , Naidoo Kewreshini K. , Mabuka Jenniffer , Ndung’u Thumbi , Madlala Paradise
Published: January 2022

Background

Bone marrow stromal antigen 2 (BST-2) also known as Tetherin (CD317/HM1.24), is a host restriction factor that blocks the release of HIV-1 virions from infected cells. Previous studies reported that BST-2 genetic variants or single nucleotide polymorphims (SNPs) have a preventative role during HIV-1 infection. However, the influence of BST-2 SNPs on expression levels remains unknown. In this study, we investigated the influence of BST-2 SNPs on expression levels and disease outcome in HIV-1 subtype C chronically infected antiretroviral therapy naïve individuals.

Results

We quantified BST-2 mRNA levels in peripheral blood mononuclear cells (PBMCs), determined BST-2 protein expression on the surface of CD4+ T cells using flow cytometry and genotyped two intronic single nucleotide polymorphisms (SNPs) rs919267 and rs919266 together with one SNP rs9576 located in the 3’ untranslated region (UTR) of bst-2 gene using TaqMan assays from HIV-1 uninfected and infected participants. Subsequently, we determined the ability of plasma antibody levels to mediate antibody-dependent cellular phagocytosis (ADCP) using gp120 consensus C and p24 subtype B/C protein. Fc receptor-mediated NK cell degranulation was evaluated as a surrogate for ADCC activity using plasma from HIV-1 positive participants. BST-2 mRNA expression levels in PBMCs and protein levels on CD4+ T cells were lower in HIV-1 infected compared to uninfected participants (p = 0.075 and p < 0.001, respectively). rs919267CT (p = 0.042) and rs919267TT (p = 0.045) were associated with lower BST-2 mRNA expression levels compared to rs919267CC in HIV-1 uninfected participants. In HIV-1 infected participants, rs919267CT associated with lower CD4 counts, (p = 0.003), gp120-IgG1 (p = 0.040), gp120-IgG3 (p = 0.016) levels but higher viral loads (p = 0.001) while rs919267TT was associated with lower BST-2 mRNA levels (p = 0.046), CD4 counts (p = 0.001), gp120-IgG1 levels (p = 0.033) but higher plasma viral loads (p = 0.007). Conversely, rs9576CA was associated with higher BST-2 mRNA expression levels (p = 0.027), CD4 counts (p = 0.079), gp120-IgG1 (p = 0.009), gp120-IgG3 (p = 0.039) levels but with lower viral loads (p = 0.037).

Conclusion

Our findings show that bst-2 SNPs mediate BST-2 expression and disease outcome, correlate with gp120-IgG1, gp120-IgG3 levels but not p24-IgG levels, ADCC and ADCP activity.

Graphical Abstract
Motorized 2–3 wheelers death rates over a decade: a global study
Authors: Yasin Yasin J. , Grivna Michal , Abu-Zidan Fikri M.
Published: January 2022

Background

Motorized 2–3-wheelers-related death is high due to the exposed body of the driver/passenger and the high speed. The United Nation (UN) Decade of Action for road safety aimed to reduce road traffic deaths by 50% by the year 2020. We aimed to study the factors affecting the death rates of motorized 2–3 wheelers injured victims and whether the reduction in the death rates has met the UN target.

Methods

Data were retrieved from the WHO Global Status Reports on Road Safety published over 2009 to 2018 which covered the years of 2007 to 2016. Studied variables included motorized 2–3 wheelers death rates, percentage of helmet-wearing rate, helmet law enforcement, speed law enforcement, gross national income per capita, vehicles/person ratio, and motorized 2–3 wheelers/person ratio. A mixed linear model was used to define factors affecting the change of motorized 2–3 wheelers death rates over time.

Results

The global mean motorized 2–3 wheelers death rates increased from 2.37/100,000 population to 3.23/100,000 population over the studied decade (a relative ratio of 1.36) which was not statistically significant. Factors that affected mortality included GNI (p = 0.025), motorized 2–3 wheelers per person ratio (p < 0.0001), percentage of helmet wearing rate (p = 0.046), and the interaction between vehicle/person ratio and motorized 2–3 wheelers/person ratio (p = 0.016). There was a significant increase in the death rates over time in the low-income countries (a relative ratio of 2.52, p = 0.019, Friedman test), and middle-income countries (a relative ratio of 1.46, p < 0.0001, Friedman test), compared with a significant decrease in the high-income countries (a relative ratio of 0.72, p < 0.0001, Friedman test).

Conclusions

Global mortality of motorized 2–3 wheelers has increased by a relative ratio of 1.36 over a recent decade. The UN target of reducing death was not met. The increase was related to the increase in motorized 2–3 wheelers per person ratio and economic inequity which has to be addressed globally. The economic global gap significantly impacts the mortality rates of motorized 2–3 wheelers.
A 6-year case series of resuscitative thoracotomies performed by a helicopter emergency medical service in a mixed urban and rural area with a comparison of blunt versus penetrating trauma
Authors: Almond Phillip , Morton Sarah , OMeara Matthew , Durge Neal
Published: January 2022

Background

Resuscitative thoracotomy (RT) is an intervention that can be performed in the prehospital setting for relieving cardiac tamponade and/or obtaining vascular control of suspected sub-diaphragmatic haemorrhage in patients in traumatic cardiac arrest. The aim of this retrospective case study is to compare the rates of return of spontaneous circulation (ROSC) in RTs performed for both penetrating and blunt trauma over 6 years in a mixed urban and rural environment.

Methods

The electronic records of a single helicopter emergency medical service were reviewed between 1st June 2015 and 31st May 2021 for RTs. Anonymised data including demographics were extracted for relevant cases. Data were analysed with independent t-tests and Χ2 tests. A p value < 0.05 was considered statistically significant.

Results

Forty-four RTs were preformed within the 6 years (26 for blunt trauma). Eleven ROSCs were achieved (nine blunt, two penetrating) but no patient survived to discharge. In contrast to RTs for penetrating trauma, twelve of the RTs for blunt trauma had a cardiac output present on arrival of the prehospital team (p = 0.01). Two patients had an RT performed in a helicopter (one ROSC) and two on a helipad (both achieving ROSC), likely due to the longer transfer times seen in a more rural setting. Four of the RTs for blunt trauma (15%) were found to have a cardiac tamponade versus seven (39%) of the penetrating trauma RTs.

Conclusion

Prehospital RT remains a procedure with low rates of survival but may facilitate a ROSC to allow patients to reach hospital and surgery, particularly when distances to hospitals are greater. A higher-than-expected rate of cardiac tamponade was seen in RTs for blunt trauma, although not caused by a right ventricular wound but instead due to underlying vessel damage.
Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study
Authors: Geczik Ashley M. , Falk Roni T. , Xu Xia , Ansong Daniel , Yarney Joel , Wiafe-Addai Beatrice , Edusei Lawrence , Dedey Florence , Vanderpuye Verna , Titiloye Nicholas , Adjei Ernest , Aitpillah Francis , Osei-Bonsu Ernest , Oppong Joseph , Biritwum Richard , Nyarko Kofi , Wiafe Seth , Awuah Baffour , Clegg-Lamptey Joe-Nat , Ahearn Thomas U. , Figueroa Jonine , Garcia-Closas Montserrat , Brinton Louise A. , Trabert Britton
Published: January 2022

Background

Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study.

Methods

Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case–control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders.

Results

Measured BMI (≥ 30 vs. 18.5–24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57–93.53) vs. 50.89 (43.47–59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47–36.07) vs. 13.26 (10.37–16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women.

Conclusions

We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.
CellPhy: accurate and fast probabilistic inference of single-cell phylogenies from scDNA-seq data
Authors: Kozlov Alexey , Alves Joao M. , Stamatakis Alexandros , Posada David
Published: January 2022

We introduce CellPhy, a maximum likelihood framework for inferring phylogenetic trees from somatic single-cell single-nucleotide variants. CellPhy leverages a finite-site Markov genotype model with 16 diploid states and considers amplification error and allelic dropout. We implement CellPhy into RAxML-NG, a widely used phylogenetic inference package that provides statistical confidence measurements and scales well on large datasets with hundreds or thousands of cells. Comprehensive simulations suggest that CellPhy is more robust to single-cell genomics errors and outperforms state-of-the-art methods under realistic scenarios, both in accuracy and speed. CellPhy is freely available athttps://github.com/amkozlov/cellphy.