bluuebunny/crossref_metadata_2025 huggingface dataset:
Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses
Authors: Chih Hui Ju , Elias Flavia T. S. , Gaudet Laura , Velez Maria P.
Published: June 2021

Background

Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC).

Methods

We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups.

Results

Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60–1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20–1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00–6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58–1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33–1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively).

Conclusions

Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.
Pregnancy and birth characteristics of Aboriginal twins in two Australian states: a data linkage study
Authors: Gibberd Alison J. , Tyler Jessica , Falster Kathleen , Preen David B. , Hanly Mark , Clarke Marilyn J. , McNamara Bridgette J. , Eades Sandra J. , Scurrah Katrina J.
Published: June 2021

Introduction

Perinatal outcomes for singleton pregnancies are poorer, on average, for Aboriginal people than non-Aboriginal people, but little is known about Aboriginal multifetal pregnancies. Yet multifetal pregnancies and births are often more complicated and have poorer outcomes than singleton pregnancies. We describe the pregnancies, births and perinatal outcomes for Aboriginal twins born in Western Australia (WA) and New South Wales (NSW) with comparisons to Aboriginal singletons in both states and to non-Aboriginal births in NSW.

Materials and methods

Whole-population birth records and birth and death registrations were linked for all births during 2000–2013 (WA) and 2002–2008 (NSW). Hospital records and the WA Register of Developmental Anomalies - Cerebral Palsy were linked for all WA births and hospital records for a subset of NSW births. Descriptive statistics are reported for maternal and child demographics, maternal health, pregnancy complications, births and perinatal outcomes.

Results

Thirty-four thousand one hundred twenty-seven WA Aboriginal, 32,352 NSW Aboriginal and 601,233 NSW non-Aboriginal births were included. Pregnancy complications were more common among mothers of Aboriginal twins than Aboriginal singletons (e.g. 17% of mothers of WA twins had hypertension/pre-eclampsia/eclampsia vs 8% of mothers of singletons) but similar to mothers of NSW non-Aboriginal twins. Most Aboriginal twins were born in a principal referral, women’s or large public hospital. The hospitals were often far from the mother’s home (e.g. 31% of mothers of WA Aboriginal twins gave birth at hospitals located more than 3 h by road from their home). Outcomes were worse for Aboriginal liveborn twins than Aboriginal singletons and non-Aboriginal twins (e.g. 58% of NSW Aboriginal twins were preterm compared to 9% of Aboriginal singletons and 49% non-Aboriginal twins).

Conclusions

Mothers of Aboriginal twins faced significant challenges during the pregnancy, birth and the postnatal period in hospital and, in addition to accessible specialist medical care, these mothers may need extra practical and psychosocial support throughout their journey.
Treatment and pregnancy outcomes of pregnant women exposed to second-line anti-tuberculosis drugs in South Africa
Authors: Mokhele Idah , Jinga Nelly , Berhanu Rebecca , Dlamini Thandi , Long Lawrence , Evans Denise
Published: June 2021

Background

Multi-drug resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in pregnant women is a cause for concern globally; few data have described the safety of second-line anti-TB medications during pregnancy. We aim to describe TB treatment and pregnancy outcomes among pregnant women receiving second-line anti-tuberculosis treatment for MDR/RR-TB in Johannesburg, South Africa.

Methods

We conducted a retrospective record review of pregnant women (≥ 18 years) who received treatment for MDR/RR-TB between 01/2010–08/2016 at three outpatient treatment sites in Johannesburg, South Africa. Demographic, treatment and pregnancy outcome data were collected from available medical records. Preterm birth (< 37 weeks), and miscarriage were categorized as adverse pregnancy outcomes.

Results

Out of 720 women of child-bearing age who received MDR/RR-TB treatment at the three study sites, 35 (4.4%) pregnancies were identified. Overall, 68.7% (24/35) were HIV infected, 83.3% (20/24) were on antiretroviral therapy (ART). Most women, 88.6% (31/35), were pregnant at the time of MDR/RR-TB diagnosis and four women became pregnant during treatment.

Pregnancy outcomes were available for 20/35 (57.1%) women, which included 15 live births (11 occurred prior to 37 weeks), 1 neonatal death, 1 miscarriage and 3 pregnancy terminations. Overall, 13/20 (65.0%) women with known pregnancy outcomes had an adverse pregnancy outcome. Of the 28 women with known TB treatment outcomes 17 (60.7%) completed treatment successfully (4 were cured and 13 completed treatment), 3 (10.7%) died and 8 (28.6%) were lost-to-follow-up.

Conclusions

Pregnant women with MDR/RR-TB suffer from high rates of adverse pregnancy outcomes and about 60% achieve a successful TB treatment outcome. These vulnerable patients require close monitoring and coordinated obstetric, HIV and TB care.
The relationship between insomnia symptoms and work productivity among blue-collar and white-collar Japanese workers engaged in construction/civil engineering work: a cross-sectional study
Authors: Kayaba Momoko , Sasai-Sakuma Taeko , Takaesu Yoshikazu , Inoue Yuichi
Published: June 2021

Background

The situation of work productivity loss due to sleep disorders/problems among workers in industrialized societies remains unclear. The purpose of this study was to clarify the prevalence of insomnia symptoms and actual situation of work productivity by job type (white-collars/blue-collars) among construction/civil engineering workers in Japan and evaluate the association between insomnia symptoms and work productivity adjusting for sleep duration and sociodemographic, work-related, and health-related variables.

Methods

This cross-sectional study included 17,828 construction/civil engineering workers (15,837 males and 1991 females) aged 40 to 74 years in Japan. The questionnaire consisted of socio-demographic characteristics, information on work productivity (work performance and absence), respective insomnia symptoms (difficulty initiating sleep; DIS, difficulty maintaining sleep; DMS, and early morning awakening; EMA), bedtime schedule, work-related factors (job type, working hours), and perceived health condition. To identify the associated factors of work productivity, the logistic regression analyses were conducted.

Results

The percentages of workers who reported to be experiencing DIS, DMS, and EMA were 7.9, 16.3, and 13.1%, respectively. Poor work performance was associated with every insomnia symptom in both the blue-collar and white-collar workers. Meanwhile, absence was associated with DIS in blue-collar workers and both DIS and DMS in white-collar workers; however, not with EMA in both the groups. In blue-collar workers, engagement in shift work was associated with poor work performance.

Conclusions

The present study revealed the association between insomnia symptoms and work productivity, suggesting the necessity of early prevention of insomnia among both blue-collar and white-collar workers.
Understanding norovirus reporting patterns in England: a mixed model approach
Authors: Ondrikova N. , Clough H. E. , Cunliffe N. A. , Iturriza-Gomara M. , Vivancos R. , Harris J. P.
Published: June 2021

Background

Norovirus has a higher level of under-reporting in England compared to other intestinal infectious agents such as Campylobacter or Salmonella, despite being recognised as the most common cause of gastroenteritis globally. In England, this under-reporting is a consequence of the frequently mild/self-limiting nature of the disease, combined with the passive surveillance system for infectious diseases reporting. We investigated heterogeneity in passive surveillance system in order to improve understanding of differences in reporting and laboratory testing practices of norovirus in England.

Methods

The reporting patterns of norovirus relating to age and geographical region of England were investigated using a multivariate negative binomial model. Multiple model formulations were compared, and the best performing model was determined by proper scoring rules based on one-week-ahead predictions. The reporting patterns are represented by epidemic and endemic random intercepts; values close to one and less than one imply a lower number of reports than expected in the given region and age-group.

Results

The best performing model highlighted atypically large and small amounts of reporting by comparison with the average in England. Endemic random intercept varied from the lowest in East Midlands in those in the under 5 year age-group (0.36, CI 0.18–0.72) to the highest in the same age group in South West (3.00, CI 1.68–5.35) and Yorkshire & the Humber (2.93, CI 1.74–4.94). Reporting by age groups showed the highest variability in young children.

Conclusion

We identified substantial variability in reporting patterns of norovirus by age and by region of England. Our findings highlight the importance of considering uncertainty in the design of forecasting tools for norovirus, and to inform the development of more targeted risk management approaches for norovirus disease.
Use of the margin of stability to quantify stability in pathologic gait – a qualitative systematic review
Authors: Watson Fraje , Fino Peter C. , Thornton Matthew , Heracleous Constantinos , Loureiro Rui , Leong Julian J. H.
Published: June 2021

Background

The Margin of Stability (MoS) is a widely used objective measure of dynamic stability during gait. Increasingly, researchers are using the MoS to assess the stability of pathological populations to gauge their stability capabilities and coping strategies, or as an objective marker of outcome, response to treatment or disease progression. The objectives are; to describe the types of pathological gait that are assessed using the MoS, to examine the methods used to assess MoS and to examine the way the MoS data is presented and interpreted.

Methods

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA) in the following databases: Web of Science, PubMed, UCL Library Explore, Cochrane Library, Scopus. All articles measured the MoS of a pathologically affected adult human population whilst walking in a straight line. Extracted data were collected per a prospectively defined list, which included: population type, method of data analysis and model building, walking tasks undertaken, and interpretation of the MoS.

Results

Thirty-one studies were included in the final review. More than 15 different clinical populations were studied, most commonly post-stroke and unilateral transtibial amputee populations. Most participants were assessed in a gait laboratory using motion capture technology, whilst 2 studies used instrumented shoes. A variety of centre of mass, base of support and MoS definitions and calculations were described.

Conclusions

This is the first systematic review to assess use of the MoS and the first to consider its clinical application. Findings suggest the MoS has potential to be a helpful, objective measurement in a variety of clinically affected populations. Unfortunately, the methodology and interpretation varies, which hinders subsequent study comparisons. A lack of baseline results from large studies mean direct comparison between studies is difficult and strong conclusions are hard to make. Further work from the biomechanics community to develop reporting guidelines for MoS calculation methodology and a commitment to larger baseline studies for each pathology is welcomed.
Clinical and demographic features among patients with type 1 diabetes mellitus in Henan, China
Authors: Yang Liguo , Yang Guangxing , Li Xialian
Published: June 2021

Background

The hallmark of type 1 diabetes (T1D) is an absolute lack of insulin. However, many studies showed a tendency to heterogeneity in TID. We aimed to investigate the demographic and clinical characteristics in T1D and the differences in young-onset and adult-onset patients.

Methods

This retrospective study was conducted among 1943 patients with clinically diagnosed T1D. Medical records on patients’ demographics, anthropometric measurements, and clinical manifestation were collected. According to the age at onset, the newly diagnosed patients were divided into the young-onset group (< 18 years, 234 patients, mean age 11 years) and adult-onset group (≥ 18 years, 219 patients, mean age 27 years). Pancreatic β-cell function was assessed by fasting C-peptide (FCP) and 2-h C-peptide (2-h CP).

Results

The median age of patients at disease onset was 22 years. The median duration of patients was 3 years. The overall median glycated hemoglobin (HbA1c) value was 10.3 % [89(mmol/mol)]. The prevalence of diabetic retinopathy was 25.1 %. The overall rate of DKA at onset in the new-onset patients was 59.6 %. The frequency of overall dyslipidemia was 37.8 %. The most frequent dyslipidemia was low high-density lipoprotein-cholesterol (HDL) (29 %). The proportion of patients with anti-glutamic acid decarboxylase (GADA), insulin antibody (IAA) and islet cell antibody (ICA) were 28.1 %, 6.4 % and 21.6 %, respectively. The mean HbA1c showed a downward trend with age. Increasing or decreasing trends of overweight and obesity in this population during the period 2012 to 2018 was not found.

Compared with young-onset T1D, adult-onset patients comprised better islet function (FCP: 0.4 vs. 0.3 ng/ml,P < 0.001; 2-h CP: 0.9 vs. 0.7 ng/mlP < 0.001, respectively) and glycemic control [12.9 % (117mmol/mol) vs. 11.7 % (104mmol/mol),P < 0.001], higher prevalence of diabetes condition in the male gender (64.4 % vs. 51.3 %,P = 0.006), higher proportion of obesity or overweight (24.6 % vs. 9.5 %,P = 0.002), higher frequency of GADA (33.7 % vs. 23.3 %,P = 0.025), and lower frequency of diabetic ketoacidosis at disease onset (64.5 % vs. 43.5 %,P < 0.001).

Conclusions

This population was characterized by poor overall blood glucose control, high prevalence of DKA, dyslipidemia and diabetic retinopathy, and low prevalence of islet-related antibodies, and overweight or obesity. Adult-onset patients with T1D were not uncommon and had better clinical manifestations than young-onset patients. Any findings related to body mass index (BMI) and autoantibodies should be considered strictly exploratory due to excessive missing data.
Adherence with reporting of ethical standards in COVID-19 human studies: a rapid review
Authors: O’Sullivan Lydia , Killeen Ronan P. , Doran Peter , Crowley Rachel K.
Published: June 2021

Background

Patients with COVID-19 may feel under pressure to participate in research during the pandemic. Safeguards to protect research participants include ethical guidelines [e.g. Declaration of Helsinki and good clinical practice (GCP)], legislation to protect participants’ privacy, research ethics committees (RECs) and informed consent. The International Committee of Medical Journal Editors (ICMJE) advises researchers to document compliance with these safeguards. Adherence to publication guidelines has been suboptimal in other specialty fields. The aim of this rapid review was to determine whether COVID-19 human research publications report compliance with these ethical safeguards.

Methods

A rapid systematic literature review was conducted in MEDLINE using the search term ‘COVID-19’. The search was performed in April 2020 with no start date and repeated to include articles published in November 2020. Filters were ‘Full free text available’ and ‘English Language’. Two reviewers assessed article title, abstracts and full texts. Non-COVID-19 articles and non-clinical studies were excluded. Independent reviewers conducted a second assessment of a random 20% of articles. The outcomes included reporting of compliance with the Declaration of Helsinki and GCP, REC approval, informed consent and participant privacy.

Results

The searches yielded 1275 and 1942 articles of which 247 and 717 were deemed eligible, from the April  search and November respectively. The majority of journals had editorial policies which purported to comply with ICMJE ethical standards. Reporting of compliance with ethical guidelines was low across all study types but was higher in the November search for case series and observational studies. Reporting of informed consent for case studies and observational studies was higher in the November search, but similar for case series. Overall, participant confidentiality was maintained but some case studies included a combination of details which would have enabled participant identification. Reporting of REC approval was higher in the November search for observational studies.

Conclusions

While the majority of journal’s editorial policies purported to support the ethical safeguards, many COVID-19 clinical research publications identified in this rapid review lacked documentation of these important safeguards for research participants. In order to promote public trust, ethical declarations should be included consistently.
Diabetes self-management in online health communities: an information exchange perspective
Authors: Min Jing , Chen Yan , Wang Li , He Ting , Tang Sha
Published: June 2021

Background

Online health communities (OHCs), with a wealth of multi-source information exchange, have provided a convenient way for people with diabetes to actively participate in their self-management and have been widely used. Information exchange assists people with diabetes with health-related decisions to actively engage in their care, and reduce the occurrence of potential complications of diabetes. However, there has been relatively little research on the information exchange behaviors and their effect on health in professional online medical platforms—OHCs.

Objective

Using a social exchange theory, this study focuses on two sources of information (doctors and people with diabetes) to investigate information exchange behaviors and consequences. Moreover, we also examine moderating effects of information price as patients need to pay prices for consulting with doctors to obtain medical information on OHCs.

Methods

By using the Python program, a rich dataset contained 22,746 doctor-patient dialogues from December 2017 to December 2018 is collected from the biggest OHC in China. Then the logistic and ordinal regression models are used to get empirical results.

Results

We found that first information sharing from doctors and other people with diabetes can promote their information sharing behavior. Second, the moderating effects of information price are heterogeneous and change with the exchange participants. Third, rich information exchange supports self-management of people with diabetes and improves their health status.

Conclusion

This study is among the first that tests the information exchange behavior and consequence for diabetes in OHCs and examines the moderating effects of the information price. The present study produces several insights, which have implications for social exchange, patient behavior, online health communities, and information technology in diabetes self-management literature.
On the predictability of postoperative complications for cancer patients: a Portuguese cohort study
Authors: Gonçalves Daniel , Henriques Rui , Santos Lúcio Lara , Costa Rafael S.
Published: June 2021

Postoperative complications are still hard to predict despite the efforts towards the creation of clinical risk scores. The published scores contribute for the creation of specialized tools, but with limited predictive performance and reusability for implementation in the oncological context. This work aims to predict postoperative complications risk for cancer patients, offering two major contributions. First, to develop and evaluate a machine learning-based risk score, specific for the Portuguese population using a retrospective cohort of 847 cancer patients undergoing surgery between 2016 and 2018, for 4 outcomes of interest: (1) existence of postoperative complications, (2) severity level of complications, (3) number of days in the Intermediate Care Unit (ICU), and (4) postoperative mortality within 1 year. An additional cohort of 137 cancer patients from the same center was used for validation. Second, to improve the interpretability of the predictive models. In order to achieve these objectives, we propose an approach for the learning of risk predictors, offering new perspectives and insights into the clinical decision process. For postoperative complications the Receiver Operating Characteristic Curve (AUC) was 0.69, for complications’ severity AUC was 0.65, for the days in the ICU the mean absolute error was 1.07 days, and for 1-year postoperative mortality the AUC was 0.74, calculated on the development cohort. In this study, predictive models which could help to guide physicians at organizational and clinical decision making were developed. Additionally, a web-based decision support tool is further provided to this end.
Associations of GP practice characteristics with the rate of ambulatory care sensitive conditions in people living with dementia in England: an ecological analysis of routine data
Authors: Eyles Emily , Redaniel Maria Theresa , Purdy Sarah , Tilling Kate , Ben-Shlomo Yoav
Published: June 2021

Background

Hospital admissions for Ambulatory Care Sensitive Conditions (ACSCs) are potentially avoidable. Dementia is one of the leading chronic conditions in terms of variability in ACSC admissions by general practice, as well as accounting for around a third of UK emergency admissions.

Methods

Using Bayesian multilevel linear regression models, we examined the ecological association of organizational characteristics of general practices (ACSC n=7076, non-ACSC n=7046 units) and Clinical Commissioning Groups (CCG n=212 units) in relation to ACSC and non-ACSC admissions for people with dementia in England.

Results

The rate of hospital admissions are variable between GP practices, with deprivation and being admitted from home as risk factors for admission for ACSC and non-ACSC admissions. The budget allocated by the CCG to mental health shows diverging effects for ACSC versus non-ACSC admissions, so it is likely there is some geographic variation.

Conclusions

A variety of factors that could explain avoidable admissions for PWD at the practice level were examined; most were equally predictive for avoidable and non-avoidable admissions. However, a high amount of variation found at the practice level, in conjunction with the diverging effects of the CCG mental health budget, implies that guidance may be applied inconsistently, or local services may have differences in referral criteria. This indicates there is potential scope for improvement.
Conducting a psychosocial and lifestyle assessment as part of an integrated care approach for childhood obesity: experiences, needs and wishes of Dutch healthcare professionals
Authors: Koetsier L. W. , van Mil M. M. A. , Eilander M. M. A. , van den Eynde E. , Baan C. A. , Seidell J. C. , Halberstadt J.
Published: June 2021

Background

The causes and consequences of childhood obesity are complex and multifaceted. Therefore, an integrated care approach is required to address weight-related issues and improve children’s health, societal participation and quality of life. Conducting a psychosocial and lifestyle assessment is an essential part of an integrated care approach. The aim of this study was to explore the experiences, needs and wishes of healthcare professionals with respect to carrying out a psychosocial and lifestyle assessment of childhood obesity.

Methods

Fourteen semi-structured interviews were conducted with Dutch healthcare professionals, who are responsible for coordinating the support and care for children with obesity (coordinating professionals, ‘CPs’). The following topics were addressed in our interviews with these professionals: CPs’ experiences of both using childhood obesity assessment tools and their content, and CPs’ needs and wishes related to content, circumstances and required competences. The interviews comprised open-ended questions and were recorded and transcribed verbatim. The data was analysed using template analyses and complemented with open coding in MAXQDA.

Results

Most CPs experienced both developing a trusting relationship with the children and their parents, as well as establishing the right tone when engaging in weight-related conversations as important. CPs indicated that visual materials were helpful in such conversations. All CPs used a supporting assessment tool to conduct the psychosocial and lifestyle assessment but they also indicated that a more optimal tool was desirable. They recognized the need for specific attributes that helped them to carry out these assessments, namely: sufficient knowledge about the complexity of obesity; having an affinity with obesity-related issues; their experience as a CP; using conversational techniques, such as solution-focused counselling and motivational interviewing; peer-to-peer coaching; and finally, maintaining an open-minded, non-stigmatizing stance and harmonizing their attitude with that of the child and their parents.

Conclusions

Alongside the need for a suitable tool for conducting a psychosocial and lifestyle assessment, CPs expressed the need for requisite knowledge, skills and attitudes. Further developing a supporting assessment tool is necessary in order to facilitate CPs and thereby improve the support and care for children with obesity and their families.
Bronchial thermoplasty in asthma: an exploratory histopathological evaluation in distinct asthma endotypes/phenotypes
Authors: Papakonstantinou Eleni , Koletsa Triantafyllia , Zhou Liang , Fang Lei , Roth Michael , Karakioulaki Meropi , Savic Spasenija , Grize Leticia , Tamm Michael , Stolz Daiana
Published: June 2021

Background

Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes.

Methods

Endobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining.

Results

In all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034).

In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes.

Conclusions

Bronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.
Effect and mechanisms of reproductive tract infection on oxidative stress parameters, sperm DNA fragmentation, and semen quality in infertile males
Authors: Liu Kang-Sheng , Mao Xiao-Dong , Pan Feng , An Rui Fang
Published: June 2021

Recent years have seen a rising incidence of male infertility, mostly caused by the decline of sperm quality. The ratio of infertile males to infertile females has escalated from 3:7 in 2013 to current 5:5, which turns male infertility into the research focus of reproductive medicine. This study aimed to clarify the effect of reproductive tract infection by ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) on the DNA integrity and routine semen parameters of infertile males. A retrospective study was performed. A total of 259 infertile males who were treated at the Andrological Laboratory Examination and Reproductive Medicine Center in our hospital were analyzed. qRT-PCR was used to examine the infection status of CT and UU. According to the eligibility criteria, we evaluated the semen parameters and biochemical data of 253 men. Based on the results of PCR, the subjects were divided into four groups: Group I (CT positive, 63 cases), Group II (UU positive, 60 cases), Group III (CT positive and UU positive, 62 cases), and Group IV (no infection, 68 cases). DNA fragmentation index (DFI), sperm count, vitality and morphology, elastase level, seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Compared to Group IV, three groups (Group I, Group II and Group III) showed difference in semen volume, proportion of sperm with normal morphology, sperm motility, progressive motility, and vitality (P < 0.05). Compared to Group IV, Group II and Group III showed difference in DFI (P < 0.05). Compared to Group IV, Group II and Group III showed difference in elastase level(P < 0.05). VCL, VSL, VAP, WOB, ROS, TM, HDS showed differences between groups of abnormal/normal WBC (*P < 0.01).

UU infection significantly increased the level of seminal leukocytes only in Group II, but not in the other three groups, indicating that UU is a factor to increase the level of seminal leukocytes. Compared with the normal leukocyte group, there were significant differences in total motility, forward motility and normal sperm ratio between the two groups. The proportion of sperm with abnormal morphology (mostly in the head) showed obvious difference between groups of high and normal seminal leukocytic levels. At the same time, in this study, SCGE and SCD verified that leukocytes could damage sperm DNA by increasing ROS, which ultimately affects male fertility.
A novel surgical model for the preclinical assessment of the osseointegration of dental implants: a surgical protocol and pilot study results
Authors: AlOtaibi Noura M. , Dunne Michael , Ayoub Ashraf F. , Naudi Kurt B.
Published: June 2021

Background

Dental implants are considered the gold standard replacement for missing natural teeth. The successful clinical performance of dental implants is due to their ability to osseointegrate with the surrounding bone. Most dental implants are manufactured from Titanium and it alloys. Titanium does however have some shortcomings so alternative materials are frequently being investigated. Effective preclinical studies are essential to transfer the innovations from the benchtop to the patients. Many preclinical studies are carried out in the extra-oral bones of small animal models to assess the osseointegration of the newly developed materials. This does not simulate the oral environment where the dental implants are subjected to several factors that influence osseointegration; therefore, they can have limited clinical value.

Aim

This study aimed to develop an appropriatein-vivomodel for dental implant research that mimic the clinical setting. The study evaluated the applicability of the new model and investigated the impact of the surgical procedure on animal welfare.

Materials and methods

The model was developed in male New Zealand white rabbits. The implants were inserted in the extraction sockets of the secondary incisors in the maxilla. The model allows a split-mouth comparative analysis. The implants’ osseointegration was assessed clinically, radiographically using micro-computed tomography (µ-CT), and histologically. A randomised, controlled split-mouth design was conducted in 6 rabbits. A total of twelve implants were inserted. In each rabbit, two implants; one experimental implant on one side, and one control implant on the other side were applied. Screw-shaped implants were used with a length of 8 mm and a diameter of 2 mm.

Results

All the rabbits tolerated the surgical procedure well. The osseointegration was confirmed clinically, histologically and radiographically. Quantitative assessment of bone volume and mineral density was measured in the peri-implant bone tissues. The findings suggest that the new preclinical model is excellent, facilitating a comprehensive evaluation of osseointegration of dental implants in translational research pertaining to the human application.

Conclusion

The presented model proved to be safe, reproducible and required basic surgical skills to perform.
Interobserver variability in organ at risk delineation in head and neck cancer
Authors: van der Veen J. , Gulyban A. , Willems S. , Maes F. , Nuyts S.
Published: June 2021

Background

In radiotherapy inaccuracy in organ at risk (OAR) delineation can impact treatment plan optimisation and treatment plan evaluation. Brouwer et al. showed significant interobserver variability (IOV) in OAR delineation in head and neck cancer (HNC) and published international consensus guidelines (ICG) for OAR delineation in 2015. The aim of our study was to evaluate IOV in the presence of these guidelines.

Methods

HNC radiation oncologists (RO) from each Belgian radiotherapy centre were invited to complete a survey and submit contours for 5 HNC cases. Reference contours (OARref) were obtained by a clinically validated artificial intelligence-tool trained using ICG. Dice similarity coefficients (DSC), mean surface distance (MSD) and 95% Hausdorff distances (HD95) were used for comparison.

Results

Fourteen of twenty-two RO (64%) completed the survey and submitted delineations. Thirteen (93%) confirmed the use of delineation guidelines, of which six (43%) used the ICG. The OARs whose delineations agreed best with the OARref were mandible [median DSC 0.9, range (0.8–0.9); median MSD 1.1 mm, range (0.8–8.3), median HD95 3.4 mm, range (1.5–38.7)], brainstem [median DSC 0.9 (0.6–0.9); median MSD 1.5 mm (1.1–4.0), median HD95 4.0 mm (2.3–15.0)], submandibular glands [median DSC 0.8 (0.5–0.9); median MSD 1.2 mm (0.9–2.5), median HD95 3.1 mm (1.8–12.2)] and parotids [median DSC 0.9 (0.6–0.9); median MSD 1.9 mm (1.2–4.2), median HD95 5.1 mm (3.1–19.2)]. Oral cavity, cochleas, PCMs, supraglottic larynx and glottic area showed more variation. RO who used the consensus guidelines showed significantly less IOV (p = 0.008).

Conclusions

Although ICG for delineation of OARs in HNC exist, they are only implemented by about half of RO participating in this study, which partly explains the delineation variability. However, this study highlights that guidelines alone do not suffice to eliminate IOV and that more effort needs to be done to accomplish further treatment standardisation, for example with artificial intelligence.
New neural network classification method for individuals ancestry prediction from SNPs data
Authors: Soumare H. , Rezgui S. , Gmati N. , Benkahla A.
Published: June 2021

Artificial Neural Network (ANN) algorithms have been widely used to analyse genomic data. Single Nucleotide Polymorphisms(SNPs) represent the genetic variations, the most common in the human genome, it has been shown that they are involved in many genetic diseases, and can be used to predict their development. DevelopingANNto handle this type of data can be considered as a great success in the medical world. However, the high dimensionality of genomic data and the availability of a limited number of samples can make the learning task very complicated. In this work, we propose a New Neural Network classification method based on input perturbation. The idea is first to useSVDto reduce the dimensionality of the input data and to train a classification network, which prediction errors are then reduced by perturbing theSVDprojection matrix. The proposed method has been evaluated on data from individuals with different ancestral origins, the experimental results have shown the effectiveness of the proposed method. Achieving up to96.23%of classification accuracy, this approach surpasses previous Deep learning approaches evaluated on the same dataset.
Direct long-read RNA sequencing identifies a subset of questionable exitrons likely arising from reverse transcription artifacts
Authors: Schulz Laura , Torres-Diz Manuel , Cortés-López Mariela , Hayer Katharina E. , Asnani Mukta , Tasian Sarah K. , Barash Yoseph , Sotillo Elena , Zarnack Kathi , König Julian , Thomas-Tikhonenko Andrei
Published: June 2021

Resistance to CD19-directed immunotherapies in lymphoblastic leukemia has been attributed, among other factors, to several aberrantCD19pre-mRNA splicing events, including recently reported excision of a cryptic intron embedded withinCD19exon 2. While “exitrons” are known to exist in hundreds of human transcripts, we discovered, using reporter assays and direct long-read RNA sequencing (dRNA-seq), that theCD19exitron is an artifact of reverse transcription. Extending our analysis to publicly available datasets, we identified dozens of questionable exitrons, dubbed “falsitrons,” that appear only in cDNA-seq, but never in dRNA-seq. Our results highlight the importance of dRNA-seq for transcript isoform validation.
VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome
Authors: Lleó Alberto , Carmona-Iragui Maria , Videla Laura , Fernández Susana , Benejam Bessy , Pegueroles Jordi , Barroeta Isabel , Altuna Miren , Valldeneu Silvia , Xiao Mei-Fang , Xu Desheng , Núñez-Llaves Raúl , Querol-Vilaseca Marta , Sirisi Sònia , Bejanin Alexandre , Iulita M. Florencia , Clarimón Jordi , Blesa Rafael , Worley Paul , Alcolea Daniel , Fortea Juan , Belbin Olivia
Published: June 2021

Background

There is an urgent need for objective markers of Alzheimer’s disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression, and assess response to disease-modifying therapies. Previously, GluA4 and neuronal pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here, we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment.

Methods

We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF biomarkers, CSF Aβ42:40ratio, CSF Aβ1-42, CSF p-tau, and CSF NFL. P values were adjusted for multiple testing.

Results

In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recalladj.p= .04) and age (adj.p= .0008) and was the best correlate of CSF Aβ42:40(adj.p= .0001), p-tau (adj.p <.0001), and NFL (adj.p <.0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p= .02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4, and Syntaxin-1B all strongly correlated with NPTX2 (p< .0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p< .002).

Conclusion

These data show proof-of-concept for CSF VAMP-2 as a potential marker of synapse degeneration that correlates with CSF AD and axonal degeneration markers and cognitive performance.
Comparison of chondrogenesis-related biological behaviors between human urine-derived stem cells and human bone marrow mesenchymal stem cells from the same individual
Authors: Sun Jiachen , Xing Fei , Zou Min , Gong Min , Li Lang , Xiang Zhou
Published: June 2021

Background

Stem cells are the main choice for seed cells in tissue engineering, but using most traditional stem cells requires invasive and complicated procedures. Human urine-derived stem cells (hUSCs) are an alternative stem cell source with the advantages of being isolated noninvasively and repetitively from the same individual. The aim of this study was to compare chondrogenesis-related biological behaviors between hUSCs and human bone marrow mesenchymal stem cells (hBMSCs) from the same individual.

Methods

hUSCs and hBMSCs were isolated from six patients who underwent iliac bone grafting. Cell morphology, proliferation, colony-forming, migration, and multidifferentiation analyses were performed in vitro. Then, acellular cartilage extracellular matrix (ACM) scaffolds were fabricated for in vivo implantation. The comparisons of cell viability, morphology, proliferation, and chondrogenesis between hUSCs and hBMSCs cultured on scaffolds were performed before implantation. The scaffolds loaded with hUSCs or hBMSCs were implanted into a rabbit knee model to repair cartilage defects. Magnetic resonance imaging (MRI) and micro-computed tomography (μCT) Analyses, inflammation and toxicity assays, gross observation, and histological evaluation were performed to evaluate the cartilage repair effects.

Results

In in vitro experiments, hUSCs had better capacity for proliferation, colony-forming, and migration compared to hBMSCs in the same passage, while hBMSCs had greater osteogenic, adipogenic, and chondrogenic abilities compared to hUSCs in the same passage. Both hUSCs and hBMSCs at passage 3 had the strongest potential for proliferation, colony-forming, and multilineage differentiation compared to cells in other passages. The ACM scaffolds loaded with hUSCs or hBMSCs both significantly promoted the repair of cartilage defects in the rabbit knee model at 12 weeks’ postimplantation, and the new tissue was mainly hyaline cartilage. However, there was no significant difference in cartilage repair effects between hUSCs and hBMSCs.

Conclusions

In in vitro experiments, hUSCs presented better capacity for proliferation, while hBMSCs had greater chondrogenic ability. However, hUSCs and hBMSCs had similar cartilage repair effects in vivo. Results indicated that hUSCs can be a stem cell alternative for cartilage regeneration and provide a powerful platform for cartilage tissue engineering and clinical transformation.

Graphical abstract
Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy
Authors: Tseng Wei-Cheng , Lee Pei-Ying , Tsai Ming-Tsun , Chang Fu-Pang , Chen Nien-Jung , Chien Chiang-Ting , Hung Shih-Chieh , Tarng Der-Cherng
Published: June 2021

Background

Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear.

Methods

Renal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI.

Result

HMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1β, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery.

Conclusion

The present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.