bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world clinical outcomes following treatment intensification with GLP-1 RA, OADs or insulin in patients with type 2 diabetes on two oral agents (PATHWAY 2-OADs)
Authors: Desouza Cyrus , Kirk Andreas R , Mangla Kamal K , Wolden Michael L , Lingvay Ildiko
Published: December 2020

Introduction

Most patients with type 2 diabetes require sequential addition of glucose-lowering agents to maintain long-term glycemic control. In this retrospective, observational study, we compared intensification with a glucagon-like peptide-1 receptor agonist (GLP-1 RA), oral antidiabetic drugs (OADs), and insulin in patients receiving two OADs, using US electronic health records and claims data.

Research design and methods

For inclusion, patients in the IBM MarketScan Explorys database were required to have claims for two different OADs in the 180-day baseline period and ≥1 claim for a different OAD/GLP-1 RA/insulin at index date (treatment intensification). Changes in glycated hemoglobin (HbA1c) and weight from baseline were assessed at 180 days postindex. Patients were propensity score-matched by baseline characteristics and exact-matched by HbA1ccategory (HbA1ccohort and weight/composite outcomes cohort) and body mass index (BMI) category (weight/composite outcomes cohort only) to obtain balanced treatment arms. The primary endpoint was the percentage of patients reaching target HbA1c<7% (53 mmol/mol).

Results

Significantly more patients intensifying with a GLP-1 RA achieved HbA1c<7% than those receiving OAD(s) (OR: 1.35; 95% CI 1.03 to 1.77; p=0.032) or insulin (OR: 1.77; 95% CI 1.27 to 2.47; p<0.001). GLP-1 RAs were also associated with a significantly greater chance of not gaining weight; significantly greater HbA1cand weight decreases from baseline; and a significantly greater chance of HbA1c<7%, no weight gain and discontinuation of ≥1 baseline OAD (composite outcome), compared with OAD(s) or insulin.

Conclusions

In propensity score-matched cohorts, GLP-1 RAs demonstrated significant benefits for both glycemic control and weight management over additional OAD(s) or insulin, respectively, indicating that they may represent the optimal choice at these points in the treatment pathway.
Gap between real-world data and clinical research within hospitals in China: a qualitative study
Authors: Jin Feifei , Yao Chen , Yan Xiaoyan , Dong Chongya , Lai Junkai , Li Li , Wang Bin , Tan Yao , Zhu Sainan
Published: December 2020

Objective

To investigate the gap between real-world data and clinical research initiated by doctors in China, explore the potential reasons for this gap and collect different stakeholders’ suggestions.

Design

This qualitative study involved three types of hospital personnel based on three interview outlines. The data analysis was performed using the constructivist grounded theory analysis process.

Setting

Six tertiary hospitals (three general hospitals and three specialised hospitals) in Beijing, China, were included.

Participants

In total, 42 doctors from 12 departments, 5 information technology managers and 4 clinical managers were interviewed through stratified purposive sampling.

Results

Electronic medical record data cannot be directly downloaded into clinical research files, which is a major problem in China. The lack of data interoperability, unstructured electronic medical record data and concerns regarding data security create a gap between real-world data and research data. Updating hospital information systems, promoting data standards and establishing an independent clinical research platform may be feasible suggestions for solving the current problems.

Conclusions

Determining the causes of gaps and targeted solutions could contribute to the development of clinical research in China. This research suggests that updating the hospital information system, promoting data standards and establishing a clinical research platform could promote the use of real-world data in the future.
Poor treatment outcomes of children on highly active antiretroviral therapy: protocol for a systematic review and meta-analysis
Authors: Atalell Kendalem Asmare , Alene Kefyalew Addis
Published: December 2020

Introduction

While access to highly active antiretroviral therapy (HAART) for children with HIV has expanded and the use of HAART has substantially reduced the morbidity and mortality of children due to HIV, poor treatment outcomes among children with HIV are still a major public health problem globally. The aim of this systematic review and meta-analysis is to quantify treatment outcomes among children with HIV.

Methods and analysis

Systematic searches will be conducted in three electronic databases (PubMed, SCOPUS and Web of Science) for recent studies published from 01 Jan 2000 up to 28 October 2020, without geographical restriction. The primary outcomes of the study will be poor treatment outcomes, which include death, treatment failure and loss to follow-up. We will include quantitative studies that report treatment outcomes among children under the age of 18 years with HIV. Studies will be excluded if they are case report, case series, conducted among adults only or do not provide data on treatment outcomes for children. Two researchers will screen the titles and abstracts of all citations identified in our search, then review the full text of the remaining papers to identify those that meet the inclusion criteria. The Newcastle–Ottawa Scale will be used for quality assessment. A random-effects meta-analysis will be used to obtain pooled estimates of the proportion of poor treatment outcomes. The heterogeneity between studies will be checked visually by using forest plots and quantitatively measured by the index of heterogeneity (I2). Pooled estimates of poor treatment outcomes will be calculated with a random-effects model. Subgroup analysis will be conducted by study settings, treatment regimen, comorbidity (such as tuberculosis), study period and HIV type (HIV-1 and HIV-2).

Ethics and dissemination

Ethical approval will not be required for this study as it will be based on published papers. The final report of this review will be published in a peer-reviewed scientific journal.
Gender-specific physical activity-related injuries and risk factors among university students in China: a multicentre population-based cross-sectional study
Authors: Cai Weicong , Chen Shangmin , Li Liping , Yue Pengying , Yu Xiaofan , Gao Lijie , Yang Wenda , Jia Cunxian , Gao Yang
Published: December 2020

Objectives

Data on the problem of physical activity-related injury (PARI) in university students and the risk factors for PARI among different genders are rare. We conducted a multicentre population-based study to investigate the occurrence of PARI and to explore the gender-specific risk factors for PARI among Chinese university students.

Design

Cross-sectional study.

Participants

A total of 5341 students in grades 1–3 at eight universities in four Chinese cities were selected to complete the online questionnaires during March and April 2017. The questionnaires assessed sociodemographic characteristics, physical activity PA) involvement, sleep duration, sedentary behaviour and PARI experiences in the past 12 months.

Main outcome measures

PARI during the past 12 months.

Results

Among the 5341 participants, 1293 suffered from at least one PARI in the past 12 months, with an overall incidence rate of 24.2% (males: 26.2%, females: 23.2%) and an injury risk of 0.38 injuries/student/year (males: 0.48, females: 0.32). Over half of the injured (57.3%) experienced a withdrawal time of PA and nearly two-fifths (39.6%) required medical attention. Irrespective of gender, Shantou and Xi’an students, sports team members and those who engaged in sports and leisure-time vigorous-intensity PA (VPA) at a higher frequency were more likely to suffer from PARI. Male students who participated in sports and leisure-time VPA for long durations had a greater likelihood of sustaining PARI, while having a chronic condition and being involved in sports and leisure-time moderate-intensity PA at a higher frequency and longer duration were potential contributors to PARI among females.

Conclusions

The occurrence of PARI and its risk factors differed by gender, which provides a direction towards developing targeted and effective gender-specific preventative programmes to protect Chinese university students from PARI.
Continuity of care: evaluating a multidisciplinary care model for people with early CKD via a nationwide population-based longitudinal study
Authors: Chen Yin-Cheng , Weng Shuen-Fu , Hsu Yu-Juei , Wei Chung-Jen , Chiu Chiung-hsuan
Published: December 2020

Objectives

To control and prevent the burdens associated with chronic kidney disease (CKD), Taiwan’s National Health Insurance Administration (NHIA) launched the ‘early-CKD programme’ in 2011 to extend care and education to patients with CKD. This study aims to evaluate the effectiveness of the early-CKD programme in terms of continuity of care (COC).

Design and participants

This study used secondary data from 2010 to 2014 provided by the NHIA to identify 86 581 participants each for the intervention and control groups. Patients with CKD who participated in the early-CKD programme between 2011 and 2013 were defined as the intervention group. For the control group, propensity score matching was used to select patients with CKD who did not participate in the programme, but were seen by the same group of physicians.

Intervention

A multidisciplinary care model for patients with early CKD launched in 2011.

Primary outcome measures

Outcome variables included the continuity of care index (COCI), which measures a physician’s COC; number of essential examinations; and resource utilisation. To better identify the difference between groups, we separated COCI into two groups based on mean: high (above mean) and low (below mean). A generalised estimating equation model was used to examine the effects of the early-CKD programme.

Results

The programme significantly increased the number of essential examinations/tests administered to patients (β=0.61, p<0.001) and improved COCI between physicians and patients (OR=4.18, p<0.001). Medical expenses (β=1.03, p<0.001) and medication expenses (β=0.23, p<0.001) significantly increased after the programme was implemented, but patients’ kidney-related hospitalisations and emergency department visits decreased (β=−0.13, p<0.001).

Conclusion

From the COC viewpoint, the programme in Taiwan showed a positive effect on COCI, number of essential examinations and resource utilisation.
Uptake of provider-initiated HIV and syphilis testing among heterosexual STD clinic patients in Guangdong, China: results from a cross-sectional study
Authors: Zhao Peizhen , Tang Weiming , Cheng Huanhuan , Huang Shujie , Zheng Heping , Yang Bin , Wang Cheng
Published: December 2020

Objectives

Underscreening of HIV and syphilis in clinical settings is pervasive in resource-constrained settings. Heavy patient loads and competing health priorities in these settings inhibit provider’s ability to meet screening coverage targets. The objective of this study was to examine determinants of provider-initiated HIV and syphilis testing uptake at sexually transmitted disease (STD) clinics in China.

Design

A cross-sectional study was performed between July 2016 and December 2016.

Setting

Seven STD clinics in Guangdong Province, China.

Participants

Heterosexual STD clinic patients met the inclusion criteria, regardless of their interest in receiving HIV or syphilis testing.

Outcome measures

The syphilis and HIV testing uptake determined by patient receipt of results.

Results

A total of 1943 individuals were recruited in this study. Among those participants, 60.6% (1177/1943) and 74.3% (1443/1943) conducted HIV testing and syphilis testing during the study, respectively, of whom, 2.2% (26/1177) and 21.5% (310/1443) were found to be HIV-positive and syphilis-positive, respectively. The most common reason for rejecting HIV and syphilis testing was a low self-perceived risk of HIV and syphilis infection. After adjusting for covariates, condom use in the last sexual act, consistent condom use in the last 6 months, having paid sex in the last 6 months and having received any kind of HIV/STD-related knowledge during the last 12 years were positively associated with both HIV and syphilis testing uptake.

Conclusions

The low-level of HIV and syphilis testing uptake, alongside with the high-level of engagement in risky sexual behaviours among heterosexual STD clinic patients, warranted a more targeted and intensive behavioural interventions to promote HIV and syphilis testing in this population.
Cross-sectional association between long working hours and liver function: the Kangbuk Samsung Health Study
Authors: Mun Eunchan , Lee Woncheol , Nam Min-Woo , Kim Hyun-Il , Kim Hyeongcheol , Lee Yesung , Park Soyoung
Published: December 2020

Objectives

Although the effects of long working hours on liver function remain unclear, in South Korea, there is a social perception that long working hours are associated with poor liver function. Thus, long working hours have recently become a major issue. This study aimed to determine the association between long working hours and liver function, as indicated by the alanine transaminase (ALT) levels.

Design

Cross-sectional study.

Setting

Large university hospitals in Seoul and Suwon, South Korea.

Participants

Workers in formal employment who underwent a comprehensive health examination at the Kangbuk Samsung Hospital Total Healthcare Centre clinics in Seoul and Suwon, South Korea, between January 2011 and December 2018. Of the 386 488 participants, 212 421 met the inclusion criteria and were included in the analysis.

Primary outcome measure

ALT elevation.

Results

The participants were predominantly well-educated (86.1%), male (69.3%) and in their 30s (49.6%). In total, 13.4% of the participants presented ALT elevation (>40 IU/L). There was no significant association between working hours and ALT elevation in the general population and in the hepatitis B surface antigen (HBsAg)-negative group. Conversely, in the HBsAg-positive group, working >60 hours per week compared with 35–40 hours per week was significantly associated with ALT elevation. The association was more pronounced in those with ALT levels >80 IU/L (OR 1.94, 95% CI 1.24 to 3.01) than in those with ALT levels >40 IU/L (OR: 1.45, 95% CI 1.20 to 1.75). The p values for trend were <0.05.

Conclusions

Long working hours were associated with ALT elevation only in hepatitis B virus carriers and not in the general population. Provided that there is adherence to the legal working hours, there is no need to further restrict working hours for liver health, irrespective of HBsAg status.
Randomised placebo-controlled multicentre effectiveness trial of adjunct betamethasone therapy in hospitalised children with community-acquired pneumonia: a trial protocol for the KIDS-STEP trial
Authors: Kohns Vasconcelos Malte , Meyer Sauteur Patrick M , Santoro Regina , Coslovsky Michael , Lurà Marco , Keitel Kristina , Wachinger Tanja , Beglinger Svetlana , Heininger Ulrich , van den Anker Johannes , Bielicki Julia Anna
Published: December 2020

Introduction

Community-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids.

Methods and analysis

The KIDS-STEP trial is a multicentre, randomised, double-blind, placebo-controlled superiority trial of betamethasone treatment on outcome of hospitalised children with CAP. Children are enrolled in paediatric emergency departments of hospitals across Switzerland and randomised to adjunct oral betamethasone for 2 days or matching placebo in addition to standard of care treatment. The co-primary outcomes are the proportion of children clinically stable 48 hours after randomisation and the proportion of children with CAP-related readmission within 28 days after randomisation. Secondary outcomes include length of hospital stay, time away from routine childcare and healthcare utilisation and total antibiotic prescriptions within 28 days from randomisation.

Each of the co-primary outcomes will be analysed separately. We will test clinical stability rates using a proportion test; to test non-inferiority in readmission rates, we will construct 1−α % CI of the estimated difference and test if it contains the pre-defined margin of 7%. Success is conditional on both tests. A simulation-based sample size estimation determined that recruiting 700 patients will ensure a power of 80% for the study.

Ethics and dissemination

The trial protocol and materials were approved by ethics committees in Switzerland (lead: Ethikkommission Nordwest und Zentralschweiz) and the regulatory authority Swissmedic. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.

Trial registration number

NCT03474991and SNCTP000002864.
Burden of diabetic macular oedema in patients receiving antivascular endothelial growth factor therapy in South Korea: a healthcare resource use and cost analysis
Authors: Jeon Ha-Lim , Lee Hyesung , Yoon Dongwon , Lee Yeonkyung , Kim Jae Hui , Jee Donghyun , Shin Ju-Young
Published: December 2020

Objective

To examine healthcare resource utilisation (HRU) and direct medical costs for patients with diabetic macular oedema (DME) treated with antivascular endothelial growth factor (anti-VEGF) in Korea by comparing with those for (1) patients with diabetes mellitus (DM) without retinopathy and (2) patients with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF.

Design

Retrospective cohort study.

Setting

The Korean National Health Insurance (NHI) database from 1 January 2014 to 31 December 2016.

Participants

We identified 1398 patients older than 30 years of age who received anti-VEGF treatment for DME in 2015 after excluding patients who had a diagnosis of nAMD in 2015 and any cancer in the preceding year.

Main outcome measures

One-year healthcare resource use and direct medical costs of patients with DME treated with anti-VEGF.

Results

In total, 1398 patients with DME receiving anti-VEGF, 12 813 patients with DM without retinopathy and 12 222 patients with nAMD receiving anti-VEGF were identified. Hospital admissions and outpatient visits were highest in patients with DME, while the number of licensed anti-VEGF injections in those with DME was about half that of those with nAMD (2.1 vs 3.9 per patient per year). Mean 1-year medical costs were also higher in patients with DME (US$6723) than in those with DM without retinopathy (US$2687) and nAMD (US$4980). In a multivariable analysis with matched cohorts, DME was associated with 66% higher medical costs for comorbid diseases (adjusted OR (aOR), 1.66; 95% CI 1.45 to 1.90) and 50% lower anti-VEGF injections (aOR, 0.50; 95% CI 0.46 to 0.54) compared with nAMD.

Conclusions

The overall HRU and economic burden for DME treated with anti-VEGF were higher than for DM without retinopathy or for nAMD treated with anti-VEGF. Meanwhile, the lower number of licensed anti-VEGF injections compared with nAMD may reflect a potential lack of ophthalmological treatment for DME supported by the NHI in Korea.
Indigenous communities’ responses to the COVID-19 pandemic and consequences for maternal and neonatal health in remote Peruvian Amazon: a qualitative study based on routine programme supervision
Authors: Reinders Stefan , Alva Angela , Huicho Luis , Blas Magaly M
Published: December 2020

Aim

To explore indigenous communities’ responses to the COVID-19 pandemic and its consequences for maternal and neonatal health (MNH) care in the Peruvian Amazon.

Methods

Mamás del Río is a community-based, MNH programme with comprehensive supervision covering monthly meetings with community health workers (CHW), community leaders and health facilities. With the onset of the lockdown, supervisors made telephone calls to discuss measures against COVID-19, governmental support, CHW activities in communities and provision of MNH care and COVID-19 preparedness at facilities. As part of the programme’s ongoing mixed methods evaluation, we analysed written summaries of supervisor calls collected during the first 2 months of Peru’s lockdown.

Results

Between March and May 2020, supervisors held two rounds of calls with CHWs and leaders of 68 communities and staff from 17 facilities. Most communities banned entry of foreigners, but about half tolerated residents travelling to regional towns for trade and social support. While social events were forbidden, strict home isolation was only practised in a third of communities as conflicting with daily routine. By the end of April, first clusters of suspected cases were reported in communities. COVID-19 test kits, training and medical face masks were not available in most rural facilities. Six out of seven facilities suspended routine antenatal and postnatal consultations while two-thirds of CHWs resumed home visits to pregnant women and newborns.

Conclusions

Home isolation was hardly feasible in the rural Amazon context and community isolation was undermined by lack of external supplies and social support. With sustained community transmission, promotion of basic hygiene and mask use becomes essential. To avoid devastating effects on MNH, routine services at facilities need to be urgently re-established alongside COVID-19 preparedness plans. Community-based MNH programmes could offset detrimental indirect effects of the pandemic and provide an opportunity for local COVID-19 prevention and containment.
Secondhand smoke (SHS) exposure before and after the implementation of the Tobacco Free Cities (TFC) initiative in five Chinese cities: a pooled cross-sectional study
Authors: Duan Zongshuan , Wang Yu , Huang Jidong , Redmon Pamela B , Eriksen Michael P
Published: December 2020

Objectives

To assess the levels of secondhand smoke (SHS) exposure before and after the implementation of the Tobacco Free Cities (TFC) initiative.

Design

City-wide representative, cross-sectional surveys (Tobacco Questions for Surveys, TQS) were conducted in each participating city before and after the implementation of TFC.

Setting

Five large Chinese cities (Chengdu, Chongqing, Wuhan, Xiamen and Xi’an) participated in the TFC initiative.

Participants

A total of 10 184 adults participated in the 2015 TQS survey, and 10 233 adults participated in the 2018 TQS survey, respectively.

Interventions

The TFC initiative, which included targeted media campaigns, educational programmes, implementing city-wide smoke-free policies and providing cessation interventions, was implemented in these five cities between 2015 and 2018.

Main outcome

Self-reported past 30-day (P30D) SHS exposure in indoor workplaces, restaurants and homes.

Data analysis

The pre-TFC and post-TFC SHS exposure levels were compared among all residents and among certain population subgroups. Multivariate logistic regressions were used to estimate the adjusted associations between P30D SHS exposure and individual characteristics.

Results

Across all five cities, the overall rate of self-reported P30D SHS exposure declined in indoor workplaces (from 49.6% (95% CI: 46.4% to 52.8%) to 41.2% (95% CI: 37.7% to 44.7%)), restaurants (from 72.4% (95% CI: 69.8% to 74.9%) to 61.7% (95% CI: 58.7% to 64.7%)) and homes (from 39.8% (95% CI: 36.9% to 42.7%) to 34.7% (95% CI: 31.5% to 37.8%)) from 2015 to 2018. These declines were statistically significant after controlling for individual characteristics. The P30D SHS exposure was associated with sex, age, education level, occupation and current smoking status. The associations varied by venues.

Conclusions

Our analysis showed that compared with the nationwide SHS exposure levels reported in concurrent national surveys, the declines in P30D SHS exposure in five Chinese cities that implemented the TFC initiative were larger in indoor workplaces and restaurants. Our findings suggest that the TFC initiative was effective in reducing SHS exposure in Chinese cities.
Exercise training modalities for heart transplant recipients: a systematic review and network meta-analysis protocol
Authors: de Lima Juliana Beust , Soares Douglas dos Santos , Ferrari Filipe , Carvas Junior Nelson , Carvalho Gabriel , Tobar Leitão Santiago Alonso , Goldraich Lívia Adams , Clausell Nadine , Stein Ricardo
Published: December 2020

Introduction

Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients.

Methods and analysis

We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.govand REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository.

Ethics and dissemination

Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal.

PROSPERO registration number

CRD42020191192.
Masculinising testosterone treatment and effects on preclinical cardiovascular disease, muscle strength and power, aggression, physical fitness and respiratory function in transgender men: protocol for a 10-year, prospective, observational cohort study in Denmark at the Body Identity Clinic (BIC)
Authors: Lehmann Christensen Louise , Glintborg Dorte , Taulbjerg Kristensen Tine , Diederichsen Axel , T’Sjoen Guy , Frystyk Jan , Skovsager Andersen Marianne
Published: December 2020

Introduction

The number of individuals with gender dysphoria seeking gender-affirming treatment is increasing. The short-term and long-term effects of masculinising treatment with testosterone are debated as serum testosterone increases up to 20-fold compared with cisgender women. We will investigate short-term and long-term effects of masculinising testosterone treatment on preclinical and clinical coronary disease, muscle strength and power, oxygen consumption (VO2) max, cardiac and respiratory function and quality of life including aggression in transgender men.

Methods and analyses

Prospective, single-centre, observational cohort study at the Body Identity Clinic (BIC), Odense University Hospital, Denmark. Investigations are performed at inclusion and following 1, 3, 5 and 10 years of testosterone therapy. Non-calcified coronary plaque volume and calcium score are estimated by coronary CT angiography. CT is only performed at inclusion and following 1 and 10 years. Upper body muscle strength and power are measured by a ‘low row’ weight stack resisted exercise machine. Evaluation of aggression and quality of life is assessed by questionnaires, VO2max is estimated by maximal testing on bike ergometer, and cardiac and respiratory functions are measured by echocardiography and spirometry, respectively. Markers of cardiovascular risk and inflammation and also cortisol and cortisone are assessed in blood, diurnal urine and/or hair samples. Our cohort (BIC), including dropouts, will be an embedded subcohort in a future national registry study in all individuals with gender dysphoria and controls. Data are available on International Statistical Classification of Diseases and Related Health Problems 10thversion diagnostic codes, prescriptions, socioeconomics and causes of death.

Ethics and dissemination

The Regional Committee on Health Research Ethics for Southern Denmark (S-20190108) and the Danish Data Protection Agency (19/27572) approved the study. Signed informed consent will be obtained from all participants. All findings will be published in peer-reviewed journals or at scientific conferences.

Trial registration number

NCT04254354.
Antiglycolipid antibodies in Guillain-Barré and Fisher syndromes: discovery, current status and future perspective
Authors: Kusunoki Susumu , Willison Hugh J , Jacobs Bart C
Published: December 2020

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are acute autoimmune neuropathies, often preceded by an infection. Antiglycolipid antibody titres are frequently elevated in sera from the acute-phase patients. Particularly, IgG anti-GQ1b antibodies are positive in as high as 90% of FS cases and thus useful for diagnosis. The development of animal models of antiglycolipid antibody-mediated neuropathies proved that some of these antibodies are directly involved in the pathogenetic mechanisms by binding to the regions where the respective target glycolipid is specifically localised. Discovery of the presence of the antibodies that specifically recognise a new conformational epitope formed by two different gangliosides (ganglioside complex) in the acute-phase sera of some patients with GBS suggested the carbohydrate–carbohydrate interaction between glycolipids. This finding indicated the need for further research in basic glycobiological science. Antiglycolipid antibodies, in particular antigangliosides antibodies, are mostly detected in acute motor axonal neuropathy type of GBS and in FS, and less frequently in the acute inflammatory demyelinating polyneuropathy (AIDP) type of GBS or in central nervous system (CNS) diseases. In the future, the search for the putative antibodies in AIDP and those that might be present in CNS diseases should continue. In addition, more efficient standardisation of antiglycolipid antibody detection methods and use as biomarkers in daily clinical practice in neurology is needed.
Refractory CIDP with chronic lymphocytic leukaemia responding to chemoimmunotherapy
Authors: Lewis Dana , Osman Chinar , Allen David , Pinto Ashwin Arnold , Duncombe Andrew , Katifi Haider A
Published: December 2020

Chronic inflammatory demyelinating polyneuropathy (CIDP) has a variable clinical course with 15% remaining refractory to treatment. We report a woman with severe refractory CIDP and coexisting chronic lymphocytic leukaemia (CLL) who improved dramatically after chemoimmunotherapy appropriate for the CLL, including rituximab. A subsequent CIDP relapse after 15 months responded again to similar treatment, and the improvement has been maintained with 3-monthly rituximab infusions as sole ongoing therapy. The case suggests that CIDP refractory to conventional treatment may have associated pathology, in this case haematological malignancy, and that treating the malignancy can effectively treat the CIDP.
Quantum corrections to the accretion onto a Schwarzschild black hole in the background of quintessence
Authors: Nozari Kourosh , Hajebrahimi Milad , Saghafi Sara
Published: December 2020

It is well known that quantum effects may lead to removal of the intrinsic singularity point of back holes. Also, the quintessence scalar field is a candidate model for describing late-time acceleration expansion. Accordingly, Kazakov and Solodukhin considered the existence of back-reaction of the spacetime due to the quantum fluctuations of the background metric to deform a Schwarzschild black hole, which led to a change of the intrinsic singularity of the black hole to a 2-sphere with a radius of the order of the Planck length. Also, Kiselev rewrote the Schwarzschild metric by taking into account the quintessence field in the background. In this study, we consider the quantum-corrected Schwarzschild black hole inspired by Kazakov–Solodukhin’s work, and the Schwarzschild black hole surrounded by quintessence deduced by Kiselev to study the mutual effects of quantum fluctuations and quintessence on the accretion onto the black hole. Consequently, the radial component of the 4-velocity and the proper energy density of the accreting fluid have a finite value on the surface of its central 2-sphere due to the presence of quantum corrections. Also, by comparing the accretion parameters in different kinds of black holes, we infer that the presence of a point-like electric charge in the spacetime is somewhat similar to some quantum fluctuations in the background metric.
Matter accretion onto a conformal gravity black hole
Authors: Abbas G. , Ditta A.
Published: December 2020

The accretion of test fluids flowing onto a black hole is investigated. Particularly, by adopting a dynamical Hamiltonian approach, we are capable to find the critical points for various cases of black hole in conformal gravity. In these cases, we have analyzed the general solutions of accretion employing the isothermal equations of state. The steady state and spherically symmetric accretion of different test fluids onto the conformal gravity black hole has been considered. Further, we have classified these flows in the context of equations of state and the cases of conformal gravity black hole. The new behavior of polytropic fluid accretion is also discussed in all three cases of black hole. Black hole mass accretion rate is the most important part of this research in which we have investigated that the Schwarzschild black hole produce a typical signature than the conformal gravity black hole and Schwarzschild–de Sitter black hole. The critical fluid flow and the mass accretion rate have been presented graphically by the impact parameters $$\beta $$
β
, $$\gamma $$
γ
, k and these parameters have great significance. Additionally, the maximum mass rate of accretion fall near the universal and Killing horizons and minimum rate of accretion occurs in between these regions. Finally, the results are compared with the different cases of black hole available in the literature.
Regular Expressions and Transducers Over Alphabet-Invariant and User-Defined Labels
Authors: Konstantinidis Stavros , Moreira Nelma , Reis Rogério , Young Joshua
Published: December 2020

We are interested in regular expressions and transducers that represent word relations in an alphabet-invariant way — for example, the set of all word pairs [Formula: see text] where [Formula: see text] is a prefix of [Formula: see text] independently of what the alphabet is. Current software systems of formal language objects do not have a mechanism to define such objects. We define transducers in which transition labels involve what we call set specifications, some of which are alphabet invariant. In fact, we give a more broad definition of automata-type objects, called labelled graphs, where each transition label can be any string, as long as that string represents a subset of a certain monoid. Then, the behavior of the labelled graph is a subset of that monoid. We do the same for regular expressions. We obtain extensions of a few classic algorithmic constructions on ordinary regular expressions and transducers at the broad level of labelled graphs and in such a way that the computational efficiency of the extended constructions is not sacrificed. For transducers with set specs we obtain further algorithms that can be applied to questions about independent regular languages as well as a decision question about synchronous transducers.
Mori ramulus and its Major Component Morusin Inhibit Herpes Simplex Virus Type 1 Replication and the Virus-Induced Reactive Oxygen Species
Authors: Kim Tae In , Kwon Eun-Bin , Oh You-Chang , Go Younghoon , Choi Jang-Gi
Published: December 2020

Herpes simplex virus type 1 (HSV-1) is ubiquitous in many populations despite the use of acyclovir or related nucleoside analogs for treating infection. Drug resistance impairs the treatment of HSV-infected individuals who have immune deficits, underscoring the need for new safe and effective antiviral agents. Mori ramulus (the young twig of Morus alba L.) has long been used to treat diseases in Korea, Japan, and China. Recent studies have reported multiple pharmacological activities of Mori ramulus and its constituent morusin, but their effects on HSV-1 remain unknown. Here, we found that treatment with Mori ramulus ethanol extract (MRE) significantly reduced the replication of fluorescently labeled HSV-1 in Vero cells and inhibited the expression of HSV-1 envelope glycoprotein D (gD) and tegument protein VP16. MRE, furthermore, blocked HSV-1-induced production of reactive oxygen species (ROS), and this mediated the inhibition of viral replication. We identified morusin as the active antiviral component of MRE and found that morusin post-treatment was sufficient to inhibit viral gD and VP16 in addition to HSV-1-induced ROS production. Therefore, the inhibition of HSV-1-induced ROS may explain the antiviral activity of MRE against HSV-1. MRE or its component morusin may be potentially developed for anti-HSV-1 agents.
Gossypol Reduces Metastasis and Epithelial-Mesenchymal Transition by Targeting Protease in Human Cervical Cancer
Authors: Hsieh Yih-Shou , Chu Shu-Chen , Huang Shih-Chien , Kao Shao-Hsuan , Lin Meng-Shuan , Chen Pei-Ni
Published: December 2020

Metastasis is the most prevalent cause of cancer-associated deaths amongst patients with cervical cancer. Epithelial–mesenchymal transition (EMT) is essential for carcinogenesis, and it confers metastatic properties to cancer cells. Gossypol is a natural polyphenolic compound with anti-inflammation, anti-oxidant, and anticancer activities. In this study, we investigated the antimetastatic and antitumour effects of gossypol on human cervical cancer cells (HeLa and SiHa cells). Gossypol exerted a strong inhibition effect on the migration and invasion of human cervical cancer cells. It reduced the focal adhesion kinase (FAK) pathway-mediated expression of matrix metalloproteinase-2 and urokinase-type plasminogen activator, subsequently inhibiting the invasion of SiHa cells. In addition, gossypol reversed EMT induced by transforming growth factor beta 1 (TGF-[Formula: see text]1) and up-regulated epithelial markers, such as E-cadherin but significantly suppressed Ras homolog family member (Rho)A, RhoB, and p-Samd3. The tail vein injection model showed that gossypol treatment via oral gavage reduced lung metastasis. Gossypol also decreased tumour growth in vivo in the nude mouse xenograft model. All these findings suggest that gossypol suppressed the invasion and migration of human cervical cancer cells by targeting the FAK signaling pathway and reversing TGF-[Formula: see text]1-induced EMT. Hence, gossypol warrants further attention for basic mechanistic studies and drug development.
Deterministic interface modes in two-dimensional acoustic systems
Authors: huo Shao-Yong , Huang Hong-Bo , Wang Lin-Jun , Chen Jiu-Jiu
Published: December 2020

The interface state in two-dimensional (2D) sonic crystals (SCs) was obtained based on trying or cutting approach, which greatly limits its practical applications. In this paper, we theoretically demonstrate that one category of interface states can deterministically exist at the boundary of two square-lattice SCs due to the geometric phase transitions of bulk bands. First, we derive a tight-binding formalism for acoustic waves and introduce it into the 2D case. Furthermore, the extended 2D Zak phase is employed to characterize the topological phase transitions of bulk bands. Moreover, the topological interface states can be deterministically found in the nontrivial bandgap. Finally, two kinds of SCs with the [Formula: see text] symmetry closely resembling the 2D Su–Schrieffer–Heeger (SSH) model are proposed to realize the deterministic interface states. We find that tuning the strength of intermolecular coupling by contacting or expanding the scatterers can effectively induce the bulk band inversion between the trivial and nontrivial crystals. The presence of acoustic interface states for both cases is further demonstrated. These deterministic interface states in 2D acoustic systems will be a great candidate for future waveguide applications.
Salinity and temperature detection for seawater based on a 1D-defective photonic crystal material
Authors: Qutb Sameeha R. , Aly Arafa H. , Sabra Walied
Published: December 2020

In this work, we demonstrate the sensing principle to simultaneously detect the salinity and temperature of seawater using a 1D-defective photonic crystal structure. We designed a one-dimensional defective mode photonic crystal based on the well-known transfer matrix method (TMM) for detecting the seawater salinity and temperature. Our proposed optical sensor is based on the following concept. Since the concentration of the salinity in the seawater changes the refractive index of the seawater, the sensitivity can be calculated by a peak wavelength shift happening in the output transmission spectrum for its variation of different concentration of samples. By adjusting the design parameters of our proposed structure such as the thickness of the defect layer, the temperature and the salinity, we investigated the corresponding optical properties response where the resulted transmittance peak can be turned over the considered range.
3-Manifolds with nilpotent embeddings in S4
Authors: Hillman J. A.
Published: December 2020

We consider embeddings of 3-manifolds [Formula: see text] in [Formula: see text] such that the two complementary regions [Formula: see text] and [Formula: see text] each have nilpotent fundamental group. If [Formula: see text] is odd then these groups are abelian and [Formula: see text]. In general [Formula: see text] and [Formula: see text] have 3-generator presentations, and [Formula: see text]. We give two examples illustrating our results.
GENERALIZED SYNCHRONIZATION AND PARAMETERS IDENTIFICATION OF DIFFERENT-DIMENSIONAL CHAOTIC SYSTEMS IN THE COMPLEX FIELD
Authors: LIU JIAN , CHEN GUANRONG , ZHAO XIU
Published: December 2020

Generalized synchronization is a typical dynamical phenomenon in nonlinear systems, for which the real-valued setting has been widely investigated. The complex-valued functions relationship in generalized synchronization is equally important for complex-valued dynamical systems, which however are seldom studied. Complex parameters identification on the synchronization manifold remains an open problem owing to the absence of the persistent excitation (PE) condition in the complex field. This paper investigates generalized synchronization via a complex-valued vector mapping (CGS) for different-dimensional complex-variable chaotic (hyper-chaotic) systems (CVCSs) with complex parameters identification. Based on Lyapunov stability theory in the complex field and using an adaptive control method, some sufficient criteria are established to achieve CGS for CVCSs. Moreover, some necessary and sufficient criteria are derived to ensure complex parameters identification. Finally, the theoretical results are verified and demonstrated by reduced-order and increased-order simulation examples.
HERMITE–HADAMARD TYPE LOCAL FRACTIONAL INTEGRAL INEQUALITIES FOR GENERALIZED s-PREINVEX FUNCTIONS AND THEIR GENERALIZATION
Authors: SUN WENBING
Published: December 2020

In this paper, the definition of generalized s-preinvex function on Yang’s fractal sets [Formula: see text] is proposed, and the generalized Hermite–Hadamard’s inequality for this class of functions is established. By using this convexity, some generalized Hermite–Hadamard type integral inequalities with parameters are established. For these inequalities, the absolute values of twice local fractional order derivative of the functions are generalized s-preinvex functions. Some special integral inequalities can be obtained by assigning special values to the obtained inequalities, and two examples are given to illustrate our results. Finally, we propose the applications of the results in numerical integration and error estimation.
Divisibility properties of the Fourier coefficients of (mock) modular functions and Ramanujan
Authors: Kang Soon-Yi
Published: December 2020

We survey divisibility properties of the Fourier coefficients of modular functions inspired by Ramanujan. Then using recent results of the generalized Hecke operator on harmonic Maass functions and known divisibility of Fourier coefficients of modular functions, we establish congruence relations of the Fourier coefficients of certain modular functions and mock modular functions of various levels.
Pharmacological Network Reveals the Active Mechanism of Qi‐Replenishing, Spleen‐Strengthening, Phlegm‐Dispelling, and Blood‐Nourishing Fufang on Coronary Heart Disease
Authors: Zhang Fan , Liu Yue , Zheng Sicheng , Dang Boyi , Wang Jianan , Zhang Zhe
Published: December 2020

This study aimed to investigate the potential targets and pathways of qi‐replenishing, spleen‐strengthening, phlegm‐dispelling, and blood‐nourishing Fufang in the treatment of coronary heart disease (CHD). The composition of Fufang was identified, followed by screening of the active components using ADME. The targets of active components were predicted and screened based on the TCMSP and BATMAN databases and were cross‐validated using the CTD database and DisGeNET. A functional enrichment analysis was performed using the ClueGO + CluePedia plugins and clusterProfiler in the R package. The protein‐protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Finally, a pharmacological network was constructed. A total of 27 overlapping targets were obtained after cross‐validation. ALB, IL‐6, and TNF were the hub genes in the PPI network. The pharmacological network included 59 nodes and 189 relation pairs. Among the 59 nodes, there were 2 herbal medicine nodes (Salvia miltiorrhiza and Astragalus mongholicus), 8 chemical component nodes (magnesium lithospermate B, neocryptotanshinone II, heteratisine, daphneolone, tanshinone IIA, tanshinone IIB, soyasapogenol B, and astragaloside II), 27 target protein nodes (such as ALB, TNF, IL‐6, NFKB1, APOA1, APOA2, CYP1A1, and CYP1A2), and 22 pathway nodes (such as the toll‐like receptor signaling pathway, IL‐17 signaling pathway, and TNF signaling pathway). Therefore, we found that the genes TNF, IL‐6, NFKB1, ALB, CYP1A1, CYP1A2, APOA1, and APOA2 might be important targets of the key active compounds neocryptotanshinone II and astragaloside II. These genes targeted by the key active compounds might regulate inflammation‐related pathways and the level of albumin and cholesterol in CHD.