bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of participation in organized sports and physical activity in preschool children: a cross-sectional study
Authors: Chen Chu , Sellberg Fanny , Ahlqvist Viktor H. , Neovius Martin , Christiansen Filip , Berglind Daniel
Published: July 2020

Background

Participation in organized sports is associated with higher physical activity (PA) levels in school-aged-children. Yet, little is known about PA determinants in preschool-aged-children. We examined associations between organized sports participation and preschoolers’ daily PA.

Methods

The study comprised 290 3–5 years old children and PA was measured for 1 week via accelerometers. Organized sports participation was parent-reported and preschool arrival and departure time was teacher-recorded. The preschool duration reported by teachers was matched with time-stamped accelerometer data to distinguish PA during preschool time and PA outside preschool time. Linear mixed models, nested on preschool level, were used to examine associations between organized sports participation and children’s PA outside preschool time, during preschool time and throughout the day.

Results

In total, 146 children (50.3%) participated in organized sports at least 1 h/week. Participation in organized sports was associated with 6.0 more minutes of moderate-to-vigorous PA (MVPA) (95% CI: 0.6, 11.3) throughout the day and 5.7 more minutes of MVPA (95% CI: 1.6, 9.7) outside preschool time after adjustment. There was no association between organized sports participation and PA during preschool time.

Conclusions

This is the first study to show positive associations between organized sports participation and preschoolers’ PA levels outside preschool time and throughout the day. In addition, findings from this study do not support PA compensation. Therefore, targeting organized sports may be successful in improving PA, even among preschoolers.
Adherence among HIV-positive injection drug users undergoing methadone treatment in Taiwan
Authors: Chao En , Hung Chia-Chun , Lin Ching-Po , Ku Yi-Chien Jacob , Ain Qurat Ul , Metzger David S. , Lee Tony Szu-Hsien
Published: July 2020

Aims

The study aims were to investigate adherence to methadone maintenance treatment (MMT) and to identify associated clinical factors in patients who inject drugs diagnosed with human immunodeficiency virus (HIV) infection in Taiwan.

Methods

Data were from the National Health Surveillance System on HIV and the National Drug Treatment System on MMT. HIV-positive people who inject drugs (HIVPWID) were defined as the study population. Information obtained included age, sex, education, marital status, employment, methadone dose, and date of diagnosis of HIV infection. Adherence was defined as taking methadone for the past 90, 180 and 365 days, then categorized as high (> 90%), moderate (51 to 90%), or low (<=50%) adherent respectively.

Results

Of 1641 HIVPWID registered in the datasets from 2007 to 2012, 961 (58.56%) had received MMT. For HIVPWID evaluated at 90 days (n = 951), 271 (28.5%), 382 (40.2%), and 298 (31.3%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 180 days (n = 936), 190 (20.3%), 349 (37.3%), and 397 (42.4%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 365 days (n = 919), 133 (14.5%), 271 (29.5%), and 515 (56.0%) were classified as high, moderate, and low adherent respectively. After controlling for sociodemographics, results showed that methadone dose, location of MMT clinic, and date of HIV diagnosis were significantly associated with MMT adherence.

Conclusions

Study findings underscore the importance to MMT adherence of methadone dosage, early diagnosis of patient’s HIV infection, and area of patient residence.
Crowdsourcing to promote hepatitis C testing and linkage-to-care in China: a randomized controlled trial protocol
Authors: Wong William C. W. , Yang Nancy S. , Li Jingjing , Li Hang , Wan Eric Y. F. , Fitzpatrick Thomas , Xiong Yuan , Seto Wai-Kay , Chan Polin , Liu Ruihong , Tang Weiming , Tucker Joseph D.
Published: July 2020

Background

Hepatitis C virus (HCV) is a growing public health problem with a large disease burden worldwide. In China many people living with HCV are unaware of their hepatitis status and not connected to care and treatment. Crowdsourcing is a technique that invites the public to create health promotion materials and has been found to increase HIV testing uptake, including in China. This trial aims to evaluate crowdsourcing as a strategy to improve HCV awareness, testing and linkage-to-care in China.

Methods

A randomized controlled, two-armed trial (RCT) is being conducted in Shenzhen with 1006 participants recruited from primary care sectors of The University of Hong Kong-Shenzhen Hospital. Eligible participants are ≥30 years old; a resident in Shenzhen for at least one month after recruitment; no screening for HCV within the past 12 months and not known to have chronic HCV; and, having a WeChat social media account. Allocation is 1:1. Both groups will be administered a baseline and a follow-up survey (4-week post-enrollment). The intervention group will receive crowdsourcing materials to promote HCV testing once a week for two weeks and feedback will be collected thereafter, while the control group will receive no promotional materials. Feedback collected will be judged by a panel and selected to be implemented to improve the intervention continuously.

Those identified positive for HCV antibodies will be referred to gastroenterologists for confirmation and treatment. The primary outcome will be confirmed HCV testing uptake, and secondary outcomes include HCV confirmatory testing and initiation of HCV treatment with follow-ups with specialist providers. Data will be collected on Survey Star@ via mobile devices.

Discussion

This will be the first study to evaluate the impact of crowdsourcing to improve viral hepatitis testing and linkage-to-care in the health facilities. This RCT will contribute to the existing literature on interventions to improve viral hepatitis testing in primary care setting, and inform future strategies to improve HCV care training for primary care providers in China.

Trial registration

Chinese Clinical Trial Registry. ChiCTR1900025771. Registered September 7th, 2019, http://www.chictr.org.cn/showprojen.aspx?proj=42788
Effectiveness and safety of surgical interventions for treating adolescent idiopathic scoliosis: a Bayesian meta-analysis
Authors: Chen Long , Sun Zeyu , He Jingming , Xu Yunwen , Li Zhuhai , Zou Qian , Li Bo
Published: July 2020

Background

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in children and adolescents which presents as complex three-dimensional (3D) deformity of the spine and rib cage. This study aimed to estimate the effectiveness and safety of surgical interventions for AIS using Bayesian meta-analysis.

Methods

The PubMed, EMBASE, and Cochrane Controlled Register of Trials were searched through Oct 1, 2019, without language restrictions. Relevant studies evaluating combined effectiveness and safety of surgical interventions for AIS were included according to eligibility criteria. The primary outcome measures included pulmonary function (change of absolute forced vital capacity and forced expiratory volume in 1 second from pre-operation to post-operation) and incidence of complications. The secondary outcome measure was change of Cobb angle from pre-operation to post-operation. Data was pooled using a random effects model in pairwise meta-analysis. Bayesian meta-analysis combined direct and indirect evidence using a Bayesian framework.

Results

Twenty-eight case-controlled studies with totally 1970 participants were included. This Bayesian meta-analysis combining direct and indirect evidences indicated that posterior fusion with instrumentation without thoracoplasty (PSF) had the highest probability to achieve better pulmonary function and lower complication rate; video assisted anterior fusion with instrumentation without thoracoplasty (VAT) had the highest probability to obtain better Cobb angle correction based on analysis of rank probability.

Conclusion

This Bayesian meta-analysis demonstrated that PSF had the highest probability to achieve better post-surgical pulmonary function and lower complication rate, which gives a practical recommendation of PSF as a primary surgical treatment for AIS. The results also support statistics that current surgeries adopted more PSF but less open anterior approach surgery and thoracoplasty. More research work is required to address the effectiveness and safety of VAT for treating AIS more convincingly.
Revealing the sedative-hypnotic effect of the extracts of herb pair Semen Ziziphi spinosae and Radix Polygalae and related mechanisms through experiments and metabolomics approach
Authors: Luo Hong , Sun Sheng-jie , Wang Yan , Wang Ying-li
Published: July 2020

Background

Semen Ziziphi spinosae and Radix Polygalae, two herbs commonly used together in Traditional Chinese Medicine for the treatment of insomnia and anxiety. The study aims to study the sedative-hypnotic effect of the active components of the herbal pair, the possible mechanisms of such effect, and related metabolic pathways in vivo.

Methods

The sedative and hypnotic effect of the active components (EI30) of the herbal pair was studied by recording influence on the proportion of sleeping within 30 min, sleep latency and sleep length of pentobarbital sodium-induced sleeping on mice. Possible mechanisms of the sedative-hypnotic effect of the active components were investigated by measuring the content of neurotransmitters in the total protein of mice brain tissue. The main chemical compounds of the herbal pair were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Serum samples of mice were studied, and related differential metabolites between the normal group and model group, and between model group and treatment group were identified by Gas Chromatography Time-Of-Flight Mass Spectrometry (GC-TOF-MS), Principal Components Analysis (PCA), and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA).

Results

Compared with the control group, high dose EI30 group and the Clonazepam group were with significantly higher proportions of sleep within 30 min (P = 0.027 and 0.005 respectively). Compared with the control group, all of the high, medium and low dose of EI30 groups were with significantly shorter sleep latency (P < 0.01) and prolonged sleeping time (P < 0.01). The herbal pair has good sedative-hypnotic effects, although it is weaker than the effect of Clonazepam. The sedative-hypnotic effect of EI30 is possibly related to the adjustment of neurotransmitters 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in the total protein of mice brain tissue. There are five metabolic pathways in vivo most related to the sedative-hypnotic effect of EI30, and they are biosynthesis of valine, leucine, and isoleucine, metabolism of glyceride, metabolism of alanine, aspartic acid and glutamic acid, metabolism of phenylalanine, and metabolism of cysteine and methionine.

Conclusions

This study reveals the mechanisms of sedative and hypnotic effects of herbal pair Semen Ziziphi spinosae and Radix Polygalae by using metabolomics methods. This study provides a basis for further development and utilization of this herbal pair.
Use of profession-role exchange in an interprofessional student team-based community health service-learning experience
Authors: Wang Jun , Guo Jie , Wang Yubin , Yan Dan , Liu Juan , Zhang Yinghong , Hu Xianmin
Published: July 2020

Background

During interprofessional clinical practice, compared to understanding of one’s own professional role and function, it might be more difficult to clarify the roles and contributions of the other health-care team members because of the inter-professional barrier. In order to provide students the opportunity for real experience with other professions in team environments and enhance their perceptions of other professions’ roles, this study developed a comprehensive and multi-dimension extracurricular interprofessional education (IPE) model through designing and integrating a profession-role exchange component, that was medical students as pharmacists or nurses, pharmacy students as physicians or nurses, and nursing students as physicians or pharmacists in the interprofessional health-care student team, into the service learning experience in a real community setting.

Methods

In this pre/post-intervention study, the effect of integrated profession-role exchange experiences on the students’ attitudes towards interprofessional collaboration and their role clarification was evaluated among 60 student volunteers (20 medical students, 20 pharmacy students and 20 nursing students). All involved students were divided into the profession-role exchange intervention group and the control group. Subjects in the control group did not participate the profession-role exchange experiences, the other IPE procedures were the same for both groups. Three survey instruments for attitudes toward interprofessional clinical collaboration were respectively used to measure the students’ attitudes toward physician-pharmacist, physician-nurse and nurse-pharmacist collaborations. “Roles and responsibilities” subscale of Readiness for Interprofessional Learning Scale was used to evaluate the overall role clarification during IPE.

Results

Compared to the control IPE activity, the addition of profession-role exchange component resulted in the significant increase in students’ positive attitudes towards interprofessional collaboration, and the enhancement of students’ role awareness.

Conclusions

The profession-role exchange might be more effective and better initiate students to the practice of interprofessional collaboration, and could be used as an effective IPE tool for improving the role awareness of health-care students.
Nursing staff’s and physicians’ acquisition of competences and attitudes to interprofessional education and interprofessional collaboration in pediatrics
Authors: Straub Christine , Heinzmann Andrea , Krueger Marcus , Bode Sebastian F. N.
Published: July 2020

Background

Interprofessional education (IPE) is deemed essential for interprofessional collaboration (IPC) in healthcare systems. IPC has positive effects for both patients and healthcare professionals. Especially in pediatrics, IPC is paramount for adequate care of patients and their families though there is a lack of data on the attitudes towards IPE and IPC and acquisition of respective competences in pediatric nursing and medical staff.

Methods

Frequencies of interactions and attitudes towards IPE and IPC, with a focus on acquisition of competences for IPE and IPC, of nurses (N = 79) and physicians (N = 70) in a large pediatric university hospital were evaluated with an online questionnaire.

Results

All participants worked as part of interprofessional teams, mostly consisting of nurses and physicians. The majority (94.9% (n = 75) of nurses and 100% (n = 70) of physicians) highly valued IPC. Medical doctors acquired most competences important for IPC during day-to-day work and reported a substantial lack of IPE. Nursing staff on the other hand did report significant interprofessional education during their training as well as ongoing interprofessional learning during day-to-day work. Nurses also appreciated IPE more.

Conclusions

Even though IPC is commonly reported in nurses and physicians working at a large pediatric university hospital there is a lack of structured IPE. A focus should be on IPE for nurses and physicians to enable them to effectively collaborate together. Political and local initiatives for IPE are gaining momentum but still need to be established nationally and internationally.
Moral competence, moral teamwork and moral action - the European Moral Case Deliberation Outcomes (Euro-MCD) Instrument 2.0 and its revision process
Authors: de Snoo-Trimp J. C. , de Vet H. C. W. , Widdershoven G. A. M. , Molewijk A. C. , Svantesson M.
Published: July 2020

Background

Clinical Ethics Support (CES) services are offered to support healthcare professionals in dealing with ethically difficult situations. Evaluation of CES is important to understand if it is indeed a supportive service in order to inform and improve future implementation of CES. Yet, methods to measure outcomes of CES are scarce. In 2014, the European Moral Case Deliberation Outcomes Instrument (Euro-MCD) was developed to measure outcomes of Moral Case Deliberation (MCD). To further validate the instrument, we tested it in field studies and revised it. This paper presents the Euro-MCD 2.0 and describes the revision process.

Methods

The revision process comprised an iterative dialogue among the authors as Euro-MCD-project team, including empirical findings from six Euro-MCD field-studies and input from European experts in CES and theory. Empirical findings contained perceptions and experiences of MCD outcomes among healthcare professionals who participated in MCDs in various settings in Norway, Sweden and the Netherlands. Theoretical viewpoints on CES, literature on goals of CES and MCD and ethics theory guided the interpretation of the empirical findings and final selection of MCD outcomes.

Results

The Euro-MCD 2.0 Instrument includes three domains: Moral Competence, Moral Teamwork and Moral Action. Moral Competence consists of items about moral sensitivity, analytical skills and virtuous attitude. Moral Teamwork includes open dialogue and supportive relationships and Moral Action refers to moral decision-making and responsible care. During the revision process, we made decisions about adding and reformulating items as well as decreasing the number from 26 to 15 items. We also altered the sentence structure of items to assess the current status of outcomes (e.g. ‘now’) instead of an assumed improvement over time (e.g. ‘better’) and we omitted the question about perceived importance.

Conclusions

The Euro-MCD 2.0 is shorter, less complex and more strongly substantiated by an integration of empirical findings, theoretical reflections and dialogues with participants and experts. Use of the Euro-MCD 2.0 will facilitate evaluation of MCD and can thereby monitor and foster implementation and quality of MCD. The Euro-MCD 2.0 will strengthen future research on evaluation of outcomes of MCD.
How good is our diagnostic intuition? Clinician prediction of bacteremia in critically ill children
Authors: Hoops Katherine E. M. , Fackler James C. , King Anne , Colantuoni Elizabeth , Milstone Aaron M. , Woods-Hill Charlotte
Published: July 2020

Background

Clinical intuition and nonanalytic reasoning play a major role in clinical hypothesis generation; however, clinicians’ intuition about whether a critically ill child is bacteremic has not been explored. We endeavored to assess pediatric critical care clinicians’ ability to predict bacteremia and to evaluate what affected the accuracy of those predictions.

Methods

We conducted a retrospective review of clinicians’ responses to a sepsis screening tool (“Early Sepsis Detection Tool” or “ESDT”) over 6 months. The ESDT was completed during the initial evaluation of a possible sepsis episode. If a culture was ordered, they were asked to predict if the culture would be positive or negative. Culture results were compared to predictions for each episode as well as vital signs and laboratory data from the preceding 24 h.

Results

From January to July 2017, 266 ESDTs were completed. Of the 135 blood culture episodes, 15% of cultures were positive. Clinicians correctly predicted patients with bacteremia in 82% of cases, but the positive predictive value was just 28% as there was a tendency to overestimate the presence of bacteremia. The negative predictive value was 96%. The presence of bandemia, thrombocytopenia, and abnormal CRP were associated with increased likelihood of correct positive prediction.

Conclusions

Clinicians are accurate in predicting critically ill children whose blood cultures, obtained for symptoms of sepsis, will be negative. Clinicians frequently overestimate the presence of bacteremia. The combination of evidence-based practice guidelines and bedside judgment should be leveraged to optimize diagnosis of bacteremia.
Short- and long-term impact of vaccination against cytomegalovirus: a modeling study
Authors: Rozhnova Ganna , E. Kretzschmar Mirjam , van der Klis Fiona , van Baarle Debbie , Korndewal Marjolein , C. Vossen Ann , van Boven Michiel
Published: July 2020

Background

Infection with cytomegalovirus (CMV) is highly prevalent worldwide and can cause severe disease in immunocompromised persons and congenitally infected infants. The disease burden caused by congenital CMV infection is high, especially in resource-limited countries. Vaccines are currently under development for various target groups.

Methods

We evaluated the impact of vaccination strategies and hygiene intervention using transmission models. Model parameters were estimated from a cross-sectional serological population study (n=5179) and a retrospective birth cohort (n=31,484), providing information on the age- and sex-specific CMV prevalence and on the birth prevalence of congenital CMV (cCMV).

Results

The analyses show that vertical transmission and infectious reactivation are the main drivers of transmission. Vaccination strategies aimed at reducing transmission from mother to child (vaccinating pregnant women or women of reproductive age) can yield substantial reductions of cCMV in 20 years (31.7–71.4% if 70% of women are effectively vaccinated). Alternatively, hygiene intervention aimed at preventing CMV infection and re-infection of women of reproductive age from young children is expected to reduce cCMV by less than 2%. The effects of large-scale vaccination on CMV prevalence can be substantial, owing to the moderate transmissibility of CMV at the population level. However, as CMV causes lifelong infection, the timescale on which reductions in CMV prevalence are expected is in the order of several decades. Elimination of CMV infection in the long run is only feasible for a vaccine with a long duration of protection and high vaccination coverage.

Conclusions

Vaccination is an effective intervention to reduce the birth prevalence of cCMV. Population-level reductions in CMV prevalence can only be achieved on a long timescale. Our results stress the value of vaccinating pregnant women and women of childbearing age and provide support for the development of CMV vaccines and early planning of vaccination scenarios and rollouts.
Dynamics and interactions of cobalamin and folate status during advanced aging – a longitudinal study in a community-dwelling cohort with multiple follow-ups
Authors: Jungert Alexandra , Zenke-Philippi Carola , Neuhäuser-Berthold Monika
Published: July 2020

Background

Older people are reported to be prone to imbalances between cobalamin and folate status with possible adverse effects on health. This longitudinal study investigates dynamics and interactions of cobalamin and folate status in a cohort of community-dwelling older adults by considering possible influencing factors.

Methods

In total, 332 subjects ≥ 60 years were investigated over a mean observation period of 12 years. Data collection included serum cobalamin, folate and creatinine, dietary intakes of cobalamin, folate and alcohol, use of supplements, body composition, smoking behavior, and diseases. Linear mixed-effects models with repeated measurements were used to investigate the influence of variables on serum cobalamin and folate.

Results

At baseline, median cobalamin intake exceeded the dietary reference value (DRV), while median folate intake was considerably below DRV. In most subjects, serum concentrations of both vitamins were within reference ranges. For serum cobalamin, apart from supplement use (Parameter estimate [95% confidence interval]: 130.17 [53.32, 207.01]), the main positive predictor was serum folate (4.63 [2.64, 6.62]). For serum folate, serum creatinine (10.85 [4.85, 16.86]), use of supplements (7.86 [5.05, 10.67]), serum cobalamin (0.01 [< 0.01, 0.01]), and dietary folate intake (0.02 [0.01, 0.03]) were positive predictors. No main effects of age, sex, body composition, alcohol intake or smoking were found after adjusting for simultaneous inference.

Conclusions

Advancing age, per se, is no risk factor for a decline in serum concentrations of cobalamin or folate in subjects ≥ 60 years. Suboptimal folate intake may limit the function of folate regarding the supply of methyl groups for methylation of cobalamin and subsequent creatine biosynthesis. The positive association of serum creatinine with folate deserves further exploration with regard to its possible relevance for maintaining energy dependent functional integrity in the course of ageing.
The effect of ursodeoxycholic acid on the relative expression of the lipid metabolism genes in mouse cholesterol gallstone models
Authors: Fan Ning , Meng Ke , Zhang Yuqing , Hu Yong , Li Donghua , Gao Qiaoying , Wang Jianhua , Li Yanning , Wu Shangwei , Cui Yunfeng
Published: July 2020

Background

Many studies indicate that gallstone formation has genetic components. The abnormal expression of lipid-related genes could be the basis for particular forms of cholesterol gallstone disease. The aim of this study was to obtain insight into lipid metabolism disorder during cholesterol gallstone formation and to evaluate the effect of ursodeoxycholic acid (UDCA) on the improvement of bile lithogenicity and its potential influence on the transcription of lipid-related genes.

Methods

Gallstone-susceptible mouse models were induced by feeding with a lithogenic diet (LD) for 8 weeks. Bile and liver tissues were obtained from these mouse models after 0, 4 and 8 weeks. Bile lipids were measured enzymatically, and the cholesterol saturation index (CSI) was calculated to evaluate the bile lithogenicity by using Carey’s critical tables. Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of farnesoid X receptor (FXR), liver X receptor (LXR), adenosine triphosphate-binding cassette subfamily G member 5/8 (ABCG5/8), cholesterol 7-α hydroxylase (CYP7A1), oxysterol 7-α hydroxylase (CYP7B1), sterol 27-α hydroxylase (CYP27A1), peroxisome proliferator-activated receptor alpha (PPAR-α) and adenosine triphosphate-binding cassette subfamily B member 11 (ABCB11).

Results

The rate of gallstone formation was 100% in the 4-week group but only 30% in the UDCA-treated group. The UDCA-treated group had a significantly lower CSI compared with other groups. Of special note, the data on the effects of UDCA showed higher expression levels of ABCG8, ABCB11 and CYP27A1, as well as lower expression levels of LXR and PPAR-α, compared to the model control group.

Conclusions

UDCA exhibits tremendously potent activity in restraining lipid accumulation, thus reversing the lithogenic effect and protecting hepatocytes from serious pathological damage. The abnormal expression of ABCG8, CYP7A1, CYP27A1, LXR and PPAR-α might lead to high lithogenicity of bile. These results are helpful in exploring new lipid metabolism pathways and potential targets for the treatment of cholesterol stones and for providing some basis for the study of the pathogenesis and genetic characteristics of cholelithiasis. Research on the mechanism of UDCA in improving lipid metabolism and bile lithogenicity may be helpful for clinical treatment and for reducing the incidence of gallstones.
Promising application of monoclonal antibody against chikungunya virus E1-antigen across genotypes in immunochromatographic rapid diagnostic tests
Authors: Suzuki Keita , Huits Ralph , Phadungsombat Juthamas , Tuekprakhon Aekkachai , Nakayama Emi E. , van den Berg Riemsdijk , Barbé Barbara , Cnops Lieselotte , Rahim Rummana , Hasan Abu , Iwamoto Hisahiko , Leaungwutiwong Pornsawan , van Esbroeck Marjan , Rahman Mizanur , Shioda Tatsuo
Published: July 2020

Background

Three different genotypes of chikungunya virus (CHIKV) have been classified: East/Central/South African (ECSA), West African (WA), and Asian. Previously, a rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity for certain ECSA-genotype viruses, but this test showed poor performance against the Asian-genotype virus that is spreading in the American continents. We found that the reactivity of one monoclonal antibody (MAb) used in the IC rapid diagnostic test (RDT) is affected by a single amino acid substitution in E1. Therefore, we developed new MAbs that exhibited specific recognition of all three genotypes of CHIKV.

Methods

Using a combination of the newly generated MAbs, we developed a novel version of the IC RDT with improved sensitivity to Asian-genotype CHIKV. To evaluate the sensitivity, specificity, and cross-reactivity of the new version of the IC RDT, we first used CHIKV isolates and E1-pseudotyped lentiviral vectors. We then used clinical specimens obtained in Aruba in 2015 and in Bangladesh in 2017 for further evaluation of RDT sensitivity and specificity. Another alphavirus, sindbis virus (SINV), was used to test RDT cross-reactivity.

Results

The new version of the RDT detected Asian-genotype CHIKV at titers as low as 10^4 plaque-forming units per mL, a concentration that was below the limit of detection of the old version. The new RDT had sensitivity to the ECSA genotype that was comparable with that of the old version, yielding 92% (92 out of 100) sensitivity (95% confidence interval 85.0–95.9) and 100% (100 out of 100) specificity against a panel of 100 CHIKV-positive and 100 CHIKV-negative patient sera obtained in the 2017 outbreak in Bangladesh.

Conclusions

Our newly developed CHIKV antigen-detecting RDT demonstrated high levels of sensitivity and lacked cross-reactivity against SINV. These results suggested that our new version of the CHIKV E1-antigen RDT is promising for use in areas in which the Asian and ECSA genotypes of CHIKV circulate. Further validation with large numbers of CHIKV-positive and -negative clinical samples is warranted. (323 words).
Histopathological findings for prediction of liver cirrhosis and survival in biliary atresia patients after Kasai procedure
Authors: Gunadi  , Sirait Dian Nirmala , Budiarti Leila Rakhma , Paramita Vincentia Meta Widya , Fauzi Aditya Rifqi , Ryantono Fiko , Afandy Dwiki , Yoshuantari Naomi , Rinonce Hanggoro Tri , Makhmudi Akhmad
Published: July 2020

Background

Without early recognition and Kasai procedure, biliary atresia (BA) results in liver cirrhosis and leads to either transplantation or death at a young age. We aimed to characterize the liver histopathological findings for prediction of cirrhosis and survival in BA patients after Kasai surgery.

Methods

We retrospectively reviewed all histopathological results for BA patients who underwent liver biopsy during Kasai surgery from August 2012 to December 2018 in Dr. Sardjito Hospital, Yogyakarta, Indonesia.

Results

Fifty infants with BA were ascertained in our study, of whom 27 were males and 23 were females. The median age of Kasai procedure was 102.5 days (interquartile range (IQR), 75.75–142.25 days). There were 33 (66%) and 17 (34%) BA patients with and without liver cirrhosis, respectively, while the overall survival was 52%. The patients with a severe bile duct proliferation, severe cholestasis, and severe portal inflammation have a higher risk by 27-, 22-, and 19.3-fold, respectively, to develop liver cirrhosis compared with patients with a moderate/mild bile duct proliferation, moderate/mild/without cholestasis, and moderate/mild portal inflammation, respectively (p = 3.6 × 10− 6, 5.6 × 10− 4, and 1.6 × 10− 3, respectively), while the giant cell transformation was not associate with the development of liver cirrhosis (p = 0.77). The bile duct proliferation was strongly correlated with cholestasis and portal inflammation (p = 7.3 × 10− 5 and 2 × 10− 4, respectively), and cholestasis was also significantly correlated with portal inflammation (p = 0.016). Interestingly, the age at Kasai procedure was strongly associated with the development of liver cirrhosis (p = 0.02), but not with the patients’ survival (p = 0.33), while the degree of fibrosis and cholestasis were significantly correlated with the patients’ survival, with HR of 3.9 (95% CI = 1.7–9.0; p = 0.017) and 3.1 (95% CI = 1.4–7.0; p = 0.016), respectively.

Conclusions

Histopathological findings of bile duct proliferation, cholestasis, and portal inflammation can predict the liver cirrhosis development in patients with BA. Furthermore, degree of fibrosis and cholestasis affect the patients’ survival following the Kasai operation.
Inhaled granulocyte-macrophage colony stimulating factor for mild-to-moderate autoimmune pulmonary alveolar proteinosis - a six month phase II randomized study with 24 months of follow-up
Authors: Tian Xinlun , Yang Yanli , Chen Lulu , Sui Xin , Xu Wenshuai , Li Xue , Guo Xiaobei , Liu Lingshan , Situ Yusen , Wang Jun , Zhao Yang , Meng Shuzhen , Song Wei , Xiao Yonglong , Xu Kai-Feng
Published: July 2020

Background

Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidence of benefit from GM-CSG inhalation for mild to moderate aPAP patients is limited.

Methods

In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either the GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients received follow-up for another 18 months without treatment. Physiological features of the patients were analyzed.

Results

There were 36 patients (19 in the treatment group, 17 in the control group) included. There were no significant differences in the primary endpoints as measured by the change of alveolar arterial oxygen gradient (A-aDO2) from the baseline values to the values obtained during treatment or during the following 18-month non-treatment observation period [control group vs. treatment group: 0.51 ± 12.09 mmHg vs. -0.35 ± 13.76 mmHg, p = 0.848 (3 month); 1.85 ± 11.21 mmHg vs. 7.31 ± 8.81 mmHg, p = 0.146 (6 months); 6.05 ± 11.14 mmHg vs. 6.61 ± 10.64 mmHg, p = 0.899 (24 months)]). Percentage of diffusion capacity predicted (DLCO%) and percentage of total lung capacity predicted (TLC%), however, were significantly improved in the treatment group by the end of the study (P = 0.010 and 0.027). St. George Respiratory questionnaire (SGRQ) scores were better after 6 months treatment with GM-CSF compared to the control group, and the benefits of treatment were maintained throughout the observation period. No severe side effects were observed during the study.

Conclusion

Six months of inhaled GM-CSF treatment had no effect on the alveolar–arterial oxygen gradient in patients with mild to moderate pulmonary alveolar proteinosis. There were changes in some clinical or laboratory measures, but no clinically important changes were noted at the end of study. (Clinical Trial Registry: NCT02243228, Registered on September 17, 2014, https://www.clinicaltrials.gov/ct2/show/NCT02243228?term=NCT02243228&draw=2&rank=1)
Neural circuit analysis using a novel intersectional split intein-mediated split-Cre recombinase system
Authors: Khoo Audrey Tze Ting , Kim Paul Jong , Kim Ho Min , Je H. Shawn
Published: July 2020

The defining features of a neuron are its functional and anatomical connections with thousands of other neurons in the brain. Together, these neurons form functional networks that direct animal behavior. Current approaches that allow the interrogation of specific populations of neurons and neural circuits rely heavily on targeting their gene expression profiles or connectivity. However, these approaches are often unable to delineate specific neuronal populations. Here, we developed a novel intersectional split intein-mediated split-Cre recombinase system that can selectively label specific types of neurons based on their gene expression profiles and structural connectivity. We developed this system by splitting Cre recombinase into two fragments with evolved split inteins and subsequently expressed one fragment under the influence of a cell type-specific promoter in a transgenic animal, and delivered the other fragment via retrograde viral gene transfer. This approach results in the reconstitution of Cre recombinase in only specific population of neurons projecting from a specific brain region or in those of a specific neuronal type. Taken together, our split intein-based split-Cre system will be useful for sophisticated characterization of mammalian brain circuits.
Autoantibody signature in hepatocellular carcinoma using seromics
Authors: Zhang Shu , Liu Yuming , Chen Jing , Shu Hong , Shen Siyun , Li Yin , Lu Xinyuan , Cao Xinyi , Dong Liangqing , Shi Jieyi , Cao Ya , Wang Xiaoying , Zhou Jian , Liu Yinkun , Chen Lei , Fan Jia , Ding Guangyu , Gao Qiang
Published: July 2020

Background

Alpha-fetoprotein (AFP) is a widely used biomarker for hepatocellular carcinoma (HCC) early detection. However, low sensitivity and false negativity of AFP raise the requirement of more effective early diagnostic approaches for HCC.

Methods

We employed a three-phase strategy to identify serum autoantibody (AAb) signature for HCC early diagnosis using protein array-based approach. A total of 1253 serum samples from HCC, liver cirrhosis, and healthy controls were prospectively collected from three liver cancer centers in China. The Human Proteome Microarray, comprising 21,154 unique proteins, was first applied to identify AAb candidates in discovery phase (n= 100) and to further fabricate HCC-focused arrays. Then, an artificial neural network (ANN) model was used to discover AAbs for HCC detection in a test phase (n= 576) and a validation phase (n= 577), respectively.

Results

Using HCC-focused array, we identified and validated a novel 7-AAb panel containing CIAPIN1, EGFR, MAS1, SLC44A3, ASAH1, UBL7, and ZNF428 for effective HCC detection. The ANN model of this panel showed improvement of sensitivity (61.6–77.7%) compared to AFP (cutoff 400 ng/mL, 28.4–30.7%). Notably, it was able to detect AFP-negative HCC with AUC values of 0.841–0.948. For early-stage HCC (BCLC 0/A) detection, it outperformed AFP (cutoff 400 ng/mL) with approximately 10% increase in AUC.

Conclusions

The 7-AAb panel provides potentially clinical value for non-invasive early detection of HCC, and brings new clues on understanding the immune response against hepatocarcinogenesis.
Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis
Authors: Potere Nicola , Valeriani Emanuele , Candeloro Matteo , Tana Marco , Porreca Ettore , Abbate Antonio , Spoto Silvia , Rutjes Anne W. S. , Di Nisio Marcello
Published: July 2020

Background

The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19.

Methods

MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses.

Results

A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies).

Conclusions

Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting.

Trial registration

PROSPERO registration ID for this study is CRD42020177243 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243).
Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III
Authors: Jiang Yongpeng , Huang Jie , Lun Kehuan , Li Boyuan , Zheng Haonan , Li Yuanjun , Zhou Rong , Duan Wenjia , Wang Chenlu , Feng Yuanqing , Yao Hong , Li Cheng , Ji Xiong
Published: July 2020

Background

The relationship between transcription and the 3D chromatin structure is debated. Multiple studies have shown that transcription affects global Cohesin binding and 3D genome structures. However, several other studies have indicated that inhibited transcription does not alter chromatin conformations.

Results

We provide the most comprehensive evidence to date to demonstrate that transcription plays a relatively modest role in organizing the local, small-scale chromatin structures in mammalian cells. We show degraded Pol I, Pol II, and Pol III proteins in mESCs cause few or no changes in large-scale 3D chromatin structures, selected RNA polymerases with a high abundance of binding sites or active promoter-associated interactions appear to be relatively more affected after the degradation, transcription inhibition alters local, small loop domains, as indicated by high-resolution chromatin interaction maps, and loops with bound Pol II but without Cohesin or CTCF are identified and found to be largely unchanged after transcription inhibition. Interestingly, Pol II depletion for a longer time significantly affects the chromatin accessibility and Cohesin occupancy, suggesting that RNA polymerases are capable of affecting the 3D genome indirectly. These direct and indirect effects explain the previous inconsistent findings on the influence of transcription inhibition on the 3D genome.

Conclusions

We conclude that Pol I, Pol II, and Pol III loss alters local, small-scale chromatin interactions in mammalian cells, suggesting that the 3D chromatin structures are pre-established and relatively stable.
Differences in gait analysis and clinical outcome after TightRope® or screw fixation in acute syndesmosis rupture: study protocol for a prospective randomized pilot study
Authors: Doll Julian , Waizenegger Stefan , Bruckner Thomas , Schmidmaier Gerhard , Wolf Sebastian I. , Fischer Christian
Published: July 2020

Background

Ankle sprains and fractures are most common injuries in orthopedic and trauma surgery. The concurrent occurrence of syndesmosis ruptures in these injuries represents a more complex problem, as they often remain undetected.

A proper and accurate treatment of injuries of the syndesmosis, both isolated and combined with fractures, is necessary to avoid long-term consequences (chronic instability, cartilage damage, and post-traumatic osteoarthritis). The most popular treatment option is a static screw fixation and the newly developed dynamic TightRope® (Arthrex, Naples, FL, USA).

The aim of this pilot study is to compare monitor ankle range of motion and maximum ankle power in gait as functional outcome parameters of instrumented gait analysis, as well as clinical and radiographic outcome for assessing the stabilization of acute syndesmosis rupture with either a static implant (a 3.5 mm metallic screw) or a dynamic device (TightRope®).

Methods

This prospective, randomized, controlled, clinical trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Adult patients, who suffer from an acute syndesmosis rupture, both isolated and in combination with fractures of the lateral malleolus (Weber C and Maisonneuve fractures) and who are undergoing surgery at our trauma center will be included in our study. The patients will be randomized to the different treatment options (screw fixation or “TightRope®”). Subsequent to the surgical treatment, all patients will receive the same standardized follow-up procedures including a gait analysis and MRI of the ankle at 6 months follow-up.

The primary endpoint of the study is the successful healing of the syndesmosis and biomechanical investigation with gait analysis.

Discussion

The results of the gait analysis from the current study will help to impartially and reliably evaluate the clinical and biomechanical outcome of both treatment options of acute syndesmosis ruptures. We hypothesize that the dynamic fixation provides an equivalent or better biomechanical, clinical, and radiographic outcome in comparison to the screw fixation.

Trial registration

German Clinical Trials Register (DRKS) DRKS00013562. Registered on July, 12, 2017.
High susceptibility to collagen-induced arthritis in mice with progesterone receptors selectively inhibited in osteoprogenitor cells
Authors: Liu Lixian , Jia Junjing , Jiang Min , Liu Xueping , Dai Chenling , Wise Barton L. , Lane Nancy E. , Yao Wei
Published: July 2020

Background

Progesterone receptor (PR) affects immunomodulation, and lack of PR in osteoprogenitor cells primarily affects pathways associated with immunomodulation, especially in males. In this study, we selectively deleted PR from osteoprogenitor cells using Prx1-Cre to evaluate the tissue-specific effects of PR on the pathegenesis of inflammatary arthritis (IA).

Methods

Collagen-induced arthritis (CIA) was used as an IA animal model. Both male and female PRΔPrx1mice and their wild-type (WT) littermates were immunized with collagen II (CII) emulsified complete Freund’s adjuvant (CFA). Joint erosion, inflammation, and cartilage damage were assessed using a semiquantitative histologic scoring system. Bone volume and erosions in knee and ankle joints were quantitated using microCT and histology.

Results

Bone erosions developed in both paw joints in 37.5% and 41.7% of the WT and PRΔPrx1female mice and in 45.4 and 83.3% of the WT and PRΔPrx1male mice, respectively. Also, both joint damage and subchondral bone erosions were significantly more severe in male PRcKO-CIA mice than in male WT-CIA mice. Female PRΔPrx1mice also developed higher bone loss in the knee joints than the KO-normal or WT-CIA females although with less severity compared to the male mice.

Conclusions

The presence of PR in osteoprogenitor cells decreased the development of collagen-induced arthritis and might help to explain the sex differences observed in human inflammatory arthritis.
Correction to: Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis
Authors: Emery Paul , Tanaka Yoshiya , Cardillo Tracy , Schlichting Douglas , Rooney Terence , Beattie Scott , Helt Cameron , Smolen Josef S.
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.