bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and reliability of social anxiety disorder diagnoses in the Swedish National Patient Register
Authors: Vilaplana-Pérez Alba , Isung Josef , Krig Sonja , Vigerland Sarah , Jolstedt Maral , Bjureberg Johan , Högström Jens , Isomura Kayoko , Rautio Daniel , Serlachius Eva , Rück Christian , Mataix-Cols David , Fernández de la Cruz Lorena
Published: May 2020

Background

Population-based administrative registers are often used for research purposes. However, their potential usefulness depends on the validity of the registered information. This study assessed the validity of the recorded codes for social anxiety disorder (SAD), also known as social phobia, in the Swedish National Patient Register (NPR).

Methods

The personal identification numbers of 300 randomly selected individuals with a diagnosis of SAD recorded in the NPR were obtained from the Swedish National Board of Health and Welfare. The medical files of these individuals were then requested from clinics nationally. A total of 117 files were received and two independent raters reviewed each file to assess the presence or absence of SAD, according to the definition of the International Classification of Diseases, Tenth Edition (ICD-10) and the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). When disagreements between the two raters were found, a third rater reviewed the file to establish a best estimate diagnosis. Positive predictive values (PPV) and agreement between the two initial raters (using Cohen’s kappa) were calculated. Additionally, raters completed the Clinical Global Impression – Severity (CGI-S) and the Global Assessment of Functioning (GAF) rating scales for each file. Inter-rater agreement for the CGI-S and the GAF was assessed using intraclass correlation coefficients (ICC).

Results

After exclusion of files not containing sufficient information, 95 files were included in the analyses. Of these, 77 files (81.05%) were considered to be ‘true positive’ cases (PPV = 0.81, 95% confidence interval = 0.72–0.88). Inter-rater agreement regarding the presence or absence of SAD was substantial (κ = 0.72). CGI-S and GAF scores indicated that patients were in the moderate range of severity and functional impairment. Inter-rater agreement for the CGI-S and the GAF was moderate to good (ICC = 0.72 and ICC = 0.82, respectively).

Conclusions

The ICD-10 codes for SAD in the Swedish NPR are generally valid and reliable, but we recommend sensitivity analyses in future register-based studies to minimise the impact of potential diagnostic misclassification. Most patients were moderately severe and impaired, suggesting that results from register-based studies of SAD may be generalizable.
Adherence to ready-to-use food and acceptability of outpatient nutritional therapy in HIV-infected undernourished Senegalese adolescents: research-based recommendations for routine care
Authors: Niasse Fatou , Varloteaux Marie , Diop Karim , Ndiaye Sidy Mokhtar , Diouf François Niokhor , Mbodj Pape Birane , Niang Babacar , Diack Aminata , Cames Cecile
Published: May 2020

Background

Ready-to-use food (RUF) is increasingly used for nutritional therapy in HIV-infected individuals. However, practical guidance advising nutrition care to HIV-infected adolescents is lacking, so that little is known about the acceptability of such therapy in this vulnerable population. This study assesses the overall acceptability and perception of a RUF-based therapy and risk factors associated with sub-optimal RUF intake in HIV-infected undernourished adolescents in Senegal.

Methods

Participants 5 to 18 years of age with acute malnutrition were enrolled in 12 HIV clinics in Senegal. Participants were provided with imported RUF, according to WHO prescription weight- and age-bands (2009), until recovery or for a maximum of 9–12 months. Malnutrition and recovery were defined according to WHO growth standards. Adherence was assessed fortnightly by self-reported RUF intake over the period. Sub-optimal RUF intake was defined as when consumption of the RUF provision was < 50%. RUF therapy acceptability and perceptions were assessed using a structured questionnaire at week 2 and focus group discussions (FGDs) at the end of the study. Factors associated with sub-optimal RUF intake at week 2 were identified using a stepwise logistic regression model.

Results

We enrolled 173 participants, with a median age of 12.5 years (Interquartile range: 9.5–14.9), of whom 61% recovered from malnutrition within the study period. Median follow-up duration was 66 days (21–224). RUF consumption was stable, varying between 64 and 57% of the RUF provided, throughout the follow-up. At week 2, sub-optimal RUF intake was observed in 31% of participants. Dislike of the taste of RUF (aOR = 5.0, 95% CI: 2.0–12.3), HIV non-disclosure (5.1, 1.9–13.9) and food insecurity (2.8, 1.1–7.2) were the major risk factors associated with sub-optimal RUF intake at week 2. FGDs showed that the need to hide from others to avoid sharing and undesirable effects were other constraints on RUF feeding.

Conclusions

This study revealed several factors reducing the acceptability and adherence to RUF therapy based on WHO guidelines in HIV-infected adolescents. Tailoring prescription guidance and empowering young patients in their care are crucial levers for improving the acceptability of RUF-based therapy in routine care.

Trial registration

ClinicalTrials.gov identifier: NCT03101852, 04/04/2017.
Multilevel analysis of factors associated with unmet need for family planning among Malawian women
Authors: Nkoka Owen , Mphande Watanja M. , Ntenda Peter A. M. , Milanzi Edith B. , Kanje Victor , Guo Shiaau J. G.
Published: May 2020

Background

Malawi has a high fertility rate which is also characterized by a relatively high prevalence of unmet need for contraception. However, little is known about the influence of individual- and community- level characteristics on unmet need in Malawi. This study examined the individual- and community- level factors associated with unmet need for family planning (FP) among Malawian women.

Methods

Data from the 2015–16 Malawi demographic and health survey were used to analyze 15, 931 women. The association between individual- and community- level factors and unmet need was assessed using multilevel binary logistic regression models.

Results

The prevalence of total unmet need was 21.0%. Women aged ≥35 years were more likely to have total unmet need [adjusted odds ratio (aOR) = 1.19, 95% confidence interval (CI) = 1.04–1.35] compared with those aged 15–24 years. Women who were married [aOR = 0.41, 95% CI = 0.35–0.48], and those employed [aOR = 0.78, 95% CI = 0.71–0.85] were associated with less likelihood of having total unmet need compared with unmarried, and unemployed women, respectively. At community-level, women from communities with a high percentage of women from rich households [aOR = 0.81, 95% CI = 0.67–0.96], and those from communities with a middle and high percentage of educated women [aOR = 0.86, 95% CI = 0.76–0.96 and aOR = 0.81, 95% CI = 0.70–0.93, respectively] were less likely to have total unmet need for FP compared with those from communities with low percentages of rich and educated women, respectively. The proportional change in variance showed that about 36.0% of total variations in the odds of unmet need across the communities were explained by both individual- and community-level factors. Moreover, the intraclass correlation showed that about 3.0% of the total variation remained unexplained even after controlling for both individual- and community-level factors.

Conclusion

Both individual- and community- level factors influenced unmet need for FP in Malawi. Public health practitioners should conduct community profiling and consider individual and community factors when designing FP programs.
Values of different specimen preparation methods for the diagnosis of lung cancer by endobronchial ultrasound guided transbronchial needle aspiration
Authors: Xu Youzu , Lin Jian , Chen Meifang , Zheng Haihong , Feng Jiaxi
Published: May 2020

Background

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has been become an important procedure for the diagnosis and staging of lung cancer. Our research identified the effects of different pathological preparation on the diagnosis of lung cancer for specimens obtained by biopsy.

Methods

Patients were clinically considered if lung cancer was accompanied by mediastinal or hilar lymph node enlargement between March 2014 and November 2017. Specimens obtained by EBUS-TBNA were treated by three methods: traditional smear cytology, liquid-based cytology (LBC) and histopathology.

Results

Of a total of 154 puncture sites from 153 patients, the total positive rate of combination for the three pathological treatment types (histopathology, direct traditional smear, and LBC) was 77.3%. The diagnostic positive rate for histopathology was 68.6%, direct traditional smear was 65.6%, and LBC was 60.4%; there was no significant differences among the three single pathological treatment types (P = 0.29), but there was a statistically significant difference between the combination of three treatments and any single pathological treatment type (P = 0.01). The diagnostic sensitivities of histopathology combined with traditional smear and histopathology combined LBC were 94.4 and 92.8%, respectively, the specificities and PPVs were both 100%, and the diagnostic accuracies were 95.5 and 94.2%, respectively; the sensitivities, specificities and diagnostic accuracies above were all higher than those of single specimen treatment and lower than those of the three combined.

Conclusion

When EBUS-TBNA is used for the diagnosis and staging of lung cancer, the use of histopathological sections combined with direct cytological smear should be sufficient and is the most economical choice.
In vivo assessment of the elastic properties of women’s pelvic floor during pregnancy using shear wave elastography: design and protocol of the ELASTOPELV study
Authors: Gachon Bertrand , Fritel Xavier , Pierre Fabrice , Nordez Antoine
Published: May 2020

Background

Animal studies have reported an increase in pelvic floor muscle stiffness during pregnancy, which might be a protective process against perineal trauma at delivery. Our main objective is to describe the changes in the elastic properties of the pelvic floor muscles (levator ani, external anal sphincter) during human pregnancy using shear wave elastography (SWE) technology. Secondary objectives are as follows: i) to look for specific changes of the pelvic floor muscles compared to peripheral muscles; ii) to determine whether an association between the elastic properties of the levator ani and perineal clinical and B-mode ultrasound measures exists; and iii) to provide explorative data about an association between pelvic floor muscle characteristics and the risk of perineal tears.

Methods

Our prospective monocentric study will involve three visits (14–18, 24–28, and 34–38 weeks of pregnancy) and include nulliparous women older than 18 years, with a normal pregnancy and a body mass index (BMI) lower than 35 kg.m− 2. Each visit will consist of a clinical pelvic floor assessment (using the Pelvic Organ Prolapse Quantification system), an ultrasound perineal measure of the anteroposterior hiatal diameter and SWE assessment of the levator ani and the external anal sphincter muscles (at rest, during the Valsalva maneuver and during pelvic floor contraction), and SWE assessment of both the biceps brachii and the gastrocnemius medialis (at rest, extension and contraction). We will collect data about the mode of delivery and the occurrence of perineal tears. We will investigate changes in continuous variables collected using the Friedman test. We will look for an association between the elastic properties of the levator ani muscle and clinical / ultrasound measures using a Spearman test at each trimester. We will investigate the association between the elastic properties of the pelvic floor muscles and perineal tear occurrence using a multivariate analysis with logistic regression.

Discussion

This study will provide original in vivo human data about the biomechanical changes of pregnant women’s pelvic floor. The results may lead to an individualized risk assessment of perineal trauma at childbirth.

Trial registration

This study was registered on https://clinicaltrials.gov on July 26, 2018 (NCT03602196).
Association of vitamin D2 and D3 with type 2 diabetes complications
Authors: Ahmed Lina H. M. , Butler Alexandra E. , Dargham Soha R. , Latif Aishah , Robay Amal , Chidiac Omar M. , Jayyousi Amin , Al Suwaidi Jassim , Crystal Ronald G. , Atkin Stephen L. , Abi Khalil Charbel
Published: May 2020

Aims

Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM.

Methods

Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis.

Results

All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D2 nor vitamin D3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D2 and vitamin D3 showed no difference.

Conclusions

In this Qatari cohort, vitamin D2 was associated with hypertension and dyslipidemia, whilst vitamin D3 levels were associated with diabetic retinopathy. Vitamin D2 levels were higher, whilst vitamin D3 were lower in diabetics and females, likely due to ingestion of vitamin D2 supplements.
Sustained effects of faculty leadership development modules for clinical instructors of core competences education in Taiwan: a four-year explanatory case study
Authors: Lee Fa-Yauh , Yang Ying-Ying , Huang Chia-Chang , Huang Ling-Ju , Chang Ching-Chih , Liang Jen-Feng , Huang Shiau-Shian , Lee Wei-Shin , Lu Dai-Yin , Chuang Chiao-Lin , Yang Ling-Yu , Huang Hui-Chun , Shulruf Boaz , Chen Chen-Huan , Kao Shou-Yen
Published: May 2020

Background

The Accreditation Council for Graduate Medical Education (ACGME) core competencies (CC) in general medicine-based primary care are essential for junior medical trainees. In this country, aregularfaculty development (FD) program aimed at training faculty in instructing (teaching and assessing) these CC had operated. However, leadership was not emphasized. In a newinterventionmodule, the roles and associated responsibilities ofclinical instructorstoconduct,design, andleadCC-based education were emphasis.

Aims

This follow-up explanatory case study compares the effectiveness ofinterventionmodule with that of the previousregularmodule.

Methods

Theregulargroup (n = 28) comprised clinical instructors who participated in the FD module during the 2013–2014 year while theinterventiongroup (n = 28) was composed of 2015–2016 participants. Prior to the formal (hands-on) training, participants in theinterventiongroup were asked to study the online materials of theregularmodule. These participants then received a 30-h hands-on training inconducting,designing, andleadingskills. Finally, they prepared a 10-h reflective end-of-module presentation of their real-world practices.

Results

Following the training, a higher degree improvement in participants self-reported familiarity with CC education, self-confidence in their ability to deliver CC education and sustained involve CC education were noted among theinterventionFD group, compared with theregularFD group. In theinterventiongroup,senioracademicians (associate and full professor) are more substantially involved indesigningandleadingCC-based courses than junior academicians (lecturers and assistant professors). Among non-teaching award winners of in theinterventionFD group, the follow-up degree of sustained involvement indelivering, designing and leadingCC-based courses was significantly higher than that of theregulargroup.

Conclusions

Our study demonstrated that leadership training in theinterventionFD modules substantially motivated clinical instructors to become leaders in CC education.
Variability in clinicians’ understanding and reported methods of identifying high-risk surgical patients: a qualitative study
Authors: Selwood Amanda , Blakely Brette , Senthuran Siva , Lane Paul , North John , Clay-Williams Robyn
Published: May 2020

Background

High-risk patients presenting for surgery require complex decision-making and perioperative management. However, given there is no gold standard for identifying high-risk patients, doing so may be challenging for clinicians in practice. Before a gold standard can be established, the state of current practice must be determined. This study aimed to understand how working clinicians define and identify high-risk surgical patients.

Methods

Clinicians involved in the care of high-risk surgical patients at a public hospital in regional Australia were interviewed as part of an ongoing study evaluating a new shared decision-making process for high-risk patients. The new process, Patient-Centred Advanced Care Planning (PC-ACP) engages patients, families, and clinicians from all relevant specialties in shared decision-making in line with the patient’s goals and values. The semi-structured interviews were conducted before the implementation of the new process and were coded using a modified form of the ‘constant comparative method’ to reveal key themes. Themes concerning patient risk, clinician’s understanding of high risk, and methods for identifying high-risk surgical patients were extricated for close examination.

Results

Thirteen staff involved in high-risk surgery at the hospital at which PC-ACP was to be implemented were interviewed. Analysis revealed six sub-themes within the major theme of factors related to patient risk: (1) increase in high-risk patients, (2) recognising frailty, (3) risk-benefit balance, (4) suitability and readiness for surgery, (5) avoiding negative outcomes, and (6) methods in use for identifying high-risk patients. There was considerable variability in clinicians’ methods of identifying high-risk patients and regarding their definition of high risk. This variability occurred even among clinicians within the same disciplines and specialties.

Conclusions

Although clinicians were confident in their own ability to identify high-risk patients, they acknowledged limitations in recognising frail, high-risk patients and predicting and articulating possible outcomes when consenting these patients. Importantly, little consistency in clinicians’ reported methods for identifying high-risk patients was found. Consensus regarding the definition of high-risk surgical patients is necessary to ensure rigorous decision-making.
Identification of single-nucleotide variants associated with susceptibility to Salmonella in pigs using a genome-wide association approach
Authors: Schut Corinne H. , Farzan Abdolvahab , Fraser Russell S. , Ainslie-Garcia Margaret H. , Friendship Robert M. , Lillie Brandon N.
Published: May 2020

Background

Salmonella enterica serovars are a major cause of foodborne illness and have a substantial impact on global human health. In Canada, Salmonella is commonly found on swine farms and the increasing concern about drug use and antimicrobial resistance associated with Salmonella has promoted research into alternative control methods, including selecting for pig genotypes associated with resistance to Salmonella. The objective of this study was to identify single-nucleotide variants in the pig genome associated with Salmonella susceptibility using a genome-wide association approach. Repeated blood and fecal samples were collected from 809 pigs in 14 groups on farms and tonsils and lymph nodes were collected at slaughter. Sera were analyzed for Salmonella IgG antibodies by ELISA and feces and tissues were cultured for Salmonella. Pig DNA was genotyped using a custom 54 K single-nucleotide variant oligo array and logistic mixed-models used to identify SNVs associated with IgG seropositivity, shedding, and tissue colonization.

Results

Variants in/near PTPRJ (p = 0.0000066), ST6GALNAC3 (p = 0.0000099), and DCDC2C (n = 3, p < 0.0000086) were associated with susceptibility to Salmonella, while variants near AKAP12 (n = 3, p < 0.0000358) and in RALGAPA2 (p = 0.0000760) may be associated with susceptibility.

Conclusions

Further study of the variants and genes identified may improve our understanding of neutrophil recruitment, intracellular killing of bacteria, and/or susceptibility to Salmonella and may help future efforts to reduce Salmonella on-farm through genetic approaches.
Determinants of catastrophic health expenditures in Iran: a systematic review and meta-analysis
Authors: Doshmangir Leila , Yousefi Mahmood , Hasanpoor Edris , Eshtiagh Behzad , Haghparast-Bidgoli Hassan
Published: May 2020

Background

Catastrophic health expenditures (CHE) are of concern to policy makers and can prevent individuals accessing effective health care services. The exposure of households to CHE is one of the indices used to evaluate and address the level of financial risk protection in health systems, which is a key priority in the global health policy agenda and an indicator of progress toward the UN Sustainable Development Goal for Universal Health Coverage. This study aims to assess the CHE at population and disease levels and its influencing factors in Iran.

Methods

This study is a systematic review and meta-analysis. The following keywords and their Persian equivalents were used for the review: Catastrophic Health Expenditures; Health Equity; Health System Equity; Financial Contribution; Health Expenditures; Financial Protection; Financial Catastrophe; and Health Financing Equity. These keywords were searched with no time limit until October 2019 in PubMed, Web of Science, Scopus, ProQuest, ScienceDirect, Embase, and the national databases of Iran. Studies that met a set of inclusion criteria formed part of the meta-analysis and results were analyzed using a random-effects model.

Results

The review identified 53 relevant studies, of which 40 are conducted at the population level and 13 are disease specific. At the population level, the rate of CHE is 4.7% (95% CI 4.1% to 5.3%, n = 52). Across diseases, the percentage of CHE is 25.3% (95% CI 11.7% to 46.5%, n = 13), among cancer patients, while people undergoing dialysis face the highest percentage of CHE (54.5%). The most important factors influencing the rate of CHE in these studies are health insurance status, having a household member aged 60–65 years or older, gender of the head of household, and the use of inpatient and outpatient services.

Conclusion

The results suggest that catastrophic health spending in Iran has increased from 2001 to 2015 and has reached its highest levels in the last 5 years. It is therefore imperative to review and develop fair health financing policies to protect people against financial hardship. This review and meta-analysis provides evidence to help inform effective health financing strategies and policies to prioritise high-burden disease groups and address the determinants of CHE.
Jiao-tai-wan for insomnia symptoms caused by the disharmony of the heart and kidney: a study protocol for a randomized, double-blind, placebo-controlled trial
Authors: Zeng Congcong , Liu Xi , Hu Lufeng , Feng Yuan , Xia Nengzhi , Zeng Haihuan , Luo Lin , Ye Ren , Yuan Zhengzhong
Published: May 2020

Background

Insomnia seriously affects people’s normal lives and work. However, effective treatment strategies are scarce. The purpose of this study is to explore the efficacy and safety of Jiao-tai-wan (JTW) for ameliorating insomnia symptoms caused by disharmony of the heart and kidney.

Design

This is a randomized, double-blind, placebo-controlled pilot clinical trial. A total of 124 participants suffering from insomnia symptoms will be randomly assigned to the JTW or placebo group in an equal ratio. The participants will be asked to take JTW or placebo granules twice a day for 1 week. All data will be gathered at baseline and at the end of the drug intervention. The primary outcome measures will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) from baseline to the end of the drug intervention. Secondary outcome measures will include the altered sleep parameters in polysomnography, 1H-magnetic resonance spectroscopy (1H-MRS) evaluation, the Disharmony of Heart and Kidney Scoring System score, and blood tests, including the levels of serum adenosine and melatonin. A laboratory test will be taken before and after treatment to assess the safety of JTW.

Discussion

The outcomes of this study will confirm the efficacy of JTW for the treatment of insomnia symptoms and will also be used to monitor the safety of JTW.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800019239. Registered on 1st November 2018.
Steps to recovery: body weight-supported treadmill training for critically ill patients: a randomized controlled trial
Authors: Kwakman Robin C. H. , Sommers Juultje , Horn Janneke , Nollet Frans , Engelbert Raoul H. H. , van der Schaaf Marike
Published: May 2020

Background

Early mobilization has been proven effective for patients in intensive care units (ICUs) to improve functional recovery. However, early mobilization of critically ill, often mechanically ventilated, patients is cumbersome because of the attachment to tubes, drains, monitoring devices and muscle weakness. A mobile treadmill with bodyweight support may help to initiate mobilization earlier and more effectively. The aim of this study is to assess the effectiveness of weight-supported treadmill training in critically ill patients during and after ICU stay on time to independent functional ambulation.

Methods

In this randomized controlled trial, a custom-built bedside body weight-supported treadmill will be used and evaluated. Patients are included if they have been mechanically ventilated for at least 48 hours, are able to follow instructions, have quadriceps muscle strength of Medical Research Council sum-score 2 (MRC 2) or higher, can sit unsupported and meet the safety criteria for physical exercise. Exclusion criteria are language barriers, no prior walking ability, contraindications for physiotherapy or a neurological condition as reason for ICU admission. We aim to include 88 patients and randomize them into either the intervention or the control group. The intervention group will receive usual care plus bodyweight-supported treadmill training (BWSTT) daily. The BWSSTT consists of walking on a mobile treadmill while supported by a harness. The control group will receive usual care physiotherapy treatment daily consisting of progressive activities such as bed-cycling and active functional training exercises. In both groups, we will aim for a total of 40 minutes of physiotherapy treatment time every day in one or two sessions, as tolerated by the patient. The primary outcome is time to functional ambulation as measured in days, secondary outcomes include walking distance, muscle strength, status of functional mobility and symptoms of post-traumatic stress. All measurements will be done by assessors who are blinded to the intervention on the regular wards until hospital discharge.

Discussion

This will be the first study comparing the effects of BWSTT and conventional physiotherapy for critically ill patients during and after ICU stay. The results of this study contribute to a better understanding of the effectiveness of early physiotherapy interventions for critically ill patients.

Trial registration

Dutch Trial Register (NTR) ID: NL6766. Registered at 1 December 2017.
Biosynthesis of acetylacetone inspired by its biodegradation
Authors: Zhou Yifei , Ding Yamei , Gao Wenjie , Wang Jichao , Liu Xiutao , Xian Mo , Feng Xinjun , Zhao Guang
Published: May 2020

Background

Acetylacetone is a commercially bulk chemical with diverse applications. However, the traditional manufacturing methods suffer from many drawbacks such as multiple steps, harsh conditions, low yield, and environmental problems, which hamper further applications of petrochemical-based acetylacetone. Compared to conventional chemical methods, biosynthetic methods possess advantages such as being eco-friendly, and having mild conditions, high selectivity and low potential costs. It is urgent to develop biosynthetic route for acetylacetone to avoid the present problems.

Results

The biosynthetic pathway of acetylacetone was constructed by reversing its biodegradation route, and the acetylacetone was successfully produced by engineered Escherichia coli (E. coli) by overexpression of acetylacetone-cleaving enzyme (Dke1) from Acinetobacter johnsonii. Several promising amino acid residues were selected for enzyme improvement based on sequence alignment and structure analysis, and the acetylacetone production was improved by site-directed mutagenesis of Dke1. The double-mutant (K15Q/A60D) strain presented the highest acetylacetone-producing capacity which is 3.6-fold higher than that of the wild-type protein. Finally, the strain accumulated 556.3 ± 15.2 mg/L acetylacetone in fed-batch fermentation under anaerobic conditions.

Conclusions

This study presents the first intuitive biosynthetic pathway for acetylacetone inspired by its biodegradation, and shows the potential for large-scale production.
Lufenuron can be transferred by gravid Aedes aegypti females to breeding sites and can affect their fertility, fecundity and blood intake capacity
Authors: Gonzalez Paula V. , Harburguer Laura
Published: May 2020

Background

Aedes aegypti (L.) is the main vector of dengue, yellow fever, Zika and chikungunya viruses. A new method for controlling this mosquito has been developed based on the possibility that wild adult mosquitoes exposed to artificial resting sites contaminated with a larvicide, can disseminate it to larval breeding sites, is named “auto-dissemination”. The present study was undertaken to evaluate if a chitin synthesis inhibitor like lufenuron can be disseminated to larval breeding sites and prevent adult emergence and also if forced contact of Ae. aegypti females with treated surfaces can affect its fertility, fecundity, and blood intake capacity.

Methods

Larval susceptibility to lufenuron was measured through EI50 and EI90. On the other hand, gravid females were exposed by tarsal contact to lufenuron-treated papers, we used the WHO susceptibility test kit tube to line the papers, and 1, 3 or 5 females for the transference. We also evaluated if the exposure of female mosquitoes to lufenuron-treated papers (0.4 and 1 mg a.i./cm2) has an effect on their fertility, fecundity or in the ability to feed on blood. In each assay 12–15 female mosquitoes were exposed to lufenuron for 1 h, 24 h before blood meal (BBM) or 24 h after a blood meal (ABM).

Results

Lufenuron proved to be very active against Ae. aegypti larvae with an EI50 of 0.164 ppb and EI90 of 0.81 ppb. We also found that lufenuron can be transferred by females from treated surfaces to clean containers causing the inhibition of emergence of the larvae (between 30 and 50%). This effect was dependent on the concentration applied on the paper and the number of females added to each cage.

Conclusions

This study introduces an innovation by first exploring the possibility that an insect growth regulator (IGR) belonging to the group of benzoylphenyl ureas, such as lufenuron, can be transferred by gravid females to breeding sites and that at the same time can have an effect on fertility, fecundity and blood intake capacity of adult mosquitoes.
Regulation and analysis of the diversity of intestinal microbiota in SD rats by Danggui Buxue Tang (DBT) fermented with Bacillus subtilis
Authors: Chen Keyuan , Gao Yan , Wang Xinjian , Cheng Feng , Haq Shahbaz Ul , Liang Yun , Yang Zhiwei , Li Bo , Liu Yuan , Wang Yonggang , Liang Jianping , Hao Baocheng
Published: May 2020

Purpose

To investigate the effect of Danggui Buxue Tang (DBT) on intestinal microbiota diversity after fermentation by Bacillus subtilis.

Methods

B. subtilis was used to ferment DBT. Sprague Dawley (SD) rats were randomly divided into the following four groups with six rats in each group: the control group, DBT nonfermentation group, B. subtilis group, and DBT fermentation group. Rats were fed continuously for 14 days. The 16S rRNA of faecal samples was analysed by high-throughput Illumina sequencing.

Results

In total, 3483 operational taxonomical units (OTUs) were identified in this study, and 1236 OTUs were shared among all samples. Moreover, the most abundant phyla identified in this study were Bacteroidetes (29.65–38.19%) and Firmicutes (48.30–67.04%). The F/B ratios of the DBT nonfermentation group (1.07%) and the DBT fermentation group (1.78%) were slightly lower than those of the control group (2.29%). Lactobacillus was most upregulated in the DBT fermentation group (38.4%), followed by the DBT nonfermentation group (18.97%), control group (14.61%), and probiotics group (8.39%). Moreover, the pathogenic bacteria Alistipes and Parabacteroides were found to be downregulated in the DBT fermentation group (the percentages of Alistipes and Parabacteroides were as follows: control group, 8.09% and 0.16%; DBT nonfermentation group, 4.31% and 0.37%; DBT fermentation group, 1.96 and 0.09%; and probiotics group, 6.25% and 0.12%, respectively).

Conclusion

This study is the first to research systematically the effects of DBT on the diversity of rat intestinal microbiota before and after fermentation. The structural characteristics of complex bacterial community in each group were clearly analysed, and DBT significantly increases probiotics and inhibits pathogenic bacterial growth in the intestinal tract of rats after fermentation, which plays a significant role in maintaining the balance of the intestinal microbiota of the rats. This research provides new insights into the development and utilization of traditional Chinese medicine.
The China tuberculosis clinical trials consortium network: a model for international TB clinical trials capacity building
Authors: Liu Yu-Hong , Chen Shu , Gao Jing-Tao , Zhang Yao , Booher Kimberly , Ding Xiao-Fen , Shu Wei , Du Jian , Bao Jing , Hafner Richard , Hamilton Carol D. , Li Liang
Published: May 2020

Background

With the second largest tuberculosis (TB) burden globally, China is committed to actively engage in international TB clinical trials to contribute to global TB research. However, lack of research capacity among local sites has been identified as a barrier.

Main text

The China Tuberculosis Clinical Trials Consortium (CTCTC) was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013, as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials. The program aims to: 1) recruit leading hospitals that care for TB patients; 2) conduct on-site assessment to identify capacity gaps and needs for improvement; 3) design and deliver capacity building activities; 4) attract and deliver high quality results for TB clinical trials.

A total of 24 sites have joined CTCTC, covering 20 provinces in China. Twenty-two sites have been accredited by the National Medical Products Administration (NMPA) to be qualified to conduct TB clinical trials. The onsite assessment, extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials. The establishment and growth of the CTCTC network has benefited from the good leadership, effective international cooperation and local commitment. Issues in human resources, regulatory environment and sustainability have been challenging the network from continuing growth. Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist. The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network.

Conclusions

The CTCTC, with mature management structure and sustainable development model, which are distilled five key lessons for other developing countries or investigators of interest. They are the respectively using assessment-based approach to design tailored training package, understanding the availability of clinical researchers, providing solutions to maintain sustainability, understanding local regulatory environments and working with an international organization with local on-site team, respectively. Although, the experiences and capacity of China’s TB hospitals in conducting clinical research vary. Considerable efforts to continue building the capacity are still needed, although the gap is smaller for a few top-tier hospitals.
Role of extra cellular proteins in gastric cancer progression and metastasis: an update
Authors: Abbaszadegan Mohammad Reza , Mojarrad Majid , Moghbeli Meysam
Published: May 2020

Background

Gastric cancer (GC) is one of the most common cancers in the world with a high ratio of mortality. Regarding the late diagnosis, there is a high ratio of distant metastasis among GC cases. Despite the recent progresses in therapeutic modalities, there is not still an efficient therapeutic method to increase survival rate of metastatic GC cases.

Main body

Apart from the various intracellular signaling pathways which are involved in tumor cell migration and metastasis, the local microenvironment is also a critical regulator of tumor cell migration. Indeed, the intracellular signaling pathways also exert their final metastatic roles through regulation of extra cellular matrix (ECM). Therefore, it is required to assess the role of extra cellular components in biology of GC.

Conclusion

In the present review, we summarize 48 of the significant ECM components including 17 ECM modifying enzymes, seven extracellular angiogenic factors, 13 cell adhesion and cytoskeletal organizers, seven matricellular proteins and growth factors, and four proteoglycans and extra cellular glycoproteins. This review paves the way of determination of a specific extra cellular diagnostic and prognostic panel marker for the GC patients.
Grant reviewer perceptions of the quality, effectiveness, and influence of panel discussion
Authors: Gallo Stephen A. , Schmaling Karen B. , Thompson Lisa A. , Glisson Scott R.
Published: May 2020

Background

Funding agencies have long used panel discussion in the peer review of research grant proposals as a way to utilize a set of expertise and perspectives in making funding decisions. Little research has examined the quality of panel discussions and how effectively they are facilitated.

Methods

Here, we present a mixed-method analysis of data from a survey of reviewers focused on their perceptions of the quality, effectiveness, and influence of panel discussion from their last peer review experience.

Results

Reviewers indicated that panel discussions were viewed favorably in terms of participation, clarifying differing opinions, informing unassigned reviewers, and chair facilitation. However, some reviewers mentioned issues with panel discussions, including an uneven focus, limited participation from unassigned reviewers, and short discussion times. Most reviewers felt the discussions affected the review outcome, helped in choosing the best science, and were generally fair and balanced. However, those who felt the discussion did not affect the outcome were also more likely to evaluate panel communication negatively, and several reviewers mentioned potential sources of bias related to the discussion. While respondents strongly acknowledged the importance of the chair in ensuring appropriate facilitation of the discussion to influence scoring and to limit the influence of potential sources of bias from the discussion on scoring, nearly a third of respondents did not find the chair of their most recent panel to have performed these roles effectively.

Conclusions

It is likely that improving chair training in the management of discussion as well as creating review procedures that are informed by the science of leadership and team communication would improve review processes and proposal review reliability.
RETRACTED ARTICLE: Evaluation of obstructed defecation syndrome (ODS) using magnetic resonance defecography (MRD)
Authors: Parry Arshed Hussain , Wani Abdul Haseeb
Published: May 2020

Background

Obstructed defecation syndrome is associated with varying combinations of a host of ano-rectal abnormalities, and no physical examination can demonstrate these abnormalities. The present study was aimed to evaluate the spectrum of various pelvic floor abnormalities in obstructed defecation syndrome (ODS).

Results

Of the total 302 patients imaged with age range of 18–72 years (mean age 54 years), 218 were females, and 84 were males. Ano-rectal junction descent was the commonest abnormality observed in 273 (90.3%) patients followed by rectocele (232) (76.8%), rectal intussusception (93) (30.7%), and cystocele (92) (30.4%). Cervical descent was observed in 78 (35.7%) of female patients. Spastic perineum was seen in 27 (8.9%) patients.

Conclusion

MRD serves as single stop shop for demonstrating and grading a gamut of pelvic organ abnormalities underpinning ODS which in turn helps in choosing the best treatment plan for the patient.
The Tyranny of Content: “Content Coverage” as a Barrier to Evidence-Based Teaching Approaches and Ways to Overcome It
Authors: Petersen Christina I. , Baepler Paul , Beitz Al , Ching Paul , Gorman Kristen S. , Neudauer Cheryl L. , Rozaitis William , Walker J. D. , Wingert Deb
Published: May 2020

This article proposes that a content-coverage approach to teaching can be a barrier to adopting more learner-centered active-learning approaches to teach biology. It includes strategies that instructors can implement to move to a learner-centered approach incorporating active learning.
Entering Research Learning Assessment (ERLA): Validity Evidence for an Instrument to Measure Undergraduate and Graduate Research Trainee Development
Authors: Butz Amanda R. , Branchaw Janet L.
Published: May 2020

The Entering Research Learning Assessment (ERLA) measures undergraduate and graduate research trainee learning gains in the seven areas of trainee development described in the Entering Research conceptual framework. Validity evidence for the ERLA trainee self-assessment and mentor assessment of trainee learning gains and recommendations for use are presented.
Three challenges that the COVID-19 pandemic represents for psychiatry
Authors: Kesner Ladislav , Horáček Jiří
Published: May 2020

The evolving COVID-19 pandemic and its likely consequences add to the already substantial psychosocial burden caused by global problems, existential threats and heightened uncertainty, which are increasingly confronting communities worldwide. Here we briefly outline three challenges for clinical psychiatry and research, related to coping with the social epidemiology of negative moods, stress and socially mediated traumatic experiences brought on by these adverse developments.
ROHHAD(NET) Syndrome: Systematic Review of the Clinical Timeline and Recommendations for Diagnosis and Prognosis
Authors: Harvengt Julie , Gernay Caroline , Mastouri Meriem , Farhat Nesrine , Lebrethon Marie-Christine , Seghaye Marie-Christine , Bours Vincent
Published: May 2020

Context

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHHAD[NET]) is a rare and potentially fatal disease. No specific diagnostic biomarker is currently available, making prompt diagnosis challenging. Since its first definition in 2007, a complete clinical analysis leading to specific diagnosis and follow-up recommendations is still missing.

Objective

The purpose of this work is to describe the clinical timeline of symptoms of ROHHAD(NET) and propose recommendations for diagnosis and follow-up.

Design

We conducted a systematic review of all ROHHAD(NET) case studies and report a new ROHHAD patient with early diagnosis and multidisciplinary care.

Methods

All the articles that meet the definition of ROHHAD(NET) and provide chronological clinical data were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis individual patient data guidelines. The data were grouped into 7 categories: hypothalamic dysfunction, autonomic dysregulation, hypoventilation, NET, psychiatric symptoms, other clinical manifestations, and outcome.

Results

Forty-three individual patient data descriptions were analyzed. The timeline of the disease shows rapid-onset obesity followed shortly by hypothalamic dysfunction. Dysautonomia was reported at a median age of 4.95 years and hypoventilation at 5.33 years, or 2.2 years after the initial obesity. A NET was reported in 56% of the patients, and 70% of these tumors were diagnosed within 2 years after initial weight gain.

Conclusion

Because early diagnosis improves the clinical management and the prognosis in ROHHAD(NET), this diagnosis should be considered for any child with rapid and early obesity. We propose guidance for systematic follow-up and advise multidisciplinary management with the aim of improving prognosis and life expectancy.
Effect of Glucagon on Ischemic Heart Disease and Its Risk Factors: A Mendelian Randomization Study
Authors: Ng Jack C M , Schooling C Mary
Published: May 2020

Context

Glucagon acts reciprocally with insulin to regular blood glucose. However, the effect of glucagon on cardiovascular disease has not been widely studied. It has been suggested that insulin may increase the risk of ischemic heart disease.

Objective

To investigate whether glucagon, the main counteracting hormone of insulin, plays a role in development of ischemic heart disease.

Design, Setting, and Participants

In this 2-sample Mendelian randomization study, we estimated the causal effect of glucagon on ischemic heart disease and its risk factors using the inverse-variance weighted method with multiplicative random effects and multiple sensitivity analyses. Genetic associations with glucagon and ischemic heart disease and its risk factors, including type 2 diabetes and fasting insulin, were obtained from publicly available genome-wide association studies.

Main Outcome Measure

Odds ratio for ischemic heart disease and its risk factors per 1 standard deviation change in genetically predicted glucagon.

Results

Twenty-four single-nucleotide polymorphisms strongly (P < 5 × 10−6) and independently (r2 < 0.05) predicting glucagon were obtained. Genetically predicted higher glucagon was associated with an increased risk of ischemic heart disease (inverse-variance weighted odds ratio, 1.03; 95% confidence interval, 1.0003-1.05) but not with type 2 diabetes (inverse-variance weighted odds ratio, 0.998, 95% confidence interval, 0.97-1.03), log-transformed fasting insulin (inverse-variance weighted beta, 0.002, 95% confidence interval, -0.01 to 0.01), other glycemic traits, blood pressure, reticulocyte, or lipids.

Conclusion

Glucagon might have an adverse impact on ischemic heart disease. Relevance of the underlying pathway to existing and potential interventions should be investigated.