bluuebunny/crossref_metadata_2025 huggingface dataset:
A modular cloning toolkit for genome editing in plants
Authors: Hahn Florian , Korolev Andrey , Sanjurjo Loures Laura , Nekrasov Vladimir
Published: April 2020

Background

CRISPR/Cas has recently become a widely used genome editing tool in various organisms, including plants. Applying CRISPR/Cas often requires delivering multiple expression units into plant and hence there is a need for a quick and easy cloning procedure. The modular cloning (MoClo), based on the Golden Gate (GG) method, has enabled development of cloning systems with standardised genetic parts, e.g. promoters, coding sequences or terminators, that can be easily interchanged and assembled into expression units, which in their own turn can be further assembled into higher order multigene constructs.

Results

Here we present an expanded cloning toolkit that contains 103 modules encoding a variety of CRISPR/Cas-based nucleases and their corresponding guide RNA backbones. Among other components, the toolkit includes a number of promoters that allow expression of CRISPR/Cas nucleases (or any other coding sequences) and their guide RNAs in monocots and dicots. As part of the toolkit, we present a set of modules that enable quick and facile assembly of tRNA-sgRNA polycistronic units without a PCR step involved. We also demonstrate that our tRNA-sgRNA system is functional in wheat protoplasts.

Conclusions

We believe the presented CRISPR/Cas toolkit is a great resource that will contribute towards wider adoption of the CRISPR/Cas genome editing technology and modular cloning by researchers across the plant science community.
Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients
Authors: Kunimoto Mitsuhiro , Shimada Kazunori , Yokoyama Miho , Matsubara Tomomi , Aikawa Tatsuro , Ouchi Shohei , Shimizu Megumi , Fukao Kosuke , Miyazaki Tetsuro , Kadoguchi Tomoyasu , Fujiwara Kei , Abulimiti Abidan , Honzawa Akio , Yamada Miki , Shimada Akie , Yamamoto Taira , Asai Tohru , Amano Atsushi , Smit Andries J. , Daida Hiroyuki
Published: April 2020

Background

Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD.

Methods

We enrolled 319 consecutive CVD patients aged ≥40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF).

Results

The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P <  0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P <  0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13–4.05; P = 0.02).

Conclusion

High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM.
Trauma care and capture rate of variables of World Health Organisation data set for injury at regional hospitals in Tanzania: first steps to a national trauma registry
Authors: Sawe Hendry R. , Reynolds Teri A. , Weber Ellen J. , Mfinanga Juma A. , Coats Timothy J. , Wallis Lee A.
Published: April 2020

Background

In Tanzania, there is no national trauma registry. The World Health Organization (WHO) has developed a data set for injury that specifies the variables necessary for documenting the burden of injury and patient-related clinical processes. As a first step in developing and implementing a national Trauma Registry, we determined how well hospitals currently capture the variables that are specified in the WHO injury set.

Methods

This was a prospective, observational cross-sectional study of all trauma patients conducted in the Emergency Units of five regional referral hospitals in Tanzania from February 2018 to July 2018. Research assistants observed the provision of clinical care in the EU for all patients, and documented performed assessment, clinical interventions and final disposition. Research assistants used a purposefully designed case report form to audit the injury variable capture rate, and to review Ministry of Health (MoH) issued facility Register book recording the documentation of variables. We present descriptive statistics for hospital characteristics, patient volume, facility infrastructure, and capture rate of trauma variables.

Results

During the study period, 2891 (9.3%) patients presented with trauma-related complaints, 70.7% were male. Overall, the capture rate of all variables was 33.6%. Documentation was most complete for demographics 71.6%, while initial clinical condition, and details of injury were documented in 20.5 and 20.8% respectively. There was no documentation for the care prior to Emergency Unit arrival in all hospitals. 1430 (49.5%) of all trauma-related visits seen were documented in the facility Health Management Information System register submitted to the MoH. Among the cases reported in the register book, the date of EU care was correctly documented in 77% cases, age 43.6%, diagnosis 66.7%, and outcome in 38.9% cases. Among the observed procedures, initial clinical condition (28.7%), interventions at Emergency Unit (52.1%), investigations (49.0%), and disposition (62.9%) were documented in the clinical charts.

Conclusions

In the regional hospitals of Tanzania, there is inadequate documentation of the minimum trauma variables specified in the WHO injury data set. Reasons for this are unclear, but will need to be addressed in order to improve documentation to inform a national injury registry.
What was visualized? A method for describing content of performance summary displays in feedback interventions
Authors: Lee Dahee , Panicker Veena , Gross Colin , Zhang Jessica , Landis-Lewis Zach
Published: April 2020

Background

Visual displays such as charts and tables may significantly moderate the effects of audit and feedback interventions, but the systematic study of these intervention components will likely remain limited without a method for isolating the information content of a visual display from its form elements. The objective of this study is to introduce such a method based on an application of visualization frameworks to enable a systematic approach to answer the question, “What was visualized?” in studies of audit and feedback.

Methods

The proposed method uses 3 steps to systematically identify and describe the content of visual displays in feedback interventions: 1) identify displays, 2) classify content, and 3) identify elements. The use of a visualization framework led us to identify information content types as representations of measures (metrics or indicators), ascribees (feedback recipients and comparators), performance levels, and time intervals. We illustrate the proposed method in a series of 3 content analyses, one for each step, to identify visual displays and their information content in published example performance summaries.

Results

We analyzed a convenience sample of 44 published studies of audit and feedback. Through each step, two coders had good agreement. We identified 42 visual displays of performance, containing 6 unique combinations of content types. What was visualized most commonly in the sample was performance levels across a recipient and comparators (i.e. ascribees) for a single measure and single time interval (n = 16). Content types varied in their inclusion of measures, ascribees, and time intervals.

Conclusions

The proposed method appears to be feasible to use as a systematic approach to describing visual displays of performance. The key implication of the method is that it offers more granular and consistent description for empirical, theoretical, and design studies about the information content of feedback interventions.
Validity and reliability of State-Trait Anxiety Inventory in Danish women aged 45 years and older with abnormal cervical screening results
Authors: Gustafson L. W. , Gabel P. , Hammer A. , Lauridsen H. H. , Petersen L. K. , Andersen B. , Bor P. , Larsen M. B.
Published: April 2020

Background

State Trait Anxiety Inventory (STAI) scale was developed in the 1980’s and has been widely used both in clinical settings and in research. However the Danish version of STAI has not been validated. The aim of this study was to assess the validity and reliability of STAI - state anxiety scale in Danish women aged 45 years and older with abnormal cervical cancer screening results.

Methods

Women ≥45 years referred with an abnormal cervical cytology and healthy volunteers (n = 12) underwent cognitive interview after completing STAI. Further, STAI was sent out in an electronic questionnaire to women (n = 109) seen at the gynecological department with abnormal cervical cancer screening test during 2018. Validity and reliability of STAI was evaluated according to the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist by examining internal consistency, test-retest reliability, measurement error, floor and ceiling, construct validity and content validity.

Results

In the cognitive interviews the content validity was evaluated to be very good. The internal consistency of the scale was excellent with Cronbach’s α = 0.93. Test-retest reliability was good with an intra-class correlation coefficient of 0.80 and the systematic difference between test-retest results was negligible. The construct validity was good.

Conclusion

To our best knowledge, this is the first validation study of the Danish translation of STAI-state anxiety scale. This version of STAI demonstrates an acceptable reliability and validity when used in a gynecological setting.
Disconnected relationships between primary care and community-based health and social services and system navigation for older adults: a qualitative descriptive study
Authors: Valaitis Ruta , Cleghorn Laura , Ploeg Jenny , Risdon Cathy , Mangin Derelie , Dolovich Lisa , Agarwal Gina , Oliver Doug , Gaber Jessica , Chung Harjit
Published: April 2020

Background

There are gaps in knowledge and understanding about the relationships between primary care and community-based health and social services in the context of healthy aging at home and system navigation. This study examined provider perspectives on: a) older adults’ health and social needs; b) barriers to accessing services; c) the nature of relationships between primary care and health and social services; and d) ways to facilitate primary care and health and social services navigation to optimize older adults’ health.

Methods

Four focus groups were conducted involving providers (n = 21) in: urban primary care clinics and health and social services organizations serving older adults in Hamilton, Ontario, Canada. Purposive sampling was employed to recruit community health and social services managers, directors or supervisors and primary health care providers in a Family Health Team via email.

Results

Health and social services needs were exacerbated for community-dwelling older adults with multiple chronic conditions. Strong family/caregiver social support and advocacy was often lacking. Access barriers for older adults included: financial challenges; lack of accessible transportation; wait times and eligibility criteria; and lack of programs to address older adults’ needs. Having multiple providers meant that assessments among providers and older adults resulted in contradictory care pathways. Primary care and health and social services linkages were deficient and complicated by poor communication with patients and health literacy barriers. Primary care had stronger links with other health services than with community-based health and social services; primary care providers were frustrated by the complex nature of health and social services navigation; and care coordination was problematic. Health and social services referred older adults to primary care for medical needs and gathered patient information to gauge program eligibility, but not without challenges.

Conclusions

Results point to strategies to strengthen primary care and health and social services system navigation for older adults including: using a person-focused approach; employing effective primary care and health and social services communication strategies; applying effective system navigation; building trust between primary care and health and social services providers; advocating for improved program access; and adapting services/programs to address access barriers and meet older adults’ needs.
Predictors of infectious meningitis or encephalitis: the yield of cerebrospinal fluid in a cross-sectional study
Authors: Dittrich Tolga , Marsch Stephan , Egli Adrian , Rüegg Stephan , De Marchis Gian Marco , Tschudin-Sutter Sarah , Sutter Raoul
Published: April 2020

Background

Cerebrospinal fluid (CSF) analyses are recommended in patients with meningitis and/or encephalitis, but evidence regarding its diagnostic yield is low. We aimed to determine predictors of infectious pathogens in the CSF of adult patients presenting with meningitis, and/or encephalitis.

Methods

Consecutive patients with meningitis and/or encephalitis form 2011–17 at a Swiss academic medical care center were included in this cross-sectional study. Clinical, neuroradiologic, and laboratory data were collected as exposure variables. Infectious meningitis and/or encephalitis were defined as the composite outcome.

For diagnosis of bacterial meningitis the recommendations of the European Society of Clinical Microbiology and Infectious Diseases were followed. Viral meningitis was diagnosed by detection of viral ribonucleic or deoxyribonucleic acid in the CSF. Infectious encephalitis was defined according to the International Encephalitis Consortium (IEC). Meningoencephalitis was diagnosed if the criteria for meningitis and encephalitis were fulfilled. Multinomial logistic regression was performed to identify predictors of the composite outcome. To quantify discriminative power, the c statistic analogous the area under the receiver-operating curve (AUROC) was calculated. An AUROC between 0.7–0.8 was defined as “good”, 08–0.9 as “excellent”, and > 0.9 as “outstanding”. Calibration was defined as “good” if the goodness of fit tests revealed insignificantp-values.

Results

Among 372 patients, infections were diagnosed in 42.7% presenting as meningitis (51%), encephalitis (32%), and meningoencephalitis (17%). Most frequent infectious pathogens wereStreptococcus pneumoniae,Varicella zoster, and Herpes simplex 1&2.While in multivariable analysis lactate concentrations and decreased glucose ratios were the only independent predictors of bacterial infection (AUROCs 0.780, 0.870, and 0.834 respectively), increased CSF mononuclear cells were the only predictors of viral infections (AUROC 0.669). All predictors revealed good calibration.

Conclusions

Prior to microbiologic workup, CSF data may guide clinicians when infection is suspected while other laboratory and neuroradiologic characteristics seem less useful. While increased CSF lactate and decreased glucose ratio areisthe most reliable predictors of bacterial infections in patients with meningitis and/or encephalitis, only mononuclear cell counts predicted viral infections.

Trial registration

ClinicalTrials.gov identifierNCT03856528. Registered on February 26th 2019.
Potential contributions of an on-site nurse mentoring program on neonatal mortality reductions in rural Karnataka state, South India: evidence from repeat community cross-sectional surveys
Authors: Banadakoppa Manjappa Ramesh , Kar Arin , Jayanna Krishnamurthy , Hallad Jyothi S. , Cunningham Troy , Potty Rajaram , Mohan H. L. , Crockett Maryanne , Bradley Janet , Fischer Elizabeth , Sudarshan H. , Blanchard James F. , Moses Stephen , Avery Lisa
Published: April 2020

Background

We assessed the effects of a nurse mentoring program on neonatal mortality in eight districts in India.

Methods

From 2012 to 2015, nurse mentors supported improvements in critical MNCH-related practices among health providers at primary health centres (PHCs) in northern Karnataka, South India. Baseline (n = 5240) and endline (n = 5154) surveys of randomly selected ever-married women were conducted. Neonatal mortality rates (NMR) among the last live-born children in the three years prior to each survey delivered in NM and non-NM-supported facilities were calculated and compared using survival analysis and cumulative hazard function. Mortality rates on days 1, 2–7 and 8–28 post-partum were compared. Cox survival regression analysis measured the adjusted effect on neonatal mortality of delivering in a nurse mentor supported facility.

Results

Overall, neonatal mortality rate in the three years preceding the baseline and endline surveys was 30.5 (95% CI 24.3–38.4) and 21.6 (95% CI 16.3–28.7) respectively. There was a substantial decline in neonatal mortality between the survey rounds among children delivered in PHCs supported by NM: 29.4 (95% CI 18.1–47.5) vs. 9.3 (95% CI 3.9–22.3) (p = 0.09). No significant declines in neonatal mortality rate were observed among children delivered in other facilities or at home. In regression analysis, among children born in nurse mentor supported facilities, the estimated hazard ratio at endline was significantly lower compared with baseline (HR: 0.23, 95% CI: 0.06–0.82, p = 0.02).

Conclusion

The nurse mentoring program was associated with a substantial reduction in neonatal mortality. Further research is warranted to delineate whether this may be an effective strategy for reducing NMR in resource-poor settings.
Prognostic implications of Fibroblast growth factor receptor 1 (FGFR1) gene amplification and protein overexpression in hypopharyngeal and laryngeal squamous cell carcinoma
Authors: Kim Eun Kyung , Cho Yoon Ah , Koh Yoon Woo , Shin Hyang Ae , Cho Byoung Chul , Yoon Sun Och
Published: April 2020

Background

The gene encoding fibroblast growth factor receptor 1 (FGFR1) is emerging as a therapeutic and prognostic biomarker in various cancer types, including head and neck squamous cell carcinoma (SCC). Here, we investigated the clinicopathologic implication of FGFR1 gene amplification and protein overexpression in hypopharyngeal and laryngeal SCC.

Methods

Fluorescence in situ hybridization and immunohistochemistry were performed to determine FGFR1 gene amplification and protein overexpression in 209 surgically resected cases.

Results

FGFR1 amplification observed in 8 (8/66, 12.1%; 6 hypopharynx and 2 larynx) patients and high FGFR1 expression in 21 (21/199, 10.6%) patients significantly correlated with lymph node metastasis and advanced pathological stages. FGFR1 amplification was also associated with worse disease-free survival in multivariate analysis (hazard ratio = 4.527, P = 0.032). High FGFR1 expression was more frequently observed, consistent with the worsening of the degree of histologic differentiation.

Conclusions

FGFR1 amplification may serve as an independent prognostic factor for disease-free survival in hypopharyngeal and laryngeal SCC. Aberrant FGFR signaling caused by FGFR1 gene amplification or protein overexpression may play a crucial role in the malignant evolution and progression of hypopharyngeal and laryngeal SCC, and offer novel therapeutic opportunities in patients with hypopharyngeal and laryngeal SCC that usually lack specific therapeutic targets.
Health workers’ views on factors affecting caregiver engagement with bubble CPAP
Authors: Salimu Sangwani , Kinshella Mai-Lei Woo , Vidler Marianne , Banda Mwai , Newberry Laura , Dube Queen , Molyneux Elizabeth M. , Goldfarb David M. , Kawaza Kondwani , Nyondo-Mipando Alinane Linda
Published: April 2020

Background

Severe respiratory distress is a leading cause of mortality among neonates in Malawi. Despite evidence on the safety, cost effectiveness and efficacy of bubble continuous positive airway pressure (CPAP) in managing the condition, its use in Malawian health facilities is limited and little is known about caregivers’ engagement with perspectives of bubble CPAP. The purpose of this study was to explore caregiver perspectives for bubble CPAP at both central and district hospitals and key factors that enable effective caregiver engagement in Malawi.

Methods

This was a descriptive qualitative study employing secondary analysis of 46 health care worker in-depth interviews. We interviewed the health workers about their thoughts on caregiver perspectives regarding use of bubble CPAP. We implemented the study at a tertiary facility and three district hospitals in southern Malawi. This was a part of a larger study to understand barriers and facilitators to implementing neonatal innovations in resource-constrained hospitals. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). Health workers were purposively selected to include nurses, clinicians and district health management involved in the use of bubble CPAP.

Results

Emerging issues included caregiver fears around bubble CPAP equipment as potentially harmful to their new-borns and how inadequate information provided to caregivers exacerbated knowledge gaps and was associated with refusal of care. However, good communication between health care providers and caregivers was associated with acceptance of care. Caregivers’ decision-making was influenced by relatives and peer advocates were helpful in supporting caregivers and alleviating fears or misconceptions about bubble CPAP.

Conclusions

Since caregivers turn to relatives and peers for support, there is need to ensure that both relatives and peers are counselled on bubble CPAP for improved understanding and uptake. Health workers need to provide simplified, accurate, up-to-date information on the intervention as per caregivers’ level of understanding. Notably, contextualised comprehensible information will help alleviate caregivers’ fear and anxieties about bubble CPAP.
What is the impact of psychiatric decision units on mental health crisis care pathways? Protocol for an interrupted time series analysis with a synthetic control study
Authors: Goldsmith L. P. , Smith J. G. , Clarke G. , Anderson K. , Lomani J. , Turner K. , Gillard S.
Published: April 2020

Background

The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult – 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility – psychiatric decision units (also known as mental health decision units) – have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway.

Methods

Data from four mental health Trusts in England will be analysed using an interrupted time series (ITS) design with the primary outcomes of the rate of (i) ED psychiatric presentations and (ii) voluntary admissions to mental health wards. This will be supplemented with a synthetic control study with the same primary outcomes, in which a comparable control group is generated for each outcome using a donor pool of suitable National Health Service Trusts in England. The methods are well suited to an evaluation of an intervention at a service delivery level targeting population-level health outcome and the randomisation or ‘trialability’ of the intervention is limited. The synthetic control study controls for national trends over time, increasing our confidence in the results. The study has been designed and will be carried out with the involvement of service users and carers.

Discussion

This will be the first formal evaluation of psychiatric decision units in England. The analysis will provide estimates of the effect of the decision units on a number of important service use indicators, providing much-needed information for those designing service pathways.

Trial registration

primary registry: isrctn.com Identifying number: ISRCTN77588384 Link: Date of registration in primary registry: 27/02/2020.

Primary sponsor

St George’s, University of London, Cramner Road, Tooting, SW17 ORE. Primary contact: Joe Montebello.
The characteristics of the frequent exacerbator with chronic bronchitis phenotype and non-exacerbator phenotype in patients with chronic obstructive pulmonary disease: a meta-analysis and system review
Authors: Wu Jian-jun , Xu Hong-ri , Zhang Ying-xue , Li Yi-xuan , Yu Hui-yong , Jiang Liang-duo , Wang Cheng-xiang , Han Mei
Published: April 2020

Background

Chronic obstructive pulmonary disease (COPD) patients with different phenotypes show different clinical characteristics. Therefore, we conducted a meta-analysis to explore the clinical characteristics between the non-exacerbator (NE) phenotype and the frequent exacerbator with chronic bronchitis (FE-CB) phenotype among patients with COPD.

Methods

CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases were searched from the times of their inception to April 30, 2019. All studies that reported the clinical characteristics of the COPD phenotypes and which met the inclusion criteria were included. The quality assessment was analyzed by Cross-Sectional/Prevalence Study Quality recommendations. The meta-analysis was carried out using RevMan5.3.

Results

Ten cross-sectional observation studies (n = 8848) were included. Compared with the NE phenotype, patients with the FE-CB phenotype showed significantly lower forced expiratory volume in 1 s percent predicted (FEV1%pred) (mean difference (MD) -8.50, 95% CI -11.36–-5.65, P < 0.001, I2 = 91%), forced vital capacity percent predicted (FVC%pred) [MD − 6.69, 95% confidence interval (CI) -7.73–-5.65, P < 0.001, I2 = 5%], and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (MD -3.76, 95% CI -4.58–-2.95,P < 0.001, I2 = 0%); in contrast, Charlson comorbidity index (MD 0.47, 95% CI 0.37–0.58, P < 0.001, I2 = 0], COPD assessment test (CAT) score (MD 5.61, 95% CI 4.62–6.60, P < 0.001, I2 = 80%), the quantity of cigarettes smoked (pack-years) (MD 3.09, 95% CI 1.60–4.58, P < 0.001, I2 = 41%), exacerbations in previous year (2.65, 95% CI 2.32–2.97, P < 0.001, I2 = 91%), modified Medical British Research Council (mMRC) score (MD 0.72, 95% CI 0.63–0.82, P < 0.001, I2 = 57%), and body mass index (BMI), obstruction, dyspnea, exacerbations (BODEx) (MD 1.78, 95% CI 1.28–2.28, P < 0.001, I2 = 91%), I2 = 34%) were significantly higher in patients with FE-CB phenotype. No significant between-group difference was observed with respect to BMI (MD-0.14, 95% CI -0.70–0.42, P = 0.62, I2 = 75%).

Conclusion

COPD patients with the FE-CB phenotype had worse pulmonary function and higher CAT score, mMRC scores, frequency of acute exacerbations, and the quantity of cigarettes smoked (pack-years) than those with the NE phenotype.
Pain intensity and pressure pain thresholds after a light dynamic physical load in patients with chronic neck-shoulder pain
Authors: Grimby-Ekman A. , Ahlstrand C. , Gerdle B. , Larsson B. , Sandén H.
Published: April 2020

Background

To investigate the development of pain intensity and pressure pain thresholds during and 24 h after a light dynamic physical load among patients with chronic neck-shoulder pain.

Methods

Twenty-six patients with chronic neck-shoulder pain and 12 healthy controls were included. The participants arm-cycled on an ergometer. Effort was rated with the Borg Rating of Perceived Exertion scale (RPE), and pain intensity with an numeric rating scale (NRS). Pressure pain thresholds were measured by an algometer. Participants started a pain diary 1 week before the physical exercise and continued until 1 week after. Pain intensity was assessed before, during and the following two evenings after arm-cycling. Pressure pain thresholds were assessed before, 15 min after, 105 min after and 24 h after.

Results

The chronic pain group showed increased pain intensity during, and the following two evenings after the arm cycling, and decreased pain thresholds immediately after the arm cycling involving painful regions. In the patient group there were no impact on pain thresholds in the neck the following day.

Conclusions

Patients with chronic neck-shoulder pain reported increased pain intensity during and in the evenings after a light dynamic load involving painful regions. In addition, they showed decreased pain thresholds close to the exercise, indicating mechanical hyperalgesia.
Vaginal repaired cesarean section diverticulum is beneficial in women with two prior cesarean sections
Authors: Wang Yizhi , Li Jiarui , Wang Husheng , Wang Xipeng
Published: April 2020

Background

The aim of this study was to evaluate the effect of vaginal repair in patients with cesarean section diverticulum (CSD) who had one or two previous cesarean sections (CSs).

Methods

From January 2012 to December 2014, 248 women with CSD underwent vaginal repair surgery in Shanghai First Maternity and Infant Hospital. These included 193 women with one previous cesarean section and 55 women with two previous cesarean sections. Excision and suture of CSD was performed through a vaginal approach. The duration of menstruation, the length, width and depth of the CSD and thickness of the remaining muscular layer (TRM) were evaluated before and after surgery by transvaginal three-dimensional (3D) color Doppler ultrasound.

Results

A total of 221 (89.11%) women were followed-up for more than 3 months, and 168 (67.74%) women were followed-up for more than 6 months. There were significant differences in the average duration of menstruation (7.77 ± 2.05 and 8.02 ± 2.06 days VS 13.99 ± 3.71 days), the average size of CSD (5.54*9.19*5.60 and 5.75*9.04*6.18 mm VS 7.99*12.43*6.62 mm) and the TRM (7.61 ± 2.52 and 7.60 ± 3.00 mm VS 2.51 ± 1.02 mm) after surgery compared with those figures before surgery. The results of this study reveal that vaginal repair could shorten the duration of menstruation and improve anatomical defects (P < 0.05). Moreover, there was no significant difference in the effect of clinical repair between women with one or two previous cesarean sections (P > 0.05).

Conclusion

In CSD patients, the clinical effectiveness of vaginal repair was equivalent between women with one or two previous cesarean sections.
Is individual practice in an immersive and interactive virtual reality application non-inferior to practicing with traditional equipment in learning systematic clinical observation? A randomized controlled trial
Authors: Berg Helen , Steinsbekk Aslak
Published: April 2020

Background

The aim was to investigate if individual self-practice of the ABCDE approach (Airways, Breathing, Circulation, Disability, Exposure) in an immersive and interactive virtual reality (VR) application gave non-inferior learning outcome compared to using traditional equipment (TP) in first year medical and nursing students.

Methods

A non-inferior parallel group randomized controlled trial. The study was linked to a regular teaching program conducted in August and September 2019. All students participated in a 15-min ABCDE introduction session, before they self-practiced the ABCDE approach for 20 min in either a fully immersive and interactive VR application using hand controllers with some haptic feedback (Individual VR) or with blood pressure gauge, ear-thermometer and oximeter (Individual TP). The primary outcome was the number of students who documented all the eight predefined observations in the ABCDE approach in the correct order in a practical test on an advanced simulator manikin with a time limit of 5 min, done immediately after the self-practice. The predefined one-sided non-inferiority limit was 13% points.

Results

Of all eligible students, 84% participated in the study and randomly allocated to VR (n = 149) or TP (n = 140). The primary outcome showed non-inferiority of the VR application with 24.8% in individual VR doing all observations in correct order compared to 27.1% TP (absolute difference 2.3% points, one sided 95% CI 2.3 to 10.8). The secondary outcomes were similar between the groups, but more students in VR reported liking the way they practiced (absolute difference 46% points, 95% CI 36.5 to 56.6) and that it was a good way to learn (36.9% points, 95% CI 26.8 to 47). VR also scored high on the System Usability Scale (mean difference 6.4% points, 95% CI 2.8–10.1).

Conclusions

Individual self-practicing the ABCDE approach in VR was non-inferior to individual self-practicing with traditional equipment.
The changes of inflammatory mediators and vasoactive substances in dairy cows’ plasma with pasture-associated laminitis
Authors: Zhang Xianhao , Ding Jiafeng , Li Yuepeng , Song Qiaozhi , Li Shuaichen , Hayat Muhammad Abid , Zhang Jiantao , Wang Hongbin
Published: April 2020

Background

Hoof disease is one of the three major diseases that often occur in dairy cows. The impact of this disease on dairy farming is second only to mastitis. Laminitis is a diffuse, aseptic, serous, non-purulent inflammation of the dermal papillae and vascular layers of the cow’s hoof wall. In the pasture, laminitis occurs mostly in the laminae, that is, inside the hoof shell. No lesions can be seen on the surface. Therefore, laminitis cannot attract the attention of veterinarians. However, laminitis has become a major factor that seriously affects the health and welfare of dairy cows, making it an important cause of hindering the performance of dairy cows.

Methods

The study was conducted at a dairy farm in Harbin, Heilongjiang province, China. We selected a sample of the laminitis cows based on the veterinary diagnosis, took blood from the jugular vein and then separated the plasma, and measured the index with the Elisa kit. In this study, the markers of inflammatory and vasoactive substances status in dairy cows consisted of subclinical laminitis (SCL, n = 20), chronic laminitis (CL, n = 20) and healthy dairy cows (CON, n = 20) under the local management conditions were investigated.

Results

Compared with healthy cattle, HIS, IL-6, LPS, and TNF-α in subclinical laminitis group significantly increased (P < 0.05), especially HIS, LPS, TNF-α (P < 0.01); in chronic laminitis cows, COX-2, HIS, IL-6, LPS, and TNF-α increased significantly (P < 0.05), especially COX-2, HIS, TNF-α (P < 0.01). iNOS (P < 0.05), TXB2 (P < 0.01) in chronic laminitis cows had significantly increased.

Conclusion

This study reported for the first time that pasture laminitis was divided into subclinical laminitis and clinical chronic laminitis. Through research on the inflammatory factors and vasoactive substances of dairy cows, it is found that there is a close relationship between them, which affects the metabolic cycle of dairy cows. These indicators are abnormally expressed and cause hoof microcirculation disorders.
Modified entropy-based procedure detects gene-gene-interactions in unconventional genetic models
Authors: Malten Jörg , König Inke R.
Published: April 2020

Background

Since it is assumed that genetic interactions play an important role in understanding the mechanisms of complex diseases, different statistical approaches have been suggested in recent years for this task. One interesting approach is the entropy-based IGENT method by Kwon et al. that promises an efficient detection of main effects and interaction effects simultaneously. However, a modification is required if the aim is to only detect interaction effects.

Methods

Based on the IGENT method, we present a modification that leads to a conditional mutual information based approach under the condition of linkage equilibrium. The modified estimator is investigated in a comprehensive simulation based on five genetic interaction models and applied to real data from the genome-wide association study by the North American Rheumatoid Arthritis Consortium (NARAC).

Results

The presented modification of IGENT controls the type I error in all simulated constellations. Furthermore, it provides high power for detecting pure interactions specifically on unconventional genetic models both in simulation and real data.

Conclusions

The proposed method uses the IGENT software, which is free available, simple and fast, and detects pure interactions on unconventional genetic models. Our results demonstrate that this modification is an attractive complement to established analysis methods.
Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania
Authors: Finda Marceline F. , Christofides Nicola , Lezaun Javier , Tarimo Brian , Chaki Prosper , Kelly Ann H. , Kapologwe Ntuli , Kazyoba Paul , Emidi Basiliana , Okumu Fredros O.
Published: April 2020

Background

Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania.

Methods

In this exploratory qualitative study, Focus group discussions were held with policy-makers, regulators, research scientists and community members. Malaria control interventions discussed were: (a) improved housing, (b) larval source management, (c) mass drug administration (MDA) with ivermectin to reduce vector densities, (d) release of modified mosquitoes, including genetically modified or irradiated mosquitoes, (e) targeted spraying of mosquito swarms, and (f) spatial repellents.

Results

Larval source management and spatial repellents were widely supported across all stakeholder groups, while insecticide-spraying of mosquito swarms was the least preferred. Support for MDA with ivermectin was high among policy makers, regulators and research scientists, but encountered opposition among community members, who instead expressed strong support for programmes to improve housing for poor people in high transmission areas. Policy makers, however, challenged the idea of government-supported housing improvement due to its perceived high costs. Techniques of mosquito modification, specifically those involving gene drives, were viewed positively by community members, policy makers and regulators, but encountered a high degree of scepticism among scientists. Overall, policy-makers, regulators and community members trusted scientists to provide appropriate advice for decision-making.

Conclusion

Stakeholder opinions regarding alternative malaria interventions were divergent except for larval source management and spatial repellents, for which there was universal support. MDA with ivermectin, housing improvement and modified mosquitoes were also widely supported, though each faced concerns from at least one stakeholder group. While policy-makers, regulators and community members all noted their reliance on scientists to make informed decisions, their reasoning on the benefits and disadvantages of specific interventions included factors beyond technical efficiency. This study suggests the need to encourage and strengthen dialogue between research scientists, policy makers, regulators and communities regarding new interventions.
Effectiveness comparison of indocyanine green retention test with the cirrhotic severity scoring in evaluating the pathological severity of liver cirrhosis in patients with hepatocellular carcinoma and Child-Pugh grade A liver function
Authors: Gu Jin , Zhang Erlei , Liang Binyong , Zhang Zunyi , Chen Xiaoping , Huang Zhiyong
Published: April 2020

Background

Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown.

Methods

Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared.

Results

Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality.

Conclusions

CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.
Traditional Chinese medicine Biqi capsule compared with leflunomide in combination with methotrexate in patients with rheumatoid arthritis: a randomized controlled trial
Authors: Wang Zhang , Wu Jiaqi , Li Dongyun , Tang Xuan , Zhao Yue , Cai Xiao , Chen Xianghong , Chen Xiumin , Huang Qingchun , Huang Runyue
Published: April 2020

Background

Biqi capsule is a traditional Chinese medicine widely used as a complementary and alternative treatment for rheumatoid arthritis (RA). The objective is to understand the efficacy, safety and mechanism of Biqi combined with methotrexate (MTX) in RA.

Methods

We present a randomized, controlled pilot trial on Biqi combined with MTX against patients with active RA. Seventy patients were randomized 1:1 to receive Biqi + MTX or Leflunomide (LEF) + MTX for 24 weeks, and were assessed at baseline, 4, 12 and 24 weeks. Serum and urine samples were collected for metabolomics.

Results

Overall, 81.2% patients in Biqi group achieved ACR20 at 24 weeks. No statistically significant differences were observed in primary or secondary outcomes between the two groups. A better safety profile was observed for Biqi with significantly fewer adverse effects reported (11.4%) compared to LEF group (40%, P < 0.05). Comparison between treatment responders and non-responders indicated a unique urine metabolic profile of enriched fatty acids and decreased acylcarnitines associated with Biqi responders, indicating a restored energy homeostasis in response to Biqi. The gene targets of these metabolites were significantly enriched in interleukin-4 and interleukin-13 pathways, implying that Biqi could ameliorate Th2-derived inflammatory response. Multivariate network analysis indicated that patient morning stiffness and SJC were key factors associated with metabolomics in Biqi-treated patients, whereas CRP was the main factor in LEF group. Therefore, Biqi and LEF likely work by influencing different patient clinical parameters.

Conclusions

Our study suggests that Biqi capsule can be a promising alternative option in combination with MTX for RA treatment, and demonstrates the capability of using metabolomics to interrogate mechanism of action for traditional Chinese medicine.

Trial registration This trial is registered with ChiCTR, No. ChiCTR-IPR-16009029. Registered August 15, 2016. http://www.chictr.org.cn/showprojen.aspx?proj=15034
A young girl with right ovarian torsion and left ovarian ectopy
Authors: Morabito Giuliana , Daidone Alessandro , Murru Flora , Iaquinto Marianna , Faleschini Elena , Barbi Egidio , Cozzi Giorgio
Published: April 2020

Background

Mayer-Rokitansky-Küster-Hauser (MRKHS) syndrome refers to congenital hypoplasia/aplasia of the uterus, the cervix and the upper 2/3 of the vagina, in females with normal ovaries and fallopian tubes, secondary sexual characteristics and 46 XX karyotype. This condition originates from abnormal development of Müller’s paramesonephric ducts in the early stages of embryonic development. Kidney agenesis or malformations are the most commonly associated with unilateral kidney agenesis. Ovaries may be ectopic in 16–19% of MRKHS patients. Primary amenorrhoea, due to the absence of the uterus, is the most common presentation. Female karyotype confirmation is mandatory to differentiate it from complete androgen insensitivity syndrome and 17-alpha-hydroxylase deficiency. The management of MRKHS is multidisciplinary in order to encompass psychological, medical and surgical issues.

Case presentation

A four-year-old girl, presented to the emergency department complaining of left groin swelling noted 2 days earlier. The patient had recently been evaluated for an episode of acute abdominal pain and vomiting, with a final diagnosis of right ovarian torsion. At that time, the ultrasound imaging was not able to identify the left kidney, the left ovary and uterus. Surgical abdominal exploration confirmed the right ovarian torsion and was not able to identify the left kidney and the left ovary. Only a remnant of the uterus was present. Therefore, the right ovary was removed, and a diagnosis of MRKHS was made. Ultrasound imaging showed a left inguinal hernia. The hernial sac consisted of a solid oval vascularized formation suggestive of an annexe. The patient underwent a surgical procedure to correct the left inguinal hernia. In the operating setting, the presence of a vascularized, ectopic ovary carrying the tuba inside the hernial sac was observed.

Conclusions

In front of a patient with ovarian torsion and anatomical features suggestive of MRKHS, both the ovaries should always be searched for, with a high suspicion threshold for extrapelvic ovary. Identifying the ectopic ovary, in this case, helped to preserve patient fertility, avoiding a possible torsion.