bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental and individual factors associated with quality of life of adults who underwent bariatric surgery: a cohort study
Authors: de Oliveira Lima Marina Dayrell , da Silva Thales Philipe Rodrigues , de Menezes Mariana Carvalho , Mendes Larissa Loures , Pessoa Milene Cristine , de Araújo Lauro Pinheiro Ferreira , Andrade Roberto Guimarães Cabezas , D’Assunção Alexandra Dias Moreira , Manzo Bruna Figueiredo , dos Reis Corrêa Allana , Santos Fernanda Batista Oliveira , Lachtim Sheila Aparecida Ferreira , de Freitas Giselle Lima , de Andrade Lucas Adailton Viana , de Sousa Marco Aurélio , Matozinhos Fernanda Penido
Published: March 2020

Introduction

Obesity is a multifactorial chronic condition associated with genetic, behavioral and environmental factors. Understanding the role of the built and social environment in Quality of Life (QOL) is critical to reducing the negative impacts of the environment on health.

Objective

To estimate the built and social environmental and individual factors that influence the QOL of adults who underwent bariatric surgery.

Methods

A prospective cohort study conducted with adults who underwent bariatric surgery. Using longitudinal linear regression analysis, we verified the association between the domains of World Health Organization Quality of Life in version bref (WHOQOL-Bref) – General QOL and domains psychological, physical health, social relations and environment – and possible influencing factors.

Results

The increase in Body Mass Index (BMI) reduces on average 0.47 points in physical domain assessment score. The increase of healthy establishments within the buffer increases on average 0.52 points in the physical domain score. Being female reduces, on average, 5.35 points in the psychological domain evaluation score. Adults who practiced less than 150 min a week of leisure-time physical activity had a 3.27 point average reduction in the social relations domain assessment score. The increase in the number of Supermarkets and Hypermarkets in the buffer increases on average 2.18 points from the Social Relations domain score.

Conclusions

Individual and contextual factors were associated with the QOL of adults who underwent bariatric surgery. Although the surgery yields positive results, the maintenance of same is strongly related to changes in lifestyle, the built environment and multi-professional guidance.
A biopsychosocial-cultural model for understanding oral-health-related quality of life among adolescent orthodontic patients
Authors: Ao Hua , Deng Xiao , She Ying , Wen Xin , Wu Qingrong , Chen Fuguo , Gao Xiao
Published: March 2020

Background

Based on previous theoretical oral-health-related quality of life (OHRQoL) models and most recently framework, as well as sociocultural model of body image dissatisfaction, the current study aimed to investigate the effect of individual (dental aesthetics and dental appearance social comparison) and sociocultural factors (social reinforcement from parents, peers and mass media on dental aesthetics) as well as their interaction on psychosocial dimension of OHRQoL among adolescent orthodontic patients.

Methods

In this cross-sectional study comprising 427 adolescent orthodontic patients (151 boys and 276 girls) aged between 11 and 16 years old, the psychosocial dimension of OHRQoL was measured by Psychosocial Impact of Dental Aesthetics Questionnaire. Individual predictor of dental aesthetics was defined by the Aesthetic Component of the Index of Orthodontic Treatment Need, and dental appearance social comparison was assessed by four items adapted from Physical Appearance Comparison Scale. Sociocultural predictor of social reinforcement was measured by six items adapted from Perceived Sociocultural Pressure Scale. Spearman correlations, path analyses, and structural equation modeling were used to build up several predictive models.

Results

As hypothesized, two direct pathways were observed that patients’ dental aesthetics and all three sources of social reinforcement directly predicted the psychosocial dimension of OHRQoL. Meanwhile, we observed one indirect pathway, that three sources of social reinforcement predicted the psychosocial dimension of OHRQoL, in part, through dental appearance social comparison.

Conclusions

This study provides preliminary evidence indicating that dental aesthetics, social reinforcement and dental appearance comparison are reliable predictors of psychosocial dimension of OHRQoL among adolescent orthodontic patients.
Emerging therapies for smoke inhalation injury: a review
Authors: Mercel Alexandra , Tsihlis Nick D. , Maile Rob , Kibbe Melina R.
Published: March 2020

Background

Smoke inhalation injury increases overall burn mortality by up to 20 times. Current therapy remains supportive with a failure to identify an optimal or targeted treatment protocol for smoke inhalation injury. The goal of this review is to describe emerging therapies that are being developed to treat the pulmonary pathology induced by smoke inhalation injury with or without concurrent burn injury.

Main body

A comprehensive literature search was performed using PubMed (1995–present) for therapies not approved by the U.S. Food and Drug Administration (FDA) for smoke inhalation injury with or without concurrent burn injury. Therapies were divided based on therapeutic strategy. Models included inhalation alone with or without concurrent burn injury. Specific animal model, mechanism of action of medication, route of administration, therapeutic benefit, safety, mortality benefit, and efficacy were reviewed. Multiple potential therapies for smoke inhalation injury with or without burn injury are currently under investigation. These include stem cell therapy, anticoagulation therapy, selectin inhibition, inflammatory pathway modulation, superoxide and peroxynitrite decomposition, selective nitric oxide synthase inhibition, hydrogen sulfide, HMG-CoA reductase inhibition, proton pump inhibition, and targeted nanotherapies. While each of these approaches shows a potential therapeutic benefit to treating inhalation injury in animal models, further research including mortality benefit is needed to ensure safety and efficacy in humans.

Conclusions

Multiple novel therapies currently under active investigation to treat smoke inhalation injury show promising results. Much research remains to be conducted before these emerging therapies can be translated to the clinical arena.
Cerebrospinal fluid dynamics in non-acute post-traumatic ventriculomegaly
Authors: Lalou Afroditi D. , Levrini Virginia , Czosnyka Marek , Gergelé Laurent , Garnett Matthew , Kolias Angelos , Hutchinson Peter J. , Czosnyka Zofia
Published: March 2020

Background

Post-traumatic hydrocephalus (PTH) is potentially under-diagnosed and under-treated, generating the need for a more efficient diagnostic tool. We aim to report CSF dynamics of patients with post-traumatic ventriculomegaly.

Materials and methods

We retrospectively analysed post-traumatic brain injury (TBI) patients with ventriculomegaly who had undergone a CSF infusion test. We calculated the resistance to CSF outflow (Rout), AMP (pulse amplitude of intracranial pressure, ICP), dAMP (AMPplateau-AMPbaseline) and compensatory reserve index correlation coefficient between ICP and AMP (RAP). To avoid confounding factors, included patients had to be non-decompressed or with cranioplasty > 1 month previously and Rout > 6 mmHg/min/ml. Compliance was assessed using the elasticity coefficient. We also compared infusion-tested TBI patients selected for shunting versus those not selected for shunting (consultant decision based on clinical and radiological assessment and the infusion results). Finally, we used data from a group of shunted idiopathic Normal Pressure Hydrocephalus (iNPH) patients for comparison.

Results

Group A consisted of 36 patients with post-traumatic ventriculomegaly and Group B of 45 iNPH shunt responders. AMP and dAMP were significantly lower in Group A than B (0.55 ± 0.39 vs 1.02 ± 0.72; p < 0.01 and 1.58 ± 1.21 vs 2.76 ± 1.5; p < 0.01. RAP baseline was not significantly different between the two. Elasticity was higher than the normal limit in all groups (average 0.18 1/ml). Significantly higher Rout was present in those with probable PTH selected for shunting compared with unshunted. Mild/moderate hydrocephalus, ex-vacuo ventriculomegaly/encephalomalacia were inconsistently reported in PTH patients.

Conclusions

Rout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus or atrophy reported on CT/MRI. Compliance appears reduced in PTH.
Heat-health vulnerability in temperate climates: lessons and response options from Ireland
Authors: Paterson Shona K. , Godsmark Christie Nicole
Published: March 2020

Background

In Ireland, rising temperatures remains the climate projection that national climate scientists associate with the highest degree of confidence. However, the health challenge of heat has been largely absent from Ireland’s public health sector. This is epitomised by the lack of a comprehensive public health-focused heat-health action plan or country-specific codes of practice for heat-health when working outdoors. Our objective is to highlight the anticipated heat-health challenges in Ireland, and other temperate regions, through analysing vulnerable groups and systems, reinforcing the need to respond.

Methods

A scoping literature review was conducted to determine how heat affects health of the vulnerable in temperate climatic regions, with a focus on Ireland. Additionally, national Google Trends data was coarsely analysed to determine whether heat is a growing societal concern.

Results and discussion

The heat-vulnerable include: older people; chronically ill; infants, pregnant women, children; outdoor workers; socio-economically disadvantaged; urban dwellers; food systems and the health sector. Google Trends data suggest an increase in heat-related health searches over time, demonstrating rising levels of concern to temperature increases, reinforcing a gap in national policy associated with communication of, and response to, the heat-health challenge. Specific, actionable recommendations for adaptation and mitigation strategies are proposed.

Conclusion

Heat poses a public and occupational health challenge, receiving limited attention in Ireland. Lack of a co-ordinated effort, places vulnerable populations at risk. Our recommendations, with reference to vulnerable groups and acknowledging the multi-sectoral nature of heat-health and climate change, advocate for the adoption of a “health and climate change in all policies” approach and the development of a public health-focused heat-health action plan.
A cross-sectional study of website claims related to diagnoses and treatment of non-musculoskeletal conditions
Authors: Jensen Rikke Krüger , Agersted Mie Elisa Irgens , Nielsen Heike Aaby , O’Neill Søren
Published: March 2020

Background

The Danish Authorisation Act sets out the chiropractic scope of practice. Under this legislation the scope of practice is diagnostics, prevention and treatment of biomechanical disorders of the spine, pelvis and extremities. Despite this and an international movement toward a scientifically active, evidence-based profession with a focus on treatment of musculoskeletal disorders, a large proportion of chiropractors still offer treatment of non-musculoskeletal disorders.

This study aimed to investigate the content and characteristics of website claims by chiropractors in Denmark on non-musculoskeletal conditions and to assess whether these were aligned with the Danish Authorisation Act of the chiropractic scope of practice.

Methods

In this cross-sectional study data on a representative sample were collected from chiropractic clinic websites in Denmark. Information on non-musculoskeletal conditions from the websites was categorised. For each non-musculoskeletal condition, it was noted whether a clarifying explanation justifying the presence of the diagnosis was available and what it said. These explanations were assessed and categorised according to agreement or disagreement with the chiropractic scope of practice as defined by the Danish Authorisation Act. In addition, data on geographic location, clinic size, reimbursement coverage, country of education and special clinical focus (children, athletes, etc) were collected. Differences in characteristics of the clinics and the frequency of reporting non-musculoskeletal conditions were tested using Pearson’s chi-squared or Fisher’s exact test.

Results

A geographically stratified, random sample of 139 (57%) websites was included from chiropractic clinics in Denmark. In total, 36 (26%) of the sampled websites mentioned conditions of non-musculoskeletal origin that was not accompanied by a clarifying explanation in agreement with the chiropractic scope of practice. A positive association between advertising infant or children’s care and advertising treatment for non-musculoskeletal disorders (without adequate explanation) was observed.

Conclusions

A total of 36 (26%) of the sampled chiropractic websites in Denmark mentioned diagnoses or symptoms of non-musculoskeletal origin on their websites without presenting an adequate clarifying explanation in agreement with the chiropractic scope of practice as defined by the Danish Authorisation Act. This could be misleading for patients seeking care for non-musculoskeletal conditions and consequently lead to inappropriate treatment.
Illegal trade of songbirds: an analysis of the activity in an area of northeast Brazil
Authors: de Oliveira Wallisson Sylas Luna , Borges Anna Karolina Martins , de Faria Lopes Sérgio , Vasconcellos Alexandre , Alves Rômulo Romeu Nóbrega
Published: March 2020

Background

This study aimed to analyze the chain and dynamics of the trade of wild birds between keepers and traders in an area of northeast Brazil. Profit from the purchase and sale of these animals in the trade chain was also estimated.

Methods

The information was obtained through interviews with direct participants in the wild bird trade chain.

Results

We recorded a total of 34 bird species involved in illegal trade. In general, the purchase and sale values of songbirds are associated with the attractiveness and songs of the birds. Regarding the commercial potential of the species, those with high numbers of traded individuals had higher average purchase values and, especially, sale values. Birds with lower purchase values showed higher sale profits and were sold in large numbers. The purchase and sale values of songbirds in the present study show a significant economic return for those involved in this activity.

Conclusions

The results of this study may provide data to support future studies on the conservation of wild birds, assisting in monitoring illegal trade, a persistent problem in the region studied.
A convenient, rapid and efficient method for establishing transgenic lines of Brassica napus
Authors: Zhang Kai , He Jianjie , Liu Lu , Xie Runda , Qiu Lu , Li Xicheng , Yuan Wenjue , Chen Kang , Yin Yongtai , Kyaw May Me Me , San Aye Aye , Li Shisheng , Tang Xianying , Fu Chunhua , Li Maoteng
Published: March 2020

Background

Brassica napus is an important oilseed crop that offers a considerable amount of biomass for global vegetable oil production. The establishment of an efficient genetic transformation system with a convenient transgenic-positive screening method is of great importance for gene functional analysis and molecular breeding. However, to our knowledge, there are few of the aforementioned systems available for efficient application in B. napus.

Results

Based on the well-established genetic transformation system in B. napus, five vectors carrying the red fluorescence protein encoding gene from Discosoma sp. (DsRed) were constructed and integrated into rapeseed via Agrobacterium-mediated hypocotyl transformation. An average of 59.1% tissues were marked with red fluorescence by the visual screening method in tissue culture medium, 96.1% of which, on average, were amplified with the objective genes from eight different rapeseed varieties. In addition, the final transgenic-positive efficiency of the rooted plantlets reached up to 90.7% from red fluorescence marked tissues, which was much higher than that in previous reports. Additionally, visual screening could be applicable to seedlings via integration of DsRed, including seed coats, roots, hypocotyls and cotyledons during seed germination. These results indicate that the highly efficient genetic transformation system combined with the transgenic-positive visual screening method helps to conveniently and efficiently obtain transgenic-positive rapeseed plantlets.

Conclusion

A rapid, convenient and highly efficient method was developed to obtain transgenic plants, which can help to obtain the largest proportion of transgene-positive regenerated plantlets, thereby avoiding a long period of plant regeneration. The results of this study will benefit gene functional studies especially in high-throughput molecular biology research.
Clinical analysis of surgery for type III esophageal atresia via thoracoscopy: a study of a Chinese single-center experience
Authors: Zhang Jianqin , Wu Qiang , Chen Liu , Wang Yunjin , Cui Xu , Huang Wenhua , Zhou Chaoming
Published: March 2020

Purpose

The purpose of this study was to investigate the effectiveness and safety of the operation for type III esophageal atresia using a thoracoscope.

Methods

The clinical data for 92 patients with type III esophageal atresia in our hospital from January 2015 to December 2018 were analyzed retrospectively. There were 49 patients in group A who underwent thoracoscopic surgery and 43 patients in group B who underwent conventional surgery.

Results

The mechanical ventilation time (55.7 ± 11.4 h vs 75.6 ± 19.2 h), intensive care time (3.6 ± 1.8d vs 4.7 ± 2.0d), postoperative hospitalization time (13.1 ± 2.2d vs 16.8 ± 4.3d), thoracic drainage volume (62.7 ± 25.5 ml vs 125.4 ± 46.1 ml), blood transfusion volume (30.5 ± 10.4 ml vs 55.3 ± 22.7 ml) and surgical incision length (2.0 ± 0.5 cm vs 8.0 ± 1.8 cm) in group A were lower than those in group B, and the differences were statistically significant (P < 0.05). Among the postoperative complications, the incidences of postoperative severe pneumonia (8.2% vs 23.3%), poor wound healing (2.0% vs 14.0%) and chest wall deformity (0% vs 11.6%) in group A were significantly lower than those in group B (P < 0.05). There was no significant difference in the incidence of anastomotic stricture, tracheomalacia or gastroesophageal reflux between the two groups after surgery and early during follow-up (P > 0.05), and there were no complications such as achalasia signs and esophageal diverticulum in either group.

Conclusion

Surgery for type III esophageal atresia via thoracoscopy has the same safety and clinical effectiveness as traditional surgery and has the advantages of smaller incision and chest wall deformity.
Perspectives of mental healthcare providers on pathways to improved employment for persons with mental disorders in two lower middle-income countries
Authors: Ebuenyi Ikenna D. , Regeer Barbara J. , Aguocha Chinyere , Bunders-Aelen Joske F. G. , Guxens Mònica
Published: March 2020

Background

Mental disorders affect employment and the ability to work, and mental healthcare providers are important in the promotion of health and employment for affected individuals. The objective of this study is to explore the perspectives of mental healthcare providers on pathways to improved employment for persons with mental disorders in two lower middle-income countries.

Methods

Our study participants included mental healthcare providers (psychiatrists, occupational physicians, psychologists, and social care workers) from Kenya and Nigeria. Qualitative interviews and a focus group discussion were conducted with 15 professionals in Kenya and online questionnaires were completed by 80 professionals from Nigeria.

Results

The study participants suggested that work is important for the recovery and wellbeing of persons with mental disorders. A complex interplay of factors related to the health of persons with mental disorders and the socioeconomic system in their setting were identified as barriers to their work ability and employment. Participants proposed four pathways to improved employment: including information on reducing stigma, better healthcare, policy advocacy in employment, and government commitment to healthcare and social welfare. Public education to reduce stigma and better healthcare were the highest reported facilitators of employment.

Conclusions

Persons with mental disorders require multilevel support and care in obtaining and retaining employment. A better mental healthcare system is essential for the employment of persons with mental disorders.
Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study
Authors: Chang Ying-Jun , Wang Yu , Xu Lan-Ping , Zhang Xiao-Hui , Chen Huan , Chen Yu-Hong , Wang Feng-Rong , Wei-Han  , Sun Yu-Qian , Yan Chen-Hua , Tang Fei-Fei , Mo Xiao-Dong , Liu Yan-Rong , Liu Kai-Yan , Huang Xiao-Jun
Published: March 2020

Background

Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation.

Methods

We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT (n= 169) or MSDT (n= 39).

Results

The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19–33%) and 44% (95% CI, 28–60%) for HIDT and MSDT, respectively (P= 0.043). Compared to the HIDT cohort, the MSDT cohort had a higher 3-year cumulative incidence of relapse (CIR; 47%, 95% CI, 31–63% vs. 23%, 95% CI, 17–29%;P= 0.006) and lower 3-year probability of leukemia-free survival (LFS; 43%, 95% CI, 27–59% vs. 65%, 95% CI, 58–72%;P= 0.023) and overall survival (OS; 46%, 95% CI, 30–62% vs. 68%, 95% CI, 61–75%;P= 0.039), without a difference in non-relapse-mortality (10%, 95% CI, 1–19% vs. 11%, 95% CI, 6–16%;P= 0.845). Multivariate analysis showed that HIDT is associated with a low CIR (HR = 0.364; 95% CI, 0.202–0.655;P= 0.001) and better LFS (HR = 0.414; 95% CI, 0.246–0.695;P= 0.001) and OS (HR = 0.380; 95% CI, 0.220–0.656;P= 0.001).

Conclusions

HIDT is better than MSDT in view of favorable anti-leukemia activity for patients with pre-transplantation MRD positive ALL. The current study paves the way to determine that haploidentical donors are the preferred choice regardless of available matched sibling donors in a subgroup population.

Trial registration

ClinicalTrials.gov Identifier: NCT02185261. Registered July 9, 2014.https://clinicaltrials.gov/ct2/show/NCT02185261?term=NCT02185261&draw=2&rank=1.
Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer
Authors: Feng Li-yuan , Li Li
Published: March 2020

Background

Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis.

Methods

High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter.

Results

In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-β signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS.

Conclusions

NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.
MKRN3 and KISS1R mutations in precocious and early puberty
Authors: Pagani Sara , Calcaterra Valeria , Acquafredda Gloria , Montalbano Chiara , Bozzola Elena , Ferrara Pietro , Gasparri Manuela , Villani Alberto , Bozzola Mauro
Published: March 2020

Background

Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing.

Methods

We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age.

Results

Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C > T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient.

Conclusion

In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP.
Development of a Core Outcome Set for Studies on Cardiac Disease in Pregnancy (COSCarP): a study protocol
Authors: D’Souza Rohan , Hall Chelsea , Sermer Mathew , Siu Samuel , Silversides Candice
Published: March 2020

Background

Clinical studies looking at interventions to optimize pregnancy and long-term outcomes for women with cardiac disease and their babies are inconsistent in their reporting of clinical outcomes, making it difficult to compare results across studies and draw meaningful conclusions. The development of a core outcome set (COS)—a standardized, minimum set of outcomes that must be collected and reported in all studies—is a practical solution to this problem.

Methods/design

We will follow a five-step process in developing a COS for studies on pregnant women with cardiac disease. First, a systematic literature review will identify all reported outcomes (including patient-reported outcomes) and definitions. Second, semi-structured interviews with stakeholders involved in the care of pregnant women with cardiac disease will determine their perspective and add new outcomes that they consider important. Third, an international electronic Delphi survey will narrow outcomes obtained through the first two steps, in an attempt to arrive at a consensus. Fourth, a face-to-face consensus meeting will deliberate to finalize the COS. Finally, measurement tools and definitions for included outcomes will be determined through a series of literature reviews and Delphi surveys.

Discussion

This protocol provides an overview of the steps involved in the development of a COS that must be reported in studies involving pregnant women with cardiac disease, in an attempt to harmonize outcome reporting and ensure the validity of study results that will not only inform clinical practice and future research but also encourage the development of COS in other areas of medicine.

COMET core outcome set registration

http://www.cometinitiative.org/studies/details/834
Synthesis, bioactivities and phloem uptake of dipeptide-chlorantraniliprole derivatives
Authors: Zheng Shijie , Lin Xiaomin , Wu Hanxiang , Zhao Chen , Xu Hanhong
Published: March 2020

Phloem systemicity is a desirable property for insecticides to control sucking insects. However, the development of phloem systemic insecticides is challenging. One possible strategy is to link existed insecticides with endogenous substances so that the resulting conjugates can be transported by specific transporters into the phloem. In this study, novel dipeptide promoieties were introduced into chlorantraniliprole, which is an efficient and broad-spectrum anthranilic diamide insecticide without phloem mobility. Twenty-two new dipeptide-chlorantraniliprole conjugates have been synthesized. Systemic tests showed that all conjugates exhibited phloem mobility in Ricinus communis. In particular, compound 4g with alanyl-alanine dipeptide fragment was able to accumulate in phloem sap (114.49 ± 11.10 μM) in the form of its hydrolysis product 5g. Results of bioassay showed that conjugates 4g and 5g were able to exhibit comparable insecticidal activity against Plutella xylostella L. and Spodoptera exigua compared to its parent compound chlorantraniliprole. This work demonstrated that the dipeptide structures were able to contribute to the improvement of the uptake and phloem mobility of chlorantraniliprole, and two phloem mobile conjugates with satisfactory in vivo insecticidal effect was obtained as new candidates for high-efficient insecticides.
Ability of near-infrared spectroscopy and chemometrics to predict the age of mosquitoes reared under different conditions
Authors: Ong Oselyne T. W. , Kho Elise A. , Esperança Pedro M. , Freebairn Chris , Dowell Floyd E. , Devine Gregor J. , Churcher Thomas S.
Published: March 2020

Background

Practical, field-ready age-grading tools for mosquito vectors of disease are urgently needed because of the impact that daily survival has on vectorial capacity. Previous studies have shown that near-infrared spectroscopy (NIRS), in combination with chemometrics and predictive modeling, can forecast the age of laboratory-reared mosquitoes with moderate to high accuracy. It remains unclear whether the technique has utility for identifying shifts in the age structure of wild-caught mosquitoes. Here we investigate whether models derived from the laboratory strain of mosquitoes can be used to predict the age of mosquitoes grown from pupae collected in the field.

Methods

NIRS data from adult female Aedes albopictus mosquitoes reared in the laboratory (2, 5, 8, 12 and 15 days-old) were analysed against spectra from mosquitoes emerging from wild-caught pupae (1, 7 and 14 days-old). Different partial least squares (PLS) regression methods trained on spectra from laboratory mosquitoes were evaluated on their ability to predict the age of mosquitoes from more natural environments.

Results

Models trained on spectra from laboratory-reared material were able to predict the age of other laboratory-reared mosquitoes with moderate accuracy and successfully differentiated all day 2 and 15 mosquitoes. Models derived with laboratory mosquitoes could not differentiate between field-derived age groups, with age predictions relatively indistinguishable for day 1–14. Pre-processing of spectral data and improving the PLS regression framework to avoid overfitting can increase accuracy, but predictions of mosquitoes reared in different environments remained poor. Principal components analysis confirms substantial spectral variations between laboratory and field-derived mosquitoes despite both originating from the same island population.

Conclusions

Models trained on laboratory mosquitoes were able to predict ages of laboratory mosquitoes with good sensitivity and specificity though they were unable to predict age of field-derived mosquitoes. This study suggests that laboratory-reared mosquitoes do not capture enough environmental variation to accurately predict the age of the same species reared under different conditions. Further research is needed to explore alternative pre-processing methods and machine learning techniques, and to understand factors that affect absorbance in mosquitoes before field application using NIRS.
A comprehensive overview of bull sperm-borne small non-coding RNAs and their diversity across breeds
Authors: Sellem Eli , Marthey Sylvain , Rau Andrea , Jouneau Luc , Bonnet Aurelie , Perrier Jean-Philippe , Fritz Sébastien , Le Danvic Chrystelle , Boussaha Mekki , Kiefer Hélène , Jammes Hélène , Schibler Laurent
Published: March 2020

Background

Mature sperm carry thousands of RNAs, including mRNAs, lncRNAs, tRNAs, rRNAs and sncRNAs, though their functional significance is still a matter of debate. Growing evidence suggests that sperm RNAs, especially sncRNAs, are selectively retained during spermiogenesis or specifically transferred during epididymis maturation, and are thus delivered to the oocyte at fertilization, providing resources for embryo development. However , a deep characterization of the sncRNA content of bull sperm and its expression profile across breeds is currently lacking. To fill this gap, we optimized a guanidinium–Trizol total RNA extraction protocol to prepare high-quality RNA from frozen bull sperm collected from 40 representative bulls from six breeds. Deep sequencing was performed (40 M single 50-bp reads per sample) to establish a comprehensive repertoire of cattle sperm sncRNA.

Results

Our study showed that it comprises mostly piRNAs (26%), rRNA fragments (25%), miRNAs (20%) and tRNA fragments (tsRNA, 14%). We identified 5p-halves as the predominant tsRNA subgroup in bull sperm, originating mostly from Gly and Glu isoacceptors. Our study also increased by ~ 50% the sperm repertoire of known miRNAs and identified 2022 predicted miRNAs. About 20% of sperm miRNAs were located within genomic clusters, expanding the list of known polycistronic pri-miRNA clusters and defining several networks of co-expressed miRNAs. Strikingly, our study highlighted the great diversity of isomiRs, resulting mainly from deletions and non-templated additions (A and U) at the 3p end. Substitutions within miRNA sequence accounted for 40% of isomiRs, with G>A, U>C and C>U substitutions being the most frequent variations. In addition, many sncRNAs were found to be differentially expressed across breeds.

Conclusions

Our study provides a comprehensive overview of cattle sperm sncRNA, and these findings will pave the way for future work on the role of sncRNAs in embryo development and their relevance as biomarkers of semen fertility.
Burden of tumor mutations, neoepitopes, and other variants are weak predictors of cancer immunotherapy response and overall survival
Authors: Wood Mary A. , Weeder Benjamin R. , David Julianne K. , Nellore Abhinav , Thompson Reid F.
Published: March 2020

Background

Tumor mutational burden (TMB; the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as a result. However, TMB harbors intrinsic variability across cancer types, and its assessment and interpretation are poorly standardized.

Methods

Using a standardized approach, we quantify the robustness of TMB as a metric and its potential as a predictor of immunotherapy response and survival among a diverse cohort of cancer patients. We also explore the additive predictive potential of RNA-derived variants and neoepitope burden, incorporating several novel metrics of immunogenic potential.

Results

We find that TMB is a partial predictor of immunotherapy response in melanoma and non-small cell lung cancer, but not renal cell carcinoma. We find that TMB is predictive of overall survival in melanoma patients receiving immunotherapy, but not in an immunotherapy-naive population. We also find that it is an unstable metric with potentially problematic repercussions for clinical cohort classification. We finally note minimal additional predictive benefit to assessing neoepitope burden or its bulk derivatives, including RNA-derived sources of neoepitopes.

Conclusions

We find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma.
Quantitative assessment of German Holstein dairy cattle colostrum and impact of thermal treatment on quality of colostrum viscosity and immunoglobulins
Authors: Hassan Abdulwahed Ahmed , Ganz Sebastian , Schneider Florian , Wehrend Axel , Khan Izhar U. H. , Failing Klaus , Bülte Michael , Abdulmawjood Amir
Published: March 2020

Objective

This study aimed to determine the color, fat, viscosity, IgG concentration, %Brix and refractive index of fresh postpartum colostrum of German Holstein dairy cattle and assess the impact of different thermal treatments on the visual and dynamic viscosity, in association to IgG concentration, of colostrum that can be used for pasteurization process.

Results

Of the total 40 fresh postpartum colostrum, the color of colostrum (ranging from white-pale yellow to yellow and dark-yellowish), fat (1.4–8.2 100 g−1), IgG (4–116 mg mL−1), %Brix (8.5–35.4%), refractive index (1.3454–1.3905 nD), visual (ranging from watery to liquid and thick) and dynamic (4.9–219 cp) viscosity, were recorded. Statistical analysis between visual and dynamic viscosity of fresh colostrum showed significant correlation coefficients (rs = 634). Moreover, a significant correlation between viscosity and three IgG concentrations was also observed. Heat-treated colostrum showed dynamic viscosity ranged from 25 to 3066 cP, where dynamic viscosity of colostrum before- and after heat-treatment showed no significant correlation. Treated colostrum at 60 °C/60 min and 63.5 °C/30 min containing IgG concentration ≤ 80 mg mL−1 and ≤ 68 mg mL−1 showed no significant change in the viscosity and can successfully be applied for pasteurization of first postpartum colostrum.
Effects of pharmacist intervention on polypharmacy in patients with type 2 diabetes in Japan
Authors: Horii Takeshi , Atsuda Koichiro
Published: March 2020

Objective

Investigation of polypharmacy in patients with type 2 diabetes revealed that medications administered according to the patient’s symptoms and complaints strongly contributed to polypharmacy. We explored the effects of clinical ward pharmacy service, which evaluated the need for symptomatic treatment, therefore minimizing polypharmacy by reducing inappropriate medications.

Results

The number of drugs (hospitalization vs. discharge: 9 [1–17] vs. 7 [1–16], P < 0.001) and rate of polypharmacy (hospitalization vs. discharge: 75.4% vs. 61.1%, P < 0.001) were significantly lower at discharge. Since hospital admission, the number of drugs increased (n = 6, 11%), remained unchanged (n = 15, 28%), decreased by 1 drug (n = 4, 8%), decreased by 2 drugs (n = 3, 6%), and decreased by more than 2 drugs (n = 25, 47%). Daily drug costs were significantly reduced (hospitalization vs. discharge: $8.3 vs. $6.1, P < 0.001).
A naturally-occurring 22-bp coding deletion in Ugt86Dd reduces nicotine resistance in Drosophila melanogaster
Authors: Macdonald Stuart J. , Highfill Chad A.
Published: March 2020

Objective

Segregating genetic variants contribute to the response to toxic, xenobiotic compounds, and identifying these causative sites can help describe the mechanisms underlying metabolism of toxic compounds. In previous work we implicated the detoxification gene Ugt86Dd in the genetic control of larval nicotine resistance in Drosophila melanogaster. Furthermore, we suggested that a naturally-occurring 22-bp deletion that leads to a stop codon in exon 2 of the gene markedly reduces resistance. Here we use homology directed CRISPR/Cas9 gene editing to specifically test this hypothesis.

Results

We edited chromosome three from an inbred strain named A4 which carries the insertion allele at Ugt86Dd, successfully generated four alleles carrying the 22-bp Ugt86Dd deletion, and substituted edited chromosomes back into the A4 background. The original A4 strain, and an un-edited control strain in the same A4 background, show no significant difference in egg-to-adult or larva-to-adult viability on either control media or nicotine-supplemented media, and only slightly delayed development in nicotine media. However, strains carrying the 22-bp deletion showed reduced viability in nicotine conditions, and significantly longer development. Our data strongly suggest that the naturally-occurring 22-bp insertion/deletion event in Ugt86Dd directly impacts variation in nicotine resistance in D. melanogaster.
The study of factors associated with pregnancy outcomes in patients with systemic lupus erythematosus
Authors: Zamani Batool , Shayestehpour Mohammad , Esfahanian Farifteh , Akbari Hossein
Published: March 2020

Objectives

Systemic lupus erythematosus (SLE) is an autoimmune disease that can lead to unfavorable pregnancy complications in women. This study aimed to evaluate the factors associated with pregnancy outcomes in patients with SLE.

Results

Fifty-nine pregnant women with SLE (121 pregnancies) participated in this retrospective cohort study. The mean age of the patients was 33.74 ± 3.80 years (range 21 to 48 years). Fetal loss occurred in 43.8% of pregnancies. The most common laboratory findings in SLE patients were antinuclear antibody (81.4%) and anti-ds DNA positivity (54.2%). High levels of C-reactive protein (CRP) during pregnancy, renal involvement, anti-double-stranded DNA positivity, anti-phospholipid antibody (APA) positivity and younger age at disease onset were significantly correlated with unfavourable pregnancy outcomes. A significant difference was observed between duration of SLE and low birth weight (P = 0.003), pre-eclampsia (P = 0.012) and still birth (P = 0.036). High CRP, APA positivity, anti-dsDNA positivity and kidney involvement were predictors of adverse pregnancy outcomes in SLE patients. Renal involvement increased risk of pregnancy with complication 8.5 times (OR = 8.5, 95% CI 1.396–63.373, P = 0.017). Antiphospholipid syndrome (APS) also was associated with an odds ratio of 5.18 (95% CI 1.681–13.647, P = 0.001).
The association of DNA methylation with body mass index: distinguishing between predictors and biomarkers
Authors: Reed Zoe E. , Suderman Matthew J. , Relton Caroline L. , Davis Oliver S. P. , Hemani Gibran
Published: March 2020

Background

DNA methylation is associated with body mass index (BMI), but it is not clear if methylation scores are biomarkers for extant BMI or predictive of future BMI. Here, we explore the causal nature and predictive utility of DNA methylation measured in peripheral blood with BMI and cardiometabolic traits.

Methods

Analyses were conducted across the life course using the ARIES cohort of mothers (n = 792) and children (n = 906), for whom DNA methylation and genetic profiles and BMI at multiple time points (3 in children at birth, in childhood and in adolescence; 2 in mothers during pregnancy and in middle age) were available. Genetic and DNA methylation scores for BMI were derived using published associations between BMI and DNA methylation and genotype. Causal relationships between methylation and BMI were assessed using Mendelian randomisation and cross-lagged models.

Results

The DNA methylation scores in adult women explained 10% of extant BMI variance. However, less extant variance was explained by scores generated in the same women during pregnancy (2% BMI variance) and in older children (15–17 years; 3% BMI variance). Similarly, little extant variance was explained in younger children (at birth and at 7 years; 1% and 2%, respectively). These associations remained following adjustment for smoking exposure and education levels. The DNA methylation score was found to be a poor predictor of future BMI using linear and cross-lagged models, suggesting that DNA methylation variation does not cause later variation in BMI. However, there was some evidence to suggest that BMI is predictive of later DNA methylation. Mendelian randomisation analyses also support this direction of effect, although evidence is weak. Finally, we find that DNA methylation scores for BMI are associated with extant cardiometabolic traits independently of BMI and genetic score.

Conclusion

The age-specific nature of DNA methylation associations with BMI, lack of causal relationship and limited predictive ability of future BMI indicate that DNA methylation is likely influenced by BMI and might more accurately be considered a biomarker of BMI and related outcomes rather than a predictor. Future epigenome-wide association studies may benefit from further examining associations between early DNA methylation and later health outcomes.
Cortical ischaemic patterns in term partial-prolonged hypoxic-ischaemic injury—the inter-arterial watershed demonstrated through atrophy, ulegyria and signal change on delayed MRI scans in children with cerebral palsy
Authors: Chacko Anith , Andronikou Savvas , Mian Ali , Gonçalves Fabrício Guimarães , Vedajallam Schadie , Thai Ngoc Jade
Published: March 2020

The inter-arterial watershed zone in neonates is a geographic area without discernible anatomic boundaries and difficult to demarcate and usually not featured in atlases. Schematics currently used to depict the areas are not based on any prior anatomic mapping, compared to adults.

Magnetic resonance imaging (MRI) of neonates in the acute to subacute phase with suspected hypoxic-ischaemic injury (HII) can demonstrate signal abnormality and restricted diffusion in the cortical and subcortical parenchyma of the watershed regions.

In the chronic stage of partial-prolonged hypoxic-ischaemic injury, atrophy and ulegyria can make the watershed zone more conspicuous as a region. Our aim is to use images extracted from a sizable medicolegal database (approximately 2000 cases), of delayed MRI scans in children with cerebral palsy, to demonstrate the watershed region.

To achieve this, we have selected cases diagnosed on imaging as having sustained a term pattern of partial-prolonged HII affecting the hemispheric cortex, based on the presence of bilateral, symmetric atrophy with ulegyria. From these, we have identified those patients demonstrating injury along the whole watershed continuum as well as those demonstrating selective anterior or posterior watershed predominant injury for demonstration.

Recognition of this zone is essential for diagnosing partial-prolonged hypoxic-ischaemic injury sustained in term neonates. The images presented in this pictorial review provide a template for identifying the cortical watershed distribution when there is milder regional (anterior, parasagittal, peri-Sylvian and posterior) watershed injury and for more severe injury where multiple regions are injured in combination or as a continuum.