bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioassay and molecular monitoring of insecticide resistance status in Aedes albopictus populations from Greece, to support evidence-based vector control
Authors: Balaska Sofia , Fotakis Emmanouil Alexandros , Kioulos Ilias , Grigoraki Linda , Mpellou Spyridoula , Chaskopoulou Alexandra , Vontas John 
Published: June 2020

Abstract
Background: Aedes albopictus has a well-established presence in southern European countries, associated with recent disease outbreaks (e.g. chikungunya). Development of insecticide resistance in the vector is a major concern as its control mainly relies on the use of biocides. Data on the species’ resistance status are essential for efficient and sustainable control. To date the insecticide resistance status of Ae. albopictus populations from Greece against major insecticides used in vector control remains largely unknown. Methods: We investigated the insecticide resistance status of 19 Ae. albopictus populations from 11 regions of Greece. Bioassays were performed against diflubenzuron (DFB), Bacillus thuringiensis var. israelensis (Bti), deltamethrin and malathion. Known insecticide resistance loci were molecularly analysed, i.e. voltage-gated sodium channel (VGSC) mutations associated with pyrethroid resistance; presence and frequency of carboxylesterases 3 (CCEae3a) and 6 (CCEae6a) gene amplification associated with organophosphate (OP) resistance and; chitin synthase-1 (CHS-1) for the possible presence of DFB resistance mutations. Results: Bioassays showed full susceptibility to DFB, Bti and deltamethrin, but resistance against the OP malathion (range of mortality: 55.30–91.40%). VGSC analysis revealed a widespread distribution of the mutations F1534C (in all populations, with allelic frequencies between 6.6–68.3%), and I1532T (in 6 populations; allelic frequencies below 22.70%), but absence of V1016G. CCE gene amplifications were recorded in 8 out of 11 populations (overall frequency: 33%). Co-presence of the F1534C mutation and CCEae3a amplification was reported in 39 of the 156 samples analysed by both assays. No mutations at the CHS-1 I1043 locus were detected. Conclusions: The results indicate: (i) the suitability of larvicides DFB and Bti for Ae. albopictus control in Greece; (ii) possible incipient pyrethroid resistance due to the presence of kdr mutations; and (iii) possible reduced efficacy of OPs, in a scenario of re-introducing them for vector control. The study highlights the need for systematic resistance monitoring for developing and implementing appropriate evidence-based control programmes.
Ovarian reserve after three-step laparoscopic surgery for endometriomas utilizing dienogest: a non-randomized prospective pilot study.
Authors: Kitajima Michio , Matsumoto Kanako , Murakami Naoko , Harada Ayumi , Kitajima Yuriko , Masuzaki Hideaki , Miura Kiyonori 
Published: June 2020

Abstract
Background Surgery for endometriomas may cause detrimental effects on ovarian reserve. In this study, we evaluated the safety of three-step laparoscopic surgery for endometriomas utilizing novel progestin, dienogest in terms of post -surgical ovarian reserve.Methods Twelve women received first look laparoscopy (FLL) with fenestration and drainage. Immediately after the surgery, they took oral dienogest 2mg for three months, then they received second look laparoscopy (SLL) with cystectomy. We compared the effects on ovarian reserve by serum AMH levels between women had three step management with dienogest and another twelve women had　conventional one-step surgery without medications. In women had three-step surgery with dienogest, the changes in concentration of proinflammatory cytokines and chemokines (interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1) in peritoneal fluids were evaluated.Results Serum AMH levels were significantly decreased after three months of dienogest following FLL. AMH levels were also significantly decreased 3-6 month both after SLL and after one-step surgery, however, recovery of serum AMH levels at 9-12 months after surgery were evident in women had three-step surgery comparing to those of women had one-step surgery. Proinflammatory cytokines and chemokines in peritoneal fluids were down regulated at the time of SLL comparing to those of FLL.Conclusions Three-step surgery with dienogest may be a beneficial approach to protect ovarian reserve. Dienogest may exert its effects in part by lowering proinflammatory cytokines and chemokines.
Sports activity participation after curved periacetabular osteotomy for acetabular dysplasia
Authors: Takahashi Yoshiki , Takahira Naonobu , Uchiyama Katsufumi , Fukushima Kensuke , Moriya Mitsutoshi , Shibuya Manaka , Tsuda Kouji , Tozaki Kiyoshi , Kudo Sho , Kaneda Hiroaki , Sekita Junya , Takaso Masashi 
Published: June 2020

Abstract
Background: Curved periacetabular osteotomy (CPO) was developed to treat acetabular dysplasia. Given that CPO can improve physical function in the early post-operative period, patients might be able to participate in sports activities post-operatively. Therefore, this study examined the post-operative sports activity participation and characteristics of acetabular dysplasia patients who have undergone CPO.Methods: A total of 52 patients who underwent CPO for acetabular dysplasia were given a questionnaire on pre- and post-operative sports activities; 43 patients responded. We surveyed patients’ sports activities, satisfaction, and physical function. Patients were divided according to whether they participated in sports activities after CPO. Physical function was compared before and after CPO.Results: The pre- and post-operative sports activity participation rates were 55.8% and 72.1%, respectively. Patients mostly performed low-impact sports activities. Moreover, patients who participated in sports activities post-operatively had smaller pre-operative range of motion of hip flexion and returned to full weight bearing earlier.Conclusions: Among acetabular dysplasia patients who underwent CPO, 72.1% participated in sports activities post-operatively. Post-operatively, patients participated not only in low-impact sports activities, but also in high-impact ones. These findings might be useful for advising patients who are concerned about participating in sports activities after CPO.
Qualitative analysis of clinicians’ perspectives on the use of a computerized decision aid in the treatment of psychotic disorders
Authors: Roebroek Lukas , Bruins Jojanneke , Delespaul Philippe A. , Boonstra Albert , Castelein Stynke 
Published: June 2020

Abstract
Background: Clinical decision aids are used in various medical fields to support patients and clinicians when making healthcare decisions. Few attempts have been made to implement such tools in psychiatry. We developed Treatment E-Assist (TREAT); a routine outcome monitoring based computerized clinical decision aid, which generates personalized treatment recommendations in the care of people with psychotic disorders. The aim of this study is to investigate how TREAT is used and evaluated by clinicians and how this tool can be improved. Methods: Clinicians working with TREAT during a clinical trial were asked to participate in semi-structured interviews. The unified theory of acceptance and use of technology (UTAUT) was used as a sensitizing theory to structure a part of the interview questions. The transcripts were coded. An inductive thematic analysis was followed to identify the main themes. Results: 13 clinicians (mean age: 49) of which eight psychiatrists and five nurse practitioners, participated in this study. Eight clinicians experienced TREAT as beneficial, whereas five experienced no additional benefits. Thematic analysis revealed five themes about how TREAT was used and evaluated by clinicians, views on TREAT’s visual structuring of routine outcome monitoring results, guideline based treatment recommendations, contextual factors, effects on patients and effects on shared decision-making. Performance and effort expectancy were perceived as high by clinicians. The facilitating conditions were optimal and perceived social influence was low. Conclusion: This article presents a qualitative evaluation by clinicians of a computerized clinical decision aid in psychosis care. TREAT was viewed by most clinicians as beneficial during their consultations. The visual representation of routine outcome monitoring results was well-appreciated and provided input to discuss treatment planning with patients. The treatment recommendations did not change most treatment decisions but supported clinical reasoning. However, some clinicians were unconvinced about TREAT’s benefits. The delivery, applicability and the availability of resources require improvement to increase TREAT’s efficacy. Not all patients responded well to TREAT but the observed facilitation of shared decision-making is promising. All four predictors of the unified theory of acceptance and use of technology were positively evaluated by the majority of clinicians..
Temperature, Precipitation, Ozone Pollution, and Daily Fatal Unintentional Injuries in Jiangsu Province, China during 2015-2017
Authors: Robertson Leon , Zhou Lian , Chen Kai 
Published: June 2020

Abstract
Background The correlation of unintentional injury mortality to rising temperatures found in several studies could result from changes in behavior that increases exposure to hazards or risk when exposed. Temperature, precipitation and air pollutants may contribute to symptoms and distractions that increase risk or avoidance behavior that reduces risk. This study examines data that allows estimates of the relation of daily maximum temperature, precipitation and ozone pollution to injury mortality risk, each corrected statistically for the correlation with the others.Methods Daily data on unintentional injury deaths and exposures to temperature, precipitation and ozone in 9 cities in Jiangsu Province, China during 2015-2017 were analyzed using Poisson regression. The regression estimates were adjusted for weekends, holidays, an anomalous difference in death rates in Nanjing, and population size.Results Non transport injury death risk increased substantially in relation to higher temperatures when temperatures were in the moderate range and even more so at temperatures 35 degrees (C) and higher. Transport deaths were related to increasing deaths when temperatures were low but the correlation reversed at higher temperatures. Deaths were lower on rainy days when temperatures were cool and moderate with the exception of non-transport injuries when temperatures were moderate. Higher ozone concentrations were associated with more deaths except when temperatures were low. Injury mortality on weekends and holidays varied in relation to temperature as well. Conclusions The variations in deaths in relation to temperature, precipitation and ozone suggest that people are behaving differently or are in different environments when specific combinations of the predictor variables are prevalent, putting them at greater or less risk. More study of the behaviors and circumstances that result in injury under those conditions is needed.
Ex-Utero Intrapartum Treatment (EXIT): indications and outcome in fetal cervical and oropharyngeal masses
Authors: García-Díaz Lutgardo , Chimenea Ángel , de Agustín Juan Carlos , Pavón Antonio , Antiñolo Guillermo 
Published: June 2020

Abstract
Background

The “Ex-Utero Intrapartum Treatment” (EXIT) procedure allows to ensure fetal airway before completion of delivery and umbilical cord clamping, while keeping uteroplacental circulation. Airway obstruction in fetal oropharyngeal and cervical masses can be life-threatening at birth. In those situations, a controlled access to fetal airway carried out by a trained multidisciplinary team allows a safe airway management, while feto-maternal circulation is preserved. We aim to review the indications and outcome of EXIT procedure in a cases series of fetal cervical and oropharyngeal masses.

Methods

We performed a retrospective review of all patients with fetal cervical and oropharyngeal masses who underwent an EXIT procedure between 2008 and 2019. Variables evaluated included indication for EXIT, ultrasound and MRI findings, need of amnioreduction, gestational age at EXIT, birth weight, complications, operative time, survival rate, pathological findings and postnatal evolution. Five patients are included in this series. One additional case has already been published.

Results

The diagnosis were cervical teratoma (n=1), epulis (n=1) and lymphangioma (n=3). Polyhydramnios was present in 2 patients, requiring amnioreduction in one of them. Mean gestational age at EXIT was 36-37 weeks (range, 34-38 weeks). Median EXIT time in placental support was 9 minutes (range, 3-22 minutes). Access to airway was successfully established in EXIT in all cases. All children born by EXIT are currently healthy and without complications.

Conclusion

The localization and characteris­tics of the mass, its relationship to the airway and the presence of polyhydramnios seems to be major factors determining indications for EXIT and clinical outcome.
New Mechanisms to Fund Independent Clinical Trials for Repurposing Off-Patent or Generic Medicines
Authors: Verbaanderd Ciska , Rooman Ilse , Huys Isabelle 
Published: June 2020

Abstract
Finding new therapeutic uses for approved, off-patent or generic medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in this type of research. Consequently, potential new uses for off-patent or generic medicines are mainly studied in independent proof-of-concept clinical trials initiated and led by researchers from academia, research institutes or collaborative groups. Yet, these researchers need additional financial support to conduct expensive phase III clinical trials to confirm the results from exploratory research. In this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms. Traditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds or crowdfunding, is not yet known. Interviewees stated that there is a substantial need for additional financial support in health research, especially in disease domains where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, increased collaboration and centralisation at a European and international level is recommended to make clinical research more efficient and reduce the need for additional funding. New funding mechanisms to support clinical research may become more important in the future, but the unresolved issues warrant further exploration in pilot projects.
TILT: Time-Lapse Imaging Trial: A pragmatic, Multi-Centre, Three-Arm Randomised Controlled Trial to Assess the Clinical Effectiveness and Safety of Time-Lapse Imaging in in-Vitro Fertilisation Treatment.
Authors: Bhide Priya , Srikanthara Arasaratnam , Lanz Doris , Dodds Julie , Collins Bonnie , Zamora Javier , Chan David YL , Thangaratinam Shakila , Khan Khalid 
Published: June 2020

Abstract
• Background: Subfertility is a common problem for which in-vitro fertilisation (IVF) treatment is commonly recommended. Success rates following IVF are suboptimal and have remained static over the last few years. This imposes a considerable financial burden on overstretched healthcare resources. Time-lapse imaging (TLI) of developing embryos in IVF treatment is hypothesised to improve the success rates of treatment. This may be either by providing undisturbed culture conditions and/or improving the predictive accuracy for optimal embryo selection from a cohort of available embryos. However, current best evidence for its effectiveness is inconclusive. • Methods: The time-lapse imaging trial is a pragmatic, multi-centre, three-arm parallel group randomised controlled trial using re-randomisation. The primary objective of the trial is to determine if the use of TLI or undisturbed culture in IVF treatment results in a higher live birth rate when compared to current standard methods of embryo incubation and assessment. Secondary outcomes include measures of clinical efficacy and safety. The trial will randomise 1575 participants to detect an increase in live birth from 26.5% to 35.25%.• Discussion: In the absence of high quality evidence, there is no current national guidance, recommendation or policy for the use of TLI. The use of TLI is not consistently incorporated into standard IVF care. A large, pragmatic, multicentre, trial will provide much needed definitive evidence regarding the effectiveness of TLI. If proven to be effective, its incorporation into standard care would translate into significant clinical and economic benefits. If not, it would allow allocation of resources to more effective interventions.• Trial registration: ISRCTN registry, ISRCTN17792989, 18/04/2018, prospectively registered.
Lipidomics Profiling of Skin Surface Lipids in Senile Pruritus
Authors: Ma xiaolei , Lu Lulu , Zhao Zheng , Cai Mingru , Gao Na , Han Gangwen 
Published: June 2020

Abstract
Background: Senile pruritus is common, yet its etiology remains unknown. Aging-associated skin barrier defects and skin surface lipids (SSL) alterations have been postulated to play important roles in its occurrence. In the present study, the lipidomic profiles of SSLs in elderly patients were examined to better understand the potential causes of senile pruritus. Methods: Transepidermal water loss (TEWL) was evaluated to assess the skin barrier function. The Ameliorated Kawashima Itch Scale score was used to measure the pruritus severity. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and multivariate data analysis were employed to investigate SSL alterations. Results: The results showed that senile pruritus patients had higher TEWL values than control subjects (13.13±4.28 versus 6.71±2.45, P<0.01). LC-MS/MS revealed significant differences in the lipidomic profiles and identified 81 species of SSLs that differed between the two groups. Compared with control subjects, senile pruritus patients had increased levels of ceramides (Cers), diacylglycerols, fatty acids, phosphatidylcholines, phosphatidylethanolamines, phytosphingosines, sphingosines, diacylceryl-3-O-carboxyhydroxymethylcholine, diacylglyceryl trimethylhomoserine, and unsaturated free fatty acids, but decreased levels of triacylglycerol. Cer-EOS, Cer-NDS, and Cer-NS were positively correlated with TEWL value (P<0.05). Pruritus severity score was positively correlated with sphingomyelin, Cer-NP, Cer-AS, Cer-NDS, and Cer-NS, but negatively correlated with Cer-BS, Cer-EODS, Cer-EOS, and Cer-AP. Conclusions: The present study indicated that patients with senile pruritus have impaired skin barrier function and altered SSL composition. Certain SSL species identified in this study may be potential targets for future studies on the pathogenesis of senile pruritus.Trial registration: Peking University International Hospital (Number: YN2018QN04; date: January 2019).
Development of an in vitro 3D model for investigating ligamentum flavum hypertrophy
Authors: Lin Cheng-Li , Kuo Yi-Ting , Tsao Che-Hao , Shyong Yan-Jye , Shih Shu-Hsien , Tu Ting-Yuan 
Published: June 2020

Abstract
Background
Ligamentum flavum hypertrophy (LFH) is one of the most crucial factors in degenerative lumbar spinal stenosis, which can cause back pain, lower extremity pain, cauda equina syndrome and neurogenic claudication. The exact pathogenesis of LFH remains elusive, despite extensive research. Most in vitro studies of LFH have been carried out using conventional 2D cell cultures, which do not resemble in vivo conditions, as they lack crucial pathophysiological factors found in three-dimensional (3D) LFH tissue, such as enhanced cell proliferation and cell cluster formation. In this study, we generated LF clusters using spheroid cultures derived from primary LFH tissue.
Results
The cultured LF spheroids exhibited good viability and growth on the ULA 96-plate platform according to live/dead staining. Our results showed that 100-cell culture continued to grow in size, while 1000-cell culture maintained the size and 5000-cell culture exhibited a decreasing trend as the culture time increased, and long-term culture was validated for at least 28 days. The LF spheroids also maintained the extracellular matrix (ECM) phenotype, i.e. fibronectin, elastin, and collagen I and III. 2D culture and 3D culture were further compared by cell cycle and Western blot analyses. Finally, we utilized hematoxylin and eosin (H&E) staining to demonstrate 3D spheroids has resembled part of the cell arrangement in LF hypertrophic tissue.
Conclusions
The developed LF spheroid model has great potential, as it provides a stable culture platform in a 3D model that can further improve our understanding of the pathogenesis of LFH and has applications in future studies.
Aggresome Formation and Liquid-liquid Phase Separation Independently Induce Cytoplasmic Aggregation of TAR DNA-binding protein 43
Authors: Yamanaka Koji , Watanabe Seiji , Inami Hidekazu , Oiwa Kotaro , Murata Yuri , Sakai Shohei , Komine Okiru , Sobue Akira , Iguchi Yohei , Katsuno Masahisa 
Published: June 2020

Abstract
Background Cytoplasmic inclusion of TAR DNA-binding protein 43 (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and a subtype of frontotemporal lobar degeneration (FTLD). Recent studies have suggested that the formation of cytoplasmic TDP-43 aggregates is dependent on a liquid-liquid phase separation (LLPS) mechanism. However, it is unclear whether TDP-43 pathology is induced through a single intracellular mechanism such as LLPS.Methods We established a TDP-43 aggregation screening system using a cultured neuronal cell line stably expressing EGFP-fused TDP-43 and a mammalian expression library of the inherited ALS/FTLD causative genes. We performed a screening to identify the intracellular mechanisms responsible for TDP-43 aggregation. An immunofluorescence study was conducted using the sporadic ALS spinal cord sections.Results We found that microtubule-related proteins (MRPs) and RNA-binding proteins (RBPs) co-aggregated with TDP-43. MRPs and RBPs sequestered TDP-43 into the cytoplasmic aggregates through distinct mechanisms such as microtubules and LLPS, respectively. The MRPs-induced TDP-43 aggregates were co-localized with aggresomal markers and dependent on histone deacetylase 6 (HDAC6), suggesting that aggresome formation induced the co-aggregation. However, the MRPs-induced aggregates were not affected by 1,6-hexanediol, an LLPS inhibitor. On the other hand, the RBPs-induced TDP-43 aggregates were sensitive to 1,6-hexanediol, but not dependent on microtubules or HDAC6. In sporadic ALS patients, approximately half of skein-like TDP-43 inclusions were co-localized with HDAC6, but round and granular type inclusion were not. Moreover, HDAC6-positive and HDAC6-negative inclusions were found in the same ALS patient, suggesting that the two distinct pathways are both involved in TDP-43 pathology.Conclusion Our findings suggest that at least two distinct pathways (i.e., aggresome formation and LLPS ) are involved in inducing the TDP-43 pathologies.