bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective, single-centre, single-arm, open label study of the long term use of a gonadotropin releasing hormone agonist (Triptorelin SR, 11.25 mg) in combination with Tibolone add-back therapy in the management of chronic cyclical pelvic pain
Authors: Alshehre Sallwa M. , Duffy Sheila , Jones Georgina , Ledger William L. , Metwally Mostafa 
Published: April 2020

Abstract
Background
Chronic cyclic pelvic pain (CCPP) affects women’s quality of life and pituitary downregulation is often used for symptomatic relief. However, prolonged suppression of ovarian function is associated with menopausal side effects and can lead to osteoporosis. Currently, the use of gonadotropin releasing hormone agonists (GnRHa) for treatment of CCPP is usually restricted to 6–9 months, limiting their efficacy. There is limited information regarding safety and efficacy with longer-term use. The aim of this study is to examine the safety and efficacy of long-term (24 months) pituitary down-regulation with the GnRHa (Triptorelin SR) with add-back therapy (ABT) using Tibolone for symptom relief in women with CCPP.

Methods
A single-arm, prospective clinical trial at a Tertiary University Teaching Hospital of 27 patients receiving Triptorelin SR (11.25 mg) and Tibolone (2.5 mg). Outcomes measures were the safety of treatment assessed by clinical examination, haematological markers, liver and renal function tests and bone mineral density (BMD) at 12, 18 and 24 months as well as at 6 months post-treatment. Pain and health-related quality of life (HR-QoL) assessed using the endometriosis health profile (EHP-30) and chronic pain grade (CPG) questionnaires.

Results
There was no evidence for any significant harmful effects on any of the measured haematological, renal or liver function tests. Although results regarding the effect on BMD are not conclusive there is an increased risk of development of osteopaenia after 12 months of treatment. Pain and HRQoL assessments showed significant improvement during medication, but with deterioration after treatment cessation.

Conclusion
Long- term Triptorelin plus Tibolone add-back therapy in women suffering from CCPP does not appear to be associated with significant serious adverse events apart from the possibility of deterioration in the BMD that needs to be monitored. This mode of therapy appears to be effective in pain relief and in improving quality of life over a 24-month period.

Trial registration
Clinical trials database NCT00735852.
Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice
Authors: Early Alexandria N. , Gorman Amy A. , Van Eldik Linda J. , Bachstetter Adam D. , Morganti Josh M. 
Published: April 2020

Abstract
Background
Older-age individuals are at the highest risk for disability from a traumatic brain injury (TBI). Astrocytes are the most numerous glia in the brain, necessary for brain function, yet there is little known about unique responses of astrocytes in the aged-brain following TBI.

Methods
Our approach examined astrocytes in young adult, 4-month-old, versus aged, 18-month-old mice, at 1, 3, and 7 days post-TBI. We selected these time points to span the critical period in the transition from acute injury to presumably irreversible tissue damage and disability. Two approaches were used to define the astrocyte contribution to TBI by age interaction: (1) tissue histology and morphological phenotyping, and (2) transcriptomics on enriched astrocytes from the injured brain.

Results
Aging was found to have a profound effect on the TBI-induced loss of astrocyte function needed for maintaining water transport and edema—namely, aquaporin-4. The aged brain also demonstrated a progressive exacerbation of astrogliosis as a function of time after injury. Moreover, clasmatodendrosis, an underrecognized astrogliopathy, was found to be significantly increased in the aged brain, but not in the young brain. As a function of TBI, we observed a transitory refraction in the number of these astrocytes, which rebounded by 7 days post-injury in the aged brain. Transcriptomic data demonstrated disproportionate changes in genes attributed to reactive astrocytes, inflammatory response, complement pathway, and synaptic support in aged mice following TBI compared to young mice. Additionally, our data highlight that TBI did not evoke a clear alignment with the previously defined “A1/A2” dichotomy of reactive astrogliosis.

Conclusions
Overall, our findings point toward a progressive phenotype of aged astrocytes following TBI that we hypothesize to be maladaptive, shedding new insights into potentially modifiable astrocyte-specific mechanisms that may underlie increased fragility of the aged brain to trauma.
Reverse-genetics studies of lncRNAs—what we have learnt and paths forward
Authors: Gao Fan , Cai Ye , Kapranov Philipp , Xu Dongyang 
Published: April 2020

AbstractLong non-coding RNAs (lncRNAs) represent a major fraction of the transcriptome in multicellular organisms. Although a handful of well-studied lncRNAs are broadly recognized as biologically meaningful, the fraction of such transcripts out of the entire collection of lncRNAs remains a subject of vigorous debate. Here we review the evidence for and against biological functionalities of lncRNAs and attempt to arrive at potential modes of lncRNA functionality that would reconcile the contradictory conclusions. Finally, we discuss different strategies of phenotypic analyses that could be used to investigate such modes of lncRNA functionality.
Principal component analysis of adipocytokines and insulin associate with risk factors of cardiovascular diseases
Authors: Yarizadeh Habib , Setayesh Leila , Askarpoor Moein , Pooyan Sara , Sajjadi Seyedeh Forough , Badrooj Negin , Roberts Caroline , Mirzaei Khadijeh 
Published: April 2020

Abstract
Objectives
Obesity plays an important role in the development of chronic diseases like cardiovascular diseases and diabetes. The possible underlying mechanism for this connection is that adipose tissue secretes an array of chemical messenger adipokines proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). This study aimed to investigate the linkage between adipocytokines and insulin with the cardiovascular disease risk, with particular reference to the adipokines galectin-3, plasminogen activator inhibitor-1, and interleukin-1-beta, C-reactive protein, and monocyte chemoattractant protein.

Result
Two patterns were identified. The first pattern was galectin-3, plasminogen activator inhibitor-1 and interleukin-1-beta and the second one was C-reactive protein, insulin and monocyte chemoattractant protein-1. The second pattern was strongly associated with the higher scores for resting metabolic rate, diastolic blood pressure, homeostasis model insulin resistance index, lipid profile (except low density lipoprotein, total cholesterol), and body composition parameters (except fat free mass index and waist hip ratio), while negatively associated with age and high density lipoprotein level (all p < 0.05). The first pattern was, however, significantly associated with body fat mass, obesity degree percentage, waist circumference, fat mass index, and waist hip ratio (p < 0.05 for all).
This is a retrospective study. Ethics approval (IR.TUMS.VCR.REC.1395.1597).
Virtual reality as a non-pharmacologic analgesic for fasciotomy wound infections in acute compartment syndrome: a case report
Authors: Esumi Ryo , Yokochi Ayumu , Shimaoka Motomu , Kawamoto Eiji 
Published: April 2020

Abstract
Background
Fasciotomy is a life-saving procedure to treat acute compartment syndrome, a surgical emergency. As fasciotomy dramatically improves wound pain, it should be performed as soon as possible. Moreover, delays in the use of fasciotomy can increase the rate of wound infections. Once the fasciotomy wound is infected, pain control is achieved via the long-term use of opioids or anti-inflammatory analgesics. However, the administration of high doses of opioids may cause complications, such as respiratory depression, over-sedation, and constipation. Therefore, treatment methods other than narcotic administration should be established to better manage the pain caused by fasciotomy wound infections.
Virtual reality has recently been introduced in analgesic therapy as a replacement, or complement, to conventional pharmacological treatments. Its use has been extensively studied in the pain management of patients with burns. An increasing number of painful conditions are being successfully treated with virtual reality. Here, we report a case of acute compartment syndrome complicated by fasciotomy wound infection.

Case presentation
A 40-year-old Japanese man suffering from acute compartment syndrome of his leg due to a car accident trauma was treated with a fasciotomy to decompress intra-compartmental pressure and restore tissue perfusion, and admitted to an intensive care unit. Unfortunately, as the open fasciotomy wound was complicated by infection, he complained of hyperalgesia and severe pain during wound debridement. He was therefore given acetaminophen and high-dose intravenous patient-controlled analgesic fentanyl (35 μg/kg per day) to reduce the pain. Despite these efforts, the pain was poorly controlled and opioid-induced side effects such as respiratory depression were observed. An immersive virtual reality analgesic therapy aimed at distraction and relaxation was used and effectively alleviated the pain. Three sessions of virtual reality analgesic therapy over 2 days produced sustainable analgesic effects, which led to a 25–75% dose reduction in fentanyl administration and the concomitant alleviation of respiratory depression.

Conclusions
This case suggests the feasibility of virtual reality analgesic therapy for pain management of fasciotomy wound complications in acute compartment syndromes. Virtual reality represents a treatment option that would reduce analgesic consumption and eliminate opioid-induced respiratory depression to treat fasciotomy wound infection.
KnowTox: pipeline and case study for confident prediction of potential toxic effects of compounds in early phases of development
Authors: Morger Andrea , Mathea Miriam , Achenbach Janosch H. , Wolf Antje , Buesen Roland , Schleifer Klaus-Juergen , Landsiedel Robert , Volkamer Andrea 
Published: April 2020

AbstractRisk assessment of newly synthesised chemicals is a prerequisite for regulatory approval. In this context, in silico methods have great potential to reduce time, cost, and ultimately animal testing as they make use of the ever-growing amount of available toxicity data. Here, KnowTox is presented, a novel pipeline that combines three different in silico toxicology approaches to allow for confident prediction of potentially toxic effects of query compounds, i.e. machine learning models for 88 endpoints, alerts for 919 toxic substructures, and computational support for read-across. It is mainly based on the ToxCast dataset, containing after preprocessing a sparse matrix of 7912 compounds tested against 985 endpoints. When applying machine learning models, applicability and reliability of predictions for new chemicals are of utmost importance. Therefore, first, the conformal prediction technique was deployed, comprising an additional calibration step and per definition creating internally valid predictors at a given significance level. Second, to further improve validity and information efficiency, two adaptations are suggested, exemplified at the androgen receptor antagonism endpoint. An absolute increase in validity of 23% on the in-house dataset of 534 compounds could be achieved by introducing KNNRegressor normalisation. This increase in validity comes at the cost of efficiency, which could again be improved by 20% for the initial ToxCast model by balancing the dataset during model training. Finally, the value of the developed pipeline for risk assessment is discussed using two in-house triazole molecules. Compared to a single toxicity prediction method, complementing the outputs of different approaches can have a higher impact on guiding toxicity testing and de-selecting most likely harmful development-candidate compounds early in the development process.
Possible effects of potential lahars from Cotopaxi volcano on housing market prices
Authors: Echegaray-Aveiga Richard Caleb , Rodríguez-Espinosa Fabian , Toulkeridis Theofilos , Echegaray-Aveiga Richard Damian 
Published: April 2020

AbstractThe recent awakening of the Cotopaxi volcano in Ecuador set the conditions to estimate and verify the possible effects of potential lahars on residential housing unit prices. About 300,000 people live in the Los Chillos valley, which is the northern natural drainage of Cotopaxi’s lahars; therefore, the effects on house values can be significant. We have used housing information from 2016 of 240 properties to settle a hedonic price model within and outside of the lahar’s area. The regression model has a significant R2 value of about 0.723. The variable that determined the effects of potential lahar on the hedonic model demonstrates that the value of a residence house unit will increase its price by 41.99 USD for each meter away from the lahar path. Our study suggests that environmental disamenities generated by natural hazards will have a negative effect on residential house unit prices and we infer that consumers would be willing to pay a higher price in order to avoid such potential disamenities.
Adaptive changes in physiological and perceptual responses during 10-day heat acclimation training using a water-perfused suit
Authors: Ko Yelin , Seol Seon-Hong , Kang Juho , Lee Joo-Young 
Published: April 2020

Abstract
Background
While active heat acclimation strategies have been robustly explored, not many studies highlighted passive heat acclimation strategies. Particularly, little evidence demonstrated advantages of utilizing a water-perfused suit as a passive heating strategy. This study aimed to explore heat adaptive changes in physiological and perceptual responses during 10-day heat acclimation training using a water-perfused suit.

Methods
Nineteen young males were divided into three experimental groups: exercise condition (N = 6, HAEXE, 1-h exercise at 6 km h−1 followed by 1-h rest in a sitting position), exercise and passive heating condition (N = 6, HAEXE+SUIT, 1-h exercise at 6 km h−1 followed 1-h passive heating in a sitting position), and passive heating condition (N = 7, HASUIT, 2-h passive heating in a sitting position). All heating programs were conducted for 10 consecutive days in a climatic chamber maintained at 33 °C with 60% relative humidity. The passive heating was conducted using a newly developed water-perfused suit with 44 °C water.

Results
Greater whole-body sweat rate and alleviated perceptual strain were found in HASUIT and HAEXE+SUIT after 5 and/or 10 days (P < 0.05) but not in the exercise-only condition (HAEXE). Lower rectal temperature and heart rate were found in all conditions after the training (P < 0.05). Heat adaptive changes appeared earlier in HASUIT except for sweat responses.

Conclusions
For heat acclimation in hot humid environments, passive and post-exercise heat acclimation training using the suit (water inflow temperature 44 °C) were more effective than the mild exercise (1-h walking at 6 km h−1). This form of passive heating (HASUIT) may be an especially effective strategy for the elderly and the disabled who are not able to exercise in hot environments.
Different fundus imaging modalities and technical factors in AI screening for diabetic retinopathy: a review
Authors: Lim Gilbert , Bellemo Valentina , Xie Yuchen , Lee Xin Q. , Yip Michelle Y. T. , Ting Daniel S. W. 
Published: April 2020

AbstractBackgroundEffective screening is a desirable method for the early detection and successful treatment for diabetic retinopathy, and fundus photography is currently the dominant medium for retinal imaging due to its convenience and accessibility. Manual screening using fundus photographs has however involved considerable costs for patients, clinicians and national health systems, which has limited its application particularly in less-developed countries. The advent of artificial intelligence, and in particular deep learning techniques, has however raised the possibility of widespread automated screening.Main textIn this review, we first briefly survey major published advances in retinal analysis using artificial intelligence. We take care to separately describe standard multiple-field fundus photography, and the newer modalities of ultra-wide field photography and smartphone-based photography. Finally, we consider several machine learning concepts that have been particularly relevant to the domain and illustrate their usage with extant works.ConclusionsIn the ophthalmology field, it was demonstrated that deep learning tools for diabetic retinopathy show clinically acceptable diagnostic performance when using colour retinal fundus images. Artificial intelligence models are among the most promising solutions to tackle the burden of diabetic retinopathy management in a comprehensive manner. However, future research is crucial to assess the potential clinical deployment, evaluate the cost-effectiveness of different DL systems in clinical practice and improve clinical acceptance.
Low-cost FDM 3D-printed modular electrospray/electrospinning setup for biomedical applications
Authors: Huang Jing , Koutsos Vasileios , Radacsi Norbert 
Published: April 2020

AbstractHere, we report on the inexpensive fabrication of an electrospray/electrospinning setup by fused deposition modelling (FDM) 3D printing and provide the files and parameters needed to print this versatile device. Both electrospray and electrospinning technologies are widely used for pharmaceutical, healthcare and bioengineering applications. The setup was designed to be modular, thus its parts can be exchanged easily. The design provides a safe setup, ensuring that the users are not exposed to the high voltage parts of the setup. PLA, PVA, and a thermoplastic elastomer filament were used for the 3D printing. The filament cost was $100 USD and the rig was printed in 6 days. An Ultimaker 3 FDM 3D printer was used with dual print heads, and the PVA was used as a water-soluble support structure. The end part of the setup had several gas channels, allowing a uniform gas flowing against the direction of the nanoparticles/nanofibers, enhancing the drying process by enhancing the evaporation rate. The setup was tested in both electrospray and electrospinning modes successfully. Both the .sldprt and .stl files are provided for free download.
The case for gender considerate tobacco control policies in Albania
Authors: Guliani Harminder , Çule Monika 
Published: April 2020

AbstractBackgroundTobacco use is a serious health concern in Albania. While the prevalence of tobacco smoking has traditionally been higher for men, the increasing prevalence of smoking for women is becoming a concern. The 2007 Tobacco Control policy mandated smoke-free indoor spaces, banned various forms of tobacco advertising, required written health warnings on packaging and levied excise taxes on cigarette sales. Since smoking behavior varies among different demographic groups, each group’s response to a uniform policy will differ, blunting the effectiveness of these efforts as a result. This study examines various socioeconomic, demographic and behavioral factors affecting both the likelihood and frequency of smoking in Albanian households in order to provide insights on targeting various populations more effectively.MethodsThe study utilizes data from Albanian 2008–09 and 2017–18 Demographic and Health Surveys consisting of adults aged 15–49 years. The outcome variable includes respondents’ current tobacco smoking behaviour and its frequency. The exposure variables include respondents’ sociodemographic and lifestyle characteristics. We use a two-level random intercept model with the two-stage residual inclusion estimation method to determine the association between outcome and exposure variables. By including a time variable, we capture the change in smoking behavior during the 2009–2018 period. We also extend the analysis by assessing the differential influence of gender on the likelihood of smoking, both by income quintiles and education.ResultsThe results suggest that the likelihood of smoking decreased by 23% in 2017–18 compared to 2008–09, after controlling for various socioeconomic and demographic factors. Tobacco smoking is also found to be linked to alcohol consumption, with binge drinkers 59% more likely to smoke tobacco compared to moderate drinkers. We also found significant inter-quintile and inter-educational differences in smoking practices within each gender category. While the likelihood of tobacco smoking decreases with increasing wealth and educational attainment among men, the opposite (for wealth) or more involved (for educational attainment) patterns are true among women.ConclusionsTo further enhance the effectiveness of the current Tobacco Control policy, the Government of Albania should target various demographic groups (such as poor males, rich and educated females) in a differentiated fashion.
Proximal fibular resection improves knee biomechanics and enhances tibial stress fracture healing in patients with osteoarthritis with varus deformity: a prospective, randomized control analysis
Authors: Shah Vikram Indrajit , Upadhyay Sachin , Shah Kalpesh , Sheth Ashish , Kshatriya Amish , Patil Jayesh 
Published: April 2020

AbstractBackgroundThe present study aimed to evaluate the functional outcome of single-stage total knee arthroplasty using long-stem tibial component with proximal fibular resection (PFR) for patients with knee osteoarthritis with varus deformity associated with tibial stress fracture.MethodA cohort of 62 patients with a mean age 71.63 ± 7.40 years who met the criteria were randomized to a study group and a control group. Patients in the study group underwent single-stage total knee arthroplasty using long-stem tibial component with PFR. The control group received conventional treatment. All patients were followed at 1, 3, 6 and 12 month(s) after surgery. Standard anteroposterior and lateral weight bearing knee X-rays were analyzed. Western Ontario and Mc-master Universities Osteoarthritis Index score (WOMAC) and the visual analog scale (VAS) score were used to assess the functional outcome. The level of significance was set atp < 0.05 levels.ResultsOne patient in the study group was lost to follow-up, leaving 61 patients for final assessment. The WOMAC total score and mean VAS score were significantly better in study group than in control group at final follow-up (p < 0.05). All fractures were successfully united in a mean time of 12.26 ± 1.20 weeks in study group. A total of 16 patients in control group had delayed union, five had established nonunion and required further interventions. No complications relating to surgery was detected.ConclusionTotal knee arthroplasty with PFR for knee arthritis with varus deformity associated with tibial stress fractures restores limb alignment, improves biomechanics, enhances fracture healing and provides excellent functional outcome.