bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the methamphetamine approach-avoidance training (MAAT) trial, a randomised controlled trial of personalised approach bias modification for methamphetamine use disorder
Authors: Garfield Joshua B. B. , Piercy Hugh , Arunogiri Shalini , Lubman Dan I. , Campbell Samuel C. , Sanfilippo Paul G. , Gavin Jeff , Hopwood Malcolm , Kotler Eli , George Suzanne , Okedara Goke , Piccoli Lara R. , Manning Victoria 
Published: January 2021

Abstract
Background
Globally, methamphetamine use has increased in prevalence in recent years. In Australia, there has been a dramatic increase in numbers of people seeking treatment, including residential rehabilitation, for methamphetamine use disorder (MUD). While residential rehabilitation is more effective for MUD than withdrawal treatment (i.e. “detoxification”) alone, relapse rates remain high, with approximately half of rehabilitation clients using methamphetamine within 3 months of rehabilitation. “Approach bias modification” (ABM) is a computerised cognitive training approach that aims to dampen automatically triggered impulses to approach drugs and drug-related stimuli. ABM has been demonstrated to reduce alcohol relapse rates, but no randomised controlled trials of ABM for MUD have yet been conducted. We aim to test whether a novel “personalised” form of ABM, delivered during rehabilitation, reduces post-treatment methamphetamine use, relative to a sham-training control condition. Secondary outcomes will include dependence symptoms, cravings, and approach bias.

Methods
We aim to recruit 100 participants attending residential rehabilitation for MUD at 3 sites in the Melbourne metropolitan area. Participants will complete baseline measures of methamphetamine use, craving, dependence severity, and approach bias before being randomised to receiving 6 sessions of ABM or “sham” training. In the active condition, ABM will be personalised for each participant, using those methamphetamine images that they rate as most relevant to their recent methods of methamphetamine use as “avoidance” images and using positive images representing their goals or healthy sources of pleasure as “approach” images. Approach bias and craving will be re-assessed following completion of training, and methamphetamine use, dependence, and craving will be assessed 4 weeks and 3 months following discharge from residential treatment.

Discussion
This study is the first randomised controlled trial of ABM for MUD and also the first ABM study to test using a personalised set of both approach and avoid images for ABM training. If effective, the low cost and easy implementation of ABM means it could be widely implemented as a standard part of MUD treatment.

Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12620000072910. Registered on 30 January 2020 (prospectively registered): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378804&isReview=true
The intranasal dexmedetomidine plus ketamine for procedural sedation in children, adaptive randomized controlled non-inferiority multicenter trial (Ketodex): a statistical analysis plan
Authors:   on behalf of the PERC-KIDSCAN Ketodex Study Group, Heath Anna , Rios Juan David , Pullenayegum Eleanor , Pechlivanoglou Petros , Offringa Martin , Yaskina Maryna , Watts Rick , Rimmer Shana , Klassen Terry P. , Coriolano Kamary , Poonai Naveen 
Published: January 2021

AbstractBackgroundProcedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide adequate sedation for closed reductions. The Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation (Ketodex) study is a Bayesian phase II/III, non-inferiority trial in children undergoing PSA for closed reductions that aims to address both these research questions. This article presents in detail the statistical analysis plan for the Ketodex trial and was submitted before the outcomes of the trial were available for analysis.Methods/designThe Ketodex trial is a multicenter, four-armed, randomized, double-dummy controlled, Bayesian response adaptive dose finding, non-inferiority, phase II/III trial designed to determine (i) whether IN ketodex is non-inferior to IV ketamine for adequate sedation in children undergoing a closed reduction of a fracture or dislocation in a pediatric emergency department and (ii) the combination dose for IN ketodex that provides optimal sedation. Adequate sedation will be primarily measured using the Pediatric Sedation State Scale. As secondary outcomes, the Ketodex trial will compare the length of stay in the emergency department, time to wakening, and adverse events between study arms.DiscussionThe Ketodex trial will provide evidence on the optimal dose for, and effectiveness of, IN ketodex as an alternative to IV ketamine providing sedation for patients undergoing a closed reduction. The data from the Ketodex trial will be analyzed from a Bayesian perspective according to this statistical analysis plan. This will reduce the risk of producing data-driven results introducing bias in our reported outcomes.Trial registrationClinicalTrials.govNCT04195256. Registered on December 11, 2019.
Efficacy of simultaneous aerobic exercise and cognitive training in subjective cognitive decline: study protocol for randomized controlled trial of the Exergames Study
Authors: Salisbury Dereck , Plocher Tom , Yu Fang 
Published: January 2021

AbstractBackgroundSubjective cognitive decline (SCD) is an early manifestation of Alzheimer’s disease (AD) and offers a therapeutic window where interventions have strong potential to prevent or delay the progression of AD. Aerobic exercise and cognitive training represent two promising interventions for AD prevention, but their synergistic effect has yet to be assessed in persons with SCD.Methods/designThe purpose of this single-blinded, 3-parallel group randomized controlled trial is to test the synergistic efficacy of an exergame intervention (simultaneous moderate-intensity aerobic cycling and cognitive training) on cognition and aerobic fitness in community-dwelling older adults with SCD. The Exergames Study will randomize 96 participants on a 2:1:1 allocation ratio to 3-month exergame, cycling only, or attention control (stretching). Primary outcomes include global cognition and aerobic fitness, which will be assessed at baseline and after 3 months. The specific aims of the Exergames Study are to (1) determine the efficacy of the exergame in older adults with SCD and (2) assess the distraction effect of exergame on aerobic fitness. Data will be analyzed using ANOVA following intention-to-treat.DiscussionThis study will test the synergistic effects of exergame on cognition and aerobic fitness. It has the potential to advance prevention research for AD by providing effect-size estimates for future trials.Trial registrationClinicalTrials.govNCT04311736. Registered on 17 March 2020.
Adapting the randomised controlled trial (RCT) for precision medicine: introducing the nested-precision RCT (npRCT)
Authors: Kappelmann Nils , Müller-Myhsok Bertram , Kopf-Beck Johannes 
Published: January 2021

AbstractAdaptations to the gold standard randomised controlled trial (RCT) have been introduced to decrease trial costs and avoid high sample sizes. To facilitate development of precision medicine algorithms that aim to optimise treatment allocation for individual patients, we propose a new RCT adaptation termed the nested-precision RCT (npRCT). The npRCT combines a traditional RCT (intervention A versus B) with a precision RCT (stratified versus randomised allocation to A or B). This combination allows online development of a precision algorithm, thus providing an integrated platform for algorithm development and its testing. Moreover, as both the traditional and the precision RCT include participants randomised to interventions of interest, data from these participants can be jointly analysed to determine the comparative effectiveness of intervention A versus B, thus increasing statistical power. We quantify savings of the npRCT compared to two independent RCTs by highlighting sample size requirements for different target effect sizes and by introducing an open-source power calculation app. We describe important practical considerations such as blinding issues and potential biases that need to be considered when designing an npRCT. We also highlight limitations and research contexts that are less suited for an npRCT. In conclusion, we introduce the npRCT as a novel precision medicine trial design strategy which may provide one opportunity to efficiently combine traditional and precision RCTs.
Dengue fever transmission between a construction site and its surrounding communities in China
Authors: Liu Xingchun , Zhang Meng , Cheng Qu , Zhang Yingtao , Ye Guoqiang , Huang Xiqing , Zhao Zeyu , Rui Jia , Hu Qingqing , Frutos Roger , Chen Tianmu , Song Tie , Kang Min 
Published: January 2021

AbstractBackgroundDue to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities.MethodsThe Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO).ResultsA total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days).ConclusionsTo control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community.Graphical Abstract
Assessment of the usefulness of anti-Wb123 antibody for post-elimination surveillance of lymphatic filariasis
Authors: Dorkenoo Ameyo Monique , Koba Adjaho , Halatoko Wemboo A. , Teko Minongblon , Kossi Komlan , Yakpa Kossi , Bronzan Rachel N. 
Published: January 2021

Abstract
Background
The World Health Organization has targeted lymphatic filariasis (LF) for elimination as a public health problem and recommends, among other measures, post-elimination surveillance of LF. The identification of sensitive and specific surveillance tools is therefore a research priority. The Wuchereria bancrofti-specific antigen Wb123-based enzyme-linked immunosorbent assay (Wb123 ELISA) detects antibodies to the recombinant Wb123 antigen of W. bancrofti and may be useful as a surveillance tool for LF. Six years after stopping mass drug administration to eliminate LF and recording successful results on two post-treatment transmission assessment surveys, a study was conducted in Togo aimed at helping to identify the role of the Wb123 ELISA in post-validation surveillance of LF.

Methods
This was a cross-sectional study in eight previously LF-endemic districts and one non-endemic district in Togo. In each sub-district of these nine districts, two schools were selected and 15 children aged 6 to 9 years old at each school provided finger-stick blood for testing for antibodies to Wb123 using the Filaria Detect™ IgG4 ELISA kit® (InBios, International, Inc., Seattle, WA, USA).

Results
A total of 2654 children aged 6 to 9 years old were tested in 134 schools in the nine districts. Overall, 4.7% (126/2654) children tested positive for antibodies to the Wb123 antigen of W. bancrofti. The prevalence of Wb123 antibodies varied across the eight previously endemic LF districts, from 1.56 to 6.62%. The highest prevalence, 6.99%, was found in the non-endemic district, but this was not significantly different from the average of all the LF districts (4.49%, P = 0.062).

Conclusions
The Wb123 ELISA was positive in 4.7% of Togolese school-age children who were almost certainly unexposed to LF. This apparent lack of specificity in the Togo context makes it difficult to establish a seroprevalence threshold that could serve to signal LF resurgence in the country, precluding the use of this test for post-validation surveillance in Togo. There remains a need to develop a useful and reliable test for post-elimination surveillance for LF in humans.

Graphical Abstract
Improved analysis of CRISPR fitness screens and reduced off-target effects with the BAGEL2 gene essentiality classifier
Authors: Kim Eiru , Hart Traver 
Published: January 2021

AbstractBackgroundIdentifying essential genes in genome-wide loss-of-function screens is a critical step in functional genomics and cancer target finding. We previously described the Bayesian Analysis of Gene Essentiality (BAGEL) algorithm for accurate classification of gene essentiality from short hairpin RNA and CRISPR/Cas9 genome-wide genetic screens.ResultsWe introduce an updated version, BAGEL2, which employs an improved model that offers a greater dynamic range of Bayes Factors, enabling detection of tumor suppressor genes; a multi-target correction that reduces false positives from off-target CRISPR guide RNA; and the implementation of a cross-validation strategy that improves performance ~ 10× over the prior bootstrap resampling approach. We also describe a metric for screen quality at the replicate level and demonstrate how different algorithms handle lower quality data in substantially different ways.ConclusionsBAGEL2 substantially improves the sensitivity, specificity, and performance over BAGEL and establishes the new state of the art in the analysis of CRISPR knockout fitness screens. BAGEL2 is written in Python 3 and source code, along with all supporting files, are available on github (https://github.com/hart-lab/bagel).
Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study
Authors: Hartley April , Hardcastle Sarah A. , Frysz Monika , Parkinson Jon , Paternoster Lavinia , McCloskey Eugene , Poole Kenneth E. S. , Javaid Muhammad K. , Aye Mo , Moss Katie , Williams Martin , Tobias Jon H. , Gregson Celia L. 
Published: January 2021

AbstractBackgroundIndividuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes.MethodsWe analysed an adult cohort with and without HBM (L1 and/or total hip BMDZ-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering.ResultsOf 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBMβosteophyte = 0.30 [0.01, 0.58],p = 0.019 andβJSN = 0.10 [0.01, 0.18],p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98],p = 0.032).ConclusionsHBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation.
Changes in character strengths after watching movies: when to use rasch analysis
Authors: Siritikul Sirinut , Chalanunt Sirikorn , Utrapiromsook Chitipat , Mungara Suchanard , Wongpakaran Tinakon , Wongpakaran Nahathai , Kuntawong Pimolpun , Wedding Danny 
Published: January 2021

AbstractObjectiveProfessionalism is a critical part of a medical education, and various activities have been proposed to enhance professionalism among medical students. Watching films is an activity to promote character related to professionalism. Limitation of such is a single group pre-posttest design raising concerns about the errors of measurement. The study aimed to demonstrate a method to deal with this design using Rasch analysis.ResultsThis study used a pre-posttest design with 40 first year medical students. All participated in a 3-day activity that involved watching four selected movies:Twilight, Gandhi,The Shawshank RedemptionandAmélie.These films offer compelling illustrations of the themes of self-regulation, humility, prudence and gratitude, respectively. All participants completed a 10-item composite scale (PHuSeG) addressing these themes before and after watching the movies. When determining who benefitted from the intervention, paired t-tests on the results of a Rasch analysis were used to evaluate changes between pre- and posttest. Using Rasch analyses, we could document the stability of the items from pre- to posttest, and significant changes at both the individual and group levels, which is a useful and practical approach for pre- and posttest design. Moreover, it helps validate the psychometric property of the instrument used.
Data set for demography, clinical characteristics, and risk factors of trigeminal neuralgia patients in Addis Ababa, Ethiopia
Authors: Ayele Biniyam A. , Zewde Yared Zenebe , Degefa Mikyas Tilahun , Mengesha Abenet Tafesse 
Published: January 2021

Abstract
Objectives
Pain is one of the most ignored clinical symptoms in resource limited country such as Ethiopia. Trigeminal neuralgia (TN) is one of the most painful medical illnesses known to human. Very little was reported about TN from the sub Saharan Africa (SSA), especially from Ethiopia. We aimed to study the demographic, clinical characteristics, and risk factors of TN in sixty-one patients at two public and two private health facilities in Addis Ababa Ethiopia. These data will be vital to researchers and clinicians interested in knowing the pattern of TN in SSA in order to compare and contrast with similar data from the west.

Data description
The data set contains characteristics of TN patients. All the variables in the data set were coded by self-explanatory codes. The data set contains: demographic data, which contains age ranges and duration of illness; clinical characteristics data contains clinical characteristics, and risk factors includes such as structural brain abnormalities, family history, and dental extraction. Nearly 90% of the patients had Classical TN. The right side and mandibular branch of trigeminal nerve was commonly involved. Close to 40% reported previous tooth extraction history. Majority of the patients reported satisfactory pain control with carbamazepine.
Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice
Authors: Wanner Nicole M. , Colwell Mathia , Drown Chelsea , Faulk Christopher 
Published: January 2021

Abstract
Background
Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively.

Results
F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms.

Conclusions
These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.