bluuebunny/crossref_metadata_2025_split huggingface dataset:
Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outlets after over a decade of Copayment mechanism in Uganda
Authors: Ocan Moses , Nambatya Winnie , Otike Caroline , Nakalembe Loyce , Nsobya Sam 
Published: November 2023

AbstractBackgroundMalaria remains one of the leading causes of morbidity, and mortality in Uganda. A large proportion of malaria symptomatic patients seek healthcare in the private sector. However, availability and affordability are major barriers to access to effective treatment. The private sector copayment mechanism in Uganda aims to increase availability and affordability of antimalarial agents. Our study assessed the availability, price, and market share of quality assured artemisinin-based combination therapies (QAACTs) in private drug outlets after over a decade of copayment mechanism in the private sector in Uganda.MethodsThis was a cross-sectional survey of anti-malarial agents in private drug outlets in high (Tororo, and Apac districts) and low (Kabale and Mbarara districts) malaria transmission settings. Following the World Health Organization Health Action International (WHO/HAI) criteria, an audit of the antimalarial agents was done using a checklist to determine availability, price, and market share of QAACTs. Data was entered in Epi-data and analyzed in STATAver14.0 at 95% confidence level.ResultsA total of twenty-eight (28) private drug outlets (pharmacies and drug shops) were included in the survey. One in seven Artemisinin-based combination therapies (ACTs) in the drug outlets were quality assured (QAACTs). Artemether-lumefantrine (AL), 8.9% (11/124) and Artesunate-Amodiaquine (AQ), 7.3% (9/124) were the only QAACTs present in the drug outlets at the time of the survey. The majority, 86.1%% (124/144) of antimalarial agents present in stock in the drug outlets were artemisinin based. The most common, 38.9% (56/144) ACT in the drug outlets was Dihydroartemisinin-Piperaquine (DHP). Most, 69.4% (100/144) of the antimalarial agents were in high malaria transmission settings. The cost of ACT antimalarial agents is high in the country, USD 1.4 (Artemether-Lumefantrine, AL), USD 2.4 (Dihydroartemisinin-Piperaquine, DP), the first line and second-line agents respectively for treatment of uncomplicated malaria in Uganda. There was a statistically significant difference between the dispensing price of the ‘Green leaf’ ACTs and the recommended price (p<0.001).ConclusionQuality assured artemisinin-based combination therapies (QAACTs) are not common in private drug outlets in low and high malaria transmission settings. All the drug outlets had at least one ACT antimalarial agent present on the day of the survey. The dispensing price of QAACTs was significantly higher than the recommended markup price. There is need for awareness creation, surveillance, and monitoring of the implementation of Copayment mechanism in the country.
Exploring virtual funding committee practices in the allocation of National Institute for Health and Care Research funding: A netnographic study
Authors: Blatch-Jones Amanda Jane , Boxall Cherish , Asante Emmanuel , Meadmore Katie 
Published: November 2023

AbstractObjectivesFunding committees, comprising members with a range of knowledge, skills, and experience, are considered integral to the decision-making process of funding organisations for recommending or allocating research funding. However, there is limited research investigating the decision-making processes, the role of members and their social interactions during funding committee meetings conducted both virtually and face-to-face.MethodsUsing a mixed-methods design and following netnography principles, the study observed nine National Institute for Health and Care Research programmes funding committee meetings conducted virtually during October 2020 to December 2021; complemented by interviews with committee chairs and members (18 interviews) and NIHR staff (12 interviews); an online survey (50 responses); and documentary analysis. Personal reflections through immersive journals also formed part of the analysis.ResultsThree main themes were identified from the observations, interviews, and online survey:efficiency of virtual committee meetings(importance of preparation, and the role of formality, process, and structure);understanding the effect of virtual committee meetings on well-being(effects of fatigue and apprehension, and the importance of work life balance); and,understanding social interactions and engagement(levels of engagement, contribution and inclusivity, awareness of unconscious bias and the value of social networking).ConclusionsExamining the decision-making practices of one funding organisation across several research programmes, across multiple committee meetings over one year has generated new insights around funding committee practices that previous studies have not been able to explore or investigate. Overall, it was observed that fair and transparent funding recommendations and outcomes can be achieved through virtual funding committees. However, whilst virtual funding committees have many benefits and opportunities, such as the potential to increase membership diversity and inclusivity, and be more environmentally sustainable, more evidence is needed to evaluate their effectiveness, with particular focus on issues of fatigue, engagement, and committee cohesion, especially when new committee members join.
Effect of real-time feedback-based core stabilization training using a sling on balance and gait in patients with stroke: Randomized Controlled Trial
Authors: Yoo Ja-young , An Jungae , Lee Byounghee 
Published: November 2023

AbstractBackgroundBalance impairments commonly occur in patients after stroke. Research is warranted to improve the efficiency of rehabilitation by combining core stabilization training, such as trunk exercises, and real-time feedback. This study aimed to evaluate the effect of real-time feedback-based core stabilization training (RFCST) using a sling on the dynamic balance and gait of patients with stroke.MethodsThirty-eight patients with stroke were randomly assigned to either RFCST using a sling group (n=19) or a control group (n=19). Each group was trained for 30 min daily, 3 times a week for 4 weeks. The Trunk Impairment Scale (TIS), Functional Reach Test (FRT), Postural Assessment Scale for Stroke (PASS), Timed Up and Go (TUG) test, and gait parameters were assessed using the GAITRite system before and after the intervention.ResultsThe results showed a significant interaction between Group*Time effect F(1, 36)= 36.068,p<0.001, η²p= 0.5 in TIS; F(1, 36)= 63.890,p<0.001, η²p= 0.640 in FRT; F(1, 36)= 89.283,p<0.001, η²p= 0.713 in PASS, F(1, 36)= 150.893,p<0.001, η²p= 0.807 in TUG; F(1, 36)= 27.275,p<0.001, η²p= 0.431 in gait velocity; F(1, 36)= 54.401,p<0.001, η²p= 0.447 in cadence; F(1, 36)= 5.601,p=0.023, η²p= 0.135 in step length; F(1, 36)= 22.559,p<0.001, η²p= 0.385 in stride length; F(1, 36)= 15.516,p<0.001, η²p= 0.301 in swing phase rate; and F(1, 36)= 28.451,p<0.001, η²p= 0.441 in stance phase rate.ConclusionBased on these results, it can be concluded that RFCST using a sling can improve dynamic balance and gait parameters in patients with stroke.
Improving Individualized Treatment Decisions: A Bayesian Multivariate Hierarchical Model for Developing a Treatment Benefit Index using Mixed Types of Outcomes
Authors: Wu Danni , Goldfeld Keith S. , Petkova Eva , Park Hyung G. 
Published: November 2023

AbstractBackgroundPrecision medicine has led to the development of targeted treatment strategies tailored to individual patients based on their characteristics and disease manifestations. Although precision medicine often focuses on a single health outcome for individualized treatment decision rules (ITRs), relying only on a single outcome rather than all available outcomes information leads to suboptimal data usage when developing optimal ITRs.MethodsTo address this limitation, we propose a Bayesian multivariate hierarchical model that leverages the wealth of correlated health outcomes collected in clinical trials. The approach jointly models mixed types of correlated outcomes, facilitating the “borrowing of information” across the multivariate outcomes, and results in a more accurate estimation of heterogeneous treatment effects compared to using single regression models for each outcome. We develop a treatment benefit index, which quantifies the relative treatment benefit of the experimental treatment over the control treatment, based on the proposed multivariate outcome model.ResultsWe demonstrate the strengths of the proposed approach through extensive simulations and an application to an international Coronavirus Disease 2019 (COVID-19) treatment trial. Simulation results indicate that the proposed method reduces the occurrence of erroneous treatment decisions compared to a single regression model for a single health outcome. Additionally, the sensitivity analysis demonstrates the robustness of the model across various study scenarios. Application of the method to the COVID-19 trial exhibits improvements in estimating the individual-level treatment efficacy (indicated by narrower credible intervals for odds ratios) and optimal ITRs.ConclusionThe study jointly models mixed types of outcomes in the context of developing ITRs. By considering multiple health outcomes, the proposed approach can advance the development of more effective and reliable personalized treatment
Fast and accurate local ancestry inference with Recomb-Mix
Authors: Wei Yuan , Zhi Degui , Zhang Shaojie 
Published: November 2023

AbstractThe availability of large genotyped cohorts brings new opportunities for revealing the high-resolution genetic structure of admixed populations via local ancestry inference (LAI), the process of identifying the ancestry of each segment of an individual haplotype. Though current methods achieve high accuracy in standard cases, LAI is still challenging when reference populations are more similar (e.g., intra-continental), when the number of reference populations is too numerous, or when the admixture events are deep in time, all of which are increasingly unavoidable in large biobanks. Here, we present a new LAI method, Recomb-Mix. Recomb-Mix integrates the elements of existing methods of the site-based Li and Stephens model and introduces a new graph collapsing trick to simplify counting paths with the same ancestry label readout. Through comprehensive benchmarking on various simulated datasets, we show that Recomb-Mix is more accurate than existing methods in diverse sets of scenarios while being competitive in terms of resource efficiency. We expect that Recomb-Mix will be a useful method for advancing genetics studies of admixed populations.
Neurotechnology-based intensive upper-extremity supplementary training for inpatients with sub-acute stroke: A feasibility study
Authors: Binyamin-Netser Reut , Handelzalts Shirley , Goldhamer Noy , Avni Inbar , Tayer Adi Yeshurun , Koren Yogev , Levy Ofri Bibas , Kramer Shilo , Haim Simona Bar , Shmuelof Lior 
Published: November 2023

AbstractBackgroundIntensive and high-dose upper extremity training, concentrating on movement quality in the early phase after a stroke, can enhance motor recovery compared to standard care. Unfortunately, such programs do not exist due to limited resources, patient compliance, and administrative challenges.ObjectiveTo examine the feasibility and potential efficacy, and to evaluate the resources of an intensive technology-based upper extremity training emphasizing movement quality during inpatient stroke rehabilitation.MethodsTwelve subjects with hemiparesis underwent 40 60-minute sessions over a 4-week period, in addition to standard care. The training included two game-based virtual reality platforms to practice proximal (tech 1) and distal (tech 2) movements with daily assessments.ResultsEight subjects completed the entire protocol, three subjects completed 34–38 sessions, and one subject completed only 27 sessions. The mean time on each task was 35±4 (tech 1) and 37±2 (tech 2) minutes per hour. The intervention was perceived as motivating and enjoyable [Intrinsic Motivation Inventory (IMI) enjoyment and interest= 6.49±0.66 out of 7] and was not associated with pain [Visual Analogue Scale (VAS) mean= 2.00±2.32]. Subjects showed large improvements in all impairment measurements (mean FMA delta= 16.5 points and ARAT delta= 22.9 points).ConclusionsThe results support the feasibility of a high-dose high-intensity supplementary training protocol during sub-acute hospitalization and provide suggestive evidence of its efficacy.
Diurnal variation of 8-hydroxy-2’-deoxyguanosine in continuous time series of two breast cancer survivors
Authors: Geuter Joschua , Seizer Lennart , Cornelissen Guillaume Germaine , Engin Ayse Basak , Fuchs Dietmar , Schubert Christian 
Published: November 2023

Abstract8-hydroxy-2’deoxyguanosine (8-OHdG) is an oxidative product removed from DNA following radical oxygen species-induced damage. Being water-soluble, it can be measured non-invasively in the urine and has thus been established as a marker for ‘whole-body’ oxidative stress. Its validity and reliability as an oxidative stress marker in various chronic diseases and early carcinogenesis screening in clinical diagnosis and research are widely debated. To determine optimal measurement timing and duration, it is essential to establish the circadian profile of 8-OHdG under everyday life conditions and use reliable sampling methods. Here, we show the presence of day-night differences for 8-OHdG normalized by creatinine or urine volume in continuous time series of two breast cancer survivors who participated in integrative single-case studies and sampled their urine in 12-h-pooled collections over one month. These findings support the importance of appropriately considering the dynamic characteristics of stress indicators to reduce the risk of inconsistent or false results in clinical diagnostics.
Brain-derived Tau for Monitoring Brain Injury in Acute Ischemic Stroke
Authors: Vlegels Naomi , Gonzalez-Ortiz Fernando , Knuth Nicoló Luca , Khalifeh Nada , Gesierich Benno , Müller Franziska , Müller Philipp , Klein Matthias , Dimitriadis Konstantinos , Franzmeier Nicolai , Liebig Thomas , Duering Marco , Reidler Paul , Dichgans Martin , Karikari Thomas K. , Blennow Kaj , Tiedt Steffen 
Published: November 2023

ABSTRACTThe evolution of infarcts varies widely among patients with acute ischemic stroke (IS) and influences treatment decisions. Neuroimaging is not applicable for frequent monitoring and there is no blood-based biomarker to track ongoing brain injury in acute IS. Here, we examined the utility of plasma brain-derived tau (BD-tau) as a biomarker for brain injury in acute IS. We conducted the prospective, observational Precision Medicine in Stroke [PROMISE] study with serial blood sampling upon hospital admission and at days 2, 3, and 7 in patients with acute ischemic stroke (IS) and for comparison, in patients with stroke mimics (SM). We determined the temporal course of plasma BD-tau, its relation to infarct size and admission imaging-based metrics of brain injury, and its value to predict functional outcome. Upon admission (median time-from-onset, 4.4h), BD-tau levels in IS patients correlated with ASPECTS (ρ=-0.21,P<.0001) and were predictive of final infarct volume (ρ=0.26,P<.0001). In contrast to SM patients, BD-tau levels in IS patients increased from admission (median, 2.9 pg/ml [IQR, 1.8-4.8]) to day 2 (median time-from-onset, 22.7h; median BD-tau, 5.0 pg/ml [IQR, 2.6-10.3];P<.0001). The rate of change of BD-tau from admission to day 2 was significantly associated with collateral supply (R2=0.10,P<.0001) and infarct progression (ρ=0.58,P<.0001). At day 2, BD-tau was predictive of final infarct volume (ρ=0.59,P<.0001) and showed superior value for predicting the 90-day mRS score compared with final infarct volume. In conclusion, in 502 patients with acute IS, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. Further research is needed to determine whether BD-tau assessments can inform decision-making in stroke care.
Optical constraints on two-photon voltage imaging
Authors: Brooks F. Phil , Davis Hunter C. , Wong-Campos J. David , Cohen Adam E. 
Published: November 2023

AbstractSignificanceGenetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural circuitsin vivo, but the relative merits and limitations of one-photon (1P) vs. two-photon (2P) voltage imaging are not well characterized.AimWe consider the optical and biophysical constraints particular to 1P and 2P voltage imaging and compare the imaging properties of commonly used GEVIs under 1P and 2P excitation.ApproachWe measure brightness and voltage sensitivity of voltage indicators from commonly used classes under 1P and 2P illumination. We also measure the decrease in fluorescence as a function of depth in mouse brain. We develop a simple model of the number of measurable cells as a function of reporter properties, imaging parameters, and desired signal-to-noise ratio (SNR). We then discuss how the performance of voltage imaging would be affected by sensor improvements and by recently introduced advanced imaging modalities.ResultsCompared to 1P excitation, 2P excitation requires ∼104-fold more illumination power per cell to produce similar photon count rates. For voltage imaging with JEDI-2P in mouse cortex with a target SNR of 10 (spike height:baseline shot noise), a measurement bandwidth of 1 kHz, a thermally limited laser power of 200 mW, and an imaging depth of > 300 μm, 2P voltage imaging using an 80 MHz source can record from no more 12 cells simultaneously.ConclusionsDue to the stringent photon-count requirements of voltage imaging and the modest voltage sensitivity of existing reporters, 2P voltage imagingin vivofaces a stringent tradeoff between shot noise and tissue photodamage. 2P imaging of hundreds of neurons with high SNR at depth > 300 μm will require either major improvements in 2P GEVIs or qualitatively new approaches to imaging.
Cell morphology QTL reveal gene by environment interactions in a genetically diverse cell population
Authors: O’Connor Callan , Keele Gregory R. , Martin Whitney , Stodola Timothy , Gatti Daniel , Hoffman Brian R. , Korstanje Ron , Churchill Gary A. , Reinholdt Laura G. 
Published: November 2023

AbstractGenetically heterogenous cell lines from laboratory mice are promising tools for population-based screening as they offer power for genetic mapping, and potentially, predictive value forin vivoexperimentation in genetically matched individuals. To explore this further, we derived a panel of fibroblast lines from a genetic reference population of laboratory mice (the Diversity Outbred, DO). We then used high-content imaging to capture hundreds of cell morphology traits in cells exposed to the oxidative stress-inducing arsenic metabolite monomethylarsonous acid (MMAIII). We employed dose-response modeling to capture latent parameters of response and we then used these parameters to identify several hundred cell morphology quantitative trait loci (cmQTL). Response cmQTL encompass genes with established associations with cellular responses to arsenic exposure, includingAbcc4andTxnrd1, as well as novel gene candidates likeXrcc2. Moreover, baseline trait cmQTL highlight the influence of natural variation on fundamental aspects of nuclear morphology. We show that the natural variants influencing response include both coding and non-coding variation, and that cmQTL haplotypes can be used to predict response in orthogonal cell lines. Our study sheds light on the major molecular initiating events of oxidative stress that are under genetic regulation, including the NRF2-mediated antioxidant response, cellular detoxification pathways, DNA damage repair response, and cell death trajectories.
In VivoPhenotypic Vascular Dysfunction Extends Beyond the Aorta in a Mouse Model for Fibrillin-1 (FBN1) Mutation
Authors: Curry T , Barrameda M.E. , Currier Thomas T. , Esfandiarei M. 
Published: November 2023

AbstractIn individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (FBN1C1041G/+) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. Although the MFS mouse model presents an accelerated-aging phenotype in elastic organs (e.g., lung, skin), the impact ofFBN1mutations on other central and peripheral arteries function and structure with the consideration of the impact of sex remains underexplored. In this study, we investigate ifFBN1mutation contributes to sex-dependent alterations in central and cerebral vascular function similar to phenotypic changes associated with normal aging in healthy control mice.In vivoultrasound imaging of central and cerebral vasculature was performed in 6-month-old male and female MFS and C57BL/6 mice and sex-matched 12-month-old (middle-aged) healthy control mice. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters. Coronary artery blood flow velocity (BFV) in diastole was not different but left pulmonary artery BFV was decreased in MFS and 12-month-old control mice regardless of sex. At 6 months of age, MFS male mice show decreased posterior cerebral artery BFV as compared to age-matched control males, with no difference observed between female cohorts. Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex. Male MFS mice also demonstrated left ventricular hypertrophy. Overall, these results underscore the significance of biological sex in vascular function and structure in MFS mice, while highlighting a trend of pre-mature vascular aging phenotype in MFS mice that is comparable to phenotypes observed in older healthy controls.
Herbivore insect small RNA effector suppress plant defense by cross-kingdom gene silencing
Authors: Han Wen-Hao , Ji Shun-Xia , Zhang Feng-Bin , Song Hong-Da , Wang Jun-Xia , Xie Rui , Wang Xiao-Wei 
Published: November 2023

AbstractHerbivore insects deploy salivary effectors to manipulate the defense of their host plants, however, whether insect small RNAs (sRNAs) act as effectors to regulate plant-insect interaction is currently unclear. Here, we report that a microRNA (miR29-b) from the saliva of phloem-feeding insects can transfer into the host plant phloem and fine-tune the host defense. The salivary gland’s abundant miR29-b was produced by insect Dicer 1 and insect salivary exosome is involved in its transferring and releasing into the host plant. Insect miR29-b effector hijacks plant Argonaute 1 to silence host defense geneBcl-2-associated athanogene 4(BAG4). Silencing ofBAG4suppressed the expression of phenylalanine ammonia-lyase and the accumulation of salicylic acid (SA), therefore negatively regulating host defense against herbivore insects. miR29-b is highly conserved in Hemiptera, Coleoptera, Hymenoptera, Orthoptera, and Blattaria insects and also targets theBAG4gene. Notably,BAG4orthologs exist in a wide range of plant species and may as the target of insect miR29-b. Our work provides new insight into the intriguing defense and counter-defense between herbivores and plants.TeaserPhloem-feeding insects produce and transfer small RNA into the host plants to fine-tune plant basal defense by cross-kingdom gene silencing.