bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scenario Design for Infectious Disease Projections: Integrating Concepts from Decision Analysis and Experimental Design
Authors: Runge Michael C. , Shea Katriona , Howerton Emily , Yan Katie , Hochheiser Harry , Rosenstrom Erik , Probert William J.M. , Borchering Rebecca , Marathe Madhav V. , Lewis Bryan , Venkatramanan Srinivasan , Truelove Shaun , Lessler Justin , Viboud Cécile 
Published: October 2023

AbstractAcross many fields, scenario modeling has become an important tool for exploring long-term projections and how they might depend on potential interventions and critical uncertainties, with relevance to both decision makers and scientists. In the past decade, and especially during the COVID-19 pandemic, the field of epidemiology has seen substantial growth in the use of scenario projections. Multiple scenarios are often projected at the same time, allowing important comparisons that can guide the choice of intervention, the prioritization of research topics, or public communication. The design of the scenarios is central to their ability to inform important questions. In this paper, we draw on the fields of decision analysis and statistical design of experiments to propose a framework for scenario design in epidemiology, with relevance also to other fields. We identify six different fundamental purposes for scenario designs (decision making, sensitivity analysis, value of information, situational awareness, horizon scanning, and forecasting) and discuss how those purposes guide the structure of scenarios. We discuss other aspects of the content and process of scenario design, broadly for all settings and specifically for multi-model ensemble projections. As an illustrative case study, we examine the first 17 rounds of scenarios from the U.S. COVID-19 Scenario Modeling Hub, then reflect on future advancements that could improve the design of scenarios in epidemiological settings.
Light exposure during sleep is associated with irregular sleep timing: the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Wallace Danielle A , Qiu Xinye , Schwartz Joel , Huang Tianyi , Scheer Frank A.J.L. , Redline Susan , Sofer Tamar 
Published: October 2023

ABSTRACTObjectiveExposure to light at night (LAN) may influence sleep timing and regularity. Here, we test whether greater light exposure during sleep (LEDS) associates with greater irregularity in sleep onset timing in a large cohort of older adults.MethodsLight exposure and activity patterns, measured via wrist-worn actigraphy (ActiWatch Spectrum), were analyzed in 1,933 participants with 6+ valid days of data in the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep Study. Summary measures of LEDS averaged across nights were evaluated in linear and logistic regression analyses to test the association with standard deviation (SD) in sleep onset timing (continuous variable) and irregular sleep onset timing (SD≥1.36 hours, binary). Night-to-night associations between LEDS and absolute differences in nightly sleep onset timing were also evaluated with distributed lag non-linear models and mixed models.ResultsIn between-individual linear and logistic models adjusted for demographic, health, and seasonal factors, every 5-lux unit increase in LEDS was associated with an increase of 7.8 minutes in sleep onset SD (β=0.13 hours, 95%CI:0.09-0.17) and 40% greater odds (OR=1.40, 95%CI:1.24-1.60) of irregular sleep onset. In within-individual night-to-night mixed model analyses, every 5-lux unit increase in LEDS the night prior (lag0) was associated with a 2.2-minute greater deviation of sleep onset the next night (β=0.036 hours, p<0.05). Conversely, every 1-hour increase in sleep deviation (lag0) was associated with a 0.35-lux increase in future LEDS (β=0.347 lux, p<0.05).ConclusionLEDS was associated with greater irregularity in sleep onset in between-individual analyses and subsequent deviation in sleep timing in within-individual analyses, supporting a role for LEDS in exacerbating irregular sleep onset timing. Greater deviation in sleep onset was also associated with greater future LEDS, suggesting a bidirectional relationship. Maintaining a dark sleeping environment and preventing LEDS may promote sleep regularity and following a regular sleep schedule may limit LEDS.
What do Iranians value most when choosing a hospital? Evidence from a discrete choice experiment
Authors: Ranjbar Mohammad , Bazyar Mohammad , Pahlevanshamsi Fatemeh , Angell Blake , Assefa Yibeltal 
Published: October 2023

AbstractBackgroundIndividual preferences have preceded the use of health care services, and it has been affected by different hospital attributes. This study aimed to elicit the Iranians’ preferences in choosing hospitals using a discrete choice experiment.MethodsA discrete choice experiment (DCE) was conducted through face to face interviews with 301 respondents. The DCE was constructed by six attributes were included based on a literature review, qualitative interviews, Focus Group Discussion (FGD) and stakeholder consultation: waiting time, quality of care, travel time, hospital type, provider competency, and hospital facilities. individuals’ preferences for hospital attributes were analyzed using a mixed logit model, and interaction terms were used to assess preference heterogeneity among individuals with different sociodemographic characteristics.ResultsParticipants had strong and significant preferences for care delivered in hospitals with ‘full’ (β=0.6052, p<0.001) or ‘moderate’ (β=0.5882, p<0.001) hospital equipment and with ‘excellent’ provider competency (β=0.2637, p<0.001). The estimated coefficients for the “waiting time of 120 minutes” (β=−0.1625, p<0.001) and the “travel time of 30 minutes” (β=−0.1157, p<0.001) were negative and significant. The results also show that the personal characteristics such as age, education level, and income significantly affected individual preferences in choosing a hospital.ConclusionConsidering people’s preferences can be important given the more active role of today’s patients in decision-making about their treatment processes. The results of this study should be taken into consideration by health policymakers and all stakeholders to be aware of differences in preferences of people and maximize their satisfaction. In this case, it is important to continuously involve people and consider their preferences in the design, topology, construction, and equipment of hospitals.
Differentiated care for youth across the HIV care cascade in Zimbabwe
Authors: Chikwari Chido Dziva , Kranzer Katharina , Simms Victoria , Patel Amani , Tembo Mandikudza , Mugurungi Owen , Sibanda Edwin , Mufare Onismo , Ndlovu Lilian , Muzangwa Joice , Vundla Rumbidzayi , Chibaya Abigail , Hayes Richard , Mackworth-Young Constance , Bernays Sarah , Mavodza Constancia , Hove Fadzanayi , Bandason Tsitsi , Dauya Ethel , Ferrand Rashida Abbas 
Published: October 2023

AbstractIntroductionYouth living with HIV are at higher risk than adults of disengaging from HIV care. Differentiated models of care such as community antiretroviral therapy (ART) may improve treatment outcomes, including viral suppression.MethodsThis study was nested in a cluster-randomised controlled trial (CHIEDZA: Clinicaltrials.gov, Registration Number:NCT03719521) which was conducted in Harare, Bulawayo and Mashonaland East Provinces in Zimbabwe and aimed to investigate the impact of a youth-friendly community-based package of HIV services, integrated with sexual and reproductive health services for youth (16–24 years), on population-level HIV viral load (VL). HIV services included HIV testing, ART initiation and continuous care, VL testing, and adherence support. Coverage percentages across the HIV care cascade were analysed.ResultsOverall 377 youth were newly diagnosed with HIV at CHIEDZA, linkage to HIV care was confirmed for 265 (70.7%, 234 accessed care at CHIEDZA and 31 with other providers); 250 (94.3%) started ART. Among those starting ART at CHIEDZA attrition within 6 months of starting ART was 38% and viral suppression (<1000 copies/ml) among those who had a test at 6 months was 90%. In addition 1162 youth already diagnosed with HIV accessed CHIEDZA; 714 (61.4%) had a VL test, of those 565 (79.1%) were virally suppressed.ConclusionThis study shows that provision of differentiated services for youth in the community is feasible. Linkage to care and retention during the initial months of ART was the main challenge as has been shown in other studies. Retention throughout the HIV-care journey for youth needs to become a priority programme goal to achieve the ambitious 95-95-95 UNAIDS targets.
Improving neglected tropical disease services and integration into primary healthcare in Southern Nations, Nationalities and People’s Region (SNNPR), Ethiopia: results from a mixed methods intervention evaluation
Authors: Donovan Laura , Habte Tedila , Batisso Esey , Getachew Dawit , Stratil Ann-Sophie , Tekalegne Agonafer , Seife Fikre , Mariam Damen , Baker Kevin 
Published: October 2023

AbstractBackgroundEthiopia is one of the countries with the highest burden of neglected tropical diseases (NTDs), with 16 of 20 recognised NTDs considered a public health problem, twelve of which have been identified as public health priorities by the Ethiopian Federal Ministry of Health. However, until recently NTDs have not received adequate attention at national and subnational levels in the country.MethodsThis study was conducted in Damot Gale district, Wolaita Zone in (Southern Nation Nationalities Peoples Region) SNNPR, Ethiopia and used a mixed methods approach to evaluate an intervention integrating four common NTDs (trachoma, lymphatic filariasis, schistosomiasis and podoconiosis) into Ethiopia’s primary healthcare system. The intervention consisted of adapted job aids, supportive supervision, and improved supplies of medical tools to improve diagnosis, management and reporting.Resultsfound that the intervention was successful at improving the detection, management and reporting across the four common NTD’s included and had a high level of acceptance from health workers. The intervention demonstrated cost-effectiveness.ConclusionThe findings highlight the need for further investment and consideration of integrating and scaling up NTD interventions at the primary healthcare level in Ethiopia, demonstrating that providing a package of interventions to support integration can be a cost-effective method.Author SummaryBuilding on the findings of a previous small-scale operational study and formative phase, this study involved implementing an intervention to integrate the prevention, diagnosis, management and reporting of four common NTDs — trachoma, lymphatic filariasis, schistosomiasis and podoconiosis — into Ethiopia’s primary healthcare system. The intervention consisted of providing health workers with adapted job aids, supportive supervision and improved diagnostic and medical supplies to facilitate NTD diagnosis, management, and reporting. It was implemented for six months in one hospital, one health centre and five health posts in Damot Gale district, Ethiopia and the feasibility, acceptability and cost-effectiveness were evaluated. Results indicate that the capacity of all enrolled health facilities for detecting, managing, and recording target NTDs improved over time. The use of intervention materials by health workers also increased over time. The intervention tools proved to be highly acceptable to health workers who viewed them as helpful, relevant, and easy to use. The findings highlight that providing a package of interventions to support integration can be a cost-effective method and that the integration and scale of NTD interventions at the primary healthcare level in Ethiopia should be considered.
Nepeta catariaL. (catnip) can serve as a chassis for the engineering of secondary metabolic pathways
Authors: Geissler Marcus , Neubauer Christoph , Sheludko Yuriy V. , Brückner Adrian , Warzecha Heribert 
Published: October 2023

AbstractObjectiveEvaluation ofNepeta catariaas a host with specific endogenous metabolite background for transient expression and metabolic engineering of secondary biosynthetic sequences.ResultsThe reporter geneGFP::licBM3 as well as three biosynthetic genes leading to the formation of the cannabinoid precursor olivetolic acid were adopted to the modular cloning standard GoldenBraid, transiently expressed in two chemotypes ofN. catariaand compared toNicotiana benthamiana. To estimate the expression efficiency in both hosts, quantification of the reporter activity was carried out with a sensitive and specific lichenase assay. WhileN. benthamianaexhibited lichenase activity of 676 ± 94 μmol g-1s-1(Gerasimenko et al. 2019),N. catariacultivar ‘1000’, and the cultivar ‘Citriodora’ showed an activity of 37 ± 8 μmol g-1s-1and 18 ± 4 μmol g-1s-1, respectively. Further, combinatorial expression of genes involved in cannabinoid biosynthetic pathwayacylactivating enzyme 1(aae1),olivetol synthase(ols) andolivetolic acid cyclase(oac) inN. catariacv. resulted presumably in thein vivoproduction of olivetolic acid glycosides.ConclusionNepeta catariais amenable toAgrobacterium-mediated transient expression and could serve as a novel chassis for the engineering of secondary metabolic pathways and transient evaluation of heterologous genes.
Utilising an in silico model to predict outcomes in senescence-driven acute liver injury
Authors: Ashmore-Harris Candice , Antonopoulou Evangelia , Aird Rhona E. , Man Tak Yung , Finney Simon M. , Speel Annelijn M. , Lu Wei-Yu , Forbes Stuart J. , Gadd Victoria L. , Waters Sarah L. 
Published: October 2023

AbstractCurrently liver transplantation is the only treatment option for liver disease, but organ availability cannot meet demand and transplant recipients require lifelong immunosuppression. The identification of alternative treatments, e.g. cell therapies, able to tip resolution of injury from inflammation to regeneration requires an understanding of the host response to the degree of injury. We adopt a combinedin vivo-in silicoapproach and develop a mathematical model of acute liver disease able to predict the host response to injury. We utilise the Mdm2fl/flmouse model together with a single Cre induction through intravenous injection of the hepatotropic Adeno-associated Virus Serotype 8 Cre (AAV8.Cre) to model acute liver injury. We derive a complementary ordinary differential equation model to capture the dynamics of the key cell players in the injury response together with the extracellular matrix. We show that the mathematical model is able to predict the host response to moderate injury via qualitative comparison of the model predictions with the experimental data. We then use the model to predict the host response to mild and severe injury, and test these predictionsin vivo, obtaining good qualitative agreement.
Reduced S-acylation of SQSTM1/p62 in Huntington disease is associated with impaired autophagy
Authors: Abrar F. , Davies M.C. , Kumar A. , Dang A. , Nguyen Y.T.N. , Collins J. , Caron N. , Choudhary J.S. , Sanders S.S. , Collins M.O. , Hayden M.R. , Martin D.D.O. 
Published: October 2023

AbstractDisruption of macroautophagy/autophagy has emerged as a common feature in many neurodegenerative diseases. Autophagy is a membrane-dependent pathway that requires many key regulators to quickly localize on and off membranes during induction promoting membrane fusion. Previously, our bioinformatic approaches have shown that autophagy and Huntington disease (HD) are enriched in S-acylated proteins. S-acylation involves the reversible addition of long chain fatty acids to promote membrane binding. Herein, we show that inhibition of S-acylation regulates the abundance of several key regulators of autophagy and leads to a partial block of autophagic flux. We show that the autophagy receptor SQSTM1/p62 (sequestosome 1) is S-acylated and directed to the lysosome. Importantly, we see that SQSTM1 S-acylation is significantly reduced in HD patient and mouse model brains, thus providing a novel mechanism for the generation of empty autophagosomes previously seen in HD models and patient cells.
Role of RANKL in Alveolar Epithelial Cell Regeneration: Potential Novel Contributor to Lung Tissue Repair
Authors: Habibie Habibie , Song Shanshan , Boorsma Carian E , Putri Kurnia S.S. , Reker-Smit Catharina , Vlasma Jelmer , Ruigrok Mitchel J.R. , Cool Robbert H , Wu Xinhui , Wang Yizhou , Quax Wim , Olinga Peter , Brandsma Corry-Anke , Timens Wim , Burgess Janette , Melgert Barbro N 
Published: October 2023

ABSTRACTReceptor activator for NF-κβ (RANK) ligand (RANKL) is found in lung tissue and elevated in lung diseases like chronic obstructive pulmonary disease (COPD), cystic fibrosis and silica-induced pulmonary fibrosis. RANKL is a well-known stimulator of bone tissue degradation, which may explain the association between these lung diseases and osteoporosis. However, RANKL is also reported to be involved in epithelial cell regeneration in breast and thymus. We hypothesized that RANKL, which is produced directly in lung tissue, is involved in the regeneration of lung epithelial cells. Therefore, we aimed to clarify the specific role of RANKL in this process.Using an organoid model of lung epithelial development by co-culturing primary EpCAM+ lung epithelial cells with fibroblasts, we found higher numbers of alveolar organoids after soluble RANKL treatment compared to control. Importantly, this effect was similar in human RANKL-treated organoids derived from epithelial cells isolated from lung tissue of COPD patients. The effect of RANKL was abrogated upon addition of osteoprotegerin, the soluble inhibitor of RANKL. We also found that RANKL stimulated phosphorylation of Akt suggesting involvement of its receptor RANK in the signaling pathway. Moreover,in vivoRANKL administration resulted in more type II alveolar epithelial cells in lungs of mice with silica-induced pulmonary fibrosis.In conclusion, we found that RANKL promotes type II alveolar epithelial cell regeneration and may therefore be a novel contributor to lung tissue repair.New and NoteworthyOur study provides compelling evidence demonstrating an as of yet unknown function of receptor activator for NF-κβ ligand (RANKL) in lung tissue regeneration. We found that RANKL plays a role in the regeneration of lung epithelial cells, particularly type II alveolar epithelial cells. This may also have clinical implications as promotion of alveolar epithelial cell regeneration may enhance lung tissue repair, an important target in patients with lung diseases like COPD and fibrosis.
An eco-physiological model of forest photosynthesis and transpiration under combined nitrogen and water limitation
Authors: Fransson Peter , Lim Hyungwoo , Zhao Peng , Tor-ngern Pantana , Peichl Matthias , Laudon Hjalmar , Henriksson Nils , Näsholm Torgny , Franklin Oskar 
Published: October 2023

AbstractAlthough the separate effects of water and nitrogen (N) limitations on forest growth are well known, the question of how to predict their combined effects remains a challenge for modeling of climate change impacts on forests. Here, we address this challenge by developing a new eco-physiological model that accounts for plasticity in stomatal conductance and leaf N concentration. Based on an optimality principle, our model determines stomatal conductance and leaf N concentration by balancing carbon uptake maximization, hydraulic risk and cost of maintaining photosynthetic capacity. We demonstrate the accuracy of the model predictions by comparing them against gross primary production estimates from eddy covariance flux measurements and sap-flow scaled canopy transpiration in a long-term fertilized and an unfertilized Scots pine (Pinus sylvestrisL.) forest in northern Sweden. The model also explains the response to N fertilization as a consequence of (i) reduced carbon cost of N uptake and (ii) increased leaf area per hydraulic conductance. The results suggest that leaves optimally coordinate N concentration and stomatal conductance both on short (weekly) time scales in response to weather conditions and on longer time scales in response to soil water and N availabilities.
Histone H3 E50K mutation confers oncogenic activity and supports an EMT phenotype
Authors: Sad Kirti , Jones Celina Y , Fawwal Dorelle V , Hill Emily J , Skinner Katie , Adams Miranda , Lustenberger Severin , Lee Richard S , Lohano Sandhya V , Elayavalli Satvik R , Farhi Jonathan , Lemon Laramie D , Fasken Milo B , Hong Andrew L , Sloan Steven A , Corbett Anita H , Spangle Jennifer M 
Published: October 2023

AbstractSequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype in human cells. Expression of H3E50K is sufficient to transform human cells as evidenced by a dramatic increase in cell migration and invasion, and a statistically significant increase in proliferation and clonogenicity. H3E50K also increases the invasive phenotype in the context of co-occurring BRAF mutations, which are present in patient tumors characterized by H3E50K. H3E50 lies on the globular domain surface in a region that contacts H4 within the nucleosome. We find that H3E50K perturbs proximal H3 post-translational modifications globally and dysregulates gene expression, activating the epithelial to mesenchymal transition. Functional studies usingS. cerevisiaereveal that, while yeast cells that express H3E50K as the sole copy of histone H3 show sensitivity to cellular stressors, including caffeine, H3E50K cells display some genetic interactions that are distinct from the characterized H3K36M oncohistone yeast model. Taken together, these data suggest that additional histone H3 mutations have the potential to be oncogenic drivers and function through distinct mechanisms that dysregulate gene expression.SummaryRecurrent missense mutation that alter histone H3E50 were identified in patient tumorsH3E50K expression dysregulates global H3 post-translational modification, gene expression and may govern a transcriptional program associated with metastatic phenotypeshht2-E50Kyeast cells exhibit growth defects in the presence of DNA damaging agents