bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and protocol for a safety, tolerability and feasibility randomized, parallel group, double-blind, placebo-controlled, pilot study of a novel ketone ester targeting frailty via immunometabolic geroscience mechanisms
Authors: Stubbs Brianna J. , Alvarez-Azanedo Gabriela , Peralta Sawyer , Roa-Diaz Stephanie , Gray Wyatt , Alexander Laura , Silverman-Martin Wendie , Garcia Thelma , Blonquist Traci M. , Upadhyay Vaibhav , Turnbaugh Peter J. , Johnson James B. , Newman John C. 
Published: October 2023

AbstractBackgroundFrailty is a geriatric syndrome characterized by chronic inflammation and metabolic insufficiency that creates vulnerability to poor outcomes with aging. We hypothesize that geroscience interventions, which target mechanisms of aging, could ameliorate frailty. Metabolites such as ketone bodies are candidate geroscience interventions, having pleiotropic effects on inflammo-metabolic aging mechanisms. Ketone esters (KEs) induce ketosis without dietary changes, but KEs have not been studied in an older adult population. Our long-term goal is to examine if KEs modulate geroscience mechanisms and clinical outcomes relevant to frailty in older adults.ObjectivesThe primary objective of this randomized, placebo-controlled, double-blinded, parallel-group, pilot trial is to determine tolerability of 12-weeks of KE ingestion in a generalizable population of older adults (≥ 65 years). Secondary outcomes include safety and acute blood ketone kinetics. Exploratory outcomes include physical function, cognitive function, quality of life, aging biomarkers and inflammatory measures.MethodsCommunity-dwelling adults who are independent in activities of daily living, with no unstable acute medical conditions (n=30) will be recruited. The study intervention is a KE or a taste, appearance, and calorie matched placebo beverage. Initially, acute 4-hour ketone kinetics after 12.5g or 25g of KE consumption will be assessed. After collection of baseline safety, functional, and biological measurements, subjects will randomly be allocated to consume KE 25g or placebo once daily for 12-weeks. Questionnaires will assess tolerability daily for 2-weeks, and then via phone interview at bi-monthly intervals. Safety assessments will be repeated at week 4. All measures will be repeated at week 12.ConclusionThis study will evaluate feasibility, tolerability, and safety of KE consumption in older adults and provide exploratory data across a range of geroscience-related endpoints. This data will inform design of larger trials to rigorously test KE effects on geroscience mechanisms and clinical outcomes relevant to frailty.
Association between combined sewer overflow events and gastrointestinal illness in Massachusetts municipalities with and without river-sourced drinking water, 2014-2019
Authors: Haley Beth M. , Sun Yuantong , Jagai Jyotsna S. , Leibler Jessica H. , Fulweiler Robinson , Ashmore Jacqueline , Wellenius Gregory A. , Heiger-Bernays Wendy 
Published: October 2023

AbstractBackgroundCombined sewer overflow (CSO) events release untreated wastewater into surface waterbodies during heavy precipitation or snowmelt. Combined sewer systems serve approximately 40 million people in the United States, primarily in urban and suburban municipalities in the Midwest and Northeast. Predicted increases in heavy precipitation events driven by climate change underscore the importance of quantifying potential health risks associated with CSO events.ObjectivesThe aims of this study were: to 1) estimate the association between CSO events (2014-2019) and emergency department (ED) visits for acute gastrointestinal illness (AGI) among Massachusetts municipalities that border a CSO-impacted river, and 2) determine if associations differ by municipal drinking water source.MethodsA case time series design was used to estimate the association between daily cumulative upstream CSO discharge in the prior four days and ED visits for AGI, adjusting for temporal trends, temperature, and precipitation. Associations between CSO events and AGI were also compared by municipal drinking water source (CSO-impacted river vs. other sources).ResultsExtreme upstream CSO discharge events (>95th percentile by cumulative volume) were associated with a cumulative risk ratio (CRR) of AGI of 1.22 (95% CI: 1.05, 1.42) over the next four days for all municipalities, and the association was robust after adjusting for precipitation (1.17 [0.98, 1.39]). In municipalities with CSO-impacted drinking water sources, the adjusted association was somewhat less pronounced following 95th percentile CSO events (1.05 [0.82, 1.33]). The adjusted CRR of AGI was 1.62 in all municipalities following 99th percentile CSO events (95% CI: 1.04, 2.51) and not meaningfully different across strata defined by drinking water source.DiscussionIn municipalities bordering a CSO-impacted river in Massachusetts, extreme CSO events are associated with higher risk of AGI within four days. The largest CSO events are associated with increased risk of AGI regardless of drinking water source.
Navigating vaccination choices: The intersecting dynamics of institutional trust, belonging and message perception among Congolese migrants in the UK (A reflexive thematic analysis)
Authors: Crawshaw Alison F , Vandrevala Tushna , Knights Felicity , Deal Anna , Lutumba Laura Muzinga , Nkembi Sarah , Kitoko Lusau Mimi , Hickey Caroline , Forster Alice S , Hargreaves Sally 
Published: October 2023

AbstractBackgroundThe COVID-19 pandemic has disproportionately impacted intersectionally marginalised migrants, revealing systemic disparities in health outcomes and vaccine uptake. An in-depth understanding of the underlying social and structural factors influencing health behaviours is necessary to develop tailored interventions for migrants but has been seldom explored. Therefore, this qualitative study aimed to explore the contextual factors shaping COVID-19 vaccination decision-making among Congolese migrants in the UK.MethodsA community-based participatory research study was designed and led by a community-academic partnership in London, UK (2021–2022). Peer-led, semi-structured interviews were conducted in Lingala with 32 adult Congolese migrants and explored beliefs, perceptions and lived experiences of migration, healthcare and vaccination and the pandemic. Reflexive thematic analysis generated two themes and a model conceptualising the vaccination decision-making process was developed. Participants and community partners were financially compensated, and the study received ethical approval from the University of London ethics committee (REC: 2021.0128).FindingsParticipants highlighted the incompatibility of lockdown restrictions with their communal culture, which intensified feelings of exclusion and alienation. Concerns about COVID-19 vaccination were attributed to safety and effectiveness, partly informed by experiences and legacies of discrimination and exploitation of Black Africans. Inequality in the pandemic response and COVID-19 outcomes heightened participants’ sense that their views and needs were being overlooked and government sources and information were perceived as coercive. Drawing on this data, our model depicts the interplay between institutional trust, belonging, and message perception which shaped participants’ vaccination decisions and led to (non-)engagement with COVID-19 vaccination.ConclusionThis research enhances understanding of how social and contextual factors may influence migrants’ engagement with health interventions. It underscores the necessity of partnering with migrant communities to understand their needs in context and co-design tailored interventions and inclusive messaging strategies which foster trust and belonging. Implementing systemic changes to address structural inequalities will be crucial to create an environment that supports engagement with health-protective behaviours and enhances health outcomes among migrant communities.
Both HFrEF and HFpEF Should be Included in Calculating CHA2DS2–VASc score: a Taiwanese Longitudinal Cohort
Authors: Cheng Chien-Chien , Huang Pang-Shuo , Chen Jien-Jiun , Chiu Fu-Chun , Chang Sheng-Nan , Wang Yi-Chih , Wu Cho-Kai , Hwang Juey-Jen , Tsai Chia-Ti 
Published: October 2023

AbstractBackgroundCongestive heart failure (CHF) in the context of AF-related stroke risk, was coined when it mainly referred to patients with left ventricular systolic dysfunction (HFrEF). However, the term now encompasses patients with preserved ejection fraction (HFpEF) as well. Given this change, it becomes essential to investigate the variation in stroke risk between atrial fibrillation (AF) patients with HFpEF and HFrEF for enhancing risk assessment and subsequent management strategies.MethodsIn a longitudinal study utilizing the National Taiwan University Hospital Integrated Medical Database (iMED), 8358 patients with AF were followed up for 10 years from January 2010 to December 2020 (mean follow-up 3.76 years). The study evaluated the risk of ischemic stroke, using Cox models adjusted for potential risk factors of AF-related stroke.ResultsComparing AF patients of different CHF subgroups, HFpEF patients had a higher mean CHA2DS2–VASc score (4.08±1.502 vs. 3.83±1.571, p<0.001) and a higher risk of stroke during follow-up (HR 1.151 (1.013-1.308), p=0.031). In contrast, patients with HFrEF had a higher prevalence of myocardial infarction (MI) and coronary artery disease (CAD). After adjusting for other risk factors, there was no significant difference in the risk of new-onset stroke between HFpEF and HFrEF patients (HR 1.001 (0.877-1.142), p=0.994).ConclusionAfter adjusting for other risk factors of stroke, both HFpEF and HFrEF were found to have a similar risk of stroke in AF patients. Therefore, it is important to extend the criteria for “C” in the CHA2DS2–VASc score to include HFpEF patients. Prior to multivariable adjustment, HFpEF patients had a higher risk than those with HFrEF, likely due to their higher CHA2DS2–VASc score, indicating a greater prevalence of stroke-related comorbidities.
Temporally distinct roles of Aurora A in polarization of theC. eleganszygote
Authors: Manzi Nadia I. , de Jesus Bailey N. , Shi Yu , Dickinson Daniel J. 
Published: October 2023

AbstractDuring asymmetric cell division, coordination of cell polarity and the cell cycle is critical for proper inheritance of cell fate determinants and generation of cellular diversity. InCaenorhabditis elegans(C. elegans), polarity is established in the zygote and is governed by evolutionarily conserved Partitioning defective (PAR) proteins that localize to distinct cortical domains. At the time of polarity establishment, anterior and posterior PARs segregate to opposing cortical domains that specify asymmetric cell fates. Timely establishment of these PAR domains requires a cell cycle kinase, Aurora A (AIR-1 inC.elegans). Aurora A depletion by RNAi causes a spectrum of phenotypes including no posterior domain, reversed polarity, and excess posterior domains. How depletion of a single kinase can cause seemingly opposite phenotypes remains obscure. Using an auxin-inducible degradation system, drug treatments, and high-resolution microscopy, we found that AIR-1 regulates polarity via distinct mechanisms at different times of the cell cycle. During meiosis I, AIR-1 acts to prevent the formation of bipolar domains, while in meiosis II, AIR-1 is necessary to recruit PAR-2 onto the membrane. Together these data clarify the origin of the multiple polarization phenotypes observed in RNAi experiments and reveal multiple roles of AIR-1 in coordinating PAR protein localization with the progression of the cell cycle.
Elevated epigenetic age in wild compared to lab-raised house mice
Authors: Hanski Eveliina , Joseph Susan , Raulo Aura , Wanelik Klara M , O’Toole Áine , Knowles Sarah C L , Little Tom J 
Published: October 2023

AbstractAge is a key parameter in population ecology, with myriad biological processes changing with age as organisms develop early in life and later senesce. As age is often hard to accurately measure with non-lethal methods, epigenetic methods of age estimation (epigenetic clocks) have become a popular tool in animal ecology, and are often developed or calibrated using captive animals of known age. However, few studies have directly compared epigenetic age estimates between wild and captive or lab-reared animals of the same species, even though age-related epigenetic changes can be influenced by environmental conditions. Here, we built an epigenetic clock from standard laboratory house mice (C57BL/6,Mus musculus)and then used it to estimate age in a population of wild mice (Mus musculus domesticus) of unknown age. We show that this clock accurately predicts adult wild mice to be older than juveniles and that wild mice typically increase in epigenetic age over time, but with wide variation in epigenetic ageing rate among wild individuals. We further show that, for a given body mass, wild mice are epigenetically older than lab mice, and that this difference is not explained by accelerated ageing post-capture but is observed even among the smallest juvenile mice. This suggests different epigenetic age profiles in mice with contrasting genetic and environmental backgrounds arise very early in life and may be driven by peri- and postnatal effects on offspring DNA methylation.
DEVELOPMENT AND EVALUATION OF COATED RICOTTA CHEESE WITH WHEY PROTEIN AND CLOVE OIL
Authors: Aamir Muhammad , Sarwar Eram , Ahmad Aftab , Saeed Farhan , Ikram Ali , Afzaal Muhammad , Kiran Faiza , Ateeq Huda , Akram Noor , Hussain Shahzad , Khan Mahbubur Rehman 
Published: October 2023

ABSTRACTCheese, oldest dairy product which is used to preserve the nutrients of milk for long time. It is available in different shapes, sizes, flavors and textures. Ricotta is fresh soft cheese, is prepared through coagulating the whey proteins. It is a value-added product manufactured from cheese whey. Microbial spoiling occurs as a result of unmanaged conditions, resulting in the unfavorable changes in odor, flavor, and texture. That leads to food poisoning when infected food is consumed. Natural preservatives are preferred by consumers over synthetic preservatives since they are safer and extend the shelf life of food goods. Synthetic preservatives are poisonous and have negative health consequences. Edible coatings are biodegradable, natural films that can improve the product’s safety, quality, and nutritional content until it is consumed. This research was carried out to analyse the effect of whey protein and clove essential oil on the shelf life of ricotta cheese due to their excellent gas barrier properties, antioxidant and antimicrobial properties. Different concentrations of clove oil (0.1, 0.2, 0.3 %) are incorporated in whey protein coating solution (2.5,5,7.5%). The overall findings for all groups showed that there was gradual decrease in acidity and moisture content. Therefore, sample TRC3treated with 0.75 % whey protein and 0.3% clove oil showed significant results (P<0.05). They showed less microbial count, increased fat and protein value. But it also had great impact on sensory analysis such as on color, texture, aroma while it showed significant overall acceptability due to high clove oil and whey protein concentrations. Hence, this study showed significant effect on shelf life of ricotta cheese and its shelf life increased from 7 to 21 days.
Lifecycle of a predatory bacterium vampirizing its prey through the cell envelope and S-layer
Authors: Santin Yoann G. , Sogues Adrià , Bourigault Yvann , Remaut Han K. , Laloux Géraldine 
Published: October 2023

AbstractPredatory bacteria feed upon and kill other bacteria in various natural environments. Obligate epibiotic predators likeBdellovibrio exovorusconsume their prey whilst remaining attached to the outside of the prey. How these predators achieve epibiotic feeding through the prey cell envelope has not been explored previously. Whereas the S-layer is the only proposed defensive structure against predatory bacteria, it remains unclear how this thin outer layer of the envelope might prevent epibiotic attacks. Similarly, the lifecycle ofB. exovorusduring the predator-prey interaction is poorly understood, with current models suggesting a binary division. Here we imaged the entire predatory lifecycle ofB. exovorusand the fate of itsCaulobacter crescentusprey by time-lapse microscopy and cryo-electron microscopy to monitor predator attack, growth and division and assess the impact of the S-layer on epibiotic predation. Our data reveal thatB. exovorususes non-binary division in a novel proliferation pattern that mainly generates three progenies. Moreover, we found thatB. exovoruspredates regardless of the presence of an S-layer, calling for revisiting its protective role against predators. Finally, our results indicate that epibiotic predation relies on the establishment of a secured junction between the prey and predator outer membranes, which must be resolved unilaterally to maintain cellular integrity of the predator departing from the prey surface.
The prevalence ofFusobacterium nucleatumsubspecies in the oral cavity stratifies by local health status
Authors: Krieger Madeline , AbdelRahman Yasser M. , Choi Dongseok , Palmer Elizabeth A. , Yoo Anna , McGuire Sean , Kreth Jens , Merritt Justin 
Published: October 2023

AbstractThe ubiquitous inflammophilic pathobiontFusobacterium nucleatumis widely recognized for its strong association with a variety of human dysbiotic diseases such as periodontitis and oral/extraoral abscesses, as well as multiple types of cancer. F. nucleatumis currently subdivided into four subspecies:F. nucleatumsubspeciesnucleatum(Fn. nucleatum), animalis(Fn. animalis), polymorphum(Fn. polymorphum), andvincentii/fusiforme(Fn. vincentii). Although these subspecies have been historically considered as functionally interchangeable in the oral cavity, direct clinical evidence is largely lacking for this assertion. Consequently, we assembled a collection of oral clinical specimens to determine whetherF. nucleatumsubspecies prevalence in the oral cavity stratifies by local oral health status. Patient-matched clinical specimens of both disease-free dental plaque and odontogenic abscess were analyzed with newly developed culture-dependent and culture-independent approaches using 44 and 60 oral biofilm/tooth abscess paired specimens, respectively. Most oral cavities were found to simultaneously harbor multipleF. nucleatumsubspecies, with a greater diversity present within dental plaque compared to abscesses. In dental plaque,Fn. polymorphumis clearly the dominant organism, but this changes dramatically within odontogenic abscesses whereFn. animalisis heavily favored over all other fusobacteria. Surprisingly, the most commonly studiedF. nucleatumsubspecies,Fn. nucleatum,is only a minor constituent in the oral cavity. To gain further insights into the genetic basis for these phenotypes, we subsequently performed pangenome, phylogenetic, and functional enrichment analyses of oral fusobacterial genomes using the Anvi’o platform, which revealed significant genotypic distinctions amongF. nucleatumsubspecies. Accordingly, our results strongly support a taxonomic reassignment of eachF. nucleatumsubspecies into distinctFusobacteriumspecies. Of these,Fn. animalisshould be considered as the most clinically relevant at sites of active inflammation, despite being among the least characterized oral fusobacteria.
Role of Dopamine Neurons in Familiarity
Authors: Fleury Sixtine , Kolaric Rhonda , Espera Justin , Ha Quan , Tomaio Jacquelyn , Gether Ulrik , Sørensen Andreas Toft , Mingote Susana 
Published: October 2023

AbstractDopamine neurons signal the salience of environmental stimuli, influencing learning and motivation. However, research has not yet identified whether dopamine neurons also modulate the salience of memory content. Dopamine neuron activity in the ventral tegmental area (VTA) increases in response to novel objects and diminishes as objects become familiar through repeated presentations. We proposed that the declined rate of dopamine neuron activity during familiarization affects the salience of a familiar object’s memory. This, in turn, influences the degree to which an animal distinguishes between familiar and novel objects in a subsequent novel object recognition (NOR) test. As such, a single familiarization session may not sufficiently reduce dopamine activity, allowing the memory of a familiar object to maintain its salience and potentially attenuating NOR. In contrast, multiple familiarization sessions could lead to more pronounced dopamine activity suppression, strengthening NOR. Our data in mice reveals that, compared to a single session, multiple sessions result in decreased VTA dopamine neuron activation, as indicated by c-Fos measurements, and enhanced novelty discrimination. Critically, when VTA dopamine neurons are chemogenetically inhibited during a single familiarization session, NOR improves, mirroring the effects of multiple familiarization sessions. In summary, our findings highlight the pivotal function of dopamine neurons in familiarity and suggest a role in modulating the salience of memory content.
Highly-parallel production of designer organoids by mosaic patterning of progenitors
Authors: Porter Catherine M. , Qian Grace C. , Grindel Samuel H. , Hughes Alex J. 
Published: October 2023

AbstractHuman organoids are a promising approach for disease modeling and regenerative medicine. However, organoid variability and limited control over morphological outcomes remain significant challenges. Here we extend a DNA ‘velcro’ cell patterning approach, precisely controlling the number and ratio of human stem cell-derived progenitors contributing to nephron and mosaic nephron/ureteric bud organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints.
Structure-preserving fixation allows Scanning Electron Microscopy to reveal biofilm microstructure and interactions with immune cells
Authors: Wells Marilyn , Mikesh Michelle , Gordon Vernita 
Published: October 2023

AbstractPseudomonas aeruginosais a pathogen that forms robust biofilms which are commonly associated with chronic infections and cannot be successfully cleared by the immune system. Neutrophils, the most common white blood cells, target infections with pathogen-killing mechanisms that are rendered largely ineffective by the protective physicochemical structure of a biofilm. Visualization of the complex interactions between immune cells and biofilms will advance understanding of how biofilms evade the immune system and could aid in developing treatment methods that promote immune clearance with minimal harm to the host. Scanning electron microscopy (SEM) distinguishes itself as a powerful, high-resolution tool for obtaining strikingly clear and detailed topographical images. However, taking full advantage of SEM’s potential for high-resolution imaging requires that the fixation process simultaneously preserve both intricate biofilm architecture and the morphologies and structural signatures characterizing neutrophils responses at an infection site. Standard aldehyde-based fixation techniques result in significant loss of biofilm matrix material and morphologies of responding immune cells, thereby obscuring the details of immune interactions with the biofilm matrix. Here we show an improved fixation technique using the cationic dye alcian blue to preserve and visualize neutrophil interactions with the three-dimensional architecture ofP. aeruginosabiofilms.