bluuebunny/crossref_metadata_2025_split huggingface dataset:
iPAR: a new reporter for eukaryotic cytoplasmic protein aggregation
Authors: Lecinski Sarah , Howard Jamieson A.L. , MacDonald Chris , Leake Mark C. 
Published: February 2024

AbstractBackgroundCells employ myriad regulatory mechanisms to maintain protein homeostasis, termed proteostasis, to ensure correct cellular function. Dysregulation of proteostasis, which is often induced by physiological stress and ageing, often results in Protein Aggregation in cells. These aggregated structures can perturb normal physiological function, compromising cell integrity and viability, a prime example being early onset of several neurodegenerative diseases. Understanding aggregate dynamicsin vivois therefore of strong interest for biomedicine and pharmacology. However, factors involved in formation, distribution and clearance of intracellular aggregates are not fully understood.MethodsHere, we report an improved methodology for production of fluorescent aggregates in model budding yeast which can be detected, tracked and quantified using fluorescence microscopy in live cells. This new openly-available technology, iPAR (inducible Protein Aggregation Reporter), involves monomeric fluorescent protein reporters fused to a ΔssCPY* aggregation biomarker, with expression controlled under the copper-regulatedCUP1promoter.ResultsMonomeric tags overcome challenges associated with non-physiological reporter aggregation, whilstCUP1provides more precise control of protein production. We show that iPAR and the associated bioimaging methodology enables quantitative study of cytoplasmic aggregate kinetics and inheritance featuresin vivo. We demonstrate that iPAR can be used with traditional epifluorescence and confocal microscopy as well as single-molecule precise Slimfield millisecond microscopy. Our results indicate that cytoplasmic aggregates are mobile and contain a broad range of number of iPAR molecules, from tens to several hundred per aggregate, whose mean value increases with extracellular hyperosmotic stress.DiscussionTime lapse imaging shows that although larger iPAR aggregates associate with nuclear and vacuolar compartments, and for the first time we show directly that these proteotoxic accumulations are not inherited by daughter cells, unlike nuclei and vacuoles. If suitably adapted, iPAR offers new potential for studying diseases relating to protein oligomerization processes in other model cellular systems.
Comparing structure and dynamics of transition graphs by the symmetric difference metric over an edge-filtration
Authors: Pascual Belén García , Salbu Lars M. , Renz Jessica , Giannakis Konstantinos , Johnston Iain G. 
Published: February 2024

AbstractTransition graphs or transition diagrams, describing the rates and probabilities with which a system changes between discrete states, are common throughout the sciences. In many cases, parameterisations of transition graphs are inferred from different datasets, for example in the context of Markov or hidden Markov models. An important task for followup analysis is to find efficient and effective ways to compare transition graphs with different parameterisations. Here, we introduce the Weight-Filtration Comparison Curve (WFCC), an approach by which the differences between two or more parameterisations of a transition graph can be quantified and compared. Borrowing from topological data analysis, the WFCC allows graphs learned from different datasets and/or null models to be systematically compared, and differences in both the fine- and coarse-grained structure and dynamics of transition graphs to be quantitatively assessed. We demonstrate WFCC with simple illustrative cases and real-world cases of transition graphs inferred from global data on the evolution of antimicrobial resistance in different countries, showing how different inferred dynamics, and different levels of uncertainty, are reported by structural aspects of these comparison curves.
StaVia: Spatially and temporally aware cartography with higher order random walks for cell atlases
Authors: Stassen Shobana V. , Kobashi Minato , Huang Yuanhua , Ho Joshua W. K. , Tsia Kevin K. 
Published: February 2024

AbstractSingle-cell atlases are critical for unraveling the cellular basis of health and disease, yet their sheer diversity and vast data landscape in time and space pose daunting computational challenges pertaining to the delineation of multiple simultaneously emerging lineages, the integration of spatial and temporal information, and the visualization of trajectories across large atlases with enough resolution to observe localized transitions. To tackle this intricacy, we introduce StaVia, a computational framework that synergizes multi-faceted single-cell data—spanning time-series data, spatial gene expression patterns, and directional trends from RNA velocity— with higher-order random walks that leverage the memory of cells’ past states. StaVia fuses this method with a cartographic “Atlas View” that offers intuitive graph visualization, simultaneously capturing the nuanced details of cellular development at single-cell resolution as well as the broader connectivity of cell lineages, avoiding common pitfalls of merged distinct trajectories or missed transitional states seen in existing methods which are all memoryless. Notably, we demonstrate that StaVia unlocks new insights into placode development, radial glia pluripotency during neurulation, and the transitions pivotal to these processes in a large-scale Zebrafish developmental atlas. StaVia also allows spatially aware cartography that captures relationships between cell populations based on their spatial location as well as their gene expressions in a MERFISH dataset - underscoring its potential to dissect complex biological landscapes in both spatial and temporal contexts.
Targeting PD-L1 in solid cancer with myeloid cells expressing a CAR-like immune receptor
Authors: Chen Kayla Myers , Grun Daniel , Gautier Brian , Venkatesha Shivaprasad , Maddox Michael , Zhang Ai-Hong , Andersen Peter 
Published: February 2024

AbstractMyeloid cells are prevalent in solid cancers, but they frequently exhibit a pro-tumor phenotype, hindering cancer immunotherapy. Their abundance makes engineered myeloid cell therapy an intriguing approach to tackle challenges posed by solid cancers, such as tumor trafficking and infiltration along with tumor cell heterogenicity and immunosuppressive tumor microenvironment (TME). Solid cancers often upregulate the checkpoint molecule PD-L1 to evade immune responses. Thus, we devised an adoptive cell therapy strategy based on myeloid cells expressing a Chimeric Antigen Receptor (CAR)-like immune receptor (CARIR). The extracellular domain of CARIR is derived from the natural inhibitory receptor PD-1, while the intracellular domain(s) are derived from CD40 and/or CD3ξ. To assess the efficacy of CARIR-engineered myeloid cells, we conducted proof-of-principle experiments using co-culture and flow cytometry-based phagocytosis assaysin vitro. Additionally, we employed a fully immune-competent syngeneic tumor mouse model to evaluate the strategy’s effectivenessin vivo. Co-culturing CARIR-expressing human monocytic THP-1 cells with PD-L1+target cells lead to upregulation of the co-stimulatory molecule CD86 along with expression of proinflammatory cytokines TNF-1α and IL-1β. Moreover, CARIR expression significantly enhanced phagocytosis of multiple PD-L1+human solid tumor cell linesin vitro. Similar outcomes were observed with CARIR-expressing human primary macrophages. In experiments conducted on Balb/c mice bearing aggressive 4T1 mammary tumors, infusing murine myeloid cells expressing a murine version of CARIR significantly slowed tumor growth and prolonged survival. Taken together, our results demonstrate that adoptive transfer of PD-1 CARIR-engineered myeloid cells may be an effective strategy in treating PD-L1+solid tumors.Graphic AbstractIn BriefWe described here an adoptive cell therapy approach employing PD-L1-specific CAR-like immune receptor (CARIR) modified myeloid cells as a potential immune cell therapy strategy for treating PD-L1+solid cancer.CARIR expression directed human THP-1 macrophages to recognize PD-L1+target cells, which led to an upregulation of co-stimulatory molecule CD86 and production of proinflammatory cytokines TNF-α and IL-1β.CARIR expression in human THP-1 macrophages had increased % phagocytosis and killing against PD-L1+tumor cellsin vitro.Adoptive transfer of CARIR transduced myeloid cells in immunocompetent syngeneic mice with established aggressive 4T1 tumor significantly slowed tumor growth and prolonged survival.
Association ofBlastocystisand Gut Microbiota in Type 2 Diabetic Mellitus Patients and non-Diabetic Individuals
Authors: Mohd Shaari Nurul Saadah , Wan Sulaiman Wan Shahida , Omar Mohd Rahman , Umaisara Nadeeya’Ayn , Lee Ii Li , Anuar Tengku Shahrul , Abdullah Noradilah Samseh 
Published: February 2024

AbstractThe influence of anaerobic protozoanBlastocystison human gut health is not well understood. WhileBlastocystisspecies frequently inhabit the gut, their clinical importance and ecological function remain ambiguous. A study onBlastocystiswas carried out enrolling a total of 203 participants including T2DM patients and non-diabetic individuals to evaluate the prevalence ofBlastocystisand its association in gut microbiota.Blastocystissubtypes were identified by PCR and faecal microbiome was accessed by targeting V4 region of the bacterial 16S ribosomal gene. The prevalence ofBlastocystisin T2DM was 25.49% and 17.82% in non-diabetic individuals with the most prevalent subtype on total population was ST3, followed by ST1 and ST2. The composition of gut microbiota was significantly different betweenBlastocystis-positive andBlastocystis-negative individuals.Blastocystiscarriage was positively associated with higher alpha diversity in T2DM patients and non-diabetic individuals. Interestingly, at the phylum level, the T2DM group had an obvious increase of Bacteroidetes and a marked increase of Actinobacteria with the present ofBlastocystis. The findings suggested that the presence ofBlastocystiswas linked to increased diversity and richness in the gut bacterial composition, signifying at a potentially beneficial association betweenBlastocystisand the gut microbiota.Author SummaryType 2 Diabetes Mellitus Patients (T2DM), a prevalent global disease, affects a significant portion of the population across the world. Thus, there is need to better understanding onBlastocystisinfection among T2DM that could lead to the alteration toward gut health. We evaluated the association betweenBlastocystisand gut microbiota, where involving two groups; T2DM patients and non-Diabetic individuals. The research revealed a higherBlastocystisin T2DM patients compared to non-diabetic individuals, emphasizing on assumption toward its pathogenicity. However, amplicon-based sequencing of 16S rRNA genes indicates thatBlastocystiscarriers exhibit increased gut microbiota diversity. Our result suggested that,Blastocystishighlighted its potential role as a component of a balanced microbiota. Notably, optimal alteration in Actinobacteria and Bacteroidetes may contribute to the several gut health. Hence, the study could prompt for further exploration regarding ofBlastocystissubtypes and gut microbiota specifically in T2DM to propose for more precise assessment ofBlastocystisand gut microbial diversity.
The Burnout Syndrome among Dietitians in Arar, Saudi Arabia
Authors: Alqahtani Nasser , Albadareen Bushra , Mohammad-Mahmood Amna 
Published: February 2024

AbstractThis study identified and described the status of burnout experienced by Saudi dietitians in various settings. A questionnaire was sent to 160 members who were invited to participate via informal networks. The Copenhagen Burnout Inventory (CBI) scale was used to measure burnout status. The CBI comprises three subscales: personal burnoutPB(six items), work burnoutWB(seven items), and client-related burnoutCB(six items). Among the 160 participants in this study, 94 participants (58.75%) experienced burnout. most of the participants had moderate PB (n = 49, 30.6%), low WB (n = 58, 36.3%), and moderate CB (n = 73, 45.6%). These results suggest that the Saudi dietitians as a group perceive themselves to be moderately personal and client-related burnout, and to have a low level of work burnout. Further analysis also suggests that Saudi dietitians in nontraditional settings experience more burnout than those in healthcare clinical settings.
A deep-learning-based two-compartment predictive model (PKRNN-2CM) for vancomycin therapeutic drug monitoring
Authors: Mao Bingyu , Xie Ziqian , Nigo Masayuki , Rasmy Laila , Zhi Degui 
Published: February 2024

AbstractObjectiveVancomycin is a widely used antibiotic that requires therapeutic drug monitoring (TDM) for optimized individual dosage. The deep learning-based model PKRNN-1CM has shown the advantage of leveraging time series electronic health record (EHR) data for individualized estimation of vancomycin pharmacokinetic (PK) parameters. While one-compartment (1CM) PK models are commonly used because of their simplicity and previous trough-based clinical practices for dose adjustment, the pre-deep learning literature suggests the superiority of two-compartment models (2CM). Motivated by this, we introduce a novel deep-learning-based approach, PKRNN-2CM, for vancomycin TDM.MethodsPKRNN-2CM combines RNN-driven PK parameter estimation with a 2CM PK model to predict vancomycin concentration trajectories. Training on both simulated data and real-world EHR data allows for a comprehensive evaluation of its performance.ResultsExperiments based on simulated data highlight PKRNN-2CM’s superiority over the simpler 1CM model PKRNN-1CM (PKRNN-2CM RMSE=1.30, PKRNN-1CM RMSE=2.50). Application to real data showcases significant improvement over PKRNN-1CM (PKRNN-2CM RMSE=5.62, PKRNN-1CM RMSE=5.84, two-sample unpaired t-test p-value=0.01), with potential further gains expected with non-trough level measurements.ConclusionPKRNN-2CM is an important improvement in vancomycin TDM, demonstrating enhanced accuracy and performance compared to the PKRNN-1CM model. This deep learning model holds potential for future individualized vancomycin TDM optimization and broader application in diverse clinical scenarios.
A cluster-randomized trial of client and provider directed financial interventions to align incentives with appropriate case management in private medicine retailers: results of the TESTsmART Trial in Lagos, Nigeria
Authors: Visser T. , Laktabai J. , Kimachas E. , Kipkoech J. , Menya D. , Arthur D. , Zhou Y. , Chepkwony T. , Abel L. , Robie E. , Amunga M. , Ambani G. , Uhomoibhi P. , Ogbulafor N. , Oshinowo B. , Ogunsola O. , Woldeghebriel M. , Garber E. , Olaleye T. , Eze N. , Nwidae L. , Mudabai P. , Gallis J.A. , Fashanu C. , Saran I. , Woolsey A. , Turner E.L. , O’Meara W. Prudhomme 
Published: February 2024

AbstractMalaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemether Combination Therapies (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria’s private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that RDTs could reduce ACT overconsumption in Nigeria’s private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Clinical Trials Registration Number:NCT04428307
Supporting carers: Study protocol of a meta-review of psychosocial interventions for carers of people with cancer
Authors: Nic Giolla Easpaig Bróna , Newman Bronwyn , Johnson Judith , Laidsaar-Powell Rebekah , Sansom-Daly Ursula M , Jones Lucy , Hofstätter Lukas , Robertson Eden G , Mears Stephen , Sattarshetty Kabir , Harrison Reema 
Published: February 2024

AbstractBackgroundWhile there is a clear need for psychosocial interventions that promote cancer carer wellbeing, the corresponding evidence base is disparate, complex and difficult for end-users to navigate and interpret. Carers remain under-supported with a lack of dedicated, effective, evidence-based programs. We will conduct a meta-review to synthesise this evidence and determine the state of science in this field.ObjectivesThis study aims to address the question of: “What psychosocial interventions are available to promote the wellbeing of carers for people with cancer?”MethodsA meta-review will synthesise relevant reviews of psychosocial interventions that have been developed and/ or evaluated with carers for people with cancer. Four electronic databases (PsychInfo, Medline, CINAHL and Cochrane Database of Systematic Reviews) will be searched for reviews published between Jan 2013 and Dec 2023. A team-based approach will be taken to screening and assessment of the returned records against the eligibility criteria to determine inclusion. Included reviews will be critically appraised using JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Relevant data of study characteristics, carer and patient populations, intervention details and psychosocial outcomes will be extracted, synthesised and the findings will be presented in a narrative format. This study is registered with the International Prospective Register of Systematic Reviews (reference: CRD42023403219).ResultsIt is anticipated that the study will be completed by April 2024.ConclusionEnsuring that carers have access to evidence-based programs which promote their wellbeing as they care for loved ones is critical. This meta-review will contribute to program development and translation efforts through providing a clear picture of the cancer carer intervention evidence-base, identifying notable strengths, weaknesses, and gaps across the literature. The findings are anticipated to offer future directions to advance research in the field.
Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of acute coronary syndrome
Authors: Koch Pia F. , García-Hidalgo María C. , Labus Josephine , Biener Moritz , Thum Thomas , de Gonzalo-Calvo David , Bär Christian 
Published: February 2024

AbstractAimLong noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers owing to their dynamic regulation in response to pathological conditions and their detection in clinically relevant samples. Here, we explored the utility of the cardiac expressed and plasma detectable lncRNA PDE4DIPP6 as a biomarker for acute coronary syndrome (ACS). The final goal was to improve the diagnostic efficacy of state-of-the-art tests, particularly the high-sensitivity cardiac troponin assay (hs-cTnT).MethodsThe study enrolled individuals presenting with suspected ACS at the emergency department (ED). LncRNA quantification was performed in plasma samples using RT-qPCR. Discriminatory performance was evaluated by calculating the Area Under the Curve (AUC). Reclassification metrics, including the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) indexes, were employed to assess enhancements in diagnostic accuracy.ResultsThe sample comprised 252 patients, 50.8% were diagnosed with ACS and 13.9% with Non-ST Segment Elevation Myocardial Infarction (NSTEMI). Elevated levels of PDE4DIPP6 were observed in ACS patients compared to non-ACS subjects. There was no significant correlation between lncRNA and hs-cTnT levels (rho=0.071), and no association between PDE4DIPP6 levels and potential confounding factors was observed. The inclusion of PDE4DIPP6 on top of troponin T significantly enhanced the discrimination and classification of ACS patients reflected in an improved AUC of 0.734, an IDI of 0.066 and NRI of 0.471. Similarly, elevated levels of the lncRNA were observed in NSTEMI patients compared to ACS patients without NSTEMI. Consistent with previous findings, the addition of PDE4DIPP6 to hs-cTnT improved the discrimination and classification of patients, evident in an increased AUC from 0.859 to 0.944, IDI of 0.237, and NRI of 0.658.ConclusionPDE4DIPP6 offers additional diagnostic insights beyond hs-cTnT, suggesting its potential to improve the clinical management of patients with ACS.
Patterns of Herbal Medicine Use in a General Outpatient Clinic in Nigeria- A Cross-sectional Study
Authors: Maiyegun Afisulahi Abiodun , Akangoziri Mark Divine , Grema Bukar Alhaji , Mutalub Yahkub Babatunde , Ibrahim Farida Buhari , Ibraheem AbdulRauf Segun 
Published: February 2024

AbstractBackgroundHerbal medicine use remains an important part of primary care and the World Health Organization has mandated member countries to conduct research into this and other forms of traditional medicine. However, research into traditional medicine remains scanty, even in the developing where it is often a major health option.Objectiveto determine the prevalence, types and sources of herbal medicine used among the study population.MethodsThree hundred and forty-one questionnaires were administered to adult patients attending the general outpatient clinic of a tertiary hospital in Northern Nigeria. The data was collected and analysed using EPI INFO version 7.2.5.0 software.ResultsThe prevalence of herbal medicine use was 85.34%; the commonest herbs were moringa (59.8%), black seed (36.8%), and olive oil (34.4%); and the commonest source of the herbs were herbal practitioners and herbal medicine vendors (79.04%). Herbal medicine use was associated with religion (P= 0.0005) and residential area (P= 0.01). Only 18.12% of participants ever discussed herbal medicine use with their doctors.Conclusionherbal medicine use remains high even among patients attending outpatient clinics in tertiary hospitals in Nigeria. However, health workers are often not the source of herbal medicine and patients rarely disclose its use to them.