bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the cultural environment of the outpatient care setting for patients with dementia receiving cancer treatment: a qualitative study
Authors: Farrington Naomi , Dantanus Katherine , Richardson Alison , Bridges Jackie 
Published: May 2022

AbstractIntroductionPeople with dementia have poorer cancer outcomes than those without, and experience inequalities in access to, and quality of, care. Outpatient environments, where radiotherapy, chemotherapy and immunotherapy cancer treatments typically take place, have largely been excluded from research. This study was conducted to understand provision of treatment and support and experiences of care for people with dementia undergoing cancer treatment in the outpatient setting.Materials and methodsUsing observation, interviews and document analysis, data were collected to scrutinise the cultural environment of ambulatory care, comprising the physical fabric of the care setting; interactions, behaviours and perceptions of those in the care setting; and the organizational, clinical and interactional processes involved in care delivery. The study was conducted in the outpatient oncology departments of two large teaching hospitals in England between January 2019-July 2021.ResultsData were gathered from a wide range of sources, including 15 hours of observation, and interviews with patients (n=2), caregivers (n=7) and staff (n=20). Evidence from this study suggests the cultural environment of the outpatient care setting reflects and supports the standardised processing of people for cancer treatment. Dementia introduces a wider set of care requirements not catered for by this standardised treatment model and associated processes. Data showed the needs of patients with dementia could be addressed most effectively when individualised, as opposed to standardised care, was offered.ConclusionThere is work to be done in outpatient cancer services to ensure responsiveness to individual patient need. This could be achieved by having an established way (or ways) of eliciting needs, preferences and expectations, a belief that a person’s needs and expectations are legitimate, and that effort should be made to address them, with the ability to accommodate these needs and expectations.Patient or public contributionpatients and caregivers were involved in the study design and development of study materials including the interview topic guide. They also assisted with discussion and clarification of study findings.
Early detection of acute kidney injury in critically ill children: Predictive value of renal arterial Doppler assessment
Authors: de Carvalho Aline Vaconcelos , Ferraz Isabel de Siqueira , de Souza Fabiane Mendes , Brandão Marcelo Barciela , Nogueira Roberto José Negrão , Alves Daniela Fernanda Santos , de Souza Tiago H. 
Published: May 2022

ABSTRACTObjectiveRenal resistive index (RRI) and renal pulsatility index (RPI) are Doppler-based variables proposed to assess renal perfusion at the bedside in critically ill patients. This study aimed to assess the accuracy of such variables to predict acute kidney injury (AKI) in mechanically ventilated children.DesignProspective single-center observational studySettingPediatric intensive care unit of a quaternary care teaching hospital.Patients84 children under controlled ventilation (median age of 5.1 months and weight of 6.6 kg).InterventionsConsecutive children underwent renal Doppler ultrasound examination within 24 hours of invasive mechanical ventilation. Renal resistive index (RRI) and renal pulsatility index (RPI) were measured. The primary outcome was severe AKI (KDIGO stage 2 or 3) on day 3. Secondary outcomes included the persistence of severe AKI on day 5.ResultsOn day 3, 22 patients were classified as having AKI (any stage), of which 12 were severe. RRI could effectively predict severe AKI (area under the ROC curve [AUC] 0.94; 95% CI 0.86 – 0.98; p < 0.001) as well as RPI (AUC 0.86; 95% CI 0.76 – 0.92; p < 0.001). The AUC of the IRR was significantly greater than that obtained from the RPI (p = 0.023). The optimal cutoff for RRI was 0.85 (sensitivity, 91.7%; specificity, 84.7%; positive predictive value, 50.0%; and negative predictive value 98.4%). Similar results were obtained when the accuracy to predict AKI on day 5 was assessed. Significant correlations were observed between RRI and estimated glomerular filtration rate at enrollment (ρ = -0.495, p<0.001) and on day 3 (ρ = -0.467, p <0.001).ConclusionsRenal Doppler ultrasound may be a promising tool to predict AKI in critically ill children under invasive mechanical ventilation.
Comparative transcriptomics and metabolomics reveal specialized metabolite drought stress responses in switchgrass (Panicum virgatumL.)
Authors: Tiedge Kira , Li Xingxing , Merrill Amy T. , Davisson Danielle , Chen Yuxuan , Yu Ping , Tantillo Dean J. , Last Robert L. , Zerbe Philipp 
Published: May 2022

SUMMARYSwitchgrass (Panicum virgatum) is a bioenergy model crop valued for its energy efficiency and drought tolerance resilience. The related monocot species rice (Oryza sativa) and maize (Zea mays) deploy species-specific, specialized metabolites as core stress defenses. By contrast, specialized chemical defenses in switchgrass are largely unknown.To investigate specialized metabolic drought responses in switchgrass, we integrated tissue-specific transcriptome and metabolite analyses of the genotypes Alamo and Cave-in-Rock that feature different drought tolerance.The more drought-susceptible Cave-in-Rock featured an earlier onset of transcriptomic changes and significantly more differentially expressed genes in response to drought compared to Alamo. Specialized pathways showed moderate differential expression compared to pronounced transcriptomic alterations in carbohydrate and amino acid metabolism. However, diterpenoid-biosynthetic genes showed drought-inducible expression in Alamo roots, contrasting largely unaltered triterpenoid and phenylpropanoid pathways. Metabolomic analyses identified common and genotype-specific flavonoids and terpenoids. Consistent with transcriptomic alterations, several root diterpenoids showed significant drought-induced accumulation, whereas triterpenoid abundance remained predominantly unchanged. Structural analysis of drought-responsive root diterpenoids verified these metabolites as oxygenated furanoditerpenoids.Drought-dependent transcriptome and metabolite profiles provide the foundation to understand the molecular mechanisms underlying switchgrass environmental resilience. Accumulation of specialized root diterpenoids and corresponding pathway transcripts supports a role in drought stress tolerance for these compounds.Significance statementWith an increasing demand for renewable energy opposed by rising climate-driven crop losses, understanding, and leveraging plant natural defenses can enable the development of sustainable crop production systems. Here, we integrated comparative transcriptomics and metabolomics analyses to gain a detailed understanding of the diversity and physiological relevance of specialized metabolites in upland and lowland switchgrass ecotypes and provide resources for future investigations of drought response mechanisms in switchgrass.
Scalable and model-free detection of spatial patterns and colocalization
Authors: Liu Qi , Hsu Chih-Yuan , Shyr Yu 
Published: May 2022

ABSTRACTThe expeditious growth in spatial omics technologies enable profiling genome-wide molecular events at molecular and single-cell resolution, highlighting a need for fast and reliable methods to characterize spatial patterns. We developed SpaGene, a model-free method to discover any spatial patterns rapidly in large scale spatial omics studies. Analyzing simulation and a variety of spatial resolved transcriptomics data demonstrated that SpaGene is more powerful and scalable than existing methods. Spatial expression patterns by SpaGene reconstructed unobserved tissue structures. SpaGene also successfully discovered ligand-receptor interactions through their colocalization.
Replicative ageing perturbs the metabolic signature of murine C2C12 skeletal myotubes
Authors: Sadler Daniel G. , Phelan Marie M , Barlow Jonathan , Draijer Richard , Jones Helen , Thijssen Dick H. J. , Stewart Claire E. 
Published: May 2022

AbstractIntroductionChronological ageing is associated with mitochondrial dysfunction and increased reactive oxygen species (ROS) production in skeletal muscle. However, the effects of replicative ageing on skeletal muscle cellular metabolism are not well known. Using an established myoblast model of cellular (replicative) ageing, we investigated the impact of ageing on energy metabolism in murine C2C12 myotubes.MethodsControl (P7-11) and replicatively ‘aged’ (P48-51) C2C12 myoblasts were differentiated over 72-120 h. Mitochondrial bioenergetics were investigated by respirometry and mitochondrial superoxide and cellular ROS were measured in the absence and presence of antimycin A (AA). Genes related to mitochondrial remodelling and the antioxidant response were quantified by RT-qPCR. Intracellular metabolites were quantified using an untargeted 1H-NMR metabolomics pipeline.ResultsMitochondrial coupling efficiency (Control: 79.5 vs. Aged: 70.3%, P=0.006) and relative oxidative ATP synthesis (Control: 48.6 vs. Aged: 31.7%, P=0.022) were higher in control vs. aged myotubes, but rates of mitochondrial superoxide production were lower (Control: 2.4×10−5 ± 0.4 × 10−5 vs. Aged: 9.7×10−5 ± 1.6×10−5 RFU/sec/cell; P=0.035). Replicatively aged myotubes had greater mRNA expression of mfn2 and Tfam compared to control. Yet, Nrf2 and PGC-1α expression were 2.8-fold and 3.0-fold higher in control versus aged myotubes over 24 h and 48 h (P<0.05), respectively. Branched chain amino acids L-leucine, L-isoleucine and L-valine, and L-carnitine were less abundant in aged versus control myotubes.Conclusion(s)Replicative ageing is associated with bioenergetic uncoupling, increased ROS production and impaired amino acid metabolism. Our findings suggest that cellular mitochondrial dysfunction and altered energy metabolism may exacerbate the age-related decline in skeletal muscle mass and function.
Radiologist observations of chest X-rays (CXR) predict sputum smear microscopy status in TB Portals, a real-world database of tuberculosis (TB) cases
Authors: Rosenfeld Gabriel , Gabrielian Andrei , Meyer Alyssa , Rosenthal Alex 
Published: May 2022

AbstractThe Tuberculosis (TB) Portals is an international program of 14 countries connecting clinical, genomic, and radiologist specialists to develop an openly available repository of deidentified TB cases with multi-modal data such as case clinical characteristics, pathogen genomics, and radiomics. This real-world data resource contains over 4000 TB cases, principally drug resistant cases, with over 4000 chest X-rays (CXR) images. The scope of curated data offers a case-focused perspective into the drivers of disease incorporating the chronological context of the presented CXR data. Here, we analyze a cohort consisting of new TB cases to understand the relationship between baseline sputum microscopy status and nearby Chest X rays images. The Timika score, a lung biomarker of disease severity, was derived for each CXR using available radiologist observations. The Timika score along with the radiologist observations were compared for predictive performance of baseline sputum microscopy status. Baseline sputum microscopy status is a useful marker of pre-treatment disease severity and infectiousness. The modeling results support that both the radiologist observations as well as Timika score are predictive of smear status and that Timika score performs similarly to the top 5 radiologist features by feature selection. Moreover, inferential statistical analysis identifies the factors having the greatest association with sputum smear positivity such as presence of radiologist observations in both lungs, presence of cavity, presence of nodule, and Timika score itself. The results are consistent with prior reports showing Timika Score utility for predicting baseline sputum smear and disease status. We report testing of Timika Score on the largest, openly available real-world dataset of TB cases that can serve as a reference to explore extant and new TB disease severity scores bridging radiological, microbiological, and clinical data. To illustrate, we visualize Timika score from images in our database with other cases characteristics demonstrating that this score captures lung biomarker status consistent with known clinical risk factors.
Trends in TSH, free T4, and anti-thyroid peroxidase and treatment status: Canadian Health Measures Survey 2012 to 2015
Authors: Chao Yi-Sheng 
Published: May 2022

AbstractBackgroundPrevious studies in Canada focused on the prevalence of thyroid conditions have not reported on the levels of the thyroid-stimulating hormone (TSH) and thyroid hormones. To address this issue, the present study describes the trends in TSH, free T4, and anti-thyroid peroxidase and their treatment status for the patients who have clinically high or low levels.MethodsWe used data from the Canadian Health Measures Survey (CHMS) cycles 3 and 4 conducted between 2012 and 2015. The thyroid measures studied were TSH, free T4, and anti-thyroid peroxidase. We used clinical reference ranges to identify abnormality in these measures. We labelled abnormality in these measures as treated if relevant conditions were diagnosed or a disease-specific prescription was reported. Untreated individuals were those with an abnormality in thyroid measures without any medication use or relevant diagnoses. We presented the trends of thyroid measures in mean values and ratios, compared to the values first measured.ResultsThe levels of TSH, free T4, and anti-peroxidase in cycle 4 were not significantly different from those in cycle 3. The proportions of Canadians with clinically high levels of free T4, anti-thyroid peroxidase, and TSH were 0.03 to 0.017, 0.005 to 0.005, and 0.30 to 0.43 for cycles 3 to 4, respectively. The proportions of Canadians with clinically low levels of TSH and free T4 were 0.02 to 0.021 and 0.18 to 0.11 for cycles 3 to 4, respectively. The change in the proportions of treatment statuses varied across the thyroid measures of the Canadians studied.ConclusionThis descriptive study demonstrates the trends in TSH, free T4, and anti-thyroid peroxidase; their distributions in the population; and the proportions of Canadians with clinically high or low levels. We believe the information on the treatment status of those with uncontrolled high levels can be used to design patient screening programs.
Population genomics of the island thrush elucidates one of earth’s great archipelagic radiations
Authors: Reeve Andrew Hart , Gower Graham , Pujolar José Martín , Smith Brian Tilston , Petersen Bent , Olsson Urban , Haryoko Tri , Koane Bonny , Maiah Gibson , Blom Mozes P. K. , Ericson Per G. P. , Irestedt Martin , Racimo Fernando , Jønsson Knud Andreas 
Published: May 2022

ABSTRACTTropical islands are renowned as natural laboratories for evolutionary study. Lineage radiations across tropical archipelagos are ideal systems for investigating how colonization, speciation, and extinction processes shape biodiversity patterns. The expansion of the island thrush across the Indo-Pacific represents one of the largest yet most perplexing island radiations of any songbird species. The island thrush exhibits a complex mosaic of pronounced plumage variation across its range, and is arguably the world’s most polytypic bird. It is a sedentary species largely restricted to mountain forests, yet it has colonized a vast island region spanning a quarter of the globe. We conducted comprehensive sampling of island thrush populations and obtained genome-wide SNP data, which we used to reconstruct its phylogeny, population structure, gene flow, and demographic history. The island thrush evolved from migratory Palearctic ancestors and radiated explosively across the Indo-Pacific during the Pleistocene, with numerous instances of gene flow between populations. Its bewildering plumage variation masks a biogeographically intuitive stepping stone colonization path from the Philippines through the Greater Sundas, Wallacea and New Guinea to Polynesia. The island thrush’s success in colonizing Indo-Pacific mountains can be understood in light of its ancestral mobility and adaptation to cool climates; however, shifts in elevational range, degree of plumage variation and apparent dispersal rates in the eastern part of its range raise further intriguing questions about its biology.
CLN7 mutation causes aberrant redistribution of protein isoforms and contributes to Batten disease pathobiology
Authors: Sharaireh Aseel M. , Guevara-Ferrer Marta , Herranz-Martin Saul , Garcia-Macia Marina , Phillips Alexander , Tierney Anna , Hughes Michael P , Coombe-Tennant Oliver , Nelvagel Hemanth , Burrows Alysha E. , Fielding Stuart , FitzPatrick Lorna M. , Thornton Christopher D. , Storch Stephan , Mole Sara E. , Dowsey Andrew , Unwin Richard , Bolanos Juan P. , Rahim Ahad A. , McKay Tristan R. 
Published: May 2022

AbstractThe variant late infantile form of the inherited neurodegenerative Batten disease (BD) is caused by mutations in the CLN7/MFSD8 gene and represents a strong candidate for gene therapy. Post-natal intracerebral administration of AAV9-hCLN7 toCln7Δex2knockout mice resulted in extended lifespan but dose escalation resulted in reduced acuity in neurophysiology tests, cerebral atrophy and elevated neuroinflammation. Comparing patient and control iPSC-derived neural progenitor cells (iNPC) we discovered that CLN7 localizes to the nucleus as well as the endolysosomal network and is differentially distributed in BD iNPC. Proteomics identified a profound nuclear defect in BD iNPC that compounds with mitochondrial and lysosomal metabolic defects resulting in elevated apoptosis. We further identified a 50kDa common nuclear CLN7 isoform and a 37kDa isoform that accumulates only in BD iNPC nuclei. Our findings suggest that successful treatment of CLN7 BD will require combinatorial therapies addressing both loss and aberrant gain of protein function.
Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers
Authors: Xie Yeming , Ruan Fengying , Li Yaning , Luo Meng , Zhang Chen , Chen Zhichao , Xie Zhe , Weng Zhe , Chen Weitian , Chen Wenfang , Fang Yitong , Sun Yuxin , Guo Mei , Wang Juan , Xu Shouping , Wang Hongqi , Tang Chong 
Published: May 2022

AbstractAs the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by capturing the epigenetic information in single-molecular resolution while simultaneously resolving the genome conformation. Using SCA-seq, we are able to examine the spatial interaction of chromatin accessibility (e.g. enhancer-promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus.
Antibody Responses In Non-Severe SARS-CoV-2 Infections Are Driven By CD4+ T cells and Age
Authors: Murrell Amelie E. , Eyoh Ewono , Shaffer Jeffrey G. , Dietrich Monika L. , Trinh Ivy V. , Yockachonis Thomas J. , Bai Shuangyi , Zheng Crystal Y. , Mayne Celia V. , Cabrera Sofia E. , Aviles-Amaro Anyssa , Stone Addison E. , Rambaran Saraswatie , Chandra Sruti , Elliott Debra H. , Smira Ashley R. , Harris Sara N. , Olson Katharine E. , Bilton Samantha J. , Gabriel Medea J. , Falgout Nicole D. , Engel Emily J. , Prystowsky Alisha D. , Ning Bo , Hu Tony , Kolls Jay K. , Landry Samuel J. , Drury Stacy S. , Schieffelin John S. , Zwezdaryk Kevin J. , Robinson James E. , Gunn Bronwyn M. , Norton Elizabeth B. 
Published: May 2022

SUMMARYSARS-CoV-2 infection causes a spectrum of clinical outcomes and diverse memory responses. Population studies indicate that viral neutralizing antibody responses are protective, but do not always develop post-infection. Other antiviral antibody effector functions, T-cell responses, or immunity to seasonal coronaviruses (OC43, 229E) have been implicated but not defined in all ages. Here, we identify that children and adult subjects generate polyfunctional antibodies to the spike protein after asymptomatic infection or mild disease, with some subjects developing cellular responses without seroconversion. Diversity in immunity was explained by two clusters distinguished by CD4+ T-cell cytokines, age, and antibodies to seasonal coronaviruses. Post-vaccination neutralizing responses were predicted by specific post-infection immune measures, including IL-2, spike-IgA, OC43-IgG1, 229E-IgM. We confirm a key role for CD4+ T cell cytokines in functionality of anti-spike antibodies, and show that antibody diversity is impacted by age, Th/Th2 cytokine biases, and antibody isotypes to SARS-CoV-2 and seasonal coronaviruses.
Strategies to investigate and mitigate collider bias in genetic and Mendelian randomization studies of disease progression
Authors: Mitchell Ruth E. , Hartley April , Walker Venexia M. , Gkatzionis Apostolos , Yarmolinsky James , Bell Joshua A. , Chong Amanda H. W. , Paternoster Lavinia , Tilling Kate , Smith George Davey 
Published: May 2022

AbstractGenetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors which influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as “index event”) bias since the disease progression phenotype can only be observed for individuals who have the disease. This applies equally to observational and genetic studies, including genome-wide association studies and Mendelian randomization analyses. In this paper, our aim is to review several statistical methods that can be used to detect and adjust for index event bias in studies of disease progression, and how they apply to genetic and Mendelian Randomization studies using both individual and summary-level data. Methods to detect the presence of index event bias include the use of negative controls, a comparison of associations between risk factors for incidence in individuals with and without the disease, and an inspection of Miami plots. Methods to adjust for the bias include inverse probability weighting (with individual-level data), or Slope-hunter and Dudbridge’s index event bias adjustment (when only summary-level data are available). We also outline two approaches for sensitivity analysis. We then illustrate how three methods to minimise bias can be used in practice with two applied examples. Our first example investigates the effects of blood lipid traits on mortality from coronary heart disease, whilst our second example investigates genetic associations with breast cancer mortality.