bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractal-Thermodynamic System Analogy and Complexity of Plant Leaves
Authors: Vishnu M , Jaishanker R 
Published: July 2022

AbstractMore precise measurements of the complexity of leaf shapes can open new pathways to understanding plant adaptation and resilience in the face of changing environments. We present a method to measure the complexity of plant leaf shapes by relating their fractal dimensions to topological entropy. Our method relies on ‘segmental fractal complexity’ and stems from a fractal-thermodynamic system analogy. The complexity of plant leaf shapes is an algebraic combination of the fractal dimensions of the components of the leaf-image system. We applied this method to leaf forms of 30 tropical plant species. While topological entropy is positively correlated with the leaf dissection index, it is an improvement over the leaf dissection index because of its ability to capture the spatial positioning of the leaf lamina, the leaf edges, and the leaf background. The topological entropy method is also an advancement over conventional geometric and fractal dimension-based measures of leaf complexity because it does not entail information loss due to the pre-processing and is perceptibly simple.
Differential transport of a guild of mutualistic root aphids by the ant Lasius flavus
Authors: Parmentier Thomas 
Published: July 2022

ABSTRACTMutually beneficial associations are widespread in ecological networks. They are typically assembled as multispecies guilds of symbionts that compete for one or more host species. The ant Lasius flavus engages in an intriguing and obligate mutualistic association with a community of aphids that are cultivated on plant roots in its nests. The ant displays a repertoire of amicable behaviours towards the aphids, including their transport. I examined whether L. flavus preferentially carried some of the root aphids. Using a no-choice and a choice experiment, I comparatively analysed the transport rate of five obligate and one loosely associated species back to the ant nest and used the transport rate of the ant larvae as a reference. All associated root aphids were carried back to the nest, but in a clear preferential hierarchy. Geoica utricularia, Forda Formicaria and Trama rara were rapidly transported, but slower than the own larvae. Tetraneura ulmi and Geoica setulosa were collected at a moderate rate and the loosely associated Aploneura lentisci was slowly retrieved. In contrast, different species of unassociated aphids were not transported and even provoked aggressive behaviour in L. flavus. This study revealed that co-occurring symbionts may induce different degrees of host attraction, which ultimately may affect the coexistence and assembly of ant-symbiont communities.
Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic pathways, Inflammation, and Atherosclerosis
Authors: Liu Huan , Hastings Margaret Hallauer , Kitchen Robert , Xiao Chunyang , Guerra Justin Ralph Baldovino , Kuznetsov Alexandra , Rosenzweig Anthony 
Published: July 2022

BACKGROUNDAtherosclerosis is an inflammatory vascular disease marked by hyperlipidemia and hematopoietic stem cell (HSC) expansion. Activin A, a member of the Activin/GDF/TGFβ/BMP family is broadly expressed and increases in human atherosclerosis, but its functional effects in vivo in this context remain unclear.METHODSWe studied LDLR-/- mice on a Western diet for 12 weeks and used adeno-associated viral vectors with a liver-specific thyroxine binding globulin (TBG) promoter to express Activin A or GFP (control). Atherosclerotic lesions were analyzed by oil red staining. Blood lipid profiling was performed by HPLC (High Performance Liquid Chromatography), and immune cells were evaluated by flow cytometry. Liver RNA-sequencing was performed to explore the underlying mechanisms.RESULTSActivin A expression decreased in both livers and aortae from LDLR-/- mice fed a Western diet compared with chow. AAV-TBG-Activin A increased Activin A hepatic expression (∼10-fold at 12-weeks, p<0.0001) and circulating Activin A levels (∼2000pg/ml vs ∼50pg/ml, p<0.001, compared with controls). Hepatic Activin A expression decreased plasma total and low-density lipoprotein (LDL) cholesterol (∼60% and ∼40%, respectively), reduced inflammatory cells in aortae and proliferating hematopoietic stem cells (HSC) in bone marrow, and reduced atherosclerotic lesion area in the aortic arch by ∼60%. Activin A also attenuated liver steatosis and expression of the lipogenesis genes, Srebp1 and Srebp2. RNA sequencing revealed Activin A not only blocked expression of genes involved in hepatic de novo lipogenesis but also fatty acid uptake, and liver inflammation. In addition, Activin A expressed in the liver also reduced white fat tissue accumulation, decreased adipocyte size, and improved glucose tolerance.CONCLUSIONSOur studies reveal hepatic Activin A expression reduces inflammation, HSC expansion, liver steatosis, circulating cholesterol, and fat accumulation, which likely all contribute to the observed protection against atherosclerosis. The reduced Activin A observed in LDLR-/- mice on a Western diet appears maladaptive and deleterious for atherogenesis.
A Buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72h in mouse femoral fracture models
Authors: Wolter Angelique , Bucher Christian H. , Kurmies Sebastian , Schreiner Viktoria , Konietschke Frank , Hohlbaum Katharina , Klopfleisch Robert , Löhning Max , Thöne-Reineke Christa , Buttgereit Frank , Huwyler Jörg , Jirkof Paulin , Rapp Anna E. , Lang Annemarie 
Published: July 2022

AbstractAdequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as an alternative product within Europe. Pharmacokinetics indicate a potential effectiveness for about 72h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse femoral fracture models and could therefore serve as a potent alternative to the application of Tramadol via drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72h, comparable to the effectiveness of Tramadol in drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for laboratory animals in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare.
Outline and divergence time of subkingdom Mucoromyceta: two new phyla, five new orders, six new families and seventy-three new species
Authors: Zhao Heng , Dai Yu-Cheng , Liu Xiao-Yong 
Published: July 2022

AbstractZygomycetes are phylogenetically early diverged, ecologically diverse, industrially valuable, agriculturally beneficial, and clinically pathogenic fungi. Although new phyla and subphyla have been constantly established to accommodate specific members and a subkingdom, Mucoromyceta, was erected to unite core zygomycetous fungi, their phylogenetic relationships have not been well resolved. Taking account of the information of monophyly and divergence time estimated from ITS and LSU rDNA sequences, the present study updates the classification framework of the subkingdom Mucoromyceta from the phylum down to the generic rank: six phyla (including two new phyla Endogonomycota and Umbelopsidomycota), eight classes, 15 orders (including five new orders Claroideoglomerales, Cunninghamellales, Lentamycetales, Phycomycetales and Syncephalastrales), 41 families (including six new families Circinellaceae, Gongronellaceae, Protomycocladaceae, Rhizomucoraceae, Syzygitaceae and Thermomucoraceae), and 121 genera. The taxonomic hierarchy was calibrated with estimated divergence times: phyla 810–639 Mya, classes 651–585 Mya, orders 570–400 Mya, and families 488–107 Mya. Along with this outline, 71 genera are annotated and 73 new species are described. In addition, three new combinations are proposed. In this paper, we update the taxonomic backbone of the subkingdom Mucoromyceta and reinforce its phylogeny. We also contribute numerous new taxa and enrich the diversity of Mucoromyceta.
Clinical utility of fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis
Authors: Hazan Jemma , Wing Michelle , Liu Kathy , Reeves Suzanne , Howard Robert 
Published: July 2022

AbstractBackgroundThe analytical and clinical validity of fluid biomarkers, measured typically in cerebrospinal (CSF) serum or plasma, has been extensively researched in dementia. Further work is needed to assess the ability of these biomarkers to improve diagnosis, management, and health outcomes in the clinical settingObjectivesTo assess the added value and clinical utility of fluid biomarkers in the diagnostic assessment of cognitively impaired patients under evaluation for Alzheimer’s disease (AD).MethodsSystematic literature searches of Medline, EMBASE, PsycINFO, Web of Science research databases were conducted on 17th December 2022. Data from relevant studies were extracted and independently screened for quality using a tool for bias. Clinical utility was measured by clinicians’ changes in diagnosis, diagnostic confidence, and patient management (when available), after their examination of patients’ fluid biomarkers. Cost-effectiveness was assessed by consideration of additional cost per patient and quality-adjusted life years (QALY).ResultsSearches identified 18 studies comprising 2199 patient participants and 599 clinicians. The meta-analysis revealed that clinicians’ use of fluid biomarkers resulted in a pooled percentage change in diagnosis of 25% (95% CI: 14–37), an increase in diagnostic confidence of 14% (95% CI: 9–18) and a pooled proportion of patients whose management changed of 31% (95% CI 12–50). CSF biomarkers were deemed cost effective, particularly in memory services, where pre-test AD prevalence is higher compared to a primary care setting.ConclusionsFluid biomarkers can be a helpful additional diagnostic tool for clinicians assessing patients with cognitive impairment. In particular, CSF biomarkers consistently improved clinicians’ confidence in diagnosing AD and influenced on diagnostic change and patient management. Further research is needed to study the clinical utility of blood-based biomarkers in the clinical setting.
Cross-sectional evolution of pain management policies and practices in Portuguese pediatric emergency departments
Authors: Garrido André , Manuel Ana Rute , Araújo Ricardo , Mascarenhas Inês , Almeida Helena , Abadesso Clara 
Published: July 2022

ABSTRACTThe prevalence of pediatric pain, either related to the child’s hospital visit or as a result of diagnostic and/or therapeutical interventions, is of primordial importance in pediatric emergency departments (PEDs).In this study, we evaluate the evolution of pain assessment and management in Portuguese PEDs through eleven years. To this end, we prepared a questionnaire addressed to head physicians of 45 the Portuguese PEDs in 2007 and compared the responses to those provided in 2018, where we also posed these questions to nurse managers.Pain assessment in Portuguese PEDs has significantly improved, namely with establishment of local protocols and widespread use of pain scales. However, effective adoption of pain management remains insufficient, as mild to moderate pain is still far from being universally treated. Nonetheless, there seems to be an adequate treatment of severe pain and respective common use of opioids, but correct practices were not generally adopted when specific types of pain were analyzed. Procedural sedation and use of non-pharmacological techniques has significantly increased, but are not yet universally practiced. These inadequacies are reflected by the staff’s perception that pain management remains suboptimal, and more training is needed, effectively urging for a nationwide plan and better knowledge translation of correct pediatric pain management.
Chemotherapy use and outcomes in patients with stage III or IV small-cell lung cancer in relation to age: An analysis of the English Systemic Anti-Cancer Treatment (SACT) dataset
Authors: Pilleron S. , Morris EJA. , Dodwell D. , Franks K.N. 
Published: July 2022

AbstractIntroductionSurvival from small cell lung cancer (SCLC) is poor and there has been little progress in treatment. There is little evidence on outcomes in patients aged 75+. We described patterns of chemotherapy use and outcomes using the national Systemic Anti-Cancer Treatment dataset in patients with stage III or IV SCLC in relation to age.MethodWe included 7,966 SCLC (67.6% stage IV) diagnosed between 2014-17 in England, treated with chemotherapy and followed up through 2017. Patterns of chemotherapy use, 30- and 90-mortality rates, 6-,12-month and median overall survival (OS) from the start of the first chemotherapy cycle were compared between those below and above the age of 75. OS was estimated using Kaplan Meier estimator and modeled using a flexible hazard regression model.ResultsOlder patients were 6-7 times less likely to receive curative treatment than younger patients regardless of stage. There were more frequent adjustments of treatment and dose reduction (stage III) in older than younger patients but no age-related differences in reduction of doses (stage IV), treatment delayed or stopped earlier than planned. Although 30-day mortality rates were similar across age groups in stage III SCLC (∼4%), older patients had higher early mortality and poorer OS than younger peers. In both stages, 6 and 12-month OS by age decreased around the age of 70-75 and were worse in patients with performance status scores ≥2.ConclusionThis study offers a snapshot of chemotherapy use and outcomes in advanced SCLC, notably in older patients, in the pre-immunotherapy era.
A systematic review of dengue outbreak prediction models: current scenario and future directions
Authors: Leung Xing Yu , Islam Rakibul M. , Adhami Mohammadmehdi , Ilic Dragan , McDonald Lara , Palawaththa Shanika , Diug Basia , Munshi Saif U. , Karim M.D. Nazmul 
Published: July 2022

AbstractDengue is among the fastest-spreading vector-borne infectious disease, with outbreaks often overwhelm the health system and result in huge morbidity and mortality in its endemic populations in the absence of an efficient warning system. A large number of prediction models are currently in use globally. As such, this study aimed to systematically review the published literature that used quantitative models to predict dengue outbreaks and provide insights about the current practices. A systematic search was undertaken, using the Ovid MEDLINE, EMBASE, Scopus and Web of Science databases for published citations, without time or geographical restrictions. Study selection, data extraction and management process were devised in accordance with the ‘Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies’ (‘CHARMS’) framework. A total of 78 models were included in the review from 51 studies. Most models sourced climate (89.7%) and climate change (82.4%) data from agency reports and only 59.0% of the models adjusted for reporting time lag. All included models used climate predictors; 65.4% of them were built with only climate factors. Climate factors were used in combination with climate change factors (10.3%), both climate change and demographic factors (10.3%), vector factors (5.1%), and demographic factors (5.1%). Machine learning techniques were used for 38.5% of the models. Of these, random forest (20.0%), neural networks (23.3%) and ensemble models (13.3%) were notable. Among the statistical (61.5%) models, linear regression (20.8%), Poisson regression (18.8%), generalized additive models (16.7%) and time series/autoregressive models (18.8%) were notable. Around 24.4% of the models reported no validation at all and only 6.4% reported external validation. The reporting of methodology and model performance measures were inadequate in many of the existing prediction models. This review collates plausible predictors and methodological approaches, which will contribute to robust modelling in diverse settings and populations.
Fromcereusto anthrax and back again: The role of the PlcR regulator in the “cross-over” strainBacillus cereusG9241
Authors: Manoharan Shathviga , Taylor-Joyce Grace , Brooker Thomas A. , Hernandez-Rodriguez Carmen Sara , Hapeshi Alexia , Baldwin Victoria , Baillie Les , Oyston Petra C. F. , Waterfield Nicholas R. 
Published: July 2022

ABSTRACTBacillus cereusG9241 was isolated from a Louisiana welder suffering from an anthrax-like infection. The organism carries two transcriptional regulators that have previously been proposed to be incompatible with each other: the pleiotropic transcriptional regulator PlcR found in most members of theBacillus cereusgroup but truncated in allBacillus anthracisisolates, and the anthrax toxin regulator AtxA found in allB. anthracisstrains and a fewB. cereussensu stricto strains. Here we report cytotoxic and haemolytic activity of cell freeB. cereusG9241 culture supernatants cultured at 25 °C to various eukaryotic cells. However, this is not observed at the mammalian infection relevant temperature 37 °C, behaving much like the supernatants generated byB. anthracis. Using a combination of genetic and proteomic approaches to understand this unique phenotype, we identified several PlcR-regulated toxins to be secreted highly at 25 °C compared to 37 °C. Furthermore, we demonstrate that differential expression of the protease involved in processing the PlcR quorum sensing activator molecule PapR appears to be the limiting step for the production of PlcR-regulated toxins at 37 °C, giving rise to the temperature-dependent haemolytic and cytotoxic activity of the culture supernatants. This study provides an insight on howB. cereusG9241 is able to ‘switch’ betweenB. cereusandB. anthracis–like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.
An integrated ‘omics approach highlights the role of epigenetic events to explain and predict response to neoadjuvant chemotherapy and bevacizumab
Authors: Fleischer Thomas , Haugen Mads Haugland , Ankill Jørgen , Silwal-Pandit Laxmi , Børresen-Dale Anne-Lise , Hedenfalk Ingrid , Hatschek Thomas , Tost Jörg , Engebraaten Olav , Kristensen Vessela N. 
Published: July 2022

AbstractHere we present an integrated ‘omics approach for DNA methylation profiling using copy number alteration, gene expression and proteomic data to predict response to therapy and to pinpoint response-related epigenetic events. Fresh frozen tumor biopsies taken before, during and after treatment from patients receiving neoadjuvant chemotherapy with or without the anti-angiogenic drug bevacizumab were subjected to molecular profiling. Our previous studies have shown that administration of bevacizumab in addition to chemotherapy (combination treatment) may confer improved response for patients; here we report that DNA methylation at enhancer CpGs related to cell cycle regulation can predict response to chemotherapy and bevacizumab for ER positive patients with high fidelity (AUC=0.874), and we validate this observation in an independent patient cohort with similar treatment regimen (AUC=0.762). When combining the DNA methylation score with a previously reported proteomic score (ViRP), the prediction accuracy further improved in the validation cohort (AUC=0.784). We also show that tumors receiving the combination treatment underwent more extensive epigenetic alterations than tumors receiving only chemotherapy. Finally, we performed an integrative emQTL analysis on alterations in DNA methylation and gene expression levels, showing that the epigenetic alterations that occur during treatment are different between responders and non-responders and that these differences may be explained by the proliferation-EMT axis through the activity of the transcription factor GRHL2. Taken together, these results illustrate the clinical benefit of the addition of bevacizumab to chemotherapy if administered to the correct patients.
Diversity and task-dependence of task representations in V1 during freely-moving decisions
Authors: Zhang Anqi , Zador Anthony M. 
Published: July 2022

AbstractNeurons in primary visual cortex (area V1) are strongly driven by both sensory stimuli and non-sensory events. However, although the representation of sensory stimuli has been well characterized, much less is known about the representation of non-sensory events. Here, we characterize the specificity and organization of non-sensory representations in rat V1 during a freely-moving visual decision task. We find that single neurons encode diverse combinations of task features simultaneously and across task epochs. Despite heterogeneity at the level of single neuron response patterns, both visual and non-visual task variables could be reliably decoded from small neural populations (5-40 units) throughout a trial. Interestingly, in animals trained to make an auditory decision following passive observation of a visual stimulus, some but not all task features could also be decoded from V1 activity. Our results support the view that even in V1— the earliest stage of the cortical hierarchy—bottom-up sensory information is combined with top-down non-sensory information in a task-dependent manner.
XDec Simplex Map of Breast Cancer Cell States Enables Precise Modeling and Targeting of Breast Cancer
Authors: Murillo Oscar D. , Petrosyan Varduhi , LaPlante Emily L. , Dobrolecki Lacey E. , Lewis Michael T. , Milosavljevic Aleksandar 
Published: July 2022

SUMMARYThe characterization of cancer cell states within the tumor microenvironment is a key to understanding tumor biology and an important step toward the development of precision therapies. To reconstruct this information from bulk RNA-seq profiles, we developed the XDec Simplex Mapping (XDec-SM) approach, a reference-optional deconvolution method that leverages single-cell information, when such information is available, to map tumors and the states of constituent cells onto a biologically interpretable, low-dimensional space. When applied to breast tumors in The Cancer Genome Atlas (TCGA), XDec-SM infers the identity of constituent cell types and their proportions. XDec-SM also infers cancer cells states within individual tumors that associate with DNA methylation patterns, driver somatic mutations, pathway activation and metabolic coupling between stromal and breast cancer cells. By projecting tumors, cancer cell lines, and PDX models onto the same map, we identify both in vitro and in vivo models with matching cancer cell states. Map position is also predictive of therapy response, thus opening the prospects for precision therapy informed by experiments in model systems matched to tumors in vivo by cancer cell state.