bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia
Authors: Cohen Emily B. , Geck Renee C. , Toker Alex 
Published: April 2020

AbstractThe vasculature within a tumor is highly disordered both structurally and functionally. Endothelial cells that comprise the vasculature are poorly connected causing vessels to be leaky and exposing the endothelium to a hypoxic microenvironment. Therefore, most anti-angiogenic therapies are generally inefficient and result in acquired resistance to increased hypoxia due to elimination of the vasculature. Recent studies have explored the efficacy of targeting metabolic pathways in tumor cells in combination with anti-angiogenic therapy. However, the metabolic alterations of endothelial cells in response to hypoxia has been relatively unexplored. Here, we measured polar metabolite levels in microvascular endothelial cells exposed to short- and long-term hypoxia with the goal of identifying metabolic vulnerabilities that can be targeted to normalize tumor vasculature and improve drug delivery. Many amino acid-related metabolites were altered by hypoxia exposure, especially within alanine-aspartate-glutamate, serine-threonine, and cysteine-methionine metabolism. Additionally, there were significant changes inde novopyrimidine synthesis as well as glutathione and taurine metabolism. These results provide key insights into the metabolic alterations that occur in endothelial cells in response to hypoxia, which serve as a foundation for future studies to develop therapies that lead to vessel normalization and more efficient drug delivery.
Assessments of hepatitis B virus-like particles and Crm197 as carrier proteins in melioidosis glycoconjugate vaccines
Authors: Bayliss Marc , Donaldson Matthew I. , Pergolizzi Giulia , Scott Andrew E. , Nepogodiev Sergey A. , Beales Lucy , Whelan Michael , Rosenberg William , Peyret Hadrien , Lomonossoff George P. , Harmer Nicholas J. , Atkins Tim , Field Robert A. , Prior Joann L. 
Published: April 2020

AbstractThe Tier 1 select agentBurkholderia pseudomalleiis the causative agent of melioidosis, a global pathogen and a major cause of pneumonia and sepsis for which no licensed vaccines currently exist. Previous work has shown the potential forBurkholderiacapsular polysaccharide (CPS) to be used as a vaccine antigen but the T-cell independent nature of the immune response to this molecule requires the use of this polysaccharide as a glycoconjugate for vaccination. Recent studies have focussed on the use of Crm197 (a non-toxic mutant protein derived from diphtheria toxin) as the carrier but there are concerns regarding its potential to cause interference with other vaccines containing Crm197. Therefore research with alternative carrier proteins would be beneficial. In this study, CPS was isolated from the non-pathogenicB. thailandensisstrain E555. This was chemically conjugated to Crm197, or Tandem Core™ virus-like particles (TCVLP) consisting of hepatitis B core protein, which is the first documented use of VLPs in melioidosis vaccine development. Analysis of CPS-specific IgG antibody titres showed that mice vaccinated with the Crm197 conjugate generated significantly higher titres than the mice that received TCVLP-CPS but both conjugate vaccines were able to protect mice against intraperitonealB. pseudomalleistrain K96243 challenges of multiple median lethal doses.
Complete representation of a tapeworm genome reveals chromosomes capped by centromeres, necessitating a dual role in segregation and protection
Authors: Olson Peter D. , Tracey Alan , Baillie Andrew , James Katherine , Doyle Stephen R. , Buddenborg Sarah K. , Rodgers Faye H. , Holroyd Nancy , Berriman Matt 
Published: April 2020

AbstractBackgroundChromosome-level assemblies are indispensable for accurate gene prediction, synteny assessment and understanding higher-order genome architecture. Reference and draft genomes of key helminth species have been published but little is yet known about the biology of their chromosomes. Here we present the complete genome of the tapewormHymenolepis microstoma,providing a reference-quality, end-to-end assembly that represents the first fully assembled genome of a spiralian/lophotrochozoan, revealing new insights into chromosome evolution.ResultsLong-read sequencing and optical mapping data were added to previous short-read data enabling complete re-assembly into six chromosomes, consistent with karyology. Small genome size (169 Mb) and lack of haploid variation (1 SNP/3.2 Mb) contributed to exceptionally high contiguity with only 85 gaps remaining in regions of low complexity sequence. Resolution of repeat regions reveals novel gene expansions, micro-exon genes, and spliced leader transsplicing, and illuminates the landscape of transposable elements, explaining observed length differences in sister chromatids. Syntenic comparison with other parasitic flatworms shows conserved ancestral linkage groups indicating that theH. microstomakaryotype evolved through fusion events. Strikingly, the assembly reveals that the chromosomes terminate in centromeric arrays, indicating that these motifs play a role not only in segregation, but also in protecting the linear integrity and full lengths of chromosomes.ConclusionsDespite strong conservation of canonical telomeres, our results show that they can be substituted by more complex, species-specific sequences, as represented by centromeres. The assembly provides a robust platform for investigations that require complete genome representation.
Targeted Eicosanoid Profiling Reveals MicroRNA-155 Shifts PGE2/PGD2 Balance Towards Oncogenic State
Authors: Kim Sinae , Lee Eun Sung , Lee Eun ji , Jung Jae Yun , Lee Sae Byul , Lee Hee Jin , Kim Jisun , Kim Hee Jung , Lee Jong Won , Son Byung Ho , Gong Gyungyub , Ahn Sei Hyun , Chang Suhwan 
Published: April 2020

ABSTRACTmicroRNA-155 is a strong oncogenic microRNAs with multiple functions. To reveal its novel function in cancer metabolism, we performed a targeted metabolomic analysis of icosanoids, the key metabolites of inflammation-related carcinogenesis. We found miR-155-depleted cells expressed unbalanced prostaglandins, especially in PGE2 and PGD2. Subsequent analysis of primary cancer cells and 20 TNBC specimen indicated a positive correlation between miR-155 and PGE2/PGD2 ratio. Mechanistically, miR-155 controls the prostaglandin shift by up-regulating PGE2-producing enzymes PTGES/PTGES2 and down-regulating PGD2-producing enzyme PTGDS. Further analysis showed that the up-regulation ofPTGES2is driven by miR-155-cMYC axis whereasPTGESis transactivated by miR-155-KLF4 axis, indicating a dual-regulatory mode for the metabolic enzyme expression drives a shift in PGE2/PGD2 balance. Lastly, we show the miR-155-driven cellular proliferation is significantly restored by the siRNA of PTGES1/2, of which expression also correlates with patients’ survival. Taken altogether, our study reveals an unprecedented oncogenic function of miR-155 on prostaglandin regulation.
Clathrin adaptor AP-1 and Stratum act in parallel pathways to control Notch activation inDrosophilaSensory Organ Precursor Cells
Authors: Bellec Karen , Pinot Mathieu , Gicquel Isabelle , Le Borgne Roland 
Published: April 2020

AbstractDrosophilasensory organ precursors divide asymmetrically to generate pIIa/pIIb cells whose identity relies on the differential activation of Notch at cytokinesis. While Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, only the basal pool of Notch is reported to contribute to Notch activation in the pIIa cell. Correct intra-lineage signalling requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We previously reported that AP-1 and Stratum regulate the intracellular trafficking of Notch and Sanpodo from thetrans-Golgi network to the basolateral membrane. Loss of AP-1 or Stratum caused mildNotchgain-of-function phenotypes. Here, we report that the concomitant loss of AP-1 and Stratum results in a much more penetrantNotchgain-of-function phenotype indicating that AP-1 and Strat control two parallel pathways. While unequal partitioning of cell fate determinants and cell polarity were unaffected, Numb-mediated symmetry breaking is impaired. We further observed increased amounts of signaling competent Notch as well as Delta and Sanpodo at the apical pIIa-pIIb interface and the loss of the basal pool of Notch. We propose that AP-1 and Stratum operate in two parallel pathways to ensure the correct apico-basal localization of Notch controlling where receptor activation takes place.
Requirement of DNMT1 to orchestrate epigenomic reprogramming during NPM-ALK driven T cell lymphomagenesis
Authors: Redl Elisa , Sheibani-Tezerji Raheleh , Hamminger Patricia , Timelthaler Gerald , Hassler Melanie Rosalia , Lagger Sabine , Dillinger Thomas , Hofbauer Lorena , Zrimšek Maša , Tiefenbacher Andreas , Kothmayer Michael , Dietz Charles H. , Ramsahoye Bernard H. , Kenner Lukas , Bock Christoph , Seiser Christian , Ellmeier Wilfried , Schweikert Gabriele , Egger Gerda 
Published: April 2020

ABSTRACTMalignant transformation depends on genetic and epigenetic events that result in a burst of deregulated gene expression and chromatin changes. To dissect the sequence of events in this process, we used a T cell-specific lymphoma model based on the human oncogenic NPM-ALK translocation. We find that transformation of T cells shifts thymic cell populations to an undifferentiated immunophenotype, which occurs only after a period of latency, accompanied by induction of the MYC-NOTCH1 axis and deregulation of key epigenetic enzymes. We discover aberrant DNA methylation patterns, overlapping with regulatory regions, plus a high degree of epigenetic heterogeneity between individual tumors. In addition, ALK positive tumors show a loss of collaborative methylation patterns of neighboring CpG sites. Notably, deletion of the maintenance DNA methyltransferase DNMT1 completely abrogates lymphomagenesis in this model, despite oncogenic signaling through NPM-ALK, suggesting that faithful maintenance of tumor-specific methylation through DNMT1 is essential for sustained proliferation and tumorigenesis.STATEMENT OF SIGNIFICANCEEpigenetic alterations are causally involved in tumorigenesis. Here we show that induction of a single human oncogene in murine T cells induces specific deregulation of epigenetic enzymes resulting in epigenomic alterations similar to human tumors. Our findings are of broader implication to understand how epigenomic processes are shaped by oncogene induced transformation.
Numerical analysis of dynamic properties of wrinkled thin membranes
Authors: Wang Xiaofeng , Chu Haoyue , Yang Qingshan 
Published: April 2020

Purpose
This paper aims to numerically study the effects of boundary conditions, pre-stress, material constants and thickness on the dynamic performance of a wrinkled thin membrane.

Design/methodology/approach
Based on the stability theory of plates and shells, the dynamic equations of a wrinkled thin membrane were developed, and they were solved with the Lanczos method

Findings
The effects of wrinkle-influencing factors on the dynamic performance of a wrinkled membrane are determined by the wrinkling stage. The effects are prominent when wrinkling deformation is evolving, but they are very small and can hardly be observed when wrinkling deformation is stable. Mode shapes of a wrinkled membrane are sensitive to boundary conditions, pre-stress and Poisson’s ratio, but its natural frequencies are sensitive to all these five factors.

Practical implications
The research work in this paper is expected to help understand the dynamic behavior of a wrinkled membrane and present access to ensuring its dynamic stability by controlling the wrinkle-influencing factors.

Originality/value
Very few documents investigated the dynamic properties of wrinkled membranes. No attention has yet been paid by the present literature to the global dynamic performance of a wrinkled membrane under the influences of the factors that play a pivotal role in the wrinkling deformation. In view of this, this paper numerically studied the global modes and corresponding frequencies of a wrinkled membrane and their variation with the wrinkle-influencing factors. The results indicate that the global dynamic properties of a wrinkled membrane are sensitive to these factors at the stage of wrinkling evolution.
Packaging strategies: knowledge outlook on consumer buying behaviour
Authors: Rambabu Lavuri , Porika Ramlal 
Published: April 2020

PurposePackaging is a mantra for encountering a period of immense potential. It keeps on being seen as a key component in the buying decision, and also it is exhibited as a brand communication gadget that goes past the products and can interface with customers in both the physical and virtual forms. The research aspiration is to establish that the speculation of packaging approaches will influence on buyers’ purchasing mode. An attempt has been made to examine and present the results. This research facilitates to discern the perception of consumer in the direction of packaging strategies and to spot the power of packaging factors, elements and strategies of product packaging on purchasing mode of buyers.Design/methodology/approachData were collected from 836 respondents from the four major cities of two states in India through structure questionnaire. Every age of the respondents was targeted in the this study to get their perception and buying mode of them, and the analysis was done by using analysis of variance, correlation and regression analysis by using 23.0 version of SPSS.FindingsThe consequence of research reveals that media exposures, packaging strategies and elements have better influence on the buyers’ buying mode. Business people must produce innovative bundling designs for their items to market. These allow the keeping and catching the new and existed customers, because packaging has superior influence and also helps in acquiring and retaining the new consumers for their new products.Research limitations/implicationsThis study being at micro level considered that the city customers may not be similar to the rural customers. Hence, the perception of rural and urban may not be much different. A sample size is 836 drawn from the four major cities of two states in India; therefore, the sample may not represent the whole population of India. Hence, the limitation of generalization will be there. The elicited opinion of consumers may not be reliable all the times, and study considered only some of FMCG products.Originality/valueThe study theme is to establish the theory as stated earlier, and it's proved consumers are considering the packaging styles and designs while purchasing the products, which promotes to meet the expectations of the present and potential customers.
Changes in climate and land use interact to create an ecological trap in a migratory species
Authors: Buderman Frances E. , Devries Jim H. , Koons David N. 
Published: April 2020

AbstractAnthropogenic landscape alteration and climate change can have multiscale and interrelated effects on ecological systems. Such changes to the environment can disrupt the connection between habitat quality and the cues that species use to identify quality habitat, which can result in an ecological trap. Ecological traps are typically difficult to identify without fine‐scale information on individual survival and fitness, but this information is rarely available over large temporal and spatial scales.The Prairie Pothole Region (PPR) of the United States and Canada has undergone extensive changes in the latter half of the 20th century due to advancements in agricultural technologies, water management practices and climate change. Historically, the PPR has been a highly productive area for breeding waterfowl. While the overall trends for dabbling ducks in the PPR have exhibited increasing abundances since the late 1980s, some species, such as the northern pintail, have been declining in abundance.We used a long‐term dataset of pintail counts across the PPR to separate count data into a demographic process and a habitat selection process using a hierarchical model. The hierarchical model provided an alternative way of identifying ecological traps in the absence of individual survival and fitness. Our model also allowed us to account for the indirect pathways by which climate and agriculture impact pintail through their additional contribution to wetland availability, which is a primary driver of pintail demography and habitat selection.Decoupling these processes allowed us to identify an ecological trap related to increasing cropland land cover, in which pintail selected for cropland over alternative nesting habitat, likely due to the similarities with productive native mixed‐grass prairie. However, large proportions of cropland within a region resulted in fewer pintail the following year, likely due to nest failures from predation and agricultural practices. In addition, we identified several regions in Canada where this ecological trap is contributing significantly to mismatches between habitat selection and demographic processes.
Pleurisy and pulmonary embolism: physician sees through patient eyes
Authors: Cochrane Belinda 
Published: April 2020

AbstractAs a respiratory physician personally affected by pulmonary thromboembolism, I bring a unique perspective to managing this condition. It has made me realise that sometimes we do not see in detail the ways our colleagues practise, even working alongside them, although general management principles are the same. While banned from work, but permitted ‘as much paperwork as I like’ (the sole compromise that would ensure this patient's adherence), I sought to learn from my time as patient, hoping that other clinicians might gain from my experience in both roles. When it came to deciding which insights would be most useful to impart for the benefit of our patients, the leading concepts were not novel but important to emphasise in our current medical world, which prioritises both efficiency and quality of patient care.
Comorbidity phenotypes and risk of mortality in patients with ischaemic heart disease in the UK
Authors: Crowe Francesca , Zemedikun Dawit T , Okoth Kelvin , Adderley Nicola Jaime , Rudge Gavin , Sheldon Mark , Nirantharakumar Krishnarajah , Marshall Tom 
Published: April 2020

ObjectivesThe objective of this study is to use latent class analysis of up to 20 comorbidities in patients with a diagnosis of ischaemic heart disease (IHD) to identify clusters of comorbidities and to examine the associations between these clusters and mortality.MethodsLongitudinal analysis of electronic health records in the health improvement network (THIN), a UK primary care database including 92 186 men and women aged ≥18 years with IHD and a median of 2 (IQR 1–3) comorbidities.ResultsLatent class analysis revealed five clusters with half categorised as a low-burden comorbidity group. After a median follow-up of 3.2 (IQR 1.4–5.8) years, 17 645 patients died. Compared with the low-burden comorbidity group, two groups of patients with a high-burden of comorbidities had the highest adjusted HR for mortality: those with vascular and musculoskeletal conditions, HR 2.38 (95% CI 2.28 to 2.49) and those with respiratory and musculoskeletal conditions, HR 2.62 (95% CI 2.45 to 2.79). Hazards of mortality in two other groups of patients characterised by cardiometabolic and mental health comorbidities were also higher than the low-burden comorbidity group; HR 1.46 (95% CI 1.39 to 1.52) and 1.55 (95% CI 1.46 to 1.64), respectively.ConclusionsThis analysis has identified five distinct comorbidity clusters in patients with IHD that were differentially associated with risk of mortality. These analyses should be replicated in other large datasets, and this may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters.
Influence of postexercise fasting on hunger and satiety in adults
Authors: Hamilton Courteney C. , Wiseman Steve B. , Copeland Jennifer L. , Bomhof Marc R. 
Published: April 2020

Research demonstrates that exercise acutely reduces appetite by stimulating the secretion of gut-derived satiety hormones. Currently there is a paucity of research examining the impact of postexercise nutrient intake on appetite regulation. The objective of this study was to examine how postexercise fasting versus feeding impacts the postexercise appetite response. In a randomized crossover intervention, 14 participants (body mass index: 26.9 ± 3.5 kg·m−2; age: 26.8 ± 6.7 years) received 1 of 2 recovery beverages: (i) water control (FAST) or (ii) sweetened-milk (FED) after completing a 45-min (65%–70% peak oxygen uptake) evening exercise session (∼1900 h). Energy intake was assessed through a fasted ad libitum breakfast meal and 3-day food diaries. Perceived appetite was assessed using visual analogue scales. Appetite-regulating hormones glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and acyl-ghrelin were assessed pre-exercise, 1 h after exercise, and the morning following exercise. FAST increased subjective hunger compared with FED (P < 0.05). PYY and GLP-1 after exercise were decreased and acyl-ghrelin was increased in FAST, with these differences disappearing the day after exercise (P < 0.05). Ad libitum energy intake at breakfast the following morning did not differ between trials. Overall, in the absence of postexercise macronutrient consumption, there was a pronounced increase in objective and subjective appetite after exercise. The orexigenic effects of postexercise fasting, however, were not observed the morning following exercise. Novelty Postexercise fasting leads to reduced GLP-1 and PYY and increased hunger. Reduced GLP-1 and PYY after exercise is blunted by postexercise nutrient intake. Energy intake the day after exercise is not influenced by postexercise fasting.
A case report with a literature review: cerebral meningioma diagnosed by convulsion and consciousness disorder on initiating hemodialysis
Authors: Uwatoko Miki , Tokunaga Koki , Kawano Mako , Kamimura Masahisa , Ibi Yutaro , Otsuka Masayuki , Minami Masato , Yoshimine Haruhito , Hamada Fujio , Ido Akio 
Published: April 2020

Abstract
Background
Neurological symptoms sometimes occur in hemodialysis patients, with causes including cerebral infarction, cerebral hemorrhaging, meningitis, and encephalitis. Dialysis disequilibrium syndrome (DDS) is widely known as a complication of hemodialysis and is typically encountered in severe uremic patients newly started on hemodialysis. The pathogenesis of DDS is thought to be brain edema that manifests as neurological symptoms, including headache, nausea, confusion, seizures, and coma. However, the relationship between brain tumors and neurological manifestations during hemodialysis is poorly understood.

Case presentation
The patient was a 55-year-old man with severe renal dysfunction and uremia symptoms. Blood chemistry showed severe azotemia and acidosis. The patient was placed on short-duration hemodialysis (2 h) with a relatively small surface area, low blood flow (100 mL/min), and intradialytic glycerol infusion to prevent DDS. However, after his first hemodialysis treatment, he complained of disturbed consciousness. We diagnosed his neurological condition as DDS and observed the progress carefully. The next morning, his symptoms had completely resolved, so the patient was started on his second hemodialysis session with the same conditions. However, 2 h after starting the second hemodialysis session, he suffered convulsions accompanied by impaired consciousness. Brain computed tomography (CT) revealed a convexity meningioma and cerebral edema with a midline shift. Before starting the hemodialysis, he had shown no history of seizures, morning headache, or other neurological symptoms. In this case, meningioma was diagnosed based on an increase in the intracranial pressure which occurred after the initiation of hemodialysis.

Conclusion
We report this suggestive case to prompt physicians to consider the potential effect of hemodialysis introduction on the brain pressure.