bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized 3D-Printed Transparent Liver Model Using the Hepatobiliary Phase MRI
Authors: Joo Ijin , Kim Jung Hoon , Park Sang Joon , Lee Kyoungbun , Yi Nam-Joon , Han Joon Koo 
Published: October 2018

Purpose
The aim of this study was to investigate the usefulness of a personalized, 3-dimensional (3D)–printed, transparent liver model with focal liver lesions (FLLs) for lesion-by-lesion imaging-pathologic matching.

Materials and Methods
This preliminary, prospective study was approved by our institutional review board, and written informed consent was obtained. Twenty patients (male-to-female ratio, 13:7; mean age, 56 years) with multiple FLLs, including at least one presumed malignant, or an indeterminate lesion 10 mm or less on the preoperative gadoxetic acid–enhanced magnetic resonance imaging (MRI), were included. After digital segmentation of hepatobiliary phase MRI, a transparent, 3D-printed liver model with colored anatomical structures and FLLs was produced. During the gross examination of the liver specimen, the per-lesion detection rates were compared between those without (routine protocol) and those with the aid of the 3D-printed liver model.

Results
Among 98 MRI-detected FLLs (11.5 ± 12.5 mm), the per-lesion detection rate on gross examination using the 3D-printed liver model was 99.0% (97/98), which was significantly higher than that obtained on routine examination (82.7% [81/98]; P < 0.001). In the subgroup analysis, according to the tumor size, 23.9% (16/67) of FLLs 10 mm or less were additionally detected using the liver model, whereas none were additionally detected in greater than 10 mm. The additionally detected 16 FLLs in 12 patients included histologic diagnoses of viable metastases, pathologic complete response of metastases, hepatocellular carcinomas, focal nodular hyperplasia–like nodules, and hemangiomas.

Conclusions
A personalized, 3D-printed liver model with FLLs may improve the lesion-by-lesion imaging-pathologic matching for small FLLs, thus leading to accurate pathologic tumor staging and obtaining a reliable reference for imaging-detected FLLs.
Incidence, Patient Characteristics, Mode of Drug Delivery, and Outcomes of Septic Shock Patients Treated With Vasopressors in the Arise Trial
Authors: Udy Andrew A. , Finnis Mark , Jones Daryl , Delaney Anthony , Macdonald Stephen , Bellomo Rinaldo , Peake Sandra 
Published: October 2018

ABSTRACT

Introduction:
To describe the utilization of vasopressors (VP) in patients enrolled in the Australasian Resuscitation In Sepsis Evaluation (ARISE) trial, and to explore the association between time to VP and 90-day mortality.

Methods:
The primary exposure variable was VP use after arrival in the emergency department (ED). Vasoactive agents considered as VP included: norepinephrine, epinephrine, metaraminol, or vasopressin. Time-to-event analysis, multivariable logistic regression, and propensity-matched treatment effects modeling were used to assess the association between time to VP and 90-day mortality.

Results:
In total 1,102 of 1,588 patients (69%) in ARISE received VP at any point. The median [interquartile range (IQR)] time from ED presentation to commencing VP was 4.4 [2.7, 7.1] h, and 38% did so prior to central venous access. The median [IQR] volume of intravenous (i.v.) fluid administered prior to commencing VP was 3.1 [2.3, 4.3] L. Increasing age and volume of i.v. fluid therapy were associated with a lower likelihood of commencing VP early (within 4 h of ED presentation), while greater illness severity was associated with a higher likelihood, P < 0.001, respectively. In those who subsequently died within 90 days, the sub-hazard ratio (95% confidence interval) for commencing VP was 1.4 (1.20, 1.68), P < 0.001, adjusted for age, acute physiology and chronic health evaluation II score, study group, inclusion criteria, plasma lactate, i.v. fluid prior to VP, study institution, and site of infection.

Discussion:
50% of the ARISE cohort commenced VP within 4.4 h of ED presentation, and many did so prior to central venous access. Earlier initiation of VP was associated with greater crude and adjusted 90-day mortality.
Assessment of risk to hoary squash bees (Peponapis pruinosa) and other ground-nesting bees from systemic insecticides in agricultural soil
Authors: Willis Chan D. Susan , Prosser Ryan S. , Rodríguez-Gil Jose L. , Raine Nigel E. 
Published: October 2018

AbstractUsing the hoary squash bee (Peponapis pruinosa) as a model, we provide the first probabilistic risk assessment of exposure to systemic insecticides in soil for ground-nesting bees. To assess risk in acute and chronic exposure scenarios inCucurbitaand field crops, concentrations of clothianidin, thiamethoxam and imidacloprid (neonicotinoids) and chlorantraniliprole (anthranilic diamide) in cropped soil were plotted to produce an environmental exposure distribution for each insecticide. The probability of exceedance of several exposure endpoints (LC50s) was compared to an acceptable risk threshold (5%). InCucurbitacrops, under acute exposure, risk to hoary squash bees was below 5% for honey bee LC50s for all residues evaluated but exceeded 5% for clothianidin and imidacloprid using a solitary bee LC50. ForCucurbitacrops in the chronic exposure scenario, exposure risks for clothianidin and imidacloprid exceeded 5% for all endpoints, and exposure risk for chlorantraniliprole was below 5% for all endpoints. In field crops, risk to ground-nesting bees was high from clothianidin in all exposure scenarios and high for thiamethoxam and imidacloprid under chronic exposure scenarios. Risk assessments for ground-nesting bees should include exposure impacts from soil and could use the hoary squash bee as an ecotoxicology model.
Temperature is a dominant driver of distinct annual seasonality of leaf litter production of equatorial tropical rain forests
Authors: Kitayama Kanehiro , Ushio Masayuki , Aiba Shin-ichiro 
Published: October 2018

ABSTRACTIntra-annual periodicity of canopy photosynthetic activity and leaf development has been documented in seasonal and weakly-seasonal tropical forests in the Amazon and elsewhere. However, vegetative periodicity such as leaf flush and fall in apparently “aseasonal” equatorial tropical forests has not been well documented. Moreover, causal drivers of the vegetative periodicity in those forests have not been identified largely because of the difficulty in performing manipulative experiments targeting whole forest ecosystem dynamics.Here we show a distinct annual seasonality in canopy dynamics using a Fourier analysis with a statistical significance test on the long-term, fortnightly monitored dataset of leaf litterfall in nine evergreen tropical rain forests on Mount Kinabalu, Borneo. Statistically significant annual periodicity occurs across altitudes and soil types in all years irrespective of the year-to-year climatic variability, suggesting that fluctuations in regional climate rather than local micro-climatic, edaphic and/or biotic conditions cause the precise 1-year periodicity.We examine climatic factors that have causative effects on the distinct 1-year periodicity using the spectrum convergent cross mapping that we developed in the present study to distinguish causal relationships from seasonality-driven synchronization. According to the analysis, we find that mean daily air temperature is most strongly, causatively related to the 1-year periodicity of leaf litterfall. However, knowledge on ecophysiolocial and molecular mechanisms underlying temperature-control of tropical tree growth is limited and further studies are required to understand the detailed mechanisms.(Synthesis) We suggest that intra-annual temperature changes in association with the movement of the intertropical convergence zone cause the distinct annual vegetative periodicity. Because vegetative periodicity can be transmitted to the dynamics of higher trophic levels through a trophic cascade, interactions between vegetative periodicity and daily air temperature, not rainfall, would more strongly cause changes in the dynamics of equatorial tropical rain forests. Our results show that clear vegetative periodicity (i.e., annual seasonality) can be found in equatorial tropical rain forests under diverse local environments, and that air temperature is a more important factor than the other climate variables in the climate-forest ecosystem interactions.
SV40 polyomavirus activates the Ras-MAPK signaling pathway for vacuolization, cell death, and virus release
Authors: Motamedi Nasim , Sewald Xaver , Luo Yong , Mothes Walther , DiMaio Daniel 
Published: October 2018

ABSTRACTPolyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe disease in immunosuppressed individuals. Studies with SV40, a well-studied model polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to the nucleus, viral transcription and DNA replication, and cell transformation. In contrast, little is known about host factors or cellular signaling pathways involved in the late steps of productive infection leading to polyomavirus release. We previously showed that cytoplasmic vacuolization, a characteristic late cytopathic effect of SV40, depends on the specific interaction between the major viral capsid protein VP1 and its cell surface ganglioside receptor GM1. Here we show that late during infection, SV40 activates a signaling cascade in permissive CV-1 monkey cells involving Ras, Rac1, MKK4 and JNK to induce SV40-specific cytoplasmic vacuolization and subsequent cell lysis and virus release. Inhibition of individual components of this signaling pathway inhibits vacuolization, lysis and virus release, even though high-level intracellular virus replication occurs. The identification of this pathway for SV40-induced vacuolization and virus release provides new insights into the late steps of non-enveloped virus infection and reveals potential drug targets for the treatment of diseases caused by these viruses.IMPORTANCEThe polyomaviruses are small DNA viruses that include important model viruses and human pathogens that can cause fatal disease, including cancer, in immunosuppressed individuals. There are no vaccines or specific antiviral agents for any polyomavirus. Here, we show that late during infection, SV40 activates a signaling cascade involving Ras, Rac, and JNK that is required for cytoplasmic vacuolization and efficient virus release. This pathway may represent a new point of intervention to control infection by these viruses.
BspA and Pmp proteins ofTrichomonas vaginalismediate adherence to host cells
Authors: Handrich Maria R. , Garg Sriram G. , Sommerville Ewen W. , Hirt Robert P. , Gould Sven B. 
Published: October 2018

AbstractTrichomonas vaginalisis one of the most widespread, sexually transmitted pathogens. The infection involves a morphological switch from a free-swimming pyriform trophozoite to an amoeboid cell upon adhesion to host epithelial cells. While details on how the switch is induced and to what proteins of the host surface the parasite adheres remain poorly characterized, several surface proteins of the parasite itself have been identified as potential candidates. Among those are two expanded protein families that harbor domains that share similarity to functionally investigated surface proteins of prokaryotic oral pathogens; these are the BspA proteins of Bacteroidales and Spirochaetales, and the Pmp proteins of Chlamydiales. We sequenced the transcriptomes of five Trichomonads and screened for the presence of BspA and Pmp domain-containing proteins and tested the ability of individualT. vaginaliscandidates to mediate adhesion. Here we demonstrate that (i) BspA and Pmp domain-containing proteins are specifically expanded inT. vaginalisin comparison to other Trichomonads, and that (ii) individual proteins of both families have the ability to increase adhesion performance in a non-virulentT. vaginalisstrain andTetratrichomonas gallinarum, a parasite usually known to infect birds but not humans. Our results initiate the functional characterization of these two broadly distributed protein families, whose origin we trace back to the origin of Trichomonads themselves.
Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders
Authors: Erli Filippo , Palmos Alish B. , Raval Pooja , Mukherjee Jayanta , Sellers Katherine J. , Gatford Nicholas J.F. , Moss Stephen J. , Brandon Nicholas J. , Penzes Peter , Srivastava Deepak P. 
Published: October 2018

AbstractLoss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17β-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17β-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17β-estradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17β-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17β-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17β-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon. Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number.
Heteromerization of endogenous mu and delta opioid receptors tunes mu opioid receptor signaling and trafficking
Authors: Derouiche Lyes , Ugur Muzeyyen , Pierre Florian , Mann Anika , Doridot Stéphane , Ory Stéphane , Schulz Stefan , Massotte Dominique 
Published: October 2018

AbstractIncreasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures andin vivo. We established ligand selective mu-delta co-internalization upon activation by exogenous ligands and provide evidence for mu-delta co-internalization by the endogenous opioid peptide met-enkephalin, but not β-endorphin. Co-internalization was driven by the delta opioid receptor, required an active conformation of both receptors and led to sorting to the lysosomal compartment. This alteration in the mu opioid receptor intracellular fate was accompanied by sustained ERK1/2 phosphorylation. In addition, increased mu-delta neuronal co-localization in the rostral ventromedial medulla in a chronic neuropathic state suggests that mu-delta heteromers are involved in the regulation of nociceptive transmission
Nucleosome positions alone determine micro-domains in yeast chromosomes
Authors: Wiese O. , Marenduzzo D. , Brackley C. A. 
Published: October 2018

AbstractWe use molecular dynamics simulations based on publicly available MNase-seq data for nucleosome positions to predict the 3-D structure of chromatin in the yeast genome. Our main aim is to shed light on the mechanism underlying the formation of micro-domains, chromosome regions of around 0.5-10 kbp which show enriched self-interactions, which were experimentally observed in recent MicroC experiments. We show that the sole input of nucleosome positioning data is already sufficient to determine the patterns of chromatin interactions and domain boundaries seen experimentally to a high degree of accuracy. Since the nucleosome spacing so strongly affects the larger-scale domain structure, we next examine the genome-wide linker-length distribution in more detail, finding that it is highly irregular, and varies in different genomic regions such as gene bodies, promoters, and active and inactive genes. Finally we use our simple simulation model to characterise in more detail how irregular nucleosome spacing may affect local chromatin structure.
The Markov link method: a nonparametric approach to combine observations from multiple experiments
Authors: Loper Jackson , Bakken Trygve , Sumbul Uygar , Murphy Gabe , Zeng Hongkui , Blei David , Paninski Liam 
Published: October 2018

AbstractThis paper studiesmeasurement linkage. An example from cell biology helps explain the problem: imagine for a given cell we can either sequence the cell’s RNA or we can examine its morphology, but not both. Given a cell’s morphology, what do we expect to see in its RNA? Given a cell’s RNA, what do we expect in its morphology? More broadly, given a measurement of one type, can we predict measurements of the other type? This measurement linkage problem arises in many scientific and technological fields. To solve this problem, we develop a nonparametric approach we dub the “Markov link method” (MLM). The MLM makes a conditional independence assumption that holds in many multi-measurement contexts and provides a way to estimate thelink, the conditional probability of one type of measurement given the other. We derive conditions under which the MLM estimator is consistent and we use simulated data to show that it provides accurate measures of uncertainty. We evaluate the MLM on real data generated by a pair of single-cell RNA sequencing techniques. The MLM characterizes the link between them and helps connect the two notions of cell type derived from each technique. Further, the MLM reveals that some aspects of the link cannot be determined from the available data, and suggests new experiments that would allow for better estimates.Significance StatementNovel experimental techniques are developing quickly, and each technique gives new perspectives. Ideally we would build theories that account for many perspectives at once. This is not easy. One challenge is that many experiments use measurement techniques that alter or destroy the subject, making it impossible to measure the same subject with both techniques and difficult to combine data from different experiments. In this paper we develop the Markov Link Method, a new tool that overcomes this challenge.
Non-High Frequency Heart Rate Chaos: A Noninvasive Marker of REM Sleep and Obstructive Sleep Apnea Syndrome in Children
Authors: Deng Zhi-De , Arzeno Natalia M. , Katz Eliot S. , Chang Helena , Marcus Carole L. , Poon Chi-Sang 
Published: October 2018

AbstractObstructive sleep apnea syndrome (OSAS) is a highly prevalent condition associated with considerable metabolic, cardiovascular, and neurocognitive morbidity. Childhood OSAS is underdiagnosed due to a limited number of sleep laboratories and the lack of a screening test, and the subtlety of daytime symptoms in children compared to adults. A potential marker of OSAS is apnea-induced sympathoexcitation, which is likely to be exacerbated during rapid-eyemovement (REM) sleep. However, traditional methods of assessing sympathetic activity are either too invasive or insensitive/nonspecific for clinical use, particularly as a screening test. Study population comprised pediatric patients with OSAS (16 moderate/severe, 18 mild) and 18 normal non-snoring controls. We show that the chaotic dynamics of heart rate variability (HRV) as assessed by a sensitive noise titration assay is significantly increased during REM compared to non-REM sleep in children, particularly those with OSAS. The increase in heart rate chaos prevails in the face of decreased parasympathetic-mediated high-frequency component of the HRV power spectrum, indicating that the chaos was correlated to sympathetic instead of parasympathetic activity. Receiver operating characteristic analysis shows that such non-high frequency chaos reveals changing sympathetic–parasympathetic activities that are not discernible by conventional HRV metrics such as low- to high-frequency power ratio or sample entropy, with sensitivity and specificity sufficient to detect even mild OSAS in children. Results suggest a possible role for non-high frequency heart rate chaos as a selective noninvasive marker of sympathoexcitation in REM sleep, OSAS and potentially other cardiovascular abnormalities such as congestive heart failure.
Biological adaptation under fluctuating selection
Authors: Liu Ming , Rubenstein Dustin R. , Liu Wei-Chung , Shen Sheng-Feng 
Published: October 2018

AbstractBet-hedging—an evolutionary strategy that reduces fitness variance at the expense of lower mean fitness—is the primary explanation for most forms of biological adaptation to environmental unpredictability. However, most applications of bet-hedging theory to biological problems have largely made unrealistic demographic assumptions, such as non-overlapping generations and fixed population sizes. Consequently, the generality and applicability of bet-hedging theory to real world phenomena remains unclear. Here we use continuous-time, stochastic Lotka-Volterra models to relax overly restrictive demographic assumptions and explore a suite of biological adaptations to fluctuating environments. We discover a novel “rising-tide strategy” that—unlike the bet-hedging strategy—generates both a higher mean and variance in fitness. The positive fitness effects of the rising-tide strategy’s specialization to good years can overcome any negative effects of higher fitness variance in unpredictable environments. Moreover, we show not only that the rising-tide strategy will be selected for over a much broader range of environmental conditions than the bet-hedging strategy, but also under more realistic demographic circumstances. Ultimately, our model demonstrates that there are likely to be a wide range of ways that organisms respond to environmental unpredictability.
Deep gastropod relationships resolved
Authors: Tauana Junqueira Cunha , Gonzalo Giribet 
Published: October 2018

AbstractGastropod mollusks are arguably the most diverse and abundant animals in the oceans, and are successful colonizers of terrestrial and freshwater environments. Here we resolve deep relationships between the five major gastropod lineages - Caenogastropoda, Heterobranchia, Neritimorpha, Patellogastropoda and Vetigastropoda - with highly congruent and supported phylogenomic analyses. We expand taxon sampling for underrepresented lineages with new transcriptomes, and conduct analyses accounting for the most pervasive sources of systematic errors in large datasets, namely compositional heterogeneity, site heterogeneity, heterotachy, variation in evolutionary rates among genes, matrix completeness and gene tree conflict. We find that vetigastropods and patellogastropods are sister taxa, and that neritimorphs are the sister group to caenogastropods and heterobranchs. With this topology, we reject the traditional Archaeogastropoda, which united neritimorphs, vetigastropods and patellogastropods, and is still used in the organization of collections of many natural history museums. Several traits related to development and life history support our molecular results. Importantly, the time of differentiation of the embryonic 4d cell (mesentoblast, responsible for mesoderm formation), differs between the two major clades, highlighting the degree of conservation and significance of development in the evolution of gastropods, as it is also known for spiralian animals more broadly.