bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) Infection on Mortality of the Sylvatic Triatomine Vector, Mepraia spinolai (Heteroptera: Reuviidae), Under Fasting
Authors: Garcia Vanessa , Graterol Johsmar , López Angélica , Ortiz Sylvia , Solari Aldo 
Published: July 2019

Abstract
The etiologic agent of Chagas disease, Trypanosoma cruzi, is transmitted by hematophagous insect vectors that subsist on repeated blood meals over their lives separated by periods of fasting. Using naturally infected Mepraia spinolai, we measured the influence of parasite infection on this host vector’s mortality during regular feeding and after fasting. After their capture, the insects were fed twice with uninfected mice to evaluate parasitic infection in their fecal samples by microscopic observation and PCR. Then the insects were subjected to a fasting period, followed by a third (final) feeding. After each feeding, a fecal sample was obtained to evaluate T. cruzi infection. To determine its progress through ontogeny, mortality and ecdysis of the infected and uninfected nymphs and adults were recorded on three occasions, over 140 d, and analyzed. Detections of infection by T. cruzi between the two first feedings increased, but this detection level was generally reduced after final feeding unless reinfected. For nymphs (stages III–V), their mortality was highest when infected after the fasting period, whereas adults were equally resistant to death after fasting when infected with T. cruzi. Metacyclic trypomastigotes were principally excreted in the fecal samples. Our results confirm that T. cruzi is pathogenic to its invertebrate hosts under nutritional stress conditions, when nymphs’ mortality is higher while infected than uninfected when they were hungry. These results are epidemiologically important because T. cruzi harms the fasting vector M. spinolai, reducing its lifespan and competence as a disease vector, and thereby its rates of parasite transmission.
Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign
Authors: Patterson Lina , Firbank Michael J , Colloby Sean J , Attems Johannes , Thomas Alan J , Morris Christopher M 
Published: July 2019

Abstract
The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS.
Papillary Solitary Fibrous Tumor/Hemangiopericytoma: An Uncommon Morphological Form With NAB2-STAT6 Gene Fusion
Authors: Yao Zhi-Gang , Wu Hai-Bo , Hao Ying-Hua , Wang Xing-Fu , Ma Guang-Zhen , Li Jia , Li Ji-Feng , Lin Chun-Hu , Zhong Xiu-Ming , Wang Zhou , Wang Dai-Zhong 
Published: July 2019

AbstractSolitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are mesenchymal tumors characterized by “staghorn” blood vessels and collagen deposition. Little is known about SFT/HPCs with papillary architecture. We summarized the clinicopathologic features of 12 patients with papillary SFT/HPCs (8 males and 4 females; median age: 59 years), including 8 previously reported cases. Tumors were present in the meninges (75%, 9/12), adrenal gland (8%, 1/12), orbit (8%, 1/12), or spinal canal (8%, 1/12). Six tumors (50%) had a true papillary architecture with fibrovascular cores and 6 tumors (50%) had a pseudopapillary architecture with vascular cores. Nuclear staining for STAT6 was present in all tested tumors (10/10). RT-PCR indicated NAB2 ex6-STAT6 ex17 fusion in 4 tumors (80%, 4/5) and NAB2 ex4-STAT6 ex2 fusion in 1 tumor (20%, 1/5). Five patients (42%, 5/12), all with tumors in the meninges, developed local recurrence at a median of 61 months after surgery (range: 56–165 months; mean: 88.6 months). These results indicated that the papillary architecture is a morphological form of SFT/HPCs. The recognition of this pattern, with appropriate immunohistochemical analysis and assessment of NAB2-STAT6 fusion, should facilitate the distinction of these rare neoplasms from morphologically similar tumors in the meninges, lung, pleura, and soft tissue.
The day after: correlates of patient-reported outcomes with actigraphy-assessed sleep in cancer patients at home (inCASA project)
Authors: Komarzynski Sandra , Huang Qi , Lévi Francis A , Palesh Oxana G , Ulusakarya Ayhan , Bouchahda Mohamed , Haydar Mazen , Wreglesworth Nicholas I , Morère Jean-François , Adam René , Innominato Pasquale F 
Published: July 2019

Abstract
Subjective sleep assessment in cancer patients poorly correlates with actigraphy parameters that usually encompass multiple nights. We aimed to determine the objective actigraphy measures that best correlated with subjective sleep ratings on a night-by-night basis in cancer patients. Thirty-one cancer patients daily self-rated sleep disturbances using the single dedicated item of the MD Anderson Symptom Inventory (0–10 scale) with 18 other items, and continuously wore a wrist actigraph for 30 days. Objective sleep parameters were computed from the actigraphy nighttime series, and correlated with subjective sleep disturbances reported on the following day, using repeated measures correlations. Multilevel Poisson regression analysis was performed to identify the objective and subjective parameters that affected subjective sleep rating. Poor subjective sleep score was correlated with poor sleep efficiency (rrm = −0.13, p = 0.002) and large number of wake episodes (rrm = 0.12, p = 0.005) on the rated night. Multilevel analysis demonstrated that the expected sleep disturbance score was affected by the joint contribution of the wake episodes (exp(β) = 1.01, 95% confidence interval = 1.00 to 1.02, p = 0.016), fatigue (exp(β) = 1.35, 95% confidence interval = 1.15 to 1.55, p &lt; 0.001) and drowsiness (exp(β) = 1.70, 95% confidence interval = 1.19 to 2.62, p = 0.018), self-rated the following evening, and sleep disturbance experienced one night before (exp(β) = 1.77, 95% confidence interval = 1.41 to 2.22, p &lt; 0.001). The night-by-night approach within a multidimensional home tele-monitoring framework mainly identified the objective number of wake episodes computed from actigraphy records as the main determinant of the severity of sleep complaint in cancer patients on chemotherapy. This quantitative information remotely obtained in real time from cancer patients provides a novel framework for streamlining and evaluating interventions toward sleep improvement in cancer patients.
Specific diagnostic method for St. Louis Encephalitis Virus using a non-structural protein as antigen
Authors: Simari M.B. , Goñi S.E. , Luppo V.C , Fabbri C.M. , Argüelles M.H. , Lozano M.E. , Morales M.A. , Iglesias N.G. 
Published: July 2019

AbstractSt. Louis encephalitis virus (SLEV) is a mosquito-borne reemerging flavivirus in Argentina. It is currently necessary to develop specific serological tests that can efficiently discriminate the flaviviruses that circulate in our country. The immunoassays to diagnose SLEV lack specificity because they are based on the detection of structural viral proteins and the human immunoglobulins produced during infection against these proteins cross-react with other flaviviruses. Here, we describe an enzyme-immunoassay designed to detect human IgG antibodies specific to the viral nonstructural protein NS5. The results indicate that NS5 is a promising antigen useful to discriminate SLEV from other circulating flaviviruses.
Is therapeutic inertia present in primary diabetes care in Malaysia? A prospective study
Authors: Chew Boon-How , Hussain Husni , Supian Ziti Akthar 
Published: July 2019

AbstractAimsThis prospective study aimed to determine the proportions of therapeutic inertia when treatment targets not achieved in adults T2D at three public health clinics in Malaysia.MethodsThe index prescriptions were those when the annual blood tests were reviewed. Prescriptions were verified and classified as 1) no change, 2) stepping up and 3) stepping down. Multivariable logistic regression and sensitive analyses were conducted.ResultsAt follow-up, 552 participants were available for the assessment of therapeutic inertia (78.9% response rate). The mean (SD) age and diabetes duration were 60.0 (9.9) years and 5.0 (6.0) years, respectively. High therapeutic inertia were observed in oral anti-diabetic (61-72%), anti-hypertensive (34-65%) and lipid-lowering therapies (56-77%), and lesser in insulin (34- 52%). Insulin therapeutic inertia was more likely among those with shorter diabetes duration (adjusted OR 0.9, 95% CI 0.87, 0.98). Those who did not achieve treatment targets were less likely to experience therapeutic inertia: HbA1c ≥ 7.0%: adjusted OR 0.10 (0.04, 0.24); BP ≥ 140/90 mmHg: 0.28 (0.16, 0.50); LDL-cholesterol ≥ 2.6 mmol/L: 0.37 (0.22, 0.64).ConclusionsAlthough therapeutic intensifications were more likely in the present of non- achieved treatment targets but the proportions of therapeutic inertia were high.Trial registrationNCT02730754 https://clinicaltrials.gov/ct2/show/NCT02730754HighlightsProbably the first study in Malaysia or Asian countriesAssessing three main therapeutic inertia among T2D at primary diabetes careProportions of therapeutic inertia were highTherapeutic inertia was unlikely in non-achieved treatment targetsPossible causes of therapeutic inertia require identification and rectification
Rfx6 promotes the differentiation of peptide-secreting enteroendocrine cells while repressing genetic programs controlling serotonin production
Authors: Piccand Julie , Vagne Constance , Blot Florence , Meunier Aline , Beucher Anthony , Strasser Perrine , Lund Mari L. , Ghimire Sabitri , Nivlet Laure , Lapp Céline , Petersen Natalia , Engelstoft Maja S. , Thibault-Carpentier Christelle , Keime Céline , Correa Sara Jimenez , Schreiber Valérie , Molina Nacho , Schwartz Thue W. , De Arcangelis Adèle , Gradwohl Gérard 
Published: July 2019

ABSTRACTObjectiveEnteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake and storage. Our goal is to decipher the gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied the role of the transcription factor Rfx6 which had been identified as the cause of Mitchell-Riley syndrome characterized by neonatal diabetes and congenital malabsorptive diarrhea. We previously reported that Rfx6 was essential for pancreatic beta cell development and function, however, the role of Rfx6 in EECs differentiation remained to be elucidated.MethodsWe examined the molecular, cellular and metabolic consequences of constitutive and conditional deletion of Rfx6 in the embryonic and adult mouse intestine. We performed single cell and bulk RNA-Seq to characterize EECs diversity and identify Rfx6-regulated genes.ResultsRfx6 is expressed in the gut endoderm; later it is turned on in, and restricted to, enteroendocrine progenitors and persists in hormone-positive EECs. In the embryonic intestine, the constitutive lack of Rfx6 leads to gastric heterotopia, suggesting a role in the maintenance of intestinal identity. In the absence of intestinal Rfx6, EECs differentiation is severely impaired both in the embryo and adult. However, the number of serotonin-producing enterochromaffin cells and mucosal 5-HT content are increased. Concomitantly, Neurog3-positive enteroendocrine progenitors accumulate. Combined analysis of single-cell and bulk RNA-Seq data revealed that enteroendocrine progenitors differentiate in two main cell trajectories, the enterochromaffin (EC) cells and the Peptidergic Enteroendocrine (PE) cells, whose differentiation programs are differentially regulated by Rfx6. Rfx6 operates upstream of Arx, Pax6 and Isl1 to trigger the differentiation of peptidergic EECs such as GIP-, GLP-1- or CCK-secreting cells. On the contrary, Rfx6 represses Lmx1a and Tph1, two genes essential for serotonin biosynthesis. Finally, we identified transcriptional changes uncovering adaptive responses to the prolonged lack of enteroendocrine hormones and leading to malabsorption and lower food efficiency ratio in Rfx6-deficient mouse intestine.ConclusionThese studies identify Rfx6 as an essential transcriptional regulator of EECs specification and shed light on the molecular mechanisms of intestinal failures in human RFX6-deficiencies such as Mitchell-Riley syndrome.
TREEasy: an automated workflow to infer gene trees, species trees, and phylogenetic networks from multilocus data
Authors: Mao Yafei , Hou Siqing , Economo Evan P. 
Published: July 2019

AbstractMultilocus genomic datasets can be used to infer a rich set of information about the evolutionary history of a lineage, including gene trees, species trees, and phylogenetic networks. However, user-friendly tools to run such integrated analyses are lacking, and workflows often require tedious reformatting and handling time to shepherd data through a series of individual programs. Here, we present a tool written in Python—TREEasy—that performs automated sequence alignment (with MAFFT), gene tree inference (with IQ-Tree), species inference from concatenated data (with IQ-Tree), species tree inference from gene trees (with ASTRAL, MP-EST, and STELLS2), and phylogenetic network inference (with SNaQ and PhyloNet). The tool only requires FASTA files and nine parameters as inputs. The Tool can be run as command line or through a Graphical User Interface (GUI). As examples, we reproduced a recent analysis of staghorn coral evolution, and performed a new analysis on the evolution of the WGD clade of yeast. The latter revealed novel inferences that were not identified by previous analyses. TREEasy represents a reliable and simple tool to accelerate research in systematic biology (https://github.com/MaoYafei/TREEasy).
Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice
Authors: Eid Rand S. , Lieblich Stephanie E. , Wong Sarah J. , Galea Liisa A.M. 
Published: July 2019

AbstractOvarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones have immunomodulatory properties. However, how ovarian hormones can influence the inflammatory outcomes of stress exposure is poorly understood. Here, we examined the effects of long-term ovariectomy on the behavioral and neuroinflammatory outcomes of sub-chronic stress exposure in middle-aged mice. Briefly, sham-operated and ovariectomized mice were assigned to non-stress groups or exposed to 6 days of variable stress. Mice were assessed on a battery of behavioral tests, and cytokine concentrations were quantified in the frontal cortex and hippocampus. In the frontal cortex, postsynaptic density protein-95 expression was examined as an index of excitatory synapse number and/or stability, and phosphorylated mitogen-activated protein kinases (MAPKs) were measured to explore potential cell signaling pathways elicited by stress exposure and/or ovarian hormones. Long-term ovariectomy modified the central cytokine profile by robustly reducing cytokine concentrations in the frontal cortex and modestly increasing concentrations in the hippocampus. Under non-stress conditions, long-term ovariectomy also reduced extracellular signal-regulated kinase (ERK) phosphoprotein expression in the frontal cortex and increased some measures of depressive-like behavior. The effects of sub-chronic stress exposure were however more pronounced in sham-operated mice. Notably, in sham-operated mice only, sub-chronic stress exposure increased IL-1β and IL-6:IL-10 ratio in the frontal cortex and hippocampus and reduced pERK1/2 expression in the frontal cortex. Further, although sub-chronic stress exposure increased anhedonia-like behavior regardless of ovarian status, it increased passive-coping behavior in sham-operated mice only. These data indicate that long-term ovariectomy has potent effects on the central cytokine milieu and dictates the neuroinflammatory and behavioral effects of sub-chronic stress exposure in middle-aged mice. These findings therefore suggest that the immunomodulatory properties of ovarian hormones are of relevance in the context of stress and possibly depression.
BIAFLOWS: A collaborative framework to reproducibly deploy and benchmark bioimage analysis workflows
Authors: Rubens Ulysse , Mormont Romain , Paavolainen Lassi , Bäcker Volker , Michiels Gino , Pavie Benjamin , Scholz Leandro A. , Maška Martin , Ünay Devrim , Ball Graeme , Hoyoux Renaud , Vandaele Rémy , Golani Ofra , Chessel Anatole , Stanciu Stefan G. , Sladoje Natasa , Paul-Gilloteaux Perrine , Marée Raphaël , Tosi Sébastien 
Published: July 2019

AbstractAutomated image analysis has become key to extract quantitative information from scientific microscopy bioimages, but the methods involved are now often so refined that they can no longer be unambiguously described using written protocols. We introduce BIAFLOWS, a software tool with web services and a user interface specifically designed to document, interface, reproducibly deploy, and benchmark image analysis workflows. BIAFLOWS allows image analysis workflows to be compared fairly and shared in a reproducible manner, safeguarding research results and promoting the highest quality standards in bioimage analysis. A curated instance of BIAFLOWS is available online; it is currently populated with 34 workflows that can be triggered to process image datasets illustrating 15 common bioimage analysis problems organized in 9 major classes. As a complete case study, the open benchmarking of 7 nuclei segmentation workflows, including classical and deep learning techniques, was performed on this online instance. All the results presented can be reproduced online.
REAVER: Improved Analysis of High-resolution Vascular Network Images Revealed Through Round-robin Rankings of Accuracy and Precision
Authors: Corliss Bruce A. , Doty Richard , Mathews Corbin , Yates Paul A. , Zhang Tingting , Peirce Shayn M. 
Published: July 2019

AbstractAlterations in vascular networks, including angiogenesis and capillary regression, play key roles in disease, wound healing, and development. Imaging of microvascular networks can reveal their spatial structures, but effective study of network architecture requires methods to accurately quantify them using a variety of metrics. We present REAVER (Rapid Editable Analysis of Vessel Elements Routine), a freely available open source tool that researchers can use to analyze and quantify high resolution fluorescent images of blood vessel networks, and assess its performance compared to alternative state-of-the-art image analysis software programs. Top performing programs for each metric are identified by assigning a rank based on statistical multiple comparisons of accuracy and precision, modeled as matches in a round-robin style tournament. This comparison method yields a clearly defined and consistent standard for characterizing program performance, avoiding the use of non-standard ad hoc interpretations of multiple comparisons between programs. Using this comparison method and a dataset of manually analyzed images as a ground-truth, we show that REAVER was the top ranked program for both accuracy and precision for all metrics quantified, including vessel length density, vessel area fraction, mean vessel diameter, and branchpoint count. REAVER can be used to quantify differences in blood vessel architectures between study groups, which makes it particularly useful in experiments designed to evaluate the effects of different external perturbations (e.g. drugs or disease states).
A conserved SUMO-Ubiquitin pathway directed by RNF4/SLX5-SLX8 and PIAS4/SIZ1 drives proteasomal degradation of topoisomerase DNA-protein crosslinks
Authors: Sun Yilun , Jenkins Lisa M. Miller , Su Yijun P. , Nitiss Karin C. , Nitiss John L. , Pommier Yves 
Published: July 2019

SUMMARYTopoisomerase cleavage complexes (TOPccs) can be stalled physiologically and by the anticancer drugs camptothecins (TOP1 inhibitors) and etoposide (TOP2 inhibitor), yielding irreversible TOP DNA-protein crosslinks (TOP-DPCs). Here we elucidate how TOP-DPCs are degraded via the SUMO-ubiquitin (Ub) pathway. We show that in human cells, TOP-DPCs are promptly and sequentially conjugated by SUMO-2/3, SUMO-1 and Ub. SUMOylation is catalyzed by the SUMO ligase PIAS4, which forms a complex with both TOP1 and TOP2α and β. RNF4 acts as the SUMO-targeted ubiquitin ligase (STUbL) for both TOP1- and TOP2-DPCs in a SUMO-dependent but replication/transcription-independent manner. This SUMO-Ub pathway is conserved in yeast with Siz1 the ortholog of PIAS4 and Slx5-Slx8 the ortholog of RNF4. Our study reveals a conserved SUMO-dependent ubiquitylation pathway for proteasomal degradation of both TOP1- and TOP2-DPCs and potentially for other DPCs.Abstract FigureIn BriefTopoisomerase DNA-protein crosslinks (TOP-DPCs) are the therapeutic mechanism of clinical TOP inhibitors (camptothecin and etoposide). TOP-DPCs induce rapid and sequential conjugation of SUMO-2/3- SUMO-1 and ubiquitin catalyzed by activation of PIAS4 through its DNA-binding SAP domain and RNF4 through its SIM domains. This SUMO-ubiquitin cascade triggers proteasomal degradation of TOP-DPCs.HIGHLIGHTSAbortive topoisomerase I (TOP1) and II (TOP2) cleavage complexes resulting in DNA-protein crosslinks (TOP-DPCs) are rapidly and sequentially modified by SUMO-2/3, SUMO-1 and ubiquitin before their proteasomal degradation.PIAS4 SUMOylates TOP-DPCs via its DNA-binding SAP domain independently of DNA transactions and DNA damage responses.RNF4 ubiquitylates SUMOylated TOP-DPCs and drives their proteasomal degradation.TOP-DPC processing by the SUMO-Ub pathways is conserved in yeast and human cells.