bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Plk1 with siRNNs in primary cells from pediatric B-cell acute lymphoblastic leukemia patients
Authors: Goroshchuk Oksana , Vidarsdottir Linda , Björklund Ann-Charlotte , Hamil Alexander S. , Kolosenko Iryna , Dowdy Steven F. , Palm-Apergi Caroline 
Published: February 2020

AbstractB-cell acute lymphoblastic leukemia (B-ALL) accounts for nearly one fifth of all childhood cancers and current challenges in B-ALL treatment include resistance, relapse and late-onset side effects due to the chemotherapy. To overcome these hurdles, novel therapies need to be investigated. One promising target is Polo-like kinase 1 (Plk1), a key regulator of the cell cycle. In this study, the Plk family expression is investigated in primary peripheral blood and bone marrow mononuclear cells from ten pediatric B-ALL patients. For the first time, short interfering RiboNucleic Neutrals (siRNNs) that enter cells without a transfection reagent are used to target Plk1 mRNA in primary cells from pediatric B-ALL patients. Our results show that the expression of Plk1 and Plk4 is significantly higher in pediatric B-ALL patients compared to healthy donors. Moreover, treatment of primary peripheral blood and bone marrow mononuclear cells from pediatric B-ALL patients, culturedex vivo, with Plk1-targeting siRNNs results in cleavage of Plk1 mRNA. Importantly, the Plk1 knockdown is specific and does not affect other Plk members in contrast to many small molecule Plk1 inhibitors. Thus, Plk1 is a potential therapeutic target in pediatric B-ALL and selective targeting of Plk1 can be achieved by the use of siRNNs.
High-contrast, synchronous volumetric imaging with selective volume illumination microscopy
Authors: Truong Thai V. , Holland Daniel B. , Madaan Sara , Andreev Andrey , Keomanee-Dizon Kevin , Troll Josh V. , Koo Daniel E. S. , McFall-Ngai Margaret J. , Fraser Scott E. 
Published: February 2020

AbstractLight-field fluorescence microscopy uniquely provides fast, synchronous volumetric imaging by capturing an extended volume in one snapshot, but often suffers from low contrast due to the background signal generated by its wide-field illumination strategy. We implemented light-field-based selective volume illumination microscopy (SVIM), where illumination is confined to only the volume of interest, removing the background generated from the extraneous sample volume, and dramatically enhancing the image contrast. We demonstrate the capabilities of SVIM by capturing cellular-resolution 3D movies of flowing bacteria in seawater as they colonize their squid symbiotic partner, as well as of the beating heart and brain-wide neural activity in larval zebrafish. These applications demonstrate the breadth of imaging applications that we envision SVIM will enable, in capturing tissue-scale 3D dynamic biological systems at single-cell resolution, fast volumetric rates, and high contrast to reveal the underlying biology.
An isothermal shift assay for proteome scale drug-target identification
Authors: Ball Kerri A. , Webb Kristofor J. , Coleman Stephen J. , Cozzolino Kira A. , Jacobsen Jeremy , Jones Kevin R. , Stowell Michael H. B. , Old William M. 
Published: February 2020

AbstractMost small molecule drugs act on living systems by physically interacting with specific proteins and modulating target function. Identification of drug binding targets, within the complex milieu of the human proteome, remains a challenging task of paramount importance in drug discovery. Existing approaches for target identification employ complex workflows with limited throughput. Here, we present the isothermal shift assay (iTSA), a mass spectrometry method for proteome-wide identification of drug targets within lysates or living cells. Compared with prevailing methods, iTSA uses a simplified experimental design with increased statistical power to detect thermal stability shifts that are induced by small molecule binding. Using a pan-kinase inhibitor, staurosporine, we demonstrate improved performance over commonly used thermal proteome profiling methods, identifying known targets in cell lysates and living cells. We also demonstrate the identification of both known targets and additional candidate targets for the kinase inhibitor harmine in cell and tissue lysates.
Seeds of Life in Space (SOLIS)
Authors: Taquet V. , Codella C. , De Simone M. , López-Sepulcre A. , Pineda J. E. , Segura-Cox D. , Ceccarelli C. , Caselli P. , Gusdorf A. , Persson M. V. , Alves F. , Caux E. , Favre C. , Fontani F. , Neri R. , Oya Y. , Sakai N. , Vastel C. , Yamamoto S. , Bachiller R. , Balucani N. , Bianchi E. , Bizzocchi L. , Chacón-Tanarro A. , Dulieu F. , Enrique-Romero J. , Feng S. , Holdship J. , Lefloch B. , Jaber Al-Edhari A. , Jiménez-Serra I. , Kahane C. , Lattanzi V. , Ospina-Zamudio J. , Podio L. , Punanova A. , Rimola A. , Sims I. R. , Spezzano S. , Testi L. , Theulé P. , Ugliengo P. , Vasyunin A. I. , Vazart F. , Viti S. , Witzel A. 
Published: February 2020

Context. Low-mass protostars drive powerful molecular outflows that can be observed with millimetre and submillimetre telescopes. Various sulfuretted species are known to be bright in shocks and could be used to infer the physical and chemical conditions throughout the observed outflows.
Aims. The evolution of sulfur chemistry is studied along the outflows driven by the NGC 1333-IRAS4A protobinary system located in the Perseus cloud to constrain the physical and chemical processes at work in shocks.
Methods. We observed various transitions from OCS, CS, SO, and SO2 towards NGC 1333-IRAS4A in the 1.3, 2, and 3 mm bands using the IRAM NOrthern Extended Millimeter Array and we interpreted the observations through the use of the Paris-Durham shock model.
Results. The targeted species clearly show different spatial emission along the two outflows driven by IRAS4A. OCS is brighter on small and large scales along the south outflow driven by IRAS4A1, whereas SO2 is detected rather along the outflow driven by IRAS4A2 that is extended along the north east–south west direction. SO is detected at extremely high radial velocity up to + 25 km s−1 relative to the source velocity, clearly allowing us to distinguish the two outflows on small scales. Column density ratio maps estimated from a rotational diagram analysis allowed us to confirm a clear gradient of the OCS/SO2 column density ratio between the IRAS4A1 and IRAS4A2 outflows. Analysis assuming non Local Thermodynamic Equilibrium of four SO2 transitions towards several SiO emission peaks suggests that the observed gas should be associated with densities higher than 105 cm−3 and relatively warm (T > 100 K) temperatures in most cases.
Conclusions. The observed chemical differentiation between the two outflows of the IRAS4A system could be explained by a different chemical history. The outflow driven by IRAS4A1 is likely younger and more enriched in species initially formed in interstellar ices, such as OCS, and recently sputtered into the shock gas. In contrast, the longer and likely older outflow triggered by IRAS4A2 is more enriched in species that have a gas phase origin, such as SO2.
Chirurgisches Vorgehen bei einem Vaginalfaltenvorfall in der Läufigkeit bei einer Deutschen Dogge
Authors: Ganz Sebastian , Wehrend Axel , Georgiev Plamen 
Published: February 2020

ZusammenfassungBeschrieben wird die chirurgische Versorgung eines östrogenbedingten Vaginalfaltenvorfalls Grad IV bei einer Deutschen Dogge. Weiterhin werden die Möglichkeiten
der konservativen Therapie bei dieser Erkrankung dargestellt und auf eine neuere Operationstechnik sowie den postoperativen Verlauf eingegangen. Prinzip der
konservativen Behandlung ist, den Zyklus der Hündin durch Induktion der Ovulation zu verkürzen, um dadurch den Einfluss von Östrogenen auf das prolabierte
Gewebe zu reduzieren. Die Vorteile der beiden therapeutischen Ansätze werden diskutiert. Interessant an diesem Fall ist, dass die konservative Therapie nicht
zum Erfolg führte. Die Ursache ist unklar.
Stress und muskuloskelettale Symptome
Authors: Boettcher Edmund 
Published: February 2020

ZusammenfassungStressbelastungen können mit muskuloskelettalen Symptomen verbunden sein oder diese sogar auslösen. Oft liegen verschiedene Ursachen zugrunde.Die Behandlung zur Stressregulation sollte vor allem auf Entspannung und Regeneration abzielen.
Prognosefaktoren bei Katzen mit septischer Peritonitis
Authors: Betz Daniela Simon 
Published: February 2020

Scotti KM, Koenigshof A, Sri-Jayantha LSH et al. Prognostic indicators in cats with septic peritonitis (2002–2015): 83 cases. Vet Emerg Crit Care 2019; 29:
647–652
Die septische Peritonitis (SP) ist eine lebensbedrohliche Erkrankung, bei der in der Regel eine Laparotomie indiziert ist. Es liegen nur wenige Informationen
zu prognostisch verwertbaren Parametern für Katzen vor. Ionisiertes Kalzium und Laktat wurden in diesem Zusammenhang in vorangegangenen Untersuchungen
beschrieben. Ziel dieser Studie war zu prüfen, inwiefern sich Befunde von Allgemein- und Laboruntersuchungen sowie Zeitintervall bis zur Operation,
empirischer Antibiotikaeinsatz und Ergebnisse der mikrobiologischen Untersuchung als Prognoseindikatoren eignen.
Peritoneallavage bei septischer Peritonitis des Hundes
Authors: Betz Daniela Simon 
Published: February 2020

Marshall H, Sinnott-Stutzman V, Ewing P et al. Effect of peritoneal lavage on bacterial isolates in 40 dogs with confirmed septic peritonitis. J Vet Emerg Crit
Care 2019; 29 (6): 635–642
Septische Peritonitis (SP) ist eine Infektion der Peritonealhöhle, die häufig durch eine Ruptur im Bereich des Gastrointestinal-, Hepatobiliär- oder
Urogenitaltrakts bedingt ist. In der Humanmedizin gilt eine Peritoneallavage (PL) bei SP als nicht unumstritten, stellt dennoch eine häufig angewandte
Behandlungsmethode dar. Bei Hunden mit SP liegen nur wenige Erkenntnisse zur Zusammensetzung des bakteriellen Spektrums und der Antibiotika-Resistenzlage
bzw. deren Veränderung im Verlauf einer PL vor. Ziel dieser Studie war, die mikrobiologische Zusammensetzung, die Antibiotikasensitivität und das
Antibiotika-Resistenzmuster der Bakterien in der Bauchhöhlenflüssigkeit von Hunden mit SP vor und nach einer PL zu untersuchen.
Effektivität von Imepitoin bei Geräuschangst des Hundes
Authors: Betz Daniela Simon 
Published: February 2020

Engel O, Müller HW, Klee R et al. Effectiveness of imepitoin for the control of anxiety and fear associated with noise phobia in dogs. J Vet Intern Med 2019; 33
(6): 2675–2684
Geräuschbedingte Unruhe oder Angst ist beim Hund mit einer Prävalenz von bis zu 49 % eine häufige Verhaltensveränderung. Ein Teil der betroffenen Hunde agiert
auf Geräusche mit extremen Reaktionen, die einer Phobie beim Menschen ähneln. Imepitoin, ein partieller GABAA-Agonist mit anxiolytischer und
antikonvulsiver Wirksamkeit, ist in vielen Ländern (auch Deutschland) zur Therapie der idiopathischen Epilepsie des Hundes zugelassen. Ziel dieser Studie
war, die Effektivität und Verträglichkeit von Imepitoin als Anxiolytikum bei Geräuschangst des Hundes im Vergleich zu einem Plazebo zu untersuchen.
Clozapp
Authors: Nisbet Kelly , Généreux Michel , Anderson Blake , Kuperman Victor 
Published: February 2020

Abstract
This paper introduces a freely available and easy to use Java application for the collection and recording of
Cloze probability ratings. Clozapp presents participants with text fragments of the researchers’ choice and collects guesses
regarding upcoming words. It can also collect basic demographic information about participants. Available modes of data collection
include elicitation of responses to a limited number of omitted words in a text or to all words in a text. Clozeapp can be
customized to present instructions and experimental stimuli in any given language and to collect multiple types of demographic
data. This paper presents the application by detailing the states and actions available, as well as descriptions of how to
customize the app to fit different experimental needs including possible input and output details. The application manual is
provided. As a proof of concept, we used Clozapp to conduct a replication study of two existing collections of Cloze probability
norms. The Clozapp norms showed strong reliable correlations (r > 0.7) with both existing data sets,
suggesting a high convergence between modes of data collection. The application provides an efficient and customizable way of
collecting predictability norms for language research.
Bladder Cancer Involving Smooth Muscle of Indeterminate Type or Muscularis Mucosae in Transurethral Biopsy Specimens
Authors: Hwang Michael J , Kamat Ashish M , Dinney Colin P , Czerniak Bogdan , Guo Charles C 
Published: February 2020

Abstract

Objectives
Bladder cancers invading the muscularis mucosae (MM) are treated differently from those invading the muscularis propria (MP). However, it may be difficult to determine the type of smooth muscle in transurethral resection (TUR) or biopsy specimens. We aimed to investigate the clinicopathologic features of bladder cancers involving smooth muscle of indeterminate type (SMIT) in TUR specimens in comparison with those invading the MM.

Methods
We identified 103 patients with bladder cancer involving SMIT (n = 27) or the MM (n = 76) in TUR specimens. All patients underwent subsequent restaging TUR or cystectomy.

Results
Bladder cancer with SMIT invasion showed a significantly higher rate of MP invasion in the subsequent specimens than those invading the MM (52% vs 29%). Lack of MP in the TUR specimens had a significantly higher risk of MP invasion in the subsequent specimens than those with the MP (61% vs 40%). The overall survival time for patients with SMIT invasion was significantly shorter than those with MM invasion.

Conclusions
Bladder cancers with SMIT invasion in TUR specimens show more frequent cancer upstaging in the subsequent specimens and a poorer clinical outcome than those invading the MM, which highlights the importance of a cancer restaging procedure for these patients.
The Ex-Middle Problem for Law-and-Economics
Authors: Levmore Saul 
Published: February 2020

Abstract
Law-and-economics has an ex-middle problem. First, there is the problem of preserving law’s deterrent power, and its ability to influence later behavior, even when it is sensible to renegotiate incentives later on. The issue is hardly limited to contract renegotiation, and the ubiquity of this kind of ex-middle thinking is examined here. Second, there is the idea that the more our thinking is driven by an ex-ante perspective, the more it distances itself from common ethical intuitions that tend to involve ex-post observations, or simply results. Solving ex-middle problems by tinkering with incentives leads to increased objections from ethically oriented audiences, who find efficiency claims unattractive when they burden individuals in the interest of future unidentifiable beneficiaries. This conflict makes it hard for law-and-economics to have its deserved influence on lawmaking. When law renegotiates with positive incentives, it reduces its ex-ante impact; when it relies on negative incentives, either ex-post or ex-middle, accompanied by a readjustment of the optimal ex-ante rule, it runs the risk of offending ethical sentiments, and then it rarely takes hold. One aim here is to draw attention to ex-middle recalibrations, and the second aim is to suggest that a law-and-economics approach is most successful when it devises efficient rules that are not at odds with ethical sentiments.
Greater basking opportunity and warmer nights during late pregnancy advance modal birth season in a live-bearing gecko, lowering the risk of reduced embryonic condition
Authors: Moore Georgia , Penniket Sophie , Cree Alison 
Published: February 2020

AbstractThermal conditions during pregnancy affect the length of gestation and phenotype of offspring in viviparous lizards. However, past studies have typically exposed females to basking treatments throughout pregnancy, meaning that effects specific to late pregnancy (including cues for parturition) or to night temperatures are poorly understood. We examined effects of thermal treatments during late-embryonic development on Woodworthia ‘Otago/Southland’, a viviparous gecko with an unusual capacity to reproduce annually or biennially. Among females from a cool-climate, biennially reproducing population, elevated levels of basking opportunity and night temperature during late summer together increased the proportion of births occurring before winter in the laboratory. Offspring born before winter also had higher mass and body condition than those born after winter. Regardless of the season, the daytime body temperature of females declined shortly before parturition (putatively assisting survival of fully developed embryos in utero), then increased immediately after parturition to match that of neonates. Overall, the combined effects of warmer days and nights could help to explain geographical variation in birth season for this species. Furthermore, climate change might shift the modal birth season at cool sites from spring to the preceding autumn, with loss of offspring mass in utero over warm winters also potentially favouring a shift in birth season over time.
Geographically dependent individual-level models for infectious diseases transmission
Authors: Mahsin M D , Deardon Rob , Brown Patrick 
Published: February 2020

SummaryInfectious disease models can be of great use for understanding the underlying mechanisms that influence the spread of diseases and predicting future disease progression. Modeling has been increasingly used to evaluate the potential impact of different control measures and to guide public health policy decisions. In recent years, there has been rapid progress in developing spatio-temporal modeling of infectious diseases and an example of such recent developments is the discrete-time individual-level models (ILMs). These models are well developed and provide a common framework for modeling many disease systems; however, they assume the probability of disease transmission between two individuals depends only on their spatial separation and not on their spatial locations. In cases where spatial location itself is important for understanding the spread of emerging infectious diseases and identifying their causes, it would be beneficial to incorporate the effect of spatial location in the model. In this study, we thus generalize the ILMs to a new class of geographically dependent ILMs, to allow for the evaluation of the effect of spatially varying risk factors (e.g., education, social deprivation, environmental), as well as unobserved spatial structure, upon the transmission of infectious disease. Specifically, we consider a conditional autoregressive (CAR) model to capture the effects of unobserved spatially structured latent covariates or measurement error. This results in flexible infectious disease models that can be used for formulating etiological hypotheses and identifying geographical regions of unusually high risk to formulate preventive action. The reliability of these models is investigated on a combination of simulated epidemic data and Alberta seasonal influenza outbreak data ($2009$). This new class of models is fitted to data within a Bayesian statistical framework using Markov chain Monte Carlo methods.
Monocytes and neutrophils are associated with clinical features in amyotrophic lateral sclerosis
Authors: McGill Raquel B , Steyn Frederik J , Ngo Shyuan T , Thorpe Kathryn A , Heggie Susan , Ruitenberg Marc J , Henderson Robert D , McCombe Pamela A , Woodruff Trent M 
Published: February 2020

Abstract
Immunity has emerged as a key player in neurodegenerative diseases such as amyotrophic lateral sclerosis, with recent studies documenting aberrant immune changes in patients and animal models. A challenging aspect of amyotrophic lateral sclerosis research is the heterogeneous nature of the disease. In this study, we investigate the associations between peripheral blood myeloid cell populations and clinical features characteristic of amyotrophic lateral sclerosis. Peripheral blood leukocytes from 23 healthy controls and 48 patients with amyotrophic lateral sclerosis were analysed to measure myeloid cell alterations. The proportion of monocytes (classical, intermediates and non-classical subpopulations) and neutrophils, as well as the expression of select surface markers, were quantitated using flow cytometry. Given the heterogeneous nature of amyotrophic lateral sclerosis, multivariable linear analyses were performed to investigate associations between patients’ myeloid profile and clinical features, such as the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, bulbar subscore of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale over disease duration and respiratory function. We demonstrate a shift in monocyte subpopulations in patients with amyotrophic lateral sclerosis, with the ratio of classical to non-classical monocytes increased compared with healthy controls. In line with this, patients with greater disease severity, as determined by a lower Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score, had reduced non-classical monocytes. Interestingly, patients with greater bulbar involvement had a reduction in the proportions of classical, intermediate and non-classical monocyte populations. We also revealed several notable associations between myeloid marker expression and clinical features in amyotrophic lateral sclerosis. CD16 expression on neutrophils was increased in patients with greater disease severity and a faster rate of disease progression, whereas HLA-DR expression on all monocyte populations was elevated in patients with greater respiratory impairment. This study demonstrates that patients with amyotrophic lateral sclerosis with distinct clinical features have differential myeloid cell signatures. Identified cell populations and markers may be candidates for targeted mechanistic studies and immunomodulation therapies in amyotrophic lateral sclerosis.
Temporal Patterns of Emergence and Spatial Distribution of Sulcal Pits During Fetal Life
Authors: Yun Hyuk Jin , Vasung Lana , Tarui Tomo , Rollins Caitlin K , Ortinau Cynthia M , Grant P Ellen , Im Kiho 
Published: February 2020

Abstract
Sulcal pits are thought to represent the first cortical folds of primary sulci during neurodevelopment. The uniform spatial distribution of sulcal pits across individuals is hypothesized to be predetermined by a human-specific protomap which is related to functional localization under genetic controls in early fetal life. Thus, it is important to characterize temporal and spatial patterns of sulcal pits in the fetal brain that would provide additional information of functional development of the human brain and crucial insights into abnormal cortical maturation. In this paper, we investigated temporal patterns of emergence and spatial distribution of sulcal pits using 48 typically developing fetal brains in the second half of gestation. We found that the position and spatial variance of sulcal pits in the fetal brain are similar to those in the adult brain, and they are also temporally uniform against dynamic brain growth during fetal life. Furthermore, timing of pit emergence shows a regionally diverse pattern that may be associated with the subdivisions of the protomap. Our findings suggest that sulcal pits in the fetal brain are useful anatomical landmarks containing detailed information of functional localization in early cortical development and maintaining their spatial distribution throughout the human lifetime.