bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroendocrine tumours and their microenvironment
Authors: de Hosson Lotte D. , Takkenkamp Tim J. , Kats-Ugurlu Gursah , Bouma Grietje , Bulthuis Marian , de Vries Elisabeth G. E. , van Faassen Martijn , Kema Ido P. , Walenkamp Annemiek M. E. 
Published: April 2020

AbstractTumours can escape the immune system by expressing programmed death-ligand-1 (PD-L1), which allows them to bind to PD-1 on T-cells and avoid recognition by the immune system. Regulatory T-cells (Tregs), indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) also play a role in immune suppression. Knowledge about the interaction of neuroendocrine tumours (NETs) with their immune microenvironment and the role of immunotherapy in patients with NET is scarce. Here, we investigated the immune microenvironment of serotonin-producing (SP) and non-serotonin-producing NETs (NSP-NETs). Tumours of 33 patients with SP-NET and 18 patients with NSP-NET were studied. Immunohistochemical analyses were performed for PD-L1, T-cells, IDO, TDO, mismatch repair proteins (MMRp) and activated fibroblasts. PD-L1 expression was seen in < 1% of tumour and T-cells. T-cells were present in 33% of NETs, varying between 1 and 10% T-cells per high power field. IDO was expressed in tumour cells in 55% of SP-NETs and 22% of NSP-NETs (p = 0.039). TDO was expressed in stromal cells in 64% of SP-NETs and 13% of NSP-NETs (p = 0.001). No tumours had loss of MMRp. TDO-expressing stromal cells also strongly expressed α-SMA and were identified as cancer-associated fibroblasts (CAFs). Factors that are associated with a response to checkpoint inhibitor treatment were absent or only present to a limited extent in the tumour microenvironment of NETs. The expression of IDO and TDO in a substantial part of NETs and the presence of CAFs suggest two mechanisms that could be responsible for the cold immune microenvironment, which should be explored to enhance anti-tumour immunity and clinical responses.
Memento for interprofessional learning
Authors: Groenen Patricia J. T. A. , Langerak A. W. , Fend F. , van Krieken J. H. J. M. 
Published: April 2020

AbstractThe vast increase of technical, diagnostic, and treatment possibilities and deepened understanding of molecular biology has revolutionized diagnosis and treatment of cancer and thus has great impact on pathology. Different professionals are responsible for proper evaluation of the results and their translating into an accurate diagnosis and appropriate treatment. Next to expertise, a close interaction between clinical molecular biologists, pathologists, and oncologists is required; it is crucial that these professionals speak “the same language.” Key to this is communication skills and creating possibilities for collaboration in a meaningful context. Here, we present an interprofessional, educational workshop model and we describe the parameters that contribute to effective learning by specialists.
Climate change-driven elevational changes among boreal nocturnal moths
Authors: Keret Netta M. , Mutanen Marko J. , Orell Markku I. , Itämies Juhani H. , Välimäki Panu M. 
Published: April 2020

AbstractClimate change has shifted geographical ranges of species northwards or to higher altitudes on elevational gradients. These changes have been associated with increases in ambient temperatures. For ectotherms in seasonal environments, however, life history theory relies largely on the length of summer, which varies somewhat independently of ambient temperature per se. Extension of summer reduces seasonal time constraints and enables species to establish in new areas as a result of over-wintering stage reaching in due time. The reduction of time constraints is also predicted to prolong organisms’ breeding season when reproductive potential is under selection. We studied temporal change in the summer length and its effect on species’ performance by combining long-term data on the occurrence and abundance of nocturnal moths with weather conditions in a boreal location at Värriötunturi fell in NE Finland. We found that summers have lengthened on average 5 days per decade from the late 1970s, profoundly due to increasing delays in the onset of winters. Moth abundance increased with increasing season length a year before. Most of the species occurrences expanded upwards in elevation. Moth communities in low elevation pine heath forest and middle elevation mountain birch forest have become inseparable. Yet, the flight periods have remained unchanged, probably due to unpredictable variation in proximate conditions (weather) that hinders life histories from selection. We conclude that climate change-driven changes in the season length have potential to affect species’ ranges and affect the structure of insect assemblages, which may contribute to alteration of ecosystem-level processes.
The economic costs of Hurricane Harvey attributable to climate change
Authors: Frame David J. , Wehner Michael F. , Noy Ilan , Rosier Suzanne M. 
Published: April 2020

AbstractHurricane Harvey is one of the costliest tropical cyclones in history. In this paper, we use a probabilistic event attribution framework to estimate the costs associated with Hurricane Harvey that are attributable to anthropogenic influence on the climate system. Results indicate that the “fraction of attributable risk” for the rainfall from Harvey was likely about at least a third with a preferable/best estimate of three quarters. With an average estimate of damages from Harvey assessed at about US$90bn, applying this fraction gives a best estimate of US$67bn, with a likely lower bound of at least US$30bn, of these damages that are attributable to the human influence on climate. This “bottom-up” event-based estimate of climate change damages contrasts sharply with the more “top-down” approach using integrated assessment models (IAMs) or global macroeconometric estimates: one IAM estimates annual climate change damages in the USA to be in the region of US$21.3bn. While the two approaches are not easily comparable, it is noteworthy that our “bottom-up” results estimate that one single extreme weather event contributes more to climate change damages in the USA than an entire year by the “top-down” method. Given that the “top-down” approach, at best, parameterizes but does not resolve the effects of extreme weather events, our findings suggest that the “bottom-up” approach is a useful avenue to pursue in future attempts to refine estimates of climate change damages.
A case of cardiac strangulation following epicardial pacemaker implantation
Authors: Miyagi Chihiro , Ochiai Yoshie , Ando Yusuke , Hisahara Manabu , Baba Hironori , Takigawa Tomoya , Tokunaga Shigehiko 
Published: April 2020

AbstractAn 8-year-old boy had undergone permanent epicardial pacemaker implantation with a Y-shaped bipolar ventricular lead on day 6 after birth for treatment of congenital complete atrioventricular block. He was found to have pulmonary stenosis and mitral stenosis by follow-up echocardiography. Further studies including computed tomography and cardiac catheterization revealed that the pacemaker lead had completely encircled the cardiac silhouette and was in a state of “cardiac strangulation”. We removed the previous pacing leads and generator and implanted a new epicardial dual-chamber pacing system in the right atrium and right ventricle. Additionally, an expanded polytetrafluoroethylene sheet was placed between the new leads and the heart to prevent recurrence of cardiac strangulation.
Variation and change in the short vowels of Delhi English
Authors: Domange Raphaël 
Published: April 2020

AbstractAlthough the sound system of Indian English has been the object of numerous publications over the years, there has been a remarkable scarcity of variationist sociolinguistic research carried out on the topic. The present study addresses this gap by describing the short front vowels of 22 lifelong English-speaking Delhi residents born between 1948 and 1992. Focusing more specifically on variation in the relative configuration oftrap/æ/,dress/ɛ/, andkit/ɪ/, the study provides apparent-time evidence for a series of interrelated changes affecting the system. Those include an ongoing lowering of /æ/ and /ɛ/, as well as age-related variation in a previously unreported allophonic split of /ɪ/. I argue that these apparent-time patterns are amenable to an analysis in terms of chain shift, and I discuss the implications of such a claim, linking the phenomenon described to similar patterns reported in various other parts of the English-speaking world.
Integrative genomics analysis of eQTL and GWAS summary data identifies PPP1CB as a novel bone mineral density risk genes
Authors: Zhai Yu , Yu Lu , Shao Yang , Wang Jianwei 
Published: April 2020

Abstract
In recent years, multiple genome-wide association studies (GWAS) have identified numerous susceptibility variants and risk genes that demonstrate significant associations with bone mineral density (BMD). However, exploring how these genetic variants contribute risk to BMD remains a major challenge. We systematically integrated two independent expression quantitative trait loci (eQTL) data (N = 1890) and GWAS summary statistical data of BMD (N = 142,487) using Sherlock integrative analysis to reveal whether expression-associated variants confer risk to BMD. By using Sherlock integrative analysis and MAGMA gene-based analysis, we found there existed 36 promising genes, for example, PPP1CB, XBP1, and FDFT1, whose expression alterations may contribute susceptibility to BMD. Through a protein–protein interaction (PPI) network analysis, we further prioritized the PPP1CB as a hub gene that has interactions with predicted genes and BMD-associated genes. Two eSNPs of rs9309664 (PeQTL = 1.42 × 10−17 and PGWAS = 1.40 × 10−11) and rs7475 (PeQTL = 2.10 × 10−6 and PGWAS = 1.70 × 10−7) in PPP1CB were identified to be significantly associated with BMD risk. Consistently, differential gene expression analysis found that the PPP1CB gene showed significantly higher expression in low BMD samples than that in high BMD samples based on two independent expression datasets (P = 0.0026 and P = 0.043, respectively). Together, we provide a convergent line of evidence to support that the PPP1CB gene involves in the etiology of osteoporosis.
Comprehensive analysis of PPARγ agonist activities of stereo-, regio-, and enantio-isomers of hydroxyoctadecadienoic acids
Authors: Umeno Aya , Sakashita Mami , Sugino Sakiko , Murotomi Kazutoshi , Okuzawa Tsugumi , Morita Naoki , Tomii Kentaro , Tsuchiya Yuko , Yamasaki Kazuhiko , Horie Masanori , Takahara Kentaro , Yoshida Yasukazu 
Published: April 2020

AbstractHydroxyoctadecadienoic acids (HODEs) are produced by oxidation and reduction of linoleates. There are several regio- and stereo-isomers of HODE, and their concentrations in vivo are higher than those of other lipids. Although conformational isomers may have different biological activities, comparative analysis of intracellular function of HODE isomers has not yet been performed. We evaluated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ), a therapeutic target for diabetes, and analyzed PPARγ agonist activity of HODE isomers. The lowest scores for docking poses of 12 types of HODE isomers (9-, 10-, 12-, and 13-HODEs) were almost similar in docking simulation of HODEs into PPARγ ligand-binding domain (LBD). Direct binding of HODE isomers to PPARγ LBD was determined by water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiments. In contrast, there were differences in PPARγ agonist activities among 9- and 13-HODE stereo-isomers and 12- and 13-HODE enantio-isomers in a dual-luciferase reporter assay. Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products.
Immunomodulating Effects Depend on Prolactin Levels in Patients with
Hyperprolactinemia
Authors: Ernerudh Jan , Wahlberg Jeanette , Ewerman Lea , Landberg Eva , Hellberg Sandra , Hovland Mina , Sundin Anna , Jenmalm Maria C. , Ekman Bertil 
Published: April 2020

AbstractProlactin is known to have immune modulatory effects acting through the prolactin
receptor, which is present on a variety of immune cells. Certain chemokines
contribute to form the type of T helper (Th) preponderance in the immune
response. The objective of this work was to assess if hyperprolactinemia not
related to pregnancy is associated with changes in circulating levels of
chemokines and other immunological markers. In this cross sectional study, 35
patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men)
were included. Serum levels of Th1- Th2- and Th17-associated chemokines,
C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13
were assessed. The hyperprolactinemic group had significantly higher levels of
Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001),
B cell attracting CXCL13 (p=0.003), and C-reactive protein
(p<0.001) compared to controls, and these proteins were also positively
correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and
C-reactive protein were present in patients with low or moderate
hyperprolactinemia, no differences were observed at high
(>3600 mU/l) prolactin levels. To evaluate a possible
dose-associated response to prolactin, an in vitro model was used, showing
prolactin-induced increase in T-helper cell activation at moderate levels, while
activation decreased at higher levels. Hyperprolactinemia seems to have several
immunomodulatory effects and was associated with increased levels of chemokines
associated with Th2 and Th17 responses and B cell attraction. However, patients
with greatly increased prolactin had normal levels of chemokines, and in vitro,
high levels of prolactin decreased T-helper cell activation.
Adipositas und Depression in der Primärversorgung
Authors: Schwenke Maria , Löbner Margrit , Riedel-Heller Steffi , Luppa Melanie 
Published: April 2020

Zusammenfassung
Anliegen Untersuchung der Prävalenz von depressiven Störungen bei von Adipositas betroffenen Patienten einer Mitteldeutschen Allgemeinarztstichprobe.
Methoden 131 Patienten der INTERACT-Studie mit Adipositas (BMI ≥ 30); Einsatz des PHQ-9 zur Erfassung depressiver Störungen.
Ergebnisse 29 % der Patienten mit Adipositas zeigen eine Major Depression, 31 % eine subklinische depressive Störung.
Schlussfolgerung Die hohe Komorbidität von Adipositas mit depressiven Störungen auf klinischem sowie subklinischem Niveau birgt besondere Herausforderungen für die Behandlung in der Primärversorgung.
Zervikale Lymphadenitis durch atypische Mykobakterien bei Kindern mit unterschiedlichem Wohnsitz
Authors: Papatsoutsos Efstathios , Aumann Volker , Vorwerk Peter , Redlich Antje , Tammer Ina , Arens Christoph , Vorwerk Ulrich 
Published: April 2020

Zusammenfassung
Hintergrund Die atypischen Mykobakterien stellen eine inhomogene Gruppe dar. Obwohl mehr als 140 Spezies identifiziert wurden, stehen nur 25 mit der atypischen Mykobakteriose beim Menschen in Beziehung. Die häufigste Manifestation bei immunkompetenten Kindern ist die zervikale Lymphadenitis. Das Ziel der vorliegenden Arbeit ist die Korrelation des Lebensraums mit den Patientendaten und dem Krankheitsbild, die Auswertung der sonografischen Befunde und der operativen Therapiemethoden und die Erstellung eines Diagnose- und Therapiealgorithmus.
Material und Methoden Die Patienten wurden nach einer systematischen Suche in der klinischen, mikrobiologischen und pathologischen Datenbank der HNO-Klinik identifiziert. Eine statistische Analyse der Ergebnisse wurde durchgeführt.
Ergebnisse 32 Patienten wurden ausgewertet. Eine signifikante Korrelation zwischen dem Wohnort und der Manifestation oder dem Verlauf der Erkrankung konnte nicht nachgewiesen werden. Echoarme Lymphknoten mit intraglandulärer Nekrose und niedriger Durchblutung wurden bei der Mehrheit der Patienten beobachtet. Die verwendeten operativen Methoden schlossen die Abszessinzision mit Biopsie, die diagnostische Lymphadenektomie, die selektive Neck-Dissection und die laterale Parotidektomie ein. Die Rezidivrate war signifikant höher nach Abszessinzision als nach Lymphadenektomie oder selektiver Neck-Dissection.
Schlussfolgerungen Um den Einfluss des Wohnsitzes auf das Krankheitsbild deutlich zu definieren, sind größere prospektive Studien notwendig. Die sonografischen Befunde sind diagnostisch wegweisend. Eine vollständige Resektion trägt zur Diagnose und Therapie bei und stellt eine risikoarme Therapieoption dar.
Early Virus Clearance and Delayed Antibody Response in a Case of Coronavirus Disease 2019 (COVID-19) With a History of Coinfection With Human Immunodeficiency Virus Type 1 and Hepatitis C Virus
Authors: Zhao Juanjuan , Liao Xuejiao , Wang Haiyan , Wei Lanlan , Xing Mingzhao , Liu Lei , Zhang Zheng 
Published: April 2020

Abstract
The effect of host immune status on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Here, we report the first case of coronavirus disease 2019 (COVID-19) with human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus coinfection, who showed a persistently negative SARS-CoV-2 RNA test but delayed antibody response in the plasma. This case highlights the influence of HIV-1–induced immune dysfunction on early SARS-CoV-2 clearance.
Parental dependence on the nest’s spatial cues in offspring recognition decreases with nestling growth in the azure-winged magpie
Authors: Gao Li-Fang , Zhang Wen , Zhang Hai-Yang , Zhu Zhen-Qin , Zhang Xiao-Dan , Du Bo 
Published: April 2020

AbstractIn altricial birds, to address which cues are used by parents to recognize their offspring, and when they switch between cues during reproduction, it has not been well determined. In this study, we address this question in a Tibetan population of the azure-winged magpie Cyanopica cyanus, by examining the dependence of parents on a nest’s spatial position in offspring recognition. During the egg and nestling phases, azure-winged magpie nests were translocated to new positions across various distances from their original site, and parental responses to the translocated nests were investigated. Our findings show that a nest’s spatial position is not connected with the survival of its young, but might be used as a cue in parental offspring recognition. When nests are translocated to a new position within a certain distance, parents could recognize their nests and returned to resume their parenting behaviors. Parental dependence on the nest’s spatial position in offspring recognition is higher during the egg phase than during the nestling phase, and it decreases with the growth of nestlings. After nestlings reach a certain age, the nest’ s spatial position was no longer used by parents as the single cue for offspring recognition. These findings suggest that azure-winged magpies switch their cues in offspring recognition during the different stages of reproduction. After parent–offspring communication has been established, the offspring’s phenotypic traits may become a more reliable cue than the nest’s spatial position in offspring recognition.
Genital Shedding of Human Immunodeficiency Virus Type-1 (HIV) When Antiretroviral Therapy Suppresses HIV Replication in the Plasma
Authors: Bull Marta , Mitchell Caroline , Soria Jaime , Styrchak Sheila , Williams Corey , Dragavon Joan , Ryan Kevin J , Acosta Edward , Onchiri Frankline , Coombs Robert W , La Rosa Alberto , Ticona Eduardo , Frenkel Lisa M 
Published: April 2020

Abstract

Background
During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication.

Methods
ART-naive Peruvians initiating ART were observed for DS over 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points.

Results
Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas, and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit of quantification and not reproducible. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman was associated with inflammation.

Conclusions
HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.
M16-Type Metallopeptidases Are Involved in Virulence for Invasiveness and Diffusion of Leptospira interrogans and Transmission of Leptospirosis
Authors: Ge Yu-Mei , Sun Ai-Hua , Ojcius David M , Li Shi-Jun , Hu Wei-Lin , Lin Xu’ai , Yan Jie 
Published: April 2020

Abstract

Background
Leptospirosis is a global zoonotic infectious disease caused by Leptospira interrogans. The pathogen rapidly invades into hosts and diffuses from bloodstream into internal organs and excretes from urine to cause transmission of leptospirosis. However, the mechanism of leptospiral invasiveness remains poorly understood.

Methods
Proteolytic activity of M16-type metallopeptidases (Lep-MP1/2/3) of L. interrogans was determined by spectrophotometry. Expression and secretion of Lep-MP1/2/3 during infection of cells were detected by quantitative reverse-transcription polymerase chain reaction, Western blot assay, and confocal microscopy. Deletion and complementation mutants of the genes encoding Lep-MP1/2/3 were generated to determine the roles of Lep-MP1/2/3 in invasiveness using transwell assay and virulence in hamsters.

Results
Leptospira interrogans but not saprophytic Leptospira biflexa strains were detectable for Lep-MP-1/2/3-encoding genes. rLep-MP1/2/3 hydrolyzed extracellular matrix proteins, but rLep-MP1/3 displayed stronger proteolysis than rLep-MP2, with 123.179/340.136 μmol/L Km and 0.154/0.159 s-1 Kcat values. Expression, secretion and translocation of Lep-MP1/2/3 during infection of cells were increased. ΔMP1/3 but not ΔMP2 mutant presented attenuated transmigration through cell monolayers, decreased leptospiral loading in the blood, lungs, liver, kidneys, and urine, and 10/13-fold decreased 50% lethal dose and milder histopathologic injury in hamsters.

Conclusions
Lep-MP1 and 3 are involved in virulence of L. interrogans in invasion into hosts and diffusion in vivo, and transmission of leptospirosis.