bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-Related Quality of Life After the 2015 Gorkha Earthquakes, Among Older Adults Living in Lalitpur District of Central Nepal
Authors: Wagle Sabina , Amnatsatsue Kwanjai , Adhikari Bipin , Kerdmongkol Patcharaporn , Van der Putten Marc , Silpasuwan Pimpan
Published: February 2020

Objective:

Health-related quality of life (HQL) among older adults is often neglected and underprioritized in developing countries and is further burdened during natural disasters, such as earthquakes. The main objective of this study was to explore the factors affecting HQL among older adults living in Lalitpur District of Nepal.

Methods:

A total of 362 older adults participated in this study. Questionnaires were used to interview the respondents on various aspects, such as posttraumatic stress disorder (PTSD) and depression, functional ability, and social support. An analysis was made to explore the factors affecting HQL.

Results:

HQL scores ranged between 3.13 and 90.63. A majority of the respondents (215/362; 59.4%) scored ≤ 50, indicating poorer HQL. The multivariate analysis found the impact of the following factors on HQL: functional status (β = 0.295; P < 0.001), PTSD (β = −0.225; P < 0.001), chronic disease (β = −0.168; P < 0.001), social support (β = 0.120; P = 0.019), injury (β = −0.104; P = 0.024), age (β = −0.116; P < 0.001), and accessibility to resources.

Conclusion:

Poor HQL of older adults was dependent on various factors. The disaster preparedness program in Nepal needs urgent attention to address the concerns of older adults by incorporating the findings from this study.
Tobacco smoking as a risk factor for tuberculous pleural effusion: a case-control study
Authors: Tewatia Pavit , Kaushik Rajeev Mohan , Kaushik Reshma , Kumar Sanjeev
Published: February 2020

This study assessed the tobacco smoking-associated risk for tuberculous pleural effusion (TPE) in India. Ninety-two patients with TPE and 184 controls were randomly selected and assessed regarding their tobacco-smoking status and type, quantity and duration of tobacco used. Odds ratios (ORs) for the association of smoking cigarette, beedi and cigarette or beedi with TPE were 19.22 (p < 0.0001), 2.89 (p = 0.0006) and 4.57 (p < 0.0001) respectively. ORs for developing TPE increased with an increase in beedi/cigarette consumption, duration and pack years of smoking (p < 0.001 each). TPE was significantly associated with confounding risk factors viz., regular alcohol use (OR = 1.89, p = 0.019), history of contact with tuberculosis (TB) patient (OR = 8.07, p < 0.0001), past history of TB (OR = 22.31, p < 0.0001), family history of TB (OR = 9.05, p = 0.0002) and underweight (OR = 3.73, p = 0.0009). Smoking (OR = 3.07, p < 0.001), regular alcohol use (OR = 2.10, p = 0.018), history of contact with TB patient (OR = 4.01, p = 0.040), family history of TB (OR = 10.80, p = 0.001) and underweight (OR = 5.04, p < 0.001) were independently associated with TPE. Thus, both cigarette- and beedi-smoking have a significant association with TPE. The risk for TPE in tobacco smokers is dose- and duration-dependent.
Approach to the Study of the Phenomenon of Multiple Burials at El Caño, Panama
Authors: Mayo Torné Julia , Mayo Torné Carlos , Guinea Bueno Mercedes , Hervás Herrera Miguel Ángel , Herrerín López Jesus
Published: February 2020

In this article we present a study that seeks to explain the nature of, and the mortuary practices behind, the burials containing multiple individuals at the site of El Caño, Panama (part of the “Gran Coclé” archaeological tradition, ca. AD 700–1000). We set out to test our first impression of these burials as products of sumptuous funerals held upon the death of the rulers that included, among other practices, human sacrifice. With this in mind, our research aims to elucidate the status relationships between individuals, the circumstances of their deaths, and the religious and symbolic significance of their burials. The results reveal the presence of an individual of higher status within every tomb, the existence of a pattern with respect to the status of those who accompany that individual, the practice of mortuary treatments typical of sacrificial contexts, toxic substances, an iconography referring to human sacrifice, and the clear intention of using a burial as a representation of social order. Considering all this, we conclude that multiple burials at this site should be interpreted as high status. Our study highlights the practice of human sacrifice in funerary rituals linked to that status.
Paul Graham'sAmerican Nightand the Politics of Exposure
Authors: GIUDICE NICOLÓ
Published: February 2020

In his photobookAmerican Night(2003), the photographer Paul Graham evokes the passage of a walker who draws the outline of a composite and dialectic map of the American city. This article will examine how the book's structure and its division into zones is symptomatic of the explosion of the city and of its spatial, social and racial inequalities. These zones are also spaces of invisibility and visibility, of over-/perfect/under-exposure, illuminating the social/racial contrasts that underpin the urban environment and the mechanisms of their perpetuation. In this sense,American Nightultimately exposes the biopolitical struggle that underscores the American city.
Letters to a Nun: Monastic Music in Early Modern Malta
Authors: DINGLI PETRA CARUANA
Published: February 2020

This article examines the performance of music in a Maltese female Benedictine monastery in the early modern period in relation to prevailing attitudes towards monastic music and polyphony. By placing these letters in their social and cultural context, it also offers fresh insights into female literacy in early modern Malta. The discussion centres on a set of fifteen unpublished letters that provide a rare example of a woman in early eighteenth-century Malta engaged in a written exchange of theological and philosophical ideas.
Do Excess Control Rights Benefit Creditors? Evidence from Dual-Class Firms
Authors: Xu Ting
Published: February 2020

Excess control rights by inside shareholders have been documented to hurt minority shareholders. This paper shows that such governance feature may benefit creditors. Using a sample of U.S. dual-class firms, I show that these firms take less operational and financial risk than similar single-class firms, consistent with insiders’ emphasis on long-term survival to access ongoing private control benefits. Such risk avoidance translates into lower borrowing costs for dual-class firms. Further, lenders are able to use specific covenants to prevent potential expropriations by insiders. The overall relationship between excess control rights and firm value may be less negative than previously thought.
Updated ranges of the Vulnerable cheetah and Endangered African wild dog in Angola
Authors: Monterroso Pedro , Rocha Filipe , van Wyk Stefan , António Telmo , Chicomo Milcíades , Kosmas Selma , Lages Fernanda , Fabiano Ezequiel , Godinho Raquel
Published: February 2020

The civil unrest that ravaged Angola for nearly 30 years took a heavy toll on the country's wildlife, and led to a lengthy absence of reliable information for many threatened species, including the cheetah Acinonyx jubatus and African wild dog Lycaon pictus. Using camera trapping we assessed the status of these two species in two areas of southern Angola, and complemented our findings by reviewing recent survey reports and observations to provide an update on the species' status. We found unequivocal evidence that African wild dogs are resident and reproducing in Bicuar National Park, where cheetahs appear to be absent. Conversely, cheetahs may be resident in western Cuando Cubango province, where African wild dogs may only be transient. Based on these and other recent records in Angola, we recommend a revision of these species' distribution ranges and note the need for monitoring of these remnant populations and for appropriate attention to any threats.
Production and characterization of monoclonal antibodies against Toxoplasma gondii ROP18 with strain-specific reactivity
Authors: Zhang Famin , Su Rui , Han Chengjian , Wang Yang , Li Jingyang , Zhu Jinjin , Luo Qingli , Chen Lingzhi , Zhang Junling , Ding Xiaojuan , Du Jian , Chu Deyong , Cai Yihong , Shen Jilong , Yu Li
Published: February 2020

The rhoptry kinase 18 of Toxoplasma gondii (TgROP18) has been identified as a key virulence factor that allows the parasite to escape from host immune defences and promotes its proliferation in host cells. Although much research is focused on the interaction between host cells and TgROP18, the development of monoclonal antibodies (mAbs) against TgROP18 has not been reported till date. To produce mAbs targeting TgROP18, two hybridomas secreting mAbs against TgROP18, designated as A1 and T2, were generated using cell fusion technology. The subtypes of the A1 and T2 mAbs were identified as IgG3 λ and IgM κ, and peptide scanning revealed that the core sequences of the antigenic epitopes were 180LRAQRRRSELVFE192 and 351NYFLLMMRAEADM363, respectively. The T2 mAb specifically reacted with both T. gondii type I and Chinese I, but not with T. gondii type II, Plasmodium falciparum or Schistosoma japonicum. Finally, the sequences of heavy chain and light chain complementarity-determining regions of T2 were amplified, cloned and characterized, making the modification of the mAb feasible in the future. The development of mAbs against TgROP18 would aid the investigation of the molecular mechanisms underlying the modulation of host cellular functions by TgROP18, and in the development of strategies to diagnose and treat Toxoplasmosis.
Ascarids exposed: a method for in vitro drug exposure and gene expression analysis of anthelmintic naïve Parascaris spp
Authors: Scare J. A. , Dini P. , Norris J. K. , Steuer A. E. , Scoggin K. , Gravatte H. S. , Howe D. K. , Slusarewicz P. , Nielsen M. K.
Published: February 2020

Ascarid parasites infect a variety of hosts and regular anthelmintic treatment is recommended for all species. Parascaris spp. is the only ascarid species with widespread anthelmintic resistance, which allows for the study of resistance mechanisms. The purpose of this study was to establish an in vitro drug exposure protocol for adult anthelmintic-naïve Parascaris spp. and report a preliminary transcriptomic analysis in response to drug exposure. Live worms were harvested from foal necropsies and maintained in RPMI-1640 at 37 °C. Serial dilutions of oxibendazole (OBZ) and ivermectin (IVM) were prepared for in vitro drug exposure, and worm viability was monitored over time. In a second drug trial, worms were used for transcriptomic analysis. The final drug concentrations employed were OBZ at 40.1 μm (10 μg mL−1) and IVM at 1.1 μm (1 μg mL−1) for 24 and 3 h, respectively. The RNA-seq analysis revealed numerous differentially expressed genes, with some being potentially related to drug detoxification and regulatory mechanisms. This report provides a method for in vitro drug exposure and the phenotypic responses for Parascaris spp., which could be extrapolated to other ascarid parasites. Finally, it also provides preliminary transcriptomic data following drug exposure as a reference point for future studies of Parascaris spp.
The Scope of Possibilities for User Influence in Norwegian Municipal Care Services
Authors: ANDERSEN JAN
Published: February 2020

The importance of service-user participation has been growing in the care services, but what possibilities do service users have to influence these services? This article analyses how structural factors have an impact on the scope of possibilities for user influence in care services, especially with respect to how established structures and frameworks determine users’ opportunities to influence both the allocation and the provision of services. A study of five Norwegian municipalities where managers at different levels and within different areas of the services have been interviewed forms the basis of the empirical material. In the managers’ general opinion, over time there has been a stronger individual adjustment of the services and stronger user influence over both the allocation and the provision of services. However, if we look more closely at the service-delivery process, several structural factors limiting the scope of possibilities for user influence become apparent. These factors are discussed in light of different user typologies.
Enacting policies in digital health: a case for smart legal contracts and distributed ledgers?
Authors: Milosevic Zoran
Published: February 2020

This paper presents an approach for the enactment of policies in digital health based on our earlier work on the implementation of digital contracts in distributed systems. A formal policy model and an abstract policy language for the expression of healthcare policies are first proposed, leveraging the semantics of the ISO Reference Model for Open Distributed Processing enterprise language standard. Healthcare consent policies included in the HL7 Fast Health Interoperability Resource (FHIR®) standard are used to illustrate the modelling approach. Several distributed ledger and smart legal contract options were considered next as target platforms for implementation. Their benefits are highlighted along with considerations on their use reflecting business concerns of risk, trust and cost.
Four-Dimensional Trajectory Generation for UAVs Based on Multi-Agent Q Learning
Authors: Zhao Wenjie , Fang Zhou , Yang Zuqiang
Published: February 2020

A distributed four-dimensional (4D) trajectory generation method based on multi-agent Q learning is presented for multiple unmanned aerial vehicles (UAVs). Based on this method, each vehicle can intelligently generate collision-free 4D trajectories for time-constrained cooperative flight tasks. For a single UAV, the 4D trajectory is generated by the bionic improved tau gravity guidance strategy, which can synchronously guide the position and velocity to the desired values at the arrival time. Furthermore, to optimise trajectory parameters, the continuous state and action wire fitting neural network Q (WFNNQ) learning method is applied. For multi-UAV applications, the learning is organised by the win or learn fast-policy hill climbing (WoLF-PHC) algorithm. Dynamic simulation results show that the proposed method can efficiently provide 4D trajectories for the multi-UAV system in challenging simultaneous arrival tasks, and the fully trained method can be used in similar trajectory generation scenarios.
Using image-to-text recognition technology to facilitate vocabulary acquisition in authentic contexts
Authors: Shadiev Rustam , Wu Ting-Ting , Huang Yueh-Min
Published: February 2020

A vocabulary acquisition learning activity was designed and a learning system featuring image-to-text recognition technology to support the activity was developed. The effectiveness of the system with regard to facilitating vocabulary acquisition was tested. The perceptions of learners toward this tool and the affordances of the system for vocabulary acquisition were also explored. To this end, we designed an experiment in which 40 native speakers of Russian learning English as a foreign language from an elementary school participated. They were assigned to either a control condition or an experimental condition. All learners learned new vocabulary in class and then applied their new knowledge to contexts with a realistic simulation of the real world by completing a learning task. The learners in the control group used a traditional approach (e.g. the learners learned vocabulary from corresponding pictures in a textbook), whereas the learners in the experimental group used the proposed learning system (e.g. the learners learned vocabulary using the system). A pre-test–post-test/delayed post-test design was employed to test the effectiveness of the treatment on vocabulary acquisition. Learner perceptions and perceived affordances of the system for vocabulary acquisition were explored through a questionnaire survey and interviews. The quantitative results showed that the learners in the experimental group outperformed their counterparts on both the vocabulary post-test and delayed post-test. The qualitative results revealed that most learners in the experimental group had positive perceptions of the system. In addition, the qualitative results showed the three main categories of affordances. Based on these results, several suggestions and implications are provided for the teaching and research community.
‘SALAMELICA’: NEW THOUGHTS ON VOLPINO AND HIS ARIA IN ACT III OF LO SPEZIALE
Authors: MAYES CATHERINE
Published: February 2020

Recently, as I was doing research for a project on eighteenth-century dances, I came across the following entry in Charles Compan's Dictionnaire de danse (1787):

Salamalec. Salut à la Turque, qui signifie, Dieu vous garde. On s'est servi longtems à Paris de cette expression, pour saluer une personne en buvant à sa santé. Salamalec, ou, comme prononcent les Turcs, Selamalec, n'est pas seulement une salutation des Turcs, mais encore des Arabes, & même de tous les peuples Mahométans.

Salamalec. Turkish greeting meaning ‘May God keep you’. This expression has long been used in Paris as a toast when drinking to someone's health. ‘Salamalec’, or as the Turks pronounce it, ‘Selamalec’, is not only a greeting of the Turks, but of Arabs and even of all Muslim peoples.
Merkmalsintegration und Abruf als wichtige Prozesse der Handlungssteuerung – eine Paradigmen-übergreifende Perspektive
Authors: Frings Christian , Koch Iring , Rothermund Klaus , Dignath David , Giesen Carina , Hommel Bernhard , Kiesel Andrea , Kunde Wilfried , Mayr Susanne , Moeller Birte , Möller Malte , Pfister Roland , Philipp Andrea
Published: February 2020

Zusammenfassung. Die Kognitionspsychologische Grundlagenforschung zur Handlungskontrolle hat inzwischen eine große Zahl sehr spezifischer Aspekte von Handlungen in diversen Experimentalparadigmen isoliert und beleuchtet, sodass der gegenwärtige Forschungsstand durch eine kaum übersehbare Flut unverbundener Phänomene und paradigmen-spezifischer Modellvorstellungen gekennzeichnet ist. In dem hier vorgeschlagenen Rahmenmodell ( Binding and Retrieval in Action Control, BRAC) werden die für Handlungen wichtigsten Prozesse paradigmen-übergreifend beschrieben, systematisch eingeordnet und in ein Rahmenmodell transferiert, bei dem Merkmalsintegration und Merkmalsabruf als wichtige Mechanismen der Handlungssteuerung dienen. Wir zeigen exemplarisch auf, wie das Rahmenmodell etablierte, aber bislang unabhängig voneinander untersuchte Phänomene der Handlungs-Forschung mithilfe derselben Mechanismen erklärt. Dieses Modell birgt neben seiner Ordnungs- und Integrationsfunktion die Möglichkeit, Phänomen auch aus anderen Forschungskontexten in der Sprache des Modells zu reformulieren. Das Modell soll Wissen aus der Kognitionsforschung bzw. Allgemeinen Psychologie innovativ kondensieren und anderen Disziplinen zur Verfügung stellen.
High Injection Rates Counteract Formation of Far‐Reaching Fluid Migration Pathways at The Geysers Geothermal Field
Authors: Lasocki Stanisław , Orlecka‐Sikora Beata
Published: February 2020

Deep underground water injections induce seismicity. When the seismic fractures coalesce into far‐reaching pathways for fluid migration, the migrating fluid may reach preexisting faults and, by decreasing fault strength, can trigger major seismic events. We assume that the potential for building such pathways depends on closeness of hypocenters, similarity of fracture planes orientations, and closeness of radii taking off from the injection point, on which events locate. We define this potential as the average distance between seismic events in the space of parameters quantifying the above conditions. We show that in the studied case from The Geysers geothermal field, this potential is highly correlated with injection rate. When the overall level of injection rate is high, the higher the injection rate is, the more the potential for building far‐reaching pathways for fluid migration is reduced.
Accommodation of East African Rifting Across the Turkana Depression
Authors: Knappe E. , Bendick R. , Ebinger C. , Birhanu Y. , Lewi E. , Floyd M. , King R. , Kianji G. , Mariita N. , Temtime T. , Waktola B. , Deresse B. , Musila M. , Kanoti J. , Perry M.
Published: February 2020

Geodetic observations in the Turkana Depression of southern Ethiopia and northern Kenya constrain the kinematic relay of extension from a single rift in Ethiopia to parallel rifts in Kenya and Uganda. Global Position System stations in the region record approximately 4.7 mm/year of total eastward extension, consistent with the ITRF14 Euler pole for Nubia‐Somalia angular velocity. Extension is partitioned into high strain rates on localized structures and lower strain rates in areas of elevated topography, as across the Ethiopian Plateau. Where high topography is absent, extension is relayed between the Main Ethiopian Rift and the Eastern Rift across the Turkana Depression exclusively through localized extension on and immediately east of Lake Turkana (up to 0.2 microstrain/year across Lake Turkana). The observed scaling and location of active extension in the Turkana Depression are inconsistent with mechanical models predicting distributed stretching due to either inherited lithospheric weakness or reactivated structures oblique to the present‐day extension direction.
Early Ground‐Based Work by Auroral Pioneer Carl Størmer on the High‐Altitude Detached Subauroral Arcs Now Known as “STEVE”
Authors: Hunnekuhl Michael , MacDonald Elizabeth
Published: February 2020

STEVE (Strong Thermal Emission Velocity Enhancement) phenomenon related structures have received much attention from space weather audiences in recent years. MacDonald et al. (2018, https://doi.org/10.1126/sciadv.aaq0030), reports on a link between these ionospheric structures and the subauroral ion drift for the first time. This commentary summarizes previously overlooked observations of a distinct type of detached subauroral arc by the aurora pioneer Carl Størmer in Norway between 1911 and 1940, including coordinated simultaneous multistation‐based altitude measurements. This commentary points out that his phenomenological descriptions and height measurements show a striking resemblance to modern descriptions and measurements of STEVE.
Controls on Rift Faulting in the North Basin of the Malawi (Nyasa) Rift, East Africa
Authors: Shillington Donna J. , Scholz Christopher A. , Chindandali Patrick R. N. , Gaherty James B. , Accardo Natalie J. , Onyango Evans , Ebinger Cynthia J. , Nyblade Andrew A.
Published: February 2020

The North Basin of the Malawi Rift is an active, early‐stage rift segment that provides the opportunity to quantify cumulative and recent faulting patterns in a young rift, assess contributions of intrarift faults to accommodating rift opening, and examine controls on spatial patterns of faulting. Multichannel seismic reflection data acquired in Lake Malawi (Nyasa) in 2015 together with legacy multichannel seismic data image a system of synthetic intrarift faults within this border‐fault‐bounded, half‐graben basin. A dense wide‐angle seismic reflection/refraction dip profile acquired with lake bottom seismometer data constrains sediment velocities that are used to convert fault throws from travel time to depth. Observed extension on intrarift faulting in the northern and central parts of the North Basin is approximately twice what would be predicted for hanging wall flexure, implying that the intrarift faults contribute to basin opening. The cumulative throw on intrarift faults is higher in the northern part of the rift segment than the south and is anticorrelated with throw on the border fault, which is largest in the southern part of the North Basin. This change in faulting coincides with a change in the orientation of the North Basin from a N‐S trend in the south to a NNW‐SSE trend in the north. We infer that the distribution of extension is influenced by rift orientation with respect to the regional extension direction. Almost all intrarift faults substantially offset late Quaternary synrift sediments, suggesting they are likely active and need to be considered in hazard assessments.
A CRHR1 antagonist prevents synaptic loss and memory deficits in a trauma-induced delirium-like syndrome
Authors: Cursano Silvia , Battaglia Chiara R. , Urrutia-Ruiz Carolina , Grabrucker Stefanie , Schön Michael , Bockmann Jürgen , Braumüller Sonja , Radermacher Peter , Roselli Francesco , Huber-Lang Markus , Boeckers Tobias M.
Published: February 2020

Older patients with severe physical trauma are at high risk of developing neuropsychiatric syndromes with global impairment of cognition, attention, and consciousness. We employed a thoracic trauma (TxT) mouse model and thoroughly analyzed age-dependent spatial and temporal posttraumatic alterations in the central nervous system. Up to 5 days after trauma, we observed a transient 50% decrease in the number of excitatory synapses specifically in hippocampal pyramidal neurons accompanied by alterations in attention and motor activity and disruption of contextual memory consolidation. In parallel, hippocampal corticotropin-releasing hormone (CRH) expression was highly upregulated, and brain-derived neurotrophic factor (BDNF) levels were significantly reduced. In vitro experiments revealed that CRH application induced neuronal autophagy with rapid lysosomal degradation of BDNF via the NF-κB pathway. The subsequent synaptic loss was rescued by BDNF as well as by specific NF-κB and CRH receptor 1 (CRHR1) antagonists. In vivo, the chronic application of a CRHR1 antagonist after TxT resulted in reversal of the observed histological, molecular, and behavioral alterations. The data suggest that neuropsychiatric syndromes (i.e., delirium) after peripheral trauma might be at least in part due to the activation of the hippocampal CRH/NF-κB/BDNF pathway, which results in a dramatic loss of synaptic contacts. The successful rescue by stress hormone receptor antagonists should encourage clinical trials focusing on trauma-induced delirium and/or other posttraumatic syndromes.
Glial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids
Authors: Dang Jason , Tiwari Shashi Kant , Agrawal Kriti , Hui Hui , Qin Yue , Rana Tariq M.
Published: February 2020

Methamphetamine (METH) is a potent stimulant that induces a euphoric state but also causes cognitive impairment, neurotoxicity and neurodevelopmental deficits. Yet, the molecular mechanisms by which METH causes neurodevelopmental defects have remained elusive. Here we utilized human cerebral organoids and single-cell RNA sequencing (scRNA-seq) to study the effects of prenatal METH exposure on fetal brain development. We analyzed 20,758 cells from eight untreated and six METH-treated cerebral organoids and found that the organoids developed from embryonic stem cells contained a diverse array of glial and neuronal cell types. We further identified transcriptionally distinct populations of astrocytes and oligodendrocytes within cerebral organoids. Treatment of organoids with METH-induced marked changes in transcription in multiple cell types, including astrocytes and neural progenitor cells. METH also elicited novel astrocyte-specific gene expression networks regulating responses to cytokines, and inflammasome. Moreover, upregulation of immediate early genes, complement factors, apoptosis, and immune response genes suggests a neuroinflammatory program induced by METH regulating neural stem cell proliferation, differentiation, and cell death. Finally, we observed marked METH-induced changes in neuroinflammatory and cytokine gene expression at the RNA and protein levels. Our data suggest that human cerebral organoids represent a model system to study drug-induced neuroinflammation at single-cell resolution.
Alternative promoters control UGT2B17-dependent androgen catabolism in prostate cancer and its influence on progression
Authors: Lévesque Eric , Labriet Adrien , Hovington Hélène , Allain Éric P. , Melo-Garcia Luciana , Rouleau Michèle , Brisson Hervé , Turcotte Véronique , Caron Patrick , Villeneuve Lyne , Leclercq Mickaël , Droit Arnaud , Audet-Walsh Etienne , Simonyan David , Fradet Yves , Lacombe Louis , Guillemette Chantal
Published: February 2020

Background

Perturbation of the major UGT2B17-dependent androgen catabolism pathway has the potential to affect prostate cancer (PCa) progression. The objective was to evaluate UGT2B17 protein expression in primary tumours in relation to hormone levels, disease characteristics and cancer evolution.

Methods

We conducted an analysis of a high-density prostate tumour tissue microarray consisting of 239 localised PCa cases treated by radical prostatectomy (RP). Cox proportional hazard ratio analysis was used to evaluate biochemical recurrence (BCR), and a linear regression model evaluated variations in circulating hormone levels measured by mass spectrometry. The transcriptome of UGT2B17 in PCa was established by using RNA-sequencing data.

Results

UGT2B17 expression in primary tumours was associated with node-positive disease at RP and linked to circulating levels of 3α-diol-17 glucuronide, a major circulating DHT metabolite produced by the UGT2B17 pathway. UGT2B17 was an independent prognostic factor linked to BCR after RP, and its overexpression was associated with development of metastasis. Finally, we demonstrated that distinctive alternative promoters dictate UGT2B17-dependent androgen catabolism in localised and metastatic PCa.

Conclusions

The androgen-inactivating gene UGT2B17 is controlled by overlooked regulatory regions in PCa. UGT2B17 expression in primary tumours influences the steroidome, and is associated with relevant clinical outcomes, such as BCR and metastasis.
Blocking the autocrine regulatory loop of Gankyrin/STAT3/CCL24/CCR3 impairs the progression and pazopanib resistance of clear cell renal cell carcinoma
Authors: Wang Chao , Wang Yuning , Hong Tianyu , Cheng Bing , Gan Sishun , Chen Linbao , Zhang Jing , Zuo Li , Li Jian , Cui Xingang
Published: February 2020

The poor prognosis of clear-cell renal cell carcinoma (ccRCC) patients is due to progression and targeted drug resistance, but the underlying molecular mechanisms need further elucidation. This study examined the biological function and related mechanisms of gankyrin in ccRCC based on the results of our previous study. To this end, in vitro functional experiments; in vivo models of subcutaneous tumor formation, lung metastasis, and orthotopic ccRCC; and antibody chip detection, co-IP, ChIP assays were performed to examine the biological role and molecular mechanisms of gankyrin in ccRCC. Two hundred fifty-six ccRCC patients were randomly divided into training and validation cohorts to examine the prognostic value of gankyrin and other markers through IHC and statistical analyses. We observed that the gankyrin-overexpressing ccRCC cell lines 786-O and 769-P exhibited increased proliferation, invasion, migration, tumorigenicity, and pazopanib resistance and decreased apoptosis, while gankyrin knockdown achieved the opposite results. Mechanistically, gankyrin recruited STAT3 via direct binding, and STAT3 binding to the CCL24 promoter promoted its expression. Reciprocally, an increase in autocrine CCL24 enhanced the expression of gankyrin and STAT3 activation via CCR3 in ccRCC, forming a positive autocrine-regulatory loop. Furthermore, in vivo experimental results revealed that blocking the positive loop through gankyrin knockdown or treatment with the CCR3 inhibitor SB328437 reversed the resistance to pazopanib and inhibited lung metastasis in ccRCC. Moreover, a positive correlation between gankyrin and STAT3 or CCL24 expression in ccRCC specimens was observed, and improved accuracy for ccRCC patient prognosis was achieved by combining gankyrin and STAT3 or CCL24 expression with existing clinical prognostic indicators, including the TNM stage and SSIGN score. In summary, targeting the gankyrin/STAT3/CCL24/CCR3 autocrine-regulatory loop may serve as a remedy for patients with advanced ccRCC, and combining gankyrin and STAT3 or CCL24 expression with the current clinical indicators better predicts ccRCC patient prognosis.
Tripartite phase separation of two signal effectors with vesicles priming B cell responsiveness
Authors: Wong Leo E. , Bhatt Arshiya , Erdmann Philipp S. , Hou Zhen , Maier Joachim , Pirkuliyeva Sona , Engelke Michael , Becker Stefan , Plitzko Jürgen , Wienands Jürgen , Griesinger Christian
Published: February 2020

Antibody-mediated immune responses rely on antigen recognition by the B cell antigen receptor (BCR) and the proper engagement of its intracellular signal effector proteins. Src homology (SH) 2 domain-containing leukocyte protein of 65 kDa (SLP65) is the key scaffold protein mediating BCR signaling. In resting B cells, SLP65 colocalizes with Cbl-interacting protein of 85 kDa (CIN85) in cytoplasmic granules whose formation is not fully understood. Here we show that effective B cell activation requires tripartite phase separation of SLP65, CIN85, and lipid vesicles into droplets via vesicle binding of SLP65 and promiscuous interactions between nine SH3 domains of the trimeric CIN85 and the proline-rich motifs (PRMs) of SLP65. Vesicles are clustered and the dynamical structure of SLP65 persists in the droplet phase in vitro. Our results demonstrate that phase separation driven by concerted transient interactions between scaffold proteins and vesicles is a cellular mechanism to concentrate and organize signal transducers.
Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma
Authors: Galvani Elena , Mundra Piyushkumar A. , Valpione Sara , Garcia-Martinez Pablo , Smith Matthew , Greenall Jonathan , Thakur Rohit , Helmink Beth , Andrews Miles C. , Boon Louis , Chester Christopher , Gremel Gabriela , Hogan Kate , Mandal Amit , Zeng Kang , Banyard Antonia , Ashton Garry , Cook Martin , Lorigan Paul , Wargo Jennifer A. , Dhomen Nathalie , Marais Richard
Published: February 2020

Although immune checkpoint inhibitors (ICIs) have achieved unprecedented results in melanoma, the biological features of the durable responses initiated by these drugs remain unknown. Here we show the genetic and phenotypic changes induced by treatment with programmed cell death-1 (PD-1) blockade in a genetically engineered mouse model of melanoma driven by oncogenic BRAF. In this controlled system anti-PD-1 treatment yields responses in ~35% of the tumors, and prolongs survival in ~27% of the animals. We identify increased stroma remodeling and reduced expression of proliferation markers as features associated with prolonged response. These traits are corroborated in two independent early on-treatment anti-PD-1 melanoma patient cohorts. These insights into the biological responses of tumors to ICI provide a strategy for identification of durable response early during the course of treatment and could improve patient stratification for checkpoint inhibitory drugs.
Edge-driven nanomembrane-based vertical organic transistors showing a multi-sensing capability
Authors: Nawaz Ali , Merces Leandro , de Andrade Denise M. , de Camargo Davi H. S. , Bof Bufon Carlos C.
Published: February 2020

The effective utilization of vertical organic transistors in high current density applications demands further reduction of channel length (given by the thickness of the organic semiconducting layer and typically reported in the 100 nm range) along with the optimization of the source electrode structure. Here we present a viable solution by applying rolled-up metallic nanomembranes as the drain-electrode (which enables the incorporation of few nanometer-thick semiconductor layers) and by lithographically patterning the source-electrode. Our vertical organic transistors operate at ultra-low voltages and demonstrate high current densities (~0.5 A cm−2) that are found to depend directly on the number of source edges, provided the source perforation gap is wider than 250 nm. We anticipate that further optimization of device structure can yield higher current densities (~10 A cm−2). The use of rolled-up drain-electrode also enables sensing of humidity and light which highlights the potential of these devices to advance next-generation sensing technologies.
Light intensity-induced photocurrent switching effect
Authors: Podborska Agnieszka , Suchecki Maciej , Mech Krzysztof , Marzec Mateusz , Pilarczyk Kacper , Szaciłowski Konrad
Published: February 2020

A better control over processes responsible for the photocurrent generation in semiconductors and nanocomposites is essential in the fabrication of photovoltaic devices, efficient photocatalysts and optoelectronic elements. Therefore, new approaches towards photochemical properties tuning are intensively searched for. Among numerous parameters, the photocurrent polarity is of great importance to the overall performance of a device. Usually, the polarity is controlled through an alignment of electronic states/bands, tailoring of applied potential or suitable selection of incident light wavelengths. In most scenarios though, the influence of light intensity is somehow neglected and either some arbitrarily chosen, natural conditions are mimicked or this parameter is varied only in a narrow range. Here we present a ternary nanocomposite in which the persistent photocurrent polarity switching is achieved through changes in the light intensity. We also present arguments suggesting this behaviour is of a general character and should be considered also in other photochemical systems.
A 12-lead electrocardiogram database for arrhythmia research covering more than 10,000 patients
Authors: Zheng Jianwei , Zhang Jianming , Danioko Sidy , Yao Hai , Guo Hangyuan , Rakovski Cyril
Published: February 2020

This newly inaugurated research database for 12-lead electrocardiogram signals was created under the auspices of Chapman University and Shaoxing People’s Hospital (Shaoxing Hospital Zhejiang University School of Medicine) and aims to enable the scientific community in conducting new studies on arrhythmia and other cardiovascular conditions. Certain types of arrhythmias, such as atrial fibrillation, have a pronounced negative impact on public health, quality of life, and medical expenditures. As a non-invasive test, long term ECG monitoring is a major and vital diagnostic tool for detecting these conditions. This practice, however, generates large amounts of data, the analysis of which requires considerable time and effort by human experts. Advancement of modern machine learning and statistical tools can be trained on high quality, large data to achieve exceptional levels of automated diagnostic accuracy. Thus, we collected and disseminated this novel database that contains 12-lead ECGs of 10,646 patients with a 500 Hz sampling rate that features 11 common rhythms and 67 additional cardiovascular conditions, all labeled by professional experts. The dataset consists of 10-second, 12-dimension ECGs and labels for rhythms and other conditions for each subject. The dataset can be used to design, compare, and fine-tune new and classical statistical and machine learning techniques in studies focused on arrhythmia and other cardiovascular conditions.
Population genetics of the European rabbit along a rural-to-urban gradient
Authors: Ziege Madlen , Theodorou Panagiotis , Jüngling Hannah , Merker Stefan , Plath Martin , Streit Bruno , Lerp Hannes
Published: February 2020

The European rabbit (Oryctolagus cuniculus) is declining in large parts of Europe but populations in some German cities remained so far unaffected by this decline. The question arises of how urbanization affects patterns of population genetic variation and differentiation in German rabbit populations, as urban habitat fragmentation may result in altered meta-population dynamics. To address this question, we used microsatellite markers to genotype rabbit populations occurring along a rural-to-urban gradient in and around the city of Frankfurt, Germany. We found no effect of urbanization on allelic richness. However, the observed heterozygosity was significantly higher in urban than rural populations and also the inbreeding coefficients were lower, most likely reflecting the small population sizes and possibly on-going loss of genetic diversity in structurally impoverished rural areas. Global FST and G′ST-values suggest moderate but significant differentiation between populations. Multiple matrix regression with randomization ascribed this differentiation to isolation-by-environment rather than isolation-by-distance. Analyses of migration rates revealed asymmetrical gene flow, which was higher from rural into urban populations than vice versa and may again reflect intensified agricultural land-use practices in rural areas. We discuss that populations inhabiting urban areas will likely play an important role in the future distribution of European rabbits.
Novel liver fibrosis model in Macaca fascicularis induced by thioacetamide
Authors: Matsuo Megumi , Murata Soichiro , Hasegawa Shunsuke , Hatada Yumi , Ohtsuka Masayuki , Taniguchi Hideki
Published: February 2020

Although transplantation is the only definitive treatment for liver cirrhosis, there remains a shortage of donors, necessitating that novel treatments be developed. We aimed to establish a liver fibrosis model in Macaca fascicularis that can help accelerate preclinical research. Liver fibrosis was induced by administering thioacetamide (TAA) and carbon tetrachloride (CCl4). Analysis of residual liver function and fibrosis progression was based on clinical indices, such as the Child–Pugh score or fibrotic markers, besides histology. TAA-induced marked fibrosis, whereas CCl4 did not induce fibrosis. Concerning residual liver function, both of TAA and CCl4 worsened the indices of the Child–Pugh score, but only the TAA model increased the retention ratio of indocyanine green. The TAA-induced fibrosis model in Macaca fascicularis worsens fibrosis and residual liver function, mimicking Child–Pugh grade B. Given that our model was evaluated by clinical indices, it could be applicable to preclinical research.
Model-based Comparisons of the Abundance Dynamics of Bacterial Communities in Two Lakes
Authors: Dam Phuongan , Rodriguez-R Luis M. , Luo Chengwei , Hatt Janet , Tsementzi Despina , Konstantinidis Konstantinos T. , Voit Eberhard O.
Published: February 2020

Lake Lanier (Georgia, USA) is home to more than 11,000 microbial Operational Taxonomic Units (OTUs), many of which exhibit clear annual abundance patterns. To assess the dynamics of this microbial community, we collected time series data of 16S and 18S rRNA gene sequences, recovered from 29 planktonic shotgun metagenomic datasets. Based on these data, we constructed a dynamic mathematical model of bacterial interactions in the lake and used it to analyze changes in the abundances of OTUs. The model accounts for interactions among 14 sub-communities (SCs), which are composed of OTUs blooming at the same time of the year, and three environmental factors. It captures the seasonal variations in abundances of the SCs quite well. Simulation results suggest that changes in water temperature affect the various SCs differentially and that the timing of perturbations is critical. We compared the model results with published results from Lake Mendota (Wisconsin, USA). These comparative analyses between lakes in two very different geographical locations revealed substantially more cooperation and less competition among species in the warmer Lake Lanier than in Lake Mendota.
EEG microstates associated with intra- and inter-subject alpha variability
Authors: Croce Pierpaolo , Quercia Angelica , Costa Sergio , Zappasodi Filippo
Published: February 2020

Variation of the magnitude of posterior alpha rhythm (8–12 Hz) has functional and behavioural effects in sensory processing and cognitive performances. Electrical brain activity, as revealed by electroencephalography (EEG), can be represented by a sequence of microstates of about 40–120 ms duration, in which distributed neural pools are synchronously active and generate stable spatial potential topographies on the scalp. Microstate dynamics may reflect transitions between global states characterized by selective inhibition of specific intra-cortical regions, mediated by alpha activity. We investigated the intra-subject and inter-subject relationship between microstate features and alpha band. High-density EEG signals were acquired in 29 healthy subjects during ten minutes of eyes closed rest. Individual EEG signal epochs were classified into four groups depending on the amount of occipital alpha power, and microstate metrics (duration, coverage and frequency of occurrence) were calculated and compared across groups. Correlations between alpha power and microstate metrics between individuals were also performed. To assess if microstate parameter variations are specific for the alpha band, the same analysis was also performed for theta and beta bands, as well as for global field power. We observed an increase in the metrics of microstate, previously associated to the visual system, with the level of intra-subject amplitude alpha oscillations, together with lower coverage of microstate associated with executive attention network and a higher frequency of microstate associated with task negative network. Other modulation effects of broad-band EEG power level on microstate metrics were observed. These effects are not specific for the alpha band, since they can equally be attributed to fluctuations in other frequency bands. We can interpret our results as a regulation mechanism mediated by posterior alpha level, dynamically interacting with other frequency bands, responsible for the switching between active areas.
Poor resolution at the back of the tongue is the bottleneck for spatial pattern recognition
Authors: Pamir Zahide , Canoluk M. Umut , Jung Jae-Hyun , Peli Eli
Published: February 2020

Spatial patterns presented on the tongue using electro-tactile sensory substitution devices (SSDs) have been suggested to be recognized better by tracing the pattern with the tip of the tongue. We examined if the functional benefit of tracing is overcoming the poor sensitivity or low spatial resolution at the back of the tongue or alternatively compensating for limited information processing capacity by fixating on a segment of the spatial pattern at a time. Using a commercially available SSD, the BrainPort, we compared letter recognition performance in three presentation modes; tracing, static, and drawing. Stimulation intensity was either constant or increased from the tip to the back of the tongue to partially compensate for the decreasing sensitivity. Recognition was significantly better for tracing, compared to static and drawing conditions. Confusion analyses showed that letters were confused based on their characteristics presented near the tip in static and drawing conditions. The results suggest that recognition performance is limited by the poor spatial resolution at the back of the tongue, and tracing seems to be an effective strategy to overcome this. Compensating for limited information processing capacity or poor sensitivity by drawing or increasing intensity at the back, respectively, does not improve the performance.