bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of a morphine-conditioned place preference does not change the size of evoked potentials in the ventral hippocampus–nucleus accumbens projection
Authors: Sakae D. Y. , Martin S. J. 
Published: March 2019

AbstractIn opioid addiction, cues and contexts associated with drug reward can be powerful triggers for drug craving and relapse. The synapses linking ventral hippocampal outputs to medium spiny neurons of the accumbens may be key sites for the formation and storage of associations between place or context and reward, both drug-related and natural. To assess this, we implanted rats with electrodes in the accumbens shell to record synaptic potentials evoked by electrical stimulation of the ventral hippocampus, as well as continuous local-field-potential activity. Rats then underwent morphine-induced (10 mg/kg) conditioned-place-preference training, followed by extinction. Morphine caused an acute increase in the slope and amplitude of accumbens evoked responses, but no long-term changes were evident after conditioning or extinction of the place preference, suggesting that the formation of this type of memory does not lead to a net change in synaptic strength in the ventral hippocampal output to the accumbens. However, analysis of the local field potential revealed a marked sensitization of theta- and high-gamma-frequency activity with repeated morphine administration. This phenomenon may be linked to the behavioral changes—such as psychomotor sensitization and the development of drug craving—that are associated with chronic use of addictive drugs.
Automated tumour budding quantification by machine learning augments TNM staging in muscle-invasive bladder cancer prognosis
Authors: Brieu Nicolas , Gavriel Christos G. , Nearchou Ines P. , Harrison David J. , Schmidt Günter , Caie Peter D. 
Published: March 2019

AbstractTumour budding has been described as an independent prognostic feature in several tumour types. We report for the first time the relationship between tumour budding and survival evaluated in patients with muscle invasive bladder cancer. A machine learning-based methodology was applied to accurately quantify tumour buds across immunofluorescence labelled whole slide images from 100 muscle invasive bladder cancer patients. Furthermore, tumour budding was found to be correlated to TNM (p = 0.00089) and pT (p = 0.0078) staging. A novel classification and regression tree model was constructed to stratify all stage II, III, and IV patients into three new staging criteria based on disease specific survival. For the stratification of non-metastatic patients into high or low risk of disease specific death, our decision tree model reported that tumour budding was the most significant feature (HR = 2.59, p = 0.0091), and no clinical feature was utilised to categorise these patients. Our findings demonstrate that tumour budding, quantified using automated image analysis provides prognostic value for muscle invasive bladder cancer patients and a better model fit than TNM staging.
Synergistic improvement in spring maize yield and quality with micro/nanobubbles water oxygation
Authors: Zhou Yunpeng , Li Yunkai , Liu Xiujuan , Wang Keyuan , Muhammad Tahir 
Published: March 2019

AbstractSoil oxygen shortages in root areas have negative effects on crop growth and decrease crops yield and quality, and soil hypoxia conditions will be aggravated by application of subsurface drip irrigation (SDI). A two-year field experiment was conducted to evaluate the response of maize to micro/nanobubbles oxygation (MNBO) at three dissolved oxygen (DO) concentrations (10, 20 and 30 mg/L) and seven MNBO periods (vegetative stage, reproductive stage, filling and ripening stage, combination of two stages and the whole growth stage) in addition to a control treatment (CK, no oxygation during the growth period). Our results revealed that the MNBO treatments increased maize root dry weight, root length density and root surface area in 0–20 cm soil. The highest yield was obtained in O20A (MNBO at 20 mg/L DO during the growth period), with an increase of 11.66% relative to CK. Crude ash, starch and vitamin C were improved by application of MNBO at 20 mg/L DO. However, excessive oxygen adversely affected maize growth, decreasing the maize yield in 2013 relative to CK. The results suggest that application of MNBO at 20 mg/L DO during the growth period of spring maize was appropriate.
Effect of oestrogen-dependent vasopressin on HPA axis in the median eminence of female rats
Authors: Nishimura Kazuaki , Yoshino Kiyoshi , Sanada Kenya , Beppu Hiroki , Akiyama Yasuki , Nishimura Haruki , Tanaka Kentaro , Sonoda Satomi , Ueno Hiromichi , Yoshimura Mitsuhiro , Maruyama Takashi , Ozawa Hitoshi , Ueta Yoichi 
Published: March 2019

AbstractThe median eminence (ME) anatomically consists of external (eME) and internal (iME) layers. The hypothalamic neurosecretory cells terminate their axons in the eME and secrete their neurohormones regulating anterior pituitary hormone secretion involved in stress responses into the portal vein located in the eME. Magnocellular neurosecretory cells (MNCs) which produce arginine vasopressin (AVP) and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON) terminate their axons in the posterior pituitary gland (PP) through the iME. Here, we provide the first evidence that oestrogen modulates the dynamic changes in AVP levels in the eME axon terminals in female rats, using AVP-eGFP and AVP-DREADDs transgenic rats. Strong AVP-eGFP fluorescence in the eME was observed at all oestrus cycle stages in adult female rats but not in male transgenic rats. AVP-eGFP fluorescence in the eME was depleted after bilateral ovariectomy but re-appeared with high-dose 17β-oestradiol. AVP-eGFP fluorescence in the MNCs and PP did not change significantly in most treatments. Peripheral clozapine-N-oxide administration induced AVP-DREADDs neurone activation, causing a significant increase in plasma corticosterone levels in the transgenic rats. These results suggest that stress-induced activation of the hypothalamic-pituitary-adrenal axis may be caused by oestrogen-dependent upregulation of AVP in the eME of female rats.
Regulation of differential proton-coupled folate transporter gene expression in human tumors: transactivation by KLF15 with NRF-1 and the role of Sp1
Authors: Hou Zhanjun , O'Connor Carrie , Frühauf Josephine , Orr Steve , Kim Seongho , Gangjee Aleem , Matherly Larry H. 
Published: March 2019

Abstract
Tumors can be therapeutically targeted with novel antifolates (e.g. AGF94) that are selectively transported by the human proton-coupled folate transporter (hPCFT). Studies were performed to determine the transcription regulation of hPCFT in tumors and identify possible mechanisms that contribute to the highly disparate levels of hPCFT in HepG2 versus HT1080 tumor cells. Transfection of hPCFT-null HT1080 cells with hPCFT restored transport and sensitivity to AGF94. Progressive deletions of the hPCFT promoter construct (−2005 to +96) and reporter gene assays in HepG2 and HT1080 cells confirmed differences in hPCFT transactivation and localized a minimal promoter to between positions −50 and +96. The minimal promoter included KLF15, GC-Box and NRF-1 cis-binding elements whose functional importance was confirmed by promoter deletions and mutations of core consensus sequences and reporter gene assays. In HepG2 cells, NRF-1, KLF15 and Sp1 transcripts were increased over HT1080 cells by ∼5.1-, ∼44-, and ∼2.4-fold, respectively. In Drosophila SL2 cells, transfection with KLF15 and NRF-1 synergistically activated the hPCFT promoter; Sp1 was modestly activating or inhibitory. Chromatin immunoprecipitation and electrophoretic mobility shift assay (EMSA) and supershifts confirmed differential binding of KLF15, Sp1, and NRF-1 to the hPCFT promoter in HepG2 and HT1080 cells that paralleled hPCFT levels. Treatment of HT1080 nuclear extracts (NE) with protein kinase A increased Sp1 binding to its consensus sequence by EMSA, suggesting a role for Sp1 phosphorylation in regulating hPCFT transcription. A better understanding of determinants of hPCFT transcriptional control may identify new therapeutic strategies for cancer by modulating hPCFT levels in combination with hPCFT-targeted antifolates.
Personalisierte Krebsmedizin im klinischen Alltag – Reflektion und Perspektive
Authors: Denschlag Dominik , Jansen Gunther , Huelsewig Carolin , Laib Anna , Stecker Katrin , Giesecke Dagmar , Knoblauch Bernd , Löhr J.-Matthias , Heringlake Stefan 
Published: March 2019

Zusammenfassung
Hintergrund Präzisionsmedizin will die richtige Medikation zur richtigen Zeit an den richtigen Patienten bringen, basierend auf dem molekularen Profil des jeweiligen individuellen Tumors. Trotz dieses großartigen Versprechens ist die Umsetzung in die klinische Praxis sehr ernüchternd.
Material und Methodik Im Rahmen eines Präzisionsmedizinprogramms in einem kommunalen Krankenhaus der Maximalversorgung wurden insgesamt 11 Patienten/Patientinnen (9 mit gynäkologischen Tumoren und 2 mit gastrointestinalen Karzinomen) mittels Hochdurchsatzsequenzierung und einer evidenzbasierten Software analysiert. Sämtliche Patienten/-innen waren zum Zeitpunkt der Analyse bereits multipel vorbehandelt und ohne Chance auf einen kurativen Therapieansatz.
Ergebnisse Im Vergleich zur bisherigen konventionellen Analyse konnte insgesamt in 8 Fällen ein Zugewinn an Information festgestellt werden. In der jeweiligen Tumorkonferenz wurden basierend auf der Software-gestützten Analyse insgesamt 6 Therapieempfehlungen ausgesprochen, hiervon allerdings lediglich 1 zugelassene Medikation bzw. 5 off-label-use Empfehlungen. Zwei Patientinnen sind an fulminant progredientem Tumorleiden verstorben, ohne dass eine Empfehlung umgesetzt werden konnte. Bei 3 Patienten/-innen wurden keine Hinweise auf spezifisch wirksame Medikamente gefunden.
Schlussfolgerungen Der personalisierte Zugang in der Tumortherapie ist im Rahmen der klinischen Routineversorgung machbar, obwohl die meisten Therapieempfehlungen off-label sind in der jeweiligen Indikation. Von Vorteil ist daher ein molekulares Tumorboard, in dem alle onkologischen Disziplinen zusammen mit der Pathologie die Fälle besprechen und die Therapieentscheidung gemeinsam tragen.
Friendly Fire: Autoimmune Pneumonitis nach Checkpoint-Inhibitor-Therapie
Authors: Holzhauer Peter , Grosse Christina 
Published: March 2019

ZusammenfassungDie Therapie mit Checkpoint-Inhibitoren hat mittlerweile einen festen Platz in der Therapie von immer mehr Tumorentitäten gefunden. Gerade beim nichtkleinzelligen Bronchialkarzinom können mittlerweile bisher nicht möglich scheinende Ansprechraten und oft auch ein verlängertes Gesamtüberleben bei geeigneten Patienten, realisiert werden. Besonders Patienten mit einer hohen PD-L1-Expression im Tumorgewebe profitieren von dieser Behandlung. Der Checkpoint-Inhibitor Pembrolizumab ist bei diesen Patienten für den 1st line Einsatz zugelassen 1. Checkpoint-Inhibitoren sind in der Regel gut verträglich. Dennoch können sich bei einigen Patienten immunbezogene Reaktion an verschiedenen Organen, wie Lunge, Kolon oder Schilddrüse einstellen. Das Management dieser autoimmunen Nebenwirkungen (immune-related adverse events) erfordert ein schnelles therapeutisches Handeln und ist in Algorithmen zur Vorgehensweise publiziert 3. Hier wird der Behandlungsverlauf einer Patientin vorgestellt, die schon nach der ersten Gabe Pembrolizumab mit einer sehr ausgeprägten Pneumonitis konfrontiert wurde.
Reducing debt improves psychological functioning and changes decision-making in the poor
Authors: Ong Qiyan , Theseira Walter , Ng Irene Y. H. 
Published: March 2019

Significance
The impact of chronic debt on the poor is psychological, not just financial. We hypothesize that chronic debt impairs psychological functioning and decision-making, contributing to the poverty trap. This is because debt is not considered fungible and is viewed as costly mental accounts that consume cognitive bandwidth. We test this using quasiexperimental evidence from a one-off, unanticipated debt-relief program worth several months’ household income. Comparing the poor before and after debt relief, those with more debt accounts paid off experienced greater improvements in cognitive functioning, reported less anxiety, and became less present-biased. These findings provide actionable evidence for poverty-alleviation policy.
Increasing valence pushes DNA nanostar networks to the isostatic point
Authors: Conrad Nathaniel , Kennedy Tynan , Fygenson Deborah K. , Saleh Omar A. 
Published: March 2019

SignificanceMaxwell (1864) predicted that 3D networks of beams fixed to junctions through freely rotating joints will be rigid only if at least six beams emanate from each junction. This concept is key to macroscopic design of trussed structures, but its relevance to microscopic networks, where thermal fluctuations are large, such as in biomolecular gels, is not as clear. Here, we exploit DNA nanotechnology to create gels of defined connectivity and demonstrate that gel mechanics are controlled by an interplay between entropic effects, network structure, and Maxwell’s rigidity criterion.
The Importance of Identification When Measuring Performance in Addiction Treatment
Authors: Garnick Deborah , Horgan Constance , Mark Tami L. , Lee Margaret , Acevedo Andrea , Neager Sarah , O'Brien Peggy , Hashmi Ali , Marder Bill , Miller Kay 
Published: March 2019

Background Identifying and effectively treating individuals with substance use disorders (SUDs) is an important priority for state Medicaid programs, given the enormous toll that SUDs take on individuals, their families, and their communities. In this paper, we describe how the Healthcare Effectiveness Data and Information Set (HEDIS) measure “Identification of Alcohol and Other Drug Services” can be used, along with eligible population prevalence rates, to expand states’ ability to track how well their Medicaid programs identify enrollees with SUDs and link them with treatment (measured by initiation and engagement performance measures). Methods We use the 2009 Medicaid MAX data on utilization and enrollment along with information from the National Survey of Drug Use and Health (NSDUH) to obtain state-level estimates of alcohol and drug abuse and dependence among Medicaid beneficiaries for 7 illustrative states. We calculate identification, initiation, and engagement measures using specifications from the National Committee on Quality Assurance (NCQA). Results NSDUH data showed that the eligible population prevalence rate (the average rate of alcohol or drug abuse or dependence) among the 7 states was 10.0%, whereas the average identification rate was 2.9%. The gap between the prevalence and identification rates ranged from 5.1% to 11.0% among the 7 states. The initiation rates ranged from 36.9% to 57.1%. The states’ engagement rates ranged from 11.8% to 31.1%, although rates differ by age, gender, and race/ethnicity in some states. Conclusion Including identification along with initiation and engagement measures allows states to determine how well they are performing in a more complete spectrum from need, to recognition and documentation of enrollees with SUDs, to initiation of treatment, to continuation of early treatment.
Highly sensitive piezotronic pressure sensors based on undoped GaAs nanowire ensembles
Authors: Calahorra Yonatan , Husmann Anke , Bourdelain Alice , Kim Wonjong , Vukajlovic-Plestina Jelena , Boughey Chess , Jing Qingshen , Fontcuberta i Morral Anna , Kar-Narayan Sohini 
Published: March 2019

Abstract
Semiconducting piezoelectric materials have attracted considerable interest due to their central role in the emerging field of piezotronics, where the development of a piezo-potential in response to stress or strain can be used to tune the band structure of the semiconductor, and hence its electronic properties. This coupling between piezoelectricity and semiconducting properties can be readily exploited for force or pressure sensing using nanowires, where the geometry and unclamped nature of nanowires render them particularly sensitive to small forces. At the same time, piezoelectricity is known to manifest more strongly in nanowires of certain semiconductors. Here, we report the design and fabrication of highly sensitive piezotronic pressure sensors based on GaAs nanowire ensemble sandwiched between two electrodes in a back-to-back diode configuration. We analyse the current–voltage characteristics of these nanowire-based devices in response to mechanical loading in light of the corresponding changes to the device band structure. We observe a high piezotronic sensitivity to pressure, of ~7800 meV MPa−1. We attribute this high sensitivity to the nanowires being fully depleted due to the lack of doping, as well as due to geometrical pressure focusing and current funnelling through polar interfaces.
Observation of accelerated beam ion population during edge localized modes in the ASDEX Upgrade tokamak
Authors: Galdon-Quiroga J. , Garcia-Munoz M. , McClements K.G. , Nocente M. , Denk S.S. , Freethy S. , Jacobsen A.S. , Orain F. , Rivero-Rodriguez J.F. , Salewski M. , Sanchis-Sanchez L. , Suttrop W. , Viezzer E. , Willensdorfer M. 
Published: March 2019

Abstract
The interaction between fast-ions and edge localized modes (ELMs) is investigated by means of fast-ion loss detector measurements. Fast-ion losses are increased during ELMs exhibiting a 3D filamentary-like behaviour. An accelerated beam ion population has been observed during ELMs in a tokamak for the first time. Tomographic inversion of the measured fast-ion losses reveal multiple velocity-space structures. Attending to the experimental observations, an acceleration mechanism is proposed based on a resonant interaction between the beam ions and parallel electric fields emerging during the ELM crash. The key experimental observations can be qualitatively reproduced by full-orbit following simulations of fast-ions in the presence of the ELM magnetic and electric perturbation fields. Our findings may shed light on the possible contribution of fast-ions to the ELM stability and the transient heat loads on plasma facing components.
Colonic Mucosa With Polypoid Hyperplasia
Authors: Hissong Erika , Fernandes Helen , Jessurun Jose 
Published: March 2019

Abstract

Objectives
Define the morphologic and molecular features of colonic polyps with subtle histologic features.

Methods
Two hundred specimens were obtained of surveillance colonoscopies. Endoscopic findings were reviewed. Histologic features of the polyps were compared with the flat mucosa. Next-generation sequencing was performed on 30 study polyps and 20 control samples.

Results
Polyps with subtle changes comprised 12% of all polyps. All polyps were sessile and small (<0.5 cm) and were located predominantly in the distal colon (60%). Synchronous hyperplastic, sessile serrated, and dysplastic polyps were found in 30%, 7%, and 51% of patients, respectively. A total of 169 (84.5%) polyps showed wide, nonserrated crypts, increased intraluminal mucus, and patent openings. KRAS alterations were present in 30% of polyps.

Conclusions
Most polyps with subtle histologic features have recognizable morphologic changes. About one-third harbored KRAS alterations. These polyps should not be regarded as variants of hyperplastic polyps.
Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile
Authors: Koutros Stella , Lubin Jay H , Graubard Barry I , Blair Aaron , Stewart Patricia A , Beane Freeman Laura E , Silverman Debra T 
Published: March 2019

AbstractWe extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.
Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease
Authors: Gupta Amita , Swindells Susan , Kim Soyeon , Hughes Michael D , Naini Linda , Wu Xingye , Dawson Rodney , Mave Vidya , Sanchez Jorge , Mendoza Alberto , Gonzales Pedro , Kumarasamy Nagalingeswaran , Comins Kyla , Conradie Francesca , Shenje Justin , Fontain Sandy Nerette , Garcia-Prats Anthony , Asmelash Aida , Nedsuwan Supalert , Mohapi Lerato , Lalloo Umesh G , Ferreira Ana Cristina Garcia , Mugah Christopher , Harrington Mark , Jones Lynne , Cox Samyra R , Smith Betsy , Shah N Sarita , Hesseling Anneke C , Churchyard Gavin 
Published: March 2019

Abstract

Background
We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial.

Methods
We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing.

Results
From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged &lt;5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy.

Conclusions
The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.