bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phonotactic steering and representation of directional information in the ascending auditory pathway of a cricket
Authors: Lv M. , Zhang X. , Hedwig B. 
Published: January 2020

Directional hearing is crucial for animals depending on acoustic signals to locate a mate. We focused on crickets to explore the reliability of directional information forwarded to the brain by the ascending auditory interneuron AN1, which is crucial for phonotactic behavior. We presented calling song from −45° to +45° in steps of 3° and compared the phonotactic steering of females walking on a trackball with the directional responses of AN1. Forty percent of females showed good steering behavior and changed their walking direction when the speaker passed the body’s longitudinal axis. The bilateral latency difference between right and left AN1 responses was small and may not be reliable for auditory steering. In respect to spike count, all AN1 recordings presented significant bilateral differences for angles larger than ±18°, yet 35% showed a mean significant difference of 1–3 action potentials per chirp when the frontal stimulus deviated by 3° from their length axis. For small angles, some females had a very similar AN1 activity forwarded to the brain, but the accuracy of their steering behavior was substantially different. Our results indicate a correlation between directional steering and the response strength of AN1, especially for large angles. The reliable steering of animals at small angles would have to be based on small bilateral differences of AN1 activity, if AN1 is the only source providing directional information. We discuss whether such bilateral response difference at small angles can provide a reliable measure to generate auditory steering commands descending from the brain, as pattern recognition is intensity independent.NEW & NOTEWORTHY The ascending auditory interneuron AN1 has been implicated in cricket auditory steering, but at small acoustic stimulation angles, it does not provide reliable directional information. We conclude that either the small bilateral auditory activity differences of the AN1 neurons are enhanced to generate reliable descending steering commands or, more likely, directional auditory steering is mediated via a thoracic pathway, as indicated by the reactive steering hypothesis.
Selective Inhibition of HDAC3 Targets Synthetic Vulnerabilities and Activates Immune Surveillance in Lymphoma
Authors: Mondello Patrizia , Tadros Saber , Teater Matt , Fontan Lorena , Chang Aaron Y. , Jain Neeraj , Yang Haopeng , Singh Shailbala , Ying Hsia-Yuan , Chu Chi-Shuen , Ma Man Chun John , Toska Eneda , Alig Stefan , Durant Matthew , de Stanchina Elisa , Ghosh Sreejoyee , Mottok Anja , Nastoupil Loretta , Neelapu Sattva S. , Weigert Oliver , Inghirami Giorgio , Baselga José , Younes Anas , Yee Cassian , Dogan Ahmet , Scheinberg David A. , Roeder Robert G. , Melnick Ari M. , Green Michael R. 
Published: January 2020

Abstract

CREBBP mutations are highly recurrent in B-cell lymphomas and either inactivate its histone acetyltransferase (HAT) domain or truncate the protein. Herein, we show that these two classes of mutations yield different degrees of disruption of the epigenome, with HAT mutations being more severe and associated with inferior clinical outcome. Genes perturbed by CREBBP mutation are direct targets of the BCL6–HDAC3 onco-repressor complex. Accordingly, we show that HDAC3-selective inhibitors reverse CREBBP-mutant aberrant epigenetic programming, resulting in: (i) growth inhibition of lymphoma cells through induction of BCL6 target genes such as CDKN1A and (ii) restoration of immune surveillance due to induction of BCL6-repressed IFN pathway and antigen-presenting genes. By reactivating these genes, exposure to HDAC3 inhibitors restored the ability of tumor-infiltrating lymphocytes to kill DLBCL cells in an MHC class I and II–dependent manner, and synergized with PD-L1 blockade in a syngeneic model in vivo. Hence, HDAC3 inhibition represents a novel mechanism-based immune epigenetic therapy for CREBBP-mutant lymphomas.

Significance:
We have leveraged the molecular characterization of different types of CREBBP mutations to define a rational approach for targeting these mutations through selective inhibition of HDAC3. This represents an attractive therapeutic avenue for targeting synthetic vulnerabilities in CREBBP-mutant cells in tandem with promoting antitumor immunity.
This article is highlighted in the In This Issue feature, p. 327
Exceeding (Low) Expectations: Autonomy, Bureaucratic Integrity, and Capacity in the 2010 Elections
Authors: Calimbahin Cleo 
Published: January 2020

Building quality democracy takes time. It requires a constant review of the performance of institutions that are tasked to deliver in concrete ways the democratic ideal. Improving democratic institutions requires sustained reform efforts. Election administration and election commissions need to be examined against this backdrop of broader democratization issues. Given the importance of election administration in the study of democratic processes, there are very few studies that focus on election administration. By focusing on a specific institution tasked to replicate the ideals of democracy such as the COMELEC, this study offers insights into a deeper understanding of autonomy, bureaucratic integrity and capacity. Though mostly overlooked, election administration plays a vital role in the study of broader democratization questions. Elections promise continuity and stability. But if election administration is done poorly due to the lack of autonomy, integrity, and capacity then it becomes an unsettling and destabilizing exercise.
With democratic structures in place for years, the Philippines continues to have problems with the most basic elements of election administration: accuracy in maintaining voter lists, counting votes and adjudicating disputes. The COMELEC oversees election administration, serving as referee and gatekeeper in the Philippines’ electoral arena. The COMELEC is a constitutional commission with ostensible autonomy and power, yet it is also a bureaucracy. The May 2010 election was the first automated election in the Philippines. Widely regarded as a success, there were many issues and incidents that show it was also business as usual for COMELEC. The speed of the canvass count astounded the voting populace, and perhaps operators, but the May 2010 election continues to show embedded problems within the commission that needs to be addressed in order to strengthen the COMELEC as an institution that can provide election administration efficiently and accurately in subsequent elections.
Improved Estimation of Proxy Sea Surface Temperature in the Arctic
Authors: Banzon Viva , Smith Thomas M. , Steele Michael , Huang Boyin , Zhang Huai-Min 
Published: January 2020

AbstractArctic sea surface temperatures (SSTs) are estimated mostly from satellite sea ice concentration (SIC) estimates. In regions with sea ice the SST is the temperature of open water or of the water under the ice. A number of different proxy SST estimates based on SIC have been developed. In recent years more Arctic quality-control buoy SSTs have become available, allowing better validation of different estimates and the development of improved proxy estimates. Here proxy SSTs from different approaches are evaluated and an improved proxy SST method is shown. The improved proxy SSTs were tested in an SST analysis, and showed reduced bias and random errors compared to the Arctic buoy SSTs. Almost all reduction in errors is in the warm melt season. In the cold season the SIC is typically high and all estimates tend to have low errors. The improved method will be incorporated into an operational SST analysis.
Image Guided Sclerotherapy of Masseteric Venous Malformations
Authors: Kumar Subhash , Bhavana Kranti , Kumar Bindey , Sinha Amit Kumar , Kumar Prem 
Published: January 2020

Objective: To describe results of image guided sclerotherapy of venous malformations (VM) localized in the masseter muscle. Methods: Retrospective review of prospectively maintained data was done to include consecutive cases treated over 5-year period, with minimum 6 months follow-up. Sclerotherapy was done using ultrasound (US) guided needle puncture(s) of the lesions percutaneously, and 3% polidocanol foam injected under image guidance. Results: Seventeen cases (10 male, 7 female) with mean age 15.6 years (range 6-28 years) were identified. Clinical presentation was with facial asymmetry, becoming pronounced on jaw clenching, and three cases had mild local pain. On US, the lesions appeared as partially compressible masses with anechoic spaces, showing color filling on releasing probe pressure. Fourteen had phleboliths. Eight patients had undergone magnetic resonance imaging, lesions appearing as oval, homogenous, lobulated, T2 hyperintense masses, with heterogeneous contrast enhancement. Number of sclerotherapy sessions were—single in four cases, two in eight cases and three in five cases, for total of 35 sessions (average 2.05 session per patient). The mean dose of drug injected per session was 1.85 mL and total mean dose per patient was 2.79 mL. Post-procedure vomiting occurred in one patient while all had local swelling and mild pain, lasting between 3 to 7 days. No facial nerve palsy or sloughing/ulceration/skin necrosis was noted. On US follow-up (6-26 months, mean 15.9 months), 12 patients had small echogenic masses without any vascularity, and five had small anechoic areas <25%. All patients had complete resolution of swelling and pain. Conclusions: For VMs localized to the masseter muscle, image guided sclerotherapy is highly effective and safe, and recommended as first line treatment.
Perspectives of End Users on the Potential Use of Trunk Exoskeletons for People With Low-Back Pain: A Focus Group Study
Authors: Baltrusch Saskia J. , Houdijk Han , van Dieën Jaap H. , van Bennekom Coen A. M. , de Kruif Anja J. T. C. M. 
Published: January 2020

Objective The objective of this study was to identify criteria to be considered when developing an exoskeleton for low-back pain patients by exploring the perceptions and expectations of potential end users. Background Psychosocial, psychological, physical load, and personality influence incidence of low-back pain. Body-worn assistive devices that passively support the user’s trunk, that is exoskeletons, can decrease mechanical loading and potentially reduce low-back pain. A user-centered approach improves patient safety and health outcomes, increases user satisfaction, and ensures usability. Still, previous studies have not taken psychological factors and the early involvement of end users into account. Method We conducted focus group studies with low-back pain patients ( n = 4) and health care professionals ( n = 8). Focus group sessions were audio-recorded, transcribed, and analyzed, using the general inductive approach. The focus group discussions included trying out an available exoskeleton. Questions were designed to elicit opinions about exoskeletons, desired design specifications, and usability. Results Important design characteristics were comfort, individual adjustability, independency in taking it on and off, and gradual adjustment of support. Patients raised concerns over loss of muscle strength. Health care professionals mentioned the risk of confirming disability of the user and increasing guarded movement in patients. Conclusion The focus groups showed that implementation of a trunk exoskeleton to reduce low-back pain requires an adequate implementation strategy, including supervision and behavioral coaching. Application For health care professionals, the optimal field of application, prevention or rehabilitation, is still under debate. Patients see potential in an exoskeleton to overcome their limitations and expect it to improve their quality of life.
Why and How to Approach User Experience in Safety-Critical Domains: The Example of Health Care
Authors: Grundgeiger Tobias , Hurtienne Jörn , Happel Oliver 
Published: January 2020

Objective To highlight the importance of the personal experience of users who interact with technology in safety-critical domains and summarize three interaction concepts and the associated theories that provide the means for addressing user experience. Background In health care, the dominant concepts of interaction are based on theories arising from classic cognitive psychology. These concepts focus mainly on safety and efficiency, with too little consideration being given to user experience. Method Users in complex socio-technical and safety-critical domains such as health care interact with many technological devices. Enhancing the user experience could improve the design of technology, enhance the well-being of staff, and contribute to modern safety management. We summarize concepts of “interaction” based on modern theories of human–computer interaction, which include the personal experience of users as an important construct. Results and Conclusion Activity theory, embodiment, and interaction as experience provide a theoretical foundation for considering user experience in safety-critical domains. Using an example from anesthesiology, we demonstrate how each theory provides a unique but complementary view on experience. Finally, the methodological possibilities for considering personal experience in design and evaluations vary among the theories. Application Considering user experience in health care and potentially other safety-critical domains can provide an additional means of optimizing interaction with technology, contributing to the well-being of staff, and improving safety.
The effect of an integrated multidisciplinary rehabilitation programme alternating inpatient interventions with home-based activities for patients with chronic low back pain: a randomized controlled trial
Authors: Schmidt Anne Mette , Schiøttz-Christensen Berit , Foster Nadine E , Laurberg Trine Bay , Maribo Thomas 
Published: January 2020

Objective:To compare the effectiveness of an integrated rehabilitation programme with an existing rehabilitation programme in patients with chronic low back pain.Design:A single-centre, pragmatic, two-arm parallel, randomized controlled trial (1:1 ratio).Setting:A rheumatology inpatient rehabilitation centre in Denmark.Subjects:A total of 165 adults (aged ⩾ 18 years) with chronic low back pain.Interventions:An integrated rehabilitation programme comprising an alternation of three weeks of inpatient stay and 12 weeks of home-based activities was compared with an existing rehabilitation programme of four weeks of inpatient stay.Main measures:Patient-reported outcomes were collected at baseline and at the 26-week follow-up. The primary outcome was back-specific disability (Oswestry Disability Index). Secondary outcomes included pain intensity (Numerical Rating Scale), pain self-efficacy (Pain Self-Efficacy Questionnaire), health-related quality of life (EuroQol-5 Domain 5-level (EQ-5D)), and depression (Major Depression Inventory). A complete case analysis was performed.Results:A total of 303 patients were assessed for eligibility of whom 165 (mean age: 50 years (SD 13) and mean Oswestry Disability Index score 42 (SD 11)) were randomized (83 to existing rehabilitation programme and 82 to integrated rehabilitation programme). Overall, 139 patients provided the 26-week follow-up data. Baseline demographic and clinical characteristics were comparable between programmes. The between-group difference in the Oswestry Disability Index score when adjusting for the corresponding baseline score was −0.28 (95% confidence interval (CI): −4.02, 3.45) which was neither statistically nor clinically significant. No significant differences were found in the secondary outcomes.Conclusion:An integrated rehabilitation programme was no more effective than an existing rehabilitation programme at the 26-week follow-up.
Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth
Authors: Kidnapillai Srisaiyini , Wade Ben , Bortolasci Chiara C , Panizzutti Bruna , Spolding Briana , Connor Timothy , Crowley Tamsyn , Jamain Stéphane , Gray Laura , Leboyer Marion , Berk Michael , Walder Ken 
Published: January 2020

Background: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs. Methods: The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at p<0.05. Results: We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( p<0.05). Putative target genes of these microRNAs targeted pathways including those identified as “neuron projection development” and “axonogenesis”. Many of the target genes are inhibitors of neurite outgrowth and neurogenesis and were downregulated following bipolar disorder drug combination treatment (all p<0.05). The bipolar disorder drug combination tended to decrease the expression of the target genes ( NOVA1, GRIN3A, and VIM), however this effect could be reversed by the application of microRNA inhibitors. Conclusions: We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.
Effect of lurasidone treatment on chronic mild stress-induced behavioural deficits in male rats: The potential role for glucocorticoid receptor signalling
Authors: Calabrese Francesca , Brivio Paola , Sbrini Giulia , Gruca Piotr , Lason Magdalena , Litwa Ewa , Niemczyk Monika , Papp Mariusz , Riva Marco A 
Published: January 2020

Background: Stress represents one of the main precipitating factors for psychiatric diseases, characterised by an altered function of glucocorticoid receptors (GR), known to play a role in mood and cognitive function. We investigated the ability of the antipsychotic lurasidone to modulate the involvement of genomic and non-genomic GR signalling in the behavioural alterations due to chronic stress exposure Methods: Male Wistar rats were exposed to seven weeks of chronic mild stress (CMS) and treated with lurasidone (3 mg/kg/day) starting from the second week of stress for more five weeks. Gene expression and protein analyses were conducted in dorsal hippocampus. Results: Seven weeks of CMS induced anhedonia and cognitive impairment, which were normalised by lurasidone. At molecular level, CMS rats showed an increase of GR protein levels by 60% ( p<0.001 vs. CTRL/VEH) in the membrane compartment, which was paralleled by an up-regulation of phosphoSINAPSYN Ia/b by 88% ( p<0.01 vs. CTRL/VEH) and of the mitochondrial marker Cox3 by 21% ( p<0.05 vs. CTRL/VEH). Moreover, while exposure to the novel object recognition test increased the nuclear translocation of GRs by 96% ( p<0.01 vs. CTRL/VEH/Naïve) and their transcriptional activity in non-stressed rats, such mechanisms were impaired in CMS rats. Interestingly, the genomic and non-genomic alterations of GR, induced by CMS, were normalised by lurasidone. Conclusion: Our results further support the role of glucocorticoid signalling in the dysfunction associated with stress exposure. We provide novel insights on the mechanism of lurasidone, suggesting its effectiveness on different domains associated with psychiatric disorders.
Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling
Authors: Gomes-de-Souza Lucas , Costa-Ferreira Willian , Oliveira Leandro A , Benini Ricardo , Crestani Carlos C 
Published: January 2020

Background: Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. Aims: The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. Methods: The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. Results: Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. Conclusions: Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.