bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioural activation for overweight and obese adolescents with low mood delivered in a community setting: feasibility study
Authors: Arnott Bronia , Kitchen Charlotte Emma Wray , Ekers David , Gega Lina , Tiffin Paul Alexander 
Published: April 2020

BackgroundMood and weight problems are common in young people, yet few treatments address both conditions concurrently. Behavioural activation (BA) has shown promise as a treatment for adults with comorbid obesity and depression. This study aimed to examine the feasibility and acceptability of a manualised BA treatment targeting weight and mood problems in young people.MethodsYoung people with low mood and weight difficulties were identified via a school-based screening process. Following a diagnostic interview, young people with clinically significant mood problems and concurrent overweight/obesity were invited to participate. A total of 8–12 sessions of BA were delivered by a graduate therapist to eight adolescents (four male) aged 12–15 years. Weight, mood and functioning were assessed before, during and after treatment, and a semistructured qualitative interview was conducted, along with selected outcome measures at 4 months’ follow-up.ResultsLow attrition and positive qualitative feedback suggested the intervention was acceptable. Trends towards a reduction in reported depression symptoms and improved functioning scores were observed at follow-up, with more mixed results for change in body mass index. Of those attending the 4-month follow-up, 57% (4/7) no longer met the screening threshold for major depressive disorder. However, low screening and baseline recruitment rates would pose challenges to executing a larger trial.ConclusionsBA delivered by a graduate therapist in a British community setting is an acceptable, feasible treatment for comorbid mood and weight problems in adolescence, and its effectiveness should be evaluated in an adequately powered randomised controlled trial.
Utility of balloon aortic valvuloplasty in the transcatheter aortic valve implantation era
Authors: Dawson Luke , Huang Alex , Selkrig Laura , Shaw James A , Stub Dion , Walton Antony , Duffy Stephen J 
Published: April 2020

BackgroundBalloon aortic valvuloplasty (BAV) has seen renewed interest since the advent of transcatheter aortic valve implantation (TAVI). The study aimed to characterise a contemporary BAV cohort and determinants of clinical outcomes.MethodsPatients undergoing BAV at a single tertiary centre were retrospectively reviewed over a 10-year period, and functional and mortality outcomes were reported with up to a 2-year follow-up.Results224 patients (aged 82.5±8.3 years; 48% female) underwent BAV over the study period. Indications were either destination treatment (39%) or bridge-to-valve replacement (61%)—including bridge-to-decision (29%), symptom relief while on the waitlist (27%), and temporary contraindications to TAVI/aortic valve replacement (AVR) (5%). The mean reduction of aortic mean pressure gradient was 38%. Procedural mortality occurred in 0.5%, stroke in 1.3%, and major bleeding in 0.9%. Twelve-month mortality was 36% overall, and 26% and 50% in the bridging and destination groups, respectively. New York HeartAssociation (NYHA) class improved by ≥1 at 30 days in 50%. Among the bridge-to-TAVI/AVR group, 40% proceeded to TAVI/AVR within 12 months following BAV. In multivariate analysis, active malignancy at baseline (OR: 4.4, 95% CI: 1.3 to 15.1, p=0.02), smoking history (OR: 3.3, 95% CI: 1.3 to 7.9, p<0.01), LVEF ≤30% at baseline (OR: 3.2, 95% CI: 1.3 to 7.6, p<0.01), destination treatment (OR: 2.2, 95% CI: 1.0 to 4.9, p=0.04) were all associated with 12-month mortality.ConclusionsBAV remains a useful procedure with relatively low rates of complications, however, 1-year mortality rates are high. Contemporary indications for BAV include a bridge to definitive valve replacement or destination treatment.
Successful correction of a prefemoral hernia with free coelomic yolk in a Texas tortoise (Gopherus berlandieri)
Authors: Reinoso Rodrigo , Arguedas Randall 
Published: April 2020

An approximately 10‐year‐old female Texas tortoise (Gopherus berlandieri) with a large right prefemoral fossa mass was presented after brumation. Based on CT and fine needle aspiration, the animal was diagnosed with a hernia. Following surgery to correct the defect, free yolk was detected in the coelomic cavity and several saline lavages were employed. A polypropylene mesh was used to ensure correction of the hernia. We suggest that the excessive follicular development caused tension to the muscular wall and that the coelomic yolk caused severe irritation, and the inflammatory reaction weakened and finally caused a disruption of the coelomic membrane, resulting in rupture of the muscular wall. The patient fed voluntarily 6 days after surgery and remained normal over 1 year postsurgery.
Exploring the CPT violation and birefringence of gravitational waves with ground- and space-based gravitational-wave interferometers
Authors: Wang Sai 
Published: April 2020

AbstractIn the gravitational sector, we study the CPT violation and birefringence in gravitational waves. In presence of the CPT violation, a relative dephasing is generated between two circular polarization states of gravitational waves. This effect induces the birefringence of gravitational waves. Given the gravitational waveform modified by the CPT violation, we estimate the expected constraints on the CPT violation from Advanced Laser Interferometer Gravitational-Wave Observatory, Einstein Telescope and Laser Interferometer Space Antenna.
Non-Hermitian coupled cluster method for non-stationary systems and its interaction-picture reinterpretation
Authors: Bishop R. F. , Znojil M. 
Published: April 2020

AbstractThe interaction picture in a non-Hermitian realization is discussed in detail and considered for its practical use in many-body quantum physics. The resulting non-Hermitian interaction-picture (NHIP) description of dynamics, in which both the wave functions and operators belonging to physical observables cease to remain constant in time, is a non-Hermitian generalization of the traditional Dirac picture of standard quantum mechanics, which itself is widely used in quantum field theory calculations. Particular attention is paid here to the variational (or, better, bivariational) and dynamical (i.e., non-stationary) aspects that are characteristic of the coupled cluster method (CCM) techniques that nowadays form one of the most versatile and most accurate of all available formulations of quantum many-body theory. In so doing we expose and exploit multiple parallels between the NHIP and the CCM in its time-dependent versions.
Overexpression of RUNX3 Represses RUNX1 to Drive Transformation of Myelodysplastic Syndrome
Authors: Yokomizo-Nakano Takako , Kubota Sho , Bai Jie , Hamashima Ai , Morii Mariko , Sun Yuqi , Katagiri Seiichiro , Iimori Mihoko , Kanai Akinori , Tanaka Daiki , Oshima Motohiko , Harada Yuka , Ohyashiki Kazuma , Iwama Atsushi , Harada Hironori , Osato Motomi , Sashida Goro 
Published: April 2020

Abstract

RUNX3, a RUNX family transcription factor, regulates normal hematopoiesis and functions as a tumor suppressor in various tumors in humans and mice. However, emerging studies have documented increased expression of RUNX3 in hematopoietic stem/progenitor cells (HSPC) of a subset of patients with myelodysplastic syndrome (MDS) showing a worse outcome, suggesting an oncogenic function for RUNX3 in the pathogenesis of hematologic malignancies. To elucidate the oncogenic function of RUNX3 in the pathogenesis of MDS in vivo, we generated a RUNX3-expressing, Tet2-deficient mouse model with the pancytopenia and dysplastic blood cells characteristic of MDS in patients. RUNX3-expressing cells markedly suppressed the expression levels of Runx1, a critical regulator of hemaotpoiesis in normal and malignant cells, as well as its target genes, which included crucial tumor suppressors such as Cebpa and Csf1r. RUNX3 bound these genes and remodeled their Runx1-binding regions in Tet2-deficient cells. Overexpression of RUNX3 inhibited the transcriptional function of Runx1 and compromised hematopoiesis to facilitate the development of MDS in the absence of Tet2, indicating that RUNX3 is an oncogene. Furthermore, overexpression of RUNX3 activated the transcription of Myc target genes and rendered cells sensitive to inhibition of Myc-Max heterodimerization. Collectively, these results reveal the mechanism by which RUNX3 overexpression exerts oncogenic effects on the cellular function of and transcriptional program in Tet2-deficient stem cells to drive the transformation of MDS.

Significance:
This study defines the oncogenic effects of transcription factor RUNX3 in driving the transformation of myelodysplastic syndrome, highlighting RUNX3 as a potential target for therapeutic intervention.
Identification of a Small-Molecule Inhibitor That Disrupts the SIX1/EYA2 Complex, EMT, and Metastasis
Authors: Zhou Hengbo , Blevins Melanie A. , Hsu Jessica Y. , Kong Deguang , Galbraith Matthew D. , Goodspeed Andrew , Culp-Hill Rachel , Oliphant Michael U.J. , Ramirez Dominique , Zhang Lingdi , Trinidad-Pineiro Jennyvette , Mathews Griner Lesley , King Rebecca , Barnaeva Elena , Hu Xin , Southall Noel T. , Ferrer Marc , Gustafson Daniel L. , Regan Daniel P. , D'Alessandro Angelo , Costello James C. , Patnaik Samarjit , Marugan Juan , Zhao Rui , Ford Heide L. 
Published: April 2020

AbstractMetastasis is the major cause of mortality for patients with cancer, and dysregulation of developmental signaling pathways can significantly contribute to the metastatic process. The Sine oculis homeobox homolog 1 (SIX1)/eyes absent (EYA) transcriptional complex plays a critical role in the development of multiple organs and is typically downregulated after development is complete. In breast cancer, aberrant expression of SIX1 has been demonstrated to stimulate metastasis through activation of TGFβ signaling and subsequent induction of epithelial–mesenchymal transition (EMT). In addition, SIX1 can induce metastasis via non-cell autonomous means, including activation of GLI-signaling in neighboring tumor cells and activation of VEGFC–induced lymphangiogenesis. Thus, targeting SIX1 would be expected to inhibit metastasis while conferring limited side effects. However, transcription factors are notoriously difficult to target, and thus novel approaches to inhibit their action must be taken. Here we identified a novel small molecule compound, NCGC00378430 (abbreviated as 8430), that reduces the SIX1/EYA2 interaction. 8430 partially reversed transcriptional and metabolic profiles mediated by SIX1 overexpression and reversed SIX1-induced TGFβ signaling and EMT. 8430 was well tolerated when delivered to mice and significantly suppressed breast cancer–associated metastasis in vivo without significantly altering primary tumor growth. Thus, we have demonstrated for the first time that pharmacologic inhibition of the SIX1/EYA2 complex and associated phenotypes is sufficient to suppress breast cancer metastasis.Significance:These findings identify and characterize a novel inhibitor of the SIX1/EYA2 complex that reverses EMT phenotypes suppressing breast cancer metastasis.
Tumor Microenvironment Remodeling Enables Bypass of Oncogenic KRAS Dependency in Pancreatic Cancer
Authors: Hou Pingping , Kapoor Avnish , Zhang Qiang , Li Jiexi , Wu Chang-Jiun , Li Jun , Lan Zhengdao , Tang Ming , Ma Xingdi , Ackroyd Jeffrey J. , Kalluri Raghu , Zhang Jianhua , Jiang Shan , Spring Denise J. , Wang Y. Alan , DePinho Ronald A. 
Published: April 2020

Abstract

Oncogenic KRAS (KRAS*) is a key tumor maintenance gene in pancreatic ductal adenocarcinoma (PDAC), motivating pharmacologic targeting of KRAS* and its effectors. Here, we explored mechanisms involving the tumor microenvironment (TME) as a potential basis for resistance to targeting KRAS*. Using the inducible KrasG12D;Trp53−/− PDAC mouse model, gain-of-function screens of epigenetic regulators identified HDAC5 as the top hit enabling KRAS* independent tumor growth. HDAC5-driven escaper tumors showed a prominent neutrophil-to-macrophage switch relative to KRAS*-driven tumors. Mechanistically, HDAC5 represses Socs3, a negative regulator of chemokine CCL2, resulting in increased CCL2, which recruits CCR2+ macrophages. Correspondingly, enforced Ccl2 promotes macrophage recruitment into the TME and enables tumor recurrence following KRAS* extinction. These tumor-associated macrophages in turn provide cancer cells with trophic support including TGFβ to enable KRAS* bypass in a SMAD4-dependent manner. Our work uncovers a KRAS* resistance mechanism involving immune cell remodeling of the PDAC TME.

Significance:
Although KRAS* is required for PDAC tumor maintenance, tumors can recur following KRAS* extinction. The capacity of PDAC cancer cells to alter the TME myeloid cell composition to support KRAS*-independent tumor growth illuminates novel therapeutic targets that may enhance the effectiveness of therapies targeting KRAS* and its pathway components.
See related commentary by Carr and Fernandez-Zapico, p. 910.
This article is highlighted in the In This Issue feature, p. 890
Healthy Strut Coverage After Coronary Stent Implantation
Authors: Jinnouchi Hiroyuki , Otsuka Fumiyuki , Sato Yu , Bhoite Rahul R. , Sakamoto Atsushi , Torii Sho , Yahagi Kazuyuki , Cornelissen Anne , Mori Masayuki , Kawakami Rika , Kolodgie Frank D. , Virmani Renu , Finn Aloke V. 
Published: April 2020

Background:
Struts have been considered as covered when tissue overlying the struts is >0 μm by optical coherence tomography (OCT). However, there is no confirmatory study to validate this definition by histology which is the gold standard. The aim of the present study was to assess the appropriate cutoff value of neointimal thickness of stent strut coverage by OCT with histology confirmation.

Methods:
We performed ex vivo OCT imaging of human coronary arteries with stents at autopsy. A total of 46 stents in 39 vessels from 25 patients were examined in this study, and a total of 165 cross-sectional images were co-registered with histology to determine the optimal cutoff value for strut coverage by OCT which was defined as luminal endothelial cells with 2 abluminal layers of smooth muscles cells and matrix. Considering the resolution of OCT is 10 to 20 μm, the cutoff values were assessed at ≥20, ≥40, and ≥60 μm.

Results:
A total of 2235 struts were reviewed by histology, 1216 were considered as well-matched struts which were analyzed in this study. By histology, 160 struts were identified as uncovered, while 1056 struts were covered. The OCT assessment without consideration of neointimal thickness yielded a poor specificity of 37.5% and sensitivity 100%. Of 3 cutoff values, the cutoff value of ≥40 μm yielded the best sensitivity (99.3%), specificity (91.0%), positive predictive value (98.6%), and negative predictive value (95.6%) as compared with ≥20 and ≥60 μm.

Conclusions:
Neointimal thickness ≥40 μm by OCT yielded the most accurate cutoff value to identify stent strut coverage validated by histology.
Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression
Authors: Sharma Monika , Schlegel Martin P. , Afonso Milessa S. , Brown Emily J. , Rahman Karishma , Weinstock Ada , Sansbury Brian E. , Corr Emma M. , van Solingen Coen , Koelwyn Graeme J. , Shanley Lianne C. , Beckett Lauren , Peled Daniel , Lafaille Juan J. , Spite Matthew , Loke P’ng , Fisher Edward A. , Moore Kathryn J. 
Published: April 2020

Rationale:
Regression of atherosclerosis is an important clinical goal; however, the pathways that mediate the resolution of atherosclerotic inflammation and reversal of plaques are poorly understood. Regulatory T cells (Tregs) have been shown to be atheroprotective, yet the numbers of these immunosuppressive cells decrease with disease progression, and whether they contribute to atherosclerosis regression is not known.

Objective:
We investigated the roles of Tregs in the resolution of atherosclerotic inflammation, tissue remodeling, and plaque contraction during atherosclerosis regression.

Methods and Results:

Using multiple independent mouse models of atherosclerosis regression, we demonstrate that an increase in plaque Tregs is a common signature of regressing plaques. Single-cell RNA-sequencing of plaque immune cells revealed that unlike Tregs from progressing plaques that expressed markers of natural Tregs derived from the thymus, Tregs in regressing plaques lacked
Nrp1
expression, suggesting that they are induced in the periphery during lipid-lowering therapy. To test whether Tregs are required for resolution of atherosclerotic inflammation and plaque regression, Tregs were depleted using CD25 monoclonal antibody in atherosclerotic mice during apolipoprotein B antisense oligonucleotide-mediated lipid lowering. Morphometric analyses revealed that Treg depletion blocked plaque remodeling and contraction, and impaired hallmarks of inflammation resolution, including dampening of the T helper 1 response, alternative activation of macrophages, efferocytosis, and upregulation of specialized proresolving lipid mediators.

Conclusions:
Our data establish essential roles for Tregs in resolving atherosclerotic cardiovascular disease and provide mechanistic insight into the pathways governing plaque remodeling and regression of disease.
Novel pH-sensitive drug-loaded electrospun nanofibers based on regenerated keratin for local tumor chemotherapy
Authors: Zhang Jing , Li Jiashen , Xu Chengshu , Xi Zhihua , Ren Yan , Song Qingwen , Lu Shaofeng 
Published: April 2020

The present work developed keratin-based pH-sensitive nanofibers and explored the kinetics of the controlled-release effect. Extracted from wool fibers, keratin was firstly synthesized with 5- fluorouracil (5-FU). Then 5-FU/keratin was blended with poly (L-Lactide) PLLA solution and electrospun altogether to fabricate a nanofibrous scaffold, for local tumor chemotherapy. 5-FU/keratin/PLLA nanofibrous scaffolds were characterized by Fourier transform infrared spectroscopy to confirm that 5-FU was loaded within the nanofibers successfully. Scanning electron microscopy and transmission electron microscope images indicated the smooth and uniform structure of the nanofibers. Thermo-gravimetric analysis differential scanning calorimeter and X-ray diffraction techniques indicated 5-FU particles distributed in nanofibers at a molecular level. Compared with 5-FU from pure drug and 5-FU/PLLA nanofibers without keratin, the dissolution results indicated that 5- FU/keratin/PLLA nanofibers had a pH-stimuli responsive character in the acidic environment. HCT-116 tumor cell line was applied to investigate the antitumor effect of the composite nanofibers. The MTS assay indicated that adding keratin into the system increased the inhabitation of tumor cells after 120 hours observation. Zeta potential analysis was introduced to analyze the interaction effect between 5-FU and keratin. The in vitro drug release kinetics analysis indicated that due to the electrostatic interaction between keratin and 5-FU molecules, the composite nanofibers can extend the release period of 5-FU in the acidic environment which suggested a longer effective inhibition in local tumor chemotherapy.
Nightly Hypoxia Does Not Seem to Lead to Otolith Dysfunction in Patients With Obstructive Sleep Apnea
Authors: Birk Richard , Dietz Miriam , Sommer Jörg Ulrich , Stuck Boris A. , Hörmann Karl , Rotter Nicole , Maurer Joachim T. , Kramer Benedikt , Hülse Roland , Schell Angela 
Published: April 2020

Objectives: Obstructive sleep apnea (OSA) is a common sleep disorder, which is associated with recurrent oxygen desaturation during sleep. It has already been shown that nocturnal hypoxia may lead to cochlear dysfunction in patients with OSA. Less is known whether hypoxia during sleep also impacts vestibular function in those patients. Thus, the aim of the presented study was to assess a potential vestibulotoxic effect of nightly desaturations with hypoxia in patients with OSA by investigating a possible correlation between respiratory parameters and vestibular function tests. Methods: A total of 56 patients were included in the study and underwent a fully attended cardiorespiratory polysomnography (PSG). Vestibular function was assessed using video head impulse test to evaluate horizontal semicircular canal function and cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials (oVEMPs) to measure otolith function. Descriptive data analysis was conducted and correlation analysis between selected PSG parameters and the results of vestibular testing was performed using Kendall τ coefficient. Results: A significant correlation between vestibular function and respiratory polysomnographic parameters could not be demonstrated in the study ( P > .05) but cVEMP and oVEMP results showed a trend toward a correlation with oxygen desaturation indices and apnea–hypopnea index. Additionally, otolith hypofunction was more prevalent in patients with hypertension as well as OSA. Conclusion: The results of our study show that there is no significant correlation between vestibular function and sleep apnea parameters, although otolith dysfunction might be more prevalent in patients with OSA and hypertension.
Composite active range of motion (CXA) and relationship with active function in upper and lower limb spastic paresis
Authors: Bayle Nicolas , Maisonobe Pascal , Raymond Romain , Balcaitiene Jovita , Gracies Jean-Michel 
Published: April 2020

Objective: The aim of this study is to evaluate a novel composite measure of active range of motion (XA) and determine whether this measure correlates with active function. Design: Post hoc analysis of two randomized, placebo-controlled, double-blind studies with open-label extensions exploring changes in active function with abobotulinumtoxinA. Setting: Tertiary rehabilitation centers in Australia, Europe, and the United States. Subjects: Adults with upper ( n = 254) or lower ( n = 345) limb spastic paresis following stroke or brain trauma. Interventions: AbobotulinumtoxinA (⩽5 treatment cycles) in the upper or lower limb. Main measures: XA was used to calculate a novel composite measure (CXA), defined as the sum of XA against elbow, wrist, and extrinsic finger flexors (upper limb) or soleus and gastrocnemius muscles (lower limb). Active function was assessed by the Modified Frenchay Scale and 10-m comfortable barefoot walking speed in the upper limb and lower limb, respectively. Correlations between CXA and active function at Weeks 4 and 12 of open-label cycles were explored. Results: CXA and active function were moderately correlated in the upper limb ( P < 0.0001–0.0004, r = 0.476–0.636) and weakly correlated in the lower limb ( P < 0.0001–0.0284, r = 0.186–0.285) at Weeks 4 and 12 of each open-label cycle. Changes in CXA and active function were weakly correlated only in the upper limb (Cycle 2 Week 12, P = 0.0160, r = 0.213; Cycle 3 Week 4, P = 0.0031, r = 0.296). Across cycles, CXA improvements peaked at Week 4, while functional improvements peaked at Week 12. Conclusion: CXA is a valid measure for functional impairments in spastic paresis. CXA improvements following abobotulinumtoxinA injection correlated with and preceded active functional improvements.