bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma
Authors: Carvalho Diana , Taylor Kathryn R. , Olaciregui Nagore Gene , Molinari Valeria , Clarke Matthew , Mackay Alan , Ruddle Ruth , Henley Alan , Valenti Melanie , Hayes Angela , Brandon Alexis De Haven , Eccles Suzanne A. , Raynaud Florence , Boudhar Aicha , Monje Michelle , Popov Sergey , Moore Andrew S. , Mora Jaume , Cruz Ofelia , Vinci Mara , Brennan Paul E. , Bullock Alex N. , Carcaboso Angel Montero , Jones Chris 
Published: May 2019

AbstractDiffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug target, little has been done to-date to systematically evaluate the role of ACVR1 in DIPG, nor to screen currently available inhibitors in patient-derived tumour models. Here we show the dependence of DIPG cells on the mutant receptor, and the preclinical efficacy of two distinct chemotypes of ALK2 inhibitor in vitro and in vivo. We demonstrate the pyrazolo[1,5-a]pyrimidine LDN-193189 and the pyridine LDN-214117 to be orally bioavailable and well-tolerated, with good brain penetration. Treatment of immunodeprived mice bearing orthotopic xenografts of H3.3K27M, ACVR1R206H mutant HSJD-DIPG-007 cells with 25 mg/kg LDN-193189 or LDN-214117 for 28 days extended survival compared with vehicle controls. Development of ALK2 inhibitors with improved potency, selectivity and advantageous pharmacokinetic properties may play an important role in therapy for DIPG patients.
Lactobacillus maintains healthy gut mucosa by producing L-Ornithine
Authors: Qi Houbao , Li Yuanyuan , Yun Huan , Zhang Tong , Huang Yugang , Zhou Jiang , Yan Hui , Wei Jianmei , Liu Yingquan , Zhang Zhiqian , Gao Yunhuan , Che Yongzhe , Su Xiaomin , Zhu Dashuai , Zhang Yuan , Zhong Jin , Yang Rongcun 
Published: May 2019

AbstractGut mucosal layers are crucial in maintaining the gut barrier function. Gut microbiota regulate homeostasis of gut mucosal layer via gut immune cells such as RORγt (+) IL-22(+) ILC3 cells, which can influence the proliferation of mucosal cells and the production of mucin. However, it is unclear how gut microbiota execute this regulation. Here we show that lactobacilli promote gut mucosal formation by producing L-Ornithine from arginine. L-Ornithine increases the level of aryl hydrocarbon receptor ligand L-kynurenine produced from tryptophan metabolism in gut epithelial cells, which in turn increases RORγt (+)IL-22(+) ILC3 cells. Human REG3A transgenic mice show an increased proportion of L-Ornithine producing lactobacilli in the gut contents, suggesting that gut epithelial REG3A favors the expansion of L-Ornithine producing lactobacilli. Our study implicates the importance of a crosstalk between arginine metabolism in Lactobacilli and tryptophan metabolism in gut epithelial cells in maintaining gut barrier.
Topological soliton-polaritons in 1D systems of light and fermionic matter
Authors: Fraser Kieran A. , Piazza Francesco 
Published: May 2019

AbstractQuantum nonlinear optics is a quickly growing field with large technological promise, at the same time involving complex and novel many-body phenomena. In the usual scenario, optical nonlinearities originate from the interactions between polaritons, which are hybrid quasi-particles mixing matter and light degrees of freedom. Here we introduce a type of polariton which is intrinsically nonlinear and emerges as the natural quasi-particle in presence quantum degenerate fermionic matter. It is a composite object made of a fermion trapped inside an optical soliton forming a topological defect in a spontaneously formed crystalline structure. Each of these soliton-polaritons carries a Z2 topological quantum number, as they create a domain wall between two crystalline regions with opposite dimerization so that the fermion is trapped in an interphase state. These composite objects are formally equivalent to those appearing in the Su-Schrieffer-Heeger (SSH) model for electrons coupled to lattice phonons.
A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells
Authors: Mboge Mam Y. , Chen Zhijuan , Khokhar Daniel , Wolff Alyssa , Ai Lingbao , Heldermon Coy D. , Bozdag Murat , Carta Fabrizio , Supuran Claudiu T. , Brown Kevin D. , McKenna Robert , Frost Christopher J. , Frost Susan C. 
Published: May 2019

Abstract
The most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here, we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform-selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX co-operates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple-negative breast cancer, appears to co-ordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+ shuttle system in CA IX to facilitate proton efflux through MCT4.
Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice
Authors: Wan Bing , Li Yan , Sun Shuangshuang , Yang Yang , LV Yanling , Wang Li , Song Meijuan , Chen Meizi , Wu Chengjiang , Pan Hangcheng , Zhang Xiuwei 
Published: May 2019

AbstractThe present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.
Down-regulation of CCNE1 expression suppresses cell proliferation and sensitizes gastric carcinoma cells to Cisplatin
Authors: Zhang Chao , Zhu Qiang , Gu Jianzhong , Chen Shan , Li Qian , Ying Liping 
Published: May 2019

Abstract
A novel oncogene CCNE1 (cyclin E) is considered to be associated with the development of various tumor types, its role in gastric carcinoma (GC) is little studied and the effect of CCNE1 on chemotherapy also remains unclear. We recruited 55 cases of GC tissues and corresponding normal tissues. Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to detect the expression of CCNE1. We also examined the expression of CCNE1 in gastric mucosal GES-1 cells and five GC cell lines. Silencing CCNE1 was used to assess its effect on proliferation and cell cycle in MGC-803 and NCI-N87 cells, as performed by Cell counting kit-8 (CCK-8) and flow cytometry assay. Meanwhile, cell cycle related genes were also detected through qRT-PCR and Western blot. The results showed CCNE1 up-regulation mainly expressed in GC tissues and GC cell lines, also was associated with tumor node metastasis (TNM) stage and lymphatic invasion. Three-year survival curve analysis showed CCNE1 with high expression had a poor prognosis. Silencing CCNE1 significantly reduced cell viability in 48 h, cultured and arrested cell cycle in G1 phase, moreover, Cyclin A, D1 and C-myc all revealed down-regulation in both MGC-803 and NCI-N87 cells. CCNE1 expression was significantly increased at low and moderate concentrations of Cisplatin. Down-regulation of CCNE1 expression would remarkably promote cell apoptosis induced by Cisplatin, and regulate the rate of Bax/Bcl-2. Down-regulation of CCNE1 expression could inhibit cell proliferation and enhance GC cells sensibility to Cisplatin, possibly involving the regulation of Bcl-2 family.
ALMA reveals the magnetic field evolution in the high-mass star forming complex G9.62+0.19
Authors: Dall’Olio D. , Vlemmings W. H. T. , Persson M. V. , Alves F. O. , Beuther H. , Girart J. M. , Surcis G. , Torrelles J. M. , Van Langevelde H. J. 
Published: May 2019

Context.The role of magnetic fields during the formation of high-mass stars is not yet fully understood, and the processes related to the early fragmentation and collapse are as yet largely unexplored. The high-mass star forming region G9.62+0.19 is a well known source, presenting several cores at different evolutionary stages.Aims.We seek to investigate the magnetic field properties at the initial stages of massive star formation. We aim to determine the magnetic field morphology and strength in the high-mass star forming region G9.62+0.19 to investigate its relation to the evolutionary sequence of the cores.Methods.We made use of Atacama Large Millimeter Array (ALMA) observations in full polarisation mode at 1 mm wavelength (Band 7) and we analysed the polarised dust emission. We estimated the magnetic field strength via the Davis–Chandrasekhar–Fermi and structure function methods.Results.We resolve several protostellar cores embedded in a bright and dusty filamentary structure. The polarised emission is clearly detected in six regions: two in the northern field and four in the southern field. Moreover the magnetic field is orientated along the filament and appears perpendicular to the direction of the outflows. The polarisation vectors present ordered patterns and the cores showing polarised emission are less fragmented. We suggest an evolutionary sequence of the magnetic field, and the less evolved hot core exhibits a stronger magnetic field than the more evolved hot core. An average magnetic field strength of the order of 11 mG was derived, from which we obtain a low turbulent-to-magnetic energy ratio, indicating that turbulence does not significantly contribute to the stability of the clump. We report a detection of linear polarisation from thermal line emission, probably from methanol or carbon dioxide, and we tentatively compared linear polarisation vectors from our observations with previous linearly polarised OH masers observations. We also compute the spectral index, column density, and mass for some of the cores.Conclusions.The high magnetic field strength and smooth polarised emission indicate that the magnetic field could play an important role in the fragmentation and the collapse process in the star forming region G9.62+019 and that the evolution of the cores can be magnetically regulated. One core shows a very peculiar pattern in the polarisation vectors, which can indicate a compressed magnetic field. On average, the magnetic field derived by the linear polarised emission from dust, thermal lines, and masers is pointing in the same direction and has consistent strength.
Time variability in the bipolar scattered light nebula of L1527 IRS: a possible warped inner disk
Authors: Cook Brian T. , Tobin John J. , Skrutskie Michael F. , Nelson Matthew J. 
Published: May 2019

Context. The bipolar outflows associated with low-mass protostars create cavities in the infalling envelope. These cavities are illuminated by the central protostar and inner disk, creating a bipolar scattered light nebula at near-infrared and mid-infrared wavelengths. The variability of the scattered light nebula in both total intensity and intensity as a function of position in the scattered light nebula can provide important insights into the structure of the inner disk that cannot be spatially resolved.
Aims. We aim to determine the likelihood that a warped inner disk is the origin of the surface brightness variability in the bipolar scattered light nebula associated with L1527 IRS.
Methods. We present results from near-IR imaging conducted over the course of seven years, with periods of monthly cadence monitoring. We used Monte Carlo radiative transfer models to interpret the observations.
Results. We find a time varying, asymmetrical brightness in the scattered light nebulae within the outflow cavities of the protostar. Starting in 2007, the surface brightnesses of the eastern and western outflow cavities were roughly symmetric. Then, in 2009, the surface brightnesses of the cavities were found to be asymmetric, with a substantial increase in surface brightness and a larger increase in the eastern outflow cavity. More regular monitoring was conducted from 2011 to 2014, revealing a rotating pattern of surface brightness variability in addition to a slow change of the eastern and western outflow cavities toward symmetry, but still not as symmetric as observed in 2007. We find that an inner disk warp is a feasible mechanism to produce the rotating pattern of surface brightness variability.
Displaced Acetabular Fracture in Elderly Patients: Is Acute Arthroplasty an Effective Option?
Authors: Yang Zhengming , Röhrl Stephan Maximillian , Nordsletten Lars 
Published: May 2019

Abstract
Background and study aim Elderly individuals are the most rapidly growing subgroup of patients currently sustaining acetabular fractures, and total hip arthroplasty (THA) is being applied more and more in the treatment of acetabular fractures. The purpose of this study was to review the available literature regarding displaced acetabular fractures in elderly patients treated with acute THA.
Study design A search was conducted using the electronic databases Medline, PubMed, ISI Web of Knowledge, and Scopus on papers published between January 1960 and November 2018 using the terms “acetabular fracture” plus “elderly patients” plus “arthroplasty”. A systematic review of the literature on the different treatment options for acute THA is presented.
Results The search yielded a total of 320 articles, and 9 articles were selected for review. The indications, techniques, approaches, and complications of THA are discussed, and a treatment recommendation based on the selected articles is given.
Conclusion We consider acute arthroplasty an effective treatment option for displaced acetabular fractures in elderly patients, while different techniques should be used for different displaced acetabular fractures in this patient group.
Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto’s Thyroiditis? A Double Blind, Randomized Clinical Trial
Authors: Chahardoli Reza , Saboor-Yaraghi Ali-Akbar , Amouzegar Atieh , Khalili Davood , Vakili Azita , Azizi Fereidoun 
Published: May 2019

AbstractHashimoto’s thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.
Photoredox Fischer Indole Synthesis
Authors: Kaga Atsushi , Fukushima Tomohiro , Shimokawa Jun , Kitamura Masato 
Published: May 2019

Visible light photoredox conditions were applied to the traditional Fischer indole synthesis. N,N-Diarylhydrazones were efficiently converted into the corresponding indoles even at 30 °C by treatment with bromotrichloromethane in the presence of Ru(bpy)3Cl2·6H2O as the photocatalyst. Electrochemical study revealed the viability of oxidative quenching cycle for the photocatalysis, which set the basis for proposing the redox-based reaction mechanism.
Does a relationship exist between the number of training or competition hours and the presence of sonographic alterations in the shoulder of CrossFit athletes?
Authors: Vigar Claudia Juan , Medina-Mirapeix Francesc 
Published: May 2019

Introduction CrossFit is a sport that is on the rise and has a known injury rate thanks to studies that have affirmed that the shoulder is the area that suffers the most damage. To date, no objective tool has been used to evaluate this. The aim of the present study was to determine the frequency of structural sonographic alterations in CrossFit athletes and its relationship with accumulated hours of practice and/or competition in the sport and shoulder pain.
Material and Methods A cross-sectional descriptive study was conducted with sonographic assessments performed on 208 shoulders of 104 participants at official CrossFit gyms in Barcelona, between April and May 2017. The participants were requested to complete a specific questionnaire on CrossFit sports practice that included demographic data, the existence of pain, data on training routines, and clinical history. Ultrasound (US) examinations were made on the supraspinatus tendons (SST), on the long head of the biceps (LHB), and on the acromioclavicular (AC) joint.
Results The presence of focal hypoechoic areas (FHAs) in the LHB (48.1%) and in the SST (60.6%) were the most common alterations in this sample, whereas, at the level of the AC joint, the most common disorder was the presence of cortical defects (30.3%). Shoulder pain was present in 37.5% of the participants. The probability of experiencing pain increased when the athletes accumulated > 1,000 hours of training (odds ratio [OR] = 2.0). In these athletes, the probability of presenting a focal hypoechoic area (FHA) decreased in the LHB (OR = 0.3), and the width of the SST increased a mean of 0.5 mm (p < 0.01). In athletes who participated in competitions, the sonographic pattern also presented an increased width of the SST and LHB tendons; however, this was not related with an increased probability of experiencing pain.
Conclusions The sonographic pattern of the shoulder of CrossFit athletes presented structural changes in the SST and LHB tendons when subjects accumulated > 1,000 hours of training or when they participated in competitions. It is essential to relate the sonographic findings with the clinical findings of a patient to define whether these findings are, indeed, pathological. The probability of experiencing pain in the shoulder doubles when > 1,000 hours of CrossFit training are accumulated. This finding bears no relation with competing.
Timing of Delivery in Pregnancies Complicated by Suspected Fetal Growth Restriction without Doppler Abnormalities
Authors: Pineles Beth L. , Crimmins Sarah , Turan Ozhan 
Published: May 2019

Abstract
Objective This study aimed to identify the optimal gestational age for delivery of pregnancies complicated by fetal growth restriction (FGR) without Doppler abnormalities.
Study Design Cases of FGR (ultrasound-estimated fetal weight less than the 10th or abdominal circumference less than the 5th percentile for gestational age) without fetal Doppler abnormalities were identified from a fetal ultrasound database. The primary outcome was a composite of perinatal mortality and morbidity. The risk of the primary outcome for each gestational age was compared with pregnancies delivered at 390/7 to 406/7 weeks. Odds ratios were adjusted for potential confounders.
Results The analysis included 1,024 pregnancies. FGR was identified at a median of 235/7 weeks (range: 20–42 weeks). Four cases of fetal death (234/7—376/7 weeks) and no neonatal deaths were included. The primary outcome occurred in 209 patients (20.4%). This was greater for patients delivered at less than 37 weeks' gestation than for those delivered at or after 39 weeks' gestation, with no increased risk after 40 weeks.
Conclusion Among pregnancies complicated by suspected FGR without Doppler abnormalities, delivery at 39 weeks is safe with no difference in perinatal outcomes from 37 to 42 weeks.
Analysis of Radiographic Relationship between Distal Radius, Ulna, and Lunate
Authors: Mwaturura Tendai , Cloutier Frédéric-Charles , Daneshvar Parham 
Published: May 2019

Background Wrist anatomy variability is associated with differing susceptibility to pathology. For example, a flat radial inclination is associated with Kienbock's disease. Lunate facet inclination (LFI) also exhibits variability. Its relationship with other wrist features is poorly documented.
Purposes We tested the hypothesis that high LFI is associated with increased uncovering of the lunate, negative ulnar variance (UV), and type 2 lunates to balance forces across wrists.
Methods In total, 50 bilateral and 100 unilateral wrist posteroanterior radiographs were reviewed. Lunate type, lunate uncovering index (LUI), lunate tilting angle (LTA), UV, and sigmoid notch angle (SNA) were measured, and correlation with LFI was assessed on 150 right wrist radiographs followed by an assessment of differences based on lunate morphology. Symmetry of 50 bilateral wrists was assessed.
Results There was no correlation of LFI with lunate morphology, LUI, and LTA. There was a low correlation of LFI with SNA and UV. There was an inverse relationship between UV and SNA. Wrists with type 2 lunates had more oblique sigmoid notches and higher LTA in comparison to wrists with type 1 lunates. Side-to-side comparison revealed strong correlation except for LUI, which exhibited moderate correlation.
Conclusions There is no correlation between LFI, LUI, and lunate morphology. Type 2 lunates are associated with higher LTA and more oblique SNA. Wrists were symmetrical.
Clinical Relevance Factors other than lunate morphology are essential in balancing forces across wrists. A better understanding of soft tissue and other factors will improve the understanding of wrist biomechanics and pathology. Contralateral wrist radiographs can guide reconstructive surgery.