bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality indicators for in-hospital geriatric co-management programmes: a systematic literature review and international Delphi study
Authors: Van Grootven Bastiaan , McNicoll Lynn , Mendelson Daniel A , Friedman Susan M , Fagard Katleen , Milisen Koen , Flamaing Johan , Deschodt Mieke 
Published: March 2018

ObjectiveTo find consensus on appropriate and feasible structure, process and outcome indicators for the evaluation of in-hospital geriatric co-management programmes.DesignAn international two-round Delphi study based on a systematic literature review (searching databases, reference lists, prospective citations and trial registers).SettingWestern Europe and the USA.ParticipantsThirty-three people with at least 2 years of clinical experience in geriatric co-management were recruited. Twenty-eight experts (16 from the USA and 12 from Europe) participated in both Delphi rounds (85% response rate).MeasuresParticipants rated the indicators on a nine-point scale for their (1) appropriateness and (2) feasibility to use the indicator for the evaluation of geriatric co-management programmes. Indicators were considered appropriate and feasible based on a median score of seven or higher. Consensus was based on the level of agreement using the RAND/UCLA Appropriateness Method.ResultsIn the first round containing 37 indicators, there was consensus on 14 indicators. In the second round containing 44 indicators, there was consensus on 31 indicators (structure=8, process=7, outcome=16). Experts indicated that co-management should start within 24 hours of hospital admission using defined criteria for selecting appropriate patients. Programmes should focus on the prevention and management of geriatric syndromes and complications. Key areas for comprehensive geriatric assessment included cognition/delirium, functionality/mobility, falls, pain, medication and pressure ulcers. Key outcomes for evaluating the programme included length of stay, time to surgery and the incidence of complications.ConclusionThe indicators can be used to assess the performance of geriatric co-management programmes and identify areas for improvement. Furthermore, the indicators can be used to monitor the implementation and effect of these programmes.
Effect of copayment policies on initial medication non-adherence according to income: a population-based study
Authors: Aznar-Lou Ignacio , Pottegård Anton , Fernández Ana , Peñarrubia-María María Teresa , Serrano-Blanco Antoni , Sabés-Figuera Ramón , Gil-Girbau Montserrat , Fajó-Pascual Marta , Moreno-Peral Patricia , Rubio-Valera Maria 
Published: March 2018

ObjectiveCopayment policies aim to reduce the burden of medication expenditure but may affect adherence and generate inequities in access to healthcare. The objective was to evaluate the impact of two copayment measures on initial medication non-adherence (IMNA) in several medication groups and by income level.DesignA population-based study was conducted using real-world evidence.SettingPrimary care in Catalonia (Spain) where two separate copayment measures (fixed copayment and coinsurance) were introduced between 2011 and 2013.ParticipantEvery patient with a new prescription issued between 2011 and 2014 (3 million patients and 10 million prescriptions).OutcomesIMNA was estimated throughout dispensing and invoicing information. Changes in IMNA prevalence after the introduction of copayment policies (immediate level change and trend changes) were estimated through segmented logistic regression. The regression models were stratified by economic status and medication groups.ResultsBefore changes to copayment policies, IMNA prevalence remained stable. The introduction of a fixed copayment was followed by a statistically significant increase in IMNA in poor population, low/middle-income pensioners and low-income non-pensioners (OR from 1.047 to 1.370). In high-income populations, there was a large statistically non-significant increase. IMNA decreased in the low-income population after suspension of the fixed copayment and the introduction of a coinsurance policy that granted this population free access to medications (OR=0.676). Penicillins were least affected while analgesics were affected to the greatest extent. IMNA to medications for chronic conditions increased in low/middle-income pensioners.ConclusionEven nominal charge fixed copayment may generate inequities in access to health services. An anticipation effect and expenses associated with IMNA may have generated short-term costs. A reduction in copayment can protect from non-adherence and have positive, long-term effects. Copayment scenarios could have considerable long-term consequences for health and costs due to increased IMNA in medication for chronic physical conditions.
The black hole interior and the type II Weyl fermions
Authors: Zubkov M. A. 
Published: March 2018

It was proposed recently that the black hole may undergo a transition to the state, where inside the horizon the Fermi surface is formed that reveals an analogy with the recently discovered type II Weyl semimetals. In this scenario, the low energy effective theory outside of the horizon is the Standard Model, which describes excitations that reside near a certain point [Formula: see text] in momentum space of the hypothetical unified theory. Inside the horizon the low energy physics is due to the excitations that reside at the points in momentum space close to the Fermi surface. We argue that those points may be essentially distant from [Formula: see text] and, therefore, inside the black hole the quantum states are involved in the low energy dynamics that are not described by the Standard Model. We analyze the consequences of this observation for the physics of the black holes and present the model based on the direct analogy with the type II Weyl semimetals, which illustrates this pattern.
Nonperturbative quark–gluon thermodynamics at finite density
Authors: Andreichikov M. A. , Lukashov M. S. , Simonov Yu. A. 
Published: March 2018

Thermodynamics of the quark–gluon plasma at finite density is studied in the framework of the Field Correlator Method, where thermodynamical effects of Polyakov loops and color magnetic confinement are taken into account. Having found good agreement with numerical lattice data for zero density, we calculate pressure [Formula: see text], for [Formula: see text] MeV and [Formula: see text] MeV. For the first time, the explicit integral form is found in this region, demonstrating analytic structure in the complex [Formula: see text] plane. The resulting multiple complex branch points are found at the Roberge–Weiss values of [Formula: see text], with [Formula: see text] defined by the values of Polyakov lines and color magnetic confinement.
Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages
Authors: Che Xiumei , Park Ki Cheong , Park Soo Jung , Kang You Hyun , Jin Hyun A , Kim Joo Wan , Seo Dong Hyuk , Kim Dae Kyu , Kim Tae Il , Kim Won Ho , Kim Seung Won , Cheon Jae Hee 
Published: March 2018

Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound-healing assay using HT-29 cells was performed. Colitis in wild-type and IL-10-, Toll-like receptor 4 (TLR4)-, and myeloid differentiation primary response 88 (MyD88)-deficient mice was induced via the administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon. In both in vitro and in vivo experiments, guggulsterone suppressed intestinal inflammation amplified by TREM-1 stimulation, in which the suppression of NF-κB, activating protein-1, and proteasome pathways was involved. In the TNBS-induced colitis model, guggulsterone reduced disease activity index scores and TREM-1 expression, stimulated IL-10 production, and improved survival in wild-type mice. These effects were not observed in IL-10-, TLR4-, and MyD88-deficient mice. Guggulsterone also suppressed M1 polarization, yet induced the M2 phenotype in macrophages from IBD patients as well as from mice. These findings indicate that guggulsterone blocks the hyperactivation of macrophages via TREM-1 suppression and induces M2 polarization via IL-10 mediated by the TLR4 signaling pathway. Furthermore, this study provides a new rationale for the therapeutic potential of guggulsterone in the treatment of IBD. NEW & NOTEWORTHY We found that guggulsterone attenuates triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated hyperactivation of macrophages and polarizes macrophages toward the M2 phenotype. This was mediated by IL-10 and partly Toll-like receptor 4 signaling pathways. Overall, these data support that guggulsterone as a natural plant sterol modulates macrophage phenotypes in colitis, which may be of novel therapeutic importance in inflammatory bowel disease treatment.
Primary cilia disruption differentially affects the infiltrating and resident macrophage compartment in the liver
Authors: Zimmerman Kurt A. , Song Cheng Jack , Gonzalez-Mize Nancy , Li Zhang , Yoder Bradley K. 
Published: March 2018

Hepatorenal fibrocystic disease (HRFCD) is characterized by cysts in the kidney and liver with associated fibrosis and is the result of defects in proteins required for cilia function or assembly. Previous reports indicate that macrophages, mainly M2-like macrophages, contribute to HRFCD, although the origin of these cells (yolk sac-derived resident macrophages vs. bone marrow-derived infiltrating macrophages) and their contribution to the observed phenotypes are unknown. We utilize a congenital model of cilia dysfunction (IFT88Orpk) to study the importance of macrophages in HRFCD. Our data show a rapid expansion of the bile duct region and development of fibrosis between 2 and 4 wk of age. Immunofluorescence microscopy analysis reveals an accumulation of F4/80+ macrophages in regions exhibiting biliary hyperplasia in IFT88Orpk mice. Flow cytometry data show that cilia dysfunction leads to an accumulation of infiltrating macrophages (CD11bhi, F4/80lo) and a reduction of resident macrophage (CD11blo, F4/80hi) number. A majority of the infiltrating macrophages are Ly6chi profibrogenic macrophages. Along with the accumulation of immune cells, expression of proinflammatory and profibrotic transcripts, including TGF-β, TNF-α, IL-1β, and chemokine (C-C) motif ligand 2, is increased. Quantitative RT-PCR analysis of flow-sorted cells shows enhanced expression of CCL2 in cholangiocytes and enhanced expression of VEGF-A and IL-6 in Ly6chi macrophages. Genetic inhibition of Ly6chi macrophage accumulation in IFT88Orpk FVB CCR2−/− mice reduced biliary fibrosis but did not affect epithelial expansion. Collectively, these studies suggest that biliary epithelium with defects in primary cilia preferentially recruits Ly6chi infiltrating macrophages, which promote fibrotic progression in HRFCD pathogenesis. NEW & NOTEWORTHY These studies are the first to address the contribution of the infiltrating and resident macrophage niche during progression of hepatorenal fibrocystic disease (HRFCD). We show that the number of infiltrating macrophages is significantly upregulated in HRFCD mouse models. Finally, we show that prevention of Ly6chi infiltrating macrophage accumulation significantly reduces biliary fibrosis, but not biliary hyperplasia, suggesting that this population may be responsible for the fibrotic progression of the disease in HRFCD patients.
Impact of chronic hypoxia on proximal pulmonary artery wave propagation and mechanical properties in rats
Authors: Su Junjing , Logan Charmilie C. , Hughes Alun D. , Parker Kim H. , Dhutia Niti M. , Danielsen Carl Christian , Simonsen Ulf 
Published: March 2018

Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals/group), animals underwent transthoracic echocardiography and PA catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis was performed. Artery rings obtained from the pulmonary trunk, right and left PAs, and aorta were subjected to a tensile test to rupture. Collagen and elastin content were determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus, and wall viscosity increased, whereas the elastin-to-collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased, and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in hypoxic and normoxic animals with negligible wave reflection. In contrast, the aortic maximal elastic modulus remained unchanged, whereas wall viscosity decreased. In conclusion, there was no evidence of altered arterial wave propagation in proximal PAs of hypoxic rats while the extracellular matrix protein composition was altered and collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo.NEW & NOTEWORTHY In rats exposed to chronic hypoxia, we have shown that pulse wave velocity in the proximal pulmonary arteries increased and pressure dependence of the pulse wave velocity was steeper in vivo than ex vivo leading to a more prominent increase in vivo.
One-week cocoa flavanol intake increases prefrontal cortex oxygenation at rest and during moderate-intensity exercise in normoxia and hypoxia
Authors: Decroix Lieselot , Tonoli Cajsa , Lespagnol Elodie , Balestra Constantino , Descat Amandine , Drittij-Reijnders Marie José , Blackwell Jamie R. , Stahl Wilhelm , Jones Andrew M. , Weseler Antje R. , Bast Aalt , Meeusen Romain , Heyman Elsa 
Published: March 2018

During exercise in hypoxia, O2 delivery to brain and muscle is compromised, and oxidative stress is elicited. Cocoa flavanols (CF) have antioxidant capacities and can increase blood flow by stimulating endothelial function. We aimed to examine the effects of 7-day CF intake on oxidative stress, nitric oxide production, and tissue oxygenation in response to exercise in normobaric hypoxia (14.3% O2). In a randomized, double-blind, cross-over study, 14 well-trained male cyclists completed four trials: exercise in normoxia or hypoxia, after 7-day CF or placebo intake. Flow-mediated dilation (FMD) was measured before intake of the last dose CF or placebo. One hundred minutes later, 20-min steady-state (SS; 45% V̇o2max) and 20-min time trial (TT) (cycling) were performed. Blood samples were taken. Prefrontal and muscular oxygenation was assessed by near-infrared spectroscopy. At baseline, FMD was increased by CF. Hypoxia increased exercise-induced elevations in lipid peroxidation and antioxidant capacity. CF suppressed exercise-induced lipid peroxidation but did not influence antioxidant capacity. At rest and during SS, prefrontal and muscular oxygenation was decreased by hypoxia. CF elevated prefrontal oxygenation but did not impact muscular oxygenation. During TT, hypoxia accelerated the exercise-induced decrease in prefrontal oxygenation, but not in muscular oxygenation. During TT, CF did not alter prefrontal and muscular oxygenation. CF did not change plasma nitrite, nitrate, and arginine:citrulline. During high-intensity exercise, CF improved neither tissue oxygenation nor performance in well-trained athletes. At rest and during moderate-intensity exercise, CF reduced exercise-induced lipid peroxidation and partially restored the hypoxia-induced decline in prefrontal oxygenation. NEW & NOTEWORTHY For the first time, we showed that CF had beneficial effects on endothelial function at rest, as well as on prefrontal oxygenation at rest and during moderate-intensity exercise, both in normoxia and hypoxia. Moreover, we showed that CF intake inhibited oxidative stress during exhaustive exercise in hypoxia.
Mutant IDH1 Cooperates with ATRX Loss to Drive the Alternative Lengthening of Telomere Phenotype in Glioma
Authors: Mukherjee Joydeep , Johannessen Tor-Christian , Ohba Shigeo , Chow Tracy T. , Jones Lindsey , Pandita Ajay , Pieper Russell O. 
Published: March 2018

Abstract
A subset of tumors use a recombination-based alternative lengthening of telomere (ALT) pathway to resolve telomeric dysfunction in the absence of TERT. Loss-of-function mutations in the chromatin remodeling factor ATRX are associated with ALT but are insufficient to drive the process. Because many ALT tumors express the mutant isocitrate dehydrogenase IDH1 R132H, including all lower grade astrocytomas and secondary glioblastoma, we examined a hypothesized role for IDH1 R132H in driving the ALT phenotype during gliomagenesis. In p53/pRb–deficient human astrocytes, combined deletion of ATRX and expression of mutant IDH1 were sufficient to create tumorigenic cells with ALT characteristics. The telomere capping complex component RAP1 and the nonhomologous DNA end joining repair factor XRCC1 were each downregulated consistently in these tumorigenic cells, where their coordinate reexpression was sufficient to suppress the ALT phenotype. RAP1 or XRCC1 downregulation cooperated with ATRX loss in driving the ALT phenotype. RAP1 silencing caused telomere dysfunction in ATRX-deficient cells, whereas XRCC1 silencing suppressed lethal fusion of dysfunctional telomeres by allowing IDH1-mutant ATRX-deficient cells to use homologous recombination and ALT to resolve telomeric dysfunction and escape cell death. Overall, our studies show how expression of mutant IDH1 initiates telomeric dysfunction and alters DNA repair pathway preferences at telomeres, cooperating with ATRX loss to defeat a key barrier to gliomagenesis.
Significance: Studies show how expression of mutant IDH1 initiates telomeric dysfunction and alters DNA repair pathway preferences at telomeres, cooperating with ATRX loss to defeat a key barrier to gliomagenesis and suggesting new therapeutic options to treat low-grade gliomas. Cancer Res; 78(11); 2966–77. ©2018 AACR.
Acquired Resistance to a MET Antibody In Vivo Can Be Overcome by the MET Antibody Mixture Sym015
Authors: Pollmann Sofie Ellebaek , Calvert Valerie S. , Rao Shruti , Boca Simina M. , Madhavan Subha , Horak Ivan D. , Kjaer Andreas , Petricoin Emanuel F. , Kragh Michael , Poulsen Thomas Tuxen 
Published: March 2018

Abstract
Failure of clinical trials due to development of resistance to MET-targeting therapeutic agents is an emerging problem. Mechanisms of acquired resistance to MET tyrosine kinase inhibitors are well described, whereas characterization of mechanisms of resistance toward MET-targeting antibodies is limited. This study investigated mechanisms underlying in vivo resistance to two antibody therapeutics currently in clinical development: an analogue of the MET-targeting antibody emibetuzumab and Sym015, a mixture of two antibodies targeting nonoverlapping epitopes of MET. Upon long-term in vivo treatment of a MET-amplified gastric cancer xenograft model (SNU-5), emibetuzumab-resistant, but not Sym015-resistant, tumors emerged. Resistant tumors were isolated and used to establish resistant cell lines. Characterization of both tumors and cell lines using extensive protein and signaling pathway activation mapping along with next-generation sequencing revealed two distinct resistance profiles, one involving PTEN loss and the other involving activation of the PI3K pathway, likely via MYC and ERBB3 copy number gains. PTEN loss left one model unaffected by PI3K/AKT targeting but sensitive to mTOR targeting, while the PI3K pathway–activated model was partly sensitive to targeting of multiple PI3K pathway proteins. Importantly, both resistant models were sensitive to treatment with Sym015 in vivo due to antibody-dependent cellular cytotoxicity–mediated tumor growth inhibition, MET degradation, and signaling inhibition. Taken together, our data provide key insights into potential mechanisms of resistance to a single MET-targeting antibody, demonstrate superiority of Sym015 in preventing acquired resistance, and confirm Sym015 antitumor activity in tumors resistant to a single MET antibody. Mol Cancer Ther; 17(6); 1259–70. ©2018 AACR.
TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma
Authors: Zhao Zhijian , Zhang Mengping , Duan Xiaolu , Chen Yiwen , Li Ermao , Luo Lianmin , Wu Wenqi , Peng Zhenwei , Qiu Huijuan , Zeng Guohua 
Published: March 2018

Abstract
Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of in vitro and in vivo assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation in vitro and tumor growth in vivo. Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3′-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease.
Implications: TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. Mol Cancer Res; 16(6); 1013–23. ©2018 AACR.
АКТУАЛЬНІСТЬ ПІДГОТОВКИ МЕНЕДЖЕРІВ ДЛЯ ВПРОВАДЖЕННЯ ДЕРЖАВНО-ПРИВАТНОГО ПАРТНЕРСТВА В ОХОРОНІ ЗДОРОВ'Я
Authors: Kravchenko V. V. 
Published: March 2018

Мета роботи: Обґрунтувати необхідність підготовки менеджерів для реалізації державно-приватного партнерства у системі охорони здоров'я.Матеріали та методи дослідження. Для досягнення поставленої мети у роботі використані загальнонаукові методи аналізу, синтезу, узагальнення, інтерпретації наукових даних, а також системний і структурно-функціональний підходи.Результати. Обґрунтовано доцільність підготовки менеджерів з навичками ефективного економічного управління для закладів охорони здоров'я комунального і регіонального рівня, які переходять на принципи ДПП.Висновки. Управлінський апарат діючих державних і комунальних закладів охорони здоров'я не в змозі використати економічні важелі та підвищити соціальну та економічну ефективність охорони здоров'я. Пріоритетними напрямками розвитку медичних закладів у нових економічних умовах є формування їх господарського механізму на принципах державно-приватного партнерства та підготовка менеджерів для управління новим типом закладів.