bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive reduction in the checkpoint inhibitor, CTLA-4, does not accelerate SLE in NZM 2328 mice
Authors: Stohl William , Yu Ning , Chalmers Samantha A , Putterman Chaim , Jacob Chaim O 
Published: February 2019

Background/objectiveTreatment with immune checkpoint inhibitors (ICIs) in oncology patients is increasing. Although ICIs trigger rheumatic immune-related adverse events, development of SLE features has been rare. Whether long-term treatment with ICIs would promote SLE features remains unknown. To begin to address this, we generated SLE-prone NZM 2328 mice with lifelong reduction in CTLA-4 expression.MethodsSince CTLA-4-deficient (Ctla4−/−) NZM mice developed a lethal lymphoproliferative disorder by 3–6 weeks of age, development of SLE in these mice could not be studied.Ctla4haploinsufficient NZM.Ctla4+/−mice were assessed in parallel with littermate female NZM.Ctla4+/+mice. Evaluations included CTLA-4 expression and lymphocyte profiles, assessed by fluorescence-activated cell sorting; serological profiles, assessed by ELISA; renal immunopathology, assessed by histology and immunofluorescence; and clinical courses, assessed by mortality.ResultsCTLA-4 expression was lower in NZM.Ctla4+/−mice than in NZM.Ctla4+/+mice. Spleen mononuclear cells, B cells, plasma cells, CD4+cells, recently activated CD4+cells and CD4+T regulatory (Treg) cells were increased in NZM.Ctla4+/−mice (p≤0.042). The serological profile, degree of renal immunopathology and mortality in NZM.Ctla4+/−mice remained unaffected.ConclusionLifelong reduction in CTLA-4 expression in NZM mice neither accelerated nor aggravated SLE. Expansion in Treg cells may have played a protective role. Our observations raise the hope that long-term treatment of patients with SLE with an anti-CTLA-4 agent, should the need arise, would not adversely affect SLE disease activity.
“Residents get no… satisfaction”a problem to face during internal medicine rotations: development and psychometric properties of the IMPRINT-15
Authors: Díaz Luis Antonio , Sepúlveda Paola , Abbott Eduardo , Fuentes-López Eduardo , Letelier Luz María , Riquelme Arnoldo , Aizman Andrés 
Published: February 2019

AbstractClinical rotations are an essential part of Internal Medicine (IM) residency programmes, where curricular objectives are carried out. To our knowledge, there are no validated instruments to assess IM clinical rotations. Our objective was to develop an instrument for residents to assess the quality of clinical rotations in an IM residency programme, and to test the psychometric properties of the instrument. A mixed methodology was used, including qualitative and quantitative phases. Items were proposed by a group of experts based on previously identified residency needs, followed by a quantitative phase to generate consensus among educators and residents to define which items would be included in the instrument (Delphi panel). After generating the instrument, psychometric tests were performed to assess construct validity (factor analysis) and reliability (Raykov’s reliability coefficient). We obtained a 15-item instrument after two Delphi rounds: Internal Medicine Program Instrument 15-items (IMPRINT-15). Sixty-two residents answered 428 surveys using a Likert scale during 7 months (response rate 98.9%). The median score was 4.3 (IQR 3.9–4.7) (scale from 1 to 5). The factor analysis showed two domains in the clinical rotation assessment: (1) teaching and care activities; (2) evaluation and feedback. The instrument is reliable with Raykov’s reliability coefficient of 0.86. Also, Raykov’s reliability coefficient for the domains were 0.89 and 0.83, respectively. The IMPRINT-15 instrument is a bi-dimensional, valid and reliable questionnaire to evaluate the perceived quality by residents of the IM clinical rotations. Also, it constitutes the first validated instrument in this field worldwide.
Time-resolved quantification of the dynamic extracellular space in the brain during short-lived event: methodology and simulations
Authors: Chen Kevin C. , Zhou Yi , Zhao Hui-Hui 
Published: February 2019

Two macroscopic parameters describe the interstitial diffusion of substances in the extracellular space (ECS) of the brain, the ECS volume fraction α and the diffusion tortuosity λ. Past methods based on sampling the extracellular concentration of a membrane-impermeable ion tracer, such as tetramethylammonium (TMA+), can characterize either the dynamic α( t) alone or the constant α and λ in resting state but never the dynamic α( t) and λ( t) simultaneously in short-lived brain events. In this work, we propose to use a sinusoidal method of TMA+to provide time-resolved quantification of α( t) and λ( t) in acute brain events. This method iontophoretically injects TMA+in the brain ECS by a sinusoidal time pattern, samples the resulting TMA+diffusion waveform at a distance, and analyzes the transient modulations of the amplitude and phase lag of the sampled TMA+waveform to infer α( t) and λ( t). Applicability of the sinusoidal method was verified through computer simulations of the sinusoidal TMA+diffusion waveform in cortical spreading depression. Parameter sensitivity analysis identified the sinusoidal frequency and the interelectrode distance as two key operating parameters. Compared with other TMA+-based methods, the sinusoidal method can more accurately capture the dynamic α( t) and λ( t) in acute brain events and is equally applicable to other pathological episodes such as epilepsy, transient ischemic attack, and brain injury. Future improvement of the method should focus on high-fidelity extraction of the waveform amplitude and phase angle.NEW & NOTEWORTHY An iontophoretic sinusoidal method of tetramethylammonium is described to capture the dynamic brain extracellular space volume fraction α and diffusion tortuosity λ. The sinusoidal frequency and interelectrode distance are two key operating parameters affecting the method’s accuracy in capturing α( t) and λ( t). High-fidelity extraction of the waveform amplitude and phase lag is critical to successful sinusoidal analyses.
Planning face, hand, and leg movements: anatomical constraints on preparatory inhibition
Authors: Labruna Ludovica , Tischler Claudia , Cazares Christian , Greenhouse Ian , Duque Julie , Lebon Florent , Ivry Richard B. 
Published: February 2019

Motor-evoked potentials (MEPs), elicited by transcranial magnetic stimulation (TMS) over the motor cortex, are reduced during the preparatory period in delayed response tasks. In this study we examined how MEP suppression varies as a function of the anatomical organization of the motor cortex. MEPs were recorded from a left index muscle while participants prepared a hand or leg movement in experiment 1 or prepared an eye or mouth movement in experiment 2. In this manner, we assessed if the level of MEP suppression in a hand muscle varied as a function of the anatomical distance between the agonist for the forthcoming movement and the muscle targeted by TMS. MEP suppression was attenuated when the cued effector was anatomically distant from the hand (e.g., leg or facial movement compared with finger movement). A similar effect was observed in experiment 3 in which MEPs were recorded from a muscle in the leg and the forthcoming movement involved the upper limb or face. These results demonstrate an important constraint on preparatory inhibition: it is sufficiently broad to be manifest in a muscle that is not involved in the task, but it is not global, showing a marked attenuation when the agonist muscle belongs to a different segment of the body. NEW & NOTEWORTHY Using transcranial magnetic stimulation, we examined changes in corticospinal excitability as people prepared to move. Consistent with previous work, we observed a reduction in excitability during the preparatory period, an effect observed in both task-relevant and task-irrelevant muscles. However, this preparatory inhibition is anatomically constrained, attenuated in muscles belonging to a different body segment than the agonist of the forthcoming movement.
Parallel distributed networks resolved at high resolution reveal close juxtaposition of distinct regions
Authors: Braga Rodrigo M. , Van Dijk Koene R. A. , Polimeni Jonathan R. , Eldaief Mark C. , Buckner Randy L. 
Published: February 2019

Examination of large-scale distributed networks within the individual reveals details of cortical network organization that are absent in group-averaged studies. One recent discovery is that a distributed transmodal network, often referred to as the “default network,” comprises two closely interdigitated networks, only one of which is coupled to posterior parahippocampal cortex. Not all studies of individuals have identified the same networks, and questions remain about the degree to which the two networks are separate, particularly within regions hypothesized to be interconnected hubs. In this study we replicate the observation of network separation across analytical (seed-based connectivity and parcellation) and data projection (volume and surface) methods in two individuals each scanned 31 times. Additionally, three individuals were examined with high-resolution (7T; 1.35 mm) functional magnetic resonance imaging to gain further insight into the anatomical details. The two networks were identified with separate regions localized to adjacent portions of the cortical ribbon, sometimes inside the same sulcus. Midline regions previously implicated as hubs revealed near complete spatial separation of the two networks, displaying a complex spatial topography in the posterior cingulate and precuneus. The network coupled to parahippocampal cortex also revealed a separate region directly within the hippocampus, at or near the subiculum. These collective results support that the default network is composed of at least two spatially juxtaposed networks. Fine spatial details and juxtapositions of the two networks can be identified within individuals at high resolution, providing insight into the network organization of association cortex and placing further constraints on interpretation of group-averaged neuroimaging data.NEW & NOTEWORTHY Recent evidence has emerged that canonical large-scale networks such as the “default network” fractionate into parallel distributed networks when defined within individuals. This research uses high-resolution imaging to show that the networks possess juxtapositions sometimes evident inside the same sulcus and within regions that have been previously hypothesized to be network hubs. Distinct circumscribed regions of one network were also resolved in the hippocampal formation, at or near the parahippocampal cortex and subiculum.
β-Arrestins Regulate Stem Cell-Like Phenotype and Response to Chemotherapy in Bladder Cancer
Authors: Kallifatidis Georgios , Smith Diandra K. , Morera Daley S. , Gao Jie , Hennig Martin J. , Hoy James J. , Pearce Richard F. , Dabke Isha R. , Li Jiemin , Merseburger Axel S. , Kuczyk Markus A. , Lokeshwar Vinata B. , Lokeshwar Bal L. 
Published: February 2019

Abstract
β-Arrestins are classic attenuators of G-protein–coupled receptor signaling. However, they have multiple roles in cellular physiology, including carcinogenesis. This work shows for the first time that β-arrestins have prognostic significance for predicting metastasis and response to chemotherapy in bladder cancer. β-Arrestin-1 (ARRB1) and β-arrestin-2 (ARRB2) mRNA levels were measured by quantitative RT-PCR in two clinical specimen cohorts (n = 63 and 43). The role of ARRBs in regulating a stem cell-like phenotype and response to chemotherapy treatments was investigated. The consequence of forced expression of ARRBs on tumor growth and response to Gemcitabine in vivo were investigated using bladder tumor xenografts in nude mice. ARRB1 levels were significantly elevated and ARRB2 levels downregulated in cancer tissues compared with normal tissues. In multivariate analysis only ARRB2 was an independent predictor of metastasis, disease-specific-mortality, and failure to Gemcitabine + Cisplatin (G+C) chemotherapy; ∼80% sensitivity and specificity to predict clinical outcome. ARRBs were found to regulate stem cell characteristics in bladder cancer cells. Depletion of ARRB2 resulted in increased cancer stem cell markers but ARRB2 overexpression reduced expression of stem cell markers (CD44, ALDH2, and BMI-1), and increased sensitivity toward Gemcitabine. Overexpression of ARRB2 resulted in reduced tumor growth and increased response to Gemcitabine in tumor xenografts. CRISPR-Cas9–mediated gene-knockout of ARRB1 resulted in the reversal of this aggressive phenotype. ARRBs regulate cancer stem cell-like properties in bladder cancer and are potential prognostic indicators for tumor progression and chemotherapy response.
Characterization of Bacterial Communities in Bioaerosols over Northern Chinese Marginal Seas and the Northwestern Pacific Ocean in Spring
Authors: Ma Manman , Zhen Yu , Mi Tiezhu 
Published: February 2019

AbstractStudies of the community structures of bacteria in marine aerosols of different particle sizes have not been reported. Aerosol samples were collected using a six-stage bioaerosol sampler over the Bohai Sea, the Yellow Sea, and northwestern Pacific Ocean in the spring of 2014. The diversity and composition of these samples were investigated by Illumina high-throughput sequencing, and 130 genera were detected in all of the samples; the most abundant bacterial genus was Bacteroides, followed by Prevotella and Megamonas. The Chao1 and Shannon diversity indices ranged from 193 to 1044 and from 5.44 to 8.33, respectively. The bacterial community structure in coarse particles (diameter larger than 2.1 μm) was more complex and diverse than that in fine particles (diameter less than 2.1 μm) in marine bioaerosols from over the Yellow Sea and northwestern Pacific Ocean, while the opposite trend was observed for samples collected over the Bohai Sea. Although we were sampling over marine regions, the sources of the bioaerosols were mostly continental. Temperature and wind speed significantly influenced the bacterial communities in marine aerosols of different particle sizes. There may be a bacterial background in the atmosphere in the form of several dominant taxa, and the bacterial communities are likely mixed constantly during transmission.
Interannual Variability and Seasonality of Precipitation in the Indus River Basin
Authors: Minallah Samar , Ivanov Valeriy Y. 
Published: February 2019

AbstractThe Indus River basin is highly vulnerable to water scarcity due to increasing population, unsustainable management practices, and climate change. Yet the regional hydroclimate and precipitation dynamics remain poorly understood. Using running trend and spectral analysis with multiple gauge-based, remote sensing, and reanalysis precipitation datasets, this study analyzes precipitation temporal variability, its subregional variations, and the main seasonal drivers, particularly the South Asian monsoon. The results uncover remarkable alternation of long-term positive and negative interdecadal precipitation trends in the basin over the past half century. These trends have led to substantial changes in water input over the region at the time scales comparable to climate assessment periods (30 years), and therefore this high intrinsic variability must be accounted for in climate change adaptation studies. This study also reconstructs onset and withdrawal dates of the South Asian monsoon that exhibit interdecadal variability, but their dominant modes differ from that of annual precipitation. The findings hypothesize that higher-frequency variability in El Niño–Southern Oscillation is likely to have a pronounced impact on monsoon onset and duration in the studied region.
Land Surface Parameter and State Perturbations in the Global Ensemble Forecast System
Authors: Gehne Maria , Hamill Thomas M. , Bates Gary T. , Pegion Philip , Kolczynski Walter 
Published: February 2019

AbstractThe National Centers for Environmental Prediction (NCEP) Global Ensemble Forecast System (GEFS) is underdispersive near the surface, a common characteristic of ensemble prediction systems. Here, several methods for increasing the spread are tested, including perturbing soil initial conditions, soil tendencies, and surface parameters, with physically based perturbations. Perturbations are applied to the soil initial conditions based on empirical orthogonal functions (EOFs) of differences between normalized soil moisture states from two land surface models (LSMs). Perturbations to roughness lengths for heat and momentum, soil hydraulic conductivity, stomatal resistance, vegetation fraction, and albedo are applied, with the amplitude and perturbation scales based on previous research. Soil moisture and temperature tendencies are also perturbed using a stochastic perturbation scheme. The results show that surface perturbations, through their impact on 2-m temperature spread, have a modest positive impact on the skill of short-range ensemble forecasts. However, adjusting the forecasts using an estimate of the systematic bias shows that bias correction has a greater impact on the forecast reliability than surface perturbations, indicating that systematic bias in the model needs to be addressed as well.
Comparison between intra-articular Botulinum toxin type A, corticosteroid, and saline in knee osteoarthritis: a randomized controlled trial
Authors: Mendes Jamille Godoy , Natour Jamil , Nunes-Tamashiro José Carlos , Toffolo Sandra Regina , Rosenfeld André , Furtado Rita Nely Vilar 
Published: February 2019

Objective: To compare the effectiveness of intra-articular injection (IAI) with Botulinum toxin type A (BTA), triamcinolone hexacetonide (TH), and saline in primary knee osteoarthritis. Design: A randomized controlled trial, with blinded patients and assessor. Setting: Outpatient rheumatology service. Subjects: Patients with knee osteoarthritis grades II and III. Interventions: Patients received IAI with 100 IU BTA, 40 mg TH, or isotonic saline solution (SS) 0.9%. Main measures: Patients were assessed at baseline and at 4, 8, and 12 weeks with the following instruments: visual analog scale for pain during movement (VASm; primary outcome) and visual analog scale for pain at rest (VASr), Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, 6-minute walk test, Timed Up and Go test, Short Form (SF)-36 questionnaire, range of motion of knee, and ultrasound (US) measurement of synovial hypertrophy. Results: In total, 105 patients were randomized, with 35 in each group; 96 were female (91.4%) and 9 were male (8.6%), with a mean age of 64.2 years (±6.9). At 12 weeks, the TH group showed better results only for VASm. At four weeks, the TH group showed better results than the BTA and SS groups for VASm (–68.9% (37.8) vs. –35.3% (40.3) vs. –35.9% (51.4)), WOMAC pain (–56.0% (30.7) vs. –30.8% (34.3) vs. –30.0% (39.9)), WOMAC stiffness (–53.4% (38.4) vs. –17.2% (59.3) vs. –17.3% (78.1)), WOMAC function (–48.2% (34.6) vs. 30.8% (33.6) vs. –13.6% (64.9)), WOMAC total score (–51.2% (31.0) vs. –30.9% (30.0) vs. –18.8% (54.8)), and US measurement of synovial hypertrophy (–11.6% (44.9) vs. –1.5% (47.9) vs. +28.6% (81.3)). Conclusion: IAI with TH had a higher effectiveness than that with TBA or SS in the short-term assessment (four weeks) for pain in movement, WOMAC, and US measurement of synovial hypertrophy.
Clinical experience of magnetic resonance imaging in patients with cardiac pacing devices: unrestricted patient population
Authors: Vuorinen Aino-Maija , Pakarinen Sami , Jaakkola Ilkka , Holmström Miia , Kivistö Sari , Kaasalainen Touko 
Published: February 2019

Background Magnetic resonance imaging (MRI) in patients with cardiac pacing devices has become available despite previously being considered absolutely contraindicated. However, most institutional safety protocols have included several limitations on patient selection, leaving MRI unavailable for many patients. Purpose To evaluate the first 1000 MRI examinations conducted on patients with cardiac pacing devices at Helsinki University Hospital for any potential safety hazards and also to evaluate the long-term functionality of the safety protocol in “real-life” clinical practice. Material and Methods A total of 1000 clinically indicated MRI scans were performed with a 1.5-T MRI scanner according to the safety protocol. The following information was collected from the electronic medical record (EMR): patients’ date of birth; sex; pacing device generator model; date of MRI scan; date of the latest pacing device generator implantation; and the body region scanned. The EMR of these patients was checked and especially searched for any pacing device related safety hazards or adverse outcomes during or after the MRI scan. Results Only one potentially dangerous adverse event was noted in our study group. In addition, patients with abandoned leads, temporary pacing devices, and newly implanted pacing device generators were scanned successfully and safely. Conclusion MRI scans can be performed safely in patients with cardiac pacing devices if the dedicated safety protocol is followed.
The prevalence of resistant Gram-negative bacteraemia among hospitalized patients in Tucson, Arizona over a 12-month period; A retrospective single center study
Authors: Almulhim Abdulaziz Saleh , Alamer Ahmad 
Published: February 2019

Introduction The objectives of this retrospective review were to: (a) determine the prevalence of resistant Gram-negative bacteraemia among hospitalized patients; (b) evaluate antibiotic use; (c) determine the time taken for Gram staining to final species identification. Methods For this retrospective study, information was extracted from patients’ electronic medical records. Eligible patients had been admitted to a 300-bed tertiary care hospital in Tucson, Arizona from October 2015 to October 2016, were over 18 years of age and had a positive blood culture for Gram-negative bacteraemia. Results In total, 84 patients with Gram-negative bacteraemia were identified; urinary tract infection was the most common source of infection (71%). ESBL-producing microorganisms were isolated from five (6%) patients and no MDR pathogens were identified. The, median time to Gram stain was 20.5 hours and the median time to final identification was 54.5 hours. Delayed de-escalation of broad-spectrum antibiotics (i.e., >24 hours after final culture) occurred in 25% patients with a median length of hospital stay of 118 hours (range: 56–552 hours) compared with a median length of hospital stay of 89 hours (range: 5–334 hours) in the early de-escalation group. Conclusion The prevalence of bacteraemia due to resistant Gram-negative microorganisms is low (6%) in this institution. However, there may be room for improvement in the antimicrobial stewardship program with regard to rapid diagnostic testing.