bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shear wave velocity is sensitive to changes in muscle stiffness that occur independently from changes in force
Authors: Bernabei Michel , Lee Sabrina S. M. , Perreault Eric J. , Sandercock Thomas G. 
Published: September 2019

Clinical assessments for many musculoskeletal disorders involve evaluation of muscle stiffness, although it is not yet possible to obtain quantitative estimates from individual muscles. Ultrasound elastography can be used to estimate the material properties of unstressed, homogeneous, and isotropic materials by tracking the speed of shear wave propagation; these waves propagate faster in stiffer materials. Although elastography has been applied to skeletal muscle, there is little evidence that shear wave velocity (SWV) can directly estimate muscle stiffness since this tissue violates many of the assumptions required for there to be a direct relationship between SWV and stiffness. The objective of this study was to evaluate the relationship between SWV and direct measurements of muscle force and stiffness in contracting muscle. Data were collected from six isoflurane-anesthetized cats. We measured the short-range stiffness in the soleus via direct mechanical testing in situ and SWV via ultrasound imaging. Measurements were taken during supramaximal activation at optimum muscle length, with muscle temperature varying between 26°C and 38°C. An increase in temperature causes a decrease in muscle stiffness at a given force, thus decoupling the tension-stiffness relationship normally present in muscle. We found that increasing muscle temperature decreased active stiffness from 4.0 ± 0.3 MPa to 3.3 ± 0.3 MPa and SWV from 16.9 ± 1.5 m/s to 15.9 ± 1.6 m/s while force remained unchanged (mean ± SD). These results demonstrate that SWV is sensitive to changes in muscle stiffness during active contractions. Future work is needed to determine how this relationship is influenced by changes in muscle structure and tension. NEW & NOTEWORTHY Shear wave ultrasound elastography is a noninvasive tool for characterizing the material properties of muscle. This study is the first to compare direct measurements of stiffness with ultrasound measurements of shear wave velocity (SWV) in a contracting muscle. We found that SWV is sensitive to changes in muscle stiffness, even when controlling for muscle tension, another factor that influences SWV. These results are an important step toward developing noninvasive tools for characterizing muscle structure and function.
A Transcriptionally Definable Subgroup of Triple-Negative Breast and Ovarian Cancer Samples Shows Sensitivity to HSP90 Inhibition
Authors: Shee Kevin , Wells Jason D. , Ung Matthew , Hampsch Riley A. , Traphagen Nicole A. , Yang Wei , Liu Stephanie C. , Zeldenrust Megan A. , Wang Liewei , Kalari Krishna R. , Yu Jia , Boughey Judy C. , Demidenko Eugene , Kettenbach Arminja N. , Cheng Chao , Goetz Matthew P. , Miller Todd W. 
Published: September 2019

Abstract

Purpose:
We hypothesized that integrated analysis of cancer types from different lineages would reveal novel molecularly defined subgroups with unique therapeutic vulnerabilities. On the basis of the molecular similarities between subgroups of breast and ovarian cancers, we analyzed these cancers as a single cohort to test our hypothesis.

Experimental Design:
Identification of transcriptional subgroups of cancers and drug sensitivity analyses were performed using mined data. Cell line sensitivity to Hsp90 inhibitors (Hsp90i) was tested in vitro. The ability of a transcriptional signature to predict Hsp90i sensitivity was validated using cell lines, and cell line- and patient-derived xenograft (PDX) models. Mechanisms of Hsp90i sensitivity were uncovered using immunoblot and RNAi.

Results:
Transcriptomic analyses of breast and ovarian cancer cell lines uncovered two mixed subgroups comprised primarily of triple-negative breast and multiple ovarian cancer subtypes. Drug sensitivity analyses revealed that cells of one mixed subgroup are significantly more sensitive to Hsp90i compared with cells from all other cancer lineages evaluated. A gene expression classifier was generated that predicted Hsp90i sensitivity in vitro, and in cell line- and PDXs. Cells from the Hsp90i-sensitive subgroup underwent apoptosis mediated by Hsp90i-induced upregulation of the proapoptotic proteins Bim and PUMA.

Conclusions:
Our findings identify Hsp90i as a potential therapeutic strategy for a transcriptionally defined subgroup of ovarian and breast cancers. This study demonstrates that gene expression profiles may be useful to identify therapeutic vulnerabilities in tumor types with limited targetable genetic alterations, and to identify molecularly definable cancer subgroups that transcend lineage.
Alterations in the Transcriptional Programs of Myeloma Cells and the Microenvironment during Extramedullary Progression Affect Proliferation and Immune Evasion
Authors: Ryu Daeun , Kim Seok Jin , Hong Yourae , Jo Areum , Kim Nayoung , Kim Hee-Jin , Lee Hae-Ock , Kim Kihyun , Park Woong-Yang 
Published: September 2019

Abstract

Purpose:
In multiple myeloma, extramedullary progression is associated with treatment resistance and a high mortality rate. To understand the molecular mechanisms controlling the devastating progression of myeloma, we applied single-cell RNA-sequencing (RNA-seq) to myeloma in the bone marrow and myelomatous pleural effusions or ascites.

Experimental Design:
Bone marrow or extramedullary myeloma samples were collected from 15 patients and subjected to single-cell RNA-seq. The single-cell transcriptome data of malignant plasma cells and the surrounding immune microenvironment were analyzed.

Results:
Comparisons of single-cell transcriptomes revealed the systematic activation of proliferation, antigen presentation, proteasomes, glycolysis, and oxidative phosphorylation pathways in extramedullary myeloma cells. The myeloma cells expressed multiple combinations of growth factors and receptors, suggesting autonomous and pleiotropic growth potential at the single-cell level. Comparisons of the tumor microenvironment revealed the presence of cytotoxic T lymphocytes and natural killer (NK) cells in both the bone marrow and extramedullary ascites, demonstrating a gene-expression phenotype indicative of functional compromise. In parallel, isolated myeloma cells persistently expressed class I MHC molecules and upregulated inhibitory molecules for cytotoxic T and NK cells.

Conclusions:
These data suggest that myeloma cells are equipped with specialized immune evasion mechanisms in cytotoxic microenvironments. Taken together, single-cell transcriptome analysis revealed transcriptional programs associated with aggressive myeloma progression that support autonomous cell proliferation and immune evasion.
Comprehensive Transcriptomic Profiling Identifies Breast Cancer Patients Who May Be Spared Adjuvant Systemic Therapy
Authors: Sjöström Martin , Chang S. Laura , Fishbane Nick , Davicioni Elai , Hartman Linda , Holmberg Erik , Feng Felix Y. , Speers Corey W. , Pierce Lori J. , Malmström Per , Fernö Mårten , Karlsson Per 
Published: September 2019

AbstractPurpose:There is currently no molecular signature in clinical use for adjuvant endocrine therapy omission in breast cancer. Given the unique trial design of SweBCG91-RT, where adjuvant endocrine and chemotherapy were largely unadministered, we sought to evaluate the potential of transcriptomic profiling for identifying patients who may be spared adjuvant endocrine therapy.Experimental Design:We performed a whole-transcriptome analysis of SweBCG91-RT, a randomized phase III trial of ± radiotherapy after breast-conserving surgery for node-negative stage I–IIA breast cancer. Ninety-two percent of patients were untreated by both adjuvant endocrine therapy and chemotherapy. We calculated 15 transcriptomic signatures from the literature and combined them into an average genomic risk, which was further used to derive a novel 141-gene signature (MET141). All signatures were then independently examined in SweBCG91-RT and in the publicly available METABRIC cohort.Results:In SweBCG91-RT, 454 patients were node-negative, postmenopausal, and systemically untreated with ER-positive, HER2-negative cancers, which constitutes a low-risk subgroup and potential candidates for therapy omission. Most transcriptomic signatures were highly prognostic for distant metastasis, but considerable discordance was observed on the individual patient level. Within the MET141 low-risk subgroup (lowest 25th percentile of scores), 95% of patients were free of metastasis at 15 years, even in the absence of adjuvant endocrine therapy. In a clinically low-risk subgroup of the METABRIC cohort not treated with systemic therapy, no breast cancer death occurred among the MET141 low-risk patients.Conclusions:Transcriptomic profiling identifies patients with an excellent outcome without any systemic adjuvant therapy in clinically low-risk patients of the SweBCG91-RT and METABRIC cohorts.
Winter food habits of the Common Palm Civet Paradoxurus hermaphroditus (Mammalia: Carnivora: Viverridae) in Patna Bird Sanctuary, India
Authors: Khan Khursid Alam , Khan Jamal Ahmad , Ahmad Khursheed , Mohan Narendra 
Published: September 2019

Food habits of the Common Palm Civet Paradoxurus hermaphroditus were investigated using scat analysis method, a technique widely used to study small and medium sized mammals. We analyzed 112 scats of Common Palm Civet between November 2012 and March 2013 from the Patna Bird Sanctuary and found a total of nine food items. Out of 112 scats, 32.09% scats contained three food items, 29.62% scats had two items, 24.69% scats contained four prey items, and 3.7% scats had seven prey items. The results show that the Common Palm Civet is more frugivorous (ca. 39.28%) than insectivores (ca. 29.46%). Percent frequency of occurrence showed that insects contributed maximum in the diet of Civet (29.46±2.29) followed by fruits of Ficus religiosa (19.64±1.13), Prosopis juliflora (11.60±0.18), and Date Palm (Phoenix sylvestrix) (8.03±0.23), while birds contributed 9.82±0.02 and rodents 6.25±0.44. Rufous-tailed Hare (Lepus nigricollis ruficaudatus) (1.78±0.96) contributed the minimum in the Common Palm Civet diet. PBS is an Important Bird Area site and it harbours thousands of migratory birds during winter. But the results show that birds are a less preferred diet item of the Common Palm Civet.
Copper Transporter ATP7A (Copper-Transporting P-Type ATPase/Menkes ATPase) Limits Vascular Inflammation and Aortic Aneurysm Development
Authors: Sudhahar Varadarajan , Das Archita , Horimatsu Tetsuo , Ash Dipankar , Leanhart Silvia , Antipova Olga , Vogt Stefan , Singla Bhupesh , Csanyi Gabor , White Joseph , Kaplan Jack H. , Fulton David , Weintraub Neal L. , Kim Ha Won , Ushio-Fukai Masuko , Fukai Tohru 
Published: September 2019

Objective:
Copper (Cu) is essential micronutrient, and its dysregulation is implicated in aortic aneurysm (AA) development. The Cu exporter ATP7A (copper-transporting P-type ATPase/Menkes ATPase) delivers Cu via the Cu chaperone Atox1 (antioxidant 1) to secretory Cu enzymes, such as lysyl oxidase, and excludes excess Cu. Lysyl oxidase is shown to protect against AA formation. However, the role and mechanism of ATP7A in AA pathogenesis remain unknown.

Approach and Results:

Here, we show that Cu chelator markedly inhibited Ang II (angiotensin II)–induced abdominal AA (AAA) in which ATP7A expression was markedly downregulated. Transgenic ATP7A overexpression prevented Ang II–induced AAA formation. Conversely, Cu transport dysfunctional ATP7A
mut/+
/ApoE
−/−
mice exhibited robust AAA formation and dissection, excess aortic Cu accumulation as assessed by X-ray fluorescence microscopy, and reduced lysyl oxidase activity. In contrast, AAA formation was not observed in Atox1
−/−
/ApoE
−/−
mice, suggesting that decreased lysyl oxidase activity, which depends on both ATP7A and Atox1, was not sufficient to develop AAA. Bone marrow transplantation suggested importance of ATP7A in vascular cells, not bone marrow cells, in AAA development. MicroRNA (miR) array identified miR-125b as a highly upregulated miR in AAA from ATP7A
mut/+
/ApoE
−/−
mice. Furthermore, miR-125b target genes (histone methyltransferase Suv39h1 and the NF-κB negative regulator TNFAIP3 [tumor necrosis factor alpha induced protein 3]) were downregulated, which resulted in increased proinflammatory cytokine expression, aortic macrophage recruitment, MMP (matrix metalloproteinase)-2/9 activity, elastin fragmentation, and vascular smooth muscle cell loss in ATP7A
mut/+
/ApoE
−/−
mice and reversed by locked nucleic acid-anti-miR-125b infusion.

Conclusions:
ATP7A downregulation/dysfunction promotes AAA formation via upregulating miR-125b, which augments proinflammatory signaling in a Cu-dependent manner. Thus, ATP7A is a potential therapeutic target for inflammatory vascular disease.
Angiographically Guided Complete Revascularization Versus Selective Stress Echocardiography–Guided Revascularization in Patients With ST-Segment–Elevation Myocardial Infarction and Multivessel Disease
Authors: Calviño-Santos Ramón , Estévez-Loureiro Rodrigo , Peteiro-Vázquez Jesús , Salgado-Fernández Jorge , Rodríguez-Vilela Alejandro , Franco-Gutiérrez Raúl , Bouzas-Mosquera Alberto , Rodríguez-Fernández José Ángel , Mesías-Prego Alejandro , González-Juanatey Carlos , Aldama-López Guillermo , Piñón-Esteban Pablo , Flores-Ríos Xacobe , Soler-Martín Rita , Seoane-Pillado Teresa , Vázquez-González Nicolás , Muñiz Javier , Vázquez-Rodríguez José Manuel 
Published: September 2019

Background:
Recent trials suggest that complete revascularization in patients with acute ST-segment–elevation myocardial infarction and multivessel disease is associated with better outcomes than infarct-related artery (IRA)–only revascularization. There are different methods to select non-IRA lesions for revascularization procedures. We assessed the clinical outcomes of complete angiographically guided revascularization versus stress echocardiography–guided revascularization in patients with ST-segment–elevation myocardial infarction.

Methods:
We performed a randomized clinical trial in patients with multivessel disease who underwent a successful percutaneous coronary intervention of the IRA to test differences in prognosis (composite end point included cardiovascular mortality, nonfatal reinfarction, coronary revascularization, and readmission for heart failure after 12 months of follow-up) between complete angiographically guided revascularization (n=154) or stress echocardiography–guided revascularization (n=152) of the non-IRA lesions in an elective procedure before hospital discharge.

Results:

The trial was prematurely stopped after the inclusion of 77% of the planned study population. As many as 152 (99%) patients in the complete revascularization group and 44 (29%) patients in the selective revascularization group required a percutaneous coronary intervention procedure of a non-IRA lesion before discharge. The primary end point occurred in 21 (14%) patients of the stress echocardiography–guided revascularization group and 22 (14%) patients of the complete angiographically guided revascularization group (hazard ratio, 0.95; 95% CI, 0.52–1.72;
P
=0.85).

Conclusions:
In patients with ST-segment–elevation myocardial infarction and multivessel disease, stress echocardiography–guided revascularization may not be significantly different to complete angiographically guided revascularization, thereby reducing the need for elective revascularization before hospital discharge.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov.
Unique identifier: NCT01179126.
Intensity of Lipid Lowering With Statin Therapy in Patients With Cerebrovascular Disease Versus Coronary Artery Disease: Insights from the PALM Registry
Authors: Xian Ying , Navar Ann Marie , Li Shuang , Li Zhuokai , Robinson Jennifer , Virani Salim S. , Louie Michael J. , Koren Andrew , Goldberg Anne , Roger Veronique L. , Wilson Peter W. F. , Peterson Eric D. , Wang Tracy Y. 
Published: September 2019

Background

Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients’ perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease (
CAD
) versus cerebrovascular disease (Ce
VD
) versus both
CAD
and Ce
VD
(
CAD
&Ce
VD
).

Methods and Results

The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low‐density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133
US
clinics. Among individuals with Ce
VD
only (n=403),
CAD
only (n=2202), and Ce
VD
&
CAD
(n=627), no significant differences were observed in patient‐perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with Ce
VD
only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95%
CI
0.45–0.91), or guideline‐recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95%
CI
0.45–0.81) than those with
CAD
only. Individuals with Ce
VD
only were also less likely to achieve low‐density lipoprotein cholesterol <100 mg/
dL
(59.2% versus 69.7%; adjusted odds ratio 0.79, 95%
CI
0.64–0.99) than individuals with
CAD
alone. There were no significant differences in the use of any statin therapy or guideline‐recommended statin intensity between individuals with
CAD
&Ce
VD
and those with
CAD
only.

Conclusions

Despite lack of significant differences in patient‐perceived cardiovascular risk or statin beliefs, patients with Ce
VD
were significantly less likely to receive higher intensity statin or achieve low‐density lipoprotein cholesterol <100 mg/
dL
than those with
CAD
only.
Delirium in an Acute Stroke Setting, Occurrence, and Risk Factors
Authors: Shaw Robert , Drozdowska Bogna , Taylor-Rowan Martin , Elliott Emma , Cuthbertson Gillian , Stott David J. , Quinn Terence J. 
Published: September 2019

Background and Purpose—
Delirium is a common and serious complication of acute illness. We describe delirium occurrence in an unselected, acute stroke population.

Methods—
We collected data from consecutive stroke admissions. We performed comprehensive cognitive assessment within the first week including Diagnostic Statistical Manual-5–based delirium diagnosis. We reported proportion with delirium and the clinical and demographic associations with delirium using multiple logistic regression.

Results—
Of 708 patients, median age of 71 years (interquartile range, 59–80), we recorded delirium in 187 of 708 (26.4%; 95% CI, 23.0–30.0). Across 395 patients with complete risk factor data (105 delirium), factors independently associated with delirium were: age (odds ratio, 1.05; 95% CI, 1.03–1.08), drug/alcohol misuse (odds ratio, 2.64; 95% CI, 1.10–6.26), and stroke severity (odds ratio, 1.22; 95% CI, 1.14–1.31).

Conclusions—
Delirium is common in acute stroke, affecting 1 in 4. It may be possible to predict those at risk using prestroke and stroke-specific factors.

Clinical Trial Registration—

URL:
researchregistry.com
. Protocol: 1147.
The Financial and Supervisory Role of the Federal National Council in the United Arab Emirates
Authors: Aljobair Ahmad 
Published: September 2019

Abstract
This article deals with the role of the UAE Federal National Council (FNC) as a legislative authority. It explains how it differs from other parliaments around the world in terms of composition and the role it plays as a final authoritative legislative power. The FNC has neither the power to legislate nor the right to control laws, although the Constitution allows it to discuss and comment upon draft laws. However, the FNC’s opinion is not binding on the promulgation of the laws. The President may reject the amendments and promulgate the law after it has been sanctioned by the Supreme Council. The Constitution also gives the Council of Ministers the power to promulgate laws in case of necessity and absence of the FNC. These constitutional texts contradict the internal regulations of the FNC which give this Council the right to amend the legal texts of the draft budget.
Summer- and Wintertime Variations of the Surface and Near-Surface Urban Heat Island in a Semiarid Environment
Authors: Palou Francisco Salamanca , Mahalov Alex 
Published: September 2019

Abstract
This paper examines summer- and wintertime variations of the surface and near-surface urban heat island (UHI) for the Phoenix metropolitan area using the Moderate Resolution Imaging Spectroradiometer (MODIS), near-surface meteorological observations, and the Weather Research and Forecasting (WRF) Model during a 31-day summer- and a 31-day wintertime period. The surface UHI (defined based on the urban–rural land surface temperature difference) is found to be higher at night and during the warm season. On the other hand, the morning surface UHI is low and frequently exhibits an urban cool island that increases during the summertime period. Similarly, the near-surface UHI (defined based on the urban–rural 2-m air temperature difference) is higher at night and during summertime. On the other hand, the daytime near-surface UHI is low but rarely exhibits an urban cool island. To evaluate the WRF Model’s ability to reproduce the diurnal cycle of near-surface meteorology and surface skin temperature, two WRF Model experiments (one using the Bougeault and Lacarrere turbulent scheme and one with the Mellor–Yamada–Janjić turbulent parameterization) at high spatial resolution (1-km horizontal grid spacing) are conducted for each 31-day period. Modeled results show that the WRF Model (coupled to the Noah-MP land surface model) tends to underestimate to some extent surface skin temperature during daytime and overestimate nighttime values during the wintertime period. In the same way, the WRF Model tends to accurately reproduce the diurnal cycle of near-surface air temperature, including maximum and minimum temperatures, and wind speed during summertime, but notably overestimates nighttime near-surface air temperature during wintertime. This nighttime overestimation is especially remarkable with the Bougeault and Lacarrere turbulent scheme for both urban and rural areas.