ph [Molecular Pathology] Pharmacologic Approaches for Adapting Proteostasis in the Secretory Pathway to Ameliorate Protein Conformational Diseases By cshperspectives.cshlp.org Published On :: 2020-05-01T06:30:16-07:00 Maintenance of the proteome, ensuring the proper locations, proper conformations, appropriate concentrations, etc., is essential to preserve the health of an organism in the face of environmental insults, infectious diseases, and the challenges associated with aging. Maintaining the proteome is even more difficult in the background of inherited mutations that render a given protein and others handled by the same proteostasis machinery misfolding prone and/or aggregation prone. Maintenance of the proteome or maintaining proteostasis requires the orchestration of protein synthesis, folding, trafficking, and degradation by way of highly conserved, interacting, and competitive proteostasis pathways. Each subcellular compartment has a unique proteostasis network compromising common and specialized proteostasis maintenance pathways. Stress-responsive signaling pathways detect the misfolding and/or aggregation of proteins in specific subcellular compartments using stress sensors and respond by generating an active transcription factor. Subsequent transcriptional programs up-regulate proteostasis network capacity (i.e., ability to fold and degrade proteins in that compartment). Stress-responsive signaling pathways can also be linked by way of signaling cascades to nontranscriptional means to reestablish proteostasis (e.g., by translational attenuation). Proteostasis is also strongly influenced by the inherent kinetics and thermodynamics of the folding, misfolding, and aggregation of individual proteins, and these sequence-based attributes in combination with proteostasis network capacity together influence proteostasis. In this review, we will focus on the growing body of evidence that proteostasis deficits leading to human pathology can be reversed by pharmacologic adaptation of proteostasis network capacity through stress-responsive signaling pathway activation. The power of this approach will be exemplified by focusing on the ATF6 arm of the unfolded protein response stress responsive-signaling pathway that regulates proteostasis network capacity of the secretory pathway. Full Article
ph Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P < 5 x 10–8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance–weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI). Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00–1.30) and MZL (OR = 1.09; 95% CI, 1.01–1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83–0.99), all at nominal significance (P < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99–1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing. Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes. Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding. Full Article
ph Objectively-Measured Light-Intensity Physical Activity and Risk of Cancer Mortality: A Meta-analysis of Prospective Cohort Studies By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: The impact of light-intensity physical activity (LPA) in preventing cancer mortality has been questioned. To address this concern, the present meta-analysis aimed to quantify the association between objectively-measured LPA and risk of cancer mortality. Methods: We conducted a systematic literature search in PubMed and Scopus to January 2020. Prospective cohort studies reporting the association between objectively-measured LPA using activity monitors (e.g., accelerometers) and risk of cancer mortality in the general population were included. The summary hazard ratios (HR) per 30 min/day of LPA and 95% confidence intervals (CI) were obtained using a random-effects model. Dose–response analysis was used to plot their relationship. Results: Five prospective cohort studies were included, in which the definition of LPA based on accelerometer readings was mainly set within 100 to 2,100 counts/min. The summary HR for cancer mortality per 30 min/day of LPA was 0.86 (95% CI, 0.79–0.95; I2 < 1%), and the association between LPA and risk reduction in cancer mortality was linearly shaped (Pnonlinearity = 0.72). LPA exhibited a comparable magnitude of risk reduction in cancer mortality of moderate-to-vigorous physical activity regardless of equal time-length (0.87 per 30 min/day vs. 0.94 per 30 min/day, Pinteraction = 0.46) or equal amount (0.74 vs. 0.94 per 150 metabolic equivalents-min/day, Pinteraction = 0.11). Furthermore, replacing sedentary time by LPA of 30 min/day decreased the risk of cancer mortality by 9%. Conclusions: Objectively-measured LPA conferred benefits in decreasing the risk of cancer mortality. Impact: LPA should be considered in physical activity guidelines to decrease the risk of cancer mortality. Full Article
ph Alcohol and Tobacco Use in Relation to Mammographic Density in 23,456 Women By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood. Methods: We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis. Results: Alcohol use was positively associated with PD (Ptrend = 0.01), unassociated with DA (Ptrend = 0.23), and inversely associated with NDA (Ptrend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (Ptrend = 0.0008), unassociated with DA (Ptrend = 0.93), and positively associated with NDA (Ptrend<0.0001). These trends were stronger in normal and overweight women than in obese women. Conclusions: These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA. Impact: PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health. Full Article
ph Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies. Methods: We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case–control studies of postmenopausal breast (950 case–control pairs) and colorectal (831 case–control pairs) cancer in an independent sample in MEC. Abdominal MRI–derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed. Results: The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm2 was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer [OR (95% confidence interval [CI]) by increasing tertiles: 1.00, 1.09 (0.86–1.39), 1.48 (1.16–1.89); Ptrend = 0.002] but not with colorectal cancer (P = 0.84), although an association [1.00, 0.98 (0.68–1.39), 1.24 (0.88–1.76); Ptrend = 0.08] was suggested for this cancer after excluding cases that occurred within 7 years of blood draw (Pheterogeneity = 0.06). Conclusions: The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations. Impact: These findings provide specific evidence for a role of VAT in breast cancer. Full Article
ph Assessing Cancer Treatment Information Using Medicare and Hospital Discharge Data among Women with Non-Hodgkin Lymphoma in a Los Angeles County Case-Control Study By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: We assessed the ability to supplement existing epidemiologic/etiologic studies with data on treatment and clinical outcomes by linking to publicly available cancer registry and administrative databases. Methods: Medical records were retrieved and abstracted for cases enrolled in a Los Angeles County case–control study of non-Hodgkin lymphoma (NHL). Cases were linked to the Los Angeles County cancer registry (CSP), the California state hospitalization discharge database (OSHPD), and the SEER-Medicare database. We assessed sensitivity, specificity, and positive predictive value (PPV) of cancer treatment in linked databases, compared with medical record abstraction. Results: We successfully retrieved medical records for 918 of 1,004 participating NHL cases and abstracted treatment for 698. We linked 59% of cases (96% of cases >65 years old) to SEER-Medicare and 96% to OSHPD. Chemotherapy was the most common treatment and best captured, with the highest sensitivity in SEER-Medicare (80%) and CSP (74%); combining all three data sources together increased sensitivity (92%), at reduced specificity (56%). Sensitivity for radiotherapy was moderate: 77% with aggregated data. Sensitivity of BMT was low in the CSP (42%), but high for the administrative databases, especially OSHPD (98%). Sensitivity for surgery reached 83% when considering all three datasets in aggregate, but PPV was 60%. In general, sensitivity and PPV for chronic lymphocytic leukemia/small lymphocytic lymphoma were low. Conclusions: Chemotherapy was accurately captured by all data sources. Hospitalization data yielded the highest performance values for BMTs. Performance measures for radiotherapy and surgery were moderate. Impact: Various administrative databases can supplement epidemiologic studies, depending on treatment type and NHL subtype of interest. Full Article
ph Purification of Recombinant Adeno-Associated Virus 2 (rAAV2) by Heparin Column Affinity Chromatography By cshprotocols.cshlp.org Published On :: 2020-05-01T06:29:31-07:00 This protocol describes a simple single-step column purification (SSCP) of rAAV2 by gravity flow based on its affinity to heparin, without ultracentrifugation. Full Article
ph Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women By cancerpreventionresearch.aacrjournals.org Published On :: 2020-05-04T05:35:14-07:00 Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1–5 kg/m2 from age 10, women who had a BMI gain of 5.1–10 kg/m2 had a 24.4% decrease [95% confidence interval (CI), 6.0%–39.2%] in volumetric percent density; women who had a BMI gain of 10.1–15 kg/m2 had a 46.1% decrease (95% CI, 33.0%–56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m2 had a 56.5% decrease (95% CI, 46.0%–65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density. Full Article
ph Retraction: Insulin-Like Growth Factor I Suppresses Bone Morphogenetic Protein Signaling in Prostate Cancer Cells by Activating mTOR Signaling By cancerres.aacrjournals.org Published On :: 2020-05-04T05:35:17-07:00 Full Article
ph Dasatinib Is an Effective Treatment for Angioimmunoblastic T-cell Lymphoma By cancerres.aacrjournals.org Published On :: 2020-05-04T05:35:17-07:00 Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10–78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment.Significance:Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib. Full Article
ph [PERSPECTIVES] RNA Regulators in Leukemia and Lymphoma By perspectivesinmedicine.cshlp.org Published On :: 2020-05-01T06:30:15-07:00 Posttranscriptional regulation of mRNA is a powerful and tightly controlled process in which cells command the integrity, diversity, and abundance of their protein products. RNA-binding proteins (RBPs) are the principal players that control many intermediary steps of posttranscriptional regulation. Recent advances in this field have discovered the importance of RBPs in hematological diseases. Herein we will review a number of RBPs that have been determined to play critical functions in leukemia and lymphoma. Furthermore, we will discuss the potential therapeutic strategies that are currently being studied to specifically target RBPs in these diseases. Full Article
ph Comparison of Enhancement of the Vestibular Perilymph between Variable and Constant Flip Angle-Delayed 3D-FLAIR Sequences in Meniere Disease [HEAD & NECK] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Endolymphatic hydrops in patients with Menière disease relies on delayed postcontrast 3D-FLAIR sequences. The purpose of this study was to compare the degree of perilymphatic enhancement and the detection rate of endolymphatic hydrops using constant and variable flip angles sequences. MATERIALS AND METHODS: This was a retrospective study performed in 16 patients with Menière disease who underwent 3T MR imaging 4 hours after gadolinium injection using two 3D-FLAIR sequences with a constant flip angle at 140° for the first and a heavily-T2 variable flip angle for the second. The signal intensity ratio was measured using the ROI method. We graded endolymphatic hydrops and evaluated the cochlear blood-labyrinth barrier impairment. RESULTS: Both for symptomatic and asymptomatic ears, the median signal intensity ratio was significantly higher with the constant flip angle than with the heavily-T2 variable flip angle (7.16 versus 1.54 and 7.00 versus 1.45, P < .001). Cochlear blood-labyrinth barrier impairment was observed in 4/18 symptomatic ears with the heavily-T2 variable flip angle versus 8/19 with constant flip angle sequences. With heavily-T2 variable flip angle sequences, endolymphatic hydrops was observed in 7–10/19 symptomatic ears versus 12/19 ears with constant flip angle sequences. We found a significant association between the clinical symptomatology and the presence of endolymphatic hydrops with constant flip angle but not with heavily-T2 variable flip angle sequences. Interreader agreement was always perfect with constant flip angle sequences while it was fair-to-moderate with heavily-T2 variable flip angle sequences. CONCLUSIONS: 3D-FLAIR constant flip angle sequences provide a higher signal intensity ratio and are superior to heavily-T2 variable flip angle sequences in reliably evaluating the cochlear blood-labyrinth barrier impairment and the endolymphatic space. Full Article
ph Assessment of Apparent Internal Carotid Tandem Occlusion on High-Resolution Vessel Wall Imaging: Comparison with Digital Subtraction Angiography [EXTRACRANIAL VASCULAR] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Not all tandem occlusions diagnosed on traditional vascular imaging modalities, such as MRA, represent actual complete ICA occlusion. This study aimed to explore the utility of high-resolution vessel wall imaging in identifying true ICA tandem occlusions and screening patients for their suitability for endovascular recanalization. MATERIALS AND METHODS: Patients with no signal in the ICA on MRA were retrospectively reviewed. Two neuroradiologists independently reviewed their high-resolution vessel wall images to assess whether there were true tandem occlusions and categorized all cases into intracranial ICA occlusion, extracranial ICA occlusion, tandem occlusion, or near-occlusion. DSA classified patient images into the same 4 categories, which were used as the comparison with high-resolution vessel wall imaging. The suitability for recanalization of occluded vessels was evaluated on high-resolution vessel wall imaging compared with DSA. RESULTS: Forty-five patients with no ICA signal on MRA who had available high-resolution vessel wall imaging and DSA images were included. Among the 34 patients (34/45, 75.6%) with tandem occlusions on DSA, 18 cases also showed tandem occlusions on high-resolution vessel wall imaging. The remaining 16 patients, intracranial ICA, extracranial ICA occlusions and near-occlusions were found in 2, 6, and 8 patients, respectively, on the basis of high-resolution vessel wall imaging. A total of 20 cases (20/45, 44.4%) were considered suitable for recanalization on the basis of both DSA and high-resolution vessel wall imaging. Among the 25 patients deemed unsuitable for recanalization by DSA, 11 were deemed suitable for recanalization by high-resolution vessel wall imaging. CONCLUSIONS: High-resolution vessel wall imaging could allow identification of true ICA tandem occlusion in patients with an absence of signal on MRA. Findings on high-resolution vessel wall imaging can be used to screen more suitable candidates for recanalization therapy. Full Article
ph Save the Brain First: CTA and Mechanical Thrombectomy in Patients at Risk for Contrast-Induced Nephropathy [article-commentary] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 Full Article
ph Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study [INTERVENTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm. MATERIALS AND METHODS: In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study. RESULTS: In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best ( ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial ( > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters’ judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial ( ≤ 0.6). CONCLUSIONS: The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH. Full Article
ph CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error. MATERIALS AND METHODS: Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation. RESULTS: The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions. CONCLUSIONS: Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome. Full Article
ph Polymorphous Low-Grade Neuroepithelial Tumor of the Young as a Partially Calcified Intra-Axial Mass in an Adult [RADIOLOGY-PATHOLOGY CORRELATION] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 SUMMARY: Polymorphous low-grade neuroepithelial tumors of the young (PLNTYs) are recently described CNS tumors. Classically, PLNTYs are epileptogenic and are a subtype of a heterogeneous group of low-grade neuroepithelial tumors that cause refractory epilepsy, such as angiocentric gliomas, oligodendrogliomas, gangliogliomas, and pleomorphic xanthoastrocytomas. Although they are a relatively new entity, a number of imaging and histologic characteristics of PLNTYs are already known. We present the imaging and pathologic findings of such a tumor as well as the surgical approach and clinical management. Full Article
ph MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging [ADULT BRAIN] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 SUMMARY: The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability. Full Article
ph Bán Shophouse chân đế Sky Oasis, trung tâm quảng trường nhìn ra Vịnh Đảo & Chợ Đêm. LH 0911938633 By batdongsan.com.vn Published On :: Wed, 06 May 2020 16:26:37 GMT Cần bán căn shop đẹp nhất phía Đông Hà Nội tại Chân tòa chung cư Sky Oasis Ecopark. DT: Tổng 163m2 (2 tầng). Tầng 1: 82,4m2 - tầng 2: 81,1 m2. Hai tầng KD (tầng 1 cao 5m, tầng 2 cao 5.9m). Hình thức sở hữu: Sổ lâu dài, linh hoạt tách 2 sổ chuyển nhượng được. Đặc điểm: Gần bể bơi ... Full Article
ph Mặt bằng kinh doanh 7,8x10m, 1 trệt 1 lầu, mặt tiền phạm thế hiển, phục vụ hơn 2000 hộ dân cư By batdongsan.com.vn Published On :: Thu, 07 May 2020 10:33:10 GMT Tìm mặt bằng kinh doanh đâu mà được giá rẻ như đây, tổng khu vừa là mặt tiền Phạm Thế Hiền 3 block, có 1 block có trung tâm thương mại 4 tầng, có siêu thị Coopmart hoạt động, vừa ở vừa kinh doanh phục vụ cho hơn 2000 hộ kinh doanh tại đây. Mặt sau là trường tiểu học Bùi Minh Trực... Full Article
ph Sở hữu ngay Shophouse Metro Star mặt tiền Song Hành Xa Lộ Hà Nội giá chỉ 70 triệu/m2 Lh: 0933836751 By batdongsan.com.vn Published On :: Thu, 07 May 2020 15:13:13 GMT Chỉ cần thanh toán 15% sở hữu ngay Shophouse Metro Star.- Chiết khấu lên đến 10%.- Cam kết cho thuê 111,305 triệu/tháng trong 3 năm.- Cam kết mua lại sau 24 tháng với lợi nhuận 22%.- Shophouse Metro Star vị trí vàng cửa ngõ khu Đông.- Nằm ngay mặt tiền Song Hành, Xa Lộ Hà Nội, li... Full Article
ph Shophouse Green River quận 8, chung cư nằm trên mặt tiền Phạm Thế Hiển, phục vụ hơn 4000 cư dân By batdongsan.com.vn Published On :: Thu, 07 May 2020 15:30:28 GMT * Chỉ còn 12 ngày cơ hội cho khách hàng chọn mua siêu phẩm shophouse Green River 4 mặt tiền tại Phạm Thế Hiển - Quận 8. Quý KH nào chưa mua hoặc đang phân vân về dự án hãy chọn cho mình 1 căn trong siêu dự án tiềm năng tăng giá cực kì cao này nhé. - Liên hệ trưởng phòng kinh doan... Full Article
ph Cần bán nhanh shophouse block B chung cư Citi Home, Phường Cát Lái, Quận 2, TP HCM By batdongsan.com.vn Published On :: Fri, 08 May 2020 08:32:01 GMT Cần bán nhanh shophouse block B chung cư Citi Home, Phường Cát Lái, Quận 2, TP HCM. Mã căn: B0 - 05, tầng trệt + lửng, block B thuộc dự án chung cư Citi Home, Phường Cát Lái, Quận 2, Tp HCM. Diện tích: Tổng 86.5m2. Được thiết kế vừa kinh doanh, vừa ở với diện tích tầng trệt 54,9m2, tầng lửng 31,6m2. Chung cư block B Citihome và các Block citihome bên cạnh với 17 tầng đã phủ đầy... Full Article
ph Chính chủ cần bán Shophouse BG05, đang cho thuê giá 12tr/tháng. Thanh toán 50%, 1,1 tỷ thương lượng By batdongsan.com.vn Published On :: Fri, 08 May 2020 09:01:05 GMT Hiện đang thuê làm Nail và Tóc hợp đồng 3 năm tăng giá 10%. Ưu tiên khách mua giữ lại hợp đồng thuê vì mới gia hạn thêm 3 năm nữa. Chị thuê dễ thương, và sạch sẽ gọn gàng. Anh chị nào mua liên hệ chính chủ 0917424365 A Nhất. Các bạn môi giới chào khách dùm nhé, phí cao. Cảm ơn an... Full Article
ph Duy nhất 1 căn Shophouse 90m2 GĐ1 của CĐT mặt tiền đường Xa Lộ Hà Nội Q9, đối diện ga Metro số 10 By batdongsan.com.vn Published On :: Fri, 08 May 2020 09:37:35 GMT - Chủ đầu tư mở bán giai đoạn 1 duy nhất còn 1 căn diện tích 90m2 Shophouse Metro Star góc 2 mặt tiền tiện kinh doanh hoặc cho thuê sau này. - Shophouse Metro Star nằm đối diện trạm metro số 10 tuyến số 1 có cầu bộ hành kết nối trực tiếp vào tầng 2 của trung tâm thương mại của dự án. - Hiện tại tuyến Metro số 1 đã hoàn thiện hơn 70% tiến độ, dự kiến sẽ đi vào vận hành vào cuối ... Full Article
ph Shophouse Metro Star, hot nhất khu Đông, cầu bộ hành nối liền tầng 2 của dự án vào nhà ga số 10 By batdongsan.com.vn Published On :: Fri, 08 May 2020 09:38:22 GMT Lấy cảm hứng từ Myeongdong - khu phố mua sắm, giải trí nổi tiếng bậc nhất Seoul Một Myeongdong Hàn Quốc sẽ được tái hiện sống động ngay tại khu Đông Sài Gòn hứa hẹn tạo nên không gian sầm uất của phố thị rực rỡ.Tập trung hàng trăm thương hiệu thời trang nổi tiếng, không gian ẩm t... Full Article
ph Cần bán Shophouse CC An Thịnh, An Phú An Khánh, Quận 2, TDT 201,9m2, hướng ĐN, sổ đỏ, giá 20 tỷ By batdongsan.com.vn Published On :: Fri, 08 May 2020 10:53:37 GMT - Cần bán Shophouse chung cư An Thịnh, An Phú An Khánh, Quận 2. Tổng diện tích 201,9m2, đường 20m (mặt tiền đường Thái Thuận giao nhau với đường Nguyễn Quý Đức) hướng Tây Bắc, sổ hồng, giá 20 tỷ. - Vị trí đẹp nhất ở quận 2, thích hợp mở quán cafe, mini shop... Gần Metro, trường h... Full Article
ph Cần bán shophouse Park Hill 2 mặt tiền, đã có sổ đỏ By batdongsan.com.vn Published On :: Fri, 08 May 2020 13:28:00 GMT Mình cần bán gấp shophouse căn góc 2 mặt tiền Times City, Park Hill 8, quận Hai Bà Trưng - Hà Nội, đã có sổ đỏ. Diện tích: 100m2 x 2 tầng. Phía trước là đài phun nước; sân chơi nước kết hợp trình diễn ánh sáng; quảng trường ánh sáng, khu vui chơi trẻ em Vinperland, sân vui ... Full Article
ph Bán shophouse Homyland 3 ngay trung tâm Quận 2, vô cùng phù hợp để kinh doanh, DT 90m2 giá 7.5 tỷ By batdongsan.com.vn Published On :: Fri, 08 May 2020 14:53:57 GMT Em Nhi chuyên bán căn hộ Homyland 3, shophouse, căn hộ officetel. Gọi ngay 0944 589 718 (zalo). Vị trí Homyland đắc địa ngay khu dân cư sầm uất, rất dễ kinh doanh mở quán café. Hiện tại giỏ hàng công ty em có. Cho thuê căn 02 - 40 triệu, 03 - 30 triệu, 08 - 30 triệu, 09 - 35 triệ... Full Article
ph Bán shophouse Midtown - The Signature M7 Phú Mỹ Hưng - Shop 44 - 45.9 tỷ 0946.699.009 By batdongsan.com.vn Published On :: Fri, 08 May 2020 17:49:00 GMT Bán ShopHouse căn 44 - Toà nhà hình trứng - The Signature M7, vị trí đẹp độc nhất dự án Midtown Phú Mỹ Hưng. Phú Mỹ Hưng Midtown nằm trên thế đất địa linh, vượng khí sinh tài lộc mà không phải dự án nào trong Phú Mỹ Hưng cũng sở hữu: + Cách một cây cầu là đến khu Thương mại... Full Article
ph Shophouse TM mặt đường Võ Chí Công sở hữu lâu dài, mặt trước toà chung cư Udic Westlake. 0982943269 By batdongsan.com.vn Published On :: Sat, 09 May 2020 15:11:51 GMT Shophouse mặt đường Võ Chí Công, mặt trước chung cư cao cấp Udic Westlake, xây thông 3 tầng, nhận bàn giao luôn, đặc biệt cấp sổ đỏ sở hữu lâu dài. Duy nhất 14 lô. Liên hệ PKD: 0982943269. -----------------------------* Tổng quan dự án: Tên dự án: Shophouse khối đế chung cư cao c... Full Article
ph Bán shophouse Udic Westlake mặt đường Võ Chí Công, 3 tầng, 300m2, nhận nhà ngay, sổ đỏ lâu dài By batdongsan.com.vn Published On :: Sat, 09 May 2020 16:28:35 GMT Bán shophouse Udic Westlake mặt đường Võ Chí Công, đối diện trung tâm thương mại Lotte đang triển khai. Shophouse 3 tầng, mặt sàn trung bình 100m2, tổng diện tích từ 280m2 đến 350m2. Hướng Đông Nam, hướng mặt đường Võ Chí Công. Mặt tiền từ 7,2m đến 10m. Hiện đã hoàn thành và bàn ... Full Article
ph Chính chủ cần tiền bán lỗ shophouse Hope Garden (Phúc Yên 3) giá rẻ 3.2 tỷ ( giá mua HĐ gần 3,4 tỷ) By batdongsan.com.vn Published On :: Mon, 04 May 2020 11:00:58 GMT Tôi cần tiền nên bán gấp shophouse Hope Garden (Phúc Yên 3) mặt tiền đường Phan Huy Ích - Diện tích: 80m2. - Bàn giao phần thô có thể xây dựng thêm 1 tầng lửng- Mặt tiền đường tiện mở văn phòng, công ty, coffee shop, siêu thị...- An ninh bảo vệ 24/24, bảo trì bảo dưỡng cần luôn ... Full Article
ph Ra mắt shophouse 2 mặt tiền hot nhất Ecopark, Văn Giang, Hưng Yên By batdongsan.com.vn Published On :: Tue, 05 May 2020 19:03:58 GMT Mở bán Shophouse 2 Mặt tiền dự án Sky Oasis thuộc khu đô thị Ecopark. Nhanh tay sở hữu ngay shop chân đế vĩnh viễn. Diện tích 40 - 150m2. Nằm trên tuyến phố đi bộ 2.5km thiết kế phong cách Hàn, Nhật theo chủ đề. Phố shoping, giải trí, Check - in... Lưu lượng 10 tòa chung cư với h... Full Article
ph Cần bán shophouse The Sun Avenue - Giá tốt nhất 5.8 tỷ - 0903989800 By batdongsan.com.vn Published On :: Thu, 07 May 2020 11:04:54 GMT Thông tin mô tả. Quản lý 100% căn hộ tại dự án The Sun Avenue, Mai Chí Thọ, quận 2. Chúng tôi cam kết sẽ đem lại dịch vụ cho thuê và mua bán với giá cả tốt nhất thị trường, liên hệ phòng kinh doanh căn hộ The Sun Avenue gọi 0903 989 800.Nhận ký gửi mua bán cho thuê giao dịch nhan... Full Article
ph Bán cây xăng - góc 2MT Đồng Đen & Hồng Lạc, phường 13, Tân Bình. Hơn 600m2 sang cả GPKD giá 115 tỷ By batdongsan.com.vn Published On :: Sat, 02 May 2020 10:41:34 GMT Bán cây xăng - Góc 2MT Đồng Đen & Hồng Lạc - Phường 13, Quận Tân Bình. - Diện tích: 15.6 (17m) x38m, DTSD: 614m2. - Vị trí: Ngay góc ngã 4 đèn đỏ, đường rộng 20m mỗi bên, có lề rộng, khu vực xe cộ qua lại tấp nập. - Đang kinh doanh xăng dầu, có 4 trụ bơm. Lượng khách rất đông và ổn định. Cần vốn đầu tư nên bán lại và sang luôn cả Giấy phép Kinh Doanh. - Sổ hồng pháp lý rõ ràng,... Full Article
ph Shophouse Phạm Thế Hiển ở liền - giữ tiền cho anh chị mùa Covid. LH ngay em: 0901 636 577 By batdongsan.com.vn Published On :: Sun, 03 May 2020 10:47:31 GMT Bán shophouse mặt tiền quận 8 thanh toán 3,4 tỷ. Còn lại trả góp. - Hình thức: 1 trệt 1 lầu (được xây thêm 1 lửng). - Sổ hồng vĩnh viễn.Diện tích 151m2 đối diện công viên, gần trường học và dân cư và lưu lượng khách vài ngàn người mỗi ngày.Liên hệ: Mỹ Linh: Trưởng phòng kinh doan... Full Article
ph Bán sàn thương mại kinh doanh tầng 1, tòa tháp đôi chung cư Đông Đô Học Viện Quốc Phòng. Siêu hot By batdongsan.com.vn Published On :: Tue, 05 May 2020 08:07:56 GMT Bán sàn kiot thương mại kinh doanh tầng 1 chân đế tòa tháp đôi chung cư Đông Đô Học Viện Quốc Phòng cao 33 tầng. Diện tích 573m2, có 2 mặt đường trước và sau, giá bán 45 triệu/m2. Vị trí kinh doanh siêu đẹp, cách ngã tư Hoàng Quốc Việt và Nguyễn Văn Huyên 100m, xung quanh có nhiề... Full Article
ph Bán căn shop Q7 Boulevard MT Nguyễn Lương Bằng-Phú Mỹ Hưng Q7 sắp nhận nhà, CK7-10%. LH: 0901378179 By batdongsan.com.vn Published On :: Thu, 07 May 2020 14:58:10 GMT Tiếp nối những thành công từ các dự án Florita, Sài Gòn Mia, Citizen, 91 Phạm Văn Hai, Sky Center, Melody Residences, dòng sản phẩm 8X... Chủ đầu tư Hưng Thịnh tiếp tục cho ra đời căn hộ cao cấp Q7 Boulevard liền kề Phú Mỹ Hưng quận 7 vị trí vàng cực kỳ đắc địa. 1. Tổng quan về d... Full Article
ph Vinhomes Ba Son Q1, CH đa năng giá phải chăng, 1PN 16tr, 2PN 20tr, 3PN 28tr, 4PN 60tr. 0903049288 By batdongsan.com.vn Published On :: Thu, 30 Apr 2020 21:57:34 GMT Vinhomes Golden River.- 1PN 50m2 có bồn tắm nằm giá 16tr - 17tr/th bao phí. - 2PN 70 - 87m2 có bồn nằm giá 20tr - 25tr/th bao phí. - 3PN 100 - 121 m2 có bồn nằm giá 29tr - 42tr/th bao phí. - 4PN 154m2 - 159m2 giá 70 - 80tr/th không bao phí.Lưu Ý: Giá trên là giá thực tế, thương l... Full Article
ph Khu đô thị Phương Đông By batdongsan.com.vn Published On :: Sat, 12 Jan 2019 14:04:34 GMT Khu đô thị Phương Đông là khu phức hợp nằm ngay cửa ngõ đặc khu kinh tế Vân Đồn với 200 lô biệt thự đơn lập, song lập cùng 500 lô liền kề và shophouse. Full Article
ph Phoenix Legend Ha Long Bay By batdongsan.com.vn Published On :: Wed, 16 Jan 2019 19:01:11 GMT Phoenix Legend Ha Long Bay Hotel and Residences được thiết kế là khu phức hợp hiện đại gồm căn hộ nghỉ dưỡng, khu biệt thự cao cấp, khách sạn tiêu chuẩn quốc tế 5 sao. Full Article
ph An Phú New City By batdongsan.com.vn Published On :: Thu, 03 Oct 2019 14:36:36 GMT An Phú New City là tổ hợp căn hộ và nhà phố thương mại do Công ty TNHH Xây Dựng và Kinh Doanh Nhà Phú Nhuận làm chủ đầu tư, phát triển tại phường An Phú, quận 2, Tp.HCM. Full Article
ph Royal Landmark & Shophouse Quảng Bình By batdongsan.com.vn Published On :: Thu, 24 Oct 2019 14:26:43 GMT Dự án Royal Landmark & Shophouse Quảng Bình là Tổ hợp nhà phố thương mại shophouse kết hợp kinh doanh khách sạn nghỉ dưỡng, dịch vụ thương mại nằm ngay bên bờ sông Nhật Lệ, TP. Đồng Hới (Quảng Bình). Full Article
ph The Light Phú Yên By batdongsan.com.vn Published On :: Thu, 14 Nov 2019 11:34:42 GMT Dự án The Light Phú Yên được đầu tư bởi Công ty cổ phần Đầu tư Xây dựng Constrexim với quy mô gồm 1 block với 20 tầng nổi và 2 tầng hầm trên quỹ đất rộng gần 1.000m2 tại số 220 đường Trần Hưng Đạo, TP. Tuy Hòa. Full Article
ph Công ty CP Đầu tư Đại Phong Nguyên By batdongsan.com.vn Published On :: Wed, 19 Feb 2014 10:55:00 GMT Full Article
ph Công ty CP Chứng khoán Ngân hàng Đầu tư và Phát triển By batdongsan.com.vn Published On :: Wed, 19 Feb 2014 11:03:00 GMT Full Article
ph Công ty chứng khoán Phương Đông By batdongsan.com.vn Published On :: Wed, 19 Feb 2014 14:26:00 GMT Full Article
ph Công ty CP Chứng khoán Alpha By batdongsan.com.vn Published On :: Wed, 19 Feb 2014 14:37:00 GMT Full Article
ph Công ty CP chứng khoán Hải Phòng By batdongsan.com.vn Published On :: Wed, 19 Feb 2014 15:09:00 GMT Full Article