bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical considerations for maximizing heat production in a novel thermobrachytherapy seed prototype
Authors: Gautam Bhoj , Warrell Gregory , Shvydka Diana , Subramanian Manny , Ishmael Parsai E. 
Published: January 2014

Purpose:A combination of hyperthermia and radiation in the treatment of cancer has been proven to provide better tumor control than radiation administered as a monomodality, without an increase in complications or serious toxicities. Moreover, concurrent administration of hyperthermia and radiation displays synergistic enhancement, resulting in greater tumor cell killing than hyperthermia and radiation delivered separately. The authors have designed a new thermobrachytherapy (TB) seed, which serves as a source of both radiation and heat for concurrent brachytherapy and hyperthermia treatments when implanted in solid tumors. This innovative seed, similar in size and geometry to conventional seeds, will have self‐regulating thermal properties.Methods:The new seedˈs geometry is based on the standard BEST Model 2301125I seed, resulting in very similar dosimetric properties. The TB seed generates heat when placed in an oscillating magnetic field via induction heating of a ferromagnetic Ni–Cu alloy core that replaces the tungsten radiographic marker of the standard Model 2301. The alloy composition is selected to undergo a Curie transition near 50 °C, drastically decreasing power production at higher temperatures and providing for temperature self‐regulation. Here, the authors present experimental studies of the magnetic properties of Ni–Cu alloy material, the visibility of TB seeds in radiographic imaging, and the ability of seed prototypes to uniformly heat tissue to a desirable temperature. Moreover, analyses are presented of magnetic shielding and thermal expansion of the TB seed, as well as matching of radiation dose to temperature distributions for a short interseed distance in a given treatment volume.Results:Annealing the Ni–Cu alloy has a significant effect on its magnetization properties, increasing the sharpness of the Curie transition. The TB seed preserves the radiographic properties of the BEST 2301 seed in both plain x rays and CT images, and a preliminary experiment demonstrates thermal self‐regulation and adequate heating of a tissue‐mimicking phantom by seed prototypes. The effect of self‐shielding of the seed against the external magnetic field is small, and only minor thermal stress is induced in heating of the seeds from room temperature to well above the seed operating temperature. With proper selection of magnetic field parameters, the thermal dose distribution of an arrangement of TB and hyperthermia‐only seeds may be made to match with its radiation dose distribution.Conclusions:The presented analyses address several practical considerations for manufacturing of the proposed TB seeds and identify critical issues for the prototype implementation. The authors’ preliminary experiments demonstrate close agreement with the modeling results, confirming the feasibility of combining sources of heat and radiation into a single thermobrachytherapy seed.
Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer
Authors: Jeselsohn Rinath , Yelensky Roman , Buchwalter Gilles , Frampton Garrett , Meric-Bernstam Funda , Gonzalez-Angulo Ana Maria , Ferrer-Lozano Jaime , Perez-Fidalgo Jose A. , Cristofanilli Massimo , Gómez Henry , Arteaga Carlos L. , Giltnane Jennifer , Balko Justin M. , Cronin Maureen T. , Jarosz Mirna , Sun James , Hawryluk Matthew , Lipson Doron , Otto Geoff , Ross Jeffrey S. , Dvir Addie , Soussan-Gutman Lior , Wolf Ido , Rubinek Tamar , Gilmore Lauren , Schnitt Stuart , Come Steven E. , Pusztai Lajos , Stephens Philip , Brown Myles , Miller Vincent A. 
Published: January 2014

Abstract
Purpose: We undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout the natural history of hormone-dependent breast cancer and to delineate the functional roles of the most commonly detected alterations.
Experimental Design: We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER-positive (ER+/HER2−) and, as controls, 115 ER-negative (ER−) tumors. The ER+ samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next-generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes.
Results: Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER+ metastatic disease. Overall, the frequency of these mutations was 12% [9/76; 95% confidence interval (CI), 6%–21%] in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25; 95% CI, 7%–41%). These mutations were not detected in primary or treatment-naïve ER+ cancer or in any stage of ER− disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments.
Conclusions: In this study, we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER+ breast cancer. Clin Cancer Res; 20(7); 1757–67. ©2014 AACR.
Hamacantha (Hamacantha) boomerang sp. nov. from deep-sea coral mounds at Campos Basin, SW Atlantic, and redescription of H. (H.) schmidtii (Carter, 1882) (Hamacanthidae, Poecilosclerida, Demospongiae)
Authors: HAJDU EDUARDO , CASTELLO-BRANCO CRISTIANA 
Published: January 2014

There are 22 species of Hamacantha registered from all over the world, and frequently from deep-waters, only two of which had previously been reported from the SW Atlantic. Here we describe a third species for this area, Hamacantha (H.) boomerang sp. nov., collected from deep-sea coral mounds at Campos Basin (off Rio de Janeiro state). We found oxeas 271–630 µm long, diancistras in three size classes, 125–155, 45–69 and 20–29 µm, and toxas, 58–82 µm. This is the only Hamacantha combining oxeas and toxas, but the latter are very rare. The species approaches the Caribbean H. (H.) schmidtii (Carter, 1882), where we observed oxeas 390–495 µm long, and diancistras in three size classes, 109–124, 44–54 and 26–41 μm, however toxas appear to be absent. Both species are clearly distinct by micrometric values, as well as the overall morphology of the smaller diancistras, distinct from the intermediate category in the new species, but quite similar in H. (H.) schmidtii. Hamacantha (Vomerula) falcula approaches the new species very closely in microsclere dimensions and morphology, but is set apart by its styloid and smaller megascleres.
miRNA-130a regulates C/EBP-ε expression during granulopoiesis
Authors: Larsen Maria T. , Häger Mattias , Glenthøj Andreas , Asmar Fazila , Clemmensen Stine N. , Mora-Jensen Helena , Borregaard Niels , Cowland Jack B. 
Published: January 2014

Key Points
miRNA-130a is expressed in myeloblasts and promyelocytes and inhibits translation of CEBPE mRNA encoding transcription factor C/EBP-ε. Regulation of CEBPE mRNA by miRNA-130a is required for timed expression of secondary granule proteins and cell cycle exit.
Clinical features of dementia with lewy bodies in 35 Chinese patients
Authors: Han Ding , Wang Qiong , Gao Zhongbao , Chen Tong , Wang Zhenfu 
Published: January 2014

Abstract

Objective
To investigate the clinical features of dementia with Lewy bodies (DLB) in a Chinese population.

Methods
Computer-based online searches through China Biology Medicine disc and China National Knowledge Infrastructure were performed to collect case reports of DLB published between 1980 and 2012. Clinical characteristics were analyzed.

Results
A total of 18 studies comprising 35 patients (26 males and 9 females) were included. The mean age at onset was 67.2 ± 9.8 years. Onset was characterized by memory impairment and accounted for 58.8% of all cases, followed by parkinsonism (11.8%), visual hallucinations (8.8%), and compulsive personality disorder (2.9%). The other patients (17.6%) presented two of the three core features of DLB at onset. With disease progression, parkinsonism was reported in 100% of cases, followed by visual hallucinations (97.1%), psychiatric symptoms (85.7%), severe neuroleptic sensitivity (81.8%), fluctuating cognition (68.6%), repeated falls (40.0%), sleep disorders (22.9%), and transient loss of consciousness (17.1%). 26 patients who were subjected to Mini-Mental State Examination scored ≤ 24. 10 patients presented relative preservation of hippocampus and medial temporal lobe structures on CT/MRI scan. Occipital hypometabolism occurred in 2 of 3 patients who underwent SPECT/PET perfusion scan. 12 patients showed an increasing of slow frequency activity on EEG, prominently in frontal and temporal lobes.

Conclusions
DLB often strikes elderly individuals. Its clinical core features are dementia, fluctuating cognition, recurrent visual hallucinations and spontaneous features of parkinsonism. Neuropsychological, neuroimaging and EEG examinations may improve the diagnostic accuracy and discriminate DLB from other dementias.
High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis
Authors: Clark Edward , Molnar Amber O , Joannes-Boyau Olivier , Honoré Patrick M , Sikora Lindsey , Bagshaw Sean M 
Published: January 2014

Abstract
Introduction
High-volume hemofiltration (HVHF) is an attractive therapy for the treatment of septic acute kidney injury (AKI). Small experimental and uncontrolled studies have suggested hemodynamic and survival benefits at higher doses of HVHF than those used for the high-intensity arms of the RENAL and ATN studies. Our aim was to evaluate the effects of high-volume hemofiltration (HVHF) compared with standard-volume hemofiltration (SVHF) for septic AKI.

Methods
A systematic review and meta-analysis of publications between 1966 and 2013 was performed. The review was limited to randomized-controlled trials that compared HVHF (effluent rate greater than 50 ml/kg per hour) versus SVHF in the treatment of sepsis and septic shock. The primary outcome assessed was 28-day mortality. Other outcomes assessed were recovery of kidney function, lengths of ICU and hospital stays, vasopressor dose reduction, and adverse events.

Results
Four trials, including 470 total participants, were included. Pooled analysis for 28-day mortality did not show any meaningful difference between HVHF compared with SVHF (OR, 0.76; 95% CI, 0.45 to 1.29). No included studies reported statistically significant differences between groups for any of the secondary outcomes. Adverse events, including hypophosphatemia and hypokalemia, were more commonly observed in HVHF-treated patients, although reporting was inconsistent across studies.

Conclusions
Insufficient evidence exists of a therapeutic benefit for routine use of HVHF for septic AKI, other than on an experimental basis. Given the logistic challenges related to patient recruitment along with an incomplete understanding of the biologic mechanisms by which HVHF may modify outcomes, further trials should focus on alternative extracorporeal therapies as an adjuvant therapy for septic AKI rather than HVHF.
Global target mRNA specification and regulation by the RNA-binding protein ZFP36
Authors: Mukherjee Neelanjan , Jacobs Nicholas C , Hafner Markus , Kennington Elizabeth A , Nusbaum Jeffrey D , Tuschl Thomas , Blackshear Perry J , Ohler Uwe 
Published: January 2014

Abstract
Background
ZFP36, also known as tristetraprolin or TTP, and ELAVL1, also known as HuR, are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embryonic kidney cells, and examined the combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1.

Results
Targets bound and negatively regulated by ZFP36 include transcripts encoding proteins necessary for immune function and cancer, and transcripts encoding other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance upon ZFP36 overexpression independent of effects from confounding features. Genes with increased mRNA half-lives in ZFP36 knockout versus wild-type mouse cells were significantly enriched for our human ZFP36 targets. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes, and found that ZFP36 degrades transcripts through specific AU-rich sequences, representing a subset of the U-rich sequences ELAVL1 interacts with to stabilize transcripts.

Conclusions
ZFP36-RNA target specificities in vivo are quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to unravel in vivo combinatorial regulation by RNA-binding proteins.
Activins and Inhibins in Endocrine and Other Tumors
Authors: Risbridger Gail P. , Schmitt Jacqueline F. , Robertson David M. 
Published: January 2014

AbstractInhibin and activin are members of the TGFβ superfamily of growth and differentiation factors. They were first identified as gonadal-derived regulators of pituitary FSH and were subsequently assigned multiple actions in a wide range of tissues. More recently, the inhibin α subunit was considered as a tumor suppressor based on functional studies employing transgenic mouse models. This review evaluates the functional and molecular evidence that the inhibin α subunit is a tumor suppressor in endocrine cancers. The evaluation highlights the discrepant results from the human and mouse studies, as well as the differences between endocrine tumor types. In addition, we examine the evidence that the activin-signaling pathway is tumor suppressive and identify organ-specific differences in the actions and putative roles of this pathway in endocrine tumors. In summary, there is a considerable body of evidence to support the role of inhibins and activins in endocrine-related tumors. Future studies will define the mechanisms by which inhibins and activins contribute to the process of initiation, promotion, or progression of endocrine-related cancers.
Vascular Endothelial Estrogen Receptor α Is Modulated by Estrogen Status and Related to Endothelial Function and Endothelial Nitric Oxide Synthase in Healthy Women
Authors: Gavin Kathleen M. , Seals Douglas R. , Silver Annemarie E. , Moreau Kerrie L. 
Published: January 2014

ABSTRACT

Context and Objective
Estrogen receptor α (ERα), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ERα is influenced by estrogen status and is related to vascular endothelial function in healthy women.

Methods
ERα protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women.

Results
In premenopausal women (n = 10), ERα expression was 30% lower (P &lt; 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ERα expression was 33% lower (P &lt; 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ERα expression was strongly related (r = 0.67; P &lt; 0.001) to EDD, which was reduced in postmenopausal women. ERα abundance was positively related to expression of eNOS (r = 0.54; P = 0.009; n = 21) and ser1177 phosphorylated eNOS (r = 0.59; P = 0.006; n = 20).

Conclusions
These results provide the first evidence that expression of ERα in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ERα expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.
The TRH Gene Is Regulated by Thyroid Hormone at the Level of Transcription in Vivo
Authors: Sugrue Michelle L. , Vella Kristen R. , Morales Crystal , Lopez Marisol E. , Hollenberg Anthony N. 
Published: January 2014

ABSTRACT
The expression of the TRH gene in the paraventricular nucleus (PVH) of the hypothalamus is required for the normal production of thyroid hormone (TH) in rodents and humans. In addition, the regulation of TRH mRNA expression by TH, specifically in the PVH, ensures tight control of the set point of the hypothalamic-pituitary-thyroid axis. Although many studies have assumed that the regulation of TRH expression by TH is at the level of transcription, there is little data available to demonstrate this. We used two in vivo model systems to show this. In the first model system, we developed an in situ hybridization (ISH) assay directed against TRH heteronuclear RNA to measure TRH transcription directly in vivo. We show that in the euthyroid state, TRH transcription is present both in the PVH and anterior/lateral hypothalamus. In the hypothyroid state, transcription is activated in the PVH only and can be shut off within 5 h by TH. In the second model system, we employed transgenic mice that express the Cre recombinase under the control of the genomic region containing the TRH gene. Remarkably, TH regulates Cre expression in these mice in the PVH only. Taken together, these data affirm that TH regulates TRH at the level of transcription in the PVH only and that genomic elements surrounding the TRH gene mediate its regulation by T3. Thus, it should be possible to identify the elements within the TRH locus that mediate its regulation by T3 using in vivo approaches.
Granulosa Cell-expressed BMPR1A and BMPR1B have Unique Functions in Regulating Fertility but Act Redundantly to Suppress Ovarian Tumor Development
Authors: Edson Mark A. , Clementi Caterina , Nalam Roopa L. , Franco Heather L. , DeMayo Francesco J. , Lyons Karen M. , Pangas Stephanie A. , Matzuk Martin M. 
Published: January 2014

ABSTRACT
Bone morphogenetic proteins (BMPs) have diverse roles in development and reproduction. Although several BMPs are produced by oocytes, thecal cells, and granulosa cells of developing follicles, the in vivo functions of most of these ligands are unknown. BMP signals are transduced by multiple type I and type II transforming growth factor β (TGFβ) family receptors, and of the type I receptors, BMP receptor 1A (BMPR1A) and BMP receptor 1B (BMPR1B) are known to be expressed in rodent granulosa cells. Female mice homozygous null for Bmpr1b are sterile due to compromised cumulus expansion, but the function of BMPR1A in the ovary is unknown. To further decipher a role for BMP signaling in mouse granulosa cells, we deleted Bmpr1a in the granulosa cells of the ovary and found Bmpr1a conditional knockout females to be subfertile with reduced spontaneous ovulation. To explore the redundant functions of BMP receptor signaling in the ovary, we generated Bmpr1a Bmpr1b double mutant mice, which developed granulosa cell tumors that have evidence of increased TGFβ and hedgehog signaling. Thus, similar to SMAD1 and SMAD5, which have redundant roles in suppressing granulosa cell tumor development in mice, two type I BMP receptors, BMPR1A and BMPR1B, function together to prevent ovarian tumorigenesis. These studies support a role for a functional BMP signaling axis as a tumor suppressor pathway in the ovary, with BMPR1A and BMPR1B acting downstream of BMP ligands and upstream of BMP receptor SMADs.
Obesity-Linked Variants of Melanocortin-4 Receptor Are Misfolded in the Endoplasmic Reticulum and Can Be Rescued to the Cell Surface by a Chemical Chaperone
Authors: Granell Susana , Mohammad Sameer , Ramanagoudr-Bhojappa Ramanagouda , Baldini Giulia 
Published: January 2014

Abstract
Melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in the brain where it controls food intake. Many obesity-linked MC4R variants are poorly expressed at the plasma membrane and are retained intracellularly. We have studied the intracellular localization of four obesity-linked MC4R variants, P78L, R165W, I316S, and I317T, in immortalized neurons. We find that these variants are all retained in the endoplasmic reticulum (ER), are ubiquitinated to a greater extent than the wild-type (wt) receptor, and induce ER stress with increased levels of ER chaperones as compared with wt-MC4R and appearance of CCAAT/enhancer-binding protein homologous protein. Expression of the X-box-binding-protein-1 with selective activation of a protective branch of the unfolded protein response did not have any effect on the cell surface expression of MC4R-I316S. Conversely, the pharmacological chaperone 4-phenyl butyric acid (PBA) increased the cell surface expression of wt-MC4R, MC4R-I316S, and I317T by more than 40%. PBA decreased ubiquitination of MC4R-I316S and prevented ER stress induced by expression of the mutant, suggesting that the drug functions to promote MC4R folding. MC4R-I316S rescued to the cell surface is functional, with a 52% increase in agonist-induced cAMP production, as compared with untreated cells. Also direct inhibition of wt-MC4R and MC4R-I316S ubiquitination by a specific inhibitor of the ubiquitin-activating enzyme 1 increased by approximately 40% the expression of the receptors at the cell surface, and the effects of PBA and ubiquitin-activating enzyme 1 were additive. These data offer a cell-based rationale that drugs that improve MC4R folding or decrease ER-associated degradation of the receptor may function to treat some forms of hereditary obesity.
Stressor Specificity of Sex Differences in Hypothalamo-Pituitary-Adrenal Axis Activity: Cortisol Responses to Exercise, Endotoxin, Wetting, and Isolation/Restraint Stress in Gonadectomized Male and Female Sheep
Authors: Turner A. I. , Rivalland E. T. A. , Clarke I. J. , Tilbrook A. J. 
Published: January 2014

Abstract
Sex differences in the stress-induced activity of the hypothalamo-pituitary-adrenal axis in sheep appear to be dependent on the stressor encountered and occur irrespective of the presence of gonadal steroids. We tested the hypotheses that cortisol responses to exercise, endotoxin, wetting (experiment 1), and isolation/restraint (experiment 2) stress differ between gonadectomized male and female sheep. At weekly intervals (in experiment 1), we subjected gonadectomized rams and ewes (n = 6/group) to control conditions, to exercise stress, to iv injection of endotoxin, and to wetting stress. In a second experiment (experiment 2), we subjected gonadectomized rams and ewes (n = 5/group) to control conditions or to isolation/restraint stress. In both experiments, we measured plasma concentrations of cortisol before, during, and after stress at a frequency of at least 15 min with samples collected (from an indwelling jugular catheter) at a greater frequency around the time of the stressor. Cortisol responses to wetting (experiment 1) and isolation/restraint (experiment 2) stress were significantly higher in females compared with males but in response to exercise (experiment 1) and endotoxin (experiment 1) stress, there were no differences between the sexes. For some stressors, there are sex differences in sheep in the stress-induced activity of the hypothalamo-pituitary-adrenal axis that are independent of the presence of the sex steroids, but the existence of these sex differences and the direction of these sex differences differs, depending on the stressor imposed.