bluuebunny/crossref_metadata_2025_split huggingface dataset:
How the Neoproterozoic S-isotope record illuminates the genesis of vein gold systems: an example from the Dalradian Supergroup in Scotland
Authors: Hill Nyree J. , Jenkin Gawen R. T. , Boyce Adrian J. , Sangster Christopher J. S. , Catterall David J. , Holwell David A. , Naden Jonathan , Rice Clive M. 
Published: November 2013

Abstract

The genesis of quartz vein-hosted gold mineralization in the Neoproterozoic–early Palaeozoic Dalradian Supergroup of Scotland remains controversial. An extensive new dataset of S-isotope analyses from the Tyndrum area, together with correlation of the global Neoproterozoic sedimentary S-isotope dataset to the Dalradian stratigraphy, demonstrates a mixed sedimentary and magmatic sulphur source for the mineralization. δ
34
S values for early molybdenite- and later gold-bearing mineralization range from −2 to +12‰, but show distinct populations related to mineralization type. Modelling of the relative input of magmatic and sedimentary sulphur into gold-bearing quartz veins with δ
34
S values of +12‰ indicates a maximum of 68% magmatic sulphur, and that S-rich, SEDEX-bearing, Easdale Subgroup metasedimentary rocks lying stratigraphically above the host rocks represent the
only
viable source of sedimentary sulphur in the Dalradian Supergroup. Consequently, the immediate host rocks were not a major source of sulphur to the mineralization, consistent with their low bulk sulphur and lack of metal enrichment. Recent structural models of the Tyndrum area suggest that Easdale Subgroup metasedimentary rocks, enriched in
34
S, sulphur and metals, are repeated at depth owing to folding, and it is suggested that these are the most likely source of sedimentary sulphur, and possibly metals, for the ore fluids.
Sillimanite deformation mechanisms within a Grt-Sil-Bt gneiss: effect of pre-deformation grain orientations and characteristics on mechanism, slip-system activation and rheology
Authors: Piazolo Sandra , Jaconelli Paulina 
Published: November 2013

Abstract

Sillimanite-bearing metapelites are common in the middle to lower crust and play an important role in the rheology of these crustal levels. We report deformation microstructures in a metasedimentary gneiss (Greenland) produced during simple shear at
c.
700 °C and
c.
4.5 kbar. Electron backscatter diffraction analysis shows activation of the (001)[010] and (001)[100] slip systems in large grains. Additionally, (100)[001] and (010)[001] are activated in needles with their c-axes parallel to lineation. Medium-grained sillimanite aggregates mixed with biotite show a weak crystallographic preferred orientation (CPO) suggesting activation of (001)[010] and (001)[100] together with grain boundary sliding (GBS). GBS is the dominant deformation mechanism in the outer parts of fine-grained clusters of sillimanite stemming from andalusite replacement. Associated features are phase mixing, clockwise dispersion of c-axis orientations and change of misorientation axes from original c-axis rotation to rotation close to the kinematic Y axis. The latter features which result in strain localization around these clusters allow their ‘preservation’. Rheologically, the medium-grained aggregates together with zones around clusters take up most of the deformation. Our study shows that deformation mechanism and slip-system activation, and CPOs are strongly dependent on the orientation relationship between stress axes and pre-deformation grain orientations and characteristics.
Cyclophilin B Supports Myc and Mutant p53-Dependent Survival of Glioblastoma Multiforme Cells
Authors: Choi Jae Won , Schroeder Mark A. , Sarkaria Jann N. , Bram Richard J. 
Published: November 2013

Abstract
Glioblastoma multiforme is an aggressive, treatment-refractory type of brain tumor for which effective therapeutic targets remain important to identify. Here, we report that cyclophilin B (CypB), a prolyl isomerase residing in the endoplasmic reticulum (ER), provides an essential survival signal in glioblastoma multiforme cells. Analysis of gene expression databases revealed that CypB is upregulated in many cases of malignant glioma. We found that suppression of CypB reduced cell proliferation and survival in human glioblastoma multiforme cells in vitro and in vivo. We also found that treatment with small molecule inhibitors of cyclophilins, including the approved drug cyclosporine, greatly reduced the viability of glioblastoma multiforme cells. Mechanistically, depletion or pharmacologic inhibition of CypB caused hyperactivation of the oncogenic RAS–mitogen-activated protein kinase pathway, induction of cellular senescence signals, and death resulting from loss of MYC, mutant p53, Chk1, and Janus-activated kinase/STAT3 signaling. Elevated reactive oxygen species, ER expansion, and abnormal unfolded protein responses in CypB-depleted glioblastoma multiforme cells indicated that CypB alleviates oxidative and ER stresses and coordinates stress adaptation responses. Enhanced cell survival and sustained expression of multiple oncogenic proteins downstream of CypB may thus contribute to the poor outcome of glioblastoma multiforme tumors. Our findings link chaperone-mediated protein folding in the ER to mechanisms underlying oncogenic transformation, and they make CypB an attractive and immediately targetable molecule for glioblastoma multiforme therapy. Cancer Res; 74(2); 484–96. ©2013 AACR.
Beyond the Cancer Cell: Progression-Level Determinants Highlight the Multiscale Nature of Carcinogenesis Risk
Authors: Hlatky Lynn , Hahnfeldt Philip 
Published: November 2013

Abstract
Over the last several decades, improved awareness of the prevalence of carcinogens in the environment, along with a growing appreciation of the complexity of the carcinogenesis process, has shifted policy on cancer risk from one of strict avoidance of carcinogens to one of adherence to exposure limits deemed “safe” based on quantitative risk estimation. Meanwhile, given the mutagenic nature of most carcinogens, attention has gravitated to developing a genetic rationale for measuring and comparing risks. This focus has culminated in the now well-established multistage mutational paradigm, which holds that a stepwise sequence of mutations drives cell “initiation” and the subsequent “transformation” of an initiated cell into a cancer cell, and that, once created, a cancer cell will inevitably undergo “progression” to become overt disease. Unanticipated by this paradigm is the effect progression-phase population- and tissue-level bottleneck events may have on this process. Attesting to this is the prevalence of tumor dormancy, a state of arrested growth of an otherwise fully malignant, often microscopic cancer mass, maintained by interactions among cancer cells and between cancer and host cells. The proper inclusion of such progression-modifying influences would clearly behoove risk estimation and improve our understanding of the natural history of cancer by accounting for the less-than-certain risk of eventual cancer disease even when cancer cells are present. Such an improved understanding, in turn, stands to better inform policy-making and influence such clinical practice decisions as whether to treat the increasingly smaller tumors detectable with advancing technologies. Cancer Res; 74(3); 659–64. ©2013 AACR.
Molecular Pathways: How Can BRCA-Mutated Tumors Become Resistant to PARP Inhibitors?
Authors: Bouwman Peter , Jonkers Jos 
Published: November 2013

Abstract
PARP inhibition is synthetic lethal with defective DNA repair via homologous recombination. Phase I and II clinical trials show that PARP inhibitors are effective at well-tolerated doses and have antitumor activity for BRCA1- and BRCA2-associated cancers. However, not all patients respond equally well and tumors may eventually become resistant. Thus far, the only resistance mechanism that has been found in human tumors is genetic reversion that corrects or bypasses the original BRCA1- or BRCA2-inactivating mutation. However, data from fundamental and preclinical research suggest that resistance to PARP inhibitors may be induced by additional mechanisms involving hypomorphic activity of mutant BRCA1 alleles, upregulation of drug efflux pumps, and rewiring of the DNA damage response. Preclinical models will be instrumental to develop methods for adequate patient stratification, as well as treatment strategies that prevent or counteract resistance to PARP inhibitors. Clin Cancer Res; 20(3); 540–7. ©2013 AACR.
Molecular Pathways: Targeting Inhibitor of Apoptosis Proteins in Cancer—From Molecular Mechanism to Therapeutic Application
Authors: Fulda Simone 
Published: November 2013

Abstract
Inhibitor of apoptosis (IAP) proteins play a critical role in the control of survival and cell death by regulating key signaling events such as caspase activation and NF-κB signaling. Because aberrantly high expression of IAP proteins represents a frequent oncogenic event in human cancers, therapeutic targeting of IAP proteins is considered as a promising approach. Several small-molecule pharmacologic inhibitors of IAP proteins that mimic the binding domain of the endogenous IAP antagonist second mitochondrial activator of caspases (Smac) to IAP proteins have been developed over the past few years. IAP antagonists have been shown in various preclinical cancer models to either directly initiate cell death or, alternatively, to prime cancer cells for cytotoxic therapies by lowering the threshold for cell death induction. IAP antagonists (i.e., GDC-0917/CUDC-427, LCL161, AT-406, HGS1029, and TL32711) are currently under evaluation in early clinical trials alone or in combination regimens. Thus, the concept to therapeutically target IAP proteins in human cancer has in principle been successfully transferred into a clinical setting and warrants further evaluation as a treatment approach. Clin Cancer Res; 20(2); 289–95. ©2013 AACR.
Molecular Pathways: Gene–Environment Interactions Regulating Dietary Fiber Induction of Proliferation and Apoptosis via Butyrate for Cancer Prevention
Authors: Bultman Scott J. 
Published: November 2013

Abstract
Gene–environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low–moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression. Clin Cancer Res; 20(4); 799–803. ©2013 AACR.
Impact of Incident Venous Thromboembolism on Risk of Arterial Thrombotic Diseases
Authors: Lind Caroline , Flinterman Linda E. , Enga Kristin F. , Severinsen Marianne T. , Kristensen Søren R. , Brækkan Sigrid K. , Mathiesen Ellisiv B. , Njølstad Inger , Cannegieter Suzanne C. , Overvad Kim , Hansen John-Bjarne 
Published: November 2013

Background—
Growing evidence supports an association between venous thromboembolism (VTE) and arterial thrombotic diseases (ie, myocardial infarction and ischemic stroke). We aimed to study the association between VTE and future arterial events and to determine the population attributable risk of arterial events by VTE in a large prospective cohort recruited from the general population.

Methods and Results—
In 1994 to 1995 and 1993 to 1997, 81 687 subjects were included in the Tromsø Study and in the Diet, Cancer and Health Study and followed up to the date of incident venous and arterial events (myocardial infarction or ischemic stroke), death or migration, or to the end of the study period (2010 and 2008, respectively). There were 1208 cases of VTE and 90 subsequent arterial events during a median follow-up of 12.2 years. An association between VTE and future arterial events was found in all women and men aged <65 years but not in men aged >65 years. Women <65 years old with VTE had 3.3-fold higher risk of arterial disease (adjusted hazard ratio, 3.28; 95% confidence interval, 1.69–6.35) compared with women of the same age without VTE. The corresponding hazard ratio in men aged <65 years was 2.06 (95% confidence interval, 1.32–3.20). Only 0.9% of the arterial events were attributed to VTE, and the VTE explained 63.8% of the risk of arterial events among VTE patients.

Conclusions—
Our findings imply that women and young men with VTE have higher risk of arterial thrombotic disease than those without VTE. However, only 1% of the arterial thrombotic events in the population are attributed to VTE.
Role for DNA Damage Signaling in Pulmonary Arterial Hypertension
Authors: Meloche Jolyane , Pflieger Aude , Vaillancourt Mylène , Paulin Roxane , Potus François , Zervopoulos Sotirios , Graydon Colin , Courboulin Audrey , Breuils-Bonnet Sandra , Tremblay Ève , Couture Christian , Michelakis Evangelos D. , Provencher Steeve , Bonnet Sébastien 
Published: November 2013

Background—
Pulmonary arterial hypertension (PAH) is associated with sustained inflammation known to promote DNA damage. Despite these unfavorable environmental conditions, PAH pulmonary arterial smooth muscle cells (PASMCs) exhibit, in contrast to healthy PASMCs, a pro-proliferative and anti-apoptotic phenotype, sustained in time by the activation of miR-204, nuclear factor of activated T cells, and hypoxia-inducible factor 1-α. We hypothesized that PAH-PASMCs have increased the activation of poly(ADP-ribose) polymerase-1 (PARP-1), a critical enzyme implicated in DNA repair, allowing proliferation despite the presence of DNA-damaging insults, eventually leading to PAH.

Methods and Results—
Human PAH distal pulmonary arteries and cultured PAH-PASMCs exhibit increased DNA damage markers (53BP1 and γ-H2AX) and an overexpression of PARP-1 (immunoblot and activity assay), in comparison with healthy tissues/cells. Healthy PASMCs treated with a clinically relevant dose of tumor necrosis factor-α harbored a similar phenotype, suggesting that inflammation induces DNA damage and PARP-1 activation in PAH. We also showed that PARP-1 activation accounts for miR-204 downregulation (quantitative reverse transcription polymerase chain reaction) and the subsequent activation of the transcription factors nuclear factor of activated T cells and hypoxia-inducible factor 1-α in PAH-PASMCs, previously shown to be critical for PAH in several models. These effects resulted in PASMC proliferation (Ki67, proliferating cell nuclear antigen, and WST1 assays) and resistance to apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling and Annexin V assays). In vivo, the clinically available PARP inhibitor ABT-888 reversed PAH in 2 experimental rat models (Sugen/hypoxia and monocrotaline).

Conclusions—
These results show for the first time that the DNA damage/PARP-1 signaling pathway is important for PAH development and provide a new therapeutic target for this deadly disease with high translational potential.
Beliefs about mental disorder treatment and prognosis: Comparison of health professionals with the Australian public
Authors: Morgan Amy J , Reavley Nicola J , Jorm Anthony F 
Published: November 2013

Objective: In the 1990s, large differences in beliefs about the helpfulness of treatments for mental disorders were observed between the Australian public and health professionals. This study evaluates whether gaps in public and professional beliefs remain by comparing beliefs of the public and health professionals on the helpfulness of interventions and likely prognosis for six mental health problems: depression, depression with suicidal thoughts, early schizophrenia, chronic schizophrenia, social phobia, and post-traumatic stress disorder. Methods: Mental health literacy surveys based around a vignette of a person with a mental disorder were carried out in a nationally representative sample of the Australian public ( n=6019) in 2011 and samples of Australian general practitioners, psychiatrists, and psychologists ( n=1536) in 2012. Respondents were asked to rate the helpfulness of a range of interventions and the likely outcome with or without appropriate professional treatment. Differences between groups were examined with chi-square tests. Results: There were many significant differences in treatment beliefs, but most of these were small in size. Medium-sized differences tended to be consistent across vignettes and relate to the greater belief by the public in the helpfulness of close family or friends, a counsellor, vitamins and minerals, a special diet or avoiding certain foods, and having an occasional alcohol drink to relax. In contrast, professionals showed a greater belief in psychotherapy and cognitive behaviour therapy for depression and anxiety, and antipsychotics for schizophrenia. Findings on prognosis showed mostly small differences in beliefs. Conclusions: Overall, the results indicate that the views of the public and professionals are more aligned than in the 1990s. There are now few large gaps in treatment beliefs, but there remain some areas that could be improved.
Solving the system of linear operator equations over generalized bisymmetric matrices
Authors: Hajarian Masoud 
Published: November 2013

This paper proposes an iterative method based on the conjugate gradient method on the normal equations for finding the generalized bisymmetric solution [Formula: see text] to the system of linear operator equations [Formula: see text] where [Formula: see text] are linear operators. By the iterative method, the solvability of this system over the generalized bisymmetric matrix [Formula: see text] can be determined automatically. When the system of linear operator equations is consistent over the generalized bisymmetric matrix [Formula: see text], the iterative method with any generalized bisymmetric initial iterative matrix [Formula: see text] can compute the generalized bisymmetric solution within a finite number of iterations in the absence of roundoff errors. In addition, by the proposed iterative method, the least Frobenius norm generalized bisymmetric solution can be derived when a special initial generalized bisymmetric matrix is chosen. Finally, two numerical examples are presented to support the theoretical results of this paper.
AlloDerm with Split‐Thickness Skin Graft for Coverage of the Forearm Free Flap Donor Site
Authors: Wester Jacob L. , Pittman Amy L. , Lindau Robert H. , Wax Mark K. 
Published: November 2013

ObjectiveMajor causes of donor site morbidity after free flap harvest are lack of split‐thickness skin graft (STSG) take and tendon exposure. Long‐term cosmesis remains poor. AlloDerm has shown cosmetically better donor site healing, albeit prolonged healing. We sought to evaluate the use of STSG with AlloDerm compared with STSG alone.Study DesignCase series with chart review.SettingAcademic tertiary care medical center.Methods and SubjectsInstitutional review board–approved study. Microvascular database queried from 2002 to 2012. Subjects with forearm free flaps and either AlloDerm + STSG or STSG alone for donor site reconstruction were included. Morbidity outcomes were compared.ResultsEighty patients (50 male, 30 female) received AlloDerm + STSG at the donor site. Major and minor donor site complications were 15.0% and 18.8% in the AlloDerm + STSG group compared with 10.2% and 16.9% in the STSG‐only group (P =. 30 and P =. 72), respectively. Complete STSG loss (5.0% vs 3.0%, P =. 48), tendon exposure (5.0% vs 5.4%, P = 1.0), functional impairment (2.5% vs 1.8%, P =. 66), infection (8.8% vs 9.6%, P = 1.0), hematoma/seroma (5.0% vs 3.6%, P =. 73), and paresthesia (1.3% vs 3.6%, P =. 43) were not significant. No patients required a second STSG after loss in the AlloDerm + STSG group compared with 60% (P =. 17). Cosmetic results were superior in the AlloDerm + STSG group as rated by the surgeon (3.5 vs 2.6, P =. 03) and patients (3.7 vs 2.9, P =. 05) on a scale of 1 to 5.ConclusionOur results suggest that the use of AlloDerm with STSG can provide thicker coverage of the forearm defect, with minimal donor site morbidity and superior cosmetic results compared with STSG alone.
Postsplenectomy left lower lobe bronchiectasis
Authors: Sersar Sameh I 
Published: November 2013

Background Bronchiectasis has decreased significantly. I describe a new underestimated clinicopathological entity of postsplenectomy left lower lobe bronchiectasis. Methods This is a retrospective study on 24 patients who had a left lower lobectomy for left lower lobe bronchiectasis after splenectomy. The mean age was 34.6 years (range 18 to 63 years); there were 19 men and 5 women. The available data included history, radiological investigations (ultrasonography and computed tomography of the chest and abdomen), operative data, postoperative complications, and follow-up data. Results All patients had a history of splenectomy and 10 had undergone subphrenic collection drainage either percutaneously or through open drainage a few years prior to the left lower lobectomy. Fourteen patients were lost to follow-up. The mean follow-up in 10 patients was 5.8 years (range 2 to 13 years). Conclusions Postsplenectomy left lower lobe bronchiectasis is an underestimated clinicopathological entity of bronchiectasis. It can be managed by a left lower lobectomy, with acceptable results.
Primary tetralogy of Fallot repair: Predictors of intensive care unit morbidity
Authors: Egbe Alexander C , Uppu Santosh C , Mittnacht Alexander JC , Joashi Umesh , Ho Deborah , Nguyen Khanh , Srivastava Shubhika 
Published: November 2013

Background Primary repair of tetralogy of Fallot has low surgical mortality, but some patients still experience significant postoperative morbidity. Our objectives were to review our institutional experience with primary tetralogy of Fallot repair, and identify predictors of intensive care unit morbidity. Methods We reviewed all patients with tetralogy of Fallot who underwent primary repair in infancy from 2001 to 2012. Preoperative, operative, and postoperative demographic and morphologic data were analyzed. Intensive care unit morbidity was defined as prolonged intensive care unit stay (≥7 days) and/or prolonged duration of mechanical ventilation (≥48 h). Results 97 patients who underwent primary surgical repair during the study period were included in the study. The median age was 4.9 months (range 1–9 months) and the median weight was 5.3 kg (range 3.1–9.8 kg). There was no early surgical mortality. The incidence of junctional ectopic tachycardia and persistent complete heart block was 2% and 1%, respectively. The median intensive care unit stay was 6 days (range 2–21 days) and the median duration of mechanical ventilation was 19 h (range 0–136 h). Age and weight were independent predictors of intensive care unit stay, while surgical era predicted the duration of mechanical ventilation. Conclusion Primary tetralogy of Fallot repair is a safe procedure with low mortality and morbidity in a medium-sized program with outcomes comparable to national standards. Age and weight at the time of surgery were significant predictors of morbidity.