bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Triassic stratigraphic succession of Nakhlak (Central Iran), a record from an active margin
Authors: Balini Marco , Nicora Alda , Berra Fabrizio , Garzanti Eduardo , Levera Marco , Mattei Massimo , Muttoni Giovanni , Zanchi Andrea , Bollati Irene , Larghi Cristiano , Zanchetta Stefano , Salamati Reza , Mossavvari Fathullah 
Published: April 2009

Abstract
An important, 2.4 km-thick Triassic succession is exposed at Nakhlak (central Iran). This succession was deformed during the Cimmerian orogeny and truncated by an angular unconformity with undeformed Upper Cretaceous sediments. This integrated stratigraphic study of the Triassic included bed-by-bed sampling for ammonoids, conodonts and bivalves, as well as limestone and sandstone petrographic analyses. The Nakhlak Group succession consists of three formations: Alam (Olenekian–Anisian), Bāqoroq (?Upper Anisian–Ladinian) and Ashin (Upper Ladinian). The Alam Formation records several shifts from carbonate to siliciclastic deposition, the Bāqoroq Formation consists of continental conglomerates and the Ashin Formation documents the transition to deep-sea turbiditic sedimentation.
Petrographic composition has been studied for sandstones and conglomerates. Provenance analysis for Alam and most of the Ashin samples suggests a volcanic arc setting, whereas the samples from the Bāqoroq Formation are related to exhumation of a metamorphic basement. The provenance data, together with the great thickness, the sudden change of facies, the abundance of volcaniclastic supply, the relatively common occurrence of tuffitic layers and the orogenic calc-alkaline affinity of the volcanism, point to sedimentation along an active margin in a forearc setting.
A comparison between the Triassic of Nakhlak and the Triassic succession exposed in the erosional window of Aghdarband (Koppeh Dag, NE Iran) indicates that both were deposited along active margins. However, they do not show the same type of evolution. Nakhlak and Aghdarband have quite different ammonoid faunal affinities during the Early Triassic, but similar faunal composition from the Bithynian to Late Ladinian. These results argue against the location of Nakhlak close to Aghdarband.
Five-Year Efficacy and Safety Analysis of the Adenoma Prevention with Celecoxib Trial
Authors: Bertagnolli Monica M. , Eagle Craig J. , Zauber Ann G. , Redston Mark , Breazna Aurora , Kim KyungMann , Tang Jie , Rosenstein Rebecca B. , Umar Asad , Bagheri Donya , Collins Neal T. , Burn John , Chung Daniel C. , Dewar Thomas , Foley T. Raymond , Hoffman Neville , Macrae Finlay , Pruitt Ronald E. , Saltzman John R. , Salzberg Bruce , Sylwestrowicz Thomas , Hawk Ernest T. ,   for the Adenoma Prevention with Celecoxib Study Investigators
Published: March 2009

Abstract
The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P &lt; 0.0001) for those receiving low-dose celecoxib, and 60.1% (P &lt; 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P &lt; 0.0001) of those taking low dose celecoxib and 15.8% (P &lt; 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease.
Current GCMs’ Unrealistic Negative Feedback in the Arctic
Authors: Boé Julien , Hall Alex , Qu Xin 
Published: March 2009

Abstract
The large spread of the response to anthropogenic forcing simulated by state-of-the-art climate models in the Arctic is investigated. A feedback analysis framework specific to the Arctic is developed to address this issue. The feedback analysis shows that a large part of the spread of Arctic climate change is explained by the longwave feedback parameter. The large spread of the negative longwave feedback parameter is in turn mainly due to variations in temperature feedback. The vertical temperature structure of the atmosphere in the Arctic, characterized by a surface inversion during wintertime, exerts a strong control on the temperature feedback and consequently on simulated Arctic climate change. Most current climate models likely overestimate the climatological strength of the inversion, leading to excessive negative longwave feedback. The authors conclude that the models’ near-equilibrium response to anthropogenic forcing is generally too small.
Repeat Revision of Anterior Cruciate Ligament Reconstruction
Authors: Wegrzyn Julien , Chouteau Julien , Philippot Rémi , Fessy Michel-Henri , Moyen Bernard 
Published: March 2009

Background To the authors’ knowledge, no previous published study has focused on management and outcome of repeat revision of anterior cruciate ligament reconstruction in terms of functional result and meniscus and articular cartilage status. Hypothesis Repeat revision of anterior cruciate ligament reconstruction improves knee stability, but with inferior results for functional outcome compared with primary anterior cruciate ligament reconstruction. Meniscal tears and subsequent articular cartilage degeneration are more prevalent with successive revisions due to recurrent laxity. Study Design Case series; Level of evidence, 4. Materials and Methods: Between February 2003 and November 2006, a consecutive series of 10 patients with an average age at 30 years (range, 17-48) were operated on for a repeat revision of anterior cruciate ligament reconstruction (2 revisions after a primary reconstruction) with arthroscopic procedures. A clinical and a radiographic evaluation were performed to assess anterior cruciate ligament reconstruction failures, outcome of revisions, and causes of failures. Meniscal tears and articular cartilage lesions were analyzed. Results The average follow-up of the second revision was 38 months (range, 12-61). At latest follow-up, final International Knee Documentation Committee assessment was excellent or good in 7 cases. Postoperatively, only 2 patients recovered to the same sports activity level they had before their first anterior cruciate ligament reconstruction. Four had a lower level, and 4 discontinued sports activity. The postoperative average side-to-side KT-1000 arthrometer maximum manual difference was 1.3 ± 1.9 mm. Nine patients had meniscal tears and 7 had articular cartilage lesions. Meniscal tears, meniscectomies, and articular cartilage degeneration increased after the second revision ( P = .016, P = .0098, and P = .0197, respectively). Severe articular cartilage degeneration (International Cartilage Repair Society grade III and IV lesions) was found in patients with bad functional outcome (final International Knee Documentation Committee assessment C or D) ( P = .0472). Incidence of articular cartilage degeneration was found to be more prevalent in cases of meniscal tears and partial meniscectomy at the same tibiofemoral compartment ( P = .0157). Index anterior cruciate ligament reconstruction and first revision failures were caused by recurrent trauma (60% and 70%, respectively) or a surgical technical error with tunnel malpositioning (40% and 10%, respectively). Conclusion Outcome of repeat revision of anterior cruciate ligament reconstruction was excellent or good in 70% of the cases, although decreased after the second revision, in relation to the occurrence of meniscal tears and articular cartilage lesions. Meniscal and articular cartilage lesions were more frequent and more severe with recurrent laxity. The cause of failures was mainly recurrent trauma, followed by surgical technical errors.
The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer
Authors: Akkiprik Mustafa , Hu Limei , Sahin Aysegul , Hao Xishan , Zhang Wei 
Published: April 2009

Abstract

Background
Insulin-like growth factor binding protein 5 (IGFBP5) has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly located in the nucleus. We hypothesized that subcellular localization of IGFBP5 affects its functions in host cells.

Methods
To test this hypothesis, we generated wild-type and mutant IGFBP5 expression constructs. The mutation occurs within the nuclear localization sequence (NLS) of the protein and is generated by site-directed mutagenesis using the wild-type IGFBP5 expression construct as a template. Next, we transfected each expression construct into MDA-MB-435 breast cancer cells to establish stable clones overexpressing either wild-type or mutant IGFBP5.

Results
Functional analysis revealed that cells overexpressing wild-type IGFBP5 had significantly lower cell growth rate and motility than the vector-transfected cells, whereas cells overexpressing mutant IGFBP5 demonstrated a significantly higher ability to proliferate and migrate. To illustrate the subcellular localization of the proteins, we generated wild-type and mutant IGFBP5-pDsRed fluorescence fusion constructs. Fluorescence microscopy imaging revealed that mutation of the NLS in IGFBP5 switched the accumulation of IGFBP5 from the nucleus to the cytoplasm of the protein.

Conclusion
Together, these findings imply that the mutant form of IGFBP5 increases proliferation and motility of breast cancer cells and that mutation of the NLS in IGFBP5 results in localization of IGFBP5 in the cytoplasm, suggesting that subcellular localization of IGFBP5 affects its cell growth and migration functions in the breast cancer cells.
Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias
Authors: Perea-Milla Emilio , Olalla Julián , Sánchez-Cantalejo Emilio , Martos Francisco , Matute-Cruz Petra , Carmona-López Guadalupe , Fornieles Yolanda , Cayuela Aurelio , García-Alegría Javier ,   the ANCA Group
Published: April 2009

Abstract

Background
Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias.

Methods
A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and pre-hospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables.

Results
Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93).

Conclusion
Pre-hospital oral antibiotherapy appears to reduce IMD mortality.
A novel HIV-1 restriction factor that is biologically distinct from APOBEC3 cytidine deaminases in a human T cell line CEM.NKR
Authors: Zhou Tao , Han Yanxing , Dang Ying , Wang Xiaojun , Zheng Yong-Hui 
Published: April 2009

AbstractBackgroundIsolation of novel retroviral restriction factors will open new avenues for anti-HIV/AIDS treatment. Although HIV-1 replication is restricted by APOBEC3G/APOBEC3F, TRIM5α, and CD317, none defend HIV-1 infection under natural conditions. Previously, we demonstrated a host factor from the human T cell line CEM.NKR that potently restricted wild-type HIV-1 replication. Interestingly, this restriction resembled the APOBEC3G/APOBEC3F pattern in that viral replication was inhibited from the second round of replication cycle at a post-entry step.ResultsHere, we further characterized this factor and found it distinguishable from the known anti-HIV APOBEC3 proteins. Although CEM.NKR cells expressed both APOBEC3G and APOBEC3F, their levels were at least 10 or 4-fold lower than those in H9 cells, and importantly, Vif effectively neutralized their activity. Among eight subclones isolated from CEM.NKR cells, one was relatively permissive, four were semi-permissive, and three were completely non-permissive for HIV-1 replication. When the levels of APOBEC3 expression were determined, all these clones retained similar low levels of APOBEC3DE, APOBEC3F, APOBEC3G and APOBEC3H expression, and no APOBEC3B expression was detected. Since theviffrom SIVmac can effectively neutralize APOBEC3B and APOBEC3H, recombinant HIV-1 expressing this SIV gene were created. However, these viruses still failed to replicate in CEM.NKR cells. We also confirmed that HIV-1 restriction in CEM.NKR was not due to a loss of calnexin expression.ConclusionTaken together, these results not only demonstrate that all these aforementioned anti-HIV APOBEC3 proteins do not contribute to this HIV-1 restriction, but also shed light on a novel and potent HIV-1 inhibitor in CEM.NKR cells.
Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance
Authors: Juruena Mario F. , Pariante Carmine M. , Papadopoulos Andrew S. , Poon Lucia , Lightman Stafford , Cleare Anthony J. 
Published: March 2009

BackgroundPeople with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function.AimsTo obtain a physiological assessment of hypothalamic–pituitary–adrenal (HPA) axis feedback status in an in-patient sample with depression and to relate this to prospectively determined severe treatment resistance.MethodThe prednisolone suppression test was administered to 45 in-patients with depression assessed as resistant to two or more antidepressants and to 46 controls, prior to intensive multimodal in-patient treatment.ResultsThe patient group had higher cortisol levels than controls, although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ. Nonresponse to in-patient treatment was predicted by a more dysfunctional HPA axis (higher cortisol levels postprednisolone and lower percentage suppression).ConclusionsIn patients with severe depression, HPA axis activity is reset at a higher level, although feedback remains intact. However, prospectively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone.
Continuity of care coordination, health needs and social deprivation
Authors: Heffernan John F. , Husni Mariwan 
Published: March 2009

Aims and MethodContinuity of care is an important aspect of service provision. We retrospectively examined the number of changes over a 2-year period in care coordinator for new patients on enhanced care in a London borough. Deprivation score, length of hospital stay, and health and social needs were examined for association with continuity of care.ResultsTwenty-six patients met the inclusion criteria; ten patients (39%) had a change in care coordinator. Patients having one or more changes in care coordinator were found to live in significantly more deprived council wards (P=0.004), but their needs score (P=0.863) or length of hospital stay (P=0.368) were not significantly different than in those who did not have changes in care coordinator.Clinical ImplicationsSocial deprivation affects relational continuity of care in community teams but the mechanism requires evaluation.
Comparisons of Patient and Physician Expectations for Cancer Survivorship Care
Authors: Cheung Winson Y. , Neville Bridget A. , Cameron Danielle B. , Cook E. Francis , Earle Craig C. 
Published: March 2009

Purpose To compare expectations for cancer survivorship care between patients and their physicians and between primary care providers (PCPs) and oncologists. Methods Survivors and their physicians were surveyed to evaluate for expectations regarding physician participation in primary cancer follow-up, screening for other cancers, general preventive health, and management of comorbidities. Results Of 992 eligible survivors and 607 physicians surveyed, 535 (54%) and 378 (62%) were assessable, respectively. Among physician respondents, 255 (67%) were PCPs and 123 (33%) were oncologists. Comparing patients with their oncologists, expectations were highly discrepant for screening for cancers other than the index one (agreement rate, 29%), with patients anticipating significantly more oncologist involvement. Between patients and their PCPs, expectations were most incongruent for primary cancer follow-up (agreement rate, 35%), with PCPs indicating they should contribute a much greater part to this aspect of care. Expectations between patients and their PCPs were generally more concordant than between patients and their oncologists. PCPs and oncologists showed high discordances in perceptions of their own roles for primary cancer follow-up, cancer screening, and general preventive health (agreement rates of 3%, 44%, and 51%, respectively). In the case of primary cancer follow-up, both PCPs and oncologists indicated they should carry substantial responsibility for this task. Conclusion Patients and physicians have discordant expectations with respect to the roles of PCPs and oncologists in cancer survivorship care. Uncertainties around physician roles and responsibilities can lead to deficiencies in care, supporting the need to make survivorship care planning a standard component in cancer management.
Characterization of ASC-2 as an Antiatherogenic Transcriptional Coactivator of Liver X Receptors in Macrophages
Authors: Kim Geun Hyang , Park Keunhee , Yeom Seon-Yong , Lee Kyung Jin , Kim Gukhan , Ko Jesang , Rhee Dong-Kwon , Kim Young Hoon , Lee Hye Kyung , Kim Hae Won , Oh Goo Taeg , Lee Ki-Up , Lee Jae W. , Kim Seung-Whan 
Published: April 2009

AbstractActivating signal cointegrator-2 (ASC-2) functions as a transcriptional coactivator of many nuclear receptors and also plays important roles in the physiology of the liver and pancreas by interacting with liver X receptors (LXRs), which antagonize the development of atherosclerosis. This study was undertaken to establish the specific function of ASC-2 in macrophages and atherogenesis. Intriguingly, ASC-2 was more highly expressed in macrophages than in the liver and pancreas. To inhibit LXR-specific activity of ASC-2, we used DN2, which contains the C-terminal LXXLL motif of ASC-2 and thereby acts as an LXR-specific, dominant-negative mutant of ASC-2. In DN2-overexpressing transgenic macrophages, cellular cholesterol content was higher and cholesterol efflux lower than in control macrophages. DN2 reduced LXR ligand-dependent increases in the levels of ABCA1, ABCG1, and apolipoprotein E (apoE) transcripts as well as the activity of luciferase reporters driven by the LXR response elements (LXREs) of ABCA1, ABCG1, and apoE genes. These inhibitory effects of DN2 were reversed by overexpression of ASC-2. Chromatin immunoprecipitation analysis demonstrated that ASC-2 was recruited to the LXREs of the ABCA1, ABCG1, and apoE genes in a ligand-dependent manner and that DN2 interfered with the recruitment of ASC-2 to these LXREs. Furthermore, low-density lipoprotein receptor (LDLR)-null mice receiving bone marrow transplantation from DN2-transgenic mice showed accelerated atherogenesis when administered a high-fat diet. Taken together, these results indicate that suppression of the LXR-specific activity of ASC-2 results in both defective cholesterol metabolism in macrophages and accelerated atherogenesis, suggesting that ASC-2 is an antiatherogenic coactivator of LXRs in macrophages.
The effect of leg alignment on the outcome of unicompartmental knee replacement
Authors: Gulati A. , Pandit H. , Jenkins C. , Chau R. , Dodd C. A. F. , Murray D. W. 
Published: March 2009

Varus malalignment after total knee replacement is associated with a poor outcome. Our aim was to determine whether the same was true for medial unicompartmental knee replacement (UKR). The anatomical leg alignment was measured prospectively using a long-arm goniometer in 160 knees with an Oxford UKR. Patients were then grouped according to their mechanical leg alignment as neutral (5° to 10° of valgus), mild varus (0° to 4° of valgus) and marked varus (> 0° of varus). The groups were compared at five years in terms of absolute and change in the Oxford Knee score, American Knee Society score and the incidence of radiolucent lines. Post-operatively, 29 (18%) patients had mild varus and 13 (8%) had marked varus. The mean American Knee Society score worsened significantly (p < 0.001) with increasing varus. This difference disappeared if a three-point deduction for each degree of malalignment was removed. No other score deteriorated with increasing varus, and the frequency of occurrence of radiolucent lines was the same in each group. We therefore conclude that after Oxford UKR, about 25% of patients have varus alignment, but that this does not compromise their clinical or radiological outcome. Following UKR the deductions for malalignment in the American Knee Society score are not justified.