bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated suicide attempts among suicidal cases: Outcome of one‐year follow‐up
Authors: Lee Yu , Lin Pao‐Yen , Yeh Wei‐Chiang , Chiu Nien‐Mu , Hung Chi‐Fa , Huang Tsan‐Yu , Hsu Su‐Ting , Lee Chun‐Yi , Chen Chien‐Chih , Lin Huang‐Chi , Chong Mian‐Yoon 
Published: April 2012

AbstractIntroductionTo assess the mortality rates and risk factors involved in repeated suicide attempts.MethodsPatients with a record of suicidal attempts were recruited from the emergency department of a medical center in Taiwan from August 2004 to July 2006. Their conditions were prospectively monitored for 12 months. The suicidal intention of the patients was ascertained using structured interview questions while their psychiatric diagnosis and depressive symptoms were assessed through the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression.ResultsA total of 46 males and 99 females were recruited and 70% (n = 102) of them were successfully monitored for one year. Among them, 38.2% had repeated suicide attempt(s) and 3.4% died as a result of suicide. Severe depression, aggression and positive suicide ideation were significantly associated with the repeated suicide attempts. Pessimistic repeaters had more previous suicide attempt(s) than the others.Conclusion A higher rate of repeated suicide attempts and mortality rates were found among suicide attempters from the one‐year outcome. Repeated suicide attempts increased the risk of mortality while persevering suicide thoughts and previous suicide attempts were risks for repeated suicidal behavior.
Polymorphism of the serotonin transporter gene (5‐HTTLPR) in major depressive disorder patients in Malaysia
Authors: Mohamed Saini Suriati , Muhamad Radzi Azizah , Abdul Rahman Abdul Hamid 
Published: April 2012

AbstractIntroductionThe serotonin transporter promoter (5‐HTTLPR) is a potential susceptibility locus in the pathogenesis of major depressive disorder. However, data from Malaysia is lacking. The present study aimed to determine the association between the homozygous short variant of the serotonin transporter promoter gene (5‐HTTLPR) with major depressive disorder.MethodsThis is a candidate gene case‐control association study. The sample consists of 55 major depressive disorder probands and 66 controls. They were Malaysian descents and were unrelated. The Axis I diagnosis was determined using Mini International Neuropsychiatric Interview (M.I.N.I.). The control group comprised healthy volunteers without personal psychiatric history and family history of mood disorders. Participants' blood was sent to the Institute Medical Research for genotyping.ResultsThe present study failed to detect an association between 5‐HTTLPR ss genotype with major depressive disorder (χ2 = 3.67, d.f. = 1, P = 0.055, odds ratio 0.25, 95% confidence interval = 0.07‐1.94). Sub‐analysis revealed that the frequency of l allele in healthy controls was higher (78.0%) than that of Caucasian and East Asian population. However, in view of the small sample size this study may be prone to type II error (and type I error).DiscussionThis preliminary study suggests that the homozygous short variant of the 5‐HTTLPR did not appear to be a risk factor for increasing susceptibility to major depressive disorder.
Interrogative suggestibility: Was it just compliance or a genuine false memory?
Authors: Mastroberardino Serena , Marucci Francesco S. 
Published: April 2012

Purpose.Interrogative suggestibility, as measured by the Gudjonsson Suggestibility Scales (GSS), is an independent form of suggestibility arising in the forensic/legal context. So far, an unresolved issue that may have different implications when measuring suggestibility is to what extent the scales measure internalization of suggested materials or just compliance with the interrogator.Methods. Internalization of suggested materials and compliance were here measured using a source identification task. In Experiment 1, participants were administered the GSS2 and immediately afterwards asked to perform the source identification task on the items presented in the scale. In Experiment 2, half of the participants were administered the source identification task immediately and half after a 24‐hr delay.Results. In both experiments a higher proportion of compliant responses were found. Participants internalized more suggested information after questioning (Yield 1) and made more compliant responses after negative feedback (Shift). In Experiment 2, participants in the delayed condition internalized less material than those in the immediate condition.Conclusions: Different processes appear to underlie Yield 1 and Shift scores in the GSS2. The former may include both internalization of suggested materials and compliance, while the second appears to be mostly due to compliance with the interrogator. When administering the GSS2 in a forensic/legal context as vulnerability predictor for making false confessions, or proneness to develop false memories through the internalization of suggested material, including a source identification task may provide additional information on the type of coping style and memory characteristics of the examinee.
Evaluation of the geometric accuracy of surrogate‐based gated VMAT using intrafraction kilovoltage x‐ray images
Authors: Li Ruijiang , Mok Edward , Han Bin , Koong Albert , Xing Lei 
Published: April 2012

Purpose:To evaluate the geometric accuracy of beam targeting in external surrogate‐based gated volumetric modulated arc therapy (VMAT) using kilovoltage (kV) x‐ray images acquired during dose delivery.Methods:Gated VMAT treatments were delivered using a Varian TrueBeam STx Linac for both physical phantoms and patients. Multiple gold fiducial markers were implanted near the target. The reference position was created for each implanted marker, representing its correct position at the gating threshold. The gating signal was generated from the RPM system. During the treatment, kV images were acquired immediately before MV beam‐on at every breathing cycle, using the on‐board imaging system. All implanted markers were detected and their 3D positions were estimated using in‐house developed software. The positioning error of a marker is defined as the distance of the marker from its reference position for each frame of the images. The overall error of the system is defined as the average over all markers. For the phantom study, both sinusoidal motion (1D and 3D) and real human respiratory motion was simulated for the target and surrogate. In the baseline case, the two motions were synchronized for the first treatment fraction. To assess the effects of surrogate–target correlation on the geometric accuracy, a phase shift of 5% and 10% between the two motions was introduced. For the patient study, intrafraction kV images of five stereotactic body radiotherapy (SBRT) patients were acquired for one or two fractions.Results:For the phantom study, a high geometric accuracy was achieved in the baseline case (average error: 0.8 mm in the superior–inferior or SI direction). However, the treatment delivery is prone to geometric errors if changes in the target–surrogate relation occur during the treatment: the average error was increased to 2.3 and 4.7 mm for the phase shift of 5% and 10%, respectively. Results obtained with real human respiratory curves show a similar trend. For a target with 3D motion, the technique is able to detect geometric errors in the left–right (LR) and anterior–posterior (AP) directions. For the patient study, the average intrafraction positioning errors are 0.8, 0.9, and 1.4 mm and 95th percentile errors are 1.7, 2.1, and 2.7 mm in the LR, AP, and SI directions, respectively.Conclusions:The correlation between external surrogate and internal target motion is crucial to ensure the geometric accuracy of surrogate‐based gating. Real‐time guidance based on kV x‐ray images overcomes the potential issues in surrogate‐based gating and can achieve accurate beam targeting in gated VMAT.
Development of a Fourfold Multiplexed Opsonophagocytosis Assay for Pneumococcal Antibodies against Additional Serotypes and Discovery of Serological Subtypes in Streptococcus pneumoniae Serotype 20
Authors: Burton Robert L. , Nahm Moon H. 
Published: April 2012

ABSTRACT

Opsonophagocytic killing assays (OPAs) are important
in vitro
surrogate markers of protection in vaccine studies of
Streptococcus pneumoniae
. We have previously reported the development of a 4-fold multiplexed OPA (MOPA) for the 13 serotypes in Prevnar 13. Because new conjugate vaccines with increased valence are being developed, we developed 4-fold MOPAs for an additional 13 serotypes: serotypes 6C and 6D, plus the 11 serotypes contained in Pneumovax but not in Prevnar 13. A high level of nonspecific killing (NSK) was observed for three serotypes (10A, 15B, and 33F) in multiple batches of baby rabbit complement. The NSK could be reduced by preadsorbing the complement with encapsulated, as well as unencapsulated, pneumococcal strains. The MOPA results compared well with the results of single-serotype OPA for all serotypes except for serotype 3. For serotype 3, the results obtained from the MOPA format were ∼40% higher than those of the single-serotype format. Interassay precision of MOPA was determined with 5 serum samples, and the coefficient of variation was generally <30% for all serotypes. MOPA was also specific for all serotypes except for serotype 20; i.e., free homologous polysaccharide (PS), but not unrelated PS, could completely and efficiently inhibit opsonization. However, serotype 20 PS from ATCC could efficiently inhibit opsonization of one serotype 20 target strain but not three other type 20 target strains even at a high (>80 mg/liter) PS concentration. This suggests the presence of serologic heterogeneity among serotype 20 strains.
Mutations in the GM1 Binding Site of Simian Virus 40 VP1 Alter Receptor Usage and Cell Tropism
Authors: Magaldi Thomas G. , Buch Michael H. C. , Murata Haruhiko , Erickson Kimberly D. , Neu Ursula , Garcea Robert L. , Peden Keith , Stehle Thilo , DiMaio Daniel 
Published: April 2012

ABSTRACT
Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM1 more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution.
Elite Controllers with Low to Absent Effector CD8
+
T Cell Responses Maintain Highly Functional, Broadly Directed Central Memory Responses
Authors: Ndhlovu Zaza M. , Proudfoot Jacqueline , Cesa Kevin , Alvino Donna Marie , McMullen Ashley , Vine Seanna , Stampouloglou Eleni , Piechocka-Trocha Alicja , Walker Bruce D. , Pereyra Florencia 
Published: April 2012

ABSTRACT

Analyses of the breadth and specificity of virus-specific CD8
+
T cell responses associated with control of HIV have largely relied on measurement of cytokine secretion by effector T cells. These have resulted in the identification of HIV elite controllers with low or absent responses in which non-T-cell mechanisms of control have been suggested. However, successful control of HIV infection may be associated with central memory T cells, which have not been consistently examined in these individuals. Gag-specific T cells were characterized using a peptide-based cultured enzyme-linked immunosorbent spot assay (ELISpot). Peripheral blood mononuclear cells from HIV elite controllers (
n
= 10), progressors (
n
= 12), and antiretroviral-treated individuals (
n
= 9) were cultured with overlapping peptides for 12 days. Specificity was assessed by tetramer staining, functional features of expanded cells were assessed by cytokine secretion, and virus inhibition and phenotypic characteristics were assessed by cell sorting and coculture assays. After peptide stimulation, elite controllers showed a greater number of previously undetectable (new) responses compared to progressors (
P
= 0.0008). These responses were highly polyfunctional, with 64.5% of responses having 3 to 5 functions. Expandable epitope-specific CD8
+
T cells from elite controllers had strong virus inhibitory capacity and predominantly displayed a central memory phenotype. These data indicate that elite controllers with minimal T cell responses harbor a highly functional, broadly directed central memory T cell population that is capable of suppressing HIV
in vitro
. Comprehensive examination of this cell population could provide insight into the immune responses associated with successful containment of viremia.
Evasion of the Innate Immune Response: the Old World Alphavirus nsP2 Protein Induces Rapid Degradation of Rpb1, a Catalytic Subunit of RNA Polymerase II
Authors: Akhrymuk Ivan , Kulemzin Sergey V. , Frolova Elena I. 
Published: April 2012

ABSTRACT

The Old World alphaviruses are emerging human pathogens with an ability to cause widespread epidemics. The latest epidemic of Chikungunya virus, from 2005 to 2007, affected over 40 countries in Africa, Asia, and Europe. The Old World alphaviruses are highly cytopathic and known to evade the cellular antiviral response by inducing global inhibition of transcription in vertebrate cells. This function was shown to be mediated by their nonstructural nsP2 protein; however, the detailed mechanism of this phenomenon has remained unknown. Here, we report that nsP2 proteins of Sindbis, Semliki Forest, and Chikungunya viruses inhibit cellular transcription by inducing rapid degradation of Rpb1, a catalytic subunit of the RNAPII complex. This degradation of Rpb1 is independent of the nsP2-associated protease activity, but, instead, it proceeds through nsP2-mediated Rpb1 ubiquitination. This function of nsP2 depends on the integrity of the helicase and
S
-adenosylmethionine (SAM)-dependent methyltransferase-like domains, and point mutations in either of these domains abolish Rpb1 degradation. We go on to show that complete degradation of Rpb1 in alphavirus-infected cells occurs within 6 h postinfection, before other previously described virus-induced changes in cell physiology, such as apoptosis, autophagy, and inhibition of STAT1 phosphorylation, are detected. Since Rpb1 is a subunit that catalyzes the polymerase reaction during RNA transcription, degradation of Rpb1 plays an indispensable role in blocking the activation of cellular genes and downregulating cellular antiviral response. This indicates that the nsP2-induced degradation of Rpb1 is a critical mechanism utilized by the Old World alphaviruses to subvert the cellular antiviral response.
Glycoprotein B of Herpes Simplex Virus 2 Has More than One Intracellular Conformation and Is Altered by Low pH
Authors: Muggeridge Martin I. 
Published: April 2012

ABSTRACT
The crystal structure of herpes simplex virus (HSV) gB identifies it as a class III fusion protein, and comparison with other such proteins suggests this is the postfusion rather than prefusion conformation, although this is not proven. Other class III proteins undergo a pH-dependent switch between pre- and postfusion conformations, and a low pH requirement for HSV entry into some cell types suggests that this may also be true for gB. Both gB and gH undergo structural changes at low pH, but there is debate about the extent and significance of the changes in gB, possibly due to the use of different soluble forms of the protein and different assays for antigenic changes. In this study, a complementary approach was taken, examining the conformations of full-length intracellular gB by quantitative confocal microscopy with a panel of 26 antibodies. Three conformations were distinguished, and low pH was found to be a major influence. Comparison with previous studies indicates that the intracellular conformation in low-pH environments may be the same as that of the soluble form known as s-gB at low pH. Interestingly, the antibodies whose binding was most affected by low pH both have neutralizing activity and consequently must block either the function of a neutral pH conformation or its switch from an inactive form to an activated form. If one of the intracellular conformations is the fusion-active form, another factor required for fusion is presumably absent from wherever that conformation is present in infected cells so that inappropriate fusion is avoided.
Feline Tetherin Is Characterized by a Short N-Terminal Region and Is Counteracted by the Feline Immunodeficiency Virus Envelope Glycoprotein
Authors: Celestino Michele , Calistri Arianna , Del Vecchio Claudia , Salata Cristiano , Chiuppesi Flavia , Pistello Mauro , Borsetti Alessandra , Palù Giorgio , Parolin Cristina 
Published: April 2012

ABSTRACT

Tetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2
504
and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2
504
is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2
504
failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2
504
was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2
504
also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.
Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial
Authors: Garg Amit X , Devereaux P J , Yusuf Salim , Cuerden Meaghan S , Parikh Chirag R , Coca Steven G , Walsh Michael , Cook Richard J , Whitlock Richard P , Noiseux Nicolas , Novick Richard J , Ou Yongning , Lamy Andre 
Published: April 2012

IntroductionCORONARY is a large international randomised controlled trial comparing coronary artery bypass graft (CABG) surgery done with and without a bypass pump. Compared with on-pump, off-pump surgery may prevent acute kidney injury (AKI) in the short term and may better preserve kidney function 1 year following surgery. Secondary analyses may also clarify whether effects are similar in patients with and without pre-operative chronic kidney disease and whether AKI avoidance mediates preserved 1-year kidney function.Methods and analysisWith respect to the study schedule, the last of 4752 patients from 79 sites in 19 countries were randomised in November 2011 to cardiac surgery performed with an on-pump or off-pump procedure. The authors will use regression models to compare the groups in the outcome of peri-operative AKI (per cent change in serum creatinine, ≥50% increase in serum creatinine) and 1-year kidney function (per cent change in estimated glomerular filtration rate (eGFR), ≥20% eGFR loss 1 year after surgery). The authors will use interaction terms in regression models to determine if there is a differential impact of the intervention in those with and without pre-existing chronic kidney disease. The authors will use regression-based tests to determine the proportion of the total effect of surgery type (off-pump vs on-pump CABG) on 1-year eGFR that is mediated by peri-operative AKI.Ethics and disseminationIn the year 2009, the authors were competitively awarded a grant from the Canadian Institutes of Health Research to answer these kidney questions in CORONARY. Ethics approval was obtained for additional renal data collection in centres that agreed to study participation (>90% of participating centres). This collection began for patients enrolled after 1 January 2010. Remaining 1-year renal outcome data will be collected throughout 2012. Results will be reported in 2013.Clinical trial registration numberNCT 00463294.
Pten Regulates Aurora-A and Cooperates with Fbxw7 in Modulating Radiation-Induced Tumor Development
Authors: Kwon Yong-Won , Kim Il-Jin , Wu Di , Lu Jing , Stock William A. , Liu Yueyong , Huang Yurong , Kang Hio Chung , DelRosario Reyno , Jen Kuang-Yu , Perez-Losada Jesus , Wei Guangwei , Balmain Allan , Mao Jian-Hua 
Published: April 2012

Abstract
The Aurora-A kinase gene is frequently amplified and/or overexpressed in a variety of human cancers, leading to major efforts to develop therapeutic agents targeting this pathway. Here, we show that Aurora-A is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7 in a process that is regulated by GSK3β. Using a series of truncated Aurora-A proteins and site-directed mutagenesis, we identified distinct FBXW7 and GSK3β-binding sites in Aurora-A. Mutation of critical residues in either site substantially disrupts degradation of Aurora-A. Furthermore, we show that loss of Pten results in the stabilization of Aurora-A by attenuating FBXW7-dependent degradation of Aurora-A through the AKT/GSK3β pathway. Moreover, radiation-induced tumor latency is significantly shortened in Fbxw7+/−Pten+/− mice as compared with either Fbxw7+/− or Pten+/− mice, indicating that Fbxw7 and Pten appear to cooperate in suppressing tumorigenesis. Our results establish a novel posttranslational regulatory network in which the Pten and Fbxw7 pathways appear to converge on the regulation of Aurora-A level. Mol Cancer Res; 10(6); 834–44. ©2012 AACR.