bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human T-Cell Leukemia Virus Type 1 Tax Enhances Serum Response Factor DNA Binding and Alters Site Selection
Authors: Winter Heather Y. , Marriott Susan J. 
Published: March 2007

ABSTRACT

Human T-cell leukemia virus type I (HTLV-1) is the etiological agent of adult T-cell leukemia. The viral transforming protein Tax regulates the transcription of viral and cellular genes by interacting with cellular transcription factors and coactivators. The effects of Tax on cellular gene expression have an important impact on HTLV-1-mediated cellular transformation. Expression of the c-
fos
cellular oncogene is regulated by serum response factor (SRF), and Tax is known to induce c-
fos
gene expression by activating SRF-responsive transcription. SRF activates cellular gene expression by binding to a consensus DNA sequence (CArG box) located within a serum response element (SRE). Since SRF activates transcription of many growth regulatory genes, this pathway is likely to have a significant impact on Tax-mediated transformation. Here we demonstrate that Tax interacts with SRF and enhances the binding of SRF to SREs located in the c-
fos
, Nur77, and viral promoters. Also, we establish that in the presence of Tax, SRF selects more divergent CArG box sequences than in the absence of Tax, revealing a novel mechanism for regulating SRF-responsive gene expression. Finally, increased association of SRF with chromatin and specific promoters was observed in Tax-expressing cells, correlating with increased c-
fos
and Nur77 mRNA levels in Tax-expressing cells. These results suggest that Tax activates SRF-responsive transcription by enhancing its binding affinity to multiple different SRE sequences.
A Combination of Naturally Occurring Mutations in North American West Nile Virus Nonstructural Protein Genes and in the 3′ Untranslated Region Alters Virus Phenotype
Authors: Davis C. Todd , Galbraith Sareen E. , Zhang Shuliu , Whiteman Melissa C. , Li Li , Kinney Richard M. , Barrett Alan D. T. 
Published: March 2007

ABSTRACT

We previously reported mutations in North American West Nile viruses (WNVs) with a small-plaque (
sp
), temperature-sensitive (
ts
), and/or mouse-attenuated (
att
) phenotype. Using an infectious clone, site-directed mutations and 3′ untranslated region (3′UTR) exchanges were introduced into the WNV NY99 genome. Characterization of mutants demonstrated that a combination of mutations involving the NS4B protein (E249G) together with either a mutation in the NS5 protein (A804V) or three mutations in the 3′UTR (A10596G, C10774U, A10799G) produced
sp
,
ts
, and/or
att
variants. These results suggested that the discovery of North American WNV-phenotypic variants is rare because of the apparent requirement of concurrent polygenic mutations.
Conformation-Specific Antibodies Targeting the Trimer-of-Hairpins Motif of the Human T-Cell Leukemia Virus Type 1 Transmembrane Glycoprotein Recognize the Viral Envelope but Fail To Neutralize Viral Entry
Authors: Mirsaliotis Antonis , Nurkiyanova Kulpash , Lamb Daniel , Woof Jenny M. , Brighty David W. 
Published: March 2007

ABSTRACTHuman T-cell leukemia virus type 1 (HTLV-1) entry into cells is dependent upon the viral envelope glycoprotein-catalyzed fusion of the viral and cellular membranes. Following receptor activation of the envelope, the transmembrane glycoprotein (TM) is thought to undergo a series of fusogenic conformational transitions through a rod-like prehairpin intermediate to a compact trimer-of-hairpins structure. Importantly, synthetic peptides that interfere with the conformational changes of TM are potent inhibitors of membrane fusion and HTLV-1 entry, suggesting that TM is a valid target for antiviral therapy. To assess the utility of TM as a vaccine target and to explore further the function of TM in HTLV-1 pathogenesis, we have begun to examine the immunological properties of TM. Here we demonstrate that a recombinant trimer-of-hairpins form of the TM ectodomain is strongly immunogenic. Monoclonal antibodies raised against the TM immunogen specifically bind to trimeric forms of TM, including structures thought to be important for membrane fusion. Importantly, these antibodies recognize the envelope on virally infected cells but, surprisingly, fail to neutralize envelope-mediated membrane fusion or infection by pseudotyped viral particles. Our data imply that, even in the absence of overt membrane fusion, there are multiple forms of TM on virally infected cells and that some of these display fusion-associated structures. Finally, we demonstrate that many of the antibodies possess the ability to recruit complement to TM, suggesting that envelope-derived immunogens capable of eliciting a combination of neutralizing and complement-fixing antibodies would be of value as subunit vaccines for intervention in HTLV infections.
Epstein-Barr Virus Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication in Primary Effusion Lymphomas
Authors: Xu Dongsheng , Coleman Tricia , Zhang Jun , Fagot Ashley , Kotalik Catherine , Zhao Lingjun , Trivedi Pankaj , Jones Clinton , Zhang Luwen 
Published: March 2007

ABSTRACT
The majority of AIDS-associated primary effusion lymphomas (PEL) are latently infected with both Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). PELs harboring two viruses have higher oncogenic potential, suggesting functional interactions between EBV and KSHV. The KSHV replication and transcription activator (K-RTA) is necessary and sufficient for induction of KSHV lytic replication. EBV latent membrane protein 1 (LMP-1) is essential for EBV transformation and establishment of latency in vitro. We show EBV inhibits chemically induced KSHV lytic replication, in part because of a regulatory loop in which K-RTA induces EBV LMP-1 and LMP-1 in turn inhibits K-RTA expression and furthermore the lytic gene expression of KSHV. Suppression of LMP-1 expression in dually infected PEL cells enhances the expression of K-RTA and lytic replication of KSHV upon chemical induction. Because LMP-1 is known to inhibit EBV lytic replication, KSHV-mediated induction of LMP-1 would potentiate EBV latency. Moreover, KSHV infection of EBV latency cells induces LMP-1, and K-RTA is involved in the induction. Both LMP-1 and K-RTA are expressed during primary infection by EBV of KSHV latency cells. Our findings provide evidence that an interaction between EBV and KSHV at molecular levels promotes the maintenance and possibly establishment of viral latency, which may contribute to pathogenesis of PELs.
Is performance on the Wechsler test of adult reading affected by traumatic brain injury?
Authors: Mathias J. L. , Bowden S. C. , Bigler E. D. , Rosenfeld J. V. 
Published: March 2007

Objectives The validity of the National Adult Reading Test (NART) as a predictor of premorbid IQ when used with patients who have sustained a traumatic brain injury (TBI) has been questioned in recent years. This study examined whether performance on the Wechsler Test of Adult Reading (WTAR) is similarly affected by TBI in the first year after an injury.Design and Method The WTAR scores of participants who had sustained a mild TBI (N=82), moderate TBI (N=73), severe TBI (N=61) or an orthopaedic injury (N=95) were compared (cross‐sectional study). A subset of 21 mild TBI, 31 moderate TBI, 26 severe TBI and 21 control group participants were additionally reassessed 6 months later to assess the impact of recovery on WTAR scores (longitudinal study).Results The severe TBI group had significantly lower scores on the WTAR than the mild TBI, moderate TBI and control groups in the cross‐sectional study, despite being matched demographically. The findings from the longitudinal study revealed a significant group difference and a small improvement in performance over time but the interaction between group and time was not significant, suggesting that the improvements in WTAR performance over time were not restricted to more severely injured individuals whose performance was temporarily suppressed.Conclusions These findings suggest that reading performance may be affected by severe TBI and that the WTAR may underestimate premorbid IQ when used in this context, which may cause clinicians to underestimate the cognitive deficits experienced by these patients.
An integrative complexity analysis of cognitive behaviour therapy sessions for borderline personality disorder
Authors: Davidson Kate , Livingstone Steven , McArthur Katherine , Dickson Lindsay , Gumley Andrew 
Published: March 2007

Objectives. Integrative complexity (IC), a measure of cognitive style, was used to analyse discourse in Cognitive Behaviour Therapy (CBT) sessions from patients with borderline personality disorder treated in the BOSCOT trial. It was predicted that patients' level of integrative complexity would be positively associated with the outcome of therapy. That is, an increase in patients' level of integrative complexity would be associated with good outcome. We also predicted that therapists would also show an increase in the level of complexity associated with their patient's increase in integrative complexity and good outcome.Design. Ten patients who received CBT were categorized according to the outcome, good (N=5) and poor (N=5), using an algorithm that incorporated the number of suicide attempts and magnitude of change in severity of depression during therapy.Method. For each patient and their therapist, an early and a late therapy session were transcribed and coded for integrative complexity (IC) (N=20 sessions transcribed). IC scores for patients and therapists were compared across early and late therapy sessions and for good and poor outcomes of therapy.Results. The majority of discourse was at the lower levels of IC. Higher levels of IC at baseline were related to depression and anxiety. Good outcome was not associated with a change in the level of IC between earlier and later CBT sessions. Therapists, however, showed an increase in IC when patient's outcome was poor. In addition, an increase in patient's IC was associated with improvement in social functioning.Conclusions. Therapists may overcompensate for patient's poor outcome by giving more complex explanations to patients. Higher complexity does not necessarily lead to better outcomes.
Laboratory Efficacy of Florfenicol against Streptococcus iniae Infection in Sunshine Bass
Authors: Darwish Ahmed M. 
Published: March 2007

Abstract
An experimental feeding trial was performed to evaluate the efficacy of florfenicol (FFC) in controlling Streptococcus iniae infection in sunshine bass (female white bass Morone chrysops × male striped bass M. saxatilis). Five dosage levels of FFC in medicated feed were administered daily: 0, 5, 10, 15, and 30 mg of active ingredient/kg of fish body weight. Treatment was started within 22–24 h postchallenge by waterborne exposure to virulent S. iniae. The FFC medication was continued for 10 consecutive days, followed by a 25-d posttreatment observation. At the conclusion of the experiment, FFC treatment significantly increased the survival of S. iniae-challenged sunshine bass from 4.2% in the nonmedicated (positive control) group to 69.2% in the 5-mg/kg dosage group, 86.7% in the 10-mg/kg group, and 94.2% in the 15- and 30-mg/kg groups. Survival was significantly higher in the 15- and 30-mg/kg treatment groups than in the 5-mg/kg treatment group; differences among the 10-mg/kg and higher dosage groups were not significant. Survival curve analysis using a log-rank test indicated no significant difference between curves for the 10- and 15-mg/kg groups but a significant difference between curves for the 5- and 10-mg/kg groups. At the end of the experiment, no carriers were detected in any challenged group receiving an FFC-medicated diet, but the bacterium was recovered from the nonmedicated challenged survivors of the infection. The results of the experiment suggest that the optimum therapeutic daily dose of FFC is between 10 and 15 mg/kg body weight for 10 d.
Outcome Measurement Instruments Used to Evaluate Dermatologic Adverse Events in Cancer Trials
Authors: Shaigany Sheila , Mastacouris Nicole , Tannenbaum Rachel , Strunk Andrew , Luan Christopher , Burshtein Joshua , Burshtein Aaron , Carvajal Richard , Garg Amit , Alloo Allireza 
Published: March 2024

ImportanceAssessment of type, severity, and impact of dermatologic adverse events (DAEs) necessitates well-developed and validated clinician-reported outcome measures (ClinROMs) and patient-reported outcome measures (PROMs) that evaluate concepts specific to mucocutaneous toxic effects and that allow appropriate interpretation and comparison of DAEs across trials.ObjectiveTo evaluate heterogeneity and quality of ClinROMs and PROMs used to assess DAEs from systemic cancer therapy.Evidence ReviewTwo systematic reviews were conducted by searching PubMed and Embase databases from inception through March 7, 2023, and April 12, 2023. The first search included randomized clinical trials and observational studies reporting systemic cancer treatment–induced DAEs assessed by a ClinROM or PROM. The second included studies evaluating measurement properties of frequently used ClinROM and PROM instruments. The Consensus-Based Standards for the Selection of Health Measurement Instruments risk of bias tool was used to evaluate methodologic quality of validation assessments.FindingsA total of 395 studies were included. The Common Terminology Criteria for Adverse Events (CTCAE) was utilized in 331 studies meeting inclusion criteria (83.8%). At least 1 skin-related PROM was infrequently utilized in systemic chemotherapy clinical trials (79 studies [20.0%]). Most frequently utilized PROMs were the Dermatology Life Quality Index (DLQI; 34 studies [8.6%]) and Skindex-16 (20 studies [5.1%]). Among studies capturing DAEs, 115 (29.1%) reported a nondescript term (ie, rash) as the only DAE. Eight studies described 44 property assessments of the CTCAE, DLQI, and Skindex. There were no studies evaluating content validity, intrarater reliability, or measurement error for the CTCAE, DLQI, or Skindex. There were no studies evaluating structural validity, internal consistency, and responsiveness of DLQI or Skindex. Interrater reliability and responsiveness were each assessed for 1 DAE-related component of the CTCAE. Construct validity for CTCAE, DLQI, and Skindex was evaluated in 29 (65.9%), 3 (6.8%), and 9 (20.5%) assessments, respectively.Conclusions and RelevanceIn this systematic review, there was a narrow spectrum of ClinROMs and PROMs with limited validity for the measurement of DAEs in the context of systemic chemotherapy interventions in clinical trials. Report of trial DAEs often had low morphologic specificity and meaning. Based on existing gaps in measurement and report of DAEs, a frequent and impactful adverse event to chemotherapy, the framework for evaluating cutaneous toxic effects in oncology trials may need collaborative reevaluation.
Racial Implicit Bias and Communication Among Physicians in a Simulated Environment
Authors: Gonzalez Cristina M. , Ark Tavinder K. , Fisher Marla R. , Marantz Paul R. , Burgess Diana J. , Milan Felise , Samuel Malika T. , Lypson Monica L. , Rodriguez Carlos J. , Kalet Adina L. 
Published: March 2024

ImportanceRacial implicit bias can contribute to health disparities through its negative influence on physician communication with Black patients. Interventions for physicians to address racial implicit bias in their clinical encounters are limited by a lack of high-fidelity (realistic) simulations to provide opportunities for skill development and practice.ObjectiveTo describe the development and initial evaluation of a high-fidelity simulation of conditions under which physicians might be influenced by implicit racial bias.Design, Setting, and ParticipantsThis cross-sectional study, performed on an online platform from March 1 to September 30, 2022, recruited a convenience sample of physician volunteers to pilot an educational simulation.ExposuresIn the simulation exercise, physicians saw a 52-year-old male standardized patient (SP) (presenting as Black or White) seeking urgent care for epigastric pain, nausea, and vomiting. The case included cognitive stressors common to clinical environments, including clinical ambiguity, stress, time constraints, and interruptions. Physicians explained their diagnosis and treatment plan to the SP, wrote an assessment and management plan, completed surveys, and took the Race Implicit Association Test (IAT) and Race Medical Cooperativeness IAT. The SPs, blinded to the purpose of the study, assessed each physician’s communication using skills checklists and global rating scales.Main Outcomes and MeasuresAssociation between physicians’ IAT scores and SP race with SP ratings of communication skills.ResultsIn 60 physicians (23 [38.3%] Asian, 4 [6.7%] Black, 23 [38.3%] White, and 10 [16.7%] other, including Latina/o/x, Middle Eastern, and multiracial; 31 [51.7%] female, 27 [45.0%] male, and 2 [3.3%] other), the interaction of physicians’ Race IAT score and SP race was significant for overall communication (mean [SD] β = −1.29 [0.41]), all subdomains of communication (mean [SD] β = −1.17 [0.52] to −1.43 [0.59]), and overall global ratings (mean [SD] β = −1.09 [0.39]). Black SPs rated physicians lower on communication skills for a given pro-White Race IAT score than White SPs; White SP ratings increased as physicians’ pro-White bias increased.Conclusions and RelevanceIn this cross-sectional study, a high-fidelity simulation calibrated with cognitive stressors common to clinical environments elicited the expected influence of racial implicit bias on physicians’ communication skills. The outlined process and preliminary results can inform the development and evaluation of interventions that seek to address racial implicit bias in clinical encounters and improve physician communication with Black patients.
Baseline Antipsychotic Dose and Transition to Psychosis in Individuals at Clinical High Risk
Authors: Raballo Andrea , Poletti Michele , Preti Antonio 
Published: March 2024

ImportanceEmerging meta-analytical evidence indicates that baseline exposure to antipsychotics is associated with an increased risk of transitioning to psychosis in individuals at clinical high-risk for psychosis (CHR-P) and that such effect is not a result of pretest risk enrichment. However, to maximize its translational utility for prognostic stratification in clinical practice, testing for the potential presence of a dose-response association is crucial.ObjectiveTo test whether the negative prognostic effect of baseline antipsychotic exposure in individuals at CHR-P follows a dose-effect pattern, as indicated by mean chlorpromazine equivalent doses (CPZ-ED).Data SourcesMEDLINE and Cochrane Library, performed up to August 31, 2023, searching for English-language studies on individuals at CHR-P reporting data on exposure to antipsychotics at baseline and detailed information on dosage by transition status.Study SelectionStudies that provided information on antipsychotic exposure at baseline and included detailed dosage data categorized by transition status.Data Extraction and SynthesisEligible studies were identified following PRISMA guidelines and evaluated independently by 2 reviewers with the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses.Main Outcomes and MeasuresThe primary outcome was transition to psychosis in individuals at CHR-P who were receiving antipsychotic treatment at baseline, measured by baseline mean CPZ-ED in individuals at CHR-P who transitioned to psychosis compared to those who did not.ResultsEight studies were included in the systematic review and meta-analysis. Among 290 individuals at CHR-P (mean [SD] age, 19.4 [2.6] years) who were exposed to antipsychotics at baseline and remained in contact up to the completion of the study, 66 converted to psychosis and 224 did not. The mean CPZ-ED ranged 60 to 395 mg/d in those who converted and 13 to 224 mg/d in those who did not. Those who converted to psychosis had higher CPZ-ED than those who did not in both the common-effects model (Hedges g, 0.41; 95% CI, 0.12-0.70; z, 2.78; P = .005) and in the random-effects model (Hedges g, 0.41; 95% CI, 0.15-0.67; z, 3.69; P = .008; τ2, 0.0). There was no relevant heterogeneity (Cochran Q, 3.99; df, 7; P = .78; I2, 0.0%; 95% CI, 0.0-68.0). The radial plot indicated a good fit of the model.Conclusions and RelevanceIn individuals at CHR-P who were exposed to antipsychotics at baseline, those receiving higher antipsychotic doses demonstrated an increased likelihood of transitioning to psychosis. This meta-analytic evidence of putative dose-effect association confirms that baseline antipsychotic exposure and the corresponding dosage carry salient prognostic information that could improve current CHR-P criteria-based risk stratification at inception.
Discovery of Stable Surfaces with Extreme Work Functions by High‐Throughput Density Functional Theory and Machine Learning
Authors: Schindler Peter , Antoniuk Evan R. , Cheon Gowoon , Zhu Yanbing , Reed Evan J. 
Published: March 2024

AbstractThe work function is the key surface property that determines the energy required to extract an electron from the surface of a material. This property is crucial for thermionic energy conversion, band alignment in heterostructures, and electron emission devices. This work presents a high‐throughput workflow using density functional theory (DFT) to calculate the work function and cleavage energy of 33,631 slabs (58,332 work functions) that are created from 3,716 bulk materials. The number of calculated surface properties surpasses the previously largest database by a factor of ≈27. Several surfaces with an ultra‐low (<2 eV) and ultra‐high (>7 eV) work function are identified. Specifically, the (100)‐Ba‐O surface of BaMoO3and the (001)‐F surface of Ag2F have record‐low (1.25 eV) and record‐high (9.06 eV) steady‐state work functions. Based on this database a physics‐based approach to featurize surfaces is utilized to predict the work function. The random forest model achieves a test mean absolute error (MAE) of 0.09 eV, comparable to the accuracy of DFT. This surrogate model enables rapid predictions of the work function (≈ 105faster than DFT) across a vast chemical space and facilitates the discovery of material surfaces with extreme work functions for energy conversion and electronic device applications.
High‐Areal‐Capacity and Long‐Cycle‐Life All‐Solid‐State Lithium‐Metal Battery by Mixed‐Conduction Interface Layer
Authors: Yang Ming , Wu Yujing , Yang Kaiqi , Wang Zhixuan , Ma Tenghuan , Wu Dengxu , Xu Fuqiang , Yang Li , Lu Pushun , Peng Jian , Gao Qifa , Zhu Xiang , Jiang Zhiwen , Chen Liquan , Li Hong , Wu Fan 
Published: March 2024

AbstractThe rapid growth of lithium dendrites has seriously hindered the development and practical application of high‐energy‐density all‐solid‐state lithium metal batteries (ASSLMBs). Herein, a soft carbon (SC)‐nano Li6.4La3Zr1.4Ta0.6O12 (LLZTO) (with high ionic conductivity and diffusion coefficient) mixed ionic and electronic conducting interface layer is designed to promote the rapid migration of Li+ at the interfacial layer, induce the uniform deposition of lithium metal on nanoscale (nano) LLZTO ion‐conducting network inside the interface layer, effectively suppress the growth of lithium dendrites, and significantly improve the electrochemical performance of ASSLMBs. LiZrO2@LiCoO2(LZO@LCO)/Li6PS5Cl(LPSCl)‐nano LLZTO/Li ASSLMB achieves high current density (12.5 mA cm−2), ultra‐high areal capacity (15 mAh cm−2, corresponding to LZO@LCO mass loadings of 111.11 mg cm−2), and ultra‐long cycle life (20 000 cycles). Therefore, the introduction of SC‐nano LLZTO mixed conducting interface layer can greatly improve the interfacial stability between solid‐state electrolyte (SSE) and lithium metal anode to enable dendrite‐free ASSLMBs.