bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmid Vectors Encoding Cholera Toxin or the Heat-Labile Enterotoxin fromEscherichia coliAre Strong Adjuvants for DNA Vaccines
Authors: Arrington Joshua , Braun Ralph P. , Dong Lichun , Fuller Deborah H. , Macklin Michael D. , Umlauf Scott W. , Wagner Sarah J. , Wu Mary S. , Payne Lendon G. , Haynes Joel R. 
Published: July 2002

ABSTRACTTwo plasmid vectors encoding the A and B subunits of cholera toxin (CT) and two additional vectors encoding the A and B subunits of theEscherichia coliheat-labile enterotoxin (LT) were evaluated for their ability to serve as genetic adjuvants for particle-mediated DNA vaccines administered to the epidermis of laboratory animals. Both the CT and the LT vectors strongly augmented Th1 cytokine responses (gamma interferon [IFN-γ]) to multiple viral antigens when codelivered with DNA vaccines. In addition, Th2 cytokine responses (interleukin 4 [IL-4]) were also augmented by both sets of vectors, with the effects of the LT vectors on IL-4 responses being more antigen dependent. The activities of both sets of vectors on antibody responses were antigen dependent and ranged from no effect to sharp reductions in the immunoglobulin G1 (IgG1)-to-IgG2a ratios. Overall, the LT vectors exhibited stronger adjuvant effects in terms of T-cell responses than did the CT vectors, and this was correlated with the induction of greater levels of cyclic AMP by the LT vectors following vector transfection into cultured cells. The adjuvant effects observed in vivo were due to the biological effects of the encoded proteins and not due to CpG motifs in the bacterial genes. Interestingly, the individual LT A and B subunit vectors exhibited partial adjuvant activity that was strongly influenced by the presence or absence of signal peptide coding sequences directing the encoded subunit to either intracellular or extracellular locations. Particle-mediated delivery of either the CT or LT adjuvant vectors in rodents and domestic pigs was well tolerated, suggesting that bacterial toxin-based genetic adjuvants may be a safe and effective strategy to enhance the potency of both prophylactic and therapeutic DNA vaccines for the induction of strong cellular immunity.
Further study of the cation ordering in phengite 3T by neutron powder diffraction
Authors: Pavese A. , Ferraris G. , Pischedda V. , Radaelli P. 
Published: July 2002

AbstractPhengite 3T (Dora-Maira massif, Italian western Alps), with chemical composition K0.96Na0.01Al1.44Mg0.56(Si3.59 Al0.41)O10(OH)2 has been investigated using powder neutron diffraction, at the ILL (Institut Laue-Langevin) Facility, on the D2B diffractometer. Data sets were collected at 293 and 873 K, and the present results are compared with those obtained previously using the time-of-flight (TOF) technique, on the same compound. In the octahedral sheet, Al tends to order into the M2 site, in accordance with the measurements mentioned above, whereas the Al/Si tetrahedral ordering we observe (i.e. Si fully into T1 site) is at variance with that determined previously. These discrepancies are ascribed to the presence of talc impurities in the sample used previously (∼6 wt.%), which affected the results obtained.
SHP2 and cbl participate in α-chemokine receptor CXCR4–mediated signaling pathways
Authors: Chernock Rebecca D. , Cherla Rama P. , Ganju Ramesh K. 
Published: July 2002

AbstractStromal cell–derived factor (SDF)-1α and its receptor, CXCR4, play an important role in cell migration, embryonic development, and human immunodeficiency virus infection. However, the cellular signaling pathways that mediate these processes are not fully elucidated. We and others have shown that the binding of SDF-1α to CXCR4 activates phosphatidylinositol-3 kinase (PI-3 kinase), p44/42 mitogen-associated protein kinase, and the transcription factor nuclear factor–κB, and it also enhances the tyrosine phosphorylation and association of proteins involved in the formation of focal adhesions. In this study, we examined the role of phosphatases in CXCR4-mediated signaling pathways. We observed significant inhibition of SDF-1α–induced migration by phosphatase inhibitors in CXCR4-transfected pre-B lymphoma L1.2 cells, Jurkat T cells, and peripheral blood lymphocytes. Further studies revealed that SDF-1α stimulation induced robust tyrosine phosphorylation in the SH2-containing phosphatase SHP2. SHP2 associated with the CXCR4 receptor and the signaling molecules SHIP, cbl, and fyn. Overexpression of wild-type SHP2 increased SDF-1α–induced chemotaxis. Enhanced activation of fyn and lyn kinases and the tyrosine phosphorylation of cbl were also observed. In addition, SDF-1α stimulation enhanced the association of cbl with PI-3 kinase, Crk-L, and 14-3-3β proteins. Our results suggest that CXCR4-mediated signaling is regulated by SHP2 and cbl, which collectively participate in the formation of a multimeric signaling complex.
HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients
Authors: Hosmalin Anne , Samri Assia , Dumaurier Marie-Jeanne , Dudoit Yasmine , Oksenhendler Eric , Karmochkine Marina , Autran Brigitte , Wain-Hobson Simon , Cheynier Rémi 
Published: July 2002

AbstractHuman immunodeficiency virus (HIV) infection is characterized by the massive infiltration of secondary lymphoid organs with activated CD8+ T lymphocytes. While converging data indicated that these cells were HIV-specific cytotoxic T lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was lacking. Here, the presence of HIV-specific effector CTLs was demonstrated directly ex vivo in 15 of 24 microdissected splenic white pulps from an untreated patient and in 1 of 24 tonsil germinal centers from a second patient with incomplete viral suppression following bitherapy. These patients had plasma HIV RNA loads of 5900 and 820 copies per milliliter. The frequencies of HIV-1 DNA+ cells in their lymphoid organs were more than 1 in 50 and 1 in 175, respectively. Spliced viral messenger RNA (a marker for ongoing viral replication) was present in most immunocompetent structures tested. Conversely, CTL activity was not found in spleens from 2 patients under highly active antiretroviral therapy, with undetectable plasma viral load. These patients had much lower spleen DNA+ cell frequencies (1 in 2700 and 1 in 3800) and no white pulps containing spliced RNA. CTL effector activity as well as spliced viral messenger RNA were both concentrated in the white pulps and germinal centers. This colocalization indicates that viral replication in immunocompetent structures of secondary lymphoid organs triggers anti-HIV effector CTLs to these particular locations, providing clues to target therapeutic intervention.
Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada
Authors: Sun Li , Wei Xia , Fierheller Caitlin T. , Dawson Lesa , Oxley Samuel , Kalra Ashwin , Sia Jacqueline , Feldman Fabio , Peacock Stuart , Schrader Kasmintan A. , Legood Rosa , Kwon Janice S. , Manchanda Ranjit 
Published: September 2024

ImportancePopulation-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice.ObjectiveTo estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada.Design, Setting, and ParticipantsFor this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024.Main Outcomes and MeasuresOutcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty.ResultsIn the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population.Conclusions and RelevanceIn this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.
Amygdala Reactivity, Antidepressant Discontinuation, and Relapse
Authors: Erdmann Tore , Berwian Isabel M. , Stephan Klaas Enno , Seifritz Erich , Walter Henrik , Huys Quentin J. M. 
Published: September 2024

ImportanceAntidepressant discontinuation substantially increases the risk of a depression relapse, but the neurobiological mechanisms through which this happens are not known. Amygdala reactivity to negative information is a marker of negative affective processes in depression that is reduced by antidepressant medication, but it is unknown whether amygdala reactivity is sensitive to antidepressant discontinuation or whether any change is related to the risk of relapse after antidepressant discontinuation.ObjectiveTo investigate whether amygdala reactivity to negative facial emotions changes with antidepressant discontinuation and is associated with subsequent relapse.Design, Setting, and ParticipantsThe Antidepressiva Absetzstudie (AIDA) study was a longitudinal, observational study in which adult patients with remitted major depressive disorder (MDD) and currently taking antidepressants underwent 2 task-based functional magnetic resonance imaging (fMRI) measurements of amygdala reactivity. Patients were randomized to discontinuing antidepressants either before or after the second fMRI measurement. Relapse was monitored over a 6-month follow-up period. Study recruitment took place from June 2015 to January 2018. Data were collected between July 1, 2015, and January 31, 2019, and statistical analyses were conducted between June 2021 and December 2023. The study took place in a university setting in Zurich, Switzerland, and Berlin, Germany. Of 123 recruited patients, 83 were included in analyses. Of 66 recruited healthy control individuals matched for age, sex, and education, 53 were included in analyses.ExposureDiscontinuation of antidepressant medication.OutcomesTask-based fMRI measurement of amygdala reactivity and MDD relapse within 6 months after discontinuation.ResultsAmong patients with MDD, the mean (SD) age was 35.42 (11.41) years, and 62 (75%) were women. Among control individuals, the mean (SD) age was 33.57 (10.70) years, and 37 (70%) were women. Amygdala reactivity of patients with remitted MDD and taking medication did not initially differ from that of control individuals (t125.136 = 0.33; P = .74). An increase in amygdala reactivity after antidepressant discontinuation was associated with depression relapse (3-way interaction between group [12W (waited) vs 1W2 (discontinued)], time point [MA1 (first scan) vs MA2 (second scan)], and relapse: β, 18.9; 95% CI, 0.8-37.1; P = .04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; P = .01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; P = .02).Conclusions and RelevanceAn increase in amygdala reactivity was associated with risk of relapse after antidepressant discontinuation and may represent a functional neuroimaging marker that could inform clinical decisions around antidepressant discontinuation.
Characterization of kilovoltage x‐ray image guidance system with a novel post‐processing algorithm on a new slip ring‐mounted radiotherapy system
Authors: Zhu Heling , Dong Tingting , Pang Tingtian , Guan Qiu , Yang Jingru , Zhao Feini , Yang Bo , Qiu Jie 
Published: September 2024

AbstractPurposeThis study evaluates the performance of a kilovoltage x‐ray image‐guidance system equipped with a novel post‐processing optimization algorithm on the newly introduced TAICHI linear accelerator (Linac).MethodsA comparative study involving image quality tests and radiation dose measurements was conducted across six scanning protocols of the kV‐cone beam computed tomography (CBCT) system on the TAICHI Linac. The performance assessment utilized the conventional Feldkamp–Davis–Kress (FDK) algorithm and a novel Non‐Local Means denoising and adaptive scattering correction (NLM‐ASC) algorithm. Image quality metrics, including spatial resolution, contrast‐to‐noise ratio (CNR), and signal‐to‐noise ratio (SNR), were evaluated using a Catphan 604 phantom. Radiation doses for low‐dose and standard protocols were measured using a computed tomography dose index (CTDI) phantom, with comparative measurements from the Halcyon Linac's iterative CBCT (iCBCT).ResultsThe NLM‐ASC algorithm significantly improved image quality, achieving a 300%–1000% increase in CNR and SNR over the FDK‐only images and it also showed a 100%–200% improvement over the iCBCT images from Halcyon's head protocol. The optimized low‐dose protocols yielded higher image quality than the standard FDK protocols, indicating potential for reduced radiation exposure. Clinical implementation confirmed the TAICHI system's utility for precise and adaptive radiotherapy.ConclusionThe kV‐IGRT system on the TAICHI Linac, with its novel post‐processing algorithm, demonstrated superior image quality suitable for routine clinical use, effectively reducing image noise without compromising other quality metrics.
Impact of Sex, Serostatus, and Smoking on Risk for Rheumatoid Arthritis–Associated Interstitial Lung Disease Subtypes
Authors: McDermott Gregory C. , Hayashi Keigo , Juge Pierre‐Antoine , Gill Ritu , Byrne Suzanne , Gagne Staci , Wang Xiaosong , Paudel Misti L. , Moll Matthew , Cho Michael H. , Vanni Kathleen , Kowalski Emily , Qian Grace , Bade Katarina , Saavedra Alene , Kawano Yumeko , DiIorio Michael , Wolfgang Taylor , Kim Edy Y. , Dellaripa Paul F. , Weinblatt Michael E. , Shadick Nancy , Doyle Tracy J. , Sparks Jeffrey A. 
Published: September 2024

ObjectiveRheumatoid arthritis–associated interstitial lung disease (RA‐ILD) includes multiple subtypes with varying histopathology, prognosis, and potential treatments. Limited research has investigated risk factors for different RA‐ILD subtypes. Therefore, we examined demographic, serologic, and lifestyle associations with RA‐ILD subtypes.MethodsWe systematically identified RA‐ILD cases and RA controls without ILD (RA‐noILD) in the Brigham RA Sequential Study and Mass General Brigham Biobank RA cohort. We determined RA‐ILD subtype (usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP], and other/indeterminate) through chest high‐resolution computed tomography imaging pattern. We investigated associations of demographic, lifestyle, and serologic factors with major RA‐ILD subtypes using multivariable logistic regression.ResultsAmong 3,328 patients with RA, we identified 208 RA‐ILD cases and 547 RA‐noILD controls. RA‐UIP was associated with older age (odds ratio [OR] 1.03 per year, 95% confidence interval [95% CI] 1.01–1.05), male sex (OR 2.15, 95% CI 1.33–3.48), and seropositivity (OR 2.08, 95% CI 1.24–3.48), whereas RA‐NSIP was significantly associated only with seropositive status (OR 3.21, 95% CI 1.36–7.56). Nonfibrotic ILDs were significantly associated with smoking (OR 2.81, 95% CI 1.52–5.21). Having three RA‐ILD risk factors (male, seropositive, smoking) had an OR of 6.89 (95% CI 2.41–19.7) for RA‐UIP compared with having no RA‐ILD risk factors.ConclusionOlder age, seropositivity, and male sex were strongly associated with RA‐UIP, whereas RA‐related autoantibodies were associated with RA‐NSIP. These findings suggest RA‐ILD sex differences may be driven by RA‐UIP and emphasize the importance of further studies to clarify RA‐ILD heterogeneity and optimize screening and treatment approaches.
Design of Visualized Ratiometric Mechanoluminescent Materials for High‐Resolution Pressure Sensing
Authors: Zhang Pengfei , Wu Yuanting , Guo Ziyi , Song Yunmei , Hu Jingyue , Liu Haojin , Zhao Lei 
Published: September 2024

AbstractOptical sensing technology based on mechanoluminescent (ML) materials offers advantages such as rapid response, real‐time monitoring, visual signal output, and multi‐functional sensing, making it promising for various applications. However, traditional sensing techniques based on the absolute intensity of ML suffer from issues of low accuracy and large errors, which have a significant impact on the reliability and visual effectiveness of the sensor. To address these problems, this study employs a ratiometric ML pressure sensing method. By utilizing the primary color recognition of human cone cells, transition metal ion Mn2+ and rare earth ion Tb3+ are selected as luminescent centers. The rich intermediate colors ensure a wide range of colors that are easily distinguishable by the human eye. Through studies involving mechanical stimulation and similar high‐energy radiation, it is confirmed that the differences in sensitivity between rare earth ions and transition metal ions, as well as the contributions of shallow trap states, are the reasons for the dynamic changes in the ratiometric ML intensity. Finally, a conceptual application of pressure sensing is realized by combining homogeneous gas compression with pipeline monitoring for dynamic visualization, self‐referencing, and high‐precision mechanical sensing.
Stable 2e−/2CO2 Electrochemistry Triggered by Enriched Interfacial Oxygen Mo2N@Ti3C2O2 Elcetrocatalyst for High Rates and High Energy Efficiency Li‐CO2 Batteries
Authors: Zheng Ruixin , Yang Mengmeng , Zhu Xiaoqi , Fang Qisheng , Wang Xilin , Lei Pengyang , Zhou Jingwen , Wang Bin , Cheng Jianli 
Published: September 2024

AbstractRechargeable lithium‐carbon dioxide (Li‐CO2) batteries present a compelling strategy for carbon capture and utilization techniques. Nevertheless, the formation of Li2CO3 as the main discharge product in the 4e−/3CO2 electrochemistry of Li‐CO2 batteries necessitates an elevated applied voltage to achieve full decomposition, which leads to severe performance issues in Li‐CO2 batteries. In this work, a stable lithium oxalate (Li2C2O4) electrochemistry involving a 2e−/2CO2 process triggered by Mo2N@Ti3C2O2 electrocatalyst is proposed, which facilitates highly reversible redox reactions in Li‐CO2 batteries. The presence of enriched ‐O terminations at the interface between Mo2N and Ti3C2O2 strengthens charge redistribution of Mo 3d orbital electron and enhances the coupling between Mo 3d orbitals and O 2p orbitals in Li2C2O4. The adsorption energy of Li2C2O4 on Mo2N@Ti3C2O2 surface and energy barrier for self‐disproportionation reaction of Li2C2O4 are further increased, enabling the stable Li2C2O4 electrochemistry. Therefore, the Mo2N@Ti3C2O2 based Li‐CO2 battery can produce Li2C2O4 discharge products even at a high discharge rate of 500 mA g−1 (ten times to previous studies) and during deep cycling processes. Due to the stable Li2C2O4 electrochemistry, Li‐CO2 batteries exhibit excellent electrochemical performance, including ultra‐low overpotential (0.55 V), ultra‐high energy efficiency (82.9%), and excellent cycling stability electrode (800 h).
Covalent Grafting of Tanfloc on Titania Nanotube Arrays: An Approach to Mitigate Bacterial Adhesion and Improve the Antibacterial Efficacy of Titanium Implants
Authors: Singh Ramesh , Madruga Liszt Y. C. , Savargaonkar Aniruddha , Martins Alessandro F. , Kipper Matt J. , Popat Ketul C. 
Published: September 2024

AbstractImplanted medical devices often face the challenge of infections, which can compromise their successful integration and use. To address this issue, this study demonstrates the covalent grafting of a tannin‐based antimicrobial biopolymer tanfloc (TAN) onto the titania nanotube arrays (TiNTs) surface to enhance antibacterial properties. Due to its polyphenolic and ionic structural configuration, tanfloc possesses unique properties that enable it to interact with and disrupt bacterial cell walls and membranes. Combining the topographical effect of TiNTs with the inherent antibacterial properties of tanfloc, this approach aims to mitigate bacterial threats on medical implants effectively. The successful attachment of tanfloc on TiNTs is confirmed through X‐ray photoelectron spectroscopy (XPS) and Fourier‐transform infrared spectroscopy (FT‐IR). The antibacterial and antibiofilm efficacy of the tanfloc‐functionalized TiNTs is evaluated against Staphylococcus aureus (Gram‐positive) and Pseudomonas aeruginosa (Gram‐negative) bacteria. The findings suggest that the covalent conjugation of tanfloc onto TiNTs is a promising approach to improve the infection resistance of titanium‐based medical implants, with potential applications in orthopedic, dental, and other biomedical device areas.
Microwave‐Assisted Rhodium (III)‐Catalyzed [3+3] Annulation of 2‐Benzyl‐2H‐Indazole‐6‐carboxylic Acids with Iodonium Ylides: A Regioselective Synthesis of Indazole‐Fused Chromenes
Authors: Chen Hong‐Ren , Barve Indrajeet J. , Hsieh Hung‐Sheng , Liu Kuan‐Miao , Pawar Ganesh P. , Sun Chung‐Ming 
Published: September 2024

AbstractA Rh(III)‐catalyzed redox‐neutral C−H activation/[3+3] cyclization of 2‐benzyl‐2H‐indazole‐6‐carboxylic acids with iodonium ylides under microwave irradiation for the synthesis of indazole‐fused chromenes has been reported. The critical feature of this method is that the C−H activation of the C7−H bond of 2‐benzyl‐2H‐indazole‐6‐carboxylic acid proceeds regioselectively in the presence of the proximate C5−H bond without the need of external oxidant. Microwave irradiation reduced the reaction time as compared to conventional heating. The detailed mechanistic study disclosed the mechanistic pathway of the reaction.