cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.26213334.v2
title: A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity

description: The lack of success in clinical trials for HIV vaccines highlights the need to explore novel strategies for vaccine development. Research on highly exposed seronegative (HESN) HIV-resistant Kenyan female sex workers revealed naturally protective immunity is correlated with a focused immune response mediated by virus-specific CD8 T cells. Further studies indicated that the immune response is unconventionally focused on highly conserved sequences around HIV viral protease cleavage sites (VPCS). Thus, taking an unconventional approach to HIV vaccine development, we designed lipid nanoparticles loaded with mRNA that encodes multi-epitopes of VPCS (MEVPCS-mRNA LNP), a strategic design to boost antigen presentation by dendritic cells, promoting effective cellular immunity. Furthermore, we developed a novel cold-chain compatible mRNA LNP formulation, ensuring long-term stability and compatibility with cold-chain storage/transport, widening accessibility of mRNA LNP vaccine in low-income countries. The <i>in-vivo</i> mouse study demonstrated that the vaccinated group generated VPCS-specific CD8 memory T cells, both systemically and at mucosal sites of viral entry. The MEVPCS-mRNA LNP vaccine-induced CD8 T cell immunity closely resembled that of the HESN group and displayed a polyfunctional profile. Notably, it induced minimal to no activation of CD4 T cells. This proof-of-concept study underscores the potential of the MEVPCS-mRNA LNP vaccine in eliciting CD8 T cell memory specific to the highly conserved multiple VPCS, consequently having a broad coverage in human populations and limiting viral escape mutation. The MEVPCS-mRNA LNP vaccine holds promise as a candidate for an effective prophylactic HIV vaccine.
DOI: 10.25549/webster-c100-39636
title: Inter-agency team, final report, 1992

description: Inter-Agency Team Final Report, Appendix: Local police departments, materials collected by the Inter-Agency Team regarding the policies, procedures, and operations of several local police departments aside from the Los Angeles Police Department, 1992. PART OF SERIES: In addition to analyzing the 1992 riots as a whole, the Webster Commission also divided into several smaller task forces and study groups, each of which addressed one specific aspect of the civil disturbance. The series consists of reports and appendices produced by five of these groups: the Chronology Team, the Public Officials and Community Team, the LAPD Team, the Comparisons Study Group, and the Inter-Agency Team. Also included are two copies of Webster Scope, a report that interprets the riots and their cumulative effects primarily through graphs, charts, statistics, and figures, and several research memoranda that discuss the legality of several riot-response tactics. PART OF SUBSERIES: Materials related to a final report issued by the Webster Commission's Inter-Agency Team. which evaluated the collaboration between the LAPD and other law enforcement agencies in the advent of the 1992 riots. Included is a copy of the final report and the report's appendices, which are comprised of interviews, memoranda, statistical analyses, handbooks, and other miscellaneous documents.
DOI: 10.6084/m9.figshare.24865646
title: Detection and phylogenetic analysis of contemporary H14N2 Avian influenza A virus in domestic ducks in Southeast Asia (Cambodia)

description: Avian influenza virus (AIV) in Asia is a complex system with numerous subtypes and a highly porous wild birds-poultry interface. Certain AIV subtypes, such as H14, are underrepresented in current surveillance efforts, leaving gaps in our understanding of their ecology and evolution. The detection of rare subtype H14 in domestic ducks in Southeast Asia comprises a geographic region and domestic bird population previously unassociated with this subtype. These H14 viruses have a complex evolutionary history involving gene reassortment events. They share sequence similarity to AIVs endemic in Cambodian ducks, and Eurasian low pathogenicity and high pathogenicity H5Nx AIVs. The detection of these H14 viruses in Southeast Asian domestic poultry further advances our knowledge of the ecology and evolution of this subtype and reinforces the need for continued, longitudinal, active surveillance in domestic and wild birds. Additionally, <i>in vivo</i> and <i>in vitro</i> risk assessment should encompass rare AIV subtypes, as they have the potential to establish in poultry systems.
DOI: 10.6084/m9.figshare.24865646.v2
title: Detection and phylogenetic analysis of contemporary H14N2 Avian influenza A virus in domestic ducks in Southeast Asia (Cambodia)

description: Avian influenza virus (AIV) in Asia is a complex system with numerous subtypes and a highly porous wild birds-poultry interface. Certain AIV subtypes, such as H14, are underrepresented in current surveillance efforts, leaving gaps in our understanding of their ecology and evolution. The detection of rare subtype H14 in domestic ducks in Southeast Asia comprises a geographic region and domestic bird population previously unassociated with this subtype. These H14 viruses have a complex evolutionary history involving gene reassortment events. They share sequence similarity to AIVs endemic in Cambodian ducks, and Eurasian low pathogenicity and high pathogenicity H5Nx AIVs. The detection of these H14 viruses in Southeast Asian domestic poultry further advances our knowledge of the ecology and evolution of this subtype and reinforces the need for continued, longitudinal, active surveillance in domestic and wild birds. Additionally, <i>in vivo</i> and <i>in vitro</i> risk assessment should encompass rare AIV subtypes, as they have the potential to establish in poultry systems.
DOI: 10.6084/m9.figshare.25262876
title: Poor virus-specific T-cell responses early after tick-borne encephalitis virus infection correlate with disease severity

description: Tick-borne encephalitis virus (TBEV) infection may cause acute central nervous system inflammation varying in clinical manifestations and severity. A possible correlation of TBEV-specific antibody and cell-mediated immune responses, shortly after infection, with clinical manifestations, severity and long-term outcome has been poorly investigated. In a cohort of thirty early tick-borne encephalitis (TBE) patients, we assessed the magnitude, specificity and functional properties of TBEV-specific T-cell and antibody responses. These responses early during disease were assessed in view of clinical manifestations, severity and long-term outcome. TBEV-specific T-cell responses to C, E, NS1, and NS5 proteins were significantly lower in patients with severe acute illness than in patients with mild TBE. Lower T-cell responses to E, NS1, and NS5 proteins also correlated with the development of meningoencephalomyelitis. Virus-specific antibody titres early after infection did not correlate with disease severity, clinical manifestations, or long-term outcome in this study, possibly due to the small number of patients of which matching serum and peripheral blood mononuclear cells were available. The findings suggest that virus-specific T cells afford a certain degree of protection against the development of severe TBEV-induced disease.
DOI: 10.6084/m9.figshare.25262876.v1
title: Poor virus-specific T-cell responses early after tick-borne encephalitis virus infection correlate with disease severity

description: Tick-borne encephalitis virus (TBEV) infection may cause acute central nervous system inflammation varying in clinical manifestations and severity. A possible correlation of TBEV-specific antibody and cell-mediated immune responses, shortly after infection, with clinical manifestations, severity and long-term outcome has been poorly investigated. In a cohort of thirty early tick-borne encephalitis (TBE) patients, we assessed the magnitude, specificity and functional properties of TBEV-specific T-cell and antibody responses. These responses early during disease were assessed in view of clinical manifestations, severity and long-term outcome. TBEV-specific T-cell responses to C, E, NS1, and NS5 proteins were significantly lower in patients with severe acute illness than in patients with mild TBE. Lower T-cell responses to E, NS1, and NS5 proteins also correlated with the development of meningoencephalomyelitis. Virus-specific antibody titres early after infection did not correlate with disease severity, clinical manifestations, or long-term outcome in this study, possibly due to the small number of patients of which matching serum and peripheral blood mononuclear cells were available. The findings suggest that virus-specific T cells afford a certain degree of protection against the development of severe TBEV-induced disease.
DOI: 10.6084/m9.figshare.24925288
title: Capsid protein mediated evasion of IRAK1-dependent signalling is essential to Sindbis virus neuroinvasion and virulence in mice

description: Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection <i>in vitro</i>, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis <i>in vivo</i> using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the <i>in vivo</i> data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.
DOI: 10.6084/m9.figshare.24925288.v2
title: Capsid protein mediated evasion of IRAK1-dependent signalling is essential to Sindbis virus neuroinvasion and virulence in mice

description: Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection <i>in vitro</i>, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis <i>in vivo</i> using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the <i>in vivo</i> data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.
DOI: 10.25549/webster-c100-32765
title: Roundtable 7, discussion, 1990-09-13

description: Roundtable discussion with officials of the United States Customs Service, Heinrich, Luksic, Pidd, Vigna, and Winkowski about its role in the civil disturbance, its adequacy in responding to the violence and unrest, and the adequacy of other law enforcement agencies in curtailing the disturbance, 1990 September 13. PART OF SERIES: After the violence had subsided, the Webster Commission met of a variety of public officials, law enforcement personnel, activists, and community leaders to discuss the rioting, its root causes, and the adequacy of the LAPD's response. The series includes summaries of these meetings, including questions and comments along of the interviewers' own mental impressions, conclusions, and opinions. Materials are arranged in alphabetical order, according to the last name of the interviewee.
DOI: 10.6084/m9.figshare.25427582
title: Mpox virus Clade IIb infected Cynomolgus macaques via mimic natural infection routes closely resembled human mpox infection

description: Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.
DOI: 10.6084/m9.figshare.25427582.v2
title: Mpox virus Clade IIb infected Cynomolgus macaques via mimic natural infection routes closely resembled human mpox infection

description: Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.
DOI: 10.25549/webster-c100-39964
title: Webster scope

description: A report that assesses the 1992 riots using a wide variety of socioeconomic indicators. PART OF SERIES: In addition to analyzing the 1992 riots as a whole, the Webster Commission also divided into several smaller task forces and study groups, each of which addressed one specific aspect of the civil disturbance. The series consists of reports and appendices produced by five of these groups: the Chronology Team, the Public Officials and Community Team, the LAPD Team, the Comparisons Study Group, and the Inter-Agency Team. Also included are two copies of Webster Scope, a report that interprets the riots and their cumulative effects primarily through graphs, charts, statistics, and figures, and several research memoranda that discuss the legality of several riot-response tactics.
DOI: 10.6084/m9.figshare.26823720
title: Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study

description: Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.
DOI: 10.6084/m9.figshare.26823720.v2
title: Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study

description: Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.
DOI: 10.6084/m9.figshare.27612955
title: Overexpression of <i>bla</i><sub>SHV-12</sub> caused by tandem amplification contributed to ceftazidime/avibactam resistance in hypervirulent and carbapenem-resistant <i>Klebsiella pneumoniae</i>

description: We identified a novel ceftazidime/avibactam (CAZ/AVI) resistance mechanism in endemic sequence type 11 hypervirulent and carbapenem-resistant <i>Klebsiella pneumoniae</i> isolated from a patient who had not been exposed CAZ/AVI. Overexpression of <i>bla</i><sub>SHV-12</sub> caused by tandem gene amplification contributed to CAZ/AVI resistance instead of the carriage of <i>bla</i><sub>KPC-2</sub>. Enhanced genomic surveillance is essential to identify emerging variants.
DOI: 10.6084/m9.figshare.27612955.v1
title: Overexpression of <i>bla</i><sub>SHV-12</sub> caused by tandem amplification contributed to ceftazidime/avibactam resistance in hypervirulent and carbapenem-resistant <i>Klebsiella pneumoniae</i>

description: We identified a novel ceftazidime/avibactam (CAZ/AVI) resistance mechanism in endemic sequence type 11 hypervirulent and carbapenem-resistant <i>Klebsiella pneumoniae</i> isolated from a patient who had not been exposed CAZ/AVI. Overexpression of <i>bla</i><sub>SHV-12</sub> caused by tandem gene amplification contributed to CAZ/AVI resistance instead of the carriage of <i>bla</i><sub>KPC-2</sub>. Enhanced genomic surveillance is essential to identify emerging variants.