bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional analyses of viral H2 protein of the vaccinia virus entry fusion complex
Authors: Kao Chi-Fei , Liu Chang-Yi , Hsieh Chia-Lin , Carillo Kathleen Joyce D. , Tzou Der-Lii M. , Wang Hao-Ching , Chang Wen 
Published: November 2023

ABSTRACT

Virus-mediated membrane fusion involves conformational changes of the viral fusion protein to fuse the opposing viral and host lipid bilayers. Unlike all other known viruses that contain a single fusion protein, poxviruses harbor a multimeric protein complex of 11 subunits, termed the entry fusion complex (EFC), to mediate fusion with host membranes. Yet, how the poxviral EFC mediates membrane fusion remains enigmatic. To establish the mechanism of EFC-triggered membrane fusion, we are deciphering the structure and function of individual EFC components. Here, we determined the crystal structure of the H2 ectodomain by X-ray diffraction, revealing a folded conformation comprising a central five-stranded β-sheet and three cladding α-helices. We reconstructed the full-length H2 by
in silico
prediction, revealing that the N-terminal region (amino acids 51–90) of H2 protein may fold as a long helix connecting the ectodomain and transmembrane region. Using alanine-mutagenesis screening in a transient complementation system, coimmunoprecipitation, isothermal titration calorimetry, and mature virion (MV)-triggered membrane fusion assays, we concluded that the surface of the ectodomain of H2 protein, including two loop regions,
170
LGYSG
174
and
125
RRGTGDAW
132
, constitutes a broad A28-binding region. Moreover, although not involved in A28 binding, the N-terminal helical region approximal to the transmembrane part, encompassing
64
RIK
66
,
72
W, and
83
ESDRGR
88
, is also crucial for viral EFC formation and MV infectivity.

IMPORTANCE

Vaccinia virus infection requires virus-cell membrane fusion to complete entry during endocytosis; however, it contains a large viral fusion protein complex of 11 viral proteins that share no structure or sequence homology to all the known viral fusion proteins, including type I, II, and III fusion proteins. It is thus very challenging to investigate how the vaccinia fusion complex works to trigger membrane fusion with host cells. In this study, we crystallized the ectodomain of vaccinia H2 protein, one component of the viral fusion complex. Furthermore, we performed a series of mutational, biochemical, and molecular analyses and identified two surface loops containing
170
LGYSG
174
and
125
RRGTGDAW
132
as the A28-binding region. We also showed that residues in the N-terminal helical region (amino acids 51–90) are also important for H2 function.
Draft genome sequence of
Vibrio lentus
VLO8, recovered from the larval culture of the Chilean scallop (
Argopecten purpuratus
)
Authors: Hurtado Luz , Urtubia Rocío , Concha Christopher , Rodríguez Sergio , Barja Juan L. , Rojas Rodrigo 
Published: November 2023

ABSTRACT

This announcement reports the genome of
Vibrio lentus
VLO8 recovered from the larval culture of Chilean scallop. The genomes of strain VLO8 have two contigs with a total length of 5,499,980 bp, an average G + C content of 44.22%, a total number of protein-coding genes of 6,439, and 170 RNAs.
Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences
Authors: Saputri Dianita S. , Ismanto Hendra S. , Nugraha Dendi K. , Xu Zichang , Horiguchi Yasuhiko , Sakakibara Shuhei , Standley Daron M. 
Published: November 2023

ABSTRACT
Recent advances in adaptive immune receptor repertoire sequencing have provided abundant B cell receptor (BCR) sequences under various conditions, including vaccination and disease. However, determining target antigen and epitope specificity of the corresponding antibodies is a major challenge due to their exceptional sequence diversity. Here, we introduce a novel method to cluster antibodies sharing antigenic targets based on their complementarity determining region (CDR) sequences. Using the proposed method, we demonstrate that SARS-CoV-2 spike protein receptor-binding domain (RBD) binders and non-RBD binders from publicly available BCR data were classified correctly, with a cluster purity of 95%. These clusters were then leveraged for annotating unlabeled COVID-19 patient BCR data, enabling the discovery of novel anti-RBD antibodies. We further validated the method by clustering BCR repertoires obtained from single-cell immune profiling of diphtheria-tetanus-pertussis (DTP)-vaccinated donors. Antibody expression and antigen-binding assays demonstrated that the clusters exhibited 96% antigen purity, surpassing the apparent 82% purity achieved by assigning antigens to the same B cells using fluorescently labeled DTP antigen probes. Moreover, antibodies within certain clusters were found to possess neutralizing activity, suggesting that CDR clusters contain epitope-level information. Together, this study offers a simple approach for antigen- and epitope-specific BCR discovery that is reproducible, inexpensive, and applicable to a wide range of antigen targets.

IMPORTANCE
Determining antigen and epitope specificity is an essential step in the discovery of therapeutic antibodies as well as in the analysis adaptive immune responses to disease or vaccination. Despite extensive efforts, deciphering antigen specificity solely from BCR amino acid sequence remains a challenging task, requiring a combination of experimental and computational approaches. Here, we describe and experimentally validate a simple and straightforward approach for grouping antibodies that share antigen and epitope specificities based on their CDR sequence similarity. This approach allows us to identify the specificities of a large number of antibodies whose antigen targets are unknown, using a small fraction of antibodies with well-annotated binding specificities.
Efficacy of combined COVID-19 convalescent plasma with oral RNA-dependent RNA polymerase inhibitor treatment versus neutralizing monoclonal antibody therapy in COVID-19 outpatients: a multi-center, non-inferiority, open-label randomized controlled trial (PlasMab)
Authors: Siripongboonsitti Taweegrit , Nontawong Nuttakant , Tawinprai Kriangkrai , Suptawiwat Ornpreya , Soonklang Kamonwan , Poovorawan Yong , Mahanonda Nithi 
Published: November 2023

ABSTRACT
The effectiveness of neutralizing monoclonal antibodies against emerging variants with spike protein mutations has been limited. Early high-titer convalescent plasma therapy (CPT) tends to be effective and a potential treatment option for COVID-19 outpatient treatment. An open-label, 1:1, randomized controlled trial compared the efficacy of high neutralizing titer CPT with favipiravir (CPT-FPV) versus sotrovimab. The study aimed to evaluate the non-inferiority of CPT-FPV treatment compared to sotrovimab in preventing hospitalization within 14 and 28 days. Among the 136 randomized participants, 68 received CPT-FPV, while 68 received sotrovimab. The study demonstrated that CPT-FPV was non-inferior to sotrovimab in preventing hospitalization within 14 and 28 days. No significant differences between the two treatment arms were observed in emergency room visits, oxygen supplementation, or mortality. Although there were no significant disparities in radiological, virological, or inflammatory marker outcomes, sotrovimab exhibited a more pronounced reduction in IL-6 levels during days 2–5 and lower MCP-1 levels on day 14. High neutralizing titer convalescent plasma and favipiravir demonstrated non-inferior to sotrovimab in preventing hospitalization, emergency room visit, oxygen supplementation, and mortality in mild-to-moderate COVID-19. The evidence may be a choice for treatment for new variants despite the need for further study. (The trial protocol was registered in the Thai clinical trials registry no. 20220319002.)

IMPORTANCE
This pivotal study reveals that high neutralizing titer COVID-19 convalescent plasma therapy (CPT) combined with favipiravir (FPV) is non-inferior to sotrovimab in preventing hospitalization and severe outcomes in outpatients with mild-to-moderate COVID-19 and high-risk comorbidities. It underscores the potential of CPT-FPV as a viable alternative to neutralizing monoclonal antibodies like sotrovimab, especially amid emerging variants with spike protein mutations. The study’s unique approach, comparing a monoclonal antibody with CPT, demonstrates the efficacy of early intervention using high neutralizing antibody titer CPT, even in populations with a significant proportion of elderly patients. These findings are crucial, considering the alternative treatment challenges, especially in resource-limited countries, posed by the rapidly mutating SARS-CoV-2 virus and the need for adaptable therapeutic strategies.
Sinonasal schwannoma masquerading as an IgG4-related nasal mass
Authors: Roy Shrimoyee , Mehta Aditi , Muraleedharan Manjul , Virk Ramandeep Singh 
Published: November 2023

An elderly (8th decade) diabetic patient presented with insidious, painless protrusion of the right eye for 1 month, associated with nasal congestion. Past history included healed serous chorioretinopathy in the right eye (>30 years back) and recently diagnosed (1 year prior) autoimmune IgG4-related pancreatitis for which he was on long-term corticosteroids. On nasal endoscopic examination, a well circumscribed mass was found in the right nasal cavity.Keeping in mind the systemic diagnosis, the sinonasal mass was suspected to be a IgG4-related disease. An endoscopic biopsy was performed and revealed a surprise diagnosis of grade 1 nasal schwannoma.
CLYC as a neutron detector in low background conditions
Authors: Plaza J. , Bécares V. , Cano-Ott D. , Gómez C. , Martínez T. , Mendoza E. , de Rada A. Pérez , Pesudo V. , Sáez-Vergara J. C. , Santorelli R. , Villamarín D. , Ianni A. , Peña C. , Balibrea-Correa J. , Boeltzig A. , Imbriani G. 
Published: November 2023

AbstractWe report on the thermal neutron flux measurements carried out at the Laboratorio Subterráneo de Canfranc (LSC) with two commercial $$2^{\prime \prime } \times 2^{\prime \prime }$$

2
″

×

2
″

CLYC detectors. The measurements were performed as part of an experimental campaign at LSC with $$^{3}$$

3

He detectors, for establishing the sensitivity limits and use of CLYCs in low background conditions. A careful characterization of the intrinsic $$\alpha $$
α
and $$\gamma $$
γ
-ray background in the detectors was required and done with dedicated measurements. It was found that the $$\alpha $$
α
activities in the two CLYC crystals differ by a factor of three, and the use of Monte Carlo simulations and a Bayesian unfolding method allowed us to determine the specific $$\alpha $$
α
activities from the $$^{238}$$

238

U and $$^{232}$$

232

Th decay chains. The simulations and unfolding also revealed that the $$\gamma $$
γ
-ray background registered in the detectors is dominated by the intrinsic activity of the components of the detector such as the aluminum housing and photo-multiplier and that the activity within the crystal is low in comparison. The data from the neutron flux measurements with the two detectors were analyzed with different methodologies: one based on an innovative $$\alpha $$
α
/neutron pulse shape discrimination method and one based on the subtraction of the intrinsic $$\alpha $$
α
background that masks the neutron signals in the region of interest. The neutron sensitivity of the CLYCs was calculated by Monte Carlo simulations with MCNP6 and GEANT4. The resulting thermal neutron fluxes are in good agreement with complementary flux measurement performed with $$^{3}$$

3

He detectors, but close to the detection limit imposed by the intrinsic $$\alpha $$
α
activity.
Theory of localized light
Authors: Toyoda Tadashi , Fujita Maho , Uchida Tomohisa , Yamada Kazuhiro , Hiraiwa Nobuyoshi 
Published: November 2023

A theory of the spatially localized light observed by Hau et al. [Nature 397 (1999) 594] is formulated on the basis of the Maxwell equations, where the dynamics of the electron currents due to the electromagnetic fields is also taken into account within the self-consistent linear response approximation. Formulae for the energy, momentum and angular momentum of the localized light are derived.
Multifactorial Remodeling of the Cancer Immunopeptidome by IFNγ
Authors: Newey Alice , Yu Lu , Barber Louise J. , Choudhary Jyoti S. , Bassani-Sternberg Michal , Gerlinger Marco 
Published: November 2023

Abstract

IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity on cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated and IFNγ-treated colorectal cancer patient-derived organoids and combined this with transcriptomic and HLA-I immunopeptidomics data to dissect mechanisms that lead to remodeling of the immunopeptidome through IFNγ. IFNγ-induced changes in the abundance of source proteins, switching from the constitutive to the immunoproteasome, and differential upregulation of different HLA alleles explained some, but not all, observed peptide abundance changes. By selecting for peptides which increased or decreased the most in abundance, but originated from proteins with limited abundance changes, we discovered that the amino acid composition of presented peptides also influences whether a peptide is upregulated or downregulated on HLA-I through IFNγ. The presence of proline within the peptide core was most strongly associated with peptide downregulation. This was validated in an independent dataset. Proline substitution in relevant core positions did not influence the predicted HLA-I binding affinity or stability, indicating that proline effects on peptide processing may be most relevant. Understanding the multiple factors that influence the abundance of peptides presented on HLA-I in the absence or presence of IFNγ is important to identify the best targets for antigen-specific cancer immunotherapies such as vaccines or T-cell receptor engineered therapeutics.

Significance:
IFNγ remodels the HLA-I–presented immunopeptidome. We showed that peptide-specific factors influence whether a peptide is upregulated or downregulated and identified a preferential loss or downregulation of those with proline near the peptide center. This will help selecting immunotherapy target antigens which are consistently presented by cancer cells.
A prática feminina de si: identificações da mulher encarcerada em cartas
Authors: Cesar Thays Carvalho , Remenche Maria de Lourdes Rossi 
Published: November 2023

O presente trabalho busca identificar a influência do meio prisional na produção de identificações das mulheres privadas de liberdade, utilizando a escrita de si (FOUCAULT, 1992; MCLAREN, 2016) como arcabouço teórico principal. Para tanto, analisamos cartas de mulheres encarceradas em uma unidade destinada a mulheres em fase final de cumprimento de pena da região de Curitiba/PR e fizemos um mapeamento das manifestações do feminino no cárcere. A análise sustenta-se nas teorias sobre escrita de si e estudos sobre identidade. O corpus se constitui de cartas de quatro mulheres privadas de liberdade, coletado durante oficinas de leitura realizadas no período de 07 a 23/11/2022. A análise das produções demonstrou que o cárcere provoca uma reconfiguração nas identificações dessas mulheres. A ação de contar-se é materializada nas missivas e apresenta o sujeito como um ser social, que vive em um contexto que promove identificações, ora para suportar a dor da ausência daqueles que ama, ora para ressignificar experiências pretéritas.
Large‐Vessel Occlusion Stroke Knowledge and Training for Stroke Severity Assessment Among Emergency Medical Services Personnel in the United States
Authors: Asif Kaiz S. , Novakovic Robin , Nguyen Thanh N. , Ortega‐Gutierrez Santiago , Kim Youngran , Jagolino‐Cole Amanda , Aroor Sushanth , Castonguay Alicia , Kumar Prateek , Jhadav Ashutosh P. , Yavagal Dileep , Nour May , Toth Gabor , Mokin Maxim , Sheth Sunil A. , Jumaa Mouhammad A. , Al‐bayati Alhamza , Teleb Mohamed , Mansour Ossama Y. , Desai Shashvat M. , Hartman Joshua , Liebeskind David S. , Hassan Ameer E. , Mehta Brijesh P. ,   SVIN Education and SPEED Committees
Published: November 2023

Background
Prehospital identification of large‐vessel occlusion (LVO) stroke facilitates the development of a regional triage protocol that could lead to an improvement in intrahospital and interhospital workflows. This requires stroke education of emergency medical services (EMS) personnel to improve stroke recognition, severity assessment, and prenotification. However, the current state of EMS personnel's knowledge of LVO stroke, their training for stroke severity assessment, and their preferences for educational methods are unknown. We conducted a nationwide EMS survey across the United States to glean insights that can inform and customize future EMS educational efforts.

Methods

The Society of Vascular and Interventional Neurology, in collaboration with
EMS World
, created an online questionnaire for EMS personnel. It included 12 multiple‐choice and free‐response questions designed to test participants’ clinical knowledge of LVO, knowledge of stroke center certification levels, prior LVO educational experiences, preferences for educational content delivery, and perspectives on prehospital hurdles to stroke care. All subscribers of
EMS World
received a survey link via email.

Results

Of the 38 486 subscribers of
EMS World
, the survey email was opened by 1830, of whom 1107 completed the survey across all states in the United States, with a response rate of 2.9%. Most of the respondents identified themselves as paramedics/emergency medical technicians (91%). The number of patients with stroke that survey participants transported in the past year was <10 for 618 (56%). Only 285 (26%) participants answered both LVO knowledge questions correctly, and only 128 (12%) respondents correctly identified all types of stroke centers with thrombectomy capability. A total of 362 EMS personnel (33%) denied receiving training to perform LVO severity assessment. Respondents who received training to perform an LVO scale demonstrated nearly twice the prevalence of LVO knowledge (30.6% versus 15.7%; prevalence ratio, 1.94 [95% CI, 1.50–2.53]) than respondents who did not receive training. The top hurdle to prehospital LVO education was identified as the lack of standardized LVO training by 535 (48%) respondents.

Conclusions
EMS providers in the United States reported inadequate LVO training and demonstrated gaps in knowledge of LVO, stroke severity scales, and stroke center levels. Systematic efforts to enhance and standardize the educational content and delivery of LVO education are needed.
Environmental Private Law
Authors: Halfmeier Axel 
Published: November 2023

Abstract
This article looks at the relationship between private law and environmental concerns. It describes the history of this relationship and some of its legal foundations in German, European, and international law. It also provides a critical overview of modern theoretical approaches in this field. With a view to developments currently underway, it discusses two cases from Germany and the Netherlands. The article concludes that steps are being taken towards a more eco-friendly concept of private law but that the German Federal Court in particular has not yet sufficiently integrated environmental concerns into its concept of private law.
2. Knowledge, Language and Reason
Authors: Ingram David 
Published: November 2023

The story starts long ago, with the gradual conceptualization of knowledge as an encyclopaedia—a circle of learning. This chapter traces a path from the invention of medicine in classical times, through philosophy, language and logic, and through mathematics, natural science and computer science into the modern era of information technology and health care. It follows the librarian’s dilemma over the ages—discovering how best to position books and documents within collections and search them in pursuit of learning.
The chapter proceeds to consider languages as expressions of knowledge, and the different forms they take—spoken, written, artistic, mathematical, logical and computational. This sets the scene for introducing computational discipline that grew from endeavours to formulate rigorous logical foundations of mathematics, in earlier times, and the development of formal logic in support of rigorous reasoning. From there, the computer has become integral to how we express and reason with knowledge, and to problem solving and the discovery of new knowledge. These are twenty-first-century frontiers of machine learning and artificial intelligence.
Moving to the complex world of medical language and terminology, used in representing knowledge about medicine and health care, the chapter discusses difficulties faced in evolving their corpora of terms and classifications, from pragmatic organizations into reliably computable forms. Notable pioneering initiatives and their leaders are profiled, highlighting some ideas that have acquired staying power and others that have not, looking for patterns of success and failure.
Finally, the chapter moves to a discussion of some pioneering computer-based systems for capturing, storing and reasoning with medical knowledge, such as for guiding the prescription of antimicrobial drugs. It closes with a light-hearted take on how we use the terms knowledge, information and data, and a reflection on the traction that is needed in the unfolding of new knowledge and its application in practical contexts.
6. Life and Information
Authors: Ingram David 
Published: November 2023

This chapter steps away from the practical engineering of Chapter Five into a new dimension, to consider where information itself, as an idea, now connects within life science and medicine. The current era has seen radical transition in scientific understanding of the nature of both information and life. Like particles and waves in quantum theory, perhaps they will come to be seen, in some emergent way, as another example of complementarity. Life as somewhere between material entity and immaterial essence. Information as somewhere between material and measurable entity and immaterial abstraction.
The question ‘What is Life?’, and its connection with the nature of information as a scientific concept, has captivated luminary thinkers, who have informed and challenged one another, and written landmark books on this theme. I have a collection of these, written from physics, life science, mathematics, computer science and cognitive neuroscience perspectives. I look in turn at an eclectic selection, over time. My purpose is to illustrate how these great and imaginative contributors have applied their evolving insights to elucidate connection of their disciplines with ideas about the nature of information and life.
The chapter concludes with a reflection on information policy for health care services in the present era of still extremely rapid transition on all fronts of information technology and life science. There can be no more important global goals than those that seek balance, continuity and governance of the natural environment. In health care, these three also predominate as concerns of our age. They pose challenges that can only be tackled based on shared knowledge and methods that connect coherently and transcend from local to global scale, building on common ground.