bluuebunny/crossref_metadata_2025 huggingface dataset:
El ecocidio, la matabilidad inimputable de la vida y el dispositivo biopolítico de la excepción. Nuevas fronteras para el derecho como obligación
Authors: Bartolomé Ruiz Castor Mari Martín , Martín Óscar
Published: October 2023

En la presente investigación proponemos profundizar en el concepto de ecocidio y sus implicaciones ético-políticas, relacionándolo con los conceptos de soberanía y estado de excepción de Giorgio Agamben. El concepto de excepción, en la tradición jurídica y filosófica, está referido al ámbito de la vida de las personas y no al daño producido a la vida en la naturaleza. Sin embargo, partiendo del presupuesto de que hay una interdependencia de la vida humana con la vida de la naturaleza, se analizan los desdoblamientos ético-políticos a los que esa interdependencia nos conduce, teniendo como eje el concepto de ecocidio. Para este análisis proponemos recorrer los vínculos entre ecocidio y estado de excepción como dos prácticas asimiladas que, para destruir la vida, la reducen a una insignificancia ética a través de un vacío jurídico.
Methods for Estimating Hydrogen Fuel Tank Characteristics
Authors: Klymyshyn Nicholas A. , Brooks Kriston , Barrett Nathan
Published: October 2023

The pressure vessels needed to store hydrogen for next-generation hydrogen fuel cell vehicles are expected to be a substantial portion of the total system mass, volume, and cost. Gravimetric capacity, volumetric capacity, and cost per kilogram of usable hydrogen are key performance metrics that the U.S. Department of Energy (DOE) uses to determine the viability of hydrogen fuel cell systems. Research and development related to hydrogen storage systems covers a wide range of potential operating conditions, from cryogenic temperatures to high temperatures (above ambient) and low pressure to high pressure. Researchers at PNNL have developed methods for estimating these key pressure vessel characteristics to support on-board hydrogen storage system design and performance evaluation and to support decision-making about DOE hydrogen storage system research investments. This article describes the pressure tank estimation methodology that has been used as a stand-alone calculation and has been incorporated into larger system evaluation tools. The methodology estimates the geometry, mass, and material cost of type I, type III, and type IV pressure vessels based on operating pressure and material strength at the system's operating temperature, using classical thin-wall and thick-wall pressure vessel stress calculations. The geometry, mass, and material cost requirements of the pressure vessel have significant impacts on the total system performance. For example, hydrogen storage materials that can separately achieve a very high hydrogen density can be deemed impractical for use in fuel cell vehicle hydrogen storage systems because the pressure tank containing them is too large, heavy, or expensive. This article describes the design philosophy and analytical process of the tank characteristic estimation methodology, which has been implemented in spreadsheet calculation tools and system-level analysis tools used by DOE researchers. Each of the three tank types (type I, type III, and type IV) uses a different analysis methodology with some common elements. This article also provides examples of implementing the methodology to perform parametric studies of all three pressure vessel types. The goal of this article is to present the methodology in sufficient detail so it can be implemented in other hydrogen fuel cell vehicle design and analysis tools.
Influences of Sediment Particles on Air Vessel Water Hammer Protection Effect in the Long-Distance Water Supply Systems
Authors: Wang Yiran , Yu Xiaodong , Liu Jiachun , Shi Lin , Zhang Jian
Published: October 2023

Long-distance water supply systems are important measures to improve the water resources distribution, and the water hammer protection devices such as air vessels are usually added in the project to ensure the safety and stable operation. However, the sediment particles are always ignored in the design. Hence, a numerical model and program were established for sediment laden water hammer based on the method of characteristics (MOC). Using the proposed model, the water hammer protection influences of sediment particles parameters are simulated for the same pipeline system of a water supply project. The result shows that the resistance loss of sediment-laden water in pipelines is larger than that of water, and the initial head of pump needed to be increased to ensure the water levels of downstream reservoirs are consistent. After power failure and pump stopping, the negative pressure wave of sediment-laden water is 2.97 m higher than that of water, and the theoretical minimum internal pressure along pipelines is 7.8 m lower. With the same air vessel protection, the lowest minimum internal pressure heads along pipelines decrease with the increase of quantities of sediment, while the results show no obvious influence by changes of median particle diameters. The lowest absolute pressure of pipeline could reach −0.69 m under the condition of 50 kg/m3 quantity of sediment and 0.05 mm median particle diameter. The relevant research results are of great significance sediment-laden water hammer numerical simulation and water hammer protection design.
Improving Weldability of Press Hardened Steel Through Combining Stepped Current Pulse and Magnetically Assisted Resistance Spot Welding Process
Authors: Li ZhuoRan , Zhang DianPing , Chen RuiMing , Wang SongLin , Xia YuJun , Lou Ming , Li YongBing
Published: October 2023

Press-hardened steel (PHS), characterized by its extremely high strength, has wide applications in vehicle body manufacturing as an innovative lightweight material. Nevertheless, the poor weldability of PHS results in poor weld toughness and a high risk of interfacial fracture (IF), posing challenges to the resistance spot welding (RSW) process. Introducing an external magnetic field in the welding process to perform electromagnetic stirring (EMS), the magnetically assisted RSW (MA-RSW) process has been proven an effective method to improve the weld toughness of high-strength steel, but it may increase the risk of expulsion. In response to these challenges, this study introduces a new process called SPMA-RSW to improve the weldability of PHS by combining MA-RSW and the stepped-current pulses (SP) technique, which can enlarge the weld lobe. Nugget appearance, microstructure, microhardness, and mechanical properties were systematically investigated by comparing traditional RSW, MA-RSW, SP-RSW, and SPMA-RSW. The result showed that the SPMA-RSW process would significantly increase the nugget size, inhibit the shrinkage voids, finer the grain size of PHS welds, and harden the nugget region. This increased the lap-shear strength and changed the fracture mode from brittle IF mode to ductile plug fracture (PF) mode at the same heat input. Specifically, the peak load and energy absorption were increased by 32.3% and 84.2%, respectively. Then, an analytical model was developed to reveal the mechanism of the effect of EMS on the fracture mode transition and was verified by experiment. This work can help improve the weld quality and thermal efficiency of the RSW process for PHS.
Exploring Physics of Acoustic Flow Control Over Airfoils Toward Potential Application to High Work and Lift Turbines
Authors: Celik Acar , Mitra Abhijit , Agarwal Tapish , Clark John , Jacobi Ian , Cukurel Beni
Published: October 2023

In this study, acoustic actuation was applied experimentally to massively separated flows on simplified hump geometries, which mimic the pressure distribution over high-work-and-lift low Reynolds airfoils. The acoustic excitation demonstrated significant control over flow separation, resulting in higher relative lift enhancement than standard, localized actuation techniques with similar momentum coefficients. Full-field velocity measurements were used to examine the transient behavior of the actuated flow in order to explain the physical mechanism of separation control. The velocity measurements revealed the presence of a viscous wall mode that organized the vorticity upstream of the separation point. A spatio-temporal correlation analysis found that the generation of these wall modes in the attached flow was the dominant cause of the subsequent reorganization of the separating shear layer and the change in separation dynamics. The importance of wall modes to acoustic flow control mechanism has important implications for the design of new acoustic control strategies for high-speed turbomachinery. Along these lines, the ramifications of this phenomena are explored over geometries, which are designed to approximate flow fields in high-speed turbomachinery. At the conducive Strouhal number, which scale linearly with the square root of Reynolds numbers, up to 22% lift enhancement is observed for excitation amplitudes in the range of ∼128 dB, typical to the engine environment. Of the many diverse flow control techniques, acoustics can be effectively employed in low Reynolds turbine blades, which are prone to flow separation in the off-design conditions with the ever increasing demand for higher flow turning.
Impacts of Injection Parameters on the Mixture Formation and Performance of Two-Stroke Spark-Ignition Direct-Injection Aviation Kerosene Engine
Authors: Wang Ying , Zhou Qiongyang
Published: October 2023

Two-stroke spark-ignition engines play a significant role in the field of power sources of small and medium unmanned aerial vehicles. There is a certain transition from burning gasoline to aviation kerosene (or heavy oil) and from carburetor or inlet injection system to direct-injection fuel system. However, the performance of two-stroke spark-ignition direct-injection engines fueled with aviation kerosene was not very ideal under heavy loads. Generally, the mixture formation is very important for engine combustion and performance, while injection parameters have great effects on mixture formation. Thus, various injection parameters of a two-stroke direct-injection kerosene engine were examined here. The results showed too early or too late injection timing (tinj) would deteriorate the mixture formation, resulting in lower brake power and brake thermal efficiency. Here the most suitable tinj was 150 deg CA BTDC. Too high or too low injection pressure (pinj) caused fuel short circuit loss and poor mixture quality, so the optimum pinj was 10 MPa. Too large injector installation angle (β) easily results in fuel spray impingement, and too small β causes fuel short circuit loss. Therefore, the best β was concluded to be 30 deg in this paper.
Multi-Objective Numerical Optimization of Radial Turbines
Authors: Fuhrer Christopher , Kovachev Nikola , Vogt Damian M. , Raja Mahalingam Ganesh , Mann Stuart
Published: October 2023

The growing demand of high flexibility and wide operating ranges of radial turbines in turbocharger applications necessitates new methods in the turbomachinery design process. Often, design criteria such as high performance at certain operating conditions or low inertia contradict the requirement for high durability. This article demonstrates a newly developed optimization approach for radial turbines that allows to optimize for several design objectives. The presented approach is based on a parametric model of the turbine wheel geometry. On the one hand, the model is designed to capture the most important geometry and design features, and on the other hand, it is flexible for use on various machines. A surrogate model-based genetic algorithm is used to optimize the geometries with respect to several objectives, including efficiency, durability (HCF), low-cycle fatigue (LCF), inertia, and mass. Certain operating points or criteria can be particularly emphasized and specified constraints throughout the process allow for customized optimization. The simulations underlying the optimization are state-of-the-art computational fluid dynamics (CFD) and finite element (FE) analyses, involving the respective components. The newly developed and fully automated approach includes tasks of different disciplines. In the end, a selection of several promising geometries is examined more intimately to finally find a most suitable geometry for the given application. For the current study, this geometry has been manufactured and tested on a hot gas test facility to successfully validate the design process.
U.S. High School Coaches’ Knowledge, Perception, and Current Practices Regarding Exertional Heat Illness
Authors: Thompson Bailey , Hillman Angela R. , Payne Ellen K.
Published: October 2023

Exertional heat illness (EHI) is a dangerous, but preventable and treatable condition that affects approximately 9,000 athletes each year in the United States. Unfortunately, less than 30% of schools in the United States have access to an athletic trainer, making coaches responsible for the safety of the athletes during practices and games. The purpose of this study was to evaluate the knowledge, perception, and procedures of high school coaches in the United States regarding heat illness recognition, prevention, and treatment. An online survey including Likert items and open-ended questions was completed by 1,676 coaches from 16 states and compared between age, coaching experience, gender, education level, experience handling EHI, state, and the completion of either a general coaching certification or a heat safety certification. Average knowledge score among coaches was 74%. Coaches with experience handling or witnessing EHI, more years of coaching experience, older age, and the completion of a coaching certification had significantly higher level of knowledge than others. Results revealed that evidence-based strategies and state mandates aimed at preventing EHI are not being implemented. More training in prevention, recognition, and treatment of EHI is necessary for all individuals involved with high school athletes to prevent avoidable deaths.
Incorporating Mental Health Literacy Into the Sport Management Curriculum
Authors: Beasley Lauren , Cox Amy E. , Hardin Robin
Published: October 2023

Mental health is an emerging area of interest in sport, but there is a paucity of educational initiatives in sport management curricula to train the next generation of sport managers to address the mental health needs of athletes, a type of knowledge that the mental health literature operationalizes as mental health literacy. One goal of accrediting bodies such as the Commission on Sport Management Accreditation is for excellence in sport management education; thus, due to the changing landscape of sport, sport management curricula should incorporate mental health literacy competencies. This educational research review provides justification for the inclusion of mental health literacy competencies in sport management curricula and accreditation standards, as well as pedagogical strategies for implementation.
The Case for Marxist–Leninist Sport: Going Beyond the Limitations of Western Liberalism
Authors: Mwaniki Munene
Published: October 2023

The sociology of sport has developed within and been intricately involved in the critique of neoliberalism. While important, there are certain limitations to this scholarship that are related to the nature of Western liberalism and academia. This paper attempts to argue a role for Marxist–Leninist thought in the sociology of sport. Historically excluded from academia after World War II, this bias is part of what Gabriel Rockhill has described as the “Global Theory Industry,” that decries socialism while remaining favorable to Western liberal capitalism. The anti-communism of the theory industry means that much of the work on neoliberalism and Marxism in the sociology of sport has ignored the experiences and efforts of socialist countries, as well as theorists from the Global South. This article broadly critiques existing neoliberal and Marxist studies of sport while arguing that a Marxist–Leninist approach may give those in the field a better account of sport and its relationship to domestic and global politics.
A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options
Authors: Sun Lulu , Kang Xindan , Ju Houyu , Wang Chong , Yang Guizhu , Wang Rui , Sun Shuyang
Published: October 2023

Mucosal melanoma (MM), an aggressive rare subtype of melanoma, is distinct from cutaneous melanoma and has poor prognoses. We addressed the lack of cell models for MM by establishing 30 organoids of human oral MM (OMM), which retained major histopathological and functional features of parental tumors. Organoid groups derived from chronologically or intratumorally distinct lesions within the same individual displayed heterogeneous genetics, expression profiles, and drug responses, indicating rapid tumor evolution and poor clinical response. Furthermore, transcriptome analysis revealed receptor tyrosine kinases (RTKs) signaling, particularly
NGFR
, a nerve growth factor receptor, was significantly up-regulated in OMMs and organoids from patients resistant to anti–programmed cell death protein 1 (anti–PD-1) therapy. Combining anti–PD-1 with anlotinib (a phase 2 multitarget RTK inhibitor for OMM) or NGFR knockdown enhanced the effective activity of immune cells in organoid–immune cell coculture systems. Together, our study suggested that OMM organoids serve as faithful models for exploring tumor evolution and immunotherapy combination strategies.
BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination
Authors: Ghouil Rania , Miron Simona , Sato Koichi , Ristic Dejan , van Rossum-Fikkert Sari E. , Legrand Pierre , Ouldali Malika , Winter Jean-Marie , Ropars Virginie , David Gabriel , Arteni Ana-Andreea , Wyman Claire , Knipscheer Puck , Kanaar Roland , Zelensky Alex N. , Zinn-Justin Sophie
Published: October 2023

In meiotic homologous recombination (HR), BRCA2 facilitates loading of the recombinases RAD51 and DMC1 at the sites of double-strand breaks (DSBs). The HSF2BP-BRME1 complex interacts with BRCA2. Its absence causes a severe reduction in recombinase loading at meiotic DSB. We previously showed that, in somatic cancer cells ectopically producing HSF2BP, DNA damage can trigger HSF2BP-dependent degradation of BRCA2, which prevents HR. Here, we report that, upon binding to BRCA2, HSF2BP forms octameric rings that are able to interlock into a large ring-shaped 24-nucleotide oligomer. Addition of BRME1 leads to dissociation of both of these ring structures and cancels the disruptive effect of HSF2BP on cancer cell resistance to DNA damage. It also prevents BRCA2 degradation during interstrand DNA crosslink repair in
Xenopus
egg extracts. We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.
Subglacial discharge accelerates future retreat of Denman and Scott Glaciers, East Antarctica
Authors: Pelle Tyler , Greenbaum Jamin S. , Dow Christine F. , Jenkins Adrian , Morlighem Mathieu
Published: October 2023

Ice shelf basal melting is the primary mechanism driving mass loss from the Antarctic Ice Sheet, yet it is unknown how the localized melt enhancement from subglacial discharge will affect future Antarctic glacial retreat. We develop a parameterization of ice shelf basal melt that accounts for both ocean and subglacial discharge forcing and apply it in future projections of Denman and Scott Glaciers, East Antarctica, through 2300. In forward simulations, subglacial discharge accelerates the onset of retreat of these systems into the deepest continental trench on Earth by 25 years. During this retreat, Denman Glacier alone contributes 0.33 millimeters per year to global sea level rise, comparable to half of the contemporary sea level contribution of the entire Antarctic Ice Sheet. Our results stress the importance of resolving complex interactions between the ice, ocean, and subglacial environments in future Antarctic Ice Sheet projections.
Selective control of transposable element expression during T cell exhaustion and anti–PD-1 treatment
Authors: Bonté Pierre-Emmanuel , Metoikidou Christina , Heurtebise-Chretien Sandrine , Arribas Yago A. , Sutra Del Galy Aurélien , Ye Mengliang , Niborski Leticia Laura , Zueva Elina , Piaggio Eliane , Seguin-Givelet Agathe , Girard Nicolas , Alanio Cécile , Burbage Marianne , Goudot Christel , Amigorena Sebastian
Published: October 2023

In chronic infections and cancer, T cells are exposed to prolonged antigen stimulation, resulting in loss of function (or exhaustion) and impairment of effective immunological protection. Exhausted T cells are heterogeneous and include early progenitors (Tpex) and terminally exhausted cells (Tex). Here, we used bulk and single-cell transcriptomics to analyze expression of transposable elements (TEs) in subpopulations of mouse and human CD8
+
tumor-infiltrating T lymphocytes (TILs). We show that in mice, members of the virus-like murine VL30 TE family (mostly intact, evolutionary young ERV1s) are strongly repressed in terminally exhausted CD8
+
T cells in both tumor and viral models of exhaustion. Tpex expression of these VL30s, which are mainly intergenic and transcribed independently of their closest gene neighbors, was driven by Fli1, a transcription factor involved in progression from Tpex to Tex. Immune checkpoint blockade (ICB) in both mice and patients with cancer increased TE expression (including VL30 in mice), demonstrating that TEs may be applicable as ICB response biomarkers. We conclude that expression of TEs is tightly regulated in TILs during establishment of exhaustion and reprogramming by ICB. Analyses of TE expression on single cells and bulk populations open opportunities for understanding immune cell identity and heterogeneity, as well as for defining cellular gene expression signatures and disease biomarkers.
Safety of early oral ambulatory treatment of adult patients with bloodstream infections discharged from the emergency department
Authors: Casado Ana , Gimeno Adelina , Aguilar-Guisado Manuela , García Manuel , Rodríguez Jesús Francisco , Rivas Pedro Antonio , Bueno Claudio , Lepe Jose Antonio , Cisneros José Miguel , Molina José
Published: October 2023

This study evaluates the safety of early oral ambulatory treatment of adult patients diagnosed with bacteremia after their discharge from the emergency department. A cohort of 206 febrile ambulatory patients was assessed. Bacteremic low-risk patients were recommended an oral treatment and were compared with matched febrile non-bacteremic outpatients. Rates of 14-day mortality and unplanned re-consultations were similar and below 5% in both cohorts, highlighting the safety of oral therapy of low-risk bacteremia, even from its onset.
Development of a dual fluorescent reporter system to identify inhibitors of
Staphylococcus aureus
virulence factors
Authors: Tao Zhanhua , Ke Ke , Shi Deqiang , Zhu Libo
Published: October 2023

Staphylococcus aureus
is a leading cause of bacterial infections due to its resistance to most antibiotics and the production of diverse virulence factors. Various alternative approaches to treating staphylococcal infections have been proposed, including targeting the virulence factors or mechanisms that regulate their synthesis. The accessory gene regulator (
agr
) and the
S. aureus
exoprotein expression (
sae
) are two major virulence regulators of
S. aureus
. Here, we describe a dual reporter system capable of simultaneously monitoring the transcriptional activities of
agr
and
sae
in
S. aureus
. The reporter plasmid contained two fluorescent protein cassettes arranged back-to-back, with the mCherry cassette driven by the
agr
P3 promoter and the GFP cassette driven by the
sbi
promoter. We examined the fluorescent responses of wild-type,
agr
, and
sae
mutant strains using fluorescence microscopy and found that the activities of
agr
and
sae
systems could be detected without significant crosstalk in the dual reporter strain. The dual reporter system could be used to monitor the dynamic changes in
agr
and
sae
activities during batch growth in
S. aureus
. Additionally, we evaluated the responsiveness of the reporter strain to virulence inhibitors by treating it with several known inhibitors, including autoinducing peptides (AIPs) containing culture supernatants, indole, and flavone. The results suggested that the dual reporter system was sensitive to both
agr
and
sae
inhibitors. This reporter construct enables the characterization of the activity of a substance against two different targets in one screening round, significantly reducing screening time and expense.

IMPORTANCE

Staphylococcus aureus
is a formidable pathogen responsible for a wide range of infections, and the emergence of antibiotic-resistant strains has posed significant challenges in treating these infections. In this study, we have established a novel dual reporter system capable of concurrently monitoring the activities of two critical virulence regulators in
S. aureus
. By incorporating both reporters into a single screening platform, we provide a time- and cost-efficient approach for assessing the activity of compounds against two distinct targets in a single screening round. This innovative dual reporter system presents a promising strategy for the identification of molecules capable of modulating virulence gene expression in
S. aureus
, potentially expediting the development of antivirulence therapies.
Preclinical screen for protection efficacy of chlamydial antigens that are immunogenic in humans
Authors: Lu Chunxue , Wang Jie , Zhong Guangming
Published: October 2023

To search for subunit vaccine candidates, immunogenic chlamydial antigens identified in humans were evaluated for protection against both infection and pathology in a mouse genital tract infection model under three different immunization regimens. The intramuscular immunization regimen was first used to evaluate 106 chlamydial antigens, which revealed that two antigens significantly reduced while 11 increased genital chlamydial burden. The two infection-reducing antigens failed to prevent pathology and 23 additional antigens even exacerbated pathology. Thus, intranasal mucosal immunization was tested next since intranasal inoculation with live
Chlamydia muridarum
prevented both genital infection and pathology. Two of the 29 chlamydial antigens evaluated were found to prevent genital infection but not pathology and three exacerbate pathology. To further improve protection efficacy, a combinational regimen (intranasal priming + intramuscular boosting + a third intraperitoneal/subcutaneous boost) was tested. This regimen identified four infection-reducing antigens, but only one of them prevented pathology. Unfortunately, this protective antigen was not advanced further due to its amino acid sequence homology with several human molecules. Two pathology-exacerbating antigens were also found. Nevertheless, intranasal mucosal priming with viable
C. muridarum
in control groups consistently prevented both genital infection and pathology regardless of the subsequent boosters. Thus, screening 140 different chlamydial antigens with 21 repeated multiple times in 17 experiments failed to identify a subunit vaccine candidate but demonstrated the superiority of viable chlamydial organisms in inducing immunity against both genital infection and pathology, laying the foundation for developing a live-attenuated Chlamydia vaccine.
Complex norovirus transmission dynamics at hospital wards revealed by deep sequencing
Authors: Widström Julia , Andersson Maria E. , Westin Johan , Wahllöf Martina , Lindh Magnus , Rydell Gustaf E.
Published: October 2023

Detailed knowledge regarding norovirus transmission within hospitals is limited. We investigated a norovirus hospital outbreak affecting 65 patients at five different wards. PCR showed that 61 (94%) of the patients were infected with genotype II.4 strains. Successful Ion Torrent deep sequencing of GII.4 positive samples from 59 patients followed by phylogenetic analysis revealed that all sequences but two clustered into four distinct clades. Two of the clades belonged to GII.4 Sydney 2012, while the other two belonged to GII.4 New Orleans 2009. One of the clades was predominant at two wards, while two clades were predominant at one ward each. The fourth clade was found in sporadic cases at several wards. Thus, at four out of five wards, variants from one clade were predominant. At one ward, a single clade accounted for all cases, while at three wards the predominant clade accounted for 60%–71% of cases. Analysis of quasispecies variation identified positions that could further discriminate between variants from separate wards. The results illustrate a complex transmission of healthcare-associated norovirus infections and show that sequencing can be used to discriminate between related and unrelated cases.
Valid and accepted novel bacterial taxa derived from human clinical specimens and taxonomic revisions published in 2022
Authors: Munson Erik , Carella Arianna , Carroll Karen C.
Published: October 2023

Although some nomenclature changes have caused consternation among clinical microbiologists, the discovery of novel taxa and improving classification of existing groups of organisms is exciting and adds to our understanding of microbial pathogenesis. In this mini-review, we present an in-depth summary of novel taxonomic designations and revisions to prokaryotic taxonomy that were published in 2022. Henceforth, these bacteriology taxonomic summaries will appear annually. Several of the novel Gram-positive organisms have been associated with disease, namely, the
Corynebacterium kroppenstedtii
-like organisms
Corynebacterium parakroppenstedtii
sp. nov. and
Corynebacterium pseudokroppenstedtii
sp. nov. A newly described
Streptococcus
species,
Streptococcus toyakuensis
sp. nov., is noteworthy for exhibiting multi-drug resistance. Among the novel Gram-negative pathogens,
Vibrio paracholerae
sp. nov. stands out as an organism associated with diarrhea and sepsis and has probably been co-circulating with pandemic
Vibrio cholerae
for decades. Many new anaerobic organisms have been described in this past year largely from genetic assessments of gastrointestinal microbiome collections. With respect to revised taxa, as discussed in previous reviews, the genus
Bacillus
continues to undergo further division into additional genera and reassignment of existing species into them. Reassignment of two subspecies of
Fusobacterium nucleatum
to species designations (
Fusobacterium animalis
sp. nov. and
Fusobacterium vincentii
sp. nov.) is also noteworthy. As was typical of previous reviews, literature updates for selected clinically relevant organisms discovered between 2017 and 2021 have been included.
Update on novel validly published taxa of bacteria isolated from domestic animals described in 2022
Authors: Lawhon Sara D. , Burbick Claire R. , Munson Erik , Thelen Elizabeth , Zapp Amanda , Wilson Anastasia
Published: October 2023

Expansion of our knowledge of the microbial world continues to progress at a rapid rate and carries with it an associated need for recognizing and understanding the implications of those changes. Here, we describe additions of novel taxa from domestic animals published in 2022 that are validly published per the International Code of Nomenclature of Prokaryotes. These included new members of
Staphylococcaceae
,
Moraxella nasovis
sp. nov. in sheep with respiratory disease, three additions to
Campylobacteraceae
(including one from chickens with spotty liver disease), and multiple additions of organisms from the microbiota of dogs, pigs, and especially honeybees and other important pollinators. Noteworthy additions were associated with diseases of cattle, including mastitis, endocarditis, orchitis, and endometritis. Also described in 2022 was
Pseudochrobactrum algeriense
sp. nov., a member of the
Brucellaceae
family, isolated from the mammary lymph nodes of cows.
Benchmarking of virome metagenomic analysis approaches using a large, 60+ members, viral synthetic community
Authors: Schönegger Deborah , Moubset Oumaima , Margaria Paolo , Menzel Wulf , Winter Stephan , Roumagnac Philippe , Marais Armelle , Candresse Thierry
Published: October 2023

In contrast to microbial metagenomics, there has still been only limited efforts to benchmark performance of virome analysis approaches in terms of faithfulness to community structure and of completeness of virome description. While natural communities are more readily accessible, synthetic communities assembled using well-characterized isolates allow more accurate performance evaluation. Starting from authenticated, quality-controlled reference isolates from the DSMZ Plant Virus Collection, we have assembled synthetic communities of varying complexity up to a highly complex community of 72 viral agents (115 viral molecules) comprising isolates from 21 viral families and 61 genera. These communities were then analyzed using two approaches frequently used in ecology-oriented plant virus metagenomics: a virion-associated nucleic acids (VANA)-based strategy and a highly purified double-stranded RNAs (dsRNAs)-based one. The results obtained allowed to compare diagnostic sensitivity of these two approaches for groups of viruses and satellites with different genome types and confirmed that the dsRNA-based approach provides a more complete representation of the RNA virome. However, for viromes of low to medium complexity, VANA appears a reasonable alternative and would be the preferred choiceif analysis of DNA viruses is of importance. They also allowed to identify several important parameters and to propose hypotheses to explain differences in performance, in particular, differences in the imbalance in the representation of individual viruses using each approach. Remarkably, these analyses highlight a strong direct relationship between the completeness of virome description and sample sequencing depth which should prove useful in further virome analysis efforts.

IMPORTANCE

We report here efforts to benchmark performance of two widespread approaches for virome analysis, which target either virion-associated nucleic acids (VANA) or highly purified double-stranded RNAs (dsRNAs). This was achieved using synthetic communities of varying complexity levels, up to a highly complex community of 72 viral agents (115 viral molecules) comprising isolates from 21 families and 61 genera of plant viruses. The results obtained confirm that the dsRNA-based approach provides a more complete representation of the RNA virome, in particular, for high complexity ones. However, for viromes of low to medium complexity, VANA appears a reasonable alternative and would be the preferred choice if analysis of DNA viruses is of importance. Several parameters impacting performance were identified as well as a direct relationship between the completeness of virome description and sample sequencing depth. The strategy, results, and tools used here should prove useful in a range of virome analysis efforts.
KSHV RTA utilizes the host E3 ubiquitin ligase complex RNF20/40 to drive lytic reactivation
Authors: Spires Lauren McKenzie , Wind Eleanor , Papp Bernadett , Toth Zsolt
Published: October 2023

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus whose lytic replication cycle is induced and driven by the viral transcription factor RTA (replication and transcription activator). Identifying what cellular and viral proteins RTA is interacting with during lytic reactivation can help to better understand how RTA promotes the lytic cycle. Using a proteomic approach, we identified the cellular E3 ubiquitin ligase complex RNF20/40 as a novel interacting partner of RTA. One of the major roles of this protein complex is the monoubiquitylation of histone H2B at lysine 120 on cellular chromatin, which is a hallmark of transcriptionally active genes. While the role of RNF20/40 has been studied on different host genomes, its potential to regulate viral genes remains largely unexplored. Here, we show that the shRNA inhibition of RNF20 expression impairs RTA-induced host and viral lytic gene expression, viral DNA replication, and virus production. In addition, we found that the association of RNF20 with the KSHV episome increases during lytic reactivation, and the binding of RTA to viral promoters is required for the synergistic promoter activation by RTA and RNF20/40. Interestingly, the inhibition of RNF20 expression during lytic reactivation of KSHV did not affect H2BK120ub level but it did reduce RNA polymerase II occupancy on viral promoters. Overall, our data suggest that RTA is hijacking the cellular E3 ligase complex RNF20/40 to increase the level of transcriptionally active RNA polymerase II on viral gene promoters thereby facilitating lytic gene expression to advance the viral lytic cycle.

IMPORTANCE

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-causing human herpesvirus that establishes a persistent infection in humans. The lytic viral cycle plays a crucial part in lifelong infection as it is involved in the viral dissemination. The master regulator of the KSHV lytic replication cycle is the viral replication and transcription activator (RTA) protein, which is necessary and sufficient to push the virus from latency into the lytic phase. Thus, the identification of host factors utilized by RTA for controlling the lytic cycle can help to find novel targets that could be used for the development of antiviral therapies against KSHV. Using a proteomics approach, we have identified a novel interaction between RTA and the cellular E3 ubiquitin ligase complex RNF20/40, which we have shown to be necessary for promoting RTA-induced KSHV lytic cycle.
Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study
Authors: Gurram Venkata Sujith Kumar Reddy , Lodha Abhay , Hicks Matthew , Jain Amish , Lapointe Anie , Makary Hala , Kanungo Jaideep , Lee Kyong-Soon , Ye Xiang , Shah Prakesh S , Soraisham Amuchou S
Published: October 2023

Objective

To assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).

Methods

In this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18–24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO.

Results

Of the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18–24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12).

Conclusions

In preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18–24 months CA.
Xylitol for the prevention of acute otitis media episodes in children aged 1–5 years: a randomised controlled trial
Authors: Persaud Navindra , Azarpazhooh Amir , Keown-Stoneman Charles , Birken Catherine S , Isaranuwatchai Wanrudee , Maguire Jonathon L , Mamdani Muhammad , Allen Christopher , Mason Dalah , Kowal Christine , Jaleel Mateenah , Bazeghi Farnaz , Thorpe Kevin E , Laupacis Andreas , Parkin Patricia C
Published: October 2023

Objective

To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries.

Design

Blinded randomised controlled trial with a 6-month study period.

Setting

Enrolment took place at 11 primary care practices in Ontario, Canada.

Patients

Children aged 1–5 years who did not use xylitol or sorbitol at enrolment.

Interventions

Children were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months.

Main outcome measures

Primary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries.

Results

Among the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol).

Conclusions

Regular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious.

Trial registration number

NCT03055091.
Outcomes of low-level light therapy before and after cataract surgery for the prophylaxis of postoperative dry eye: a prospective randomised double-masked controlled clinical trial
Authors: Giannaccare Giuseppe , Rossi Costanza , Borselli Massimiliano , Carnovale Scalzo Giovanna , Scalia Giovanni , Pietropaolo Rocco , Fratto Benedetta , Pellegrini Marco , Yu Angeli Christy , Scorcia Vincenzo
Published: October 2023

Background

Despite increasing evidence shows that optimising ocular surface before cataract surgery is fundamental in patients with pre-existing dry eye disease (DED) to achieve the desired postoperative outcomes, the prophylactic treatment of healthy patients undergoing surgery aiming at preventing iatrogenic DED is worth investigating.

Methods

This was a prospective, interventional, randomised, controlled, double-masked clinical trial. Patients were randomly assigned 1:1 to receive either low-level light therapy (LLLT) or sham treatment (LLLT with a power output <30%). Patients underwent two treatment sessions: 7±2 days before cataract surgery (T0) and 7±2 days after (T1). Outcome measures evaluated 30±4 days after surgery (T2) included Ocular Surface Disease Index (OSDI) questionnaire, non-invasive break-up time (NIBUT), tear meniscus height, meibomian gland loss (MGL) and redness score.

Results

Out of 153 patients randomised to receive LLLT (n=73) or sham treatment (n=80), 131 (70 men, 61 women, mean age 73.53±7.29 years) completed regularly the study. Patients treated with LLLT had significantly lower OSDI scores compared with controls at T1 and T2 (respectively, 7.2±8.8 vs 14.8±13.0 and 9.0±9.0 vs 18.2±17.9; both p<0.001), higher NIBUT values at T2 (12.5±6.6 vs 9.0±7.8; p=0.007) and lower MGL Meiboscore values at T1 (1.59±0.70 vs 1.26±0.69; p=0.008). Unlike controls, patients treated with LLLT had significantly lower OSDI scores and higher NIBUT values at T2 compared with T0 (respectively, 9.0±9.0 vs 21.2±16.1; p<0.001 and 12.5±6.6 vs 9.7±7.2; p=0.007).

Conclusion

Two sessions of LLLT performed before and after cataract surgery were effective in ameliorating tear film stability and ocular discomfort symptoms.

Trial registration number

NCT05754437.
Ultrasound Directed Reduction of Colles’ type distal radial fractures in ED (UDiReCT): a feasibility randomised controlled trial
Authors: Malik Hamza , Wood Darryl , Stone Oliver , Gough Anthony , Taylor Gordon , Knapp Karen M , Heggs Daniel , Appelboam Andrew
Published: October 2023

Background

There is a high rate of surgical fixation of displaced Colles’ type distal radial wrist fractures despite fracture manipulation in the ED. Point-of-care ultrasound has been used to guide ED manipulations but its effect on the quality of fracture reduction or subsequent need for surgical fixation is unknown. This study aims to assess the feasibility of conducting a definitive randomised controlled trial to assess the use of ultrasound to guide these fracture manipulations.

Methods

We conducted a pragmatic randomised controlled feasibility trial in two EDs in England over a 6-month period (7 October 2019 to 6 April 2020). Adult patients with wrist fractures undergoing manipulation in the ED were randomised 1:1 to ultrasound-guided distal radial fracture manipulation or manipulation with sham ultrasound. The primary outcome for this study was trial recruitment rate. Other measures were recorded to assess potential future definitive trial outcomes and feasibility.

Results

Of 120 patients meeting inclusion criteria, 48 (40%) were recruited and randomised in the two centres, giving overall recruitment rates of 0.3 and 1.8 participants per week at each site, respectively, and 1 participant per week overall. The most common reason that patients were not included was research staff availability. After 6 weeks, six patients in each group (26% intervention, 24% control) had undergone surgical fixation, with 98% data completeness for this potential definitive trial primary outcome. Randomisation, blinding and data collection processes were effective but there were data limitations in the X-ray assessment of fracture positions.

Conclusion

A definitive study of a similar design would be feasible within UK ED practice but organisational factors and research staff availability should be considered when estimating the predicted recruitment rate and required sites. 6-week surgical fixation rate was the most reliable outcome measure.

Trial registration

ClinicalTrials.gov (NCT03868696).
Drop attacks: a practical guide
Authors: Manford Evelyn , Garg Anupam , Manford Mark
Published: October 2023

‘Drop attacks’ encompass both falls and transient loss of consciousness, but the term is not clearly defined. We offer our definition and explore the differential diagnoses. The most common causes are cardiovascular. We discuss clinical and electrographic criteria that suggest underlying arrhythmia or other serious cardiac disorders that require further investigation, and the potential diagnoses that may underlie these ‘worrying syncopes’. Vestibular dysfunction also commonly causes collapses, sometimes without typical vertigo. These two common conditions may coexist especially in the elderly. Falls in elderly people often require assessment through a lens of frailty and multifactorial risk factors, rather than seeking a unitary diagnosis. Some drop attacks may be due to longstanding epilepsy and we discuss how to approach these cases. Functional neurological disorder is a common cause in younger people, for which there may also be clinical clues. We review the rarer causes of collapse that may be described as drop attacks, including cataplexy and hydrocephalic attacks.