bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virulence and transmission biology of the widespread, ecologically important pathogen of zooplankton,
Spirobacillus cienkowskii
Authors: Wale Nina , Freimark Claire B. , Ramirez Justin , Dziuba Marcin K. , Kafri Ahmad Y. , Bilich Rebecca , Duffy Meghan A. 
Published: September 2024

ABSTRACT

Spirobacillus cienkowskii
(
Spirobacillus,
hereafter) is a widely distributed bacterial pathogen that has significant impacts on the population dynamics of zooplankton (
Daphnia spp
.)
,
particularly in months when
Daphnia
are asexually reproducing. However, little is known about
Spirobacillus’
virulence, transmission mode, and dynamics. As a result, we cannot explain the dynamics of
Spirobacillus
epidemics in nature or use
Spirobacillus
as a model pathogen, despite
Daphnia’s
tractability as a model host. Here, we work to fill these knowledge gaps experimentally. We found that
Spirobacillus
is among the most virulent of
Daphnia
pathogens, killing its host within a week and reducing host fecundity. We further found that
Spirobacillus
did not transmit horizontally among hosts unless the host died or was destroyed (i.e., it is an “obligate killer”). In experiments aimed at quantifying the dynamics of horizontal transmission among asexually reproducing
Daphnia
, we demonstrated that
Spirobacillus
transmits poorly in the laboratory. In mesocosms,
Spirobacillus
failed to generate epidemics; in experiments wherein individual
Daphnia
were exposed,
Spirobacillus’
transmission success was low. In the (limited) set of conditions we considered,
Spirobacillus’
transmission success did not change with host density or pathogen dose and declined following environmental incubation. Finally, we conducted a field survey of
Spirobacillus’
prevalence within egg cases (ephippia) made by sexually reproducing
Daphnia
. We found
Spirobacillus
DNA in ~40% of ephippia, suggesting that, in addition to transmitting horizontally among asexually reproducing
Daphnia
,
Spirobacillus
may transmit vertically from sexually reproducing
Daphnia
. Our work fills critical gaps in the biology of
Spirobacillus
and illuminates new hypotheses vis-à-vis its life history.

IMPORTANCE

Spirobacillus cienkowskii
is a bacterial pathogen of zooplankton, first described in the 19
th
century and recently placed in a new family of bacteria, the
Silvanigrellaceae
.
Spirobacillus
causes large epidemics in lake zooplankton populations and increases the probability that zooplankton will be eaten by predators. However, little is known about how
Spirobacillus
transmits among hosts, to what extent it reduces host survival and reproduction (i.e., how virulent it is), and what role virulence plays in
Spirobacillus
’ life cycle. Here, we experimentally quantified
Spirobacillus’
virulence and showed that
Spirobacillus
must kill its host to transmit horizontally. We also found evidence that
Spirobacillus
may transmit vertically via
Daphnia’
s seed-like egg sacks. Our work will help scientists to (i) understand
Spirobacillus
epidemics, (ii) use
Spirobacillus
as a model pathogen for the study of host-parasite interactions, and (iii) better understand the unusual group of bacteria to which
Spirobacillus
belongs.
PRRSV non-structural protein 5 inhibits antiviral innate immunity by degrading multiple proteins of RLR signaling pathway through FAM134B-mediated ER-phagy
Authors: Wang Jing , Sun Huiqin , Li Rui , Xu Shixuan , Guo Junqing , Xing Guangxu , Jia Bin , Qiao Songlin , Chen Xin-xin , Zhang Gaiping 
Published: September 2024

ABSTRACT

Viruses employ various evasion strategies to establish prolonged infection, with evasion of innate immunity being particularly crucial. Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in swine industry, characterized by reproductive failures in sows and respiratory distress in pigs of all ages, leading to substantial economic losses globally. In this study, we found that the non-structural protein 5 (Nsp5) of PRRSV antagonizes innate immune responses via inhibiting the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs), which is achieved by degrading multiple proteins of RIG-I-like receptor (RLR) signaling pathway (RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7). Furthermore, we showed that PRRSV Nsp5 is located in endoplasmic reticulum (ER), where it promotes accumulation of RLR signaling pathway proteins. Further data demonstrated that Nsp5 activates reticulophagy (ER-phagy), which is responsible for the degradation of RLR signaling pathway proteins and IFN-I production. Mechanistically, Nsp5 interacts with one of the ER-phagy receptor family with sequence similarity 134 member B (FAM134B), promoting the oligomerization of FAM134B. These findings elucidate a novel mechanism by which PRRSV utilizes FAM134B-mediated ER-phagy to elude host antiviral immunity.

IMPORTANCE
Innate immunity is the first line of host defense against viral infections. Therefore, viruses developed numerous mechanisms to evade the host innate immune responses for their own benefit. PRRSV, one of the most important endemic swine viruses, poses a significant threat to the swine industry worldwide. Here, we demonstrate for the first time that PRRSV utilizes its non-structural protein Nsp5 to degrade multiple proteins of RLR signaling pathways, which play important roles in IFN-I production. Moreover, FAM134B-mediated ER-phagy was further proved to be responsible for the protein’s degradation. Our study highlights the critical role of ER-phagy in immune evasion of PRRSV to favor replication and provides new insights into the prevention and control of PRRSV.
Genetic characteristics of human parainfluenza viruses 1–4 associated with acute lower respiratory tract infection in Chinese children, during 2015–2021
Authors: Zhu Yun , Sun Yun , Li Changchong , Lu Gen , Jin Rong , Xu Baoping , Shang Yunxiao , Ai Junhong , Wang Ran , Duan Yali , Chen Xiangpeng , Xie Zhengde 
Published: September 2024

ABSTRACT

Human parainfluenza viruses (HPIVs) are a significant cause of acute lower respiratory tract infections (ALRTIs) among young children and elderly individuals worldwide. The four types of HPIVs (HPIV1–4) can cause recurrent infections and pose a significant economic burden on health care systems globally. However, owing to the limited availability of complete genome sequences, the genetic evolution of these viruses and the development of vaccines and antiviral treatments are hampered. To address this issue, this study utilized next-generation sequencing to obtain 156 complete genome sequences of HPIV1–4, which were isolated from hospitalized children with ALRTIs in six regions of China between 2015 and 2021. This study revealed multiple clades, lineages, or sublineages of HPIVs circulating in mainland China, with a novel clade D of HPIV1 identified as geographically restricted to China. Moreover, this study identified the endemic dominant genotype of HPIV3, lineage C3, which has widely spread and continuously circulated in China. Bioinformatic analysis of the genome sequences revealed that the proteins of HPIV3 possessed the most variable sites, with the P protein showing more diversity than the other proteins among all types of HPIVs. The HN proteins of HPIV1–3 are all under negative/purifying selection, and two amino acid substitutions in the HN proteins correspond to known mAb neutralizing sites in the two HPIV3 strains. These findings provide crucial insights into the genetic diversity and evolutionary dynamics of HPIVs circulating among children in China and may facilitate research on the molecular diagnosis, vaccine development, and surveillance of HPIVs.

IMPORTANCE
Phylogenetic analysis revealed the prevalence of multiple clades, lineages, or sublineages of human parainfluenza viruses (HPIVs) circulating in mainland China. Notably, a unique evolutionary branch of HPIV1 containing only Chinese strains was identified and designated clade D. Furthermore, in 2023, HPIV3 strains from Pakistan and Russia formed a new lineage within clade C, named C6. The first HPIV4b sequence obtained in this study from China belongs to lineage C2. Evolutionary rate assessments revealed that both the HN and whole-genome sequences of HPIV3 presented the lowest evolutionary rates compared with those of the other HPIV types, with rates of 6.98E−04 substitutions/site/year (95% HPD: 5.87E−04 to 8.25E−03) and 5.85E−04 substitutions/site/year (95% HPD: 5.12E−04 to 6.62E−04), respectively. Recombination analysis revealed a potential recombination event in the F gene of an HPIV1 strain in this study. Additionally, all the newly obtained HPIV1–3 strains exhibited negative selection pressure, and two mutations were identified in the HN protein of two HPIV3 strains at monoclonal antibody-binding sites.
Exploring pangenomic diversity and CRISPR-Cas evasion potential in jumbo phages: a comparative genomics study
Authors: Magar Sharayu , Kolte Vaishnavi , Sharma Gaurav , Govindarajan Sutharsan 
Published: September 2024

ABSTRACT

Jumbo phages are characterized by their remarkably large-sized genome and unique life cycles. Jumbo phages belonging to Chimalliviridae family protect the replicating phage DNA from host immune systems like CRISPR-Cas and restriction-modification system through a phage nucleus structure. Several recent studies have provided new insights into jumbo phage infection biology, but the pan-genome diversity of jumbo phages and their relationship with CRISPR-Cas targeting beyond Chimalliviridae are not well understood. In this study, we used pan-genome analysis to identify orthologous gene families shared among 331 jumbo phages with complete genomes. We show that jumbo phages lack a universally conserved set of core genes but identified seven “soft-core genes” conserved in over 50% of these phages. These genes primarily govern DNA-related activities, such as replication, repair, or nucleotide synthesis. Jumbo phages exhibit a wide array of accessory and unique genes, underscoring their genetic diversity. Phylogenetic analyses of the soft-core genes revealed frequent horizontal gene transfer events between jumbo phages, non-jumbo phages, and occasionally even giant eukaryotic viruses, indicating a polyphyletic evolutionary nature. We categorized jumbo phages into 11 major viral clusters (VCs) spanning 130 sub-clusters, with the majority being multi-genus jumbo phage clusters. Moreover, through the analysis of hallmark genes related to CRISPR-Cas targeting, we predict that many jumbo phages can evade host immune systems using both known and yet-to-be-identified mechanisms. In summary, our study enhances our understanding of jumbo phages, shedding light on their pan-genome diversity and remarkable genome protection capabilities.

IMPORTANCE
Jumbo phages are large bacterial viruses known for more than 50 years. However, only in recent years, a significant number of complete genome sequences of jumbo phages have become available. In this study, we employed comparative genomic approaches to investigate the genomic diversity and genome protection capabilities of the 331 jumbo phages. Our findings revealed that jumbo phages exhibit high genetic diversity, with only a few genes being relatively conserved across jumbo phages. Interestingly, our data suggest that jumbo phages employ yet-to-be-identified strategies to protect their DNA from the host immune system, such as CRISPR-Cas.
Radiolarian-based stratigraphic reconstruction along the western Yarlung-Tsangpo suture zone, southern Tibet, and its implication for Neo-Tethyan late-stage evolution
Authors: Cheng Jianbo , Li Yalin , Li Xin , Xiao Siqi , Li Shuai , Bi Wenjun , He Zhihao , Ma Xingduo , Li Zijian , Zhou Rui 
Published: September 2024

Abstract
Mélange complexes and continental marginal deposits along suture zones can provide crucial insights into the subduction-accretion processes of oceanic lithosphere and continent-continent collisions. Herein, moderately to well-preserved Late Jurassic–Early Cretaceous and late Paleocene radiolarian assemblages, including 86 species within 52 genera, were identified in the Jiangmuna mélange and the adjacent Tethyan Himalayan sedimentary strata along the western Yarlung-Tsangpo suture zone, southern Tibet. Reconstruction of the ocean plate stratigraphy revealed that the Jiangmuna mélange represents the products of fragmentation and mixing of Early Jurassic–Late Cretaceous ocean plate materials originally accumulated in different portions of the central Neo-Tethyan domain. The bottom-up lithological transition and the southward-younger seamount system indicate that the Neo-Tethyan oceanic lithosphere was subducted northward beneath the Zhongba microterrane, and then the Jiangmuna mélange was accreted one unit after another along the southern margin of the Zhongba microterrane during the Late Cretaceous. The adjacent Tethyan Himalayan sedimentary strata were originally deposited in a continental slope-basin environment along the northern margin of the Indian plate since the Middle Jurassic. The occurrence of Selandian–Thanetian radiolarian assemblages implies that deep-water sedimentation persisted along the northern margin of the Indian plate until at least the late Paleocene. Our findings, combined with previously published data, indicate that the Neo-Tethys Ocean existed at least from the Early Jurassic to late Paleocene, and the Neo-Tethyan late-stage evolution involved at least two subduction-accretion systems along the southern margins of the Lhasa block and the Zhongba microterrane, respectively, prior to the two-stage India-Eurasia collision.
Exploring gaps, opportunities, barriers and enablers in malnutrition policy through key informant interviews: a qualitative inquiry from the CANDReaM initiative
Authors: Ford Katherine L , Nasser Roseann , Basualdo-Hammond Carlota , Laur Celia , Quintanilha Maira , Keller Heather , Gramlich Leah 
Published: September 2024

ObjectivesDisease-related malnutrition (DRM) presents in up to half of adults and one-third of children admitted to Canadian hospitals and significantly impacts health outcomes. Strategies to screen, diagnose and treat DRM exist but policy to facilitate implementation and sustainability are lacking. The purpose of this study was to explore gaps, opportunities, barriers and enablers for DRM policy in Canada.MethodsA qualitative study was conducted with multi-national key informants in DRM and/or health policy. Purposive sampling identified participants for a semi-structured interview. The health policy triangle framework informs policy outcomes by considering actors, content, context and processes, and was used to guide this work. Inductive thematic analysis was completed, followed by deductive analysis based on the framework.ResultsDRM policy actors were seen as champions in healthcare, senior leaders in healthcare administration and individuals with lived experience. Policy content focused on screening, diagnosis and treatment of DRM. Key areas related to policy context included system specifics related to setting, cost and capacity, and social determinants of health. DRM policy processes were viewed as cross-sectoral and multi-level governance, mandating and other reinforcement strategies, windows of opportunity, and evaluation and research.ConclusionsDRM care has advanced substantially, yet policy-level changes are sparse, and gaps exist. DRM policy is facilitated by similar content around the globe and needs to be tailored to address setting-specific needs. Actors, content, context and processes inform policy and can be a dominant lever to accelerate nutrition care best practices.
Multinational trends in sepsis mortality between 1985 and 2019: a temporal analysis of the WHO Mortality Database
Authors: Komorowski Matthieu , Salciccioli Justin D , Shalhoub Joseph , Gordon Anthony C , Marshall Dominic C 
Published: September 2024

ObjectivesUnderstanding the burden of disease of sepsis is essential for monitoring the effectiveness of international strategies to improve sepsis care. Our objective was to describe the multinational trend of sepsis-related mortality for the period 1985–2019 from the WHO Mortality Database.DesignRetrospective analysis of the WHO Mortality Database.SettingWe included data from all countries defined by the WHO as having ‘high usability data’ and at least 10 years of total available data.ParticipantsFrom the WHO list of 50 countries with high usability data, 14 (28%) were excluded due to excessive missingness. We included and analysed data separately for male and female.Primary and secondary outcome measuresWe analysed age-standardised mortality rates (ASMR) (weighted average of the age-specific mortality rates per 100 000 people, where the weights are the proportions of people in the corresponding age groups of the WHO standard population).ResultsWe included 1104 country-years worth of data from 36 countries with high usability data, accounting for around 15% of the world’s population. The median ASMR for men decreased from 37.8 deaths/100 000 (IQR 28.4–46.7) in 1985–1987 to 25.8 deaths/100 000 (IQR 19.2–37) in 2017–2019, an approximately 12% absolute (31.8% relative) decrease. For women, the overall ASMR decreased from 22.9 deaths/100 000 (IQR 17.7–32.2) to 16.2 deaths/100 000 (IQR 12.6–21.6), an approximately 6.7% absolute decrease (29.3% relative decrease). The analysis of country-level data revealed wide variations in estimates and trends.ConclusionsWe observed a decrease in reported sepsis-related mortality across the majority of analysed nations between 1985 and 2019. However, significant variability remains between gender and health systems. System-level and population-level factors may contribute to these differences, and additional investigations are necessary to further explain these trends.
Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989
Authors: Mak Lung Yi , Wooddell Christine I , Lenz Oliver , Schluep Thomas , Hamilton James , Davis Heather L , Mao Xianhua , Seto Wai-Kay , Biermer Michael , Yuen Man-Fung 
Published: September 2024

Background and aimsRNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression.MethodsWe prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months.ResultsAmong the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or <100 IU/mL at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg <100 IU/mL and >100 IU/mL at nadir or ≤24 weeks from last dose could maintain or achieve HBsAg <100 IU/mL at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs 0.21 log IU/mL/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r=−0.427, p=0.001).ConclusionShort-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants.
Core outcome set for intervention research on snakebite envenomation in South Asia
Authors: Bhaumik Soumyadeep , Beri Deepti , Santra Vishal , Gopalakrishnan Maya , Faiz Mohammad Abul , Williamson Paula R , Clarke Mike , Sharma Sanjib Kumar , Jagnoor Jagnoor 
Published: September 2024

BackgroundThe 2019 WHO strategy to reduce snakebite burden emphasises the need for fostering research on snakebite treatments. A core outcome set (COS) is a consensus minimal list of outcomes that should be measured in research on a particular condition. We aimed to develop a COS for snakebite research in South Asia, the region with the highest burden.MethodsWe used data from a systematic review of outcomes to develop a long list of outcomes which were rated in two rounds of online Delphi survey with healthcare providers, patients and the public, and potential COS users to develop a COS for intervention research on snakebite treatments in South Asia for five intervention groups. Subsequently, meetings, consultations and workshops were organised to reach further consensus. We defined the consensus criteria a priori.ResultsOverall, 72 and 61 people, including patients and the public, participated in round I and round II of the Delphi, respectively. Consensus COSs (including definition and time points) were developed for interventions that prevent adverse reaction to snake antivenom (three outcomes), specifically manage neurotoxic manifestations (five outcomes), specifically manage haematological manifestations (five outcomes) and those that act against snake venom (seven) outcomes. A priori criteria for inclusion in COS were not met for COS on interventions for management of the bitten part.ConclusionThe COS contributes to improving research efficiency by standardising outcome measurement in South Asia. It also provides methodological insights for future development of COS, beyond snakebite.
Education-related inequalities in disability during the last years of life: a full population register-based study
Authors: Stolz Erwin , Oberndorfer Moritz , Freidl Wolfgang 
Published: September 2024

Background
Little is known about education-related inequalities in late-life disability. Here, we use individual-level register data on the receipt of the Austrian long-term care allowance (ALTCA) to assess education-related inequalities in the duration of late-life disability.

Methods
In this retrospective mortality follow-back study, we analyse receipt of ALTCA, a universal cash benefit based on physician-assessed disability in activities of daily living, during the last 5 years of life among all decedents aged 65 years and over from 2020 in Austria (n=76 772).

Results
The higher the level of education, the shorter the period for which ALTCA was received. Over the last 5 years of life, those with the primary/lower secondary education received ALTCA for 47% or 10 months (men), respectively, 38% or 12 months (women) longer than those with tertiary education. Education-related inequalities decreased with time to death and age at death.

Conclusion
We found education-related inequalities in the duration of late-life disability, that is, higher education was associated with a prolonged ability to live independently during the last years of life. Inequalities in disability decreased with time to death and age at death, pointing to a gradual levelling due to mortality-related declines as well as selective mortality.