bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron variants in mice and hamsters
Authors: Case James Brett , Scheaffer Suzanne M. , Darling Tamarand L. , Bricker Traci L. , Adams Lucas J. , Harastani Houda H. , Trende Reed , Sanapala Shilpa , Fremont Daved H. , Boon Adrianus C. M. , Diamond Michael S. 
Published: September 2023

ABSTRACT
The continued evolution and emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a recently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-human ACE2 (hACE2) transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters. In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in substantial weight loss, a characteristic seen in pre-Omicron variants. BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, in C57BL/6J mice, 129S2 mice, and Syrian hamsters, BQ.1.1 did not cause increased respiratory tract infection or disease compared to animals administered BA.5.5. Moreover, the rates of direct contact or airborne transmission in hamsters were not significantly different after BQ.1.1 and BA.5.5 infections. Taken together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in rodent species that express hACE2, possibly due to the acquisition of unique spike mutations relative to earlier Omicron variants.

IMPORTANCE
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, there is a need to rapidly assess the efficacy of vaccines and antiviral therapeutics against newly emergent variants. To do so, the commonly used animal models must also be re-evaluated. Here, we determined the pathogenicity of the BQ.1.1 SARS-CoV-2 variant in multiple SARS-CoV-2 animal models including transgenic mice expressing human ACE2 (hACE2), two strains of conventional laboratory mice, and Syrian hamsters. While BQ.1.1 and BA.5.5 infection resulted in similar levels of viral burden and clinical disease in hamsters and the conventional strains of laboratory mice tested, increases in lung infection were detected in hACE2-expressing transgenic mice, which corresponded with greater levels of pro-inflammatory cytokines and lung pathology. Taken together, our data highlight important differences in two closely related Omicron SARS-CoV-2 variant strains and provide a foundation for evaluating countermeasures.
ER-dependent membrane repair of mycobacteria-induced vacuole damage
Authors: Anand Aby , Mazur Anna-Carina , Rosell-Arevalo Patricia , Franzkoch Rico , Breitsprecher Leonhard , Listian Stevanus A. , Hüttel Sylvana V. , Müller Danica , Schäfer Deise G. , Vormittag Simone , Hilbi Hubert , Maniak Markus , Gutierrez Maximiliano G. , Barisch Caroline 
Published: September 2023

ABSTRACT

Several intracellular pathogens, such as
Mycobacterium tuberculosis,
damage endomembranes to access the cytosol and subvert innate immune responses. The host counteracts endomembrane damage by recruiting repair machineries that retain the pathogen inside the vacuole. Here, we show that the endoplasmic reticulum (ER)-Golgi protein oxysterol-binding protein (OSBP) and its
Dictyostelium discoideum
homolog OSBP8 are recruited to the
Mycobacterium
-containing vacuole (MCV) dependent on the presence of the ESX-1 secretion system, suggesting that their mobilization is associated with membrane damage. Lack of OSBP8 causes a hyperaccumulation of phosphatidylinositol-4-phosphate (PI4P) on the MCV and decreased cell viability. OSBP8-depleted cells had reduced lysosomal and degradative capabilities of their vacuoles that favored mycobacterial growth. In agreement with a potential role of OSBP8 in membrane repair, human macrophages infected with
M. tuberculosis
recruited OSBP in an ESX-1-dependent manner. These findings identified an ER-dependent repair mechanism for restoring MCVs in which OSBP8 functions to equilibrate PI4P levels on damaged membranes.

IMPORTANCE

Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen.
Mycobacterium tuberculosis
, the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the endoplasmic reticulum (ER)-Golgi lipid transfer protein OSBP8 in the
Dictyostelium discoideum
/
Mycobacterium marinum
system. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defense mechanism against intracellular pathogens such as
M. tuberculosis
.
Phylogenetic lineages and antimicrobial resistance determinants of clinical
Klebsiella oxytoca
spanning local to global scales
Authors: Ikhimiukor Odion O. , Souza Stephanie S. R. , Akintayo Ifeoluwa J. , Marcovici Michael M. , Workman Adrienne , Martin Isabella W. , Andam Cheryl P. 
Published: September 2023

ABSTRACT

Klebsiella oxytoca
is an opportunistic pathogen causing serious nosocomial infections. Knowledge about the population structure and diversity of healthcare-associated
K. oxytoca
from a genomic standpoint remains limited. Here, we characterized the phylogenetic relationships and genomic characteristics of 20
K
.
oxytoca sensu stricto
isolates recovered from bloodstream infections at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA from 2017 to 2021. Results revealed a diverse population consisting of 15 sequence types (STs) that together harbored 10 variants of the intrinsic beta-lactamase gene
bla
OXY-2
, conferring resistance to penicillins. Similar sets of antimicrobial resistance (AMR) determinants reside in multiple distinct lineages, with no one lineage dominating the local population. To place the New Hampshire
K. oxytoca
in a broader context, we compared them to 304 publicly available genomes of clinical isolates from 18 countries. This global clinical
K. oxytoca sensu stricto
population is represented by over 65 STs that together harbored resistance genes against 14 antimicrobial classes, including eight
bla
OXY-2
variants. Three dominant STs in the global population (ST2, ST176, ST199) circulate across multiple countries and were also present in the New Hampshire population. The global
K. oxytoca
population is genetically diverse, but there is evidence for broad dissemination of a few lineages carrying distinct set of AMR determinants. Our findings reveal the clinical diversity of
K. oxytoca sensu stricto
and its importance in surveillance efforts aimed at monitoring the evolution of this drug-resistant nosocomial pathogen.

IMPORTANCE

The opportunistic pathogen
Klebsiella oxytoca
has been increasingly implicated in patient morbidity and mortality worldwide, including several outbreaks in healthcare settings. The emergence and spread of antimicrobial resistant strains exacerbate the disease burden caused by this species. Our study showed that clinical
K. oxytoca sensu stricto
is phylogenetically diverse, harboring various antimicrobial resistance determinants and
bla
OXY-2
variants. Understanding the genomic and population structure of
K. oxytoca
is important for international initiatives and local epidemiological efforts for surveillance and control of drug-resistant
K. oxytoca
.
Morphogenesis and metabolomics reveal the compatible relationship among
Suillus bovinus
,
Phialocephala fortinii
, and their co-host,
Pinus massoniana
Authors: Sun Xueguang , Zhao Yanzhen , Ding Guijie 
Published: September 2023

ABSTRACT

Ectomycorrhizal (ECM) fungi and dark septate endophytes (DSEs) can both form a symbiotic relationship with the same host plant. However, the interactions that occur among these two types of fungi and their co-hosts are largely unknown. Here, we investigated interactions that occur among the ECM fungus
Suillus bovinus
, the DSE
Phialocephala fortinii
, and their co-host
Pinus massoniana
. We used both scanning electron microscopy and optical microscopy to characterize the morphogenesis of the two symbionts and employed the ultra-high-performance liquid chromatography–tandem mass spectrometry technique to assess the effects of fungal inoculation on the root metabolome. Under pure culture conditions, no synergistic or antagonistic effects were observed between
Phi. fortinii
and
S. bovinus
. Generally,
S. bovinus
and
Phi. fortinii
can simultaneously colonize
P. massoniana
roots without affecting each other’s symbiotic processes.
S. bovinus
can colonize the root locus where
Phi. fortinii
has already invaded but not vice versa, which may be due to the physical barrier effect of the mantle. Both fungi can significantly promote the growth of
P. massoniana
, and they have a synergistic effect on host N and K uptake. Metabolite accumulation patterns in roots inoculated with
Phi. fortinii
and/or
S. bovinus
were greatly altered, especially with respect to organic acids, flavonoids, lipids, and phenolic acids.
S. bovinus
inoculation significantly enhanced root flavonoid biosynthesis, whereas
Phi. fortinii
and dual-inoculation treatments mainly induced phenylpropanoid biosynthesis. These findings reveal compatible relationships among
P. massoniana
,
S. bovinus
, and
Phi. fortinii
, and suggest a theoretical basis for ECM fungi and DSE co-application when cultivating seedlings.

IMPORTANCE

The prevalence of both ectomycorrhizal fungi and dark septate endophytes in the roots of a wide spectrum of tree species is well recognized. In this study, we investigated the interactions that occur among the ECM fungus
S. bovinus
, the DSE
Phi. fortinii
, and their co-host,
P. massoniana
. The two fungi can simultaneously colonize
P. massoniana
roots without affecting each other’s symbiotic processes.
S. bovinus
appears to be superior to
Phi. fortinii
in microniche competition, which may be due to the physical barrier effect of the mantle. The two fungi have different effects on root metabolite accumulation patterns.
S. bovinus
inoculation significantly enhanced root flavonoid biosynthesis, whereas
Phi. fortinii
and dual-inoculation treatments mainly induced phenylpropanoid biosynthesis. This is the first study revealing the morphological and metabolic mechanisms that contribute to the compatible relationship among ECM fungi, DSEs, and their co-host.
Tick-to-host transmission differs between
Borrelia afzelii
strains
Authors: Genné Dolores , Jiricka Whitney , Sarr Anouk , Voordouw Maarten J. 
Published: September 2023

ABSTRACT

Many vector-borne pathogens establish multiple-strain infections in the vertebrate host and the arthropod vector. Multiple-strain infections in the host influence strain acquisition by naive vectors. Whether multiple-strain infections in the vector influence strain-specific transmission to naive hosts remains unknown. The spirochete,
Borrelia afzelii
, causes Lyme borreliosis and multiple-strain infections are common in both the tick vector and vertebrate host. Our study used two
B. afzelii
strains: Fin-Jyv-A3 and NE4049. Donor mice were infected with Fin-Jyv-A3 alone, NE4049 alone, or with both strains. Larval ticks fed on donor mice and molted into nymphal ticks infected with either strain or both strains. These nymphs were fed on test mice to determine whether multiple-strain infections in the nymph influence nymph-to-host transmission (NHT). Multiple-strain infection in the donor mice reduced the acquisition of both strains by ticks by 23%. Thus, a substantial fraction of infected nymphs from the multiple strain treatment were infected with the “wrong” competitor strain rather than the “right” focal strain. As a result, nymphs from the multiple strain treatment were 46% less likely to infect the test mice with the focal strain compared to nymphs from the single strain treatment. However, multiple-strain infection in the nymphal tick had no effect on the NHT of either strain. The nymphal spirochete load of Fin-Jyv-A3 was 1.9 times higher compared to NE4049. NHT of Fin-Jyv-A3 (79%) was 1.5 times higher compared to NE4049 (53%). Our study suggests that
B. afzelii
strains with higher nymphal spirochete loads have higher NHT.

IMPORTANCE

For many vector-borne pathogens, multiple-strain infections in the vertebrate host or arthropod vector are common. Multiple-strain infections in the host reduce strain acquisition by feeding vectors. Whether multiple-strain infections in the vector influence strain transmission to the host remains unknown. In our study, we used two strains of the tick-borne spirochete
Borrelia afzelii
, which causes Lyme borreliosis, to investigate whether multiple-strain infections in the nymphal tick influenced nymph-to-host transmission (NHT) of strains. Multiple-strain infections in mice reduced the acquisition of both
B. afzelii
strains by nymphal ticks. As a result, nymphs from the multiple strain treatment were less likely to infect naive test mice with the focal strain. Multiple-strain infection in the nymphal ticks did not influence the NHT of either strain. The strain with the higher bacterial abundance in the nymph had higher NHT. Our study suggests that pathogen abundance in the arthropod vector is important for vector-to-host transmission.
Association between maternal HIV infection and the risks of preterm birth and low birth weight in Chengdu, China: a propensity score matching approach
Authors: Yingjuan Luo , Peng Jieru , Liu Yang , Xia Wu , Chen Shan , Yongcheng Sheng , Lin Yonghong 
Published: September 2023

ObjectivesTo estimate the effect of HIV infection on the risk of preterm birth (PTB) and low birth weight (LBW) among Chinese pregnancy women.DesignA retrospective cohort study included HIV-positive pregnant women who gave birth to singletons in Chengdu between 2011 and 2020 and and HIV-negative pregnant women who delivered singletons at the Chengdu Women’s and Children’s Central Hospital in 2020.SettingData of pregnant women living with HIV were extracted from China’s Information System of Prevention of Mother-to-Child Transmission of HIV Management. Additionally, information for HIV-negative pregnant women was extracted from the electronic medical record system of the Chengdu Women’s and Children’s Central Hospital.Participants755 HIV-positive women and 15,094 HIV-negative pregnant women were included.Primary outcome measuresPTB and LBW rates, which were defined by gestational weeks and birth weight.ResultsThe incidences of PTB and LBW (13.51% and 14.17%, respectively) were significantly higher in the HIV-positive group compared with the HIV-negative group (6.82% and 4.65%). Propensity score matching was performed to improve comparability of the two groups, resulting in 1590 pregnancies with 558 HIV-positive and 1032 HIV-negative women in the final analysis. Conditional logistic regression was used to estimate the effect of maternal HIV status on adverse pregnancy outcomes. After propensity score matching and controlling the potential confounders, HIV infection was strongly associated with higher chances of LBW and PTB with adjusted odd ratios (95% confidence interval) of 2.53 (1.74 to 3.68) and 1.95 (1.33 to 2.85), respectively.ConclusionsHIV infection was significantly associated with increased risks of PTB and LBW in Chinese pregnant women. Future studies should focus on investigating the mechanisms underlying the association between HIV infection and adverse birth outcomes, and on identifying strategies to reduce the incidence of PTB and LBW in pregnant women living with HIV.
COVID-19 pandemic hits differently: examining its consequences for women’s livelihoods and healthcare access – a cross-sectional study in Kinshasa DRC
Authors: Nkweleko Fankam Falone , Ugarte William , Akilimali Pierre , Ewane Etah Junior , Åkerman Eva 
Published: September 2023

ObjectivesThe emergence of the COVID-19 pandemic led to multiple preventive actions as primary interventions to contain the spread of the virus. Globally, countries are facing enormous challenges with consequences for use of social, economic and health services. The Democratic Republic of Congo (DRC) was among the African countries implementing strict lockdown at the start of the pandemic, resulting in shortages and decreased access to services. The adverse effects of the pandemic had unpleasant consequences for the country. This study aimed to examine the association between COVID-19 pandemic-related factors, sociodemographic factors, and the need to visit healthcare facilities, including family planning services, among women aged 15–49 years in the DRC.MethodsWe conducted a secondary analysis of a performance monitoring for action (PMA) cross-sectional COVID-19 phone survey in Kinshasa, DRC, which had a response rate of 74.7%. In total, 1325 randomly selected women aged 15–49 years from the Kinshasa province who had previously participated in the PMA baseline survey participated in the survey. Bivariate and multivariate logistic regressions were used to assess associations.ResultsThe COVID-19 pandemic and related factors affected 92% of women in the Kinshasa province socioeconomically. A majority were highly economically dependent on their partner or some other sources for their basic needs to be met, and even more worried about the future impact of the pandemic on their household finances. Over 50% of women did not attempt visiting a health service, with some of the top reasons being fear of being infected with COVID-19 and not being able to afford services. We found a significant association between age groups and contraceptive use. The need for and use of contraceptives was higher among women aged 25–34 years than those aged 15–24 or 35–49 years.ConclusionEffective social/economic support to women and girls during pandemics and in crises is essential as it can have lasting beneficial effects on many domains of their lives, including their ability to access health services and the contraceptives of their choice.
Associations between experiencing violence, owning a firearm for protection and firearm storage: a nationally representative analysis of US caregivers of teens
Authors: Sokol Rebeccah Lyn , Lee Daniel , Rowhani-Rahbar Ali , Pelletier Karissa , Zimmerman Marc , Carter Patrick M 
Published: September 2023

ObjectiveTo study the interaction between violence exposure and motivations for firearm ownership in their associations with firearm storage among caregivers of teens in the United States.MethodsIn June–July 2020, we conducted a national survey of 2924 caregivers of US teens. We estimated multivariable logistic regressions among caregivers who owned a firearm (n=1095) to evaluate associations between the exposures of community violence, interpersonal violence, and firearm ownership motivations (protection motivations vs non-protection motivations) and the outcome of firearm storage patterns (locked and unloaded vs unlocked and/or loaded). We assessed for a potential interaction between violence exposures and motivations for firearm ownership in their associations with firearm storage.ResultsWe observed no associations between community (adjusted OR [aOR]: 0.86; 95% CI [0.55 to 1.36]) or interpersonal violence exposure (aOR: 0.60; 95% CI [0.22 to 1.65]) and firearm storage behaviours, and these associations did not vary according to firearm ownership motivations (relative excess risk due to interaction: −0.09 [−1.90 to 1.73]; −2.04 [−6.00 to 1.92]). Owning a firearm for protection was associated with increased odds of storing at least one firearm unlocked and/or loaded (aOR: 3.48; 95% CI [2.11 to 5.75]), and this association persisted across all strata of violence exposures (aORs: 1.51–3.98; 95% CIs [0.52 to 8.31]−[1.96 to 8.08]).ConclusionsThe motivation to own a firearm for protection was associated with storing a firearm unlocked and/or loaded. The results suggest the associations between violence exposure and firearm storage are more complicated than anticipated because (1) exposure to violence was not associated with firearm storage practices and (2) motivations for firearm ownership do not appear to explain why people differ in firearm storage following violence exposure.
Intraoperative physiology augments atlas-based data in awake deep brain stimulation
Authors: Paulo Danika L , Johnson Graham W , Doss Derek J , Allen Jackson H , González Hernán F J , Shults Robert , Li Rui , Ball Tyler J , Bick Sarah K , Hassell Travis J , D’Haese Pierre-François , Konrad Peter E , Dawant Benoit M , Narasimhan Saramati , Englot Dario J 
Published: September 2023

BackgroundDeep brain stimulation (DBS) is commonly performed with patients awake to perform intraoperative microelectrode recordings and/or macrostimulation testing to guide final electrode placement. Supplemental information from atlas-based databases derived from prior patient data and visualised as efficacy heat maps transformed and overlaid onto preoperative MRIs can be used to guide preoperative target planning and intraoperative final positioning. Our quantitative analysis of intraoperative testing and corresponding changes made to final electrode positioning aims to highlight the value of intraoperative neurophysiological testing paired with image-based data to optimise final electrode positioning in a large patient cohort.MethodsData from 451 patients with movement disorders treated with 822 individual DBS leads at a single institution from 2011 to 2021 were included. Atlas-based data was used to guide surgical targeting. Intraoperative testing data and coordinate data were retrospectively obtained from a large patient database. Medical records were reviewed to obtain active contact usage and neurologist-defined outcomes at 1 year.ResultsMicroelectrode recording firing profiles differ per track, per target and inform the locations where macrostimulation testing is performed. Macrostimulation performance correlates with the final electrode track chosen. Centroids of atlas-based efficacy heat maps per target were close in proximity to and may predict active contact usage at 1 year. Overall, patient outcomes at 1 year were improved for patients with better macrostimulation response.ConclusionsAtlas-based imaging data is beneficial for target planning and intraoperative guidance, and in conjunction with intraoperative neurophysiological testing during awake DBS can be used to individualize and optimise final electrode positioning, resulting in favourable outcomes.