bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients
Authors: Martinez Sydni , Sindu Devika , Nailor Michael D. , Cherrier Lauren , Tokman Sofya , Walia Rajat , Goodlet Kellie J. 
Published: May 2024

AbstractBackgroundLung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off‐label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients.MethodsThis retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post‐LET initiation; secondary outcomes included hematologic changes.ResultsA total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R‐), with LET initiated a median of 9.6 months post‐transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1–5.6) at LET initiation which increased to 5.1 (3.9–7.2) at the end of follow‐up (p <.001). For VGCV controls, WBC was 4.8 (3.4–7.2) at baseline and 5.4 (3.6–7.2) at the end of follow‐up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001).ConclusionLET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.
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Outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning
Authors: von Pfeil Dirsko J. F. , Tan Desmond , Adams Robert , Glassman Mathieu 
Published: May 2024

AbstractObjectiveTo report the outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning (FGNMP).Study designRetrospective case series.AnimalsA total of 15 client owned dogs and two cats with 57 metabone fractures.MethodsDescription of FGNMP and reporting of the following data: signalment, pre‐ and postoperative radiographs, intramedullary pin diameter used, anesthesia, surgery and coaptation times, duration to normal weightbearing and bone union, postoperative care and complications.ResultsMedian surgery time was 54 min (range: 26–99), median duration of coaptation was 14 days (range: 1–5 weeks), median time to normal weightbearing was 16 days (range: 2–45) and median time to bone union was 6 weeks (range: 4–12). All cases had at least 12 months of post‐surgical follow‐up with a median follow‐up of 18 months (range: 12–70). No major complications occurred. Mild radiographic changes associated with subchondral bone sclerosis were noted on follow‐up radiographs in 13/57 fractures. All cases returned to normal gait and full (15) or acceptable (2) function.ConclusionIn this study, FGNMP was an effective and safe technique for metabone fracture repair, requiring only short‐term external coaptation in most patients. Time to bone union and return to normal function compared favorably to previously reported techniques.Clinical relevanceFluoroscopically guided normograde metabone pinning provides an alternative technique for treatment of metabone fractures.
Inhibition of endocytic uptake of severe acute respiratory syndrome coronavirus 2 and endo-lysosomal acidification by diphenoxylate
Authors: Shin Jin Soo , Jang Yejin , Kim Dong-Su , Jung Eunhye , Lee Myoung Kyu , Kim Byungil , Ahn Sunjoo , Shin Yeonju , Jang Su San , Yun Chang Soo , Yoo Jongman , Lim Young Chang , Han Soo Bong , Kim Meehyein 
Published: May 2024

ABSTRACT

Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.
Host immunity involvement in the outcome of phage therapy against hypervirulent
Klebsiella pneumoniae
infections
Authors: Tang Miran , Yao Zhuocheng , Liu Yan , Ma Zhexiao , Zhao Deyi , Mao Zhenzhi , Wang Yue , Chen Lijiang , Zhou Tieli 
Published: May 2024

ABSTRACT

Highly encapsulated hypervirulent
Klebsiella pneumoniae
(hvKp) causes severe infections. Bacteriophage therapy, an antibiotic alternative, effectively treats bacterial infections. Phage φFK1979 encoding polysaccharide depolymerases can target and disarm the capsule of hvKp FK1979, showing promise against FK1979 infection. Resistant strains induced by φFK1979 are possibly eliminated by host immunity and new phage phiR3 targeting them. We constructed varied immunocompromised FK1979 infection mouse models to assess the therapy efficacy of φFK1979 alone or in combination with phiR3. Survival rates, bacterial loads, histopathology, inflammation, and immune cell distribution of mice were studied. Prompt and adequate administration of φFK1979, rather than phiR3, significantly improved survival rates in mice with different immune statuses. However, immunocompromised mice showed lower efficacy due to reduced tolerance to low-virulence φFK1979-resistant bacteria compared to immunocompetent mice. Adding phiR3 sequentially greatly enhanced therapy efficacy for them, leading to increased survival rates and notable improvements in pathology and inflammation. Immunocompetent mice exhibited the most favorable response to φFK1979 monotherapy, as their immune system cleared φFK1979-resistant bacteria while avoiding a robust response to phiR3 combating φFK1979-resistant bacteria. This study revealed host immunity involvement in the outcome of phage therapy against infections and introduced, for the first time, personalized phage therapy strategies for hvKp-infected mice with varying immune statuses.

IMPORTANCE

Hypervirulent
Klebsiella pneumoniae
(hvKp), with high capsular polysaccharide production, can cause severe invasive infections. Capsule-targeting phage poses the potential to fight against hvKp. We previously elucidated that the capsule-targeting phage induces resistance in hvKp, while phage-resistant strains exhibit sensitivity to host innate immunity and new phages targeting them. This indicated that phage-resistant strains can be eliminated by the immune system in immunocompetent patients, whereas they may require treatment with phages targeting resistant bacteria in immunocompromised patients. HvKp can infect individuals with varying immune statuses, including both immunocompetent and immunocompromised/deficient patients. This study, for the first time, developed personalized phage therapy strategies for hvKp-infected mice with different immune statuses, optimizing phage therapy against hvKp infections. This research is expected to provide a theoretical foundation and novel insights for clinical phage therapy against hvKp infections, offering significant societal benefits and clinical value.
Discovery of novel treponemes associated with pododermatitis in elk (
Cervus canadensis
)
Authors: Deb Sushanta , Wild Margaret A. , LeClair Thomas , Shah Devendra H. 
Published: May 2024

ABSTRACT

Pododermatitis, also known as treponeme-associated hoof disease (TAHD), presents a significant challenge to elk (
Cervus canadensis
) populations in the northwestern USA, with
Treponema
spp. consistently implicated in the lesion development. However, identifying species-specific
Treponema
strains from these lesions is hindered by its culture recalcitrance and limited genomic information. This study utilized shotgun sequencing,
in silico
genome reconstruction, and comparative genomics as a culture-independent approach to identify metagenome-assembled
Treponema
genomes (MATGs) from skin scraping samples collected from captive elk experimentally challenged with TAHD. The genomic analysis revealed 10 new MATGs, with 6 representing novel genomospecies associated with pododermatitis in elk and 4 corresponding to previously identified species
—Treponema pedis
and
Treponema phagedenis
. Importantly, genomic signatures of novel genomospecies identified in this study were consistently detected in biopsy samples of free-ranging elk diagnosed with TAHD, indicating a potential etiologic association. Comparative metabolic profiling of the MATGs against other
Treponema
genomes showed a distinct metabolic profile, suggesting potential host adaptation or geographic uniqueness of these newly identified genomospecies. The discovery of novel
Treponema
genomospecies enhances our understanding of the pathogenesis of pododermatitis and lays the foundation for the development of improved molecular surveillance tools to monitor and manage the disease in free-ranging elk.

IMPORTANCE

Treponema
spp. play an important role in the development of pododermatitis in free-ranging elk; however, the species-specific detection of
Treponema
from pododermatitis lesions is challenging due to culture recalcitrance and limited genomic information. The study utilized shotgun sequencing and
in silico
genome reconstruction to identify novel
Treponema
genomospecies from elk with pododermatitis. The discovery of the novel
Treponema
species opens new avenues to develop molecular diagnostic and epidemiologic tools for the surveillance of pododermatitis in elk. These findings significantly enhance our understanding of the genomic landscape of the
Treponemataceae
consortium while offering valuable insights into the etiology and pathogenesis of emerging pododermatitis in elk populations.
Loss of YhcB results in overactive fatty acid biosynthesis
Authors: Stanley Hannah M. , Trent M. Stephen 
Published: May 2024

ABSTRACT

Loss of the
Escherichia coli
inner membrane protein YhcB results in pleomorphic cell morphology and clear growth defects. Prior work suggested that YhcB was directly involved in cell division or peptidoglycan assembly. We found that loss of YhcB is detrimental in genetic backgrounds in which lipopolysaccharide (LPS) or glycerophospholipid (GPL) synthesis is altered. The growth defect of Δ
yhcB
could be rescued through inactivation of the Mla pathway, a system responsible for the retrograde transport of GPLs that are mislocalized to the outer leaflet of the outer membrane. Interestingly, this rescue was dependent upon the outer membrane phospholipase PldA that cleaves GPLs at the bacterial surface. Since the freed fatty acids resulting from PldA activity serve as a signal to the cell to increase LPS synthesis, this result suggested that outer membrane lipids are imbalanced in Δ
yhcB
. Mutations that arose in Δ
yhcB
populations during two independent suppressor screens were in genes encoding subunits of the acetyl coenzyme A carboxylase complex, which initiates fatty acid biosynthesis (FAB). These mutations fully restored cell morphology and reduced GPL levels, which were increased compared to wild-type bacteria. Growth of Δ
yhcB
with the FAB-targeting antibiotic cerulenin also increased cellular fitness. Furthermore, genetic manipulation of FAB and lipid biosynthesis showed that decreasing FAB rescued Δ
yhcB
filamentation, whereas increasing LPS alone could not. Altogether, these results suggest that YhcB may play a pivotal role in regulating FAB and, in turn, impact cell envelope assembly and cell division.

IMPORTANCE

Synthesis of the Gram-negative cell envelope is a dynamic and complex process that entails careful coordination of many biosynthetic pathways. The inner and outer membranes are composed of molecules that are energy intensive to synthesize, and, accordingly, these synthetic pathways are under tight regulation. The robust nature of the Gram-negative outer membrane renders it naturally impermeable to many antibiotics and therefore a target of interest for antimicrobial design. Our data indicate that when the inner membrane protein YhcB is absent in
Escherichia coli
, the pathway for generating fatty acid substrates needed for all membrane lipid synthesis is dysregulated which leads to increased membrane material. These findings suggest a potentially novel regulatory mechanism for controlling the rate of fatty acid biosynthesis.
Genome reduction and horizontal gene transfer in the evolution of Endomicrobia—rise and fall of an intracellular symbiosis with termite gut flagellates
Authors: Mies Undine S. , Hervé Vincent , Kropp Tom , Platt Katja , Sillam-Dussès David , Šobotník Jan , Brune Andreas 
Published: May 2024

ABSTRACT

Bacterial endosymbionts of eukaryotic hosts typically experience massive genome reduction, but the underlying evolutionary processes are often obscured by the lack of free-living relatives. Endomicrobia, a family-level lineage of host-associated bacteria in the phylum
Elusimicrobiota
that comprises both free-living representatives and endosymbionts of termite gut flagellates, are an excellent model to study evolution of intracellular symbionts. We reconstructed 67 metagenome-assembled genomes (MAGs) of
Endomicrobiaceae
among more than 1,700 MAGs from the gut microbiota of a wide range of termites. Phylogenomic analysis confirmed a sister position of representatives from termites and ruminants, and allowed to propose eight new genera in the radiation of
Endomicrobiaceae
. Comparative genome analysis documented progressive genome erosion in the new genus
Endomicrobiellum
, which comprises all flagellate endosymbionts characterized to date. Massive gene losses were accompanied by the acquisition of new functions by horizontal gene transfer, which led to a shift from a glucose-based energy metabolism to one based on sugar phosphates. The breakdown of glycolysis and many anabolic pathways for amino acids and cofactors in several subgroups was compensated by the independent acquisition of new uptake systems, including an ATP/ADP antiporter, from other gut microbiota. The putative donors are mostly flagellate endosymbionts from other bacterial phyla, including several, hitherto unknown lineages of uncultured
Alphaproteobacteria
, documenting the importance of horizontal gene transfer in the convergent evolution of these intracellular symbioses. The loss of almost all biosynthetic capacities in some lineages of
Endomicrobiellum
suggests that their originally mutualistic relationship with flagellates is on its decline.

IMPORTANCE
Unicellular eukaryotes are frequently colonized by bacterial and archaeal symbionts. A prominent example are the cellulolytic gut flagellates of termites, which harbor diverse but host-specific bacterial symbionts that occur exclusively in termite guts. One of these lineages, the so-called Endomicrobia, comprises both free-living and endosymbiotic representatives, which offers the unique opportunity to study the evolutionary processes underpinning the transition from a free-living to an intracellular lifestyle. Our results revealed a progressive gene loss in energy metabolism and biosynthetic pathways, compensated by the acquisition of new functions via horizontal gene transfer from other gut bacteria, and suggest the eventual breakdown of an initially mutualistic symbiosis. Evidence for convergent evolution of unrelated endosymbionts reflects adaptations to the intracellular environment of termite gut flagellates.
Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model
Authors: Spurgeon Megan E. , Townsend Elizabeth C. , Blaine-Sauer Simon , McGregor Stephanie M. , Horswill Mark , den Boon Johan A. , Ahlquist Paul , Kalan Lindsay , Lambert Paul F. 
Published: May 2024

ABSTRACT

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female
FVB/N
mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.

IMPORTANCE
Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.
Life Cycle Characteristics and Distribution of Giant Grenadier Coryphaenoides pectoralis (Macrouridae) in Northwest Bering Sea
Authors: Alferof A. I. , Kurnosov D. S. 
Published: May 2024

Abstract
The outcomes from the survey research in distribution of the giant grenadier Coryphaenoides pectoralis at different stages of development in the Northwest Bering Sea over 1963–2020 have been reported. The data for 37 thousand catches performed with the bottom and multi-depth trawls at the depths between 0–1200 m are processed. It has been revealed that the species fish tend to spawn throughout the year, with two periods of peak spawning activity in the second half of a spring season and from the late summer season to the first half of an autumn season. The female fish ready to spawn migrate down the water column, keeping deeper than 600 m, where the males ready to spawn are concentrated. After spawning, they come back to the feeding areas of less water depths. The juvenile giant grenadier less than 30 cm in length can be encountered in the mesopaelagic and upper bathypelagic zones, which do not appear to form dense aggregations. The majority of the specimens less than 30–40 cm in length and smaller commonly leave this water column layer to occupy the bottom water layers along the continental shelf. Such differentiation between the juvenils and the sexually mature specimens can provide the opportunity to avoid cannibalism and to use the habitat food sources efficiently.
Maps of Soil Organic Carbon Sequestration Potential in the Russian Croplands
Authors: Romanenkov V. A. , Meshalkina J. L. , Gorbacheva A. Yu. , Krenke A. N. , Petrov I. K. , Golozubov O. M. , Rukhovich D. I. 
Published: May 2024

Abstract
Adoption of the farming systems that aim to sequester carbon in agricultural soils is one of the ways to mitigate global climate change. This study focuses on the estimation of organic carbon sequestration potential of the Russian croplands in the upper (0–30 cm) soil layer by creating a set of maps using the data from global and national databases as the input data. The maps are generated within the FAO Global Soil Organic Carbon Sequestration Potential Map (GSOCseq) project according to the unified methodology using the RothC model to predict the rate of carbon sequestration in 2020–2040 under a business as usual scenario (BAU), as well as under sustainable soil management scenarios with additional different C input (+5, +10, and +20%) resulting from the use of sustainable soil management (SSM) scenarios. The total potential sequestration rate by the croplands of the Russian Federation in the 0–30-cm layer under a BAU scenario is assessed at 8.5 Mt/year and the estimate under SSM scenarios, up to 25.5 Mt/year. The carbon sequestration by the cropland of each soil ecological zone (except for the light chestnut (Eutric Cambisols (Protocalcic)) and brown semidesert (Luvic Calcisols) soils, where it is around zero) and on a national scale is positive. The Altai krai, Omsk oblast, Novosibirsk oblast, and Krasnoyarsk krai have the greatest potential for sequestration. Several subjects of the Russian Federation—Krasnodar krai, Republic of Crimea, Rostov oblast, Primorskii krai, Republic of Adygea, and Kaliningrad oblast—demand the adoption of sustainable management of soil resources.
On the Existence of Global Solutions for the Vlasov–Poisson System in a Half-space and Plasma Confinement
Authors: Skubachevskii A. L. 
Published: May 2024

Abstract
We consider the Vlasov–Poisson system with external magnetic field in a half-space with the Neumann boundary condition for the electric potential and specular reflection on a boundary. For arbitrary compactly supported initial density distribution functions, we obtain sufficient conditions for external magnetic field, which provide global existence of density distribution functions with compact supports lying at some distance from a boundary.