bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between magnetic resonance imaging findings and histological grade in spinal peripheral nerve sheath tumors in dogs
Authors: Morabito Simona , Specchi Swan , Di Donato Pamela , Pollard Danica , Dennis Ruth , De Risio Luisa , Bacon Nicholas J. , Potamopoulou Maria , Rupp Stefan , Corlazzoli Daniele , Ribeiro João , Cozzi Francesca , Jurina Konrad , Cappello Rodolfo , Mercuriali Edy , Beckmann Katrin , Flegel Thomas , Menchetti Marika , König Florian , Matiasek Kaspar , Rosati Marco 
Published: September 2023

AbstractBackgroundPeripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location.Hypothesis/ObjectivesIdentify magnetic resonance imaging (MRI) features predictive of PNST histologic grade.AnimalsForty‐four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation.MethodsA multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board‐certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board‐certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis.ResultsForty‐four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low‐grade), 19 were PNSTs Grade 2 (medium‐grade), and 9 were PNSTs Grade 3 (high‐grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade.Conclusions and Clinical ImportanceGrade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high‐grade PNSTs including tumor size and peripheral contrast enhancement.
Effects of SARPE and MISMARPE on correction of transverse maxillary deficiency: A preliminary comparative evaluation
Authors: da Silva Andreza Vieira , da Rosa Bibiana Mello , Matje Paulo R. B. , Rizzatto Susana Maria Deon , de Oliveira Rogério Belle , Haas Orion L. , de Menezes Luciane Macedo 
Published: September 2023

AbstractAimThe present study was designed to compare, on cone‐beam computed tomography imaging, the skeletal and dental effects of the SARPE (Surgically assisted rapid palatal expansion) and MISMARPE (Minimally Invasive Surgical and Miniscrew‐Assisted Rapid Palatal Expansion) techniques.Materials and methodsThe sample of adult patients with transverse maxillary deficiency (TMD) was divided into two groups, and scans were obtained preoperatively (T0) and immediately after completion of expansion (T1). The posterior and anterior linear transverse distances of the maxilla and the angulation of the maxillary first molars were evaluated. The data were entered into a generalized estimating equations model to verify the postoperative effects of the different techniques.ResultsNone of the techniques caused any appreciable change in the angulation of the molars. The skeletal changes were similar, with significantly greater gains in the nasal fossa and intermaxillary distance when using the MISMARPE.ConclusionThe technique can be an effective and lower morbidity alternative to SARPE.
Selecting biomaterials in the reconstructive therapy of peri‐implantitis
Authors: Monje Alberto , Pons Ramón , Nart José , Miron Richard J. , Schwarz Frank , Sculean Anton 
Published: September 2023

AbstractPeri‐implantitis is a pathogenic inflammatory condition characterized by progressive bone loss and clinical inflammation that may compromise the stability of dental implants. Therapeutic modalities have been advocated to arrest the disorder and to establish peri‐implant health. Reconstructive therapy is indicated for bone defects exhibiting contained/angular components. This therapeutic modality is based upon the application of the biological and technical principles of periodontal regeneration. Nonetheless, the comparative efficacy of reconstructive therapy and nonreconstructive modalities remains unclear. Therefore, the aim of this narrative review is to address major clinical concerns regarding the efficacy, effectiveness, and feasibility of using biomaterials in peri‐implantitis therapy. In particular, the use of bone grafting materials, barrier membranes, and biologics is comprehensively explored.
PEP reward reactivity moderates the effects of RSA reactivity on antisocial behavior and substance use
Authors: Chen Frances R. , French Katherine 
Published: September 2023

AbstractIntegrating Polyvagal Theory and Reinforcement Sensitivity Theory (RST), we examined pre‐ejection period (PEP) reward reactivity, which was suggested to index trait impulsivity, as a moderator between respiratory sinus arrhythmia (RSA) reactivity and antisocial behavior (ASB), and substance use in an urban male, adult sample. To understand the inconsistent findings between RSA reactivity and externalizing problems, we proposed to study both negatively and positively valenced tasks for RSA reactivity and to include PEP reward reactivity as a moderator for the RSA‐behavior link. Data were collected from an urban sample of 131 male adults (active offenders, demographic controls, and college students). ICG (impedance cardiography) and ECG (electrocardiogram) were recorded, computing PEP (sympathetic nervous system activity marker) and RSA (parasympathetic nervous system activity marker), while participants completed the modified Trier Social Stress Test and a simple reward task. Reactivity was calculated by subtracting the baseline from the task activity. Consistent with prior studies, more RSA withdrawal to stress and less PEP shortening to reward predicted the most ASB and substance use. Less RSA withdrawal to reward and more PEP shortening to reward predicted the most ASB and substance use. We incorporated autonomic space, RST, and Polyvagal Theory to discuss our findings, and specifically highlight how clarifying what each reactivity captures based on the task demand (e.g., presence of social threat, need for vagal‐mediated social affiliative behavior) can illuminate our understanding of the result patterns.
A US-based national surveillance study for the susceptibility and epidemiology of
Clostridioides difficile
isolates with special reference to ridinilazole: 2020–2021
Authors: Snydman D. R. , McDermott L. A. , Thorpe C. M. , Goldstein E. J. C. , Schuetz A. N. , Johnson S. , Gerding D. N. , Gluck L. , Bourdas D. , Carroll K. C. , Lancaster C. K. , Garey K. W. , Wang Q. , Walk S. T. , Duperchy E. 
Published: September 2023

ABSTRACT

We have previously reported on the susceptibility and epidemiology of
Clostridioides difficile
isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020–2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators.
C. difficile
isolates or stools from patients with
C. difficile
antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014–020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078–126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent
in vitro
activity against
C. difficile
isolates collected between 2020 and 2021 in the United States, independent of ribotype.
Diethylcarbamazine elicits Ca
2+
signals through TRP-2 channels that are potentiated by emodepside in
Brugia malayi
muscles
Authors: Williams Paul D. E. , Kashyap Sudhanva S. , Robertson Alan P. , Martin Richard J. 
Published: September 2023

ABSTRACT

Filarial nematode infections are a major health concern in several countries. Lymphatic filariasis is caused by
Wuchereria bancrofti
and
Brugia
spp. affecting over 120 million people. Heavy infections can lead to elephantiasis, which has serious effects on individuals’ lives. Although current anthelmintics are effective at killing microfilariae in the bloodstream, they have little to no effect against adult parasites found in the lymphatic system. The anthelmintic diethylcarbamazine is one of the central pillars of lymphatic filariasis control. Recent studies have reported that diethylcarbamazine can open transient receptor potential (TRP) channels in the muscles of adult female
Brugia malayi,
leading to contraction and paralysis. Diethylcarbamazine has synergistic effects in combination with emodepside on
Brugia,
inhibiting motility: emodepside is an anthelmintic that has effects on filarial nematodes and is under trial for the treatment of river blindness. Here, we have studied the effects of diethylcarbamazine on single
Brugia
muscle cells by measuring the change in Ca
2+
fluorescence in the muscle using Ca
2+
-imaging techniques. Diethylcarbamazine interacts with the transient receptor potential channel, C classification (TRPC) ortholog receptor TRP-2 to promote Ca
2+
entry into the
Brugia
muscle cells, which can activate Slopoke (SLO-1) Ca
2+
-activated K
+
channels, the putative target of emodepside. A combination of diethylcarbamazine and emodepside leads to a bigger Ca
2+
signal than when either compound is applied alone. Our study shows that diethylcarbamazine targets TRP channels to promote Ca
2+
entry that is increased by emodepside activation of SLO-1 K
+
channels.
Sensitivity of rapid antigen tests against SARS-CoV-2 Omicron and Delta variants
Authors: Rao Anuradha , Westbrook Adrianna , Bassit Leda , Parsons Richard , Fitts Eric , Greenleaf Morgan , McLendon Kaleb , Sullivan Julie A. , O’Sick William , Baugh Tyler , Bowers Heather B. , Frank Filipp , Wang Ethan , Le Mimi , Frediani Jennifer , Roychoudhury Pavitra , Greninger Alexander L. , Jerris Robert , Pollock Nira R. , Ortlund Eric A. , Roback John D. , Lam Wilbur A. , Piantadosi Anne 
Published: September 2023

ABSTRACT

Rapid antigen tests (RATs) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of 10 commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using both individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR cycle threshold (C
T
) value (a rough proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using
C

T

value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.
Assessment and validation of enrichment and target capture approaches to improve
Mycobacterium tuberculosis
WGS from direct patient samples
Authors: Mann B. C. , Jacobson K. R. , Ghebrekristos Y. , Warren R. M. , Farhat M. R. 
Published: September 2023

ABSTRACT

Within-host
Mycobacterium tuberculosis
(Mtb) diversity may detect antibiotic resistance or predict tuberculosis treatment failure and is best captured through sequencing directly from sputum. Here, we compared three sample pre-processing steps for DNA decontamination and studied the yield of a new target enrichment protocol for optimal whole-genome sequencing (WGS) from direct patient samples. Mtb-positive NALC-NaOH-treated patient sputum sediments were pooled, and heat inactivated, split in replicates, and treated by either a wash, DNase I, or benzonase digestion. Levels of contaminating host DNA and target Mtb DNA were assessed by quantitative PCR (qPCR), followed by WGS with and without custom dsDNA target enrichment. The pre-treatment sample has a high host-to-target ratio of DNA (6,168 ± 1,638 host copies/ng to 212.3 ± 59.4 Mtb copies/ng) that significantly decreased with all three treatments. Benzonase treatment resulted in the highest enrichment of Mtb DNA at 100-fold compared with control (3,422 ± 2,162 host copies/ng to 11,721 ± 7,096 Mtb copies/ng). The custom dsDNA probe panel successfully enriched libraries from as little as 0.45 pg of Mtb DNA (100 genome copies). Applied to direct sputum the dsDNA target enrichment panel increased the percent of sequencing reads mapping to the Mtb target for all three pre-processing methods. Comparing the results of the benzonase sample sequenced both with and without enrichment, the percent of sequencing reads mapping to the Mtb increased to 90.95% from 1.18%. We demonstrate a low limit of detection for a new custom dsDNA Mtb target enrichment panel that has a favorable cost profile. The results also demonstrate that pre-processing to remove contaminating extracellular DNA prior to cell lysis and DNA extraction improves the host-to-Mtb DNA ratio but is not adequate to support average coverage WGS without target capture.
L. pneumophila
resists its self-harming metabolite HGA via secreted factors and collective peroxide scavenging
Authors: Holland Mische , Farinella Danielle N. , Cruz-Lorenzo Emily , Laubscher Madelyn I. , Doakes Darian A. , Ramos Maria A. , Kubota Nanami , Levin Tera C. 
Published: September 2023

ABSTRACT

Many pathogenic bacteria, including
Legionella pneumophila
, infect humans from environmental reservoirs. To survive in these reservoirs, bacteria must withstand microbe-on-microbe competition. We previously discovered that
L. pneumophila
can compete with neighboring bacteria via an antimicrobial metabolite called homogentisic acid (HGA). Curiously,
L. pneumophila
strains that secrete HGA are not wholly immune to its effects: low-density bacteria are strongly inhibited by HGA, whereas high-density cells are tolerant. How do these bacteria tolerate HGA and avoid self-harm during interbacterial competition? Here, we find that HGA toxicity occurs via the production of toxic hydroperoxides, and multiple factors facilitate high-density tolerance. First, HGA becomes fully toxic only after >1 h of oxidation. While this manifests as a delay in killing within well-mixed liquid cultures, in a biofilm environment, this could provide time for HGA to diffuse away before becoming toxic. Second, HGA generates quantities of hydroperoxides that can be collectively scavenged by high-density, but not low-density, cells. Third, high-density cells produce one or more secreted factors that are transiently protective from HGA. In combination, we propose that the bacteria are able to deploy HGA to generate a pool of reactive oxygen species surrounding their own biofilms while maintaining non-toxic conditions within them. Overall, these findings help to explain how broadly toxic molecules can be used as inter-bacterial weapons. They also provide insights about why some of our current decontamination methods to control
L. pneumophila
are ineffective, leading to recurrent disease outbreaks.

IMPORTANCE

Before environmental opportunistic pathogens can infect humans, they must first successfully grow and compete with other microbes in nature, often via secreted antimicrobials. We previously discovered that the bacterium
Legionella pneumophila
, the causative agent of Legionnaires’ disease, can compete with other microbes via a secreted molecule called HGA. Curiously,
L. pneumophila
strains that produce HGA is not wholly immune to its toxicity, making it a mystery how these bacteria can withstand the “friendly fire” of potentially self-targeting antimicrobials during inter-bacterial battles. Here, we identify several strategies that allow the high-density bacterial populations that secrete HGA to tolerate its effects. Our study clarifies how HGA works. It also points to some explanations of why it is difficult to disinfect
L. pneumophila
from the built environment and prevent disease outbreaks.
Gene duplication, gene loss, and recombination events with variola virus shaped the complex evolutionary path of historical American horsepox-based smallpox vaccines
Authors: Souza Aline R. V. , Brinkmann Annika , Esparza José , Nitsche Andreas , Damaso Clarissa R. 
Published: September 2023

ABSTRACT
Vaccinia virus is the active component of all modern smallpox vaccines after the mid-20th century, but it is uncertain to what extent cowpox, vaccinia, and horsepox viruses were used to produce vaccines before then. Genome sequences of six smallpox vaccines used in the United States between 1850 and 1902, namely VK01, VK02, VK05, VK08, VK12, and Mulford_1902 vaccines, revealed >99.5% similarity with a 1976 strain of horsepox in the genome core. However, how these historical vaccines relate to horsepox and vaccinia viruses is still unknown. Here, we present a detailed investigation of the gene content and genomic structure of these historical smallpox vaccines. Except for VK05, all historical vaccines differ from horsepox in the genomic architecture of the flanking variable regions showing complex patterns of gene duplication/transposition, gene fragmentation, and gene loss. The Mulford_1902 vaccine is the closest virus to contemporary vaccinia viruses and the VK02 vaccine is the most different, with several stretches of variola virus genes recombined in its genome. Our data suggest that in the late 19th and early 20th centuries, different horsepox-based vaccines and probably related unsampled progenitors of modern vaccinia virus coexisted. A better understanding of the evolutionary path of the now extinct horsepox-based vaccines will increase our knowledge of the origins of contemporary vaccinia viruses and the pathways that led to the consolidation of current smallpox vaccines. This is particularly important now that the resumption of production of smallpox vaccines for use against mpox is widely discussed, as is the improvement of available vaccines.

IMPORTANCE
Modern smallpox vaccines, such as those used against mpox, are made from vaccinia viruses, but it is still unknown whether cowpox, horsepox, or vaccinia viruses were used in the early 20th century or earlier. The mystery began to be solved when the genomes of six historical smallpox vaccines used in the United States from 1850 to 1902 were determined. Our work analyzed in detail the genomes of these six historical vaccines, revealing a complex genomic structure. Historical vaccines are highly similar to horsepox in the core of their genomes, but some are closer to the structure of vaccinia virus at the ends of the genome. One of the vaccines is a recombinant virus with parts of variola virus recombined into its genome. Our data add valuable information for understanding the evolutionary path of current smallpox vaccines and the genetic makeup of the potentially extinct group of horsepox viruses.
Metabolic proteins with crucial roles in
Edwardsiella tarda
antioxidative adaptation and intracellular proliferation
Authors: Wang Xinhui , Sun Boguang 
Published: September 2023

ABSTRACT

Edwardsiella tarda
is a severe fish pathogen, featured by its capacity to live inside host phagocytes. For intracellular survival, it is crucial for
E. tarda
to neutralize the deleterious effect of host reactive oxygen species (ROS). Accumulating evidence suggests that bacterial metabolism is closely connected to oxidative resistance. However, the roles of
E. tarda
metabolic proteins in antioxidative adaptation and intracellular proliferation remain elusive. In this study, we performed a proteomic analysis on
E. tarda
and identified 111 proteins responsive to H
2
O
2
-mediated oxidative stress. Based on this data, we further obtained eight crucial proteins, including seven metabolic proteins, for
E. tarda
antioxidation and intracellular infection. Among them, two C4-dicarboxylate transporters were found necessary for
E. tarda
to disseminate in fish tissues. Furthermore, the substrate of the two transporters was identified as L-aspartate, which was proven to be essential for the full antioxidative capacity of
E. tarda
. Our results indicate that reprogramming the metabolic flux to the production of pyruvate, a ketoacid capable of neutralizing ROS, was likely a pivotal strategy of
E. tarda
to survive the oxidative environments inside host cells. Together, the findings of this study highlight the significance of metabolic reprogramming for bacterial redox homeostasis and intracellular infection.

Importance

Edwardsiella tarda
is a significant fish pathogen that can live in challenging environments of reactive oxygen species (ROS), such as inside the phagocytes. Metabolic reconfiguration has been increasingly associated with bacterial oxidative tolerance and virulence. However, the metabolic proteins of
E. tarda
involved in such processes remain elusive. By proteomic analysis and functional characterization of protein null mutants, the present study identified eight crucial proteins for bacterial oxidative resistance and intracellular infection. Seven of them are metabolic proteins dictating the metabolic flux toward the generation of pyruvate, a key metabolite capable of scavenging ROS molecules. Furthermore, L-aspartate uptake, which can fuel the pyruvate generation, was found essential for the full antioxidative capacity of
E. tarda
. These findings identified seven metabolic proteins involved in bacterial oxidative adaptation and indicate that metabolic reprogramming toward pyruvate was likely a pivotal strategy of bacteria for antioxidative adaptation and intracellular survival.