bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of bupivacaine liposome injectable solution and fentanyl for postoperative analgesia in dogs undergoing limb amputation
Authors: Paul Snighdha , Strelchik Alena , O'Day Jack , Guedes Alonso G. P. , Gordon‐Evans Wanda J. 
Published: February 2024

AbstractObjectiveThe objectives of the study were to compare the clinical efficacy and adverse effects of two analgesic protocols consisting of bupivacaine liposome injectable solution (BLIS) and 0.5% bupivacaine and fentanyl for postsurgical analgesia in dogs undergoing limb amputation.Study designRandomized, double‐blind, prospective, controlled, intent‐to‐treat, clinical noninferiority trial.AnimalsForty client‐owned dogs.MethodsDogs undergoing amputation were randomly assigned to either the BLIS or control group. Postoperative pain, sedation, nausea, and amount eaten were assessed using appropriate scales at 6, 12, 18, and 24 h by trained individuals blinded to the treatment protocol. Rescue analgesia was provided for Glasgow composite measure pain scale (short form) (CMPS‐SF) scores of 5 or above. Clients were requested to pain score their dogs at home using a visual analogue scale (VAS) for 48 h following discharge.ResultsForty dogs completed this study (20 control dogs and 20 BLIS dogs). The BLIS and control groups were equivalent for sedation, nausea, amount eaten, and pain, at all time periods except at 6 h (p < .01), when the BLIS group pain score was lower.ConclusionThe BLIS provided equivalent analgesia with fewer adverse effects than fentanyl constant rate infusion (CRI) following limb amputation. Rescue analgesia was provided to five dogs in the BLIS group and four in the control group, and there was no statistical difference. Nausea scores did not differ statistically.Clinical significanceAs BLIS provides equivalent analgesia, this may allow for decreased reliance on opioids in the immediate postoperative period.
On the existence of products of primes in arithmetic progressions
Authors: Szabó Barnabás 
Published: February 2024

AbstractWe study the existence of products of primes in arithmetic progressions, building on the work of Ramaré and Walker. One of our main results is that if is a large modulus, then any invertible residue class mod contains a product of three primes where each prime is at most . Our arguments use results from a wide range of areas, such as sieve theory or additive combinatorics, and one of our key ingredients, which has not been used in this setting before, is a result by Heath‐Brown on character sums over primes from his paper on Linnik's theorem.
A p$p$‐adic approach to the existence of level‐raising congruences
Authors: Thorne Jack A. 
Published: February 2024

AbstractWe construct level‐raising congruences between ‐ordinary automorphic representations, and apply this to the problem of symmetric power functoriality for Hilbert modular forms. In particular, we prove the existence of the symmetric power lift of a Hilbert modular eigenform of regular weight for each odd integer . In a future work with James Newton, we will use these results to establish the existence of the symmetric power lift for all .
Sensitizing methicillin-resistant
Staphylococcus aureus
(MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine
Authors: Ersoy Selvi C. , Proctor Richard A. , Rose Warren E. , Abdelhady Wessam , Fan Sook-Ha , Madrigal Sabrina L. , Elsayed Ahmed M. , Chambers Henry F. , Sobral Rita G. , Bayer Arnold S. 
Published: February 2024

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains are a major challenge for clinicians due, in part, to their resistance to most β-lactams, the first-line treatment for methicillin-susceptible
S. aureus
. A phenotype termed “NaHCO
3
-responsiveness” has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care β-lactams in the presence of physiologically relevant concentrations of NaHCO
3
,
in vitro
and
ex vivo
; moreover, such “NaHCO
3
-responsive” isolates can be effectively cleared by β-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO
3
exposure on NaHCO
3
-responsive MRSA is to repress WTA synthesis. This NaHCO
3
effect mimics the phenotype of
tarO
-deficient MRSA, including sensitization to the PBP2-targeting β-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO
3
exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO
3
and/or TCP enhanced susceptibility to CFX
in vitro
, by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an
ex vivo
simulated endocarditis vegetations (SEV) model, in NaHCO
3
-responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO
3
), pre-exposure to TCP prior to infection sensitized the NaHCO
3
-responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO
3
is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific β-lactam agents.
Molecular diagnosis of Cytomegalovirus infection: clinical performance of the Aptima transcription-mediated amplification assay toward conventional qPCR chemistry on whole blood samples
Authors: Bottino Paolo , Pastrone Lisa , Zanotto Elisa , Sidoti Francesca , Cavallo Rossana , Costa Cristina 
Published: February 2024

ABSTRACT

Human Cytomegalovirus (HCMV) infection is life-threatening for immunocompromised patients. Quantitative molecular assays on whole blood or plasma are the gold standard for the diagnosis of invasive HCMV infection and for monitoring antiviral treatment in individuals at risk of HCMV disease. For these reasons, an accurate standardization toward the WHO 1st International Standard among different centers and diagnostic kits represents an effort for better clinical management of HCMV-positive patients. Herein, we evaluate, for the first time, the performance of a new transcription-mediated amplification (TMA) assay versus quantitative polymerase chain reaction (qPCR) chemistry, used as a routine method, on whole blood samples. A total of 755 clinical whole blood specimens were collected and tested simultaneously with TMA and qPCR assays. The data showed a qualitative agreement of 99.27% for positive quantified samples and 89.39% for those undetected between the two tested methods. Evaluation of viremia in positive samples highlighted a good correlation between TMA and qPCR chemistries in terms of International Units (ΔLog
10
IU/mL: −0.29 ± 0.40). The TMA assay showed a significant correlation with qPCR in patients monitored for up to 3 months, thus allowing an accurate assessment of viremia in transplant patients. Therefore, TMA chemistry showed good agreement with qPCR testing, used as a current diagnostic routine. It also offers important advantages, such as FDA approval on plasma and
In Vitro
Diagnostic (IVD) on both plasma and whole blood, automated workflow with minimal hands-on time, and random access loading, thus enabling a rapid and reliable diagnostic in HCMV-infected patients.

IMPORTANCE
In this paper, we describe the clinical performance of a novel transcription-mediated amplification (TMA) assay for the detection and quantification of human Cytomegalovirus (HCMV) DNA from whole blood samples. This is a pivotal analysis in immunocompromised patients [transplanted, HIV-positive, and Hematopoietic Stem Cell (HSC) recipients], and molecular tests with high sensitivity and specificity are necessary to evaluate the HCMV viral load in these patients. To our knowledge, this is the first in-depth evaluation of TMA chemistry for HCMV diagnosis on whole blood samples. Moreover, also technical aspects of this assay make it suitable for clinical diagnostics.
Lyssavirus M protein degrades neuronal microtubules by reprogramming mitochondrial metabolism
Authors: Yuan Yueming , Fang An , Wang Haoran , Wang Caiqian , Sui Baokun , Zhao Jianqing , Fu Zhen F. , Zhou Ming , Zhao Ling 
Published: February 2024

ABSTRACT

Infection with neurotropic viruses may result in changes in host behavior, which are closely associated with degenerative changes in neurons. The lyssavirus genus comprises highly neurotropic viruses, including the rabies virus (RABV), which has been shown to induce degenerative changes in neurons, marked by the self-destruction of axons. The underlying mechanism by which the RABV degrades neuronal cytoskeletal proteins remains incomplete. In this study, we show that infection with RABV or overexpression of its M protein can disrupt mitochondrial metabolism by binding to Slc25a4. This leads to a reduction in NAD
+
production and a subsequent influx of Ca
2+
from the endoplasmic reticulum and mitochondria into the cytoplasm of neuronal cell lines, activating Ca
2+
-dependent proteinase calpains that degrade α-tubulin. We further screened the M proteins of different lyssaviruses and discovered that the M protein of the dog-derived RABV strain (DRV) does not degrade α-tubulin. Sequence analysis of the DRV M protein and that of the lab-attenuated RABV strain CVS revealed that the 57th amino acid is vital for M-induced microtubule degradation. We generated a recombinant RABV with a mutation at the 57th amino acid position in its M protein and showed that this mutation reduces α-tubulin degradation
in vitro
and axonal degeneration
in vivo
. This study elucidates the mechanism by which lyssavirus induces neuron degeneration.

IMPORTANCE

Previous studies have suggested that RABV (rabies virus, the representative of lyssavirus) infection induces structural abnormalities in neurons. But there are few articles on the mechanism of lyssavirus’ effect on neurons, and the mechanism of how RABV infection induces neurological dysfunction remains incomplete. The M protein of lyssavirus can downregulate cellular ATP levels by interacting with Slc25a4, and this decrease in ATP leads to a decrease in the level of NAD
+
in the cytosol, which results in the release of Ca
2+
from the intracellular calcium pool, the endoplasmic reticulum, and mitochondria. The presence of large amounts of Ca
2+
in the cytoplasm activates Ca
2+
-dependent proteases and degrades microtubule proteins. The amino acid 57 of M protein is the key site determining its disruption of mitochondrial metabolism and subsequent neuron degeneration.
Two complete 1918 influenza A/H1N1 pandemic virus genomes characterized by next-generation sequencing using RNA isolated from formalin-fixed, paraffin-embedded autopsy lung tissue samples along with evidence of secondary bacterial co-infection
Authors: Xiao Yongli , Sheng Zong-Mei , Williams Stephanie L. , Taubenberger Jeffery K. 
Published: February 2024

ABSTRACT

The 1918 influenza pandemic was the most devastating respiratory pandemic in modern human history, with 50–100 million deaths worldwide. Here, we characterized the complete genomes of influenza A virus (IAV) from two fatal cases during the fall wave of 1918 influenza A (H1N1) pandemic in the United States, one from Walter Reed Army Hospital in Washington, DC, and the other from Camp Jackson, SC. The two complete IAV genomes were obtained by combining Illumina deep sequencing data from both total RNA and influenza viral genome-enriched libraries along with Sanger sequencing data from PCR across the sequencing gaps. This study confirms the previously reported 1918 IAV genomes and increases the total number of available complete or near-complete influenza viral genomes of the 1918 pandemic from four to six. Sequence comparisons among them confirm that the genomes of the 1918 pandemic virus were highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases. Interestingly, in the Washington, DC, case, evidence is presented of the first reported
Rhodococcus
-influenza virus co-infection.

IMPORTANCE

This study applied modern molecular biotechnology and high-throughput sequencing to formalin-fixed, paraffin-embedded autopsy lung samples from two fatal cases during the fall wave of the 1918 influenza A (H1N1) pandemic in the United States. Complete influenza genomes were obtained from both cases, which increases the total number of available complete or near-complete influenza genomes of the 1918 pandemic virus from four to six. Sequence analysis confirms that the 1918 pandemic virus was highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases, including the first reported evidence of
Rhodococcus
-influenza co-infection. Overall, this study offers a detailed view at the molecular level of the very limited samples from the most devastating influenza pandemic in modern human history.
The effect of site-specific recombinases XerCD on the removal of over-replicated chromosomal DNA through outer membrane vesicles in bacteria
Authors: Mansky Johannes , Wang Hui , Wagner-Döbler Irene , Tomasch Jürgen 
Published: February 2024

ABSTRACT

Outer membrane vesicles (OMVs) are universally produced by Gram-negative bacteria and play important roles in symbiotic and pathogenic interactions. The DNA from the lumen of OMVs from the Alphaproteobacterium
Dinoroseobacter shibae
was previously shown to be enriched for the region around the terminus of replication
ter
and specifically for the recognition sequence
dif
of the two site-specific recombinases XerCD. These enzymes are highly conserved in bacteria and play an important role in the last phase of cell division. Here, we show that a similar enrichment of
ter
and
dif
is found in the DNA inside OMVs from
Prochlorococcus marinus
,
Pseudomonas aeruginosa, Vibrio cholerae,
and
Escherichia coli
. The deletion of
xerC
or
xerD
in
E. coli
reduced the enrichment peak directly at the
dif
sequence, while the enriched DNA region around
ter
became broader, demonstrating that either enzyme influences the DNA content inside the lumen of OMVs. We propose that the intra-vesicle DNA originated from over-replication repair and the XerCD enzymes might play a role in this process, providing them with a new function in addition to resolving chromosome dimers.

IMPORTANCE

Imprecise termination of replication can lead to over-replicated parts of bacterial chromosomes that have to be excised and removed from the dividing cell. The underlying mechanism is poorly understood. Our data show that outer membrane vesicles (OMVs) from diverse Gram-negative bacteria are enriched for DNA around the terminus of replication
ter
and the site-specific XerCD recombinases influence this enrichment. Clearing the divisome from over-replicated parts of the bacterial chromosome might be a so far unrecognized and conserved function of OMVs.
Detection of resistance to macrolides and fluoroquinolones in
Mycoplasma genitalium
by targeted next-generation sequencing
Authors: Chiribau Calin B. , Schmedes Sarah , Dong Yibo , Tarigopula Namratha , Tekin Omer , Cannons Andrew , Roberts Jill , Haiduven Donna , Crowe Susanne R. 
Published: February 2024

ABSTRACT

Mycoplasma genitalium
is fastidious to culture, and its detection in human clinical specimens relies mainly on molecular methods. Phenotypic determination of antibiotic susceptibility for this bacterium is not a timely or feasible option for most clinical laboratories. This study sought to determine whether next-generation sequencing technologies can effectively be employed in determining genetic mutations associated with drug resistance in
M. genitalium
samples collected in Aptima Hologic tubes and possibly integrating them into viable workflows in public health laboratories. Following analysis by a custom-designed bioinformatics pipeline, at least one mutation/sample has been identified in 94/98 specimens in at least one of seven loci (macrolides:
rrl
,
rplD
,
rplV
; fluoroquinolones:
parC
,
parE
,
gyrA
,
gyrB
) described previously to be connected to antibiotic resistance. This method identified a total of 469 single nucleotide polymorphisms (SNPs) (452 mutations): 134 of 23S rRNA SNPs and 318 amino acid mutations: 114 substitutions and 204 synonymous; the turnaround time (sample to analyzed sequence) was typically 3 days. The assays and workflows described in this work demonstrated that the determination of a drug resistance profile for macrolides and fluoroquinolones of
M. genitalium
samples by using next-generation sequencing in clinical samples is a feasible approach that can be implemented in clinical laboratories, following thorough and extensive validation studies.

IMPORTANCE

The mechanisms of drug resistance in
Mycoplasma genitalium
are complex and involve several genetic loci. The molecular methods for accurately characterizing resistance to fluoroquinolones and macrolides in this organism are often not available or approved for patient use and do not cover all genetic determinants. To this end, we propose a next-generation sequencing-based method with a turnaround time of 3 days that includes the investigation of all drug resistance loci of
M. genitalium
. Following adaptation, validation, and verification for routine clinical use, assays based on this method may yield molecular results that can be used to guide proper treatment regimens and for surveillance of drug resistance in the general population.
Liquid biopsy approach to monitor the efficacy and response to CAR-T cell therapy
Authors: Shishido Stephanie N , Hart Olivia , Jeong Sujin , Moriarty Aidan , Heeke Darren , Rossi John , Bot Adrian , Kuhn Peter 
Published: February 2024

BackgroundChimeric antigen receptor (CAR)-T cells are approved for use in the treatment of hematological malignancies. Axicabtagene ciloleucel (YESCARTA) and brexucabtagene autoleucel (TECARTUS) genetically modified autologous T cells expressing an anti-CD19 scFv based on the FMC63 clone have shown impressive response rates for the treatment of CD19+B cell malignancies, but there remain challenges in monitoring long-term persistence as well as the functional characterization of low-level persisting CAR-T cells in patients. Furthermore, due to CD19-negative driven relapse, having the capability to monitor patients with simultaneous detection of the B cell malignancy and persisting CAR-T cells in patient peripheral blood is important for ensuring timely treatment optionality and understanding relapse.MethodsThis study demonstrates the development and technical validation of a comprehensive liquid biopsy, high-definition single cell assay (HDSCA)-HemeCAR for (1) KTE-X19 CAR-T cell identification and analysis and (2) simultaneously monitoring the CD19-epitope landscape on neoplastic B cells in cryopreserved or fresh peripheral blood. Proprietary anti-CD19 CAR reagents, healthy donor transduced CAR-T cells, and patient samples consisting of malignant B cell fractions from manufacturing were used for assay development.ResultsThe CAR-T assay showed an approximate limit of detection at 1 cell in 3 million with a sensitivity of 91%. Genomic analysis was additionally used to confirm the presence of the CAR transgene. This study additionally reports the successful completion of two B cell assays with multiple CD19 variants (FMC63 and LE-CD19) and a unique fourth channel biomarker (CD20 or CD22). In patient samples, we observed that CD19 isoforms were highly heterogeneous both intrapatient and interpatient.ConclusionsWith the simultaneous detection of the CAR-T cells and the B cell malignancy in patient peripheral blood, the HDSCA-HemeCAR workflow may be considered for risk monitoring and patient management.
Three-family supersymmetric Pati–Salam models with symplectic groups from intersecting D6-branes
Authors: Mansha Adeel , Li Tianjun , Sabir Mudassar , Wu Lina 
Published: February 2024

AbstractWe construct new three-family $${{\mathcal {N}}}=1$$

N
=
1

supersymmetric Pati–Salam models from intersecting D6-branes with original gauge group $$\textrm{U}(4)_C \times \textrm{USp}(2)_L \times \textrm{U}(2)_R$$

U

(
4
)

C

×
USp

(
2
)

L

×
U

(
2
)

R

on a Type IIA $${\mathbb {T}}^6/({\mathbb {Z}}_2\times {\mathbb {Z}}_2)$$

T

6

/

(

Z
2

×

Z
2

)

orientifold. We find that replacing a $$\textrm{U}(2)$$

U
(
2
)

with a $$\textrm{USp}(2)$$

USp
(
2
)

group severely restricts the number of three-generation supersymmetric models such that there are only five inequivalent models. Exchanging the left and right sectors, we obtain five dual models with gauge group $$\textrm{U}(4)_C \times \textrm{U}(2)_L \times \textrm{USp}(2)_R$$

U

(
4
)

C

×
U

(
2
)

L

×
USp

(
2
)

R

. These ten models have different gauge coupling relations at string scale. The highest wrapping number is 4, and one of the models contains no filler O6-planes. Moreover, we discuss in detail the particle spectra, the composite particles through strong coupling dynamics, and the exotic particle decouplings. Also, we study how to realize the string-scale gauge coupling relations in some models.
ЯКІСТЬ ЖИТТЯ ПАЦІЄНТІВ З ПЕРВИННИМ ОСТЕОАРТРОЗОМ У КОМОРБІДНОСТІ ЗІ ЗАХВОРЮВАННЯМИ, ЯКІ СУПРОВОДЖУЮТЬСЯ ЕКЗОКРИННОЮ НЕДОСТАТНІСТЮ ПІДШЛУНКОВОЇ ЗАЛОЗИ
Authors: Галабіцька І. М. 
Published: February 2024

РЕЗЮМЕ. Остеоартроз (ОА) – це гетерогенна група захворювань різної етіології, але зі схожими біологічними, морфологічними і клінічними проявами та наслідками. Це захворювання впливає на всі компоненти суглоба, зокрема хрящ, субхондральну кістку, синовіальну оболонку, зв’язки та м’язи, що оточують суглоб. ОА є постійно прогресуючою хворобою, яка серйозно впливає на якість життя, особливо, якщо дане захворювння перебігає за умов коморбідності з хронічними захворюваннями, які супроводжуються екзокринною недостатністю підшлункової залози (ЕкНПЗ).
Мета дослідження – проаналізувати зміни показників якості життя за шкалами опитувальника SF-36 у пацієнтів з первинним ОА за умов коморбідності зі захворюваннями шлунково-кишкового тракту (ШКТ), що супроводжуються ЕкНПЗ.
Матеріал і методи дослідження. Було обстежено 304 пацієнти з первинним ОА у коморбідності зі захворюваннями ШКТ, що супроводжуються ЕкНПЗ, поза загостренням. Групу порівняння склали 30 практично здорових осіб, які не мали клініко-анамнестичних та інструментальних ознак захворювань ШКТ і суглобів.
Для оцінки якості життя хворих на первинний ОА в коморбідності зі захворюваннями, що супроводжуються ЕкНПЗ, використовувався загальний опитувальник SF-36.
Результати й обговорення. Встановлено статистично достовірний вплив коморбідної гастроентерологічної патології при первинному ОА на показники шкал фізичного та психологічного здоров’я опитувальника SF-36 (р<0,05).
Висновок. Проведений post hoc аналіз показав наступний рейтинг коморбідної гастроентерологічної патології, що супроводжується ЕкНПЗ, при первинному ОА за рівнем показників шкал фізичного і психологічного здоров’я опитувальника SF-36, починаючи з найнижчого: ЦД2 > ХП > хронічний некаменевий холецистит і функціональні захворювання жовчного міхура та жовчновидільної системи > хронічний гастродуоденіт (р<0,05).