bluuebunny/crossref_metadata_2025_split huggingface dataset:
The establishment of reference intervals for the ClotPro thromboelastometry device in healthy dogs
Authors: Day Samantha K. , Nash Katherine J. , Midwinter Mark J. , Purcell Sarah L. , Goodwin Wendy A. 
Published: November 2024

AbstractObjectiveTo establish reference intervals using a new point‐of‐care thromboelastometry device in dogs for the extrinsically activated test (EX‐test), intrinsically activated test (IN‐test), fibrin polymerization test (FIB‐test), ecarin test (ECA‐test), and tissue plasminogen activator test (TPA‐test) and to investigate the effects of storage time on the results.DesignProspective clinical study in 2022.SettingUniversity teaching hospital.AnimalsForty‐eight healthy privately or university‐owned dogs were prospectively enrolled and included on the basis of normal physical examination and normal baseline laboratory results (CBC, biochemistry profile, prothrombin time, and activated partial thromboplastin time [aPTT]).InterventionsAfter a 30‐minute storage time, the EX‐test, IN‐test, FIB‐test, ECA‐test, and TPA‐test were performed on citrated blood samples. To determine the effect of storage time, 11 samples had the EX‐test, FIB‐test, and IN‐test repeated 90 and 150 minutes after sample collection.Measurements and Main ResultsTen thromboelastometry parameters were evaluated for each test. Reference intervals were calculated using the robust method for parametric data, and the robust Box–Cox transformed or nonparametric methods were used for nonparametric data. Increasing storage time resulted in more hypocoagulable tracings. A correlation was found between the IN‐test and aPTT (r = 0.62, P < 0.0001). Other weak to moderate correlations were seen between thromboelastometry parameters and platelet count and hematocrit.Conclusions and Clinical ImportanceThe development of reference intervals for the thromboelastometry device allows for the clinical use of this technology. Analyzing samples after a prolonged storage time of more than 30 minutes may result in erroneous results. Results may also be affected by an abnormal hematocrit or platelet count.
Analysis of cannabinoids in plasma from 38 cases of suspected cannabinoid intoxication in dogs
Authors: Loewen Jennifer M. , Munn‐Patterson Meara L. , McEwen Katelyn E. , Vuong Stephanie , Alcorn Jane , Chicoine Alan L. 
Published: November 2024

AbstractObjectiveTo quantify and characterize plasma cannabinoid concentrations in cases of suspected cannabis toxicity in dogs, identify potential correlations between clinical signs and plasma concentrations, and assess the specificity of cannabis toxicity diagnosis based on clinical signs alone.DesignObservational study.SettingVeterinary teaching hospital.AnimalsThirty‐eight client‐owned animals.InterventionsBlood was collected from dogs presenting to the emergency room for suspected cannabinoid intoxication based on history or physical examination findings. Samples were analyzed using a validated liquid chromatography–tandem mass spectrometry method for the cannabinoids Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), and their active metabolites.Measurements and Main ResultsThe most common abnormality observed was ataxia (35/38 dogs), with urinary incontinence, lethargy, and hyperesthesia also commonly noted. Cannabinoids were quantifiable in 37 of 38 plasma samples (97.4%), with THC the predominant cannabinoid (range: 1.99–2748 ng/mL). Lower concentrations of CBD (up to 115.3 ng/mL) and cannabinoid metabolites were detected. Of the clinical signs recorded, only abnormal reflexes were statistically correlated with the THC concentration at the time of sampling (P = 0.01).ConclusionsA diagnosis of suspected cannabinoid toxicity based on case history and clinical presentation was confirmed via quantifiable plasma concentrations in nearly all cases. Although the range of plasma cannabinoid concentrations was broad, the clinical signs observed were generally similar. Other than the presence of abnormal reflexes, clinical signs were not associated with plasma THC concentrations. Subsequent confirmation of cannabinoids in plasma indicates that cannabis toxicity in dogs can be diagnosed with high specificity by veterinarians based only on history and clinical abnormalities.
The use of a nursing implementation framework to enhance the uptake of an evidence‐based intervention
Authors: Karim Kesley , Trower Sommer , Segre Lisa S. 
Published: November 2024

AbstractBackgroundEvidence‐based practices (EBPs) are instrumental in improving patient outcomes and ensuring high‐quality nursing care, yet their implementation often encounters substantial barriers. The Iowa Implementation for Sustainability Framework and the Precision Implementation Approach© offer systematic strategies for overcoming barriers and enhancing EBP implementation and sustainability in health care settings.AimThis project aimed to use the Iowa Implementation for Sustainability Framework and the Precision Implementation Approach© to support the use of an evidence‐based maternal depression intervention within Iowa's Title V Maternal Health Program that serves mothers of young children living in poverty.MethodsThis practice‐based implementation was accomplished in three steps: (1) hold intervention‐focused staff meetings, (2) identify barriers to using the intervention, and (3) identify and deliver implementation strategies. Collected data included barriers identified, selected implementation strategies, and evaluation of meeting attendance and impact on confidence.ResultsFour of the monthly virtual staff meetings focused on Listening Visits (LV) use. The 7 strategies comprising our approach to supporting LV use addressed three categories of identified barriers: lack of confidence, logistical issues, and not understanding intervention procedures. In the LV‐focused meetings, representation of the 14 maternal health clinics was high, although attendance by individual staff was inconsistent. Post‐meeting polls indicated that 40% to 65% of attendees felt more confident using intervention skills.Linking evidence to actionThis practical nursing‐implementation framework facilitated EBP adoption, and our well‐structured targeted strategies effectively increased staff confidence. Nursing managers and educators should consider using this framework to enhance their organizations' capacity to implement EBPs sustainably.
College Students’ Perceptions of English-medium Instruction: A Survey in a Local Chinese University
Authors: Zhang Xiaoxiao , Hu Fumao 
Published: November 2024

With the internationalization and globalization of recent decades, English has increasingly become a medium of instruction at universities worldwide. This survey was conducted in a local Chinese university, and focused on college students’ needs and satisfaction regarding content, instructors, and assessment. A mixed method was employed, combining quantitative data from a questionnaire and qualitative data from interviews. The quantitative data were analyzed in SPSS 26.0, and qualitative data were analyzed in NVivo 12 plus. The findings reveal that students generally have a positive attitude towards the needs, content, instructor, and assessment satisfaction in EMI programs, which increased steadily. There is no significant difference in students’ perceptions by gender and self-proficiency, and perceptions of needs, instructor, content, and assessment satisfaction are closely correlated with the overall satisfaction. The study suggests that course design tailored students’ practical needs and advanced teaching techniques are crucial for enhancing EMI courses. Feedback was limited in students’ participation and class size. Gender differences tend to diminish in EMI university settings and English proficiency should be assessed effectively. Needs and satisfaction with content, instructor, and assessment are vital in the overall satisfaction. These insights contribute valuable recommendations for the effective implementation of EMI programs and propose avenues for further research.
Chow–Witt rings and topology of flag varieties
Authors: Hudson Thomas , Matszangosz Ákos K. , Wendt Matthias 
Published: November 2024

AbstractThe paper computes the Witt‐sheaf cohomology rings of partial flag varieties in type A in terms of the Pontryagin classes of the subquotient bundles. The proof is based on a Leray–Hirsch‐type theorem for Witt‐sheaf cohomology for the maximal rank cases, and a detailed study of cohomology ring presentations and annihilators of characteristic classes for the general case. The computations have consequences for the topology of real flag manifolds: we show that all torsion in the integral cohomology is 2‐torsion, which was not known in full generality previously. This allows for example to compute the Poincaré polynomials of complete flag varieties for cohomology with twisted integer coefficients. The computations also allow to describe the Chow–Witt rings of flag varieties, and we sketch an enumerative application to counting flags satisfying multiple incidence conditions to given hypersurfaces.
Load‐dependence of the activation of myosin filaments in heart muscle
Authors: Wang Yanhong , Fusi Luca , Ovejero Jesus G. , Hill Cameron , Juma Samina , Cullup Flair Paradine , Ghisleni Andrea , Park‐Holohan So‐Jin , Ma Weikang , Irving Thomas , Narayanan Theyencheri , Irving Malcolm , Brunello Elisabetta 
Published: November 2024

AbstractContraction of heart muscle requires activation of both the actin and myosin filaments. The mechanism of myosin filament activation is unknown, but the leading candidate hypothesis is direct mechano‐sensing by the filaments. Here, we tested this hypothesis by activating intact trabeculae from rat heart by electrical stimulation under different loads and measuring myosin filament activation by X‐ray diffraction. Unexpectedly, we found that the distinct structural changes in the myosin filament associated with activation had different dependences on the load. In early activation, all the structural changes indicated faster activation at higher load, as expected from the mechano‐sensing hypothesis, but, at later times, the helical order of the myosin motors characteristic of the inactivated state was lost even at very low load. We conclude that mechano‐sensing does operate in heart muscle, but it is supplemented by a previously undescribed mechanism that links myosin filament activation to actin filament activation.
imageKey points
Myosin filament activation controls the strength and speed of contraction in heart muscle.
Early activation of the myosin filament is determined by the filament load.
At later times, myosin filament activation is controlled by a load independent pathway.
This load independent pathway provides new targets and assays for drug development.
Rapid Attitude Controller Design Enabled by Flight Data
Authors: Huang Yunshen , Vu Minh , He Wenbo , Zeng Shen 
Published: November 2024

Abstract
In this work, we present a new approach that enables rapid learning and design of the attitude controller for quadcopters. The proposed technique leverages the dynamic structure of the system to efficiently learn an accurate linear model around the hovering position from a small batch of flight data. An linear quadratic regulator-based attitude controller is designed based on the estimation accordingly. In our approach, we may not need to conduct multiple experiments to fine-tune the controller and can accomplish such a control design with a single experiment. We further develop this approach into an onboard design framework where the attitude controller can be directly learned online and recursively fine-tunes itself with the limited onboard computation resources. The practicality and efficacy of the proposed approaches are demonstrated in both simulation and a physical quadcopter platform.
Retrospective analysis of antimicrobial susceptibility profiles of non-
diphtheriae Corynebacterium
species from a tertiary hospital and reference laboratory, 2012–2023
Authors: Khodadadi Ryan B. , El Zein Said , Rivera (O'Connor) Christina G. , Stevens Ryan W. , Schuetz Audrey N. , Abu Saleh Omar M. , Fida Madiha 
Published: November 2024

ABSTRACT

A total of 1,925
Corynebacterium
isolates were tested for antimicrobial susceptibility at the Mayo Clinic Microbiology laboratory (Rochester, Minnesota) from January 2012 to March 2023, with
C. striatum
(35.6%) and
C. amycolatum
(24.4%) identified as the predominant species. Species known to potentially carry diphtheria toxin were excluded. Common sources of isolation included skin and soft tissue (56.8%), bone and/or native joint synovial fluid (14.2%), urine (13.1%), sputum (6.1%), and blood (5.9%). For penicillin, susceptibility decreased from 47.5% (58 of 122) in 2012 to 20.6% (14 of 68) in 2023. Isolates also showed a decrease in susceptibility to erythromycin from 22.4% (26 of 116) in 2012 to 13.2% (9 of 68) in 2023. Susceptibility to trimethoprim-sulfamethoxazole averaged around 50% throughout the period. Notably, linezolid and vancomycin were universally effective
in vitro
against all species. The highest susceptibility rates among tested oral agents were to linezolid and doxycycline for non-
C
.
striatum
species. Daptomycin minimal inhibitory concentrations (MICs) of >256 µg/mL were observed for one
C. amycolatum
isolate, one
C. tuberculostearicum
isolate, and for seven
C. striatum
isolates, all from patients with prior daptomycin exposure. Daptomycin MICs of 2 µg/mL (nonsusceptible) were observed in one
C. striatum
isolate recovered from a daptomycin-naïve patient and in six
C. jeikeium
isolates, from both daptomycin-exposed and non-exposed patients. Significant variation in susceptibility profiles across different
Corynebacterium
species underscores the importance of performing antimicrobial susceptibility testing to guide effective treatment. Moreover, multidrug resistance observed in
C. striatum
poses substantial therapeutic challenges especially in patients requiring prolonged or chronic antibiotic suppression.
Small but mighty: targeted antifungal liposomes of a smaller size are superior in treating cryptococcal meningitis
Authors: Pham Tuyetnhu , Zhang Peter , Ambati Suresh , Meagher Richard B. , Lin Xiaorong 
Published: November 2024

ABSTRACT

Cryptococcal meningoencephalitis (CME) is deadly. CME is responsible for 19% of deaths in AIDS patients, and its global mortality is greater than 60%. The recommended CME therapy requires amphotericin B (AmB), a fungicidal drug targeting fungal ergosterol. AmB also binds to the host’s cholesterol and is highly toxic. Liposomal AmB (AmB-LLs), relative to deoxycholate-solubilized AmB, has lower toxicity and longer tissue retention, but it requires high doses for treatment and its efficacy in treating CME remains unsatisfactory. To improve the effectiveness of AmB-LLs, we previously developed DectiSomes-targeted AmB-LLs decorated with host dectins that recognize fungal polysaccharides. DectiSomes, relative to untargeted AmB-LLs, modestly improve efficacy against systemic cryptococcosis, in contrast to the drastic improvement observed in candidiasis or aspergillosis models. We speculated that limited tissue penetration of the regular-sized DectiSomes might have contributed to the modest improvement in treating systemic cryptococcosis. Here, we discovered that DectiSomes of a smaller size (~50 nm), compared with DectiSomes of the regular size (~100 nm) or untargeted AmB-LLs of either size, had a much better capability in reducing cryptococcal burden of various organs including the brain and in prolonging the survival of mice with systemic cryptococcosis. The performance of small DectiSomes was far superior to all other groups at two different doses of AmB tested. Furthermore, no kidney toxicity was observed in any of the treatment regimens tested. Taken together, our findings indicate that small DectiSomes can be a powerful antifungal delivery platform to drastically improve therapies against the deadly CME.

IMPORTANCE
Systemic cryptococcosis is fatal even with antifungal interventions. The most effective drug against this disease is amphotericin B (AmB). However, AmB is highly toxic as it binds to fungal ergosterol and also mammalian cholesterol. Liposomal AmB was introduced to the clinic in 1990s because it showed reduced toxicity and longer retention in various organs. However, the dose of AmB required for treatment using liposomal formulation is high and the outcome is far from satisfactory. In our previous work, we generated DectiSomes, dectin-decorated liposomes loaded with AmB that more effectively deliver the drug to the pathogen and enhance antifungal efficacy. However, the improvement in treating systemic cryptococcosis, compared with candidiasis and aspergillosis, is modest. Here, we generated DectiSomes that are half their regular size to improve tissue penetration. We discovered that small DectiSomes are superior in reducing fungal burden in various organs including the brain and in prolonging animal survival.
Vibrio cholerae
CsrA controls ToxR levels by increasing the stability and translation of
toxR
mRNA
Authors: Mey Alexandra R. , Midgett Charles R. , Kull F. Jon , Payne Shelley M. 
Published: November 2024

ABSTRACT

Intestinal colonization and virulence factor production in response to environmental cues is mediated through several regulatory factors in
Vibrio cholerae
, including the highly conserved RNA-binding global regulatory protein CsrA. We have shown previously that CsrA increases synthesis of the virulence-associated transcription factor ToxR in response to specific amino acids (NRES) and is required for the virulence of
V. cholerae
in the infant mouse model of cholera. In this study, we mapped the 5′ untranslated region (5′ UTR) of
toxR
and showed that CsrA can bind directly to an RNA sequence encompassing the 5′ UTR, indicating that the regulation of ToxR levels by CsrA is direct. Consistent with this observation, the 5′ UTR of
toxR
contains multiple putative CsrA binding sequences (GGA motifs), and mutating these motifs disrupted the CsrA-mediated increase in ToxR. Optimal binding of CsrA to a defined RNA oligonucleotide required the bridging of two GGA motifs within a single RNA strand. To determine the mechanism of regulation by CsrA, we assayed
toxR
transcript levels, stability, and efficiency of translation. Both the amount of
toxR
mRNA in NRES and the stability of the
toxR
transcript were increased by CsrA. Using an
in vitro
translation assay, we further showed that synthesis of ToxR was greatly enhanced in the presence of purified CsrA, suggesting a direct role for CsrA in the translation of
toxR
mRNA. We propose a model in which CsrA binding to the 5′ UTR of the
toxR
transcript promotes ribosomal access while precluding interactions with RNA-degrading enzymes.

IMPORTANCE

Vibrio cholerae
is uniquely adapted to marine environments as well as the human intestinal tract. Global regulators, such as CsrA, which help translate environmental cues into an appropriate cellular response, are critical for switching between these distinct environments. Understanding the pathways involved in relaying environmental signals is essential for understanding both the environmental persistence and the intestinal pathogenesis of this devastating human pathogen. In this study, we demonstrate that CsrA directly regulates the synthesis of ToxR, a key virulence factor of
V. cholerae
. Under conditions favoring high levels of active CsrA in the cell, such as in the presence of particular amino acids, CsrA increases ToxR protein levels by binding to the
toxR
transcript and enhancing both its stability and translation. By responding to nutrient availability, CsrA is perfectly poised to activate the virulence gene regulatory cascade at the preferred site of colonization in the human host, the nutrient-rich small intestinal mucosa.
Phenotypic and genomic characterization of ST11-K1 CR-hvKP with highly homologous
bla
KPC-2
-bearing plasmids in China
Authors: Han Yu-Ling , Wang Hua , Zhu Hong-Zhe , Lv Ying-Ying , Zhao Wen , Wang Yan-Yan , Wen Jian-Xun , Hu Zhi-De , Wang Jun-Rui , Zheng Wen-Qi 
Published: November 2024

ABSTRACT

Carbapenem-resistant hypervirulent
Klebsiella pneumoniae
(CR-hvKP) strains present a significant global public health threat due to their high mortality rates. This study investigated the genomic characteristics of seven ST11-K1 CR-hvKP isolates harboring highly homologous KPC-2-encoding multidrug-resistance plasmids. The strains were isolated from a Chinese tertiary hospital between 2017 and 2020. Whole-genome sequencing and bioinformatic analysis revealed various antibiotic resistance genes (ARGs) and virulence determinants. The
bla
KPC-2
-bearing plasmids that contain multiple antibiotic-resistance genes were also identified in these strains. ISfinder and Orifinder were applied to identify insertion sequences (IS) and conjugation-related factors among these
bla
KPC-2
-bearing plasmids. The
bla
KPC-2
was highly consistent in seven
bla
KPC-2
-bearing plasmids (IS
Kpn6-bla
KPC-2
-IS
Kpn27
-IS
Yps3
-IS
26
). In addition, we found a region composed of IS
IR
, Tn
5393
, and IS
26
. It was located upstream of the
bla
CTX-M-15
gene and presented in six
bla
KPC-2
-bearing plasmids, with pCR-hvKP221-KPC-P3 as an exception. Conjugation experiments demonstrated the horizontal transfer of resistance plasmids pCR-hvKP128-KPC-P1 and pCR-hvKP132-KPC-P1 across species. Notably, pLVPK-like virulence plasmids carrying virulence gene clusters pCR-hvKP173-Vir-P1, and pCR-hvKP221-Vir-P1 were also detected. A fusional plasmid pCR-hvKP221-Vir-P2, which carries virulence gene clusters and ARGs, was also identified. Five CR-hvKP strains displayed enhanced biofilm formation and high virulence
in vivo
infection models. Phylogenetic and single nucleotide polymorphism (SNP) analyses indicated a close genetic relationship among the isolates, suggesting a subclade. These findings highlight the complex genetic profiles and potential transmission mechanisms of CR-hvKP strains.

IMPORTANCE

We reported seven CR-hvKP strains all carried a highly homologous
bla
KPC-2
integrated IncFⅡ-resistant plasmid, and two strains harbored virulence plasmids. Conjugation experiments confirmed the transferability of these plasmids, indicating a potential for resistance spread. Phylogenetic analysis clarified the relationship among the CR-hvKP isolates. This study provides insights into the phenotypic and genomic characteristics of seven ST11-K1 CR-hvKP strains. The high prevalence and potential for local outbreaks emphasize the need for effective control measures.