bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical dexamethasone decelerates epithelial migration on the canine tympanic membrane
Authors: Kim Jihyun , Oh Taeho , Bae Seulgi 
Published: December 2024

AbstractBackgroundEpithelial migration (EM) is integral to normal ear structure and function. Glucocorticoids are considered the first‐line therapy for various external ear disorders; however, their effects on EM on the tympanic membrane (TM) and the external auditory canal (EAC) are understudied.Hypothesis/ObjectivesTo test the hypothesis that topical dexamethasone decelerates EM on the TM, this study aimed to evaluate the effects of topical dexamethasone on EM on the TMs of dogs.AnimalsSeven ears of four healthy dogs.Materials and MethodsThe migration distance of an ink drop deposited on the posterior quadrant of the pars tensa (TM EM rate) of dogs was calculated over 3 weeks from images captured with a video‐otoscope. The results were compared by paired Student's t‐test to those obtained from a subsequent experiment in which the same dogs were administered a fresh ink drop at the same position as previously (control group), yet additionally administered 0.1% dexamethasone (0.2 mL/ear) daily for the first 14 days (treatment group).ResultsOne of eight ears was excluded because of an anatomical problem. The TM EM rate of the remaining seven ears decreased by 46.74% in the treatment group compared with the control group (p < 0.05).Conclusions and Clinical RelevanceTopical dexamethasone decelerates EM on the TM of normal dogs' ears. In turn, it is extrapolated that debris removal from the EAC may be slowed, negatively impacting the EAC environment. Consequently, when dogs with otitis receive topical dexamethasone treatment, additional treatment, such as ear canal cleaning, may be required to minimise the effects of impaired TM EM.
Efficacy of 0.2% povidone‐iodine and 0.1% polyhexamethylene biguanide as preoperative antiseptics in equine ophthalmic procedures
Authors: Farkas Anna , Thieme Katharina , Soimala Tanawan , Jensen Charlotte K. , Eule J. Corinna 
Published: December 2024

AbstractObjectiveThis retrospective study evaluates the efficacy of povidone‐iodine (PI) and polyhexamethylene biguanide (PHMB) as preoperative antiseptics in equine ophthalmic procedures.Animals StudiedHorses that underwent routine ophthalmic surgery and procedures.ProceduresData were collected retrospectively from the medical records of equine patients undergoing ophthalmic procedures. Inclusion criteria were sampling for aerobic microbial culture at three different time points (T0: pre‐irrigation, T1: post‐irrigation, and T2: postoperatively) and T0 showing bacterial growth. Microbiological outcomes were assessed semi‐quantitatively by creating a scoring system to describe the bacterial load. Furthermore, the species detected were evaluated. Poisson regression analysis was performed to evaluate the efficacy of the disinfectants.ResultsEighty eyes (75 horses) met the inclusion criteria, with 36 cases being aseptically prepared with PI and 44 with PHMB. Both antiseptics significantly reduced the bacterial load and number of bacterial species (p < .001) between time points T0 and T1, and T0 and T2. PHMB showed a reduction in the bacterial load by 64% (CI: 51%–73%) whereas PI reduced it by 48% (CI: 36%–58%) between time points T0 and T1. The reduction in the number of bacterial species between time points T0 to T1 was significantly greater in the PHMB group (85%, CI: 70%–93%), compared to PI (47%, CI: 26%–62%).ConclusionBoth PHMB and PI reduced the bacterial load and number of species on the ocular surface and eyelids significantly, with 0.1% PHMB being superior to 0.2% PI. Therefore, PHMB can be considered as a good alternative in preoperative antisepsis in equine ophthalmic procedures.
Real‐world performance of a clinical droplet digital polymerase chain reaction assay for non‐invasive foetal blood group and platelet antigen genotyping of alloimmunized pregnant women with antibodies directed against RhD, RhE, Rhc, RhC, K1, HPA‐1a or HPA‐5b: A 1‐year experience
Authors: Calandrini Camilla , Verhagen Onno J. H. M. , Tissoudali Ahmed , Homburg Christa H. E. , Vessies Jessica , Brussee Mark , van Beers Erik H. , van der Schoot C. Ellen , de Haas Masja 
Published: December 2024

AbstractBackground and ObjectivesTo test the performance of a new droplet digital polymerase chain reaction (ddPCR) non‐invasive foetal blood group and platelet antigen genotyping assay in the setting of a Dutch reference laboratory for foetal blood group and platelet antigen genotyping. Our population comprised 229 consecutive alloimmunized pregnant women who presented between April 2022 and March 2023 with 250 requests for non‐invasive foetal RHD, RHE, RHc, RHC, K1, HPA‐1a or HPA‐5b blood group and platelet antigen genotyping.Materials and MethodsSamples were genotyped for blood group and platelet antigen alleles along with methylated RASSF1a (mRASSF1a) and sex‐determining region of Y (SRY) and DYS14 as positive foetal controls. Negative blood group and platelet antigen results were issued only when foetal controls were positive; otherwise, such samples were classified as inconclusive.ResultsThe assay achieved a success rate of 98.4% (246 of 250) because one case was lost to follow‐up, one case was solved with quantitative polymerase chain reaction (qPCR) and one case precluded foetal typing due to RHD variant mothers. Only 10 cases needed a second sample and one case a third for a valid final result. We identified 116 maternal–foetal blood group and platelet antigen incompatibilities.ConclusionClinical non‐invasive foetal blood group and platelet antigen typing of alloimmunized pregnant women via ddPCR is successful and represents an improvement over qPCR because of the addition of a foetal control and because ddPCR circumvents potential interference from maternal cell‐free DNA (cfDNA) background for foetal HPA‐1 and K1.
Zoonotic Tick‐Borne Pathogens in Ixodes ricinus Complex (Acari: Ixodidae) From Urban and Peri‐Urban Areas of Kosovo
Authors: Hoxha Ina , Xhekaj Betim , Halimi Genc , Wijnveld Michiel , Ruivo Margarida , Çaushi Driton , Matoshi Albana , Obwaller Adelheid G. , Jäger Bernhard , Weiler Martin , Walochnik Julia , Sherifi Kurtesh , Kniha Edwin 
Published: December 2024

ABSTRACTIntroductionIxodes ricinus, the castor bean tick, is the most prevalent tick species in Europe. It favours habitats such as shrubs, deciduous and mixed forests, but can also be found in urban environments. Due to its high vector competence, it is of enormous veterinary as well as medical importance, transmitting tick‐borne encephalitis (TBE) virus, Borrelia burgdorferi s. l., the causative agent of lyme borreliosis, Rickettsia spp. and Anaplasma phagocytophilum amongst many other pathogens. In Kosovo, I. ricinus is the predominant species and a few studies, mostly based on human and animal seroprevalences, indicate the circulation of tick‐borne pathogens. However, data on pathogens in I. ricinus are scarce in Kosovo, particularly in urban settings. This study aimed to provide first insights into the circulation of tic‐kborne pathogens in I. ricinus from urban and peri‐urban areas in Kosovo.MethodsUrban and peri‐urban areas were sampled by flagging 150 m transects. In total, 197 ticks were morphologicaly identified as I. ricinus, and consequently DNA and RNA were isolated. All individuals were screened for the presence of tick‐borne pathogens by using reverse line blotting (RLB) hybridisation.ResultsDNA of nine different pathogens from four genera including Borrelia spp., Rickettsia spp., Anaplasma spp. and Babesia spp. was detected in 60 (33.5%) specimens. The most frequently detected pathogens were Rickettsia spp. (16.2%), followed by Borrelia spp. (11.7%). Altogether, 54 single infections, 11 double infections and 1 triple infection were observed.ConclusionsWe provide first data on genotyping of B. burgdorferi sensu lato as well as the detection of Anaplasma, Babesia and Rickettsia from I. ricinus in this country. The data underline that particularly recreational (peri‐)urban areas could facilitate the spillover of zoonotic tick‐borne pathogens to humans in Kosovo and provide baseline data for future surveys.
Free‐Ranging Wolves (Canis lupus) are Natural Reservoirs of Intestinal Microeukaryotes of Public Health Significance in Southwestern Europe
Authors: Ortega Sheila , Figueiredo Ana M. , Moroni Barbara , Abarca Nadia , Dashti Alejandro , Köster Pamela C. , Bailo Begoña , Cano‐Terriza David , Gonzálvez Moisés , Fayos Manena , Oleaga Álvaro , Martínez‐Carrasco Carlos , Velarde Roser , Torres Rita T. , Ferreira Eduardo , Hipólito Dário , Barros Tânia , Lino Ana , Robetto Serena , Rossi Luca , Muñoz‐de‐Mier Gemma J. , Ávalos Gabriel , Calero‐Bernal Rafael , González‐Barrio David , Sánchez Sergio , García‐Bocanegra Ignacio , Carmena David 
Published: December 2024

ABSTRACTIntroductionIntestinal microeukaryote parasites are major contributors to the burden of diarrhoea in humans and domestic animals, but their epidemiology in wildlife is not fully understood. We investigated the frequency, genetic diversity and zoonotic potential of protists of animal and public health significance in free‐ranging grey wolf (Canis lupus) populations in south‐western Europe.MethodsIndividually formed faecal samples collected from necropsied wolves or scat trails in Italy (n = 47), Portugal (n = 43) and Spain (n = 225) during the period 2011–2023 were retrospectively analysed using molecular (PCR and Sanger sequencing) methods. Complementary epidemiological data were gathered when available.ResultsGiardia duodenalis was the most frequent microeukaryote found (40.3%, 127/315; 95% CI: 34.9–46.0), followed by Cryptosporidium spp. (3.5%, 11/315; 95% CI: 1.8–6.2), Enterocytozoon bieneusi and Encephalitozoon spp. (1.6%, 5/315; 95% CI: 0.5–3.7 each). Blastocystis was not identified in any of the faecal samples analysed. Sequence analyses confirmed the presence of canine‐adapted assemblage D within G. duodenalis (n = 7). Three Cryptosporidium species were identified, namely canine‐adapted C. canis (n = 9), zoonotic C. parvum (n = 1) and primarily anthroponotic C.hominis (n = 1). Genotyping tools enabled the identification of subtype family XXe2 within C. canis. Among microsporidia, the canine‐adapted genotype PtEb IX was identified within E. bieneusi. Two samples were confirmed as Enc. intestinalis and three more as Enc. cuniculi genotype IV. This is the first record of Enc. intestinalis and Enc. cuniculi in the grey wolf globally.ConclusionsSilent carriage of intestinal microeukaryotes seems common in free‐ranging grey wolves in southwestern Europe. Wolves can contribute to environmental contamination through the transmission stages (cysts, oocysts, spores) of species/genotypes potentially infective to humans. Individuals in close contact with wolf carcasses or their faecal material may be at potential risk of infection by microeukaryotic pathogens.
Development of Heat Exchanger Modeling Capability for a Finite-Volume Aeroelasticity Solver
Authors: Mitchell Sam , Tartaruga Irene , Stapelfeldt Sina 
Published: December 2024

Abstract
Heat exchangers are frequently used in aero-engines and are known to significantly affect the surrounding steady and unsteady flow. In certain applications, they may thereby also influence the aeroelastic stability of upstream or downstream components, but there is limited research on this in the public domain. This article aims to demonstrate the influence of heat exchangers on unsteady flows relevant to aeroelastic problems. This is achieved by developing heat exchanger modeling capability for an in-house finite volume aeroelasticity solver, for which heat exchanger is represented as a porous medium, as this is the established approach in existing aerodynamic studies using commercial computational fluid dynamics (CFD) software. The governing equations for a Darcy–Forchheimer porous media model suitable for unsteady and compressible flows are presented, which are derived by the application of volume-averaging theory to the Navier–Stokes equations. The implementation of this model within the time integration method used for the solver is then described and verified by comparison of results for steady flows against an established commercial CFD solver, where close agreement between both in-house and commercial solvers has been observed. Lastly, a preliminary demonstration of the capability to model unsteady heat exchanger flows is presented by application to an aeroacoustic problem, where the interaction of the pressure waves and the heat exchanger is investigated.
Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants
Authors: Watkins Michael , Zhu Yali , Griffith David C. , Loutit Jeffery S. , Margolis David , Gu Peidi 
Published: December 2024

ABSTRACT

BRII-693 is a next-generation intravenous (IV)-administered synthetic macrocyclic peptide antibiotic for infections caused by drug-resistant gram-negative pathogens. This single-center, randomized, double-blind, placebo-controlled phase 1 study investigated the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of BRII-693 in 104 healthy participants. In single-dose cohorts, 10–400 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort. In the 7-day repeat-dose cohorts, 100–200 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort. In two 14-day repeat-dose cohorts, 150 mg of BRII-693 was evaluated in 12 participants (10 active, two placebo) each of non-Chinese and Chinese descent. No participant reported a severe or serious adverse event (AE) or an AE leading to death. Across all cohorts and for non-Chinese and Chinese participants, most AEs were mild. C
max
and area under the concentration-time curve (AUC) increased in a dose-proportional manner over the dose range of single- and repeat-dosing. Mean
t
1/2
was 2.58–4.37 hours and generally similar across single doses. An accumulation of exposure was observed following multiple doses with an accumulation ratio of 1.5 to 1.7 which was within the expected 1.3 to 2.5 range at steady state. Mean total clearance (CL) was similar between single and multiple dose administration, suggesting time-independent pharmacokinetics (PK). PK exposure was statistically equivalent between non-Chinese and Chinese participants. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of BRII-693 in healthy non-Chinese and Chinese participants.

CLINICAL TRIALS

This study is registered with
ClinicalTrials.gov
as
NCT04808414
.
Time-decay patterns and irregular disturbance: contrasting roles of abundant and rare microbial communities in dynamic coastal seawater
Authors: Zhang Yulin , Song Derui , Yao Peng , Zhang Xiao-Hua , Liu Jiwen 
Published: December 2024

ABSTRACT

Microbial communities in coastal seas experience strong environmental disturbances, yet their response patterns, especially regarding differently abundant subcommunities, remain poorly understood. Here, through 16S rRNA gene amplicon sequencing, we investigated the diversity, time-decay pattern, and assembly process of abundant, conditionally rare taxa (CRT) and rare microbial subcommunities in temperate coastal waters over 60 consecutive weeks. The abundant (50.9%) and CRT (46.1%) communities each comprised approximately half of the planktonic community, while the CRT and rare communities contributed to the extremely high species diversity. Distinct temporal heterogeneity was observed among the three fractions and was associated with taxonomic level. The abundant subcommunity exhibited time-decay patterns at all taxonomic levels, while for CRT, the pattern was found only at finer levels. In contrast, variations of the rare community loosely followed a temporal rhythm and were largely confined within a specific taxonomic range, likely raised from turnovers among closely related taxa. Determinism dominated the community assembly of the abundant fraction, while the rare one was more controlled by stochasticity that may be related to pulse terrigenous inputs and anthropogenic disturbances. The rare subcommunity with narrow niche widths likely represented a stable repository to offer episodic specialists, while the abundant taxa that exhibited broader niche widths were considered the generalists in fluctuating environments. Our study revealed the distinct strategies that abundant and rare communities adopt to maintain community stability in temporal dynamics of prokaryotic plankton in the coastal seawater.

IMPORTANCE
The relative importance of rare and abundant taxa in microbial temporal patterns remains debated. Here, we identified taxonomically associated distinct diversity modes of abundant and rare subcommunities from a year-round time-series study in dynamic coastal seawater. We highlighted the significance of the rare subcommunity in maintaining community stability by serving as a repository to offer specialists driven by stochastic processes over time. The abundant subcommunity, by contrast, contributed mainly to temporal rhythmic variations. This study expands the current understanding of the temporal dynamics and stability of coastal microbial communities by revealing distinct variation patterns of subcommunities with different abundances.
The neonatal Fc receptor (FcRn) is required for porcine reproductive and respiratory syndrome virus uncoating
Authors: Yang Kang , Dong Jiarui , Li Jian , Zhou Rui , Jia Xiangchao , Sun Zhijian , Zhang Weida , Li Zili 
Published: December 2024

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Previous studies from other groups showed that CD163 is required for PRRSV uncoating and genome release. However, CD163 does not interact with nucleocapsid (N) protein. In this study, the neonatal Fc receptor (FcRn) was demonstrated to be irreplaceable for PRRSV infection by knockdown, overexpression, antibodies or IgG blocking, knockout, and replenishment assays. FcRn was further revealed to be involved in PRRSV uncoating for the first time rather than viral attachment and internalization. In detail, FcRn was determined to colocalize with CD163 and PRRSV virions in early endosomes and specially interact with N protein in early endosomes. Taken together, these results provide evidence that FcRn is an essential cellular factor for PRRSV uncoating, which will be a promising target to interfere with the viral infection.

IMPORTANCE

PRRSV infection results in a severe swine disease affecting pig farming in the world. Although CD163 has been implicated as the uncoating receptor for PRRSV but the uncoating mechanism of PRRSV remains unclear. Here, we identified that FcRn facilitated virion uncoating
via
interaction with viral N protein in early endosomes. Our work actually expands the knowledge of PRRSV infection and provides an attractive therapeutic target for the prevention and control of PRRS.
Draft genome of
Streptococcus agalactiae
serotype Ia FBC260 causing hemorrhagic septicemia with massive cellular meningitis in cultured Nile tilapia from the Philippines
Authors: Choresca Casiano H. , Legario Francis S. , De Leon Ma. Elaine E. , Santos Mary Nia M. , Bumanlag Benjamin E. , Ca-as Christine Grace P. , Gente Angelie A. , Gloria Paul Christian T. 
Published: December 2024

ABSTRACT

We report the draft genome of
Streptococcus agalactiae
serotype Ia strain FBC260, associated with hemorrhagic septicemia and massive cellular meningitis in cultured Nile tilapia from the Philippines. This genomic resource of
S. agalactiae
from the Philippines will provide valuable insights for disease management.
Backtranslation of human RNA biosignatures of tuberculosis disease risk into the preclinical pipeline is condition dependent
Authors: Painter Hannah , Larsen Sasha E. , Williams Brittany D. , Abdelaal Hazem F. M. , Baldwin Susan L. , Fletcher Helen A. , Fiore-Gartland Andrew , Coler Rhea N. 
Published: December 2024

ABSTRACT

It is unclear whether human progression to active tuberculosis disease (TB) risk signatures are viable endpoint criteria for evaluations of treatments in development. TB is the deadliest infectious disease globally and more efficacious vaccines are needed to reduce this mortality. However, the immune correlates of protection for either preventing infection with
Mycobacterium tuberculosis
or preventing TB disease have yet to be completely defined, making the advancement of candidate vaccines through the pipeline slow, costly, and fraught with risk. Human-derived correlate of risk (COR) gene signatures, which identify an individual’s risk of progressing to active TB disease, provide an opportunity for evaluating new therapies for TB with clear and defined endpoints. Though prospective clinical trials with longitudinal sampling are prohibitively expensive, the characterization of COR gene signatures is practical with preclinical models. Using a 3Rs (replacement, reduction, and refinement) approach we reanalyzed heterogeneous publicly available transcriptional data sets to determine whether a specific set of COR signatures are viable endpoints in the preclinical pipeline. We selected RISK6, Sweeney3, and BATF2 human-derived blood-based RNA biosignatures because they require relatively few genes and have been carefully evaluated across several clinical cohorts. These data suggest that in certain experimental designs and in several tissue types, human COR signatures correlate with disease progression as measured by the bacterial burden in the preclinical TB model pipeline. We observed the best performance when the model most closely reflected human infection or disease conditions. Human-derived COR signatures offer an opportunity for high-throughput preclinical endpoint criteria of vaccine and drug therapy evaluations.

IMPORTANCE
Understanding the strengths or limitations of back-translating human-derived correlate of risk (COR) RNA signatures into the preclinical pipeline may help streamline down-selection of therapeutic vaccine and drug candidates and better align preclinical models with proposed clinical trial efficacy endpoints.
Management of pain and sedation in the intensive care unit
Authors: Boncyk Christina , Rolfsen Mark L , Richards David , Stollings Joanna L , Mart Matthew F , Hughes Christopher G , Ely E Wesley 
Published: December 2024

Abstract
Advances in our approach to treating pain and sedation when caring for patients in the intensive care unit (ICU) have been propelled by decades of robust trial data, knowledge gained from patient experiences, and our evolving understanding of how pain and sedation strategies affect patient survival and long term outcomes. These data contribute to current practice guidelines prioritizing analgesia-first sedation strategies (analgosedation) that target light sedation when possible, use of short acting sedatives, and avoidance of benzodiazepines. Together, these strategies allow the patient to be more awake and able to participate in early mobilization and family interactions. The covid-19 pandemic introduced unique challenges in the ICU that affected delivery of best practices and patient outcomes. Compliance with best practices has not returned to pre-covid levels. After emerging from the pandemic and refocusing our attention on optimal pain and sedation management in the ICU, it is imperative to revisit the data that contributed to our current recommendations, review the importance of best practices on patient outcomes, and consider new strategies when advancing patient care.