bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a novel ambulatory monitoring system to support patient safety on an acute infectious disease ward during an unfolding pandemic
Authors: Buss Annika , Areia Carlos , Biggs Christopher , Edmundson Holly , Young Louise , Roman Cristian , Santos Mauro , Tarassenko Lionel , Watkinson Peter , Vollam Sarah 
Published: December 2023

AbstractAimTo gain staff feedback on the implementation and impact of a novel ambulatory monitoring system to support coronavirus patient management on an isolation ward.DesignQualitative service evaluation.MethodsSemi‐structured interviews were conducted with 15 multidisciplinary isolation ward staff in the United Kingdom between July 2020 and May 2021. Interviews were audio‐recorded, transcribed and analysed using thematic analysis.FindingsAdopting Innovation to Assist Patient Safety was identified as the overriding theme. Three interlinked sub‐themes represent facets of how the system supported patient safety. Patient Selection was developed throughout the pandemic, as clinical staff became more confident in choosing which patients would benefit most. Trust In the System described how nurses coped with discrepancies between the ambulatory system and ward observation machines. Finally, Resource Management examined how, once trust was built, staff perceived the ambulatory system assisted with caseload management. This supported efficient personal protective equipment resource use by reducing the number of isolation room entries. Despite these reported benefits, face‐to‐face contact was still highly valued, despite the risk of coronavirus exposure.ConclusionHospital wards should consider using ambulatory monitoring systems to support caseload management and patient safety. Patients in isolation rooms or at high risk of deterioration may particularly benefit from this additional monitoring. However, these systems should be seen as an adjunct to nursing care, not a replacement.Implications for the Profession and/or Patient CareNurses valued ambulatory monitoring as a means of ensuring the safety of patients at risk of deterioration and prioritizing their workload.ImpactThe findings of this research will be useful to all those developing or considering implementation of ambulatory monitoring systems in hospital wards.Reporting MethodThis manuscript follows the Consolidated criteria for Reporting Qualitative Research (COREQ) guidelines with inclusion of relevant SQUIRE guidelines for reporting quality improvement.Patient or Public ContributionNo Patient or Public Contribution.
Severe asthma in horses is associated with increased airway innervation
Authors: Leduc Laurence , Leclère Mathilde , Gauthier Laurie Girardot , Marcil Olivier , Lavoie Jean‐Pierre 
Published: December 2023

AbstractBackgroundAltered innervation structure and function contribute to airway hyperresponsiveness in human asthma, yet the role of innervation in airflow limitation in asthma in horses remains unknown.HypothesisTo characterize peribronchial innervation in horses with asthma. We hypothesized that airway innervation increases in horses with asthma compared with controls.AnimalsFormalin‐fixed lung samples from 8 horses with severe asthma and 8 healthy horses from the Equine Respiratory Tissue Biobank. Ante‐mortem lung function was recorded.MethodsBlinded case‐control study. Immunohistochemistry was performed using rabbit anti‐s100 antibody as a neuronal marker for myelinating and non‐myelinating Schwann cells. The number and cumulative area of nerves in the peribronchial region and associated with airway smooth muscle were recorded using histomorphometry and corrected for airway size.ResultsBoth the number (median [IQR]: 1.87 × 10−5 nerves/μm2 [1.28 × 10−5]) and the cumulative nerve area (CNA; 1.03 × 10−3 CNA/μm2 [1.57 × 10−3]) were higher in the peribronchial region of horses with asthma compared with controls (5.17 × 10−6 nerves/μm2 [3.76 × 10−6], 4.14 × 10−4 CNA/μm2 [2.54 × 10−4], Mann‐Whitney, P = .01). The number of nerves within or lining airway smooth muscle was significantly higher in horses with asthma (4.47 × 10−6 nerves/μm2 [5.75 × 10−6]) compared with controls (2.26 × 10−6 nerves/μm2 [1.16 × 10−6], Mann‐Whitney, P = .03).Conclusions and Clinical ImportanceAsthma in horses is associated with greater airway innervation, possibly contributing to airway smooth muscle remodeling and exacerbating severity of the disease.
Oncological impact of perioperative blood transfusion in bladder cancer patients undergoing radical cystectomy: Do we need to consider storage time of blood units, donor age, or gender matching?
Authors: Ebner Benedikt , Fleckenstein Franka , Volz Yannic , Eismann Lennert , Hermans Julian , Buchner Alexander , Enzinger Benazir , Weinhold Philipp , Wichmann Christian , Stief Christian Georg , Humpe Andreas , Pyrgidis Nikolaos , Schulz Gerald Bastian 
Published: December 2023

AbstractBackgroundThe oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching.Study Design and MethodsWe retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021. We excluded patients receiving BUs before RC, >10 BUs, or RC in a palliative setting. We assessed the effect of blood donor characteristics and storage time on overall survival (OS) and cancer‐specific survival (CSS) through univariate and multivariable Cox regression analysis. We also performed a propensity score matching with patients who received BUs and patients who did not on a 1:1 ratio.ResultsWe screened 1692 patients and included 676 patients for the propensity score matching. In the multivariable analysis, PBT was independently associated with worse OS and CSS (p < .001). Postoperative transfusions were associated with better OS (p = .004) and CSS (p = .008) compared to intraoperative or mixed transfusions. However, there was no influence of blood donor age, storage time, or gender matching on prognosis.DiscussionIn our study of BCa patients undergoing RC, we demonstrate that PBT, especially if administered intraoperatively, is an independent risk factor for a worse prognosis.However, storage time, donor age, or gender matching did not negatively affect oncological outcomes. Therefore, the specific selection of blood products does not promise any benefits.
Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential
Authors: Sakthikumar Sharadha , Warrier Manisha , Whitley Derick , Facista Salvatore , Adkins Jonathan , Aman Sara , Tsinajinnie Darwin , Duran Natalie , Siravegna Giulia , Ahmed Zeeshan , Day Kenneth , Jenkins Brooklyn , Patel Nidhi , Ryden Kirk , Nadai Joe , Banovich Kathryn , Powers Barbara , Edwards Jeffrey , Steinberg Jennifer , Fielder Susan , Wong Shukmei , Byron Sara A. , Izatt Tyler , Zismann Victoria , Boateng Martin , Zhu Zhanyang , Chuang Han‐Yu , Trent Jeffrey M. , Haworth David , Chon Esther , Hendricks William , Wang Guannan 
Published: December 2023

AbstractA genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation‐based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics‐guided medicine in canine oncology, we have developed and validated a canine cancer next‐generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation‐based biomarkers in veterinary oncology.
Distinct microbial communities degrade cellulose diacetate bioplastics in the coastal ocean
Authors: Sun Yanchen , Mazzotta Michael G. , Miller Carolyn A. , Apprill Amy , Izallalen Mounir , Mazumder Sharmistha , Perri Steven T. , Edwards Brian , Reddy Christopher M. , Ward Collin P. 
Published: December 2023

ABSTRACT

Cellulose diacetate (CDA) is a bio-based plastic widely used in consumer products. CDA is a promising alternative to conventional thermoplastics due to its susceptibility to biodegradation in various environments. Despite widespread evidence for the degradation of CDA, relatively little is known about the microorganisms that drive degradation, particularly in the ocean. Recently, we documented the biodegradation of CDA-based materials (i.e., fabric, film, and foam) in a continuous-flow natural seawater mesocosm on the timescales of months, as indicated by mass loss, enzyme activity, and respiration to carbon dioxide. These findings paved the way for the present study aimed at identifying key microbial taxa implicated in CDA degradation. Analysis based on 16S rRNA gene amplicon sequencing of bacteria and archaea revealed that material type, incubation time, material morphology (e.g., fabric vs film), and plasticizer content significantly influenced the microbial community structure. Differential abundance analysis revealed that bacterial taxa affiliated with the families of
Arenicellaceae
,
Cellvibrionaceae
,
Methyloligellaceae
,
Micavibrionaceae
,
Puniceicoccaceae
,
Spirosomaceae
, and
Thermoanaerobaculaceae
, and the order of
Pseudomonadales
potentially initiated the degradation (i.e., deacetylation) of CDA fabric and film. These taxa were notably distinct from CDA-degrading microbes reported in non-seawater environments. Collectively, the findings lend further support for CDA as a promising next-generation, high-utility, and low-environmental persistence bioplastic material.

IMPORTANCE
Cellulose diacetate (CDA) is a promising alternative to conventional plastics due to its versatility in manufacturing and low environmental persistence. Previously, our group demonstrated that CDA is susceptible to biodegradation in the ocean on timescales of months. In this study, we report the composition of microorganisms driving CDA degradation in the coastal ocean. We found that the coastal ocean harbors distinct bacterial taxa implicated in CDA degradation and these taxa have not been previously identified in prior CDA degradation studies, indicating an unexplored diversity of CDA-degrading bacteria in the ocean. Moreover, the shape of the plastic article (e.g., a fabric, film, or foam) and plasticizer in the plastic matrix selected for different microbial communities. Our findings pave the way for future studies to identify the specific species and enzymes that drive CDA degradation in the marine environment, ultimately yielding a more predictive understanding of CDA biodegradation across space and time.
Transcriptional expression of
PHR2
is positively controlled by the calcium signaling transcription factor Crz1 through its binding motif in the promoter
Authors: Jiang Linghuo , Xu Huihui , Wei Min , Gu Yiying , Yan Hongbo , Pan Lingxin , Wei Chunyu 
Published: December 2023

ABSTRACT

GH72 family of β-(1,3)-glucanosyltransferases is required for cell wall biogenesis, morphogenesis, and virulence of fungi.
Candida albicans PHR2
is an acidic pH-induced gene that encodes a GH72 enzyme involved in cross-linking of β−1,3- and β−1,6-glucans in the cell wall. In response to environmental pH changes, the expression of
PHR2
is negatively regulated by the transcription factor CaRim101 through the pH-responsive Rim101 pathway. In this study, we have generated the inactivation mutant for
PHR2
through the CRISPR/Cas9 approach. The
PHR2
mutant is sensitive to both membrane- and cell wall-disturbing agents, SDS, Calcofluor white and casponfungi, but resistant to two azole antifungals, ketoconazole and fluconazole. Although the
PHR2
mutant is not sensitive to calcium stress, it becomes sensitive to high levels of calcium stress in the presence of cyclosporin A, the specific inhibitor of calcineurin. In addition, we have demonstrated that the expression of
PHR2
, the downstream target of CaRim101, is positively controlled by the transcription factor CaCrz1 through its binding motif (5′ A
-315
TAGGCACAG 3′) in the
PHR2
promoter. Furthermore, the deletion of
PHR2
increases the cell precipitation rate in cell culture under acidic conditions.

IMPORTANCE

The fungal cell wall consists of glucans, mannoproteins, and chitin and is essential for cell viability, morphogenesis, and pathogenesis. The enzymes of the GH72 family are responsible for ß-(1,3)-glucan elongation and branching, which is crucial for the formation of the glucan-chitin polymer at the bud neck of yeast cells. In the human fungal pathogen Candida albicans, there are five GH72 enzyme-encoding genes:
PHR1, PHR2, PHR3, PGA4
, and
PGA5
. It is known that expression of
PHR1
and
PHR2
is controlled by the pH-responsive Rim101 pathway through the transcription factor Rim101. In this study, we have demonstrated that the transcription expression of
PHR2
is also controlled by the transcription factor Crz1 through its binding motif in the promoter. Therefore, we have uncovered a dual-control mechanism by which
PHR2
expression is negatively regulated via CaRim101 through the pH-responsive pathway and positively modulated by CaCrz1 through the calcium/calcineurin signaling pathway.
Evaluation of the Xpert Xpress GBS test for rapid detection of group B
Streptococcus
in pregnant women
Authors: Wang Feiling , Yi Lehui , Ming Fang , Dong Rui , Wang Feng , Chen Ruirui , Hu Xiaoling , Chen Xuri , Sun Bo , Tang Yi-Wei , Zhu Yuanfang , Wu Lijuan 
Published: December 2023

ABSTRACT

Group B
Streptococcus
(GBS) remains the leading cause of serious neonatal infection. Prenatal screening for vaginal and rectal GBS colonization is necessary in late pregnancy. Our objective was to compare the performance of four methods including the Xpert Xpress GBS, standard broth enrichment culture, real-time quantitative PCR (qPCR), and direct culture, for detecting of GBS in rectovaginal specimens. Among 939 pregnant women at 35–37 weeks of gestation recruited in the study, 168 (17.9%) were determined to be GBS-colonized by broth enrichment culture, the gold standard. The sensitivity and specificity of the Xpert Xpress GBS were 94.6% and 95.9%, respectively. The hands-on time and running time of the Xpert Xpress GBS were 1 minute and less than 1 hour, respectively. As a random-access, integrated device, the Xpert Xpress GBS test efficiently and accurately screens rectovaginal swabs for GBS colonization in pregnant women.

IMPORTANCE

This was the first study evaluating the performance of the Xpert Xpress group B
Streptococcus
(GBS) test using rectovaginal swabs from Chinese pregnant women. Compared to the other three assays, the Xpert Xpress GBS test demonstrated high sensitivity and specificity when screening 939 pregnant women for GBS in rectovaginal specimens. Additionally, its reduced time to obtain results makes it valuable for the rapid detection of GBS.
Vav proteins do not influence dengue virus replication but are associated with induction of phospho-ERK, IL-6, and viperin mRNA following DENV infection
in vitro
Authors: Cowell Evangeline , Jaber Hawraa , Kris Luke P. , Fitzgerald Madeleine G. , Sanders Valeria M. , Norbury Aidan J. , Eyre Nicholas S. , Carr Jillian M. 
Published: December 2023

ABSTRACT
Vav proteins are guanine exchange factors that activate Rac1/RhoA signaling to regulate many biological processes including inflammatory responses. Here, the expression and functional significance of Vav’s were investigated during dengue virus (DENV) infection. In primary monocyte-derived macrophages, Vav1, −2, and −3 mRNA levels demonstrate variable responses to DENV infection and correlate with DENV-induced host inflammatory (IL-6 and TNF-α), antiviral (viperin), or cell adhesion [intercellular cell adhesion molecule (ICAM-1)] mRNA induction. Strong positive correlations were seen in particular for Vav2 with TNF-α and Vav3 with IL-6 mRNA. In the retinal pigmented epithelial cell line, ARPE-19, Vav2 was the main Vav expressed and was not affected by DENV infection. Heterologous Vav1 expression in ARPE-19 cells induced an increase in basal IL-6 mRNA but did not enhance DENV-induced mRNA responses. DENV RNA and DENV-induced viperin and IL-6 mRNA responses were also unaffected by Vav2 siRNA knockdown. Treatment of DENV-infected ARPE-19 cells with EHop-016 to block Vav signaling did not affect DENV RNA levels but increased DENV-mediated induction of IL-6 mRNA. More detailed assessment of DENV-induced responses to azathioprine, a clinically used immunosuppressant that can also block Vav signaling and act as a nucleoside analog, similarly demonstrated no change in DENV RNA levels but resulted in inhibition of DENV-induced phospho-ERK and increased DENV-induced-IL-6 and viperin mRNA in ARPE-19 cells. Thus, levels of Vav are associated with DENV-induced inflammatory responses, and blocking Vav signaling pathways does not compromise control of viral replication but may influence DENV-induced host responses.

IMPORTANCE
Dengue disease is characterized by an inflammatory-mediated immunopathology, with elevated levels of circulating factors including TNF-α and IL-6. If the damaging inflammatory pathways could be blocked without loss of antiviral responses or exacerbating viral replication, then this would be of potential therapeutic benefit. The study here has investigated the Vav guanine exchange factors as a potential alternative signaling pathway that may drive dengue virus (DENV)-induced inflammatory responses, with a focus on Vav1 and 2. While Vav proteins were positively associated with mRNA for inflammatory cytokines, blocking Vav signaling didn’t affect DENV replication but prevented DENV-induction of p-ERK and enhanced IL-6 (inflammatory) and viperin (antiviral) mRNA. These initial data suggest that Vav proteins could be a target that does not compromise control of viral replication and should be investigated further for broader impact on host inflammatory responses, in settings such as antibody-dependent enhancement of infection and in different cell types.
Val43 residue of NsrR is crucial for the nitric oxide response of
Salmonella
Typhimurium
Authors: Park Hee Jeong , Jeong Hye Won , Lee Choa , Lee Mi Rae , Choi Hojung , Kim Eungseok , Bang Iel Soo 
Published: December 2023

ABSTRACT

In pathogenic bacteria, the flavohemoglobin Hmp is crucial in metabolizing the cytotoxic levels of nitric oxide (NO) produced in phagocytic cells, contributing to bacterial virulence. Hmp expression is predominantly regulated by the Rrf2 family transcription repressor NsrR in an NO-dependent manner; however, the underlying molecular mechanism in enterobacteria remains poorly understood. In this study, we identified Val43 of
Salmonella
Typhimurium NsrR (StNsrR) as a critical amino acid residue for regulating Hmp expression. The Val43-to-Ala-substituted mutant NsrR isolated through random and site-directed mutagenesis showed high binding affinity to the target DNA irrespective of NO exposure, resulting in a severe reduction in
hmp
transcription and slow NO metabolism in
Salmonella
under NO-producing conditions. Conversely, the Val43-to-Glu-substituted NsrR caused effects similar to
nsrR
null mutation, which directed
hmp
transcription and NO metabolism in a constitutive way. Comparative analysis of the primary sequences of NsrR and another NO-sensing Rrf2 family regulator, IscR, from diverse bacteria, revealed that Val43 of enterobacterial NsrR corresponds to Ala in
Pseudomonas aeruginosa
or
Streptomyces coelicolor
NsrR and Glu in enterobacterial IscR, all of which are located in the DNA recognition helix α3. The predicted structure of StNsrR in complex with the
hmp
DNA suggests dissimilar spatial stoichiometry in the interactions of Val43 and its substituted residues with the target DNA, consistent with the observed phenotypic changes in StNsrR Val43 mutants. Our findings highlight the discriminative roles of the NsrR recognition helix in regulating species-specific target gene expression, facilitating effective NO detoxification strategies in bacteria across diverse environments.

IMPORTANCE

The precise regulation of flavohemoglobin Hmp expression by NsrR is critical for bacterial fitness, as excessive Hmp expression in the absence of NO can disturb bacterial redox homeostasis. While the molecular structure of
Streptomyces coelicolor
NsrR has been recently identified, the specific molecular structures of NsrR proteins in enterobacteria remain unknown. Our discovery of the crucial role of Val43 in the DNA recognition helix α3 of
Salmonella
NsrR offers valuable insights into the Hmp modulation under NO stress. Furthermore, the observed amino acid polymorphisms in the α3 helices of NsrR proteins across different bacterial species suggest the diverse evolution of NsrR structure and gene regulation in response to varying levels of NO pressure within their ecological niches.
Impact of cord clamping on haemodynamic transition in term newborn infants
Authors: Chioma Roberto , Finn Daragh , Healy David B , Herlihy Ita , Livingstone Vicki , Panaviene Jurate , Dempsey Eugene M 
Published: December 2023

ObjectiveTo assess the haemodynamic consequences of cord clamping (CC) in healthy term infants.DesignCohort study.SettingTertiary maternity hospital.Patients46 full-term vigorous infants born by caesarean section.InterventionsEchocardiography was performed before CC, immediately after CC and at 5 min after birth.Main outcome measuresPulsed wave Doppler-derived cardiac output and the pulmonary artery acceleration time indexed to the right ventricle ejection time were obtained. As markers of loading fluctuations, the myocardial performance indexes and the velocities of the tricuspid and mitral valve annuli were determined with tissue Doppler imaging. Heart rate was derived from Doppler imaging throughout the assessments.ResultsLeft ventricular output increased throughout the first minutes after birth (mean (SD) 222.4 (32.5) mL/kg/min before CC vs 239.7 (33.6) mL/kg/min at 5 min, p=0.01), while right ventricular output decreased (306.5 (48.2) mL/kg/min before vs 272.8 (55.5) mL/kg/min immediately after CC, p=0.001). The loading conditions of both ventricles were transiently impaired by CC, recovering at 5 min. Heart rate progressively decreased after birth, following a linear trend temporarily increased by CC. The variation in left ventricular output across the CC was directly correlated to the fluctuation of left ventricular preload over the same period (p=0.03).ConclusionsThis study illustrates the cardiovascular consequences of CC in term vigorous infants and offers insight into the haemodynamic transition from fetal to neonatal circulation in spontaneously breathing newborns. Strategies that aim to enhance left ventricular preload before CC may prevent complications of perinatal cardiovascular imbalance.