bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a copper-responsive small molecule inhibitor of uropathogenic
Escherichia coli
Authors: Hanson Braden S. , Hailemariam Amanuel , Yang Yongjian , Mohamed Faras , Donati George L. , Baker Dwight , Sacchettini James , Cai James J. , Subashchandrabose Sargurunathan 
Published: June 2024

ABSTRACT

Urinary tract infections (UTIs) are a major global health problem and are caused predominantly by uropathogenic
Escherichia coli
(UPEC). UTIs are a leading cause of prescription antimicrobial use. Incessant increase in antimicrobial resistance in UPEC and other uropathogens poses a serious threat to the current treatment practices. Copper is an effector of nutritional immunity that impedes the growth of pathogens during infection. We hypothesized that copper would augment the toxicity of select small molecules against bacterial pathogens. We conducted a small molecule screening campaign with a library of 51,098 molecules to detect hits that inhibit a UPEC Δ
tolC
mutant in a copper-dependent manner. A molecule, denoted as
E. coli
inhibitor or ECIN, was identified as a copper-responsive inhibitor of wild-type UPEC strains. Our gene expression and metal content analysis results demonstrate that ECIN works in concert with copper to exacerbate Cu toxicity in UPEC. ECIN has a broad spectrum of activity against pathogens of medical and veterinary significance including
Acinetobacter baumannii, Pseudomonas aeruginosa
, and methicillin-resistant
Staphylococcus aureus
. Subinhibitory levels of ECIN eliminate UPEC biofilm formation. Transcriptome analysis of UPEC treated with ECIN reveals induction of multiple stress response systems. Furthermore, we demonstrate that L-cysteine rescues the growth of UPEC exposed to ECIN. In summary, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC.

IMPORTANCE

Urinary tract infection (UTI) is a ubiquitous infectious condition affecting millions of people annually. Uropathogenic
Escherichia coli
(UPEC) is the predominant etiological agent of UTI. However, UTIs are becoming increasingly difficult to resolve with antimicrobials due to increased antimicrobial resistance in UPEC and other uropathogens. Here, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC. In addition to
E. coli
, this small molecule also inhibits pathogens of medical and veterinary significance including
Acinetobacter baumannii, Pseudomonas aeruginosa,
and methicillin-resistant
Staphylococcus aureus
.
Performance of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of invasive pulmonary filamentous fungi infections in non-neutropenic patients
Authors: Wang Hansheng , Yu Dan , Chen Xiao , Zhou Yanhui , Qian Xin , Liu Dan , Wang Lei , Tang Yijun , Wang Meifang 
Published: June 2024

ABSTRACT

The diagnosis of invasive pulmonary fungal disease depends on histopathology and mycological culture; there are few studies on touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of pulmonary filamentous fungi infections. The purpose of the present study was to explore the detection accuracy of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the filamentous fungi, and it aims to provide a basis for initiating antifungal therapy before obtaining microbiological evidence. We retrospectively analyzed the diagnosis and treatment of 44 non-neutropenic patients with invasive pulmonary filamentous fungi confirmed by glactomannan assay, histopathology, and culture from February 2017 to December 2023. The diagnostic positive rate and sensitivity of rapid on-site evaluation for these filamentous fungi identification, including diagnostic turnaround time, were calculated. Compared with the final diagnosis, the sensitivity of rapid on-site evaluation was 81.8%, and the sensitivity of histopathology, culture of bronchoalveolar lavage fluid, and glactomannan assay of bronchoalveolar lavage fluid was 86.4%, 52.3%, and 68.2%, respectively. The average turnaround time of detecting filamentous fungi by rapid on-site evaluation was 0.17 ± 0.03 hours, which was significantly faster than histopathology, glactomannan assay, and mycological culture. A total of 29 (76.3%) patients received earlier antifungal therapy based on ROSE diagnosis and demonstrated clinical improvement. Rapid on-site evaluation showed good sensitivity and accuracy that can be comparable to histopathology in identification of pulmonary filamentous fungi. Importantly, it contributed to the triage of biopsies for further microbial culture or molecular detection based on the preliminary diagnosis, and the decision on early antifungal therapy before microbiological evidence is available.
Microbial diversity, genomics, and phage–host interactions of cyanobacterial harmful algal blooms
Authors: Krausfeldt Lauren E. , Shmakova Elizaveta , Lee Hyo Won , Mazzei Viviana , Loftin Keith A. , Smith Robert P. , Karwacki Emily , Fortman P. Eric , Rosen Barry H. , Urakawa Hidetoshi , Dadlani Manoj , Colwell Rita R. , Lopez Jose V. 
Published: June 2024

ABSTRACT

The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom “hotspots” near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of “-omics” to reveal important biological processes that could support the effective management and prediction of cyanoHABs.

IMPORTANCE
Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.
Effectiveness of nirsevimab immunoprophylaxis against respiratory syncytial virus-related outcomes in hospital and primary care settings: a retrospective cohort study in infants in Catalonia (Spain)
Authors: Coma Ermengol , Martinez-Marcos Montserrat , Hermosilla Eduardo , Mendioroz Jacobo , Reñé Anna , Fina Francesc , Perramon-Malavez Aida , Prats Clara , Cereza Gloria , Ciruela Pilar , Pineda Valentí , Antón Andrés , Ricós-Furió Gemma , Soriano-Arandes Antoni , Cabezas Carmen 
Published: June 2024

BackgroundIn Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab’s effectiveness across primary and hospital care outcomes.MethodsRetrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome—RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis—death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs.ResultsAmong 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection.ConclusionWe demonstrated nirsevimab’s effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns.
Identifying neonatal transport research priorities: a modified Delphi consensus
Authors: Mistry Aarti , Leslie Andrew , Ojha Shalini , Sharkey Don 
Published: June 2024

ObjectivesWith increasing advances in neonatal transport, a focused research strategy is required to increase the evidence base towards providing optimal care. We aimed to identify the most important neonatal transport research questions as prioritised by parents and healthcare professionals (HCPs).DesignKey stakeholders participated in a modified three-stage Delphi consensus process. Research questions were identified and submitted through two survey stages before the final priority setting workshop.ParticipantsParents of babies who received neonatal care, neonatal HCPs and stakeholders.OutcomeIdentify the top 10 research priorities for neonatal transport.ResultsOverall, 269 survey responses from HCPs/stakeholders (n=161) and parents (n=108) were analysed from two survey rounds. Consensus was reached on 22 of 43 research priorities for the final priority setting workshop. The agreed top research priorities covered the domains of: (1) Pain assessment and management, (2) Long-term neurological outcomes, (3) Impact of transfer on birth-related brain injury, (4) Investigating risk of transport, (5) Safety restraints for infants, (6) Optimal temperature management, (7) Respiratory management and outcomes, (8) Benchmarking of important of transport measures, (9) Understanding transport environmental exposures, (10) Mental health and burden of transfer on families.ConclusionWe have identified the top research questions for neonatal transport through an extensive process actively engaging parents, HCPs and key stakeholders. Targeted funding and research resources, directed towards addressing these prioritised research areas, will inform evidence-based practices and international frameworks specific to neonatal transport, helping minimise research waste and ultimately improve outcomes for these high-risk infants and their families.
Relevance of meeting general outpatients’ information needs to their perceptions of healthcare quality in a hospital in Ghana: a Healthcare Quality Survey using modified SERVQUAL analysis
Authors: Asare Anita Ago , Otchi Elom , Manu Adom 
Published: June 2024

BackgroundPatients determine quality of healthcare by their perception of the gap between the healthcare they experience/receive and that which they expect. This can be influenced by the ability of healthcare staff to adequately communicate information about the healthcare provided. This study assessed the level of relevance of meeting patients’ information needs with respect to their assessment of healthcare quality in a private hospital’s general outpatient department in Ghana.DesignStudy design was cross-sectional using exit self-administered questionnaires among 390 outpatients. Healthcare quality was measured using a modified form of the Service Quality model gap analysis (gap between experience and expectations). A negative gap signifies unmet patient expectations. Microsoft Excel and Stata V.15.0 were used for analysis using t-test and multiple linear regression. A p value ≤0.05 denotes statistical significance.FindingsThe mean percentage of patients’ expectations of quality of healthcare was 87.6% (SE 0.031), while patient experience was 86.0% (SE 0.029), with a significant negative gap of −0.08 (p<0.002). Their highest expectation of the quality of healthcare was for their information needs to be met, with a mean score of 4.44 (SE 0.03). Two of the four items under the information needs dimension that showed no statistically significant gaps were ‘saying all their problems’ (gap=0.00; p<0.9) and ‘explanation of treatment/medications’ (gap=0.01; p<0.6). Those with statistically significant negative gaps were ‘explanation of investigations and procedures’ (gap=−0.18; p<0.0001) and ‘explanation of the diagnoses’ (gap=−0.11; p<0.02), signifying unmet expectations.ConclusionsThe outpatient’s greatest need for quality healthcare in this study was for their information needs to be met. Providing information on patient diagnoses and investigations are the areas least likely to be adequately communicated to patients.
Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes
Authors: Cha Junha , Kim Da Hee , Kim Gamin , Cho Jae-Won , Sung Euijeong , Baek Seungbyn , Hong Min Hee , Kim Chang Gon , Sim Nam Suk , Hong Hyun Jun , Lee Jung Eun , Hemberg Martin , Park Seyeon , Yoon Sun Ock , Ha Sang-Jun , Koh Yoon Woo , Kim Hye Ryun , Lee Insuk 
Published: June 2024

BackgroundOropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC. However, the clinical benefits of immunotherapy in patients with HPV-positive OPSCC remain unclear.MethodsTo identify the cellular and molecular factors that limited the benefits associated with HPV in OPSCC immunotherapy, we performed single-cell RNA (n=20) and T-cell receptor sequencing (n=10) analyses of tonsil or base of tongue tumor biopsies prior to immunotherapy. Primary findings from our single-cell analysis were confirmed through immunofluorescence experiments, and secondary validation analysis were performed via publicly available transcriptomics data sets.ResultsWe found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. We also observed a significantly larger proportion of CD4+follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+resident memory T cells (Trm) with elevatedKLRB1(encoding CD161) expression showed an association with dampened antitumor activity in patients with HPV-positive OPSCC, which may explain their heterogeneous clinical outcomes. Notably, all HPV-positive patients, whose Trm presented elevatedKLRB1levels, showed low expression ofCLEC2D(encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade showed an inverse correlation between the density of CD161+Trm and changes in tumor size.ConclusionsWe found that CD161+Trm counteracts clinical benefits associated with HPV in OPSCC immunotherapy. This suggests that targeted inhibition of CD161 in Trm could enhance the efficacy of immunotherapy in HPV-positive oropharyngeal cancers.Trial registration numberNCT03737968.
Emotionally intelligent themes in medical leaders’ decision-making during COVID-19
Authors: White Bobbie Ann Adair , Dayag Heather Valenova , Barry Erin S , Quinn Joann Farrell 
Published: June 2024

BackgroundThe COVID-19 pandemic presented unprecedented challenges for leaders in healthcare requiring decision-making and crisis response that can often be tricky without the right level of trust. Trust is fostered and facilitated with emotional intelligence (EI); thus, a critical examination of medical leaders’ reflections was essential to understand how leaders perceived their leadership responses during the initial response to COVID-19. This exploratory study used an EI lens to investigate leaders’ perceptions of their decision-making during COVID-19.MethodsA purposeful sample of seven leaders in medicine who experienced leading during COVID were invited to participate in semi-structured interviews.ResultsFour themes around leadership response during the uncertain times of the COVID-19 were identified. The themes included communication, interprofessional collaboration including decision-making and strategic planning, internal and external awareness, and finally, trust and psychological safety.ConclusionsIncorporating EI competencies into crisis leadership education for healthcare professionals could enhance medical leaders’ preparedness to adapt, collaborate and communicate effectively in a crisis.
Monitoring estuarine fish communities: environmental DNA (eDNA) metabarcoding as a complement to beach seining
Authors: Saunders Mark D. , Steeves Royce , MacIntyre Leah P. , Knysh Kyle M. , Coffin Michael R.S. , Boudreau Monica , Pater Christina C. , van den Heuvel Michael R. , Courtenay Simon C. 
Published: June 2024

Environmental deoxyribonucleic acid (eDNA) metabarcoding offers advantages over physical capture for identifying and quantifying animals in monitoring programs. In this study, the fish community was sampled at three stations (inner, middle, and outer estuary) in three estuaries in August 2020, and four estuaries in June and August 2021 (Prince Edward Island, Canada) using both beach seining and eDNA metabarcoding. Two 12S primer sets, 12S-160 and 12S-248F, with different amplicon lengths, yielded similar results. eDNA metabarcoding consistently detected species captured by 186 co-located beach seines and revealed additional species. It also detected monthly (June–August), interannual (2020–2021), and spatial shifts in the fish community, distinguishing stations separated by as little as 0.4 km. Positive correlations existed between eDNA metabarcoding species reads and beach seining captures. These findings suggest eDNA metabarcoding complements physical capture methods for characterizing nearshore fish communities in Prince Edward Island’s estuaries. While eDNA techniques lack certain population parameter information provided by physical methods, such as size, sex, and age structure, they offer a more comprehensive diversity assessment and presence–abundance insights, especially in inaccessible environments.
An improved calculation of the $$D_{(s)}^*D_{(s)}V$$ and $$B_{(s)}^*B_{(s)}V$$ couplings from light-cone sum rules
Authors: Jin Su-Ping , Jiang Hua-Yu 
Published: June 2024

AbstractWe present an improved calculation of the $$D_{(s)}^*D_{(s)}V$$

D

(
s
)

∗

D

(
s
)

V

and $$B_{(s)}^*B_{(s)}V$$

B

(
s
)

∗

B

(
s
)

V

coupling constants, where V denotes $$\rho $$
ρ
, $$K^*$$

K
∗

, $$\omega $$
ω
, and $$\phi $$
ϕ
mesons. These couplings govern the long-distance quantum chromodynamics (QCD) in interactions between heavy pseudo-scalar/vector mesons and light vector mesons. Our analysis is conducted within the framework of QCD light-cone sum rules (LCSRs) by utilizing the light-cone distribution amplitudes (LCDAs) of light vector mesons. By systematically incorporating the subleading power corrections and higher-twist contributions at the leading order (LO) and including the next-to-leading order (NLO) corrections at leading power, we achieve enhanced accuracy in the light-cone operator product expansion (OPE) for the underlying correlation function. In assessing the reliability of the established LCSRs, we consider uncertainties arising from the choice of the quark–hadron duality region in the double dispersion relation. Building upon these improvements, we accomplish an optimized computation and analysis for the strong coupling constants $$g_{H^*HV}$$

g

H
∗

H
V

which are used to extract the effective coupling $$\lambda $$
λ
in the heavy meson chiral perturbation theory (HM$$\chi $$
χ
PT). Furthermore, we investigate the SU(3) flavor symmetry-breaking effects in detail and compare our sum rule calculations with previous studies in an exploratory way.
Hidden BPS states of electroweak monopoles and a new bound estimate
Authors: Gunawan A. , Ramadhan H. S. , Prasetyo I. 
Published: June 2024

AbstractUsing the BPS Lagrangian method, we obtain a distinct set of Bogomolny equations for the Cho–Maison monopoles from the bosonic sector of a regularized electroweak theory. In the limit of $$n\rightarrow \infty $$

n
→
∞

of the permittivity regulator, $$\epsilon \left( \rho ^n\right) $$

ϵ

ρ
n

, the mass of the monopole can be estimated as $$M_W\sim 3.56$$

M
W

∼
3.56

TeV. This value is within the latest theoretical window, 2.98–3.75 TeV. We also discuss some possible regularization mechanisms of the electroweak monopole in the Yang–Mills sector and the existence of its BPS state.