bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial peptide DiPGLa-H exhibits the most outstanding anti-infective activity among the PGLa variants based on a systematic comparison
Authors: Zheng Liangjun , Zafir Muhammad , Zhang Ziqian , Ma Yadong , Yang Fengyi , Wang Xiaokun , Xue Xuemei , Wang Chen , Li Ping , Liu Pilong , El-Gohary Fatma A. , Zhao Xin , Xue Huping 
Published: February 2025

ABSTRACT

The escalating threat of antibiotic-resistant bacteria has heightened global interest in antimicrobial peptides as promising candidates due to their potent broad-spectrum activity and low likelihood of resistance development. Despite this potential, these peptides face challenges, including modest bactericidal efficacy, insufficient safety assessment, and expensive production. In this study, we systematically evaluated a panel of nine AMP variants of PGLa, a natural AMP derived from
Xenopus laevis
. All peptides retained α-helical structures and exhibited high biocompatibility, with hemolytic concentrations above 128 µg/mL and macrophage survival rates over 80%. Among them, a tandem-repeat variant DiPGLa-H demonstrated the most potent antimicrobial activity, with a therapeutic index of 35.94, against key pathogens such as
Escherichia coli, Staphylococcus aureus,
and
Acinetobacter baumannii
. A DAMP4-DiPGLa-H fusion protein was engineered to mitigate potential host toxicity, and we achieved high-purity biosynthesis of DiPGLa-H by employing a combination of acid cleavage and non-chromatographic purification, with yields reaching 21.2 mg/mL. The biosynthesized DiPGLa-H exhibited robust stability across a wide pH range and high temperatures, effectively disrupting biofilms formed by multiple pathogenic species. Mechanistically, DiPGLa-H disrupts both the inner and outer bacterial membranes, causing cell shrinkage, vesiculation, and intracellular leakage.
In vivo
, DiPGLa-H significantly improved survival rates in mice with induced peritoneal inflammation by 31%–38% while reducing bacterial burdens in key organs by 100-fold to 1,000-fold. These findings unearthed DiPGLa-H as a highly promising AMP. Moreover, the successful development of a cost-effective, high-purity biosynthesis method for DiPGLa-H, utilizing DAMP4 fusion technology, enables its low-cost application in combating multidrug-resistant pathogens.

IMPORTANCE

AMPs are innate defense molecules in animals, plants, and microorganisms. Notably, one-third of these peptides in databases originate from amphibians. We discovered that naturally weak AMPs from this source can be enhanced through artificial design. Specifically, variant DiPGLa-H showed superior germicidal efficacy and cell selectivity both
in vivo
and
in vitro
and can be biosynthesized and purified by combining DAMP4 fusion protein strategy and a simple non-chromatographic method that facilitates large-scale production. Our focus is on understanding the structure-activity relationships of PGLa. Furthermore, the development of a non-chromatographic purification technique for AMPs offers a viable pathway for the large-scale production of these essential compounds.
Draft genome sequences of
Bordetella parapertussis
clinical isolates during an increase in confirmed cases from Colombia, 2023
Authors: Montilla-Escudero Efraín , Rojas-Baquero Fabiola , Bonilla-Bravo Valentina , Vargas-Florez Nathalia 
Published: February 2025

ABSTRACT

We report three
Bordetella parapertussis
genome sequences obtained from national pertussis surveillance in Colombia during an increase in confirmed cases not linked to outbreaks
Draft genome of
Enterococcus faecium
CV167, a bacteriocinogenic strain isolated from raw milk in Minas Gerais, Brazil
Authors: Sabino Yasmin Neves Vieira , Silva Joice Fátima Moreira , Alonso Bruna Vieira , Barbosa Isabela Vieira , Almeida Paula Aparecida Azevedo , Pinto Claudia Oliveira , Hungaro Humberto Moreira , Silva Marcio Roberto , de Souza Guilherme Nunes , Costa Geraldo Marcio , Carneiro Heloisa , Castro Karina Neoob de Carvalho , Paiva Aline Dias , Bruno Laura Maria , Ribeiro João Batista 
Published: February 2025

ABSTRACT

Here, we describe the draft genome sequence of
Enterococcus faecium
CV167, a strain isolated from raw milk in Brazil that exhibits antimicrobial activity against various pathogens. The draft genome has a completeness index of 99.3%, spans 2,736,418 base pairs, has a guanine–cytosine content of 37.93%, and encodes 2,554 proteins.
Antibiotic susceptibility of pathogens isolated in respiratory tract samples of recently hospitalized patients
Authors: Reiner-Benaim Anat , Henig Oryan , Coronel Pilar , Gimeno Mercedes , Rozenberg Gilad , Shlon Dima , Neuberger Ami 
Published: February 2025

ABSTRACT

Community-acquired lower respiratory tract infections (CA-LRTIs) treatment is largely empirical as microbiologic testing is rarely performed. Here, we provide microbiologic data of severe CA-LRTI cases requiring hospitalization. We aim to describe the distribution and susceptibility patterns of pathogens causing severe CA-LRTI. We analyzed respiratory samples from recently admitted patients with CA-LRTIs to assess pathogen distribution and antibiotic susceptibility patterns. We divided patients into three groups: CA-LRTI and no prior healthcare exposure, CA-LRTI with healthcare exposure, and patients diagnosed with LRTI 48 to 7 days of hospital admission. In a sub-cohort, we assessed the bacteria’s susceptibility to cefditoren. A total of 1,395, 2,212, and 2,760 samples were included in the three study groups. Gram-negative bacteria were the most common bacteria isolated.
Streptococcus pneumoniae
was over-represented in patients admitted to the intensive care unit (ICU) in the first two study groups, and was fully susceptible to penicillin in only ~50% of cases, and to fluoroquinolones and third-generation cephalosporins including cefditoren in >95% of cases. Susceptibility of Gram-negative bacteria to penicillins and to second-generation cephalosporins was lower than 50%. Age, admission to an ICU or surgical department, healthcare-associated infections, and infections with Gram-negative bacteria,
Staphylococcus aureus
, and
Stenotrophomonas
/
Acinetobacter baumannii
were associated with increased mortality. These results highlight pathogen diversity and concerning antibiotic susceptibility patterns in LRTI. These findings emphasize the importance of improving diagnostics and addressing antibiotic resistance in the effective management of LRTI.

IMPORTANCE
This survey aims to describe the microbiologic aspects of community-acquired lower respiratory tract infections (CA-LRTI) in a large cohort of patients recently admitted to hospital. In a small sub-study, we assessed antibiotic susceptibility to cefditoren, an oral third-generation cephalosporin not used in Israel. By analyzing specimens from recently admitted patients with CA-LRTI, we aim to provide physicians with the relevant microbiologic data of the more severe CA-LRTI cases, i.e., those that resulted in hospital admission. Such microbiological data would provide primary care and emergency room physicians with additional insights as to the causative agents of severe CA-LRTI.
Comparison of Raman spectroscopy with mass spectrometry for sequence typing of
Acinetobacter baumannii
strains: a single-center study
Authors: Liu Suling , Zhang Ni , Tang Jiawei , Chen Chong , Wang Weisha , Zhou Jingfang , Ye Long , Chen Xiaoli , Li ZhengKang , Wang Liang 
Published: February 2025

ABSTRACT

The rapid sequence typing (ST) of bacterial strains is crucial for effective nosocomial infection control and mitigating the spread of nosocomial pathogens, e.g.,
Acinetobacter baumannii
. While accurate in identifying
A. baumannii
strains, current typing methods are often impractical in clinical settings due to their time-consuming nature. This study developed a novel approach, combining surface-enhanced Raman spectroscopy (SERS) with machine-learning (ML) algorithms, to construct predictive models for
A. baumannii
sequence typing based on SERS spectra. The objective was to assess the feasibility of this integrated method for efficient sequence typing of
A. baumannii
strains. Clinically isolated
A. baumannii
strains (
N
= 267) were collected from a single hospital between 2013 and 2023. Based on multilocus sequence typing, 39 STs of
A. baumannii
were identified. Then, a SERS spectral database for all these strains was constructed, and predictive models based on eight ML algorithms were developed to predict SERS signals to determine their STs, among which the support vector machine (SVM) model had the best performance (fivefold cross-validation = 99.74%). The typing capacity of the SERS-SVM method was compared with that of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) for
A. baumannii
sequence typing, confirming the superiority of SERS-SVM over MALDI-TOF mass spectrometer. This pilot study lays the groundwork for employing the SERS-ML method to rapidly identify
A. baumannii
strain types in clinical laboratories, aiding in controlling bacterial pathogen transmission. Further studies are warranted to evaluate its potential in nosocomial surveillance systems, especially for rapidly identifying outbreaks within hospitals.

IMPORTANCE

The rapid and accurate sequence typing (ST) of bacterial pathogens is pivotal in controlling transmission within healthcare settings.
Acinetobacter baumannii
infection, known for its high transmissibility and drug resistance, presents a major challenge in nosocomial infection control. In this study, surface-enhanced Raman spectroscopy (SERS) was used to differentiate
A. baumannii
strains with distinct STs based on unique Raman spectral profiles. We then constructed and compared eight machine-learning models on SERS spectra to quickly identify bacterial STs. The results showed that the support vector machine model outperformed matrix-assisted laser desorption/ionization time-of-flight mass spectrometer in determining
A. baumannii
STs. This approach enables rapid identification of
A. baumannii
variants with different STs, supporting the early detection and control of nosocomial infections by this multidrug-resistant pathogen.
Temporary dietary fiber depletion prompts rapid and lasting gut microbiota restructuring in mice
Authors: Rous Colombe , Cadiou Julie , Yazbek Hiba , Monzel Elena , Desai Mahesh S. , Doré Joel , van de Guchte Maarten , Mondot Stanislas 
Published: February 2025

ABSTRACT

Long-term alterations of the gut microbiota and host symbiosis after a dietary perturbation remain insufficiently understood and characterized. In this study, we investigate the impact of temporary dietary fiber depletion in mice that received a diet with reduced fiber content (RFD) for 3 weeks followed by a return to a standard chow diet for 6 weeks, compared to mice that only received a chow diet. Fiber deprivation was accompanied by a reduction of microbiota diversity and an increase in mucolytic and sulfate-reducing bacteria. The activities of enzymes targeting glycans from the host mucus were increased accordingly, while those targeting plant fibers were decreased. On the host side, we report transiently higher quantities of host DNA in feces during the RFD suggesting an impaired gut barrier function. Six weeks after the return to the chow diet, lasting changes in microbiota composition were observed, as exemplified by the replacement of durably depleted amplicon sequence variants close to
Duncaniella dubosii
by other members of the
Muribaculaceae
family. The observation of two distinct gut microbial communities in mice under identical environmental and alimentary conditions at the end of the experiment suggests the existence of alternative stable microbiota states.

IMPORTANCE
In this article, the authors explore the impact of a diet with reduced fiber content on the gut microbiota-host symbiosis in a mouse model. More importantly, they examine the resilience of the intestinal symbiosis after the return to a standard (chow) diet. Some of the measured parameters (intestinal barrier impairment and bacterial glycan-degrading enzymatic activities) returned to control values. However, this was not the case for bacterial richness—the number of different bacteria observed—which remained durably reduced. Among related bacteria, some groups receded and remained undetected until 6 weeks after the return to the chow diet while others saw their abundance increase in replacement. The authors find that a temporary fiber deprivation lasting as little as 3 weeks can cause a transition to an alternative stable microbiota state, i.e., a lasting change in intestinal microbiota composition.
Serology supportive of recent coxsackievirus B infection is correlated with multisystem inflammatory syndrome in children (MIS-C)
Authors: Kordi Ramesh , Chang Arthur J. , Hicar Mark D. 
Published: February 2025

ABSTRACT

Rarely, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will lead to myocarditis associated with multisystem inflammatory syndrome in children (MIS-C). It remains unclear why MIS-C only targets specific children. To explore an association between coxsackievirus infections with MIS-C, we investigated the sero-epidemiology of CV in admitted pediatric patients in relation to the pandemic. This retrospective case–control study was performed by chart review of children (age ≤21 years) admitted to a tertiary care hospital with CV serological testing from January 2017 to August 2023. Clinical, laboratory, and imaging findings were used to classify patients as MIS-C and CV-unlikely or CV-possible for non-MIS-C patients. Out of 182 admissions (179 patients, median age, 6), CVB complement fixation (CF) assay on serotypes B1–B6 and CVA immunofluorescence assay IgG on serotypes A7, A9, A16, and A24 were positive in at least one serotype in 59.2% and 80.7% of cases, respectively. We observed a significant drop in CVB CF seropositivity during the peak of social distancing in 2020. The likelihood of elevated CVB CF titers was significantly higher in MIS-C than the CV-unlikely group (OR: 1.92, 95% CI: 1.02–3.63,
P
: 0.04) and showed a trend toward higher values in African Americans than Whites (OR: 1.57, 95% CI: 0.98–2.50,
P
: 0.057). The frequency of MIS-C was considerably higher in African Americans than Whites (18.1% versus 9%,
P
: 0.1). A higher likelihood of elevated CVB CF titers in patients with MIS-C compared with those unlikely to have acute CV infection along with a relatively higher frequency of MIS-C in African Americans warrants further investigation into the role of CVB infection in MIS-C development.

IMPORTANCE
The emergence of multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic raised major concerns in providers caring for children. This condition presents a hyper-inflammation state that can lead to severe complications, including myocarditis and cardiogenic shock. The pathogenesis of MIS-C has not been fully understood. Understanding the pathogenesis of this condition is not only important for developing effective treatments but also for applying preventive strategies. A two-hit hypothesis leading to MIS-C has been proposed. Coxsackievirus infections are prevalent during childhood and can also cause myocarditis, and coxsackievirus B specifically has been shown to cause persistent RNA presence in host cells, leading to continued inflammation. Herein, we show that elevated coxsackievirus B titers are associated with MIS-C cases, implying a role of successive infections with these viruses contributing to such a hyperinflammatory state. This study supports the need for larger investigations into this association.
Eligibility for faricimab in a real-world diabetic macular oedema population: a cross-sectional study
Authors: Westborg Inger , Al-Najjar Ayat , Norberg Helena 
Published: February 2025

PurposeTo investigate the eligibility for faricimab in a real-world diabetic macular oedema (DMO) population to the YOSEMITE and RHINE trials, and to compare the eligible DMO populations to the trial populations.Design, settings and participantsThis retrospective cross-sectional analysis used data from the Swedish Macula Registry (SMR) between 1 January 2019 and 31 August 2023. Eligibility criteria mirrored the main criteria of the YOSEMITE and RHINE trials: (1) DMO diagnosis, (2) treatment-naïve, (3) 18 years or older, (4) central retinal thickness (CRT) 325 µm or higher and (5) best-corrected visual acuity (BCVA) ranging from 25 to 73 letters. Individuals with registered proliferative diabetic retinopathy (DR) at the start of treatment were excluded. A secondary selection of eligible individuals was conducted using the same criteria, except for BCVA, which ranged from 25 to 77 letters according to national guidelines (treatment practice).Main outcome measuresCharacteristics at the initial visit of the two eligible SMR populations were compared with baseline data from the clinical trials, respectively.ResultsIn total, 3777 individuals with DMO were selected from SMR. Of these, 2357 (62.4%) individuals were treatment-naïve, all were 18 years or older, 1928 (51.0%) exhibited CRT≥325 µm, 1175 (31.1%) had 25–73 letters based on phase III studies, while 1528 (40.5%) had 25–77 letters according to treatment practice. After excluding individuals with registered proliferative DR 1171 (31.0%) individuals in the SMR met all criteria based on phase III studies, while 1522 (40.3%) individuals fulfilled the criteria according to treatment practice. The SMR and treatment practice populations were older (YOSEMITE 67.5±11.6 vs 62.8±10.0 years, p<0.001 and RHINE 67.5±11.6 vs 61.6±10.1 years, p<0.001) than those in the phase III studies and had lower CRT (YOSEMITE 446±96 vs 486±131 µm, p<0.001 and RHINE 446±96 vs 471±127 µm, p=0.001).ConclusionApproximately 30% of DMO patients in the SMR met the main trial criteria from YOSEMITE and RHINE, while around 40% met the criteria based on treatment practice. The SMR and treatment practice cohorts were older and had less severe DMO than the trial cohorts. Further research into the safety profile of faricimab in clinical settings is necessary, along with the consideration of additional eligibility criteria when implementing faricimab in ophthalmology practice.
Deaths in children in England from SARS-CoV-2 infection during the first 2 years of the pandemic: a cohort study
Authors: Odd David , Stoianova Sylvia , Williams Tom , Thursby-Pelham Anna , Ladhani Shamez N , Oligbu Godwin , Fleming Peter , Luyt Karen 
Published: February 2025

ObjectiveThe aim of this analysis was to describe the epidemiology, demographics and characteristics of children and young people (CYP) who died of SARS-CoV-2 infection in England during the first 2 years of the pandemic.DesignThe cohort investigated in this study is all CYP, born alive at, or after, 22 weeks of gestation, who died before their 18th birthday between 1 February 2020 and 31 March 2022 in England. All cases were reviewed to identify if SARS-CoV-2 probably, or possibly, contributed to death. Mortality rates were calculated, assuming a Poisson distribution, for the whole population, and split by demographics and patient characteristics.SettingEngland.Participants6389 CYP deaths in England reported to the National Child Mortality Database (NCMD).Main outcomeRisk of death.Results88 of the 6389 deaths of CYP were identified as deaths probably due to COVID-19. Thus, COVID-19 was responsible for 1.4% of all deaths of CYP in this 26-month period. Overall mortality rate due to COVID-19 in CYP was 3.59 (2.88–4.42) per 1 000 000 person years, being highest in the youngest (< 5 years; 4.68 (3.16–6.68)) and oldest (16/17 years; 4.83 (2.57–8.26)) CYP. Asian and Black CYP had higher mortality than those from white backgrounds (p<0.001), and mortality rate increased with increasing deprivation. The majority (61/77, 79.2) of CYP who died of COVID had a documented life limiting condition.ConclusionsMortality rates were highest in less than 5 years old. Despite social changes, and shielding of vulnerable CYP, children with life-limiting (but not necessarily life-threatening) conditions, appeared to have the highest mortality rates, similar to that seen in adults with comparable underlying conditions. The risk of death in more deprived neighbourhoods and in those from Asian and Black ethnic backgrounds was increased, and this was not explained by their other demographic characteristics.
Prevalence of and recommendation for measuring chronic postsurgical pain in children: an updated systematic review and meta-analysis
Authors: Rosenbloom Brittany N , Frederiksen Simona Denise , Wang Vienna , Birnie Kathryn A , Park Christine S , Gordon Grace , Rasic Nivez , Stinson Jennifer N , Rabbitts Jennifer A 
Published: February 2025

BackgroundAccording to the prior 2017 review (Rabbittset al), approximately 20% of children and adolescents develop chronic postsurgical pain (CPSP; ie, pain persisting >3 months after surgery) after major surgeries, which is associated with adverse functional and psychological consequences. A major barrier was that definitions of CPSP applied were highly variable. Since that prior review was conducted (n=4 studies in meta-analysis), numerous relevant studies have been published warranting an update.ObjectiveThe aims of this current review were to: (1) provide an updated prevalence estimate for pediatric CPSP and (2) examine definitions of pediatric CPSP applied in current research.Evidence reviewProspective, observational studies examining CPSP using a validated self-report pain intensity measure in children were included. 4884 unique publications were screened with 20 articles meeting inclusion criteria. Risk of bias using Quality in Prognostic Study tool ranged from low to high.FindingsThe pooled prevalence of CPSP among mostly major surgeries was 28.2% (95% CI 21.4% to 36.1%). Subgroup analysis of spinal fusion surgeries identified a prevalence of 31% (95% CI 21.4% to 43.5%). Using Grading of Recommendations, Assessment, Development, and Evaluation, the certainty in prevalence estimates was moderate. Studies used a range of valid pain intensity measures to classify CPSP (eg, Numeric Rating Scale), often without pain interference or quality of life measures.ConclusionsThe overall prevalence of pediatric CPSP is higher than estimated in the prior review, and quality of studies generally improved though with some heterogeneity. Standardizing the measurement of CPSP will facilitate future efforts to combine and compare data across studies.PROSPERO registration numberCRD42022306340.
Instability analysis of massive static phantom wormholes via the spectral method
Authors: Batic Davide , Dutykh Denys 
Published: February 2025

Abstract
Using the spectral method, we investigate the scalar and axial quasinormal modes (QNMs) of massive static phantom wormholes. Our results reveal the existence of purely imaginary QNMs that were not identified in previous studies, suggesting potential (in)stabilities as the ratio of the Schwarzschild radius to the wormhole throat varies within a specific range. For scalar perturbations, instabilities arise when this ratio exceeds 1.0, with the threshold value of 1.0 itself included. In the case of axial perturbations, the onset of instability occurs at smaller ratios, reflecting the impact of gravitational waves on the wormhole’s stability. The findings suggest that the wormhole remains stable when the throat size significantly exceeds the Schwarzschild radius. Our results align with existing literature but offer new insights into the stability conditions of phantom wormholes.