bluuebunny/crossref_metadata_2025_split huggingface dataset:
CemR atypical response regulator impacts energy conversion in
Campylobacteria
Authors: Noszka Mateusz , Strzałka Agnieszka , Muraszko Jakub , Hofreuter Dirk , Abele Miriam , Ludwig Christina , Stingl Kerstin , Zawilak-Pawlik Anna 
Published: July 2024

ABSTRACT

Campylobacter jejuni
and
Arcobacter butzleri
are microaerobic food-borne human gastrointestinal pathogens that mainly cause diarrheal disease. These related species of the
Campylobacteria
class face variable atmospheric environments during infection and transmission, ranging from nearly anaerobic to aerobic conditions. Consequently, their lifestyles require that both pathogens need to adjust their metabolism and respiration to the changing oxygen concentrations of the colonization sites. Our transcriptomic and proteomic studies revealed that
C. jejuni
and
A. butzleri,
lacking a
Campylobacteria
-specific regulatory protein,
C. jejuni
Cj1608, or a homolog,
A. butzleri
Abu0127, are unable to reprogram tricarboxylic acid cycle or respiration pathways, respectively, to produce ATP efficiently and, in consequence, adjust growth to changing oxygen supply. We propose that these
Campylobacteria
energy and metabolism regulators (CemRs) are long-sought transcription factors controlling the metabolic shift related to oxygen availability, essential for these bacteria’s survival and adaptation to the niches they inhabit. Besides their significant universal role in
Campylobacteria
, CemRs, as pleiotropic regulators, control the transcription of many genes, often specific to the species, under microaerophilic conditions and in response to oxidative stress.

IMPORTANCE

C. jejuni
and
A. butzleri
are closely related pathogens that infect the human gastrointestinal tract. In order to infect humans successfully, they need to change their metabolism as nutrient and respiratory conditions change. A regulator called CemR has been identified, which helps them adapt their metabolism to changing conditions, particularly oxygen availability in the gastrointestinal tract so that they can produce enough energy for survival and spread. Without CemR, these bacteria, as well as a related species,
Helicobacter pylori
, produce less energy, grow more slowly, or, in the case of
C. jejuni
, do not grow at all. Furthermore, CemR is a global regulator that controls the synthesis of many genes in each species, potentially allowing them to adapt to their ecological niches as well as establish infection. Therefore, the identification of CemR opens new possibilities for studying the pathogenicity of
C. jejuni
and
A. butzleri
.
A 2D nanoflower-like ordered mesoporous Bi
12
ZnO
20
catalyst with excellent photocatalytic antibacterial properties
Authors: Li Jingmei , Liu Shuai , Zhan Chenming 
Published: July 2024

ABSTRACT

The ordered mesoporous ZnO was successfully synthesized using the template method in this article, and Bi ions were etched into ZnO to form two-dimensional nanoflower structures of Bi
12
ZnO
20
with NA
3
SSA as a guiding agent. The crystal structure, morphology, and optical properties of the photocatalyst were characterized by X-ray diffractometer (XRD), scanning electron microscope (SEM), energy-dispersive spectrometer(EDS), and ultraviolet-visible diffuse reflectance spectrum (UV-vis DRS). Under illumination conditions, the obtained materials exhibited excellent bactericidal ability against both gram-positive and gram-negative bacteria, as well as effective inhibition against fungi. Among them, the bactericidal effect of
Pseudomonas aeruginosa
was found to be the most rapid, achieving a sterilization rate of 100% within 30 min of light irradiation. Even after three cycles of antibacterial activity testing, the Bi
12
ZnO
20
material still demonstrated good photocatalytic performance. The nanoflower-shaped materials provide an enhanced fluid adsorption capacity and more active centers for photocatalytic reactions while also improving light absorption capacity, photogenerated electron-hole separation efficiency, and electron transport efficiency. The cytotoxicity assessment of Bi
12
ZnO
20
revealed no significant toxic effects. Therefore, this study presents a nanoflower-shaped material with highly efficient photocatalytic antibacterial properties for applications in production and daily life; it holds significant importance in eliminating harmful bacteria and plays a crucial role in environmental protection.

IMPORTANCE

The flower-shaped photocatalytic material Bi
12
ZnO
20
, consisting of nanoparticles, was successfully synthesized in this study. Rigorous antibacterial experiments were conducted on various fungi using the material, yielding excellent results. Furthermore, the application of this material for antibacterial treatment of livestock and poultry manure sewage in real-life scenarios demonstrated remarkable efficacy.
Sample-to-answer direct real-time PCR detection of
Anaplasma phagocytophilum
,
Ehrlichia
spp., and
Babesia
spp. infections in whole-blood specimens
Authors: Colasante Georgia , Makari Keana , Hummel Tara I. , Murphy Caitlin 
Published: July 2024

ABSTRACT

Emerging tick-borne illnesses, such as anaplasmosis, babesiosis, or ehrlichiosis, are caused by obligate intracellular pathogens that have clinically comparable presentations. Diagnostics used in laboratories today are serologic assays and blood smear analyses, which have known diagnostic limits. This study evaluated the performance of a sample-to-answer direct real-time PCR laboratory-developed test for the multiplex qualitative detection of
Anaplasma
,
Babesia
, and
Ehrlichia
DNA in whole-blood specimens. Compared to two standard-of-care (SOC) methods, the DiaSorin tick-borne laboratory-developed test for
Anaplasma
detection demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 100% (95% CI, 0.80 to 1.0) and 89% (95% CI, 0.74 to 0.97), respectively with a discordant rate of 9.3% against microscopy. After discordant resolution, the NPA increased to 100%. For
Babesia
, the test demonstrated a PPA of 100% (95% CI, 0.90 to 1.0) and NPA of 100% (95% CI, 0.90 to 1.0). Compared to a SOC PCR method
Anaplasma
samples showed a PPA of 100% (95% CI, 0.66 to 1.0) and NPA of 100% (95% CI, 0.90 to 1.0).
Ehrlichia
results showed a PPA of 100% (95% CI, 0.69 to 1.0) and NPA of 100% (95% CI, 0.90 to 1.0). The total percent agreement was 98% (95% CI, 0.95 to 0.99) with a κ statistic of 0.95 (95% CI, 0.90 to 0.99) or almost perfect agreement compared to SOC methods. This laboratory-developed test for detecting
Anaplasma
,
Babesia
, and
Ehrlichia
DNA provides rapid and reliable detection of tick-borne infections without nucleic acid extraction.

IMPORTANCE
This work demonstrates that detection of tick-borne illnesses, such as anaplasmosis, babesiosis, or ehrlichiosis, can be performed directly from whole blood with no extraction. The assay described here has a high positive and negative percent agreement with existing methods and is used as the standard of care. An increasing incidence of tick-borne illness combined with shortage of well-trained technologists to perform traditional manual testing, testing options that can be adapted to various lab settings, are of the utmost importance.
Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus
Aspergillus fumigatus
Authors: dos Reis Thaila Fernanda , Diehl Camila , Pinzan Camila Figueiredo , de Castro Patrícia Alves , Goldman Gustavo H. 
Published: July 2024

ABSTRACT

Aspergillus fumigatus
is the primary etiological agent of aspergillosis. Here, we show that the host defense peptide mimetic brilacidin (BRI) can potentiate ibrexafungerp (IBX) against clinical isolates of
A. fumigatus
. BRI + IBX can inhibit the growth of
A. fumigatus
voriconazole- and caspofungin-resistant clinical isolates. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against viruses, bacteria, and fungi.
In vitro
, combination of BRI + IBX plays a fungicidal role, increases the fungal cell permeability, decreases the fungal survival in the presence of A549 epithelial cells, and appears as a promising antifungal therapeutic alternative against
A. fumigatus
.

IMPORTANCE

Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria.
Aspergillus fumigatus
causes a series of distinct invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria.
A. fumigatus
causes a spectrum of distinct clinical entities named aspergillosis, which the most severe form is the invasive pulmonary aspergillosis. There are few therapeutic options for treating aspergillosis and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a synergizer o fibrexafungerp (IBX) against
A. fumigatus
. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. We propose the combination of BRI and IBX as a new antifungal combinatorial treatment against aspergillosis.
Antimicrobial peptide A20L:
in vitro
and
in vivo
antibacterial and antibiofilm activity against carbapenem-resistant
Klebsiella pneumoniae
Authors: Zhou Huijing , Du Xin , Wang Yue , Kong Jingchun , Zhang Xiaodong , Wang Weixiang , Sun Yao , Zhou Cui , Zhou Tieli , Ye Jianzhong 
Published: July 2024

ABSTRACT

Antimicrobial resistance has become a growing public health threat in recent years.
Klebsiella pneumoniae
is one of the priority pathogens listed by the World Health Organization. Antimicrobial peptides are considered promising alternatives to antibiotics due to their broad-spectrum antibacterial activity and low resistance. In this study, we investigated the antibacterial activity of antimicrobial peptide A20L against
K. pneumoniae. In vitro
antibacterial activity of A20L against
K. pneumoniae
was demonstrated by broth microdilution method. We confirmed the
in vivo
efficacy of A20L by
Galleria mellonella
infection model. In addition, we found that A20L also had certain antibiofilm activity by crystal violet staining. We also evaluated the safety and stability of A20L, and the results revealed that at a concentration of ≤128 µg/mL, A20L exhibited negligible toxicity to RAW264.7 cells and no substantial toxicity to
G. mellonella
. A20L was stable at different temperatures and with low concentration of serum [5% fetal bovine serum (FBS)]; however, Ca
2+
, Mg
2+
, and high serum concentrations reduced the antibacterial activity of A20L. Scanning electron microscope (SEM) and membrane permeability tests revealed that A20L may exhibit antibacterial action by damaging bacterial cell membranes and increasing the permeability of outer membrane. Taken together, our results suggest that A20L has significant development potential as a therapeutic antibiotic alternative, which provides ideas for the treatment of
K. pneumoniae
infection.

IMPORTANCE

A20L showed antibacterial and anti-infective efficacy
in vitro
and
in vivo
against
Klebsiella pneumoniae
. It can have an antibacterial effect by disrupting the integrity of cell membranes. A20L displayed anti-biofilm and anti-inflammatory activity against carbapenem-resistant
K. pneumoniae
and certain application potential
in vivo
, which provides a new idea for the clinical treatment of biofilm-associated infections.
Comparing priority received by global health issues: a measurement framework applied to tuberculosis, malaria, diarrhoeal diseases and dengue fever
Authors: Parashar Rakesh , Nanda Sharmishtha , Smith Stephanie L , Shroff Zubin , Shawar Yusra R , Hamunakwadi Dereck L , Shiffman Jeremy 
Published: July 2024

IntroductionThe relative priority received by issues in global health agendas is subjected to impressionistic claims in the absence of objective methods of assessment of priority. To build an approach for conducting structured assessments of comparative priority health issues receive, we expand the public arenas model (2021) and offer a framework for future assessments of health issue priority in global and national health agendas.MethodsWe aimed to develop a more comprehensive set of measures for conducting multiyear priority comparisons of health issues in six agenda-setting arenas by identifying possible measures and data sources, selecting indicators based on feasibility and comparability of measures and gathering the data on selected indicators. We applied these measures to four communicable diseases—tuberculosis (TB), malaria, diarrhoeal diseases and dengue fever—given their differing impressionistic claims of priority. Where possible, we analysed the annual and/or 5-year trends from 2000 through 2022.ResultsWe observed that TB and malaria received the highest priority for most periods in the past two decades in most arenas. However, a stagnation in development funding for these two conditions over the last 8–10 years may have fuelled the neglect claims. Despite having a higher disease burden, diarrhoea has been slipping in global priority with reduced spending, fewer clinical trials and stagnating publications. Dengue remains a low-priority condition but has witnessed a sharp rise in attention from the pharmaceutical industry.DiscussionsWe expanded the arenas model by including a transnational arena (international representation) and additional measurements for various arenas. This analysis presents an approach to enable comparative trend analysis of the markers of agenda status over a multiyear period. More such analyses can bring much-desired objectivity in understanding how attention to global or national health issues changes over time in different arenas, potentiating a more equitable allocation of resources.
A temporal record of microplastic accumulation in sediment cores of the Great Lakes, North America, reflects macroeconomic and regional influences
Authors: Belontz Sara L. , Corcoran Patricia L. , Kimpe Linda , Helm Paul A. , Marvin Chris 
Published: July 2024

Documented plastic pollution throughout the Laurentian Great Lakes system prompted investigation of microplastics (MPs) in sediment cores. We examined offshore sediment cores from Lake Huron (LH43) and Lake Ontario (403A) to understand temporal trends and changes in microplastic (MP) pollution in the size range 53 µm to 2 mm. MP abundances varied from 18.1 to 280.1 particles per g of dry weight sediment ( N g−1 dw) in LH43, and 8.2–488.4 g−1 dw in core 403A. The 15 cm cores are equivalent to 56 years of accumulation in Lake Huron and 72 years of accumulation in Lake Ontario. Analysis of the two cores shows an increasing trend in MP accumulation from 1964 to 1989, which mirrors the global plastic production rate. Subsequent peaks and troughs in the MP abundance profiles reflect macroeconomic changes and regional controls. These results show how changing abundances of MPs in lake sediment cores can act as proxies for global perturbations in oil supply as well as national economic shifts.
Simulation of an entanglement-based quantum key distribution protocol
Authors: Mariani L. , Salatino L. , Attanasio C. , Pagano S. , Citro R. 
Published: July 2024

AbstractSince the 80 s when it was first proposed, Quantum Key Distribution (QKD) elicited great interest in the field of cryptography as a unique procedure for key generation that could in principle guarantee unconditionally secure communication “by the laws of Physics”. In the last fifteen years commercial solutions have started appearing on the market, showing that practical implementations of the protocol were not only possible but also competitive in terms of security and achievable secret-key rate. In this work we describe a simulation of the historical QKD protocol E91 on the IBM Quantum platform, making use of the qubit formalism to represent the quantum states received by two communicating nodes. Having implemented also the post-processing steps for the error correction and the privacy amplification, this model can represent a simple stand-alone tool to study the performance not only of one-to-one communication but of more complex systems that rely on QKD for security, one above all QKD networks.
Thymoquinone Increases the Sensitivity of SW‐480 Colon Cancer Cells to 5‐Fluorouracil
Authors: Zeinali Nima , Mahmoudzadeh Vahid , Anarjani Alireza , Ebrahimnejad Mohammad , Yousefi Bahman , Valizadeh Amir 
Published: July 2024

Background: Studies have concentrated on the therapeutic potential of thymoquinone (TQ), a natural polyphenol, in diverse malignancies, such as colorectal cancer. Nevertheless, the precise mechanisms of TQ‐mediated anticancer properties are not yet fully elucidated.Objective: The present study has been designed to scrutinize the impact of TQ on 5‐fluorouracil (5‐FU)–mediated apoptosis in SW‐480 cells.Materials and Methods: SW‐480 cells were treated with TQ, 5‐FU, and a combination of TQ + 5‐FU. MTT assay was employed to assess cell viability. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was applied to evaluate apoptotic markers comprising Bcl‐2, Bax, and caspase‐9 expression levels. The γ‐H2AX protein expression was assessed by western blotting, and Annexin V flow cytometry was implemented to determine the apoptosis rate.Results: 5‐FU significantly reversed the cell proliferation in a dose‐dependent circumstance. The concurrent administration of TQ and 5‐FU led to a substantial inhibition of cell growth in comparison to single treatments (p < 0.05). TQ also facilitated apoptosis via upregulating Bax and caspase‐9 proapoptotic markers and suppressing antiapoptotic mediators, like Bcl‐2. In addition, TQ augmented 5‐FU‐induced apoptosis in SW‐480 cells. 5‐FU, combined with TQ, increased the protein expression of γ‐H2AX in SW‐480 cells compared with groups treated with TQ and 5‐FU alone.Conclusion: The present study’s findings unveil the significance of TQ as a potential therapeutic substance in colorectal cancer, particularly through enhancing 5‐FU‐induced apoptosis.
Transcriptional Phenocopies of Deleterious KEAP1 Mutations Correlate with Survival Outcomes in Lung Cancer Treated with Immunotherapy
Authors: Scalera Stefano , Ricciuti Biagio , Marinelli Daniele , Mazzotta Marco , Cipriani Laura , Bon Giulia , Schiavoni Giulia , Terrenato Irene , Di Federico Alessandro , Alessi Joao V. , Fanciulli Maurizio , Ciuffreda Ludovica , De Nicola Francesca , Goeman Frauke , Caravagna Giulio , Santini Daniele , De Maria Ruggero , Cappuzzo Federico , Ciliberto Gennaro , Jamal-Hanjani Mariam , Awad Mark M. , McGranahan Nicholas , Maugeri-Saccà Marcello 
Published: July 2024

Abstract

Purpose:
Co-occurring mutations in KEAP1 and STK11/KRAS have emerged as determinants of survival outcomes in patients with non–small cell lung cancer (NSCLC) treated with immunotherapy. However, these mutational contexts identify a fraction of nonresponders to immune checkpoint inhibitors. We hypothesized that KEAP1 wild-type tumors recapitulate the transcriptional footprint of KEAP1 mutations and that this KEAPness phenotype can determine immune responsiveness with higher precision compared to mutation-based models.

Experimental Design:
The Cancer Genome Atlas was used to infer the KEAPness phenotype and explore its immunological correlates at the pan-cancer level. The association between KEAPness and survival outcomes was tested in two independent cohorts of patients with advanced NSCLC treated with immunotherapy and profiled by RNA sequencing (SU2C n = 153; OAK/POPLAR n = 439). The NSCLC TRACERx421 multiregion sequencing study (tumor regions, n = 947) was used to investigate evolutionary trajectories.

Results:
KEAPness-dominant tumors represented 50% of all NSCLCs and were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAPness-free cases in independent cohorts of patients with NSCLC treated with immunotherapy (SU2C PFS P = 0.042, OS P = 0.008; OAK/POPLAR PFS P = 0.0014, OS P &lt; 0.001). Patients with KEAPness tumors had survival outcomes comparable to those with KEAP1-mutant tumors. In the TRACERx421, KEAPness exhibited limited transcriptional intratumoral heterogeneity and immune exclusion, resembling the KEAP1-mutant disease. This phenotypic state occurred across genetically divergent tumors, exhibiting shared and private cancer genes under positive selection when compared to KEAP1-mutant tumors.

Conclusions:
We identified a KEAPness phenotype across evolutionary divergent tumors. KEAPness outperforms mutation-based classifiers as a biomarker of inferior survival outcomes in patients with NSCLC treated with immunotherapy.
Mixed Shock Complicating Cardiogenic Shock: Frequency, Predictors, and Clinical Outcomes
Authors: Baldetti Luca , Gallone Guglielmo , Filiberti Gaia , Pescarmona Luca , Cesari Andrea , Rizza Vincenzo , Roagna Edoardo , Gurrieri Davide , Peveri Beatrice , Nocera Lorenzo , Cianfanelli Lorenzo , Marcelli Gianluca , De Lio Giulia , Boretto Paolo , Angelini Filippo , Gramegna Mario , Pazzanese Vittorio , Sacchi Stefania , Calvo Francesco , Ajello Silvia , De Ferrari Gaetano Maria , Frea Simone , Scandroglio Anna Mara 
Published: July 2024

BACKGROUND:
Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity.

METHODS:
We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters.

RESULTS:

Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29–216) hours from CS diagnosis. Lower systolic arterial pressure (
P
=0.043), hepatic injury (
P
=0.049), and suspected/definite infection (
P
=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%;
P
=0.002) and hospital stay (21 [13–48] versus 17 [9–27] days;
P
=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39–6.63];
P
adj
=0.006), age (OR, 1.06 [95% CI, 1.03–1.10] years;
P
adj
<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19–4.98];
P
adj
=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19–2.26];
P
adj
=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17–0.75];
P
adj
=0.008).

CONCLUSIONS:
MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.