bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved metabolic regulator ArcA responds to oxygen availability, iron limitation, and cell envelope perturbations during bacteremia
Authors: Brown Aric N. , Anderson Mark T. , Smith Sara N. , Bachman Michael A. , Mobley Harry L. T. 
Published: September 2023

ABSTRACT

Gram-negative facultative anaerobes often cause bacteremia, a systemic infection associated with severe clinical outcomes. ArcAB, a two-component regulatory system that represses aerobic respiration, is a key mediator of metabolic adaptation for such bacteria. Using targeted mutational analysis informed by global genetic screens, we identified the
arcA
gene as promoting fitness of
Citrobacter freundii
,
Klebsiella pneumoniae
, and
Serratia marcescens
but not
Escherichia coli
in a murine model of bacteremia.
arcA
mutants exhibit a dysregulated response to changes in oxygen availability, iron limitation, and membrane perturbations, which bacterial cells experience during infection. The genetic response of the
arcA
mutants to the cationic antimicrobial peptide polymyxin B supports an expanded role for ArcA as an activator in response to membrane damage. ArcA function is linked to electron transport chain activity based on its response to proton motive force uncoupling by carbonylcyanide-
m
-chlorophenylhydrazone (CCCP). Differences in lactate, acetate, and lactate dehydrogenase activity between
arcA
mutant and wild-type cells following CCCP treatment support an ArcA-mediated shift to fermentation independent of oxygen availability. This study highlights the semi-conserved role of ArcA during bacteremia and consolidates infection phenotypes into a comprehensive model based on respiratory activity.

IMPORTANCE

Infections of the bloodstream are life-threatening and can result in sepsis. Gram-negative bacteria cause a significant portion of bloodstream infections, which is also referred to as bacteremia. The long-term goal of our work is to understand how such bacteria establish and maintain infection during bacteremia. We have previously identified the transcription factor ArcA, which promotes fermentation in bacteria, as a likely contributor to the growth and survival of bacteria in this environment. Here, we study ArcA in the Gram-negative species
Citrobacter freundii
,
Klebsiella pneumoniae,
and
Serratia marcescens
. Our findings aid in determining how these bacteria sense their environment, utilize nutrients, and generate energy while countering the host immune system. This information is critical for developing better models of infection to inform future therapeutic development.
Imaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions
Authors: El Najjar Farah , Castillo Santiago Restrepo , Moncman Carole L. , Wu Cheng-Yu , Isla Eduardo , Velez Ortega A. Catalina , Frolenkov Gregory I. , Cifuentes-Munoz Nicolas , Dutch Rebecca Ellis 
Published: September 2023

ABSTRACT
Human metapneumovirus (HMPV) can spread between cells through budding of virus particles or direct cell-to-cell spread. A network of budding filaments and intercellular extensions forms in HMPV-infected cells; however, the involvement of these structures in direct cell-to-cell spread of infection remains to be investigated. Utilizing advanced imaging techniques, we show that budding filaments contain the viral RNA genome, and not the antigenome, and become enriched with HMPV F protein as infection progresses. Multiple filaments containing the F protein on their surface were seen emanating from one cell to contact a neighboring cell, strongly suggesting that these are budding filamentous HMPV virions. In addition, changes in the morphology and properties of intercellular extensions following HMPV infection were detected. We show that intercellular extensions allow the transfer of a cytosolic dye only in HMPV-infected cells. In addition, using live imaging, we provide novel evidence of the direct passage of inclusion bodies from cell-to-cell across intercellular extensions. These results provide novel insights into the direct cell-to-cell spread of HMPV and suggest that this mode of transmission can occur through different mechanisms.

IMPORTANCE
Human metapneumovirus is an important respiratory pathogen that causes significant morbidity and mortality, particularly in the very young, the elderly, and the immunosuppressed. However, the molecular details of how this virus spreads to new target cells are unclear. This work provides important new information on the formation of filamentous structures that are consistent with virus particles and adds critical new insight into the structure of extensions between cells that form during infection. In addition, it demonstrates for the first time the movement of viral replication centers through these intercellular extensions, representing a new mode of direct cell-to-cell spread that may be applicable to other viral systems.
Impact of corrosion inhibitors on antibiotic resistance, metal resistance, and microbial communities in drinking water
Authors: Kimbell Lee K. , LaMartina Emily Lou , Kohls Stan , Wang Yin , Newton Ryan J. , McNamara Patrick J. 
Published: September 2023

ABSTRACT

Corrosion inhibitors, including zinc orthophosphate, sodium orthophosphate, and sodium silicate, are commonly used to prevent the corrosion of drinking water infrastructure. Metals such as zinc are known stressors for antibiotic resistance selection, and phosphates can increase microbial growth in drinking water distribution systems (DWDS). Yet, the influence of corrosion inhibitor type on antimicrobial resistance in DWDS is unknown. Here, we show that sodium silicates can decrease antibiotic resistant bacteria (ARB) and antibiotic-resistance genes (ARGs), while zinc orthophosphate increases ARB and ARGs in source water microbial communities. Based on controlled bench-scale studies, zinc orthophosphate addition significantly increased the abundance of ARB resistant to ciprofloxacin, sulfonamides, trimethoprim, and vancomycin, as well as the genes
sul1
,
qac
EΔ1, an indication of resistance to quaternary ammonium compounds, and the integron-integrase gene
intI
1. In contrast, sodium silicate dosage at 10 mg/L resulted in decreased bacterial growth and antibiotic resistance selection compared to the other corrosion inhibitor additions. Source water collected from the drinking water treatment plant intake pipe resulted in less significant changes in ARB and ARG abundance due to corrosion inhibitor addition compared to source water collected from the pier at the recreational beach. In tandem with the antibiotic resistance shifts, significant microbial community composition changes also occurred. Overall, the corrosion inhibitor sodium silicate resulted in the least selection for antibiotic resistance, which suggests it is the preferred corrosion inhibitor option for minimizing antibiotic resistance proliferation in DWDS. However, the selection of an appropriate corrosion inhibitor must also be appropriate for the water chemistry of the system (e.g., pH, alkalinity) to minimize metal leaching first and foremost and to adhere to the lead and copper rule.

IMPORTANCE
Antibiotic resistance is a growing public health concern across the globe and was recently labeled the silent pandemic. Scientists aim to identify the source of antibiotic resistance and control points to mitigate the spread of antibiotic resistance. Drinking water is a direct exposure route to humans and contains antibiotic-resistant bacteria and associated resistance genes. Corrosion inhibitors are added to prevent metallic pipes in distribution systems from corroding, and the type of corrosion inhibitor selected could also have implications on antibiotic resistance. Indeed, we found that sodium silicate can minimize selection of antibiotic resistance while phosphate-based corrosion inhibitors can promote antibiotic resistance. These findings indicate that sodium silicate is a preferred corrosion inhibitor choice for mitigation of antibiotic resistance.
Data preservation in high energy physics
Authors: Basaglia T. , Bellis M. , Blomer J. , Boyd J. , Bozzi C. , Britzger D. , Campana S. , Cartaro C. , Chen G. , Couturier B. , David G. , Diaconu C. , Dobrin A. , Duellmann D. , Ebert M. , Elmer P. , Fernandes J. , Fields L. , Fokianos P. , Ganis G. , Geiser A. , Gheata M. , Lopez J. B. Gonzalez , Hara T. , Heinrich L. , Hildreth M. , Herner K. , Jayatilaka B. , Kado M. , Keeble O. , Kohls A. , Naim K. , Lange C. , Lassila-Perini K. , Levonian S. , Maggi M. , Marshall Z. , Vila P. Mato , Mečionis A. , Morris A. , Piano S. , Potekhin M. , Schröder M. , Schwickerath U. , Sexton-Kennedy E. , Šimko T. , Smith T. , South D. , Verbytskyi A. , Vidal M. , Vivace A. , Wang L. , Watt G. , Wenaus T. ,   DPHEP Collaboration
Published: September 2023

AbstractData preservation is a mandatory specification for any present and future experimental facility and it is a cost-effective way of doing fundamental research by exploiting unique data sets in the light of the continuously increasing theoretical understanding. This document summarizes the status of data preservation in high energy physics. The paradigms and the methodological advances are discussed from a perspective of more than ten years of experience with a structured effort at international level. The status and the scientific return related to the preservation of data accumulated at large collider experiments are presented, together with an account of ongoing efforts to ensure long-term analysis capabilities for ongoing and future experiments. Transverse projects aimed at generic solutions, most of which are specifically inspired by open science and FAIR principles, are presented as well. A prospective and an action plan are also indicated.
The b quark fragmentation fractions at LHCb and meson decays with heavy quark spectators
Authors: Dib C. O. , Kim C. S. , Neill N. A. 
Published: September 2023

AbstractWe study the current estimates of $$B_c\rightarrow B_s \pi $$

B
c

→

B
s

π

to extract the fragmentation fraction $$f_c/f_s$$

f
c

/

f
s

at the LHCb. A rather robust estimate of $$Br(B_c\rightarrow B_s \pi )$$

B
r
(

B
c

→

B
s

π
)

based on factorization and lattice results for the form factor gives $$f_c/f_s \sim 0.056$$

f
c

/

f
s

∼
0.056

with a 16% error. We also revisit the extraction of $$f_s/f_d$$

f
s

/

f
d

using $$B\rightarrow D\pi $$

B
→
D
π

instead of the theoretical cleaner but more suppressed channel $$B\rightarrow DK$$

B
→
D
K

. We also find a tension on the predictions of $$Br(B_c\rightarrow J/\psi \pi )$$

B
r
(

B
c

→
J
/
ψ
π
)

and $$Br(B_c\rightarrow B_s\pi )$$

B
r
(

B
c

→

B
s

π
)

considering the measurements of these modes at LHCb, and find that, within a 23% uncertainty, only the lower end of the current prediction range $$Br(B_c\rightarrow J/\psi )\sim 0.4\% - 1.7\%$$

B
r
(

B
c

→
J
/
ψ
)
∼
0.4
%
-
1.7
%

would be consistent with the LHCb measurements.
Multiscale micro-architecture of pore space in rocks: size, shape, deformation and accessibility determined by small-angle neutron scattering (SANS)
Authors: Radlinski Andrzej P. , Blach Tomasz 
Published: September 2023

AbstractA brief summary of the evolving applications of small-angle neutron scattering (SANS) to the microstructural research on geological materials in the last few decades is provided, including new developments and possible future directions. This is an account of authors’ view of the interplay between the technical development of SANS instrumentation, methodology and sample environments and the progress of research on the evolution of organic matter, gas adsorption and desorption, fluid transport in the pore space and the microstructure of rocks, based mostly on their own research interests.
Graphical abstract
FF-10850, a Novel Liposomal Topotecan Achieves Superior Antitumor Activity via Macrophage- and Ammonia-Mediated Payload Release in the Tumor Microenvironment
Authors: Shimoyama Susumu , Okada Ken , Kimura Toshifumi , Morohashi Yasushi , Nakayama Shinji , Kemmochi Sayaka , Makita-Suzuki Keiko , Matulonis Ursula A. , Mori Mikinaga 
Published: September 2023

Abstract
Topotecan, an approved treatment for refractory or recurrent ovarian cancer, has clinical limitations such as rapid clearance and hematologic toxicity. To overcome these limitations and maximize clinical benefit, we designed FF-10850, a dihydrosphingomyelin-based liposomal topotecan. FF-10850 demonstrated superior antitumor activity to topotecan in ovarian cancer cell line-based xenograft models, as well as in a clinically relevant DF181 platinum-refractory ovarian cancer patient-derived xenograft model. The safety profile was also improved with mitigation of hematologic toxicity. The improved antitumor activity and safety profile are achieved via its preferential accumulation and payload release triggered in the tumor microenvironment. Our data indicate that tumor-associated macrophages internalize FF-10850, resulting in complete payload release. The release mechanism also appears to be mediated by high ammonia concentration resulting from glutaminolysis, which is activated by tumor metabolic reprogramming. In ammonia-rich conditions, FF-10850 released payload more rapidly and to a greater extent than liposomal doxorubicin, a currently approved treatment for ovarian cancer. FF-10850 significantly enhanced antitumor activity in combination with carboplatin or PARP inhibitor without detrimental effects on body weight in murine xenograft models, and demonstrated synergistic antitumor activity combined with anti–PD-1 antibody with the development of tumor antigen-specific immunity. These results support phase I investigation of FF-10850 for the treatment of solid tumors including ovarian cancer (NCT04047251), and further evaluation in combination settings.
Sedentary Bout Patterns and Metabolic Health in the Hispanic Community Health Study/Study of Latino Youth (SOL Youth)
Authors: Carlson Jordan A. , Hibbing Paul R. , Forseth Bethany , Diaz Keith M. , Sotres‐Alvarez Daniela , Bejarano Carolina M. , Duran Andrea T. , Castañeda Sheila F. , Garcia Melawhy L. , Perreira Krista M. , Daviglus Martha L. , Van Horn Linda , Gellman Marc D. , Isasi Carmen R. , Cai Jianwen , Delamater Alan M. , Staggs Vincent S. , Thyfault John , Gallo Linda C. 
Published: September 2023

Background
There is limited evidence on the potential negative metabolic health impacts of prolonged and uninterrupted sedentary bouts in structurally disadvantaged youth. This study investigated associations between sedentary bout variables and metabolic health markers in the Hispanic Community Health Study/SOL Youth (Study of Latino Youth).

Methods and Results

SOL Youth was a population‐based cohort of 1466 youth (age range, 8–16 years; 48.5% female); 957 youth were included in the analytic sample based on complete data. Accelerometers measured moderate‐to‐vigorous physical activity (MVPA), total sedentary time, and sedentary bout patterns (daily time spent in sedentary bouts ≥30 minutes, median sedentary bout duration, and number of daily breaks from sedentary time). Clinical measures included body mass index, waist circumference, fasting glucose, glycated hemoglobin, fasting insulin, and the homeostasis model assessment of insulin resistance. After adjusting for sociodemographics, total sedentary time, and MVPA, longer median bout durations and fewer sedentary breaks were associated with a greater body mass index percentile (b
bouts
=0.09 and b
breaks
=−0.18), waist circumference (b
bouts
=0.12 and b
breaks
=−0.20), and fasting insulin (b
bouts
=0.09 and b
breaks
=−0.21). Fewer breaks were also associated with a greater homeostasis model assessment of insulin resistance (b=−0.21). More time in bouts lasting ≥30 minutes was associated with a greater fasting glucose (b=0.18) and glycated hemoglobin (b=0.19).

Conclusions
Greater accumulation of sedentary time in prolonged and uninterrupted bouts had adverse associations with adiposity and glycemic control over and above total sedentary time and MVPA. Findings suggest interventions in Hispanic/Latino youth targeting both ends of the activity spectrum (more MVPA and less prolonged/uninterrupted sedentary patterns) may provide greater health benefits than those targeting only MVPA.
Cardiovascular Hospitalizations and Resource Use Following Atrial Fibrillation Ablation
Authors: Dhande Mehak , Barakat Amr , Canterbury Ann , Thoma Floyd , Mulukutla Suresh , Sezer Ahmet , Aronis Konstantinos N. , Bhonsale Aditya , Kancharla Krishna , Voigt Andrew H. , Wang Norman C. , Shalaby Alaa , Mark Estes N. A. , Saba Samir , Jain Sandeep K. 
Published: September 2023

Background
Over the next few years, atrial fibrillation (AF)–related morbidity and costs will increase significantly. Thus, it is prudent to examine the impact of AF treatment on health care resource use. This study examined the impact of AF ablation on hospitalization, length of stay, and resource use for patients undergoing AF ablation in a multihospital system.

Methods and Results

In an observational analysis, outcomes of total, cardiovascular, and AF hospitalizations, emergency department visits, and length of stay were compared for 3417 patients between 12 months before and 24 months following AF ablation. Use of electrical cardioversions and antiarrhythmic use were also compared 1 year before to 2 years after AF ablation. There were fewer total (0.7±1.3 versus 0.3±0.7;
P
<0.001), cardiovascular (0.7±1.2 versus 0.2±0.6;
P
<0.001), and AF (0.6±1.1 versus 0.1±0.3;
P
<0.001) hospitalizations and emergency department visits (0.8±2.1 versus 0.4±0.9;
P
<0.001) per patient‐year for the 2 years following AF ablation compared with 1 year before. Average length of stay per patient‐year (1.4±7.9 versus 3.6±5.3 days;
P
<0.0001), the percentage of patients on antiarrhythmic therapy (21.2% versus 58.5%;
P
<0.0001), and those undergoing electrical cardioversions (16.1% versus 28.1%;
P
<0.0001) were lower 2 years following AF ablation versus 1 year before.

Conclusions
We noted a decrease in total, cardiovascular, and AF hospitalizations and health care resource use during the 2‐year period after index AF ablation, compared with the 1 year before. AF ablation may portend a decline in patient morbidity and health care costs.
Penalized Model‐Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score
Authors: Sung Kuo‐Tzu , Chang Hung‐Yu , Hsu Nai‐Wei , Huang Wen‐Hung , Lin Yueh‐Hung , Yun Chun‐Ho , Hsiao Chih‐Chung , Hsu Chien‐Yi , Tsai Shin‐Yi , Chen Ying‐Ju , Tsai Cheng‐Ting , Su Cheng‐Huang , Hung Ta‐Chuan , Hou Charles Jia‐Yin , Yeh Hung‐I , Hung Chung‐Lieh 
Published: September 2023

Background
The angiotensin receptor–neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin–angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown.

Methods and Results

This study comprised a pooled 2‐center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin–angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74‐year follow‐up, phenogroup assignment provided improved prognostic discrimination beyond Meta‐Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index
P
<0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all‐cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin–angiotensin system inhibitor control as reference group.

Conclusions
Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.
Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease
Authors: Welty Francine K. , Hariri Essa , Asbeutah Abdul Aziz , Daher Ralph , Amangurbanova Maral , Chedid Georges , Elajami Tarec K. , Alfaddagh Abdulhamied , Malik Abdulaziz 
Published: September 2023

Background
Residual risk of cardiovascular events and plaque progression remains despite reduction in low‐density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors.

Methods and Results

A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low‐density lipoprotein cholesterol level was <2.07 mmol/L, and median triglyceride level was <1.38 mmol/L. Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression (
r
=0.135;
P
=0.036). Compared with regressors, progressors had higher cardiac events (5% vs 22.3%, respectively;
P
<0.001) and a 2.89‐fold increased risk of cardiac events (95% CI, 1.1–8.0;
P
=0.034). Baseline non–high‐density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression. Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction (
r
=0.35;
P
=0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio.

Conclusions
Triglyceride reduction, systolic blood pressure <125 mm Hg, and non–high‐density lipoprotein cholesterol <2.59 mmol/L were associated with coronary plaque regression and reduced cardiac events. Normotensive patients had greater benefit than hypertensive patients potentially due to lower levels of inflammation. Future studies should examine the role of inflammation in plaque regression.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01624727.