bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of amino acid residue in the
Cronobacter sakazakii
LamB responsible for the receptor compatibility of polyvalent coliphage CSP1
Authors: Kim Moosung , Kim Minsik , Ryu Sangryeol 
Published: September 2024

ABSTRACT

Polyvalent bacteriophages show the feature of infecting bacteria across multiple species or even orders. Infectivity of a polyvalent phage is variable depending on the host bacteria, which can disclose differential inhibition of bacteria by the phage. In this study, a polyvalent phage CSP1 infecting both
Cronobacter sakazakii
ATCC 29544 and
Escherichia coli
MG1655 was isolated. CSP1 showed higher growth inhibition and adsorption rate in
E. coli
compared to
C. sakazakii
, and identification of host receptors revealed that CSP1 uses
E. coli
LamB (LamB
E
) as a receptor but that CSP1 requires both
C. sakazakii
LamB (LamB
C
) and lipopolysaccharide (LPS) core for
C. sakazakii
infection. The substitution of LamB
C
with LamB
E
in
C. sakazakii
enhanced CSP1 susceptibility and made
C. sakazakii
LPS core no more essential for CSP1 infection. Comparative analysis of LamB
C
and LamB
E
disclosed that the extra proline at amino acid residue 284 in LamB
C
made a structural distinction by forming a longer loop and that the deletion of 284P in LamB
C
aligns its structure and makes LamB
C
function like LamB
E
, enhancing CSP1 adsorption and growth inhibition of
C. sakazakii
. These results suggest that 284P of LamB
C
plays a critical role in determining the CSP1-host bacteria interaction. These findings could provide insight into the elucidation of molecular determinants in the interaction between polyvalent phages and host bacteria and help us to understand the phage infectivity for efficient phage application.

IMPORTANCE

Polyvalent phages have the advantage of a broader host range, overcoming the limitation of the narrow host range of phages. However, the limited molecular biological understanding on the host bacteria-polyvalent phage interaction hinders its effective application. Here, we revealed that the ability of the polyvalent phage CSP1 to infect
Cronobacter sakazakii
ATCC 29544 is disturbed by a single proline residue in the LamB protein and that lipopolysaccharide is used as an auxiliary receptor for CSP1 to support the adsorption and the subsequent infection of
C. sakazakii
. These results can contribute to a better understanding of the interaction between polyvalent phages and host bacteria for efficient phage application.
High-throughput screening identification of apigenin that reverses the colistin resistance of mcr-1-positive pathogens
Authors: Tang Feng , Peng Wenjing , Kou Xu , Chen Zeliang , Zhang Libo 
Published: September 2024

ABSTRACT

The plasmid-mediated gene mcr-1 that makes bacteria resistant to the antibiotic colistin is spreading quickly, which means that colistin is no longer working well to treat Gram-negative bacterial infections. Herein, we utilized a computer-aided high-throughput screening drugs method to identify the natural product apigenin, a potential
mcr
-protein inhibitor, which effectively enhanced the antimicrobial activity of colistin. Several assays, including a checkerboard minimum inhibitory concentration assay, a time-kill assay, the combined disk test, molecular simulation dynamics, and animal infection models assay, were conducted to verify whether apigenin enhanced the ability of colistin to fight Gram-negative bacterial infections. The results showed that apigenin improved the antimicrobial activity of colistin against multidrug-resistant
Enterobacteriaceae
infection. Moreover, apigenin not only did not increase the toxic effect of colistin but also had the ability to effectively inhibit the frequency of bacterial resistance mutations to colistin. Studies clearly elucidated that apigenin could interfere with the thermal stability of the protein by binding to the
mcr
-1 protein. Additionally, the combination of apigenin and colistin could exert multiple effects, including disrupting bacterial membranes, the generation of bacterial nitric oxide and reactive oxygen species, as well as inhibiting bacterial adenosine triphosphate production. Furthermore, the addition of apigenin was able to significantly inhibit colistin-stimulated high expression levels of the bacterial mcr-1 gene. Finally, apigenin exhibited a characteristic anti-inflammatory effect while enhancing the antimicrobial activity of colistin against mcr-1-positive
Escherichia coli
(
E. coli
) infected animals. In conclusion, as a potential lead compound, apigenin is promising in combination with colistin in the future treatment of mcr-1-positive
E. coli
infections.

IMPORTANCE

This study found that apigenin was able to inhibit the activity of the
mcr
-1 protein using a high-throughput virtual screening method. Apigenin effectively enhanced the antimicrobial activity of colistin against multidrug-resistant
Enterobacteriaceae
, including mcr-1-positive strains,
in vitro
and
in vivo
. This study will provide new options and strategies for the future treatment of multidrug-resistant pathogen infections.
Penicillin susceptibility among
Staphylococcus aureus
skin and soft tissue infections at a children’s hospital
Authors: McNeil J. Chase , Sommer Lauren M. , Joseph Marritta , Hulten Kristina G. , Kaplan Sheldon L. 
Published: September 2024

ABSTRACT

Shortly after its introduction into clinical practice,
Staphylococcus aureus
isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible
S. aureus
(MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children’s Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for
blaZ
β-lactamase;
blaZ
-negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were
blaZ
negative and had a penicillin MIC ≤0.125 µg/mL were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). All PSSA underwent multilocus sequence typing. Medical records were reviewed. The median age of subjects was 4.2 years (IQR: 1.6–10.5). PSSA accounted for 9% of isolates during the study period. PSSA and PR-MSSA cases were similar with respect to age, demographics, and rates of prior antibiotic exposure. PSSA isolates less often had vancomycin MIC ≥1.5 µg/mL. Furthermore, 39% of PSSA were variants of sequence type 1. In multivariable analyses, penicillin susceptibility was independently associated with both hospital admission and surgical intervention. PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA SSTI is challenging. However, PSSA SSTI were independently associated with higher rates of hospital admission as well as the need for surgical intervention suggesting a significant clinical impact.

IMPORTANCE

The vast majority of
Staphylococcus aureus
in the US are penicillin resistant with most clinical labs no longer reporting penicillin susceptibility for this organism. A number of centers, however, have reported increasing penicillin susceptibility among invasive
S. aureus
infections. Skin and soft tissue infections (SSTI) are far more common than invasive infections, yet the frequency and impact of penicillin-susceptible
S. aureus
(PSSA) in this population are uncertain. Through active surveillance at a children’s hospital, we found that 9% of methicillin-susceptible
S. aureus
SSTI isolates were PSSA. PSSA were independently associated with hospital admission for the management of SSTI as well as the need for debridement in the operating room. Given that most SSTI are managed in the outpatient setting, these findings suggest a clinical impact of this phenotype and the need for a reassessment of the value in susceptibility testing and potentially even treatment with penicillin.
The timing of Missoula floods: Implications for the age of Grand Coulee (eastern Washington, USA)
Authors: Lehnigk Karin E. , Larsen Isaac J. , Quirk Brendon J. , David Scott R. 
Published: September 2024

Abstract
The Channeled Scabland of eastern Washington (USA) was formed by outburst floods from glacial Lake Missoula. Despite chronological advances, the timing of erosion in the main flood channels is unresolved. In particular, it is still uncertain whether upper Grand Coulee, the largest canyon in the Channeled Scabland, was incised during or prior to the last glaciation. We report 10Be exposure ages from erratics in upper Grand Coulee, glacial Lake Columbia, and surrounding flood routes. Flood-transported boulders on the high-elevation east rim of Grand Coulee date to ca. 17–15 ka. Ages from boulders on the floor of Grand Coulee indicate later flooding at ca. 14 ka, which post-dated canyon incision and occurred after inundation of the Telford-Crab Creek scabland at ca. 15–14.5 ka. Prior hydraulic modeling and dating suggest the entrance to Grand Coulee was blocked by rock and that canyon incision was incomplete at ca. 17 ka; hence, we interpret the 17–15 ka exposure ages on the east rim to coincide with flow over a retreating cataract during canyon incision. Our results indicate incision of Grand Coulee was completed between 17 ka and 14 ka. The short duration of canyon incision suggests that glacial Lake Missoula generated some of the most erosive outburst floods in Earth's history.
Thermodynamic Properties of NaH2PO4⋅2H2O and K2HPO4⋅3H2O Crystal Hydrates
Authors: Novikov A. A. , Yongxu Luo , Tiflova L. A. , Kurdakova S. V. , Kovalenko N. A. , Uspenskaya I. A. 
Published: September 2024

Abstract
NaH2PO4⋅2H2O and K2HPO4⋅3H2О crystal hydrates are synthesized from aqueous solutions at room temperature. The resulting samples are identified using X-ray structural analysis (XSA) and thermogravimetry (TG). The enthalpies of dissolution in water at 298.15 K are determined through the calorimetry of dissolution, and the standard enthalpies of formation for the crystal hydrates of sodium dihydrophosphate and potassium hydrophosphate are calculated. A comparison of the estimated and experimentally obtained values of the enthalpy of formation for NaH2PO4⋅2H2O and K2HPO4⋅3H2О shows they are within the limits of the error of determination.
Observed jet power and radiative efficiency of black hole candidates in the Kerr+PFDM model
Authors: Narzilloev Bakhtiyor , Abdujabbarov Ahmadjon , Ahmedov Bobomurat , Bambi Cosimo 
Published: September 2024

AbstractIn this research, we explore the electromagnetic energy emitted by astrophysical black holes within the Kerr+PFDM (Kerr + perfect fluid dark matter) spacetime, a model comprising rotating black holes surrounded by dark matter. Our investigation focuses on black holes within X-ray binary systems, namely GRS 1915+105, GRO J1655-40, XTE J1550-564, A0620-00, H1743-322, and GRS 1124-683. Our findings indicate that the Kerr+PFDM spacetime can account for the radiative efficiency of these sources as determined through the continuum-fitting method (CFM). Additionally, employing the Blandford–Znajek mechanism, we demonstrate the ability to replicate the observed jet power. By combining the outcomes of both analyses for the selected objects, we establish more rigorous constraints on the spacetime parameters. Notably, our results reveal that, similar to the Kerr spacetime, the Kerr+PFDM spacetime cannot simultaneously account for the observed jet power and radiative efficiency of GRS 1915+105.
Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non–Small Cell Lung Cancer
Authors: Smith Margaret R. , Dixon Caroline B. , Wang Yuezhu , Liu Yin , D’Agostino Ralph , Ruiz Jimmy , Oliver George , Miller Lance D. , Topaloglu Umit , Chan Michael D. , Farris Michael , Su Jing , Mileham Kathryn F. , Zhao Dawen , Li Wencheng , Sexton Tammy , Lycan Thomas , Haas Karen M. , Grayson Jason M. , Xing Fei 
Published: September 2024

Abstract
Treatment of non–small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anticancer effects of immune checkpoint inhibitors (ICI). However, only 20% of the patients with NSCLC benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 patients with NSCLC who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss-of-function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS when compared with patients with wild-type NTRK1. Notably, suppression of the NTRK1 pathway by knockdown or entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models. Comprehensive T-cell population analyses demonstrated that stem-like CD4+ T cells and effector CD4+ and CD8+ T cells were highly enriched in anti–PD-1–treated mice bearing tumors with decreased NTRK1 signaling. RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating cross-talk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcome immunotherapy resistance in patients with NSCLC with NTRK1 wild-type.
Significance: Inhibition of NTRK1 signaling confers sensitivity to immunotherapy by enhancing complement C3-mediated T-cell and macrophage functions, leading to improved responses to immune checkpoint inhibitors in patients with lung cancer with NTRK1 mutations.
ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial
Authors: Soo Ross A. , Dafni Urania , Han Ji-Youn , Cho Byoung Chul , Nadal Ernest , Yeo Chong Ming , Carcereny Enric , de Castro Javier , Sala Maria Angeles , Coate Linda , Provencio Mariano , Britschgi Christian , Vagenknecht Patrick , Dimopoulou Georgia , Kammler Roswitha , Finn Stephen P. , Peters Solange , Stahel Rolf A. ,   for the ETOP 10-16 BOOSTER Collaborators
Published: September 2024

Abstract

Purpose:
The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously.

Experimental Design:
Next-generation sequencing (Guardant360) was conducted in serial plasma samples. The association between ctDNA and efficacy outcomes was explored, and molecular alterations at progression were described.

Results:
A total of 136 patients (88% of 155 randomized) had plasma samples at baseline (68 per arm), 110 (71%) at week 9, and 65 (42%) at progression. In a multivariable model for progression-free survival (PFS), the treatment effect was found to differ by smoking status (interaction P = 0.046), with the effect of smoking also differing by baseline EGFR T790M (interaction P = 0.033), whereas both TP53 at baseline and the tissue EGFR exon 21 L858R mutation were significantly associated with worse PFS outcome. Smokers (current/former) without baseline EGFR T790M showed a significant improvement in PFS under combination treatment, albeit with small numbers (P = 0.015). Week-9 EGFR T790M clearance was associated with improved PFS in the osimertinib arm (P = 0.0097). Acquired EGFR C797S mutations were detected in 22% and 13% of patients in the combination and osimertinib arms, respectively.

Conclusions:
The differential effect of treatment by smoking was not explained by TP53 mutations or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected, but no novel molecular alterations were identified in the combination arm.
Do Children's Health Behaviors Buffer the Impact of Cumulative Environmental Stress on Emerging Cardiometabolic Risk?
Authors: Kunin‐Batson Alicia S. , Crain A. Lauren , Sherwood Nancy E. , Kelly Aaron S. , Kharbanda Elyse O. , Gunnar Megan R. , Haapala Jacob , Seburg Elisabeth M. , French Simone A. 
Published: September 2024

Background
Previous studies have found that exposure to childhood environmental stress is associated with cardiometabolic risk. However, it is not known whether individual health behaviors disrupt this relationship. This study prospectively evaluated the relationship between cumulative environmental stress in a low‐income sample and cardiometabolic risk in middle childhood and examined whether child health behaviors attenuated this relationship.

Methods and Results

In a cohort of children (n=338; 57% Hispanic children; 25% Black children), environmental stressors (family and neighborhood factors representing disadvantage/deprivation) and child health behaviors (accelerometry measured physical activity; parent‐reported screen time and diet recalls) were measured over 5 time points beginning when children were aged 2 to 4 years and ending when they were aged 7 to 11 years. Children's cardiometabolic risk factors (body mass index, blood pressure, triglyceride/high‐density lipoprotein ratio, glucose, hemoglobin A
1c
, C‐reactive protein) were measured at 7 to 11 years. Emerging cardiometabolic risk was defined as having ≥1 elevations that exceeded clinical thresholds. In adjusted path analyses, greater cumulative environmental stress was associated with higher likelihood of emerging cardiometabolic risk in middle childhood (
P
<0.001). Higher levels of moderate to vigorous physical activity and fewer sedentary minutes attenuated the positive relationship between stress and cardiometabolic risk (
P
<0.05). Children with
>
2 hours of average daily screen time had a higher likelihood of elevated cardiometabolic risk (
P
<0.01), but screen time did not moderate the stress–cardiometabolic risk relationship. Dietary intake was not related to cardiometabolic risk.

Conclusions
Interventions that promote moderate to vigorous physical activity and limit sedentary behavior may have particular importance for the cardiometabolic health of children exposed to high levels of cumulative environmental stress.
Relationship Between Infarct Artery, Myocardial Injury, and Outcomes After Primary Percutaneous Coronary Intervention in ST‐Segment–Elevation Myocardial Infarction
Authors: de Waha Suzanne , Patel Manesh R. , Thiele Holger , Udelson James E. , Granger Christopher B. , Ben‐Yehuda Ori , Kotinkaduwa Lak , Redfors Björn , Eitel Ingo , Selker Harry P. , Maehara Akiko , Stone Gregg W. 
Published: September 2024

Background
The extent to which infarct artery impacts the extent of myocardial injury and outcomes in patients with ST‐segment–elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention is uncertain.

Methods and Results

We performed a pooled analysis using individual patient data from 7 randomized STEMI trials in which myocardial injury within 30 days after primary percutaneous coronary intervention was assessed in 1774 patients by cardiac magnetic resonance (n=1318) or technetium‐99m sestamibi single‐photon emission computed tomography (n=456). Clinical follow‐up was performed at a median duration of 351 days (interquartile range, 184–368 days). Infarct size and outcomes were assessed in anterior (infarct vessel=left anterior descending) versus nonanterior (non–left anterior descending) STEMI. Median infarct size (percentage left ventricular myocardial mass) was larger in patients with anterior compared with nonanterior STEMI (19.7% [interquartile range, 9.4%–31.7%] versus 12.6% [interquartile range, 5.1%–20.5%];
P
<0.001). Patients with anterior compared with nonanterior STEMI were at higher risk for 1‐year all‐cause mortality (6.2% versus 3.6%; adjusted hazard ratio [HR], 1.66 [95% CI, 1.02–2.69];
P
=0.04) and heart failure hospitalization (4.4% versus 2.6%; adjusted HR, 1.96 [95% CI, 1.15–3.36];
P
=0.01). Infarct size was a predictor of subsequent all‐cause mortality or heart failure hospitalization in anterior STEMI (adjusted HR per 1% increase, 1.05 [95% CI, 1.03–1.07];
P
<0.001), but not in nonanterior STEMI (adjusted HR, 1.02 [95% CI, 0.99–1.05];
P
=0.19). The
P
value for this interaction was 0.04.

Conclusions
Anterior STEMI was associated with substantially greater myonecrosis after primary percutaneous coronary intervention compared with nonanterior STEMI, contributing in large part to the worse prognosis in patients with anterior infarction.
Long‐Term Risk of Cardiovascular Death in Patients With Mildly Reduced Ejection Fraction After Acute Myocardial Infarction: A Multicenter, Prospective Registry Study
Authors: Kim Hwajung , Lee Kwan Yong , Choo Eun Ho , Hwang Byeong‐Hee , Kim Jin Jin , Kim Chan Joon , Chang Kiyuk , Hong Young Joon , Kim Ju Han , Ahn Youngkeun , Choi Young ,   KAMIR‐NIH Investigators
Published: September 2024

Background
The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long‐term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction.

Methods and Results

A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long‐term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%–49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow‐up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group (
P
<0.001). In the mrEF group, age>65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high‐risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high‐risk mrEF group was comparable with the rEF group, while it was lower in the low‐risk mrEF group than in the pEF group.

Conclusions
Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high‐risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.