bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deglycosylation and truncation in the neuraminidase stalk are functionally equivalent in enhancing the pathogenicity of a high pathogenicity avian influenza virus in chickens
Authors: Kobayashi Daiki , Hiono Takahiro , Arakawa Hiromu , Kaji Hiroyuki , Ohkawara Ayako , Ichikawa Takaya , Ban Hinako , Isoda Norikazu , Sakoda Yoshihiro 
Published: February 2025

ABSTRACT

Influenza A viruses with fewer amino acids in the neuraminidase (NA) stalk domain are primarily isolated from chickens rather than wild ducks, indicating that a shortened NA stalk is considered an adaptation marker of avian influenza viruses (AIVs) to chickens. Experimental passages of an H7N7 nonpathogenic AIV (rgVac2-P0) in chickens resulted in a highly pathogenic variant (Vac2-P3L4) with a 34-amino-acid deletion in the NA stalk, encompassing five potential
N
-glycosylation sites. To investigate how amino acid truncation and deglycosylation in the NA stalk contribute to increased pathogenicity, a virus with glycosylation-deficient mutations at these sites (rgVac2-P3L4/P0NAΔGlyco) was constructed. Contrary to expectations, chickens inoculated with rgVac2-P3L4/P0NAΔGlyco exhibited variable clinical outcomes, attributed to the genetic instability of the virus. A single mutation stabilized the virus, and the mutant (rgVac2-P3L4/P0NAΔGlyco-Y65H) resulted in higher pathogenicity compared with a virus with restored glycosylation (rgVac2-P3L4/P0NA-Y65H). Glycan occupancy analysis revealed 3–4 glycans at the five potential sites. In functional analysis, glycosylation-deficient mutants, similar to the short-stalk NA virus, showed significantly reduced erythrocyte elution activity. Additionally, mutational analysis indicated variable contributions of
N
-glycans to elution activity across the sites. Moreover, the functionally most contributing sites of the five potential
N
-glycosylation motifs were consistently included in the amino acid deletions of the stalk-truncated NA in N7-subtyped field isolates, despite the varying truncation position or length. These findings suggest that the loss of glycosylation is functionally equivalent to a reduction in amino acids, and it plays a crucial role in enhancing pathogenicity in chickens and affecting NA function.

IMPORTANCE

Avian influenza poses significant economic challenges to the poultry industry and presents potential risks to human health. Understanding the molecular mechanisms that facilitate the emergence of chicken-adapted avian influenza viruses (AIVs) from non-pathogenic duck-origin influenza viruses is crucial for improving AIV monitoring systems in poultry and controlling this disease. Amino acid deletions in the neuraminidase (NA) stalk domain serve as one of the molecular markers for AIV adaptation to Galliformes. This study highlights the critical role of
N
-glycosylation in the NA stalk domain in the pathogenesis of high pathogenicity avian influenza viruses in chickens. The findings propose a novel theory that the loss of glycosylation at the NA stalk domain, rather than a reduction in stalk length, is responsible for both NA function and increased virus pathogenicity in chickens.
Characterization and therapeutic potential of newly isolated bacteriophages against
Staphylococcus
species in bovine mastitis
Authors: Cho Jae-hyun , Lee Gyu Min , Ko Seyoung , Kim Youngju , Kim Donghyuk 
Published: February 2025

ABSTRACT

Bovine mastitis, primarily caused by
Staphylococcus aureus
, significantly affects the dairy industry by reducing milk production and quality. The rise of antibiotic-resistant bacteria has prompted the need for alternative treatments. The three newly isolated bacteriophages, OPT-SA02, OPT-SC01, and OPT-SX11, were isolated from chicken fecal and sewage samples in South Korea. These bacteriophages were characterized via physiological and genomic analyses, identifying their therapeutic potential against
S. aureus
-induced mastitis. The bacteriophages were identified as members of the
Herelleviridae
family, exhibiting stability across broad pH (2–12) and temperature (37–70°C) ranges, as well as strong antibacterial activity at low multiplicity of infection (MOI) levels. Genomic analysis revealed that the conservation of lysis-related genes (holin and endolysin) is responsible for their lytic capabilities. Additionally, protein structural predictions revealed multi-domain structures in their endolysins, enhancing their lytic potential. These findings suggest that OPT-SA02, OPT-SC01, and OPT-SX11 show significant promise as alternative treatments for bovine mastitis.

IMPORTANCE

Bovine mastitis, caused by pathogens such as
Staphylococcus aureus
and
Staphylococcus xylosus
, remains a major challenge in dairy farming, leading to significant economic losses and reduced milk quality. The increasing prevalence of antibiotic-resistant strains further complicates treatment, emphasizing the need for alternative strategies. This study identifies three newly isolated bacteriophages with effective antibacterial activity against these pathogens and provides comprehensive genomic and structural insights into their mechanisms. Genomic characterization revealed conserved lytic cassettes and genetic diversity within related bacteriophages, offering a deeper understanding of their evolutionary relationships and potential applications. Furthermore, protein structure analysis of the endolysin derived from these bacteriophages identified multi-domain architectures with preserved catalytic cores, underscoring their lytic efficacy against bacterial cell walls. These findings advance the understanding of the genetic and structural mechanisms of bacteriophage-mediated lysis and highlight their potential as sustainable tools for managing bovine mastitis and improving milk quality in dairy farming.
The genetic variation of mitochondrial sequences and pathological differences of
Echinococcus multilocularis
strains from different continents
Authors: Guo Baoping , Guo Gang , Qi Wenjing , Aizezi Malike , Wu Chuanchuan , Tian Mengxiao , Casulli Adriano , Zhang Wenbao , Li Jun 
Published: February 2025

ABSTRACT

Alveolar echinococcosis is a lethal zoonotic disease caused by the fox tapeworm
Echinococcus multilocularis
. The parasite is widely distributed in the Northern Hemisphere and exhibits low genetic diversity among populations. To compare the differences among four
E. multilocularis
strains from different geographical locations, namely, Alaska (EM-AK), Japan (EM-JP), Xinjiang (EM-XJ), and Ningxia (EM-NX), their complete mitochondrial (mt) sequences were compared, and their induced pathological lesions were analyzed in mouse models. The complete mt sequence of EM-AK resulted in 0.84%–0.86% variation as compared with the other strains, which had a lower variation. Phylogenetic analysis and parsimony network indicated that EM-AK resulted in 30,000 years of evolutionary distance from the other three strains. EM-AK induced more pathological damage than the other three strains, which was likely to induce more host cell infiltration and acute granuloma in the liver. More importantly, EM-AK produced more protoscoleces than the other three strains, which may impact the transmission dynamics of the parasite. Given the geographical location of four strains, which is far from each other, and also the pathological differences, the strains of
E. multilocularis
are likely models for addressing the relationship and interfacial immune response between the host and the helminth.

IMPORTANCE

Echinococcus multilocularis
is the causative agent of alveolar echinococcosis, which is considered the most serious parasitic disease in the Northern Hemisphere. There are many genotypes, but the pathogenic and mitochondria sequence and differences are still unclear. Therefore, this study showed both pathological and genetic differences between the four strains of
E. multilocularis
. EM-AK induced more severe immune responses and especially induced more host cell infiltration, which resulted in more severe granuloma in the liver. EM-JP has metacestode lesions morphologically closer to those of
E. granulosus
with clear cyst fluid. However, this strain produced much fewer protoscoleces (PSCs). Genetically, EM-AK is more distant from other strains.
Antibiotic use among young, hospitalized children in Jordan, 2010–2023
Authors: Hayek Haya , Amarin Justin Z. , Hamdan Olla , Qwaider Yasmeen Z. , Khraise Tala , Banerjee Ritu , Spieker Andrew J. , Chappell James D. , Khuri-Bulos Najwa , Katz Sophie E. , Howard Leigh M. , Halasa Natasha B. ,   for the Jordan Viral Surveillance Studies Group
Published: February 2025

ABSTRACT

Inappropriate antibiotic use drives antimicrobial resistance, a global health threat causing increased morbidity and mortality. Understanding antibiotic practices in low-resource settings is essential to identify intervention targets. This study investigates antibiotic prescription practices in Amman, Jordan. We conducted three prospective viral surveillance studies at the largest public hospital in Amman, Jordan (2010–2013, 2020, and 2023) and included children <2 years old hospitalized with fever or respiratory symptoms. The data collected included antibiotic use and the results of blood, urine, and cerebrospinal fluid (CSF) cultures performed. We classified antibiotics according to the 2023 WHO AWaRe system. Nasal or throat samples were tested in a research laboratory for respiratory viruses using RT-PCR. The median age of the 4,724 children included was 3.5 months (IQR, 1.6–8.4). A clinical blood, urine, or CSF sample was collected from 2,565/4,712 children (54.4%), 356 (13.9%) of whom tested positive. During hospitalization, 4,375 children (92.6%) received at least one antibiotic, and 4,245 (97.0%) received at least one antibiotic from the
Watch
group. One or more respiratory viruses were detected in 3,911 children (82.8%). Providers ordered cultures most often for children 0–2 months old (
n
= 1,579 [73.5%]) and those with an admission diagnosis of rule-out sepsis (
n
= 1,164 [95.4%]). Antibiotic use and testing practices were consistent across study years, age groups, and admission diagnoses. In conclusion, widespread antibiotic use despite the preponderance of viral infections highlights a significant discrepancy in aligning treatment practices with disease etiology. Strengthening diagnostic and preventive capabilities in low-resource settings is crucial to combat antimicrobial resistance.

IMPORTANCE
In this study of 4,724 children under 2 years old hospitalized in the largest public hospital in Jordan between 2010 and 2023, 92.6% received antibiotics despite 82.8% testing positive for respiratory viruses and only 13.9% of collected cultures suggesting bacterial infection. Despite the predominance of viral infections, the widespread use of antibiotics, particularly from the World Health Organization Watch group, highlights the need for improved antibiotic stewardship and diagnostic capabilities in Jordan.
The benchmark mode $$\Omega _c \rightarrow \Omega ^-\pi ^+$$ and its related processes
Authors: Zeng Shuge , Xu Fanrong , Gu Yu 
Published: February 2025

Abstract
The benchmark mode

$$\Omega _c^0\rightarrow \Omega ^- \pi ^+$$

Ω
c
0

→

Ω
-

π
+

, which receives purely factorization contribution, is of great importance among all the decay channels of

$$\Omega _c^0$$

Ω
c
0

decays. In this work, within the framework of non-relativistic quark model (NRQM), we calculate all the 6 baryon transition form factors involving

$$\frac{1}{2} ^+\rightarrow \frac{3}{2} ^+$$

1
2

+

→

3
2

+

decays. The absolute branching fractions of non-leptonic decays

$$\Omega _c^0\rightarrow \Omega ^- \pi ^+$$

Ω
c
0

→

Ω
-

π
+

,

$$\Omega _c^0\rightarrow \Omega ^- \rho ^+$$

Ω
c
0

→

Ω
-

ρ
+

and

$$\Omega _c^0\rightarrow \Xi ^- \pi ^+$$

Ω
c
0

→

Ξ
-

π
+

as well as semi-leptonic decays

$$\Omega _c^0\rightarrow \Omega ^- \ell ^+ \nu _{\ell } \; (\ell =e,\mu )$$

Ω
c
0

→

Ω
-

ℓ
+

ν
ℓ

(
ℓ
=
e
,
μ
)

are calculated although they cannot be measured directly by current experiment. Based on the prediction

$$\mathcal {B}(\Omega _c^0\rightarrow \Omega ^-\pi ^+)=(3.43{\pm 0.48})\%$$

B

(

Ω
c
0

→

Ω
-

π
+

)

=

(
3.43

±
0.48

)

%

in our work, we further predict the ratios between interested modes and the benchmark mode, giving

$$R(\Xi ^-\pi ^+)=0.16\pm {0.06}$$

R
(

Ξ
-

π
+

)
=
0.16
±

0.06

,

$$R(\Omega ^-\rho ^+)=5.33{\pm 0.94}$$

R
(

Ω
-

ρ
+

)
=
5.33

±
0.94

,

$$R(\Omega ^- e^+\nu _e)=1.18{\pm 0.22}$$

R
(

Ω
-

e
+

ν
e

)
=
1.18

±
0.22

and

$$R(\Omega ^- \mu ^+\nu _\mu )=1.11{\pm 0.20}$$

R
(

Ω
-

μ
+

ν
μ

)
=
1.11

±
0.20

. The predictions on

$$\Omega _c^0\rightarrow \Xi ^-\pi ^+$$

Ω
c
0

→

Ξ
-

π
+

and

$$\Omega _c^0\rightarrow \Omega ^- e^+\nu $$

Ω
c
0

→

Ω
-

e
+

ν

agree well with recent measured ratios reported by LHCb in 2023 and ALICE in 2024, respectively.
The Value of Glycemic Gap for Predicting Mortality in ICU in Patients With and Without Diabetes
Authors: Lou Ran , Jiang Li , Wang Meiping , Wang Tingting , Si Quan , Su Weixue , Wang Nan , Liu Yuyan , Chen Ting , Jiang Qi , Zhu Bo 
Published: February 2025

Objective: Dysglycemia is associated with poor outcomes; the actual status of dysglycemia of critically ill patients with diabetes should refer to background glycemia. We investigated the effect of difference between mean blood glucose and basic blood glucose upon outcomes.Methods: Glycated hemoglobin A1c (HbA1c) was detected within the first 24 h and converted to A1C‐derived average glucose (ADAG) by the equation ADAG = [(HbA1c∗28.7) − 46.7]∗18−1; blood glucose measurements were fourth per day during the first 7 days after admission; the mean blood glucose level (Mean), standard deviation (SD), and coefficient of variation (CV) were calculated. GAP were calculated as admission blood glucose and Mean minus ADAG, respectively.Results: Six hundred forty‐nine patients were recruited and 428 survived at 28 days; 302 patients with diabetes had greater ADAG, blood glucose at admission (BGadm), Mean, SD, CV, GAP, and hypoglycemia incidences. The GAP between Mean and ADAG had superior predictive power, which was decreased in patients with diabetes and increased in patients without diabetes. GAP7 was related to 28‐day mortality; the death risk was decreased in patients with diabetes. Patients with lower GAP tended to survive. Nonsurvivors with diabetes suffered higher rate of hypoglycemia than survivors which was the opposite in patients without diabetes.Conclusion: The glycemic GAP between the mean level of blood glucose within the first 7 days in ICU and ADAG was independently associated with 28‐day mortality of critically ill patients, which was different between patients with and without diabetes. Hypoglycemia in patients with diabetes should be a concern.
Optimizing Biomarker Models for Biologically-Heterogeneous Cancers: A Nested Model Approach for Lung Cancer
Authors: Woodhouse Palina , Jackson Laurel , Kammer Michael N. , Godfrey Caroline M. , Antic Sanja , Zou Yong , Meyers Patrick , Gawel Susan H. , Maldonado Fabien , Grogan Eric L. , Davis Gerard J. , Deppen Stephen A. 
Published: February 2025

Abstract
Background: The heterogeneous biology of cancer subtypes, especially in lung cancer, poses significant challenges for biomarker development. Standard model building techniques often fall short in accurately incorporating various histological subtypes due to their diverse biological characteristics. This study explores a nested biomarker model to address this issue, aiming to improve lung cancer early detection. Materials: The study included 337 patients from two clinical sites. Blood biomarkers were analyzed, and various statistical methods employed to develop a nested model. This model was designed to account for the biological heterogeneity across histological subtypes, compared against traditional logistic regression models. Results: The patient cohort included a range of malignant and benign nodules and included different cancer subtypes reflecting lung cancer heterogeneity. The nested model had comparable performance overall to the Mayo Clinic Model and a standard logistic regression model with AUC of 77.6 (95%CI: 72.2, 83.0) in training and 77.3 (95%CI: 65.8, 88.9) in testing. The nested subtype versus benign model had the best performance in the training set overall and had a particular advantage for small cell subtype prediction. Conclusion: This study highlights the challenges cancer heterogeneity present for biomarker development and the potential for nested biomarker models to improve early cancer detection. Validation of this approach in larger cohorts is essential to prove its predictive benefit in biologically diverse cancers. Impact: This work addresses the challenge of biologic heterogeneity in biomarker development. A nested modeling approach may assist in developing more effective Multi-Cancer Early Detection strategies.
Informing Management of Patients Developing Cardiogenic Shock at a Spoke and Being Transferred to a Hub
Authors: Kyriakopoulos Christos P. , Taleb Iosif , Sideris Konstantinos , Maneta Eleni , Hamouche Rana , Tseliou Eleni , Krauspe Ethan , Selko Sean , Carter Spencer , Jones Tara L. , Zhang Chong , Presson Angela P. , Dranow Elizabeth , Geer Laura , Stehlik Josef , Selzman Craig H. , Goodwin Matthew L. , Tonna Joseph E. , Hanff Thomas C. , Drakos Stavros G. 
Published: February 2025

Background
Multidisciplinary teams and regionalized care systems have been suggested to improve cardiogenic shock (CS) outcomes. We sought to identify clinical factors associated with successful outcomes for patients developing CS at an outside healthcare facility (spoke) and being transferred to a quaternary medical center (hub).

Methods and Results
Consecutive patients with CS were evaluated (N=1162). Our study cohort comprised 412 patients developing CS at a spoke. Our primary end point was native heart survival (NHS) defined as survival to discharge without receiving advanced heart failure therapies. Secondary end points were survival to discharge, 30‐day and 1‐year survival after discharge, and adverse events. Association of clinical data with NHS was analyzed using logistic regression. Overall, 246 (59.7%) patients achieved NHS, 125 (30.3%) died, and 41 (10.0%) were discharged after advanced heart failure therapies. Of the 287 patients who were discharged (69.7%), 276 (67.0%) were alive at 30 days, and 250 (60.7%) at 1 year. Patients with NHS less commonly had bleeding or vascular complications or acute kidney injury requiring renal replacement therapy compared with patients who died or received advanced heart failure therapies. Significant multivariable factors associated with NHS likelihood included younger age; shorter length of stay and transfer from a secondary compared with a tertiary/quaternary level of care spoke; absence of cardiac arrest, intubation, or type 3 bleeding; lower vasoactive–inotropic score; higher left ventricular ejection fraction at admission to the hub; and shorter CS onset‐to‐temporary mechanical circulatory support deployment time.

Conclusions
We identified clinical factors reflecting disease severity and management practices including length of stay and spoke level of care, inotrope/vasopressor utilization, and CS onset‐to‐temporary mechanical circulatory support deployment time, that might inform the management of patients developing CS at a spoke.
Direct Oral Anticoagulants Compared With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease Without Mechanical Valves
Authors: Dawwas Ghadeer K. , Lewis James D. , Cuker Adam 
Published: February 2025

Background
Despite proven efficacy and safety of direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), data on patients with AF and valvular heart disease remain scarce. We aimed to evaluate the DOACs compared with warfarin among patients with AF and valvular heart disease.

Methods and Results
We conducted a retrospective cohort study of patients ≥18 years of age, who had AF and valvular heart disease, and were new users of DOACs or warfarin. The primary effectiveness outcomes were ischemic stroke or systemic embolism, and bleeding for safety. We used Cox proportional‐hazards regression after propensity score matching to estimate hazard ratios (HRs) and 95% CIs. In the matched cohort, DOAC use (versus warfarin) was associated with a lower rate of ischemic stroke or systemic embolism (HR, 0.70 [95% CI, 0.61–0.81]) and bleeding (HR, 0.72 [95% CI, 0.65–0.80]). We found a lower rate of ischemic stroke or systemic embolism with rivaroxaban (HR, 0.74 [95% CI, 0.62–0.89]) and apixaban (HR, 0.62 [95% CI, 0.52–0.74]) but not dabigatran (HR, 0.89 [95% CI, 0.63–1.26]). We found a lower rate of bleeding with rivaroxaban (HR, 0.84 [95% CI, 0.74–0.95]), apixaban (HR, 0.60 [95% CI, 0.53–0.68]), dabigatran (HR, 0.75 [95% CI, 0.58–0.97]), and edoxaban (HR, 0.21 [95% CI, 0.05–0.83]). We were unable to obtain estimates for the effectiveness outcome with edoxaban due to the small number of events.

Conclusions
In this study of patients with AF and valvular heart disease, DOAC treatment was associated with a lower risk of ischemic stroke or systemic embolism and bleeding compared with warfarin.
Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants
Authors: Iyer Kruthika R. , Clarke Shoa L. , Guarischi‐Sousa Rodrigo , Gjoni Ketrin , Heath Adam S. , Young Erica P. , Stitziel Nathan O. , Laurie Cecelia , Broome Jai G. , Khan Alyna T. , Lewis Joshua P. , Xu Huichun , Montasser May E. , Ashley Kellan E. , Hasbani Natalie R. , Boerwinkle Eric , Morrison Alanna C. , Chami Nathalie , Do Ron , Rocheleau Ghislain , Lloyd‐Jones Donald M. , Lemaitre Rozenn N. , Bis Joshua C. , Floyd James S. , Kinney Gregory L. , Bowden Donald W. , Palmer Nicholette D. , Benjamin Emelia J. , Nayor Matthew , Yanek Lisa R. , Kral Brian G. , Becker Lewis C. , Kardia Sharon L. R. , Smith Jennifer A. , Bielak Lawrence F. , Norwood Arnita F. , Min Yuan‐I , Carson April P. , Post Wendy S. , Rich Stephen S. , Herrington David , Guo Xiuqing , Taylor Kent D. , Manson JoAnn E. , Franceschini Nora , Pollard Katherine S. , Mitchell Braxton D. , Loos Ruth J. F. , Fornage Myriam , Hou Lifang , Psaty Bruce M. , Young Kendra A. , Regan Elizabeth A. , Freedman Barry I. , Vasan Ramachandran S. , Levy Daniel , Mathias Rasika A. , Peyser Patricia A. , Raffield Laura M. , Kooperberg Charles , Reiner Alex P. , Rotter Jerome I. , Jun Goo , de Vries Paul S. , Assimes Themistocles L. 
Published: February 2025

Background
Genome‐wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant‐based genome‐wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

Method and Results

We leveraged SVs detected from high‐coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans‐Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. Additionally, aggregate tests using sliding windows were performed to examine rare SVs. One genome‐wide significant association was identified for a common biallelic intergenic duplication on chromosome 6q21 (
P
=1.54E‐09, odds ratio=1.34). The sliding window‐based aggregate tests found 1 region on chromosome 17q25.3, overlapping
USP36
, to be significantly associated with coronary artery disease (
P
=1.03E‐10).
USP36
is highly expressed in arterial and adipose tissues while broadly affecting several cardiometabolic traits.

Conclusions
Our results suggest that SVs, both common and rare, may influence the risk of coronary artery disease.