bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fecal metagenomic and metabolomic analyses reveal non-invasive biomarkers of
Flavobacterium psychrophilum
infection in ayu (
Plecoglossus altivelis
)
Authors: Takeuchi Mio , Fujiwara-Nagata Erina , Kuroda Kyohei , Sakata Kenji , Narihiro Takashi , Kikuchi Jun 
Published: June 2024

ABSTRACT

With the rapid growth of inland aquaculture worldwide, side effects such as the discharge of nutrients and antibiotics pose a threat to the global environments. A sustainable future for aquaculture requires an effective management system, including the early detection of disease through the monitoring of specific biomarkers in aquaculture tanks. To this end, we investigated whether fish feces in aquaculture tanks could be used for non-invasive health monitoring using ayu (
Plecoglossus altivelis
) infected with
Flavobacterium psychrophilum
, which causes bacterial cold-water disease worldwide. Feces that were subsequently produced in the tanks were used for metagenomic and metabolomic analyses. The relative abundances of the genera
Cypionkella
(0.6% ± 1.0%, 0.1% ± 0.2%),
Klebsiella
(11.2% ± 10.0%, 6.2% ± 5.9%), and
F. psychrophilum
(0.5% ± 1.0%, 0.0% ± 0.0%) were significantly higher in the feces of the infection challenge test tanks than in those of the control tanks. The abundances of cortisol, glucose, and acetate in the feces of the infection challenge test tanks were 2.4, 2.4, and 1.3 times higher, respectively, than those of the control tanks. Metagenome analysis suggested that acetate was produced by microbes such as
Cypionkella
. The abundances of indicated microbes or metabolites increased after day 4 of infection at the earliest, and were thus considered possible biomarkers. Our results suggest that feces produced in aquaculture tanks can potentially be used for non-invasive and holistic monitoring of fish diseases in aquaculture systems.

IMPORTANCE

The aquaculture industry is rapidly growing, yet sustainability remains a challenge. One crucial task is to reduce losses due to diseases. Monitoring fish health and detecting diseases early are key to establishing sustainable aquaculture. Using metagenomic and metabolomic analyses, we found that feces of ayu infected with
Flavobacterium psychrophilum
contain various specific biomarkers that increased 4 days post-challenge, at the earliest. Our findings are the first step in establishing a novel, non-invasive, and holistic monitoring method for fish diseases in aquaculture systems, especially in ayu, which is an important freshwater fish species in Asia, promoting a sustainable future.
Tracing the possible evolutionary trends of
Morganella morganii
: insights from molecular epidemiology and phylogenetic analysis
Authors: Chen Jiawei , Wu Yun , Zhang Ge , Kang Wei , Wang Tong , Li Jin , Zhou Menglan , Zhang Li , Liu Yong , Xu Xuesong , Jia Xinmiao , Xu Yingchun , Liu Yali 
Published: June 2024

ABSTRACT

Morganella morganii
, encompassing two subspecies,
subsp. morganii
and
subsp. sibonii
, is a common opportunistic pathogen, notable for intrinsic resistance to multiple antimicrobial agents. Despite its clinical significance, research into the potential evolutionary dynamics of
M. morganii
remains limited. This study involved the analysis of genome sequences from 431
M
.
morganii
isolates, comprising 206 isolates that cause host infections, obtained from this study and 225 from the NCBI genome data sets. A diverse array of antimicrobial resistance genes (ARGs) was identified in
M. morganii
isolates, including
mcr-1
,
tet
(X4),
tmexCD-toprJ
, and various carbapenemase genes. In addition, a novel
bla
KPC-2
-bearing plasmid with demonstrated conjugative capability was discovered in
M. morganii
. The majority of virulence-related genes (VRGs), except for the
hlyCABD
gene cluster, were found in almost all
M. morganii
. Three novel genospecies of
M. morganii
were identified, designated as
M. chanii
,
M. variant1
, and
M. variant2
. Compared to
M. sibonii
,
M. chanii
genospecies possessed a greater number of flagellar-related genes, typically located within mobile genetic elements (MGEs), suggesting potential for better environmental adaptability. Phylogenetic analysis further disclosed that
M. morganii
was divided into 12 sequence clusters (SCs). Particularly, SC9 harbored an elevated abundance of ARGs and VRGs, mainly toxin-related genes, and was associated with a higher presence of MGEs compared to non-SC9 strains. The collective findings suggest that
M. morganii
undergoes evolution driven by the influence of MGEs, thereby significantly enhancing its adaptability to selective pressures of environmental changes and clinical antimicrobial agents.

IMPORTANCE

The growing clinical significance of
Morganella morganii
arises from its abundant virulence factors and antimicrobial resistance genes, resulting in elevated infection rates and increased clinical scrutiny. However, research on the molecular epidemiology and evolutionary trends of
M. morganii
has been scarce. Our study established a list of virulence-related genes (VRGs) for
M. morganii
and conducted a large-scale epidemiological investigation into these VRGs. Based on genomic classification, three novel genotypes of
M. morganii
were identified, representing evolutionary adaptations and responses to environmental challenges. Furthermore, we discovered the emergence of a sequence cluster enriched with antimicrobial resistance genes, VRGs, and mobile genetic elements, attributed to the selective pressure of antimicrobial agents. In addition, we identified a novel conjugative plasmid harboring the
bla
KPC-2
gene. These findings hold significance in monitoring and comprehending the epidemiology of
M. morganii
.
Supplemental Material: The role of Fe(II)-silicate gel in the generation of Archean and Paleoproterozoic chert
Authors: Tostevin R , Sevgen Serhat 
Published: June 2024

<p>Detailed description of methods, extended results showing the nature of the synthetic precipitate, FTIR results showing changes in the precipitate following sorption, and a discussion of potential controls on sorption behavior. </p>
Confronting multidrug-resistantKlebsiellameningitis after mid-clival Cerebrospinal Fluid leak repair: a therapeutic odyssey
Authors: Madoure Anbarasi , Gopalakrishnan Srinivasan Dharanya , Mishra Tejaswi , Penubarthi Lokesh Kumar 
Published: June 2024

A man in his 40s with type 2 diabetes mellitus had persistent right-sided watery nasal discharge for 6 months following cerebrospinal fluid (CSF) leak repair at another hospital, prompting his visit to us due to recurring symptoms. Imaging revealed a CSF leak from the mid-clivus for which revision endoscopic CSF leak repair was done. Regrettably, he developed postoperative meningitis caused by multidrug-resistant (MDR)Klebsiella pneumoniae.Managing this complex case was a challenging task due to the pathogen’s resistance to conventional drugs and the scarcity of scientific evidence. We initiated a culture-guided combination regimen with ceftazidime, avibactam, aztreonam and tigecycline. This decision stemmed from meticulous literature review and observed antibiotic synergy while testing for this organism.After 4 weeks of vigilant treatment, the patient’s symptoms improved significantly, and CSF cultures were sterile. We present our approach to effectively confront and manage a challenging instance of postoperative MDR bacterial meningitis.
Clinical effectiveness of a modified muscle sparing posterior technique compared with a standard lateral approach in hip hemiarthroplasty for displaced intracapsular fractures (HemiSPAIRE): a multicenter, parallel-group, randomized controlled trial
Authors: Ball Susan , Aylward Alex , Cockcroft Emma , Corr Aisling , Gordon Elizabeth , Kerridge Alison , McAndrew Amy , Morgan-Trimmer Sarah , Powell Roy , Price Anna , Rhodes Shelley , Timperley Andrew John , van Horik Jayden , Wickins Robert , Charity John 
Published: June 2024

ObjectivesAssess the effect of a modified muscle sparing posterior approach; SPAIRE (Save Piriformis and Internus, Repairing Externus), in hip hemiarthroplasty for displaced intracapsular fractures on postoperative mobility and function compared with a standard lateral approach.DesignPragmatic, superiority, multicenter, parallel-group, randomized controlled trial (with internal pilot). Participants, ward staff, and research staff conducting postoperative assessments were blinded to allocation. A CTU allocated treatments centrally using computer-generated lists.SettingSix hospitals in Southwest England, recruiting November 25, 2019–April 25, 2022.Participants244 adults (≥60 years) requiring hip hemiarthroplasty (122 allocated to each approach). 90 and 85 participants allocated to SPAIRE and lateral, respectively, had primary outcome data within the prespecified data collection window.InterventionsSurgery using SPAIRE or standard lateral approach. Follow-up 3 days and 120 days postoperation.Main outcome measureOxford Hip Score (OHS), via telephone at 120 days. Secondary outcomes: function and mobility (3 days), pain (3 days, 120 days), discharge destination, length of hospital stay, complications and mortality (within 120 days), quality of life and place of residence (120 days).ResultsParticipants’ mean age was 84.6 years (SD 7.2); 168 (69%) were women. Primary outcome: little evidence of a difference in OHS at 120 days; adjusted mean difference (SPAIRE—lateral) −1.23 (95% CI −3.96 to 1.49, p=0.37). Secondary outcomes: indication of lower participant-reported pain at 3 days in SPAIRE arm; no differences between arms for remaining outcomes.ConclusionsParticipants’ mobility and function are similar in the short term (3 days) and longer term (120 days), whether receiving the SPAIRE or lateral approach. Neither approach confers benefit over the other in terms of length of hospital stay, return to prefracture residence, survival within 120 days, or quality of life at 120 days. Participants receiving SPAIRE approach may experience less pain in the early postoperative period. Modifying the posterior approach in hip hemiarthroplasty to the SPAIRE approach gives equivalent patient outcomes to the lateral approach within 120 days.Trial registration numberNCT04095611.
Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China
Authors: Fei Yang , Ma Mengke , Gan Lu , Xu Midie , Yang Yu , Huang Dan , Sheng Weiqi 
Published: June 2024

AimsColorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations.MethodsThis study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses.ResultsDifferential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage andBRAFgene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates.Conclusionp21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study’s findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.
A subtraction scheme for processes involving fragmentation functions at NLO
Authors: Zidi M. S. , Guillet J. Ph. , Schienbein I. , Zaraket H. 
Published: June 2024

AbstractWe present a novel subtraction method to remove the soft and collinear divergences at next-to-leading order for processes involving an arbitrary number of fragmentation functions, where this method acts directly in the hadronic centre-of-mass frame. We provide the analytical formulae of the subtraction terms in the general case where all the final state partons fragment to hadrons and for the two special cases when one of the partons of the final state does not fragment, i.e. it is a photon or involved in a jet.
Photothermal Hyperthermia and Photodegradation Studies of Cu-Si Nanoparticles Synthesized by Laser Ablation in Liquid Media
Authors: Fazal Yusra , Ali Imran , Chen Jun , Pan Yunxiang , Bukhari Syed Nizam Uddin Shah , Liu Xiangnen , Shah Aqeel Ahmed , Shen Zhonghua 
Published: June 2024

Nanocomposites have many promising applications such as in hyperthermia and photodegradation. Laser ablation-assisted synthesis of nanocomposites offers several advantages such as it is a green synthesis method, cost-effective, ease of handling and absence of any by-products. This study included the fabrication of copper-silicon (Cu-Si) nanocomposites using liquid-phase laser ablation, followed by an investigation into their potential uses in photothermal hyperthermia and photodegradation. The surface properties, chemical composition and crystallinity were examined using X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) techniques. Spherical, capsule-like and hexagonal nanoparticles with a size of 28[Formula: see text]nm were observed from transmission electron microscopy (TEM). The near-infrared (NIR) 808[Formula: see text]nm laser was used to obtain the optimum photothermal hyperthermia temperature. At increasing concentrations of nanocomposites and operating laser powers, the temperature trend of nanofluid was monitored and revealed a rising trend. Moreover, an increasing trend in degradation efficiency of methylene green dye was observed, with values of 46.4%, 81.7% and 95.7%, corresponding to photocatalyst doses of 10[Formula: see text]mg, 20[Formula: see text]mg and 30[Formula: see text]mg, respectively. These results shed light on the potential application of contamination-free nanocomposites for hyperthermia and photodegradation.
WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma
Authors: Li Li , Xie Dacheng , Yu Shijun , Ma Muyuan , Fan Kailing , Chen Jingde , Xiu Mengxi , Xie Keping , Li Yandong , Gao Yong 
Published: June 2024

Abstract
Cellular oxidative stress plays a key role in the development and progression of hepatocellular carcinoma (HCC). A better understanding of the processes that regulate reactive oxygen species (ROS) homeostasis could uncover improved strategies for treating HCC. Herein, we identified protein kinase with-no-lysine kinase 1 (WNK1) as an antioxidative factor and therapeutic target in HCC. In human HCC, WNK1 expression was increased and correlated with poor patient prognosis. WNK1 knockdown significantly inhibited cell proliferation and xenograft tumor growth. Mechanistically, WNK1 competed with nuclear factor erythroid 2–related factor 2 (NRF2) for binding with the partial Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), reducing NRF2 ubiquitination and promoting NRF2 accumulation and nuclear translocation to increase antioxidant response. WNK1 silencing increased H2O2-induced apoptosis and inhibited cell growth by elevating ROS levels, which could be rescued by treatment with the antioxidant N-acetylcysteine and NRF2 activator tert-butylhydroquinone. Liver-specific WNK1 knockout mouse models of HCC substantiated that WNK1 promoted HCC development by regulating ROS levels. WNK463, an inhibitor of the WNK kinase family, suppressed HCC progression and altered the redox status. These findings suggest that WNK1 plays a critical role in HCC development and progression and that the WNK1-oxidative stress axis may be a promising therapeutic target for HCC.
Significance: Inhibiting WNK1 induces NRF2 degradation and reduces the oxidative stress response to suppress hepatocellular carcinoma growth, indicating that targeting the WNK1–KEAP1–NRF2 axis is a potential strategy to treat liver cancer.
Transient Differentiation-State Plasticity Occurs during Acute Lymphoblastic Leukemia Initiation
Authors: Poort Vera M. , Hagelaar Rico , van Roosmalen Markus J. , Trabut Laurianne , Buijs-Gladdines Jessica G. C. A. M. , van Wijk Bram , Meijerink Jules , van Boxtel Ruben 
Published: June 2024

Abstract
Leukemia is characterized by oncogenic lesions that result in a block of differentiation, whereas phenotypic plasticity is retained. A better understanding of how these two phenomena arise during leukemogenesis in humans could help inform diagnosis and treatment strategies. Here, we leveraged the well-defined differentiation states during T-cell development to pinpoint the initiation of T-cell acute lymphoblastic leukemia (T-ALL), an aggressive form of childhood leukemia, and study the emergence of phenotypic plasticity. Single-cell whole genome sequencing of leukemic blasts was combined with multiparameter flow cytometry to couple cell identity and clonal lineages. Irrespective of genetic events, leukemia-initiating cells altered their phenotypes by differentiation and dedifferentiation. The construction of the phylogenies of individual leukemias using somatic mutations revealed that phenotypic diversity is reflected by the clonal structure of cancer. The analysis also indicated that the acquired phenotypes are heritable and stable. Together, these results demonstrate a transient period of plasticity during leukemia initiation, where phenotypic switches seem unidirectional.
Significance: A method merging multicolor flow cytometry with single-cell whole genome sequencing to couple cell identity with clonal lineages uncovers differentiation-state plasticity in leukemia, reconciling blocked differentiation with phenotypic plasticity in cancer.
Prevalence of Epidermal Growth Factor Receptor and Programmed Death Ligand 1 Testing in a Population-Based Lung Cancer Surgical Resection Cohort from 2018 to 2022
Authors: Smeltzer Matthew P. , Akinbobola Olawale A. , Ray Meredith A. , Fehnel Carrie , Saulsberry Andrea , Dortch Kourtney R. , Pimenta Kelly , Matthews Anberitha T. , Osarogiagbon Raymond U. 
Published: June 2024

Abstract

Background:
Biomarker-directed therapy requires biomarker testing. We assessed the patterns of epidermal growth factor receptor (EGFR) and programmed death ligand 1 (PDL1) testing in a non–small cell lung cancer (NSCLC) resection cohort. We hypothesized that testing would increase but be unevenly distributed across patient-, provider- and institution-level demographics.

Methods:
We examined the population-based Mid-South Quality of Surgical Resection (MS-QSR) cohort of NSCLC resections. We evaluated the proportions receiving EGFR and PDL1 testing before and after approval of biomarker-directed adjuvant therapy (2018–2020 vs. 2021–2022). We used association tests and logistic regression to compare factors.

Results:
From 2018 to 2022, 1,687 patients had NSCLC resection across 12 MS-QSR institutions: 1,045 (62%) from 2018 to 2020 and 642 (38%) from 2021 to 2022. From 2018 to 2020, 11% had EGFR testing versus 38% in 2021 to 2022 (56% in those meeting ADAURA trial inclusion criteria, P &lt; 0.0001). From 2018 to 2020, 8% had PDL1 testing versus 20% in 2021 to 2022 (P &lt; 0.0001). EGFR testing did not significantly differ by age (P = 0.07), sex (P = 0.99), race (P = 0.33), or smoking history (P = 0.28); PDL1 testing did not differ significantly by age (P = 0.47), sex (P = 0.41), race (P = 0.51), or health insurance (P = 0.07). Testing was significantly less likely in nonteaching and non–Commission on Cancer–accredited hospitals and after resection by cardiothoracic or general surgeons (vs. general thoracic surgeons; all P &lt; 0.05).

Conclusions:
EGFR and PDL1 testing increased after approval of biomarker-directed adjuvant therapies. However, testing rates were still suboptimal and differed by institutional- and provider-level factors.

Impact:
The association of institutional, pathologist, and surgeon characteristics with differences in testing demonstrate the need for more standardization in testing processes.
Characterization of Non-Monotonic Relationships between Tumor Mutational Burden and Clinical Outcomes
Authors: Anaya Jordan , Kung Julia , Baras Alexander S. 
Published: June 2024

Abstract

Potential clinical biomarkers are often assessed with Cox regressions or their ability to differentiate two groups of patients based on a single cutoff. However, both of these approaches assume a monotonic relationship between the potential biomarker and survival. Tumor mutational burden (TMB) is currently being studied as a predictive biomarker for immunotherapy, and a single cutoff is often used to divide patients. In this study, we introduce a two-cutoff approach that allows splitting of patients when a non-monotonic relationship is present and explore the use of neural networks to model more complex relationships of TMB to outcome data. Using real-world data, we find that while in most cases the true relationship between TMB and survival appears monotonic, that is not always the case and researchers should be made aware of this possibility.

Significance:
When a non-monotonic relationship to survival is present it is not possible to divide patients by a single value of a predictor. Neural networks allow for complex transformations and can be used to correctly split patients when a non-monotonic relationship is present.
A spatially constrained independent component analysis jointly informed by structural and functional network connectivity
Authors: Fouladivanda Mahshid , Iraji Armin , Wu Lei , van Erp Theo G. M. , Belger Aysenil , Hawamdeh Faris , Pearlson Godfrey D. , Calhoun Vince D. 
Published: June 2024

Abstract
There are a growing number of neuroimaging studies motivating joint structural and functional brain connectivity. The brain connectivity of different modalities provides an insight into brain functional organization by leveraging complementary information, especially for brain disorders such as schizophrenia. In this paper, we propose a multimodal independent component analysis (ICA) model that utilizes information from both structural and functional brain connectivity guided by spatial maps to estimate intrinsic connectivity networks (ICNs). Structural connectivity is estimated through whole-brain tractography on diffusion-weighted MRI (dMRI), while functional connectivity is derived from resting-state functional MRI (rs-fMRI). The proposed structural-functional connectivity and spatially constrained ICA (sfCICA) model estimates ICNs at the subject level using a multiobjective optimization framework. We evaluated our model using synthetic and real datasets (including dMRI and rs-fMRI from 149 schizophrenia patients and 162 controls). Multimodal ICNs revealed enhanced functional coupling between ICNs with higher structural connectivity, improved modularity, and network distinction, particularly in schizophrenia. Statistical analysis of group differences showed more significant differences in the proposed model compared with the unimodal model. In summary, the sfCICA model showed benefits from being jointly informed by structural and functional connectivity. These findings suggest advantages in simultaneously learning effectively and enhancing connectivity estimates using structural connectivity.