bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence and clonal dissemination of KPC-3-producing Pseudomonas aeruginosa in China with an IncP-2 megaplasmid
Authors: Ge Haoyu , Qiao Jie , Zheng Jiahao , Xu Hao , Liu Ruishan , Zhao Junhui , Chen Ruyan , Li Chenyu , Guo Xiaobing , Zheng Beiwen 
Published: April 2023

Abstract
Background
Despite the global prevalence of Klebsiella pneumoniae Carbapenemase (KPC)-type class A β-lactamases, occurrences of KPC-3-producing isolates in China remain infrequent. This study aims to explore the emergence, antibiotic resistance profiles, and plasmid characteristics of blaKPC-3-carrying Pseudomonas aeruginosa.

Methods
Species identification was performed by MALDI-TOF-MS, and antimicrobial resistance genes (ARGs) were identified by polymerase chain reaction (PCR). The characteristics of the target strain were detected by whole-genome sequencing (WGS) and antimicrobial susceptibility testing (AST). Plasmids were analyzed by S1-nuclease pulsed-field gel electrophoresis(S1-PFGE), Southern blotting and transconjugation experiment.

Results
Five P. aeruginosa strains carrying blaKPC-3 were isolated from two Chinese patients without a history of travelling to endemic areas. All strains belonged to the novel sequence type ST1076. The blaKPC-3 was carried on a 395-kb IncP-2 megaplasmid with a conserved structure (IS6100-ISKpn27-blaKPC-3-ISKpn6-korC-klcA), and this genetic sequence was identical to many plasmid-encoded KPC of Pseudomonas species. By further analyzing the genetic context, it was supposed that the original of blaKPC-3 in our work was a series of mutation of blaKPC-2.

Conclusions
The emergence of a multidrug resistance IncP-2 megaplasmid and clonal transmission of blaKPC-3-producing P. aeruginosa in China underlined the crucial need for continuous monitoring of blaKPC-3 for prevention and control of its further dissemination in China.
CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants
Authors: Chen Zhi , Wu Chenshuo , Yuan Yuxuan , Xie Zhongjian , Li Tianzhong , Huang Hao , Li Shuang , Deng Jiefeng , Lin Huiling , Shi Zhe , Li Chaozhou , Hao Yabin , Tang Yuxuan , You Yuehua , Al-Hartomy Omar A. , Wageh Swelm , Al-Sehemi Abdullah G. , Lu Ruitao , Zhang Ling , Lin Xuechun , He Yaqing , Zhao Guojun , Li Defa , Zhang Han 
Published: April 2023

AbstractSince the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.
Prognostic analysis of 2–5 cm diameter gastric stromal tumors with exogenous or endogenous growth
Authors: Lin Chen , Sui Chao , Tao Tingting , Guan Wenxian , Zhang Haoran , Tao Liang , Wang Meng , Wang Feng 
Published: April 2023

Abstract

Background
There has been limited research on the prognosis differences in patients with gastric stromal tumor invasion of the plasma membrane surface. This study intended to investigate whether there is a difference in prognosis in patients with endogenous or exogenous 2–5 cm diameter GISTs.

Methods
We retrospectively analyzed the clinicopathological and follow-up data of gastric stromal tumor patients, all of whom underwent surgical resection for primary GIST at Nanjing Drum Tower Hospital from December 2010 to February 2022. We classified patients based on tumor growth patterns and then investigated the association between tumor growth patterns and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan‒Meier method.

Results
A total of 496 gastric stromal tumor patients were enrolled in this study, among which 276 patients had tumors of 2–5 cm in diameter. Of these 276 patients, 193 had exogenous tumors, and 83 had endogenous tumors. Tumor growth patterns were significantly related to age, rupture status, resection style, tumor site, tumor size, and intraoperative bleeding. According to Kaplan‒Meier curve analysis, the tumor growth pattern among patients with 2–5 cm diameter tumors was significantly correlated with worse progression-free survival (PFS). Ultimately, multivariate analyses identified the Ki-67 index (P = 0.008), surgical history (P = 0.031), and resection style (P = 0.045) as independent prognostic markers for PFS.

Conclusions
Although gastric stromal tumors with a diameter of 2–5 cm are classified as low risk, the prognosis is lower for exogenous tumors than for endogenous tumors, and exogenous gastric stromal tumors have a risk of recurrence. Consequently, clinicians should be vigilant regarding the prognosis of patients with this type of tumor.
Data-driven characterization of walking after a spinal cord injury using inertial sensors
Authors: Werner Charlotte , Gönel Meltem , Lerch Irina , Curt Armin , Demkó László 
Published: April 2023

Abstract
Background
An incomplete spinal cord injury (SCI) refers to remaining sensorimotor function below the injury with the possibility for the patient to regain walking abilities. However, these patients often suffer from diverse gait deficits, which are not objectively assessed in the current clinical routine. Wearable inertial sensors are a promising tool to capture gait patterns objectively and started to gain ground for other neurological disorders such as stroke, multiple sclerosis, and Parkinson’s disease. In this work, we present a data-driven approach to assess walking for SCI patients based on sensor-derived outcome measures. We aimed to (i) characterize their walking pattern in more depth by identifying groups with similar walking characteristics and (ii) use sensor-derived gait parameters as predictors for future walking capacity.

Methods
The dataset analyzed consisted of 66 SCI patients and 20 healthy controls performing a standardized gait test, namely the 6-min walking test (6MWT), while wearing a sparse sensor setup of one sensor attached to each ankle. A data-driven approach has been followed using statistical methods and machine learning models to identify relevant and non-redundant gait parameters.

Results
Clustering resulted in 4 groups of patients that were compared to each other and to the healthy controls. The clusters did differ in terms of their average walking speed but also in terms of more qualitative gait parameters such as variability or parameters indicating compensatory movements. Further, using longitudinal data from a subset of patients that performed the 6MWT several times during their rehabilitation, a prediction model has been trained to estimate whether the patient’s walking speed will improve significantly in the future. Including sensor-derived gait parameters as inputs for the prediction model resulted in an accuracy of 80%, which is a considerable improvement of 10% compared to using only the days since injury, the present 6MWT distance, and the days until the next 6MWT as predictors.

Conclusions
In summary, the work presented proves that sensor-derived gait parameters provide additional information on walking characteristics and thus are beneficial to complement clinical walking assessments of SCI patients. This work is a step towards a more deficit-oriented therapy and paves the way for better rehabilitation outcome predictions.
Identification of key ferroptosis-related biomarkers in steroid-induced osteonecrosis of the femoral head based on machine learning
Authors: Liu Jian , Han Xueliang , Qu Lianjun , Du Bencai 
Published: April 2023

Abstract
Background
This study was aimed to identify key ferroptosis-related biomarkers in steroid-induced osteonecrosis of the femoral head (SONFH) based on machine learning algorithm.

Methods
The SONFH dataset GSE123568 (including 30 SONFH patients and 10 controls) was used in this study. The differentially expressed genes (DEGs) were selected between SONFH and control groups, which were subjected to WGCNA. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEGs and module genes. Two machine learning algorithms were utilized to identify key ferroptosis-related genes, and the underlying mechanisms were analyzed by GSEA. Correlation analysis between key ferroptosis-related genes and immune cells was analyzed by Spearman method. The drug–gene relationships were predicted in CTD.

Results
Total 2030 DEGs were obtained. WGCNA identified two key modules and obtained 1561 module genes. Finally, 43 intersection genes were identified as disease-related ferroptosis-related genes. After LASSO regression and RFE-SVM algorithms, 4 intersection genes (AKT1S1, BACH1, MGST1 and SETD1B) were considered as key ferroptosis-related gene. The 4 genes were correlated with osteoclast differentiation pathway. Twenty immune cells with significant differences were obtained between the groups, and the 4 key ferroptosis-related genes were correlated with most immune cells. In CTD, 41 drug–gene relationship pairs were finally obtained.

Conclusions
The 4 key ferroptosis-related genes, AKT1S1, BACH1, MGST1 and SETD1B, were identified to play a critical role in SONFH progression through osteoclast differentiation and immunologic mechanisms. Additionally, all the 4 genes had good disease prediction effect and could act as biomarkers for the diagnosis and treatment of SONFH.
Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal
Authors: Pavlovsky Carolina , Vasconcelos Cordoba Bianca , Sanchez María Belén , Moiraghi Beatriz , Varela Ana , Custidiano Rosario , Fernandez Isolda , Freitas Maria Josefina , Ventriglia Maria Verónica , Bendek Georgina , Mariano Romina , Mela Osorio María José , Pavlovsky Miguel Angel , de Labanca Ana García , Foncuberta Cecilia , Giere Isabel , Vera Masiel , Juni Mariana , Mordoh Jose , Sanchez Avalos Julio Cesar , Cueto Gerardo , Miranda Silvia , Levy Estrella Mariel , Bianchini Michele 
Published: April 2023

AbstractTreatment-free remission (TFR) in chronic myeloid leukemia (CML) is safe under adequate molecular monitoring, but questions remain regarding which factors may be considered predictive for TFR. Argentina Stop Trial (AST) is a multicenter TFR trial showing that 65% of patients sustain molecular remission, and the prior time in deep molecular response (DMR) was associated with successful TFR. Luminex technology was used to characterize cytokines in plasma samples. Using machine learning algorithms, MCP-1 and IL-6 were identified as novel biomarkers and MCP-1low/IL-6low patients showed eightfold higher risk of relapse. These findings support the feasibility of TFR for patients in DMR and MCP-1/IL-6 plasma levels are strong predictive biomarkers.
Australian secondary school principals', parents', and students' attitudes to prescribed school footwear guidelines
Authors: Mazzella Natalie , Fox Aaron , Saunders Natalie , Trowell Danielle , Vicenzino Bill , Bonacci Jason 
Published: April 2023

AbstractBackgroundAdolescents are often required to wear footwear that adheres to uniform guidelines at secondary school. There is a paucity of literature on factors influencing school footwear choice and what drives the development of school footwear guidelines. The aims of this study were to describe (i) current school footwear guidelines in secondary schools across Australia, (ii) factors that influence footwear choice in secondary school students and their parents, and (iii) principals, parents, and students' beliefs on factors which contribute to school footwear guidelines.MethodsAn online survey was distributed to principals, secondary school students (aged 14–19 years) and their parents across Australia. The survey included questions on current school footwear guidelines, factors influencing footwear choice (for students and parents), participants beliefs on the effect footwear has on musculoskeletal health, current and previous lower limb pain, and beliefs on factors that contribute to school footwear guidelines. Parent and student responses to factors that influence their footwear choice were compared using proportional odds logistic regression. Students and parents' responses to factors influencing footwear guidelines were compared to principal responses using proportional odds logistic regression. Significance was set at an alpha of < 0.05.ResultsEighty principals, 153 parents and 120 secondary school students responded to the survey. 96% (77/80) of principals reported that their schools have set guidelines for school footwear. 88% of principals considered comfort to be important when developing school footwear guidelines. Proportional odds logistics regression showed that parents and students were 3.4 and 4.9 times more likely, respectively, than principals to rate comfort as being important when schools develop footwear guidelines. More than 40% of students reported experiencing musculoskeletal pain, and 70% of these students reported the pain to be exacerbated when in their school shoes. Less than a third of participants considered healthcare recommendations important to the development of footwear guidelines.ConclusionsNearly all principals that participated in this survey had set guidelines for school footwear. There is a discord between parents, students, and principals on the importance that factors such as comfort, play in the development of school footwear guidelines.
Using re-randomisation designs to increase the efficiency and applicability of retention studies within trials: a case study
Authors: Goulao Beatriz , Duncan Anne , Innes Karen , Ramsay Craig R. , Kahan Brennan C. 
Published: April 2023

Abstract

Background

Poor retention in randomised trials can lead to serious consequences to their validity. Studies within trials (SWATs) are used to identify the most effective interventions to increase retention. Many interventions could be applied at any follow-up time point, but SWATs commonly assess interventions at a single time point, which can reduce efficiency.

Methods
The re-randomisation design allows participants to be re-enrolled and re-randomised whenever a new retention opportunity occurs (i.e. a new follow-up time point where the intervention could be applied). The main advantages are as follows: (a) it allows the estimation of an average effect across time points, thus increasing generalisability; (b) it can be more efficient than a parallel arm trial due to increased sample size; and (c) it allows subgroup analyses to estimate effectiveness at different time points. We present a case study where the re-randomisation design is used in a SWAT.

Results
In our case study, the host trial is a dental trial with two available follow-up points. The Sticker SWAT tests whether adding the trial logo’s sticker to the questionnaire’s envelope will result in a higher response rate compared with not adding the sticker. The primary outcome is the response rate to postal questionnaires. The re-randomisation design could double the available sample size compared to a parallel arm trial, resulting in the ability to detect an effect size around 28% smaller.

Conclusion
The re-randomisation design can increase the efficiency and generalisability of SWATs for trials with multiple follow-up time points.
A practical guide for the diagnosis of abdominal angiostrongyliasis caused by the nematode Angiostrongylus costaricensis
Authors: Rodriguez Rubens , Mora Javier , Solano-Barquero Alberto , Graeff-Teixeira Carlos , Rojas Alicia 
Published: April 2023

AbstractAbdominal angiostrongyliasis (AA) is a severe parasitic infection caused by the nematode Angiostrongylus costaricensis. This disease is characterized by abdominal pain, a strong inflammatory eosinophilic response in the blood and tissues, and eventually intestinal perforation. Diagnosis of AA is challenging since there are no commercially available serological kits for A. costaricensis, and thus, histopathological analysis remains the gold standard. Herein we provide a decision flowchart for clinicians to improve the diagnosis of AA based on a patient’s clinical manifestations, laboratory findings, macroscopic observations of the gut lesions, as well as characteristic microscopic alterations in biopsies. A brief discussion of the available polymerase chain reaction and in-house serological methods is also presented. The aim of this mini-review is to improve the diagnosis of AA, which should lead to prompt detection of cases and better estimates of the epidemiology and geographical distribution of A. costaricensis.
Graphical Abstract
Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis
Authors: Fournier Dale E. , Veras Matthew A. , Brooks Courtney R. , Quinonez Diana , Millecamps Magali , Stone Laura S. , Séguin Cheryle A. 
Published: April 2023

Abstract

Background
Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by progressive calcification of spinal tissues; however, the impact of calcification on pain and function is poorly understood. This study examined the association between progressive ectopic spine calcification in mice lacking equilibrative nucleoside transporter 1 (ENT1−/−), a preclinical model of DISH, and behavioral indicators of pain.

Methods
A longitudinal study design was used to assess radiating pain, axial discomfort, and physical function in wild-type and ENT1−/− mice at 2, 4, and 6 months. At endpoint, spinal cords were isolated for immunohistochemical analysis of astrocytes (GFAP), microglia (IBA1), and nociceptive innervation (CGRP).

Results
Increased spine calcification in ENT1−/− mice was associated with reductions in flexmaze exploration, vertical activity in an open field, and self-supporting behavior in tail suspension, suggesting flexion-induced discomfort or stiffness. Grip force during the axial stretch was also reduced in ENT1−/− mice at 6 months of age. Increased CGRP immunoreactivity was detected in the spinal cords of female and male ENT1−/− mice compared to wild-type. GFAP- and IBA1-immunoreactivity were increased in female ENT1−/− mice compared to wild-type, suggesting an increase in nociceptive innervation.

Conclusion
These data suggest that ENT1−/− mice experience axial discomfort and/or stiffness and importantly that these features are detected during the early stages of spine calcification.
Extensive intratumor regional epigenetic heterogeneity in clear cell renal cell carcinoma targets kidney enhancers and is associated with poor outcome
Authors: El Khoury Louis Y. , Pan Xiaoyu , Hlady Ryan A. , Wagner Ryan T. , Shaikh Shafiq , Wang Liguo , Humphreys Mitchell R. , Castle Erik P. , Stanton Melissa L. , Ho Thai H. , Robertson Keith D. 
Published: April 2023

Abstract
Background
Clear cell renal cell cancer (ccRCC), the 8th leading cause of cancer-related death in the US, is challenging to treat due to high level intratumoral heterogeneity (ITH) and the paucity of druggable driver mutations. CcRCC is unusual for its high frequency of epigenetic regulator mutations, such as the SETD2 histone H3 lysine 36 trimethylase (H3K36me3), and low frequency of traditional cancer driver mutations. In this work, we examined epigenetic level ITH and defined its relationships with pathologic features, aspects of tumor biology, and SETD2 mutations.

Results
A multi-region sampling approach coupled with EPIC DNA methylation arrays was conducted on a cohort of normal kidney and ccRCC. ITH was assessed using DNA methylation (5mC) and CNV-based entropy and Euclidian distances. We found elevated 5mC heterogeneity and entropy in ccRCC relative to normal kidney. Variable CpGs are highly enriched in enhancer regions. Using intra-class correlation coefficient analysis, we identified CpGs that segregate tumor regions according to clinical phenotypes related to tumor aggressiveness. SETD2 wild-type tumors overall possess greater 5mC and copy number ITH than SETD2 mutant tumor regions, suggesting SETD2 loss contributes to a distinct epigenome. Finally, coupling our regional data with TCGA, we identified a 5mC signature that links regions within a primary tumor with metastatic potential.

Conclusion
Taken together, our results reveal marked levels of epigenetic ITH in ccRCC that are linked to clinically relevant tumor phenotypes and could translate into novel epigenetic biomarkers.
Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma
Authors: Sgro Agustin , Cursons Joseph , Waryah Charlene , Woodward Eleanor A. , Foroutan Momeneh , Lyu Ruqian , Yeoh George C. T. , Leedman Peter J. , Blancafort Pilar 
Published: April 2023

Abstract
Background
Epigenetic silencing of tumor suppressor genes (TSGs) is a key feature of oncogenesis in hepatocellular carcinoma (HCC). Liver-targeted delivery of CRISPR-activation (CRISPRa) systems makes it possible to exploit chromatin plasticity, by reprogramming transcriptional dysregulation.

Results
Using The Cancer Genome Atlas HCC data, we identify 12 putative TSGs with negative associations between promoter DNA methylation and transcript abundance, with limited genetic alterations. All HCC samples harbor at least one silenced TSG, suggesting that combining a specific panel of genomic targets could maximize efficacy, and potentially improve outcomes as a personalized treatment strategy for HCC patients. Unlike epigenetic modifying drugs lacking locus selectivity, CRISPRa systems enable potent and precise reactivation of at least 4 TSGs tailored to representative HCC lines. Concerted reactivation of HHIP, MT1M, PZP, and TTC36 in Hep3B cells inhibits multiple facets of HCC pathogenesis, such as cell viability, proliferation, and migration.

Conclusions
By combining multiple effector domains, we demonstrate the utility of a CRISPRa toolbox of epigenetic effectors and gRNAs for patient-specific treatment of aggressive HCC.