bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic biology approach to assemble and reboot clinically relevant
Pseudomonas aeruginosa
tailed phages
Authors: Ipoutcha Thomas , Racharaks Ratanachat , Huttelmaier Stefanie , Wilson Cole J. , Ozer Egon A. , Hartmann Erica M. 
Published: January 2024

ABSTRACT

The rise in the frequency of antibiotic resistance has made bacterial infections, specifically
Pseudomonas aeruginosa
, a cause for greater concern. Phage therapy is a promising solution that uses naturally isolated phages to treat bacterial infections. Ecological limitations, which stipulate a discrete host range and the inevitable evolution of resistance, may be overcome through a better understanding of phage biology and the utilization of engineered phages. In this study, we developed a synthetic biology approach to construct tailed phages that naturally target clinically relevant strains of
Pseudomonas aeruginosa
. As proof of concept, we successfully cloned and assembled the JG024 and DMS3 phage genomes in yeast using transformation-associated recombination cloning and rebooted these two phage genomes in two different strains of
P. aeruginosa
. We identified factors that affected phage reboot efficiency like the phage species or the presence of antiviral defense systems in the bacterial strain. We have successfully extended this method to two other phage species and observed that the method enables the reboot of phages that are naturally unable to infect the strain used for reboot. This research represents a critical step toward the construction of clinically relevant, engineered
P. aeruginosa
phages.

IMPORTANCE

Pseudomonas aeruginosa
is a bacterium responsible for severe infections and a common major complication in cystic fibrosis. The use of antibiotics to treat bacterial infections has become increasingly difficult as antibiotic resistance has become more prevalent. Phage therapy is an alternative solution that is already being used in some European countries, but its use is limited by the narrow host range due to the phage receptor specificity, the presence of antiviral defense systems in the bacterial strain, and the possible emergence of phage resistance. In this study, we demonstrate the use of a synthetic biology approach to construct and reboot clinically relevant
P. aeruginosa
tailed phages. This method enables a significant expansion of possibilities through the construction of engineered phages for therapy applications.
ALT in combination with triple-rolled TFL for reconstruction of a complex tendoachilles defect: technical details and rehabilitation regime
Authors: Ahmed Zahra , Cook Hannah , Anadkat Meera , Ioannidi Lydia , Marmery Helen , Nikkhah Dariush 
Published: January 2024

A fit man in his 60s presented with an infected Achilles tendon (AT) following two failed repairs for a traumatic rupture. Initial debridement of necrotic tissue resulted in a large soft tissue defect requiring robust coverage. Following aggressive wound management, an anterolateral thigh flap was elevated with tensor fasciae latae (TFL) which was triple-rolled to provide soft tissue coverage and tendon reconstruction.The flap remained healthy and was monitored with a flow coupler device. Initially, the foot was placed in plantarflexion before gradually increasing the angle to neutral and a thermoplastic splint was used to offload pressure on the flap. Following 1 month of non-weight-bearing, gentle mobilisation began. Three months postoperatively, the patient could walk, had resumed indoor cycling and demonstrated a comparable heel raise with the contralateral side. MRI showed a taut TFL attached to the distal AT and ultrasound showed a smoothly gliding TFL.
Association between change in cardiorespiratory fitness and prostate cancer incidence and mortality in 57 652 Swedish men
Authors: Bolam Kate A , Bojsen-Møller Emil , Wallin Peter , Paulsson Sofia , Lindwall Magnus , Rundqvist Helene , Ekblom-Bak Elin 
Published: January 2024

ObjectivesTo examine the associations between changes in cardiorespiratory fitness (CRF) in adulthood and prostate cancer incidence and mortality.MethodsIn this prospective study, men who completed an occupational health profile assessment including at least two valid submaximal CRF tests, performed on a cycle ergometer, were included in the study. Data on prostate cancer incidence and mortality were derived from national registers. HRs and CIs were calculated using Cox proportional hazard regression with inverse probability treatment weights of time-varying covariates.ResultsDuring a mean follow-up time of 6.7 years (SD 4.9), 592 (1%) of the 57 652 men were diagnosed with prostate cancer, and 46 (0.08%) died with prostate cancer as the primary cause of death. An increase in absolute CRF (as % of L/min) was associated with a reduced risk of prostate cancer incidence (HR 0.98, 95% CI 0.96 to 0.99) but not mortality, in the fully adjusted model. When participants were grouped as having increased (+3%), stable (±3%) or decreased (−3%) CRF, those with increased fitness also had a reduced risk of prostate cancer incidence compared with those with decreased fitness (HR 0.65, 95% CI 0.49 to 0.86), in the fully adjusted model.ConclusionIn this study of employed Swedish men, change in CRF was inversely associated with risk of prostate cancer incidence, but not mortality. Change in CRF appears to be important for reducing the risk of prostate cancer.
Analysis of tweets discussing the risk of Mpox among children and young people in school (May–October 2022): a retrospective observational study
Authors: Knudsen Ben , Høeg Tracy Beth , Prasad Vinay 
Published: January 2024

ObjectiveTo determine the number of tweets discussing the risk of Mpox to children and young people in school and (1) determine accuracy, (2) for inaccurate tweets, determine if risk was minimised or exaggerated and (3) describe the characteristics of the accounts and tweets which contained accurate versus inaccurate information.DesignRetrospective observational study.SettingTwitter advanced search in January 2023 of tweets spanning 18 May 2022–19 September 2022.ParticipantsAccounts labelled as: MD, DO, nurse, pharmacist, physical therapist, other healthcare provider, PhD, MPH, Ed. degree, JD, health/medicine/public policy reporter (including students or candidates) who tweeted about the risk of Mpox to children and young people in school.ExposuresTweets containing the keywords ‘school’ and ‘mpox’, ‘pox’, or ‘monkeypox’ from May to October 2022.Measures(1) The total and ratio of accurate versus inaccurate tweets, the latter further subdivided by exaggerating or minimising risk, and stratified by account author credential type. (2) The total likes, retweets and follower counts by accurate versus inaccurate tweets, by month and account credentials. (3) Twitter user exposure to inaccurate versus accurate tweets was estimated.Results262 tweets were identified. 215/262 (82%) were inaccurate and 215/215 (100%) of these exaggerated risks. 47/262 (18%) tweets were accurate. There were 163 (87%) unique authors of inaccurate tweets and 25 (13%) of accurate tweets. Among healthcare professionals, 86% (95/111) of tweets were inaccurate. Multiplying accuracy by followers and retweets, Twitter users were approximately 974× more likely to encounter inaccurate than accurate information.ConclusionCredentialed Twitter users were 4.6 times more likely to tweet inaccurate than accurate messages. We also demonstrated how incorrect tweets can be quickly amplified by retweets and popular accounts. In the case of Mpox in children and young people, incorrect information always exaggerated risks.
Møre–Vøring Composite Tectono-Sedimentary Element, Norwegian Rifted Margin, Norwegian Sea
Authors: Faleide Jan Inge , Zastrozhnov Dmitrii , Abdelmalak Mohamed Mansour , Manton Ben , Planke Sverre , Gernigon Laurent , Brekke Harald , Myklebust Reidun 
Published: January 2024

Abstract
The Møre and Vøring basins at the mid-Norwegian margin were affected by a series of rift phases separated by periods of tectonic quiescence from Caledonian collapse in the Devonian to final continental break-up in the earliest Eocene. The tectonic phases were mostly extensional in nature, and the pre-drift extension across the Møre and Vøring basins since mid-Permian time has been estimated to be of the order of 200–250 km. The pre-Cretaceous basin configuration is poorly constrained due to limited seismic resolution at great depths and a lack of borehole control. A fundamental change occurred in the crustal deformation regime: from Late Jurassic distributed stretching of the upper crust to Early Cretaceous thinning at lower-crustal levels located along the axis of the Møre and Vøring basins. A westward migration of Late Cretaceous–Paleocene depocentres in the Vøring Basin reflects the focus of deformation towards the time and line of break-up. The basin architecture and evolution are summarized in relation to tectono-sedimentary elements corresponding to the main tectonic and depositional phases, and represent characteristic megasequences in the seismic data. Finally, the exploration history and main petroleum systems of the Møre and Vøring basins are presented.
Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs
Authors: Lumeau Audrey , Bery Nicolas , Francès Audrey , Gayral Marion , Labrousse Guillaume , Ribeyre Cyril , Lopez Charlene , Nevot Adele , El Kaoutari Abdessamad , Hanoun Naima , Sarot Emeline , Perrier Marion , Pont Frederic , Cerapio Juan-Pablo , Fournié Jean-Jacques , Lopez Frederic , Madrid-Mencia Miguel , Pancaldi Vera , Pillaire Marie-Jeanne , Bergoglio Valerie , Torrisani Jerome , Dusetti Nelson , Hoffmann Jean-Sebastien , Buscail Louis , Lutzmann Malik , Cordelier Pierre 
Published: January 2024

Abstract

Cytidine deaminase (CDA) functions in the pyrimidine salvage pathway for DNA and RNA syntheses and has been shown to protect cancer cells from deoxycytidine-based chemotherapies. In this study, we observed that CDA was overexpressed in pancreatic adenocarcinoma from patients at baseline and was essential for experimental tumor growth. Mechanistic investigations revealed that CDA localized to replication forks where it increased replication speed, improved replication fork restart efficiency, reduced endogenous replication stress, minimized DNA breaks, and regulated genetic stability during DNA replication. In cellular pancreatic cancer models, high CDA expression correlated with resistance to DNA-damaging agents. Silencing CDA in patient-derived primary cultures in vitro and in orthotopic xenografts in vivo increased replication stress and sensitized pancreatic adenocarcinoma cells to oxaliplatin. This study sheds light on the role of CDA in pancreatic adenocarcinoma, offering insights into how this tumor type modulates replication stress. These findings suggest that CDA expression could potentially predict therapeutic efficacy and that targeting CDA induces intolerable levels of replication stress in cancer cells, particularly when combined with DNA-targeted therapies.

Significance:
Cytidine deaminase reduces replication stress and regulates DNA replication to confer resistance to DNA-damaging drugs in pancreatic cancer, unveiling a molecular vulnerability that could enhance treatment response.
Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11β1 on Fibroblasts to Form a Lung Metastatic Niche
Authors: Xu Yanyang , Deng Chuangzhong , Chen Hongmin , Song YiJiang , Xu Huaiyuan , Song Guohui , Wang Xinliang , Luo Tianqi , Chen Weiqing , Ma Jiahui , Zeng Anyu , Huang Shujing , Chen Zhihao , Fu Jianchang , Gong Ming , Tai Yi , Huang Anfei , Feng Huixiong , Hu Jinxin , Zhu Xiaojun , Tang Qinglian , Lu Jinchang , Wang Jin 
Published: January 2024

Abstract

Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell–like cluster with tumor cell–initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell–like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11β1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFβ and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11β1 axis inhibited fibroblast TGFβ production, enhanced CD8+ T cell–mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11β1 axis is a potential strategy to inhibit osteosarcoma lung metastasis.

Significance:
Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11β1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.
The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L. 
Published: January 2024

Abstract

Background:
American men of African ancestry (AA) have higher prostate cancer incidence and mortality rates compared with American men of European ancestry (EA). Differences in genetic susceptibility mechanisms may contribute to this disparity.

Methods:
To gain insights into the regulatory mechanisms of prostate cancer susceptibility variants, we tested the association between SNPs and DNA methylation (DNAm) at nearby CpG sites across the genome in benign and cancer prostate tissue from 74 AA and 74 EA men. Genome-wide SNP data (from benign tissue) and DNAm were generated using Illumina arrays.

Results:
Among AA men, we identified 6,298 and 2,641 cis-methylation QTLs (meQTL; FDR of 0.05) in benign and tumor tissue, respectively, with 6,960 and 1,700 detected in EA men. We leveraged genome-wide association study (GWAS) summary statistics to identify previously reported prostate cancer GWAS signals likely to share a common causal variant with a detected meQTL. We identified nine GWAS-meQTL pairs with strong evidence of colocalization (four in EA benign, three in EA tumor, two in AA benign, and three in AA tumor). Among these colocalized GWAS-meQTL pairs, we identified colocalizing expression quantitative trait loci (eQTL) impacting four eGenes with known roles in tumorigenesis.

Conclusions:
These findings highlight epigenetic regulatory mechanisms by which prostate cancer-risk SNPs can modify local DNAm and/or gene expression in prostate tissue.

Impact:
Overall, our findings showed general consistency in the meQTL landscape of AA and EA men, but meQTLs often differ by tissue type (normal vs. cancer). Ancestry-based linkage disequilibrium differences and lack of AA representation in GWAS decrease statistical power to detect colocalization for some regions.
Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years
Authors: D'Souza Gypsyamber , Tewari Sakshi R. , Troy Tanya , Webster-Cyriaque Jennifer , Wiley Dorothy J. , Lahiri Cecile Delille , Palella Frank Joseph , Gillison Maura L. , Strickler Howard D. , Struijk Linda , Waterboer Tim , Ho Ken , Kwait Jennafer , Lazar Jason , Weber Kathleen M. , Fakhry Carole 
Published: January 2024

Abstract

Background:
Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.

Methods:
Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).

Results:
Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but not lenient (clear1: 0.68, clear2: 1.15). By clear3, most incident infections cleared at 2, 5, 8 years (55.1%, 75.6%, 79.1%), contrary to prevalent infections (37.1%, 52.5%, 59.5%, respectively). In adjusted analysis, prevalent oncHPV, older age, male sex, and living with HIV were associated with reduced clearance. Of 1,833 subjects screened, 13.8% had prevalent oncHPV and 47.5% of those infections persisted ≥5 years, representing 6.5% of persons screened. Two men with prevalent oral HPV16 developed incident oropharyngeal cancer [IR = 1.62 per 100 person-years; 95% confidence interval (CI), 0.41–6.4]. Many with oral HPV16 persisted ≥5 years (and/or developed HPV-oropharyngeal cancer) among those with 2 (72.2%), ≥2 of first 3 (65.7%), or 3 (80.0%) consecutive positive oHPV16 tests, but not after 1 (39.4%).

Conclusions:
In our 10-year study, most incident infections cleared quickly. However, half of prevalent oncHPV persisted ≥5 years, suggesting increased risk with persistent oncHPV at &gt;2 visits.

Impact:
We identified groups with persistent oncHPV at increased risk of oropharyngeal cancer and contextualized risk levels for those with oral HPV16 infection.
Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke
Authors: Xu Xin , Song Yiming , Cao Wenbo , Bai Xuesong , Wang Xinyu , Gao Peng , Chen Jian , Chen Yanfei , Yang Bin , Wang Yabing , Chen Fei , Ma Qingfeng , Yu Bo , Jiao Liqun 
Published: January 2024

Background
This study aimed to investigate regional levels of TAT (thrombin‐antithrombin complex), PIC (plasmin‐α2 plasmin inhibitor complex), t‐PAIC (tissue plasminogen activator‐plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D‐dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy.

Methods and Results

We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self‐control) arterial compartments. Levels of TAT, PIC, t‐PAIC, and D‐dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1‐unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03–1.145];
P
=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087–1.644];
P
=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1‐unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016–1.139];
P
=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194–2.022];
P
=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615–0.961];
P
=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90‐day outcome (modified Rankin scale of 3–6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all
P
<0.01).

Conclusions
We observed a hyperactive state of the coagulation‐fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra‐arterial procedures may provide additional information for stroke risk stratification and therapeutic decision‐making, and warrants further investigation.
Genomic characterization of Listeria monocytogenes and Listeria innocua isolated from milk and dairy samples in Ethiopia
Authors: Wei Xiaoyuan , Hassen Anwar , McWilliams Karen , Pietrzen Karen , Chung Taejung , Acevedo Marysabel Méndez , Chandross-Cohen Tyler , Dudley Edward G. , Vipham Jessie , Mamo Hassen , Tessema Tesfaye Sisay , Zewdu Ashagrie , Kovac Jasna 
Published: January 2024

AbstractListeriosis caused by Listeria monocytogenes often poses a significant threat to vulnerable populations. Dairy products have been implicated in outbreaks of listeriosis worldwide. In Ethiopia, studies have identified Listeria spp. and L. monocytogenes in various dairy products, but the genetic diversity and phylogenetic relationships of these bacteria remain largely unknown in the low- and middle-income countries. Therefore, we conducted whole-genome sequencing on 15 L. monocytogenes and 55 L. innocua isolates obtained from different levels of the dairy supply chains across three regions in Ethiopia. Genomes were assembled and used for MLST genotyping and single nucleotide polymorphism (SNP) analysis to infer phylogenetic relationships. We identified a total of 3 L. monocytogenes (i.e., 2, 145, and 18) and 12 L. innocua (i.e., 1489, 1619, 603, 537, 1010, 3186, 492, 3007, 1087, 474, 1008, and 637) MLST sequence types among the studied isolates. Some of these sequence types showed region-specific occurrence, while others were broadly distributed across regions. Through high-quality SNP analysis, we found that among 13 L. monocytogenes identified as ST 2, 11 of them were highly similar with low genetic variation, differing by only 1 to 10 SNPs, suggesting potential selection in the dairy food supply chain. The L. innocua isolates also exhibited low intra-ST genetic variation with only 0–10 SNP differences, except for the ST 1619, which displayed a greater diversity.
Severe coagulopathy and inflammation occurred after resection of giant right ventricular intimal sarcoma with cardiopulmonary bypass: a case report
Authors: Liu Menghan , Li Xuejie , Zhou Ronghua 
Published: January 2024

Abstract
Background
Primary malignant cardiac tumors are rare in clinic, and surgical resection under cardiopulmonary bypass (CPB) remains the main treatment. The non-physiological perfusion process of CPB leads to contact activation, and the resulting coagulopathy and systemic inflammatory response syndrome (SIRS) are common complications. However, it is difficult to predict the impact of foreign tumor fragments on this pathophysiological process once they enter the bloodstream, making this phenomenon more complex and challenging.

Case Presentation
We report a case of cardiac intimal sarcoma who developed severe coagulopathy and widespread inflammation after excision of massive right ventricular tumor and replacement of tricuspid valve by median sternotomy under CPB. Although the procedure was expected to cause tumor cell necrosis and precautions were taken, uncontrolled massive postoperative bleeding, persistent fever, abnormally elevated inflammatory markers, and recurrent malignant arrhythmias occurred after surgery. In addition to common factors, the most possible underlying mechanism is contact activation triggered following surgical procedure for intimal sarcoma with CPB.

Conclusion
Patients with intracardiac malignant tumors are at a high risk for serious contact activation during CPB. Preventive application of comprehensive anti-inflammatory measures such as drugs and adsorptive CPB technology, as well as point-of-care (POC) monitoring of coagulation status will be helpful for individualized guidance and optimization of CPB management, and improvement of patient prognosis.