bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diarrhea-associated biofilm formed by enteroaggregative Escherichia coli and aggregative Citrobacter freundii: a consortium mediated by putative F pili
Authors: Pereira Alex L , Silva Thiago N , Gomes Ana CMM , Araújo Ana CG , Giugliano Loreny G 
Published: February 2010

Abstract

Background
Enteroaggregative Escherichia coli (EAEC) are enteropathogenic strains identified by the aggregative adhesion (AA) pattern that share the capability to form biofilms. Citrobacter freundii is classically considered as an indigenous intestinal species that is sporadically associated with diarrhea.

Results
During an epidemiologic study focusing on infantile diarrhea, aggregative C. freundii (EACF) and EAEC strains were concomitantly recovered from a severe case of mucous diarrhea. Thereby, the occurrence of synergic events involving these strains was investigated. Coinfection of HeLa cells with EACF and EAEC strains showed an 8-fold increase in the overall bacterial adhesion compared with single infections (P < 0.001). The synergic effect was mediated by physical interactions among the bacteria and primed in the absence of chemical signaling and without the participation of host cells. Thus, significant increases (2.7-fold on average) in bacterial adhesion were also observed during the formation of mixed biofilms on abiotic surfaces. Bacterial settling assays showed that EAEC strains harboring F-pili genes (traA) were capable of forming bacterial aggregates only in the presence of EACF. Scanning electronic microscopy analyses revealed that bacterial aggregates as well as enhanced biofilms formed by EACF and traA-positive EAEC were mediated by non-bundle forming, flexible pili. Moreover, mixed biofilms formed by EACF and traA-positive EAEC strains were significantly reduced using nonlethal concentration of zinc, a specific inhibitor of F pili. In addition, EAEC strains isolated from diarrheic children frequently produced single biofilms sensitive to zinc.

Conclusions
Putative F pili expressed by EAEC strains boosted mixed biofilm formation when in the presence of aggregative C. freundii.
BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer
Authors: Zhang Xiao-Wei , Sheng Ya-Ping , Li Qian , Qin Wei , Lu You-Wei , Cheng Yu-Fan , Liu Bing-Ya , Zhang Feng-Chun , Li Jin , Dimri Goberdhan P , Guo Wei-Jian 
Published: February 2010

Abstract

Background
The BMI1 oncogene is overexpressed in several human malignancies including gastric cancer. In addition to BMI1, mammalian cells also express Mel-18, which is closely related to BMI1. We have reported that Mel-18 functions as a potential tumor suppressor by repressing the expression of BMI1 and consequent downregulation of activated AKT in breast cancer cells. However, the mechanisms of BMI1 overexpression and the role of Mel-18 in other cancers are still not clear. The purpose of this study is to investigate the role of BMI1 and Mel-18 in gastric cancer.

Results
BMI1 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of BMI1 correlated with advanced clinical stage and lymph node metastasis; while the expression of Mel-18 negatively correlated with BMI1. BMI1 but not Mel-18 was found to be an independent prognostic factor. Downregulation of BMI1 by Mel-18 overexpression or knockdown of BMI1 expression in gastric cancer cell lines led to upregulation of p16 (p16INK4a or CDKN2A) in p16 positive cell lines and reduction of phospho-AKT in both p16-positive and p16-negative cell lines. Downregulation of BMI1 was also accompanied by decreased transformed phenotype and migration in both p16- positive and p16-negative gastric cancer cell lines.

Conclusions
In the context of gastric cancer, BMI1 acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. Mel-18 and BMI1 may regulate tumorigenesis, cell migration and cancer metastasis via both p16- and AKT-dependent growth regulatory pathways.
Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial
Authors: Kuhl Christiane , Weigel Stefanie , Schrading Simone , Arand Birke , Bieling Heribert , König Roy , Tombach Bernd , Leutner Claudia , Rieber-Brambs Andrea , Nordhoff Dennis , Heindel Walter , Reiser Maximilian , Schild Hans H. 
Published: February 2010

Purpose We investigated the respective contribution (in terms of cancer yield and stage at diagnosis) of clinical breast examination (CBE), mammography, ultrasound, and quality-assured breast magnetic resonance imaging (MRI), used alone or in different combination, for screening women at elevated risk for breast cancer. Methods Prospective multicenter observational cohort study. Six hundred eighty-seven asymptomatic women at elevated familial risk (≥ 20% lifetime) underwent 1,679 annual screening rounds consisting of CBE, mammography, ultrasound, and MRI, read independently and in different combinations. In a subgroup of 371 women, additional half-yearly ultrasound and CBE was performed more than 869 screening rounds. Mean and median follow-up was 29.18 and 29.09 months. Results Twenty-seven women were diagnosed with breast cancer: 11 ductal carcinoma in situ (41%) and 16 invasive cancers (59%). Three (11%) of 27 were node positive. All cancers were detected during annual screening; no interval cancer occurred; no cancer was identified during half-yearly ultrasound. The cancer yield of ultrasound (6.0 of 1,000) and mammography (5.4 of 1,000) was equivalent; it increased nonsignificantly (7.7 of 1,000) if both methods were combined. Cancer yield achieved by MRI alone (14.9 of 1,000) was significantly higher; it was not significantly improved by adding mammography (MRI plus mammography: 16.0 of 1,000) and did not change by adding ultrasound (MRI plus ultrasound: 14.9 of 1,000). Positive predictive value was 39% for mammography, 36% for ultrasound, and 48% for MRI. Conclusion In women at elevated familial risk, quality-assured MRI screening shifts the distribution of screen-detected breast cancers toward the preinvasive stage. In women undergoing quality-assured MRI annually, neither mammography, nor annual or half-yearly ultrasound or CBE will add to the cancer yield achieved by MRI alone.
Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients With Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma
Authors: Yamamoto Kazuhito , Utsunomiya Atae , Tobinai Kensei , Tsukasaki Kunihiro , Uike Naokuni , Uozumi Kimiharu , Yamaguchi Kazunari , Yamada Yasuaki , Hanada Shuichi , Tamura Kazuo , Nakamura Shigeo , Inagaki Hiroshi , Ohshima Koichi , Kiyoi Hitoshi , Ishida Takashi , Matsushima Kouji , Akinaga Shiro , Ogura Michinori , Tomonaga Masao , Ueda Ryuzo 
Published: February 2010

PurposeKW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL).Patients and MethodsSixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design.ResultsFifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses.ConclusionKW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted.
The treatise On those who unjustly accuse wise men, of the past and present: a new work by Theodore Metochites?
Authors: Polemis Ioannis 
Published: February 2010

Abstract
The treatise On those who wrongly accuse wise men, of the past and present, preserved anonymously in MSS. Vindobonensis theol. gr. 174, containing works ol Georgios Galesiotes, and Vaticanus gr. 112, is a product of the literary quarrels of the first quarter of the XIV c., coming from somebody belonging to the circle of Theodore Metochites. The anonymous author shares Metochites' view concerning the lasting value of the whole canon of Greel literature, refusing to admit that only Demosthenes and Aelius Aristeides are of any real help to those contemporary authors who try to imitate the Attic style.
It is possible that the Letter 11 of Manuel Gabalas was sent to the author of the treatise in question, since a passage of that Letter is very similar to a passage of the anonymous treatise. Kourouses, identifying the addressee of Letter 11 of Gabalas with Nikephoros Choumnos, thought that the author of the anonymous treatise was Georgios Oinaiotes. However, the verbal similarities between the anonymous treatise and the letters of Oinaiotes, detected by Kourouses, are rather trivial. On the other hand, there are several striking resemblances between the anonymous treatise and the rhetorical works of Metochites, which may be easily explained if we assume that the anonymous author was Metochites himself. Though the evidence presented in this paper has at best a cumulative value, our hypothesis explains the circumstances of that treatise's writing better than any other hypothesis previously put forward. It is possible that the opponents of Metochites were those narrow-minded compilers of dictionaries (like Thomas Magistros), who did not refrain from accusing prominent authors of the past of not conforming to the rules of Attic language.
Horizontal vs. Vertical Borehole-based Microseismic Monitoring: Which is Better?
Authors: Maxwell Shawn , Le Calvez Joel 
Published: February 2010

Abstract
Monitoring hydraulic fracture stimulations of horizontal well often results in potential monitoring scenarios of either the vertical section or horizontal section of neighbouring wells. Each configuration imposes different issues and challenges, and the relative pros and cons can be examined in a pre-acquisition design study. A specific geometry was examined for the potential quality of microseismic monitoring from a vertical well compared with a horizontal well. In scenarios where the horizontal well is relatively close to the horizontal treatment well, the horizontal array results in improved sensitivity to record more events and improved accuracy of in-zone microseismicity. Vertical arrays result in improved accuracy for both in-zone and out-of-zone microseismicity for regions of the treatment well close to the vertical well. The answer to which array is better depends on the specific geometry, the importance of monitoring the entire treatment well and the importance of accuracy for out-of-zone activity.
Challenges, Uncertainties and Issues Facing Gas Production from Hydrate Deposits in Geologic Systems
Authors: Moridis G. J. , Collett T. S. , Pooladi-Darvish M. , Hancock S. , Santamarina C. , Boswell R. , Kneafsey T. , Rutqvist J. , Kowalsky M. , Reagan M. T. , Sloan E. D. , Sum A. K. , Koh C. 
Published: February 2010

AbstractThe current paper complements the Moridis et al. (2009a) review of the status of the effort toward commercial gas production from hydrates. We aim to describe the concept of the gas hydrate petroleum system, to discuss advances, requirement and suggested practices in gas hydrate prospecting and GH deposit characterization, and to review the associated technical, economic and environmental challenges and uncertainties, including: the accurate assessment of producible fractions of the GH resource, the development of methodologies for identifying suitable production targets, the sampling of hydrate-bearing sediments and sample analysis, the analysis and interpretation of geophysical surveys of GH reservoirs, well testing methods and interpretation of the results, geomechanical and reservoir/well stability concerns, well design, operation and installation, field operations and extending production beyond sand-dominated GH reservoirs, monitoring production and geomechanical stability, laboratory investigations, fundamental knowledge of hydrate behavior, the economics of commercial gas production from hydrates, and the associated environmental concerns.
Use of a Large Language Model to Assess Clinical Acuity of Adults in the Emergency Department
Authors: Williams Christopher Y. K. , Zack Travis , Miao Brenda Y. , Sushil Madhumita , Wang Michelle , Kornblith Aaron E. , Butte Atul J. 
Published: May 2024

ImportanceThe introduction of large language models (LLMs), such as Generative Pre-trained Transformer 4 (GPT-4; OpenAI), has generated significant interest in health care, yet studies evaluating their performance in a clinical setting are lacking. Determination of clinical acuity, a measure of a patient’s illness severity and level of required medical attention, is one of the foundational elements of medical reasoning in emergency medicine.ObjectiveTo determine whether an LLM can accurately assess clinical acuity in the emergency department (ED).Design, Setting, and ParticipantsThis cross-sectional study identified all adult ED visits from January 1, 2012, to January 17, 2023, at the University of California, San Francisco, with a documented Emergency Severity Index (ESI) acuity level (immediate, emergent, urgent, less urgent, or nonurgent) and with a corresponding ED physician note. A sample of 10 000 pairs of ED visits with nonequivalent ESI scores, balanced for each of the 10 possible pairs of 5 ESI scores, was selected at random.ExposureThe potential of the LLM to classify acuity levels of patients in the ED based on the ESI across 10 000 patient pairs. Using deidentified clinical text, the LLM was queried to identify the patient with a higher-acuity presentation within each pair based on the patients’ clinical history. An earlier LLM was queried to allow comparison with this model.Main Outcomes and MeasuresAccuracy score was calculated to evaluate the performance of both LLMs across the 10 000-pair sample. A 500-pair subsample was manually classified by a physician reviewer to compare performance between the LLMs and human classification.ResultsFrom a total of 251 401 adult ED visits, a balanced sample of 10 000 patient pairs was created wherein each pair comprised patients with disparate ESI acuity scores. Across this sample, the LLM correctly inferred the patient with higher acuity for 8940 of 10 000 pairs (accuracy, 0.89 [95% CI, 0.89-0.90]). Performance of the comparator LLM (accuracy, 0.84 [95% CI, 0.83-0.84]) was below that of its successor. Among the 500-pair subsample that was also manually classified, LLM performance (accuracy, 0.88 [95% CI, 0.86-0.91]) was comparable with that of the physician reviewer (accuracy, 0.86 [95% CI, 0.83-0.89]).Conclusions and RelevanceIn this cross-sectional study of 10 000 pairs of ED visits, the LLM accurately identified the patient with higher acuity when given pairs of presenting histories extracted from patients’ first ED documentation. These findings suggest that the integration of an LLM into ED workflows could enhance triage processes while maintaining triage quality and warrants further investigation.
The spectrum of movement disorders in young children with ARX‐related epilepsy‐dyskinesia syndrome
Authors: Akula Shyam K. , Quiroz Vicente , D'Gama Alissa M. , Chiu Michelle Y. , Koh Hyun Yong , Saffari Afshin , Zaman Zainab , Tam Amy , Srouji Rasha , Valentine Rozalia , Wiltrout Kimberly , Pinto Anna , Harini Chellamani , Pearl Phillip L. , Poduri Annapurna , Ebrahimi‐Fakhari Darius 
Published: May 2024

AbstractChildren with developmental and epileptic encephalopathies often present with co‐occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging from focal hand dystonia to generalized dystonia with frequent status dystonicus. In this report, we present three patients with severe movement disorders as part of ARX‐associated epilepsy‐dyskinesia syndrome, including a patient with a novel pathogenic missense variant (p.R371G). These cases illustrate diagnostic and management challenges of ARX‐related disorder and shed light on broader challenges concerning epilepsy‐dyskinesia syndromes.
Age‐Related Decrease in Pellino‐1 Expression Contributes to Osteoclast‐Mediated Bone Loss
Authors: Yoon Dong Suk , Oh Seung Eun , Lee Kyoung‐Mi , Jung Sujin , Ko Eun Ae , Kim Tae‐Gyun , Park Kwang Hwan , Lee Jin Woo 
Published: May 2024

AbstractAging‐related bone loss is driven by various biological factors, such as imbalanced bone metabolism from decreased osteoblast and increased osteoclast activities. Various transcriptional and post‐transcriptional factors increase osteoclast activity with aging; however, studies regarding the post‐translational regulators of osteoclast activity are still limited. The ubiquitin E3 ligase Pellino‐1 is a well‐known post‐translational regulator of inflammation. However, how Pellino‐1 expression regulation affects osteoclast differentiation remains unclear. This study determined that Pellino‐1 levels are reduced in bone marrow monocytes (BMMs) from 40‐week‐old mice compared to 4‐week‐old mice. Interestingly, conditional Knockout (cKO) of Pellino‐1 in 6‐week‐old mice resulted in decreased bone mass, reduced body size, and lower weight than in Pellino‐1 floxed mice; however, these differences are not observed in 20‐week‐old mice. The increased number of tartrate‐resistant acid phosphatase (TRAP)‐positive cells and serum levels of C‐terminal telopeptides of type I collagen, a marker of bone resorption, in 6‐week‐old Pellino‐1 cKO mice implied a connection between Pellino‐1 and the osteoclast population. Enhanced TRAP activity and upregulation of osteoclast genes in BMMs from the cKO mice indicate that Pellino‐1 deletion affects osteoclast differentiation, leading to decreased bone mass and heightened osteoclast activity. Thus, targeting Pellino‐1 could be a potential gene therapy for managing and preventing osteoporosis.
Advancing Osteoporotic Bone Regeneration Through Tailored Tea Polyphenols Functionalized Micro‐/Nano‐ Hydroxyapatite Bioceramics
Authors: Zhao Rui , Qian Hui , Zhu Xiangdong , Zhang Xingdong , Chen Zhenhua , Yang Xiao 
Published: May 2024

AbstractEfforts to develop advanced bone substitutes for effective bone regeneration in substantial defects have led to the fabrication of tissue‐engineered scaffolds. These scaffolds, featuring hierarchical structures, specific chemical compositions, and functional qualities, are essential in mimicking native bone tissue. Inspired by the biomineralization process, hydrothermal treatment is used to synthesize micro‐/nano‐hydroxyapatite bioceramics functionalized with tea polyphenols (TP‐nwHA), closely resembling the structure of bone‐like apatite induced by hydroxyapatite bioceramics in vivo. The in vitro results demonstrate TP‐nwHA's superior biocompatibility, enhancing cell proliferation and adhesion. Furthermore, TP‐nwHA scaffolds significantly influence mesenchymal stem cells, promoting osteogenic differentiation while inhibiting osteoclastogenic differentiation. The upregulation of osteogenic proteins BMP2 and ITGB1, along with the downregulation of osteoclastic proteins FGF21 and IGFBP1, demonstrate the synergistic effect of the biomimetic structure and polyphenols on the activation of the MAPK signaling pathway. In vivo, TP‐nwHA showe early angiogenic capabilities, leading to improved bone regeneration in critical‐size femoral bone defects in osteoporotic rats. Histological staining confirms the complete bridging of defects with new bone tissue in the TP‐nwHA group, and nanoindentation tests indicate the formation of mature mineralized bone tissue. Collectively, these findings suggest a novel strategy for fabricating bone‐mimicking constructs with potential applications in disease modeling.
Large‐Area Graphene‐Based Ion‐Selective Membranes with Micro/Meso‐Pores for Osmotic Energy Harvesting
Authors: Zhi Hui , Yan Peng , Wang Dejuan , Liu Yongxu , Tang Jiebin , Yang Xuan , Liu Zixuan , Zhang Yafang , Li Ningbo , An Meng , Liu Hong , Xue Guobin 
Published: May 2024

AbstractRenewable osmotic energy between seawater and river water shows great potential in meeting global energy demand. Reverse electrodialysis (RED) technique using ion‐selective membrane is particularly outstanding for its easy operation. Preparing low‐cost and large‐area ion‐selective membranes with excellent ion transport characteristics is particularly important to promote commercial applications. Herein, large‐area ion‐selective membrane is prepared by scraping slurry of flocculated GO (graphene oxide)/PAAS (sodium polyacrylate) solution and then coated with PVA (polyvinyl alcohol)/SA (sodium alginate) gel layer. The PVA/SA molecules can penetrate into the membrane through the unique micro/meso‐pores, which together increase the ion selectivity, membrane permeability, and stability. This ion‐selective membrane can achieve a power density of 8.65 W m−2 under a 50‐fold salinity gradient (NaCl) simulating the sea/river junction environment (with the testing area of 0.0314 mm2). This work significantly promotes the application of GO in large‐area preparation of low‐cost ion‐selective membrane.
DNA Nanostructures Treat Inflammatory Bowel Disease through ROS Scavenging and Gut Microbiota Modulation
Authors: Ge Jingru , Jia Bin , Wang Yuang , Ma Yuxuan , Sun Xiaolei , Dong Jun , Jiang Shuoxing , Li Zhe 
Published: May 2024

AbstractInflammatory bowel disease (IBD) encompasses a collection of chronic inflammatory conditions impacting the gastrointestinal tract, with a discernible global rise in prevalence and severity. The overabundance of reactive oxygen species (ROS) in the intestinal environment leads disruption of local redox homeostasis, and perturbation of the gut microbiota, exacerbating IBD. Consequently, mitigating excess ROS and preserving gut microbiota homeostasis have emerged as effective approaches for IBD management. In this study, a triangular DNA origami nanostructure loaded with siRNA targeting tumor necrosis factor α (siTNF‐αtDON) is introduced for this purpose. This nanostructure demonstrates efficacy in eliminating ROS within cells closely associated with IBD, diminishing inflammation, and ameliorating disorders in gut microbiota, as evidenced in an IBD mouse model. Furthermore, this investigation demonstrates the effects of siTNF‐αtDON on related inflammatory signaling pathways, including NF‐κB, MAPK/ERK and Keap1/Nrf2. Collectively, this study offers insights into the potential utilization of DNA nanostructures as antioxidants and gut microbiota modulators, presenting promising avenues for the IBD treatment.