检索结果-内蒙古大学图书馆

Rapid whole genome characterization of antimicrobial-resistant pathogens using long-read sequencing to identify potential healthcare transmission

引用

INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY 2025年第2期46卷 129-135页

作者： Wu, Chin-Ting Shropshire, William C. Bhatti, Micah M. Cantu, Sherry Glover, Israel K. Anand, Selvalakshmi Selvaraj Liu, Xiaojun Kalia, Awdhesh Treangen, Todd J. Chemaly, Roy F. Spallone, Amy Shelburne, Samuel Univ Texas MD Anderson Canc Ctr Sch Hlth Profess Grad Program Diagnost Genet & Genom Houston TX USA Univ Texas MD Anderson Canc Ctr Dept Infect Dis Infect Control & Employee Hlth Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Lab Med Houston TX USA Univ Texas MD Anderson Canc Ctr Infect Control Chief Qual Off Houston TX USA Univ Texas MD Anderson Canc Ctr Dept Genom Med Houston TX 77030 USA Rice Univ PhD Program Synthet Biol Inst Syst Synthet & Phys Houston TX USA Rice Univ Dept Comp Sci Houston TX USA Rice Univ Dept Bioengn Houston TX USA

Objective: Whole genome sequencing (WGS) can help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time intensive. Given recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource approach providing accurate WGS-pathogen comparison within a time frame allowing for infection prevention and control (IPC) interventions. Methods: WGS was prospectively performed on pathogens at increased risk of potential healthcare transmission using the ONT MinION sequencer with R10.4.1 flow cells and Dorado basecaller. Potential transmission was assessed via Ridom SeqSphere & thorn;for core genome multilocus sequence typing and MINTyper for reference-based core genome single nucleotide polymorphisms using previously published cutoff values. The accuracy of our ONT pipeline was determined relative to Illumina. Results: Over a six-month period, 242 bacterial isolates from 216 patients were sequenced by a single operator. Compared to the Illumina gold standard, our ONT pipeline achieved a mean identity score of Q60 for assembled genomes, even with a coverage rate as low as 40x. The mean time from initiating DNA extraction to complete analysis was 2 days (IQR 2-3.25 days). We identified five potential transmission clusters comprising 21 isolates (8.7% of sequenced strains). Integrating ONT with epidemiological data, > 70% (15/21) of putative transmission cluster isolates originated from patients with potential healthcare transmission links. Conclusions: Via a stand-alone ONT pipeline, we detected potentially transmitted HAI pathogens rapidly and accurately, aligning closely with epidemiological data. Our low-resource method has the potential to assist in IPC efforts. (Received 27 August 2024;accepted 1 November 2024)

关键词：

来源：评论

学校读者我要写书评

暂无评论

Assessment of regulating ecosystem services generated by green infrastructure: A case study of Bolzano, Italy

引用

URBAN CLIMATE 2025年 60卷

作者： Sokolova, Milena, V Fath, Brian D. Buonocore, Elvira Franzese, Pier Paolo Parthenope Univ Naples UNESCO Chair Environm Resources & Sustainable Dev Dept Sci & Technol Int PhD Programme Naples Italy Int Inst Appl Syst Anal Adv Syst Anal Program Laxenburg Austria Towson Univ Dept Biol Sci Towson MD USA Masaryk Univ Dept Environm Studies Brno Czech Republic

Sustainable cities is one of the key topics of the United Nations 2030 Agenda for Sustainable Development. SDG 11 promotes the goal that cities should be inclusive, safe, resilient and sustainable human settlements. In this context, urban ecosystems, namely, Green Infrastructure (GI) can play a key role to enhance ecosystem services. GI improves ecosystem functioning and resilience, protects biodiversity, promotes societal health and well-being. The concept of GI in cities is becoming increasingly important in the development of urban policies since it improves the quality of life while mitigating the adverse effects of climate change. In this paper, we integrate biophysical method and monetary methods using i-Tree Eco software with about 12,000 trees within Bolzano, Italy. Model results are given for five assessed ecosystem services: 1) carbon storage, 2) carbon sequestration, 3) oxygen production, 4) avoided runoff, and 5) air pollution removal. Thus, our results show the significance of urban trees as a key element for better urban planning considering specific species contribution. The findings of this study will increase the awareness on the important role GIs play in urban systems to improve human well-being, informing policy-makers in charge of developing strategies to achieve impelling conservation actions and sustainability goals.

关键词： Green infrastructure Ecosystem services i-Tree Eco software SDG 11 Bolzano Urban ecosystems

来源：评论

学校读者我要写书评

暂无评论

A retrospective 'target trial emulation' comparing amiodarone and lidocaine for adult out-of-hospital cardiac arrest resuscitation

引用

RESUSCITATION 2025年 208卷 110515-110515页

作者： Smida, Tanner Crowe, Remle Price, Bradley S. Scheidler, James Martin, P. S. Shukis, Michael Bardes, James 64 Med Ctr Dr Morgantown WV 26506 USA West Virginia Univ MD PhD Program Sch Med Morgantown WV USA ESO Solut Austin TX USA West Virginia Univ John Chambers Sch Business & Econ Morgantown WV USA West Virginia Univ Dept Emergency Med Div Prehosp Med Sch Med Morgantown WV USA

Objective The administration of amiodarone or lidocaine is recommended during the resuscitation of out-of-hospital cardiac arrest (OHCA) patients presenting with defibrillation-refractory or recurrent ventricular fibrillation or ventricular tachycardia. Our objective was to use 'target trial emulation' methodology to compare the outcomes of patients who received amiodarone or lidocaine during resuscitation. Methods Adult, non-traumatic OHCA patients in the ESO Data Collaborative 2018-2023 datasets who experienced OHCA prior to EMS arrival, presented with a shockable rhythm, and received amiodarone or lidocaine during resuscitation were evaluated for inclusion. We used propensity score matching (PSM) to investigate the association between antiarrhythmic and outcomes. Return of spontaneous circulation (ROSC) was the primary outcome. Secondary outcomes included the number of post-drug defibrillations and survival to hospital discharge. Results After application of exclusion criteria, 23,263 patients from 1,707 EMS agencies were eligible for analysis. Prior to PSM, 6,010/20,284 (29.6%) of the patients who received amiodarone and 1,071/2,979 (35.9%) of the patients who received lidocaine achieved prehospital ROSC. Following PSM, lidocaine administration was associated with greater odds of prehospital ROSC (36.0 vs. 30.4%;aOR: 1.29 [1.16, 1.44], n = 2,976 matched pairs). Lidocaine administration was also associated with fewer post-drug defibrillations (median: 2 [0-4] vs. 2 [0-6], mean: 3.3 vs. 3.9, p < 0.01, n = 2,976 pairs), and greater odds of survival to discharge (35.1 vs. 25.7%;OR: 1.54 [1.19, 2.00], n = 538 pairs). Conclusion Our 'target trial emulation' suggested that lidocaine was associated with greater odds of prehospital ROSC in comparison to amiodarone when administered during resuscitation from shock refractory or recurrent VF/VT.

关键词： Amiodarone Lidocaine Antiarrhythmic Shockable Ventricular fibrillation Ventricular tachycardia Refractory Recurrent M- edication Intravenous Intraosseous

来源：评论

学校读者我要写书评

暂无评论

Mechanism for local attenuation of DNA replication at double-strand breaks

引用

NATURE 2025年第8056期639卷 1-9页

作者： Sebastian, Robin Sun, Eric G. Fedkenheuer, Michael Fu, Haiqing Jung, Seolkyoung Thakur, Bhushan L. Redon, Christophe E. Pegoraro, Gianluca Tran, Andy D. Gross, Jacob M. Mosavarpour, Sara Kusi, Nana Afua Ray, Anagh Dhall, Anjali Pongor, Lorinc S. Casellas, Rafael Aladjem, Mirit I. NCI Dev Therapeut Branch NIH Bethesda MD 20814 USA Natl Inst Arthrit & Musculoskeletal & Skin Dis NIH Mol Immunol & Inflammat Branch Bethesda MD USA Natl Inst Arthrit & Musculoskeletal & Skin Dis NIH Biodata Min & Discovery Sect Bethesda MD USA NCI High Throughput Imaging Facil HiTIF NIH Bethesda MD USA NCI CCR Microscopy Core Facil Lab Canc Biol & Genet Ctr Canc Res Bethesda MD USA HCEMM Canc Genom & Epigenet Core Grp Szeged Hungary Rockefeller Univ Mem Sloan Kettering Canc Ctr Triinst MD PhD Program Weill Cornell Med New York NY USA Univ Texas MD Anderson Canc Ctr Dept Hematopoiet Biol & Malignancy Div Canc Med Houston TX USA

DNA double-strand breaks (DSBs) disrupt the continuity of the genome, with consequences for malignant transformation. Massive DNA damage can elicit a cellular checkpoint response that prevents cell proliferation1,2. However, how highly aggressive cancer cells, which can tolerate widespread DNA damage, respond to DSBs alongside continuous chromosome duplication is unknown. Here we show that DSBs induce a local genome maintenance mechanism that inhibits replication initiation in DSB-containing topologically associating domains (TADs) without affecting DNA synthesis at other genomic locations. This process is facilitated by mediators of replication and DSBs (MRDs). In normal and cancer cells, MRDs include the TIMELESS-TIPIN complex and the WEE1 kinase, which actively dislodges the TIMELESS-TIPIN complex from replication origins adjacent to DSBs and prevents initiation of DNA synthesis at DSB-containing TADs. Dysregulation of MRDs, or disruption of 3D chromatin architecture by dissolving TADs, results in inadvertent replication in damaged chromatin and increased DNA damage in cancer cells. We propose that the intact MRD cascade precedes DSB repair to prevent genomic instability, which is otherwise observed when replication is forced, or when genome architecture is challenged, in the presence of DSBs3, 4-5. These observations reveal a previously unknown vulnerability in the DNA replication machinery that may be exploited to therapeutically target cancer cells.

关键词：

来源：评论

学校读者我要写书评

暂无评论

RNA polymerase II at histone genes predicts outcome in human cancer

引用

Science (New York, N.Y.) 2025年第6735期387卷 737-743页

作者： Henikoff, Steven Zheng, Ye Paranal, Ronald M. Xu, Yiling Greene, Jacob E. Henikoff, Jorja G. Russell, Zachary R. Szulzewsky, Frank Thirimanne, H Nayanga Kugel, Sita Holland, Eric C. Ahmad, Kami Basic Sciences Division Fred Hutchinson Cancer Center Seattle WA United States Howard Hughes Medical Institute Chevy Chase MD United States Human Biology Division Fred Hutchinson Cancer Center Seattle WA United States Molecular Medicine and Mechanisms of Disease PhD Program University of Washington Seattle WA United States

Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)-cleavage under targeted accessible chromatin method for mapping RNA polymerase II (RNAPII) genome-wide in FFPE sections. We demonstrate global RNAPII elevations in mouse gliomas and assorted human tumors in small clinical samples and discover regional elevations corresponding to de novo HER2 amplifications punctuated by likely selective sweeps. RNAPII occupancy at S-phase-dependent histone genes correlated with WHO grade in meningiomas, accurately predicted rapid recurrence, and corresponded to whole-arm chromosome losses. Elevated RNAPII at histone genes in meningiomas and diverse breast cancers is consistent with histone production being rate-limiting for S-phase progression and histone gene hypertranscription driving overproliferation and aneuploidy in cancer, with general implications for precision oncology.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Pharmacological restoration of GTP hydrolysis by mutant RAS

引用

NATURE 2025年第8044期637卷 224-229页

作者： Cuevas-Navarro, Antonio Pourfarjam, Yasin Hu, Feng Rodriguez, Diego J. Vides, Alberto Sang, Ben Fan, Shijie Goldgur, Yehuda de Stanchina, Elisa Lito, Piro Mem Sloan Kettering Canc Ctr Human Oncol & Pathogenesis Program New York NY 10029 USA Rockefeller Univ Weill Cornell Med Coll Mem Sloan Kettering Canc Ctr Triinst MD PhD Program New York NY 10065 USA Mem Sloan Kettering Canc Ctr Struct Biol Program New York NY USA Mem Sloan Kettering Canc Ctr Antitumor Assessment Core Facil New York NY USA Mem Sloan Kettering Canc Ctr Dept Med New York NY 10029 USA Weill Cornell Med Coll Dept Med New York NY 10021 USA

Approximately 3.4 million patients worldwide are diagnosed each year with cancers that have pathogenic mutations in one of three RAS proto-oncogenes (KRAS, NRAS and HRAS)1,2. These mutations impair the GTPase activity of RAS, leading to activation of downstream signalling and proliferation3, 4, 5-6. Long-standing efforts to restore the hydrolase activity of RAS mutants have been unsuccessful, extinguishing any consideration towards a viable therapeutic strategy7. Here we show that tri-complex inhibitors-that is, molecular glues with the ability to recruit cyclophilin A (CYPA) to the active state of RAS-have a dual mechanism of action: not only do they prevent activated RAS from binding to its effectors, but they also stimulate GTP hydrolysis. Drug-bound CYPA complexes modulate residues in the switch II motif of RAS to coordinate the nucleophilic attack on the gamma-phosphate of GTP in a mutation-specific manner. RAS mutants that were most sensitive to stimulation of GTPase activity were more susceptible to treatment than mutants in which the hydrolysis could not be enhanced, suggesting that pharmacological stimulation of hydrolysis potentiates the therapeutic effects of tri-complex inhibitors for specific RAS mutants. This study lays the foundation for developing a class of therapeutics that inhibit cancer growth by stimulating mutant GTPase activity.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Rethinking clinical trials for medical AI with dynamic deployments of adaptive systems

引用

NPJ DIGITAL MEDICINE 2025年第1期8卷 1-6页

作者： Rosenthal, Jacob T. Beecy, Ashley Sabuncu, Mert R. Sloan Kettering Triinst MD PhD program Weill Cornell Rockefeller New York NY 10065 USA Weill Cornell Med Dept Radiol New York NY 10065 USA Weill Cornell Med Dept Med Div Cardiol New York NY USA NewYork Presbyterian New York NY USA Cornell Tech Sch Elect & Comp Engn New York NY USA Cornell Univ New York NY USA

There is a growing recognition of the need for clinical trials to safely and effectively deploy artificial intelligence (AI) in clinical settings. We introduce dynamic deployment as a framework for AI clinical trials tailored for the dynamic nature of large language models, making possible complex medical AI systems which continuously learn and adapt in situ from new data and interactions with users while enabling continuous real-time monitoring and clinical validation.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2

引用

GENOME BIOLOGY 2025年第1期26卷 1-25页

作者： Schmidt, Henri Zhang, Minsi Chakarov, Dimitar Bansal, Vineet Mourelatos, Haralambos Sanchez-Rivera, Francisco J. Lowe, Scott W. Ventura, Andrea Leslie, Christina S. Pritykin, Yuri Princeton Univ Dept Comp Sci Princeton NJ 08544 USA Mem Sloan Kettering Canc Ctr Computat & Syst Biol Program New York NY 10021 USA Mem Sloan Kettering Canc Ctr Canc Biol & Genet Program New York NY 10021 USA Princeton Univ Lewis Sigler Inst Integrat Genom Princeton NJ 08544 USA Princeton Univ Ctr Stat & Machine Learning Princeton NJ USA Mem Sloan Kettering Tri Inst MD PhD Program Weill Cornell Rockefeller New York NY USA MIT David H Koch Inst Integrat Canc Res Cambridge MA USA MIT Dept Biol Cambridge MA USA

We present GuideScan2 for memory-efficient, parallelizable construction of high-specificity CRISPR guide RNA (gRNA) databases and user-friendly design and analysis of individual gRNAs and gRNA libraries for targeting coding and non-coding regions in custom genomes. GuideScan2 analysis identifies widespread confounding effects of low-specificity gRNAs in published CRISPR screens and enables construction of a gRNA library that reduces off-target effects in a gene essentiality screen. GuideScan2 also enables the design and experimental validation of allele-specific gRNAs in a hybrid mouse genome. GuideScan2 will facilitate CRISPR experiments across a wide range of applications.

关键词： CRISPR Guide RNA Off-targets Burrows-Wheeler transform Algorithm Software Web interface GuideScan2

来源：评论

学校读者我要写书评

暂无评论

Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression

引用

NATURE COMMUNICATIONS 2025年第1期16卷 1-15页

作者： Aboharb, Farid Davoudian, Pasha A. Shao, Ling-Xiao Liao, Clara Rzepka, Gillian N. Wojtasiewicz, Cassandra Indajang, Jonathan Dibbs, Mark Rondeau, Jocelyne Sherwood, Alexander M. Kaye, Alfred P. Kwan, Alex C. Cornell Univ Meinig Sch Biomed Engn Ithaca NY 14850 USA Weill Cornell Med Triinst MD PhD Program Rockefeller Sloan Kettering New York NY USA Yale Univ Sch Med Interdept Neurosci Program New Haven CT USA Yale Univ Sch Med Med Scientist Training Program New Haven CT USA Yale Univ Sch Med Dept Psychiat New Haven CT 06520 USA Usona Inst Fitchburg WI USA VA Natl Ctr PTSD Clin Neurosci Div West Haven CT USA Yale Univ Wu Tsai Inst New Haven CT USA Weill Cornell Med Dept Psychiat New York NY 10065 USA

Psilocybin, ketamine, and mdMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in native brain tissues. We therefore developed a pipeline for drug classification using light sheet fluorescence microscopy of immediate early gene expression at cellular resolution followed by machine learning. We tested male and female mice with a panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, mdMA, acute fluoxetine, chronic fluoxetine, and vehicle. In one-versus-rest classification, the exact drug was identified with 67% accuracy, significantly above the chance level of 12.5%. In one-versus-one classifications, psilocybin was discriminated from 5-MeO-DMT, ketamine, mdMA, or acute fluoxetine with >95% accuracy. We used Shapley additive explanation to pinpoint the brain regions driving the machine learning predictions. Our results suggest a unique approach for characterizing and validating psychoactive drugs with psychedelic properties.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Rationale and design of a randomized controlled trial evaluating the effects of blueberry consumption versus placebo on brain health in older adults

引用

CONTEMPORARY CLINICAL TRIALS 2025年 154卷 107926-107926页

作者： Uttke, Zachary Gabriel, Olivia Smith, Ceilidh Guardino, Eric T. Mukamal, Kenneth Djousse, Luc Greater Boston Med Student Aging Res Boston MA USA Brown Univ MD PhD Program Providence RI USA Univ Texas Hlth San Antonio STX MSTP San Antonio TX USA Brigham & Womens Hosp Boston MA USA Beth Israel Deaconess Med Ctr Boston MA USA Harvard Med Sch Boston MA USA Harvard TH Chan Sch Publ Hlth Boston MA USA

Background: Age-related cognitive decline results in significant clinical and public health costs. Cognitive decline predisposes individuals to dementia and leads to difficulties with activities of daily living and increased hospitalizations. While a few dietary interventions have shown considerable promise at delaying cognitive decline, studies of the effects of long-term blueberry consumption on brain health among older adults have been limited and equivocal. Objective: To test the hypothesis that a 24-week intervention with blueberry powder versus placebo will improve (i) plasma biomarkers of brain health and (ii) cognitive performance in older adults. Methods: This randomized, double-blind, placebo-controlled trial will be conducted in older Americans aged 65-99 years old. Sixty-seven participants will be randomly assigned to receive either blueberry powder (20 g/d-equivalent of one (1) cup of fresh blueberries) or a placebo powder (20 g/d) for 24 weeks. Participants will undergo four clinic visits (baseline and 8 weeks, 16 weeks, and 24 weeks after randomization) for cognitive assessments, blood pressure measurements, and blood sample collections. Primary outcomes will be plasma levels of neurofilament light chain (NFL) and phosphorylated tau protein (pTau-181). Secondary outcomes will be plasma levels of glial fibrillary acidic protein (GFAP) and non-esterified fatty acids (NEFA);blood pressure during visits;and cognitive function. Conclusion: Findings from this trial will answer the question whether a long-term intervention with blueberry powder can improve (i) plasma biomarkers of brain health and (ii) cognitive function in older adults.

关键词： Blueberries Biomarkers Cognitive function Older adults Clinical trial

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：