bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro
activity of omadacycline against clinical isolates of
Nocardia
Authors: Pham Jonathan , Benefield Russell J. , Baker Natali , Lindblom Shane , Canfield Nicholas , Gomez Carlos A. , Fisher Mark 
Published: March 2024

ABSTRACT

Nocardiosis typically requires a prolonged treatment duration of ≥6 months and initial combination therapy with 2–3 antibiotics. First-line regimens for nocardiosis are associated with considerable toxicity; therefore, alternative therapies are needed. Omadacycline is an aminomethylcycline with broad antimicrobial activity whose
in vitro
activity against
Nocardia
species has not been formally assessed. The
in vitro
potency of omadacycline was evaluated against 300
Nocardia
clinical isolates by broth microdilution. The most common
Nocardia
species tested were
N. cyriacigeorgica
(21%),
N. nova
(20%), and
N. farcinica
(12%). The most common specimens were respiratory (178 isolates, 59%) and wound (57 isolates, 19%). Omadacycline minimum inhibitory concentrations (MICs) across all
Nocardia
species ranged from 0.06 µg/mL to 8 µg/mL, with an MIC
50
of 2 µg/mL and MIC
90
of 4 µg/mL. The lowest MICs were found among
N. paucivorans
(MIC
50
= 0.25 µg/mL, MIC
90
= 0.25 µg/mL),
N. asiatica
(MIC
50
= 0.25 µg/mL, MIC
90
= 1 µg/mL),
N. abscessus
complex (MIC
50
= 0.5 µg/mL, MIC
90
= 1 µg/mL),
N. beijingensis
(MIC
50
= 0.5 µg/mL, MIC
90
= 2 µg/mL), and
N. otitidiscaviarum
(MIC
50
= 1 µg/mL, MIC
90
= 2 µg/mL). The highest MICs were found among
N. farcinica
(MIC
50
= 4 µg/mL, MIC
90
= 8 µg/mL).
In vitro
potency differed by species among
Nocardia
clinical isolates. Further studies are warranted to evaluate the potential clinical utility of omadacycline for nocardiosis.
Transposable elements impact the population divergence of rice blast fungus
Magnaporthe oryzae
Authors: Lin Lianyu , Sun Ting , Guo Jiayuan , Lin Lili , Chen Meilian , Wang Zhe , Bao Jiandong , Norvienyeku Justice , Zhang Dongmei , Han Yijuan , Lu Guodong , Rensing Christopher , Zheng Huakun , Zhong Zhenhui , Wang Zonghua 
Published: March 2024

ABSTRACT

Dynamic transposition of transposable elements (TEs) in fungal pathogens has significant impact on genome stability, gene expression, and virulence to the host. In
Magnaporthe oryzae
, genome plasticity resulting from TE insertion is a major driving force leading to the rapid evolution and diversification of this fungus. Despite their importance in
M. oryzae
population evolution and divergence, our understanding of TEs in this context remains limited. Here, we conducted a genome-wide analysis of TE transposition dynamics in the 11 most abundant TE families in
M. oryzae
populations. Our results show that these TEs have specifically expanded in recently isolated
M. oryzae
rice populations, with the presence/absence polymorphism of TE insertions highly concordant with population divergence on Geng/
Japonica
and Xian/
Indica
rice cultivars. Notably, the genes targeted by clade-specific TEs showed clade-specific expression patterns and are involved in the pathogenic process, suggesting a transcriptional regulation of TEs on targeted genes. Our study provides a comprehensive analysis of TEs in
M. oryzae
populations and demonstrates a crucial role of recent TE bursts in adaptive evolution and diversification of the
M. oryzae
rice-infecting lineage.

IMPORTANCE

Magnaporthe oryzae
is the causal agent of the destructive blast disease, which caused massive loss of yield annually worldwide. The fungus diverged into distinct clades during adaptation toward the two rice subspecies, Xian/
Indica
and Geng/
Japonica
. Although the role of TEs in the adaptive evolution was well established, mechanisms underlying how TEs promote the population divergence of
M. oryzae
remain largely unknown. In this study, we reported that TEs shape the population divergence of
M. oryzae
by differentially regulating gene expression between Xian/
Indica
-infecting and Geng/
Japonica
-infecting populations. Our results revealed a TE insertion-mediated gene expression adaption that led to the divergence of
M. oryzae
population infecting different rice subspecies.
Draft genome sequence of multidrug-resistant
Klebsiella pneumoniae
Hakim-RU strain isolated from a patient with urinary tract infections in Bangladesh
Authors: Romance M. , khan Muhib Ullah , Islam Md. Shamsul , Islam Md. Faridul , Haque Md. Hakimul 
Published: March 2024

ABSTRACT

We unveil the genomic sequence of the
Klebsiella pneumoniae
Hakim-RU strain isolated from a patient with urinary tract infections. Our assembled genome spans 4.3 Mb with 73.0× coverage, an average GC content of 57.41%, 4 plasmids, 2 CRISPR arrays, 10 prophages, 41 antibiotic resistance genes, and 6 virulence factor genes.
Microbial genome collection of aerobic granular sludge cultivated in sequencing batch reactors using different carbon source mixtures
Authors: Saini Jaspreet S. , Adler Aline , Cardona Laëtitia , Rodilla Ramírez Pilar Natalia , Pei Ruizhe , Holliger Christof 
Published: March 2024

ABSTRACT

Aerobic granular sludge (AGS) consists of a microbial consortium that has an important role in wastewater treatment. This study investigates AGS microorganisms cultivated in a laboratory-scale sequencing batch reactor. Metagenomic sequencing was conducted using PacBio and Illumina, resulting in 759 metagenome-assembled genomes, 331 of which remained after dereplication.
De Sitter Local Thermodynamics in f(R) Gravity
Authors: Volovik G. E. 
Published: March 2024

We consider the local thermodynamics of the de Sitter state in the $$f(\mathcal{R})$$ gravity. The local temperature, which is the same for all points of the de Sitter space, is $$T = H{\text{/}}\pi $$, where H is the Hubble parameter. It is twice larger than the Gibbons–Hawking temperature of the cosmological horizon, $${{T}_{{{\text{GH}}}}} = H{\text{/}}2\pi $$. The local temperature is not related to the cosmological horizon. It determines the rate of the activation processes, which are possible in the de Sitter environment. The typical example is the process of the ionization of the atom in the de Sitter environment, which rate is determined by temperature $$T = H{\text{/}}\pi $$. The local temperature determines the local entropy of the de Sitter vacuum state, and this allows to calculate the total entropy inside the cosmological horizon. The result reproduces the Gibbons–Hawking area law, which corresponds to the Wald entropy, $${{S}_{{{\text{hor}}}}} = 4\pi KA$$. Here, K is the effective gravitational coupling, $$K = df{\text{/}}d\mathcal{R}$$. In the local thermodynamic approach, K is the thermodynamic variable, which is conjugate to the Ricci scalar curvature $$\mathcal{R}$$. The holographic connection between the bulk entropy of the Hubble volume and the surface entropy of the cosmological horizon supports the suggestion that the de Sitter quantum vacuum is characterized by the local thermodynamics with the local temperature $$T = H{\text{/}}\pi $$. The local temperature $$T = H{\text{/}}\pi $$ of the de Sitter vacuum suggests that the de Sitter vacuum is locally unstable towards the creation of matter and its further heating. The decay of the de Sitter vacuum due to such processes determines the quantum breaking time of the space-times with positive cosmological constant.
No sign of weakness: a systematic review and meta-analysis of hip and calf muscle strength after anterior cruciate ligament injury
Authors: Girdwood Michael , Culvenor Adam G , Patterson Brooke , Haberfield Melissa , Rio Ebonie Kendra , Hedger Michael , Crossley Kay M 
Published: March 2024

ObjectiveWe aimed to determine hip and lower-leg muscle strength in people after ACL injury compared with an uninjured control group (between people) and the uninjured contralateral limb (between limbs).DesignSystematic review with meta-analysis.Data sourcesMEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SportDiscus to 28 February 2023.Eligibility criteriaPrimary ACL injury with mean age 18–40 years at time of injury. Studies had to measure hip and/or lower-leg muscle strength quantitatively (eg, dynamometer) and report muscle strength for the ACL-injured limb compared with: (i) an uninjured control group and/or (ii) the uninjured contralateral limb. Risk of bias was assessed according to Cochrane Collaboration domains.ResultsTwenty-eight studies were included (n=23 measured strength ≤12 months post-ACL reconstruction). Most examined hip abduction (16 studies), hip extension (12 studies) and hip external rotation (7 studies) strength. We found no meaningful difference in muscle strength between people or between limbs for hip abduction, extension, internal rotation, flexion or ankle plantarflexion, dorsiflexion (estimates ranged from −9% to +9% of comparator). The only non-zero differences identified were in hip adduction (24% stronger on ACL limb (95% CI 8% to 42%)) and hip external rotation strength (12% deficit on ACL limb (95% CI 6% to 18%)) compared with uninjured controls at follow-ups >12 months, however both results stemmed from only two studies. Certainty of evidence was very low for all outcomes and comparisons, and drawn primarily from the first year post-ACL reconstruction.ConclusionOur results do not show widespread or substantial muscle weakness of the hip and lower-leg muscles after ACL injury, contrasting deficits of 10%–20% commonly reported for knee extensors and flexors. As it is unclear if deficits in hip and lower-leg muscle strength resolve with appropriate rehabilitation or no postinjury or postoperative weakness occurs, individualised assessment should guide training of hip and lower-leg strength following ACL injury.PROSPERO registration numberCRD42020216793.
Child Health and Infection with Low Density (CHILD) malaria: a protocol for a randomised controlled trial to assess the long-term health and socioeconomic impacts of testing and treating low-density malaria infection among children in Tanzania
Authors: Jebiwott Sylvia , Gutapaka Nicolaus , Sumari Deborah , Loss Georg , Athuman Thabit , Nyandele Jane Paula , Cummins Hannah , Chemba Mwajuma , Benjamin-Chung Jade , Gangar Pamela , Wu Xue , Smith Jennifer , Chen Ingrid , Dorsey Grant , Fink Günther , Olotu Ally , Hsiang Michelle 
Published: March 2024

IntroductionAs malaria declines, low-density malaria infections (LMIs) represent an increasing proportion of infections and may have negative impacts on child health and cognition, necessitating development of targeted and effective solutions. This trial assesses the health, cognitive and socioeconomic impact of two strategies for detecting and treating LMI in a low transmission setting.Methods and analysisThe study is a 3-arm open-label individually randomised controlled trial enrolling 600 children aged 6 months to 10 years in Bagamoyo district, Tanzania. Children are randomised to one of three arms: active case detection with molecular (ACDm) testing by high volume quantitative PCR (qPCR), passive case detection also with molecular testing (PCDm) and a control of standard PCD using rapid diagnostics tests (RDTs). Over the 2-year trial, ACDm participants receive malaria testing using RDT and qPCR three times annually, and malaria testing by RDT only when presenting with fever. PCDm and PCD participants receive malaria testing by RDT and qPCR or RDT only, respectively, when presenting with fever. RDT or qPCR positive participants with uncomplicated malaria are treated with artemether lumefantrine. The primary outcome is cumulative incidence of all-cause sick visits. Secondary outcomes include fever episodes, clinical failure after fever episodes, adverse events, malaria, non-malarial infection, antibiotic use, anaemia, growth faltering, cognition and attention, school outcomes, immune responses, and socioeconomic effects. Outcomes are assessed through monthly clinical assessments and testing, and baseline and endline neurodevelopmental testing. The trial is expected to provide key evidence and inform policy on health, cognitive and socioeconomic impact of interventions targeting LMI in children.Ethics and disseminationStudy is approved by Tanzania NatHREC and institutional review boards at University of California San Francisco and Ifakara Health Institute. Findings will be reported on ClinicalTrials.gov, in peer-reviewed journals and through stakeholder meetings.Trial registration numberNCT05567016.
Development of capability lists for neonatal critical care at three levels in China: a modified Delphi study
Authors: Li Xing , Li Lei , Li Qiuping , Zhuang Lu , Zhang Yanping , Li Pengpeng , Zhang Qian , Zhang Shan , Li Ting , Kong Xiangyong , Feng Zhichun 
Published: March 2024

BackgroundThe standardised management of neonatal critical care centres can help improve health outcomes of vulnerable newborns. Guidance is required to update evidence related to construction and management of neonatal critical care centres in China.ObjectiveTo establish expert consensus on the essential capability lists for neonatal critical care at three levels in China.Design and settingAccording to China’s administrative divisions, the Chinese guidelines stratifies neonatal critical care into three levels: county level (basic and special care), city level (intensive care) and province level (comprehensive care including neonatal surgery and more subspecialty interventions). A modified Delphi study was conducted. A group of 20 neonatologists from the Chinese Association of Neonatologists rated the importance of capability items on a 5-point Likert scale.ResultsAt county level, the list consisted of 29 items related to basic and special care, and 3 items were unanimously rated very important by all experts: neonatal resuscitation, endotracheal intubation and continuous positive airway pressure ≥72 hours. At city level, group consensus defined 38 items as essential. Besides the essential items of county level, more items for intensive care were included in city level. At province level, 64 items reached consensus, including neonatal surgery and more advanced subspecialty interventions. The Kendall’s W values showed good agreement among experts in both rounds, and an increase from round 1 to round 2.ConclusionsWe developed the capability lists for neonatal critical care at three levels in China. Neonatal resuscitation should be provided by all levels. Interventions for preterm newborns are stratified according to gestational age and birth weight. Congenital abnormalities requiring surgical services need to be managed in high-level centres.
New quality outcome indicators for bone metastases: expert consensus analysis of patients, their families and specialist healthcare professionals
Authors: Downie Samantha , Chohan Hasnain , Ross Lauren , McCann Conor , Hall Peter , Stillie Alison , Moran Matthew , Sudlow Cathie , Simpson A Hamish RW 
Published: March 2024

ObjectivesAs workload increases, surgical care for patients with bone metastases is increasingly decentralised, with a shift in management away from primary bone tumour units to local centres. We must ensure that patients have similar outcomes regardless of where they receive their treatment. The aim was to develop and validate a set of quality outcome indicators (QOIs) to evaluate treatment success for patients undergoing surgery for bone metastases.MethodsOutcome recommendations were adapted from the literature and field tested in a retrospective patient cohort to determine feasibility. The provisional outcome indicators were assessed during a modified RAND/Delphi consensus process by a group of patients, relatives and healthcare professionals with validated targets added.Results1534 articles were reviewed. 38 quality objectives were extracted and assessed for feasibility using clinical records for 117 patients. 28 provisional outcome indicators proceeded to expert consensus and were reviewed by a group of 22 panellists including 10 patients and 4 relatives/carers. After two rounds, 15 QOIs were generated, with validated targets based on expert consensus. These included specific statements such as ‘surgery improves pain and reduces the need for morphine, target: at follow-up, pain is documented in 80% of individuals and 50% of these have reduced need for morphine’.ConclusionsThe published evidence and guidelines were adapted into a set of outcome indicators validated by patients, their family/carers and healthcare professionals. These can be used to compare care between centres and identify units of excellence in maximising good outcome after surgery for bone metastases.
The Deep Learning Framework iCanTCR Enables Early Cancer Detection Using the T-cell Receptor Repertoire in Peripheral Blood
Authors: Cai Yideng , Luo Meng , Yang Wenyi , Xu Chang , Wang Pingping , Xue Guangfu , Jin Xiyun , Cheng Rui , Que Jinhao , Zhou Wenyang , Pang Boran , Xu Shouping , Li Yu , Jiang Qinghua , Xu Zhaochun 
Published: March 2024

Abstract

T cells recognize tumor antigens and initiate an anticancer immune response in the very early stages of tumor development, and the antigen specificity of T cells is determined by the T-cell receptor (TCR). Therefore, monitoring changes in the TCR repertoire in peripheral blood may offer a strategy to detect various cancers at a relatively early stage. Here, we developed the deep learning framework iCanTCR to identify patients with cancer based on the TCR repertoire. The iCanTCR framework uses TCRβ sequences from an individual as an input and outputs the predicted cancer probability. The model was trained on over 2,000 publicly available TCR repertoires from 11 types of cancer and healthy controls. Analysis of several additional publicly available datasets validated the ability of iCanTCR to distinguish patients with cancer from noncancer individuals and demonstrated the capability of iCanTCR for the accurate classification of multiple cancers. Importantly, iCanTCR precisely identified individuals with early-stage cancer with an AUC of 86%. Altogether, this work provides a liquid biopsy approach to capture immune signals from peripheral blood for noninvasive cancer diagnosis.

Significance:
Development of a deep learning–based method for multicancer detection using the TCR repertoire in the peripheral blood establishes the potential of evaluating circulating immune signals for noninvasive early cancer detection.
Targeted and Shallow Whole-Genome Sequencing Identifies Therapeutic Opportunities in p53abn Endometrial Cancers
Authors: Jamieson Amy , Sobral de Barros Juliana , Cochrane Dawn R. , Douglas J. Maxwell , Shankar Sameer , Lynch Branden J. , Leung Samuel , Martin Spencer , Senz Janine , Lum Amy , Drew Yvette , Gilks C. Blake , Huntsman David G. , McAlpine Jessica N. 
Published: March 2024

Abstract

Purpose:
Shallow whole-genome sequencing (sWGS) can detect copy-number (CN) aberrations. In high-grade serous ovarian cancer (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers to identify additional prognostic stratification and therapeutic opportunities.

Experimental Design:
sWGS and targeted panel sequencing was performed on formalin-fixed, paraffin-embedded p53abn endometrial cancers. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed.

Results:
In 187 p53abn endometrial cancers, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. Twenty-two percent of potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with a high ploidy state, and CCNE1, ERBB2, and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. Twenty-eight percent of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. Thirty-four percent of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on IHC, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations.

Conclusions:
sWGS and targeted sequencing identified therapeutic opportunities in 75% of patients with p53abn endometrial cancer. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn endometrial cancers.
Best Overall Response–Associated Signature to Doxorubicin in Soft Tissue Sarcomas: A Transcriptomic Analysis from ANNOUNCE
Authors: Liu Jiangang , Moura David S. , Jones Robin L. , Aggarwal Amit , Ebert Philip J. , Wagner Andrew J. , Wright Jennifer , Martin-Broto Javier , Tap William D. 
Published: March 2024

Abstract

Purpose:
This exploratory analysis evaluated the tumor samples of the patients treated with doxorubicin (with or without olaratumab) in a negative phase III ANNOUNCE trial to better understand the complexity of advanced soft tissue sarcomas (STS) and to potentially identify its predictive markers.

Experimental Design:
RNA sequencing was performed on pretreatment tumor samples (n = 273) from the ANNOUNCE trial to evaluate response patterns and identify potential predictive treatment markers for doxorubicin. A BOR-associated signature to doxorubicin (REDSARC) was created by evaluating tumors with radiographic response versus progression. An external cohort of doxorubicin-treated patients from the Spanish Group for Research on Sarcomas (GEIS) was used for refinement and validation.

Results:
A total of 259 samples from the trial were considered for analysis. Comparative analyses by the treatment arm did not explain the negative trial. However, there was an association between the BOR signature and histologic subtype (χ2P = 2.0e−7) and grade (P = 0.002). There were no associations between the BOR signature and gender, age, ethnicity, or stage. Applied to survival outcomes, REDSARC was also predictive for progression-free survival (PFS) and overall survival (OS). Using the GEIS cohort, a refined 25-gene signature was identified and applied to the ANNOUNCE cohort, where it was predictive of PFS and OS in leiomyosarcoma, liposarcoma, and other sarcoma subtypes, but not in undifferentiated pleomorphic sarcoma.

Conclusions:
The refined REDSARC signature provides a potential tool to direct the application of doxorubicin in sarcomas and other malignancies. Validation and further refinement of the signature in other potentially subtype specific prospective cohorts is recommended.