bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of clinically relevant carbapenemase encoding genes in carbapenem-resistant Enterobacter cloacae complex and Klebsiella pneumoniae isolated from farmed freshwater fish
Authors: Dwivedi Arti , Kumar Chandra Bhushan , Kumar Anil , Soni Mayank , Sahu Vikash , Awasthi Abhishek , Rathore Gaurav 
Published: September 2023

Abstract

Aims
The present study was aimed to detect clinically relevant carbapenemase encoding genes in carbapenem-resistant Enterobacter cloacae complex (CR-ECC), Klebsiella pneumoniae (CR-KP), and Serratia plymuthica (CR-SP) isolated from farmed freshwater fish.

Methods and results
Out of 243 spatially diverse freshwater fish samples analysed, 5.3% were contaminated with CR-ECC, 1.6% with CR-KP, and 0.4% with CR-SP. The CR-ECC was further identified as E. asburiae (38.5%), E. mori (23.1%), E. cloacae (15.4%), E. hormaechei (15.4%), and E. kobei (7.7%) by 16S rRNA gene sequencing. The CR-ECC were resistant to carbapenems and cefoxitin, whereas CR-KP and CR-SP were multi-drug resistant (MDR). The CR-ECC harboured the carbapenemase gene blaIMI alone or in combination with blaTEM, blaEBC, blaCIT, blaACC, and tet(E). Whereas, CR-KP harboured carbapenemase gene, blaNDM-5 along with blaOXA-48, blaSHV, blaOXA-1, blaCTX-M-15, tet(A), sul1, and qnrB. No carbapenemase-encoding genes were detected in CR-SP. The MLST analysis showed that CR-KP belonged to ST231 and ST1561 lineages, while CR-ECC did not show exact match with any reported STs. The plasmid replicons predominantly detected were IncF and IncI1. Broth mating assays of CR-KP and CR-ECC with recipient Escherichia coli J53 indicated that blaNDM-5 was transferable but not blaIMI.

Conclusion
This study highlights the low-level contamination of carbapenem-resistant Enterobacterales (CRE) harbouring clinically relevant carbapenemase-encoding genes in farmed freshwater fish from India. The CR-ECC of fish origin did not show the potential to spread carbapenem resistance.
Phylogenomics analysis of multidrug-resistant Elizabethkingia anophelis in industrial wastewater treatment plant
Authors: Nascimento Ana Paula Alves , de Farias Beatriz Oliveira , Gonçalves-Brito Andressa Silva , Magaldi Mariana , Flores Claudia , Quidorne Camila Silva , Montenegro Kaylanne S , Bianco Kayo , Clementino Maysa Mandetta 
Published: September 2023

Abstract

Aims
This study investigated the phylogenetic relatedness of multidrug-resistant Elizabethkingia anophelis recovered from an industrial wastewater treatment plant (WWTPi).

Methods and results
The wastewater samples were plated in brain heart infusion agar (4 mg/L ceftazidime, 8 mg/L meropenem, and 2 mg/L polimixin). Four isolates recovered from four stages of WWTPi (influent, aeration, decantation, and treated effluent) were identified and evaluated of susceptibility profiles in the VITEK 2 system. These strains identified as E. meningoseptica were confirmed to be E. anophelis by whole genomic sequencing (Miseq-Illumina) and showed antimicrobial resistance genes of β-lactams, aminoglycosides, and tetracycline’s classes. The ribosomal multilocus sequence typing showed that they belong to the rST 65620 together with clinical strains. The phylogenomic tree revealed the similarity of our strains to those belonging to sublineage 11 and the single nucleotide polymorphism analysis confirmed that they belong to a single clade.

Conclusions
To the best of our knowledge, this is the first study reporting the persistence of multidrug-resistant E. anophelis sublineage 11 along the wastewater treatment.
Efficient calibration for imperfect epidemic models with applications to the analysis of COVID-19
Authors: Sung Chih-Li , Hung Ying 
Published: September 2023

Abstract
The estimation of unknown parameters in simulations, also known as calibration, is crucial for practical management of epidemics and prediction of pandemic risk. A simple yet widely used approach is to estimate the parameters by minimising the sum of the squared distances between actual observations and simulation outputs. It is shown in this paper that this method is inefficient, particularly when the epidemic models are developed based on certain simplifications of reality, also known as imperfect models which are commonly used in practice. To address this issue, a new estimator is introduced that is asymptotically consistent, has a smaller estimation variance than the least-squares estimator, and achieves the semiparametric efficiency. Numerical studies are performed to examine the finite sample performance. The proposed method is applied to the analysis of the COVID-19 pandemic for 20 countries based on the susceptible-exposed-infectious-recovered model with both deterministic and stochastic simulations. The estimation of the parameters, including the basic reproduction number and the average incubation period, reveal the risk of disease outbreaks in each country and provide insights to the design of public health interventions.
Neonate with congenital pulmonary airway malformation concurrent with enteric duplication cyst: a case report of a rare anomaly
Authors: Krishnan Amit , Schmoke Nicholas , Nemeh Christopher , Wu Yeu Sanz , Duron Vincent 
Published: September 2023

Abstract
A congenital pulmonary airway malformation (CPAM) occurring concurrently with an enteric duplication cyst is a rare anomaly. Definitive management for both abnormalities is usually surgical resection. We present the uncommon case of a neonate with a CPAM and ileal duplication cyst, including pre-natal and post-natal workup. The patient was brought to the operating room for laparoscopic duplication cyst excision at 3 months of age. The patient returned to the operating room for a thoracoscopic right lower lobectomy at five months of age. This case presents a rare congenital anomaly with the concurrent presentation of a CPAM and enteric duplication cyst, with both being successfully excised minimally invasively.
Characterization of intracellular membrane structures derived from a massive expansion of endoplasmic reticulum (ER) membrane due to synthetic ER-membrane-resident polyproteins
Authors: Sandor Andras , Samalova Marketa , Brandizzi Federica , Kriechbaumer Verena , Moore Ian , Fricker Mark D , Sweetlove Lee J 
Published: September 2023

Abstract
The endoplasmic reticulum (ER) is a dynamic organelle that is amenable to major restructuring. Introduction of recombinant ER-membrane-resident proteins that form homo oligomers is a known method of inducing ER proliferation: interaction of the proteins with each other alters the local structure of the ER network, leading to the formation large aggregations of expanded ER, sometimes leading to the formation of organized smooth endoplasmic reticulum (OSER). However, these membrane structures formed by ER proliferation are poorly characterized and this hampers their potential development for plant synthetic biology. Here, we characterize a range of ER-derived membranous compartments in tobacco and show how the nature of the polyproteins introduced into the ER membrane affect the morphology of the final compartment. We show that a cytosol-facing oligomerization domain is an essential component for compartment formation. Using fluorescence recovery after photobleaching, we demonstrate that although the compartment retains a connection to the ER, a diffusional barrier exists to both the ER and the cytosol associated with the compartment. Using quantitative image analysis, we also show that the presence of the compartment does not disrupt the rest of the ER network. Moreover, we demonstrate that it is possible to recruit a heterologous, bacterial enzyme to the compartment, and for the enzyme to accumulate to high levels. Finally, transgenic Arabidopsis constitutively expressing the compartment-forming polyproteins grew and developed normally under standard conditions.
Aeromedical Evacuation, the Expeditionary Medicine Learning Curve, and the Peacetime Effect
Authors: Hall Andrew , Olsen Cara , Dribben William , Glaser Jacob , Hanson Matthew 
Published: September 2023

ABSTRACT

Introduction
Organizational proficiency increases with experience, which is known as a learning curve. A theoretical peacetime effect occurs when knowledge and skills degrade during peacetime. In this study, the intertheater evacuation system was examined for evidence of a military learning curve and peacetime effect.

Materials and Methods
Data on medical evacuations from U.S. Central Command occurring between January 1, 2003, and December 31, 2022, were acquired from the TRANSCOM Regulating and Command & Control Evacuation System. Priority mission evacuation time corresponding to peak periods of activity in Iraq and Afghanistan and minimal activity in Afghanistan was analyzed. Any reduction or increase in the delivery time of casualties would be considered a change in proficiency.

Results
There was a marginal monthly decline of 0.019 days (27.4 min) to perform a priority evacuation from Iraq (95% confidence interval [CI], 0.009 to 0.028 days, P &lt; .001) and a decline of 0.010 days (14.4 min) from Afghanistan (95% CI, 0.003 to 0.016 days, P = .004) over 40 months from peak monthly average times. There was a monthly marginal increase in priority evacuation average time from Afghanistan of 0.008 days (11.5 min) (95% CI, 0.005 to 0.011, P &lt; .001) between January 2013 and December 2020. The number of monthly evacuations estimated to maintain or improve monthly average evacuation time is approximately 50.

Conclusions
An intertheater aeromedical evacuation system increased in proficiency during periods of conflict and declined during relative peacetime. There is evidence of a peacetime effect on intertheater aeromedical evacuation.
The galaxy cluster AC114 – II. Stellar populations and the mass–metallicity relation
Authors: Saviane Ivo , Yegorova Irina , Proust Dominique 
Published: September 2023

ABSTRACT
We investigate the mass–metallicity relation (MZR)for galaxies in the Abell cluster AC114 from 7 h of VIMOS/MR data collected at the European Southern Observatory-Very Large Telescope in 2009. The dynamical analysis completed in our previous paper allowed us to select cluster members, whose spectra are here analysed with stellar population synthesis models. Active and passive galaxies are identified based on the presence/absence of the [O ii] λ3727, [O iii] λλ4959, 5007 and/or Hβ emission lines, depending on the galaxy redshift. We find that active galaxies have lower average masses than passive ones, and have lower average metallicities. The MZR of the cluster is found to be steeper than that for galaxies in the local universe.
PREOPERATIVE BRAIN IRRADIATION IN GLIOBLASTOMA (POBIG TRIAL): FEASIBILITY AND EVALUATION OF TREATMENT RESPONSE IN ENHANCING AND NON-ENHANCING REGIONS
Authors: Waqar Mueez , Roncaroli Federico , Djoukhadar Ibrahim , Withington Lisa , Golby Christopher , Whitehurst Philip , Hewitt Lauren , Forte Gabriella , O’leary Claire , Colaco Rovel , Bailey Matthew , Karabatsou Konstantina , D’Urso Pietro , McBain Catherine , Coope David , Borst Gerben 
Published: September 2023

Abstract

AIMS
Patients with glioblastoma have dismal outcomes and there is an urgent need for new treatment modalities. The POBIG trial is the first to evaluate the safety and feasibility of single-fraction preoperative radiotherapy for newly diagnosed glioblastoma. We report the results from our first dose arm.

METHOD
POBIG is a phase I radiotherapy dose and volume escalation trial. The first dose arm received 8Gy preoperative radiotherapy to a maximum irradiation volume of 30cm3. The irradiation field included enhancing and non- enhancing FLAIR hyperintense regions judged as highest risk for remaining as postoperative residuum. Part of the tumour remained unirradiated (&lt;2Gy) with a margin for diagnostic sampling. Surgical resection took place within 1 week. Patients underwent diffusion/perfusion MRI scans before/after preoperative radiotherapy.

RESULTS
Two female and one male patient aged 61, 67 and 45 years, respectively, were enrolled. Preoperative radio- therapy was delivered at a dose of 8Gy to an irradiation volume of 7-30cm3. Near-total surgical resection was performed 2-3 days after preoperative radiotherapy treatment. Pathological examination of irradiated areas showed necrosis including fibrinoid necrosis of vessel walls. There was an increase in Ktrans permeability in both irradiated enhancing tumour (0.097,0.150) and unirradiated enhancing tumour (0.077,0.147) 24-hours after treatment. In contrast, no obvious changes were noted in irradiated (0.002,0.002) and unirradiated (0.002,0.004) non-enhancing FLAIR hyperintense regions or reference unirradiated contralateral white matter (0.000,0.000).

CONCLUSIONS
Preoperative radiotherapy is feasible in newly diagnosed glioblastoma. Very early radiotherapy changes manifest in enhancing tumour regardless of radiotherapy dose, evident as increased permeability and radiation- induced tumour necrosis.
NANO-OMICS FOR BLOOD BIOMARKER DISCOVERY IN GLIOBLASTOMA
Authors: Liu Anita , Hadjidemetriou Marilena , Kisby Thomas 
Published: September 2023

Abstract

AIMS
Glioblastoma (GBM) remains one of the most aggressive cancers with an average survival of only 12-15 months. Current diagnostic methods are burdensome and ineffective, underscoring an urgent need to improve early detection and monitoring. The application of ‘liquid-biopsy’ markers holds great promises however, despite technological advances, to date there are no clinically used blood-based biomarkers for GBM. We have recently introduced the ‘Nano-Omics’ paradigm, which utilises nanoparticles (NPs) as scavenging platforms to capture and enrich disease-associated analytes from biological fluids for omics analyses. In this study, we utilised the Nano-Omics pipeline coupled with brain tissue mass spectrometry-based proteomics, to unveil GBM specific protein biomarker candidates.

METHOD
We exploited the spontaneous interaction of nanoparticles with blood proteins to comprehensively analyse the blood proteome of GL261 glioma-bearing C57BL/6J mice. Tumoural and peritumoural brain tissue originated from the same animals were also collected, micro-dissected and analysed by label free mass spectrometry in order to correlate the nanoparticle-enriched blood-circulating proteome with the tumour tissue proteome.

RESULTS
Our data revealed a number of GBM-specific biomarker candidates in blood even at low tumour burden, followed by validation in a human GBM clinical cohort. Furthermore, the peritumoural region of glioblastoma GBM displayed unique proteomic profiling, shedding light on the mechanism behind GBM infiltration and recurrence.

CONCLUSIONS
Our work highlights the importance of integrating blood and brain tissue proteomics and opens up new possibilities for further validation of the proteomic signatures discovered with the potential for further development of a much-needed blood test for GBM early detection and monitoring.
A NOVEL THERAPEUTICS ACCELERATOR TO SUPPORT A STRONGER BRAIN TUMOUR TREATMENT PIPELINE
Authors: Huskens Nicky , Aitken Charlotte , Bushby Katie 
Published: September 2023

Abstract

AIMS
Despite several encouraging pre-clinical studies, few therapeutics make it to successful human trials. There is a need for a stronger new treatment pipeline to improve outcomes for patients with brain tumours. The Tessa Jowell Brain Cancer Mission have launched the Brain Tumour Research Novel Therapeutics Accelerator (BTR- NTA) to provide bespoke advice and support to scientists and help position their therapeutic along a realistic pathway to clinical trials

METHOD
The BTR-NTA programme is supported by an international committee of brain tumour, pre-clinical science, and pharmaceutical experts who meet twice yearly to review up to five novel brain tumour therapeutics. Both academic and industry applicants, at any stage of pre-clinical or clinical work, can apply and submit their work to date before meeting with the BTR-NTA committee to discuss their therapeutic and progress. The committee then provides a written feedback report with advice and recommendations on next steps. The committee will also facilitate connections with industry partners and funders where possible.

RESULTS
It is hoped that BTR-NTA will provide benefits for the whole brain tumour community by: increasing the number of brain tumour therapeutics reaching patients; providing applicants with constructive feedback so that avoidable pitfalls can be overcome; strengthening international relationships between academics, industry, government, and regulatory bodies; and de-risking investment into brain tumour therapeutics for funders.

CONCLUSIONS
The first BTR-NTA meeting will be held in November 2023, with applications opening mid-2023.
DEMOGRAPHICS, GENETICS, AND EPIGENETICS INflUENCE THE LESION DISTRIBUTION OF GLIOMA
Authors: Ruffle James , Mohinta Samia , Brandner Sebastian , Hyare Harpreet , Nachev Parashkev 
Published: September 2023

Abstract

AIMS
Tumour heterogeneity is increasingly recognized as a major obstacle to therapeutic innovation in neuro- oncology. Gliomas typically exhibit a spectrum of genetic mutations, reflecting multiple, potentially complex molecular interactions, and vary widely in their imaging appearances across size, morphology, texture, anatomical distribution, and many other spatial properties. This multifaceted diversity obscures the relationship be- tween tumour genotypic and imaging features, and their joint influence on disease evolution and treatment susceptibility. Though opaque to simple statistical methods, it may nonetheless be accessible to models with the expressivity to capture complex interactions between many different factors.

METHOD
Studying an international sample of 4064 IDH-wildtype glioblastoma, IDH-mutant oligodendroglioma and astrocytoma, deploying an in-house developed state-of-the-art lesion segmentation model, here we map the characteristic distribution of tumour tissue components across the brain and link their spatial properties lesion genetics and epigenetics.

RESULTS
We identify radical differences in tumour spatial topology related not only to diagnosis, but also age, sex, and genetic/epigenetic markers inclusive of TERT, EGFR, and MGMT methylation status. Lesions were equally common across left and right cerebral hemispheres, but significantly larger at presentation when right-sided (p&lt;0.0001), indicating these lesions present later. Both glioblastoma and astrocytoma were commonly temporally based, though oligodendroglioma were often frontal. EGFR amplification was more common in right temporal lesions, whilst MGMT methylation and TERT appeared more bilateral.

CONCLUSIONS
Our results reveal the deep topological structure of gliomas, enabling richer, more closely individuating phenotyping, the development of more robust predictive models of treatment and prognosis, and illuminating multi- modal associations of potential mechanistic significance.
RADIOMICS TO PREDICT THE RESPONSE OF BRAIN METASTASES TO STEREOTACTIC RADIOTHERAPY
Authors: Rozati Hamoun , Angelini Elsa , Williams Matthew 
Published: September 2023

Abstract

AIMS
Radiomics converts routinely obtained medical imaging into mineable, high-dimensionality data. We assessed its utility for incorporation into a multivariate model to predict the likelihood of response of brain metastases (BMs) to stereotactic radiotherapy (SRT).

METHOD
Patients treated with SRT over a ten-year period for BMs at three tertiary centres were retrospectively analyzed. SRT planning MRI scans were pre-processed, and radiomic features were extracted from each BM using PyRadiomics software. Follow up scans were analyzed for response and quantified by a modification of the Response Assessment in Neuro-Oncology Brain Metastases criteria. A radiomic signature predictive of BM response was created by a stepwise process involving correlation coeffcients and a binary least absolute shrinkage and se- lection operator regression analysis. A clinical predictive multivariate model for predicting response was com- pared against a combination clinical/radiomic model by McFadden’s pseudo-R-squared test.

RESULTS
520 patients were included contributing a total of 1891 BMs. 1131 radiomic features were extracted from each BM. 12 features were used to construct a radiomic signature. Mean dose and BM volume were independent predictors of response in both the clinical and radiomics models. The radiomic signature was an independent prognostic predictor for response in the radiomic model (HR=1.095-1.231). Goodness of fit for predicting response was greater in the radiomics model (McFadden’s pseudo-R-squared score 0.243 vs 0.211), and statistically significant by likelihood ratio test (p=0.021).

CONCLUSIONS
This multi-centre retrospective analysis created a unique radiomic signature for predicting BM response to SRT and is the first study to incorporate clinical factors. A prospective validation study is planned.
INCIDENCE AND PREDICTORS OF CLINICALLY SIGNIfiCANT ACUTE AND LATE TREATMENT-RELATED TOXICITY AFTER STEREOTACTIC RADIOSURGERY IN 4 OR MORE BRAIN METASTASES
Authors: Parikh Shefali , Alluri Usha , Benghiat Helen , Heyes Geoff , Meade Sara , Sawlani Vijay , Chavda Swarupsinh , Watts Colin , Hickman Mitchell , Sanghera Paul 
Published: September 2023

Abstract

AIMS
Selected patients with multiple brain metastases can benefit from stereotactic radiosurgery (SRS). Brain V12 (total brain volume receiving 12Gy including target) can predict for late toxicity in single target benign disease, however their value remains uncertain for multiple brain metastases. We report the incidence and evaluate predictors of toxicity in patients with 4 or more brain metastases treated with single fraction SRS.

METHOD
226 patients with 2160 treated metastases from 2014-21 were retrospectively studied. Severe acute toxicity, and symptomatic late toxicity (new/progressive neurological symptoms ≥ 3 months post SRS) with MRI changes suggestive of treatment-effect were analysed. Kaplan-Meier method and cumulative incidence function was used to assess survival and toxicity respectively.

RESULTS
Median number of metastases per patient was 6 (range 4-41) and median V12 was 11.3cc (range 1.5- 45.2cc). Median overall survival (mos.) was 7.6 months. Absolute incidence of acute grade 3/4 cerebral oedema/haemorrhage was 4.9%. The subgroup developing late SRS-related toxicity (16 patients) had a higher mos. than those without toxicity (25mos vs 5 mos., p &lt;0.002). 9/16 (56%) patients developed Grade 3 or 4 toxicity. 82/226 patients survived &gt;12 months and cumulative incidence function of symptomatic SRS-related late toxicity in this group was 4% at 1 year and 9.5% at 2 years.

CONCLUSIONS
Within the limits of data available a brain V12 value did not meaningfully predict for late SRS related toxicity in patients with multiple brain metastases. The cumulative incidence of clinically relevant late toxicity remains &lt;10% at 2 years despite accepting a high median V12 to treat these patients.