bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five-year analysis of the in vitro activity of tedizolid against a worldwide collection of indicated species causing clinical infections: results from the Surveillance of Tedizolid Activity and Resistance (STAR) programme
Authors: Carvalhaes Cecilia G , Sader Helio S , Streit Jennifer M , Mendes Rodrigo E 
Published: September 2022

Abstract

Objectives
The Surveillance of Tedizolid Activity and Resistance (STAR) programme monitored the tedizolid activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus anginosus group. We evaluated the antimicrobial susceptibility of 47 400 unique Gram-positive clinical isolates from the STAR programme collected from USA (21 243), Europe (17 674), Asia-Pacific (4954) and Latin America (3529) medical centres (2015–19).

Methods
All isolates were tested for susceptibility by reference broth microdilution method. WGS and in silico analysis were performed on linezolid-non-susceptible (NS) isolates.

Results
Tedizolid was active against ≥99.9% of S. aureus (100.0% of MSSA and &gt;99.9% of MRSA), E. faecalis, S. pyogenes, S. agalactiae and S. anginosus group isolates, with MIC50 values ranging from 0.12 to 0.25 mg/L and MIC90 values of 0.25 mg/L. Linezolid, vancomycin and daptomycin were also active agents against these organisms. Tedizolid inhibited all VRE and 73.1% of linezolid-NS E. faecalis isolates. Ampicillin and daptomycin retained 100.0% activity against VRE and linezolid-NS E. faecalis isolates. Linezolid-NS E. faecalis isolates carried mostly the optrA gene. G2576T alterations in the 23S rRNA were observed in one linezolid-NS S. aureus isolate and one linezolid-NS E. faecalis isolate.

Conclusions
No resistance trends were observed for tedizolid during the study period.
MDR Shigella sonnei in Spain: an ever-evolving emerging threat?
Authors: Ortiz de la Rosa José Manuel , Rodríguez-Villodres Ángel , Casimiro-Soriguer Carlos S , Ruiz-Pérez De Pipaón Maite , Briones Eduardo , Aznar Fernández María , Lepe José Antonio 
Published: September 2022

Abstract

Background
Seven CTX-M-27-producing Shigella sonnei strains were isolated at the University Hospital Virgen del Rocío (Seville, Spain) microbiology service from October to November 2021.

Objectives
To offer extensive information on the microbiological and molecular epidemiology results of the seven S. sonnei isolates and compare them with other previously documented CTX-M-27-producing S. sonnei associated with MSM transmission.

Methods
S. sonnei isolated from stool samples of patients with acute diarrhoea were identified through biochemical and serological typing. Whole characterization of the seven isolates was performed by sequencing with MinION Mk1C followed by genomic and molecular analysis.

Results
All the isolates were resistant to penicillins, cephalosporins, fluoroquinolones, cotrimoxazole and azithromycin. Sequencing showed the presence of several resistance determinants, outstanding blaCTX-M-27, azithromycin resistance genes [ermB and mph(A)], qnrB19 and mutations in the QRDRs. All isolates belonged to the same hierarchical clustering of cgMLST (HierCC) with five allele distance (HC5) scheme v1 from EnteroBase. However, they presented differences in plasmid composition, with all seven isolates harbouring IncFII, IncB/O/K/Z and ColE1-like while SH2, SH6 and SH7 had IncFIB only. Our isolates were closely related to others from Spain (HC5; 98748), Australia (HC5; 98748) and the UK (HC5; 98748), which were also associated with MSM transmission. Nevertheless, the structure of the non-chromosomal genetic elements and the genetic context of blaCTX-M-27 presented a certain variability compared with isolates from other countries and among them.

Conclusions
This study confirms the emergence of CTX-M-27-producing S. sonnei (ST152) associated with MSM transmission in Spain, adding it to the Europe outbreak list and reinforcing the necessity of active surveillance and control of this high-risk clone.
Impact of patient portal-based self-scheduling of diagnostic imaging studies on health disparities
Authors: Ganeshan Smitha , Pierce Logan , Mourad Michelle , Judson Timothy J , Kohli Marc D , Odisho Anobel Y , Brown William 
Published: September 2022

Abstract
While many case studies have described the implementation of self-scheduling tools, which allow patients to schedule visits and imaging studies asynchronously online, none have explored the impact of self-scheduling on equitable access to care.1 Using an electronic health record patient portal, University of California San Francisco deployed a self-scheduling tool that allowed patients to self-schedule diagnostic imaging studies. We analyzed electronic health record data for the imaging modalities with the option to be self-scheduled from January 1, 2021 to September 1, 2021. We used descriptive statistics to compare demographic characteristics and created a multivariable logistic regression model to identify predictors of patient self-scheduling utilization. Among all active patient portal users, Latinx, Black/African American, and non-English speaking patients were less likely to self-schedule studies. Patients with Medi-Cal, California’s Medicaid program, and Medicare insurance were also less likely to self-schedule when compared with commercially insured patients. Efforts to facilitate use of patient portal-based applications are necessary to increase equitability and decrease disparities in access.
Kolmogorov and Kuroda translations into basic predicate logic
Authors: Ardeshir Mohammad , Ruitenburg Wim 
Published: September 2022

Abstract
Kolmogorov established the principle of the double negation translation by which to embed Classical Predicate Logic ${\operatorname {CQC}}$ into Intuitionistic Predicate Logic ${\operatorname {IQC}}$. We show that the obvious generalizations to the Basic Predicate Logic of [3] and to ${\operatorname {BQC}}$ of [12], a proper subsystem of ${\operatorname {IQC}}$, go through as well. The obvious generalizations of Kuroda’s embedding are shown to be equivalent to the Kolmogorov variant. In our proofs novel nontrivial techniques are needed to overcome the absence of full modus ponens in Basic Predicate Logic. In [3] we argued that ${\operatorname {IQC}}$ is not the logic of constructive mathematics. Our doubts were far from new. New was that we put forward an alternative, ${\operatorname {BQC}}$. One concern is that ${\operatorname {BQC}}$ is too weak for serious mathematics, or even trivial. This paper is one step to alleviate such concerns.
Race, Ethnicity, and Health Disparities in US Children With COVID-19: A Review of the Evidence and Recommendations for the Future
Authors: Vicetti Miguel Claudia P , Dasgupta-Tsinikas Shom , Lamb Gabriella S , Olarte Liset , Santos Roberto P 
Published: September 2022

Abstract
Coronavirus disease 2019 (COVID-19) is an important cause of morbidity in children in the United States (U.S.). Moreover, the U.S. has witnessed significant disparities affecting American Indian/Alaska Native, Black, and Hispanic/Latino children, stemming from systemic racism and social-structural inequalities and not differences in innate biological susceptibility. We review what is known on COVID-19 and health disparities in disease burden, access to care, pharmaceutical interventions, and clinical research in children, with a focus on the U.S. context. In addition, we propose strategies to communicate scientific data in ways that do not promote racism and biological susceptibility themes, and to address pediatric disparities in clinical infectious diseases research.
Hemophilia B acquired after cadaveric liver transplantation: a case report
Authors: Machado e Silva Gomide Larissa , Weihermann Viktoria , de Oliveira Isabella Corrêa , Nissel Maria Alice Zarate , Valejo Igor Raphael Mathias , da Silva Wolff Lucas , de Aguiar Alan Junior , Verona Dunia , Degraf Ygor , de Carvalho Arouca Julianna Storace , Barros Sanches João Paulo , Cabral Rodrigo Rezende Silva , Kampa Katia Cristina , de Freitas Alexandre Coutinho Teixeira , Tefili Nertan Luiz 
Published: September 2022

Abstract
Hemophilia B is a recessive hereditary disease, and manifestations result from coagulation factor IX deficiency. Although improbable, as factor IX is produced exclusively in the liver, the possibility of developing the disease after transplantation represents an infrequent but potentially morbid complication. Standard laboratory tests may be insufficient to determine the probability of transmission of this pathology. This report describes the case of a patient who developed hemophilia B after liver transplantation whose donor had no prior knowledge of the disease.
A feeding jejunostomy causing an intussusception – case report and literature review
Authors: Tian Jane , Bhatia Shubham , Mourad Youssef , Hall Philip , Louis Martine A , Khan Noman 
Published: September 2022

Abstract
Use of enteral nutrition has increased dramatically over the past two decades due to improved nutritional formulas, better quality feeding tubes and the ability to use less invasive endoscopic, fluoroscopic and laparoscopic techniques. Intussusception accounts for 1–5% of adult intestinal obstructions, with feeding tubes acting as a lead point in &lt; 1% of cases. Since intussusception is rare, especially in adults, it is not always considered in the initial differential diagnosis of patients presenting with abdominal pain, nausea, vomiting or constipation. If left untreated, intussusception can eventually lead to bowel compromise, poor outcomes and even death. Therefore, prompt recognition and correction are necessary. We present a case of small bowel obstruction in an elderly male secondary to a tube-related intussusception. A review of the signs, symptoms and treatment recommendations is provided.
Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
Authors: Hao Shuailin , Wang Ya , Zhao Yuqin , Gao Wen , Cui Wei , Li Youhang , Cui Jian , Liu Yu , Lin Lixiu , Xu Xingzhi , Wang Hailong 
Published: September 2022

Abstract
The reversible post-translational modification (PTM) of proteins plays an important role in many cellular processes. Lysine crotonylation (Kcr) is a newly identified PTM, but its functional significance remains unclear. Here, we found that Kcr is involved in the replication stress response. We show that crotonylation of histone H2A at lysine 119 (H2AK119) and ubiquitination of H2AK119 are reversibly regulated by replication stress. Decrotonylation of H2AK119 by SIRT1 is a prerequisite for subsequent ubiquitination of H2AK119 by BMI1. Accumulation of ubiquitinated H2AK119 at reversed replication forks leads to the release of RNA Polymerase II and transcription repression in the vicinity of stalled replication forks. These effects attenuate transcription–replication conflicts (TRCs) and TRC-associated R-loop formation and DNA double-strand breaks. These findings suggest that decrotonylation and ubiquitination of H2A at lysine 119 act together to resolve replication stress-induced TRCs and protect genome stability.
Interpreting alignment-free sequence comparison: what makes a score a good score?
Authors: Swain Martin T , Vickers Martin 
Published: September 2022

AbstractAlignment-free methods are alternatives to alignment-based methods when searching sequence data sets. The output from an alignment-free sequence comparison is a similarity score, the interpretation of which is not straightforward. We propose objective functions to interpret and calibrate outputs from alignment-free searches, noting that different objective functions are necessary for different biological contexts. This leads to advantages: visualising and comparing score distributions, including those from true positives, may be a relatively simple method to gain insight into the performance of different metrics. Using an empirical approach with both DNA and protein sequences, we characterise different similarity score distributions generated under different parameters. In particular, we demonstrate how sequence length can affect the scores. We show that scores of true positive sequence pairs may correlate significantly with their mean length; and even if the correlation is weak, the relative difference in length of the sequence pair may significantly reduce the effectiveness of alignment-free metrics. Importantly, we show how objective functions can be used with test data to accurately estimate the probability of true positives. This can significantly increase the utility of alignment-free approaches. Finally, we have developed a general-purpose software tool called KAST for use in high-throughput workflows on Linux clusters.
SIQ: easy quantitative measurement of mutation profiles in sequencing data
Authors: van Schendel Robin , Schimmel Joost , Tijsterman Marcel 
Published: September 2022

Abstract
With the emergence of CRISPR-mediated genome editing, there is an increasing desire for easy-to-use tools that can process and overview the spectra of outcomes. Here, we present Sequence Interrogation and Quantification (SIQ), a simple-to-use software tool that enables researchers to retrieve, data-mine and visualize complex sets of targeted sequencing data. SIQ can analyse Sanger sequences but specifically benefit the processing of short- and long-read next-generation sequencing data (e.g. Illumina and PacBio). SIQ facilitates their interpretation by establishing mutational profiles, with a focus on event classification such as deletions, single-nucleotide variations, (templated) insertions and tandem duplications. SIQ results can be directly analysed and visualized via SIQPlotteR, an interactive web tool that we made freely available. Using insightful tornado plot visualizations as outputs, we illustrate that SIQ readily identifies sequence- and repair pathway-specific mutational signatures in a variety of model systems, such as nematodes, plants and mammalian cell culture.
KS04.5.A Development of a somatostatin receptor type 2 (SSTR2)-targeted probe for near infrared fluorescence guided meningioma surgery
Authors: Fürtjes G , Weitzenberg M , Arús B , Rolbieski H , Mawrin C , Goldbrunner R , Plettenburg O , Bruns O , Neuschmelting V 
Published: September 2022

Abstract

Background
Meningioma mostly recur at the primary resection bed requiring improvement in the intraoperative tumor visualization and surgical technique. This study aims to develop a highly specific and sensitive optical probe for intraoperative meningioma imaging to guide the tumor resection. Fluorescent dyes in the near infrared (NIR I, 700-1000nm) and shortwave infrared (NIR II, 1000-2000nm) allow detection by suitable cameras up to few millimeters in depth in real time. Our objective is to invent a fluorescent NIR I and II probe specifically targeting the somatostatin receptor type 2 (SSTR2) reliably overexpressed in meningioma independently of WHO grade and subtype.

Material and Methods
By linking a somatostatin analogue (TATE, Tyr(3)Thr(8)-Octreotid) to a new developed dye (sNIR), we synthesized a SSTR2 specific probe. Its optical properties are comparable to indocyanine green and stability as well as bleaching kinetic were observed in vitro. The probe was intravenously injected in native mice to evaluate pharmacokinetics and biodistribution and detected by a custom-built camera setup focusing on physiologically highly expressing SSTR2 tissues validated by immunohistochemistry (IHC). As proof-of-principle fluorescence guided tumor resection was performed in an ectopic and orthotopic meningioma IOMM-Lee mouse model.

Results
The SSTR2-sNIR probe is stable in aqueous solution up to 12h with favorable optical properties regarding kinetics, biodistribution and photostability compared to its IRDye800 analogue. In vivo, we observed a highly specific physiological signal uptake in the gastric epithelium, the pancreas and pituitary (they are highly expressing SSTR2 on IHC) compared to autofluorescence and negative controls (unlabeled dye and scrambled version). Given the moderate SSTR2 expression in the preclinical meningioma model we could still detect a mean tumor-to-brain ratio of 6.12 (n = 5; SD 1.8) in the orthotopic meningioma mouse model, allowing the fluorescence guidance to be feasible.

Conclusion
Our preclinical results demonstrate that the innovative SSTR2-targeted fluorescent probe is stable in various biological media over time and capable of specifically targeting the SSTR2 in vitro and in vivo potentially enabling sensitive and specific meningioma fluorescent guided surgery in the future.
KS05.6.A Oral DNA vaccination targeting VEGFR2 combined with the anti-PD-L1 antibody avelumab in patients with progressive glioblastoma - final results. NCT03750071
Authors: Wick W , Wick A , Chinot O , Sahm F , von Deimling A , Jungk C , Mansour M , Podola L , Lubenau H , Platten M 
Published: September 2022

Abstract

Background
Vascular endothelial growth factor receptor (VEGFR)2 overexpression on glioblastoma endothelia serves as a target for VEGFR2 primed T cells using VXM01 DNA vaccine encoding for VEGFR2. VXM01 is delivered in a bacterial Ty21a carrier suitable for oral administration. A previous phase I/II study in 14 patients with progressive glioblastoma showed a positive correlation of of VEGFR2 specific T cells as well as altered intra-tumoral immunity with prolonged overall survival. One partial response was reported with VXM01 alone. The current trial aimed at intensifying the efficacy signal and testing the co-administration of a checkpoint inhibitor.

Material and Methods
A multicentre, open-label phase I/II study (EudraCT 2017 003076 31) included 28 patients (25 non-resectable, 3 resectable) with progressive glioblastoma after standard chemoradiotherapy. VXM01 was administered on day 1, 3, 5, 7 followed by boostings q4w. Avelumab (800 mg) was given intravenously q2w. Treatment continued up to week 96 followed by a 2-year observation period. Endpoints included safety and tolerability, objective response rate (ORR), clinical response using immune-response assessment in Neurooncology criteria (iRANO), and immunological assays like ELISpot, FACS, and tumor immune biomarkers.

Results
Treatment with VXM01 106 or 107 CFU plus avelumab was completed in all patients. No treatment-related toxicities were observed. Three partial responses (according to iRANO) with tumor reductions of 58, 81 and 95% to baseline, respectively, were reported in the non-resectable patients (Objective response rate (ORR) was 12% (3/25)). Two of these patients were progression-free &gt; 12 months. Best response in 3 additional non-resectable patients was SD including one patient progression-free &gt; 6 months. In one resected patient, tumor shrinkage of 30% each was observed after initial treatment before resection as well as subsequent to incomplete resection, associated with survival &gt; 18 months, and accompanied by an increase of intratumoral CD8+ T-cells.

Conclusion
VXM01 in combination with avelumab was safe and produced detectable peripheral VEGFR-2-specific immune responses. Three non-resected patients had an objective response, three more patients experienced best response stable disease. For future studies a patient enrichment strategy based on immune biomarkers might be envisaged.
JS09.5.A Is Radiation Dose to Sleep-relevant Brain Structures Associated with Lower Sleep Quality in Adults with Primary Brain Tumors?
Authors: Amidi A , Haldbo-Classen L , Kallehauge J , Wu L , Lukacova S , Lassen Y , Zachariae R , Hoyer M 
Published: September 2022

Abstract

Background
Sleep plays a central role in optimal brain health and daily functioning, and poor sleep is associated with impaired cognitive functioning and reduced quality of life. Despite improved precision of modern radiotherapy (RT) for brain tumors, radiation to healthy tissue, including brain structures relevant for sleep/wake regulation, is often inevitable. In the present study, we investigate whether radiation dose to sleep/wake-relevant brain structures is associated with poorer patient-reported sleep quality in primary brain tumor patients.

Material and Methods
Patients who had received RT for non-glioblastoma primary brain tumors between 2006 and 2016 were included. They completed the Pittsburg Sleep Quality Index (PSQI) and mean radiation doses to sleep/wake-relevant structures (i.e., brainstem, thalamus, hypothalamus, and the pituitary and pineal glands) were calculated based on planning CTs and contrast-enhanced MR-images. Mean radiation dose (Dmean) to brain structures were compared between patients with and without impaired sleep outcomes using bootstrapped independent t-tests. Differences with effect sizes (ES, Cohen’s d) exceeding ± 0.3 are reported.

Results
A total of 78 patients (glioma, grade 1-3 = 28; meningioma = 22, pituitary = 16, other = 12) were included. Median time since RT was 4.6 years (range = 8.4 years). Mean global PSQI score was 5.13 (SD = 3.1). No differences were observed between tumor types, F (3,74) = 0.37, η 2= .02. Clinical sleep disturbance (PSQI &gt; 5) was reported by 37.2% (n=29). Compared with patients without sleep disturbance, those with sleep disturbance had received a higher radiation dose to the pituitary gland, Dmean = 26.11 Gy, SE = 2.59, versus 34.57 Gy, SE = 3.43, ES(d) = - 0.46, 95% CI [-0.93, 0.003]. Furthermore, compared with patients reporting normal sleep latency (SL), those with poor SL had received a higher radiation dose to the pituitary gland, Dmean = 24.55 Gy, SE = 3.71, versus 32.60 Gy, SE = 2.48, ES(d) = - 0.44, 95% CI [-0.90, 0.03], and the brain stem, Dmean = 15.32 Gy, SE = 2.71, versus 20.20 Gy, SE = 2.01, ES(d) = -3.44, 95% CI [-0.80, 0.12]. Finally, compared with patients with a high sleep efficiency (&gt;85%), those with a low sleep efficiency had received a higher radiation dose to the thalamus, Dmean = 18.11 Gy, SE = 2.36, versus 24.55 Gy, SE = 4.43, ES(d) = -0.35, 95% CI [-0.83, 0.15], and the pineal gland, Dmean = 16.20 Gy, SE = 2.48, versus 23.10 Gy, SE = 4.25, ES(d) = -0.36, 95% CI [-0.85, 0.13].

Conclusion
The prevalence of clinical sleep disturbances in patients with primary brain tumors was high (37%). Our results indicated that higher radiation doses to the pituitary gland, brain stem, thalamus, and pineal gland may be risk factors for poor sleep quality in patients with a primary brain tumor.