bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Hypertension Diagnostic Testing and Diagnosis Associated With Psychological Distress?
Authors: Green B B , Anderson M L , McClure J B , Ehrlich K , Hall Y N , Hansell L , Hsu C , Margolis K L , Munson S A , Thompson M J
Published: September 2023

BACKGROUND

Psychological impacts of hypertension diagnostic testing and new hypertension diagnoses are unclear.

METHODS

BP-CHECK was a randomized diagnostic study conducted in 2017–2019 in an integrated healthcare system. Participants with no hypertension diagnosis or medications and elevated blood pressure (BP) were randomized to one of three diagnostic regimens: (i) Clinic, (ii) Home, or (iii) Kiosk. Participants completed questionnaires at baseline, after completion of the diagnostic regimens, and at 6 months. Outcomes included changes from baseline in health-related quality of life (HRQOL), BP-related worry, and thoughts about having a stroke or heart attack.

RESULTS

Participants (n = 482) were mostly over age 50 (77.0%), and White race (80.3%). HRQOL did not significantly change from baseline to 3 weeks or 6 months. Among all participants, BP-related worry and concerns about having a heart attack or stroke increased significantly from baseline to 3 weeks, with heart attack and stroke concerns significantly higher in the Kiosk compared Clinic and Home groups. At 6 months, thoughts about having a heart attack or stroke returned to baseline overall and in the Kiosk group, however BP-related worry was significantly higher among those with, compared to those without, a new hypertension diagnosis.

CONCLUSIONS

The hypertension diagnostic process did not lead to short-term or intermediate-term changes in self-reported HRQOL. However, BP-related worry increased short-term and persisted at 6 months among individuals with a new hypertension diagnosis. Results warrant validation in more representative populations and additional exploration of the impacts of this worry on psychological well-being and hypertension control.

ClinicalTrials.gov Identifier

NCT03130257.
KAS-Analyzer: a novel computational framework for exploring KAS-seq data
Authors: Lyu Ruitu , Wu Tong , Park Gayoung , He Yu-Ying , Chen Mengjie , He Chuan
Published: September 2023

Motivation

Kethoxal-assisted ssDNA sequencing (KAS-seq) is rapidly gaining popularity as a robust and effective approach to study the nascent dynamics of transcriptionally engaged RNA polymerases through profiling of genome-wide single-stranded DNA (ssDNA). Its latest variant, spKAS-seq, a strand-specific version of KAS-seq, has been developed to map genome-wide R-loop structures by detecting imbalances of ssDNA on two strands. However, user-friendly, open-source computational tools tailored for KAS-seq data are still lacking.

Results

Here, we introduce KAS-Analyzer, the first comprehensive computational framework aimed at streamlining and enhancing the analysis and interpretation of KAS-seq and spKAS-seq data. In addition to standard analyses, KAS-Analyzer offers many novel tools specifically designed for KAS-seq data, including, but not limited to: calculation of transcription-related metrics, identification of single-stranded transcribing (SST) enhancers, high-resolution mapping of R-loops, and differential RNA polymerase activity analysis. We provided a detailed overview of KAS-seq data and its diverse applications through the implementation of KAS-Analyzer. Using the example time-course KAS-seq datasets, we further showcase the robust capabilities of KAS-Analyzer for investigating dynamic transcriptional regulatory programs in response to UVB radiation.

Availability and implementation

KAS-Analyzer is available at https://github.com/Ruitulyu/KAS-Analyzer.
WSIC: a Python package and command-line interface for fast whole slide image conversion
Authors: Pocock Johnathan , Raza Shan E Ahmed , Minhas Fayyaz , Rajpoot Nasir
Published: September 2023

Whole slide images (WSIs) are multi-gigapixel images of tissue sections, which are used in digital and computational pathology workflows. WSI datasets are commonly heterogeneous collections of proprietary or niche specialized formats which are challenging to handle. This note describes an open-source Python application for efficiently converting between WSI formats, including common, open, and emerging cloud-friendly formats. WSIC is a software tool that can quickly convert WSI files across various formats. It has a high performance and maintains the resolution metadata of the original images. WSIC is ideal for pre-processing large-scale WSI datasets with different file types.

Availability and implementation

Source code is available on GitHub at https://github.com/John-P/wsic/ under a permissive licence. WSIC is also available as a package on PyPI at https://pypi.org/project/WSIC/.
DrForna: visualization of cotranscriptional folding
Authors: Tănasie Anda Ramona , Kerpedjiev Peter , Hammer Stefan , Badelt Stefan
Published: September 2023

Motivation

Understanding RNA folding at the level of secondary structures can give important insights concerning the function of a molecule. We are interested to learn how secondary structures change dynamically during transcription, as well as whether particular secondary structures form already during or only after transcription. While different approaches exist to simulate cotranscriptional folding, the current strategies for visualization are lagging behind. New, more suitable approaches are necessary to help with exploring the generated data from cotranscriptional folding simulations.

Results

We present DrForna, an interactive visualization app for viewing the time course of a cotranscriptional RNA folding simulation. Specifically, users can scroll along the time axis and see the population of structures that are present at any particular time point.

Availability and implementation

DrForna is a JavaScript project available on Github at https://github.com/ViennaRNA/drforna and deployed at https://viennarna.github.io/drforna
An extensive benchmark study on biomedical text generation and mining with ChatGPT
Authors: Chen Qijie , Sun Haotong , Liu Haoyang , Jiang Yinghui , Ran Ting , Jin Xurui , Xiao Xianglu , Lin Zhimin , Chen Hongming , Niu Zhangmin
Published: September 2023

Motivation

In recent years, the development of natural language process (NLP) technologies and deep learning hardware has led to significant improvement in large language models (LLMs). The ChatGPT, the state-of-the-art LLM built on GPT-3.5 and GPT-4, shows excellent capabilities in general language understanding and reasoning. Researchers also tested the GPTs on a variety of NLP-related tasks and benchmarks and got excellent results. With exciting performance on daily chat, researchers began to explore the capacity of ChatGPT on expertise that requires professional education for human and we are interested in the biomedical domain.

Results

To evaluate the performance of ChatGPT on biomedical-related tasks, this article presents a comprehensive benchmark study on the use of ChatGPT for biomedical corpus, including article abstracts, clinical trials description, biomedical questions, and so on. Typical NLP tasks like named entity recognization, relation extraction, sentence similarity, question and answering, and document classification are included. Overall, ChatGPT got a BLURB score of 58.50 while the state-of-the-art model had a score of 84.30. Through a series of experiments, we demonstrated the effectiveness and versatility of ChatGPT in biomedical text understanding, reasoning and generation, and the limitation of ChatGPT build on GPT-3.5.

Availability and implementation

All the datasets are available from BLURB benchmark https://microsoft.github.io/BLURB/index.html. The prompts are described in the article.
Evidence of egg polymorphism in a host of Klaas’s cuckoo
Authors: Nahid Mominul Islam , Abernathy Virginia E , Liang Wei
Published: September 2023

Hosts may evolve more than one egg type within a population (egg polymorphism) to make mimicry of any one individual more difficult. This process of co-evolution between cuckoos and their hosts has been well studied in certain species but has been ignored in other, lesser-known species. Using avian visual modelling, reflectance spectrophotometry, digital image analysis and egg volume, we examined the degree of egg mimicry between Klaas’s cuckoo (Chrysococcyx klaas) and its host, the red-chested sunbird (Cinnyris erythrocercus), using museum collections. We found that the sunbird has evolved two distinct egg types based on luminance, colour and pattern, which we refer to as the light morph and the dark morph. Cuckoo eggs were significantly more similar to the dark morph eggs in luminance compared with the light morph eggs but were not more similar to dark morph eggs in colour, pattern or volume. To our knowledge, this is the first time that egg mimicry by Klaas’s cuckoo has been studied objectively, and egg polymorphism was described in the red-chested sunbird host. Future studies focused on living populations would help us to gain a better understanding of the co-evolutionary interactions between this cuckoo and its host species.
MicroRNA-200b-mediated reversion of a spectrum of epithelial-to-mesenchymal transition states in recessive dystrophic epidermolysis bullosa squamous cell carcinomas
Authors: Illmer Julia , Zauner Roland , Piñón Hofbauer Josefina , Wimmer Monika , Gruner Stefanie , Ablinger Michael , Bischof Johannes , Dorfer Sonja , Hainzl Stefan , Tober Vanessa , Bergson Shir , Sarig Ofer , Samuelov Liat , Guttmann-Gruber Christina , Shalom-Feuerstein Ruby , Sprecher Eli , Koller Ulrich , Laimer Martin , Bauer Johann W , Wally Verena
Published: September 2023

Background

Cutaneous squamous cell carcinoma (SCC) is the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). However, the survival time from first diagnosis differs between patients; some tumours spread particularly fast, while others may remain localized for years. As treatment options are limited, there is an urgent need for further insights into the pathomechanisms of RDEB tumours, to foster therapy development and support clinical decision-making.

Objectives

To investigate differences in RDEB tumours of diverging aggressiveness at the molecular and phenotypic level, with a particular focus on epithelial-to-mesenchymal (EMT) transition states and thus microRNA-200b (miR-200b) as a regulator.

Methods

Primary RDEB-SCC keratinocyte lines were characterized with respect to their EMT state. For this purpose, cell morphology was classified and the expression of EMT markers analysed using immunofluorescence, flow cytometry, semi-quantitative reverse transcriptase polymerase chain reaction and Western blotting. The motility of RDEB-SCC cells was determined and conditioned medium of RDEB-SCC cells was used to treat endothelial cells in an angiogenesis assay. In addition, we mined previously generated microRNA (miRNA) profiling data to identify a candidate with potential therapeutic relevance and performed transient miRNA transfection studies to investigate the candidate’s ability to reverse EMT characteristics.

Results

We observed high variability in EMT state in the RDEB-SCC cell lines, which correlated with in situ analysis of two available patient biopsies and respective clinical disease course. Furthermore, we identified miR-200b-3p to be downregulated in RDEB-SCCs, and the extent of deregulation significantly correlated with the EMT features of the various tumour lines. miR-200b-3p was reintroduced into RDEB-SCC cell lines with pronounced EMT features, which resulted in a significant increase in epithelial characteristics, including cell morphology, EMT marker expression, migration and angiogenic potential.

Conclusions

RDEB-SCCs exist in different EMT states and the level of miR-200b is indicative of how far an RDEB-SCC has gone down the EMT path. Moreover, the reintroduction of miR-200b significantly reduced mesenchymal features.
Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis
Authors: Murashima Miho , Fujii Naohiko , Goto Shunsuke , Hasegawa Takeshi , Abe Masanori , Hanafusa Norio , Fukagawa Masafumi , Hamano Takayuki
Published: September 2023

Background

Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients.

Methods

In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves.

Results

Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD.

Conclusions

Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.
What eyes do not see the heart does not grieve over? The role of intracoronary imaging in acute myocardial infarction: a case report
Authors: Blasco-Turrión Sara , Gómez-López Andrea , Morales-Ponce Francisco J , Casquero-Domínguez Sara , del Pozo-Contreras Rocío
Published: September 2023

Background

The evaluation of a three-dimensional structure with a two-dimensional imaging technique makes intracoronary diagnostic techniques essential, especially in the setting of acute myocardial infarction (AMI) when no apparent coronary lesions are detected. Expert consensus recommend their use in certain scenarios such as angiographically ambiguous disease and identification of the culprit lesion. Although both intravascular ultrasound and optical coherence tomography (OCT) allow the characterization of the atherosclerotic plaque and assess the immediate and long-term results of stent implantation, they have their own benefits and limitations that make them ideal for different types of coronary lesions.

Case summary

We present the case of a lateral ST-elevation myocardial infarction with no evident coronary lesions in angiography, in which OCT not only allowed us to confirm a diagonal branch occlusion, but it also became crucial to locate the occlusion point and to guide the procedure, allowing complete revascularization of the culprit lesion that otherwise could have been missed.

Discussion

To know the actual limitations of conventional coronary angiography to adequately assess coronary disease, intracoronary diagnostic techniques are key to evaluate the underlying mechanisms of the event, especially in the setting of AMI when no clear culprit lesion has been identified. They can be of great value to locate and revascularize acute occlusions that could go unnoticed on the angiogram, guiding the revascularization and stent implantation and, therefore, preventing myocardial injury that could become irreversible when coronary disease is not treated promptly.
Workforce affiliation in primary and secondary prevention implantable cardioverter defibrillator patients: a nationwide Danish study
Authors: Rosenkranz Simone H , Wichmand Charlotte H , Smedegaard Lærke , Møller Sidsel , Bjerre Jenny , Schou Morten , Torp-Pedersen Christian , Philbert Berit T , Larroudé Charlotte , Melchior Thomas M , Nielsen Jens C , Johansen Jens B , Riahi Sam , Holmberg Teresa , Gislason Gunnar , Ruwald Anne-Christine
Published: September 2023

Background and aim

There are a paucity of studies investigating workforce affiliation in connection with first-time implantable cardioverter defibrillator (ICD)-implantation. This study explored workforce affiliation and risk markers associated with not returning to work in patients with ICDs.

Methods

Using the nationwide Danish registers, patients with a first-time ICD-implantation between 2007 and 2017 and of working age (30–65 years) were identified. Descriptive statistic and logistic regression models were used to describe workforce affiliation and to estimate risk markers associated with not returning to work, respectively. All analyses were stratified by indication for implantation (primary and secondary prevention).

Results

Of the 4659 ICD-patients of working age, 3300 patients (71%) were members of the workforce (employed, on sick leave or unemployed) (primary: 1428 (43%); secondary:1872 (57%)). At baseline, 842 primary and 1477 secondary prevention ICD-patients were employed. Of those employed at baseline, 81% primary and 75% secondary prevention ICD-patients returned to work within 1 year, whereof more than 80% remained employed the following year. Among patients receiving sick leave benefits at baseline, 25% were employed after 1 year. Risk markers of not returning to work were ‘younger age’ in primary prevention ICD-patients, while ‘female sex’, left ventricular ejection fraction ‘LVEF ≤40’, ‘lower income’, and ‘≥3 comorbidities’ were risk markers in secondary prevention ICD-patients. Lower educational level was a risk marker in both patient groups.

Conclusion

High return-to-work proportions following ICD-implantation, with a subsequent high level of employment maintenance were found. Several significant risk markers of not returning to work were identified including ‘lower educational level’ that posed a risk in both patient groups.

Trial registration number

Capital Region of Denmark, P-2019-051.
Genome-wide methylation patterns from canine nanopore assemblies
Authors: Schall Peter Z , Winkler Paige A , Petersen-Jones Simon M , Yuzbasiyan-Gurkan Vilma , Kidd Jeffrey M
Published: September 2023

Recent advances in long-read sequencing have enabled the creation of reference-quality genome assemblies for multiple individuals within a species. In particular, 8 long-read genome assemblies have recently been published for the canine model (dogs and wolves). These assemblies were created using a range of sequencing and computational approaches, with only limited comparisons described among subsets of the assemblies. Here we present 3 high-quality de novo reference assemblies based upon Oxford Nanopore long-read sequencing: 2 Bernese Mountain Dogs (BD & OD) and a Cairn terrier (CA611). These breeds are of particular interest due to the enrichment of unresolved genetic disorders. Leveraging advancement in software technologies, we utilized published data of Labrador Retriever (Yella) to generate a new assembly, resulting in a ∼280-fold increase in continuity (N50 size of 91 kbp vs 25.75 Mbp). In conjunction with these 4 new assemblies, we uniformly assessed 8 existing assemblies for generalized quality metrics, sequence divergence, and a detailed BUSCO assessment. We identified a set of ∼400 conserved genes during the BUSCO analysis missing in all assemblies. Genome-wide methylation profiles were generated from the nanopore sequencing, resulting in broad concordance with existing whole-genome and reduced-representation bisulfite sequencing, while highlighting superior overage of mobile elements. These analyses demonstrate the ability of Nanopore sequencing to resolve the sequence and epigenetic profile of canine genomes.
Is employment group insurance financing of expensive gene therapies threatened in the United States?
Authors: Doshi Jalpa A , Eilers Morgan , Gupta Atul , Pauly Mark , Olssen Alexander L
Published: September 2023

Despite the potential of gene therapy to transform the lives of patients with rare genetic diseases, serious concern has been raised about the financing of the high up-front costs for such treatments and about the ability of the employer-sponsored insurance system in the United States, particularly in small firms, to pay for discoveries of this type. In this paper, we provide a conceptual framework and empirical evidence to support the proposition that, at present, private group insurance financing of cost-effective gene therapies is not only feasible and competitively necessary in the labor market for employers, regardless of group size, but also that, currently, the number of US workers in small firms who might be stressed by very high-priced claims is a tiny fraction of the group market for genetic treatments. The current system of employer-paid self-insurance supplemented by stop-loss coverage should be able to facilitate the use of new cost-effective gene therapies. Other alternative methods of financing that have been proposed may not be urgently needed. There are, however, some concerns about the long-term resilience of this system if stop-loss premiums continue to have high growth.
MaMADS1–MaNAC083 transcriptional regulatory cascade regulates ethylene biosynthesis during banana fruit ripening
Authors: Wei Wei , Yang Ying-ying , Wu Chao-jie , Kuang Jian-fei , Chen Jian-ye , Lu Wang-jin , Shan Wei
Published: September 2023

The hormone ethylene is crucial in the regulation of ripening in climacteric fruit, such as bananas. The transcriptional regulation of ethylene biosynthesis throughout banana fruit ripening has received much study, but the cascaded transcriptional machinery of upstream transcriptional regulators implicated in the ethylene biosynthesis pathway is still poorly understood. Here we report that ethylene biosynthesis genes, including MaACS1, MaACO1, MaACO4, MaACO5, and MaACO8, were upregulated in ripening bananas. NAC (NAM, ATAF, CUC) transcription factor, MaNAC083, a ripening and ethylene-inhibited gene, was discovered as a potential binding protein to the MaACS1 promoter by yeast one-hybrid screening. Further in vitro and in vivo experiments indicated that MaNAC083 bound directly to promoters of the five ethylene biosynthesis genes, thereby transcriptionally repressing their expression, which was further verified by transient overexpression experiments, where ethylene production was inhibited through MaNAC083-modulated transcriptional repression of ethylene biosynthesis genes in banana fruits. Strikingly, MaMADS1, a ripening-induced MADS (MCM1, AGAMOUS, DEFICIENS, SRF4) transcription factor, was found to directly repress the expression of MaNAC083, inhibiting trans-repression of MaNAC083 to ethylene biosynthesis genes, thereby attenuating MaNAC083-repressed ethylene production in bananas. These findings collectively illustrated the mechanistic basis of a MaMADS1–MaNAC083–MaACS1/MaACOs regulatory cascade controlling ethylene biosynthesis during banana fruit ripening. These findings increase our knowledge of the transcriptional regulatory mechanisms of ethylene biosynthesis at the transcriptional level and are expected to help develop molecular approaches to control ripening and improve fruit storability.
Trends in larval densities, spawning timing, and site quality of capelin (Mallotus villosus) across bays and habitats in Newfoundland, Canada
Authors: Tripp A , Murphy H M , Penton P M , Davoren G K
Published: September 2023

Capelin is a short-lived forage fish species that underwent a population collapse in 1991 on the Newfoundland and Labrador Shelf, Canada (Northwest Atlantic Fisheries Organization Divisions 2J3KL) and has not recovered. The collapsed stock is characterized by delayed spawning timing and low recruitment. As year-class strength is set early in life, long-term larval monitoring at an intertidal spawning site in Trinity Bay (TB) is used as a proxy for stock-wide recruitment. Capelin spawn at both intertidal and subtidal habitats; however, there is minimal larval information from bays with a high incidence of subtidal spawning. We aimed to (i) compare inter-annual trends in temperatures, timing of spawning, and annual larval densities between two northeastern bays [TB and Notre Dame Bay (NDB)] and (ii) compare habitat quality metrics and larval densities between subtidal and intertidal sites in NDB. The date of first spawning in TB and NDB was positively correlated, suggesting that years with delayed spawning are experienced shelf-wide. While larval density was lower in NDB compared to TB, inter-annual trends were similar. In NDB, larval densities at both intertidal and subtidal spawning habitats were similar within a year, but temperatures and the proportion of dead eggs were lower at subtidal sites. These habitat quality metrics, however, were not related to annual larval density. These findings improve our knowledge on sources of capelin productivity, including the potential importance of subtidal spawning to recruitment dynamics.
Using Climate Litigation to Strengthen Advocacy Strategies: The Life After Coal Campaign in South Africa
Authors: Chamberlain Lisa , Fourie Melissa
Published: September 2023

Activists in South Africa have a long history of using public interest litigation to realize human rights. The use of litigation is nevertheless contested and has produced rich scholarship exploring how its impact can be understood. This practice note will examine the use of litigation by the Life After Coal campaign in Earthlife Africa Johannesburg v. Minister of Environmental Affairs 2017, 2 All SA 519 (GP) (Thabametsi case). With the ultimate goal of reducing greenhouse gas emissions, Life After Coal has been campaigning since 2015 to thwart investment in new coal-fired power in South Africa. They successfully used the Thabametsi case to strengthen the use of a variety of other strategies, including protest, media advocacy, economic modelling, and pressure on investors and financial institutions. Although litigation can be painfully slow and resource intensive, in this campaign it was instrumental. Litigation delayed the regulatory approvals required for commercial close. While this was not the purpose of the litigation, its effect was to delay the flow of funds and the start of construction on the project. This in turn created time and space for an advocacy campaign to persuade financiers and investors to withdraw their backing for the project; to undertake the modelling and research required to back up the advocacy campaigns and litigation; and for clean renewable energy to become cheap enough to present a viable alternative pathway to coal. This practice note documents this rare success story and suggests what lessons concerning the use of multiple interweaving strategies it provides for climate activists in the global South.
SV2B defines a subpopulation of synaptic vesicles
Authors: Paulussen Isabelle , Beckert Hannes , Musial Timothy F , Gschossmann Lena J , Wolf Julia , Schmitt Mathieu , Clasadonte Jérôme , Mairet-Coello Georges , Wolff Christian , Schoch Susanne , Dietrich Dirk
Published: September 2023

Synaptic vesicles can undergo several modes of exocytosis, endocytosis, and trafficking within individual synapses, and their fates may be linked to different vesicular protein compositions. Here, we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy. SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone. In contrast, SV2A was found in all domains of the synapse and was slightly enriched near the active zone. SV2B and SV2A were found on the membrane in the peri-active zone, suggesting the recycling from both clusters of vesicles. SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation. Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients. The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.
Maturation of metastases in peripheral neuroblastic tumors (neuroblastoma) of children
Authors: Sarnat Harvey B , Chan Elaine S , Ng Denise , Yu Weiming
Published: September 2023

Peripheral neuroblastic tumors of childhood exhibit 3 principal neural crest lineages: primitive neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. They are unique in undergoing maturation of neurons (ganglion cells) and Schwann cells, thereby recapitulating normal fetal neuronal development in the brain. Precision in estimating neurogenesis is enhanced by immunoreactivities of markers of neuronal maturation. Whether organ tissue factors in different sites of metastases influence rates of maturation and whether metastases are similar to their primary neuroblastic tumor are incompletely documented. Four young children, 1 with a mixed primary adrenal tumor and 3 with metastases were studied at surgery or autopsy. Immunocytochemical reactivities included microtubule-associated protein-2, synaptophysin, chromogranin-A, somatostatin, keratan sulfate, vimentin, S-100β protein, and PHOX2B. Primary tumors were non-uniform with regions of either poor or enhanced maturation. Both neuronal and Schwannian lineages were represented in each tumor type but differed in proportions. Bi- or multi-nucleated ganglion cells matured equal to mononuclear forms. Ganglion cell maturation was similar in metastases regardless of the target organ. Metastases resembled primary tumors. Immunocytochemical markers of neuronal and of Schwann cell maturation provide greater diagnostic precision to supplement histological criteria. Interval between diagnosis of primary tumor and metastases, metastatic target tissues, and chemotherapy over an interval of time do not appear to influence neuroblastic or Schwann cell differentiation.
Associations of Standard Care, Intrathecal Antibiotics, and Antibiotic-Impregnated Catheters With Cerebrospinal Fluid Shunt Infection Organisms and Resistance
Authors: Sedano Sabrina , Kronman Matthew P , Whitlock Kathryn B , Zhou Chuan , Coffin Susan E , Hauptman Jason S , Heller Evan , Mangano Francesco T , Pollack Ian F , Schaffzin Joshua K , Thorell Emily , Warf Benjamin C , Simon Tamara D
Published: September 2023

Background

Infection prevention techniques used during cerebrospinal fluid (CSF) shunt surgery include: (1) standard perioperative intravenous antibiotics, (2) intrathecal (IT) antibiotics, (3) antibiotic-impregnated catheter (AIC) shunt tubing, or (4) Both IT and AIC. These techniques have not been assessed against one another for their impact on the infecting organisms and patterns of antimicrobial resistance.

Methods

We performed a retrospective longitudinal observational cohort study of children with initial CSF shunt placement between January 2007 and December 2012 at 6 US hospitals. Data were collected electronically from the Pediatric Health Information Systems+ (PHIS+) database, and augmented with standardized chart review. Only subjects with positive CSF cultures were included in this study.

Results

Of 1,723 children whose initial shunt placement occurred during the study period, 196 (11%) developed infection, with 157 (80%) having positive CSF cultures. Of these 157 subjects, 69 (44%) received standard care, 28 (18%) received AIC, 55 (35%) received IT antibiotics, and 5 (3%) received Both at the preceding surgery. The most common organisms involved in monomicrobial infections were Staphylococcus aureus (38, 24%), coagulase-negative staphylococci (36, 23%), and Cutibacterium acnes (6, 4%). Compared with standard care, the other infection prevention techniques were not significantly associated with changes to infecting organisms; AIC was associated with decreased odds of methicillin resistance among coagulase-negative staphylococci.

Conclusions

Because no association was found between infection prevention technique and infecting organisms when compared to standard care, other considerations such as tolerability, availability, and cost should inform decisions about infection prevention during CSF shunt placement surgery.
A Review of Pediatric Central Line-Associated Bloodstream Infections Reported to the National Healthcare Safety Network: United States, 2016–2022
Authors: Prestel Christopher , Fike Lucy , Patel Prachi , Dudeck Margaret , Edwards Jonathan , Sinkowitz-Cochran Ronda , Kuhar David
Published: September 2023

Central line-associated bloodstream infections (CLABSIs) are common healthcare-associated infections in pediatrics. Children’s hospital CLABSI standardized infection ratios decreased when comparing 2016–2019 (−26%, 95% CI [−31%, −20%]), and increased from 2019 to 2022 (18%, 95% CI [9%, 26%]). Resilient pediatric CLABSI prevention initiatives are needed.
Deriving the intrinsic properties of M51 with radiative transfer models
Authors: Inman Christopher J , Popescu Cristina C , Rushton Mark T , Murphy David
Published: September 2023

A quantitative derivation of the intrinsic properties of galaxies related to their fundamental building blocks, gas, dust, and stars is essential for our understanding of galaxy evolution. A fully self-consistent derivation of these properties can be achieved with radiative transfer (RT) methods that are constrained by panchromatic imaging observations. Here, we present an axi-symmetric RT model of the UV-optical-FIR/submm spectral and spatial energy distribution of the face-on spiral galaxy M51. The model reproduces reasonably well the azimuthally averaged radial profiles derived from the imaging data available for this galaxy, from GALEX, Sloan Digital Sky Survey, 2MASS, Spitzer, and Herschel. We model the galaxy with three distinct morphological components: a bulge, an inner disc, and a main disc. We derive the length parameters of the stellar emissivity and of the dust distribution. We also derive the intrinsic global and spatially resolved parameters of M51. We find a faint ‘outer disc’ bridging M51 with its companion galaxy M51b. Finally, we present and discuss an alternative model, with dust properties that change within the galaxy.
The impact of magnetic fields on cosmological galaxy mergers – II. Modified angular momentum transport and feedback
Authors: Whittingham Joseph , Sparre Martin , Pfrommer Christoph , Pakmor Rüdiger
Published: September 2023

The role of magnetic fields in galaxy evolution is still an unsolved question in astrophysics. We have previously shown that magnetic fields play a crucial role in major mergers between disc galaxies; in hydrodynamic simulations of such mergers, the Auriga model produces compact remnants with a distinctive bar and ring morphology. In contrast, in magnetohydrodynamic (MHD) simulations, remnants form radially extended discs with prominent spiral arm structure. In this paper, we analyse a series of cosmological ‘zoom-in’ simulations of major mergers and identify exactly how magnetic fields are able to alter the outcome of the merger. We find that magnetic fields modify the transport of angular momentum, systematically hastening the merger progress. The impact of this altered transport depends on the orientation of the field, with a predominantly non-azimuthal (azimuthal) orientation increasing the central baryonic concentration (providing support against collapse). Both effects act to suppress an otherwise existent bar-instability, which in turn leads to a fundamentally different morphology and manifestation of feedback. We note, in particular, that stellar feedback is substantially less influential in MHD simulations, which allows for the later accretion of higher angular momentum gas and the subsequent rapid radial growth of the remnant disc. A corollary of the increased baryonic concentration in MHD simulations is that black holes are able to grow twice as large, although this turns out to have little impact on the remnant’s development. Our results show that galaxy evolution cannot be modelled correctly without including magnetic fields.
Estimating stellar population and emission-line properties in S-PLUS galaxies
Authors: Thainá-Batista J , Cid Fernandes R , Herpich F R , Mendes de Oliveira C , Werle A , Espinosa L , Lopes A , Smith Castelli A V , Sodré L , Telles E , Kanaan A , Ribeiro T , Schoenell W
Published: September 2023

We present tests of a new method to simultaneously estimate stellar population and emission-line (EL) properties of galaxies out of the Southern Photometric Local Universe Survey (S-PLUS) photometry. The technique uses the AlStar code, updated with an empirical prior that greatly improves its ability to estimate ELs using only the survey’s 12 bands. The tests compare the output of (noise-perturbed) synthetic photometry of the Sloan Digital Sky Survey (SDSS) galaxies to properties derived from previous full spectral fitting and detailed EL analysis. For realistic signal-to-noise ratios, stellar population properties are recovered to better than 0.2 dex in masses, mean ages, metallicities, and ±0.2 mag for the extinction. More importantly, ELs are recovered remarkably well for a photometric survey. We obtain input − output dispersions of 0.05–0.2 dex for the equivalent widths of [O ii], [O iii], Hβ, Hα, [N ii], and [S ii], and even better for lines stronger than ∼5 Å. These excellent results are achieved by combining two empirical facts into a prior that restricts the EL space available for the fits. (1) Because, for the redshifts explored here, Hα and [N ii] fall in a single narrow band (J0660), their combined equivalent width is always well recovered, even when [N ii]/Hα is not. (2) We know from SDSS that $W_{\mathrm{H}\alpha +[\mathrm{N}\,\small {\rm II}] }$ correlates with [N ii]/Hα, which can be used to tell if a galaxy belongs to the left or right wings in the classical Baldwin–Phillips–Telervich (BPT) diagnostic diagram. Example applications to integrated light and spatially resolved data are also presented, including a comparison with independent results obtained with the Multi-Unit Spectroscopic Explorer (MUSE)-based integral field spectroscopy.
JS03.5.A CLINICALLY COLLECTED VARIABLES FAIL TO RELIABLY PREDICT COGNITIVE FUNCTIONING IN UNTREATED GLIOMA PATIENTS
Authors: Boelders S M , Rutten G J M , Gehring K , Ong L L , Postma E O
Published: September 2023

BACKGROUND

Previous research has identified several clinically collected variables (e.g., age and WHO grade) that are significantly related to impairments in cognitive functions before surgery in patients with a glioma. The degree to which clinically collected variables can collectively explain differences in cognitive functioning between patients, however, remains unclear, as most studies did not evaluate the total amount of variability between patients explained by a set of predictors. Furthermore, only linear or rank-based methods with a small number of variables have been used. In this study, we used various machine learning models to quantify the amount of variability in cognitive functioning we can explain using a comprehensive set of variables as identified from the literature that were collected as part of clinical care. The extent to which cognitive functioning can be reliably predicted reveals the degree to which these variables can explain individual differences between patients.

MATERIAL AND METHODS

We trained 11 machine learning models to predict pre-surgical cognitive function in patients with a glioma (n=354) across eight cognitive tests. Included variables comprised sociodemographics, tumor characteristics, medication, presenting symptoms, ASA score, comorbidities, and anxiety and depression scores. Model performance was evaluated on four objectives 1) predicting impairment on at least one cognitive test, 2) predicting the number of tests on which a patient is impaired, 3) predicting impairment for each test separately, and 4) predicting cognitive function for each test separately. Model performance, hyperparameter selection, and feature importance were analyzed and clinical implications were discussed.

RESULTS

Best-performing models demonstrated above-random performance for most objectives. Performance, however, was unreliable with poor predictions for a substantial number of patients on most objectives. Best-performing models were relatively simple and used most variables for prediction while not relying strongly on any specific variable.

CONCLUSION

Our results show that the clinically collected variables included in this study fail to reliably predict cognitive functioning. This indicates that these variables are unable to explain a considerable amount of variability between patients, despite many of these variables being significantly related to cognitive function in previous studies. Our results suggest that a multi-parametric (i.e., more holistic) view of an individual patient may be necessary to explain differences in cognitive functioning, ideally considering imaging markers, biological markers, sociodemographics, and clinical characteristics. Finally, our results stress the need to collect larger cross-center and multimodal datasets to better explain and predict individual differences in cognitive function.
JS08.6.A CSF DERIVED LIQUID BIOPSIES FOR GLIOMA DIAGNOSIS
Authors: Iser F , Güngör C , Meyer J , Dörner L , Hofmann L , Graßl N , Patel A , Wildemann B , Platten M , Wick W , Sahm F , Kessler T
Published: September 2023

BACKGROUND

Distinctive genetic changes can identify various types of gliomas. However, acquiring tumor material via surgery in the central nervous system (CNS) can pose the danger of neurological impairments, especially if the tumor is located near critical areas or in the brain stem. Gliomas discharge tumor DNA into the cerebrospinal fluid (CSF), where it mixes with circulating DNA from normal cells to generate cell-free DNA (cfDNA). Analyzing cfDNA via next-generation sequencing (NGS) is a substitute method for genomic assessments.

MATERIAL AND METHODS

We conducted targeted next-generation sequencing (NGS) of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) using a panel that encompasses 130 genes from 81 patients with MRI detected suspicion of a primary (n = 69) or recurrent (n = 12) glioma. The library preparation and raw read data preprocessing were tailored specifically for cfDNA samples. To identify single nucleotide variants (SNVs) and small insertions and deletions (Indels), a classifier based on machine learning (somaticseq) was trained using cfDNA reference standards. The on- and off-target reads were employed to develop profiles of copy-number variations (CNVs) (cnvkit).

RESULTS

The sensitivity and specificity of short variant (SNV + Indel) calling were determined to range between 36.1% - 93.3% and 66.5% - 87.1%, respectively, depending on the input amounts (2ng to 4ng) of cfDNA reference material and the circulating tumor DNA (ctDNA) content (1% to 5%). In a group of 20 CSF samples from glioblastoma patients, the detected mutations and CNVs corresponded to those found in solid tissue samples. Furthermore, two additional patients with glial tumors in the brain stem that could not be accessed surgically were found to have an IDH:p.R132C mutation and a histone H3.3:p.K28M mutation, respectively.

CONCLUSION

A clinical workflow was developed with specific sensitivity and specificity values for sequencing cerebrospinal fluid (CSF) cell-free DNA (cfDNA). This workflow was tested on a group of glioblastoma patients with matched solid tumor tissue. In two patients with suspected glial tumors but no accessible tissue, the diagnosis was confirmed by identifying characteristic mutations.
OS05.5.A NOVEL STUDY OF COGNITIVE REHABILITATION IMPROVING WORK PERFORMANCE IN PRIMARY BRAIN TUMOR
Authors: Weyer Jamora C , Brie M , Bracci P , Smith E , Luks T , Phan S , Alomomen R , Braunstein S , Rottering J , Oberheim Bush N , Butowski N , Clarke J , Daras M , de Groot J , Chang S , Hervey-Jumper S , Taylor J W , Taylor J W
Published: September 2023

BACKGROUND

Primary brain cancer survivors are living longer yet have emotional distress and cognitive impairments that negatively impact their quality of life (QOL), including returning to work. We present a novel tele-cognitive rehabilitation study in primary brain cancer survivors to improve work performance.

MATERIAL AND METHODS

Retrospective review of clinically and radiologically stable adult primary brain cancer patients off treatment and referred for cognitive rehabilitation. Neuropsychological, psychological, vocational, and QOL assessments completed. Wilcoxon rank sum and Fisher’s exact or Chi-square tests were used for between and within-group comparisons. Work status improvement defined as returning to employment and/or minimal cognitive symptoms at work.

RESULTS

79 patients with known baseline work status were analyzed. 80% opted in tele-cognitive rehabilitation services. Working (n=38), not working (n=41) had similar age, time since diagnosis, and history of radiotherapy. Not working had higher grade tumors (p=.01), worse cognitive function (executive function, attention, verbal learning all p<0.05) yet more engagement support groups (p<0.04). Subsequently, 38 patients (42% of whom were not working) received vocational tele-cognitive rehabilitation (median 11 sessions). 82% had improved work status compared to 34% non-treatment. Occupational improvements are not correlated to baseline work status and age. Glioblastoma was least improved, while Oligodendroglioma was most likely to improve (p=.05). Higher doses of radiotherapy were inversely related to work improvements (p<0.05). Higher verbal memory (p=0.05), processing speed (p=0.06), and executive functioning (p=0.02), IDH mutant tumors (p=0.06), and motivation for treatment (p=0.04) were associated with improved work status. Those with depressive symptoms who engaged in psychotherapeutic services had significantly improved work status (p=0.01).

CONCLUSION

When offered, patients want cognitive rehabilitation. Further, occupational functioning improves with tele-cognitive rehabilitation. Higher cognitive functioning, IDH mutation, radiotherapy dose, and motivation for treatment are important to consider. Despite not working and having worse cognition, patients improved similarly to their working counterparts. Depression benefitted from psychotherapeutic support. Tele-cognitive rehabilitation embedded within a multidisciplinary care model shows promise to improve work abilities in primary brain tumor patients.