bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotyping for Weak and Partial D Rh Status to Optimize Usage of Limited Blood Supplies
Authors: Hartsell Emily , Thomas Caleb , Beck Bethany , Patel Sachi , Barouqa Mohammad 
Published: October 2024

Abstract

Introduction
The Rh antigen group, expressed on erythrocytes and encoded by highly polymorphic RHD and RHCE genes on chromosome 1 (1p36-p34), is notable in transfusion medicine due to its high polymorphism, strong immunogenicity and ability to cause hemolytic transfusion reactions in patients and hemolytic disease of the fetus and newborn (HDFN). The D antigen specifically contains multiple epitopes with variations that include decreased expression (weak D) or loss of certain epitopes (partial D) which expose patients to risk of alloimmunization depending on the subtype of the Rh(D) antigen. Hence, serologic weak D testing followed by molecular testing is not performed except for donors testing negative for Rh(D) antigen and newborns typing negative for Rh(D) and born to Rh(D) negative mothers. Given the current shortages of blood supplies, understanding patients’ genotypes in the context of weak or partial D-typing and risk of alloimmunization can be essential in the management of increasingly limited supplies of red blood cell (RBC) units.

Objective
To further characterize patients that initially type negative for Rh(D) but positive for weak D with molecular testing to investigate risk of alloimmunization, retype the Rh(D) and avoid unnecessary use of Rh(D) negative RBC units during critical shortages of RBC units.

Methods
We collected the results of ABO/Rh(D) typing for patients with negative Rh(D) testing but positive weak D test over a period of four weeks in December 2023 and had D-variant molecular testing performed by a reference laboratory. Initial serologic ABO/Rh(D) was performed in tube followed by weak D testing by indirect Coombs test in tube.

Results
The total number of patients who initially tested negative for Rh(D) but positive (weak to +4) for weak-D was three patients. Two patients showed a probable genotype of RHD*01W.1 (RHD* weak type 1, 809T&gt;G (V270G)) homozygous which indicated the presence of weak D+ type 1. Patients with weak D+ type 1 can receive Rh(D) positive red cell units, and they are not at risk of alloimmunization and developing anti-D. The third patient showed a probable genotype RHD*DVI type 2 homozygous (lack of Rh(D) exons 4 through 6) and indicated the presence of partial D antigen. Patients with partial D antigen should receive RH(D) negative red cell units as they are at risk of alloimmunization and developing anti-D.

Conclusions
Although the vast majority of Transfusion Medicine services do not perform the serologic weak D test with reflex to molecular testing, characterizing patients who test negative with initial serologic Rh(D) testing with serologic and molecular D-tests may aid in retyping the Rh(D) of patients during critical shortages, particularly for patients with ABO blood group O.
Critical values for carbon monoxide in cases admitted to the emergency department in a local hospital
Authors: Topcu Dilara Bal , Oztas Yesim Er , Kahraman Ahmet Caner 
Published: October 2024

Abstract
Carbon monoxide (CO) poisoning has been an important concern in winter particularly due to malfunctioning coal stoves, in many developing countries, including Turkey. Winter months, especially February, were the most dangerous periods for CO exposure. Carbon monoxide has no color or smell so has known as the silent killer. Brain, heart, and other organs are under risk in CO poisoning. Because patients usually present with non-specific symptoms, CO poisoning should be considered in the differential diagnosis of unexplained nausea and vomiting, neurological or cardiac signs and symptoms. Carboxyhemoglobin (COHb) is a reliable marker to monitor the patient. Lactate is also important as a measure of impaired systemic oxygen delivery. Fifteen patients with a diagnosis of CO poisoning were included in the study. This is the number of all cases admitted to the emergency in the last one and a half months in our local hospital located in a town with almost 48.918 residents. Blood gas analysis was performed by ABL90 FLEX, Radiometer. Reference for COHb was 0.6-1.5 % and for lactate was 0.5-1.6 mmol/L. Troponin I levels were also analyzed in some patients to assess possible myocardial ischemia. Troponin levels were analyzed by ARCHITECT i2000, Abbott and reference range was &lt;16 ng/mL in woman, &lt;34 ng/mL in men. Graph Pad Prism program was used for statistical analysis of the data. We had 15 cases aged between 4-56 years with COHb values with panic values (&gt; 20%) except two of the cases with values 16.5% and 19%. The female-male ratio was 6/9. On admission to the Emergency Department, 46.6% of patients (n=7) had headache and vomiting, 40% of patients (n=6) had headache, 6.6% (n=1) fatigue and 6.6% of patients (n=1) had syncope. Median value of COHb % was 23.7(16.5-40.8), lactate was 1.9 (0.8-4.8), pH was 7.39 (7.30-7.47). Excluding three patients as outliers, lactate levels had a good correlation with carboxyhemoglobin values (R2=0.9413). It was notable that 1 patient had a higher-than-normal Troponin I level (24.9 ng/mL) who has highest lactate level (4.8 mmol/L). Four of the patients, from the same family was admitted for suspected food poisoning for the symptoms of nausea, vomiting, diarrhea. A diagnosis of CO poisoning was made after a COHb value between 16.5-25.7% for these patients. This was very critical for the accurate treatment given to those patients being hyperbaric oxygen treatment in CO poisoning cases. CO poisoning should be considered in patients admitting to the emergency department with complaints of headache, dizziness, weakness, nausea, and vomiting. Reporting panic values is a means of alerting the clinician for the right diagnosis.
Conducting Assessments of Community-Based Programs for Individuals with Dementia and their Family Caregivers
Authors: Heid Allison R , Zarit Steven H 
Published: October 2024

Abstract
While the gold standard for intervention science is the randomized controlled trial (RCT), there is growing emphasis on the practical implementation and evaluation of evidence-based programs into community agencies. Assessment of program efficacy by community-based organizations can confirm planned delivery of services, implementation fidelity, and demonstrate positive outcomes, which can provide justification for funding. Methods and measures used in an RCT, however, often cannot be implemented in non-research settings and different approaches are needed. This manuscript reviews the emerging literature on program evaluation work and draws upon the authors’ experiences conducting evaluations with three community-based organizations funded by Administration for Community Living to implement programs for individuals with dementia and their family care partners. This manuscript argues for an examination of the expectations of evaluation efforts for translation of research-based trials to practice and emphasizes three main strategies for assessment: (1) Development of brief tailored assessments; (2) Measuring fidelity of implementation of the program; and (3) Measuring acceptability of the program to clients.
Chevrel’s procedure for midline incisional hernia repair—not to be abandoned or forgotten
Authors: Nikolovski Andrej , Cako Dajana , Argirov Ivan , Limani Nimetula , Ulusoy Cemal 
Published: October 2024

Abstract
The Chevrel technique is a well-established procedure for open repair of midline incisional hernia. This retrospective single-center case series aims to present the outcome of patients with midline incisional hernia treated with a modified Chevrel technique. The modification itself comprehended the use of a single-layer continuous suture for the inverted anterior rectus abdominis muscle sheet for the creation of the “new linea alba” without overlapping. Between January 2017 and December 2023, 40 patients were operated. The overall postoperative morbidity rate was 65%. Hernia recurrence occurred in three patients (7.5%). When the basic principles of the Chevrel technique are respected and conducted, this leads to satisfactory results. The postoperative outcome of this case series showed rates of complications and recurrences in concordance with the already published literature. Therefore, this technique should always be considered for the open approach for midline incisional hernia repair.
Logics for at most countable first-order structures
Authors: Perović Aleksandar , Ognjanović Zoran , Stojanović Tatjana 
Published: October 2024

Abstract
In this paper we present two extensions of $\omega $-logic with infinitary inference rules, denoted $Arch$-$\omega $-logic and $non$-$Arch$-$\omega $-logic. We provide the corresponding Hilbert-style axiomatizations and prove their strong completeness with respect to countable Archimedean and non-Archimedean fields, respectively. Through several examples we illustrate a natural representation of various weight functions within the proposed framework and applications to non-monotonic reasoning and neuro-symbolic computing.
RECAPITULATING THE POST-SURGICAL BRAIN MICROENVIRONMENT OF ATYPICAL TERATOID RHABDOID TUMOURS TO IDENTIFY MEMBRANE PROTEINS FOR TARGETED THERAPY
Authors: Mistry Mr Shaylen , Porter Mr Harry , McCrorie Dr Phoebe , Snary Dr Anya , Bailey Ms Hannah , Coveney Dr Clare , Boocock Dr David , Rahman Dr Ruman , Layﬁeld Prof Robert 
Published: October 2024

Abstract

AIMS
Atypical Teratoid Rhabdoid Tumours (AT/RT) are rare aggressive tumours primarily arising in the hind brain of children under three, conferring median survival of &lt;12 months. Surgery remains the only standard treatment; however tumours recur from post-surgical residual disease. Decellularised human brain cerebellum aim to recapitulate AT/RT post-surgical brain microenvironments which retain extracellular matrix (ECM) ligands, and where AT/RT plasma membrane proteins are hypothesised to represent viable molecular therapy targets.

METHOD
AT/RT, astrocyte and human brain cerebellum (decellularised and non-decellularised) membrane protein fractions were extracted and analysed using liquid chromatography-mass spectrometry. Proteomic analysis tools were integrated to identify differential expressed proteins and identify shared correlations.

RESULTS
Decellularised cerebellar ECM exhibited an enriched membrane proteome relative to total proteome, evidence of complete removal of intracellular components. Furthermore, decellularised and non-decellularised cerebellar tissue expressed comparable levels of membrane proteins and protein networks, indicative of ECM ligand retention. AT/RT and astrocyte KEGG Pathway analysis revealed speciﬁc oncology-based pathway expression in membrane protein compared to total protein, reinforcing membrane proteins as more visible therapeutic targets. Between the top 20 expressed proteins, ATP1A1 was the only membrane protein shared exclusively between all AT/RT cells and astrocytes, suggesting a critical functional role. Membrane proteins showing shared expression when normalised against each AT/RT cell line included ATP1A1, HSPD1, GNA13 and SLC3A2, indicating biological similarities between AT/RT molecular subtypes, which may offer candidate ubiquitous therapy targets. Membrane proteins expressed similarly in AT/RT-MYC molecular subtypes include ATP1A1, SLC7A5 and EEF1A1. STRING membrane pathway analysis also identiﬁed shared proteins between AT/RT and astrocyte cell populations.

CONCLUSION
AT/RT membrane protein pathways provide ideal therapeutic targets directly amenable for drug repurposing. Future work prioritises proteomic analysis utilising 3D AT/RT spheroids and cerebellum brain tissue to maximise accurately recapitulating the AT/RT post-surgical microenvironment. Cerebellum decellularisation still permits retention of essential proteins and ligands.
MAPPING GLIOMAS: A RADIOGRAPHIC AND SPATIAL ANALYSIS ACCORDING TO THE 2021 WHO CLASSIﬁCATION
Authors: Li Mr Yonghao , Wan Mr Yizhou , Price Prof Stephen 
Published: October 2024

Abstract

AIMS
The spatial positioning of gliomas within the brain signiﬁcantly inﬂuences prognosis, potentially mirroring the genetic landscape of their precursor cells. Furthermore, the association between glioma subtypes and their spatial distribution underscores a complex interplay that may illuminate underlying pathogenetic mechanisms. This study explores the intricate relationship between the location of gliomas and their classiﬁcation according to the 2021 WHO guidelines, aiming to unravel the spatial and genetic nuances that deﬁne glioma heterogeneity.

METHOD
In this study, preoperative anatomical MRI data from 242 glioma patients were meticulously analyzed to elucidate spatial distribution patterns in relation to tumor genetics. The imaging data underwent registration to the MNI-152 standard brain space, facilitating uniform analysis. Subsequent tumor segmentation and division of the brain into 84 distinct subregions allowed for a detailed examination of tumor locations. A statistical analysis was conducted to explore the stereospeciﬁc frequency of glioma occurrence across these subregions, correlating ﬁndings with tumor grade and pivotal genetic markers, including MGMT promoter methylation, IDH1 mutation, 1p/19q co-deletion, and CDKN2A/B homozygous deletion.

RESULTS
We developed 21 distinct tumor frequency atlases based on subtypes (Glioblastoma, Oligodendroglioma, Astrocytoma), biomarker status (IDH, 1p19q, MGMT, CDKN2A/B), and grade (2, 3, 4). Employing probability vectors for statistical analysis revealed a signiﬁcant correlation among different subtypes, locations and overall survival. Furthermore, we used a Visualization tool to build a 3D heatmap for each tumor subtype, more intuitively illustrating spatial correlations.

CONCLUSION
Our study underscores the prognostic value of tumor location and its correlation with glioma subtypes and patient outcomes, suggesting a potential pathway to personalized treatments. Future efforts will focus on incorporating multi-omics data into spatial radiographic analyses.
GLIOMA MONITORING VIA LONGITUDINAL INTRACRANIAL CSF CELL-FREE DNA: ONE PATIENT AT A TIME
Authors: Riviere-Cazaux Ms Cecile , Dong Dr Xiaoxi , Mo Dr Wei , Dai Dr Chao , Campian Dr Jian , Ruff Dr Michael , Eckel-Passow Dr Jeanette , Kaufmann Dr Timothy , Kizilbash Dr Sani , Warrington Dr Arthur , Jenkins Dr Robert , Du Dr Pan , Jia Dr Shidong , Burns Dr Terry 
Published: October 2024

Abstract

AIMS
Methods for disease monitoring in glioma are currently limited. Liquid biopsies are of increasing interest within the ﬁeld but have been challenging due to the blood-brain barrier. To bypass this challenge, we aimed to assess the technical and clinical feasibility of obtaining intracranial cerebrospinal ﬂuid (CSF) for disease monitoring via cell-free DNA (cfDNA).

METHOD
Adults with gliomas were recruited for longitudinal intracranial CSF collection via CSF access devices, including Ommaya reservoirs in four patients and an existing VP shunt in one patient. cfDNA was then extracted and analyzed using two sequencing platforms, PredicineCARE for cancer variant proﬁling and PredicineSCORE for low-pass whole genome sequencing (LP-WGS). This analysis generated genomic aberration proﬁles and genome wide copy number burden (CNB) score.

RESULTS
Across ﬁve patients, thirty-ﬁve CSF samples were obtained (median volume: 3.80 mL; 0.5-5 mL), with 30 samples (85.7%) yielding suﬃcient cfDNA. Tumor fraction increased by 6.28x and 2.87x in two patients with radiographic disease progression and decreased by 0.08x and 0.04x in another two after chemoradiation. In another patient with pseudoprogression, tumor fraction decreased from 0.26 after resection to unmeasurable levels. Patient speciﬁc tumor-associated variant allelic frequencies (VAFs), including TP53, PTEN, and TERT, decreased within individual patients after resection and chemoradiation. In two patients with IDH-mutant gliomas, IDH1 VAF after resection correlated with decreased CSF D-2-hydroxyglutarate (D-2-HG) levels (0.64x and 0.62x, respectively, for the ﬁrst patient, and 0.01x and 0.07x for the other patient). Both IDH1 VAF and D-2-HG increased in a patient with radiographic progression (2.56x and 9.21x, respectively). CNB decreased below the limit of quantiﬁcation during treatment and increased above the limit at progression.

CONCLUSION
Longitudinal CSF cfDNA can feasibly be obtained via CSF access devices in patients with gliomas during their disease course. Further sample collection and analysis are ongoing to determine the thresholds of change indicative of treatment response and progression.
LOCATE-SM PROTOCOL: LOCATION ORIENTED CORTICAL AND SUB-CORTICAL ASSESSMENT FOR THERAPEUTIC EVALUATION- SENSORY-MOTOR TESTING IN AWAKE CRANIOTOMY
Authors: Stephenson Mrs Elisa , Cooper Mrs Sara , Ewan Ms Seonaid-Mairi , Bolton Mr William Stephen , Mathew Mr Ryan 
Published: October 2024

Abstract

AIMS
Awake craniotomy is a well-established surgical procedure to debulk intracranial tumours in eloquent areas (‘functional hubs’). Intraoperative mapping facilitates maximal safe debulking. Review of current sensory motor assessment tools highlighted the absence of a comprehensive ‘location to function’ protocol. We aimed to develop a new protocol that enables ‘location to function’ sensory-motor task selection in preparation for, and during, awake craniotomy.

METHOD
A literature review demonstrated multiple different intraoperative strategies exist for the preservation of sensory-motor function in awake craniotomy. Incorporating these with functional neuroanatomy, and consensus agreement in the Tessa Jowell Academy Physiotherapy Awake Craniotomy Working Group and the National Brain Mapping MDT, led to the development of testing strategies aligned with ‘location to function’ task selection. Testing strategies were peer-reviewed by three specialist Neuro-Oncology physiotherapists.

RESULTS
A protocol (LOCATE-SM) has been developed at Leeds to identify critical cortical and subcortical sensory-motor functions that are aligned with anatomo-functional models. Physiotherapists have used this to select individualised pre-, intra- and postoperative tests depending on tumour location and sensory-motor impairment. Additionally, this facilitates intraoperative mapping of eloquent functional regions that are variably located. Cases using LOCATE-SM are presented.

CONCLUSION
LOCATE-SM is a new awake sensory-motor testing protocol developed by specialised Neuro-Oncology physiotherapists at a Tessa Jowell Centre of Excellence (Leeds). Current cases demonstrate that it leads to greater consistency between physiotherapists and speciﬁcity in ‘location to function’ sensory-motor task selection. Future work will systematically analyse the outcomes (onco-functional balance) of using this protocol, and validation in other centres.
PRECISE-GBM: A RADIOGENOMIC MACHINE LEARNING BASED STUDY TO IDENTIFY PREDICTIVE RADIOMICS FOR EVALUATION OF CANCER IMMUNE SIGNATURE IN IDHW GLIOBLASTOMA
Authors: Ghimire Dr Prajwal , Modat Dr Marc , Booth Dr Thomas 
Published: October 2024

Abstract

AIMS
The aim of the study is to identify machine learning model based on radiological biomarkers that can predict immune status within tumor microenvironment of IDH wildtype glioblastoma.

METHOD
This is a retrospective multicenter machine learning based study utilizing open access anonymized matched radiogenomic data of TCGA-GBM, CPTAC, Ivy GAP and REMBRANDT datasets. REMBRANDT data acted as hold out dataset. Imaging data consisted of MRI based radiomics features extracted from deep learning based segmented tumors and transcriptomic (RNA seq/microarray) data consisted of immune scores extracted using CIBERSORTx. Outliers were identiﬁed and ﬁltered using principal component analysis. Combat and neuroCombat were utilized for data harmonization for each data type respectively. Radiomic feature selection was performed using LASSO technique with cross validation. Support vector machine (SVM) was trained and tested with 80:20 radiomics data split and a median based binary label of immune score (low and high). Validation of the trained model was performed with hold out dataset. Data query and analysis was performed using python and R statistical software.

RESULTS
One hundred one patients were included in the study with 15 being on the hold out set. Trained SVM model predicted the immune score label with AUC of 0.79 and balanced accuracy of 0.76 (recall 0.75, F1 score 0.75, precision 0.75) in the test data. In the holdout set, the model predicted the immune score with AUC of 0.70 with speciﬁcity of 75% in predicting the cold immune cases. The radiomic signature that acted as the label for this model were a group of ﬁrst order and second order radiomic features.

CONCLUSION
Radiogenomic SVM model non-invasively predicts immune status in wildtype glioblastoma microenvironment with good accuracy. This model has potential to be utilized in a prospective glioblastoma clinical trial for immunotherapy.
INVESTIGATING GLIOBLASTOMA STEM CELL DIFFERENTIATION IN HUMAN BRAIN 3D ORGANOID CO-CULTURES
Authors: Azzarelli Dr Roberta , Morcom Dr Laura , Rowitch Prof David , Philpott Prof Anna 
Published: October 2024

Abstract

AIMS
Glioblastoma (GBM) recurrence is rooted in the ability of residual stem cells to survive treatment and drive relapse. One way to eradicate glioblastoma stem cells (GSCs) is to differentiate them into post-mitotic, non-tumorigenic cell types. Here we aim to differentiate GSCs via genetic manipulation, and test how their response differs in 2D and 3D cultures.

METHOD
We generated a co-culture model to grow GSC lines with iPSC-derived 3D human brain organoids. Before co-culture, the GSC lines were genetically engineered to overexpress a Doxycycline (Dox) inducible form of the proneural transcription factor ASCL1 (wild type and phosphorylation defective). Live imaging and immunochemistry were performed to analyse tumor composition.

RESULTS
Our data show that activation of the proneural factor ASCL1 in GSCs when co-cultured with 3D human brain organoids drives reduction in tumor growth and that inhibition of ASCL1 phosphorylation only slightly improves this effect. In comparison to data in 2D cultures, the effect of ASCL1 activation seems enhanced in 3D organoids. At day 7 and 14 of ASCL1 induction, there are only few cancer cells left in the organoids, while, in 2D, wildtype ASCL1-expressing cells continue to grow, even if at a slower rate than control GSCs.

CONCLUSION
Our data show that cancer stem cells embedded in 3D human brain organoids behave differently than when in 2D culture on plastic and respond more effectively to differentiation treatments. Our model provides a platform to test novel treatments for GBM.