bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXPLORING MOLECULAR LINKS IN BRAIN TUMOUR BIOPSY TISSUES AND ALZHEIMER’S DISEASE
Authors: Montalbo Ms Kristy , Stasik Dr Izabela , Bakker Dr Emyr , Smith Dr Christopher George Severin 
Published: October 2024

Abstract

AIMS
Generate and identify putative targets in the SORL1-network by mining online databases. Analyse 21 FFPE human brain tumour biopsy tissues through transcriptome sequencing performed by CeGaT (Tübingen, Germany) to explore differentially expressed genes. These biopsy samples are from consenting patients in association with Brain Tumour North West (BTNW) and the Royal Preston Hospital.

METHOD
Group comparisons are performed with the control and cancerous sample groups (low-grade glioma staying low, low-grade glioma becoming high and high-grade staying high). Further analysis involves comparing section and resection from the same patient for each cancer tissue group. Samples are explored on four different bioinformatic levels and sequenced on the Illumina platform. In Level 1 the data is demultiplexed and trimmed and in Level 2 trimmed reads are additionally mapped. Level 3 provides insights into the cell’s metabolic state and Level 4 performs several group comparisons.

RESULTS
Gain insights into differentially expressed genes’ presence in biopsy tissues from different stages of brain cancer, expression levels and links to clinical characteristics. Bioinformatic analysis provides data on quality control of the starting material, library preparation, sequencing parameters, and the Q30 value of the sequencing.

CONCLUSION
The analysis demonstrates molecular links in the SORL1-network in tissue from section and resection from a patient cohort to better understand disease recurrent and progression. Prospective bioinformatic work would explore interactions between signiﬁcant targets identiﬁed to create a curated network that could predict druggable targets in gliomas.
GENES ENCODING CELL SURFACE RECEPTORS AS NOVEL PROGNOSIS BIOMARKERS IN BRAIN TUMORS
Authors: Roesler Prof Rafael , Bark Dr Samir , Badalotti Dr Rafael , Buffon Dr Viviane , Dalmolin Mr Matheus , Fernandes Prof Marcelo , Malafaia Prof Osvaldo , Isolan Dr Gustavo 
Published: October 2024

Abstract

AIMS
A number of cell surface receptors that bind growth factors, neurotransmitters, and hormones are known to inﬂuence cancer initiation and progression. For example, CD114 (also called GCSFR or CSFR), which is encoded by the CSF3R gene, is a receptor for the granulocyte colony stimulating factor (GCSF) and a marker of cancer stem cells expressed in various cancer types. Also, the γ-aminobutyric acid (GABA) type A (GABAA) receptor for the inhibitory neurotransmitter GABA is proposed to play a role in brain cancer. Here, we report how the mRNA expression levels of CSF3R, the gene that encodes CD114, and genes encoding subunits of the GABAA receptor, are related to prognosis of brain tumor patients assessed by overall survival (OS).

METHOD
Data were obtained from brain tumor datasets, mainly the French and The Cancer Genome Atlas (TCGA) datasets for gliomas and the Cavalli dataset for medulloblastoma. Gene expression was analyzed using the R2 Genomics Analysis and Visualization Platform. OS was calculated using the Kaplan-Meier estimate.

RESULTS
Levels of CSF3R⁄CD114 transcripts are higher in different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and glioblastoma (GBM), in comparison to non-tumoral neural tissue. Higher expression of CSF3R in gliomas is associated with poorer outcome indicated by a shorter OS. Genes for GABAA receptor subunits associated with OS in gliomas include GABRA2, GABRA3, GABRG1, GABRG2, and GABRB3. Higher GABRA5 expression was associated with shorter patient OS in Group 3 and Group 4 medulloblastoma.

CONCLUSION
These ﬁndings indicate that gene expression levels of CSF3R and GABAA receptor subunits are potential biomarkers of poorer prognosis in patients with brain tumors.
MGMT METHYLATION AND ITS PROGNOSTIC SIGNIﬁCANCE IN INOPERABLE IDH WILDTYPE GLIOBLASTOMA: A SIX-YEAR REVIEW AT A TERTIARY NEURO-ONCOLOGY CENTER
Authors: Ghimire Dr Prajwal , Ashkan Prof Keyoumars , Lavrador Mr Jose , Vergani Mr Francesco , Bhangoo Mr Ranjeev 
Published: October 2024

Abstract

AIMS
IDH wild-type glioblastoma has the worst prognosis among glioma patients. The methylation of the O6- Methylguanine-DNA Methyltransferase (MGMT) gene is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis. Patients undergoing biopsy only without subsequent treatment have poor prognosis. We aimed to study the survival impact of MGMT methylation in this subset of patients.

METHOD
We collected six-year retrospective (2017-2023) data at a tertiary neuro-oncology center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology MDT documentation. Patients were grouped into four categories according to different types of treatment received after biopsy (biopsy only, Biopsy + chemotherapy(CT), biopsy + radiotherapy(RT), biopsy + complete/incomplete STUPP, biopsy + STUPP + 2nd Line). Analysis was performed in python and R statistical software. Survival analysis was performed with Kaplan-Meier Analysis in python.

RESULTS
166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 50% (n=83) patients had unmethylated MGMT status (0-5%), 29.5% (n=49) patients had methylated MGMT status (&gt;15%) and 19.2% (n=32) patients had borderline methylated MGMT status (5-15%). 21%(n=35) patients did not receive any treatment post biopsy,, 6.6% (n=11) received CT only, 15% (n=25) RT only, 27% (n= 45) complete/incomplete STUPP therapy, whereas 13.2% (n=22) received STUPP therapy along with second line treatment. In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups.

CONCLUSION
Methylated MGMT status is a predictor for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment.
The Weight of Nutrition on Post-Resection Oncologic Morbidity and Mortality: A Systematic Review and Meta-Analysis of Nutritional Indices
Authors: Pierce Katherine , Gaskins Jeremy , Martin II Robert C G 
Published: October 2024

Abstract

Context
Nutritional status is a critical factor in the selection of patients for solid tumor resection. A variety of indices have been developed to quantify nutritional status, and they have differing degrees of predictive power for various postoperative outcomes.

Objective
This study aimed to comprehensively evaluate the predictive ability of commonly used nutritional indices in relation to postoperative complications (POCs), recurrence-free survival (RFS), and OS.

Data Sources
We performed a systematic review of 14 established nutritional indices from January 2015 to July 2022:

Data Extraction
The primary end point was OS, while the secondary end points were POCs and RFS. A subsequent meta-analysis was performed to further assess the predictive ability of these indices for OS based on general index type, primary tumor site, and the patient’s index status.

Data Analysis
In this evaluation, 38 articles reporting data on 23 970 patients were analyzed, focusing on 14 nutritional indices. The indices were categorized into phenotypic, metabolic, immunologic, and combined types. Patients within the cut-off range of any index were predicted to have lower OS (hazard ratio [HR] 2.14, 95% CI 1.84–2.49, P &lt; .01). Lower gastrointestinal (GI) and “other” sites were less predictive than upper GI primary tumors (HR 1.63, HR 1.82, and HR 2.54, respectively; all with P &lt; .01). Phenotypic indices were less predictive than combined indices (HR 1.73 vs HR 2.47, P &lt; .01). Within the combined category, there was no significant difference in the predictive ability of Prognostic Nutritional Index (PNI) vs Geriatric Nutritional Risk Index (GNRI) vs Controlling Nutritional Index (CONUT) (HR 2.63 vs HR 2.42 vs HR 2.07, P = .07).

Conclusion
The predictive efficacy of a nutritional index was found to be highly dependent on the index type, the primary tumor site, and the outcome of interest. In the context of upper GI resections, nutritional status appeared to be more of a significant predictor of OS, compared with cases involving lower GI and hepatic malignancies. Indices that integrate phenotypic, metabolic, and immunologic patient factors potentially offer greater clinical utility in forecasting OS.
Multi-Stage Evolution of the Oceanic Lithosphere beneath Heard Island, Southern Indian Ocean
Authors: Abersteiner Adam , Beier Christoph , Genske Felix , Berndt Jasper , Kamenetsky Maya , Goemann Karsten , Nekrylov Nikolai , Kamenetsky Vadim S 
Published: October 2024

Abstract
The Kerguelen Plateau is the second biggest submarine large igneous province (LIP) on Earth, however, the nature of the lithospheric mantle source underlying it remains poorly constrained. In this contribution, we provide novel insights into the oceanic lithospheric mantle underlying Heard Island (southern Indian Ocean), which represents the most recent and active phase of volcanic activity (&lt;1 Ma) in the Kerguelen Plateau. We present petrographic and geochemical data for a suite of spinel-bearing harzburgite xenoliths hosted in basanite lavas and provide detailed constraints for distinguishing in situ mantle metasomatism from post-entrapment modification of the xenoliths following interaction with the host magma. We demonstrate that the xenolith mineral compositions and textures preserve a complex multistage history of different modal and cryptic transformations that occurred in the mantle due to: i) high degrees of partial melting that produced highly refractory whole-rock Mg# (Mg# = (Mg + Fe)/Mg × 100; 88–92), major element (FeO/MgO = 0.17) and mineral compositions (e.g. highly forsteritic olivine; Fo = (Mg + Fe)/Mg × 100; 91–92 mol %); ii) solid-state re-equilibration reactions during decompression that caused exsolution of clinopyroxene and Cr-spinel from xenolith orthopyroxene to form symplectite intergrowths; iii) cryptic metasomatism affecting the composition of xenolith clinopyroxene (i.e. enrichment in Na, Th, U and light rare earth elements, and depletion in Rb, Nb, Zr, Hf and Ti) due to interaction with carbonatitic melts in the mantle. Mantle fragments, entrapped by ascending basanite magmas as xenoliths were further modified by reactions with the host magma. This resulted in the partial dissolution of mantle orthopyroxene and replacement by newly formed and compositionally distinct assemblages of clinopyroxene (Mg# 87–91), olivine (Fo: 81–88 mol %) and Cr-spinel (i.e. ‘wehrlitisation’ of the xenoliths). This study highlights the utility of combining petrography and mineral chemistry to decipher the complex and sometimes overprinting and masking effects that different processes (e.g. melting events, metasomatism) exert on the lithospheric mantle, as well as constrain the processes that modify the xenoliths during transport towards the surface.
Transcriptome analysis reveals role of transcription factor WRKY70 in early N-hydroxy-pipecolic acid signaling
Authors: Foret Jessica , Kim Jung-Gun , Sattely Elizabeth S , Mudgett Mary Beth 
Published: October 2024

Abstract
N-Hydroxy-pipecolic acid (NHP) is a mobile metabolite essential for inducing and amplifying systemic acquired resistance (SAR) following a pathogen attack. Early phases of NHP signaling leading to immunity have remained elusive. Here, we report the early transcriptional changes mediated by NHP and the role salicylic acid (SA) plays during this response in Arabidopsis (Arabidopsis thaliana). We show that distinct waves of expression within minutes to hours of NHP treatment include increased expression of WRKY transcription factor genes as the primary transcriptional response, followed by the induction of WRKY-regulated defense genes as the secondary response. Most genes induced by NHP within minutes were SA dependent, whereas those induced within hours were SA independent. These data suggest that NHP induces the primary transcriptional response under basal levels of SA and that new SA biosynthesis via ISOCHORISMATE SYNTHASE 1/SA-INDUCTION DEFICIENT 2 is dispensable for inducing the secondary transcriptional response. We demonstrate that WRKY70 is required for the induced expression of a set of genes defining some of the secondary transcriptional response, SAR protection, and NHP-dependent enhancement of reactive oxygen species production in response to flagellin treatment. Our study highlights the key genes and pathways defining early NHP responses and the role of WRKY70 in regulating NHP-dependent transcription.
Adjuvant Therapy after Esophagectomy for Esophageal Cancer: Who Needs It?: Multi-institution Worldwide Observational Study
Authors: Raja Siva , Rice Thomas W. , Lu Min , Semple Marie E. , Toth Andrew J. , Blackstone Eugene H. , Murthy Sudish C. , Ahmad Usman , McNamara Michael , Ishwaran Hemant ,   for the Worldwide Esophageal Cancer Collaboration Investigators
Published: October 2024

Objective:
Based on current practice guidelines, we hypothesized that most patients with esophageal cancer, particularly those with locally advanced cancer, would benefit from adjuvant therapy after esophagectomy versus esophagectomy alone. We sought to obtain a granular estimate of patient-level risk-adjusted survival for each therapeutic option by cancer histopathology and stage.

Background:
Although esophagectomy alone is now an uncommon therapy for treating locally advanced esophageal cancer, the value of adjuvant therapy after esophagectomy is unknown.

Methods:
From 1970 to 2014, 22,123 consecutive patients from 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration) were diagnosed with biopsy-proven adenocarcinoma (n = 7526) or squamous cell carcinoma (n = 5625), of whom 10,873 received esophagectomy alone and 2278 additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality.

Results:
For adenocarcinoma, adjuvant therapy was beneficial only in pT4NanyM0 cancers (6–8 month survival benefit) and in pTanyN3M0 cancers (4–8 month benefit); a survival decrement was observed in pT1-3N0M0 cancers, with no effect on TanyN1-2M0 cancers. In squamous cell carcinoma, there was a 4 to 21 month survival benefit for pT3-4N0M0 cancers and a 4 to 15 month survival benefit for pT2-4N1-3M0 cancers.

Conclusions:
Adjuvant therapy after esophagectomy appears to benefit most patients with node-positive squamous cell carcinoma, but for adenocarcinoma, its value is limited to deep cancers and to those with substantial nodal burden. Future studies of the role of adjuvant therapies should treat these 2 cancers differently, with guidelines reflecting the histopathologic-appropriate survival value of adjuvant therapy.
Morphological and Clinical Aspects of Pott’s Disease in Ancient Human Remains
Authors: Papa Veronica , Varotto Elena , Vaccarezza Mauro , Galassi Francesco M. 
Published: October 2024

Study Design.
The present study is a scoping review of the literature on Pott’s disease in ancient human remains.

Objective.
Comprehending the origin and history of Pott’s disease is relevant to assessing this pathological condition from an evolutionary perspective.

Summary of Background Data.
Tuberculosis (TB) is an ancient pulmonary disease that remains the leading cause of death from a single infectious agent, rating above HIV/AIDS. The disease typically affects the lungs but can also target other anatomical sites. Of those, the most common and characteristic are the skeletal changes involving the spine, such as in Pott’s disease. Spinal tuberculosis accounts for approximately half of all cases of musculoskeletal tuberculosis. It can lead to loss of function in the lower limbs due to damage to the spinal column. Nevertheless, its origin and evolution are still not fully understood and need further investigation.

Methods.
The authors investigated the published studies on Pott’s disease in ancient human remains, intending to survey the literature, map the evidence and identify gaps and future perspectives on TB in paleopathology. The search strategy was conducted between September 2021 and March 2023 using keywords including the terms “Pott disease” OR “tuberculosis” AND “skeletal remains” in PubMed Biomed Central, Scopus, and Google Scholar search engines and biomedical databases. Five hundred and three records were initially identified, and 66 studies were finally included and assessed for qualitative analysis. Finally, the included records were analyzed in terms of non-narrative data, including the type of publication, country of excavation, dating of the sample, the number of human remains, and their details. Furthermore, the type of bone lesion was indicated as well as the diagnostic method if detailed.

Results.
Among articles identified, most were classified as original articles, and were published between 2011 and 2020. Close to 77% of the records reported excavation in Europe and the Near middle east. Included studies considered a total of 3388 human remains, mostly excavated in archaeological sites and necropolis. Interestingly, the reported prevalence was higher among young males and adults.

Conclusions.
Although most of the findings are consistent with the literature, since the majority of the human remains were from Europe and the Near Middle East, more research is necessary in other sectors of the world. The suggestion of a male predominance needs to be confirmed and questions about the possible pathognomic role of rib lesions as well Serpes endocranica symmetrica (SES) represent further areas of research that need to be explored.
High-Density Lipoprotein Anti-Inflammatory Capacity and Acute Kidney Injury After Cardiac and Vascular Surgery: A Prospective Observational Study
Authors: Perkins Zoe M. , Smith Derek K. , Yancey Patricia G. , Linton MacRae F. , Smith Loren E. 
Published: October 2024

OBJECTIVES:
Acute kidney injury (AKI) predicts death after cardiac and vascular surgery. Higher preoperative high-density lipoprotein (HDL) concentrations are associated with less postoperative AKI. In animals, HDL's anti-inflammatory capacity to suppress endothelial cell adhesion molecule expression reduces kidney damage due to ischemia and hemorrhagic shock. The objective of this study is to evaluate the statistical relationship between HDL anti-inflammatory capacity and AKI after major cardiac and vascular surgery.

DESIGN:
Prospective observational study.

SETTING:
Quaternary medical center.

PATIENTS:
One hundred adults with chronic kidney disease on long-term statin therapy undergoing major elective cardiac and vascular surgery.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Apolipoprotein B-depleted serum collected at anesthetic induction was incubated with tumor necrosis factor alpha stimulated human endothelial cells. Reverse transcriptase-polymerase chain reaction was used to measure intercellular adhesion molecule-1 (ICAM-1) messenger RNA. Enzyme-linked immunosorbent assay assays were used to measure apolipoprotein A-I and postoperative soluble ICAM-1 concentrations in patient plasma. HDL concentration did not correlate with HDL ICAM-1 suppression capacity (Spearman R = 0.05; p = 0.64). Twelve patients (12%) were found to have dysfunctional, pro-inflammatory HDL. Patients with pro-inflammatory HDL had a higher rate of postoperative AKI than patients with anti-inflammatory HDL (p = 0.046). After adjustment for AKI risk factors, a higher preoperative HDL capacity to suppress endothelial ICAM-1 was independently associated with lower odds of AKI (odds ratio, 0.88; 95% CI, 0.80–0.98; p = 0.016). The association between HDL anti-inflammatory capacity and postoperative AKI was independent of HDL concentration (p = 0.018). Further, a higher long-term statin dose was associated with higher HDL capacity to suppress endothelial ICAM-1 (p = 0.045).

CONCLUSIONS:
Patients with chronic kidney disease undergoing cardiac and vascular surgery who have dysfunctional, pro-inflammatory HDL have a higher risk of postoperative AKI compared with patients with anti-inflammatory HDL. Conversely, a higher HDL anti-inflammatory capacity is associated with a lower risk of postoperative AKI, independent of HDL concentration. Higher long-term statin dose is associated with higher HDL anti-inflammatory capacity.
Science of Learning Strategy Series: Article 6, Elaboration
Authors: Van Hoof Thomas J. , Sumeracki Megan A. , Madan Christopher R. , Meehan Thomas P. 
Published: October 2024

Abstract:
The science of learning (learning science) is an interprofessional field that concerns itself with how the brain learns and remembers important information. Learning science has compiled a set of evidence-based strategies, such as distributed practice, retrieval practice, and interleaving, which are quite relevant to continuing professional development. Spreading out study and practice separated by cognitive breaks (distributed practice), testing oneself to check mastery and memory of previously learned information (retrieval practice), and mixing the learning of separate but associated information (interleaving) represent strategies that are underutilized in continuing professional development. Participants and planners alike can benefit from learning science recommendations to inform their decisions. Elaboration, the subject of this article, is another evidence-based strategy that relates to how one studies or practices priority information.
Investigating the Transfer of Lisinopril Into Human Milk: A Quantitative Analysis
Authors: Chugh Julie , Dai Jean , Datta Palika , Krutsch Kaytlin 
Published: October 2024

Abstract:
Lisinopril is commonly prescribed to manage conditions such as hypertension and heart failure. Although concerns about fetal toxicity have traditionally limited the use of lisinopril in women of reproductive age, recent American College of Obstetricians and Gynecologists guidelines promote aggressive treatment of hypertension, which may require the use of pharmacologic agents not previously considered in the postpartum period. We aimed to estimate infant exposure to maternal lisinopril through breast milk and report the tolerance of the breastfed infant. Five volunteers taking lisinopril provided samples of their human milk and their associated health information for research through the InfantRisk Center Human Milk Biorepository. The milk pharmacokinetics of lisinopril were measured using liquid chromatography-mass spectrometry. The mean milk concentration of lisinopril was 0.49 ng/mL per 10 mg daily dose. The relative infant dose was 0.06% for lisinopril, more than 100 times lower than the standard 10% safety threshold. The minimal transfer of lisinopril into human milk in this study suggests the drug is unlikely to pose a clinically significant risk to healthy breastfed infants.