bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional comparison study of Epimedium koreanum using UHPLC-QTOF/MS-based metabolomics approach
Authors: Arbianto Alfan Danny , Kim Min , Oh Seon Min , Jang Hyun-Jae , Ryu Hyung Won , Paik Jin-Hyub , Oh Sei-Ryang , Ahn Jongmin 
Published: June 2024

AbstractThe untargeted metabolomics-based molecular networking approach combined with multivariate analysis, proves to be an effective strategy for distinguishing raw materials in herbal medicine according to specific criteria. It exhibits the correlations between chemical constituents and the geographical habitats of plants, providing a valuable tool for ensuring quality control in mass production within the industry. In this study, we conducted a comprehensive investigation of the chemical compositions of Epimedium koreanum Nakai and performed comparative analyses on four extracts collected from distinct regions in South Korea using untargeted metabolomics tools. Through the comprehensive use of UPLC-QTOF/MS analysis and advanced statistical techniques, we elucidated the chemical composition, leading to the identification of key chemical markers. Additionally, the molecular networking analysis revealed distinct clusters of flavonoids and phenolic acids, highlighting the influence of regional factors on the metabolite profiles. These findings offer a promising avenue for enhancing quality control and traceability in the herbal medicine industry, underscoring the important role of geographical variation in the chemical profiles of herbal products.
Analysis of losses in physiotherapy students during the COVID-19 pandemic: a phenomenological approach
Authors: Terrón-Pérez Marta , Cortes-Amador Sara , Portolés-Simeó Juan Bautista 
Published: June 2024

Abstract
Background
During the COVID-19 pandemic, young people have experienced numerous personal losses across various aspects, impacting their quality of life. This study aimed to explore and analyze the losses experienced by physiotherapy students during the first year of the COVID-19 pandemic.

Methods
A qualitative phenomenological study was conducted using an open-format exercise carried out during the Clinical Specialties class from February to May 2021. Thirty-four (83% female) third-year physical therapy students participated. ATLAS.ti software was used for the analysis and coding by three researchers.

Results
Analysis of the categories revealed various losses experienced by the participants, including losses in psychological well-being, physical health, the social sphere (friendships, relationships with partners and family members, and experiences of death), spiritual losses (loss of freedom and identity), leisure time (travel, recreational activities and physical exercise), and different losses related to university studies (motivation and enthusiasm and clinical practices).

Conclusion
The COVID-19 pandemic has led to significant losses among physiotherapy students, with losses in the social sphere being the most prevalent. This study can serve as a foundation for developing resources aimed at enhancing the well-being of physiotherapy students, promoting optimal academic performance, improving self-care, and reducing psychosocial problems.
Examining career and technical education (CTE) pathways in historically Black colleges and universities (HBCUs)
Authors: Williams Kevin M. , Belur Vinetha , Yang Zhitong 
Published: June 2024

AbstractCareer and technical education (CTE) is considered a key academic pathway for sustainable careers in several high-growth industries. However, African–American employees are underrepresented in these industries. Historically Black colleges and universities (HBCUs) may represent invaluable options to address this inequality. Our analysis of the Integrated Postsecondary Education Data System (IPEDS) suggests that HBCUs provide fewer CTE options than a matched sample of non-HBCUs. The most commonly available CTE programs appear in less than one-quarter of HBCUs, and nearly one-quarter of CTE industries are unrepresented. Although some programs are well-positioned to address African–American employee underrepresentation, others are completely absent. Findings connecting HBCU CTE programs to occupations with high projected growth or living wage salaries are also mixed. Overall, these results may be informative for academic policymakers, administrators, and students.
Global coherence in structured and unstructured discourse types in neurotypical adults
Authors: Selvaraj Ruba , Vadakkanthara Hariharan Savitha 
Published: June 2024

Abstract
Background
Research on global coherence in neurotypical aging has predominantly focused on different methods of elicitation and their impact on age. The use of structured versus unstructured discourse tasks can have varying effects on global coherence. Comparative studies investigating this effect within Tamil language-speaking populations are scarce. This study seeks to address this gap by examining global coherence in structured and unstructured tasks among speakers of Tamil language.

Aim
This study aimed to identify any significant differences in the global coherence of discourse, as measured through structured (picture description) and unstructured (conversation) tasks, in middle-aged and older neurotypical individuals across ages and genders.

Method
Thirty Tamil-speaking individuals participated in the study, which included 15 middle-aged adults (aged 44–59 years) and 15 older adults (aged 60–80 years), with an equal number of males and females. Discourse samples were audio recorded using structured (picture description) and unstructured (conversational discourse) tasks. The picture description task included describing a single picture (of a birthday scene) and a sequential picture stimulus (depicting an argument event). The conversational task consisted of two topics of conversation (family and work) with the investigator. Each discourse task lasted for at least a minute. The recorded samples were transcribed verbatim and analyzed using a 4-point Global Coherence Rating Scale.

Results
Participants exhibited significant differences, with the unstructured discourse task having a significantly higher global coherence rating (p ≤ 0.05) than both structured discourse tasks. The varying cognitive demands, functional purposes, and contextual factors across various discourse elicitation tasks could be attributed to these differences. No significant differences were observed in the coherence ratings between middle-aged and older adults or between genders.

Conclusion
The method used to elicit discourse and the type of discourse need to be considered when exploring global coherence measures. The current study has important methodological implications for the coherence analysis of the Tamil-speaking population in both structured and unstructured tasks.
A microdeletion event at 19q13.43 in IDH-mutant astrocytomas is strongly correlated with MYC overexpression
Authors: Ülgen Ege , Gerlevik Umut , Gerlevik Sıla , Oktay Yavuz , Sezerman Osman Uğur , Turcan Şevin , Ozduman Koray 
Published: June 2024

AbstractMYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN), prompting a deeper investigation into potential novel oncogenic mechanisms. Analysing comprehensive genomics profiles of 236 “IDH-mutant 1p/19q non-co-deleted” lower-grade gliomas from The Cancer Genome Atlas, we identified somatic genomic alterations within the PMN. In tumours without PMN-alterations but with MYC-overexpression, genes correlated with MYC-overexpression were identified. Our analyses yielded that 86/236 of astrocytomas exhibited no PMN-alterations, a subset of 21/86 displaying relative MYC overexpression. Within this subset, we discovered 42 genes inversely correlated with relative MYC expression, all on 19q. Further analysis pinpointed a minimal common region at 19q13.43, encompassing 15 genes. The inverse correlations of these 15 genes with relative MYC overexpression were re-confirmed using independent scRNAseq data. Further, the micro-deleted astrocytoma subset displayed significantly higher genomic instability compared to WT cases, but lower instability compared to PMN-hit cases. This newly identified 19q micro-deletion represents a potential novel mechanism underlying MYC dysregulation in astrocytomas. Given the prominence of 19q loss in IDH-mutant gliomas, our findings bear significant implications for understanding gliomagenesis.
Immune profiling of mouse lung adenocarcinoma paraffin tissues using multiplex immunofluorescence panel: a pilot study
Authors: Zhai Jie , Tamegnon Auriole , Jiang Mei , Pandurengan Renganayaki Krishna , Parra Edwin Roger 
Published: June 2024

Abstract
Background
Immune profiling has become an important tool for identifying predictive, prognostic and response biomarkers for immune checkpoint inhibitors from tumor microenvironment (TME). We aimed to build a multiplex immunofluorescence (mIF) panel to apply to formalin-fixed and paraffin-embedded tissues in mice tumors and to explore the programmed cell death protein 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis.

Results
An automated eight-color mIF panel was evaluated to study the TME using seven antibodies, including cytokeratin 19, CD3e, CD8a, CD4, PD-1, PD-L1, F4-80 and DAPI, then was applied in six mice lung adenocarcinoma samples. Cell phenotypes were quantified by software to explore the co-localization and spatial distribution between immune cells within the TME. This mice panel was successfully optimized and applied to a small cohort of mice lung adenocarcinoma cases. Image analysis showed a sparse degree of immune cell expression pattern in this cohort. From the spatial analysis we found that T cells and macrophages expressing PD-L1 were close to the malignant cells and other immune cells.

Conclusions
Comprehensive immune profiling using mIF in translational studies improves our ability to correlate the PD-1/PD-L1 axis and spatial distribution of lymphocytes and macrophages in mouse lung cancer cells to provide new cues for immunotherapy, that can be translated to human tumors for cancer intervention.
Antegrade long giant ileocolic intussusception via colon–cecum cancer lead points: case report with focus on the sign of the python colon
Authors: Pierro Antonio , Apollonio Biagio Francesco Pio , Mirco Paolo , Vallo Antonio , Cristino Roberto , Oriente Pierpaolo , Bevere Teresa , Testa Gianluca , Totaro Antonio 
Published: June 2024

Abstract
Background
Ileocolic intussusception is a rare condition that is difficult to diagnose. A pathological lead point, usually malignant, is often the cause of adult intussusception. In emergency scenarios, radiologists must be able to identify this entity and its causes and express their opinions on associated complications.

Case presentation
The hospital's emergency room admitted a 75-year-old woman who was suffering from intermittent abdominal pain and constipation. An abdominal contrast-enhanced computed tomography revealed a long giant ileocolic intussusception. Considering the clinical stability and the absence of signs of complications on CT, the patient did not undergo an urgent surgical procedure but underwent a colonoscopy the following day. Surprisingly, the colonoscopy highlighted the spontaneous resolution and revealed the presence of the three tumour lead points in the cecum and ascending colon. A CT was performed after the colonoscopy, confirming the intussusception's resolution. The surgeon performed a right oncological hemicolectomy. The malignant lead points on histological examination were moderate to poorly differentiated adenocarcinomas.

Conclusions
A giant and long ileocolic intussusception with a long embedded visceral segment (the python colon sign) could suggest pathological lead points in the cecum and ascending colon. Despite the large size, a spontaneous resolution of the python colon is possible. In this scenario, even if, on imaging, it is impossible to macroscopically identify a lead point, in cases of giant and long ileocolic intussusceptions, every effort must be undertaken to search for the cause of the intussusception.
Cervical and ocular vestibular-evoked myogenic potentials test results and its relation to vestibular signs and symptoms in individuals with vestibular migraine
Authors: Sanitha Adithya Sreedharan , Sinha Sujeet Kumar 
Published: June 2024

Abstract
Objective
The objective of the present study was to characterize the response rate, latency, and amplitude parameters of the cervical and ocular vestibular evoked myogenic potentials in individuals with vestibular migraine. The objective was also to describe the signs and symptoms exhibited by individuals with vestibular migraine and find out an association with VEMP results.

Method
Thirty individuals with a diagnosis of vestibular migraine and thirty healthy individuals participated in the study. The diagnosis of the vestibular migraine was made based on the diagnosis criteria given by the Barany Society and the International Headache Society. Cervical and ocular vestibular evoked myogenic potentials were recorded using 500 Hz tone burst stimulus for all the participants in both groups.

Results
The latency was prolonged, and the amplitude was reduced for both the cervical and ocular vestibular evoked myogenic potentials in individuals with vestibular migraine compared with healthy individuals. There was no association between signs and symptoms exhibited by vestibular migraine individuals and VEMP results.

Conclusions
Both the sacullocollic and otolith ocular pathways are affected in vestibular migraine. Hence, there is a necessity for vestibular evaluation in all patients with vestibular migraine to understand the spectrum of the pathology.
Evaluation of the tumor microenvironment in African American and non-Hispanic White patients with non-small cell lung cancer associated with PD-L1 expression or the presence of tertiary lymphoid structures.
Authors: Trendowski Matthew Raymond , Watza Donovan , Lusk Chrissy , Lonardo Fulvio , Ratliff Valerie , Wenzlaff Angela , Mamdani Hirva , Neslund-Dudas Christine , Boerner Julie , Schwartz Ann G. , Gibson Heather M 
Published: June 2024

2627 Background: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in the tumor microenvironment and treatment response have been minimal. Due to the increasing utility of immunotherapy in the treatment of non-small cell lung cancer (NSCLC), we compared the immune cell composition and transcriptomic signature in the tumor microenvironment among African American and non-Hispanic White patients based on PD-L1 or tertiary lymphocyte structure (TLS) status to determine if there were differences of translational relevance. Methods: Using a cohort of 280 NSCLC patients from the INHALE study (non-Hispanic White: n = 155; African American: n = 125) with whole transcriptome microarray data, we determined the PD-L1 tumor proportion score (< 1% vs. ≥ 1%) and TLS status (presence/absence) within tumor tissue sections by immunohistochemistry. TLS were defined as dense aggregates of CD20 stained cells with a minimum diameter of 150 µm. Immune cell distribution within the tumor microenvironment was evaluated relative to differential gene expression. Results: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than tumors from non-Hispanic Whites. In addition, gene expression patterns in African American PD-L1 positive samples suggest these tumors contained significantly greater numbers of γδ T-cells and resting dendritic cells, along with fewer CD8+ T-cells compared to PD-L1 negative samples after adjusting for stage and histology. We also identified 22 genes that were differentially expressed between PD-L1 positive and negative tumors, along with 37 genes that were differentially expressed between TLS positive and negative tumors. Investigation of differential expression of B-cell/plasma cell related genes between the two patient populations revealed that four immunoglobulin genes in African Americans ( IGHA1, IGHD, IGKV2-29, and IGLL5) were associated with decreased mortality risk, while none of these genes were associated with overall survival in the non-Hispanic White population. Conclusions: In the first known race-stratified analysis of tumor microenvironment in lung cancer based on PD-L1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified among non-Hispanic White and African American patients that may have therapeutic implications. Future investigation of these unique aspects within the tumor microenvironment will make advances in immunotherapy more equitable, thereby reducing the health disparities African Americans currently experience.
ctDNA as a biomarker in phase II study of tepotinib in advanced solid cancers with MET exon 14 skipping mutation or amplification (KCSG AL19-17).
Authors: Yang Yaewon , Kang Eun Joo , Lee Soohyeon , Kim Yu Jung , Lim Sun Min , Ahn Myung-Ju , Lee Youngjoo , Kim Tae Min , Kim Ilhwan , Ahn Hee Kyung , Lee Soonil , Oh So Yeon , Woo Kyun Bae , Ryu Hyewon , Park Kyong Hwa , Lee Ki Hyeong 
Published: June 2024

3050 Background: Tepotinib consistently demonstrated antitumor activity in patients with MET exon 14 skipping mutation ( METex14) and promising activity in various cancers with MET amplification, according to previous reports. We assessed plasma ctDNA as a potential biomarker in MET-dysregulated advanced cancer patients with tepotinib treatment. Methods: KM-08 (KCSG AL19-17, NCT04647838) was a phase 2, multicenter study with tepotinib treatment for patients with advanced or metastatic solid cancers harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). For exploratory analyses, we analyzed the genetic profile using liquid-based NGS testing with AlphaLiquid-100 panel (IMBdx Inc. Seoul, KR) at baseline (T0), after six weeks during treatment (T1), and at the time of disease progression (T2). Results: Baseline ctDNA NGS data was available in 28 (80%) out of 35 patients enrolled in the trial. Among them, METex14 or MET amplification was detected in 18 patients, with a sensitivity of 64.3%. The most commonly co-mutated gene was TP53, followed b y PIK3CA, ATM, MYCN, and KRAS. The objective response rate (ORR) in plasma MET positive (PM+) patients was higher (81.2%) than the ORR in plasma MET negative (PM−) patients’ group (30.0%). In contrast, PM− group had a longer progression-free survival (PFS) and overall survival (OS) than PM+ group. PFS was 11.0 months (95% CI 8.1, 13.9) vs 6.0 months (95% CI 3.6, 8.3) and OS was NR vs 14.0 months (95% CI 4.7, 23.3), respectively. The molecular responder (MR, MET alteration variant allele frequency [VAF] T1/T0 <50%) was 80.0% (12/15 patients), and the molecular non-responder (MNR, METVAF T1/T0≥50%) was 20.0% (3/15 patients). ORR was higher in the MR group (91.7%) than in the MNR group (33.3%). PFS and OS were longer in the MR group than in the MNR group, 6.0 months (95% CI 0.0, 14.5) vs 3.0 months (95% CI 1.4, 4.6) with P= 0.114 and NR vs 4.0 months (95% CI 2.4, 5.6) with P= 0.067, respectively. Out of the 20 patients with samples available at T2, one had an on-target mutation on MET (D1228N, and Y1230H) while two had off-target emerging oncogenic alterations in KRAS, BRAF, and ERBB2 genes. Conclusions: In the liquid biomarker analysis in the MET-dysregulated cancer patients who were treated with tepotinib, the presence of ctDNA METalteration at baseline was associated with a higher response rate but shorter PFS and OS. The molecular response was well correlated with the radiological response and associated with better outcomes. (Funded by Merck KGaA, Darmstadt, Germany, ClinicalTrials.gov number, NCT04647838.) Clinical trial information: NCT04647838 .
Paired matched normal sequencing to accurately identify somatic clonal hematopoiesis mutations (CHm) in solid tumor tissue and plasma specimens.
Authors: Eterovic Karina , Batalini Felipe , Troxel Susan , Urban Brent , Harcar Mechelle , Shreeve Jacob , Ilsley Diane , Patel Ananddeep , Watters Matthew , Kutumbaka Kirthi , Sathyan Pratheesh , LoCoco Jennifer S. , Tierno Marni Brisson , Moss Tyler J 
Published: June 2024

3051 Background: Clonal hematopoiesis (CH), characterized by the presence of somatic mutations in blood cells, can be found in cancer-related genes when sequencing tumor tissue or plasma samples. Inability to distinguish somatic, tumor-derived mutations from CHm can lead to inaccurate treatment decisions. In this prospective study, we confirmed potential CHm in solid tumors by sequencing and analysis of paired matched normal (PMN) specimens. Methods: We prospectively enrolled 56 patients diagnosed with advanced cancer, including lung (16), colorectal (13), breast (10), gastric (7), ovarian (2), pancreatic (2), liver (2), cervix (1), uterine (1), fallopian tube (1), and perihilar bile duct (1). Targeted next-generation sequencing using a 523 gene panel was performed on paired formalin-fixed paraffin-embedded (FFPE) and circulating tumor DNA (ctDNA) samples. Additionally, whole exome sequencing was performed on PMN buffy coat samples. Analysis of all three specimens was performed to classify somatic mutations as tumor-derived or CHm. Results: We identified 21 potential CHm within the FFPE and ctDNA samples of 13 patients (23.2% of the cohort) with lung (7), breast (2), liver (2), colorectal (1), and gastric (1) cancers. CHm were further confirmed when present in buffy coat samples. The VAF of CHm in FFPE and ctDNA samples exhibited a wide range, spanning from 0.85% to 38.4%, with 7 of those identified at <2% VAF. For these same aberrations, VAF in buffy coat samples ranged from 1.6% to 48%, with seven mutations exhibiting VAF levels <5%. Four of these CHm were classified as oncogenic or likely oncogenic. Four CHm, including an oncogenic TP53 mutation, were identified in the oldest patient (75 years old, lung cancer), while an oncogenic DNMT3A mutation was detected in the youngest patient (42 years old, breast cancer). Both had a 30-year history of smoking. Conclusions: Our findings identified somatic CHm in a substantial subset (23.2%) of solid tumors, with four identified as oncogenic or likely oncogenic mutations. The broad spectrum of VAFs for CHm suggests that using VAF as a cut-off to exclude likely CHm may be unreliable. The low VAF CHm found in matched normal specimens indicates low-pass sequencing may not detect critical CHm, even in paired analysis. The diverse age range of patients with CHm (42 to 75 years old) suggests that CHm are not restricted to older populations, and that additional factors, such as smoking history, may play a role. These findings underscore the importance of incorporating routine PMN buffy coat sequencing into clinical practice, to identify somatic CHm that can impact personalized cancer treatment strategies.