Major Clusters Research Articles

708 Trends in Carotid Stenosis Literature Between 2012-2022: Applications of Endarterectomy and Translational Research

INTRODUCTION: Carotid stenosis causes 10-20% of cases with ischemic stroke. Research in this clinical domain continues to progress in improving possible treatment modalities, imaging modalities, mechanistic understandings, and risk factors. METHODS: The WebOfScience database was investigated for 6,639 publication items between 2012-2022 pertaining to neurosurgical management of carotid stenosis. Networks were constructed analyzing keywords, key terms, and countries of publication. Subsequently, items within each network were organized into clusters and average publication date was measured for each term. Relevant items were tracked over time to compare their representation and utility in literature. Additionally, relevant key terms and connections were isolated from the network. RESULTS: For each network, the top 1,000 terms were selected for analysis. Terms were arranged into six major clusters (treatments, imaging, risk factors, prognostic markers, plaque characteristics, and basic science research). The most recent terms were observed in the treatment cluster (average publication year 2021.24) and basic science cluster (average publication year 2018.4). While terms within basic science have remained consistent over time, analysis of treatments elucidated that “carotid endarterectomy” surpassed “carotid artery stenting” in popularity after 2019. Additionally, the term “mouse” in the basic science cluster was connected to all clusters with a link strength of 18,084 (average 427.6). CONCLUSIONS: Modern research in carotid stenosis is characterized by two developments: advancements in basic science and increasing publication focus on carotid endarterectomy. Despite recent advancements in endovascular treatment of carotid stenosis, open treatment continues to remain a significant focus of study. As they continue to expand into modern scientific enterprise, developing nations will continue to impact the future of carotid stenosis research.

Establishment of somatic embryogenesis regeneration system and transcriptome analysis of early somatic embryogenesis in Litchi chinensis

Litchi chinensis Sonn. is an important economic fruit tree in tropical and subtropical regions. Regrettably, the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conversion of embryos to plants. The purpose of this study was to establish a regeneration system via somatic embryogenesis from immature embryos explants in ‘Heiye’ cultivar of litchi. Our results demonstrated that MS medium supplemented with 2.0mg L−1 2,4-D was optimal for callus induction. For somatic embryo (SE) induction, MS medium containing 0.5 g L−1 activated charcoal (AC) was the most effective, while the use of zeatin (ZT) and thidiazuron (TDZ) resulted in abnormal somatic embryos. The rooting and regeneration rate of 2.15% and 17.5%, respectively, were achieved using MS medium supplemented with 0.5 g L−1 AC. Furthermore, transcriptome analysis was performed on embryogenic callus (EC), globular embryo (GE), and heart embryo (HE) to explore the molecular mechanisms of early somatic embryogenesis. 2,587 common DEGs between EC_vs_GE and EC_vs_HE were identified, and the expression patterns of these common DEGs were separated into twelve major clusters. GO annotation and KEGG pathway analysis revealed that these common DEGs were implicated in plant hormone signal transduction, auxin-activated signaling pathway, and other biological processes. Additionally, differentially expression transcription factors were identified, and the function of LcBBM2 which is specifically highly expressed during early somatic embryogenesis was verified. Overexpression of LcBBM2 in tomato promotes callus and shoot formation. Therefore, this study can provide a theoretical basis and technical support for genetic breeding improvement of litchi.

An N-body/hydrodynamical simulation study of the merging cluster El Gordo: A compelling case for self-interacting dark matter?

We used a large set N-body/hydrodynamical simulations to study the physical properties of the merging cluster El Gordo. We find that the observed X-ray structures, along with other data, can be matched fairly well by simulations with collision velocities 2000 km s−1 ≲ V ≲ 2500 km s−1 and impact parameters 600 kpc ≲ P ≲ 800 kpc. The mass of the primary is constrained to be between ∼1015 M⊙ and ∼1.6 × 1015 M⊙, in accordance with recent lensing-based mass measurements. Moreover, a returning, post-apocenter, scenario is not supported by our head-on simulations. We also considered merger models that incorporate dark matter self-interactions. The simulation results show that the observed spatial offsets between the different mass components are well reproduced in self-interacting dark matter models with an elastic cross-section in the range σDM/mX ∼ 4 − 5 cm2 gr−1. In addition, the mean relative line-of-sight radial velocity between the two brightest cluster galaxies is found to be on the order of several hundred km s−1. We argue that these findings provide an unambiguous signature of a dark matter behavior that exhibits collisional properties in a very energetic high-redshift cluster collision. The range of allowed values we find for σDM/mX is, however, inconsistent with present upper limits. To resolve this tension, we suggest the possibility that the self-interacting dark matter model used here be considered as only a low-order approximation, and that the underlying physical processes that describe the interaction of dark matter in major cluster mergers are more complex than can be adequately represented by the commonly assumed approach based on the scattering of dark matter particles.

Hierarchical and Non- Hierarchical Cluster Classification of Precipitation Time Series Data in Nigeria

Precipitation is highly unpredictable over space and time, and is an indicator for climate change. The present work classified average yearly precipitation over the 36 states and the Federal Capital Territory (FCT) in Nigeria into various groups. The hierarchical and non- hierarchical (k-means) cluster method was used in the classification of 37- years precipitation data (1984-2020). The results showed that six major clusters were formed. The Precipitation across the 36 states and the FCT in Nigeria can be classified as Light precipitation for Sokoto, Borno, Kastina, Yobe and Kano States; Moderate precipitation for Kebbi, Zamfara, Dutse, Yola, Gombe and Bauchi States; Heavy precipitation for Kaduna, Plateau, Kwara, Taraba, Nassarawa, Benue and Kogi States; Very Heavy precipitation for Osun, Ogun, FCT, Ekiti, Niger and Lagos States; Shower for Edo, Abia, Delta, Anambra, Ebonyi, Enugu, Ondo and Oyo States and lastly, Heavy Shower for Akwaibom, Imo, Rivers, Bayelsa and Cross River States.. The rangs of precipitation based on the six classification are 1.5-1.8mm (Light precipitation), 1.9-2.7mm (Moderate precipitation), 2.8-3.6mm (Heavy precipitation), 3.7-4.3mm (Very Heavy precipitation), 4.4-5.4mm (Shower) and greater than 5.5mm (Heavy Shower). The hierarchical cluster method performed better than the non- hierarchical (k-means) cluster method in structuring the precipitation data and shaping it into groups (clusters) such that observations within the same group are more similar than those in different groups. The results of this study can contribute to a better understanding of the climate condition of the36 States and the FCT in Nigeria.

Analysis of Genetic Variability of Potato Induced Mutants Using Simple Sequence Repeat (SSR) Markers

Aims: Potato (Solanum tuberosum L.) is ranked fourth amongst the world’s major stable food crop and second in Kenya after maize and thus plays a vital role in food and nutrition security and sustainable development. Despite its importance, potato production in Kenya is still low due to abiotic and biotic constraints. Traditional breeding and improvement have been difficult due to the narrow genetic diversity of the crop owed to the complex tetrasomic inheritance patterns. Induced mutation has been used to generate genetic variations in potato from which desired putative mutants are selected. In most cases the level of genetic variability is not known. The objective of this study was to determine the genetic variability of potato mutants using SSR markers. Study Design: The study involved three potato varieties; Asante, Kenya Mpya and Kenya Sherekea which are high yielding and commercially grown varieties in Kenya. Place and Duration of Study: Sample: They were irradiated at different dose rates of gamma rays at Co60 source at FAO/IAEA laboratories, Seiberdorf Austria in 2014. A total of 163 mutants were advanced to M1V4 generation at the University of Eldoret between 2015 and 2018. Methodology: Genomic DNA was extracted to assess the diversity with 20 SSRs markers. Results: All the 20 SSR primers were polymorphic with 6-19 bands amplified per primer and marker STM5127 showed the highest allele number (19) using PowerMarker software. The STRUCTURE analysis suggested that the potato mutants were clustered into six sub-populations based on the unweighted pair-group method of arithmetic averages (UPGMA) thus, the accessions were divided into three major clusters. Analysis of molecular variance (AMOVA) indicated that 8.6% of total molecular variance was attributed to diversity among sub-populations, while 91.4% of variance was associated with differences within sub-populations. Conclusion: This study highlights the most comprehensive investigation of the genetic diversity and population structure of potato mutants, and provides valuable information for genetic improvement, and systematic utilization.

Genetic discrimination of button mushroom Agaricus bisporus by DNA fingerprinting using RAPD marker

The investigation was conducted for DNA fingerprinting and genetic diversity analysis of five button mushroom strains (Agaricus bisporus-6, Agaricus bisporus-2, Agaricus bisporus-3, Agaricus bisporus-8 and Agaricus bisporus-5) using eight decamer RAPD primers (OPA01, OPA02, OPA03, OPA04, OPA07, OPB17, OPB12 and OPA10). A modified CTAB technique was used to isolate DNA. RAPD analysis resolved 152 scorable bands, 89 bands were monomorphic and 63 bands were polymorphic. The primer OPB17 amplified the highest number of band (30) and OPA01 amplified the lowest number of bands (09). The primer OPA04 produced the 8 polymorphic bands. Thus, it showed higher level of polymorphism (80%). Dendrogram based on linkage distance using Unweighted Pair Group Method of Arithmetic Means (UPGMA) indicated segregated of five button mushroom strains into two main clusters. Only Agaricus bisporus-6 (V1) grouped in cluster 1 (C1) while the major cluster C2 included all other strains, as well as V2 (Agaricus bisporus-2), V3 (Agaricus bisporus-3), V4 (Agaricus bisporus-8) and V5 (Agaricus bisporus-5). At the linkage distance of 50.5, the major cluster C2 formed sub-cluster C2A (Agaricus bisporus-3) and C2B (Agaricus bisporus-2, A. bisporus-8 & A. bisporus-5). Overall results from the dendrogram indicated that the V1 (Agaricus bisporus-6) button mushroom was shown to be outliers in the dendrogram, that is different from other strains because of its unique genetic makeup and high yields of this starin. The present work revealed that the DNA fingerprinting of five button mushroom strains based on RAPD showed significant different among the strains.

A generalizable and easy-to-use COVID-19 stratification model for the next pandemic via immune-phenotyping and machine learning.

The coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians. Three COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity. Patients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively. Overall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

Microglial sex differences in innate high anxiety and modulatory effects of minocycline

Microglia modulate synaptic refinement in the central nervous system (CNS). We have previously shown that a mouse model with innate high anxiety-related behavior (HAB) displays higher CD68+ microglia density in the key regions of anxiety circuits compared to mice with normal anxiety-related behavior (NAB) in males, and that minocycline treatment attenuated the enhanced anxiety of HAB male. Given that a higher prevalence of anxiety is widely reported in females compared to males, little is known concerning sex differences at the cellular level. Herein, we address this by analyzing microglia heterogeneity and function in the HAB and NAB brains of both sexes. Single-cell RNA sequencing revealed ten distinct microglia clusters varied by their frequency and gene expression profile. We report striking sex differences, especially in the major microglia clusters of HABs, indicating a higher expression of genes associated with phagocytosis and synaptic engulfment in the female compared to the male. On a functional level, we show that female HAB microglia engulfed a greater amount of hippocampal vGLUT1+ excitatory synapses compared to the male. We moreover show that female HAB microglia engulfed more synaptosomes compared to the male HAB in vitro. Due to previously reported effects of minocycline on microglia, we finally administered oral minocycline to HABs of both sexes and showed a significant reduction in the engulfment of synapses by female HAB microglia. In parallel to our microglia-specific findings, we further showed an anxiolytic effect of minocycline on female HABs, which is complementary to our previous findings in the male HABs. Our study, therefore, identifies the altered function of synaptic engulfment by microglia as a potential avenue to target and resolve microglia heterogeneity in mice with innate high anxiety.

Trace elements in zircon record changing magmatic processes and the multi-stage build-up of Archean proto-continental crust

Zircon trace element geochemistry has become an increasingly popular tool to track crustal evolution through time. This has been especially important in early-Earth settings where most of the crust has been lost, but in some fortuitous instances detrital zircons derived from that lost crust have been preserved in younger sediments. To study the formation and geochemical evolution of continental crust from the Hadean to the Paleoarchean, the 3.6 to 3.2 Ga Barberton Greenstone Belt in southern Africa is an excellent target due to its outstanding preservation and presence of detrital zircons that span almost a billion years. Here, we use trace elements, in combination with hafnium and oxygen isotopes, of 3.65 to 3.22 Ga detrital and tuffaceous zircons of the Moodies and Fig Tree groups and compare their geochemistry to previously studied 4.2 to 3.3 Ga detrital zircons from the Green Sandstone Bed of the Onverwacht Group. The major detrital zircon age clusters in the former at 3.55 Ga, 3.46 Ga, and 3.26–3.23 Ga overlap with episodes of TTG emplacement and felsic volcanism in the Barberton area, suggesting a local provenance. In contrast, age clusters at 3.65 Ga and 3.29 Ga of the Moodies and Fig Tree groups as well as 4.2 to 3.3 Ga detrital zircons from the Green Sandstone Bed do not have known intrusive sources and were likely derived from outside the present-day Barberton belt. This indicates that more than half of the felsic igneous events in the detrital zircon record do not have a whole-rock representation that can be directly studied. The similar compositions and inferred crustal evolution histories recorded in zircons from the Fig Tree and Moodies groups, as well as from the Green Sandstone Bed, suggest that they were derived from connected terranes experiencing similar crustal processes diachronously. Together, they show three phases of felsic continent formation, reflecting different crustal processes: (1) long-lived protocrust formed in the Hadean from undepleted mantle sources. These zircons are vastly different from younger zircons and, hence, Barberton TTGs are not good analogues of Hadean crust formation. (2) At 3.8 Ga, onset of significant crustal growth though cyclic juvenile additions and hydrous melting, possibly within a volcanic plateau setting but an arc-like setting cannot be excluded based on this data. (3) Between 3.4 and 3.3 Ga, felsic crust is generated through a previously unrecognized episode of crustal growth by shallow melting of mafic, mantle-derived sources. This is immediately followed by the onset of crustal thickening through the transport of surface-altered, hydrated materials to deep crustal levels. Since there is geological evidence for extension and shortening at that time this may reflect the onset of horizontal movement. Whether this last geodynamic setting reflects modern-style plate tectonics or not, continent formation and the onset of plate tectonics in the Barberton area occurred through complex multi-stage processes spanning almost a billion years, most of which is only accessible through the detrital zircon record.

Molecular marker-assisted genetic diversity analysis in soybean cultivars from Himalayan region of Uttarakhand, India

‘Bhat’ is the soybean variety highly valued in the traditional food and therapeutic system of Uttarakhand state in the Indian Himalayan region. It is available in diverse colors, shapes, and sizes, often linked to their nutritional parameters. The present investigation was conducted to assess the diversity and genetic relatedness in ‘bhat’ genotype indigenous to the Garhwal division of Uttarakhand. 25 polymorphic simple sequence repeats (SSR) markers were used to determine the genetic diversity and varietal identification among the 45 genotypes collected from the different villages of Uttarakhand. Out of the different markers assessed only 13 primers showed amplification with the maximum of 2–4 alleles obtained with each primer with the molecular weight ranging between 80 and 400 kb. The highest band amplification was observed in Satt 257 and Satt 197. The allelic frequencies of amplified primers ranged from 0.5 to 0.833 with a mean value of 0.645 and the mean gene diversity and PIC value was found to be 0.43 and 0.33. Satt 183, Satt 288, and Satt 389 showed the highest polymorphism, while Satt257 and Satt245 exhibited the presence of unique alleles in some samples. The phylogenetic analysis grouped the genotypes into 4 major clusters having visually distinct phenotypes in each group, indicating the mixing of population and loss of authenticity also confirming that phenotypic attributes are not indicative of genetic relatedness among the genotype under study. The results indicate the need for the development of novel ‘bhat’ specific markers for more accurate genetic identification of the nutritionally rich indigenous soybean variety.

Structural and sequence analysis of the RPO30 gene of sheeppox and goatpox viruses from India

Sheeppox and goatpox are transboundary viral diseases of sheep and goats that cause significant economic losses to small and marginal farmers worldwide, including India. Members of the genus Capripoxvirus (CaPV), namely Sheeppox virus (SPPV), Goatpox virus (GTPV), and Lumpy skin disease virus (LSDV), are antigenically similar, and species differentiation can only be accomplished using molecular approaches. The present study aimed to understand the molecular epidemiology and host specificity of SPPV and GTPV circulating in India through sequencing and structural analysis of the RNA polymerase subunit-30 kDa (RPO30) gene. A total of 29 field isolates from sheep (n = 19) and goats (n = 10) belonging to different geographical regions of India during the period: Year 2015 to 2023, were analyzed based on the sequence and structure of the full-length RPO30 gene/protein. Phylogenetically, all the CaPV isolates were separated into three major clusters: SPPV, GTPV, and LSDV. Multiple sequence alignment revealed a highly conserved RPO30 gene, with a stretch of 21 nucleotide deletion in all SPPV isolates. Additionally, the RPO30 gene of the Indian SPPV and GTPV isolates possessed several species-specific conserved signature residues/motifs that could act as genotyping markers. Secondary structure analysis of the RPO30 protein showed four α-helices, two loops, and three turns, similar to that of the E4L protein of vaccinia virus (VACV). All the isolates in the present study exhibited host preferences across different states of India. Therefore, in order to protect vulnerable small ruminants from poxviral infections, it is recommended to take into consideration a homologous vaccination strategy.

Changing food preferences and choices – A framework for analyzing households food purchases over time

Scientific interest in food consumption has grown significantly in recent decades due to its profound implications for individuals’ and societies’ health and wellbeing and implications for domestic and global systems sustainability. Food purchases can be directly and indirectly related to household and consumer characteristics. While food purchase habits may be dynamic and influenced by changing circumstances over the years, most related research presents a snapshot of the studied issues within a single year or period or focus on a specific social group or food commodity. This paper introduces and illustrates a framework for analyzing household food purchasing clusters over a period of time. It uses data from over 120,000 households in Israel to analyze household food purchases over two decades. The analysis segments the population into clusters and accounts for their food purchases through an extensive bottom-up approach. It identifies several major clusters, including small and large families and young and elderly households, each representing a unique range of food purchase patterns and a different share of the overall society. It analyses different levels of consumption, from broad categories to specific products, and examines the relationships between food purchases and household characteristics. Examining specific food categories and commodities illustrates a complex trend over the research period, including rising demand for beef, poultry, and soft drinks, steady patterns of consumption of frozen and canned vegetables and oils, and a clear decline in demand for dairy, grain, and sugar products.

Abstract 5168: Analysis of biomarker and outcomes data: 7-year update from COLUMBUS

Abstract Background: In the randomized, 2-part, phase 3 COLUMBUS study (NCT01909453), encorafenib (enco) + binimetinib (bini)—an approved regimen in the US, EU, and other countries—improved 7-year PFS and OS vs vemurafenib (vemu) in patients (pts) with BRAF V600E/K-mutant locally advanced unresectable or metastatic melanoma. We investigated genetic and transcriptional correlates of outcomes in an exploratory biomarker analysis of COLUMBUS Parts 1 and 2. Methods: In Part 1, 577 pts were randomized 1:1:1 to enco 450 mg QD + bini 45 mg BID, enco 300 mg QD, or vemu 960 mg BID; in Part 2, 344 pts were randomized 3:1 to enco 300 mg QD + bini 45 mg BID or enco 300 mg QD. Baseline tumor samples were analyzed using the ACE ImmunoID NeXT whole exome sequencing/whole transcriptome sequencing (WES/WTS) assays (Personalis). PFS and OS were analyzed (cutoff: Jan 13, 2023) by treatment arm and presence of specific genetic or transcriptomic alterations. Results: Among treated pts, 668 had WES or WTS data. K-means clustering identified 3 major transcriptional clusters: (1) microphthalmia-associated transcription factor (MITF)-low (invasive dedifferentiated tumor cell phenotype), (2) MITF-high (proliferative melanocytic phenotype), and (3) immune-high. Cluster assignments were significantly associated with biopsy site (P<0.001), with cluster 1 enriched in skin biopsies and cluster 3 in lymph node metastases; biopsy site-independent characteristics were also captured. Improved PFS with enco + bini vs vemu was most pronounced in cluster 3 (Table 1). ERBB2 expression and PI3KCA pathway mutation, previously found to be associated with reduced survival benefit with enco + bini vs vemu, were enriched in clusters 1 and 2 vs cluster 3. Conclusions: Enco + bini showed benefit across molecular subtypes in BRAF V600E/K-mutant melanoma. The contribution of bini was most pronounced in the immune-high cluster. Improved outcomes in this cluster support ongoing trials of combinations with immune checkpoint inhibitors, such as STARBOARD and PORTSIDE. Table 1. Hazard ratios of PFS and OS for enco + bini or enco vs vemu by cluster HR (95% CI) vs vemu PFS OS Enco + bini Enco Enco + bini Enco Overall n=255 vs 100 n=159 vs 100 n=255 vs 100 n=159 vs 100 0.47 (0.35, 0.63) 0.78 (0.57, 1.07) 0.66 (0.50, 0.86) 0.85 (0.63, 1.13) Clusters Cluster 1: MITF-low n=72 vs 34 n=44 vs 34 n=72 vs 34 n=44 vs 34 0.74 (0.44, 1.26) 0.92 (0.51, 1.66) 0.63 (0.40, 1.00) 0.57 (0.34, 0.96) Cluster 2: MITF-high n=120 vs 46 n=76 vs 46 n=120 vs 46 n=76 vs 46 0.48 (0.32, 0.74) 0.75 (0.48, 1.17) 0.66 (0.45, 0.97) 0.86 (0.56, 1.32) Cluster 3: Immune-high n=63 vs 20 n=39 vs 20 n=63 vs 20 n=39 vs 20 0.23 (0.12, 0.44) 0.64 (0.33, 1.21) 0.80 (0.40, 1.59) 1.55 (0.76, 3.15) Numbers are given as the number of pts included in the treatment arm vs the number of pts in the comparator arm (vemu-treated). Statistical significance (P<0.05) is shown by bold font. Bini, binimetinib; enco, encorafenib; MITF, microphthalmia-associated transcription factor; pts, patients; vemu, vemurafenib. Citation Format: Reinhard Dummer, Keith Flaherty, Shibing Deng, Tao Xie, Phineas Hamilton, Nuzhat Pathan, Caroline Robert, Ana Arance, Jan Willem de Groot, Claus Garbe, Helen J. Gogas, Ralf Gutzmer, Ivana Krajsová, Gabriella Liszkay, Carmen Loquai, Mario Mandala, Dirk Schadendorf, Naoya Yamazaki, Paolo A. Ascierto, Alessandra di Pietro, Craig B. Davis. Analysis of biomarker and outcomes data: 7-year update from COLUMBUS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5168.

Abstract 2439: Potential target genes for early stage detection in Hispanic colorectal cancer

Abstract Background: Colorectal Cancer (CRC) has become the second leading cause of death related to cancer worldwide and the third most common malignancy. CRC tumors are classified into stages to describe the cancer; early (stages I and II) and advanced (stages III and IV). Despite the available screening methods and the scientific efforts in the development of a universal biomarker panel for CRC early detection, there still exists a gap in a reliable non-invasive screening method for the Hispanic community. We aimed to elucidate the most important pathways along with the differential gene expression in early and advanced CRC stages in a Hispanic population. Methods: We examined restrospectively 7 tissue samples from a Puerto Rican Hispanic population recruited throughout the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR) IRB #A2210207. We evaluated transcriptomic changes in advance tumors (n=4) vs. early tumors (n=3) with their respective normal mucosal tissue as negative control. Extracted RNA was sequenced using the Illumina NextSeq (2 × 75bp). The higher-quality reads were aligned, annotated, and quantified to the human genome (hg38) using STAR and RSEM softwares. Gene expression analysis was performed in R statistical software (packages tximport and DESeq2). We compared significantly expressed genes (adjusted p-value <0.05) between study groups (Tumor Advance [TA] vs. Mucosal Advance [MA] and Tumor Early [TE] vs. Mucosal Early [ME]) using Venny, and we performed enrichment analyses and protein-protein interaction networks using Metascape and STRING database, respectively. Results: There were 2284 differentially expressed genes (TA vs. MA) and 984 (TE vs. ME), in which 1736 were unique to advance stages, 436 were unique to early stages and 548 were shared in both tumor stages. Significantly impacted biological processes and pathways include: granulocyte chemotaxis, regulation of inflammatory response, positive regulation of apoptotic process, tissue morphogenesis, G alpha signaling events, interleukin-10 signaling, signaling by interleukins. Additionally, physical and functional interaction networks showed 11 major clusters (≥ 5 genes), which contained several gene hubs including LYN (proto-oncogene), IL-1β, IL-1α, TNF, CCL3, CCL4, CXCR1 and CXCR2 (cytokines/chemokines) among others genes previously reported as CRC biomarkers (DKK1, AQP8, AQP9, CTNNB1, and GNAQ). Discussion/Conclusions: Differential analysis of early CRC tumor samples shows a deregulation of genes related to the inflammatory response which plays an important role in CRC. Modulation of these genes suggests significant potential targets for early detection of CRC in a Hispanic population. Future studies will be focus on the evaluation of selected target genes as a non-invasive early CRC screening method. Citation Format: Elba V. Caraballo, Camille Zenón-Meléndez, Josué Pérez-Santiago, Marcia Cruz-Correa. Potential target genes for early stage detection in Hispanic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2439.

TESTING THE DISTRIBUTIONAL DIVERGENCE IN THE PILLARS OF REGIONAL DEVELOPMENT IN MOROCCO

This article examines the distributional divergence of the pillars of regional development in Morocco using a new hierarchical clustering algorithm from the unsupervised machine learning literature. The study utilizes a unique dataset of regional indicators to identify the major clusters of development and differences in regional performance in terms of economic transformation, social inclusion, and environmental sustainability. Results from the hierarchical clustering algorithm show that the Moroccan regions are highly differentiated and the clusters identified do not necessarily coincide with the traditional administrative divisions. This suggests that the policies implemented in Morocco have not been effective in achieving balanced development across all regions. The findings of this study provide important insights into the challenges of regional development in Morocco and the potential of using machine learning algorithms to better identify and address regional disparities.

Characteristic SNPs defining the major multidrug-resistant Mycobacterium tuberculosis clusters identified by EuSeqMyTB to support routine surveillance, EU/EEA, 2017 to 2019.

BackgroundThe EUSeqMyTB project, conducted in 2020, used whole genome sequencing (WGS) for surveillance of drug-resistant Mycobacterium tuberculosis in the European Union/European Economic Area (EU/EEA) and identified 56 internationally clustered multidrug-resistant (MDR) tuberculosis (TB) clones.AimWe aimed to define and establish a rapid and computationally simple screening method to identify probable members of the main cross-border MDR-TB clusters in WGS data to facilitate their identification and track their future spread.MethodsWe screened 34 of the larger cross-border clusters identified in the EuSeqMyTB pilot study (2017-19) for characteristic single nucleotide polymorphism (SNP) signatures that could identify and define members of each cluster. We also linked this analysis with published clusters identified in previous studies and identified more distant genetic relationships between some of the current clusters.ResultsA panel of 30 characteristic SNPs is presented that can be used as an initial (routine) screen for members of each cluster. For four of the clusters, no unique defining SNP could be identified; three of these are closely related (within approximately 20 SNPs) to one or more other clusters and likely represent a single established MDR-TB clade composed of multiple recent subclusters derived from the previously described ECDC0002 cluster.ConclusionThe identified SNP signatures can be integrated into routine pipelines and contribute to the more effective monitoring, rapid and widespread screening for TB. This SNP panel will also support accurate communication between laboratories about previously identified internationally transmitted MDR-TB genotypes.

Academic Librarian Search Committee Members Identify Inclusivity Concerns with On-Campus Interview Practices

A Review of: Houk, K. & Neilson, J. (2023). Inclusive hiring in academic libraries: A qualitative analysis of attitudes and reflections of search committee members. College and Research Libraries, 84(4), 568-588. https://doi.org/10.5860/crl.84.4.568 Objective – To understand how academic librarian search committee members’ perceptions and attitudes affect the equitability and inclusiveness of the on-campus interview process. Design – Thematic text analysis of open-ended responses to short-answer questions from an online survey. Setting – Online survey conducted between February and March of 2021. Subjects – 166 academic librarians who had served on hiring committees for academic librarians in North America between 2016 and 2020. Methods – Participants for the 33-question survey were recruited through several academic library listservs and social media postings on Facebook, LinkedIn, and Twitter. The researchers first individually reviewed and coded all responses for short answer survey questions, then reviewed the codes together. Finally, a thematic map was developed after the researchers reached a consensus on their shared approach to coding and generating clusters of meanings. Main Results – Six major clusters were identified through thematic coding of participants’ text responses concerning their experiences of on-campus interview practices as hiring committee members. These themes represented challenges to the inclusiveness of academic librarian searches, and included search committees’ treatment of the interview process as either intentional or situational tests (1), reliance on the ambiguously defined selection criteria of fit (2), experience with varying levels of commitment to diversity, equity, inclusion, antiracism, and accessibility (DEIAA) values (3), frustration with prevalence of institutional bureaucracy throughout the hiring process (4), and uneven adoptions of inclusive hiring (5) or reflective practices (6). The researchers also noted a common respondent mistake of misinterpreting equal (i.e., identical) treatment of candidates as evidence of equitable interview practices. Conclusion – Findings from this study highlighted the importance of academic institutions and hiring committees adopting reflective practices to critically and intentionally incorporate DEIAA-informed practices in planning and conducting academic librarian searches. The authors also stressed the need to reduce possible biases in hiring practices favoring candidates who conforms to White, ableist, and heteronormative culture and values. Examples of these efforts included considering the necessity of each interview element for assessing candidate performances, proactively ensuring full accessibility of the interview itinerary, and operationalizing the definition of “fit” in assessing candidates’ abilities.

Multivariate Analysis of Okra [Abelmoschus esculentus (L.) Moench] Genotypes and Hybrids based on Mineral Content

Background: In 2021, the world production of okra [Abelmoschus esculentus (L.) Moench] was over 10.8 million tonnes which is led by India (about 60%). The objective of this study was to determine mineral content of genotypes and hybrids of okra identified by our in-house heterosis breeding programme. Methods: The samples were digested in a heating block using nitric acid and hydrogen peroxide and analyzed using inductively coupled plasma mass spectrometry (ICP-MS) for mineral profiling of okra samples. Result: The results were evaluated using multivariate analysis. The genotype EC169474 was with the highest concentration of minerals Na (184.91 μg/g), K (14613.52 μg/g) and Fe (268.76 μg/g), while, EC169477 was found to have highest concentration of Mg (6530.76 μg/g) and Ca (273.58 μg/g). Comparatively, in hybrids, EC 169470 x EC169474 contains highest concentration of minerals Na (177.27 μg/g) and Ca (253.01 μg/g), EC169474 x EC169477 contains highest Mg (6301.74 μg/g) and hybrid EC169468 x EC169477 contains highest K (14412.99 μg/g) and Fe (246.51 μg/g). Principal component analysis (PCA) reveals that the element that contributed most for the variability between the genotypes and hybrids was K, moderate contribution by Ca, Fe and Na, while, Mg being the least. Score plot of principal components reveals EC169470 and EC169477 among the most variable genotypes and EC169470 x EC169477 was the most variable hybrid. Hierarchical cluster analysis (HCA) tends to separate all analyzed samples in two major clusters. However, the genotypes EC169474 and EC169477 were grouped in hybrid cluster, while, hybrid EC169470 ´ EC169477 grouped with genotype cluster. The multivariate analysis revealed a systematic difference in the mineral content of okra. The results presented in this study are of great value for nutritionally dense breeding programmes for okra that provides important nutritional diversity by hybrids.

The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis

PurposeImprovement of patient care is associated with increasing publication numbers in biomedical research. However, such increasing numbers of publications make it challenging for physicians and scientists to screen and process the literature of their respective fields. In this study, we present a comprehensive bibliometric analysis of the evolution of gastrointestinal stromal tumor (GIST) research, analyzing the current state of the field and identifying key open questions going beyond the recent advantages for future studies to assess.MethodsUsing the Web of Science Core Collection, 5040 GIST-associated publications in the years 1984–2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and VOSviewer software.ResultsGIST-associated publication numbers substantially increased over time, accentuated from year 2000 onwards, and being characterized by multinational collaborations. The main topic clusters comprise surgical management, tyrosine kinase inhibitor (TKI) development/treatment, diagnostic workup, and molecular pathophysiology. Within all main topic clusters, a significant progress is reflected by the literature over the years. This progress ranges from conventional open surgical techniques over minimally invasive, including robotic and endoscopic, resection techniques to increasing identification of specific functional genetic aberrations sensitizing for newly developed TKIs being extensively investigated in clinical studies and implemented in GIST treatment guidelines. However, especially in locally advanced, recurrent, and metastatic disease stages, surgery-related questions and certain specific questions concerning (further-line) TKI treatment resistance were infrequently addressed.ConclusionIncreasing GIST-related publication numbers reflect a continuous progress in the major topic clusters of the GIST research field. Especially in advanced disease stages, questions related to the interplay between surgical approaches and TKI treatment sensitivity should be addressed in future studies.

Dietary carbohydrate sources differently prime the microbial ecosystem but not the epithelial gene expression profile along the complete gut of young calves

BackgroundRecent data indicated similar growth performance of young calves fed solely high-quality hay instead of a starter diet based on starchy ingredients. Yet, providing exclusively such distinct carbohydrate sources during early life might specifically prime the microbiota and gene expression along the gut of young calves, which remains to be explored. We investigated the effects of starter diets differing in carbohydrate composition, that is medium- or high-quality hay and without or with 70% concentrate supplementation (on fresh matter basis), across the gastrointestinal tract (GIT) of weaned Holstein calves (100 ± 4 days of age) using 16 S rRNA gene sequencing and analyses of short-chain fatty acids and host epithelial gene expressions.ResultsThe concentrate supplementation drastically decreased microbial diversity throughout the gut, which was also true to a much lesser extent for high-quality hay when compared to medium-quality hay in the foregut. Similarly, the factor concentrate strongly shaped the diet-associated common core microbiota, which was substantially more uniform along the gut with concentrate supplementation. The fermentation profile shifted towards less acetate but more propionate with concentrate supplementation in almost all gut sections, corresponding with higher abundances of starch-utilizing bacteria, while major fibrolytic clusters declined. Noteworthy, the n-butyrate proportion decreased in the rumen and increased in the colon with concentrate, showing an opposite, gut site-dependent effect. Both dietary factors modestly influenced the host epithelial gene expression.ConclusionsConcentrate supplementation clearly primed the microbial ecosystem on a starch-targeted fermentation with characteristic genera occupying this niche along the entire GIT of calves, whereas the microbial differentiation due to hay quality was less distinct. Overall, changes in the microbial ecosystem were only marginally reflected in the targeted transcriptional profile of the host epithelium.