Significant Difference In Frequency Research Articles

Research on the toxicological prognostic significance of age-related genes in endometrial cancer unveiling key factors in patient prognosis.

This study investigates the influence of aging-related genes on endometrial cancer, a prominent gynecological malignancy with rising incidence and mortality. By analyzing gene expression differences between cancerous and normal endometrial tissues, 42 aging-related genes were identified as differentially expressed. Utilizing the TCGA-UCEC sample, consensus clustering divided the samples into two molecular subgroups, Aging low and Aging high, based on their expression profiles. These subgroups showed distinct prognoses and survival rates, with the Aging high group associated with DNA repair and cell cycle pathways, and the Aging low group showing suppressed metabolic pathways and increased immune cell infiltration, suggesting a potential for better immunotherapy outcomes. Mutation analysis did not find significant differences in mutation frequencies between the groups, but a high Tumor Mutation Burden (TMB) correlated with better prognosis. A risk score model was also developed, showcasing significant prognostic power. Further analysis of the SIX1 gene revealed its overexpression in cancer cells. Drug sensitivity tests indicated that the low-risk group might respond better to chemotherapy. This research underscores the significance of aging-related genes in endometrial cancer, offering insights into their prognostic value and therapeutic potential, which could lead to personalized treatment approaches and enhanced patient management.

Vincristine-induced adverse events related to body weight in dogs treated for lymphoma.

Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. One hundred and thirty-eight dogs with newly diagnosed lymphoma were treated with vincristine. A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post-administration. Data were evaluated using logistic regression or ordinal logistic regression. Thirty-eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.

HLA alleles associated with susceptibility and severity of the COVID-19 in Vietnamese

The diversity of clinical manifestations in COVID-19 has been observed not only among individuals but also among various populations in globally. HLA molecules play a central role in physiology, protective immunity, and deleterious, disease-related autoimmune reactivity or overreaction. This study exploited the association between HLA frequencies and SARS-CoV-2 susceptibility and disease severity among the Vietnamese cohort (159 patients and 52 controls). A significant difference in frequency of both HLA class I and II in mild, moderate, and severe/fatal COVID-19 patients and negative exposure individuals - the controls were observed. Regarding SARS-CoV-2 sensitivity, HLA-A*03:01, 30:01, HLA-DQA1*01:02, DRB1*15:01, and DRB5*02:02 presented higher frequency in the control group compared with infected patients but DRB1 09:01 frequency was higher in infected patients. Regarding COVID-19 severity, HLA‐F*01:01, 01:03 and DPA1*01:03 and 02:01, DPB1*04:01, DQA1*01:02, and DQB1*05:02 alleles were detected with higher frequency in severe patients but DOB*01:01, DRB1*05:01 and 09:01 had a significantly higher frequency in the mild group than remaining groups. Surprisingly, HLA-DQA1*01:02 and DRB1*09:01 alleles were identified with both inversely potential roles in protective function and severe risk. The obtained data herein will contribute to explore on the role of host genetic background in the pathology of COVID-19 disease.

Comparison of snack characteristics by diet quality: findings from a nationally representative sample of Australian adolescents

Snacking is a common eating behaviour among adolescents accounting for more than a quarter of their total energy intake but the relationship between snacks and overall diet quality remains unclear(1). Hence, the aim of this study was to examine characteristics of snacks among Australian adolescents (12-18 years) according to their level of diet quality. This secondary analysis uses one day of 24-hour dietary recall data from the 2011 - 2012 National Nutrition and Physical Activity Survey (n = 935). Snacks were defined based on participant-identified eating occasions(2). The Dietary Guideline Index for Children and Adolescents (DGI-CA) was used to assessed adherence to the Australian Dietary Guidelines(3), with the highest tertile of the DGI-CA score indicating high adherence. The means (95% confidence intervals [CI]) for daily snack frequency and snack energy density (ED; kJ/g) were estimated for boys and girls, using linear regression, adjusted for age, area-level disadvantage, and energy misreporting. The differences in means and proportions across tertiles of DGI-CA scores were tested by using F- and Chi square-tests, respectively. The results show no significant differences in the mean frequency of snacks across tertiles of DGI-CA scores in either boys (lowest tertile mean = 2.2, 95% CI [2.0, 2.4] snacks/day, highest tertile = 2.1 [1.9, 2.3]) or girls (lowest tertile = 1.9 [1.7, 2.1] snacks/day, highest tertile = 2.2 [1.9, 2.4]). The mean ED of snacks decreased as DGI-CA scores increased in both boys (lowest tertile = 8.42, 95% CI [7.1, 10] kJ/g, highest tertile = 6.32 [5.4, 7.4] kJ/g) and girls (lowest tertile = 8.99 [7.8, 10.3] kJ/g, highest tertile = 5.92 [5.1, 6.9] kJ/g). As DGI-CA scores increased, the proportion of both boys and girls consuming discretionary foods at snacks (such as soft drinks) decreased, while foods from the five food groups (such as apples) increased (p-values < 0.05). In conclusion, snack ED, but not frequency, and the types of foods consumed by adolescents at snacks varied by a level of diet quality. Snack ED decreased with increasing diet quality and adolescents with higher diet quality had higher intakes of foods from the five food groups and lower intakes of discretionary foods at snacks. Encouraging the consumption of lower-ED foods from the five food groups at snacks presents an opportunity to enhance adolescent diet quality. Future studies should explore snack-specific strategies to improve overall diet quality of adolescents.

Characteristics of wild moose (Alces alces) vocalizations.

Moose are a popular species with recreationists but understudied acoustically. We used publicly available videos to characterize and quantify the vocalizations of moose in New Hampshire separated by age/sex class. We found significant differences in peak frequency, center frequency, bandwidth, and duration across the groups. Our results provide quantification of wild moose vocalizations across age/sex classes, which is a key step for passive acoustic detection of this species and highlights public videos as a potential resource for bioacoustics research of hard-to-capture and understudied species.

Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection

To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson's trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson's trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.

This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 μg/mL) compared with that before co-administration (88.8 ± 13.6 μg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 μg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.

Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province

The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

The 3% hypertonic saline infusion test for the differential diagnosis of diabetes insipidus and primary polydipsia: assessment of diagnostic accuracy

AIM: assessment of the diagnostic accuracy of a 3% hypertonic saline infusion test in relation to a set of clinical and laboratory data (including a water deprivation test and MRI data) for differential diagnoses of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was carried out at Endocrinology Research Centre From September 2021 to September 2023 ninety patients with polyuria-polydipsia syndrome were included. In order to assess the diagnostic characteristics, all the subjects underwent two tests with osmotic stimulation: a 3% hypertonic saline infusion test and a water deprivation test. Adverse events were assessed.RESULTS: Based on the results of clinical, anamnestic, laboratory and instrumental data, and the results of a water deprivation test, a final diagnosis of DI was made in 48 (53%) patients and PP in 42 (47%) patients. The agreement between the two samples is significant — Kappa = 0.823, 95% CI (0.707, 0.939). The operational parameters of the 3% hypertonic saline infusion test are: sensitivity 98% (95% CI: 89%; 100%); specificity 98% (95% CI: 87%; 100%), positive and negative predictive values 98% (95% CI: 89%–100%) and 98% (95% CI: 87%–100%). Respectively. Chills occurred significantly more often (31% vs. 12%), and dizziness and headache were more pronounced during the 3% hypertonic saline infusion test. The median duration of the water deprivation test in patients was 11 hours, and median duration of 3% hypertonic saline infusion test was 1.5 hour (P&lt;0.001).CONCLUSION: The 3% hypertonic saline infusion test has a high overall diagnostic accuracy 98%; 95% CI 92% to 100%)) in relation to the classical set of clinical, laboratory and instrumental data of patients (including a water deprivation test), However, it is important the advantage of the latter is its short duration and, as a consequence, better tolerability and probably better compliance, while no significant differences in adverse events frequencies during the tests were identified.

Abstract 5099: Prevalence of fibroblast growth factor receptor (FGFR) alterations (alts) and programmed death-ligand 1 (PD-L1) expression (exp) in Chinese solid tumor patients (pts)

Abstract Background: PD-L1 expression drives anti-PD(L)-1 treatment decisions across many cancer indications. FGFR inhibitors have been approved for the treatment of metastatic urothelial cancer (UC) and cholangiocarcinoma with FGFR alts. BALVERSA (erdafitinib), a selective pan-FGFR kinase inhibitor, has shown clinical activity against FGFR altered solid tumors in pts who exhausted standard treatment options. It is important to understand the prevalence of FGFR alts and relationship between FGFR alts and PD-L1 expression levels in different cancer types. Methods: In this real-world study, 9937 Chinese solid tumor pts with the PD-L1 (22C3) immunohistochemistry and OrigiMed 450-gene next-generation sequencing panel results were selected. Chi-square test and Fisher test were used to explore the association between the FGFR alts and PD-L1 expression. Results: FGFR1-4 somatic alts were found in 9.0% of Chinese cancer pts evaluated. FGFR1 amplification (amp) was the most prevalent alts identified (1.9%). There were no significant differences in frequency of FGFR alts between the Chinese cohort and MSK-IMPACT cohort in each cancer type tested. Up to 40.6% of pts evaluated were PD-L1 positive (CPS ≥1 or TPS ≥1%). The PD-L1 positive rate (TPS ≥1%) in SCLC (12.4%, n=121) and NSCLC adenocarcinoma tumors (LUAD) (26.1%, n=2902) was relatively low. In few tumor types, higher expression of PD-L1 in FGFR altered samples was observed compared with FGFR unaltered samples in pan-tumor (mean TPS 14.8% vs.8.6%, P=6.0*E-9; mean CPS 6.3 vs. 6.1, P=3*E-4). Those includes LUAD (mean TPS 14.2% vs. 7.4%, P = 1.7*E-16), colorectal tumor (mean CPS 4.6 vs. 3.9, P = 4.6*E-8), and uterine tumor (mean CPS 8.1 vs. 6.5, P = 9.6*E-5). While PD-L1 expression is lower in FGFR altered samples than FGFR unaltered samples in UC (n=154; mean CPS 3.9 vs. 6.8, P = 0.004). No relationship was observed between FGFR alts and PD-L1 expression in cholangiocarcinoma (n=610). Specific FGFR alts eligible for erdafitinib UC treatment were further investigated in UC and observed with rate 10.4%, including FGFR3 short variants (9.7%) as main alts. Specific FGFR altered tumors showed similar trend with lower PD-L1 expression than FGFR unaltered tumors in UC. The inverse relationship between FGFR alts and PD-L1 expression in UC compared to other solid tumors may explain variable role of FGFRs since the predominant FGFR alt types vary among different cancer types (FGFR3 short variants enriched in UC vs no such predominant FGFR alt types in other cancer types). Conclusion: The large Chinese solid tumor cohort analysis showed comparable FGFR alts prevalence between Chinese and Western population. Differences in relationship between FGFR alts and PD-L1 expression across tumor types reflect the differential role of predominant FGFR types in each tumor type. Citation Format: Min Qing, Fei Yang, Xiaowei Chen, Xuesong Lyu, Aodi Wang, Yanfei Yu, Shibu Thomas, Longen Zhou. Prevalence of fibroblast growth factor receptor (FGFR) alterations (alts) and programmed death-ligand 1 (PD-L1) expression (exp) in Chinese solid tumor patients (pts) [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 5099.

Abstract 1769: Pan-cancer genomic characterization of human papillomavirus associated tumors reveals patterns of somatic alteration that associate with virus status and anatomic site

Abstract Human papilloma virus (HPV) infection causes over 600,000 human cancers yearly and accounts for nearly all cervical cancers, increasing rates of head and neck squamous cell carcinomas (HNSCC), and many anogenital cancers - all with varying clinical outcomes due to a lack of personalized care. While recent integrative genomic studies have described molecular features of individual cancer types, few studies have compared genomic changes between HPV(+) and HPV(-) cancers across anatomic sites. Here, we conducted the first pan-cancer genomic analysis of HPV-associated tumors across multiple anatomic tumor types using whole exome and transcriptome data from The Cancer Genome Atlas (TCGA) cohorts of cervical (n=254) and HNSCCs (n=514), and targeted exome sequencing of 800 cancer genes plus full length HPV16/18 genomes in a clinical cohort of squamous tumors from the head and neck (n=458), cervix (n=78), vulva (n=23), anal canal (n=5), and vagina (n=2). Somatic variant calling and filtering, followed by an integrative pathway analysis of commonly altered targets, defined the catalog of somatic mutations and copy number alterations (CNAs) that drive HPV(+) and HPV(-) tumorigenesis. Sequencing reads from viral RNA or DNA determined HPV status, and HPV type, genome structure, integration events, and viral load were characterized in a subset of samples via de novo assembly of viral aligned reads followed by copy number analysis, breakpoint identification, and the calling of structural variants. Overall HPV positivity was 50% (668 out of 1334 total), with HPV16 accounting for 96%, 89%, and 60% of all HPV(+) anogenital, head and neck, and cervical tumors respectively. Significant differences in somatic mutation frequency between HPV(+) and HPV(-) tumors were observed in the full cohort, as well as in analyses stratified by anatomic site. Interestingly, we noticed recurrently mutated “hotspots” attributable to increased APOBEC-mutagenesis in HPV(+) samples across anatomic sites (PIK3CA:E545K, FGFR3:S249C, EP300:D1399N), while hotspot mutations likely caused by tobacco smoking predominate HPV(-) HNSCC (PIK3CA:H1047R/L, CDKN2A:R80*, TP53:R282W). Focal and arm level CNAs were distinctive, including gains of 11q22 in HPV(+) cervical and HPV(-) HNSCC, and losses of 11q22 in HPV(+) HNSCC. Biological pathways commonly altered include epithelial differentiation, cell death, innate immunity, growth factor/kinase signaling, and cell cycle control. In summary, pan-cancer genomic analysis revealed distinct patterns of somatic alteration of conserved biological pathways that associate with HPV status and anatomic site. These findings improve our understanding of tumor biology unique to HPV-associated cancers and may lead to novel treatment and classification strategies to improve patient outcomes in the clinical setting. Citation Format: Jeremiah Ray Holt, Paul Little, Heejoon Jo, Xiaobei Zhao, Hyo Young Choi, Vonn Walter, Benjamin Wahle, Jose P. Zevallos, Angela Mazul, Katherine A. Hoadley, Michele Hayward, David N. Hayes. Pan-cancer genomic characterization of human papillomavirus associated tumors reveals patterns of somatic alteration that associate with virus status and anatomic site [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 1769.

Association Analysis of Polymorphisms in Inflammation-Related Genes with Non-Hodgkin Lymphoma Susceptibility

Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy that develops in the lymphatic system. A20, CYLD, IFN-γ, JAK2, PI3KCA, and TP53 are known as inflammation-related genes in autoimmune diseases and cancers. In the end, 126 patients with NHL and 109 healthy individuals with well-characterized clinical profiles were enrolled. Twelve variants in the above genes were determined by the Kompetitive allele-specific PCR (KASP) assay. As a result, among genotyped 12 SNPs, the AG genotype of the rs280500 in the TYK2 gene showed significantly higher frequency in the patient group compared to healthy individuals (P=0.05). In addition, no significant differences in genotype frequencies of the other SNPs were found between the two groups. In conclusion, the rs280500 in the TYK2 gene was the risk variant for NHL susceptibility and additionally contributed to understanding the genetic basis of NHL.&#x0D;

Abstract 5585: Genetic variants of IDH and EGFR as diagnostic and prognostic biomarkers in glioblastoma multiforme: A case-control study in the Jordanian Arab population

Abstract Background: Glioblastoma multiforme (GBM) represents a highly aggressive primary brain tumor with poor prognosis. Mutation in the Isocitrate dehydrogenase (IDH1) gene and epidermal growth factor (EGFR) amplification are key diagnostic markers for GBM. However, the prognostic role of genetic variants of these genes remains unclear. Therefore, we aimed to investigate the association between specific single nucleotide polymorphisms (SNPs) for IDH and EGFR genes, and their impact on the risk and prognosis of GBM patients within the Jordanian Arab population. Methods: We carried out a case-control study involving 63 GBM patients and 226 healthy controls at King Abdullah University Hospital in Jordan. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue for GBM patients and blood samples for controls. IDH1 (rs121913500C&amp;gt;T), IDH2 (rs11540478G&amp;gt;A), EGFR (rs231677G&amp;gt;A), and EGFR (rs1468727C&amp;gt;T) SNPs were genotyped and analyzed using the Sequenom iPLEX assay sequencing technique. Overall survival (OS) was analyzed between SNPs using the univariable Cox proportional hazard model. The Cancer Genome Atlas (TCGA-GBM) cohort of 585 patients were analyzed for IDH1, IDH2, and EGFR alterations with OS, disease-free survival (DFS), and progression-free survival (PFS). Single-cell RNA analysis was performed on the following scRNA datasets from the Gene Expression Omnibus (GEO): GSE163108 (n=25,013 cells), and GSE102130 (n=3,321 cells) . Results: Our study revealed a significant difference in genotype frequency between GBM cases and controls for IDH1 rs121913500C&amp;gt;T, and EGFR rs1468727C&amp;gt;T SNPs. Univariable Cox model showed that the G/G genotype of rs231677G&amp;gt;A (EGFR) SNP was associated with better OS in the codominant model (HR: 0.24, 95% CI: 0.08-0.73, p-value=0.012), and rs11540478G&amp;gt;A (IDH2) SNP (HR: 0.02, 95% CI: 0.0-0.29, p-value=0.005) showing significantly better prognosis compared to the A/G genotype. In the TCGA validation cohort, the altered group of IDH1 were significantly associated with better OS (HR: 0.35, 95% CI: 0.24-0.50, p-value&amp;lt;0.001), DFS (HR: 0.34, 95% CI: 0.23-0.50, p-value&amp;lt;0.001) , and PFS (HR: 0.43, 95% CI: 0.30-0.62, p-value&amp;lt;0.001). The scRNA analysis showed predominant expression of IDH1, IDH2, and EGFR by malignant cells, oligodendrocyte precursor cells, and macrophages. Conclusion: Our investigation into the genetic landscape of GBM within the Jordanian population suggest that specific genetic variants, particularly in IDH1 genes and EGFR, may serve as diagnostic and prognostic biomarkers for GBM. Additionally, IDH1 alterations were associated with better prognostic outcomes. Single-cell RNA analysis further illuminates the predominant expression of IDH1, IDH2, and EGFR by malignant cells which can be used as potential avenues for targeted therapies based on genetic profiles. Citation Format: Ayah N. Al-Bzour, Sohaib M. Al-Khatib, Mohammad N. Almajali, Tariq A. Jarrad. Genetic variants of IDH and EGFR as diagnostic and prognostic biomarkers in glioblastoma multiforme: A case-control study in the Jordanian Arab population [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 5585.

Experimental Study on the Slip–Stick Vibration of Plane Gate

The slip–stick vibration intensity of a plane gate is usually large, which often brings serious safety risks to itself and the auxiliary structure. The slip–stick vibration of a plane gate is investigated using an experimental model test. The test conditions mainly focus on the gate-closing and gate-opening processes in transient flow. Based on the results, comparison diagrams of the slip–stick vibration response versus the external fluid excitation are constructed. The intensity and period of the slip–stick vibration both gradually increase with the opening degree of the plane gate decreasing. The frequency of slip–stick vibration is consistent with the natural frequency of the equivalent system, indicating that the slip–stick vibration is a nonlinear self-excited vibration. The slip–stick vibration and fluid excitation acting on the plane gate have a significant difference in response intensity and dominant frequency. In addition, a difference in gate support material can have a significant effect on the slip–stick vibration intensity. Therefore, the friction factor between gate support and track, rather than the fluid excitation, is the direct cause of slip–stick vibration, which can further prove that the slip–stick vibration is a friction-induced vibration caused by the gate’s active motion, enriching the theory of the gate’s vibration.

Effect of tobacco use on Zenker's diverticulotomy outcomes

ObjectiveTo compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). Study designSingle institution retrospective review. SettingTertiary care academic hospital. MethodsA retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. ResultsOut of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). ConclusionsThere were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.

The effect of myeloablative radiation on urinary bladder mast cells

Radiation-induced cystitis is an inflammatory condition affecting the urinary bladder, which can develop as a side effect of abdominopelvic radiotherapy, specifically external-beam radiation therapy or myeloablative radiotherapy. A possible involvement of mast cells in the pathophysiology of radiation-induced cystitis has been indicated in cases of external-beam radiation therapy; however, there is no evidence that these findings apply to the myeloablative aetiology. As such, this study investigated potential changes to urinary bladder mast cell prevalence when exposed to myeloablative radiation. Lethally irradiated C57BL/6J mice that received donor rescue bone marrow cells exhibited an increased mast cell frequency amongst host leukocytes 1 week following irradiation. By 4 weeks, no significant difference in either frequency or cell density was observed. However mast cell diameter was smaller, and a significant increase in mast cell number in the adventitia was observed. This study highlights that mast cells constitute a significant portion of the remaining host leukocyte population following radiation exposure, with changes to mast cell distribution and decreased cell diameter four weeks following radiation-induced injury.

Genetic characterization of minor carp (Labeo gonius) from Indian rivers revealed through mitochondrial ATPase 6/8 and D-loop region analysis: implications for conservation and management

India is the habitat of many freshwater fish species that make a significant contribution to endemism. However, the native species population is declining at a very fast rate due to pollution, habitat loss or degradation, new species introduction, hydrologic alterations, and overfishing. The minor carp, Labeo gonius, is one of the important fish species in the Indian river systems and holds enormous potential in culture fisheries. Therefore, the precise status of population structure is a prerequisite for the management of the species. In the present study, we assessed the potential of mtDNA ATPase 6/8 and D-loop regions as markers to determine the genetic diversity and phylogeography of L. gonius from Indian rivers. We have selected five major Indian rivers for investigation which could represent geographically distant populations of the studied fish. A total of 210 ATPase 6/8 sequences (842 bp) and 203 D-loop region sequences (683 bp) of L. gonius from the five major Indian rivers were submitted to NCBI. Results revealed that ATPase 6/8 has 17 haplotypes and 70 polymorphic sites with an overall haplotype diversity of 0.560 ± 0.036 and nucleotide diversity of 0.00347 ± 0.00. Furthermore, D-loop analysis revealed 58 haplotypes, 67 polymorphic sites, 0.954 ± 0.006 overall haplotype diversity, and 0.01914 ± 0.00 nucleotide diversity. The hierarchical AMOVA analysis indicated that a high proportion of the genetic variation (76.46% and 70.22% for the D-loop and ATPase 6/8 regions, respectively) was attributed to among-population variation under gene pool-1 (considering all the stocks from Ganga, Brahmaputra, Teesta, Narmada, and Mahanadi as a single pool). Furthermore, in gene pool-2, samples were divided into two groups: group 1 (Himalayan rivers)—Ganga, Brahmaputra, and Teesta; and group 2 (peninsular rivers)—Narmada and Mahanadi. Genetic variations in the D-loop and ATPase 6/8 regions were found among populations within groups at 70.65% and 53.48%, respectively. Haplotype network analysis revealed that there were significant differences in distributions and frequencies. The observed unique haplotypes might be useful for differentiating the stocks. In brief, the present study suggested that the D-loop and ATPase 6/8 regions are potential markers and represent a significant contribution to the genetic characterization of the minor carp L. gonius from major Indian rivers. Moreover, the L. gonius population along the east coast especially in the Himalayan rivers (Ganga, Brahmaputra, and Teesta river basin) is found to be genetically more diverse. The results would provide a scientific basis for the assessment of fisheries resources and management of this important species.

Cannulated prolactin test in the diagnosis of the hyperprolactinemia syndrome

Hyperprolactinemia (HP) is a persistent pathological increase in a prolactin serum concentration amounting to more than 20 ng/ml in males and 25 ng/ml in females and leads to developing the pathological symptom complex of HP primarily from the reproductive system. To confirm the persistent etiology of HP and to eliminate physiological short-term hormone enhancement, a number of recommendations, including Russian and Belarusian, were proposed to make several prolactin measurements.This study included 120 patients with HP (96 females, 78.0 %) and (27 males, 22.0 %) aged 18–50 years who sought medical help at the Health Institution “Minsk City Clinical Endocrinology Center” in the period from December 2022 to September 2023. After catheterizing the vein, a venous cannula was inserted and blood was taken immediately after cannulating (T0), and then in 60 minutes (T1) and 120 minutes (T2). The cannulated prolactin test results were considered positive – with HP remaining in all three samples (T0, T1, T2), questionable – if HP was kept at T0 and T1, and negative if HP was only at T0. When evaluating the cannulated test results, true HP is 36.7 %. Patients with a positive cannulated test had a higher prolactin at T0, which was 888.5 mME/L (U = 97.0; z = 7.92; p &lt; 0.001). Patients with stress-induced HP (negative test) and patients with true HP (positive test) had no statistically significant differences in age and occurrence frequency of specific and non-specific complaints and symptoms for HP.

High Peritumoral and Intratumoral T2 Signal Intensity in HER2-Positive Breast Cancers on Preneoadjuvant Breast MRI: Assessment of Associations With Histopathologic Characteristics.

BACKGROUND. Intratumoral necrosis and peritumoral edema are features of aggressive breast cancer that may present as high T2 signal intensity (T2 SI). Implications of high T2 SI in HER2-positive cancers are unclear. OBJECTIVE. The purpose of this study was to assess associations with histopathologic characteristics of high peritumoral T2 SI and intratumoral T2 SI of HER2-positive breast cancer on MRI performed before initiation of neoadjuvant therapy. METHODS. This retrospective study included 210 patients (age, 24-82 years) with 211 HER2 breast cancers who, from January 1, 2015, to July 30, 2022, underwent breast MRI before receiving neoadjuvant therapy. Two radiologists independently assessed cancers for high peritumoral T2 SI and high intratumoral T2 SI on fat-suppressed T2-weighted imaging and classified patterns of high peritumoral T2 SI (adjacent to tumor vs prepectoral extension). A third radiologist resolved discrepancies. Multivariable logistic regression analyses were performed to identify associations of high peritumoral and intratumoral T2 SI with histopathologic characteristics (associated ductal carcinoma in situ, hormone receptor status, histologic grade, lymphovascular invasion, and axillary lymph node metastasis). RESULTS. Of 211 HER2-positive cancers, 81 (38.4%) had high peritumoral T2 SI, and 95 (45.0%) had high intratumoral T2 SI. A histologic grade of 3 was independently associated with high peritumoral T2 SI (OR = 1.90; p = .04). Otherwise, none of the five assessed histopathologic characteristics were independently associated with high intratumoral T2 SI or high peritumoral T2 SI (p > .05). Cancers with high T2 SI adjacent to the tumor (n = 29) and cancers with high T2 SI with prepectoral extension (n = 52) showed no significant difference in frequency for any of the histopathologic characteristics (p > .05). Sensitivities and specificities for predicting the histopathologic characteristics ranged from 35.6% to 43.7% and from 59.7% to 70.7%, respectively, for high peritumoral T2 SI, and from 37.3% to 49.6% and from 49.3% to 62.7%, respectively, for high intratumoral T2 SI. Interreader agreement was almost perfect for high peritumoral T2 SI (Gwet agreement coefficient [AC] = 0.93), high intratumoral T2 SI (Gwet AC = 0.89), and a pattern of high peritumoral T2 SI (Gwet AC = 0.95). CONCLUSION. The only independent association between histopathologic characteristics and high T2 SI of HER2-positive breast cancer was observed between a histologic grade of 3 and high peritumoral T2 SI. CLINICAL IMPACT. In contrast with previously reported findings in broader breast cancer subtypes, peritumoral and intratumoral T2 SI had overall limited utility as prognostic markers of HER2-positive breast cancer.

Genetic parentage reveals the (un)natural history of Central Valley hatchery steelhead.

Populations composed of individuals descended from multiple distinct genetic lineages often feature significant differences in phenotypic frequencies. We considered hatchery production of steelhead, the migratory anadromous form of the salmonid species Oncorhynchus mykiss, and investigated how differences among genetic lineages and environmental variation impacted life history traits. We genotyped 23,670 steelhead returning to the four California Central Valley hatcheries over 9 years from 2011 to 2019, confidently assigning parentage to 13,576 individuals to determine age and date of spawning and rates of iteroparity and repeat spawning within each year. We found steelhead from different genetic lineages showed significant differences in adult life history traits despite inhabiting similar environments. Differences between coastal and Central Valley steelhead lineages contributed to significant differences in age at return, timing of spawning, and rates of iteroparity among programs. In addition, adaptive genomic variation associated with life history development in this species varied among hatchery programs and was associated with the age of steelhead spawners only in the coastal lineage population. Environmental variation likely contributed to variations in phenotypic patterns observed over time, as our study period spanned both a marine heatwave and a serious drought in California. Our results highlight evidence of a strong genetic component underlying known phenotypic differences in life history traits between two steelhead lineages.