bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triazophos toxicity induced histological abnormalities in Heteropneustes fossilis Bloch 1794 (Siluriformes: Heteropneustidae) organs and assessment of recovery response
Authors: Loganathan Kanniyappan , Tennyson Samuel , Arivoli Subramanian 
Published: June 2024

Abstract
Background
Agricultural pesticides have toxic effects in the aquatic ecosystem, and their persistence poses a hazard to aquatic life, as seen by fish poisoning, both acute and chronic. Triazophos, a broad-spectrum organophosphate insecticide, is used to control agricultural crops from insect pests. For a period of 10 days, Heteropneustes fossilis, a fish of great economic and therapeutic value, was exposed to various levels of triazophos toxicity (5, 10 and 15 ppm), after which they were sacrificed. For recovery tests, the treated fish were switched to clean tap water after 10 days of exposure to the toxicant, examined for another 10 days, and then sacrificed. The histological changes in the tissues of the sacrificed fishes' gill, liver, intestine, kidney, brain, and muscle (treatment and recovery) were investigated.

Results
The histology investigations revealed that the toxicant was hazardous, with histopathological changes increasing as the concentration of the toxicant increased. The gills had the most damage, with fusion of secondary lamella and epithelial hyperplasia; liver had vacuolization, pyknotic nuclei, and focal necrosis; intestine had degenerated, necrotic villi, degeneration of epithelial cells, and atropy; kidney had narrowing of the tubular lumen, pyknotic nuclei, hypertrophy, degeneration; swelling, haemorrhage, larger neuronal cells, and karyolysis were observed in the brain, whereas infiltration of leucocytes, loss of striated muscles, and an increase in intra fibril area were observed in the muscle. When compared to the treated fishes, the 10-day recovery research demonstrated tissue damage and a slower recovery pattern.

Conclusions
Triazophos caused histological changes in the gill, liver, intestine, kidney, brain and muscle of the test fish Heteropneustes fossilis. With reference to recovery response, a slow recovery was observed. Furthermore, this is the first investigation into the effects of triazophos on the recovery response in Heteropneustes fossilis.
Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis
Authors: Guo Shuai , Dong Yi , Du Ran , Liu Yu-Xing , Liu Shu , Wang Qin , Liu Ji-Shi , Xu Hui , Jiang Yu-Jie , Hao Huang , Fan Liang-Liang , Xiang Rong 
Published: June 2024

AbstractChronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3’s role in CKD’s narrative and position it as a promising therapeutic contender.
Long term follow-up results of phase II clinical trial evaluating ruxolitinib (RUX) and azacitidine (AZA) combination therapy in patients (pts) with myelofibrosis (MF).
Authors: Arora Sankalp , Senapati Jayastu , Masarova Lucia , Pemmaraju Naveen , Bose Prithviraj , Bravo Guillermo Montalban , Saenz Dyana T , Halim Habiba , Zhou Lingsha , Maiti Abhishek , Borthakur Gautam , Kadia Tapan M. , Jabbour Elias , Garcia-Manero Guillermo , Kantarjian Hagop M. , Daver Naval Guastad 
Published: June 2024

6572 Background: Monotherapy with JAK inhibitors improve spleen and symptom burden in MF, but their disease modifying effect is less clear. We conducted a phase 2 clinical trial evaluating the combination of RUX with hypomethylating agent AZA in MF. The interim analyses (Masarova et al.Blood, 2018) showed objective responses in 72% pts. We report the long-term follow-up of the full cohort of pts treated on this trial. Methods: The trial was conducted at MD Anderson Cancer Center, Houston including adult pts (≥ 18 years) with MF intermediate (Int) 1-2 or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS). Responses were assessed per the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Results: From 3/2013-10/2021, 61 pts with a median age of 66 yrs (46-87) were treated (Table). Median Hb was 10.1 g/dl (6.8-16.2), and bone marrow blasts (BM) 2% (0-14%); 14 (23%) had BM blasts ≥ 5%. JAK 2 was mutated in 35 (57%); 38 pts (62%) had Int-2 or high risk DIPSS disease. IWG-MRT responses occurred in 44 pts (72%): clinical improvement (CI) in 37 (61%), including IWG-MRT CI spleen reduction >50% in 28/46 pts (61%) with baseline length ≥5 cm below left costal margin, and 31/51 pts (61%) with baseline TSS>12 having a >50% improvement in total symptom score (TSS 50). Partial response was seen in 4 pts and cytogenetic complete remission in 3 pts. With a median follow up of 93 mos, median overall survival (OS) was 46 mos (95% CI: 25-66), median event free survival was 33 mos (95% CI: 24-43) and median duration of any objective response was 43 mos (95% CI: 24-62). Transformation to AML occurred in 14 pts (23%) with median time to transformation of 19 mos (1-46). 20 pts (33%) received a stem cell transplant (SCT), 11 (55%) with Int-2/high risk DIPPS disease. Pts in the Int-2/high risk DIPPS group who got SCT had a trend towards improved median OS vs. those who did not (38 vs 27 mos, p=0.2). Grade ≥ 3 adverse events (AE) regardless of treatment attribution occurred in 30 pts (49%), most common were pneumonia (10,16%), anemia (7,12%), and sepsis (5, 8%). 3 pts had grade 5 AEs, and 4 pts were taken off study due to toxicity. Conclusions: Long term follow up data from this phase 2 clinical trial shows good efficacy of the AZA-RUX combination in MF, with durable responses and promising survival outcomes. Clinical trial information: NCT01787487 . [Table: see text]
Epcoritamab with rituximab + lenalidomide (R2) in previously untreated (1L) follicular lymphoma (FL) and epcoritamab maintenance in FL: EPCORE NHL-2 arms 6 and 7.
Authors: Lori Leslie A. , Falchi Lorenzo , Vermaat Joost S.P. , Musuraca Gerardo , Belada David , Nijland Marcel , Christensen Jacob Haaber , Offner Fritz , Hoehn Daniela , Marek Jennifer , Wang Liwei , Mei JP , Abrisqueta Pau , Brody Joshua D. 
Published: June 2024

7014 Background: In 1L FL, more effective, less toxic treatment (tx) options that induce durable complete responses (CRs) are needed. For responders, novel maintenance approaches are needed to improve long-term outcomes. We present data from EPCORE™ NHL-2 (phase 1/2; NCT04663347), with longer follow-up for epcoritamab + R2 in 1L FL (arm 6) and the first disclosure for epcoritamab maintenance in patients (pts) with FL in CR or partial response (PR) after 1–2 lines of standard of care (SOC) tx (arm 7). Methods: Adults with CD20+ FL grade (G) 1–3A received subcutaneous epcoritamab 48 mg. In arm 6, pts received R2 for ≤12 cycles (Cs) of 28 d and epcoritamab (QW, C1–2; Q4W, C3–26). In arm 7, pts received epcoritamab (QW, C1 [28 d]; Q8W, C2–13 [56 d/C]). Pts received step-up epcoritamab dosing and corticosteroid prophylaxis in C1 to mitigate CRS. Primary endpoints were overall response rate (ORR; Lugano criteria) in arm 6 and safety/tolerability in arm 7. Results: As of Nov 22, 2023, 41 pts with 1L FL received epcoritamab + R2 (arm 6) and 20 pts in CR or PR after SOC tx received epcoritamab maintenance (arm 7). In arm 6 (median follow-up, 21.1 mo), median age was 57 y and 34% had FLIPI 3– 5. ORR was 95%; CR rate was 85%. The most common treatment-emergent AEs (TEAEs) were COVID-19 (63%), CRS (56%), and neutropenia (56%). CRS was low grade (41% G1, 15% G2) and resolved; most events occurred after the first full dose and none led to epcoritamab discontinuation. Two fatal TEAEs occurred (COVID-19 pneumonia and septic shock). In arm 7 (median follow-up, 19.7 mo), median age was 54.5 y and 25% had FLIPI 3–5; 60% had CR and 40% had PR with their last tx line. All pts had prior anti-CD20 tx, 80% had prior alkylating agents, and 50% had prior anthracyclines; 80% had 1 prior tx line. The most common TEAEs were COVID-19 (70%) and CRS (55%). CRS was G1 (40%) or G2 (15%) and resolved; events mostly occurred after the first full dose, and none led to tx discontinuation. One fatal TEAE occurred (respiratory failure; post-acute COVID syndrome after 2 Cs of tx). No ICANS or clinical tumor lysis syndrome occurred in either arm. Additional efficacy data are in Table. Conclusions: In arm 6, epcoritamab + R2 continued to show deep, durable responses in 1L FL; safety was manageable and consistent with prior reports. In arm 7, the first epcoritamab maintenance data in FL showed conversions from PR to CR, with manageable safety and no new safety signals. The data warrant further evaluation of epcoritamab-based, chemotherapy-free regimens in FL. Clinical trial information: NCT04663347 . [Table: see text]
Lisocabtagene maraleucel (liso-cel) in patients (pt) with R/R mantle cell lymphoma (MCL): Subgroup analyses by number of prior systemic lines of therapy (LOT) and by response to prior Bruton tyrosine kinase inhibitor (BTKi) from the TRANSCEND NHL 001 MCL cohort (TRANSCEND-MCL).
Authors: Palomba Maria Lia , Siddiqi Tanya , Gordon Leo I. , Kamdar Manali Kirtikumar , Lunning Matthew Alexander , Hirayama Alexandre V. , Abramson Jeremy S. , Arnason Jon , Ghosh Nilanjan , Mehta Amitkumar , Andreadis Charalambos , Solomon Scott R. , Kostic Ana , Singh Ashvin , Espinola Ricardo , Bhatnagar Rashmi , Raviele Anthony , Wang Michael 
Published: June 2024

7016 Background: In the TRANSCEND-MCL (NCT02631044) primary analysis, the CD19-directed, CAR T cell product liso-cel demonstrated a high, durable CR rate (CRR) with manageable safety in pts with heavily pretreated R/R MCL. Here, we report outcomes by number of prior LOTs and by response to prior BTKi. Methods: Pts had PET-positive R/R MCL after ≥ 2 prior systemic LOTs, including BTKi, alkylating, and CD20-targeted agents. Pts received liso-cel after lymphodepleting chemotherapy. Bridging therapy was allowed. Primary endpoints were treatment-emergent AEs (TEAE) and ORR by independent review committee (IRC) per Lugano 2014 criteria; secondary endpoints included CRR, duration of response (DOR), PFS, and OS. Results: 88 pts received liso-cel. Median follow-up was 16.1 mo (range, 0.4–60.5). For all pts, CRR was 72%; median DOR, PFS, and OS were 15.7, 15.3, and 18.2 mo, respectively (Table). ORR, CRR, and median DOR, PFS, and OS were similar to all pts for most subgroups, but numerically lower in pts with ≥ 5 prior LOTs and pts refractory to prior BTKi. Grade (gr) ≥ 3 TEAEs ranged from 67–96% across subgroups, similar to all pts (86%); most common gr ≥ 3 TEAE was neutropenia (33–58%). Most cytokine release syndrome (CRS) and neurological events (NE) were gr 1–2 (Table) with no gr 5 CRS/NE. Gr ≥ 3 infection (11–19%) and prolonged cytopenia (32–50%) in subgroups were similar to all pts (15% and 40%). Cellular kinetics will be presented. Conclusions: In TRANSCEND-MCL, all subgroups benefited from liso-cel and responses were generally comparable to the overall population, with numerically shorter duration in pts with ≥ 5 prior LOTs and disease refractory to prior BTKi, supporting study of liso-cel in earlier LOTs. Clinical trial information: NCT02631044 . [Table: see text]
Deep-learning model for real-time prediction of recurrence in early-stage non-small cell lung cancer: A multi-modal approach.
Authors: Jung Hyun Ae , Lee Daehwan , Park Boram , Lee Kiwon , Lee Ho Yun , Kim Tae Jung , Jeon Yeong Jeong , Lee Junghee , Park Seong Yong , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Park Sehhoon , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Ahn Myung-Ju 
Published: June 2024

8029 Background: The surveillance protocol for early-stage non-small cell lung cancer (NSCLC) is not contingent upon individualized risk factors for recurrence. Longitudinal risk calculation for the prediction of recurrence was based on circulating tumor DNA. This study aimed to develop a deep-learning model using comprehensive data from clinical practice for practical longitudinal monitoring. Methods: A multi-modal deep-learning model employing transformers was developed for real-time recurrence prediction using clinical, pathological, and molecular data at baseline, alongside longitudinal laboratory, and radiologic data during surveillance. Patients with histologically confirmed NSCLC (stage I-III) undergoing curative intent surgery between January 2020 and September 2022 were included. The collected data was divided into training, validation, and test sets in a 6:2:2 ratio. The primary outcome focused on predicting likelihood of recurrence within one year from the monitoring point. This study demonstrated the timely provision of risk scores (RADAR score), determined thresholds, and the corresponding Area Under the Curve (AUC). Results: A total of 14,345 patients were enrolled (10,262 with stage I, 2,380 with stage II, and 1,703 with stage III). The training, validation, and test sets comprised 8,578, 2,866, and 2,901 patients, respectively. The model incorporated 64 clinical-pathological-molecular factors at baseline, alongside longitudinal laboratory, and radiologic text data. Radiologic data of 177,246 was used (mean 12.4 chest CT scan per patient) during surveillance. Baseline RADAR score was 0.20 (standard deviation [Std] 0.17) in stage I, 0.51 (Std 0.20) in stage II, and 0.64 (Std 0.19) in stage III. The AUC for predicting relapse within one year from that monitoring point was 0.847 across all stages with the sensitivity of 80.6% and specificity of 74.4% (Table) (AUC=0.851 in stage I, AUC=0.763 in stage II, and AUC=0.721 in stage III). Conclusions: This pilot study introduces a deep-learning model utilizing multi-modal data from routine clinical practice for predicting relapse in early-stage NSCLC. It demonstrates the timely provision of risk score, RADAR score, to clinicians for recurrence prediction, potentially guiding risk- adapted surveillance strategies and aggressive adjuvant systemic treatment. Notably, the RADAR score exhibited a high prediction ability for relapse in stage I disease. [Table: see text]
Characteristics and clinical outcomes of US veterans with advanced non–small cell lung cancer (NSCLC) by KRAS subtype: A National Veterans Health Administration analysis.
Authors: Anderson Clare E. , Scobie Micaela R , Zhou Katherine I. , Maddox Mark , Kelley Michael J. , Lin Chenyu 
Published: June 2024

8581 Background: KRAS mutations have historically carried a poor prognosis in NSCLC. The most common variant, G12C, had similar survival compared to non-G12C variants. However, new KRAS G12C inhibitors have since been approved. This national VHA study evaluates the outcomes of KRAS-mutated advanced NSCLC by KRAS subtype in the era of KRAS G12C inhibitors. Methods: Patients with unresectable or metastatic NSCLC and a KRAS mutation detected between 2021-2022 were identified from the VA National Precision Oncology Program database. Analysis utilized Fisher’s exact test, logistic regression, and Cox regression. Results: 841 patients across 107 VA medical centers met search criteria. The median age was 73, and 95% were male. 21% were non-Hispanic black, 70% non-Hispanic white, and 2.5% Hispanic. 4% were never smokers. The most common KRAS mutations were G12C (35%), G12V (18%), G12D (13%), G12A (6%), Q61H (4%), and G13D (4%). The most common co-mutations to KRAS were TP53 (54%), STK11 (28%), KEAP1 (16%), and BRAF (3%). KEAP1 mutations more frequently co-occurred with KRAS Q61H (p=0.048), while BRAF mutations were more commonly seen with KRAS G13D (p=0.02) and G13C (p=0.01). In univariable analysis of overall survival (OS), KRAS G12C had a favorable OS compared to all non-G12C variants (HR 0.77, 95% CI 0.64-0.93, p=0.006). Specifically, KRAS G12D (HR 1.35, CI 1.03-1.76, p=0.03) and G12V (HR 1.42, CI 1.10-1.81, p=0.006) had significantly worse OS compared to G12C. Higher PDL1 TPS (HR 0.997, CI 0.995-0.999, p=0.02) and higher TMB (HR 0.96, CI 0.95-0.98, p<0.0001) had better OS, while older age (HR 1.02, CI 1.01-1.03, p=0.004) and co-mutations in KEAP1 (HR 1.60, CI 1.28-1.97, p<0.0001) and STK11 (HR 1.57, CI 1.31-1.88, p<0.0001) had worse OS. Social deprivation index (SDI, calculated by zip code), race/ethnicity, rural residence, and other co-mutations did not affect survival. In multivariable Cox regression, age (HR 1.02, CI 1.003-1.03), KRAS G12C (HR 0.74, CI 0.58-0.93), TMB (HR 0.97, CI 0.95-0.98), and STK11 (HR 1.62, CI 1.23-2.12) retained their association, while KEAP1 and PDL1 were no longer significant. Use of sotorasib had a borderline association with improved survival in univariable analysis (HR 0.74, CI 0.52-1.02). After adjusting for sotorasib in the multivariable model, the association of G12C with OS was no longer significant. In KRAS G12C NSCLC receiving at least 2 lines of therapy (n=90), the likelihood of receiving sotorasib did not differ by age, SDI, gender, race/ethnicity, or rural vs. urban residence. Only a history of economic instability (by ICD10 code) was associated with a lower likelihood of getting sotorasib (OR 0.22, 95% CI 0.03-0.91). Conclusions: In this cohort, KRAS G12C appears to confer a favorable prognosis compared to non-G12C variants, which may be explained in part by the adoption of sotorasib.
The Prevalence of Obstructive Sleep Apnea in Patients With Primary Aldosteronism
Authors: Sheu Jia-Yuh , Chang Li-Yang , Chen Jui-Yi , Chuang Min-Hsiang , Wu Vin-Cent , Chueh Jeff S 
Published: June 2024

Abstract

Context
Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation.

Objective
This work aimed to evaluate the prevalence of OSA in individuals diagnosed with PA and to assess the prevalence of PA within the OSA population, with a specific focus on hypertensive individuals.

Methods
An exhaustive search was performed across PubMed, Embase, CINAHL, Scopus, and Web of Science up to September 2023, without restrictions on language or publication date. Studies were selected based on their focus on the prevalence of OSA in PA patients and vice versa, specifically in hypertensive individuals. Data were extracted using standard guidelines, focusing on patient characteristics, prevalence rates, and other relevant clinical parameters.

Results
Proportional meta-analysis using a random-effects model revealed a 59.8% prevalence of OSA in hypertensive PA patients, with 45.4% exhibiting moderate-to-severe OSA. Meta-regression showed no significant effect of age, sex, body mass index, antihypertensive medication, systolic blood pressure, diastolic blood pressure, or serum potassium on OSA prevalence. However, a significant positive association was found with the glomerular filtration rate (GFR) (P &lt; .001). Subgroup analysis also revealed that a hyperfiltration rate (GFR ≥ 100 mL/min per 1.73 m2) may be associated with a higher prevalence of OSA (71%, P value for interaction &lt; .01). Among hypertensive OSA patients, 11.2% had PA.

Conclusion
A substantial prevalence of OSA in individuals with PA was identified, demonstrating a complex interplay between these conditions in hypertensive patients. Notably, the prevalence of OSA was significantly associated with kidney hyperfiltration.
Whole-exome Sequencing of Atypical Parathyroid Tumors Detects Novel and Common Genes Linked to Parathyroid Tumorigenesis
Authors: Pardi Elena , Poma Anello Marcello , Torregrossa Liborio , Pierotti Laura , Borsari Simona , Della Valentina Simone , Marcocci Claudio , Cetani Filomena 
Published: June 2024

Abstract

Context
Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or distant metastasis, leading to uncertainty regarding its malignant potential.

Objective
To characterize the molecular landscape and deregulated pathways in APT.

Methods
Whole-exome sequencing (WES) was conducted on 16 APTs. DNA from tumors and matched peripheral blood underwent WES using Illumina HiSeq3000.

Results
A total of 192 nonsynonymous variants were identified. The median number of protein-altering mutations was 9. The most frequently mutated genes included BCOR, CLMN, EZH1, JAM2, KRTAP13-3, MUC16, MUC19, and OR1S1. Seventeen mutated genes belong to the Cancer Gene Census list. The most consistent hub genes identified through STRING network analysis were ATM, COL4A5, EZH2, MED12, MEN1, MTOR, PI3, PIK3CA, PIK3CB, and UBR5. Deregulated pathways included the PI3 K/AKT/mTOR pathway, Wnt signaling, and extracellular matrix organization. Variants in genes such as MEN1, CDC73, EZH2, PIK3CA, and MTOR, previously reported as established or putative/candidate driver genes in benign adenoma (PA) and/or PC, were also identified in APT.

Conclusion
APT does not appear to have a specific molecular signature but shares genomic alterations with both PA and PC. The incidence of CDC73 mutations is low, and it remains unclear whether these mutations are associated with a higher risk of recurrence. Our study confirms that PI3 K/AKT/mTOR and Wnt signaling represents the pivotal pathways in parathyroid tumorigenesis and also revealed mutations in key epigenetic modifier genes (BCOR, KDM2A, MBD4, and EZH2) involved in chromatin remodeling, DNA, and histone methylation.
Vigorous Exercise in Patients with Hypertrophic Cardiomyopathy
Authors: Fox Nolan , Fox Nicholas , Jacobsen Alan P. , Blumenthal Roger S. , Barouch Lili A. 
Published: June 2024

Abstract
Hypertrophic cardiomyopathy is a genetic heart condition occurring in up to 1 in 200 patients in the United States, many of whom are young and otherwise healthy. This condition puts those affected at increased risk for adverse cardiac outcomes, including sudden cardiac arrest and death, with particular concern for this to occur during exercise and other forms of exertion. Recent studies aimed at evaluating the risk of exercise in hypertrophic cardiomyopathy patients have suggested that moderate and even vigorous exercise may be safe for certain patients. Clinical guidelines are changing to reflect this recent information and to encourage a shared decision-making approach, which can allow more hypertrophic cardiomyopathy patients to participate in health-promoting exercise activities.