bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amelioration of oxidative and inflammatory changes by Peganum harmala seeds in experimental arthritis
Authors: Singhai Ashish , Patil Umesh Kumar 
Published: January 2021

Abstract
Background
The present study was designed to investigate the therapeutic effects against oxidative stress and alleviative effects of Peganum harmala seeds (PH) in rats with Complete Freund’s Adjuvant (CFA) induced arthritis.

Methods
The extract was evaluated for its phytoconstituents, antiarthritic and antioxidant properties. The action of chloroform (PHC) and ethanolic (PHE) extracts of PH was evaluated in adult Lewis rats (150-200 g).with CFA induced arthritis. Arthritic rats received PH extracts 100 mg/kg orally for 28 consecutive days (Prophylactic treatment) and from 14th day of CFA injection (Therapeutic treatment).

Results
PHE significantly suppressed the arthritis severity in rats than PHC in 28 days. All complications shown significant reduction (p< 0.05) in arthritic rats including paw volume (63.09%), body weight loss, decreased locomotor activity, erythrocyte sedimentation rate and synovial/hepatic tissues lipid peroxidation and increase in cellular antioxidants superoxide dismutase (U/mg) activities and hemoglobin counts. The results showed the presence of alkaloids and flavonoids in PHE. Histology and radiographic analysis of arthritic ankle joints indicated abnormal changes. Marked reduction in inflammation and arthritic changes were observed after treatment with PHE.

Conclusion
Therefore, the investigation suggests that PHE at 100 mg/kg will be useful in the management of rheumatoid arthritis complications which may possibly be due to boosting the intracellular antioxidant defense.
Spatial scale in prescribed fire regimes: an understudied aspect in conservation with examples from the southeastern United States
Authors: Mason David S. , Lashley Marcus A. 
Published: January 2021

AbstractThe idea that not all fire regimes are created equal is a central theme in fire research and conservation. Fire frequency (i.e., temporal scale) is likely the most studied fire regime attribute as it relates to conservation of fire-adapted ecosystems. Generally, research converges on fire frequency as the primary filter in plant community assembly and structure, which is often critical to conservation goals. Thus, conservation success is commonly linked to fire frequency in fire regimes.The spatial scale of fire may also be vital to conservation outcomes, but this attribute is underrepresented in the primary literature. In our global, contemporary literature search, we found 37 published syntheses concerning the effects of prescribed fire in conservation over the last decade. In those syntheses, only 16% included studies that reported data-based inferences related to the spatial scale of the fire, whereas 73% included discussion of empirical studies on the temporal scale. Only one of the syntheses discussed studies that explicitly tested the effects of spatial extent, and none of those studies were experiments manipulating spatial scale. Further, understanding spatial-scale-dependent patterns may be relevant because two databases of fire-occurrence data from the United States indicated that spatial scale among lightning-ignited and prescribed fires may have been mismatched over the past few decades.Based on a rich ecological literature base that demonstrates pervasive scale-dependent effects in ecology, spatial-scale-dependent relationships among prescribed fire regimes and conservation outcomes are likely. Using examples from the southeastern United States, we explored the potential for scale-dependent ecological effects of fire. In particular, we highlighted the potential for spatial scale to (a) influence wildlife populations by manipulating the dispersion of habitat components, and (b) modulate plant community assembly and structure by affecting seed dispersal mechanics and spatial patterns in herbivory. Because spatial-scale-dependent outcomes are understudied but likely occurring, we encourage researchers to address the ecological effects of spatial scale in prescribed-fire regimes using comparative and manipulative approaches.
Semiautomatic fault-surface generation and interpretation using topological metrics
Authors: Lou Yihuai , Zhang Bo , Yong Pan , Fang Huijing , Zhang Yijiang , Cao Danping 
Published: January 2021

Seismic fault surfaces are compulsory input for structure modeling that unravels the structural deformation history of the subsurface. Seismic fault attributes provide geoscientists with alternative images of faults. However, seismic fault attributes only highlight possible fault locations and do not directly provide fault surfaces that are required inputs for structural modeling. Interpreters construct seismic fault surfaces using interpreted seismic fault sticks on vertical seismic slices. Interpreting fault sticks on hundreds of seismic slices is time consuming. We have semiautomatically constructed fault surfaces by simulating the procedure of manual seismic fault interpretation. Our algorithm consists of three main steps: (1) obtaining fault sticks in the inline, crossline, and time slices; (2) grouping the fault sticks according to the connectivity and mutual exclusion (topology) between the fault sticks on the inline, crossline, and time slices; and (3) generating the fault surface patches by merging the fault sticks time slice by time slice through the topology analysis. Our algorithm contains one optional step: manually merging the fault patches if needed. We test our algorithm on open access seismic data and our workflow accurately generates fault surfaces for most faults including conjugate faults in the seismic data. Considering that it usually helps to weight the estimation according to the quality of the computed fault attribute, the algorithm computes fault parameters such as fault dip and strike using weighted principal component analysis.
Minimal residual disease (MRD) detection with circulating tumor DNA (ctDNA) from personalized assays in stage II-III colorectal cancer patients in a U.K. multicenter prospective study (TRACC).
Authors: Anandappa Gayathri , Starling Naureen , Begum Ruwaida , Bryant Annette , Sharma Shruti , Renner Derrick , Aresu Maria , Peckitt Clare , Sethi Himanshu , Feber Andrew , Potter Vanessa Alice , Paraoan Marius , Abulafi Muti , George Nicol , Branagan Graham , Duff Sarah , West Nicholas , Aleshin Alexey , Chau Ian , Cunningham David ,   UK Colorectal Cancer TRACC Study Group
Published: January 2021

102 Background: Numerous studies have shown the clinical utility of ctDNA, a non-invasive biomarker to detect MRD and stratify CRC patients who are more likely to relapse. We present an analysis of MRD detection in CRC patients from a prospective multicentre UK study, who were monitored pre- and post-surgery before adjuvant chemotherapy (ACT). Methods: The study recruited patients diagnosed with stage II-III CRC (n=122), including a subset of rectal patients who underwent tri-modality treatment (TMT). All patients had their primary tumor resected and 56% (68/122) received ACT. Paired plasma samples (n=244) were collected before surgery/neaodjuvant chemoradiotherapy and after surgery; median follow-up for survival was 15.48 months (0.16 - 42.1 months). Individual tumors and matched germline DNA were whole-exome sequenced and somatic single nucleotide variants (SNVs) identified. Multiplex PCR assays were designed to track tumor-specific SNVs (Signatera, bespoke mPCR NGS assay) in plasma samples. The study evaluated ctDNA status and clinical outcomes including radiologic imaging. Cox regression was used to calculate recurrence-free survival (RFS) in patients stratified by post-op ctDNA status. Patients were also stratified into low and high-risk groups based on the clinicopathological features. Multivariate analysis was performed with covariates: ctDNA, age, gender, laterality, stage, number of lymph node resected, MSI & TMB. Results: Pre-treatment ctDNA was detected in 93.4% (100/107) of patients. Post-operative ctDNA status prior to ACT was assessed in 107 patients, of whom, 13% (14/107) were MRD-positive (MRDpos). Of the MRDpos patients 42.9% (6/14) eventually relapsed. In contrast, only 8.6% (8/93) of MRD-negative (MRDneg) cases relapsed (HR: 10; 95% CI: 3.3-30; p<0.001). MRD rates stratified by risk features in each of the stages with respective recurrence rates are shown in Table. In stage III patients (n=64), 45.4% (5/11) of the MRDpos patients relapsed, whilst only 17% (9/53) of the MRDneg cases relapsed (HR: 9; 95% CI:2.6-32; p<0.0001). In the multivariate analysis, ctDNA status was the most significant prognostic factor associated with RFS (HR: 28.8, 95% CI: 3.5-234.1; p<0.001). Conclusions: Postoperative ctDNA analysis with tumor informed assay enables detection of CRC patients at high-risk of recurrence. Early detection of MRD could guide ACT decisions in intervention trials and is currently underway in TRACC. Clinical trial information: NCT04050345. [Table: see text]
Inactivation of E-cadherin by Trop-2 drives colon cancer metastasis.
Authors: Alberti Saverio , Guerra Emanuela , Altomare Donato F. , Depalo Raffaella , Trerotola Marco 
Published: January 2021

105 Background: Tumor metastasis is the main cause of death of colon cancer patients and the biggest hurdle for cancer cure. We set to identify decisive drivers and of pivotal therapy targets for colon cancer metastasis. Methods: IHC analysis quantified the expression of target molecules in primary tumors and metastases. Cell-cell adhesion capacity was assessed in vitro and in HCT116 colon cancer cell spheroids. Pre-clinical models of orthotopic growth of KM12SM colon cancer cells and metastatic diffusion to the liver were utilized to assess metastatic spreading force of wtTrop-2 and of the constitutively-active, tail-less form of Trop-2 (Δcyto). Xenotransplant and metastasis transcriptomes were analyzed for differential induction of EMT determinants. Kaplan–Meier plots were used to illustrate survival and metastatic relapse in independent case series of colon cancer patients. Results: wtTrop-2 was shown to induce wound-healing. ΔcytoTrop-2 further increased cell migration ability. Both wtTrop-2 and ΔcytoTrop-2 induced resistance to apoptosis in vitro and in vivo. wtTrop-2 strikingly increased the metastatic capacity of KM12SM cells, raising metastasis rates from 45% for control cells to 90% for wtTrop-2 transfectants. The constitutively-active ΔcytoTrop-2 further boosted metastatic spreading, with metastatic livers reaching up to four times their normal size. Cancer metastases revealed high levels of E-cadherin, in the absence of transcriptional down-regulation. EMT transcription factors were largely missing from Trop-2-activated cells. Rather, binding to Trop-2 was shown to cause the release of E-cadherin from the cytoskeleton, loss of cell-cell adhesion and activation of β-catenin. This global, Trop-2/E-cadherin/β-catenin-driven pro-metastatic program was recapitulated in colon cancer patients and was shown to impact on colon cancer metastatic relapse and overall patient survival. Conclusions: We identify Trop-2-driven functional inactivation of E-cadherin as a widespread driver of metastatic diffusion in colon cancer, opening novel avenues for personalized diagnostic procedures and anti-cancer therapies. [Table: see text]
Characteristics of genomic alterations in circulating tumor DNA (ctDNA) in patients (Pts) with advanced gastrointestinal (GI) cancers in nationwide large-scale ctDNA screening:SCRUM-Japan Monstar-Screen.
Authors: Nakamura Yoshiaki , Fujisawa Takao , Kadowaki Shigenori , Takahashi Naoki , Goto Masahiro , Yoshida Kazuhiro , Kawakami Takeshi , Esaki Taito , Oki Eiji , Nishida Naohiro , Nishina Tomohiro , Komatsu Yoshito , Ohta Takashi , Kuramoto Naomi , Horasawa Satoshi , Sakamoto Yasutoshi , Taniguchi Hiroya , Yoshino Takayuki 
Published: January 2021

106 Background: Analysis of ctDNA has been utilized in pts with advanced GI cancer for identification of genomic alterations for targeted therapy. However, the characteristics of ctDNA genomic alterations of GI cancers compared to non-GI cancers remains unclear. Methods: Pts with advanced solid tumors were eligible in MONSTAR-SCREEN, a nationwide ctDNA screening project in Japan. Plasma samples were analyzed by an NGS-based 70-gene ctDNA assay, FoundationOne Liquid (F1L) at a CLIA-certified and CAP-accredited laboratory since Jul 2019. For treatment-naïve pts, tumor tissue samples were analyzed by FoundationOne CDx (F1CDx), a 324-gene tissue-based panel. Results: As of Jun 18 2020, out of enrolled 540 pts with advanced solid tumor, 470 pts, consisting of 133 with advanced GI cancers (67 colorectal, 48 gastric, 14 esophageal, 2 gastrointestinal tumor (GIST) and 2 small intestinal) and 337 non-GI cancers (103 hepatobiliary and pancreatic, 70 genitourinary, 64 breast, 46 head and neck, 33 gynecologic, and 21 skin), had an available ctDNA result. Sequencing success rate was similar between GI and non-GI cancers (91.7% vs. 89.3%, P = 0.50). GI cancers had a significantly higher ctDNA level (maximum variant allele fraction) than non-GI cancers (median, 11.8% vs. 0.57%; P = 1.6E-7). The most frequently altered genes were TP53 (73%), APC (73%), KRAS (30%), BRAF (15%), and PIK3CA (12%) in colorectal cancer, TP53 (44%), KRAS (19%), PIK3CA (15%), ATM (10%), and ERBB2 (10%) in gastric cancer, and TP53 (79%), ATM (21%), ERBB2 (21%) in esophageal cancer. Mutations in genes in pathways related to RAS/RAF/MEK (39.1 % vs. 21.4 %, P = 1.8E-4), receptor tyrosine kinase (20.3% vs 11.9%, P = 0.027), p53 (66.2% vs 49.6%, P = 0.0014), and Wnt (41.4% vs 4.7%, P = 4.4E-21) were significantly enriched in GI cancers compared to non-GI cancers. Tumor tissue samples were analyzed using F1CDx for 63 treatment-naïve pts, in which 51 (31.3%) of 132 alterations identified by F1L were not detected by F1CDx. Conclusions: GI cancers had higher ctDNA levels and distinct characteristics of ctDNA genomic alterations from non-GI cancers with an enrichment in several oncogenic pathways. One-third of ctDNA alterations were detected in only ctDNA, indicating the potential of ctDNA analysis to identify heterogenous genomic alterations in advanced GI cancer. Clinical trial information: UMIN000036749.
Expression of PD-L1 and PD-L2 in colorectal cancer (CRC): A post-hoc integrated analysis of SCRUM-Japan GI-SCREEN CRC.
Authors: Yuki Satoshi , Nakamura Yoshiaki , Taniguchi Hiroya , Denda Tadamichi , Nishina Tomohiro , Hamamoto Yasuo , Hara Hiroki , Esaki Taito , Kawakami Hisato , Takashima Atsuo , Satoh Taroh , Sunakawa Yu , Masuishi Toshiki , Shinozaki Eiji , Moriwaki Toshikazu , Miki Izumi , Shitara Kohei , Yoshino Takayuki 
Published: January 2021

120 Background: PD-1, PD-L1/L2 axis is responsible for cancer immune escape which facilitate disease progression. However, expression of these proteins in CRC and its significance in clinical prognosis are yet to be fully clarified. Methods: This was a post-hoc analysis using FFPE tumor samples from the Nationwide Cancer Genome Screening Project, SCRUM-Japan GI-SCREEN for metastatic CRC. Patients (Pts) with MSI-H or BRAF V600E mutant tumors were prioritized to be included. PD-L1 (22C3) and PD-L2 expressions were centrally assessed using immunohistochemical assays at QualTek and NeoGenomics, respectively. Tumor infiltrating lymphocytes (TILs) were morphologically evaluated by H&E staining. Clinical information including biomarker status and overall survival (OS) were extracted from SCRUM-Japan GI-SCREEN database. Results: In total, 200 pts were included in this study with a median age of 65 (range, 29–88) years; male/female (116/84); MSI status MSI-H/non-MSI-H/unknown (8/189/3); RAS wild-type/mutant (113/87); and BRAF V600E wild-type/mutant (173/27). Positivity rate of PD-L1 in tumor cells (TC), immune cells (IC), PD-L2 on TC and IC were 10.8%, 46.9%, 0% and 20.3%, respectively. Expression of PD-L1 on TC or IC and PD-L2 on IC were associated with TIL (p = 0.023, p = 0.009, respectively). PD-L1 on TC was highly seen in BRAF V600E-mutated tumors (p = 0.043), but not related to other factors including RAS and MSI status. The pts with PD-L1+ tumors on TC or IC had longer OS than those with PD-L1- (Median, 31.9 vs 23.5 months; HR = 0.67, 95% CI, 0.46–0.99; p = 0.040), while OS in pts with PD-L2+ tumors was similar to that with PD-L2- (Median, 21.4 vs 27.3 months; HR = 0.87, 95% CI, 0.53–1.44; p = 0.60). The PD-L1 expression was also associated with the longer OS in pts with BRAF wild-type or non-MSI-H tumors. Conclusions: Our study suggested different prognostic impact of PD-L1 and PD-L2 expression in CRC pts, which require further evaluations as potential therapeutic targets for CRC. Clinical trial information: UMIN000016343.
Differential gain of chromosomal regions 20q or 13q with loss of 8p and 18q differentiates disease-free survival in colorectal cancer.
Authors: Chao Eva , Xu Qi , Capasso Anna , Eckhardt S. Gail , Kowalski Jeanne 
Published: January 2021

126 Background: In microsatellite stable (MSS) colorectal cancer (CRC) cases, frequent amplifications in 13q and 20q regions have been reported with limited understanding of their potential role for prognosis and treatment. Based on an internal research molecular tumor board case analysis of a KRAS WT, MSS left-sided (LS), metastatic CRC patient, we noted 50% of the 11 listed variants of unknown significance were on 20q. This study aims to investigate the potential prognostic role for gain of 20q chromosomal regions relative to other chromosomal imbalances using a retrospective cohort. Methods: We performed a genome-wide CN cluster analysis using the TCGA data with resulting patient clusters compared based on Kaplan-Meier estimated disease-free interval (DFI) in months (mos) using a log-rank. We examined associations between CN-derived clusters and CRC phenotypes. Results: Using TCGA data, we identified four CN-derived patient clusters of which two had significantly different DFI’s. One longer DFI cluster (n = 83; median DFI = 28mos) was defined by a signature of copy neutral genes along Chr8p and 18q regions. The shorter DFI cluster (n = 46; median DFI = 20mos) was defined by a signature of Chr8p and 18q regions of loss. The two clusters significantly differed in terms of site (85% right-sided in the shorter vs. 85% LS in the longer DFI cluster) and MS status (81% MSS in the shorter vs. 72% MSI in the longer DFI cluster) with no significant differences in age (mean of 70 years at diagnosis) and KRAS status (around 50% WT) between clusters. The shorter DFI was able to be further differentiated based on gain of chromosomal regions 20q (n = 26; median DFI = 24mos) and 13q (n = 20; median DFI = 18mos). No significant differences in mean age, tumor stage, site, and MS status between the shorter DFI subgroups were noted. Enriched pathways in the Chr20q gain sub-cluster include cell differentiation (Hippo, Rap1, VEGF), whereas metabolic signaling pathways via AGE-RAGE and AMPK, as well as cell growth and malignant transformation via RAS are enriched in the Chr13q gain sub-cluster. Conclusions: Clinical sequencing is able to identify regions of gain in Chr20q and Chr13q as part of VUS’s. Gain of Chr20q has been reported with better survival in mCRC patients. Gain of chromosomal region 20q and loss of 18q has been reported to discriminate between Lynch Syndrome and familial colorectal cancer. Herein, we show that gain of the 20q region with 18q and 8p regions of loss is associated with shorter DFI and gain of 13q region with loss of 8p even worse prognosis.
The impact of sociodemographic characteristics on gastric cancer outcomes: A retrospective review of a large single center study.
Authors: Findakly Dawood , Forlemu Arnold , Kosa Dimas , Amar Surabhi 
Published: January 2021

172 Background: Gastric cancer (GC) remains a pervasive condition in the US with high morbidity and mortality. Race/ethnicity, lack of insurance, and poverty may all be contributing to this burden, especially in select populations. We evaluated the impact of these sociodemographic factors on GC outcomes at a hospital with high immigrant-patient populations. Methods: We conducted a retrospective study to identify patients diagnosed with GC between year 2010 and 2019. Data obtained from our institution database regarding patients' sociodemographic factors, including age, gender, race/ethnicity, insurance status and type, and neighborhood socioeconomic status. Likewise, information on tumor histology, anatomic location, and stage were also obtained. Kaplan-Meier analysis was used to plot survival curves and analyze the impact of insurance on survival outcome. Results: One hundred eleven patients were analyzed in this study, with a male-to-female ratio of 1.26:1. The median age at the time of GC diagnosis was 52.9 (range 27-87) years, with median survival time (±SD, range) of 12.7 (±17.7, 0.25-84) months. Most patients (69.4%) were uninsured—out of which 76.7% presented with advanced-stage disease. Among those, the majority (70.3%) were Hispanic, and 60.4% were non-U.S. citizens. The most common tumor histology was diffuse-type adenocarcinoma in 55% of patients. Patients insured were on public coverage (Medicaid), private insurance, and Medicare at 11.7%, 9.9%, and 9.0%, respectively. In terms of survival, lack of insurance (p = 0.012) and Medicaid insurance (p = 0.046) were associated with the worst survival outcomes in GC patients. Conclusions: Our study reflects the trends in GC outcomes distinctly linked to significant sociodemographic disparities. Patients who lack insurance coverage had the worst survival outcomes. Therefore, efforts such as increasing healthcare access for this population-type at risk of sociodemographic incongruities may enhance outcomes and are crucial in fighting GC.