bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of the chemical effect of marble and granite slurry on green mortar compressive strength
Authors: Amin Shereen K. , Allam Mostafa E. , Garas Gihan L. , Ezz Hisham 
Published: February 2020

Abstract
Background
The marble and granite industries in Egypt produce a vast amount of by-product slurry waste that could be used in green mortar production suitable for construction purposes. This research highlights the effect of the chemical constituents of marble and granite waste powders on the compressive strength of the green concrete produced. A chemical analysis of the constituents of granite and marble wastes was compared with those of the cement to study the effect of these components on the hydration reaction inside the mixture. The experiment was based on replacing the same proportions of sand and cement in the green concrete mixes with each of granite and marble waste powders after dissolving it in the water content.

Results
The study revealed that by replacing 5% of cement in (NC5) mix, 10% of sand in (NF10) mix, as well as 5% of cement and 10% of sand in (NC5 + NF10) mix, by granite waste powder, the compressive strength values increased by 33%, 39%, and 41%, respectively. This was due to the presence of more than 26% fine free silica particles in granite which undergo pozzolanic reaction with calcium hydroxide present in mortar pores producing calcium silicate hydrate (CSH) crystals resulting in high strength to the cement mortar. For the same mixes containing marble powder, the compressive strength showed less values by − 14%, 10%, and 0% for NC5, NF10, and NC5 + NF10 mixes, respectively, when compared to the control mix values.

Conclusion
Although the waste particles worked as filler, it was observed that its presence in the mixture improved the particle packing and increased the cohesion of the composites.
Liquefaction structures induced by the M5.7 earthquake on May 28, 2018 in Songyuan, Jilin Province, NE China and research implication
Authors: Shao Zhu-Fu , Zhong Jian-Hua , Howell John , Hao Bing , Luan Xi-Wu , Liu Ze-Xuan , Ran Wei-Min , Zhang Yun-Feng , Yuan Hong-Qi , Liu Jing-Jing , Ni Liang-Tian , Song Guan-Xian , Liu Jin-Lin , Zhang Wen-Xin , Zhao Bing 
Published: February 2020

AbstractAn earthquake of magnitude M5.7 occurred in Yamutu village, Songyuan City, Jilin Province, NE China (45°16′12″N/124°42′35″E) on May 28, 2018, with a focal depth of 13 km. The epicenter is located at the intersection of the Fuyu/Songyuan-Zhaodong Fault, Second Songhua River Fault and Fuyu North Fault which lies northwest of Tancheng-Lujiang Fault (Tan-Lu Fault). The earthquake-induced widespread liquefaction structures and ground surface fissures within 3 km from the epicenter, caused serious disasters to the local surroundings. The visible liquefied structures include sand volcanoes, liquefied sand mounds, sand dikes and sand sills. Sand volcanoes can be divided into sand volcano with a crater, sand volcano without a crater and water volcano (no sand). Other soft-sediment deformation structures (SSDS) induced by the earthquake include deformation lamination, load and flame structures, deformation folds, dish structures, convolute bedding and water-escape structures. The formation process of the sand volcanoes comprises three stages: (1) building up excess pore-fluid pressure in the liquefied layer, (2) cracking of the low-permeable overlying layer, and (3) mixture of sand-water venting out of the ground surface. During the upward movement, the liquefied sand is injected into the low-permeable layer to form sand veins, sand sills and various types of deformation structures. Vertical distribution of seismic liquefaction structure can be divided into four zones: the thoroughly liquefied zone, the lower liquefied zone with SSDS, the upper liquefied zone with SSDS, and the ground surface liquefied zone. The liquefaction occurred at a burial depth of 2–5 m, and the thickness of liquefied sand is 2 m. NE-SW (35°–215°) trending compressive stress is possibly the seismogenic trigger of the Songyuan M5.7 earthquake that caused the fault (Fuyu/Songyuan-Zhaodong Fault) to reactivate. The study of the Songyuan seismic liquefaction structures gives insight into the prediction of modern earthquakes and disaster-prone areas. Meanwhile it provides abundant basic material for studying earthquake-induced SSDS in both ancient and modern sediments. The research is obviously of great significance to reveal that the northern Tan-Lu Fault has entered a stage of active seismic activity since the twenty-first century.
Institutional experience with total neoadjuvant therapy for low-lying rectal tumors.
Authors: Sanders Jason , Goldbeck Lauren D. , Muller Donald A. , Dutta Sunil W. , Kunk Paul Raymond , Hedrick Traci , Hoang Sook , Reilley Matthew , Friel Charles , Le Tri Minh , Janowski Einsley-Marie 
Published: February 2020

123 Background: Surgery has traditionally been the primary treatment for rectal cancer with consideration of neoadjuvant and adjuvant therapies based on stage. Recent studies have shown that Total Neoadjuvant Therapy (TNT) may provide excellent outcomes, with a possibility of non-operative management in patients with rectal cancer. This study is an initial report of our institution’s watchful waiting strategy. Methods: Patients with Stage II-III, low rectal adenocarcinomas treated from 2015-2018 with TNT were retrospectively reviewed. Patients were surgical candidates with no planned surgery. All patients received definitive radiation (median dose 54 Gy, range 50-56 Gy, at 1.8-2 Gy/fx) with concurrent Xeloda, with additional chemotherapy delivered either prior to or following chemoradiation. Kaplan-Meier (KM) method was utilized to estimate the 2 year permanent ostomy and surgery free survivals. Univariate and multivariate analysis using binary logistic regression were performed to assess the odds ratio (OR) of the need for surgery, with 95% confidence interval (CI). Results: 28 patients were treated with TNT with a median age of 59 years (range 32-79 yrs) and median follow up of 24 months (range 6-51 mon). Reasons for TNT included: clinical trial (50%, n = 14), patient desire to avoid surgery (43%, n = 12), and history of LDR prostate brachytherapy (7%, n = 2). The majority of patients had Stage III disease (68%, n = 19). Median tumor distance from the anal verge was 3 cm (range 0-7 cm). 75% (n = 21) of patients were initially managed without surgery, with 5 patients requiring LAR and 2 requiring APR for residual disease. 4 patients initially treated without surgery experienced local recurrence (LR) requiring APR, with a median time to LR of 20 months (range 12-27 mon). The KM estimated 2 year permanent ostomy and surgery free survivals were 69% and 56% respectively. Distant metastases occurred in two patients at 2 and 7 months post RT. An incomplete response on post-treatment MRI predicted eventual receipt of surgery (p = 0.012, OR = 19.8, 95% CI 1.9-202, compared to complete responders). Conclusions: These results support the growing evidence that TNT may provide a non-surgical option for select patients with low lying rectal cancer.
Clinical utility of comprehensive circulating tumor DNA (ctDNA) testing compared to standard-of-care (SoC) tissue testing in first-line (1L) metastatic colorectal cancer (mCRC) patients (pts).
Authors: Benavides Manuel , Alcaide Julia , Alvarez Martina , Torres Esperanza , Sevilla Isabel , Gil Calle Silvia , Reyna Carmen , Alés Inmaculada , Durán Gema , Wolman Roberto , Cazorla Mireya , Jimenez Gallego Pedro , López Irene , Cantero Alexandra , Godoy Ana , Lanman Richard B. , Faull Iris , Odegaard Justin , Kim Il Jin , Alba Emilio 
Published: February 2020

15 Background: Accurate genotyping is mandatory for the management of mCRC pts. Tissue-based testing is still the SoC; however, is not available for all pts. and may be exhausted by serial testing, resulting in incomplete genotyping. We aimed to establish the validity of comprehensive non-invasive ctDNA testing in 1L mCRC pts for whom SoC tissue genotyping was available. Methods: 1L mCRC pts were tested with a comprehensive ctDNA test (Guardant360), a RAS ctDNA test (OncoBeam), and SoC tissue testing at the time of diagnosis. The primary endpoint was NCCN guideline biomarker discovery rate ( KRAS, NRAS, and BRAF mutations, ERBB2 amplification, and microsatellite instability). Results: In 91 evaluable pts, the biomarker discovery rate was 54.9% (50/91) for SoC tissue testing, 59.3% (54/91) for comprehensive ctDNA testing ( p= 0.0318 for non-inferiority vs. SoC), and 42.9% (39/91) for RAS ctDNA testing (inferiority not rejected vs. SoC). Both comprehensive and RAS ctDNA testing showed high positive agreement (85%, 44/52, and 86%, 31/36) and negative agreement (96%, 268/279, and 93%, 93/100) relative to SoC tissue testing at the gene level. Expanding genotyping beyond KRAS codon 12/13 mutations increased biomarker discovery rate by 56% for tissue testing (50/91 vs. 32/91, McNemar’s p< 0.0001) and by 64% for comprehensive ctDNA (54/91 vs. 33/91, McNemar’s p< 0.0001). Turnaround time was significantly shorter for comprehensive ctDNA testing vs. SoC tissue testing (mean 11.7 days vs. 23.0 days, paired T-test p= 0.0002). On retrospective analysis, 92% of biomarker-positive pts would have been identified at 2 weeks using the comprehensive ctDNA test for initial genotyping with reflex to tissue for biomarker-negative pts, whereas initial use of SoC tissue testing would have identified only 85% of positive pts at 4 weeks (Fisher’s exact p< 0.0001). Conclusions: As previously reported for lung cancer, comprehensive ctDNA testing in 1L mCRC identifies at least as many biomarker-positive pts as SoC tissue genotyping with high concordance to tissue and in half the turnaround time.
Effect of adding bevacizumab to chemotherapy on pathologic response to preoperative systemic therapy of potentially resectable colorectal cancer liver metastases (CLM): A systematic review and meta-analysis.
Authors: Jácome Alexandre A. , Oliveira Fernanda A. , Silva Flora De Moraes Lino , Lima João Paulo da Silveira Nogueira 
Published: February 2020

151 Background: Perioperative CT and resection of CLM are potentially curative therapies in the management of metastatic colorectal cancer (mCRC). Retrospective studies suggest that preoperative bevacizumab increases pathologic response, which is a surrogate endpoint for overall survival (OS). We conducted the first systematic review and meta-analysis addressing the effect of bevacizumab on pathologic response to preoperative therapy of CLM. Methods: We systematically searched PubMed, Cochrane Library, Embase and LILACS from January/2004 to August/2019 for studies that have compared the pathologic response to CT plus bevacizumab versus CT alone as preoperative therapy of potentially resectable CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoint was major response (MaR) (0-50% residual cancer cells or tumor regression grade (TRG) 1-3 in liver specimen). The likelihood of preoperative therapy being associated with pCR or MaR has been expressed by odds ratio (OR) and 95% confidence intervals (CI) using a random-effects model. Results: Of the 1,319 studies yielded by the search, 9 studies were retained, totaling 1,202 patients (516 CT plus bevacizumab versus 686 CT alone). The addition of bevacizumab to CT increased the pCR rate, but it did not reach statistical significance (OR: 1.24, 95% CI 0.81 – 1.92, p = 0.32). However, MaR was significantly superior in the bevacizumab group (OR: 2.20, 95% CI 1.47 – 3.29, p < 0.001). A higher percentage of patients have been submitted to oxaliplatin-based regimens in bevacizumab group compared to CT alone group (84% versus 68%, p < 0.001), while irinotecan-based regimens have been more common in the CT alone group (11% versus 28%, p < 0.001). Conclusions: The addition of bevacizumab to preoperative CT was associated with higher rates of pathologic response in liver resection of CLM. Anti-angiogenics might potentially improve the recurrence-free survival and OS in the management of potentially resectable CLM and should be evaluated as preoperative therapy in randomized clinical trials.
Use and impact of perioperative chemotherapy in patients with resectable colorectal cancer metastases.
Authors: Body Amy , Lee Margaret , Wong Hui-Li , Pope Alun , Jalali Azim , Shapiro Jeremy David , Kosmider Suzanne , Tie Jeanne , Barnett Frances Sarah , Richardson Gary Edward , Yip Desmond , Lim Stephanie Hui-Su , McKendrick Joseph James , Gibbs Peter , Wong Rachel 
Published: February 2020

159 Background: There is conflicting evidence regarding benefit of perioperative chemotherapy (p-chemo) for metastatic colorectal cancer (mCRC) patients (pts) undergoing resection of metastases (mets). Aims: To describe use of and outcomes from p-chemo in mCRC pts who underwent resection of isolated liver or lung mets. Methods: Pts were identified from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a multi-centre registry of mCRC pts. P-chemo was defined as chemotherapy within 12 weeks of surgery. Multivariate (MV) analysis using a Cox proportional hazards model was undertaken. Results: 371 pts were identified. Median age was 64 (27 – 90), 169 (45%) had de novo stage IV disease, 96% were ECOG 0-1. 284 (77%) had liver-only and 87 (23%) lung-only mets. 242 (65%) pts received p-chemo (58 pre-op alone, 134 post-op alone, 50 both). 62 (19%) pts also received a biologic agent (47/62 pre-op). Median age was 68 and 61 years in no p-chemo and p-chemo groups, respectively (p<0.0001). 53% of no p-chemo pts and 23% of p-chemo pts had had prior adjuvant chemotherapy (p<0.001). On MV analysis, p-chemo was a significant predictor of survival (HR 0.52, 95% CI 0.32-0.88, p=0.014). The other significant predictor of improved survival was ECOG PS of 0 (HR 0.58, p=0.019). Predictors of worse survival were rectal primary (HR 1.98 p=0.009), male gender (HR 1.69 p=0.03) and de-novo metastatic disease (HR 2.63, p=0.006). Prior adjuvant chemo, age, liver vs lung mets, use of perioperative biologics, BRAF and RAS status had no significant impact. In an exploratory analysis, the group considered “resectable” upfront (n=281) was analysed separately, perioperative chemotherapy was not a significant predictor of survival in this subgroup (HR 0.69, p=0.26). Conclusions: In routine care there is a variable approach to the use of p-chemo in pts with potentially resectable liver or lung mets. P-chemo is associated with improved survival in this analysis, although this was not confirmed in the separate analysis of the “resectable” subgroup. Due to the retrospective nature of the study confounding by unmeasurable factors is possible. This study supports ongoing consideration of P-chemo in pts with resectable mets.
IKKα as a potential novel target for treatment of colorectal cancer.
Authors: Quinn Jean A. , Patel Meera , Pennel Kathryn AF , Flanagan Dustin , Horgan Paul G. , McMillan Donald C. , MacKay Simon , Sansom Owen , Edwards Joanne 
Published: February 2020

174 Background: Colorectal cancer (CRC) is a heterogeneous disease leading to different survival outcomes for patients with the same stage of disease. The non-canonical NF-κB pathway has been shown to have a key role in tumorigenesis, and the aim of this study was to investigate the role of IKKα, the main catalytic component of this pathway in CRC. Methods: A tissue microarray was retrospectively constructed from a patient cohort (1033) with stage I-III CRC who underwent surgery. IHC was utilised to examine cytoplasmic and punctate IKKα expression and determine any association with clincopathological features and cancer specific survival (CSS). To assess IKKα inhibition, organoids were prepared from wild type (WT) mouse colon, mouse models of CRC (Apc and Apc.KRAS.pT53.TGFbR2 (AKPT)) and patient derived human organoids. These were treated with an IKKα inhibitor, SU1433 and organoid size and cell viability assessed. Results: High cytoplasmic expression of IKKα was associated with increasing T stage (p = 0.012), poor tumour differentiation (p = 0.010), tumour necrosis (p = 0.013) and low proliferation status (p = 0.013) but was not associated with CSS. High punctate IKKα expression associated with tumour differentiation (p = 0.001), necrosis (p = 0.004), proliferation (p = 0.044) and MMR competence (p < 0.001) and was also significantly associated with reduced CSS (HR1.20 95%CI 1.02-1.42, p < 0.001). SU1433 did not significantly impact on WT (C57/B16) organoid viability up to a concentration of 1 uM, however organoid size and cell viability was significantly reduced in a dose dependent manner in organoids from both Apc and AKPT mouse models. A similar reduction was observed in patient derived human organoids. Conclusions: Punctate IKKα expression was associated with poor cancer specific survival in CRC patients, and inhibition with SU1433, impacted on CRC mouse and patient derived human organoid size and cell viability. These results suggest that, following further investigation and confirmation, IKKα may be employed as a novel therapeutic target in CRC.
NeoRAS: Incidence of RAS reversion from RAS mutated to RAS wild type.
Authors: Henry Jason , Willis Jason , Parseghian Christine Megerdichian , Raghav Kanwal Pratap Singh , Johnson Benny , Dasari Arvind , Stone David , Jeyakumar Nikeshan , Coker Oluwadara , Raymond Victoria M. , Lanman Richard B. , Overman Michael J. , Kopetz Scott 
Published: February 2020

180 Background: RAS mutations are found in ~50% of patients (pts) with metastatic colorectal cancer (mCRC) and associated with resistance to anti-EGFR. Circulating tumor DNA (ctDNA) enables detection of resistant RASMUT arising from RASWT. Recently there has been interest in defining the converse: RASMUT tumors that revert to RASWT, with early results suggesting rates of ~7%. Clinical trials in this population are in development, though the incidence has not been validated with robust methodologies. Methods: 1) We identified 74 mCRC pts with baseline RASMUT and longitudinal ctDNA or tissue data enrolled in ATTACC (NCT01196130), a prospective genomic matching protocol utilizing paired tissue/ctDNA samples at baseline. We evaluated serial samples for RAS loss. 2) Using an external cohort of pts with mCRC and serial ctDNA with a targeted NGS assay sequencing all KRAS/ NRAS exons (Guardant360, Guardant Health), we screened pts for baseline RASMUT with no evidence of prior anti-EGFR exposure and evaluated for RAS loss. Results: 74 pts met criteria of RASMUT CRC with serial samples in ATTACC. Of these, 51 retained RASMUT. 22 pts had very low or absent levels of other clonal alterations such as APC or TP53 and are therefore unable to reliably detect RAS loss. One patient had true RAS loss with NRAS G13R, APC and TP53 mutations at baseline and persistent high-level APC and TP53 mutations without a detectable NRAS mutation, for an overall rate of RAS loss of 2% (1/52). In the second cohort we identified 162 pts, 34 of which had insufficient ctDNA to assess RAS loss on the serial sample as defined by loss of clonal alterations like APC and TP53. Of the remaining 128 patients, 11 had RAS loss (8.5%, with 1 NRAS, 10 KRAS). We next compared the relative mutant allele frequency (rMAF) between RAS retainers and RAS loss. The median baseline rMAF for pts who lost RAS was 0.74, compared to 0.86 in pts retaining RAS (p = 0.045). Conclusions: RAS reversion in mCRC from RASMUT to RASWT is uncommon and occurs at a rate between 2-8% in our two cohorts. RAS reversion is associated with a lower rMAF at baseline, suggesting subclonality. Liquid biopsies must be interpreted carefully, such that a determination of RAS mutation status is most informative in the presence of truncal APC and/or TP53 mutations.
Genetic variants in R-Spondin/RNF43 complex and gene expression levels to predict efficacy of cetuximab (cet) in patients (pts) with metastatic colorectal cancer (mCRC): Data from the FIRE-3 phase III trial.
Authors: Battaglin Francesca , Xiao Yi , Millstein Joshua , Seeber Andreas , Arai Hiroyuki , Wang Jingyuan , Puccini Alberto , Tokunaga Ryuma , Naseem Madiha , Soni Shivani , Berger Martin D. , Barzi Afsaneh , Zhang Wu , Stintzing Sebastian , Heinemann Volker , Lenz Heinz-Josef 
Published: February 2020

190 Background: Wnt signaling deregulation is a primary driver of colorectal carcinogenesis. RNF43 is a key suppressor of Wnt activation while R-Spodin inhibits RNF43 activity. RNF43 mutations are associated with the serrated neoplasia pathway, BRAF mutation and MSI. We hypothesized that genetic variants in the R-Spodin/RNF43 complex and corresponding genes expression levels may predict cetuximab efficacy in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in the randomized FIRE-3 trial was genotyped through the OncoArray, a custom array manufactured by Illumina. The impact on outcome of 17 functional SNPs within RNF43/ ZNRF3, LGR4/5 and RSPO1/2/3 was analyzed in 129 pts treated with first-line FOLFIRI/cet and 107 pts treated with FOLFIRI/bevacizumab (bev). Gene expression levels were measured from tumor tissue samples from 102 pts in the cet arm by HTG EdgeSeq Oncology Biomarker Panel. False discovery rate (FDR) for gene expression analysis was computed using the Benjamini-Hochberg approach (significant Q < 0.1). Results: In the cet cohort, pts with the C/C genotype of ZNRF3 rs132531 had significantly shorter overall survival compared to any T allele carriers (mOS: 20.3 vs 52 mo) in both univariable (HR 3.61, 95% CI 1.65-7.88, P < .001) and multivariable analysis (adjusted P = .01). Conversely, RSPO1 rs4652964 any G allele carriers showed increased tumor response (TR) rates compared to the A/A genotype (83 vs 66 %, P = .04). These associations were not observed in bev arm. Lower gene expression levels of RNF43 were associated with shorter PFS in pts with right-sided tumors receiving FOLFIRI/cet ( P = .006, Q < 0.1). RSPO1 expression levels were also associated with TR in the same subgroup (70 vs 10% in high vs low; P = .001, Q < .05). RNF43 expression was associated with TR in pts with left-sided tumors (82% in high vs 58% in low, P = .014, Q = 0.1). Conclusions: Our results provide the first evidence that germline polymorphisms and tumor gene expression levels of RNF43/ ZNRF3 and RSPO1 may have a predictive value in mCRC pts receiving first-line cetuximab-based treatment and contribute to modulate anti-EGFRs activity.