bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant food anti-nutritional factors and their reduction strategies: an overview
Authors: Samtiya Mrinal , Aluko Rotimi E. , Dhewa Tejpal 
Published: March 2020

AbstractLegumes and cereals contain high amounts of macronutrients and micronutrients but also anti-nutritional factors. Major anti-nutritional factors, which are found in edible crops include saponins, tannins, phytic acid, gossypol, lectins, protease inhibitors, amylase inhibitor, and goitrogens. Anti-nutritional factors combine with nutrients and act as the major concern because of reduced nutrient bioavailability. Various other factors like trypsin inhibitors and phytates, which are present mainly in legumes and cereals, reduce the digestibility of proteins and mineral absorption. Anti-nutrients are one of the key factors, which reduce the bioavailability of various components of the cereals and legumes. These factors can cause micronutrient malnutrition and mineral deficiencies. There are various traditional methods and technologies, which can be used to reduce the levels of these anti-nutrient factors. Several processing techniques and methods such as fermentation, germination, debranning, autoclaving, soaking etc. are used to reduce the anti-nutrient contents in foods. By using various methods alone or in combinations, it is possible to reduce the level of anti-nutrients in foods. This review is focused on different types of anti-nutrients, and possible processing methods that can be used to reduce the level of these factors in food products.Graphical abstractA brief overview of beneficial effects of anti-nutrients and reduction strategy.
Passive coherent dual-comb spectroscopy based on optical-optical modulation with free running lasers
Authors: Gu Chenglin , Zuo Zhong , Luo Daping , Deng Zejiang , Liu Yang , Hu Minglie , Li Wenxue 
Published: March 2020

AbstractDual-comb spectroscopy is a powerful spectroscopic tool with ultrahigh-resolution, high-sensitivity properties, which opens up opportunities for the parallel detection of multi-species molecules. However, in its conventional form, highly stable laser combs with sophisticated control systems are required to perform dual-comb spectroscopy. Here, a passive mutually coherent dual-comb spectroscopy system via an optical-optical modulation method is addressed, where all fast phase-locking electronics are retired. Without post computer-based phase-correction, a high degree of mutual coherence between the two combs with a relative comb-tooth linewidth of 10 mHz is achieved, corresponding to a coherent time of 100 s. To demonstrate the performance and versatility of the system, the dual comb spectrometer is applied to record the mode-resolved single molecular spectra as well as parallel detected spectra of mixed gases including CO2, CO and C2H2 that well agree with the established spectral parameters. Our technique exhibits flexible wavelength tuning capability in the near-infrared region and can be potentially extended to the mid-infrared region for more applications.
OncoMX: A Knowledgebase for Exploring Cancer Biomarkers in the Context of Related Cancer and Healthy Data
Authors: Dingerdissen Hayley M. , Bastian Frederic , Vijay-Shanker K. , Robinson-Rechavi Marc , Bell Amanda , Gogate Nikhita , Gupta Samir , Holmes Evan , Kahsay Robel , Keeney Jonathon , Kincaid Heather , King Charles Hadley , Liu David , Crichton Daniel J. , Mazumder Raja 
Published: March 2020

PURPOSE The purpose of OncoMX 1 knowledgebase development was to integrate cancer biomarker and relevant data types into a meta-portal, enabling the research of cancer biomarkers side by side with other pertinent multidimensional data types. METHODS Cancer mutation, cancer differential expression, cancer expression specificity, healthy gene expression from human and mouse, literature mining for cancer mutation and cancer expression, and biomarker data were integrated, unified by relevant biomedical ontologies, and subjected to rule-based automated quality control before ingestion into the database. RESULTS OncoMX provides integrated data encompassing more than 1,000 unique biomarker entries (939 from the Early Detection Research Network [EDRN] and 96 from the US Food and Drug Administration) mapped to 20,576 genes that have either mutation or differential expression in cancer. Sentences reporting mutation or differential expression in cancer were extracted from more than 40,000 publications, and healthy gene expression data with samples mapped to organs are available for both human genes and their mouse orthologs. CONCLUSION OncoMX has prioritized user feedback as a means of guiding development priorities. By mapping to and integrating data from several cancer genomics resources, it is hoped that OncoMX will foster a dynamic engagement between bioinformaticians and cancer biomarker researchers. This engagement should culminate in a community resource that substantially improves the ability and efficiency of exploring cancer biomarker data and related multidimensional data.
Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): A meta-analyis based on 1,640 patients (pts)
Authors: Van Glabbeke M. M. , Owzar K. , Rankin C. , Simes J. , Crowley J. ,   GIST Meta-analysis Group (MetaGIST)
Published: March 2020

10004 Background: The MetaGIST project aims to further explore the data of the two randomized studies comparing two doses of imatinib (400 mg od vs bid) for the treatment of GIST: EORTC/ISG/AGITG 62005 (EU-AUS) and SWOG/CALGB/NCI-C/ECOG/ICAS S0033 (US-CDN). Methods: End-points were progression free (PFS) and overall survival (OS). Investigated cofactors included age, sex, performance status (PS), primary tumor site, time from diagnosis, prior therapies, baseline biology, and KIT / PDGFRa mutations for a subset of 772 pts (47%). The logrank test (stratified) and the Cox multivariate model with interaction terms were used for the analysis. Results: The median follow-up was 45 months. A small but significant PFS advantage was documented for the high dose arm, consistently in both studies. OS was identical in the two arms (see table ). Males and pts with a poor PS, GIST from bowel origin, baseline low hemoglobin and high neutrophils counts (ANC) had a significant worse PFS (multivariate analysis); these factors are consistent between studies. In pts analyzed for mutations, wild type pts (HR=1.56), KIT exon 9 mutants (HR=2.17) and pts with other mutations (HR=2.56) had a worse prognosis than KIT exon 11 mutants (univariate analysis); all 3 factors remained in the multivariate model. The US-CDN study included significantly (P<0.01) more females, more GIST from bowel or stomach origin, less KIT exon 9 mutants and pts with a lower baseline ANC. In KIT exon 9 mutants, the PFS advantage with high dose imatinib previously reported in the EU- AUS study was not confirmed in the US-CDN dataset, but remains significant in the pooled dataset. The interaction between dose effect on PFS and prognostic factors was siginficant for KIT exon 9 mutations but not for other factors. Conclusions: This analysis confirms a small PFS advantage of high dose imatinib, essentially amongst KIT exon 9 mutants, but no OS advantage. Heterogeneity between the two studies is being further explored. [Table: see text] [Table: see text]
Regional hyperthermia (RHT) improves response and survival when combined with systemic chemotherapy in the management of locally advanced, high grade soft tissue sarcomas (STS) of the extremities, the body wall and the abdomen: A phase III randomised pros
Authors: Issels R. D. , Lindner L. H. , Wust P. , Hohenberger P. , Jauch K. , Daugaard S. , Mansmann U. , Hiddemann W. , Blay J. , Verweij J. 
Published: March 2020

10009 Background: Patients (Pts) with locally advanced, high-grade STS are at significant risk for local failure and for metastasis. We evaluated the ability of RHT to improve the outcome in pts who are treated with neoadjuvant chemotherapy. Methods: Eligibility included pts with STS = 5 cm, grade II/III, deep and extracompartmental, stratified according to site (E = extremity vs. Non-E = body wall and abdomen). Pts were randomly assigned to systemic chemotherapy (etoposide 250 mg/m2; ifosfamide 6 g/m2; adriamycin 50 mg/m2) alone (EIA) or to systemic chemotherapy combined with RHT (EIA + RHT) administered for 4 cycles every 3 weeks both prior and after local aggressive therapy (surgery + radiotherapy), respectively. Primary endpoints were local progression free survival (LPFS) and disease free survival (DFS). Objective (CR + PR) response rate (ORR) evaluated after 4 cycles (EIA vs EIA + RHT) was a secondary endpoint. A total of 340 pts was required to show an improvement in median LPFS of 19.2 mos for EIA + RHT (a=5% type I, 20% type II error). Results: Pts characteristics were well balanced between treatment arms. After median follow-up of 24.9 months (mos) an intention-to-treat analysis showed a significantly superior DFS for pts who received EIA + RHT (n=169) compared to those treated with EIA alone (n=172) (median DFS: 31,7 mos and 16,2 mos; log-rank p=0.003; Hazard ratio=0.65; CI95=0.48- 0.87, p=0.004). The median LPFS was estimated 45,3 mos for EIA + RHT and 23,7 mos for EIA (log-rank p=0.015; Hazard ratio=0.66; CI95=0.48 - 0.90, p=0.01). At 2 years, LPFS rates for E (149 pts) and for Non-E (192 pts) were significantly better for EIA + RHT vs EIA alone (E: 84% vs 64%; Non-E: 57% vs 39%) (p<0.02). The ORR was significantly better for EIA + RHT (28,7%) vs EIA alone (12,6%) (p=0.002). Conclusions: Compared to chemotherapy alone, RHT combined with chemotherapy yields a statistically significant improvement in tumor response , DFS and LPS, in patients with locally advanced, high-grade STS. (Supported by Deutsche Krebshilfe and HGF VH-VI- 140) [Table: see text]
Non-metastatic Ewing's family tumors: High-dose chemotherapy with stem cell rescue in poor responder patients. Preliminary results of the Italian/Scandinavian ISG/SSG III protocol
Authors: Ferrari S. , Alvegard T. , Luksch R. , Tienghi A. , Hall K. S. , Bernini G. , Brach del Prever A. , Picci P. , Bacci G. , Smeland S. 
Published: March 2020

10014 Background: Poor response to induction chemotherapy negatively affects prognosis for Ewing's sarcoma (ES) patients. To improve outcome, high-dose chemotherapy (HDCT) with stem cell rescue was added to conventional chemotherapy in patients poor responders after induction treatment. Methods: Non-metastatic ES patients aged <= 40 years were eligible. All patients received VAC (vincristin 2 mg-doxorubicin 80 mg/m2-cyclofosfamide 1,200 mg/m2) weeks 0 and 6, IVAc (ifosfamide 9g/m2-vincristin 2 mg-actinomycin 2 mg) week 3 and IE (ifosfamide 9g/m2-etoposide 450 mg/m2) week 9 as induction therapy. Poor response was histologically defined as persistence of microfoci of viable tumor cells and radiologically as persistence of soft tissue mass. As maintenance treatment good responders (GR) received three cycles of VAC-IVAc-IE. Poor responders (PR) received VAC (weeks 13,19), IE (week 22), CE (mobilizing cycle, cyclophoshamide 4g/m2, etoposide 600 mg/m2, week 16) and HDCT with BuMel (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m2 with stem cell support week 25). Results: Starting from 1999, 296 patients were enrolled with a median age of 15 years (3–40). 54 % of the tumors were located to the extremities and 46% in the axial skeleton. 274 patients underwent local treatment: surgery in 222 (81%) patients (with post operative Rxt in 70), RxT alone in 52 (19%). 10 patients progressed during treatment. No toxic deaths were recorded. Response evalutation was available for 262 patients: 135 (52%) were PR. 116 of them completed protocol treatment and 19 did not receive HDCT (5 poor harvest, 5 medical contraindication, 9 refusal).With a median follow-up of 37 months (1–89) 5-year overall and event-free survival were 74 % and 65.5% respectively. 5-year event-free survival was 71% (95% CI 62–81%) for GR, 68% (95% CI 58–78%) for PR treated with HDCT and 35% (95% CI 10–60%) for PR who did not receive HDCT. Conclusions: The preliminary survival data show for PR similar outcome as for GR. The treatment including HDCT is feasible with no toxic death recorded. Longer follow-up will confirm its efficacy. No significant financial relationships to disclose.
Rare incidence of congestive heart failure (CHF) in gastrointestinal stromal tumor (GIST) and other sarcoma patients (pts) receiving imatinib mesylate (IM) therapy
Authors: Khakoo A. Y. , Steinert D. M. , Patel S. R. , Plana J. C. , Ludwig J. , Benjamin R. S. , Trent J. C. 
Published: March 2020

10026 Background: Potential IM cardiotoxicity has not been evaluated in patients with GIST or other sarcomas. CHF has been reported in leukemia pts on IM. Objectives: To determine the incidence of CHF in GIST and other sarcoma pts receiving IM. Methods: From our clinical trial database we reviewed all Grade III/IV potential cardiac adverse events (PCAEs) including dyspnea, dyspnea on exertion, chest pain, edema, pleural effusion, ascites, cardiac ischemia, and arrhythmia. Results: 219 pts were enrolled on clinical trials with IM from Dec 27, 2000 to May 11, 2006. 18 pts (8.22%) were identified as having PCAEs. The median age was 65.5 yrs (range, 21 to 88 yrs) and 7 were women. Their diagnoses were advanced GIST (13 of 125 pts, 10.40 %), primary GIST (4 of 48 pts, 8.33 %), or osteosarcoma (1 of 46 sarcoma pts, 2.17%). The osteosarcoma pt had received prior anthracycline therapy. The median time from start of IM to a PCAE was 173.5 days (11 to 1,568 days). IM dose at the time of the PCAE was 400 mg/d in 10 pts, 600 mg/d in 4 pts, and 800 mg/d in 4 pts. 13 pts had a past medical history of risk factors for coronary artery disease (CAD) or established heart disease: diabetes (4 pts, 22.22%), hypertension (9 pts, 50%), CAD (2 pts, 11.11%), hypertrophic obstructive cardiomyopathy (1 pt, 5.56%), peripheral vascular disease (2 pts, 11.11%), hyperlipidemia (3 pts, 16.67%) or arrhythmia (1 pts, 5.56%). None of these patients had evidence of pulmonary vascular congestion by chest film. 8 pts had an ECHO or MUGA scan at the time of the PCAE, and 1 of them had documented low ejection fraction; in only 2 of these 8 pts was there an ECHO prior to IM (LVEF >50% in both). The single pt with LVEF<50% at the time of the PCAE had prior a history of hypertension, multi-vessel CAD and coronary artery bypass grafting 12 years prior to the PCAE. All of the pts continued IM therapy with dose adjustments and toxicity-specific management with no further complications. Conclusions: Pts who develop PCAEs on IM should be treated with diuretics, ACE-inhibitors, and beta-blockers with continuation of IM as clinically indicated. CHF in sarcoma patients treated with IM is rare and was observed in only one elderly patient with known prior cardiac disease. No significant financial relationships to disclose.
Objective response rate in a phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC) which has progressed during treatment with T
Authors: Baselga J. , Cameron D. , Miles D. , Verma S. , Climent M. , Ross G. , Gimenez V. , Gelmon K. 
Published: March 2020

1004 Background: T and P bind to different epitopes on the extra cellular domain of HER2. Unlike T, P binds to the dimerization domain and blocks homo- and hetero-dimerization of HER2 with other HER kinase family members. Xenograft models support the hypothesis that the complementary mechanisms of action could result in augmented efficacy when T and P are combined. Methods: Two-stage design, criteria to proceed to the 2nd stage were: ≥ 2 partial responses (PR) or 1 PR and 12 stable disease (SDs) or 13 SDs. Eligibility included: measurable, centrally-tested HER2 positive breast cancer; up to 3 lines of prior chemotherapy plus T (including adjuvant chemotherapy plus T); disease progression during T as most recent treatment for metastatic disease; baseline left ventricular ejection fraction (LVEF) ≥ 55% and no decrease of LVEF to below 50% during prior T treatment. Consenting Pts received T i.v. weekly or every 3 weeks at 2 mg/kg or 6 mg/kg respectively (with re-loading dose if required) plus 420mg fixed dose of P i.v. every 3 weeks following loading dose 840mg. Study treatment was initiated within 9 weeks of the last dose of T given as most recent therapy. An independent data safety monitoring board has overseen the 1st stage safety data. Results: Recruitment into 1st stage is complete. The main adverse events were diarrhea (71%), fatigue (46%), nausea/vomiting (38%) and rash (25%). Most AE’s were mild to moderate (there was 1 case of Grade 3 diarrhea) and none was treatment-limiting. There were no clinical cardiac events, and central review revealed no case of fall in LVEF of ≥10% and to ≤50%. Response status: 5 confirmed PR (21%); 12 SD (50%). Responses have been observed in lymph node and liver metastases. Recruitment into the 2nd stage of the trial has commenced. Conclusions: The combination of the P and T is active and well tolerated in patients with pre-treated HER2 positive breast cancer which has progressed during treatment with T. No significant financial relationships to disclose.
Perioperative morbidity in metastatic gastrointestinal stromal tumors (GIST) undergoing surgery of residual disease following imatinib (IM)
Authors: Gronchi A. , Fiore M. , Radaelli S. , Coco P. , Fumagalli E. , Stacchiotti S. , Collini P. , Tamborini E. , Pilotti S. , Casali P. G. 
Published: March 2020

10043 Background: To review the morbidity of post-IM surgery of residual disease in a consecutive series of metastatic, IM- sensitive, GIST pts. Methods: Between November 2002 and September 2006, 29 pts with metastatic GIST were operated on, being progression- free on IM for at least 6 months. Median preoperative IM duration was 17 mos. Only patients deemed to be completely resectable on CT/MRI were considered for surgery. Major surgical procedures were generally excluded. Results: Surgery consisted in explorative laparotomy with resection of residual visible disease, omentectomy in 13 cases, intestinal resections in 10, minor hepatic resections in 7, radiofrequency ablations of liver nodules in 2, spleno-pancreatectomy in 2. Macroscopically complete surgery could be performed in 90% of pts. Median operative time was 180’ (range 120–420). Median post-surgery discharge time was 9 days (range 4–35). Median preoperative Hb level was 12.2 mg/dL and the median perioperative whole blood and fresh frozen plasma units required was 1.5 and 2.9 (range 0–16 and 0–44), respectively. In 28% of pts, there was post-operative ascites (daily peritoneal effusion of >200 ml), which generally responded to medical therapy in one week. Postoperative levels of AST/ALT reached twice the baseline in 48% of pts, independently of whether liver resections had been carried out. Postoperative pneumonia was observed in 38% of patients. Major surgical complications occurred in 14% (one bleeding, one evisceration, and two anastomotic leakages). After a median follow up of 36 mos from surgery, PFS was 69% at 2 yrs (65% at 4 yrs from IM-onset). Conclusions: While this was a series of favorably selected patients, and major surgical procedures were preferably avoided, surgical perioperative morbidity turned out to be higher than expected. This reinforces the view that post-IM surgery of residual disease in metastatic GIST pts should be considered investigational, as long as its efficacy in improving prognosis is not demonstrated. [Table: see text]
Long term progression-free survival correlates with KIT/PDGFR mutational status in advanced GIST patients treated with imatinib (IM)
Authors: Cioffi A. , Emile J. F. , Domont J. , Ray-Coquard I. , Blay J. Y. , Terrier P. , Bonvalot S. , Le Péchoux C. , Perol D. , Le Cesne A. 
Published: March 2020

10053 Background: IM is the first-line treatment for advanced GIST and must be given continuously until disease progression or intolerance. The median progression free survival (PFS) of pts included in consecutive prospective trials is around 2 years. Pt characteristics and the exact mutational status of GIST who benefit the most from IM in term of prolonged response to IM and prolonged PFS are unknown. Methods: two hundred and seventy six pts were included in 2 consecutive prospective trials since 2001 in 2 centers. Pts receiving IM for at least 3 yrs (3 to 5 yrs) who have no exhibited any kind of progression and receiving IM continuously until december 2006 have been retrospectively analyzed both clinically and biologically. KIT and PDGFR mutations were analyzed using DHPLC and direct sequencing of frequently mutated exons (KIT 9, 11, 13, 14, 17, PDGFR 12, 14, 18). Results: after a median follow-up of 4 yrs (3–5yrs), 31 pts are free of progression and received IM continuously. The characteristics of these long term survivors favorable cohort of pts are as following: man (61%), small bowel origin (60%), liver involvement (80%), synchronous metastasis at inclusion (58%), and normal initial hemoglobin level (92%>10 g/dl). As of now, 15 pts are evaluable for mutational analysis. All but one (exon 9) pts had an exon 11 mutation. The most commun genetic alteration was an in frame deletion between 550 to 558. Conclusions: Pts with metastatic GIST arising from small bowel harboring an exon 11 mutation in the vicinity of codon 557–558 may be a very favorable subgroup. No significant financial relationships to disclose.
A phase II evaluation of aerosolized GM-CSF (AGM-CSF) plus standard I-MAP/ GM-CSF/MAP/ surgery/ irradiation in the reduction of pulmonary metastases (P-METS) in soft tissue sarcoma (STS) patients (PTS)
Authors: Okuno S. H. , Mahoney M. R. , Kabat B. F. , Marks R. M. , Maples W. J. , Fitch T. J. , Petersen I. A. , Beauchamp C. P. , O’ Connor M. I. , Sim F. H. 
Published: March 2020

10058 Background: P-METs remain illusive with standard treatments for STS. AGM-CSF demonstrated tolerability with promising efficacy in reducing P-METS. We evaluated the 2-yr P-MET free rate in chemonaiive pts with extremity STS. Methods: ECOG PS 0/1 and Gr 3/4 primary STS of the limb girdle/extremities, were required. Treatment sequence: 2 cycles of IMAP (Ifosfamide, Mitomycin, Doxorubicin, Cisplatin) plus s.q. GM-CSF (preload d -6 to -3, d1–14); MAP (d0, 28) during irradiation (d1–35) plus AGM-CSF 250 mcg bid (d1–7, 15- 22, 28–35); surgery; post-op irradiation plus AGM-CSF 250 mcg bid (d1–7, 15–22, 28–35, 42–49). 6 of 35 pts with P-METS in ≤ 2 yrs implied lack of efficacy w.r.t. reducing P-METS. Results: 38 eligible pts were enrolled (20 male, median age 51 yrs, 24 PS 0). Median size of tumor 9 cm (2.3–26.7 cm).Location of tumors included: proximal extremity-16, distal extremity-11, and limb girdle-12. 79% received debulking surgery; 29 rendered disease-free. 38 pts are evaluable for toxicity (see table ). More common Gr 3+ events related to treatment appear below. 79% had Gr 4 neutropenia, despite s.q. GM-CSF. 6 pts have died, with 2.5 yrs median follow-up on survivors (range .4- 4.6). No treatment related fatalities occurred. 10 pts had P-METS ≤ 2 yrs. The estimated 2 yr P-MET free rate is 75% (95% CI 62–91). Conclusions: Although high, neutropenia was as expected. AGM-CSF failed to improve the 2 yr P-MET free rate in this group of STS pts. Other strategies need to be explored. Supported by NIH Grant CA15083–32 and Berlex Corporation. Max Severity (Gr 3+) [Table: see text] No significant financial relationships to disclose.