bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in patients with inflammatory bowel disease: gene expression of TNF-α as a marker of disease severity
Authors: Zaki Moushira , Orban Hisham A. , Mahmoud Marwa , Youness Eman R. , Booles Hoda F. , Khalil Wagdy K. B. , Wafy Wafaa , El-Atrebi Kamal A. , Hamed Khaled , El-Bassyouni Hala T. 
Published: June 2024

Abstract
Background
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of unknown etiology and unpredictable course. The aim of the work was to assess the levels of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in IBD patients compared to controls and evaluate the gene expression of TNF-α as a marker of disease severity.

Methods
Adropin, fasting serum FGF-1 levels, TLR1, and TNF-α were measured in 60 IBD patients. They were also compared with 58 healthy controls matching age and gender. Moreover, the blood cells cDNA copy number of TNF-α were determined as a marker of severity.

Results
Adropin and TLR1 levels were significantly lower in patients than controls. FGF-1 was reduced but not statistically significant. The expression of TNF-α gene in the IBD patients was significantly increased (42%) in comparison with control samples (P < 0.001).

Conclusions
Adropin, IGF-I, and Toll-like receptor-1 biomarkers may have a role in the intricate pathophysiology of IBD and may possibly operate as predictors of disease activity. Thus, they may be therapeutic targets for IBD. Moreover, the expression of TNF-α gene can be used as a marker of severity.
In silico approach to investigate the potential
HKT
gene responsive to salt stress in rice
Authors: Ullah Mohammad Asad , Abdullah-Zawawi Muhammad-Redha , Sukiran Noor Liyana , Uddin Md. Imtiaz , Ismail Ismanizan , Zainal Zamri 
Published: June 2024

Abstract

Rice is frequently subjected to various environmental stresses, resulting in significant production losses, with drought and salinity are the leading causes of plant damage globally. This study aims to characterize and understand the function of rice high-affinity potassium transporters (
HKTs
) genes in response to salinity stress. Initially, the genome-wide analysis was undertaken to reveal the evolutionarily conserved function of the
OsHKT
in higher plants. To investigate the transcription level of
OsHKT
during the vegetative and reproductive stages, two microarray datasets (GSE19024 and GSE3053) were analyzed, and salt-treated samples were subsequently evaluated using real-time PCR. Differentially expressed genes (
DEGs
) were identified from microarray datasets (GSE41650 and GSE14403), followed by constructing a
DEG
network that highlighted interaction partners of the
OsHKTs
. Genome mining of rice revealed 9
HKT
genes, namely
OsHKT1;1–1;5
and
OsHKT2;1–2;4
. These genes exhibited a well-conserved domain structure called
TrkH
. Comprehensive phylogenetic and motif analyses clustered genes encoding
HKT
proteins into seven monophyletic groups, and the motifs were relatively conserved. Ka/Ks ratios indicated a high degree of purifying selection during evolutionary time. Gene ontology findings suggested the involvement of
OsHKT
in stress response. Besides, several CRE motifs in the promoter regions of
OsHKT
have demonstrated their potential roles in abiotic stress responses. Furthermore, we analyzed the top 250 significant
DEGs
from the two datasets (p-value < 0.05; fold two change ≥ 1 or ≤  − 1) to evaluate the relationship among the
DEGs
and
HKTs
. Three co-expressed
OsHKT
genes were discovered to be upregulated in seedlings under salinity treatment, including
OsP5CS2
,
OsHAK1
, and
OsNHX2
, whereas
OsP5CS1
and
OsHAK27
were downregulated. The transcripts of
OsHKT
were found to be differentially expressed in a tissue-specific manner. Analysis of microarray datasets validated by real-time PCR shows that
OsHKT1;5
had a higher expression level, followed by
OsHKT1;1
,
OsHKT1;3
, and
OsHKT2;1
after salinity treatment. In addition, several micro-RNA targets in rice
HKT
genes regulate their expression in response to stress. This study paves the way for future investigation on genes and miRNA-target interaction in plants under environmental stresses, offering potential strategies to enhance stress tolerance in crops via targeted ion transport modification.
Riedel shear structures reactivation may induce earthquakes through long-term steam injection: A case study of a heavy oil production field in northwestern China
Authors: Xu Rui , Liang Chuntao , KanNi Zhati , Wang Meijie , Li Zhongquan , Wang Chaoliang , Liu Zhijin , Chen Chunmei 
Published: June 2024

Conventional heavy oil exploitation methods involve steam stimulation and flooding. An oil field in northwestern China has been producing heavy oil via steam injection for several decades. The production area has been seismically quiet until an increase in seismicity occurred several years ago. An array of 40 seismographs has been deployed between July and October 2021 to monitor seismicity and resolve the possible causes of the recent seismicity. Using an end-to-end machine-learning-based high-precision earthquake location workflow, we analyze a microseismic sequence comprised of 178 events that occurred in the study area. Numerical simulations incorporating Coulomb failure stress suggest that prolonged steam injection can reactivate faults and induce seismic events. Similarly, fluid diffusion through conduits may achieve the same effect. Analysis of the focal mechanism solutions of 21 strike-slip and thrust events with [Formula: see text] in conjunction with the background stress regime ([Formula: see text] azimuth = N15°W) reveal that the stress distribution is compatible with a left-lateral Riedel shear structure (RSS) model. Therefore, we can speculate that steam injection may induce earthquakes by reactivating preexisting RSS fault structures. To conclude, the recent seismic events could have been induced by two possible mechanisms: (1) long-term steam injection may cause the static stress level on the faults beneath the reservoir to build up to critical levels, following which a slight stress disturbance can trigger an earthquake and (2) fluid conduits may transport condensed water to basement faults, weakening the faults through fluid diffusion.
Population-Level Identification of Patients With Lynch Syndrome for Clinical Care, Quality Improvement, and Research
Authors: Sharaf Ravi N. , Udaltsova Natalia , Li Dan , Pai Rish K. , Sinha Soham , Li Zixuan , Corley Douglas A. 
Published: June 2024

PURPOSE Identification of those at risk of hereditary cancer syndromes using electronic health record (EHR) data sources is important for clinical care, quality improvement, and research. We describe diagnostic processes, previously seldom reported, for a common hereditary cancer syndrome, Lynch syndrome (LS), using EHR data within a community-based, multicenter, demographically diverse health system. METHODS Within a retrospective cohort enrolled between 2015 and 2020 at Kaiser Permanente Northern California, we assessed electronic diagnostic domains for LS including (1) family history of LS-associated cancer; (2) personal history of LS-associated cancer; (3) LS screening via mismatch repair deficiency (MMRD) testing of newly diagnosed malignancy; (4) germline genetic test results; and (5) clinician-entered diagnostic codes for LS. We calculated proportions and overlap for each diagnostic domain descriptively. RESULTS Among 5.8 million individuals, (1) 28,492 (0.49%) had a family history of LS-associated cancer of whom 3,635 (13%) underwent genetic testing; (2) 100,046 (1.7%) had a personal history of a LS-associated cancer; and (3) 8,711 (0.1%) were diagnosed with colorectal cancer of whom 7,533 (86%) underwent MMRD screening and of the positive screens (486), 130 (27%) underwent germline testing. One thousand seven hundred and fifty-seven (0.03%) were diagnosed with endometrial cancer of whom 1,613 (92%) underwent MMRD screening and of the 195 who screened positive, 55 (28%) underwent genetic testing. (4) 30,790 (0.05%) had LS germline genetic testing with 707 (0.01%) testing positive; and (5) 1,273 (0.02%) had a clinician-entered diagnosis of LS. CONCLUSION It is feasible to electronically characterize the diagnostic processes of LS. No single data source comprehensively identifies all LS carriers. There is underutilization of LS genetic testing for those eligible and underdiagnosis of LS. Our work informs similar efforts in other settings for hereditary cancer syndromes.
Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).
Authors: Hoeppner Jens , Brunner Thomas , Lordick Florian , Schmoor Claudia , Kulemann Birte , Neumann Ulf Peter , Folprecht Gunnar , Keck Tobias , Benedix Frank , Schmeding Maximilan , Reitsamer Ernst , Bruns Christiane J. , Lock Johan F. , Reichert Benedikt , Ghadimi Michael , Wille Kai , Gockel Ines , Izbicki Jakob R. , Utzolino Stefan , Grimminger Peter Philipp 
Published: June 2024

LBA1 Background: The most effective multimodal approach for treatment of resectable locally advanced esophageal adenocarcinoma (EAC) is under debate. A prior ranking question is if neoadjuvant chemoradiation therapy or perioperative chemotherapy is superior. ESOPEC (NCT02509286) is a multicenter prospective randomized trial comparing neoadjuvant CROSS (41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative FLOT (5-FU/ leucovorin/oxaliplatin/docetaxel) and surgery for the curative treatment of EAC. Methods: Patients with cT1 cN+ cM0 or cT2-4a cNany cM0 resectable EAC were eligible. The primary endpoint is overall survival (OS; 90% power; hazard ratio [HR] 0.645, 218 events needed; one sided significance level of 2.5%). Analysis is by intention-to-treat in all randomized patients. The effect of treatment on OS is estimated using Cox regression stratified by study site, and including N stage (N0, N+), and age as covariates. Results: Between Feb 2016 and Apr 2020, 438 patients from 25 sites in Germany were randomly assigned to two treatment groups (221 FLOT; 217 CROSS). Baseline characteristics (male sex 89.3%, median age 63 [range 30-86], cT3/4 80.5%; cN+ 79.7%) were well balanced between both arms. Neoadjuvant treatment was started in 403 patients (207 FLOT; 196 CROSS). Surgery was done in 371 patients (191 FLOT; 180 CROSS). R0 resection was achieved in 351 patients (180 FLOT; 171 CROSS). 90 days postsurgical mortality was 4.3% (3.2% FLOT; 5.6% CROSS). After a median follow up of 55 months, 218 patients had died (97 FLOT; 121 CROSS). Median OS was 66 (95% CI 36 – not estimable) months in the FLOT arm, and 37 (95% CI 28 – 43) months in the CROSS arm. The 3-year OS rates were 57.4% (95% CI 50.1 – 64.0%) for FLOT and 50.7% (95% CI 43.5 – 57.5%) for CROSS (HR 0.70, 95% CI 0.53-0.92, p=0.012). In 359 patients with available tumor regression status, pathological complete response was achieved in 35 (19.3%, 95%-CI 13.9 – 25.9%) in FLOT and in 24 (13.5%, 95%-CI 8.8 – 19.4%) in CROSS. Conclusions: Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS. Funding: The trial was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 264590883. Clinical trial information: NCT02509286 .
A-BRAVE trial: A phase III randomized trial with avelumab in early triple-negative breast cancer with residual disease after neoadjuvant chemotherapy or at high risk after primary surgery and adjuvant chemotherapy.
Authors: Conte Pier Franco , Dieci Maria Vittoria , Bisagni Giancarlo , Schmid Peter , Fotia Vittoria , Piacentini Federico , De Laurentiis Michelino , Favaretto Adolfo G. , Tamberi Stefano , Bianchi Giulia Valeria , Zamagni Claudio , Cinieri Saverio , Corsi Domenico C. , Del Mastro Lucia , Ferro Antonella , Gennari Alessandra , Mion Marta , Musolino Antonino , De Salvo Gian Luca , Guarneri Valentina 
Published: June 2024

LBA500 Background: Prognosis of pts with early triple negative breast cancer (TNBC) is still poor and new effective treatments are needed. TNBC is the most immunogenic BC subtype, and this may account for sensitivity to immune checkpoint inhibitors. The A-BRAVE trial was designed to evaluate the efficacy of avelumab, an anti PD-L1 antibody, as adjuvant treatment for pts with early TNBC at high risk. Methods: This is a phase III, multicentric, randomized adjuvant study comparing 1 year of treatment with the anti PD-L1 avelumab vs observation for TNBC pts considered at high risk of relapse. Pts were enrolled after they completed standard treatment with curative intent including surgery and neoadjuvant/adjuvant chemotherapy. High risk was defined as: 1) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (Stratum A), 2) >pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (Stratum B). Pts were randomly assigned (1:1, balanced for strata A and B) to Avelumab 10 mg/kg I.V. q2w for 1 year or observation. Co-primary endpoints were disease free survival (DFS) in the total population and in Stratum A. 474 pts were needed to detect, in the total population, an improvement from 60% to 73.6% 3-year DFS rate (HR 0.6; 90% power, 1-sided test, alfa 2%). 172 DFS events were required to perform the event-driven analysis. Assuming a proportion of 70-80% pts enrolled in Stratum A, the expected power to detect an HR 0.6 at alpha allocated in this subgroup is 70-79%. Overall survival was a secondary endpoint. Results: From June 2016 to October 2020, 477 pts were randomly assigned from 64 Italian and 6 UK centers. 11 pts (3 avelumab, 8 control) withdrew consent immediately after randomisation and are excluded from further analyses. 378 pts entered Stratum A (83%), of whom 99 (57 avelumab, 42 control) received further chemotherapy after surgery prior to enrollment in the trial. Efficacy results for the two co-primary DFS endpoints and the secondary OS endpoints are reported in the table. Conclusions: One year adjuvant avelumab versus control does not significantly improve DFS in high-risk TNBC patients. Nevertheless, the secondary enpoind OS was significanlty improved with avelumab vs control. RFS and DMFS will also be reported. A centralised collection of tumor tissue, plasma and feces has been performed and will allow a number of correlative studies. Clinical trial information: NCT02926196 . [Table: see text]
Adjuvant PD-1 blockade with camrelizumab in high-risk locoregionally advanced nasopharyngeal carcinoma (DIPPER): A multicenter, open-label, phase 3, randomized controlled trial.
Authors: Ma Jun , Sun Ying , Liang Ye-Lin , Liu Xu , Shen Liangfang , Hu Weihan , Hu Guangyuan , Xie Fangyun , Huang Ying , Zou Guorong , Zhang Ning , Chen Chuanben , Chen Xiaozhong , Zhu Xiaodong , Yuan Yawei , Yang Kunyu , Jin Feng , Hong Shu-Bin , Zhao Hongyun , Li Ji-Bin 
Published: June 2024

LBA6000 Background: Patients with high-risk locoregionally advanced nasopharyngeal carcinoma (NPC) often experience disease relapse even after receiving standard-of-care treatment, e.g. induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). The benefit of PD-1 inhibitor as adjuvant treatment following IC+CCRT in locoregionally advanced NPC remains unclear. Methods: Patients with high-risk locoregionally advanced NPC (T4N1M0 or T1-4N2-3M0) who have received gemcitabine and cisplatin (GP) IC and CCRT were recruited at 11 centers in China. They were randomly assigned (1:1) within 2 weeks after the last radiation dose to receive intravenous camrelizumab (200 mg once every 3 weeks for 12 cycles; Camrelizumab Arm) or observation (Standard-therapy Arm). The primary endpoint was event-free survival (EFS). It is estimated that approximately 442 patients would provide 80% power to detect a hazard ratio (HR) of 0.52 with a log-rank test at a two-sided α level of 0.05. Quality of life (QoL) was assessed by EORTC-C30. Results: A total of 450 patients were randomly assigned to the Camrelizumab Arm (n=226) and the Standard-therapy Arm (n=224). After a median follow-up of 37 months (corresponding to 41 months when calculated from the start of standard therapy), the estimated 3-year EFS was 86.9% in the Camrelizumab Arm and 77.4% in the Standard-therapy Arm (intention-to-treat population; HR 0.61, 95% CI 0.38–0.96; P = 0.03). The incidence of grade 3-4 adverse events (AEs) was 11.2% in the Camrelizumab Arm and 3.2% in the Standard-therapy Arm, including grade 3-4 immune-related AEs in 8 (3.9%) patients in the Camrelizumab Arm. Reactive capillary endothelial proliferation was the most common adverse event related to camrelizumab (RECP, 87.8%, 4 (1.8%) patients had grade 3 RECP). Treatment-related deaths occurred in 1 (<1%) patients in the Camrelizumab group (subarachnoid hemorrhage) and 1 (<1%) patients in the Standard-therapy group (nasopharyngeal necrosis). During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of adjuvant camrelizumab. Conclusions: Adjuvant PD-1 blockade with camrelizumab significantly improved EFS in high-risk locoregionally advanced NPC, with mild toxicity and comparable quality of life. Clinical trial information: NCT03427827 . [Table: see text]
Covalent FAPI PET enables accurate management of medullary thyroid carcinoma: A prospective single-arm comparative clinical trial.
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Jian Wang , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Lin Xinfeng , Men Tianyu , An Changming , Li Nan , Liu Chen , Zhu Yi-Ming , Yang Zhi , Liu Zhibo , Liu Shaoyan 
Published: June 2024

LBA6018 Background: Localizing medullary thyroid carcinoma (MTC) lesions is crucial for treatment decision, but the detection using the current imaging modalities is unsatisfied. Previously, we reported a 68Ga-labeled targeted covalent radiopharmaceutical fibroblast activation protein inhibitor (68Ga-TCR-FAPI), which demonstrated improved and sustained tumor targeting. This study aimed to head-to-head compare the 68Ga-TCR-FAPI PET-CT and the currently approved 18F-FDG PET-CT in detecting MTC. Methods: This was a prospective, single-center, open-labeled, single-arm comparative imaging trial. MTC patients with serum calcitonin>10 pg/ml and without targeted therapy were eligible. Serum calcitonin level, 68Ga-TCR-FAPI PET-CT and 18F-FDG PET-CT were acquired within a maximum interval of 30 days. Images were independently interpreted by 3 readers to calculate the patient-based and region-based detection rate. Quantitative PET parameters were calculated from the lesion ROI and compared between 68Ga-TCR-FAPI and 18F-FDG PET-CT. The accuracy of imaging findings was validated on lesions with histopathology or calcitonin-based follow-up. The primary outcome was patient-based detection rate, and the secondary outcome included region-based detection rates, metabolic parameters comparison and diagnostic accuracy. Results: 50 patients were enrolled between May 11th, 2023 and Feb. 1st, 2024. 68Ga-TCR-FAPI exhibited significantly higher patient-based detection rate than 18F-FDG PET-CT (98% vs. 66%, p=0.0002). Detection rates were also superior for 68Ga-TCR-FAPI in head and neck (72% vs. 50%, p=0.0098), thorax (50% vs. 34%, p=0.0269), abdomen (28% vs. 10%, p=0.0077) and skeleton (54% vs. 16%, p<0.0001). On quantitative analysis, SUVmax was significantly higher in 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (11.71±9.16 vs. 2.55±1.73, p<0.0001). Diagnostic accuracy was substantially greater with 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (96.7% vs. 43.3%, p<0.0001) based on 60 histopathological validated lesions from 15 patients who underwent surgery. Notably, 60% (30/50) patients directly benefited from 68Ga-TCR-FAPI PET-CT, with 66.7% (10/15) experiencing changes in surgical plans, and 100% (6/6) of the newly diagnosed MTC with R0 resection achieved biochemical cure at 1-month post-surgery. Conclusions: 68Ga-TCR-FAPI PET-CT displayed higher detection rate, metabolic value and diagnostic accuracy than 18F-FDG PET-CT in MTC patients, and should be integrated into MTC evaluation at initial diagnosis and persistent disease. Clinical trial information: NCT06084767 . [Table: see text]
Long term results of phase 3 randomized study evaluating the addition of low dose nivolumab to palliative chemotherapy in head and neck cancer.
Authors: Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Shah Minit Jalan , Peelay Zoya Ravish , Nawale Kavita Prakash , Bhagyavant Priyanka , Sawant Riddhi , Kolkur Manali , Prabhash Kumar 
Published: June 2024

LBA6054 Background: The addition of low-dose nivolumab to metronomic chemotherapy (MC) improved 1-year overall survival in relapsed and refractory head and neck squamous cell carcinoma (HNSCC). However, sustained benefit over the long term is an important aspect of immunotherapy and it has never been studied in a prospective randomized study for low-dose nivolumab. Methods: This was an open-label randomized phase 3 superiority study. Adult patients (age= or >18 years), ECOG PS (0-1), relapsed -recurrent or newly diagnosed advanced HNSCC, and normal organ functions were eligible. Patients were randomly assigned 1:1 to oral metronomic chemotherapy consisting of methotrexate 9 mg/m2 weekly, celecoxib 200 mg twice daily, and erlotinib 150 mg daily, with (TMC-I) or without (TMC) with intravenous nivolumab 20 mg flat dose once-every-3-weeks. Systemic therapy was continued till the development of intolerable side effects or progression of disease. The primary endpoint was overall survival (OS). Landmark analysis was performed to compare OS between 2 arms. Results: The median follow-up was 32.5 months (95% CI 29.6-32.7). The 1 year, 2 year and 2.5 year OS were 20% (95%CI 11.9-29.7) versus 35.5% (95%CI 25-46.2) {Hazard ratio (HR)= 0.6534, 95%CI 0.4473 -0.956: P=0.028}, 5.3% (95%CI 1.7-12.3) versus 18.4 %(95%CI 10.7-27.8) {HR= 0.6318, 95%CI 0.4476 -0.8919: P=0.009} and 5.3% (95%CI 1.7-12.3) versus 17.1 % (95%CI 9.66.-26.3) {HR= 0.6379, 95%CI 0.4524 -0.8993: P=0.01} in the TMC and the TMC-I arms respectively. The benefit of the addition of nivolumab was independent of other factors like age, gender, ECOG PS, Site of malignancy, time to failure, PDL1 score, and previous exposure to platinum (Table). Conclusions: The addition of low-dose nivolumab to triple metronomic chemotherapy leads to a tripling of OS thus suggesting that even low-dose nivolumab has sustainable benefits. The benefit observed is irrespective of known prognostic factors in HNSCC. Clinical trial information: CTRI/2020/11/028953 . [Table: see text]