bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression
Authors: Neto Sonya , Reis Andreia , Pinheiro Miguel , Ferreira Margarida , Neves Vasco , Castanho Teresa Costa , Santos Nadine , Rodrigues Ana João , Sousa Nuno , Santos Manuel A. S. , Moura Gabriela R. 
Published: July 2024

Abstract
Background
Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual “omics” signature that distinguishes subjects with varying cognitive profiles.

Results
We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging.

Conclusions
These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.
Mechanism of a rainfall-induced landslide in a large-scale flume experiment on a weathered granite sand
Authors: Do Ngoc Ha , Goto Satoshi , Ochiai Hirotaka , Asano Shiho , Doan Huy Loi , Huynh Thanh Binh , Yoshida Junji 
Published: July 2024

Abstract
Introductions
A large-scale flume experiment was performed to evaluate the mechanism of landslide occurrence due to rainfall using weathered granite sand. The dimensions of the flume were 9 m (length), 1 m (width), and 1 m (depth). The weathered granite sand from the actual landslide site at Da Nang City, Vietnam was used. The pore water pressure was measured by a pore-water pressure transducer at two depths (middle and bottom) to determine the process of rainwater infiltration into the soil. The surface deformation was measured with extensometers at three positions of the slope. The deformation of the entire slope was determined by the 160 cylindrical-shaped makers evenly spaced in the slope and three cameras.

Results
The results showed that the rainfall infiltrated into the slope process, increasing from negative pore water pressure to approximately 0. The maximum shear strain contour has been plotted in total and in time increments. The shear band was detected from the time increments maximum shear strain contour. The localization in the shear band formed just before failure.

Conclusions
To the best of our knowledge, this is the largest scale laboratory test ever conducted to calculate the shear band. Moreover, it was found that the failure occurred when the sand was in an unsaturated phase. Failure does not seem to depend on the increase in pore water pressure but on the maximum shear strain. This feature can be used to explain the phenomenon of landslides that occur even when the groundwater level does not increase but large deformation occurs.
Investigating influencing factors on acrylamide content in fried potatoes and mitigating measures: a review
Authors: Ahmed Zahraa Adil , Mohammed Nameer Khairullah 
Published: July 2024

AbstractThermal processing of food has the potential to produce a number of unwanted chemical substances. One of these compounds that is created is acrylamide (in starch-rich foods). Additionally, it has a potential to cause cancer in rodents and in humans. Chocolate, potato, bakery foods, coffee, and chocolate products are the main dietary sources of acrylamide exposure. The fresh ingredient utilised most frequently in frying processes is potato, because of high global consumer demand. Ever since it was discovered in foods, acrylamide's mechanism and mitigation have drawn the attention of various investigations. Additionally, different frying techniques, such as deep frying, microwave frying, and air frying, have a direct impact on the development of acrylamide in products. In-depth details on acrylamide generation, incidence, dietary exposure, toxicity, and mitigation during the frying process are provided in the current work.
Graphical Abstract
Comparison of physical and mechanical properties of traditional bricks in Deli Serdang with no-burn bricks using rice husk ash
Authors: Frapanti Sri , Tanjung Liza Evianti , Riza Fetra Venny , Nasution Arya Rudi , Zulkarnain Fahrizal 
Published: July 2024

AbstractPopulation growth has increased, causing more and more housing needs; Indonesia is one of the countries where bricks are still used as the primary material in building walls. It has resulted in increased demand for bricks. One of Indonesia’s regions, Deli Serdang Regency, produces traditional bricks that burn a lot, but the process of making traditional bricks can cause environmental pollution. This research aims to find a way to reduce the effects of environmental pollution by making pressed bricks without burning and utilizing agricultural waste, namely rice husk ash (RHA). After that, a comparison was made between traditional burnt bricks from 15 sub-districts in Deli Serdang Regency and unburnt bricks made from rice husk ash (RHA). This study uses two methods, namely the method of sampling burned bricks and the method of making bricks without burning, both of which are tested for physical and mechanical properties. The results of this study use the requirements of SNI 15-2094-2000, where the test of physical properties of fuel bricks obtained a value of 76%, which meets the requirements, while bricks without burning obtained a value of 87.5%, which meets the requirements. For the results of the size of fuel bricks obtained, 66.6% of the value meets the requirements, while for bricks without burning, 100% meet the requirements. Mechanical properties test for absorption testing on fuel bricks obtained 0.135% while unburned bricks 0.130%, where the value meets the SNI requirements of a maximum absorption of 20%. Salt content testing obtained a value of 0.15% for burned bricks and 0.002% for unburned bricks, where the value meets the SNI requirements that are below 50%. Testing the compressive strength of bricks with a standard value of 5 MPa from the test results of the compressive strength of fuel bricks 3.01 MPa decreased by 39.8%, while the test of compressive strength of unburned bricks 5.17 MPa increased by 3.45%, but unburned bricks with added rice husk ash 1.98 MPa decreased by 60.4%. Based on the study’s results, the absorption and salt content parameters follow the standard. At the same time, the strength test of firebricks and unburned bricks with added rice husk ash does not meet the SNI 15-2094-2000 standard, but the results of the compressive strength test of unburned bricks meet the SNI 15-2094-2000 standard.
9MW2821, a nectin-4 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1/2a study.
Authors: Zhang Jian , Liu Rujiao , Gao Shuiping , Yang Huijuan , Chen Jian , Yuan Fang , Liu Jiyan , Guo Hongqian , Zhang Shun , Li XingYa , Yao Xin , Bai Ming , Bu Hualei , Li Yinyin , Hu Changlu , Li Xiumin , Wang Zhen , Wang ShanBing , Lou Hanmei , Feng Zhe 
Published: July 2024

3013 Background: 9MW2821 is a monoclonal ADC that delivers monomethyl auristatin E to cells expressing Nectin-4. Nectin-4 is an adhesion molecule that highly expressed in variety of solid tumors, especially urothelial cancer (UC), cervical cancer (CC), esophageal cancer (EC) and breast cancer. Here we report the updated safety and efficacy data of 9MW2821. Methods: 9MW2821 was administered by intravenous infusion at doses of 0.33-1.5mg/kg on days 1, 8 and 15 of each 28-day cycle. The study included dose escalation, dose expansion and cohort expansion period which included UC, CC, EC, triple negative breast cancer (TNBC) and other Nectin-4 positive solid tumors that progressed after ≥1 systemic treatments (Tx). Primary objectives were assessment of safety and preliminary efficacy. Results: As of Jan 15, 2024, 260 patients (pts) were enrolled with doses ranging from 0.33 to 1.5mg/kg. Only 1 out of 6 pts in 1.5mg/kg group had dose limiting toxicity (grade 4 neutropenia lasted more than 5 days). The maximum tolerated dose was not reached up to 1.5mg/kg and the RP2D was selected as 1.25mg/kg for tolerance. 240 pts were enrolled at dose of 1.25mg/kg. The most common TRAEs of 1.25mg/kg dose group (≥20%, all grade/≥5%, ≥G3) were white blood cell (WBC) count decreased (50.8%, 23.3%), neutrophil count decreased (46.3%, 27.9%), anemia (43.8%, 8.3%), aspartate aminotransferase increased (42.1%, 2.9%), alanine aminotransferase increased (35.4%, 2.1%), asthenia (32.1%, 2.9%), rash (30.0%, 5.0%), decreased appetite (28.8%, 1.3%), nausea (26.7%, 0%), hyperglycemia (25.4%, 2.1%), platelet count decreased (24.2%, 4.6%), alopecia (24.2%, 0%), hypoaesthesia (22.5%, 1.7%), constipation (21.3%, 0%), vomiting (20.9%, 1.3%), hypertriglyceridemia (20.4%, 2.1%), gamma-glutamyltransferase increased (15.8%, 5.4%). Among 190 pts treated with 9MW2821 at 1.25mg/kg or above and reached tumor assessment, objective response rate (ORR) and disease control rate (DCR) was 35.3% and 78.4%, respectively. 37 UC pts, 45 CC pts, 27 EC pts and 16 TNBC pts were enrolled at 1.25mg/kg and evaluable for tumor assessment. Median prior lines of Tx were 2 (range, 1-4). All UC, 51% CC and 93% EC pts progressed after platinum-based chemotherapy and immune checkpoint inhibitors, respectively. Objective responses were also observed in pts with other solid tumor types. Conclusions: The data indicated encouraging efficacy of 9MW2821 in advanced UC, CC, EC and TNBC. 9MW2821 is the first Nectin-4 targeting ADC showed antitumor activity in patients with CC, EC and TNBC. The safety profile showed adequate tolerability. Clinical trial information: NCT05216965 . [Table: see text]
Presence of molecular residual disease after pathologic complete response among patients with inflammatory breast cancer.
Authors: Chen Jennifer H. , Meas Salyna , Sarli Vanessa N. , Koupaei Negar , Upshaw Joshua , Roy Dhruvajyoti , Valero Vicente , Woodward Wendy A. , Lucci Anthony 
Published: July 2024

3044 Background: Inflammatory breast cancer (IBC) is known to recur more frequently than non-IBC after pathologic complete response (pCR). The presence of circulating tumor cells (CTCs), a marker of molecular residual disease (MRD), has been associated with higher likelihood of metastasis. We sought to characterize CTCs and its relationship with pCR in IBC patients. Methods: Patients diagnosed with IBC were enrolled in a prospective registry from 2005-2022. Serial blood draws were performed before, during, and after neoadjuvant systemic therapy (NST), and 6-months and 1-year post-surgery. CTCs were enumerated using CellSearch™. Patients with ≥ 1 CTC at any timepoint in the post-operative period were included in the positive CTC cohort. T-tests, one-way ANOVA, and chi-squared tests were used to compare differences between groups. Kaplan-Meier analysis was used for survival outcomes. Results: A total of 112 patients were included. The median age of diagnosis was 50.5 years (IQR 17) and BMI was 29.3 kg/m2 (IQR 11.3). Patients were predominantly White (85, 75.9%) with clinical stage IIIB-C (94, 84.9%), node-positive (107, 95.5%), and HER2-negative (66, 59.0%) disease. Almost all patients (109, 97.3%) received trimodality therapy – NST, modified radical mastectomy, and adjuvant radiation. At a median follow-up period of 7.1 years (95% CI: 4.7-9.4), the overall survival (OS) rate was 72.3%. Baseline CTC positivity rate was 61.8% (42/68). More than half of the patients (61, 54.5%) had a positive CTC at some point in the post-operative surveillance period. Among the 39 patients who achieved pCR (34.8%), 15 (38.5%) had positive CTCs during follow-up. There were no differences in age, BMI, menopause status, clinical stage, nodal status, grade, presence of LVI, and number of lymph nodes (LNs) removed by CTC status. However, patients with positive CTCs had a significantly higher number of positive LNs at resection (p = 0.01), were more likely to be HER2-negative (p = 0.001), and were less likely to achieve pCR (p = 0.01). Triple negative disease (p < 0.0001), lack of pCR (p = 0.006), and positive CTCs (0.007) were associated with poor prognosis. When pCR was combined with CTC status, patients with positive CTCs demonstrated significantly worse survival, despite having achieved pCR, compared to those with pCR and negative CTC status (5-year OS: 35.0% vs. 83.1%, respectively, p = 0.016). Conclusions: A high proportion of IBC patients who achieved pCR had MRD, as demonstrated by persistent CTCs. CTCs portended worse prognosis in patients with IBC, even after pCR. Future incorporation of longitudinal CTC monitoring may be helpful in identifying patients at risk for relapse despite having achieved a pCR. [Table: see text]
Safety analysis for BH009 vs docetaxel from a bioavailability study.
Authors: Sun Qun , Wei Xiaohua , Jiang Haihua 
Published: July 2024

e13129 Background: BH009 is a novel polysorbate 80-free formulation of docetaxel (DXT) that could eliminate hypersensitivity reactions associated with polysorbate 80. In a bioavailability study of BH009 vs docetaxel (Taxotere), we reported that the ratios for the total DXT and free-DXT fraction Cmax, AUC0-t, and AUC0-∞ of BH009 and docetaxel were within 80% to 125% (90% confidence intervals). Here, we report the safety analysis from the same study population. Methods: This multicenter, randomized, open-label, 2-way crossover study compared the pharmacokinetics and safety of BH009 and docetaxel (Winthrop docetaxel injection, an authorized generic of Taxotere). A total of 46 patients with breast, head and neck, lung, stomach, ovarian, or cervical cancers were randomized, of which 43 patients were treated with BH009 and 44 patients were treated with docetaxel. Patients received a single dose of 75 mg/m2 BH009 or Taxotere IV over 60 min, with ≥21-d washout between doses. Safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. Results: In all, 198 TEAEs were reported during the study: 94 after the administration of BH009 and 104 after the administration of docetaxel. No serious adverse events or deaths occurred. The only grade 3/4 toxicities that occurred for both arms during this study were hematologic. Overall, the incidence of grade 3/4 hematologic toxicity was significantly lower in the BH009 group than in the docetaxel group (2.3% vs 15.9%). Only one patient in BH009 arm experienced grade 3 anemia; no additional grade 3/4 hematologic adverse events were seen in the BH009 group. The incidence of grade 3/4 leukopenia, neutropenia, and lymphopenia in the Taxotere group was 6.8%, 4.6%, and 2.3%, respectively. The overall safety profile in the BH009 group was better than that in the Taxotere group. Conclusions: A better safety profile was observed in the study when BH009 group was compared to docetaxel group in grade 3/4 hematologic toxicity. Clinical trial information: NCT04889599 . [Table: see text]
Efficacy and safety of immunotherapy in patients with liver metastases in patients with esophageal cancer: A retrospective, real-world study.
Authors: Ren Tiejun , Wang Dingyi , Gu Jinjin , Zhao Lijuan 
Published: July 2024

e16033 Background: Advanced or metastatic esophageal cancer patients tend to have a poor prognosis. The liver is the most common organ of distant metastasis in esophageal cancer. The liver metastases associated with a higher risk of survival. Developing the optimal treatment modalities is especially important for those patients. The efficacy of programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitors have not been clearly clarified in liver metastasis of esophageal cancer. Methods: This is a single-center, retrospective, real-world study. We collected general information and clinical data from patients with liver metastasis of esophageal cancer who admitted to Luoyang Central Hospital between April 2020 and October 2023. All patients were first diagnosed esophageal cancer with liver metastasis and received PD-1 or PD-L1 inhibitor regimen or chemotherapy regimen for the first time. Patients treated with interventional therapy or who had received PD-1 or PD-L1 inhibitors were excluded. The efficacy and safety of patients receiving immunotherapy were evaluated, including overall survival (OS), objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), grade 3-5 treatment-related adverse events (TRAE), and immune-related adverse events (irAE). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 61 patients with a median age of 61 (44-88) years, 63.9% males; 37 in the immunotherapy group (23 in the first-line group, 62.2%) and 24 in the chemotherapy group (19 in the first-line group, 79.2%). Median OS was 14.1 (95% CI 11.4-16.8) months in the immunotherapy group and 9.2 (95% CI 8.5-9.9, p < 0.01) months in the chemotherapy group; In first-line treatment, the median OS in the two groups was 19.4 (95%CI 15.0-22.2) months and 9.6 (95%CI 8.9-10.3, p < 0.01) months. In all patients, Median PFS was 7.2 (95% CI 6.4 – 8.0) months in the immunotherapy group and 4.6 (95% CI 3.8 – 5.4) months in the chemotherapy group, p = 0.174. The ORR of immunotherapy and chemotherapy was 56.8% and 33.3%; DCR was 78.4% and 62.5%. Univariate and multivariate analysis showed that N stage and treatment regimen were significant factors related with OS. Grade 3 TRAE in immunotherapy group and chemotherapy group were 29.7% and 29.2%, respectively. The incidence of irAEs was 10.8%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors might have good efficacy and manageable safety in EC patients with liver metastases, especially in first-line patients. [Table: see text]
Camrelizumab plus chemotherapy combined with consolidative radiotherapy as first-line treatment for oligometastatic esophageal squamous cell carcinoma (ESCORT-1st-RT): A single-arm, open-label, phase 2 trial.
Authors: Han Dan , Li Baosheng , Huang Wei 
Published: July 2024

e16043 Background: Compared to chemotherapy alone, immunotherapy combined with chemotherapy as the first-line standard treatment for esophageal squamous cell carcinoma (ESCC) can increase progression-free survival (PFS) to 5.8-7.2 months. This study aimed to explore the feasibility and safety of combining camrelizumab and chemotherapy with consolidative radiotherapy in the treatment of advanced oligometastatic ESCC. Methods: This study included newly diagnosed patients with stage IV ESCC confirmed by histopathology and imaging examination who had ≤ 5 metastatic lesions in ≤ 3 organs. All patients were treated with camrelizumab combined with albumin paclitaxel and carboplatin for 4 cycles, followed by consolidative radiotherapy. The primary esophageal lesion and metastatic lymph nodes were treated with involved-field irradiation therapy, receiving 2.0 Gy per fraction over 25 daily sessions. For distant metastases in organs like the liver, lungs, brain, or bones, radiotherapy was tailored to individual clinical needs, often employing hypofractionated radiation therapy with doses starting at 3 Gy per fraction or above. The maintenance duration of camrelizumab treatment was limited to a maximum of 12 months. The primary endpoint was PFS. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 26, 2021, to September 28, 2022, 29 patients with ESCC, median age 63 (range 51-74), were enrolled; 93.1% were male. All had an ECOG score of 0 or 1 and stage IV disease. 27 (93.1%) patients completed planned radiotherapy. Of 29 evaluated patients, 23 achieved an objective response and 6 maintained stable disease. Thus, the ORR and DCR were 79.3% (95% CI 78.2-80.4) and 100% (95% CI 100-100), respectively. With 23.3 months (95%CI 21.5-25.1) of follow-up, the median PFS was13.7 months (95% CI 9.9-17.5) , the median OS has not reached and the 1-year and 2-year OS rates were established at 72.4% (95% CI 52.3-85.1) and 61.4% (95% CI 41.1-76.5), respectively. The most common treatment-emergent adverse events (TEAEs) of grade 3-4 were lymphocyte count decreased (65.5%), neutrophil count decreased (27.6%), and white blood cell count decreased (20.7%). 1 patients discontinued camrelizumab treatment due to radiation esophagitis. No grade 5 TEAEs occurred. Conclusions: Consolidative radiotherapy following camrelizumab combined with chemotherapy showed potential efficacy and manageable tolerability in patients with advanced oligometastatic ESCC.