bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precise mapping of single-stranded DNA breaks by using an engineered, error-prone DNA polymerase for sequence-templated erroneous end-labelling
Authors: Söderberg Ola , Wenson Leonie , Heldin Johan , Martin Marcel , Erbilgin Yücel , Salman Barış , Schaal Wesley , Sandbaumhüter Friederike , Jansson Erik , Chen Xingqi , Davidsson Anton , Stenerlöw Bo , Spjuth Ola 
Published: October 2024

Abstract

The ability to analyze whether DNA includes lesions is important in identifying mitogenic substances. Until now, the detection of single-stranded DNA breaks (SSBs) has lacked precise methods. To overcome this limitation, we have engineered a chimeric DNA polymerase, Sloppymerase, that is able to replicate DNA in the absence of one nucleotide. In addition to polymerase activity, Sloppymerase demonstrates 5´-3´exonuclease activity. We characterized the activity of Sloppymerase and utilized the enzyme to develop a method for sequence-templated erroneous end-labelling sequencing (STEEL-seq) that is relevant to the mapping of SSBs. Following the omission of a specific nucleotide, e.g., dATP, from the reaction mixture, Sloppymerase introduces mismatches directly downstream of SSBs at positions that should contain deoxyadenosine. The ability to retain sequence information after end-labelling ensures that hits are bona fide SSBs. STEEL-seq works with a variety of sequencing technologies, shown by our successful experiments using Sanger, Illumina, PacBio and Nanopore systems.
Single-mode Dispersion-engineered Nonlinear Integrated Waveguides for Ultra-broadband Optical Amplification and Wavelength Conversion
Authors: Andrekson Peter , Zhao Ping , Shekhawat Vijay , Girardi Marcello , He Zonglong , Torres-Company Victor 
Published: October 2024

Abstract

Four-wave mixing is a nonlinear optical phenomenon that can be utilized for wideband ultra-low-noise optical amplification as well as for wavelength conversion. This has extensively been investigated for various applications such as communications, spectroscopy, metrology, quantum computing and bio-imaging. However, there is a clear desire to implement these functionalities in a small footprint nonlinear platform, being compatible with large volume fabrication and being capable of efficient operation across a large optical bandwidth. Many such platforms, e.g., silicon, aluminum gallium arsenide, silicon nitride, nonlinear glass, etc., have been explored, but suffer from intrinsic significant performance degradation, i.e., gain and bandwidth deduction and distortion, because conventional approaches of nonlinear photonic waveguide geometry construction for dispersion engineering focus on waveguide cross section and result in always being multimode as a byproduct. Here we propose and demonstrate a methodology that utilizes not only the impact of the waveguide cross section on the modal and dispersion behavior of the waveguide but also includes the impact of the waveguide bend for cutting off high-order modes. This approach results in simultaneous single-mode operation and dispersion engineering for very broadband operation of four-wave mixing. While we implemented this in silicon nitride waveguides, which has emerged as a promising platform capable of continuous-wave optical parametric amplification, the design approach can be universally used with other platforms as well. By carefully also considering both second- and fourth-order dispersion we achieve unprecedented amplification bandwidths of approximately 300 nm in silicon nitride nonlinear waveguides of which the losses can be as record-low as 0.6 dB/m. In addition, penalty-free all-optical wavelength conversion of 100 Gbit/s data in a single optical carrier over 200 nm is realized, for the first time, without optical amplification of signal or idler waves. These single-mode hyper-dispersion-engineered nonlinear integrated waveguides can become practical building blocks in versatile nonlinear photonic devices and optical networks.
Prevalence of risk factors in patients with spontaneous intracerebral hemorrhage in Damascus _ Syria: a retrospective cross-sectional study
Authors: rashi Mohamad Ala , Alkhateeb Khaled , Altabbaa Hamza , Nakawah Aman , Hamzeh Ghassan , Alnehlawi Omar 
Published: October 2024

Abstract

Objectives: This study aims to determine the prevalence of risk factors among patients with spontaneous intracerebral hemorrhage in Syrian society and the variations in their
distribution according to age and gender.
Methods: This study is a retrospective cross-sectional study, patients data was collected by reviewing the medical records of patients from Al-Assad University Hospital, Al-Mouwasat University Hospital, Children's University Hospital, and Damascus Hospital.
Cross-tabulation tables and the Chi-square test were used to show the relationship between gender/age and the prevalence of risk factors, demonstrate statistical significance and calculate P-value.
Results: From a total of 194 patients included in the study, there were 123 males, accounting for 63.4% of the patients, while there were 71 females, accounting for 36.6%.
The most common risk factor among intracerebral hemorrhage patients was hypertension at 44.8% of the total patients, followed by antithrombotic use at 25.8%, smoking at 19.1%, diabetes at 15.5%, and hematological diseases making up 9.3% of the patients, whereas in age groups under 10 years, various hematological diseases were the most prevalent risk factors at 42.5%, followed by prematurity at 27.5%, and hyaline membrane disease at 15%.
The study showed no statistically significant differences in the distribution of risk factors between males and females except for smoking. However, the results revealed a significant difference in the distribution of risk factors according to age for Smoking, hypertension, antithrombotic use, diabetes, arteriovenous malformation, hyaline membrane disease, hematological diseases, and prematurity(p<0.05).
Conclusion: The study showed that hypertension and antithrombotic use are the most important risk factors for intracerebral hemorrhage, so controlling arterial pressure and periodic tests such as (platelet count/PT/PTT) are gold roles in preventing intracerebral hemorrhage.
ATF3-SLC7A7 Axis Regulates mTORC1 Signaling to Suppress Lipogenesis and Tumorigenesis in Hepatocellular Carcinoma
Authors: Qinglin Zhang , Fengzhi Zhu , Yin Tong , Yunxing Huang , Jiangwen Zhang 
Published: October 2024

Abstract

Background
Hepatocellular carcinoma (HCC) remains a major global health challenge with poor prognosis and high mortality. Dysregulated lipid metabolism is increasingly recognized as a key driver of HCC progression. While the transcription factor ATF3 has been implicated in tumorigenesis and lipid regulation, its precise role in HCC development and lipid biosynthesis is not fully understood.
Methods
We generated ATF3-overexpression and ATF3-knockdown HCC cell lines via lentiviral infection. To investigate ATF3’s role in HCC, we performed in vitro assays, including MTT, transwell migration, wound healing, and colony formation assays, alongside an in vivo mouse xenograft model to assess tumor growth. The correlation between ATF3 expression and lipid synthesis was analyzed using RNA-Seq data from HCC patients and further validated by qRT-PCR, Nile Red staining, lipid quantification, correlation analysis, and immunohistochemistry. The impact of ATF3 on mTORC1 signaling was evaluated through western blotting, confocal microscopy, Oil Red O staining, and lipid quantification assays. SLC7A7, identified as a potential downstream effector of ATF3, was analyzed using qRT-PCR, and its influence on mTORC1 signaling was examined in the same manner as ATF3. The binding of ATF3 to the enhancer region of SLC7A7 was identified via ChIP-Seq and confirmed through ChIP-qPCR, luciferase reporter assays, and DNA pull-down assays.
Results
We demonstrate that mTORC1 inhibition markedly reduces lipogenesis in HCC and identify a regulatory axis involving ATF3 and the amino acid transporter SLC7A7. Transcriptomic analysis reveals an inverse correlation between ATF3 expression and lipid synthesis, a finding supported by experimental data. Mechanistically, ATF3 represses mTORC1 signaling, inhibiting lipid biosynthesis, with SLC7A7 acting as a key mediator. ATF3 directly binds to the enhancer region of SLC7A7, activating its transcription and subsequently limiting mTORC1 activity. Functional assays in ATF3-overexpression and -knockdown HCC cell lines confirm ATF3’s tumor-suppressive role.
Conclusion
This study uncovers a novel ATF3-SLC7A7-mTORC1 regulatory axis that mitigates lipogenesis and tumorigenesis in HCC, highlighting a critical link between lipid metabolism and liver cancer progression. These findings present promising therapeutic targets for HCC treatment.
Meta-analysis of recurrence-free survival or disease-free survival as a potential surrogate endpoint for overall survival in esophageal cancer trials
Authors: Anyaduba Uchechukwu Love , Orababa Oluwatosin Qawiyy , Faye Zion , Rashid Nazia , Shafrin Jason , Reardon Gregory 
Published: October 2024

Abstract

Background Cancer trials increasingly use surrogate endpoints, but it is unclear how well recurrence-free (RFS) or disease-free survival (DFS), specifically, predict overall survival (OS) in resectable esophageal cancer (EC).Methods A systematic literature review identified trials with RFS/DFS and OS endpoints. A meta-analysis assessed RFS/DFS as surrogates for OS, estimating pooled hazard ratios (HRs) from trial HRs. Forest plots and heterogeneity tests showed effect sizes and pooled estimates. Unweighted linear regression and weighted sensitivity analysis estimated the correlation between OS and RFS/DFS, producing a regression plot.Results Of 975 articles identified, nine met the criteria, with two more from references. The pooled HR for OS and RFS/DFS were 0.90 and 0.87, respectively. The primary analysis showed a strong Pearson correlation between RFS/DFS and OS (ρ = 0.89, p < 0.001).Conclusion Subject to known methodological limits, RFS/DFS was demonstrated to be a potentially-suitable surrogate endpoint for OS in resectable EC.
Simultaneous determination of multi-class pesticide residues in solanaceous vegetables and selected fruits using LC-MS/MS and potential impact on consumer health with measurement uncertainty
Authors: Aralimarad Prabhuraj , Bedar Jamuna , Mahato Saraswati , Hanchinal Shivanand , Naik Nagaraj , U Shwetha , K Pavankumar , P Naveenkumar , Gavai Abhishek , Rat Ranjitha Sreemantha , Patil Mahendra 
Published: October 2024

Abstract

The present study developed and validated the liquid chromatography-tandem mass spectroscopy (LC-MS/MS) based highly sensitive, rapid and reproducible analytical method for estimating trace level residue of 39 major multiclass pesticides. A total of 480 samples of solanaceous crops (chilli, bell pepper, tomato and brinjal) and 240 from fruit crops (pomegranate and grapes) were collected from local markets of Kalyana Karnataka region for the study. The results indicated, the developed method was linear and showed excellent correlation coefficient (R2) of 0.998–0.999 in solvent and 0.993–0.999 in all the matrices analyzed. No significant matrix effect was observed for all pesticides in different matrices and within the range of ± 20%. The recovery percentage at all three levels (0.01, 0.05 and 0.1 mg/kg) ranged from 71.28-113.98% with a relative standard deviation of less than 10% for all the matrices evaluated. Measurement uncertainty values estimated at 50 µg/kg spiking level were found lower than 14 µg/kg for all tested pesticides in different matrices. Occurrence of 17 pesticides in all the tested vegetable and fruits samples which include 11 insecticides and 6 fungicides. Imidacloprid, carbendazim, acephate, profenofos, chlorantraniliprole, dimethoate, and difenoconazole were the commonly detected pesticides with 81.67, 76.67, 30.83, 21.67, 43.33 and 86.67% contamination in green chilli, bell pepper, tomato, brinjal, pomegranate and grapes, respectively. The dietary health risk assessment revealed safe for both adults and children as the hazard quotient (HQ) and hazard index (HI) values were less than 1 and would not cause any hazardous risk upon consumption.
Modeling the Land use Land cover changes and its impacts on agricultural land area by using GIS and RS at Fitche town, Central Ethiopia
Authors: Ketema Dereje , Bekele Addisu 
Published: October 2024

Abstract

The rapid expansion of urban area rose with population growth, movements and demands have a substantial impact on land use land cover change (LULCC). The study aims to Modeling and analyze LULC changes and its impacts on the surrounding Agricultural farmlands in Fitche town central Ethiopia during the periods of 2002 to 2022. The study employed satellite images of Landsat TM for 2002, Landsat OLI datasets for 2013 and 2022. Support Vector Machine Algorithm of Supervised Classification has been applied to generate LULC maps of 2002, 2013 and 2022 years by using ENVI software and the accuracy of classified land use land cover maps were checked by confusion matrix to derive overall accuracy and results were above the minimum and acceptable threshold level. The performed of modelling Land use land cover (LULC) dynamics have been assessed by Cellular Automata (CA) in Modules of Land Use Change Evaluation (MOLUSCE) Plugins using QGIS and Land Change Modeler (LCM) model to quantify the land use transitions between land cover classes, to identify gain and losses of each class categories in relation to other land cover classes and their spatial trend. Finally, Cellular Automata has been run to model LULC changes in the study area and to predict future land use changes. The parameter, such as Digital Elevation model (DEM), slope, aspect and distance from the road are used as spatial variable maps in the processes of learning in ANN-Multi layer perception to predict their influences on LULC between 2002 and 2022. The actual and projected LULC maps for 2022 indicate a good level of accuracy, with an overall Kappa value of 0.83 and with a percentage of the correctness 88.8 %. Artificial neural networks (ANN)-Multi-layer perception model is then used to forecast changes in LULC for the years 2050. Generally, the results of this study have shown that there was an increased expansion of built up areas in the last 22 years from 10.43% in 2002 to 16.92 % in 2013 and to 25.76% in 2022 and agricultural land was inclined from 66.40% in 2002 to 54.93% in 2013 and decreased to 36.41% in 2022. The simulated result indicate that built-up area covers 29.76% in 2030, 32.31% in 2040 and 35.74% in 2050 and farmlands was expected to be 29.74% in 2030, 26.56% in 2040 and 22.01% in 2050 of the total area coverage. The findings assist farmers and policy-makers in developing optimal land use plans and better management techniques for the long-term development of natural resources.
Cultural Food Preferences and Non-Communicable Diseases: a case study of cultural values assigned to food in Kiribati
Authors: Ng Zhen Ming Jeremy , Cauchi John Paul 
Published: October 2024

Abstract

The global burden of non-communicable diseases (NCDs) is increasing. This has significant implications for Pacific Island Countries and Territories (PICTs) including Kiribati, whose struggles with food security have led to an increased burden of chronic, metabolic, and lifestyle-related NCDs, particularly diabetes and cardiovascular diseases. While past studies have explored consumption patterns, no studies have examined actual cultural food preferences in Kiribati. Through freelist data collected from 399 fixed-question household surveys, this study aims to explore this gap in cultural food narratives and see if there is an association with NCD prevalence. The study used Smith’s S salience analysis to assess significance, finding food items such as fish, rice, breadfruit, chicken, and coconut as culturally important in Kiribati. Participants were also categorised into sociodemographic regions, finding nuanced differences between urban and rural communities. The analysis revealed focus foods for tailored interventions that align with cultural narratives and ‘healthy’ foods ensuring effective food security interventions that address the escalating prevalence of NCDs. Limitations were identified, such as the temporal aspect of the data collected just before the COVID-19 pandemic, potential social desirability bias, unequal sample sizes between sociodemographic regions, and disparities between reported food consumption and actual consumption patterns. The study also suggests future implications, including a comprehensive dietary investigation of Kiribati, particularly in examining food additives like sugar and salt, and the applicability of similar methodologies in exploring cultural food narratives in other PICTs.
Effects of WIN 55,212 cannabinoid and SMA-WIN 55,212 on the expression of cannabinoid receptors in different glioma cell lines.
Authors: Taha Safa , Aljishi Muna , Sultan Ameera , Sridha Kannan , Taurin Sebastien , Greish Khaled , Bakhiet Moiz 
Published: October 2024

Abstract

Background:
Glioblastoma (GBM) is a highly invasive primary malignancy of the brain that is prone to acquiring resistance to chemotherapy. Given the limited therapeutic options available, an unmet need exists for effective treatment of GBM. In the present study, we evaluated the in vitro anticancer activity of WIN 55,212 (WIN), a synthetic cannabinoid molecule, in the form of micelles conjugated with styrene-maleic acid (SMA) against the LN 18 (epithelial origin) and A172 (mesenchymal origin) glioma cell lines.
Methods:
SMA–WIN 55,212-2 micelles were prepared in vitro using a pre-validated, standard technique. The cytotoxic effects of the two treatments (WIN 55,212-2 and SMA-WIN 55,212-2) were evaluated in glioma cell lines (LN-18 and A-172), and inhibitory concentrations for killing 50% of the cells (IC50) were estimated. The expression of the CB1 (cannabinoid receptor 1), CB2 (cannabinoid receptor 2), TRPV1 (transient receptor potential vanilloid 1), and PPAR-γ (peroxisome proliferator-activated receptor gamma) receptors following treatment with the free and micellar forms of WIN 55,212-2 was detected.
Results:
We observed significantly lower IC50 values for both the LN 18 and A172 cell lines with SMA-WIN 55 and 212-2 than with WIN 55 and 212-2 alone. Similarly, the expression of the CB1 and CB2 receptors was significantly greater in the SMA-WIN 55 and 212-2 cell lines than in the WIN 55 and 212-2 cell lines in the A172 cell line. No significant changes were observed for TRPV1, while only SMA-WIN 55,212-2 increased the expression of PPAR-γ receptors.
Conclusion:
The micellar formulation of WIN 55 and 212-2 had significantly greater effects on both glioma cell lines than did the free WIN 55 and 212-2. The formulations of WIN 55 and 212-2 exhibited variable cannabinoid receptor expression levels and need further evaluation in suitable in vivo animal models. Moreover, SMA-WIN 55 and 212-2 significantly upregulate PPAR-γ, which requires further investigation.
Effects of Combined Visual-Motor Response Training on Cognitive Function and Brain Plasticity Mechanisms in Various Populations: Protocol for a Single-Center, Open-Label, Controlled Clinical Trial
Authors: Yu Wenlong , Gao Jiamin , Zhu Ping 
Published: October 2024

Background
Cognitive impairment is one of the major diseases facing the aging population. The progressive decline of cognitive function can lead to declining health or even the loss of life, work, and social ability. Exercise and behavioral stimulation can increase neurotransmitters in the brain and improve overall health and cognitive function. Reactivity training can mobilize neuromuscular function and induce changes in brain plasticity, which may effectively improve cognitive dysfunction and delay the occurrence and development of Alzheimer disease; however, the evidence supporting its effectiveness is still limited.

Objective
This study aims to explore the effectiveness and reliability of visual-motor reaction training in improving cognitive function, thereby promoting the application of novel nonpharmacological therapies.

Methods
This study is a single-center, open-label, controlled clinical trial. A total of 78 participants will be recruited for the study, including an equal number of athletes, ordinary healthy college students, and ordinary older adults in the community. Participants will receive 2 weeks of visual-motor response training. The primary outcome of this study is to assess differences in functional magnetic resonance imaging (fMRI) at 2 weeks. The secondary outcomes were the following: acousto-optic response time, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Mini Mental State Examination (MMSE), Activity of Daily Living (ADL) Scale, Subjective Cognitive Decline Questionnaire–9 (SCD-Q9), a 10-word memory test, and safety.

Results
The study was approved by the Shanghai Clinical Research Ethics Committee on January 2, 2024 (SECCR/2023-162-01). As of September 11, 2024, we have completed the recruitment of all 3 groups of volunteers. We expect to complete data collection and analysis by February 2025.

Conclusions
The purpose of this study is to compare improvements in brain perceptual motor functions and cognitive levels across different populations through response ability training and to explore the efficacy and safety of exercise-based nonpharmacological therapies in improving cognitive function. Other potential benefits include understanding the functional differences and perceptual characteristics of the brain’s perceptual-motor system between athletes and the general population and exploring the adaptability of the brain in acquiring skills during competitive sports training. This could provide an evidence base for early sports talent development and broader youth development.

Trial Registration
Chinese Clinical Trial Registry ChiCTR2400079602; https://tinyurl.com/23fbbndw

International Registered Report Identifier (IRRID)
DERR1-10.2196/56424
Narrativas turísticas y la conformación del patrimonio nacional mexicano a través del análisis de las guías turísticas de Morelos
Authors: Salinas Córdova Daniel 
Published: October 2024

Desde principios del siglo xx, las narrativas turísticas de México han utilizado elementos de su historia y cultura, influyendo en la representación y concepción del país tanto nacional como internacionalmente. La dinámica histórica de cómo se crean y evolucionan dichas narrativas turísticas, y el papel que juega el patrimonio en esos procesos, han sido poco atendidos en las discusiones sobre el pasado y presente de México como uno de los destinos turísticos más importantes del mundo.

Este artículo aborda la manera en la que se empleó el patrimonio para la promoción de México como destino durante el siglo xx. Siguiendo un enfoque interdisciplinario, la investigación analiza los discursos patrimoniales, las imágenes y la “mirada turística” generada por la industria turística en una serie de guías publicadas entre los años veinte y noventa, esto a través de un estudio de caso en el estado de Morelos. El objetivo es comprender los procesos a través de los cuales el Estado, los promotores turísticos, audiencias y agentes sociales crearon, negociaron, apropiaron y exhibieron nociones de patrimonio cultural en conjunto, conflicto y/o incluso oposición con nuevas identidades mexicanas a lo largo del siglo xx tras la Revolución Mexicana. Al examinar los cambios de las narrativas turísticas sobre Morelos descritas en las guías, esta investigación arroja luz sobre el poco reconocido papel que el turismo ha jugado en la construcción y desarrollo de las nociones de identidad y patrimonio nacional en México.