bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Tripartite Gene Editing Machinery for Highly Efficient Non-Viral Targeted Genome Integration
Authors: Wu Hao , Nam Hangu , Xie Keqiang , Majumdar Ishita , Yang Shaobo , Starzyk Jakob , Lee Danna , Shan Richard , Li Jiahe 
Published: October 2023

Abstract
Non-viral DNA donor template has been widely used for targeted genomic integration by homologous recombination (HR). This process has become more efficient with RNA guided endonuclease editor system such as CRISPR/Cas9. Circular single stranded DNA (cssDNA) has been harnessed previously as a genome engineering catalyst (GATALYST) for efficient and safe targeted gene knock-in. Here we developed enGager, a system with enhanced GATALYST associated genome editor, comprising a set of novel genome editors in which the integration efficiency of a circular single-stranded (css) donor DNA is elevated by directly tethering of the cssDNA to a nuclear-localized Cas9 fused with ssDNA binding peptides. Improvements in site-directed genomic integration and expression of a knocked-in DNA encoding GFP were observed at multiple genomic loci in multiple cell lines. The enhancement of integration efficiency, compared to unfused Cas9 editors, ranges from 1.5- to more than 6-fold, with the enhancement most pronounced for transgenes of > 4Kb in length in primary cells. enGager-enhanced genome integration prefers ssDNA donors which, unlike traditional dsDNA donors, are not concatemerized or rearranged prior to and during integration Using an enGager fused to an optimized cssDNA binding peptide, exceptionally efficient, targeted integration of the chimeric antigen receptor (CAR) transgene was achieved in 33% of primary human T cells. Enhanced anti-tumor function of these CAR-T primary cells demonstrated the functional competence of the transgenes. The ‘tripartite editors with ssDNA optimized genome engineering’ (TESOGENASETM) systems help address the efficacy needs for therapeutic gene modification while avoiding the safety and payload size limitations of viral vectors currently used for CAR-T engineering.
Efficacy and Safety of Endoscopic subserosal dissection Treatment for Gastrointetinal submucosal Tumors in the Upper Gastrointestinal Tract
Authors: Wang Aili , Niu Qiong , Chen Yan , Liu Lijuan , Xiao Xin , Liu Chengxia 
Published: October 2023

Abstract

Objective
To investigate the safety and efficacy of endoscopic subserosal dissection for patients with submucosal tumors in the upper gastrointestinal tract.
Methods
This retrospective single-center study included 16 patients who underwent ESSD. All patients were enrolled from July 2018 to Dec 2021. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time and follow-up were investigated and analyzed.
Results
Our study achieved 100% en bloc resection and 100% R0 resection. The most common location was the corpus with a mean tumor size of 2.78 ± 1.56 cm. The mean age, procedure time, were 53.4 ± 10.3 years, 85.31 ± 46.64 minutes respectively. Acocording to National Institutes of Health classification, 7 (13, 53.85%), 5 (13, 38.46%) ,and 1 (13, 7.69%) objects belonged to the very low, low, and intermediate classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 9.3 ± 2.5 months showed no recurrence or metastasis.
Conclusions
ESSD is effective and safe surgical procedure for curative removal of gastrointestinal submucosal tumors in the upper gastrointestinal tract, and it can be preferred for patients with no metastasis.
Association study between intestinal flora and renal malignancy based on genome-wide association analysis data
Authors: Gan JingZheng , Yuan Yuan , Wang Xiong , Luo PengCheng 
Published: October 2023

Abstract

Objective
Gut microbiome (GM) plays an important role in a variety of diseases, and renal malignancies have been shown to be closely associated with GM. However, the role of GM in the pathogenesis of renal malignancies has not been fully explored. The aim of this study was to investigate the potential causal association between intestinal flora and renal malignancies and the possible mechanisms of action.
Methods
We collected genome-wide association study (GWAS) data on GM and renal malignancies and applied Mendelian randomization (MR) analysis to explore the causal association between them.
Results
By MR analysis, we found that GM components associated with renal malignancies, including enterobacteria of certain orders, families, and genera, may have negative causal effects in the pathogenesis, while enterobacteria of other orders, families, and genera may have positive causal associations with renal malignancies.
Conclusion
This study reveals a possible causal association between intestinal flora and renal malignancies and identifies several genetic variants involved in this association. These findings are expected to provide new insights into the pathogenesis of renal malignancies and provide a theoretical basis for the development of therapeutic strategies targeting intestinal flora in the future.
Emergence of ferromagnetism at the onset of moiré Kondo breakdown
Authors: Mak Kin Fai , Zhao Wenjin , Shen Bowen , Tao Zui , Kim Sunghoon , Knuppel Patrick , Han Zhongdong , Zhang Yichi , Chowdhury Debanjan , Shan Jie , Watanabe Kenji , Taniguchi Takashi 
Published: October 2023

Abstract

The interaction of a lattice of localized magnetic moments with a sea of conduction electrons in Kondo lattice models induces rich quantum phases of matter, such as Fermi liquids with heavily renormalized electronic quasiparticles, quantum critical non-Fermi liquid metals and unconventional superconductors, among others 1–4. The recent demonstration of moiré Kondo lattices has opened the door to investigate the Kondo problem with continuously tunable parameters 5–10. Although a heavy Fermi liquid phase has been identified in moiré Kondo lattices, the magnetic phases and Kondo breakdown transitions remain unexplored. Here we report a density-tuned Kondo destruction in AB-stacked MoTe2/WSe2 moiré bilayers by combining magneto transport and optical studies. As the itinerant carrier density decreases, the Kondo temperature decreases. At a critical density, we observe a heavy Fermi liquid to insulator transition, and a nearly concomitant emergence of ferromagnetic order. The observation is consistent with the scenario of a ferromagnetic Anderson insulator and suppression of the Kondo screening effect. Our results pave the path for inducing other exotic quantum phase transitions in moiré Kondo lattices 6–15.
Breastfeeding Support among Healthcare Workers in Nigeria
Authors: Alao Michael Abel , Ibrahim Olayinka Rasheed , Briggs Christopher Datonye , Yekini Sakiru Abiodun , Nri-Ezedi Chisom Adaobi , Sotimehin Sikirat Adetoun , Olasinde Yetunde Toyin , Aliu Rasaki , Borokinni Ayodeji Mathew , Elo-Ilo Jacinta Chinyere , Bello Oyeronke Olubunmi , Diala Michael Udochukwu , Olaniyi-George Joyce Foluke , Oluwatoyosi Temilade , Usman Hadiza Ashiru , Tongo Oluwakemi Oluwatoyin 
Published: October 2023

Abstract

BackgroundThe exclusive breastfeeding rate in Sub-Saharan Africa is abysmally low, and based on current trends, achieving the World Health Organization's (WHO) global nutrition goal of a 50% exclusive breastfeeding rate by 2025 will require an additional three decades.MethodsThis is a cross-sectional study involving healthcare workers (HCWs) providing direct care to breastfeeding mothers in six geopolitical zones in Nigeria. HCWs were recruited using a stratified random sampling method, with a minimum sample size of 1,537. Data was collected through validated-interviewer-administered-questionnaires.ResultsThe mean age of the 1,294 study respondents is 35.2±10.0 years, with a M: F of 1:3. Although general breastfeeding knowledge was high (91.7%), specific knowledge such as breastfeeding in mothers with breast cancer (13.4%) and hepatitis B (59.4%) was inadequate. Only 18.9% correctly identified the laid-back and cross-cradle breastfeeding positions. Negative attitudes towards breastfeeding support were associated with being a female HCWs [AOR of 1.735 (95% CI: 1.287, 2.698)], and a doctor [AOR of 2.079, 95% CI: 1.085,3.948)]. Suboptimal instructional support practice was associated with lower educational levels [AOR of 4.099 (95% CI 1.276,13.161)], being a doctor [AOR of 3.469 (95% CI 1.531,7.862. Optimal general knowledge of breastfeeding was less associated with having a positive attitude toward breastfeeding support [AOR of 0.685 (95% CI 0.532, 0.881].ConclusionHCWs displayed Optimal overall knowledge of breastfeeding, but specific areas such as breastfeeding in relation to maternal illnesses, and positioning were lagging. A targeted program is necessary to enhance breastfeeding support knowledge and attitudes, particularly among female HCWs and physicians.
PITX2 functions as a transcription factor for GPX4 and protects pancreatic cancer cells from ferroptosis
Authors: Wang Zhiliang Wang , Wu Di , Zhang Yue , Chen Weibo , Yang Yang , Yang Yue , Zu Guangchen , An Yong , Yu Xianjun , Qin Yi , Xu Xiaowu , Chen Xuemin 
Published: October 2023

Abstract

Background
Ferroptosis inhibits tumor progression in pancreatic cancer cells, while PITX2 is known to function as a pro-oncogenic factor in various tumor types, protecting them from ferroptosis and thereby promoting tumor progression. In this study, we sought to investigate the regulatory role of PITX2 in tumor cell ferroptosis within the context of pancreatic cancer.
Methods
We conducted PITX2 knockdown experiments using lentiviral infection in two pancreatic cancer cell lines, namely PANC-1 and BxPC-3. We assessed protein expression through immunoblotting and mRNA expression through RT-PCR. To confirm PITX2 as a transcription factor for GPX4, we employed Chromatin Immunoprecipitation (ChIP) and Dual-luciferase assays. Furthermore, we used flow cytometry to measure reactive oxygen species (ROS), lipid peroxidation, and apoptosis and employed confocal microscopy to assess mitochondrial membrane potential. Additionally, electron microscopy was used to observe mitochondrial structural changes and evaluate PITX2's regulation of ferroptosis in pancreatic cancer cells.
Results
Our findings demonstrated that PITX2, functioning as a transcription factor for GPX4, promoted GPX4 expression, thereby exerting an inhibitory effect on ferroptosis in pancreatic cancer cells and consequently promoting tumor progression. Moreover, PITX2 enhanced the invasive and migratory capabilities of pancreatic cancer cells by activating the WNT signaling pathway. Knockdown of PITX2 increased ferroptosis and inhibited the proliferation of PANC-1 and BxPC-3 cells. Notably, the inhibitory effect on ferroptosis resulting from PITX2 overexpression in these cells could be countered using RSL3, an inhibitor of GPX4.
Conclusion
Overall, our study established PITX2 as a transcriptional regulator of GPX4 that could promote tumor progression in pancreatic cancer by reducing ferroptosis. These findings suggest that PITX2 may serve as a potential therapeutic target for combating ferroptosis in pancreatic cancer.
Thermal comfort of users of a park located in one of the hottest cities in Brazil
Authors: Justi Ana Clara Alves , Nogueira Marta Cristina de Jesus Albuquerque , Santos Fávia Maria de Moura , Zavitoski Érico Vinicius da Silva , de Paulo Sérgio Roberto , Justi Gabriel Henrique 
Published: October 2023

Abstract
Carried out for the first time, this study assessed the microclimate and thermal comfort of users of the Das Águas Park in Cuiabá, which is one of the hottest cities in Brazil. Air temperature, relative humidity, globe temperature, and wind speed were measured using moving transects at 10 points on the park’s walking track for a total of 365 measurements. Mobile transect data were validated using an official weather meteorological station and thermal comfort data were simulated using Rayman software. Regarding the characterization of the microclimate, the air temperature ranged from 17.5 to 34.6°C and the relative humidity from 42.6 to 84.8%, with wind speed ≤ 1.6 m s-1. The park’s walking track also had points without thermal comfort, most of which had strong heat stress and the Universal Thermal Climate Index (UTCI) values ranging from 17.8–38.8°C. The findings of this study reinforce the importance of research that assists the construction of new urban parks in cities with extreme climates, in order to mitigate the effects of urbanization on their microclimate and on the thermal comfort of the park’s human population.
Neuroprotection afforded by an enriched Mediterranean-like diet is modified by exercise in a rat model of cerebral ischemia
Authors: Romaus-Sanjurjo Daniel , Castañón María , López-Arias Esteban , Custodia Antía , Martín Cristina , Ouro Alberto , López-Cancio Elena , Sobrino Tomás 
Published: October 2023

Abstract

Ischemic stroke is an important cause of mortality and disability worldwide. Given that current treatments do not allow a remarkable better outcome in patients after stroke, it is mandatory to seek new approaches preventing stroke and/or complementing the current treatments or ameliorating the ischemic insult. Multiple preclinical and clinical studies highlighted the potential beneficial roles of exercise and a Mediterranean diet following stroke. Here, we examined whether a Mediterranean-like diet supplemented with hydroxytyrosol with/without physical exercise enhances the good outcome of rats submitted to a transient middle cerebral artery occlusion (tMCAO). We also assessed a potential synergistic effect with physical exercise. We found that an enriched Mediterranean-like diet decreased infarct/edema volumes, delayed acute immune response (modulates cytokines/chemokines levels) and increased acute functional recovery after ischemic injury. Strikingly, although physical exercise did improve cellular and some functional outcomes compared to control animals, it did not synergize with the Mediterranean-like diet but even impaired the positive short-term outcomes. Overall, these data provide the first preclinical evidence that an enriched Mediterranean diet mediates neuroprotection probably by the modulation of cytokines/chemokines levels downwards that eventually has an important role during the acute phase following ischemic damage.
A mixed smoothed finite element limit analysis formulation for static and seismic collapse loads
Authors: Nguyen H. C. , Zhang X. , Nazem M. 
Published: October 2023

Abstract

This paper introduces a novel stress-based upper bound limit analysis formulation based on nodal integrations for calculating static and seismic collapse loads in geotechnical engineering. Unlike the classical upper bound limit analysis, our newly proposed formulation is expressed in terms of the stress fields rather than displacement fields. Additionally, the determination of kinematically admissible displacement fields is achieved through duality theory. We demonstrate the robustness and accuracy of our numerical scheme through benchmark examples involving static and seismic collapse loads, such as bearing capacity and tunnel stability. Furthermore, we incorporate a simple non-associated plasticity scheme into the analyses to assess dilation-dependent collapse loads. The newly proposed numerical scheme is then utilised for assessing the influence of the dilation on the static and seismic collapse loads and its failure mechanism, giving some new valuable insights into the dilation-dependent collapse loads under seismic conditions.
LATCHES – A memory aide for the principles of attachment for effective breastfeeding: Findings of a regional pilot in the Northeast of England and North Cumbria
Authors: Shotton Lynette Harland , Elliot Cheryl , Nunn Roslyn , Lane Kathryn 
Published: October 2023

Abstract

Background
Breastfeeding rates have increased significantly in the last 10 years but more needs to be done to achieve the global target for 70% of mothers to exclusively breastfeed for the first 6 months by 2030 [1]. The UK has some of the lowest rates of breastfeeding, particularly in the Northeast of England, and as such more needs to be done to support mothers to breastfeed for as long as they would like to.
Methods
Key breastfeeding practitioners were brought together to select one of two memory aides for principles of attachment for effective breastfeeding. The selected memory aide was piloted with 57 participants with a key role in promotion and support of breastfeeding in the Northeast of England and North Cumbria.
Findings
Participants reported mixed views about the proposed memory aide with more experienced staff reporting more favourable opinions than student midwives and early years practitioners.
Discussion and outcomes
Findings of the pilot indicate there is a role for a mnemonic to help practitioners understand, recall and retain theory around attachment for effective breastfeeding but the piloted memory aide needs further development.
Conclusion
Using data from the pilot the memory aide was refined and the final version LATCHES agreed for wider dissemination. Future research is needed to understand its wider impact on breastfeeding practice.
Valorization of PES textile waste through glycolysis and aminolysis using bimetallic ZnO and carbon nitride nanocomposites
Authors: Anbarasu Murugan , Vinitha Viswanathan , Preeyangha Mani , Neppolian Bernaurdshaw , Sivamurugan Vajiravelu 
Published: October 2023

Abstract

Polyester (PES) textile fabrics are chemically recycled through aminolysis, and glycolysis catalyzed by nanocomposites composed of Sb (or) In-doped ZnO and g-C3N4 nanocomposites prepared by the wet-impregnation method. The nanocomposites were characterized by XRD, UV‒Vis, FT-IR, and SEM-EDS techniques. X-ray diffraction patterns as well as SEM EDS showed the presence of amorphous g-C3N4 and doped ZnO. The extent of the optical band gaps of ZnO observed in doping with g-C3N4. The optical band gap of 3.31 eV of ZnO was reduced to 2.55 to 2.65 eV after doping with g-C3N4. SEM morphological analysis showed a sheet-like structure along with ZnO nanoparticles adsorbed on the surface of g-C3N4. Glycolysis and aminolysis of colored PES waste produced BHET and BHETA, respectively, as pure monomers in excellent yield (>90%). FT-IR, MS, 1H, and 13C NMR were used to confirm the formation of BHET and BHETA.
Comparison and selection of ground motion prediction equations for the Sichuan-Yunnan area, southwest China
Authors: Liu Jingwei , Douglas John 
Published: October 2023

Abstract
The Sichuan-Yunnan area is one of the most seismically active regions in China. As ground-motion models form a key component of seismic hazard analysis, it is important to select (or develop) appropriate models for this area. The increasing number of digital ground-motion records of earthquakes in this area has allowed the development of local ground motion prediction equations (GMPEs). This study compares and, later, recommends appropriate GMPEs for the Sichuan-Yunnan area. We first evaluate the inherent quality of local GMPEs, with respect to their underlying datasets, the variables used and their functional form, to determine a set of candidate GMPEs. Then we investigate how well the predictions from the GMPEs match observations computed from strong-motion records of recent earthquakes in this area. The fit between predictions and observations varies significantly amongst the GMPEs. The results suggest that some recent local GMPEs would lead to biased ground-motion estimates due to limitations of their underlying datasets and functional forms. Based on both evaluations of inherent quality and compatibility with observations, only one local GMPE is recommended. A comparison of the predictions from three widely-used non-local GMPEs indicates that ground motions in the Sichuan-Yunnan area appear more variable than those in other regions but that predictions from these non-local GMPEs are generally unbiased. We recommend use of a mixture of robust local and non-local GMPEs within seismic hazard analyses to capture the epistemic uncertainty in ground-motion prediction for this area.
Comparison of transcriptomic and phenomic profiles for the prediction of drug mechanism
Authors: Baek In Yeop , Go Taewon , Chung Ting Ting , Kim Dongil , Lee Seung Jin 
Published: October 2023

Abstract

Transcriptomic and phenomic profiling assays analyze drug perturbations to provide unbiased information regarding the mechanisms of action (MOAs) of drugs. However, few studies have compared the bioinformatics contents derived from these assays. This study investigated the transcriptomic and phenomic features in terms of diversities and MOA prediction. From publicly available L1000 and Cell Painting datasets, transcriptomic and phenomic features for 274 compounds annotated with 30 MOAs were prepared for analyses. Feature-extraction analyses with tSNE and Isomap algorithms showed that the compound distribution based on transcriptomic features was more dispersed than that based on phenomic features. Pairwise comparison across compounds showed high correlative clusters in phenomic feature heatmap. To explore the predictive potential for the MOA of compounds, transcriptomic and/or phenomic features were used to train machine learning models. XGBoost and Extra Tree models resulted in overfitting, whereas the KNN and Adaboost models yielded a relatively lower performance. Notably, the glucocorticoid receptor agonist was the class of MOA with the highest predictability based on transcriptomic and/or phenomic features. In conclusion, L1000 features were more diverse than the Cell Painting features. Machine learning analysis suggested new similar pairs of compounds and predicted certain classes among MOAs more accurately than others.
Nanoscale friction behavior between montmorillonite and quartz: considering effects of cations, normal load and sliding velocity
Authors: He Zhenyu , Zheng Yuan-Yuan , Yin Zhen-Yu , Wei Pengchang 
Published: October 2023

Abstract

Nanoscale tribology between quartz and montmorillonite interface in soft clay is crucial for comprehending their engineering mechanism, which remains unclear in microscale. In this study, Molecular Dynamics (MD) simulation method was employed to investigate the nanoscale frictional properties between quartz and montmorillonite at dry state, where montmorillonite was set as substrate and quartz as sliding slider. The effects of normal load, interlayer cations, and sliding velocity on the frictional behavior were investigated and discussed. The simulation results indicated that the stick-slip effect during friction process was gradually weakened with increasing sliding velocity or decreasing normal load. The shear stress increased with the increasing normal load, exhibiting an approximately linear relationship. The order of friction coefficients of montmorillonite-quartz with different interlayer cations is Ca2+ > Zn2+ > Ni2+ > Pb2+ > Li+ > Rb+ > Cs+ > K+, illustrating that the friction coefficient of montmorillonite-quartz systems with divalent cations was greater than that with monovalent cations. The friction angle of montmorillonite-quartz with different interlayer cations vary from 6.96° to 17.28°. Moreover, the friction load roses linearly with the rising sliding velocity, indicating that the nanoscale friction is velocity-dependent.