bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage, demethylation and anticancer activity of DNA methyltransferase (DNMT) inhibitors
Authors: Laranjeira Angelo B. A. , Hollingshead Melinda G. , Nguyen Dat , Kinders Robert J. , Doroshow James H. , Yang Sherry X. 
Published: April 2023

AbstractRole of DNA damage and demethylation on anticancer activity of DNA methyltransferase inhibitors (DNMTi) remains undefined. We report the effects of DNMT1 gene deletion/disruption (DNMT1−/−) on anticancer activity of a class of DNMTi in vitro, in vivo and in human cancers. The gene deletion markedly attenuated cytotoxicity and growth inhibition mediated by decitabine, azacitidine and 5-aza-4′-thio-2′-deoxycytidine (aza-T-dCyd) in colon and breast cancer cells. The drugs induced DNA damage that concurred with DNMT1 inhibition, subsequent G2/M cell-cycle arrest and apoptosis, and upregulated p21 in DNMT1+/+ versus DNMT1−/− status, with aza-T-dCyd the most potent. Tumor growth and DNMT1 were significantly inhibited, and p21 was upmodulated in mice bearing HCT116 DNMT1+/+ xenograft and bladder PDX tumors. DNMT1 gene deletion occurred in ~ 9% human colon cancers and other cancer types at varying degrees. Decitabine and azacitidine demethylated CDKN2A/CDKN2B genes in DNMT1+/+ and DNMT1−/− conditions and increased histone-H3 acetylation with re-expression of p16INK4A/p15INK4B in DNMT1−/− state. Thus, DNMT1 deletion confers resistance to DNMTi, and their anti-cancer activity is determined by DNA damage effects. Patients with DNMT1 gene deletions may not respond to DNMTi treatment.
Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS
Authors: Kurlawala Zimple , McMillan Joseph D. , Singhal Richa A. , Morehouse Johnny , Burke Darlene A. , Sears Sophia M. , Duregon Eleonora , Beverly Levi J. , Siskind Leah J. , Friedland Robert P. 
Published: April 2023

AbstractThe gut microbiome is a potential non-genetic contributing factor for Amyotrophic Lateral Sclerosis. Differences in gut microbial communities have been detected between ALS subjects and healthy controls, including an increase in Escherichia coli in ALS subjects. E. coli and other gram-negative bacteria produce curli proteins, which are functional bacterial amyloids. We examined whether long-term curli overexposure in the gut can exacerbate the development and progression of ALS. We utilized the slow-developing hSOD1-G93A mouse model of ALS with their C57BL/6J WT littermate controls, including males and females, with a total of 91 animals. These mice were on a normal chow diet and fed curli-producing or curli-nonproducing (mutant) E. coli in applesauce (vehicle) 3 times/week, from 1 through 7 months of age. Male hSOD1 mice demonstrated gradual slowing in running speed month 4 onwards, while females exhibited no signs of locomotive impairment even at 7 months of age. Around the same time, male hSOD1 mice showed a gradual increase in frequency of peripheral CD19+ B cells. Among the male hSOD1 group, chronic gut exposure to curli-producing E. coli led to significant shifts in α- and β-diversities. Curli-exposed males showed suppression of immune responses in circulation, but an increase in markers of inflammation, autophagy and protein turnover in skeletal muscle. Some of these markers were also changed in mutant E. coli-exposed mice, including astrogliosis in the brainstem and demyelination in the lumbar spinal cord. Overall, chronic overexposure to a commensal bacteria like E. coli led to distant organ pathology in our model, without the presence of a leaky gut at 6 months. Mechanisms underlying gut-distant organ communication are of tremendous interest to all disciplines.
Functional and morphological renal changes in a Göttingen Minipig model of obesity-related and diabetic nephropathy
Authors: Christoffersen Berit Østergaard , Kristensen Camilla Aarup , Lindgaard Rikke , Kirk Rikke Kaae , Viuff Birgitte Martine , Kvist Peter Helding , Pedersen Henrik Duelund , Ludvigsen Trine Pagh , Skovgaard Tine , Fels Johannes Josef , Martinussen Torben , Christiansen Liselotte Bruun , Cirera Susanna , Olsen Lisbeth Høier 
Published: April 2023

AbstractObesity-related glomerulopathy and diabetic nephropathy (DN) are serious complications to metabolic syndrome and diabetes. The purpose was to study effects of a fat, fructose and cholesterol-rich (FFC) diet with and without salt in order to induce hypertension on kidney function and morphology in Göttingen Minipigs with and without diabetes. Male Göttingen Minipigs were divided into 4 groups: SD (standard diet, n = 8), FFC (FFC diet, n = 16), FFC-DIA (FFC diet + diabetes, n = 14), FFC-DIA + S (FFC diet with extra salt + diabetes, n = 14). Blood and urine biomarkers, glomerular filtration rate (GFR), blood pressure (BP) and resistive index (RI) were evaluated after 6–7 months (T1) and 12–13 months (T2). Histology, electron microscopy and gene expression (excluding FFC-DIA + S) were evaluated at T2. All groups fed FFC-diet displayed obesity, increased GFR and RI, glomerulomegaly, mesangial expansion (ME) and glomerular basement membrane (GBM) thickening. Diabetes on top of FFC diet led to increased plasma glucose and urea and proteinuria and tended to exacerbate the glomerulomegaly, ME and GBM thickening. Four genes (CDKN1A, NPHS2, ACE, SLC2A1) were significantly deregulated in FFC and/or FFC-DIA compared to SD. No effects on BP were observed. Göttingen Minipigs fed FFC diet displayed some of the renal early changes seen in human obesity. Presence of diabetes on top of FFC diet exacerbated the findings and lead to changes resembling the early phases of human DN.
Quantum loss sensing with two-mode squeezed vacuum state under noisy and lossy environment
Authors: Park Sang-il , Noh Changsuk , Lee Changhyoup 
Published: April 2023

AbstractWe investigate quantum advantages in loss sensing when the two-mode squeezed vacuum state is used as a probe. Following an experimental demonstration in PRX 4, 011049, we consider a quantum scheme in which the signal mode is passed through the target and a thermal noise is introduced to the idler mode before they are measured. We consider two detection strategies of practical relevance: coincidence-counting and intensity-difference measurement, which are widely used in quantum sensing and imaging experiments. By computing the signal-to-noise ratio, we verify that quantum advantages persist even under strong thermal background noise, in comparison with the classical scheme which uses a single-mode coherent state that directly suffers from the thermal noise. Such robustness comes from the fact that the signal mode suffers from the thermal noise in the classical scheme, while in the quantum scheme, the idler mode does. For a fairer comparison, we further investigate a different setup in which the thermal noise is introduced to the signal mode in the quantum schemes. In this new setup, we show that the quantum advantages are significantly reduced. Remarkably, however, under an optimum measurement scheme associated with the quantum Fisher information, we show that the two-mode squeezed vacuum state does exhibit a quantum advantage over the entire range of the environmental noise and loss. We expect this work to serve as a guide for experimental demonstrations of quantum advantages in loss parameter sensing, which is subject to lossy and noisy environment.
An optimal selection method for exterior design schemes of subway trains based on multi-level gray relational analysis
Authors: Zou Rui , Xiang Ze-Rui , Zhi Jin-Yi , Li Tian , Chen Hong-Tao , Ding Tie-Cheng 
Published: April 2023

AbstractTo make appropriate decisions in the evaluation phase of the exterior design of subway trains, an optimal selection method was proposed based on multi-level gray relational analysis. The exterior design factors of subway trains were analyzed to construct an index system for design evaluation. The significance of each index was compared through an analytic hierarchy process. The correlation coefficient of each index in the plan was calculated through gray relational analysis to obtain the weighted correlation degree of each design scheme. The optimal selection of the exterior design of Guangzhou Metro Line 6 in China was considered as an example. Four types of subjects were recruited: professional designers, students majoring in design, subway train design experts, and subway passengers in Guangzhou. The weight of each index in the evaluation system was calculated using questionnaire scoring. Virtual simulation software was applied to evaluate the human factors related to each scheme. The indices in each plan were then scored to calculate the correlation coefficient and the overall correlation degree; and finally, the optimal selection was obtained. The results showed that it was practical to evaluate and optimize the exterior design of subway trains based on multi-level gray relational analysis. In the evaluation index system, the weights of technology, human factors, aesthetics, and culture were 0.517, 0.297, 0.099, and 0.087, respectively, which showed that technology had the greatest impact on the system, while human factors, aesthetics, and culture were useful complements. Our results showed that Design Scheme 1 was unsuitable as an optimization scheme due to the high escape window. Meanwhile, Design Scheme 2 was optimal overall, from a technical perspective. Design Scheme 3 was the best in terms of the escape window index (a human factor). Design Schemes 3 and 4 were optimally assessed from aesthetic and cultural perspectives. This study is conducive to the optimization of the exterior design of subway trains, can be used to inform design iteration, and provides a reference for the optimal selection of design schemes for other urban rail trains.
Mid-term safety and effectiveness of macular peeling one month after intravitreal dexamethasone implant for tractional diabetic macular edema
Authors: Pignatelli Francesco , Niro Alfredo , Fallico Matteo , Passidomo Fedele , Gigliola Samuele , Nacucchi Annalisa , Bonfiglio Vincenza , Reibaldi Michele , Addabbo Giuseppe , Avitabile Teresio 
Published: April 2023

AbstractMacular peeling combined or followed by intravitreal dexamethasone implant (DEX-i) was recommended as an efficacy approach for tractional diabetic macular edema (tDME). Knowing the synergistic effect of cataract surgery and DEX-i one month earlier in eyes with DME, we compared Epiretinal Membrane/Inner Limiting Membrane (ERM/ILM) peeling preceded by DEX-i one month before versus ERM/ILM peeling alone for the treatment of tDME. A retrospective study on patients affected by tDME who underwent ERM/ILM peeling one month after DEX-i (n = 11; Group A) or ERM/ILM peeling alone (n = 10; Group B) was performed. Longitudinal comparison of best-correct visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) between the time of surgery (T0) and each time point (months 1,3,5,6) within and among the groups were assessed. To evaluate the repeated measurements of BCVA, CRT, and IOP, a linear mixed-effects model was used. In Group A, DEX-i significantly improved mean BCVA and CRT (P < 0.001) just after 1 month (T0). After ERM/ILM peeling, mean BCVA and CRT significantly improved from month 1 in Group A and month 3 in Group B. Mixed model revealed a significant difference in BCVA (P ≤ 0.0001) and CRT (P ≤ 0.02) at different time-points among the groups with better results in Group A. Neither complications nor uncontrolled IOP increase was detected. ERM/ILM peeling confirmed its effectiveness in treating tDME. DEX-i performed one month before surgery seemed to be a safe approach and ensured a greater and faster recovery considering functional and tomographic parameters.
Electric scooter accidents leading to emergency department visits: influence of alcohol and outcomes in Stockholm, Sweden
Authors: Andersson Olle , Djärv Therese 
Published: April 2023

AbstractElectric scooters are a popular form of transportation, but accidents have increased with increased usage over the last years with rising health care costs as a consequence. This study aims to quantify accidents associated with the use of alcohol and to compare injuries at the emergency department (ED) among patients who have been involved in an accident involving an electric scooter. We used data from a multi-center retrospective registry-based cohort in the Swedish Traffic Accident Data Acquisition. We included all patients that had been involved in an electric scooter accident needing a visit to all EDs in Stockholm, Sweden during 2019–2020. Data on alcohol intake was manually drawn from medical files. Out of all of the 369 patients, the majority were men (n = 223, 60%) and aged below 30 years (n = 181, 49%). In all, 102 (28%) of the patients had a positive history of alcohol intake prior to the accident. Patients with alcohol intake more often arrived nighttime than those without alcohol, via ambulance (40% and 24%, respectively, p-value < 0.01). Those with alcohol intake needed to be admitted to hospital from the ED instead of being discharged more often than those withour alcohol (17% and 9%, respectively, p-value < 0.05) even if the majority still had minor injuries. Every 33,000 trips on electric scooters are statistically accompanied by an accident leading to an ED visit. We conclude that accidents with electric scooters are often associated with alcohol intake. They often demand more resources, such as an ambulance transfer and admission to hospital, and involve multiple injuries, compared to those without alcohol intake.
Seismic background level (SBL) growth can reveal slowly developing long-term eruption precursors
Authors: Ichihara Mie , Ohminato Takao , Konstantinou Kostas I. , Yamakawa Kazuya , Watanabe Atsushi , Takeo Minoru 
Published: April 2023

AbstractThe accelerating growth of seismic unrest before eruptions has been observed at many volcanoes and utilized for eruption forecasts. However, there are still many eruptions for which no precursory unrest has been identified, even at well-monitored volcanoes. The recent eruptions of Shinmoe-dake, Japan, have been another negative example of this kind. Here we present seismological evidence that the eruption preparation had been ongoing at the shallow depths beneath Shinmoe-dake for several months to a year. We investigated the seismic background level (SBL) of eleven-year data recorded around the volcano, including two stations about 1 km from the eruptive crater. We searched for persistent weak signals, focusing on low-amplitude time windows recorded during quiet nighttime. Then the spectra of daily background noise were classified by clustering analysis. The SBL analysis successfully revealed very weak precursory tremors from more than several months before the eruption, and residual tremors to the end of the eruptive period. The precursory signals grew acceleratory in a similar way as is assumed in the material failure forecast method applied to eruption forecasts. However, their growth was significantly slower and longer compared to other cases reported in the literature. Such slow and quiet eruption preparations would not be captured by conventional seismological methods. We expect that long-term SBL analyses on proximal seismic data will help detect early precursors, even at seismically quiet volcanoes, and will also help towards judging the end of an eruptive period.
A novel corpus of molecular to higher-order events that facilitates the understanding of the pathogenic mechanisms of idiopathic pulmonary fibrosis
Authors: Nagano Nozomi , Tokunaga Narumi , Ikeda Masami , Inoura Hiroko , Khoa Duong A. , Miwa Makoto , Sohrab Mohammad G. , Topić Goran , Nogami-Itoh Mari , Takamura Hiroya 
Published: April 2023

AbstractIdiopathic pulmonary fibrosis (IPF) is a severe and progressive chronic fibrosing interstitial lung disease with causes that have remained unclear to date. Development of effective treatments will require elucidation of the detailed pathogenetic mechanisms of IPF at both the molecular and cellular levels. With a biomedical corpus that includes IPF-related entities and events, text-mining systems can efficiently extract such mechanism-related information from huge amounts of literature on the disease. A novel corpus consisting of 150 abstracts with 9297 entities intended for training a text-mining system was constructed to clarify IPF-related pathogenetic mechanisms. For this corpus, entity information was annotated, as were relation and event information. To construct IPF-related networks, we also conducted entity normalization with IDs assigned to entities. Thereby, we extracted the same entities, which are expressed differently. Moreover, IPF-related events have been defined in this corpus, in contrast to existing corpora. This corpus will be useful to extract IPF-related information from scientific texts. Because many entities and events are related to lung diseases, this freely available corpus can also be used to extract information related to other lung diseases such as lung cancer and interstitial pneumonia caused by COVID-19.
Reproducible Tract Profiles 2 (RTP2) suite, from diffusion MRI acquisition to clinical practice and research
Authors: Lerma-Usabiaga Garikoitz , Liu Mengxing , Paz-Alonso Pedro M. , Wandell Brian A. 
Published: April 2023

AbstractDiffusion MRI is a complex technique, where new discoveries and implementations occur at a fast pace. The expertise needed for data analyses and accurate and reproducible results is increasingly demanding and requires multidisciplinary collaborations. In the present work we introduce Reproducible Tract Profiles 2 (RTP2), a set of flexible and automated methods to analyze anatomical MRI and diffusion weighted imaging (DWI) data for reproducible tractography. RTP2 reads structural MRI data and processes them through a succession of serialized containerized analyses. We describe the DWI algorithms used to identify white-matter tracts and their summary metrics, the flexible architecture of the platform, and the tools to programmatically access and control the computations. The combination of these three components provides an easy-to-use automatized tool developed and tested over 20 years, to obtain usable and reliable state-of-the-art diffusion metrics at the individual and group levels for basic research and clinical practice.
The influence of polycystic ovary syndrome on abortion rate after in vitro fertilization/intracytoplasmic sperm injection fresh cycle pregnancy
Authors: Dou Qian , Ma Li-ying , Li Peng-fen , Xu Xiao-ting , Yu Guo , Zhang Dan , Xiang Yun-gai , Tan Li 
Published: April 2023

AbstractThere are many reports on clinical pregnancy outcomes in polycystic ovary syndrome (PCOS) patients receiving vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), but little research about abortion has been done and there is a debate on whether the abortion risk increases in PCOS patients receiving IVF/ICSI. Therefore, the aim of this study was to investigated the abortion in PCOS patients. Clinical data of 12055 IVF/ICSI fresh cycles performed in our hospital from January 2015 to December 2020 were collected. Based on the Rotterdam diagnostic criteria of PCOS and after propensity score matching (PSM) for baseline data of clinical pregnancy cycles, matched 599 PCOS (PCOS group) and Non-PCOS (non-PCOS group) cycles were obtained. Abortion and abortion-related outcomes were compared between the two groups. Risk factors for late abortion in twins were analyzed using binary Logistics regression. Post-PSM data showed that the late abortion rate was significantly higher in the PCOS group than in the non-PCOS group only in twin pregnancy (9.50% vs. 3.96%, OR: 2.55, 95%CI 1.10–5.89). There were no statistical differences in other pregnancy outcomes. The etiological distribution for late abortion were not statistically different between the two groups in both singletons and twins. Logistics regression indicated that PCOS and obesity [pregnancy-assisted body mass index (BMI) ≥ 28] were risk factors for late abortion in twin pregnancy. In twin pregnancy, PCOS and obese patients are more likely to have late abortion. In twin pregnancy, the late abortion risk significantly increased in the PCOS patients as compared with non-PCOS patients (OR: 2.59, 95%CI 1.11–6.03, P < 0.05), as well as in the patients with obesity (BMI ≥ 28) as compared with the patients with normal BMI (OR: 4.17, 95%CI 1.59–10.90, P < 0.05). PCOS does not significantly affect early and overall late abortion rates after IVF/ICSI fresh cycle pregnancy.
Estimation of wheel slip in 2WD mode for an agricultural tractor during plowing operation using an artificial neural network
Authors: Al-Dosary Naji Mordi Naji , Alnajjar Fai’z Mohammed , Aboukarima Abd El Wahed Mohammed 
Published: April 2023

AbstractAs artificial neural networks (ANNs) have been shown to be precise and reliable in supporting the field of artificial intelligence technology, agricultural scientists have focused on employing ANN for agricultural applications. The ANN can be an effective alternative for evaluating agricultural operations. The intended aim of this investigation was to employ both ANN and multiple linear regression (MLR) to develop a model for determining the rear wheel slip of an agricultural tractor in two-wheel drive (2WD) mode during plowing operations. The output parameter of the models was tractor rear wheel slip. The training data were collected from filed experiments using chisel, moldboard, and disk plows. The plows were operated under different conditions of soil texture, plowing depth, soil moisture content, and plowing speed. All data were acquired during field experiments in two soil textures (clay and clay loam textures). The training dataset was comprised of 319 data points, while 65 data points were employed to test both ANN and MLR models estimation capability. The ANN model with a backpropagation training algorithm was created using the commercial Qnet2000 software by changing its topology and related parameters. The best ANN model possessed a topology of 7-20-1. The estimated tractor rear wheel slip using the testing dataset displayed strong agreement with measured tractor rear wheel slip with the coefficient of determination (R2) value of 0.9977. The results definitely illustrated that the ANN model was capable of defining the correlation between the inputs and rear wheel slip. The outcomes suggest that the established ANN model is trustworthy in predicting the tractor rear wheel slip for an agricultural tractor in 2WD mode during the tillage process compared to MLR models. This study provides a useful tool for management of tillage implements during field operations.