bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritizing prognostic-associated subpopulations and individualized recurrence risk signatures from single-cell transcriptomes of colorectal cancer
Authors: Tong Mengsha , Lin Yuxiang , Yang Wenxian , Song Jinsheng , Zhang Zheyang , Xie Jiajing , Tian Jingyi , Luo Shijie , Liang Chenyu , Huang Jialiang , Yu Rongshan 
Published: March 2023

AbstractColorectal cancer (CRC) is one of the most common gastrointestinal malignancies. There are few recurrence risk signatures for CRC patients. Single-cell RNA-sequencing (scRNA-seq) provides a high-resolution platform for prognostic signature detection. However, scRNA-seq is not practical in large cohorts due to its high cost and most single-cell experiments lack clinical phenotype information. Few studies have been reported to use external bulk transcriptome with survival time to guide the detection of key cell subtypes in scRNA-seq data. We proposed scRankXMBD, a computational framework to prioritize prognostic-associated cell subpopulations based on within-cell relative expression orderings of gene pairs from single-cell transcriptomes. scRankXMBD achieves higher precision and concordance compared with five existing methods. Moreover, we developed single-cell gene pair signatures to predict recurrence risk for patients individually. Our work facilitates the application of the rank-based method in scRNA-seq data for prognostic biomarker discovery and precision oncology. scRankXMBD is available at https://github.com/xmuyulab/scRank-XMBD. (XMBD:Xiamen Big Data, a biomedical open software initiative in the National Institute for Data Science in Health and Medicine, Xiamen University, China.)
A preclinical randomized controlled multi-centre trial of anti-interleukin-17A treatment for acute ischaemic stroke
Authors: Gelderblom Mathias , Koch Simon , Strecker Jan-Kolja , Jørgensen Carina , Garcia-Bonilla Lidia , Ludewig Peter , Schädlich Ines Sophie , Piepke Marius , Degenhardt Karoline , Bernreuther Christian , Pinnschmidt Hans , Arumugam Thiruma V , Thomalla Götz , Faber Cornelius , Sedlacik Jan , Gerloff Christian , Minnerup Jens , Clausen Bettina H , Anrather Josef , Magnus Tim 
Published: March 2023

AbstractMultiple consensus statements have called for preclinical randomized controlled trials to improve translation in stroke research. We investigated the efficacy of an interleukin-17A neutralizing antibody in a multi-centre preclinical randomized controlled trial using a murine ischaemia reperfusion stroke model. Twelve-week-old male C57BL/6 mice were subjected to 45 min of transient middle cerebral artery occlusion in four centres. Mice were randomly assigned (1:1) to receive either an anti-interleukin-17A (500 µg) or isotype antibody (500 µg) intravenously 1 h after reperfusion. The primary endpoint was infarct volume measured by magnetic resonance imaging three days after transient middle cerebral artery occlusion. Secondary analysis included mortality, neurological score, neutrophil infiltration and the impact of the gut microbiome on treatment effects. Out of 136 mice, 109 mice were included in the analysis of the primary endpoint. Mixed model analysis revealed that interleukin-17A neutralization significantly reduced infarct sizes (anti-interleukin-17A: 61.77 ± 31.04 mm3; IgG control: 75.66 ± 34.79 mm3; P = 0.01). Secondary outcome measures showed a decrease in mortality (hazard ratio = 3.43, 95% confidence interval = 1.157–10.18; P = 0.04) and neutrophil invasion into ischaemic cortices (anti-interleukin-17A: 7222 ± 6108 cells; IgG control: 28 153 ± 23 206 cells; P &lt; 0.01). There was no difference in Bederson score. The analysis of the gut microbiome showed significant heterogeneity between centres (R = 0.78, P &lt; 0.001, n = 40). Taken together, neutralization of interleukin-17A in a therapeutic time window resulted in a significant reduction of infarct sizes and mortality compared with isotype control. It suggests interleukin-17A neutralization as a potential therapeutic target in stroke.
Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis
Authors: Rauf Muhammad Umaid , Hawkins Philip N , Cappelli Francesco , Perfetto Federico , Zampieri Mattia , Argiro Alessia , Petrie Aviva , Law Steven , Porcari Aldostefano , Razvi Yousuf , Bomsztyk Joshua , Ravichandran Sriram , Ioannou Adam , Patel Rishi , Starr Neasa , Hutt David F , Mahmood Shameem , Wisniowski Brendan , Martinez–Naharro Ana , Venneri Lucia , Whelan Carol , Roczenio Dorota , Gilbertson Janet , Lachmann Helen J , Wechalekar Ashutosh D , Rapezzi Claudio , Serenelli Matteo , Massa Paolo , Caponetti Angelo Giuseppe , Ponziani Alberto , Accietto Antonella , Giovannetti Alessandro , Saturi Giulia , Sguazzotti Maurizio , Gagliardi Christian , Biagini Elena , Longhi Simone , Fontana Marianna , Gillmore Julian D 
Published: March 2023

Abstract

Aims
To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease.

Methods and results
A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM.

Conclusion
The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration.
Association of long-term time in target range for systolic blood pressure with cardiovascular risk in the elderly: a Chinese veteran cohort study
Authors: Lin Zhongqiu , Xiao Zhiwen , Chen Wei , Xu Wenlong , Huang Chixiong , Xie Jingfang , Jin Ming , Wei Xiaomin , He Sisi , Xie Zhiquan , Liao Wangjun , Liao Yulin , Feng Weijing , Chen Yanmei , Bin Jianping 
Published: March 2023

Abstract

Aims
Short-term blood pressure (BP) time in target range (TTR) independently predicts cardiovascular (CV) outcomes in adults. However, there are limited data regarding long-term TTR for BP among elderly participants. We aimed to determine whether future CV risk varies for those who can maintain a long-term systolic BP (SBP) target range by assessing TTR in elderly individuals with hypertension.

Methods and results
The Chinese veteran cohort study included 943 elderly participants with hypertension aged over 75 years. The primary outcome was the first occurrence of CV events during annual visits. Time in target range was estimated over 15 years of follow-up using linear interpolation. The target range was defined as 120–140 mmHg according to guidelines. The association between SBP TTR and CV outcomes was estimated using multivariable Cox proportional hazards models. During the 15 year follow-up, the probability of CV events gradually decreased with increasing TTR for SBP. After multivariable adjustment for traditional CV risk factors and mean BP, comparing the highest vs. lowest quartiles of TTR for SBP, the hazard ratios (HRs) [95% confidence intervals (CIs)] were 0.424 (0.289–0.624) for the primary outcome. For each 1 SD increase in TTR, the risk of the primary outcome decreased by 25.4% (HR: 0.746; 95% CI: 0.666–0.834). Consistent findings were observed in sensitivity analyses.

Conclusion
Greater long-term TTR for SBP was associated with a decreased risk of CV events in elderly individuals independent of mean BP, suggesting that SBP TTR might serve as a modifiable risk factor for future CV health in elderly patients with hypertension.

Lay Summary
This ongoing Chinese veteran cohort study adds to the understanding of the relationship between higher long-term systolic blood pressure (SBP) time in target range (TTR) and cardiovascular benefits among elderly individuals with hypertension.
Refining the Treatment of Pancreatic Cancer From Big Data to Improved Individual Survival
Authors: Bailey Peter , Zhou Xu , An Jingyu , Peccerella Teresa , Hu Kai , Springfeld Christoph , Büchler Markus , Neoptolemos John P 
Published: March 2023

Abstract
Pancreatic cancer is one of the most lethal cancers worldwide, most notably in Europe and North America. Great strides have been made in combining the most effective conventional therapies to improve survival at least in the short and medium term. The start of treatment can only be made once a diagnosis is made, which at this point, the tumor volume is already very high in the primary cancer and systemically. If caught at the earliest opportunity (in circa 20% patients) surgical resection of the primary followed by combination chemotherapy can achieve 5-year overall survival rates of 30%–50%. A delay in detection of even a few months after symptom onset will result in the tumor having only borderline resectabilty (in 20%–30% of patients), in which case the best survival is achieved by using short-course chemotherapy before tumor resection as well as adjuvant chemotherapy. Once metastases become visible (in 40%–60% of patients), cure is not possible, palliative cytotoxics only being able to prolong life by few months. Even in apparently successful therapy in resected and borderline resectable patients, the recurrence rate is very high. Considerable efforts to understand the nature of pancreatic cancer through large-scale genomics, transcriptomics, and digital profiling, combined with functional preclinical models, using genetically engineered mouse models and patient derived organoids, have identified the critical role of the tumor microenvironment in determining the nature of chemo- and immuno-resistance. This functional understanding has powered fresh and exciting approaches for the treatment of this cancer.
Similarity characteristics of qualitative and quantitative regulation for adjustable ejector
Authors: Yang Yong , Ren Xiaotong , Li Yiqiao , Wang Ning , Zhang Kun , Shen Shengqiang 
Published: March 2023

Abstract
In the new era of ejector technology entering into system scale from device scale. The methodology of regulation mode of an adjustable ejector has been summarized in this paper. The similarity in characteristics of qualitative and quantitative regulation under different operating modes are researched. The results show that both qualitative and quantitative regulation have the characteristics of ‘constant capacity’. Three different ‘constant-capacity’ phenomena in ejectors have been found, and the similarity indicates that the turbulent flow in ejectors has some statistical invariances in the form of mass flow rate of jetting flow. The ejector has the similar entrainment ability by increasing primary pressure by 43% in the qualitative regulation mode or enlarging the nozzle throat opening by 47% in the quantitative regulation mode under critical mode with similar underexpanded state. The advantages of adjustable ejectors have been promoted, in particular ±5% regulation accuracy or constant regulation ability, discharging improved ability by 80% in flow rate or 10% in pressure lifting ability in subcritical mode or primary flow rate saving ability by 25% or 13% in pressure lifting ability in critical mode.
Aztreonam/avibactam activity against a large collection of carbapenem-resistant Enterobacterales (CRE) collected in hospitals from Europe, Asia and Latin America (2019–21)
Authors: Sader Helio S , Castanheira Mariana , Kimbrough John H , Kantro Valerie , Mendes Rodrigo E 
Published: March 2023

AbstractBackgroundAztreonam/avibactam is under development to treat infections caused by Gram-negative bacteria. We evaluated the in vitro activities of aztreonam/avibactam and comparators against a global collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime/avibactam-resistant isolates.MethodsIsolates were consecutively collected (24 924; 1/patient) from 69 medical centres in 36 countries during 2019–21. Isolates were susceptibility tested by CLSI broth microdilution. All CRE isolates (n = 1098; 4.4%) were in silico screened for carbapenemase (CPE) genes after genome sequencing. CRE susceptibility results were stratified by CPE, geography and resistance phenotype.ResultsAztreonam/avibactam inhibited 99.6% of CREs at ≤8 mg/L (MIC50/90, 0.25/0.5 mg/L), including 98.9% (345/349) of ceftazidime/avibactam-resistant isolates. Aztreonam/avibactam activity was consistent across geographical regions (98.9%–100.0% inhibited at ≤8 mg/L), but susceptibility to comparators varied markedly. Susceptibility (CLSI criteria) for ceftazidime/avibactam and meropenem/vaborbactam ranged from 80.2% and 77.5% in Western Europe to 39.5% and 40.3% in the Asia-Pacific region, respectively. Aztreonam/avibactam retained activity against isolates non-susceptible to colistin (99.7% inhibited at ≤8 mg/L) or tigecycline (98.6% inhibited at ≤8 mg/L). A CPE gene was identified in 972 CRE isolates (88.5%). The most common CPEs were KPC (43.1% of CREs), NDM (26.6%) and OXA-48–like (18.7%); 57 isolates (5.2%) had &gt;1 CPE gene. Aztreonam/avibactam inhibited 99.9% of CPE producers at ≤8 mg/L, whereas ceftazidime/avibactam and meropenem/vaborbactam exhibited limited activity against isolates producing MBL and/or OXA-48-like enzymes.ConclusionsAztreonam/avibactam activity was not adversely affected by clinically relevant CPEs. Our results support aztreonam/avibactam development to treat infections caused by CRE, including MBL producers.
Comparative Analysis and Structure Identification of Oxidative Metabolites and Hydrogenation Metabolite Enantiomers for 2-Fluorodeschloroketamine
Authors: Luo Xuan , Zhang Di , Zhang Fang , Luo Qiulian , Huang Kejian , Liu Xiaofeng , Yang Ning , Li Junbo , Qiao Wentao , Yang Lan 
Published: March 2023

Abstract
In this study, we used solid-phase extraction with liquid chromatography–ion trap time-of-flight mass spectrometry (LC–IT-TOF-MS) to analyze 2-fluorodeschloroketamine (2-FDCK) metabolites in human urine. The complete set of oxidative metabolites was identified, with 17 compounds divided into four groups. Furthermore, we examined the hydroxy substitution site after oxidative metabolism with theoretical calculation and 2-FDCK nuclear magnetic resonance (NMR) data. We clarified the correlation of the oxidative metabolic sites with the electron cloud density in the structure. Additionally, two enantiomers of dihydro-2-fluorodeschloroketamine (dihydro-2-FDCK) were determined by using a laboratory-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via NMR spectrometry data prediction of the ACD Labs-Structure Elucidator Suite software and theoretical calculation. Moreover, the stereoselectivity of the related enzymes in hydrogenation metabolism in vivo was clarified. These findings provide an important reference for analyzing other oxidative metabolites, laying the foundation for future analysis, prediction, elucidation and identification of the latest ketamine-type new psychoactive substance metabolites.
Automated topology design to improve the susceptibility of naval ships using geometric deep learning
Authors: Hwang Joon-Tae , Hong Suk-Yoon , Song Jee-Hun 
Published: March 2023

AbstractThe survivability of a naval ship is defined as its ability to evade or withstand a hostile environment while performing a given mission. Stealth technology, which reduces the probability of detection by enemy detection equipment using a highly advanced detection system, is one of the most important technologies to improve the survivability of naval ships. Moreover, radar cross-section (RCS) reduction is a very important factor in stealth technology because a small RCS, which is the main parameter determining susceptibility, improves the ability of ships to evade enemy detection equipment. In this study, an automated topology design for reducing susceptibility was developed by combining geometric deep learning and topology optimization. A convolutional neural network model was used as the geometric deep-learning model, and the triangular meshes of the naval ship models and equipment models were used as datasets. To compensate for the lack of training data, randomly generated meshes were additionally used as datasets. To express the feature data of the mesh as a matrix, points at equal intervals were projected orthogonally and the distance between the plane and point was set as a matrix value. The label data were defined as the highest RCS values excluding the cardinal points. After realizing the topology design for reducing susceptibility using the developed system, verification was performed through RCS analysis of the original model and the topology-designed model.
Effects of the surface irregularity of termite tunnels on food transport efficiency: a simulation study
Authors: Lee Sang-Hee , Park Cheol-Min , Lee Sang-Bin 
Published: March 2023

AbstractTermites are believed to have evolved in a way that optimizes their foraging efficiency, which involves both searching for food and transporting it efficiently. Although the search efficiency has been well-studied through tunnel pattern analysis, transport efficiency has received limited attention due to the challenges of directly observing behavior that is highly influenced by environmental conditions. In this study, we introduce an individual-based model to simulate transport behavior and examine transport efficiency (E) by considering the tunnel surface irregularities and curvature, which are critical environmental factors. The model is characterized by four control variables: tunnel curvature (k1), termite stopping time at irregularity sites (k2), irregularity distribution (k3), and irregularity density (k4). The simulation results indicate that as k1 increases, E decreases, while k3 has little impact on E. The impact of k4 on E is decisive; when k4 ≤ 6, an increase in k4 results in increased traffic jam frequency and a faster reduction in E. However, when k4 &gt; 6, the jamming frequency is not significantly affected, reducing the decrease in E. k2 strongly contributes to reducing E without significantly affecting the frequency. In the discussion section, we explore potential mechanisms that termites use to maintain transport efficiency in heterogeneous soils, and discuss how to improve the model to better reflect real-termite systems.
Comparison of ectoparasite communities of sylvatic and urban wild mesomammals and unowned community cats in north-central Florida
Authors: Mays Maestas S E , Campbell L P , Wisely S M , Dingman P A , Reeves L E , Kaufman P E 
Published: March 2023

Abstract
The adaptation of wildlife species to urban environments can drive changes in the ecology of ectoparasites and vector-borne disease. To better understand ectoparasite dynamics in an urban environment, we investigated the ectoparasite communities of 183 sylvatic and urban opossums and raccoons captured across four seasons at a rural research station and within the city of Gainesville, FL, and of 115 community cats from the Gainesville, FL area. Amblyomma americanum (L.) (Acari: Ixodidae), Dermacentor variabilis (Say), and Ixodes texanus Banks were collected from raccoons, A. americanum, D. variabilis, and Ixodes scapularis Say from opossums, and A. americanum from cats. Few ticks were collected from urban animals, although species richness of ectoparasites was similar between urban and sylvatic habitats. Ctenocephalides felis (Bouché) (Siphonaptera: Pulicidae) was collected from all sampled host species, but was particularly abundant on opossums. Additionally, Orchopeas howardi (Baker) (Siphonaptera: Ceratophyllidae) was collected from raccoons, and O. howardi and Polygenis gwyni (Fox) (Siphonaptera: Rhopalopsyllidae) from opossums. Only raccoons were infested with raccoon lice, and only cats were infested with cat lice. Primarily opossums were infested with mites. Ectoparasite community composition varied by habitat, host species, and season; seasonal variation in ectoparasite communities differed between the sylvatic and urban habitats. While urban mesomammals did not appear to play an important role in supporting tick populations in an urban habitat, urban opossums appear to serve as an alternate host for large numbers of cat fleas, which may be an important consideration for treatment and control efforts against ectoparasites of companion animals.
Breast exam use during the protracted COVID-19 pandemic, by age, race, and geography
Authors: Butler Eboneé N , Benefield Thad , Henderson Louise , Kuzmiak Cherie , Pritchard Michael , Nyante Sarah 
Published: March 2023

Abstract
In this study we analyzed data collected from the onset of the COVID-19 pandemic through March 31, 2022, to identify temporal shifts in breast exam volume. Screening mammography volume stabilized toward the end of the study period, and diagnostic exam volume varied over time and by age. Older women experienced a decline in diagnostic exam volume between August 2020 and April 2021 that was not observed among women aged younger than 50 years (50-69 years: monthly percentage change [MPC] = −6.5%; and 70 years and older: MPC = −15.7%). With respect to breast biopsy volume, women aged younger than 70 years had increased exam volume beginning in April 2020 and June 2020, whereas a corresponding increase among older women was delayed until April 2021 (70 years and older: MPC = 9.3%). Findings from our study suggest a temporal shift in the use of breast exams that could result in differential detection of breast cancer by age.
Otherwise than teaching by artificial intelligence
Authors: Lee Sang-Eun 
Published: March 2023

Abstract
Advances in digital technology are changing the methods of teaching and learning. In the course of this stream of changes, the emergence of artificial intelligence (AI) has become a topic of great interest and concern. The development of teaching AIs (artificial intelligences that teach), which can provide adaptive and personalized dialogue with students, has shifted the relationship between teachers and students, and has raised new questions regarding the role of teachers. The purpose of this paper is to rethink the meaning of the act of teaching, without denying its variety, and to reflect on the role of teachers in the relatively unfamiliar situation created by the emergence of AI teaching machines. To this end, I attempt, first, to re-examine the nature of teaching by considering two possible orientations: teaching as a return to homogeneity and teaching as exposure to heterogeneity. My purpose is to consider the characteristics and limitations of the teaching implemented by AI and to discuss the role of human teachers in overcoming these limitations. Second, I seek to reveal what it is for the teacher to speak, which is often understood as the most important aspect of teaching, again by way of two characterizations: the closed conversation, which converges on a conclusion, and the open conversation, oriented towards ethical responsibility. In doing this, I shall examine critically some characteristics of language used by AI teaching machines and suggest alternatives that might constitute openness to an ethical conversation. In furtherance of this, I shall consider the account of teaching that is central to the philosophy of Emmanuel Levinas.