bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of novel conditional ligands and large-scale detection of antigen-specific T cells for H-2Dd and H-2Kd
Authors: Sundebo Meldgaard Trine , Viborg Nadia , Suarez Hernandez Sara , Vazquez Albacete Dario , Tamhane Tripti , Reker Hadrup Sine 
Published: May 2024

AbstractThe UV-mediated peptide exchange has enabled the generation of multiple different MHC multimer specificities in parallel, surpassing tedious individual refolding of MHC molecules with peptide ligands. Murine models are acknowledged as an effective tool for preclinical research to advance our understanding of immunological mechanisms, with the potential translatability of key learnings from mouse models to the clinic. The common inbred mouse strain BALB/c is frequently used in immunological research. However, for the BALB/c histocompatibility (H)-2 alleles availability of conditional ligand has been limited. To overcome this challenge, we design and experimentally validate conditional ligands restricted to murine MHC class I alleles H2Dd and H2Kd. In addition, we demonstrate the ability of the three H2d molecules and two additional C57BL/6 H2b molecules folded in-house with conditional ligands to generate fluorescently labeled peptide-H2 tetramers that allow staining of antigen-specific CD8+ T cells in splenocyte samples. Finally, we generate large peptide-H-2 multimer libraries with a DNA-barcode labeling system for high-throughput interrogation of CD8+ T cell specificity in murine splenocyte samples. Consequently, the described techniques will contribute to our understanding of the antigen-specific CD8+ T cell repertoire in murine preclinical models of various diseases.
Reliable anti-cancer drug sensitivity prediction and prioritization
Authors: Lenhof Kerstin , Eckhart Lea , Rolli Lisa-Marie , Volkamer Andrea , Lenhof Hans-Peter 
Published: May 2024

AbstractThe application of machine learning (ML) to solve real-world problems does not only bear great potential but also high risk. One fundamental challenge in risk mitigation is to ensure the reliability of the ML predictions, i.e., the model error should be minimized, and the prediction uncertainty should be estimated. Especially for medical applications, the importance of reliable predictions can not be understated. Here, we address this challenge for anti-cancer drug sensitivity prediction and prioritization. To this end, we present a novel drug sensitivity prediction and prioritization approach guaranteeing user-specified certainty levels. The developed conformal prediction approach is applicable to classification, regression, and simultaneous regression and classification. Additionally, we propose a novel drug sensitivity measure that is based on clinically relevant drug concentrations and enables a straightforward prioritization of drugs for a given cancer sample.
Analyzing the methanation thermodynamic feasibility of steel plant byproduct gases
Authors: Ling Qiang , Li Xue , Pei Qin , Lei Zhao , Cui Ping , Xie Rui Lun 
Published: May 2024

AbstractTo improve the utilization of byproduct gases in the steel plant, the coke oven gas (COG) methanation combined with blast furnace gas (BFG) and basic oxygen furnace gas (BOFG) was proposed in viewpoint of economy and environment. The optimization mathematics model based on Gibbs free energy minimization was established to predict the thermodynamic feasibility of the proposed methanation. To solve the proposed model, the convenient method was implemented by using the Gibbs module in Aspen Plus software. Effects of operation parameters on the methanation performance were revealed to identify the optimized conditions. To reduce the solid carbon concentration, it was found that the optimized conditions of temperature, pressure and stoichiometric number were 650 °C, 30 bar and 3.0, respectively. Moreover, it was discovered that 10 mol% of BFG or BOFG could be mixed into COG to obtain the maximum methane yield. In addition, it was testified that there were the good agreements between calculated results and industrial and published data, which indicated that the proposed methanation was thermodynamically feasible. Therefore, the simple and easy method was developed to evaluate the methanation operating conditions from the aspect of thermodynamic equilibrium, which provided the basic process conditions of byproduct gases methanation to enhance the steel plant efficiency and reduce carbon emissions.
Making acute ischemic stroke thrombi visible in MRI imaging
Authors: Velasco Gonzalez Aglaé , Buerke Boris , Görlich Dennis , Sauerland Cristina , Fobker Manfred , Jeibmann Astrid , Heindel Walter , Faldum Andreas , Paulus Werner , Kugel Harald 
Published: May 2024

AbstractKnowledge of thrombus behavior and visualization on MRI in acute ischemic stroke is less than optimal. However, MRI sequences could be enhanced based on the typical T1 and T2 relaxation times of the target tissues, which mainly determine their signal intensities on imaging. We studied the relaxation times of a broad spectrum of clot analogs along with their image characteristics of three sequences analyzed: a T1-weighted turbo inversion-recovery sequence (T1w Turbo IR), a T1-weighted turbo spin echo with fat suppression (T1w TSE SPIR), and a T2-weighted 3D TSE with magnetization refocusing to remove T1 dependence (T2w TSE DRIVE). We compared their imaging behavior with the intensity values of normal brain tissue using the same imaging protocols as for clots. Each histological and biochemical clot component contributed to each of the relaxation times. Overall, histological composition correlated strongly with T1 times, and iron content, specifically, with T2 relaxation time. Using decision trees, fibrin content was selected as the primary biomarker for T1 relaxation times, inducing an increase. Up to four clot subgroups could be defined based on its distinctive T1 relaxation time. Clot signal intensity in the T1 and T2-weighted images varied significantly according to T1 and T2 relaxation times. Moreover, in comparison with normal brain tissue intensity values, T2w DRIVE images depict thrombi according to the principle of the more fibrin, the higher the intensity, and in T1w TSE, the more erythrocytes, the higher the intensity. These findings could facilitate improvements in MRI sequences for clot visualization and indicate that T2w DRIVE and T1w TSE sequences should depict the vast majority of acute ischemic stroke thrombi as more hyperintense than surrounding tissues.
A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination
Authors: Simon Katherine E. , Russell Katharine , Mondino Alejandra , Yang Chin-Chieh , Case Beth C. , Anderson Zachary , Whitley Christine , Griffith Emily , Gruen Margaret E. , Olby Natasha J. 
Published: May 2024

AbstractAge-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.
Soil moisture and soil organic carbon coupled effects in apple orchards on the Loess Plateau, China
Authors: Han Lei , Nan Guowei , He Xinyu , Wang Jinghui , Zhao Jirong , Zhang Xiangqian 
Published: May 2024

AbstractA large number of economic forests, especially apple orchards (AOs) in the Loess Plateau region of China, have been planted to develop the local economy and increase the income of farmers. The two main constraints preventing AOs on the Loess Plateau from developing sustainably and producing a high and steady yield are soil moisture content (SMC) and soil organic carbon (SOC). Nevertheless, little is currently known about the contributions of roots to these changes in the soil profile and the temporal modes of the SMC-SOC coupled effects. In our research, we analyzed the dynamic changes in SMC and SOC in AOs of various years in northern Shaanxi Province, as well as the coupled relationship between the two, and attempted to describe the function of roots in these changes. Research have shown: (1) As the age of the AOs increased, the SMC continued to decline throughout the 0–500 cm profile, especially at depths of 100–500 cm. SMC depletion mainly occurred in AOs aged 20 years (30.02%/year) and 30 years (31.18%/year). (2) Compared with abandoned land (AL), all the AOs except for the 6-year-old AO showed a carbon sequestration effect, and the carbon sequestration effect increased with age. The carbon sequestration rate of the 12-year-old AO was the highest and then decreased with age. Both surface and deeper soils showed better carbon sequestration, with a large amount of SOC being sequestered in deeper soil layers (> 100 cm). (3) The coupled effects of SMC and SOC varied with age and depth. The SMC in the deeper layers was significantly negatively correlated with SOC. Root dry weight density (RDWD) was significantly negatively correlated with SMC and significantly positively correlated with SOC. Path analysis suggested that SMC directly affects SOC at different soil depths, and regulates SOC by affecting RDWD, but these effects are significantly different at different depths. Therefore, we propose that management of AO should focus on the moisture deficit and carbon sequestration capabilities of deeper soils to ensure the sustainability of water use in AOs and the stability of agricultural carbon sequestration on the Loess Plateau.
North American pitseed goosefoot (Chenopodium berlandieri) is a genetic resource to improve Andean quinoa (C. quinoa)
Authors: Maughan Peter J. , Jarvis David E. , de la Cruz-Torres Eulogio , Jaggi Kate E. , Warner Heather C. , Marcheschi Ashley K. , Bertero H. Daniel , Gomez-Pando Luz , Fuentes Francisco , Mayta-Anco Mayela E. , Curti Ramiro , Rey Elodie , Tester Mark , Jellen Eric N. 
Published: May 2024

AbstractPitseed goosefoot (Chenopodium berlandieri) is a free-living North American member of an allotetraploid complex that includes the Andean pseudocereal quinoa (C. quinoa). Like quinoa, pitseed goosefoot was domesticated, possibly independently, in eastern North America (subsp. jonesianum) and Mesoamerica (subsp. nuttaliae). To test the utility of C. berlandieri as a resource for quinoa breeding, we produced the whole-genome DNA sequence of PI 433,231, a huauzontle from Puebla, México. The 1.295 Gb genome was assembled into 18 pseudomolecules and annotated using RNAseq data from multiple tissues. Alignment with the v.2.0 genome of Chilean-origin C. quinoa cv. ‘QQ74’ revealed several inversions and a 4A-6B reciprocal translocation. Despite these rearrangements, some quinoa x pitseed goosefoot crosses produce highly fertile hybrids with faithful recombination, as evidenced by a high-density SNP linkage map constructed from a Bolivian quinoa ‘Real-1’ × BYU 937 (Texas coastal pitseed goosefoot) F2 population. Recombination in that cross was comparable to a ‘Real-1’ × BYU 1101 (Argentine C. hircinum) F2 population. Furthermore, SNP-based phylogenetic and population structure analyses of 90 accessions supported the hypothesis of multiple independent domestications and descent from a common 4 × ancestor, with a likely North American Center of Origin.
Exploring regenerative coupling in phononic crystals for room temperature quantum optomechanics
Authors: Weituschat Lukas M. , Castro Irene , Colomar Irene , Everly Christer , Postigo Pablo A. , Ramos Daniel 
Published: May 2024

AbstractQuantum technologies play a pivotal role in driving transformative advancements across diverse fields, surpassing classical approaches and empowering us to address complex challenges more effectively; however, the need for ultra-low temperatures limits the use of these technologies to particular fields. This work comes to alleviate this problem. We present a way of phononic bandgap engineering using FEM by which the radiative mechanical energy dissipation of a nanomechanical oscillator can be significantly suppressed through coupling with a complementary oscillating mode of a defect of the surrounding phononic crystal (PnC). Applied to an optomechanically coupled nanobeam resonator in the megahertz regime, we find a mechanical quality factor improvement of up to four orders of magnitude compared to conventional PnC designs. As this method is based on geometrical optimization of the PnC and frequency matching of the resonator and defect mode, it is applicable to a wide range of resonator types and frequency ranges. Taking advantage of the, hereinafter referred to as, “regenerative coupling” in phononic crystals, the presented device is capable of reaching f × Q products exceeding 10E16 Hz with only two rows of PnC shield. Thus, stable quantum states with mechanical decoherence times up to 700 μs at room temperature can be obtained, offering new opportunities for the optimization of mechanical resonator performance and advancing the room temperature quantum field across diverse applications.
Association of obstructive sleep apnea with risk of lung cancer: a nationwide cohort study in Korea
Authors: Cho Jaeyoung , Jo Soomin 
Published: May 2024

AbstractCurrent knowledge regarding the relationship between obstructive sleep apnea (OSA) and the risk of lung cancer is limited. This study aimed to evaluate associations between OSA and the incidence of lung cancer based on the Korean National Health Information Database. The study outcome was the incidence of newly diagnosed lung cancer, and a Cox proportional hazards model was used for analysis. A total of 181,070 adult patients newly diagnosed with OSA between 2011 and 2018 were matched with those without OSA by up to 1:5 propensity score matching based on age and sex. During follow-up over (mean ± standard deviation) 9.1 ± 2.0 years, 2614 incident cases of lung cancer were identified. The incidence rate was 39.51 per 100,000 person-years in the OSA group, and 24.93 per 100,000 person-years in the control group. After adjusting for income and the presence of comorbidities, the association remained significant (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.74–2.18, p-value < 0.001). The adjusted HR for incident lung cancer was 2.14 (95% CI 1.69–2.70) in female patients with OSA, and 1.90 (95% CI 1.67–2.16) in male patients with OSA. The risk of incident lung cancer increased with age, with a HR of 2.99 (95% CI 2.46–3.64) in those aged ≥ 65 years. This nationwide study showed an independent association between OSA and an increased risk of lung cancer in the Korean population.
A case–control study on pre-, peri-, and neonatal risk factors associated with autism spectrum disorder among Armenian children
Authors: Mkhitaryan Meri , Avetisyan Tamara , Mkhoyan Anna , Avetisyan Larisa , Yenkoyan Konstantin 
Published: May 2024

AbstractWe aimed to investigate the role of pre-, peri- and neonatal risk factors in the development of autism spectrum disorder (ASD) among Armenian children with the goal of detecting and addressing modifiable risk factors to reduce ASD incidence. For this purpose a retrospective case–control study using a random proportional sample of Armenian children with ASD to assess associations between various factors and ASD was conducted. The study was approved by the local ethical committee, and parental written consent was obtained. A total of 168 children with ASD and 329 controls were included in the analysis. Multivariable logistic regression analysis revealed that male gender, maternal weight gain, use of MgB6, self-reported stress during the pregnancy, pregnancy with complications, as well as use of labor-inducing drugs were associated with a significant increase in the odds of ASD, whereas Duphaston use during pregnancy, the longer interpregnancy interval and birth height were associated with decreased odds of ASD. These findings are pertinent as many identified factors may be preventable or modifiable, underscoring the importance of timely and appropriate public health strategies aimed at disease prevention in pregnant women to reduce ASD incidence.
Spatial confinement affects the heterogeneity and interactions between shoaling fish
Authors: Kuntz Gabriel , Huang Junxiang , Rask Mitchell , Lindgren-Ruby Alex , Shinsato Jacob Y. , Bi Dapeng , Tabatabai A. Pasha 
Published: May 2024

AbstractLiving objects are able to consume chemical energy and process information independently from others. However, living objects can coordinate to form ordered groups such as schools of fish. This work considers these complex groups as living materials and presents imaging-based experiments of laboratory schools of fish to understand how activity, which is a non-equilibrium feature, affects the structure and dynamics of a group. We use spatial confinement to control the motion and structure of fish within quasi-2D shoals of fish and use image analysis techniques to make quantitative observations of the structures, their spatial heterogeneity, and their temporal fluctuations. Furthermore, we utilize Monte Carlo simulations to replicate the experimentally observed data which provides insight into the effective interactions between fish and confirms the presence of a confinement-based behavioral preference transition. In addition, unlike in short-range interacting systems, here structural heterogeneity and dynamic activities are positively correlated as a result of complex interplay between spatial arrangement and behavioral dynamics in fish collectives.
Deep learning to assess microsatellite instability directly from histopathological whole slide images in endometrial cancer
Authors: Wang Ching-Wei , Muzakky Hikam , Firdi Nabila Puspita , Liu Tzu-Chien , Lai Po-Jen , Wang Yu-Chi , Yu Mu-Hsien , Chao Tai-Kuang 
Published: May 2024

AbstractMolecular classification, particularly microsatellite instability-high (MSI-H), has gained attention for immunotherapy in endometrial cancer (EC). MSI-H is associated with DNA mismatch repair defects and is a crucial treatment predictor. The NCCN guidelines recommend pembrolizumab and nivolumab for advanced or recurrent MSI-H/mismatch repair deficient (dMMR) EC. However, evaluating MSI in all cases is impractical due to time and cost constraints. To overcome this challenge, we present an effective and efficient deep learning-based model designed to accurately and rapidly assess MSI status of EC using H&E-stained whole slide images. Our framework was evaluated on a comprehensive dataset of gigapixel histopathology images of 529 patients from the Cancer Genome Atlas (TCGA). The experimental results have shown that the proposed method achieved excellent performances in assessing MSI status, obtaining remarkably high results with 96%, 94%, 93% and 100% for endometrioid carcinoma G1G2, respectively, and 87%, 84%, 81% and 94% for endometrioid carcinoma G3, in terms of F-measure, accuracy, precision and sensitivity, respectively. Furthermore, the proposed deep learning framework outperforms four state-of-the-art benchmarked methods by a significant margin (p < 0.001) in terms of accuracy, precision, sensitivity and F-measure, respectively. Additionally, a run time analysis demonstrates that the proposed method achieves excellent quantitative results with high efficiency in AI inference time (1.03 seconds per slide), making the proposed framework viable for practical clinical usage. These results highlight the efficacy and efficiency of the proposed model to assess MSI status of EC directly from histopathological slides.
Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation
Authors: He Wentao , Marchuk Hannah , Koeberl Dwight , Kasumov Takhar , Chen Xiaoxin , Zhang Guo-Fang 
Published: May 2024

AbstractPropionic acidemia (PA), resulting fromPcca or Pccbgene mutations, impairs propionyl-CoA metabolism and induces metabolic alterations. While speculation exists that fasting might exacerbate metabolic crises in PA patients by accelerating the breakdown of odd-chain fatty acids and amino acids into propionyl-CoA, direct evidence is lacking. Our investigation into the metabolic effects of fasting inPcca-/-(A138T) mice, a PA model, reveals surprising outcomes. Propionylcarnitine, a PA biomarker, decreases during fasting, along with the C3/C2 (propionylcarnitine/acetylcarnitine) ratio, ammonia, and methylcitrate. Although moderate amino acid catabolism to propionyl-CoA occurs with a 23-h fasting, a significant reduction in microbiome-produced propionate and increased fatty acid oxidation mitigate metabolic alterations by decreasing propionyl-CoA synthesis and enhancing acetyl-CoA synthesis. Fasting-induced gluconeogenesis further facilitates propionyl-CoA catabolism without changing propionyl-CoA carboxylase activity. These findings suggest that fasting may alleviate metabolic alterations inPcca-/-(A138T) mice, prompting the need for clinical evaluation of its potential impact on PA patients.