bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pericyte detachment and renal congestion involve interstitial injury and fibrosis in Dahl salt-sensitive rats and humans with heart failure
Authors: Ito Hiroki , Hirose Takuo , Sato Shigemitsu , Takahashi Chika , Ishikawa Risa , Endo Akari , Kamada Ayaka , Oba-Yabana Ikuko , Kimura Tomoyoshi , Murakami Kazuhiro , Nakamura Yasuhiro , Takahashi Kazuhiro , Mori Takefumi 
Published: October 2023

AbstractCongestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal function. Pericyte detachment and pericyte-myofibroblast transition (PMT) were linked to renal interstitial fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats are a non-surgical renal congestion model. The relation, however, between renal interstitial damage, pericyte morphology, and PMT in the renal congestion of DahlS rats has not been reported. DahlS rats (8-week-old) were fed normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl), and the left kidney was decapsulated to reduce renal interstitial hydrostatic pressure (RIHP) at 9 weeks old. One week after capsulotomy, both kidneys were analyzed by molecular and histological techniques. Renal pericyte structure was assessed in the body donors with/without venous stasis. Markers of tubulointerstitial damage, interstitial fibrosis, and PMT were upregulated in the right non-decapsulated kidney of DahlS rats fed HS. Renal tubular injury and fibrosis were detected in the HS diet groups in histological analysis. Pericyte detachment was observed in the right non-decapsulated kidney of DahlS rats fed HS by low vacuum-scanning electron microscopy. Decapsulation in DahlS rats fed HS attenuated these findings. Also, renal pericytes detached from the vascular wall in patients with heart failure. These results suggest that pericyte detachment and PMT induced by increased RIHP are responsible for tubulointerstitial injury and fibrosis in DahlS rats and humans with renal congestion. Renal venous congestion and subsequent physiological changes could be therapeutic targets for renal damage in cardiorenal syndrome.
Clinically significant germline pathogenic variants are missed by tumor genomic sequencing
Authors: Stout Leigh Anne , Hunter Cynthia , Schroeder Courtney , Kassem Nawal , Schneider Bryan P. 
Published: October 2023

AbstractA germline pathogenic variant may be present even if the results of tumor genomic sequencing do not suggest one. There are key differences in the assay design and reporting of variants between germline and somatic laboratories. When appropriate, both tests should be completed to aid in therapy decisions and determining optimal screening and risk-reduction interventions.
Quantum simulation of preferred tautomeric state prediction
Authors: Shee Yu , Yeh Tzu-Lan , Hsiao Jen-Yueh , Yang Ann , Lin Yen-Chu , Hsieh Min-Hsiu 
Published: October 2023

AbstractPrediction of tautomers plays an essential role in computer-aided drug discovery. However, it remains a challenging task nowadays to accurately predict the canonical tautomeric form of a given drug-like molecule. Lack of extensive tautomer databases, most likely due to the difficulty in experimental studies, hampers the development of effective empirical methods for tautomer predictions. A more accurate estimation of the stable tautomeric form can be achieved by quantum chemistry calculations. Yet, the computational cost required prevents quantum chemistry calculation as a standard tool for tautomer prediction in computer-aided drug discovery. In this paper we propose a hybrid quantum chemistry-quantum computation workflow to efficiently predict the dominant tautomeric form. Specifically, we select active-space molecular orbitals based on quantum chemistry methods. Then we utilize efficient encoding methods to map the Hamiltonian onto quantum devices to reduce the qubit resources and circuit depth. Finally, variational quantum eigensolver (VQE) algorithms are employed for ground state estimation where hardware-efficient ansatz circuits are used. To demonstrate the applicability of our methodology, we perform experiments on two tautomeric systems: acetone and Edaravone, each having 52 and 150 spin-orbitals in the Slater Type Orbital - 3 Gaussian (STO-3G) basis set, respectively. Our numerical results show that their tautomeric state prediction agrees with the Coupled Cluster Singles and Doubles (CCSD) benchmarks. Moreover, the required quantum resources are efficient: in the example of Edaravone, we could achieve chemical accuracy with only eight qubits and 80 two-qubit gates.
Regioselective, catalytic 1,1-difluorination of enynes
Authors: Wang Zi-Xuan , Livingstone Keith , Hümpel Carla , Daniliuc Constantin G. , Mück-Lichtenfeld Christian , Gilmour Ryan 
Published: October 2023

AbstractFluorinated small molecules are prevalent across the functional small-molecule spectrum, but the scarcity of naturally occurring sources creates an opportunity for creative endeavour in developing routes to access these important materials. Iodine(I)/iodine(III) catalysis has proven to be particularly well-suited to this task, enabling abundant alkene substrates to be readily intercepted by in situ-generated λ3-iodanes and processed to high-value (di)fluorinated products. These organocatalysis paradigms often emulate metal-based processes by engaging the π bond and, in the case of styrenes, facilitating fluorinative phenonium-ion rearrangements to generate difluoromethylene units. Here we demonstrate that enynes are competent proxies for styrenes, thereby mitigating the recurrent need for aryl substituents, and enabling highly versatile homopropargylic difluorides to be generated in an operationally simple manner. The scope of the method is disclosed, together with application in target synthesis (>30 examples, up to >90% yield).
Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target
Authors: Roychowdhury Tanmoy , Klarin Derek , Levin Michael G. , Spin Joshua M. , Rhee Yae Hyun , Deng Alicia , Headley Colwyn A. , Tsao Noah L. , Gellatly Corry , Zuber Verena , Shen Fred , Hornsby Whitney E. , Laursen Ina Holst , Verma Shefali S. , Locke Adam E. , Einarsson Gudmundur , Thorleifsson Gudmar , Graham Sarah E. , Dikilitas Ozan , Pattee Jack W. , Judy Renae L. , Pauls-Verges Ferran , Nielsen Jonas B. , Wolford Brooke N. , Brumpton Ben M. , Dilmé Jaume , Peypoch Olga , Juscafresa Laura Calsina , Edwards Todd L. , Li Dadong , Banasik Karina , Brunak Søren , Jacobsen Rikke L. , Garcia-Barrio Minerva T. , Zhang Jifeng , Rasmussen Lars M. , Lee Regent , Handa Ashok , Wanhainen Anders , Mani Kevin , Lindholt Jes S. , Obel Lasse M. , Strauss Ewa , Oszkinis Grzegorz , Nelson Christopher P. , Saxby Katie L. , van Herwaarden Joost A. , van der Laan Sander W. , van Setten Jessica , Camacho Mercedes , Davis Frank M. , Wasikowski Rachael , Tsoi Lam C. , Gudjonsson Johann E. , Eliason Jonathan L. , Coleman Dawn M. , Henke Peter K. , Ganesh Santhi K. , Chen Y. Eugene , Guan Weihua , Pankow James S. , Pankratz Nathan , Pedersen Ole B. , Erikstrup Christian , Tang Weihong , Hveem Kristian , Gudbjartsson Daniel , Gretarsdottir Solveig , Thorsteinsdottir Unnur , Holm Hilma , Stefansson Kari , Ferreira Manuel A. , Baras Aris , Kullo Iftikhar J. , Ritchie Marylyn D. , Christensen Alex H. , Iversen Kasper K. , Eldrup Nikolaj , Sillesen Henrik , Ostrowski Sisse R. , Bundgaard Henning , Ullum Henrik , Burgess Stephen , Gill Dipender , Gallagher Katherine , Sabater-Lleal Maria ,   DiscovEHR,   Regeneron Genetics Center,   UK Aneurysm Growth Study, Dudbridge Frank , Samani Nilesh J. ,   DBDS Genomic Consortium,   VA Million Veteran Program, Surakka Ida , Jones Gregory T. , Bown Matthew J. , Tsao Philip S. , Willer Cristen J. , Damrauer Scott M. 
Published: October 2023

AbstractAbdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model.
Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial
Authors: Harrison Stephen A. , Taub Rebecca , Neff Guy W. , Lucas K. Jean , Labriola Dominic , Moussa Sam E. , Alkhouri Naim , Bashir Mustafa R. 
Published: October 2023

AbstractNonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. MAESTRO-NAFLD-1 was a 52-week randomized, double-blind, placebo-controlled phase 3 trial evaluating the safety of resmetirom in adults with nonalcoholic fatty liver disease and presumed NASH. Patients were randomized to three double-blind arms (100 mg resmetirom (n = 325), 80 mg resmetirom (n = 327) or placebo (n = 320)) or open-label 100 mg resmetirom (n = 171). The primary end point was incidence of treatment-emergent adverse events (TEAEs) over 52 weeks and key secondary end points were LDL-C, apoB, triglycerides (over 24 weeks), hepatic fat (over 16 and 52 weeks) and liver stiffness (over 52 weeks). Resmetirom was safe and well tolerated. TEAEs occurred in 86.5% (open-label 100 mg resmetirom), 86.1% (100 mg resmetirom), 88.4% (80 mg resmetirom) and 81.8% (placebo) of patients. TEAEs in excess of placebo included diarrhea and nausea at the initiation of treatment. Key secondary end points included least square means difference from placebo at 80 mg, 100 mg resmetirom: LDL-C (−11.1%, −12.6%), apoB (−15.6%, −18.0%), triglycerides (−15.4%, −20.4%), 16-week hepatic fat (−34.9%, −38.6%), (P < 0.0001) and liver stiffness (−1.02, −1.70) and 52-week hepatic fat (−28.8, −33.9). These findings demonstrate resmetirom was safe and well tolerated in adults with presumed NASH, supporting a role for further clinical development. (ClinicalTrials.gov identifier NCT04197479).
Model metamers reveal divergent invariances between biological and artificial neural networks
Authors: Feather Jenelle , Leclerc Guillaume , Mądry Aleksander , McDermott Josh H. 
Published: October 2023

AbstractDeep neural network models of sensory systems are often proposed to learn representational transformations with invariances like those in the brain. To reveal these invariances, we generated ‘model metamers’, stimuli whose activations within a model stage are matched to those of a natural stimulus. Metamers for state-of-the-art supervised and unsupervised neural network models of vision and audition were often completely unrecognizable to humans when generated from late model stages, suggesting differences between model and human invariances. Targeted model changes improved human recognizability of model metamers but did not eliminate the overall human–model discrepancy. The human recognizability of a model’s metamers was well predicted by their recognizability by other models, suggesting that models contain idiosyncratic invariances in addition to those required by the task. Metamer recognizability dissociated from both traditional brain-based benchmarks and adversarial vulnerability, revealing a distinct failure mode of existing sensory models and providing a complementary benchmark for model assessment.
Ionothermal synthesis of magnetic N-doped porous carbon to immobilize Pd nanoparticles as an efficient nanocatalyst for the reduction of nitroaromatic compounds
Authors: Taheri Sahar , Heravi Majid M. , Saljooqi Asma 
Published: October 2023

AbstractCarbon materials play important roles as catalysts or catalyst supports for reduction reactions owing to their high porosity, large specific surface area, great electron conductivity, and excellent chemical stability. In this paper, a mesoporous N-doped carbon substrate (exhibited as N–C) has been synthesized by ionothermal carbonization of glucose in the presence of histidine. The N–C substrate was modified by Fe3O4 nanoparticles (N–C/Fe3O4), and then Pd nanoparticles were stabilized on the magnetic substrate to synthesize an eco-friendly Pd catalyst with high efficiency, magnetic, reusability, recoverability, and great stability. To characterize the Pd/Fe3O4–N–C nanocatalyst, different microscopic and spectroscopic methods such as FT-IR, XRD, SEM/EDX, and TEM were applied. Moreover, Pd/Fe3O4–N–C showed high catalytic activity in reducing nitroaromatic compounds in water at ambient temperatures when NaBH4 was used as a reducing agent. The provided nanocatalyst's great catalytic durability and power can be attributed to the synergetic interaction among well-dispersed Pd nanoparticles and N-doped carbonaceous support.
Thermodynamic modelling of cements clinkering process as a tool for optimising the proportioning of raw meals containing alternative materials
Authors: Costa Ana R. D. , Coppe Mateus V. , Bielefeldt Wagner V. , Bernal Susan A. , Black Leon , Kirchheim Ana Paula , Gonçalves Jardel P. 
Published: October 2023

AbstractThe valorisation of waste or by-products in Portland clinker production is a promising alternative for developing sustainable cements. The complexity of the chemical reactions during clinkering demands an adequate dosing method that considers the effect of feedstock impurities to maximise the potential substitution of natural resources by waste or by-products, while guaranteeing the clinker reactivity requirements. This study proposes a raw meal proportioning methodology for optimising co-processing of natural feedstocks with alternative raw materials in clinker production, intending to reduce the content of natural raw materials needed, while promoting an optimal clinker reactivity. A thermodynamic modelling sequence was developed considering the variability of raw materials composition and heating temperatures. The model was then validated by comparing simulation outcomes with results reported in previous studies. An experimental case study was conducted for validation of the proposed method using a spent fluid catalytic cracking catalyst (SFCC), a by-product from the oil industry as an alternative alumina source during clinkering. The modelling simulations indicated that substitution of natural feedstocks by 15 wt% SFCC promotes the formation of reactive clinkers with more than 54% tricalcium silicate (C3S). Mixes with the potential to form the highest C3S were then produced, and heating microscopy fusibility testing was applied for evaluating the clinkers’ stability. The main factors governing the reactivity and stability of the clinker phases were the melt phase content, alumina modulus, and formation of C3S and dicalcium silicate (C2S). The self-pulverisation of clinker during cooling was observed in selected mixes, and it is potentially associated with high viscosity and low Fe content in the melt phase. The proposed framework enables optimisation of the dosing of raw meals containing alternative alumina-rich feedstocks for clinker production and allows a deeper interpretation of limited sets of empirical data.
Modeling of formation damage during smart water flooding in sandstone reservoirs
Authors: Bagrezaie Mohammad Amin , Dabir Bahram , Rashidi Fariborz , Moazzeni Ali Reza 
Published: October 2023

AbstractImpairment of permeability has been observed as an effective factor in production decline during secondary and tertiary recovery processes such as water flooding. Among different permeability damage mechanisms, fines migration and deposition is known as the main mechanism which occurs due to pore throat clogging and blocking. Because injected water and formation water are usually incompatible, permeability damage evaluation and scale formation prediction must be done before the water flooding process in the oil field is implemented. For this purpose, compatibility tests and core flood experiments are common, but experimental approaches with time and facility limitations are expensive. Thus, by decreasing the time required for conducting experiments, modeling approaches can replace the routine laboratory experiments. Based on thermodynamic balance and the solubility of ions in water, scale development due to seawater injection in an Iranian oil field was predicted in this work using the OLI ScaleChem software. After that, it was suggested that special water be introduced to help reduce the amount of scales that had accumulated in the rock pore space. The extent of permeability damage in various seawater injection scenarios was then assessed via dynamic core flood experiments. Finally, scales-seawater injection into the core was simulated using digital core analysis (DCA) results and the pore scale modeling approach. The core flood experiment data are consistent with the scale formation prediction made by the OLI ScaleChem software, which indicates that smart water can be determined by optimizing the salinity and ion content of injected water. Also, results of permeability damage prediction by our modeling approach have good agreement with the core flood experiment data. Therefore, our modeling approach can replace the conventional core flood experiments as a low-cost method with high computational efficiency and high enough accuracy to evaluate formation damage in the water flooding process.
Prevalence and predictors of tuberculosis among HIV patients who completed isoniazid preventive therapy (IPT) at Reach out Mbuya community health initiative
Authors: Sekayi Wycliff , Namyalo Edity , Namayanja Josephine , Kungu Joseph M. 
Published: October 2023

AbstractTuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals in Sub Saharan Africa, including Uganda. Isoniazid prophylaxis therapy (IPT) is a major public health intervention to limit tuberculosis disease among people living with HIV. However, there is limited information about the influence of IPT on TB disease incidence and its associated risk factors among HIV positive patients in Uganda especially at Reach out-Mbuya community health initiative hence the study. A cross sectional study was conducted among HIV positive adult patients who completed a 6-months long daily treatment of Isoniazid preventive therapy. Sputum samples and urine samples were collected and analysed using Gene Xpert and lateral flow urine Lipoarabinomannan (LF-LAM) tests respectively for presence of Tuberculosis disease. Data analysis was performed using STATA (version 14). Bivariate and multivariate logistic regression were performed to assess the risk factors associated with tuberculosis among the study population and significance estimated at 95% confidence level. A total of 103 HIV positive adults was studied. The mean age of the participants was 42.1 (10.5) and median age was 43 (IQR = 16). The prevalence of tuberculosis disease among HIV positive adult patients who completed Isoniazid preventive therapy was 5.8% (6/103). Counselling, the only significant factor, reduced the likelihood of occurrence of TB disease among HIV patients on IPT treatment (aOR:0.028, P-value < 0.001). A low prevalence of TB disease was observed among HIV patients on IPT treatment. Counselling is a protective factor of TB disease among HIV patients on IPT treatment.
Large eddy simulation on wind-induced interference effects of staggered chamfered square cylinders
Authors: Cao Wenlong , Wang Xueyan , Liu Yubo , Yin Yujie , Yang Jian , An Jianhui 
Published: October 2023

AbstractChamfered corners in buildings are the main means to reduce the control effect of wind load on the structure, and the interference effect of chamfered buildings cannot be ignored. At present, only the mutual interference coefficients of square and rectangular section buildings are given in the Chinese code, without the interference effect of chamfered buildings being specified. Therefore, in this paper, aerodynamic force and wind pressure coefficients of chamfered square cylinders of different spacing are obtained by the large eddy simulation method. Wind load characteristics, non-Gaussian characteristics and interference effects of chamfered square cylinders with different arrangements are studied based on aerodynamic coefficients, wind pressure coefficients and interference coefficients. The results show that when the wall y plus value is 1, the large eddy simulation is the most accurate to simulate the wind load and wind field parameters. Besides, the aerodynamic effects, non-Gaussian characteristics and interference effects between the chamfered square cylinders are mainly controlled by the cross-wind interval and the spacing (4.0, 4.0) is the characteristic coordinate. That means, when the spacing is smaller than this coordinate, the interference effect of the square cylinder is more obvious. When the spacing coordinate is greater than (4.0, 4.0), the aerodynamic coefficients and non-Gaussian regional distributions of the principal square cylinder and the isolated cylinder are the same, and the interference factor approaches 1.
Prognostic analysis of cutaneous Kaposi sarcoma based on a competing risk model
Authors: Qian Bei , Qian Ying , Xiao Peng , Guo Liang 
Published: October 2023

AbstractThe data regarding the prognosis of cutaneous Kaposi sarcoma (KS) was limited. The current study aimed to explore the risk factors and develop a predictive model for the prognosis of cutaneous KS patients. Data were extracted from Surveillance, Epidemiology, and End Results database from 2000 to 2018 and randomly divided into training and validation cohort. The Kaplan–Meier analysis, cumulative incidence function based on the competing risk model and Fine–Gray multivariable regression model was used to identify the prognostic factors and then construct a 5-, 10-, and 15-year KS-specific death (KSSD) nomogram for patients. The concordance index (C-index), area under the curve (AUC) of operating characteristics and calibration plots were used to evaluate the performance of the model. The clinical utility of the model was measured by decision curve analysis (DCA). In 2257 cutaneous KS patients identified from database, the overall median survival time was about 13 years. Radiotherapy (p = 0.013) and surgery (p < 0.001) could lower the KSSD, while chemotherapy (p = 0.042) and surgery (p < 0.001) could increase the overall survival (OS) of patients with metastatic and localized lesions, respectively. Race, number of lesions, surgery, extent of disease, year of diagnosis and age were identified as risk factors associated with cutaneous KS-specific survival. Performance of the nomogram was validated by calibration and discrimination, with C‐index values of 0.709 and AUC for 5-, 10-, and 15-year-KSSD of 0.739, 0.728 and 0.725 respectively. DCA indicated that the nomogram had good net benefits in clinical scenarios. Using a competing-risk model, this study firstly identified the prognostic factors, and constructed a validated nomogram to provide individualized assessment and reliable prognostic prediction for cutaneous KS patients.