bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of AlphaFold models in evaluating ligandable cysteines across E3 ligases
Authors: Koldenhof Patrick , Bemelmans Martijn P. , Ghosh Brahma , Damm‐Ganamet Kelly L. , van Vlijmen Herman W. T. , Pande Vineet 
Published: February 2024

AbstractProteolysis Targeting Chimeras (PROTACs) are an emerging therapeutic modality and chemical biology tools for Targeted Protein Degradation (TPD). PROTACs contain a ligand targeting the protein of interest, a ligand recruiting an E3 ligase and a linker connecting these two ligands. There are over 600 E3 ligases known so far, but only a handful have been exploited for TPD applications. A key reason for this is the scarcity of ligands binding various E3 ligases and the paucity of structural data available, which complicates ligand design across the family. In this study, we aim to progress PROTAC discovery by proposing a shortlist of E3 ligases that can be prioritized for covalent targeting by performing systematic structural ligandability analysis on a chemoproteomic dataset of potentially reactive cysteines across hundreds of E3 ligases. One of the goals of this study is to apply AlphaFold (AF) models for ligandability evaluations, as for a vast majority of these ligases an experimental structure is not available in the protein data bank (PDB). Using a combination of pocket features, AF model quality and additional aspects, we propose a shortlist of E3 ligases and corresponding cysteines that can be prioritized to potentially discover covalent ligands and expand the PROTAC toolbox.
Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions
Authors: Lim Iris , Masutani Taishi , Hashitani Hikaru , Chess‐Williams Russ , Sellers Donna 
Published: February 2024

AbstractThe aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre‐contracted with 5‐HT (100 μM). Upon generation of stable phasic contractions, PDE‐4 and PDE‐5 inhibitors were added cumulatively to separate tissues. PDE‐4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE‐5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5‐HT‐induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside‐induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE‐4 inhibitors are effective in attenuating 5‐HT‐induced contractility in porcine distal ureteral tissues, while PDE‐5 inhibitors are less effective. These findings suggest that PDE‐4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra‐ureteral pressure.
Hemodynamic response to inhaled nitric oxide in patients with pulmonary hypertension and chronic kidney disease: A retrospective cohort study
Authors: del Valle Kathryn T. , Krowka Michael J. , Schinstock Carrie A. , Nath Karl A. , Burger Charles D. , Reddy Yogesh N. , Frantz Robert P. , Prakash Y. S. , DuBrock Hilary M. 
Published: February 2024

AbstractPulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH‐CKD) affects approximately 20%–40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH‐CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH‐CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end‐stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc‐PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc‐PH groups. Among a small subset (n = 14) who were subsequently treated with PAH‐targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH‐CKD.
DFT study on the effects of substituents on the structure and properties of dithiophosphate collectors
Authors: Ding Mingyuan , Liu Yingchao , Chen Jianhua , Li Yuqiong 
Published: February 2024

AbstractThe structures and properties of seven substituted dithiophosphate (DTP) collectors containing three types of functional groups (O2PS2, C2PS2, and N2PS2) were studied using density functional theory. The collectors studied were dibutyl dithiophosphate (DNBDTP), diisobutyl dithiophosphate (DIBDTP), dibutoxyethyl dithiophosphate (DBOEDTP), xylenol dithiophosphate (DMPDTP), diisobutyl dithiohypophosphite (3418A), diphenylamine dithiophosphate (DTADTP), and dicyclohexylamine dithiophosphate (DCADTP). The structural analysis showed that the PS bond lengths in the C2PS2 and N2PS2 types are longer than those in the O2PS2 type, indicating that the strength of the PS bond is weaker in the former two. The frontier molecular orbital studies showed that the energy differences between the highest occupied molecular orbitals (HOMO) of 3418A (C2PS2 type) and DCADTP (N2PS2 type) and the lowest unoccupied molecular orbital (LUMO) of galena are significantly lower than those of the other collectors, suggesting that C2PS2 type and N2PS2 type with cyclohexane could enhance the interaction with galena. Using the Fukui function to calculate the nucleophilicity and electrophilicity of the sulfur atom indicated that the S atom exhibits nucleophilicity, especially in DMPDTP and DTADTP, which contain benzene rings, and the S atom exhibits strong nucleophilicity without electrophilicity. However, due to the lack of contribution from S atoms to the LUMO orbitals, the S atoms in these two compounds are not participate in any LUMO reactions. The adsorption results demonstrated that 3418A (C2PS2 type) and DCADTP (N2PS2 type) exhibit the strongest adsorption on Pb2+ ions, while DMPDTP (C2PS2 type) and DTADTP (O2PS2 type) which contain benzene rings, as well as DBOEDTP (C2PS2 type) which does not contain a benzene ring, exhibit weaker interaction compared to the other compounds. These are consistent with the results of the frontier molecular orbital and electrophilic nucleophilicity calculations.
Subsampling under distributional constraints
Authors: Combes Florian , Fraiman Ricardo , Ghattas Badih 
Published: February 2024

AbstractSome complex models are frequently employed to describe physical and mechanical phenomena. In this setting, we have an input in a general space, and an output where is a very complicated function, whose computational cost for every new input is very high, and may be also very expensive. We are given two sets of observations of , and of different sizes such that only is available. We tackle the problem of selecting a subset of smaller size on which to run the complex model , and such that the empirical distribution of is close to that of . We suggest three algorithms to solve this problem and show their efficiency using simulated datasets and the Airfoil self‐noise data set.
Rarity updated ensemble with oversampling: An ensemble approach to classification of imbalanced data streams
Authors: Nouri Zahra , Kiani Vahid , Fadishei Hamid 
Published: February 2024

AbstractToday's ever‐increasing generation of streaming data demands novel data mining approaches tailored to mining dynamic data streams. Data streams are non‐static in nature, continuously generated, and endless. They often suffer from class imbalance and undergo temporal drift. To address the classification of consecutive data instances within imbalanced data streams, this research introduces a new ensemble classification algorithm called Rarity Updated Ensemble with Oversampling (RUEO). The RUEO approach is specifically designed to exhibit robustness against class imbalance by incorporating an imbalance‐specific criterion to assess the efficacy of the base classifiers and employing an oversampling technique to reduce the imbalance in the training data. The RUEO algorithm was evaluated on a set of 20 data streams and compared against 14 baseline algorithms. On average, the proposed RUEO algorithm achieves an average‐accuracy of 0.69 on the real‐world data streams, while the chunk‐based algorithms AWE, AUE, and KUE achieve average‐accuracies of 0.48, 0.65, and 0.66, respectively. The statistical analysis, conducted using the Wilcoxon test, reveals a statistically significant improvement in average‐accuracy for the proposed RUEO algorithm when compared to 12 out of the 14 baseline algorithms. The source code and experimental results of this research work will be publicly available at
https://github.com/vkiani/RUEO.
Structural and Thermal Properties of Faba Bean Starch and Flax Seed Oil Nanoemulsion: Effect of Processing Conditions on Nanoemulsion
Authors: Sharma Madhu , Bains Aarti , Sharma Minaxi , Inbaraj Baskaran Stephen , Ali Nemat , Iqbal Muzaffar , Patil Sandip , Chawla Prince , Sridhar Kandi 
Published: February 2024

AbstractNanoemulsions derived from unconventional polysaccharides have gained attention as efficient delivery systems for bioactive compounds, helping in their enhanced absorption. Nontraditional sources of starch have been investigated in recent years due to their potential applications. Therefore, this study investigates the potential of extracting starch from faba beans and investigating their structural properties. Furthermore, the nanoemulsion is developed from starch, flax seed oil, and tween 80 and evaluated for different processing methods (temperature, pH, and NaCl). The extracted starch yields 31.20 g/100 g and X‐ray diffraction reveals its semicrystalline structure. The optimized nanoemulsion (N3) has an average droplet size of 108.62 ± 2.78 nm and a surface charge of −27.74 ± 0.12 mV. At different pH levels (2–9), temperature (30, 50, 70, and 90 °C), and ionic strengths (0.5, 1, and 2 m), the N3 nanoemulsion demonstrates significantly greater changes in stability. All the samples show excellent structural properties and stability. Overall, the results suggest that faba bean starch‐based nanoemulsion shows promise as a stable delivery system for bioactive compounds, but its stability is influenced by pH levels and ionic strengths.
Assessment of fetal growth trajectory identifies infants at high risk of perinatal mortality
Authors: Larsen M. L. , Krebs L. , Hoei‐Hansen C. E. , Kumar S. 
Published: February 2024

ABSTRACTObjectiveTo analyze perinatal risks associated with three distinct scenarios of fetal growth trajectory in the latter half of pregnancy compared with a reference group.MethodsThis cohort study included women with a singleton pregnancy that delivered between 32 + 0 and 41 + 6 weeks' gestation and had two or more ultrasound scans, at least 4 weeks apart, from 18 + 0 weeks. We evaluated three different scenarios of fetal growth against a reference group, which comprised appropriate‐for‐gestational‐age fetuses with appropriate forward‐growth trajectory. The comparator growth trajectories were categorized as: Group 1, small‐for‐gestational‐age (SGA) fetuses (estimated fetal weight (EFW) or abdominal circumference (AC) persistently < 10th centile) with appropriate forward growth; Group 2, fetuses with decreased growth trajectory (decrease of ≥ 50 centiles) and EFW or AC ≥ 10th centile (i.e. non‐SGA) at their final ultrasound scan; and Group 3, fetuses with decreased growth trajectory and EFW or AC < 10th centile (i.e. SGA) at their final scan. The primary outcome was overall perinatal mortality (stillbirth or neonatal death). Secondary outcomes included stillbirth, delivery of a SGA infant, preterm birth, emergency Cesarean section for non‐reassuring fetal status and composite severe neonatal morbidity. Associations were analyzed using logistic regression.ResultsThe final study cohort comprised 5319 pregnancies. Compared to the reference group, the adjusted odds of perinatal mortality were increased significantly in Group 2 (adjusted odds ratio (aOR), 4.00 (95% CI, 1.36–11.22)) and Group 3 (aOR, 7.71 (95% CI, 2.39–24.91)). Only Group 3 had increased odds of stillbirth (aOR, 5.69 (95% CI, 1.55–20.93)). In contrast, infants in Group 1 did not have significantly increased odds of demise. The odds of a SGA infant at birth were increased in all three groups compared with the reference group, but was highest in Group 1 (aOR, 111.86 (95% CI, 62.58–199.95)) and Group 3 (aOR, 40.63 (95% CI, 29.01–56.92)). In both groups, more than 80% of infants were born SGA and nearly half had a birth weight < 3rd centile. Likewise, the odds of preterm birth were increased in all three groups compared with the reference group, being highest in Group 3, with an aOR of 4.27 (95% CI, 3.23–5.64). Lastly, the odds of composite severe neonatal morbidity were increased in Groups 1 and 3, whereas the odds of emergency Cesarean section for non‐reassuring fetal status were increased only in Group 3.ConclusionAssessing the fetal growth trajectory in the latter half of pregnancy can help identify infants at increased risk of perinatal mortality and birth weight < 3rd centile for gestation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
Preparation and characterization of poly(vinyl alcohol)/poly(lactic acid) blends containing bio‐based plasticizers
Authors: Yan Zibo , Dou Qiang 
Published: February 2024

AbstractThe bio‐based plasticizers‐glycerol and lactic acid were used to plasticize and compatibilize PVA/PLA blends during melt blending process. It was confirmed that lactic acid significantly improved the compatibility between glycerol‐plasticized PVA and PLA. Compared with pure PVA, the melting and crystallization temperatures and crystallinities decreased but the crystal form of PVA in the blends was not changed. The thermal stabilities of PVA/glycerol (G)/lactic acid (L)/PLA blends were better than PVA/G/PLA blends. Compared to PVA/G/PLA blends, the tensile and tear strength of PVA/G/L/PLA blends were improved, however, elongation at break decreased. The water absorptions and water vapor permeances of the blends decreased with the addition of hydrophobic PLA, but they increased by incorporation of hygroscopic lactic acid. The surface resistivities of the blends augmented in combination with PLA but declined by adding lactic acid. The melt flow rates of PVA/G/PLA blends were better than PVA/G/L/PLA blends because lactic acid enhanced the interactions among the components. After the addition of lactic acid, the transmittances of the blends increased due to the refined dispersed phases by the compatibilization. The compatibility between the components was predicated by Hansen solubility parameters. These blends showed potential as a novel barrier material for food and medicine packages.Highlights
PVA, glycerol, and PLA blends were compatibilized by lactic acid.
The melting temperatures decreased with addition of glycerol and lactic acid.
The tensile and tear strengths were enhanced with addition of PLA and lactic acid.
The hydrophobicity, melt fluidity, and surface resistivity were improved by PLA.
A multi‐institutional prospective observational study to compare postoperative quality of life of patients who undergo total or proximal gastrectomy for early gastric cancer (CCOG1602)
Authors: Kanda Mitsuro , Tanaka Chie , Misawa Kazunari , Mochizuki Yoshinari , Watanabe Takuya , Sueoka Satoshi , Ishiyama Akiharu , Yamada Takanobu , Oshima Takashi , Hattori Masashi , Koike Shinya , Ishigure Kiyoshi , Teramoto Hitoshi , Murotani Kenta , Kodera Yasuhiro 
Published: February 2024

AbstractBackgroundProximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach. However, advantages of PG in postoperative quality of life (QOL) over total gastrectomy (TG) has not fully proven.MethodsWe conducted a multi‐institutional prospective observational study (CCOG1602) of patients who undergo TG or PG for cStage I gastric cancer. We used the PGSAS‐37 and EORTC‐QLQ‐C30 to evaluate the changes in body weight and QOL over a 3‐year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery.ResultsWe enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (p = 0.056, Cohen's d 0.656) during postoperative year 1% and 15.0% and 10.8% for TG and PG (p = 0.068, Cohen's d 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS‐37, the PG group experienced a better trend in the indigestion subscale (p < 0.001, Cohen's d −1.085) and total symptom score (p = 0.050, Cohen's d −0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC‐QLQ‐C30 detected no difference between the groups at any time point during 3‐year postoperative period.ConclusionsThis prospective study demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion.
Influences of blowing and internal heating processes on steady MHD mixed convective boundary layer flows of radiating titanium dioxide‐ethylene glycol nanofluids
Authors: Wakif Abderrahim , Alshehri Ahmed , Muhammad Taseer 
Published: February 2024

AbstractThe present analysis intends predominantly to explore the multiple behaviors of radiating ethylene glycol‐based titanium dioxide nanofluids during their steady boundary layer flows near a vertical permeable surface under the prominent impacts of uniform blowing and nonuniform internal heating processes. By incorporating the dynamical contribution of Lorentz and buoyancy forces in the momentum equation and adopting the single‐phase nanofluid approach along with the constitutive equations of the second‐grade rheological model and Corcione's correlations, the governing partial differential equations and their appropriate boundary conditions are derived mathematically based on the boundary layer theory and other admissible physical approximations. After several simplifications, the aforesaid differential formulation is converted into a set of ordinary differential equations and realistic boundary conditions, which are solved thereafter numerically using GDQ's‐NT method. Moreover, it is demonstrated that the strengthening in the blowing and internal heating processes has a boosting effect on the velocity and temperature profiles. However, the other influencing parameters show dissimilar dynamical and thermal trends. Furthermore, it is witnessed that the mixed convective heat transfer, the viscoelasticity trend of the nanofluidic medium, and the nanoparticles’ loading exhibit an enhancing impression on the surface heat transfer rate.
Learning from Overrated Mission-Oriented Innovation Policies: Seven Takeaways
Authors: Henrekson Magnus , Sandström Christian , Stenkula Mikael 
Published: February 2024

AbstractThis chapter integrates findings from several different case studies on mission-oriented innovation policies (MOIPs) and makes use of the existing literature to briefly describe three other missions: The War on Cancer, homeownership in the United States, and the Swedish Million Program. Together with the analyses in the other chapters of this volume, seven takeaways regarding mission-oriented innovation policies are developed and described: (1) wicked problems cannot be solved through missions, (2) politicians and government agencies are not exempt from self-interest, (3) MOIPs are subject to rent seeking and mission capture, (4) policymakers lack information to design MOIPs efficiently, (5) MOIPs distort competition, (6) government support programs distort incentives and result in moral hazard, and (7) MOIPs ignore opportunity costs. These seven takeaways are illustrated using the cases described in this chapter and elsewhere in this volume.
The Entrepreneurial State Cannot Deliver Without an Entrepreneurial Society
Authors: Sanders Mark , Stam Erik , Thurik Roy 
Published: February 2024

AbstractIn The Entrepreneurial State and Mission Economy, Mazzucato argues that the state should adopt a proactive and entrepreneurial approach, setting ambitious missions that inspire collective action nurtured by emotions of urgency. By defining clear goals, the state can mobilize resources and talent from both the public and private sectors. We do not challenge Mazzucato’s facts or discredit her analysis. We agree that states successfully have and perhaps should continue to play a role in mobilizing talent and other resources around urgent societal challenges. Healthcare, climate change, and inequality are not problems that “markets” will solve on their own, and relevant and competent government organizations are an essential tool in our toolbox to address them. We would even agree that the state would do well to formulate clear missions and approach them in an entrepreneurial fashion. That is, experiment with an open mind and be willing to fail and learn, rather than develop interventions on the drawing board and then stick to them because of bureaucratic or political lock-in. But all that effort will only pay off, often in many unexpected ways, if we do not succumb to the fallacy of hindsight. That is, a well-defined and entrepreneurially executed state-led mission can only succeed in also generating a stream of valuable but largely unanticipated spin-off innovations, if the conditions for acting on such opportunities are right.
Overcoming the Siren Song of Central Planning
Authors: Rose David C. 
Published: February 2024

AbstractThe concepts of state entrepreneurship and mission economy are the latest attempts to justify greater central planning despite the explosion of human flourishing in free market societies over the last few centuries. This is a puzzle. Why do we keep falling for this old wine in new bottles? I argue that our genes predispose us to be too skeptical about having faith in complex and evolving systems involving large numbers of people. This is because we fail to recognize that there are two different ways to control evolution. I then briefly discuss how moral beliefs might overcome this predisposition.