bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curse and Blessing of Non‐Proteinogenic Parts in Computational Enzyme Engineering
Authors: Korbeld Kerlen T. , Fürst Maximilian J. L. J. 
Published: May 2023

AbstractEnzyme engineering aims to improve or install a new function in biocatalysts for applications ranging from chemical synthesis to biomedicine. For decades, computational techniques have been developed to predict the effect of protein changes and design new enzymes. However, these techniques may have been optimized to deal with proteins composed of the standard amino acid alphabet, while the function of many enzymes relies on non‐proteogenic parts like cofactors, nucleic acids, and post‐translational modifications. Enzyme systems containing such molecules might be handled or modeled improperly by computational tools, and thus be unsuitable, or require additional tweaking, parameterization, or preparation. In this review, we give an overview of common and recent tools and workflows available to computational enzyme engineers. We highlight the various pitfalls that come with including non‐proteogenic compounds in computations and outline potential ways to address common issues. Finally, we showcase successful examples from the literature that computationally engineered such enzymes.
Ruthenium‐Catalyzed Synthesis of Aryl and Alkenyl Halides from Fluorosulfonates
Authors: Plaçais Clotilde , Kaldas Sherif J. , Donnard Morgan , Panossian Armen , Bernier David , Pazenok Sergii , Leroux Frédéric R. 
Published: May 2023

AbstractAryl and alkenyl halides are widely used as key intermediates in organic synthesis, particularly for the formation of organometallic reagents or as radical precursors. They are also found in pharmaceutical and agrochemical ingredients. In this work, the synthesis of aryl and alkenyl halides from the corresponding fluorosulfonates using commercially available ruthenium catalysts is reported. Notably, this is the first conversion of phenols to aryl halides that is efficient with chloride, bromide, and iodide. Fluorosulfonates are readily prepared using sulfuryl fluoride (SO2F2) and less expensive substitutes for triflates. Although aryl fluorosulfonates and their reactions are well known, this is the first report of an efficient coupling of alkenyl fluorosulfonates. To finish, it was demonstrated, by means of representative examples, that the reaction is possible in a one‐pot process, starting directly from phenol or aldehyde.
Quality of life with cemiplimab plus chemotherapy for first‐line treatment of advanced non–small cell lung cancer: Patient‐reported outcomes from phase 3 EMPOWER‐Lung 3
Authors: Makharadze Tamta , Quek Ruben G. W. , Melkadze Tamar , Gogishvili Miranda , Ivanescu Cristina , Giorgadze Davit , Dvorkin Mikhail , Penkov Konstantin , Laktionov Konstantin , Nemsadze Gia , Nechaeva Marina , Rozhkova Irina , Kalinka Ewa , Gessner Christian , Moreno‐Jaime Brizio , Passalacqua Rodolfo , Konidaris Gerasimos , Rietschel Petra , Gullo Giuseppe 
Published: May 2023

AbstractBackgroundEMPOWER‐Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum‐doublet chemotherapy versus placebo plus chemotherapy for first‐line treatment of advanced non–small cell lung cancer. This study evaluated patient‐reported outcomes (PROs).MethodsPROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life‐Core 30 (QLQ‐C30) and Quality of Life‐Lung Cancer Module (QLQ‐LC13) questionnaires. Prespecified analyses included a longitudinal mixed‐effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between‐arm TTD comparisons were made using a stratified log‐rank test and proportional hazards model.ResultsA total of 312 patients were assigned to receive cemiplimab plus platinum‐doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25–84). For pain symptoms (EORTC QLQ‐C30), a statistically significant overall improvement from baseline (−4.98, 95% confidence interval [CI] −8.36 to −1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26–0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20–3.19 vs. 1.08, 95% CI, –1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ‐C30 or QLQ‐LC13 scale.ConclusionCemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer‐related and lung cancer–specific symptoms and functions.
How Chemical Bonding Impacts Halide Perovskite Nanocrystals Growth to Bulk Films: Implication of Pb−X Bond on Growth Kinetics
Authors: Min Seonhong , Choe Hyejin , Hyun Jung Seo , Cho Junsang 
Published: May 2023

AbstractLead halide perovskites nanocrystals have emerged as a leading candidate in perovskite solar cells and light‐emitting diodes. Given their favorable, tunable optoelectronic properties through modifying the size of nanocrystals, it is imperative to understand and control the growth of lead halide perovskite nanocrystals. However, during the nanocrystal growth into bulk films, the effect of halide bonding on growth kinetics remains elusive. To understand how a chemical bonding of Pb−X (covalency and ionicity) impact on growth of nanocrystals, we have examined two different halide perovskite nanocrystals of CsPbCl3 (more ionic) and CsPbI3 (more covalent) derived from the same parent CsPbBr3 nanocrystals. Tracking the growth of nanocrystals by monitoring the spectral features of bulk peaks (at 445 nm for Cl and at 650 nm for I) enables us to determine the growth activation energy to be 92 kJ/mol (for CsPbCl3) versus 71 kJ/mol (for CsPbI3). The electronegativity of halides in Pb−X bonds governs the bond strength (150–240 kJ/mol), characteristics of bonding (ionic versus covalent), and growth kinetics and resulting activation energies. A fundamental understanding of Pb−X bonding provides a significant insight into controlling the size of the perovskite nanocrystals with more desired optoelectronic properties.
The Effect of Trimethoprim on Thiamine Absorption: A Transporter‐Mediated Drug‐Nutrient Interaction
Authors: Vora Bianca , Wen Anita , Yee Sook Wah , Trinh Kim , Azimi Mina , Green Elizabeth A. E. , Sirota Marina , Greenberg Andrew S. , Newman John W. , Giacomini Kathleen M. 
Published: May 2023

Trimethoprim is predicted to inhibit several thiamine transporters, including the primary thiamine intestinal absorptive transporter, ThTR‐2, and the hepatic and renal organic cation transporters, OCT1, OCT2, and MATEs. To investigate the effect of trimethoprim on thiamine absorption, studies were conducted in cells, mice, and healthy volunteers and supported by use of real‐world data. In a randomized, crossover clinical study, seven healthy volunteers were given a single oral dose of thiamine or thiamine plus trimethoprim, followed by blood sampling. The thiamine area under the curve (AUC) increased with trimethoprim co‐administration (P value = 0.031). Similar results were seen in mice. Trimethoprim appeared to act on thiamine absorption through inhibition of hepatic OCT1 as evidenced from its ability to modulate levels of isobutyrylcarnitine and propionylcarnitine, OCT1 biomarkers identified from metabolomic analyses. Real‐world data further supported this finding, showing an association between trimethoprim use and higher levels of triglycerides, LDL cholesterol, and total cholesterol, consistent with OCT1 inhibition (P values: 2.2 × 10−16, 5.75 × 10−7, and 5.82 × 10−7, respectively). These findings suggest that trimethoprim increases plasma levels of thiamine by inhibiting hepatic OCT1. Trimethoprim reduced urinary excretion and clearance of biomarkers for OCT2 and MATEs, consistent with inhibition of renal organic cation transporters. This inhibition did not appear to play a role in the observed increases in thiamine levels. This study highlights the potential for drug‐nutrient interactions involving transporters, in addition to transporters' established role in drug–drug interactions.
Isolation, Culture, and Transfection of Melanocytes
Authors: Goff Philip S. , Castle Joanna T. , Kohli Jaskaren S. , Sviderskaya Elena V. , Bennett Dorothy C. 
Published: May 2023

AbstractLocated in the basal epidermis and hair follicles, melanocytes of the integument are responsible for its coloration through production of melanin pigments. Melanin is produced in a type of lysosome‐related‐organelle (LRO) called the melanosome. In humans, this skin pigmentation acts as an ultraviolet radiation filter. Abnormalities in the division of melanocytes are quite common, with potentially oncogenic growth usually followed by cell senescence producing benign naevi (moles), or occasionally, melanoma. Therefore, melanocytes are a useful model for studying both cellular senescence and melanoma, as well as many other aspects of biology such as pigmentation, organelle biogenesis and transport, and the diseases affecting these mechanisms. Melanocytes for use in basic research can be obtained from a range of sources, including surplus postoperative skin or from congenic murine skin. Here we describe methods to isolate and culture melanocytes from both human and murine skin (including the preparation of mitotically inactive keratinocytes for use as feeder cells). We also describe a high‐throughput transfection protocol for human melanocytes and melanoma cells. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Primary explantation of human melanocytic cellsBasic Protocol 2: Preparation of keratinocyte feeder cells for use in the primary culture of mouse melanocytesBasic Protocol 3: Primary culture of melanocytes from mouse skinBasic Protocol 4: Transfection of human melanocytes and melanoma cells
Tailored Properties of Carbon for Supercapacitors by Blending Lignin and Cellulose to Mimic Biomass as Carbonaceous Precursor
Authors: Tang Yinan , Lu Lu , Zang Xiaoxian , Wang Buhuan , Ye Xiangrong 
Published: May 2023

AbstractKOH‐activated carbon materials prepared from biomass‐derived carbon source, cellulose and lignin, were compared. Mixtures of different ratios of cellulose and lignin were used to partially mimic biomass as carbon source. This allows tailoring and optimizing of the KOH activated carbon materials by getting rid of the restriction of the intrinsic proportion of cellulose and lignin in specific biomass. The results indicate that cellulose use results in a more porous structure, whereas lignin use leads to more partially activated graphite structure. The activated carbon material (CL1) prepared from blend of cellulose with lignin in mass ratio of 1 : 1 exhibits a high specific surface area of 2000.39 m2 g−1, and in TEABF4/ACN (tetraethylammonium tetrafluoroborate dissolved in acetonitrile) electrolyte it showed a maximum specific capacitance of 136.10 F g−1, a maximum energy density of 18.11 Wh kg−1, and a capacitance retention of 85.04 % under current density as high as 15 A g−1.
Macrophage metabolic reprogramming and atherosclerotic plaque microenvironment: Fostering each other?
Authors: Xiao Qi , Hou Rongyao , Xie Linlin , Niu Mengying , Pan Xudong , Zhu Xiaoyan 
Published: May 2023

AbstractMacrophages are the central immune cells in atherosclerosis (AS) and play a critical role in the initiation, progression and invasion of atherosclerotic plaques. Metabolic reprogramming is a crucial feature that determines macrophage function and is driven by a combination of intrinsic alterations in macrophages and extrinsic factors such as cytokines acting in the plaque microenvironment. Intrinsic macrophage mechanisms activate signal transduction pathways that change metabolic enzyme activity, and the expression of metabolic regulators. Extrinsic signalling mechanisms involve lipids and cytokines in the microenvironment, promoting and amplifying macrophage metabolic reprogramming. This review describes the intrinsic and extrinsic mechanisms driving macrophage metabolic reprogramming in the AS microenvironment and the interplay of these metabolic rewires in the microenvironment. Moreover, we discuss whether targeting these different pathways to treat macrophage microenvironmental changes can alter the fate of the vulnerable plaques.
Primary gastric inflammatory myofibroblastic tumor treated with non‐exposed endoscopic wall‐inversion surgery (NEWS): A case report and literature review
Authors: Masuda Yuka , Kanazawa Yoshikazu , Goto Osamu , Kakinuma Daisuke , Higuchi Kazutoshi , Koizumi Eriko , Nakata Ryosuke , Sakurazawa Nobuyuki , Ando Fumihiko , Suzuki Mikito , Yoshiyuki Toshiro , Kato Shunji , Ohashi Ryuji , Kaise Mitsuru , Iwakiri Katsuhiko , Yoshida Hiroshi 
Published: May 2023

AbstractInflammatory myofibroblastic tumor (IMT) is an intermediate malignancy with myofibroblast proliferation and inflammatory cell infiltration with malignant potential. Primary IMTs are predominantly reported in the lungs, while gastric IMTs are very rare. Therefore, no guidelines exist for the diagnosis and treatment of gastric IMTs. The present case is a 39‐year‐old man diagnosed with an asymptomatic gastric submucosal tumor. Considering the malignancy of the tumor, we selected non‐exposed endoscopic wall‐inversion surgery as the resection method and successfully performed local resection. Histopathological analysis showed myofibroblast proliferation and inflammatory cell infiltration, with a diagnosis of primary gastric IMT and negative resection margins. Immunohistochemical staining was negative for anaplastic lymphoma kinase. To the best of our knowledge, including our case, there have been 52 reported cases of primary gastric IMTs that have been treated, with several recurrent cases. In this study, we report the first case of local resection of gastric IMT using non‐exposed endoscopic wall‐inversion surgery, with a literature review.
Hair testing applied to the assessment of in utero exposure to drugs: Critical analysis of 51 cases of the University Hospital of Verona
Authors: Bertaso Anna , Gottardo Rossella , Murari Matilde , Mazzola Mara , Porpiglia Nadia Maria , Taus Francesco , Beghini Renzo , Gandini Fabio , Bortolotti Federica 
Published: May 2023

AbstractThe work discusses the results of hair and urine testing performed in 51 cases of suspected in utero drug exposure handled at the University Hospital of Verona from 2016 to 2022. On the day of birth or the day after birth, urine from mother and newborn (UM and UN) and hair from mother (HM), newborn (HN) and father (HF), if possible, were collected. Urine underwent immunoassay and GC–MS analysis, whereas hair underwent LC–MS/MS and GC–MS/MS analysis. In 50 out of 51 cases, HM and/or HN were available. In 92% of them, hair testing resulted in a positive, often (>50% cases) for more than one class of substance. The most detected substances were cocaine, opiates, methadone and cannabinoids. Maternal segmental analysis showed a prevalent decreasing concentration trend during pregnancy in case of positivity for one class of substances, whereas, as expected, a neatly prevalent increasing trend in the case of positivity for more than one class of substances. In nine cases, HF was also available, resulting in all being positive, usually for the same classes of substances identified in HM, thus questioning parental responsibility. In 33 cases, urine samples from the mother or newborn were also collected. Of them, 27 cases (82%) tested positive, showing peri‐partum drug consumption and then confirming the severity of the addiction. Hair testing showed to be a reliable diagnostic tool to investigate in utero drug exposure because of the possibility of obtaining a complete picture of maternal addictive behaviour and family background, thanks to segmental maternal hair analysis and father hair testing.
Experimental disturbance and productivity gradients drive community diversity in aquatic mesocosms
Authors: Hart Jacob D. , Jenkins David G. 
Published: May 2023

AbstractCombined effects of disturbance and productivity on ecological diversity have been considered for decades as the dynamic equilibrium model (DEM) but are rarely tested together. Instead, most studies focus on either the intermediate disturbance hypothesis or sometimes the intermediate productivity hypothesis. In addition, most analyses of disturbance and productivity effects have relied on nonexperimental patterns, limited sample sizes, inaccurate proxies for productivity, and/or simple measures of diversity. The DEM operates at regional and local scales; here, we conducted a year‐long experiment at local scales using submersed aquatic vegetation in outdoor mesocosms with a factorial combination of physical disturbance and productivity treatments. We evaluated diversity in several ways, directly measured productivity, and compared alternative hypotheses using model selection. The DEM was supported for effective diversity; both productivity and disturbance effects were clear, though productivity effects were stronger. Other diversity measures for the simple communities in the mesocosms did not clearly reflect treatments. The DEM is a valuable general framework for understanding disturbance and productivity effects on ecological systems and is made more general by minor conceptual adjustments here.
Leaf phenology as an indicator of ecological integrity
Authors: Spafford Lynsay , MacDougall Andrew H. , Vitasse Yann , Filippa Gianluca , Richardson Andrew , Steenberg James , Lever J. Jelle 
Published: May 2023

AbstractClimate change leads to an increased frequency of severe weather events as well as stressful growing conditions. Together these changes may impact the resilience of ecosystems. To keep track of such effects, conservation managers monitor the “ecological integrity” or coherence of ecosystem processes, such as the cycling of carbon and water. Networked phenocams can produce near‐continuous observations of leaf function in the context of climate change, capturing declines due to disturbance or stress. Here we explore the application of phenocams to detect responses to disturbance and stress using 14 examples from the PhenoCam Network. We selected these previously published and new examples to include a variety of disturbances in the form of hurricanes, a windstorm, frost, insect defoliation, and stress due to drought. Frost and herbivory disturbances led to both reductions and extensions in the duration of the rising section of the greenness curve, while hurricanes generally led to reductions in the duration of the plateau section and entire leaf‐on period. We found that changes of at least ±20% in the duration of the rising section in the seasonal greenness curve, ±20% in the duration of the plateau section following the seasonal greenness peak, and ±10% in the duration of the entire leaf‐on period were a reliable signal of leaf functional declines due to disturbance or stress. If such declines become increasingly frequent and severe as a consequence of climate change, this could impact ecological integrity through interruptions to ecosystem processes. Comparing the duration of these periods in a given year to the average for other years with these thresholds resulted in average true detection rates of 86% and false‐positive detection rates of 11% when sampling from probability density functions of 344 broadleaf and needleleaf PhenoCam site‐years. Here we show that phenocams are powerful ecological integrity monitoring tools, which can be efficiently applied to quantify dynamic responses to disturbance or stress.
Base‐Catalyzed Synthesis of Spiropyrazoloaminonitriles with Arylidene Pyrazolone and Vinylogous Malononitriles through a Cascade Michael Addition and Cyclization
Authors: Ittamalla Chaitanya , Chintha Saikrishna , Medishetti Nagaraju , Nanubolu Jagadeesh Babu , Atmakur Krishnaiah 
Published: May 2023

AbstractSynthesis of title compounds were accomplished by a reaction of vinyl malononitriles and arylidene pyrazolones catalyzed by base. This protocol proceeds via Michael addition followed by intramolecular cyclization leading to the formation of two new C−C bonds. Further the same reaction was also conducted with α,α‐dicyano olefins and vinyl malononitriles to furnish 1,6‐dihydro biphenyl compounds. Simple reaction conditions, high yields and compatibility are the advantages of this protocol.
Effects and distribution of semi‐active resettable springs on the seismic response of asymmetric structures
Authors: Danielian Shant Aram , Jabbari Faryar , Zareian Farzin 
Published: May 2023

AbstractThe feasibility of incorporating semi‐active resettable springs (SRSs) to mitigate torsional response of structures is investigated. The effectiveness and robustness of the SRSs in reducing seismic demand was demonstrated on a spectrum of building properties idealized with one‐story asymmetric structures. The effects of the SRSs on the edge displacements were analyzed and several system parameters were identified that significantly effect the edge displacements. Two approaches based on geometric constraints and modal analysis are proposed to determine the proper distribution of the SRSs to minimize edge displacements. Limitations and guidelines on implementation are also provided.
Distinct element modeling of the in‐plane response of a steel‐framed retrofit solution for URM structures
Authors: Damiani Nicolò , DeJong Matthew J. , Albanesi Luca , Penna Andrea , Morandi Paolo 
Published: May 2023

AbstractThis paper presents the results of a numerical study aimed at assessing the effectiveness of an innovative steel modular retrofit system on improving the in‐plane lateral capacity of unreinforced masonry (URM) load‐bearing structures. The investigated retrofit solution consists of modular steel frames fastened to the external surface of masonry piers through chemical anchors. Distinct element models are built and calibrated against experimental data coming from a series of in‐plane quasi‐static tests performed on piers in both bare and retrofitted conditions. Two different masonry typologies are considered herein: one made up with solid clay bricks and lime mortar, assembled in a header bond pattern, and the other with typical Italian hollow clay units and cement‐lime mortar, arranged in a Flemish bond pattern. A simplified microscale approach, combined with a mesh‐refinement strategy, is adopted to decrease computational demand without losing numerical accuracy. All in‐plane failure mechanisms, such as mortar and unit tensile failures, as well as masonry crushing for high compressive stresses, are included in the developed numerical models. Moreover, a methodology to explicitly account for the contribution of the investigated retrofit in the distinct element method (DEM) framework is presented and discussed. The proposed modeling strategy yielded a good prediction in terms of lateral stiffness, lateral strength, hysteretic response, and crack pattern for unreinforced and strengthened specimens. A novel set of metrics is proposed to quantitatively assess the retrofit performance benefits.