bluuebunny/crossref_metadata_2025_split huggingface dataset:
DPCPX induces Bim‐dependent apoptosis in nasopharyngeal carcinoma cells
Authors: Pan Suming , Zhang Xiangguo , Guo Yugan , Li Yin 
Published: August 2022

AbstractADORA1 promotes tumor growth and development in multiple cancers. DPCPX (a selective adenosine A1 receptor antagonist), a specific ADORA1 antagonist, has shown antitumor effects in many cancer types. Nevertheless, the function of DPCPX in nasopharyngeal carcinoma (NPC) still remains to be unraveled. In this study, we investigated the functional role of DPCPX on NPC cells. We found that DPCPX promotes NPC cells growth inhibition. DPCPX induced Bim‐dependent apoptosis in NPC cells irrespective of p53 status via the FoxO3a pathway following PI3K/AKT inhibition. Furthermore, DPCPX enhanced the antitumor effect of cisplatin, 5‐FU and Paclitaxel in NPC. Xenograft experiment revealed that deficiency of Bim in vivo stalls apoptosis and antitumor activity of DPCPX. In conclusion, the PI3K/AKT/FoxO3a/Bim axis plays a critical role in the anticancer effects of DPCPX in NPC.
Orbital atherectomy of calcified coronary ostial lesions
Authors: Chambers Jeffrey W. , Martinsen Brad J. , Sturm Robert C. , Mandair Divneet , Valle Javier A. , Waldo Stephen W. , Guzzetta Francesca , Armstrong Ehrin J. 
Published: August 2022

AbstractObjectivesTo evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions.BackgroundPercutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long‐term outcome data.MethodsData were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high‐volume PCI centers. Kaplan–Meier analysis was utilized to assess the primary endpoints of 30‐day, 1‐year, and 2‐year freedom‐from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST).ResultsA total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30‐day, 1‐year, and 2‐year, a high FF‐MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively.ConclusionsThis study represents the largest real‐world experience of coronary OA use in heavily calcified ostial lesions with long‐term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.
Cu3(HHTP)2 c‐MOF/ZnO Ultrafast Ultraviolet Photodetector for Wearable Optoelectronics
Authors: Kang Chenxu , Ahsan Iqbal Muhammad , Zhang Suyun , Weng Xiaoliang , Sun Yuting , Qi Lu , Tang Wei , Ruan Shuangchen , Zeng Yu‐Jia 
Published: August 2022

AbstractTwo‐dimensional conductive metal–organic frameworks (2D c‐MOFs) are a family of highly tunable and electrically conducting materials that can be utilized in optoelectronics. A major issue of 2D c‐MOFs for photodetection is their poor charge separation and recombination dynamics upon illumination. This study demonstrates a Cu3(HHTP)2/ZnO type‐II heterojunction ultraviolet (UV) photodetector fabricated by layer‐by‐layer (LbL) deposition, in which the charge separation of photogenerated carriers is enhanced. At optimized MOF layer cycles, the device achieves a responsivity of 78.2 A/W and detectivity of 3.8×109 Jones at 1 V. Particularly, the device can be operated in the self‐powered mode with an ultrafast response time of 70 μs, which is the record value for MOF‐based photodetectors. In addition, even after 1000‐time bending of 180°, the flexible device maintains stable performance. This flexible MOF‐based UV photodetector with anti‐fatigue and anti‐bending properties provides strong implication to wearable optoelectronics.
Leveraging Metal and Ligand Reactive Sites for One Pot Reactions: Ligand‐Centered Borenium Ions for Tandem Catalysis with Palladium
Authors: Skaria Manisha , Culpepper Johnathan D. , Daly Scott R. 
Published: August 2022

AbstractTandem catalysts that perform two different organic transformations in a single pot are highly desirable because they enable rapid and efficient assembly of simple organic building blocks into more complex molecules. Many examples of tandem catalysis rely on metal‐catalyzed reactions involving one or more metal complexes. Remarkably, despite surging interest in the development of chemically reactive (i. e., non‐innocent) ligands, there are few examples of metal complexes that leverage ligand‐centered reactivity to perform catalytic reactions in tandem with separate catalytic reactions at the metal. Here we report how multifunctional Pd complexes with triaminoborane‐derived diphosphorus ligands, called TBDPhos, appear to facilitate borenium‐catalyzed cycloaddition reactions at the ligand, and Pd‐catalyzed Stille and Suzuki cross‐coupling reactions at the metal. Both transformations can be accessed in one pot to afford rare examples of tandem catalysis using separate metal and ligand catalysis sites in a single complex.
A Lewis Acid Stabilized Ketenimine in an Unusual Variant of the Electrophilic Aromatic Substitution
Authors: Surkau Jonas , Bläsing Kevin , Bresien Jonas , Michalik Dirk , Villinger Alexander , Schulz Axel 
Published: August 2022

AbstractElectrophilic aromatic substitution (EAS) can provide a straightforward approach to the efficient synthesis of functionalized complex aromatic molecules. In general, Lewis acids serve as a beneficial stimulus for the formation of a Wheland complex, the intermediate in the classical SEAr mechanism of EAS, which is responsible for H/E (E=electrophile) substitution under formal H+ elimination. Herein, we report an unusual variant of EAS, in which a complex molecule such as the tricyanomethane, HC(CN)3, is activated with a strong Lewis acid (B(C6F5)3) to the point where it can finally be used in an EAS. However, the Lewis acid here causes the isomerization of the tricyanomethane to the ketenimine, HN=C=C(CN)2, which in turn directly attacks the aromatic species in the EAS, with simultaneous proton migration of the aromatic proton to the imino group, so that no elimination occurs that is otherwise observed in the SEAr mechanism. By this method, it is possible to build up amino‐malononitrile‐substituted aromatic compounds in one step.
Templated Generation of a Bcl‐xL Inhibitor by Isomer‐Free SPAAC Based on Azacyclonon‐5‐yne
Authors: Brauer Juliane , Mötzing Marina , Gröst Corinna , Hoffmann Ralf , Berg Thorsten 
Published: August 2022

AbstractHigh‐affinity inhibitors of large protein–protein interactions often have a high molecular weight, which compromises their cell permeability and oral bioavailability. We recently presented isomer‐free, strain‐promoted azide‐alkyne cycloaddition (iSPAAC) as a method by which to generate large, chemically uniform bioactive molecules inside living cells from two smaller components with higher cell permeability. Here, we present the synthesis of Fmoc‐protected azacyclonon‐5‐yne (Fmoc‐ACN) as the first cyclononyne suitable for iSPAAC. ACN facilitated the structure‐guided development of a single‐digit micromolar triazole inhibitor of the protein–protein interaction domain of the antiapoptotic protein Bcl‐xL. Inhibitor formation in aqueous buffer at 37 °C, templated by the target protein Bcl‐xL, proceeded 2800 times faster than the reaction between Fmoc‐ACN and benzyl azide under standard conditions in acetonitrile. Our data demonstrate the utility of cyclononynes for iSPAAC and their potential for achieving vastly accelerated templated reactions in aqueous environments.
Enantioselective Approach for Expanding the Three‐Dimensional Space of Tetrahydroquinoline to Develop BET Bromodomain Inhibitors**
Authors: Lespinasse Marie‐Ange , Wei Kaiyao , Perrin Justine , Winkler Matthias , Hamaidia Sieme , Leroy Alexis , Macek Jilkova Zuzana , Philouze Christian , Marche Patrice N. , Petosa Carlo , Govin Jérôme , Emadali Anouk , Wong Yung‐Sing 
Published: August 2022

AbstractThe pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline‐catalyzed Mannich reaction followed by the addition of BF3 ⋅ OEt2, which generates a highly electrophilic aza‐ortho‐quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one‐pot process provides access for the first time to tetrahydroquinolines with acis‐2,3 andtrans‐3,4 configuration. As proof of concept, we demonstrate that a three‐step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2‐selective BET bromodomain inhibitor with anti‐inflammatory effect.
On the fluidization of cohesive powders: Differences and similarities between micro‐ and nano‐sized particle gas–solid fluidization
Authors: Kamphorst Rens , Wu Kaiqiao , Salameh Samir , Meesters Gabrie M. H. , van Ommen J. Ruud 
Published: August 2022

AbstractThe fluidization of cohesive powders has been extensively researched over the years. When looking at literature on the fluidization of cohesive particles, one will often find papers concerned with only micro‐ or only nano‐sized powders. It is, however, unclear whether they should be treated differently at all. In this paper, we look at differences and similarities between cohesive powders across the size range of several nanometres to 10s of micrometres. Classification of fluidization behaviour based on particle size was found to be troublesome since cohesive powders form agglomerates and using the properties of these agglomerates introduces new problems. When looking at inter‐particle forces, it is found that van der Waals forces dominate across the entire size range that is considered. Furthermore, when looking into agglomeration and modelling thereof, it was found that there is a fundamental difference between the size ranges in the way they agglomerate. Where the transition between the types of agglomeration is located is, however, unknown. Finally, how models are made and agglomerate sizes are measured is currently insufficient to accurately predict or measure their sizes consistently.
Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review
Authors: Jagpal Parbir K. , Alshareef Saad , Marriott John F. , Krishna Mamidipudi Thirumala 
Published: August 2022

AbstractBackgroundMultiple drug allergy and multiple drug intolerance syndrome (MDAS/MDIS) labels are an impediment to clinical care and knowledge regarding these conditions is limited. This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco‐economics of MDAS and MDIS.MethodsSystematic literature search across 11 databases (01 January 2000–06 November 2020) for MDIS, MDAS and related terminology. Studies were reviewed for quality of evidence and risk of bias by employing Critical Appraisal Skills Programme cohort study checklist. A narrative synthesis approach facilitated by systematic textual descriptions, tabulation and thematic analysis was adopted.ResultsThere was heterogeneity in terminology and methodology. Few studies applied standard drug allergy diagnostic methods. There is some evidence to suggest that multiple drug hypersensitivity syndrome (MDHS; i.e., confirmed allergies in MDAS) is a distinct clinical entity. Prevalence of MDIS and MDAS labels in unselected & selected populations varied between 2.1%–6.4% & 4.9%–90% and 1.2% & 0%–36% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co‐morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non‐steroidal anti‐inflammatory drugs. No studies relating to clinical impact and pharmaco‐economics were found.ConclusionThere is considerable burden of MDAS and MDIS labels. Data needs cautious interpretation as majority of studies described involved unverified labels. Despite this limitation and heterogeneity of studies, there is some evidence to suggest that MDHS is a distinct clinical entity. Well‐designed multi‐centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.
Interdisciplinary intervention for the management of nonmedical opioid use among patients with cancer pain
Authors: Arthur Joseph A. , Edwards Tonya , Lu Zhanni , Tang Michael , Amaram‐Davila Jaya , Reddy Akhila , Hui David , Yennurajalingam Sriram , Anderson Aimee E. , Jennings Kristofer , Reddy Suresh , Bruera Eduardo 
Published: August 2022

BackgroundFew studies have assessed interventions aimed at managing nonmedical opioid use (NMOU) behavior among patients with cancer. The authors developed the Compassionate High‐Alert Team (CHAT) intervention to manage patients receiving opioids for cancer pain who demonstrate NMOU behavior. The objective of this study was to determine the change in frequency of NMOU behaviors, pain intensity, and opioid requirements among those who received the intervention.MethodsA total of 130 patients receiving opioids for cancer pain that had documented evidence of NMOU and received the CHAT intervention were reviewed. Demographic and clinical information such as NMOU behaviors, pain scores, and morphine equivalent daily dose at baseline, 3, and 6 months post‐intervention was obtained.ResultsNMOU behaviors significantly decreased from a median (interquartile range) of 2 (1–3) at baseline to 0 (0–1) at both 3 and 6 months post‐intervention (p < .001). A total of 45 of 75 (60%) and 31 of 50 (62%) of CHAT recipients achieved complete response to the intervention at 3 and 6 months, respectively. Higher baseline number of NMOU behaviors was independently associated with patient response to the intervention (odds ratio [OR], 1.97; 95% confidence interval [CI],1.09–4.28, p = .049 at 3 months; OR, 2.5; 95% CI, 1.20–6.47, p = .03 at 6 months). The median pain score decreased from 7 at baseline to 6 at both 3 and 6 months (p = .01). Morphine equivalent daily dose did not significantly change during that same period (143 mg/day vs. 139 mg/day, p = .13).ConclusionsMost patients who received the CHAT intervention improved in their NMOU behaviors and pain intensity scores 3 and 6 months post‐intervention. These preliminary findings support the efficacy of CHAT in managing patients receiving opioids for cancer pain who demonstrate NMOU behavior.
Comparison of the performance of different learning algorithms in leaf feature extraction and recognition using convolution neural network
Authors: Kayhan Gökhan 
Published: August 2022

SummaryPlant identification with computer systems has been developed with image processing tools and has helped researchers to identify unknown plant species with high accuracy. In this study, the leaves of five different plants were classified according to their shapes using deep learning. A database was created with leaf images of mint, echinacea, St. John's wort, melissa, and thyme plants. Images in this database were classified with a convolution neural network (CNN). For this classification, 70% training and 30% testing were randomly selected in the database. The parameters of the CNN layer consist of a set of learnable filters. In the CNN, 10 kernel matrices with stride [1 1] were used. A rectified linear unit was chosen as the activation function. Maximum pooling was performed using a filter with stride [2 2]. In this classification, five fully connected layers were created. Using CNN, the performance of different learning algorithms was compared. It was observed that CNN achieved more successful results than traditional attribute methods.
Simultaneous Broadband Suppression of Homonuclear and Heteronuclear Couplings in 1H NMR Spectroscopy
Authors: Mycroft Coral , Nilsson Mathias , Morris Gareth A. , Castañar Laura 
Published: August 2022

AbstractThe 1H NMR analysis of species containing NMR‐active heteronuclei can be difficult due to signal overlap caused by the combined effects of homonuclear and heteronuclear scalar (J) couplings. Here, a general pure shift method is presented for obtaining ultra‐high resolution 1H NMR spectra where spectral overlap is drastically reduced by suppressing both homonuclear and heteronuclear J‐couplings, giving one single signal per 1H chemical environment. Its usefulness is demonstrated in the analysis of fluorine‐ and phosphorus‐containing compounds of pharmaceutical and biochemical interest.
Production of Eukaryotic Glycoproteins for Structural and Functional Studies Using Expi293F Cells
Authors: Greven Jessica A. , Brett Tom J. 
Published: August 2022

AbstractMilligram quantities of pure proteins are required for structural, functional, and pharmaceutical screening studies. These requirements can be challenging for a majority of important therapeutic targets that are secreted glycoproteins, receptors, membrane proteins, or large cytosolic complexes. Here, we present protocols for producing and purifying large amounts of secreted glycoproteins using the mammalian cell‐based Expi293F system via large‐scale transient transfection. This system can be easily adapted for the production of membrane proteins and large cytosolic complexes. The method can be utilized to quickly evaluate numerous expression constructs to identify optimal expressers. Use of mammalian cells ensures proper post‐translational modifications, including disulfide bonds and glycosylation, that can be important for accurate functional studies. In addition, minor modifications can be introduced to produce labeled or deglycosylated proteins for structural studies by X‐ray crystallography, nuclear magnetic resonance, or cryo‐electron microscopy. © 2022 Wiley Periodicals LLC.Basic Protocol 1: Production of milligram quantities of plasmid DNA for large‐scale transient transfectionBasic Protocol 2: Large‐scale culture and transient transfection of Expi293F cellsBasic Protocol 3: Purification of hexahistidine‐tagged proteins from medium
Different temporal trends in vascular plant and bryophyte communities along elevational gradients over four decades
Authors: Becker‐Scarpitta Antoine , Auberson‐Lavoie Diane , Aussenac Raphael , Vellend Mark 
Published: August 2022

AbstractDespite many studies showing biodiversity responses to warming, the generality of such responses across taxonomic groups remains unclear. Very few studies have tested for evidence of bryophyte community responses to warming, even though bryophytes are major contributors to diversity and functioning in many ecosystems. Here, we report an empirical study comparing long‐term change in bryophyte and vascular plant communities in two sites with contrasting long‐term warming trends, using “legacy” botanical records as a baseline for comparison with contemporary resurveys. We hypothesized that ecological changes would be greater in sites with a stronger warming trend and that vascular plant communities, with narrower climatic niches, would be more sensitive than bryophyte communities to climate warming. For each taxonomic group in each site, we quantified the magnitude of changes in species' distributions along the elevation gradient, species richness, and community composition. We found contrasted temporal changes in bryophyte vs. vascular plant communities, which only partially supported the warming hypothesis. In the area with a stronger warming trend, we found a significant increase in local diversity and dissimilarity (β‐diversity) for vascular plants, but not for bryophytes. Presence–absence data did not provide sufficient power to detect elevational shifts in species distributions. The patterns observed for bryophytes are in accordance with recent literature showing that local diversity can remain unchanged despite strong changes in composition. Regardless of whether one taxon is systematically more or less sensitive to environmental change than another, our results suggest that vascular plants cannot be used as a surrogate for bryophytes in terms of predicting the nature and magnitude of responses to warming. Thus, to assess overall biodiversity responses to global change, abundance data from different taxonomic groups and different community properties need to be synthesized.
Molting phenology of a lacustrine ringed seal, Pusa hispida saimensis
Authors: Niemi Marja , Nykänen Milaja , Biard Vincent , Kurkilahti Mika , Kunnasranta Mervi 
Published: August 2022

AbstractThe timing and effect of a range of environmental variables on the annual molt of ringed seals (Pusa hispida saimensis) in Lake Saimaa were studied in 2013–2019. Molting patterns were investigated by mixed models run on photoidentification data collected by camera trapping and digital camera surveys. Photoperiod was the predominant environmental variable affecting the molt but molting of females was also linked to air temperature and ice thickness. The cumulative proportion of molting seals peaked around the 18th–20th May, when day length reached 18 h. The main molting season, when most of the seals were hauled out at the same time, lasted on average for 16 days with considerable inter‐annual differences in the duration (range 11–22 days). The results provide important baseline information on Saimaa ringed seal molt. Continued monitoring is important as the molt is an energetically demanding period for the seals, and any changes in molting behavior may indicate changes in habitat or in environmental conditions.
Impact of hydrological processes on wetland landscapes and wintering migratory birds in a large floodplain lake (Poyang Lake, China)
Authors: Du Fei , Wang Shiyan , Han Zhen , Liu Xiaobo , Liu Chang , Huang Aiping , Chen Kaiqi , Zhao Shilin , Wang Liang , Jiang Zhi 
Published: August 2022

AbstractHydrological processes are an important factor influencing the wetland landscapes and the quality of wintering migratory birds habitat in Poyang Lake. However, most of the research on a small spatiotemporal scale and there is a lack of studies on the impact of hydrological processes on migratory bird habitats. This study analysed the response of the Poyang Lake wetland landscape to low water levels from 1990 to 2016 and determined the relationship between hydrological processes, wetland landscape characteristics and migratory bird habitats. According to the results, the number of days during the study period when the maximum water level was higher than the current water level (MaxDay) and the average water level from the 40th to 50th day prior to the current day (D50) are two critical factors affecting the area of grassland in Poyang Lake. In particular, a D50 value of 9.5–11.0 m is important for maintaining the grassland area and growth of wetland vegetation. Besides, the water level should not exceed 11 m from mid–late October to early November and should be maintained between 7.58 and 7.97 m in mid–late December that can maximize the habitat area of migratory birds. Furthermore, this study used ecological threshold to propose the optimal inundation period of Cyperus rotundus L. community, Leersia japonica community, Polygonum criopolitanum community, Phragmites australis community, Triarrhena lutarioriparia community, Carex spp. community and Phalaris arundinacea community, which are 124–174, 31–101, 199–249, 65–147, 51–121, 110–190 and 175–253 days, respectively.