bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation into the effect of skin tone modulators and exogenous stress on skin pigmentation utilizing a novel bioengineered skin equivalent
Authors: Goncalves Kirsty , De Los Santos Gomez Paola , Costello Lydia , Smith Lucy , Mead Hugh , Simpson Amy , Przyborski Stefan 
Published: September 2022

AbstractHuman skin equivalents (HSEs) are a popular technology due to limitations in animal testing, particularly as they recapitulate aspects of structure and function of human skin. Many HSEs contain two basic cell types to model dermal and epidermal compartments, however this limits their application, particularly when investigating the effect of exogenous stressors on skin health. We describe the development of a novel platform technology that accurately replicates skin pigmentation in vitro. Through incorporation of melanocytes, specialized pigment producing cells, into the basal layer of the epidermis we are able to re‐create skin pigmentation in vitro. We observe apical distribution of melanin within keratinocytes and formation of supranuclear caps (SPNCs), only when the epidermal compartment is co‐cultured with a dermal compartment, leading to the conclusion that fibroblast support is essential for correct pigment organization. We also evaluate the commonly observed phenomenon that pigmentation darkens with time in vitro, which we further explore through mechanical exfoliation to remove a build‐up of melanin deposits in the stratum corneum. Finally, we demonstrate the application of a pigmented HSE to investigate drug modulation of skin tone and protection from UV‐induced damage, highlighting the importance of such a model in the wider context of skin biology.
Radium‐223 dichloride treatment in metastatic castration‐resistant prostate cancer in Finland: A real‐world evidence multicenter study
Authors: Hyväkkä Anniina , Kääriäinen Okko‐Sakari , Utriainen Tapio , Löyttyniemi Eliisa , Mattila Kalle , Reinikainen Petri , Sormunen Jorma , Jääskeläinen Minna , Auvinen Päivi , Minn Heikki , Sundvall Maria 
Published: September 2022

AbstractBackgroundRadium‐233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium‐223 compared to best supportive care in castration‐resistant prostate cancer (CRPC) with bone metastases. However, real‐world data are also needed with wider inclusion criteria.MethodsWe report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium‐223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium‐223 in Finland in 2014–2019.ResultsThe median overall survival (OS) was 13.8 months (range 0.5–57 months), and the median real‐world progression‐free survival (rwPFS) was 4.9 months (range 0.5–29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium‐223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p < 0.0001). High prostate‐specific antigen (PSA) level (≥100 μg/L) before radium‐223 treatment was associated with poor OS compared to low PSA level (<20 μg/L) (p = 0.0001). Most patients (57%) experienced pain relief. Pain relief indicated better OS (p = 0.002). Radium‐223 treatment was well tolerated. Toxicity was mostly low grade. Only 12.5% of the patients had grade III–IV adverse events, most commonly anemia, neutropenia, leucopenia, and thrombocytopenia.ConclusionRadium‐223 was well tolerated in routine clinical practice, and most patients achieved pain relief. Pain relief, ALP normalization, lower baseline PSA, and PSA decrease during radium‐223 treatment were prognostic for better survival. The efficacy of radium‐223 in mCRPC as estimated using OS was comparable to earlier randomized trial in this retrospective real‐world study. Our results support using radium‐223 for mCRPC patients with symptomatic bone metastases even in the era of new‐generation androgen receptor‐targeted agents.
The hepatocellular carcinoma modified Gustave Roussy Immune score (HCC‐GRIm score) as a novel prognostic score for patients treated with atezolizumab and bevacizumab: A multicenter retrospective analysis
Authors: Hatanaka Takeshi , Naganuma Atsushi , Hiraoka Atsushi , Tada Toshifumi , Hirooka Masashi , Kariyama Kazuya , Tani Joji , Atsukawa Masanori , Takaguchi Koichi , Itobayashi Ei , Fukunishi Shinya , Tsuji Kunihiko , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Ogawa Chikara , Nishimura Takashi , Shimada Noritomo , Kawata Kazuhito , Kosaka Hisashi , Kakizaki Satoru , Tanaka Takaaki , Ohama Hideko , Nouso Kazuhiro , Morishita Asahiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Okubo Tomomi , Arai Taeang , Imai Michitaka , Koizumi Yohei , Nakamura Shinichiro , Kaibori Masaki , Iijima Hiroko , Hiasa Yoichi , Kumada Takashi ,   the Real‐life Practice Experts for HCC (RELPEC) Study Group, and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Published: September 2022

AbstractAimThis study investigated whether or not the hepatocellular carcinoma modified Gustave Roussy Immune Score (HCC‐GRIm‐Score) serves as a prognostic indicator for HCC patients treated with atezolizumab and bevacizumab (Atez/Bev).MethodsA total of 405 HCC patients who received Atez/Bev from September 2020 to January 2022 at 22 different institutions were included in this retrospective study. The HCC‐GRIm score was based on the combination of the albumin level (<3.5 g/L = 1 point), lactate dehydrogenase (≥245 U/L = 1 point), neutrophil‐to‐lymphocyte ratio (≥4.8 = 1 point), aspartate aminotransferase‐to‐alanine aminotransferase ratio (≥1.44 = 1 point), and total bilirubin level (≥1.3 mg/dl = 1 point). Patients were divided into the low‐score group (0, 1, or 2 points) and the high‐score group (3, 4, or 5 points).ResultsThere were 89 (22.0%), 141 (34.8%), 106 (26.2%), 49 (12.1%), 16 (4.0%), and 4 (1.0%) patients with scores of 0, 1, 2, 3, 4, 5, respectively. The progression‐free survival (PFS) in the low‐score group was significantly longer than that in the high‐score group (median 7.8 vs. 3.5 months, p < 0.001). The median overall survival (OS) of the low‐score group was not reached at the time cutoff, with a 1‐year survival rate of 75.5%, whereas the median OS of the high‐score group was 8.5 months, showing a significant difference (p < 0.001). A high HCC‐GRIm score was a significant unfavorable factor associated with the PFS and OS in multivariate analyses (p = 0.002 and p < 0.001, respectively).ConclusionsThe HCC‐GRIm score serves as a novel prognostic score for HCC patients treated with Atez/Bev.
Should a luxury Brand's Chatbot use emoticons? Impact on brand status
Authors: Li Yuan , Shin Hyunju 
Published: September 2022

AbstractLuxury brands are increasingly adopting chatbots for online customer service. But, little is known about the role of adding design features such as emoticons on customers' luxury experience. This study fills this research gap by exploring the influence of a luxury brand chatbot's adoption of emoticons on status perception and its underlying mechanisms. Results from two experiments suggest that luxury brands might be better off not using emoticons in chatbot communications because it dampens the brand status perception due to perceived unexpectedness, which in turn decreases the perception of the appropriateness of the interaction with chatbots. However, this negative effect of luxury brand's use of emoticons in chatbot communication only exists for traditional luxury brands, not for masstige brands. This study advances the literature on AI, particularly regarding luxury brand‐specific chatbot applications. It also offers insights for luxury brand managers that they should be cautious in adopting emoticons in chatbot communication given the risk of ruining the brand status, especially when the brand is a traditional luxury brand as opposed to a masstige brand.
Thin‐Plate Superstructures of the Immunogenic 33‐mer Gliadin Peptide
Authors: Herrera Maria Georgina , Amundarain Maria Julia , Nicoletti Franscesco , Drechsler Marcus , Costabel Marcelo , Gentili Pier Luigi , Dodero Veronica Isabel 
Published: September 2022

AbstractGluten related‐disorders have a prevalence of 1–5 % worldwide triggered by the ingestion of gluten proteins in wheat, rye, barley, and some oats. In wheat gluten, the most studied protein is gliadin, whose immunodominant 33‐mer amino acid fragment remains after digestive proteolysis and accumulates in the gut mucosa. Here, we report the formation of 33‐mer thin‐plate superstructures using intrinsic tyrosine (Tyr) steady‐state fluorescence anisotropy and cryo‐TEM in combination with water tension measurements. Furthermore, we showed that fluorescence decay measurements of 33‐mer intrinsic fluorophore Tyr provided information on the early stages of the formation of the thin‐plate structures. Finally, conformational analysis of Tyr residues using minimalist models by molecular dynamic simulations (MD) demonstrated that changes in Tyr rotamer states depend on the oligomerization stage. Our findings further advance the understanding of the formation of the 33‐mer gliadin peptide superstructures and their relation to health and disease.
Plasma‐electrified up‐carbonization for low‐carbon clean energy
Authors: Zhou Rusen , Zhao Yadong , Zhou Renwu , Zhang Tianqi , Cullen Patrick , Zheng Yao , Dai Liming , Ostrikov Kostya (Ken) 
Published: September 2022

AbstractLow‐value, renewable, carbon‐rich resources, with different biomass feedstocks and their derivatives as typical examples, represent virtually inexhaustive carbon sources and carbon‐related energy on Earth. Upon conversion to higher‐value forms (referred to as “up‐carbonization” here), these abundant feedstocks provide viable opportunities for energy‐rich fuels and sustainable platform chemicals production. However, many of the current methods for such up‐carbonization still lack sufficient energy, cost, and material efficiency, which affect their economics and carbon‐emissions footprint. With external electricity precisely delivered, discharge plasmas enable many stubborn reactions to occur under mild conditions, by creating locally intensified and highly reactive environments. This technology emerges as a novel, versatile technology platform for integrated or stand‐alone conversion of carbon‐rich resources. The plasma‐based processes are compatible for integration with increasingly abundant and cost‐effective renewable electricity, making the whole conversion carbon‐neutral and further paving the plasma‐electrified up‐carbonization to be performance‐, environment‐, and economics‐viable. Despite the chief interest in this emerging area, no review article brings together the state‐of‐the‐art results from diverse disciplines and underlies basic mechanisms and chemistry underpinned. As such, this review aims to fill this gap and provide basic guidelines for future research and transformation, by providing an overview of the application of plasma techniques for carbon‐rich resource conversion, with particular focus on the perspective of discharge plasmas, the fundamentals of why plasmas are particularly suited for up‐carbonization, and featured examples of plasma‐enabled resource valorization. With parallels drawn and specificity highlighted, we also discuss the technique shortcomings, current challenges, and research needs for future work.
Chiral Primary Amine Catalyzed α‐Arylation of Simple Ketones via Asymmetric Retro‐Claisen Cleavage
Authors: Han Yanfang , Shi Mingying , Mi Xueling , Luo Sanzhong 
Published: September 2022

AbstractHighly enantioselective α‐arylation of simple ketones has been achieved by chiral primary amine catalyzed asymmetric retro‐Claisen cleavage of β‐diketones. This mild organocatalytic strategy enables the construction of α‐aryl tertiary carbon stereocenters in good yields and excellent enantioselectivities (up to 98 % ee) with the para‐quinone monoimines as aryl sources. Furthermore, oxidative catalytic asymmetric α‐arylation has also been realized with free p‐aminophenols.
A Stereodivergent Approach to the Synthesis of gem‐Diborylcyclopropanes
Authors: Hanania Nicole , Nassir Molhm , Eghbarieh Nadim , Masarwa Ahmad 
Published: September 2022

AbstractWe report a designed stereodivergent strategy for the synthesis of gem‐diborylcyclopropanes. The reaction provides a highly modular approach to prepare cyclopropane ring variants bearing gem‐(Bpin,Bpin), gem‐(Bpin,Bdan), and gem‐(Bpin,BF3K), with outstanding levels of stereocontrol. This was achieved by diastereoselective Pd‐catalyzed cyclopropanation reactions of gem‐diborylalkenes with α‐diazoarylacetates and α‐diazoaryl‐trifluoromethyl. The key to the success of this general protocol was the diastereoselective trifluorination reaction of gem‐diborylcyclopropanes, followed by the stereospecific interconversion of the trifluoroborate salts into the Bdan group.
Selective and Reversible Solvent Uptake in Tetra‐4‐(4‐pyridyl)phenylmethane‐based Supramolecular Organic Frameworks
Authors: Marchetti Danilo , Portone Francesca , Mezzadri Francesco , Dalcanale Enrico , Gemmi Mauro , Pedrini Alessandro , Massera Chiara 
Published: September 2022

AbstractThe dynamic behavior of supramolecular organic frameworks (SOFs) based on the rigid tetra‐4‐(4‐pyridyl)phenylmethane (TPPM) organic tecton has been elucidated through 3D electron diffraction, X‐ray powder diffraction and differential scanning calorimetry (DSC) analysis. The SOF undergoes a reversible single‐crystal‐to‐single‐crystal transformation when exposed to vapours of selected organic solvents, moving from a closed structure with isolated small voids to an expanded structure with solvated channels along the b axis. The observed selectivity is dictated by the fitting of the guest in the expanded SOF, following the degree of packing coefficient. The effect of solvent uptake on TPPM solid‐state fluorescence was investigated, evidencing a significant variation in the emission profile only in the presence of chloroform.
Clinical predictors of survival in real world practice in stage IV melanoma
Authors: Hu Hsien‐Pang , Archer Christine , Yip Desmond , Peters Geoffrey 
Published: September 2022

AbstractBackground and AimWhile studies continually identify new clinical prognostic factors in stage IV melanoma, the introduction of targeted and immunotherapies have revolutionised the prognosis of advanced melanoma since 2011. The study aims to investigate the prognostic significance of past and newly identified clinical factors in a contemporary cohort.MethodsA retrospective analysis of The Canberra Hospital melanoma database identified 161 patients with Stage IV melanoma between 2011 and 2017. Survival was analysed by demographics and clinical factors with chi‐square tests to determine significance. Logistic binary regression was performed to test the independence of the clinical factors on predicting the survival outcome.ResultsOverall, the 3‐month, 6‐month, 9‐month, and 12‐month stage IV melanoma survival rate of our cohort was 79%, 67%, 55%, and 45%, respectively. Age, sex, and BRAF mutation status were found to have no impact on survival, whereas M1d category of the American Joint Committee on Cancer (AJCC) staging (8th edition), neutrophil‐lymphocyte ratio (NLR) >3, elevated serum LDH, more than three metastatic sites, brain metastases, poorer Eastern cooperative oncology group (ECOG) status were associated with poorer survival. Binary logistic regression test identified AJCC staging, NLR (cutoff score 3), LDH, and brain metastases as independent prognostic factors.ConclusionMost clinical factors investigated in this study were found to have a statistically significant impact on survival, with AJCC (8th edition) staging M1a‐M1d, NLR (cutoff score 3), LDH, and brain metastases identified as independent prognostic factors in stage IV melanoma from a contemporary cohort treated with targeted therapies and immunotherapies.
Explaining the High Catalytic Activity in Bis(indenyl)methyl Zirconium Cation Using Combined EDA‐NOCV/QTAIM Approach
Authors: Kenouche Samir , Bachir Nassima , Martínez‐Araya Jorge I. 
Published: September 2022

AbstractThe main purpose of this study is to elucidate some discrepancies already observed in the catalytic activity values of some zirconocene methyl cations. The EDA‐NOCV scheme was employed for a theoretical description of the interactions between an ethylene molecule and five catalysts of zirconocene methyl cation. The nature of the chemical interactions has been elucidated through the QTAIM topological analysis. The steric hindrance due to the ligands was evaluated qualitatively by means of an IRI‐based analysis and quantitively through Fisher information. The findings prove that the indenyl ligand seems to favor the orbital interaction between the ethylene molecule and the metal centre of zirconocene methyl cation. Both electrostatic and orbital contributions play a crucial role in stabilising the studied complexes. Based on the NOCV deformation density contributions, the strongest orbital interaction is reached with the bis(indenyl)methyl zirconium cation, which is the only one exhibiting covalent interactions. Especially, the strong contribution of π‐back donation (occurring from the occupied orbitals of the zirconium atom to the π* anti‐bonding orbital of ethylene) may be a key to understand why this catalyst has a higher polymerisation yield than the other studied catalysts. This work suggests a perspective for predicting values of catalytic activity when theoretically designing novel catalysts of zirconocene type.
Flow cytometry immunophenotypic features of pure erythroid leukemia and the distinction from reactive erythroid precursors
Authors: Fang Hong , Wang Sa A. , You M. James , Hu Shimin , Miranda Roberto N. , Tang Zhenya , Lin Pei , Jorgensen Jeffrey L. , Xu Jie , Thakral Beenu , Schlette Ellen J. , El Hussein Siba , Bueso‐Ramos Carlos , Medeiros L. Jeffrey , Wang Wei 
Published: September 2022

AbstractBackgroundThe immunophenotype of pure erythroid leukemia (PEL) as determined by flow cytometry immunophenotypic analysis is not well characterized. The immunophenotypic difference between PEL and reactive conditions is under‐explored.MethodsWe assessed and compared the immunophenotype of 24 PEL cases and 28 reactive cases containing early erythroid precursors by flow cytometry.ResultsThe neoplastic erythroid cells in all PEL cases were positive for CD36 and CD71. CD45 was also positive in all cases, but the expression level was often dimmer than granulocytes. CD117 expression ranged from partial to uniform, and CD235a was often only positive in the CD117‐dim to negative cells, corresponding to more differentiated subset. PEL cases frequently (87%) showed decreased or negative CD38 expression, contrasting to reactive early erythroid precursors that showed bright CD38 (p < 0.0001). CD7 (25%) and CD13 (29%) aberrant expressions were only observed in PEL but not in the reactive erythroid cells. Normal early erythroid precursors in all reactive bone marrows showed partial expression of CD4; In contrast, aberrant CD4 expression was detected in 71% PEL cases, either uniformly positive (50%) or completely negative (21%). While normal/reactive bone marrows almost always contained a small subset of CD34‐positive early erythroid precursors, the neoplastic pronormoblasts in all PEL cases were CD34 negative. Although not increased in number, CD34‐positive myeloblasts were frequently detected in PEL and demonstrated an aberrant immunophenotype in 90% PEL cases.ConclusionsPEL shows a distinctive immunophenotype which can be distinguished from reactive erythroid precursors by flow cytometry immunophenotyping.
Design, synthesis, and structure–activity relationship of caffeine‐based triazoles as dual AChE and BACE‐1 inhibitors
Authors: Sharma Mohit , Sharma Ankita , Nuthakki Vijay K. , Bhatt Shipra , Nandi Utpal , Bharate Sandip B. 
Published: September 2022

AbstractNatural products have significantly contributed to drug discovery for neurodegenerative diseases. Caffeine is one of the well‐known central nervous system(CNS)‐active natural products. Besides its CNS stimulant properties, it is a mild inhibitor of acetylcholinesterase (AChE) and possesses memory‐enhancing properties. The present work aimed to improve the AChE inhibition activity of the caffeine. The rationally designed caffeine‐based triazoles were synthesized and evaluated in vitro for cholinesterase and β‐site amyloid precursor protein cleaving enzyme‐1 (BACE‐1) inhibitory activities. The attachment of triazole to the caffeine enhances its AChE inhibition activity from half‐maximal inhibitory concentration (IC50) of 129 µM to 0.49 µM (derivative, 6l). The caffeine core interacts with the peripheral anionic site, whereas the benzyl triazole occupies the catalytic anionic site located at the bottom of the active site gorge. The structure–activity relationship revealed that the four‐atom ester linker is superior to shorter linkers for connecting the caffeine core to the triazole. The 2,6‐difluorobenzyl triazole‐linked caffeine derivative, 6d, exhibits dual inhibition of AChE and BACE‐1 with IC50 values of 1.43 and 10.9 µM, respectively. The derivative 6d inhibits AChE via a mixed‐type mode with an inhibition rate constant (Ki) value of 2.35 μM, which was corroborated by docking studies. The triazole 6d has an acceptable stability profile in human liver microsomes (t1/2 = 54 min) and was found to possess CNS permeability when evaluated using the parallel artificial membrane permeability blood–brain barrier assay. The results presented herein warrant investigating caffeine‐based triazoles in preclinical models of Alzheimer's disease.