bluuebunny/crossref_metadata_2025 huggingface dataset:
Spent silkworm pupae as a renewable and sustainable source for biodiesel
Authors: Halada Nandakrishnan Meenakshi , Dhanavel Nandhini , C.B Mohan , P.G Radhakrishna , V.H Maharaddi , Reddy Narendra
Published: September 2022

Global silk production generates about 1 million tons of spent pupae annually that are generally discarded as waste but could be used to generate about 240 million liters of biodiesel every year. Spent pupae contain about 30–40% oil, 30–40% proteins and about 20–30% carbohydrates which comprise a low‐cost, renewable and sustainable source for production of biofuels, particularly biodiesel. Some studies indicate the potential of converting the pupa oil into biodiesel but there are no reports on the detailed characteristics and the properties and performance of the pupa biodiesel. In this study, oil was obtained from the pupae using mechanical and Soxhlet extraction with yield of up to 95%. The oil was transesterified using acid and alkaline catalysts under different processing conditions. A conversion ratio of more than 90% from oil to biodiesel was possible. Pupae diesel had characteristics similar to regular synthetic‐based diesel with calorific value of between 44 41 MJ kg−1. Pupae diesel was blended up to 50% with regular diesel and performance of the pure and blended fuel was tested on an engine test rig. Engine performance tests showed that the pupa diesel did not compromise the efficiency and produced emissions within the stipulated standards. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd.
Ingenieurmodell zur Vermeidung des Trümmerflugs bei Kontaktdetonation
Authors: Zircher Tobias
Published: September 2022

Die Sicherung wichtiger militärischer und politischer Infrastruktur gegen potenzielle terroristische Angriffe ist von großer Bedeutung. Hierzu sind Bauteile aus Stahlfaserbeton sehr gut geeignet und können mit dem beschriebenen Ingenieurmodell dimensioniert werden. Als Grundlage für die Entwicklung eines Ingenieurmodells wurden in der Vergangenheit Versuche mit hohen Belastungsgeschwindigkeiten aus Kontaktdetonation an aus Normal‐ und Stahlfaserbeton hergestellten Platten durchgeführt und ausgewertet. Die dabei bestimmten Kenngrößen und anhand der Bruchbilder gewonnenen Erkenntnisse dienten nun als Eingangsparameter zur Entwicklung eines Ingenieurmodells. Das Ziel der Entwicklung des Ingenieurmodells war es, in Abhängigkeit von der dynamischen Betonzugfestigkeit, der Bauteildicke und der Größe der Kontaktdetonationsladung zu bestimmen, welche Menge Stahlfasern in Vol.‐% erforderlich ist, um einen Trümmerflug auf der lastabgewandten Seite der Platte zu vermeiden. Dazu wird die aus der Kontaktdetonation erzeugte kinetische Abplatzenergie in der Platte bestimmt und im Anschluss die aufnehmbare kinetische Energie des Stahlfaserbetons in Abhängigkeit vom Stahlfasergehalt ermittelt. Um die ingenieurpraktische Verwendung zu gewährleisten, wurden die Resultate in einem Diagramm abgebildet. Somit ist es durch einfaches Ablesen möglich, den rechnerisch erforderlichen Stahlfasergehalt in Vol.‐% zur Vermeidung des Trümmerflugs auf der lastabgewandten Seite der Platte zu bestimmen.
Production, health‐promoting properties and characterization of bioactive peptides from cereal and legume grains
Authors: Aderinola Taiwo Ayodele , Duodu Kwaku Gyebi
Published: September 2022

The search for bioactive components for the development of functional foods and nutraceuticals has received tremendous attention. This is due to the increasing awareness of their therapeutic potentials, such as antioxidant, anti‐inflammatory, antihypertensive, anti‐cancer properties, etc. Food proteins, well known for their nutritional importance and their roles in growth and development, are also sources of peptide sequences with bioactive properties and physiological implications. Cereal and legume grains are important staples that are processed and consumed in various forms worldwide. However, they have received little attention compared to other foods. This review therefore is geared towards surveying the literature for an appraisal of research conducted on bioactive peptides in cereal and legume grains in order to identify what the knowledge gaps are. Studies on bioactive peptides from cereal and legume grains are still quite limited when compared to other food items and most of the research already carried out have been done without identifying the sequence of the bioactive peptides. However, the reports on the antioxidative, anticancer/inflammatory, antihypertensive, antidiabetic properties show there is much prospect of obtaining potent bioactive peptides from cereal and legume grains which could be utilized in the development of functional foods and nutraceuticals.
Mechanism and properties of emerging nanostructured hydrogen storage materials
Authors: Liu Shiyuan , Shui Jianglan
Published: September 2022

Hydrogen storage technology is one of the main challenges that restrict hydrogen utilization. Although there has been great progress in the research of hydrogen storage materials, seldom can they fulfill the criteria for onboard applications. Here, we focus on some innovative materials with complicated nanostructures and distinctive interactions with hydrogen, which may provide promising prospects. Recent advances in nano‐sized hydrides, catalytic adsorbents, multilayered materials, amorphous metal hydrides, and porous materials with open metal sites are discussed. We analyze the current problems of these hydrogen storage materials and provide suggestions for future development.
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

Human 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

Background

Radium‐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.

Methods

We 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.

Results

The 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.

Conclusion

Radium‐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

Aim

This 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).

Methods

A 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).

Results

There 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).

Conclusions

The 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

Luxury 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

Gluten 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

Low‐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

Highly 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

We 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

The 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

Background and Aim

While 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.

Methods

A 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.

Results

Overall, 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.

Conclusion

Most 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

The 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

Background

The 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.

Methods

We assessed and compared the immunophenotype of 24 PEL cases and 28 reactive cases containing early erythroid precursors by flow cytometry.

Results

The 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.

Conclusions

PEL 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

Natural 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.
Hyperkalaemia as a cause of undertreatment with mineralocorticoid receptor antagonists in heart failure
Authors: Henrysson Josefin , Thunström Erik , Chen Xiaojing , Fu Michael , Basic Carmen
Published: September 2022

Aims

To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up‐titration of guideline‐directed medical therapy (GDMT) in real‐world settings.

Methods

A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up‐titration.

Results

Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up‐titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P < 0.0001), had lower EF (P = 0.022), had higher NTproBNP (P = 0.017), had lower eGFR (P = 0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P < 0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6 months of up‐titration of GDMT (P < 0.0001). Among four groups, the incidence of hyperkalaemia throughout up‐titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P < 0.0001). In the MRA‐naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6 months of up‐titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively.

Conclusions

Hyperkalaemia increased significantly during up‐titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.
An examination of diversity rationales: How instrumental and moral diversity rationales create minority spotlight
Authors: Chaney Kimberly E.
Published: September 2022

Past research has demonstrated that organizations rationalize their commitment to diversity for instrumental or moral reasons that are differentially preferred by marginalized and privileged groups. Across four studies, the present research contends that privileged group members view instrumental diversity contexts as affording them educational opportunities and view moral diversity contexts as expecting them to afford (meta‐affordances) marginalized group members inclusion, both resulting in a minority spotlight. Moreover, marginalized group members view these diversity rationales through an inverse lens with moral diversity contexts affording them inclusion and instrumental diversity contexts resulting in education meta‐affordances and anticipated minority spotlight. The present findings advance research on implications of diversity rationales, particularly their effect on the attention privileged groups pay to marginalized groups, and marginalized groups’ (accurate) anticipation of this attention.
Research on the generality of icon sizes based on visual attention
Authors: Yan Wen , Zhang Xuwei , Deng Li , Liu Zhiyu
Published: September 2022

Icon size is one of the key factors affecting the efficiency of information search. The advent of the era of intelligent interaction has made it difficult for icon design to meet the requirements of noncontact, large information volume, and high precision proposed by natural interaction technology in the future. At the same time, with the continuous improvement of display technology, the display resolution has been increased from 720 P to 8 K. Different sizes of display carriers use different resolutions. In order for icons to have efficient recognition at different display resolutions, it is necessary to obtain the best proportional relationship between icon size and display resolution. This paper summarizes the existing relevant research, calculates the ratio of recommended icon size and display resolution as the research variables, and comprehensively evaluates the recommended optimal ratio range of 1:641–1:334 through eye movement, EEG and behavioral response experiments and entropy‐weight TOPSIS method, providing a reference for icon design in various forms of interactive interfaces in the future.
The state of pediatric tuberous sclerosis complex epilepsy care: Results from a national survey
Authors: Whitney Robyn , Zak Maria , Haile Denait , Nabavi Nouri Maryam
Published: September 2022

Objective

Epilepsy associated with tuberous sclerosis complex (TSC) can be challenging to treat and is associated with significant disease burden. Our objective was to better understand the state of epilepsy care of TSC amongst pediatric neurologists in Canada, identify gaps in care and determine whether access to a dedicated TSC clinic has an impact on epilepsy management.

Methods

A survey was developed after a literature review and discussion amongst two pediatric epileptologists and one nurse practitioner with expertise in TSC about the state of epilepsy care of TSC patients in Canada. Canadian pediatric neurologists were asked to participate in sharing their experiences via an anonymous web‐based survey through the Canadian League Against Epilepsy (CLAE) and the Canadian Neurological Sciences Federation (CNSF).

Results

Fifty‐seven responses were received. Access to a dedicated TSC clinic was reported by 25% (n = 14). Sixty percent (n = 34) reported performing serial EEG monitoring in infants with TSC and 57% (n = 33) started prophylactic antiseizure therapy when EEG abnormalities were detected, regardless of whether there was access to a TSC clinic (P = .06 andP = .29, respectively). While 52% (n = 29) did not feel comfortable prescribing mTORi for epilepsy, 65% (n = 36) indicated they would consider it with additional training. Epilepsy surgery was offered in 93% (n = 13) of centers with a dedicated TSC clinic but only 45% of centers without a TSC clinic (n = 19) (P = .002).

Significance

Our findings demonstrate the variability in neurological care of pediatric patients with TSC as it pertains to epilepsy management. There is a need for the establishment of epilepsy practice guidelines and a national network to support clinical practice, research, and education.
Groundwater potential mapping based on long time series remote sensing data in Penghu Islands, China
Authors: Cheng Zijian , Cui Huiru , Wang Daqing , Xu Haoli , Wang Yi , Lu Zhao , Zhao Xiaoning , Shi Yue , Lian Xiaoying , Tao Guolin
Published: September 2022

Islands are special bodies of land surrounded by seawater. Many islands are facing water shortages as the demand for groundwater increases, thus, highlighting the importance and urgency of the assessment, planning, and management of island groundwater resources. To facilitate the same, the groundwater potential of the Penghu Islands in China was assessed for the first time using remote sensing (RS), geographic information system (GIS), and the analytic hierarchy process (AHP). Long‐term series remote sensing studies were also conducted to monitor the dynamic change in groundwater potential and to identify groundwater potential areas. In this study, the geological environment factors were normalized, and their weight was allocated based on the AHP of RS and GIS. The groundwater potential assessment (GPA) index, established using the weighted comprehensive algorithm, was used to analyse groundwater potential and demarcate groundwater potential zones. Finally, the trend in the spatio‐temporal variation of groundwater potential was analysed using long‐term series remote sensing data. The results from 2015 to 2021 showed that the Penghu Islands can be divided into five groundwater potential zones of different grades, such as 6.3%–8.1% of grade I, 22.2%–24.2% of grade II, 23%–24.4% of grade III, 19.6%–21% of grade IV, and 25.1%–25.5% of grade V. The results of the GPA were verified by comparing them with the abundance of water‐content rock formation in hydrogeologic maps, which yielded correlation coefficients of 78.3%–88.9%. Overall, the groundwater potential zones of different grades in the study area tended to be stable all year‐round, including the zones of grades I and II. The results of this study highlighted the reliability of predicting groundwater potential based on long‐term series remote sensing data and its usability to local personnel in appropriate groundwater resource planning and management.
Incidence of childhood leukemia before and after shut down of nuclear power plants in Germany in 2011: A population‐based register study during 2004 to 2019
Authors: Russo Antonello , Blettner Maria , Merzenich Hiltrud , Wollschlaeger Daniel , Erdmann Friederike , Gianicolo Emilio
Published: September 2022

The association between leukemia and proximity to nuclear‐power‐plants (NPPs) has been assessed in several countries with inconsistent results. A case‐control study from Germany had shown an increased risk for childhood leukemia (diagnoses 1980‐2003) near NPPs. Germany began shutting down nuclear reactors in 2011, following the Fukushima disaster. We tested whether the previously observed association between leukemia and proximity to NPP persisted despite the shutdown. We used an ecological study design to investigate the incidence of leukemia during 2004 to 2019 in children aged 0 to 14 years living near NPPs where at least one reactor was shut down in 2011. We defined study and control areas as municipalities whose surface area was at least 75% within 10 km or between 10 and 50 km of NPPs, respectively. We calculated age‐standardized rates and incidence rate ratios (IRR) using control‐areas as the reference. We also computed standardized incidence ratios (SIR) separately for each NPP using incidence rates of the German population as a reference. IRR decreased from 1.20 (95% confidence interval: 0.81‐1.77) in 2004 to 2011 to 1.12 (0.75‐1.68) in 2012 to 2019. Analyses of single plants showed an excess of childhood leukemia during 2004 to 2019 for the Unterweser‐NPP, based only on three cases, and the Krümmel‐NPP (n = 14; SIR: 1.98, 1.17‐3.35). We found slightly decreasing of leukemia incidence rate ratios after the shutdown of nuclear reactors in 2011. Due to the small number of cases, risk estimates have large uncertainty. Further research including a longer follow‐up is warranted. The consistent excess of incidence cases around Krümmel may require analytical epidemiological analysis.
A sound velocity method for determining isobaric specific heat capacity
Authors: Pei Jun , Li Hezhang , Zhuang Hua‐Lu , Dong Jinfeng , Cai Bowen , Hu Haihua , Li Jing‐Wei , Jiang Yilin , Su Bin , Zhao Li‐Dong , Li Jing‐Feng
Published: September 2022

Isobaric specific heat capacity (Cp) is an important parameter not only in physics but also for most materials. Its accurate measurement is particularly critical for performance evaluation of thermoelectric materials, but the experiments by differential scanning calorimetry (DSC) often lead to large uncertainties in the measurements, especially at elevated temperatures. In this study, we propose a simple method to determine Cp by measuring the sound velocity (υ) based on lattice vibration and expansion theory. The relative standard error of the υ is smaller than 1%, showing good accuracy and repeatability. The calculated Cp at elevated temperature (>300 K) increases slightly with increasing temperature due to the lattice expansion, which is more reasonable than the Dulong–Petit value.

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An alternative construction of the Hermitian unital 2‐(28, 4, 1) design
Authors: Inoue Koichi
Published: September 2022

In this paper, we give an alternative construction of the Hermitian unital 2‐(28, 4, 1) design in such a way that it is constructed on the isotropic vectors in a unitary geometry of dimension 3 over the field . As a corollary, we can construct a unique 3‐(10, 4, 1) design (namely, the Witt system ).
Conditional inactivation of the L‐type amino acid transporter LAT1 in chondrocytes models idiopathic scoliosis in mice
Authors: Iwahashi Sayuki , Lyu Jiajun , Tokumura Kazuya , Osumi Ryoma , Hiraiwa Manami , Kubo Takuya , Horie Tetsuhiro , Demura Satoru , Kawakami Noriaki , Saito Taku , Park Gyujin , Fukasawa Kazuya , Iezaki Takashi , Suzuki Akane , Tomizawa Akane , Ochi Hiroki , Hojo Hironori , Ohba Shinsuke , Hinoi Eiichi
Published: September 2022

Scoliosis, usually diagnosed in childhood and early adolescence, is an abnormal lateral curvature of the spine. L‐type amino acid transporter 1 (LAT1), encoded by solute carrier transporter 7a5 (Slc7a5), plays a crucial role in amino acid sensing and signaling in specific cell types. We previously demonstrated the pivotal role of LAT1 on bone homeostasis in mice, and the expression of LAT1/SLC7A5 in vertebral cartilage of pediatric scoliosis patients; however, its role in chondrocytes on spinal homeostasis and implications regarding the underlying mechanisms during the onset and progression of scoliosis, remain unknown. Here, we identified LAT1 in mouse chondrocytes as an important regulator of postnatal spinal homeostasis. Conditional inactivation of LAT1 in chondrocytes resulted in a postnatal‐onset severe thoracic scoliosis at the early adolescent stage with normal embryonic spinal development. Histological analyses revealed that Slc7a5 deletion in chondrocytes led to general disorganization of chondrocytes in the vertebral growth plate, along with an increase in apoptosis and a decrease in cell proliferation. Furthermore, loss of Slc7a5 in chondrocytes activated the general amino acid control (GAAC) pathway but inactivated the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the vertebrae. The spinal deformity in Slc7a5‐deficient mice was corrected by genetic inactivation of the GAAC pathway, but not by genetic activation of the mTORC1 pathway. These findings suggest that the LAT1‐GAAC pathway in chondrocytes plays a critical role in the maintenance of proper spinal homeostasis by modulating cell proliferation and survivability.
Single‐cell RNA‐seq reveals interferon‐induced guanylate‐binding proteins are linked with sarcopenia
Authors: Peng Zhi , Zhang Ruoyu , Kuang Xiaolin , Yu Chen , Niu Shiwei , Du Yongjun , Lu Di , Li Shaobo , Teng Zhaowei , Lu Sheng
Published: September 2022

Background

Sarcopenia is defined as an age‐related progressive loss of muscle mass and/or strength. Although different factors can contribute to this disease, the underlying mechanisms remain unclear. We assessed transcriptional heterogeneity in skeletal muscles from sarcopenic and control mice at single‐cell resolution.

Methods

A mouse model was established to study sarcopenic skeletal muscles. Single‐cell RNA‐seq was performed on tibialis anterior (TA) muscle cells collected from sarcopenic and control mice. A series of bioinformatic analyses were carried out to identify and compare different cell types under different conditions. Immunofluorescence staining and western blotting were used to validate the findings from single‐cell experiments. Tube formation assays were conducted to further evaluate the effects of Gbp2 on endothelial cells during angiogenesis.

Results

A murine sarcopenia model was successfully established using a senescence‐accelerated mouse strain (SAMP6, n = 5). Sarcopenia phenotype was induced by administration of dexamethasone (20 mg/kg) and reduced physical activity. Senescence‐resistant mice strain (SAMR1) and SAMP6 strain with similar activity but injected with PBS were recruited as two control groups. As signs of sarcopenia, body weight, muscle cell counts and cross‐sectional fibre area were all significantly decreased in sarcopenic mice (P value = 0.004, 0.03 and 0.035, respectively). After quality control, 13 612 TA muscle single‐cell transcriptomes were retained for analysis. Fourteen cell clusters were identified from the profiled cells. Among them, two distinct endothelial subtypes were found to be dominant in the sarcopenia group (42.2% cells) and in the two control groups (59.1% and 47.9% cells), respectively. 191 differentially expressed genes were detected between the two endothelial subtypes. Sarcopenia‐specific endothelial cell subtype exhibited a dramatic increase in the interferon family genes and the interferon‐inducible guanylate‐binding protein (GBP) family gene expressions. For example, Igtp and Gbp2 in sarcopenic endothelial cells were 5.4 and 13.3 times higher than those in the control groups, respectively. We further validated our findings in muscle specimens of sarcopenia patients and observed that GBP2 levels were increased in endothelial cells of a subset of patients (11 of 40 patients, 27.5%), and we identified significantly higher CD31 and GBP2 co‐localization (P value = 0.001128). Finally, we overexpressed Gbp2 in human umbilical vein endothelial cells in vitro. The endothelial cells with elevated Gbp2 expression displayed compromised tube formation.

Conclusions

Our single‐cell‐based results suggested that endothelial cells may play critical roles in sarcopenia development through interferon‐GBP signalling pathways, highlighting new therapeutic directions to slow down or even reverse age‐related sarcopenia.
ILC3-like ILC2 subset increases in minimal persistent inflammation after acute type II inflammation of allergic rhinitis and inhibited by Biminkang: Plasticity of ILC2 in minimal persistent inflammation
Authors: Chen Xiang-Jing , Liu Cheng , Zhang Shan , Zhang Li-Feng , Meng Wei , Zhang Xin , Sun Meng , Zhang Yue , Wang Ren-Zhong , Yao Cheng-Fang
Published: September 2022

Minimal persistent inflammation (MPI), the local inflammation that occurs after an acute type II immune response in patients with allergic rhinitis (AR), is responsible for airway hyperreactivity and the recurrence of AR. Innate lymphoid cells (ILCs) play a crucial role in mucosal immune homeostasis, but the changes of ILC subsets in the MPI stage remain unclear. In this study, the levels of ILC-secreting cytokines in nasal lavages were analyzed from 19 AR patients and 8 healthy volunteers. AR and MPI model mice were established to study the ILC subsets. The results showed that IL-17A was significantly increased in nasal lavage of AR patients in the MPI stage by MSD technology. When compared with the AR model mice, the frequency of IL-13+ILC2 in the nasal mucosa and lungs decreased, while IL-5+ILC2 remain high in MPI model mice. A part of the IL-5+ILC2 subset displayed ILC3-like characteristics with elevated RORγt, IL-17A and IL-23R expression. Especially, these ILC3-like ILC2 exhibited up-regulation of GATA3+RORγt+ were increased in MPI model mice. After the treatment of Biminkang, the frequencies of IL-5+ILC2, IL-17A+ILC3, and GATA3+RORγt+ILC3-like ILC2 were significantly reduced, and IL-23R expression was also decreased on ILC3-like-ILC2 subset. These results suggested that the elevated IL-17A in the MPI stage has been related to or at least partly due to the increased of ILC3-like ILC2. Biminkang could effectively decrease IL-17A+ILC3 and inhibit ILC3-like ILC2 subset in the MPI stage. Biminkang is effective in administrating MPI by regulating airway ILC homeostasis.
Development of variant‐proof severe acute respiratory syndrome coronavirus 2, pan‐sarbecovirus, and pan‐β‐coronavirus vaccines
Authors: Zhou Jie , Liu Zezhong , Zhang Guangxu , Xu Wei , Xing Lixiao , Lu Lu , Wang Qian , Jiang Shibo
Published: September 2022

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants with high transmission rates and striking immune evasion have posed a serious challenge to the application of current first‐generation SARS‐CoV‐2 vaccines. Other sarbecoviruses, such as SARS‐CoV and SARS‐related coronaviruses (SARSr‐CoVs), have the potential to cause outbreaks in the future. These facts call for the development of variant‐proof SARS‐CoV‐2, pan‐sarbecovirus or pan‐β‐CoV vaccines. Several novel vaccine platforms have been used to develop vaccines with broad‐spectrum neutralizing antibody responses and protective immunity to combat the current SARS‐CoV‐2 and its variants, other sarbecoviruses, as well as other β‐CoVs, in the future. In this review, we discussed the major target antigens and protective efficacy of current SARS‐CoV‐2 vaccines and summarized recent advances in broad‐spectrum vaccines against sarbecoviruses and β‐CoVs.