bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrochemical Generation of Hypervalent Bromine(III) Compounds
Authors: Sokolovs Igors , Mohebbati Nayereh , Francke Robert , Suna Edgars
Published: April 2021

In sharp contrast to hypervalent iodine(III) compounds, the isoelectronic bromine(III) counterparts have been little studied to date. This knowledge gap is mainly attributed to the difficult‐to‐control reactivity of λ3‐bromanes as well as to their challenging preparation from the highly toxic and corrosive BrF3 precursor. In this context, we present a straightforward and scalable approach to chelation‐stabilized λ3‐bromanes by anodic oxidation of parent aryl bromides possessing two coordinating hexafluoro‐2‐hydroxypropanyl substituents. A series of para‐substituted λ3‐bromanes with remarkably high redox potentials spanning a range from 1.86 V to 2.60 V vs. Ag/AgNO3 was synthesized by the electrochemical method. We demonstrate that the intrinsic reactivity of the bench‐stable bromine(III) species can be unlocked by addition of a Lewis or a Brønsted acid. The synthetic utility of the λ3‐bromane activation is exemplified by oxidative C−C, C−N, and C−O bond forming reactions.
Synthesis of reactive self‐adhesive branched polyurethane dispersant for textile pigment printing
Authors: Zeng Tengchao , He Guiping , Li Xinxiang , Wang Chaoxia
Published: April 2021

A series of reactive branched polyurethane dispersants (BPUs) were successfully synthesized based on epoxy as reactive group and nitrogen‐containing heterocycles as anchoring group. The branched polyurethane was adopted an ''A2 + B3'' approach with diisocyanate prepolymer and trimethylolpropane. The structure, molecular weight, and thermodynamic property of BPUs were characterized. The pigment dispersions were prepared with BPUs as the dispersant by ball milling, and then the characteristic parameters such as pigment particle size, viscosity, stability, color properties, and fastness were evaluated. Excellent dispersing performances were observed that the particle size of five dispersions were below 200 nm, with the viscosity as low as 6–9 mPa·s. It is worth noting that the pigment dispersion prepared by BPU exhibited excellent stability and self‐adhesive performance. These dispersions were printed on cotton fabrics without adhesives, their water washing fastness was approximately grade 4. And the dry rubbing and wet rubbing fastnesses were 3 and 2–3, respectively.
The research progress in recording layer of the inkjet printing materials
Authors: Chen Juxiang , Zhang Ke , Zhang Kuiyuan , Yang Lei , Jiang Bo
Published: April 2021

Inkjet printing has become a prevailing printing technology due to its practicability and rapidity. The color inkjet printing as one of the inkjet printing has color comprehensive and high clarity compared with traditional printing. The key point of the color inkjet printing is the introducing of special recording layer which has great influence on the printing quality. However, the printing quality of the color inkjet printing depends on the compositions and performance of the recording layer and the infiltration behavior between the ink and the recording layer. Specially, the theoretical study of the infiltration behavior between the ink and the recording layer is the key to guiding the structural design. In this review, the types and compositions of the recording layer were clearly analyzed, the process and evaluation methods of ink infiltration and the performance evaluation system of the recording layer were also summarized. Ultimately, the current bottleneck and the development trend of the recording layer were put forward.
Carbon Nanofiber and Poly[2‐(methacryloyloxy) ethyl] Trimethylammonium Chloride Composite as a New Benchmark Carbon‐based Electrocatalyst for Sulfide Oxidation
Authors: Aziz Abdul , Shah Syed Shaheen , Jafar Mazumder Mohammad A. , Oyama Munetaka , Al‐Betar Abdul‐Rahman
Published: April 2021

There is an overwhelming desire to develop new sulfide oxidation electrocatalysts that perform at low potentials and exhibit high current density for the removal and efficient sensing of sulfide. This article describes a comparative electrochemical analysis of various commercially available carbon materials and polymer/surfactant composite electrocatalysts for direct electrooxidation of sulfide in an aqueous solution. The composites were prepared from five different carbon materials multiwalled carbon nanotubes, fullerene‐C60, graphene, glassy carbon, and carbon nanofibers (CNF) and four different polymers: chitosan, polyvinylidene fluoride, Nafion, and indigenously synthesized poly[2‐(methacryloyloxy)ethyl] trimethylammonium chloride (PMTC). The carbon@polymer composites were prepared by a simple ultrasonication technique, and the electrodes were prepared by drop‐drying the prepared composite on indium tin oxide (ITO) substrates. The CNF@PMTC showed the highest positive zeta potential that allowed an accumulation of many negatively charged sulfide ions at the CNF@PMTC surface. Cyclic voltammetry was used for the electrooxidation of sulfide in an aqueous solution of tris buffer (0.05 M; pH 8.0) and KNO3 (0.1 M). The lowest sulfide oxidation peak potential (i. e., −51 mV vs. standard hydrogen electrode) with a high catalytic current response (730 μA/cm2) of the CNF@PMTC‐modified ITO electrode among the tested and previously reported carbon‐based electrode materials make it ideal for direct sulfide electrooxidation. Taking this and its simple preparation method into account, CNF@PMTC can be considered a benchmark carbon‐based electrocatalyst for sulfide oxidation.
Ein Hochhaus mit Hüftschwung
Authors: Pfeifer Matthias
Published: April 2021

Mitte des Jahres 2020 wurde in Frankfurt am Main im derzeitigen Hochhaus‐Boom ein ungewöhnliches Exemplar fertiggestellt. Der ca. 190 m hohe Omniturm gehört zwar weder in Frankfurt geschweige denn weltweit zu den höchsten Hochhäusern, wurde jedoch aufgrund verschiedener Merkmale, seiner architektonischen Strahlkraft und der damit verbundenen tragwerkstechnischen Herausforderungen Finalist beim International Highrise Award 2020 und gehört damit zu den fünf besten Hochhäusern weltweit. Vom 14. bis zum 23. Geschoss rotieren und verschieben sich die Ebenen um mehrere Meter gegen die Vertikale. Dies ist der durch Wohnungen genutzte sog. RESI‐Bereich. Die übrigen Geschosse werden, bis auf die öffentlichen Basisgeschosse, durch Büros genutzt. Die schlanken Schleuderbetonstützen aus hochfestem Beton mit Sonderstahl folgen, deutlich schräg stehend, den Verschiebungen und Verdrehungen, vereinigen sich im unteren Drittel des RESI‐Bereichs in zwei Gebäudeecken von je zweien zu einer Stütze, durchlaufen in gekrümmter Linie den RESI‐Bereich, um sich schließlich im oberen Drittel wieder in je zwei Stützen zu teilen und dann gerade bis zur Spitze des Turms durchzulaufen. An den gegenüberliegenden Gebäudeecken führen die Verschiebungen zu immer größer werdenden Auskragungen der Decken, denen mit zusätzlichen „Rucksackstützen“ begegnet wird. In diesem Beitrag werden einige konstruktive Besonderheiten des Bauwerks beschrieben.
Bioinformatics and experimental findings reveal the therapeutic actions and targets of pachymic acid against cystitis glandularis
Authors: Feng Zihao , Shi Hailin , Liang Bojian , Ge Tianyu , Cai Menghui , Liu Feng , Huang Kunping , Wen Jintao , Chen Qiuhong , Ge Bo
Published: April 2021

Pachymic acid (PA), a bioactive ingredient isolated from Poria cocos Wolf, is reported with potential benefits of anti‐inflammatory, anti‐oxidative actions. It is reasoned that PA may play the potential benefits against cystitis glandularis (CG), an inflammation of the bladder tissue. In this study, we aimed to apply the network pharmacology and molecular docking analyses to reveal concrete anti‐CG targets and mechanisms of PA, and then the bioinformatic findings were verified by using clinical and animal samples. The methodological data from network pharmacology approach showed that 303 and 243 reporting targets of CG and PA, and other 31 shared targets of CG and PA were identified. Subsequently, all top targets of PA against CG were screened out, including cyclooxygenase‐2, epidermal growth factor receptor, tumor antigen p53 (TP53), tumor necrosis factor‐alpha (TNF), interleukin‐1 (IL‐1) beta, proto‐oncogene c‐jun. Molecular docking data demonstrated that PA exerted potent bonding capacities with TNF, TP53 proteins in CG. In human study, the findings suggested that overactivated TNF‐α expression and suppressed TP53 activation were detected in CG samples. In animal study, PA‐treated mice showed reduced intravesical IL‐1, IL‐6 levels, and lactate dehydrogenase content, downregulated TNF‐α and upregulated TP53 proteins in bladder samples. Taken together, our bioinformatics and experimental findings identify the key anti‐CG biotargets and mechanisms of PA. More markedly, these pivotal pharmacological targets of PA against CG have been screened out and verified by using computational and experimental analyses.
Curcumin: A small molecule with big functionality against amyloid aggregation in neurodegenerative diseases and type 2 diabetes
Authors: Radbakhsh Shabnam , Barreto George E. , Bland Abigail R. , Sahebkar Amirhossein
Published: April 2021

Amyloidosis is a concept that implicates disorders and complications that are due to abnormal protein accumulation in different cells and tissues. Protein aggregation‐associated diseases are classified according to the type of aggregates and deposition sites, such as neurodegenerative disorders and type 2 diabetes mellitus. Polyphenolic phytochemicals such as curcumin and its derivatives have anti‐amyloid effects both in vitro and in animal models; however, the underlying mechanisms are not understood. In this review, we summarized possible mechanisms by which curcumin could interfere with self‐assembly processes and reduce amyloid aggregation in amyloidosis. Furthermore, we discuss clinical trials in which curcumin is used as a therapeutic agent for the treatment of diseases linking to protein aggregates.
Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration
Authors: Saffari Tiam M. , Chan Katelyn , Saffari Sara , Zuo Kevin J. , McGovern Renee M. , Reid Joel M. , Borschel Gregory H. , Shin Alexander Y.
Published: April 2021

The application of scaffold‐based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration‐approved immunosuppressant) has been explored. In this study, a fibrin gel‐based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose‐derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic‐co‐glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01 and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug‐released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.
Revisiting mouse minute virus inactivation by high temperature short time treatment
Authors: Su Joleen , Rice Jonathan , Hoffman Jacob , Alvarado Shelley , Bailey Mark , Kopp Martina , Murphy Marie , Kiss Robert , Barone Paul W. , Wiebe Michael E. , Springs Stacy L. , Dehghani Houman , Chen Dayue
Published: April 2021

In recent years, high temperature short time (HTST) treatment technology has been increasingly adopted for medium treatment to mitigate the potential risk of viral contamination in mammalian cell culture GMP manufacturing facilities. Mouse minute virus (MMV), also called minute virus of mice (MVM), implicated in multiple viral contamination events is commonly used as a relevant model virus to assess the effectiveness of HTST treatment of cell culture media. However, results from different studies vary broadly in inactivation kinetics as well as log reduction factors (LRFs) achieved under given treatment conditions. To determine whether the reported discrepancies stemmed from differences in MMV strains, laboratory‐scale HTST devices, medium matrices, and/or experimental designs, we have taken a collaborative approach to systematically assess the effectiveness of HTST treatment for MMV inactivation. This effort was conceptualized based on a media treatment gap analysis conducted by the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) under the MIT Center for Biomedical Innovation (CBI). Specifically, two different MMV strains were used to evaluate the effectiveness of HTST at various treatment conditions with regard to exposure temperature and hold time duration by two independent laboratories within two different companies. To minimize experimental variations, the two sites used the same batches of MMV stocks, the same commercially purchased medium, and the same model of thermocyclers as the laboratory‐scale HTST device. The two independent laboratories yielded similar MMV inactivation kinetics and comparable LRF. No significant differences were observed between the two MMV strains evaluated, suggesting that the variations from prior studies were likely due to differences in equipment, medium matrices, or other factors. The data presented here indicate that MMV inactivation by HTST treatment obeys first‐order kinetics and can be mathematically modeled using an Arrhenius equation. The model‐based extrapolation provides a quantitative estimate of MMV inactivation by the current industry standard HTST condition (102°C for a hold time of 10 s) used for medium treatment. Finally, based on the data from the current study and the industry experience, it is recommended that any alternative virus barrier technologies adopted for medium treatment should provide a clearance of at least 3.0 LRF based on a worst‐case model virus to effectively mitigate potential risks of viral contamination.
Overview of the virtual 2020 FDA's circulatory system devices advisory panel on Neovasc reducer system
Authors: Medranda Giorgio A. , Torguson Rebecca , Waksman Ron
Published: April 2021

Refractory angina is considered a devastating condition with limited medical and therapeutic options. The Neovasc Reducer device, when implanted in the coronary sinus, is designed to alleviate anginal symptoms. However, the available clinical data are sparse. The US Food and Drug Administration (FDA) assembled the Circulatory Systems Devices Panel to discuss the Reducer's safety and effectiveness. Because of the coronavirus disease 2019 pandemic, this meeting was held virtually. In this manuscript, we detail the deliberation and discussion among the circulatory panel members, including their final vote.
CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study
Authors: Aranzulla Tiziana Claudia , Piazza Salvatore , Ricotti Andrea , Musumeci Giuseppe , Gaggiano Andrea
Published: April 2021

Background

While the experience with PCSK9i in patients with coronary artery disease has been wide, and coronary plaque regression has been documented, little is known regarding the role of these drugs on carotid plaque regression. The CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study is a randomized, single‐center, investigator‐initiated trial aiming at evaluating carotid plaque morphological stabilization and regression following, respectively, 6 and 12 months of therapy with evolocumab.

Methods

Asymptomatic patients with uni‐ or bilateral de novo carotid artery stenosis ≥50% and LDL‐C values ≥100 mg/dl despite maximum tolerated lipid lowering therapy (LLT) will be randomized to evolocumab 140 mg s.c. every 2 weeks on top of ongoing LLT, or no additional treatment. 100 patients (50 in each arm) will be enrolled. Serial carotid duplex ultra‐sonography will be performed to monitor the carotid plaque morphology and stenosis over time.

Results

The primary end point of the study is, (a) carotid plaque morphological stabilization at 6 months, defined as defined as the disappearance of ulcerations and fluffy components and the achievement of a regular plaque morphology with prevalence of fibrous atheroma and/or (b) carotid plaque regression at 12 months, defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared with baseline.

Conclusion

The CARUSO trial will test the superiority of evolocumab on top of ongoing LLT versus ongoing LLT alone regarding carotid plaque morphological stabilization and regression. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Metal Cation‐Driven Dynamic Covalent Formation of Imine and Hydrazone Ligands Displaying Synergistic Co‐catalysis and Auxiliary Amine Effects
Authors: He Meixia , Lehn Jean‐Marie
Published: April 2021

Optimizing C=N bond formation and C/N component exchange has major significance in Dynamic Covalent Chemistry (DCC). Imine and hydrazone generation from their aldehyde, amine and hydrazine components showed large accelerations in presence of AgOTf or Zn(OTf)2, up to 104 for the Zn(II)‐(p‐anisidine)imine complex. Zn(OTf)2 and auxiliary p‐anisidine together accelerated 630 times the formation of the Zn(II)‐hydrazone complex, revealing a strong synergistic effect, traced to very fast initial formation of the reactive Zn(II)‐imine complex presenting a C=N bond metallo‐activated towards reaction with the hydrazine component. Reactions involving more entities showed kinetically faster and thermodynamically simpler outputs due to dynamic competition within a mixture of higher complexity. Catalytic amounts of metal salts and auxiliary amine gave similar marked rate accelerations and turnover, indicating true catalysis. The synergistic effect achieved by combining metallo‐ and organo‐catalysis points to a powerful co‐catalysis strategy of bond‐formation in DCC through interconnected chemical transformations.
Vacant Manganese‐Based Perovskite Fluorides@Reduced Graphene Oxides for Na‐Ion Storage with Pseudocapacitive Conversion/Insertion Dual Mechanisms
Authors: Huang Yongfa , Ding Rui , Ying Danfeng , Yan Tong , Huang Yuxi , Tan Caini , Sun Xiujuan , Gao Ping , Liu Enhui
Published: April 2021

Na‐ion capacitors (NICs) and Na‐based dual‐ion batteries (Na‐DIBs) have been considered to be promising alternatives to traditional lithium‐ion batteries (LIBs) because of the abundance and low cost of the Na‐ion, but their energy density, power density and life cycle are limited. Herein, dual‐vacancy (including K+ and F− vacancies) perovskite fluoride K0.86MnF2.69@reduced graphene oxide (rGO; recorded as Mn−G) as anode for NICs and Na‐DIBs has been developed. The special conversion/intercalation dual Na‐ion energy storage mechanism and pseudocapacitive dynamics are analyzed in detail. The Mn−G//AC NICs and Mn−G//KS6 Na‐DIBs delivered a maximum energy density of 92.7 and 187.6 W h kg−1, a maximum power density of 20.2 and 21.12 kW kg−1, and long cycle performance of 61.3 and 68.4 % after 1000 cycles at 5 A g−1, respectively. Moreover, Mn−G//AC NICs and Mn−G//KS6 Na‐DIBs can work well over a wide range of temperatures (−20 to 40 °C). These results make it competitive in Na‐ion storage applications with high energy/power density over a wide temperature range.
Exploring the use of high solid loadings in enzymatic hydrolysis to improve biobutanol production from brewers' spent grains
Authors: Plaza Pedro E. , Coca Mónica , Lucas Yagüe Susana , Fernández‐Delgado Marina , López‐Linares Juan C. , García‐Cubero María T.
Published: April 2021

Brewers' spent grain (BSG) is a promising agroindustrial waste for the production of biobutanol. One critical point in the butanol production process is the optimization of the enzymatic hydrolysis step. In order to obtain the maximum efficiency, it is necessary to use high solids loadings in this process to obtain high concentrations of monosaccharides that allow high titres of butanol to be produced in the ABE fermentation process. The optimum enzyme and solids load maximizing the monosaccharide concentrations and minimizing the phenolic compounds concentrations in the enzymatic hydrolysates from pretreated BSG have been investigated. A dilute sulphuric acid pretreatment was carried out previously to the optimization of the enzymatic hydrolysis. Under optimal conditions (28.1% w/w solids load and 15.4 FPU/g DM), 47.0 g/L of glucose, 16.8 g/L of xylose, and 1.2 g/L of phenolic compounds were attained in the enzymatic hydrolysates. The enzymatic hydrolysates were subjected to an ABE fermentation process (with and without previous detoxification with activated carbon) to evaluate the production of butanol by C. beijerinckii. Maximum global yields of 31.0 g butanol/kg pretreated BSG and 46.4 g ABE/kg pretreated BSG were obtained. The detoxification process had little to no effect on the ABE fermentation process.
New Quinoxaline‐Based Blue Emitters: Molecular Structures, Aggregation‐Induced Enhanced Emission Characteristics and OLED Application
Authors: Mao Xiaoyu , Xie Fuli , Wang Xiaohui , Wang Qingsong , Qiu Zhipeng , Elsegood Mark R. J. , Bai Jie , Feng Xing , Redshaw Carl , Huo Yanping , Hu Jian‐Yong , Chen Qing
Published: April 2021

Main observation and conclusion

Three new deep blue light emitters, bearing quinoxaline with different substituents (biphenyl/pyrene) at the 1‐ or 2‐position, were synthesized by a Pd‐catalysed coupling reaction in high yields, and were fully characterized by 1H/13C NMR spectroscopy, single crystal X‐ray diffraction, and high‐resolution mass spectrometry (HRMS). The designed molecules exhibit good thermal stability (Tg > 452 oC). Single crystal X‐ray diffraction indicated the compounds containing pyrene units exhibiting π‐π stacking, and thus this family of compounds exhibited intramolecular charge transfer (ICT) and non‐typical and aggregation‐induced enhanced emission (AIEE) characteristics, possessing blue emission both in solution and in the aggregation (solid) state. Furthermore, a selected deep blue emitter was utilized as the emitting layer for the fabrication of doped organic light‐emitting diode (OLED) devices, which afforded a deep blue electroluminescence (EL) peak at 428 nm with a narrow full width at half maximum (FWHM) of 57 nm, and the Commission Internationale de L'Eclairage (CIE) chromaticity coordinates of (0.15, 0.06).
Clinical Pharmacology Worldwide: A Global Health Perspective
Authors: Wenning Larissa , Pillai Goonaseelan (Colin) , Knepper Todd C. , Ilic Katarina , Ali Ali Mohamed , Hibma Jennifer E.
Published: April 2021

Low‐ and middle‐income countries (LMICs) have the highest rates of mortality and morbidity globally, but lag behind high‐income countries in the number of clinical trials and trained researchers, as well as research data pertaining to their populations. Lack of local clinical pharmacology and pharmacometrics expertise, limited training opportunities, and lack of local genomic data may contribute to health inequalities and limit the application of precision medicine. Continuing to develop health care infrastructure, including well‐designed clinical pharmacology training and data collection in LMICs, can help address these challenges. International collaboration aimed at improving training and infrastructure and encouraging locally driven research and clinical trials will be of benefit. This review describes several examples where clinical pharmacology expertise could be leveraged, including opportunities for pharmacogenomic expertise that could drive improved recommendations for clinical guidelines. Also described are clinical pharmacology and pharmacometrics training programs in Africa, and the personal experience of a Tanzanian researcher currently on a training sabbatical in the United States, as illustrative examples of how training in clinical pharmacology can be effectively implemented in LMICs. These training efforts will benefit from advocacy for employment opportunities and career development pathways for clinical pharmacologists that are gradually being recognized and developed in LMICs. Clinical pharmacologists have a key role to play in global health, and development of training and research infrastructure to advance this expertise in LMICs will be of tremendous benefit.
Targeted Use of Placebo Effects Decreases Experimental Itch in Atopic Dermatitis Patients: A Randomized Controlled Trial
Authors: Sölle Ariane , Worm Margitta , Benedetti Fabrizio , Sabine Bartholomäus Theresa , Schwender‐Groen Lena , Klinger Regine
Published: April 2021

Evidence from pain research shows that the effectiveness of active pharmacological treatments can be enhanced by placebo effects. The “open drug administration” is superior to "hidden drug administration.​" In a randomized controlled trial, we aimed to show that the targeted use of placebo effects increases the efficacy of an antihistamine (dimetindene) infusion in participants with atopic dermatitis. We openly infused dimetindene (drug) in full sight with information (intervention group 1: OPEN‐DRUG+INST), openly infused drug with an additional classical conditioning learning experience (intervention group 2: OPEN‐DRUG+INST+COND) or infused drug without any information or sight (i.e., hidden administration (control group 1: HIDDEN‐DRUG)). Control group 2 received a placebo infusion (saline) declared as dimetindene and also experienced the conditioning experience (PLAC+INST+COND). Itch was experimentally induced with histamine via a skin prick test. Outcome was assessed at the subjective (primary end point: experimental itch intensity, numeric rating scale), and objective level (secondary end point: wheal size, mm2). Experimental‐induced itch intensity decreased in all groups but at different rates (P < 0.001). The groups with the open administration, whether it was dimetindene or placebo, had significantly stronger reductions in itch compared to the HIDDEN‐DRUG group (OPEN‐DRUG+INST+COND: P < 0.001; OPEN‐DRUG+INST: P = 0.009; and PLAC+INST+COND: P < 0.001). Additional drug conditioning mediated via expectation led to a stronger reduction of itching (P = 0.001). Results on wheal size were similar (P = 0.048), however, no significant difference between the HIDDEN‐DRUG group and the PLAC+INST+COND group (P = 0.967) was found. We conclude that specifically generated targeted placebo effects can significantly increase the action of a drug (dimetindene) and should be used in clinical practice.
IL‐17 drives salivary gland dysfunction via inhibiting TRPC1‐mediated calcium movement in Sjögren’s syndrome
Authors: Xiao Fan , Du Wenhan , Zhu Xiaoxia , Tang Yuan , Liu Lixiong , Huang Enyu , Deng Chong , Luo Cainan , Han Man , Chen Ping , Ding Liping , Hong Xiaoping , Wu Lijun , Jiang Quan , Zou Hejian , Liu Dongzhou , Lu Liwei
Published: April 2021

Objectives

This study aims to determine a role of interleukin‐17A (IL‐17) in salivary gland (SG) dysfunction and therapeutic effects of targeting IL‐17 in SG for treating autoimmune sialadenitis in primary Sjögren’s syndrome (pSS).

Methods

Salivary IL‐17 levels and IL‐17‐secreting cells in labial glands of pSS patients were examined. Kinetic changes of IL‐17‐producing cells in SG from mice with experimental Sjögren’s syndrome (ESS) were analysed. To determine a role of IL‐17 in salivary secretion, IL‐17‐deficient mice and constructed chimeric mice with IL‐17 receptor C (IL‐17RC) deficiency in non‐hematopoietic and hematopoietic cells were examined for saliva flow rates during ESS development. Both human and murine primary SG epithelial cells were treated with IL‐17 for measuring cholinergic activation‐induced calcium movement. Moreover, SG functions were assessed in ESS mice with salivary retrograde cannulation of IL‐17 neutralisation antibodies.

Results

Increased salivary IL‐17 levels were negatively correlated with saliva flow rates in pSS patients. Both IL‐17‐deficient mice and chimeric mice with non‐hematopoietic cell‐restricted IL‐17RC deficiency exhibited no obvious salivary reduction while chimeric mice with hematopoietic cell‐restricted IL‐17RC deficiency showed significantly decreased saliva secretion during ESS development. In SG epithelial cells, IL‐17 inhibited acetylcholine‐induced calcium movement and downregulated the expression of transient receptor potential canonical 1 via promoting Nfkbiz mRNA stabilisation. Moreover, local IL‐17 neutralisation in SG markedly attenuated hyposalivation and ameliorated tissue inflammation in ESS mice.

Conclusion

These findings identify a novel function of IL‐17 in driving salivary dysfunction during pSS development and may provide a new therapeutic strategy for targeting SG dysfunction in pSS patients.
Assessment of fog gauges and their effectiveness in quantifying fog in the Andean páramo
Authors: Berrones Gina , Crespo Patricio , Wilcox Bradford P. , Tobón Conrado , Célleri Rolando
Published: April 2021

In tropical highlands of the northern Andes, known as páramos, fog incidence is very frequent. Its quantification is not yet clear, mostly because of the complexity of distinguishing between fog and low‐intensity rainfall. Moreover, there is uncertainty about the performance of the various types of gauges used to capture fog in this ecosystem. This study was carried out at the Zhurucay Ecohydrological Observatory (3,800 m a.s.l.), in southern Ecuador, assessing two cylindrical (Juvik and Wire Harp types) and two flat‐screen fog collection gauges. A high‐resolution laser disdrometer was installed next to the fog gauges, to measure precipitation of very low intensities and isolate fog from rainfall. We collected data over a 12‐month period for four types of events—fog only, fog dominant, fog non‐dominant and fog negligible. We evaluated the performance of the gauges during each type of event as well as to estimate the amount, rate and duration of fog. Fog was present during 68% of the days of the study, predominantly in the early morning and at night, and the average daily contribution was 1.37 mm. Most of the events occurred at rates below 0.3 mm h−1. Measured rainfall was 1,200.1 mm, and fog estimations amounted to 340.1 mm. This fog contribution could bring total annual precipitation to about 1,540.2 mm, suggesting an extra 22% of water potentially available to the ecosystem—a very important asset for hydrological and ecological processes. This is the first study that has compared different types of fog gauges in the Andean páramo.
Diagnostic discrepancy in second opinion reviews of primary epithelial neoplasms involving salivary gland: An 11‐year experience from a tertiary referral center focusing on useful pathologic approaches and potential clinical impacts
Authors: Xu Bin , Ghossein Ronald , Ho Alan , Viswanathan Kartik , Khimraj Anjanie , Saliba Maelle , Cracchiolo Jennifer R. , Katabi Nora
Published: April 2021

Aims

In the era of precision medicine, accurate pathologic diagnoses are crucial for appropriate management.

Methods

We herein described the histologic features and clinical impacts of 66 salivary gland epithelial neoplasms in which the diagnosis was altered after expert review.

Results

The most common revised diagnosis was that of salivary duct carcinoma (SDC, n = 12), adenoid cystic carcinoma (n = 12), and myoepithelial carcinoma (n = 10). The most common initial diagnosis was mucoepidermoid carcinoma (n = 19) with SDC being the most common revised diagnosis (7/19). Thirteen salivary gland carcinomas were initially diagnosed as benign entities, whereas five benign tumors were initially interpreted as carcinoma. The change in diagnosis was considered to be clinically significant in 65 (97%) cases.

Conclusions

Given their rarity, salivary gland neoplasms are prone to diagnostic inaccuracy and discrepancy. A constellation of histologic features and ancillary studies are useful in reaching the correct diagnosis, which can have significant clinical impacts.
Hepatocyte SH3RF2 Deficiency Is a Key Aggravator for NAFLD
Authors: Yang Xia , Sun Dating , Xiang Hui , Wang Sichen , Huang Yongping , Li Ling , Cheng Xu , Liu Hui , Hu Fengjiao , Cheng Yanjie , Ma Tengfei , Hu Manli , Tian Han , Tian Song , Zhou Yan , Zhang Peng , Zhang Xiao‐Jing , Ji Yan‐Xiao , Hu Yufeng , Li Hongliang , She Zhi‐Gang
Published: April 2021

Background and Aims

NAFLD has become the most common liver disease worldwide but lacks a well‐established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain‐containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms.

Methods and Results

In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet‐induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl–coenzyme A production, and promotes its K48‐linked ubiquitination‐dependent degradation. Consistently, acetyl–coenzyme A was significantly accumulated in Sh3rf2‐knockout hepatocytes and livers compared with wild‐type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition.

Conclusion

SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.
An evaluation of the healthcare costs associated with adverse events in patients with breast cancer
Authors: Wang Lin‐Chien , Chen Hsuan‐Ming , Chen Jin‐Hua , Lin Yi‐Chun , Ko Yu
Published: April 2021

Objective

Despite the increasing prevalence and costs of breast cancer (BC), little is known about its adverse event (AE)‐related costs in Asia. This study aimed to estimate the healthcare expenditures of AEs in patients with BC in Taiwan.

Methods

This is a retrospective claims database analysis. The medical costs associated with BC AEs during the first‐line treatment period were estimated by use of both a matching method and the generalized linear model (GLM).

Results

A total of 50,010 patients diagnosed with breast cancer were identified. Using the case‐control matching method, pneumonitis/pneumonia was the AE associated with the greatest total healthcare costs (NT$ 66,889), followed by arthralgia (NT$55,380). In the GLM, the estimated costs ranged from NT$ 1,045 for fatigue to NT$ 116,652 for left heart failure. Moreover, the estimated total healthcare incremental cost increased with the number of AEs (NT$18,157 for 1 AE, NT$33,827 for 2 AEs, NT$39,052 for 3 AEs, NT$53,348 for 4 AEs, and NT$54,215 for 5 AEs and above).

Conclusions

The findings indicate that AEs among patients with BC were associated with a substantial economic burden, and healthcare expenditure rose significantly as the number of AEs increased.
Early abortion care during the COVID‐19 public health emergency in Ireland: Implications for law, policy, and service delivery
Authors: Spillane Alison , Taylor Maeve , Henchion Caitriona , Venables Róisín , Conlon Catherine
Published: April 2021

Early abortion care became available in Ireland in January 2019. Service delivery involves two consultations with a medical practitioner, separated by a mandatory 3‐day waiting period. The Model of Care for termination of pregnancy initially required in‐person visits. The onset of the COVID‐19 pandemic necessitated significant reductions in in‐person interactions in healthcare. A revised Model of Care for termination of pregnancy, issued for the duration of the pandemic, permits delivery of early abortion care by remote consultation. Significantly, this was introduced without amending the 2018 abortion law. The pandemic precipitated a rapid development in the delivery of abortion care that was not anticipated at the time of abortion law reform only 18 months earlier. We outline the work undertaken to maintain access to abortion care in early pregnancy through the lens of a single community‐level provider and explore what these developments may mean for abortion law, policy, and service delivery.
Promoting healthy trajectories for urban middle school youth through county‐funded, parks‐based after‐school programming
Authors: Goodman Allison C. , Ouellette Rachel R. , D'Agostino Emily M. , Hansen Eric , Lee Theodore , Frazier Stacy L.
Published: April 2021

Ongoing pressure for public schools to prioritize academics has increased attention on after‐school settings as a critical space for social‐emotional learning (SEL). After‐school programs are uniquely positioned to build protective and promotive factors that contribute to positive future orientation, especially within communities where systemic inequities create barriers to high school graduation, higher education, employment, and earnings. This study examines Fit2Lead Youth Enrichment and Sports (YES), a county‐funded, parks‐based after‐school collaboration for middle schoolers that merges mental health and recreation to promote healthy trajectories. Eight Miami neighborhood parks were selected based on county data indicating high rates of violence. An open trial design (N = 9 parks, 198 youth; ages 9–15; 40.5% female; 66.5% Black/African American, 24.9% Hispanic/Latinx, and 76.3% low‐income) tested hypotheses that participation for adolescents exposed to community violence would disrupt a commonly reported decline in self‐regulation and self‐efficacy, and mitigate risk for anxiety and depression. Youth completed questionnaires at the beginning and end of one school year. Paired t‐tests revealed no changes from pre to post, and no differences by baseline levels of youth and parent mental health. Findings highlight the promise of prevention programs to disrupt downward trajectories for youth during the risky time of early adolescence.
Reimagining the pipeline: Saturday Academy at New York University College of Dentistry goes virtual
Authors: Burns Lorel E. , Pezzullo Cheryline , Dief Sandy , Conde Giannina , Mejia Eugenia E.
Published: April 2021

Purpose/objectives

This study describes and evaluates efforts to transition an established pre‐dental pipeline program to a remote platform, in response to the coronavirus disease 2019 pandemic.

Methods

The semester‐long pipeline program, Saturday Academy at New York University College of Dentistry, was conducted remotely through Zoom, and materials for hands‐on, pre‐clinical activities, were mailed to participants. Saturday Academy aims to educate underrepresented minority and low‐income high school students about the college application process and the dental profession. After the program's completion, program applications and engagement data were analyzed. An anonymous online survey was administered to the high school student participants. The survey questions included topics about their interest in the profession of dentistry, satisfaction with the Saturday Academy programming, and program engagement.

Results

In its remote format, Saturday Academy had an average attendance of 87.8% at each session. All (60/60, 100%) of the high school student participants responded to the anonymous program satisfaction survey. Sixty‐seven percent reported an interest in the profession of dentistry before participating in the program and 82% after participating in the program. Ninety‐eight percent agreed with the statement “I enjoyed my experience participating in Saturday Academy.” Additionally, 97% agreed with the statement “Saturday Academy's virtual programming was effective.” There were no statistically significant differences in program satisfaction when data from the virtual program were compared to 2 years of in‐person program satisfaction data.

Conclusion

Challenges to fulfilling the missions of dental institutions in response to the coronavirus pandemic impact service and recruitment efforts, in addition to formal dental education. Transitioning pipeline programming efforts, with hands‐on components, to a remote format is possible and was met with favorable engagement and responses from program participants.
Role of FTO gene polymorphisms in Wilms tumor predisposition: A five‐center case–control study
Authors: Hua Rui‐Xi , Fu Wen , Lin Ao , Zhou Haixia , Cheng Jiwen , Zhang Jiao , Li Suhong , Liu Guochang , Xia Huimin , Zhuo Zhenjian , He Jing
Published: April 2021

Background

Wilms tumor is the most frequently occurring renal malignancy in pediatrics. The FTO gene exhibits a featured genetic contribution to cancer development. Nonetheless, its single nucleotide polymorphism (SNP) contribution to Wilms tumor remains unknown.

Methods

In the present study, 402 Wilms tumor patients and 1198 healthy controls were successfully genotyped for FTO gene SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G and rs8047395 A>G) using TaqMan SNP genotyping assays. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from unconditional logistic regression, were applied to quantify the effects of FTO gene SNPs on Wilms tumor risk.

Results

We found that the rs8047395 A>G polymorphism was significantly correlated with an increased risk for Wilms tumor (GG versus AA/AG: adjusted OR = 1.38, 95% CI = 1.04–1.85, p = 0.027). Carriers with 1 and 1–2 risk genotypes are more susceptible of developing Wilms tumor than those without risk genotypes. Stratified analysis of rs8047395 and risk genotypes revealed more significant relationships with Wilms tumor risk in certain subgroups. Preliminary functional annotations revealed that the rs8047395 A allele increases expression levels of the FTO gene as determined by expression quantitative trait locus analysis.

Conclusions

The present study provides evidence that rs8047395 may regulate FTO gene expression and thus confer susceptibility to Wilms tumor. The candidate FTO gene rs8047395 A>G polymorphism identified in this study warrants independent investigation.
Difference in orientation of the talar articular facets between healthy ankle joints and ankle joints with chronic instability
Authors: Kleipool Roeland P. , Stufkens Sjoerd A. S. , Dahmen Jari , Vuurberg Gwendolyn , Streekstra Geert J. , Dobbe Johannes G. G. , Blankevoort Leendert , Knupp Markus
Published: April 2021

Since both the talocrural and subtalar joints can be involved in chronic ankle instability, the present study assessed the talar morphology as this bone is the key player between both joint levels. The 3D orientation and curvature of the superior and the posteroinferior facet between subjects with chronic ankle instability and healthy controls were compared. Hereto, the talus was segmented in the computed tomography images of a control group and a chronic ankle instability group, after which they were reconstructed to 3D surface models. A cylinder was fitted to the subchondral articulating surfaces. The axis of a cylinder represented the facet orientation, which was expressed by an inclination and deviation angle in a coordinate system based on the cylinder of the superior talar facet and the geometric principal axes of the subject's talus. The curvature of the surface was expressed as the radius of the cylinder. The results demonstrated no significant differences in the radius or deviation angle. However, the inclination angle of the posteroinferior talar facet was significantly more plantarly orientated (by 3.5°) in the chronic instability group (14.7 ± 3.1°) compared to the control group (11.2 ± 4.9°) (p < 0.05). In the coronal plane this corresponds to a valgus orientation of the posteroinferior talar facet relative to the talar dome. In conclusion, a more plantarly and valgus orientated posteroinferior talar facet may be associated to chronic ankle instability.
Prevalence of malnutrition diagnosed by the Global Leadership Initiative on Malnutrition and Mini Nutritional Assessment in older adult outpatients and comparison between the Global Leadership Initiative on Malnutrition and Mini Nutritional Assessment energy‐protein intake: A cross‐sectional study
Authors: Ozer Nurhayat Tugra , Akin Sibel , Gunes Sahin Gulsah , Sahin Serap
Published: April 2021

Background

The Global Leadership Initiative on Malnutrition (GLIM) published malnutrition identification criteria. The Mini Nutritional Assessment (MNA) is malnutrition assessment tool commonly used in older adults. This study aimed to determine prevalence of malnutrition and the relationship between the GLIM and the MNA long form (MNA‐LF) and short form (MNA‐SF) and energy‐protein intake.

Methods

A total of 252 older adult outpatients (aged 68.0 years, 61% females) were included. Malnutrition was defined according to the GLIM, MNA‐LF, and MNA‐SF. Food intake was assessed using the 24‐h dietary recall. We analyzed the cutoff value on the MNA‐LF score, MNA‐SF score, and energy‐protein intake for GLIM criteria–defined malnutrition severity with receiver operating characteristic analysis.

Results

Malnutrition was present in 32.2%, 12.7%, and 13.1% of patients according to the GLIM criteria, MNA‐LF, and MNA‐SF, respectively. It was determined that 92.7% and 89.0% of patients, based on GLIM criteria, had malnutrition with the MNA‐LF and MNA‐SF, respectively. The daily energy‐protein intake was less in patients with malnutrition according to GLIM, as in the MNA‐LF and MNA‐SF classifications (p < .05). For the MNA‐LF and MNA‐SF score, the cutoff value of 11 and 9 points for severe malnutrition (area under curve [AUC] 0.92; p < .001 and 0.90; p < .001), 22 and 11 points for moderate malnutrition (AUC 0.79; p < .001 and 0.76; p < .001) were determined.

Conclusion

According to GLIM criteria, one‐third of outpatient older adults were malnourished, whereas the prevalence was much lower applying both the MNA‐LF and the MNA‐SF.
High prevalence of pulmonary embolism prior to cancer therapies in patients with ovarian and endometrial cancers detected by contrast‐enhanced CT using D‐dimer as an index
Authors: Habu Yuji , Mitsuhashi Akira , Hanawa Shinsuke , Usui Hirokazu , Horikoshi Takuro , Uno Takashi , Shozu Makio
Published: April 2021

Objective

We aimed to evaluate the prevalence of pulmonary embolism (PE) before cancer therapies in patients with ovarian and endometrial cancers with enhanced computed tomography (CT) using D‐dimer (DD), and determine the optimal cut‐off level of DD.

Methods

Since 2009, we have performed preoperative venous thromboembolism (VTE) screening of patients with ovarian and endometrial cancer. For patients with DD levels of more than 1.0 μg/ml, enhanced CT images were obtained from the pulmonary apex to the foot to detect PE and deep venous thrombosis (DVT) simultaneously.

Results

Among patients with ovarian cancer, 84 of 413 (20.3%) had VTEs (DVT alone, n = 31 [7.5%]; PE with or without DVT, n = 53 [12.8%]; PE alone, n = 12 [2.9%]). Among patients with endometrial cancer, 50 of 455 (11.0%) had VTEs (DVT alone, n = 19 [4.2%]; PE with or without DVT, n = 31 [6.8%], PE alone, n = 14 [3.1%]). The optimal cut‐off level of DD was estimated to be ≥1.5 and ≥1.2 μg/ml in ovarian and endometrial cancers, respectively.

Conclusion

Our study revealed a high prevalence of PE before cancer therapies in patients with ovarian and endometrial cancers by enhanced CT using DD.