bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Investigation for Raw and Processed Products of Euodiae Fructus Based on High‐Performance Liquid Chromatography Fingerprints and Chemical Pattern Recognition
Authors: Li Huanhuan , Feng Tao , Wen Yingli , Li Li , Liu Yanan , Ren Xiaoliang , Dou Zhiying
Published: June 2021

As a traditional Chinese medicine, Euodiae Fructus is widely used due to its analgesic, anti‐inflammatory, and antihypertensive effects. However, Euodiae Fructus has also been documented to be toxic, and the toxic effects can be reduced by processing. To distinguish Euodiae Fructus from its processes products and study the changes of raw and processed products before and after processing, we evaluated four auxiliary material processing methods including vinegar, Zingiberis Rhizoma, Coptidis Rhizoma, and Glycyrrhizae Radix et Rhizoma. The raw Euodiae Fructus and four processed Euodiae Fructus samples were analyzed and compared based on the high‐performance liquid chromatography (HPLC) fingerprints combined with chemometrics, including principal component analysis (PCA), partial least squares‐discriminant analysis (PLS‐DA), and principal component analysis‐class (PCA‐Class). A total of 27 common peaks were obtained by fingerprint analysis. The fingerprint similarity of raw and processed samples was between 0.86–0.999. We also determined the contents of the main active ingredients ‐ Evodiamine and Rutaecarpine. PCA and PLS‐DA analyses were used to distinguish between the raw and processed samples of Euodiae Fructus, and 14 chemical markers were screened out. Four kinds of processed products were further analyzed and the results showed that they could be successfully distinguished under the established models, and 12 chemical markers were labeled. PCA‐Class results revealed that the classification models constructed in this study had adequate discrimination ability. The method combined with HPLC fingerprinting and multi‐component chemical pattern recognition technology could be used to differentiate raw and processed Euodiae Fructus with adequate predictive power. Our findings confirmed the rationality of the pharmacopoeial method and provided a reference for the quality control of the Glycyrrhizae Radix et Rhizoma processed Euodiae Fructus.
Carbon Nanomaterials for Wastewater Treatment
Authors: Abbo Hanna S. , Gupta K. C. , Khaligh Nader G. , Titinchi Salam J. J.
Published: June 2021

The research progress made in recent years in removal of organic‐inorganic pollutants from wastewater using various types of carbon materials as adsorbents such as carbon nanotubes, carbon nanofibers, graphenes, graphitic carbon nitride, fullerene, activated carbon spheres, and carbon quantum dots is reviewed. These carbon nanomaterials with hierarchical structures are efficient and economical adsorbents. The techniques of metal impregnation and doping help to control the porosity and surface area of nanomaterials. Electrostatic forces, π‐π and π‐e interactions, van der Waals weak forces, and oxygen‐containing groups are considered responsible for the removal of pollutants from wastewater. The carbon nanomaterial‐based photocatalysts are applied successfully in decomposition of persistent dyes under visible light. Fe3O4 magnetic material is employed as recyclable adsorbent after treatment of wastewater. Freundlich and Langmuir models are found more suitable to calculate the adsorption efficiency and adsorption kinetics of pollutants. Criteria and properties of carbon nanomaterials are discussed that might play a significant role in remediation of wastewater.
Use and outcomes of cerebral embolic protection for transcatheter aortic valve replacement: A US nationwide study
Authors: Khan Muhammad Zia , Zahid Salman , Khan Muhammad U. , Kichloo Asim , Ullah Waqas , Sattar Yasar , Munir Muhammad Bilal , Singla Atul , Goldsweig Andrew M. , Balla Sudarshan
Published: June 2021

Background

Outcomes data on the use of cerebral embolic protection devices (CPDs) with transcatheter aortic valve replacement (TAVR) remain limited. Previous randomized trials were underpowered for primary outcomes of stroke prevention and mortality.

Methods

The National Inpatient Sample and Nationwide Readmissions Database were queried from 2017 to 2018 to study utilization and inpatient mortality, neurological complications (ischemic stroke, hemorrhagic stroke, and transient ischemic attack), procedural complications, resource utilization, and 30‐day readmissions with and without use of CPD. A 1:3 ratio propensity score matched model was created.

Results

Among 108,315 weighted encounters, CPD was used in 4380 patients (4.0%). Adjusted mortality was lower in patients undergoing TAVR with CPD (1.3% vs. 0.5%, p < 0.01). Neurological complications (2.5% vs. 1.7%, p < 0.01), hemorrhagic stroke (0.2% vs. 0%, p < 0.01) and ischemic stroke (2.2% vs. 1.4%, p < 0.01) were also lower in TAVR with CPD. Multiple logistic regression showed CPD use was associated with lower adjusted mortality (odds ratio (OR], 0.34 [95% confidence interval [CI], 0.22–0.52), p < 0.01) and lower adjusted neurological complications (OR, 0.68 (95% CI, 0.54–0.85], p < 0.01). On adjusted analysis, 30‐day all‐cause readmissions (Hazard ratio, HR 0.839, [95% CI, 0.773–0.911], p < 0.01) and stroke (HR, 0.727 [95% CI, 0.554–0.955), p = 0.02) were less likely in TAVR with CPD.

Conclusion

We report real‐world data on utilization and in‐hospital outcomes of CPD use in TAVR. CPD use is associated with lower inpatient mortality, neurological, and clinical complications as compared to TAVR without CPD.
Review of Cathode in Advanced Li−S Batteries: The Effect of Doping Atoms at Micro Levels
Authors: Ren Xiaodan , Liu Zhifei , Zhang Meng , Li Dongsheng , Yuan Shuxia , Lu Chunxiang
Published: June 2021

In recent years, the atom‐doping strategy has attracted extensive attention in lithium‐sulfur batteries. The reasonable structure design and introduction of doping atoms into sulfur cathode materials not only improve the utilization rate of active materials but also catalyze the redox kinetics of polysulfides, which greatly improves the electrochemical performance of the lithium‐sulfur batteries. However, the understanding of the functional mechanism and conversion mechanism of the doping atoms at micro levels is still limited. Hence, it is very crucial to explore the influence of doping atoms on the electronic arrangement and electrochemical active sites. Herein, the development of atomic doping in lithium‐sulfur batteries is reviewed, and the structure‐activity relationship between doped atoms and the adsorption of lithium polysulfide is analyzed. Furthermore, the catalytic mechanisms of catalytic materials were unmasked from microscopic perspectives, namely ion transport, surface electronic structure, energy band structure and state density.
Real‐time Conversion of Electrochemical Currents into Fluorescence Signals Using 8‐Hydroxypyrene‐1,3,6‐trisulfonic Acid (HPTS) and Amplex Red as Fluorogenic Reporters
Authors: Djoumer Rabia , Chovin Arnaud , Demaille Christophe , Dejous Corinne , Hallil Hamida
Published: June 2021

This paper elaborates on an instrumental scheme for translating electrochemical reactions occurring at an electrode under potentiostatic control into fluorescent signals. We examine the performance enhancement of this device using recently introduced water‐soluble fluorescent reporter systems, either the pH‐sensitive 8‐hydroxypyrene‐1,3,6‐trisulfonic acid (HPTS) system or the electrofluorogenic Amplex Red species. The conversion of stationary and transient, cathodic and anodic electrochemical currents into fluorescence is demonstrated. We show that pure capacitive currents can also be converted to fluorescence by our setup, highlighting the rarely observed coupling between a faradaic reaction at one electrode and capacitive charging at another.
G‐Quadruplex Formation by DNA Sequences Deficient in Guanines: Two Tetrad Parallel Quadruplexes Do Not Fold Intramolecularly
Authors: Kejnovská Iva , Stadlbauer Petr , Trantírek Lukáš , Renčiuk Daniel , Gajarský Martin , Krafčík Daniel , Palacký Jan , Bednářová Klára , Šponer Jiří , Mergny Jean‐Louis , Vorlíčková Michaela
Published: June 2021

Guanine quadruplexes (G4s) are noncanonical forms of nucleic acids that are frequently found in genomes. The stability of G4s depends, among other factors, on the number of G‐tetrads. Three‐ or four‐tetrad G4s and antiparallel two‐tetrad G4s have been characterized experimentally; however, the existence of an intramolecular (i. e., not dimeric or multimeric) two‐tetrad parallel‐stranded DNA G4 has never been experimentally observed. Many sequences compatible with two‐tetrad G4 can be found in important genomic regions, such as promoters, for which parallel G4s predominate. Using experimental and theoretical approaches, the propensity of the model sequence AATGGGTGGGTTTGGGTGGGTAA to form an intramolecular parallel‐stranded G4 upon increasing the number of GGG‐to‐GG substitutions has been studied. Deletion of a single G leads to the formation of intramolecular G4s with a stacked G‐triad, whose topology depends on the location of the deletion. Removal of another guanine from another G‐tract leads to di‐ or multimeric G4s. Further deletions mostly prevent the formation of any stable G4. Thus, a solitary two‐tetrad parallel DNA G4 is not thermodynamically stable and requires additional interactions through capping residues. However, transiently populated metastable two‐tetrad species can associate to form stable dimers, the dynamic formation of which might play additional delicate roles in gene regulation. These findings provide essential information for bioinformatics studies searching for potential G4s in genomes.
Ionic gelation of chitosan with sodium tripolyphosphate using a novel combined nebulizer and falling film system
Authors: Poureghbal Yeganeh , Rahimi Masoud , Akbari Mona
Published: June 2021

Nanoparticle technology has made an essential contribution to the pharmaceutical industry and has received considerable attention in comparison with the other domains. In the present study, ionic gelation via a novel combined system of nebulizer and falling film (IG‐NFF) has been proposed. The purpose of the design of this system is to increase the contact surface between the chitosan and sodium tripolyphosphate (STPP) for the preparation of monodisperse and spherical chitosan nanoparticles, because in both nebulizer and falling film systems, the surface‐to‐volume ratio of liquid increases. The formation of these nanoparticles is based on ionic interactions between the negatively charged phosphate groups in the STPP and positively charged amine groups on the chitosan. In this research, the effects of chitosan concentration, STPP concentration, the distance of the nebulizer from the inclined plate, gas to liquid flow rate ratio, and the initial chitosan solution pH on the z‐average size, polydispersity index (PDI), and morphology of nanoparticles formed by IG‐NFF were studied. The results showed that the IG‐NFF process has the ability to produce spherical particles with highly uniform sizes. The mean size of obtained chitosan nanoparticles was in the range of 80–320 nm, and the PDI value ranged from 0.08–0.30.
Intra‐Ring Bridging: A Strategy for Molecular Design of Highly Energetic Nitramines
Authors: Wen Linyuan , Yu Tao , Lai Weipeng , Shi Jinwen , Liu Maochang , Liu Yingzhe , Wang Bozhou
Published: June 2021

Main observation and conclusion

Important progress has been made in the development of energetic molecules with high performance by computer‐aided molecular design in recent years, but structural novelty of organic scaffolds is insufficient. In this work, we propose an intra‐ring bridging strategy inspired by the known energetic nitramines to design novel polycyclic and cage energetic molecules. More than 100 energetic structures were designed by introducing the C—C bridges and increasing the ring size. The synthesis difficulty is considered besides the two most concerned properties of EMs, energy and safety. After a comprehensive estimation, a symmetric cage molecule labeled as 8U‐30 was finally selected because of its relatively high detonation performance, and comparable impact sensitivity as well as synthetic accessibility with CL‐20. Hopefully, the proposed strategy could be utilized in further molecular design to gain various scaffolds, especially cage structures, for different demands.
An Enzyme‐Free Amperometric Sensor Based on Self‐Assembling Ferrocene‐Conjugated Oligopeptide for Specific Determination of L‐Arginine
Authors: Zhu Kai‐Jie , Zhou Li , Wu Ling , Feng Sai‐Fei , Hu Hui‐Ying , He Jing‐Lin , He Yu‐Min , Feng Ze‐Meng , Yin Yu‐Long , Yu Donghong , Cao Zhong
Published: June 2021

Main observation and conclusion

An enzyme‐free amperometric sensor based on a heptadecapeptide possessing an electroactive ferrocene (Fc) linker as ferrocene‐Gly‐Gly‐Gly‐Gly‐Phe‐Gly‐His‐Ile‐His‐Glu‐Gly‐Tyr‐Gly‐Gly‐Gly‐Gly‐Lys‐(CH2)4‐dithiocyclopentane self‐assembled on gold substrate was designed and fabricated for specific determination of L‐arginine (L‐Arg). The detection mechanism is based on conformational change of surface‐immobilized peptide induced by the target L‐Arg, which was confirmed via SEM, TEM, AFM, XPS, and SPR studies. The binding affinity and the recognition feasibility of immobilized specific and non‐specific peptides were also assessed using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). The proposed method can serve as “signal‐on” sensor for detection of L‐Arg down to 31 pmol/L with broad linear range (0.0001 to 10 μmol/L). Furthermore, the Fc‐conjugated specific peptide sensor was successfully applied to the determination of L‐Arg in pig serums with a recovery rate of 97.5%—106.9%, and its test results are in good agreement with that of chromatographic instrument, evidencing that the oligopeptide‐based sensor can be served as a simple and enzyme‐free biosensing platform towards L‐Arg for future application.
Synthesis of Donor‐Acceptor π‐Conjugated Macrocycles by Post‐Functionalization†
Authors: Wang Junting , Wan Qingyun , Liu Junzhi
Published: June 2021

Main observation and conclusion

In this paper, two novel donor‐acceptor (D‐A) macrocyclic compounds 5 and 7 were successfully synthesized by post‐functionalization of a planar dimer macrocycle (1) and a highly twisted trimer macrocycle (2), respectively, via controllable oxidation of methoxy groups and condensation between diketones and phenylenediamine in succession. Compared with unembellished 9,10‐dimethoxyphenanthrene, the resultant dibenzo[a,c]phenazine motif is electron‐deficient rather than electron‐rich, yielding two D‐A π‐conjugated macrocycles with more contractive energy gaps. Density functional theory (DFT) calculations further support the unequivocal evidence of the D‐A properties of macrocycles 5 and 7. The difference of their photophysical properties was investigated by the aid of ultraviolet‐visible absorption and fluorescence spectrophotometers. Furthermore, the stacking patterns of 7 and its contrast π‐conjugated macrocycle trimer (2) were compared via the analysis of X‐ray single crystal, in which the electron‐deficient dibenzo[a,c]phenazine unit provides extra interaction sites, resulting in orderly arrangement of 7 in the solid state.
Lepithiohydimerins A—D: Four Pairs of Neuroprotective Thiohydantoin Dimers Bearing a Disulfide Bond from Maca (Lepidium meyenii Walp.)
Authors: Peng Xing‐Rong , Zhang Ran‐Ran , Liu Jun‐Hong , Li Zhong‐Rong , Zhou Lin , Qiu Ming‐Hua
Published: June 2021

Main observation and conclusion

An HPLC‐UV‐guided separation was performed and four pairs of unprecedented macathiohydantoin dimers, lepithiohydimerins A—D (1—4) bearing a rare disulfide bond were isolated from the tubers of Maca. Their structures were unambiguously confirmed by NMR spectroscopic, X‐ray crystallographic and electronic circular dichroism (ECD) analyses. At the concentration of 20 μmol/L, compounds 2‐1, 2‐2, and 4‐1 increased the viability of PC12 cells with the cell viability at (72.06 ± 1.14)%, (72.64 ± 1.49)%, and (70.93 ± 1.22)%, respectively. Furthermore, the serial concentration experiment showed that they can protect PC12 cells in a dose‐dependent manner.
Regulating Mechanical Properties of Polymer‐Supramolecular Double‐Network Hydrogel by Supramolecular Self‐assembling Structures
Authors: Wang Tiankuo , Zhang Yu , Gu Zichen , Cheng Wei , Lei Hai , Qin Meng , Xue Bin , Wang Wei , Cao Yi
Published: June 2021

Main observation and conclusion

Polymer‐supramolecular double‐network hydrogels (PS‐DN hydrogels) often show much improved recovery rates than conventional double‐network hydrogels because of the fast self‐assembling properties, making them attractive candidates for tissue engineering and flexible electronics. However, as the supramolecular network is dynamic and susceptible to break under low strains, the overall mechanical properties of PS‐DN hydrogels are still limited. Here, we report the mechanical properties for PS‐DN hydrogels can be significantly improved by tuning the supramolecular network structures. A single amino acid change of the self‐assembling peptide can tune the assembled structures from nanofiber to nanoribbon. Such a microscopic structural change can greatly increase the Young's modulus (107.4 kPa), fracture stress (0.48 MPa), and toughness (0.38 MJ·m–3) of the PS‐DN hydrogels. Moreover, the structural change also leads to slightly faster recovery rates (< 1 s). We propose that such dramatically different mechanical properties can be understood by the impact of individual peptide rupture events on the overall network connectivity in the two scenarios. Our study may provide new inspirations for combining high mechanical strength and fast recovery in double network hydrogels by tuning the supramolecular network structures.
Does continuous positive airway pressure therapy benefit patients with coronary artery disease and obstructive sleep apnea? A systematic review and meta‐analysis
Authors: Chen Yasha , Chen Yihong , Wen Feng , He Zhiqing , Niu Wenhao , Ren Changzhen , Li Na , Wang Qinqin , Ren Yusheng , Liang Chun
Published: June 2021

The prevalent co‐morbidity of coronary artery disease (CAD) and obstructive sleep apnea (OSA) has attracted great interest. However, effects of continuous positive airway pressure (CPAP) in patients with OSA and CAD for cardiovascular outcomes and deaths are still controversial. Usage of CPAP among patients with CAD and OSA could decrease the risk of cardiovascular events and death in adults. PubMed, EMBASE, Web of science, and Cochrane Library were systematically searched. Studies that described association of CPAP treatment with cardiovascular events in CAD and OSA patients were included. The main outcome was the major adverse cardiovascular events (MACE), including all‐cause death, cardiovascular death, myocardial infarction (MI), stroke, and repeat revascularization. Summary relative risks (risk ratios [RRs]) and 95% confidence intervals (CIs) of outcomes were pooled and heterogeneity was assessed with the I2 statistic. Nine studies enrolling 2590 participants with OSA and CAD were included and extracted data. There was significant association of CPAP with reduced risk of MACE (RR, 0.73, 95% CI [0.55, 0.96]), particularly among those with AHI less than 30 events/h (RR, 0.43, 95% CI [0.22, 0.84]). Similarly, the same result was found in all‐cause death (RR, 0.66, 95% CI, [0.46, 0.94]) and cardiovascular death (RR, 0.495, 95% CI [0.292, 0.838]). Our data suggested that CPAP usage, compared to usual care, was associated with reduced risks of cardiovascular outcomes or death in patients with OSA and CAD, particularly in the subgroup with AHI less than 30 events/h, which still needs further studies to confirm.
Effects of Itraconazole and Rifampin on the Pharmacokinetics of Mobocertinib (TAK‐788), an Oral Epidermal Growth Factor Receptor Inhibitor, in Healthy Volunteers
Authors: Zhang Steven , Jin Shu , Griffin Celina , Feng Zhongling , Lin Jianchang , Venkatakrishnan Karthik , Gupta Neeraj
Published: June 2021

Mobocertinib (TAK‐788) is an investigational oral tyrosine kinase inhibitor targeting epidermal growth factor receptor and human epidermal growth factor 2. A phase 1 open‐label, 2‐period, fixed‐sequence, 2‐part study (NCT03928327) characterized effects of a strong CYP3A4 inhibitor (itraconazole) and inducer (rifampin) on the pharmacokinetics (PK) of mobocertinib and its active metabolites, AP32960 and AP32914. Healthy volunteers (n = 12 per part) received a single dose of mobocertinib alone (20 mg, part 1; 160 mg, part 2) and with multiple doses of itraconazole 200 mg once daily (part 1) or rifampin 600 mg once daily (part 2). Coadministration of itraconazole with mobocertinib increased the combined molar area under the plasma concentration‐time curve from time 0 to infinity (AUC0‐∞) of mobocertinib, AP32960, and AP32914 by 527% (geometric least‐squares mean [LSM] ratio, 6.27; 90% confidence interval [CI], 5.20‐7.56). Coadministration of rifampin with mobocertinib decreased the combined molar AUC0‐∞ of mobocertinib, AP32960, and AP32914 by 95% (geometric LSM ratio, 0.05; 90%CI, 0.04‐0.07). Based on these results, the strong CYP3A inhibitor itraconazole and inducer rifampin significantly influenced the PK of mobocertinib and its active metabolites. Coadministration of mobocertinib with moderate and strong CYP3A inhibitors or inducers is not recommended in ongoing clinical trials.
Cost to Medicare of Delayed Adalimumab Biosimilar Availability
Authors: Lee ChangWon C. , Najafzadeh Mehdi , Kesselheim Aaron S. , Sarpatwari Ameet
Published: June 2021

Launched in 2002, originator adalimumab (Humira) is the top revenue‐generating drug in the United States. Between 2016 and 2019, the US Food and Drug Administration approved 5 adalimumab biosimilars, yet none have been marketed owing to patent dispute settlements. We sought to calculate the cost of this delayed entry to Medicare over this period by estimating the difference between reported spending on originator adalimumab and estimated spending on originator and biosimilar adalimumab products assuming timely biosimilar market entry. Estimates of potential biosimilar spending were calculated based on the following evidence‐based projections: (i) market capture of 15% for the first biosimilar and 5.5% for successive biosimilars in their first year on the market, and 5% annually thereafter; (ii) price reductions of 3.5% per year and 2.4% per additional biosimilar entry for originator adalimumab; and (iii) price discounts of 25% at launch, 3.4% per year, and 1.7% per additional biosimilar entry for biosimilar adalimumab. Based on these assumptions, had adalimumab biosimilars launched upon approval, estimated non‐rebate spending on them would have been $18.3 million in 2016, $225.7 million in 2017, $436.2 million in 2018, and $727.7 million in 2019, whereas estimated non‐rebate spending on originator adalimumab would have been $2.33 billion, $2.04 billion, $1.78 billion, and $1.42 billion. Cumulative spending on adalimumab would have thus been $8.98 billion instead of an observed $12.11 billion. Accounting for estimated rebates, total predicted savings would have been $2.19 billion. Reforms for timely biosimilar availability will be critical in ensuring optimal savings for Medicare after biosimilar approval.
Analysis on Dielectric, Thermal, and Mechanical Characteristics of Nickel Boro Phthalate NLO Crystal for Optoelectronic Applications
Authors: Divya M. , Malliga P. , Sagayaraj P. , Joseph Arul Pragasam A.
Published: June 2021

Dielectric, thermal, and mechanical behavior of an efficient nonlinear crystal, nickel boro phthalate (NBP), grown by a slow evaporation solution growth technique, is characterized for optoelectronic applications. Ultraviolet absorption study identifies the lower cutoff wavelength as 281 nm. This low value along with transparency in the visible and infrared regions establishes that NBP is a probable nonlinear material. The frequency and the temperature dependency of dielectric constant and dielectric loss are probed. AC conductivity and activation energy are computed, to examine the semiconducting ability of the crystal. Thermal gravimetric analysis and differential thermal analysis are carried out to determine the decomposition temperature. Mechanical characterization is performed by the Vickers microhardness test. The study reveals that NBP comes under the category of soft material. Mechanical properties such as the elastic stiffness constant, brittleness index, yield strength, and fracture toughness are explored.
Animal‐borne video systems provide insight into the reproductive behavior of the Asian black bear
Authors: Naganuma Tomoko , Tanaka Mii , Tezuka Shiori , M.J.G. Steyaert Sam , Tochigi Kahoko , Inagaki Akino , Myojo Hiroaki , Yamazaki Koji , Koike Shinsuke
Published: June 2021

Previous studies on the mating system of the Asian black bear (Ursus thibetanus) have been limited to observations of captive populations and estimations of multiple paternities. Hence, the mating system of wild bears remains poorly understood. Animal‐borne camera systems (i.e., cameras mounted on animals) provide novel tools to study the behavior of elusive animals. Here, we used an animal‐borne video system to record the activities of wild bears during the mating season. Video camera collars were attached to four adult Asian black bears (male “A” and “B,” and female “A” and “B”) captured in Tokyo, central Japan, in May and June 2018. The collars were retrieved in July 2018, after which the video data were downloaded and analyzed in terms of bear activity and mating behavior. All the bears were found to interact with other uniquely identifiable bears for some of the time (range 9–22 days) during the deployment period (range 36–45 days), and multiple mating in males was documented. Both males and females exhibited different behaviors on social days (i.e., days when the bear interacted with conspecifics) compared with solitary days (i.e., days with no observed interactions with conspecifics). Compared with solitary days, the bears spent a lower proportion of time on foraging activities and higher proportion of time on resting activities on social days. Our results suggest that Asian black bears have a polygamous mating system, as both sexes consort and potentially mate with multiple partners during a given mating season. Furthermore, bears appeared to reduce their foraging activities on social days and engaged more in social interactions.
Trajectory of left ventricular geometry and diastolic dysfunction in hereditary transthyretin cardiac amyloidosis
Authors: Akatsuka Tatsuya , Fujimoto Naoki , Ishiyama Masaki , Nakamori Shiro , Imanaka‐Yoshida Kyoko , Dohi Kaoru
Published: June 2021

Amyloid transthyretin (ATTR) depositions cause left ventricular (LV) hypertrophy, diastolic dysfunction, and heart failure. The time course of changes in LV geometry and diastolic dysfunction has not been fully reported in patients with ATTR cardiomyopathy. A 79‐year‐old woman with previous myocardial infraction presented with shortness of breath on exertion, and progressive bilateral lower extremity weakness and polyneuropathy. She was diagnosed with Val30Met hereditary ATTR cardiomyopathy by cardiac biopsy and genetic testing. During the past 5 year period, significant LV concentric remodelling with small LV cavity occurred, resulting in an increased LV stiffness and prolonged LV relaxation. This case report highlights the time course of changes in LV geometry and diastolic function and the importance of early diagnosis of ATTR cardiomyopathy.
Synthesis, Structure, and Bonding Properties of Hypercoordinate Triorganotin Compounds Featuring Three O→Sn Interactions
Authors: Kameo Hajime , Izumi Daisuke , Matsuzaka Hiroyuki
Published: June 2021

Here, heptacoordinate and hexacoordinate triorganotin compounds [o‐{(Ph2)(O)P}C6H4]3SnX (X=F (2 a), Cl (2 b), Me (2 f)) featuring three O→Sn interactions were synthesized. Chloro (2 b) and methyl (2 f) compounds were obtained from the oxygenation of the heptacoordinate triorganotin compounds {o‐(Ph2P)C6H4}3SnX (X=Cl (1 b), Me (1 f)) bearing three P donors. The fluorination of 2 b using tetrabutylammonium fluoride (TBAF) yielded the fluoro analogue 2 a. Structural studies were performed on a series of hypercoordinate triorganotin compounds, 2. The chloro analogue (2 b) exhibited a hexacoordinate geometry attributed to the Sn−Cl bond cleavage, where the highly electrophilic stannyl cation was stabilized by three O donors. In contrast, both the fluoro (2 a) and methyl (2 f) analogues exhibited heptacoordinate structures. Although 2 f adopted a tricapped tetrahedral geometry, 2 b is classified to adopt a distinctly rare bicapped trigonal pyramidal geometry featuring one strong LP(O)→σ*(Sn−F) interaction and two weak LP(O)→σ*(Sn−C) interactions (LP: lone pair electrons). The origin of the structural alternations depending on the substituent is discussed using density functional theory (DFT) calculations.
Characterization of Aggregated Building Heating, Ventilation, and Air Conditioning Load as a Flexibility Service Using Gray‐Box Modeling
Authors: Kohlhepp Peter , Gröll Lutz , Hagenmeyer Veit
Published: June 2021

Integrating large amounts of volatile renewable power into the electricity grid requires ancillary services (ASs) from multiple providers including flexible demand. These should be comparable by uniform and efficiently evaluable performance criteria. The objective is to characterize the technical flexibility of aggregated building heating, ventilation, and air conditioning (HVAC) under different operating conditions. New bounds of flexible power and holding durations, accordingly pay‐back power and recovery times, and ramping rates are derived, using a new gray‐box model of stochastically actuated aggregations of thermostatically controlled loads (TCLs) that can serve as well for load control. New closed formulas of the expected switching temperatures are derived using survival processes and hazard functions. This ex‐ante characterization enables fast decision tools for AS feasibility testing and planning by demand aggregators, as it neither relies on simulation or optimization, nor on the identification and clustering of unit‐level parameters. The estimates are explored in a sensitivity study of urban‐level heat pump heating with respect to six key input factors. A case study using dynamic regulation signals from Pennsylvania–New Jersey–Maryland (PJM) demonstrates the benefit, in terms of tracking precision, of the refined energy measures over pure energy or power capacity bounds.
The variations of free radical and index gas CO in spontaneous combustion of coal gangue under different oxygen concentrations
Authors: Jiang Xiaoyuan , Yang Shengqiang , Zhou Buzhuang , Song Wanxin , Cai Jiawen , Xu Qin , Zhou Quanchao , Yang Kai
Published: June 2021

In order to study the effect of oxygen concentrations on the change of active groups in the oxidation process of coal gangue, the airflows of different oxygen concentrations were prepared to simulate the oxidation and heating process of coal gangue under oxygen concentrations of 0%, 5%, 10%, 15%, and 21%. During the oxidation and heating process, the free radical parameters were measured at different temperatures in real time. The results show that in the early stage of coal gangue oxidation, the g factor remains at a lower level and do not start to increase until certain temperatures are reached. Besides, the higher the oxygen concentration is, the lower the temperature at which the g factor begins to increase. When the oxygen concentrations are 0%, 5%, 10%, 15%, and 21%, the corresponding temperatures are 225, 200, 150, 150, and 125°C, respectively. Furthermore, with the increase of oxidation temperature, the free radical concentrations experience four stages, namely, the slow increase stage, the rapid increase stage, the stagnant increase stage, and the final increase stage. And the higher the oxygen concentration is, the shorter the free radical stagnant increase stage is. During the oxidation of coal gangue, the line widths decrease slowly before 150°C, and then start to plunge and finally stabilize near the minimum at 350°C. Moreover, the higher the oxygen concentration is, the smaller the minimum values of line widths are. In the oxidation process of coal gangue, the gas product CO amounts are first at a lower level, and then begin to increase rapidly after 150°C. At the same temperature, the increased rates of CO production in coal gangue under the oxygen concentrations of 10%, 15%, and 21% are significantly higher than those under the oxygen concentrations of 0% and 5%. Based on the variation law of free radical parameters in coal gangue under different oxygen concentrations, the actual spontaneous combustion of gangue hills was analyzed and the free radical reaction mechanism of spontaneous combustion of gangue hills was discussed. The research results are of guiding significance for the treatment of spontaneous combustion of coal gangue.
Oral nano‐curcumin formulation efficacy in the management of mild to moderate outpatient COVID‐19: A randomized triple‐blind placebo‐controlled clinical trial
Authors: Ahmadi Reza , Salari Soofia , Sharifi Mohammad Davood , Reihani Hamidreza , Rostamiani Mohammad Bagher , Behmadi Morteza , Taherzadeh Zhila , Eslami Saeed , Rezayat Seyed Mahdi , Jaafari Mahmoud Reza , Elyasi Sepideh
Published: June 2021

Background

Curcumin, a natural polyphenolic compound, is proposed as a potential treatment option for patients with coronavirus disease by inhibiting the entry of virus to the cell, encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. In this study, the efficacy and safety of nanocurcumin oral formulation has been evaluated in patients with mild‐moderate Coronavirus disease 2019 (COVID‐19) in outpatient setting.

Methods

In this triple‐blind randomized placebo‐controlled clinical trial, sixty mild to moderate COVID‐19 patients in outpatient setting who fulfilled the inclusion criteria were randomly allocated to treatment (n = 30) group to receive oral nanocurcumin formulation (Sinacurcumin soft gel which contains 40 mg curcuminoids as nanomicelles), two soft gels twice a day after food for 2 weeks or placebo (n = 30) group. Patients’ symptoms and laboratory data were assessed at baseline and during follow‐up period and compared between two groups.

Results

All symptoms except sore throat resolved faster in the treatment group and the difference was significant for chills, cough and smell and taste disturbances. The CRP serum level was lower in the treatment group at the end of two weeks and the lymphocyte count was significantly higher in treatment group. No significant adverse reaction reported in the treatment group.

Conclusion

Oral nanoformulation of curcumin can significantly improve recovery time in patients with mild to moderate COVID‐19 in outpatient setting. Further studies with larger sample size are recommended.
Microbial characterization of the Japanese traditional pickle senmaizuke produced by two different manufacturing processes
Authors: Iguchi Hiroyuki
Published: June 2021

Senmaizuke, a traditional turnip pickle, prepared in Kyoto, Japan, is produced via two types of manufacturing processes: with and without vinegar for fermentation. The aim of this study was to reveal the microbial community and growth behavior in the products and manufacturing processes of two types of senmaizuke. Microbial growth analysis of commercial senmaizuke products showed that both types harbored 102–108 colony forming units (CFU)/g of lactic acid bacteria (LAB) and 102–104 of yeast. The fermented‐type products showed successive growth of LAB during the pickling and ripening processes, whereas LAB in vinegar‐type products showed growth only at the preliminary pickling step before vinegar addition; however, the bacteria were viable at the ripening step. LAB in the vinegar‐type products showed growth when the pH of the pickle was neutralized, indicating that acidification via vinegar retards LAB growth. Metagenomic sequencing showed that the fermented‐type products harbored Lactobacillus, Leuconostoc, and other halophilic and psychrophilic bacteria, with a higher bacterial diversity than in the vinegar‐type products. In the vinegar‐type products, Lactobacillus, Leuconostoc, or both were predominant. Culture tests using LAB isolates and turnip medium suggested that a change in the dominance of Leuconostoc to Lactobacillus members observed in the fermented‐type products during pickling and ripening processes was attributed to the low pH sensitivity of Leuconostoc as well as a relatively long lag phase of growth for adapting to the pickling environment. The findings of this study will be useful for the appropriate quality control and assurance procedure of senmaizuke.
Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain
Authors: Nutma Erik , Gebro Emeline , Marzin Manuel C. , van der Valk Paul , Matthews Paul M. , Owen David R. , Amor Sandra
Published: June 2021

To monitor innate immune responses in the CNS, the 18 kDa Translocator protein (TSPO) is a frequently used target for PET imaging. The frequent assumption that increased TSPO expression in the human CNS reflects pro‐inflammatory activation of microglia has been extrapolated from rodent studies. However, TSPO expression does not increase in activated human microglia in vitro. Studies of multiple sclerosis (MS) lesions reveal that TSPO is not restricted to pro‐inflammatory microglia/macrophages, but also present in homeostatic or reparative microglia. Here, we investigated quantitative relationships between TSPO expression and microglia/macrophage phenotypes in white matter and lesions of brains with MS pathology. In white matter from brains with no disease pathology, normal appearing white matter (NAWM), active MS lesions and chronic active lesion rims, over 95% of TSPO+ cells are microglia/macrophages. Homeostatic microglial markers in NAWM and control tissue are lost/reduced in active lesions and chronic active lesion rims, reflecting cell activation. Nevertheless, pixel analysis of TSPO+ cells (n = 12,225) revealed that TSPO expression per cell is no higher in active lesions and chronic active lesion rims (where myeloid cells are activated) relative to NAWM and control. This data suggests that whilst almost all the TSPO signal in active lesions, chronic active lesion rims, NAWM and control is associated with microglia/macrophages, their TSPO expression predominantly reflects cell density and not activation phenotype. This finding has implications for the interpretation of TSPO PET signal in MS and other CNS diseases, and further demonstrates the limitation of extrapolating TSPO biology from rodents to humans.
Microglia contribute to social behavioral adaptation to chronic stress
Authors: Piirainen Sami , Chithanathan Keerthana , Bisht Kanchan , Piirsalu Maria , Savage Julie Conner , Tremblay Marie‐Eve , Tian Li
Published: June 2021

Microglial activation has been regarded mainly as an exacerbator of stress response, a common symptom in psychiatric disorders. This study aimed to determine whether microglia contribute to adaptive response of the brain and behavior toward stress using a mild and adaptive stress model – chronic restraint stress (CRS) – with wild type (WT) and CX3CR1‐GFP (CX3CR1[G]) mice and human schizophrenia patients' data. Our results revealed that CRS did not exacerbate anxiety and depressive‐like behaviors, but instead strengthened social dominance and short‐term spatial learning in WT mice. Compared to WT and CX3CR1(+/G) heterozygous mice, CX3CR1(G/G) homozygotes were subordinate in social interaction before and after CRS. Microglia in WT mice underwent a series of region‐specific changes involving their phagocytosis of presynaptic vesicular glutamate transporter 2 protein, contacts with synaptic elements, CD206+microglial proportion, and gene expressions such as Cx3cr1. By contrast, CX3CR1‐deficient microglia showed decreased CD206+ while increased MHCII+ subpopulations and hypo‐ramification in the hippocampus, as well as sensitized polarization and morphological change in response to CRS. Furthermore, CD206+ microglial abundancy was positively correlated with social dominancy and microglial ramification in CX3CR1‐GFP mice. Moreover, CX3CR1 mRNA level was reduced in CRS‐treated mouse brains and showed a smaller interactome with other brain genes in the dorsal‐lateral prefrontal cortices of patients with schizophrenia. Our findings overall highlight microglia and its receptor CX3CR1 as key contributors in regulation of social behavioral adaptation to chronic stress.
Differences in survival and mortality in minority ethnic groups with dementia: A systematic review and meta‐analysis
Authors: Co Melissa , Couch Elyse , Gao Qian , Martinez Andrea , Das‐Munshi Jayati , Prina Matthew
Published: June 2021

Objectives

Although there are disparities in both risk of developing dementia and accessibility of dementia services for certain minority ethnic groups in the United States and United Kingdom, disparities in survival after a dementia diagnosis are less well‐studied. Our objective was to systematically review the literature to investigate racial/ethnic differences in survival and mortality in dementia.

Methods

We searched Embase, Ovid MEDLINE, Global Health and PsycINFO from inception to November 2018 for studies comparing survival or mortality over time in at least two race/ethnicity groups. Studies from any country were included but analysed separately. We used narrative synthesis and random‐effects meta‐analysis to synthesise findings. The Newcastle–Ottawa Scale was used to assess quality and risk of bias in individual studies.

Results

We identified 22 articles, most from the United States (n = 17), as well as the United Kingdom (n = 3) and the Netherlands (n = 1). In a meta‐analysis of US studies, hazard of mortality was lower in Black/African American groups (Pooled Hazard Ratio = 0.86, 95% CI = 0.82–0.91, I2 = 17%, from four studies) and Hispanic/Latino groups (Pooled HR = 0.65, 95% CI = 0.50–0.84, I2 = 86%, from four studies) versus comparison groups. However, study quality was mixed, and in particular, quality of reporting of race/ethnicity was inconsistent.

Conclusion

Literature indicates that Black/African American and Hispanic/Latino groups may experience lower mortality in dementia versus comparison groups in the United States, but further research, using clearer and more and consistent reporting of race/ethnicity, is necessary to understand what drives these patterns and their implications for policy and practice.
Reply to Letter to the Editor regarding “Elective neck dissection and its extent in Salivary gland cancers: A Dilemma”
Authors: Westergaard‐Nielsen Marie , Godballe Christian , Eriksen Jesper Grau , Larsen Stine Rosenkilde , Kiss Katalin , Agander Tina , Ulhøi Benedicte Parm , Wittenborg Charabi Birgitte , Klug Tejs Ehlers , Jacobsen Henrik , Johansen Jørgen , Kristensen Claus Andrup , Andersen Elo , Andersen Maria , Bjørndal Kristine
Published: June 2021

see page 2859‐2860
Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer
Authors: Chaudhary Nazia , Choudhary Bhagya Shree , Shah Sanket Girish , Khapare Nileema , Dwivedi Nehanjali , Gaikwad Anagha , Joshi Neha , Raichanna Jinsy , Basu Srikanta , Gurjar Murari , P.K. Smitha , Saklani Avanish , Gera Poonam , Ramadwar Mukta , Patil Prachi , Thorat Rahul , Gota Vikram , Dhar Sujan K. , Gupta Sanjay , Das Manjula , Dalal Sorab N.
Published: June 2021

Lipocalin 2 is a siderophore‐binding protein that regulates iron homeostasis. Lipocalin 2 expression is elevated in multiple tumor types; however, the mechanisms that drive tumor progression upon Lipocalin 2 expression remain unclear. When Lipocalin 2 is over‐expressed, it leads to resistance to 5‐fluorouracil in colon cancer cell lines in vitro and in vivo by inhibiting ferroptosis. Lipocalin 2 inhibits ferroptosis by decreasing intracellular iron levels and stimulating the expression of glutathione peroxidase4 and a component of the cysteine glutamate antiporter, xCT. The increase in xCT levels is dependent on increased levels of ETS1 in Lipocalin 2 over‐expressing cells. Inhibiting Lipocalin 2 function with a monoclonal antibody leads to a decrease in chemo‐resistance and transformation in vitro, and a decrease in tumor progression and chemo‐resistance in xenograft mouse models. Lipocalin 2 and xCT levels exhibit a positive correlation in human tumor samples suggesting that the pathway we have identified in cell lines is operative in human tumor samples. These results indicate that Lipocalin 2 is a potential therapeutic target and that the monoclonal antibody described in our study can serve as the basis for a potential therapeutic in patients who do not respond to chemotherapy.
Interference of eltrombopag with bilirubin measurements on the Vitros 5600 analyzer
Authors: Poventud‐Fuentes Izmarie , Garnett Emily , Despotovic Jenny , Devaraj Sridevi
Published: June 2021

Background

Eltrombopag is a thrombopoietin‐receptor agonist used to restore platelet count to hemostatic levels in chronic immune thrombocytopenia. The drug has shown to have hepatobiliary adverse effects, but also positive interference with the analytical measurement of bilirubin. Understanding the degree of interference of this drug with bilirubin testing becomes relevant in the clinical management of these patients.

Methods

Eltrombopag at concentrations ranging from 10 to 150 µg/ml was spiked into plasma samples with different baseline concentrations of bilirubin. Total bilirubin, conjugated, and unconjugated bilirubin were measured for each sample using VITROS TBILI and BuBc slides on the Vitros 5600 automated chemistry platform, and interference was assessed.

Results

Plasma samples spiked with eltrombopag yielded falsely elevated bilirubin measurements compared to baseline, with the degree of elevation increasing with greater concentrations of eltrombopag. Bilirubin values were increased relative to baseline across all groups, except in conjugated bilirubin measurements in samples with low baseline conjugated bilirubin. For samples with low total bilirubin at baseline, >100 µg/ml of eltrombopag resulted in an error of >+0.6 mg/dl on the measured total bilirubin. For samples with low unconjugated bilirubin at baseline, the error for the same concentrations was >+0.7 mg/dl.

Conclusion

Our results show that, at supra‐physiologically high concentrations, eltrombopag can positively interfere with bilirubin measurements on Vitros 5600 platform.
Urea derivatives of piperazine doped with pyrazole‐4‐carboxylic acids: Synthesis and antimicrobial evaluation
Authors: Phougat Harshita , Devi Vandana , Rai Sanjay , Reddy T. Shreedhar , Singh Karan
Published: June 2021

A series of novel N‐cycloalkyl/aryl‐4‐(1,3‐diphenyl‐1H‐pyrazole‐4‐carbonyl)piperazine‐1‐carboxamides 9a‐g has been synthesized for biological interest by simple base catalyzed reaction of various N‐cycloalkyl/aryl isocyanates with (1,3‐diphenyl‐1H‐pyrazol‐4‐yl)(piperazin‐1‐yl)methanone hydrochloride 8. The compound 8 was synthesized in excellent yield by the reaction of 1,3‐diphenyl‐1H‐pyrazole‐4‐carbonyl chloride with boc‐piperazine followed by deprotection of boc group with dioxane‐HCl. All the novel intermediates and urea derivatives have been screened for antimicrobial activity. The compound 9a was found an excellent compound to be active against all Gram (−ve) and Gram (+ve) bacterial strains E. coli, Y. enterocolitica, B. cereus, and S. aureus. It also showed comparable antifungal activity against C. albicans with MIC 78.1 μg/ml as compared to reference standard miconazole.