bluuebunny/crossref_metadata_2025 huggingface dataset:
ATP‐Responsive Smart Hydrogel Releasing Immune Adjuvant Synchronized with Repeated Chemotherapy or Radiotherapy to Boost Antitumor Immunity
Authors: Sun Lele , Shen Fengyun , Tian Longlong , Tao Huiquan , Xiong Zijian , Xu Jun , Liu Zhuang
Published: March 2021

Certain chemotherapeutics and forms of ionizing radiation can induce immunogenic cell death (ICD). If there simultaneously exist immune adjuvants within the tumor, such antitumor immunity would be further amplified. However, as clinical chemo/radiotherapies are usually repeatedly given at low individual doses, it would be impractical to administrate immune adjuvants into tumors at each dose of chemo/radiotherapies. Thus, a smart hydrogel is developed that releases immune adjuvants in response to repeatedly applied chemo‐/radiotherapies. Herein, alginate is conjugated with an adenosine triphosphate (ATP)‐specific aptamer, which is hybridized with immunoadjuvant CpG oligonucleotide. Upon intratumoral injection, alginate‐based hydrogel is formed in situ. Interestingly, low doses of oxaliplatin or X‐rays, while inducing ICD of tumor cells, could trigger release of ATP, which competitively binds with ATP‐specific aptamer to trigger CpG release. Therefore, the smart hydrogel could release the immune adjuvant synchronized with low‐dose repeated chemo/radiotherapies, achieving remarkable synergistic responses in eliminating established tumors, as well as immune memory to reject re‐challenged tumors. Moreover, repeated radiotherapies assisted by the smart hydrogel could inhibit distant tumor metastases, especially in combination with immune checkpoint blockade. The study presents a conceptually new strategy to boost cancer immunotherapy coherent with repeated low‐dose chemo‐/radiotherapies following a clinically relevant manner.
Reconstructable Gradient Structures and Reprogrammable 3D Deformations of Hydrogels with Coumarin Units as the Photolabile Crosslinks
Authors: Zhu Chao Nan , Li Chen Yu , Wang Hu , Hong Wei , Huang Feihe , Zheng Qiang , Wu Zi Liang
Published: March 2021

Morphing hydrogels have versatile applications in soft robotics, flexible electronics, and biomedical devices. Controlling component distribution and internal stress within a hydrogel is crucial for shape‐changing. However, existing gradient structures of hydrogels are usually non‐reconstructable, once encoded by chemical reactions and covalent bonds. Fabricating hydrogels with distinct gradient structures is inevitable for every new configuration, resulting in poor reusability, adaptability, and sustainability that are disadvantageous for diverse applications. Herein, a hydrogel containing reversible photo‐crosslinks that enable reprogramming of the gradient structures and 3D deformations into various configurations is reported. The hydrogel is prepared by micellar polymerization of hydrophobic coumarin monomer and hydrophilic acrylic acid. The presence of hexadecyltrimethylammonium chloride micelles increases the local concentration of coumarin units and also improves the mechanical properties of the hydrogel by forming robust polyelectrolyte/surfactant complexes that serve as the physical crosslinks. High‐efficiency photodimerization and photocleavage reactions of coumarins are realized under 365 and 254 nm light irradiation, respectively, affording reversible tuning of the network structure of the hydrogel. Through photolithography, different gradient structures are sequentially patterned in one hydrogel that direct the deformations into distinct configurations. Such a strategy should be applicable for other photolabile hydrogels toward reprogrammable control of network structures and versatile functions.
Current Trends on Surface Acoustic Wave Biosensors
Authors: Zida Serge Ismael , Lin Yue‐Der , Khung Yit Lung
Published: March 2021

The development of rapid biosensing platforms is an integral part for the detection of many diseases, as well as important clinical biomarkers. So far, many new biosensing technologies have been described in literature but many of these novel platforms remain noncommercializable due to challenges in fabrication process, operational conditions as well as other cost concerns. Hence, there is a need to develop efficient and cost‐effective biosensing platforms and of the types available from literature, surface acoustic wave (SAW) biosensors have certain standout attributes. The simple manufacturing requirements of SAW‐based biosensor and its wide operating frequency range have produced promising outcome for bio‐detection and this has rendered this technological platform as a serious contender for point‐of‐care biosensor design. So far, SAW devices are reported for the detection of various bioactive targets of clinical importance and several designs are already commercialized. In this review, the latest development of SAW technologies in recent years for the detection of a broad range of biomolecules is presented and some of the challenges as well as potential future developments of SAW biosensors are highlighted.
Assembly of 5‐Aminoimidazoles via Palladium‐Catalysed Double Isocyanide Insertion Reaction
Authors: Wang Xu , Fu Jin‐Ping , Mo Jia‐Hui , Tian Yu‐Hong , Liu Chun‐You , Tang Hai‐Tao , Sun Zi‐Jun , Pan Ying‐Ming
Published: March 2021

A palladium‐catalysed tandem cyclisation reaction of amidoximes, isocyanides and amines to produce 5‐aminoimidazoles was developed. Various 5‐aminoimidazoles were prepared in good to excellent yields under mild conditions. This elegant domino process involves the effective cleavage of the N−O bond and the formation of new C−C and C−N bonds in a single operation.

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3D‐Printed Multi‐Channel Metal Lattices Enabling Localized Electric‐Field Redistribution for Dendrite‐Free Aqueous Zn Ion Batteries
Authors: Zhang Guanhua , Zhang Xianan , Liu Huaizhi , Li Jinhao , Chen Yiqin , Duan Huigao
Published: March 2021

Rechargeable Zn ion batteries are regarded as a preferable candidate for next‐generation energy storage systems owing to their merits of environmental benignity, low cost, and high safety. Nevertheless, unsatisfactory cycling stability stemming from dendrite growth and undesired side reactions of Zn anodes prevent their widespread commercial adoption. Here, a novel 3D Zn metal anode with multi‐channel lattice structures employing the combined 3D printing and electroless plating/electroplating techniques is reported. The constructed 3D Ni–Zn anode with multi‐channel lattice structure and super‐hydrophilic surface can effectively ameliorate the electric‐field distribution and induce the uniform deposition of Zn without Zn dendrite growth, as confirmed by simulation of current density distribution of the electrode in electrolyte and in situ microscopic observation of Zn plating/stripping. As expected, the 3D Ni–Zn cell shows highly reversible Zn plating/stripping with satisfactory Coulombic efficiency due to the low Zn nucleation overpotential and homogeneous distribution of localized electric field. Consequently, a full cell built with a 3D printed Zn anode and polyaniline‐intercalated vanadium oxide cathode exhibits remarkable performance. The simple and cost‐effective fabrication of conductive metal lattices with tunable 3D multi‐channel architecture opens up new opportunities to develop other high‐performance metal (such as Li, Na, K, Mg, Al) batteries.
Amorphous Carbon Nitride with Three Coordinate Nitrogen (N3C) Vacancies for Exceptional NOx Abatement in Visible Light
Authors: Duan Youyu , Wang Yang , Gan Liyong , Meng Jiazhi , Feng Yajie , Wang Kaiwen , Zhou Kai , Wang Cong , Han Xiaodong , Zhou Xiaoyuan
Published: March 2021

Over the past several decades, much effort has been applied to atmospheric nitrogen oxide (NOx) abatement. The current techniques require high energy consumption and result in secondary pollution. Particularly, the removal of low dose (<200 ppm) of NOx has been very challenging. Though graphitic carbon nitride (g‐CN), an eco‐friendly and sustainable material was tried as a promising metal‐free photocatalyst for NOx abatement. Herein, a one‐step, energy efficient calcination approach is developed to prepare amorphous carbon nitride (ACN) with N3C‐site vacancies. The visible‐light responsive range is expanded and the activation barrier of NO triple bonds is sharply decreased by one order of magnitude; 0.19 eV when compared to the 2.22 eV of g‐CN. These modifications allow the NOx removal efficiency of ACN to reach 57.1% which is among the highest in visible light. The unique N3C‐site vacancies are well maintained after photocatalytic NO oxidation, which shows an exceptional structural stability. This boosts the generation of singlet oxygen (1O2) and superoxide radical (•O2−) for complete NO removal. This study sheds light on the active site design and photocatalytic performance enhancement of g‐CN based materials by vacancy engineering.
Construction and Operating Mechanism of High‐Rate Mo‐Doped Na3V2(PO4)3@C Nanowires toward Practicable Wide‐Temperature‐Tolerance Na‐Ion and Hybrid Li/Na‐Ion Batteries
Authors: Liang Longwei , Li Xiaoying , Zhao Fei , Zhang Jinyang , Liu Yang , Hou Linrui , Yuan Changzhou
Published: March 2021

The growing demand for cost‐efficiency and safe energy storage systems has stimulated enormous interest worldwide in advanced cathodes for practicle “beyond‐Li‐ion” batteries. Herein, a feasible electrospinning/annealing avenue for the construction of 1D Mo‐doped Na3V2(PO4)3 nanowires in situ coated with carbon nanoshell (MNVP@C NWs) toward next‐generation Na‐ion batteries (NIBs) and hybrid Li/Na‐ion batteries (HLNIBs) as a high‐rate cathode material, is reported. Particularly, the intrinsic hybrid Li/Na‐ion storage mechanism of the MNVP@C NWs is unveiled for the HLNIBs with comprehensive characterizations. The resultant MNVP@C NWs demonstrate rapid electronic/ionic transport and rigid structural tolerance within operating temperatures from ‐25 to 55 °C, benefiting from its unique structural/compositional merits. More competitively, the MNVP@C NWs assembled pouch‐type NIBs (‐15 to 25 °C) and HLNIBs (‐25 to 55 °C) both exhibit remarkable wide‐temperature‐tolerance electrochemical properties in terms of high‐rate capabilities and long‐duration cycling lifespan, along with material‐level energy densities of ≈262.4 and ≈186.1 Wh kg‐1 at 25 °C, respectively. The contribution here is expected to exert a stimulative impact upon the future design of versatile cathodes for advanced high energy/power rechargeable batteries.
The Alzheimer's Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid β and tau
Authors: Hansson Oskar , Batrla Richard , Brix Britta , Carrillo Maria C. , Corradini Veronika , Edelmayer Rebecca M. , Esquivel Rianne N. , Hall Christina , Lawson John , Bastard Nathalie Le , Molinuevo José Luis , Nisenbaum Laura K. , Rutz Sandra , Salamone Salvatore J. , Teunissen Charlotte E. , Traynham Christopher , Umek Robert M. , Vanderstichele Hugo , Vandijck Manu , Wahl Simone , Weber Christopher J. , Zetterberg Henrik , Blennow Kaj
Published: March 2021

The core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers amyloid beta (Aβ42 and Aβ40), total tau, and phosphorylated tau, have been extensively clinically validated, with very high diagnostic performance for AD, including the early phases of the disease. However, between‐center differences in pre‐analytical procedures may contribute to variability in measurements across laboratories. To resolve this issue, a workgroup was led by the Alzheimer's Association with experts from both academia and industry. The aim of the group was to develop a simplified and standardized pre‐analytical protocol for CSF collection and handling before analysis for routine clinical use, and ultimately to ensure high diagnostic performance and minimize patient misclassification rates. Widespread application of the protocol would help minimize variability in measurements, which would facilitate the implementation of unified cut‐off levels across laboratories, and foster the use of CSF biomarkers in AD diagnostics for the benefit of the patients.
Neurodegenerative Disease Diagnosis via Ion‐Level Detection in the Brain
Authors: Chen Ying , Wei Min , Lee Jiyoung , Zhao Jing , Lin Peihua , Wang Qiyue , Li Fangyuan , Ling Daishun
Published: March 2021

Metal ions are heavily involved in the membrane potential and intracellular activities of cells. Increasing evidences have shown that it is critical to evaluate the ion levels and monitor their dynamic changes in the brain for the diagnosis of neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington disease, amyotrophic lateral sclerosis, and so on. Herein, the roles of metal ions in the occurrence and development of NDDs are intensively discussed, and the recent advances in probes and sensors for ion‐level detection are summarized. Finally, the further applications of ingenious ion‐selective probes and sensors are outlined, highlighting the future opportunities for the metal ion‐based diagnosis of NDDs.
Ultrastable and Efficient Visible‐light‐driven CO2 Reduction Triggered by Regenerative Oxygen‐Vacancies in Bi2O2CO3 Nanosheets
Authors: Zu Xiaolong , Zhao Yuan , Li Xiaodong , Chen Runhua , Shao Weiwei , Wang Zhiqiang , Hu Jun , Zhu Junfa , Pan Yang , Sun Yongfu , Xie Yi
Published: March 2021

Herein, we first design a fast low‐pressure ultraviolet light irradiation strategy for easily regenerating the nearly equivalent surface vacancies. Taking the defective Bi2O2CO3 nanosheets as an example, nearly equal amount of oxygen vacancies can be regenerated under UV light irradiation. Synchrotron‐radiation quasi in situ X‐ray photoelectron spectra disclose the Bi sites in the O‐defective Bi2O2CO3 nanosheets can act as the highly active sites, which not only help to activate CO2 molecules, but also contribute to stabilizing the rate‐limiting COOH* intermediate. Also, in situ Fourier transform infrared spectroscopy and in situ mass spectrometry unravel the UV light irradiation contributes to accelerating CO desorption process. As a result, the O‐defective Bi2O2CO3 nanosheets achieve a stability up to 2640 h over 110 cycling tests and a high evolution rate of 275 μmol g−1 h−1 for visible‐light‐driven CO2 reduction to CO.
Ergonomic Challenges in the Perioperative Setting
Authors: Apple Brandi , Letvak Susan
Published: March 2021

Working in health care can be physically stressful. The perioperative setting, which is largely concealed from other health care workers and the general public, places unique physical demands on its workers. Perioperative personnel are responsible for a variety of physical tasks, including moving and positioning patients, holding extremities, and moving equipment and supplies. As the nursing workforce ages, the physical demands of the perioperative environment may affect the development of musculoskeletal disorders in older nurses. The purpose of this article is to review published research and describe the ergonomic challenges of working in the OR. There currently is a paucity of literature on the effects of ergonomic risk factors on perioperative nurses in the United States. This article also provides some recommendations for perioperative staff members and leaders that may assist them with creating and maintaining a healthy and safe work environment.
OR Traffic and Surgical Site Infections: A Quality Improvement Project
Authors: Parent Marc
Published: March 2021

Operating rooms are dynamic places with a lot of movement and people working as a concerted team. Operating room traffic can be necessary (eg, retrieving an unusual supply) or unnecessary (eg, a social visit). This quality improvement project aimed to reduce the amount of OR traffic to only necessary traffic and reduce the surgical site infection rates for the orthopedic ORs in a northern California community hospital. There were three principle interventions: door signs discouraging traffic, staff member relief in batches, and preference card review for accuracy. During the six‐week post‐intervention period, there were no reported surgical site infections for orthopedic procedures, and the standardized infection ratio decreased from 1.75 to 0 in 10 weeks. Operating room traffic decreased after implementation by 46.9%. The number of door openings per minute decreased from 1.96 per minute to 1.04 per minute at the project’s conclusion. Staff members’ awareness of OR traffic increased.
Design, synthesis, docking, ADMET profile, and anticancer evaluations of novel thiazolidine‐2,4‐dione derivatives as VEGFR‐2 inhibitors
Authors: El‐Adl Khaled , Sakr Helmy , El‐Hddad Sanadelaslam S. A. , El‐Helby Abdel‐Ghany A. , Nasser Mohamed , Abulkhair Hamada S.
Published: March 2021

The anticancer activity of novel thiazolidine‐2,4‐diones was evaluated against HepG2, HCT‐116, and MCF‐7 cells. Among the tested cancer cell lines, HCT‐116 was the most sensitive one to the cytotoxic effect of the new derivatives. In particular, compounds 18, 11, and 10 were found to be the most potent derivatives among all the tested compounds against the HepG2, HCT‐116, and MCF‐7 cancer cell lines, with IC50 values ranging from 38.76 to 53.99 µM. The most active antiproliferative derivatives (7–14 and 15–19) were subjected to further biological studies to evaluate their inhibitory potentials against VEGFR‐2. The tested compounds displayed a good‐to‐medium inhibitory activity, with IC50 values ranging from 0.26 to 0.72 µM. Among them, compounds 18, 11, and 10 potently inhibited VEGFR‐2 at IC50 values in the range of 0.26–0.29 µM, which are nearly three times that of the sorafenib IC50 value (0.10 µM). Although our derivatives showed lower activities than the reference drug, they could be useful as a template for future design, optimization, adaptation, and investigation to produce more potent and selective VEGFR‐2 inhibitors with higher anticancer analogs. The ADMET profile showed that compounds 18, 11, and 10 do not violate any of Lipinski's rules and have a comparable intestinal absorptivity in humans. Also, the new derivatives could not inhibit cytochrome P3A4. Unlike sorafenib and doxorubicin, compounds 18, 11, and 10 are expected to have prolonged dosing intervals. Moreover, compounds 10 and 18 displayed a wide therapeutic index and higher selectivity against cancer cells as compared with their cytotoxicity against normal cells.
Dietary intake and growth deficits in Rett syndrome—A cross‐section study
Authors: Wong Lee Chin , Chen Yen‐Tsz , Tsai Shu‐Mei , Lin Yen‐Ju , Hsu Chia‐Jui , Wang Hsin‐Pei , Hu Su‐Ching , Shen Hsiu‐Yu , Tsai Wen‐Che , Lee Wang‐Tso
Published: March 2021

Growth deficit is a common comorbidity and one of the supportive criteria in Rett syndrome (RTT). This study aimed to investigate the impact of dystonia, dietary intakes, and clinical severities on growth patterns in a Taiwanese cohort of RTT. We recruited 44 RTT patients with MECP2 mutation for analysis. For individuals ≤18 years of age, in comparison to the RTT‐specific growth chart which comprised American RTT cohort, the body height was right‐shifted to a higher percentile, whereas the body weight was left‐shifted to a lower percentile. Furthermore, the body mass index was significantly decreased when compared to RTT‐specific growth chart (p = 0.01). Higher degree of overall disease severity (odd ratio = 1.159; 95% CI = 1.063–1.264; p = 0.001) and hand use impairment (odd ratio = 2.017; 95% CI = 1.037, 3.921; p = 0.039) were associated with more severe growth patterns. All individuals had dystonia at certain variable degrees. The dystonia worsened with age (p < 0.001) but did not have significant impact on growth deficit. Most of our cohort had adequate protein (97.37%) and energy (58.97%) intakes. The fiber intakes were generally low, with about 38 (97.4%) individuals did not meet the daily reference intakes of fiber. The protein intake was significantly lower in individuals with severe growth deficit (p = 0.04). Our study shows that ethnicity should be considered when comparing RTT individuals' growth pattern to the RTT‐specific growth chart. Further, disease severity, genotypes, and nutrition exert important impacts on RTT‐growth pattern.

Lay Summary

Growth impairment is an important issue in Rett syndrome and the underlying patho‐mechanism is multifactorial. Higher degree of overall disease severity and hand use impairment were associated with more severe growth pattern deficits. Although all individuals had dystonia at certain variable degrees and the dystonia worsened with age, but it did not have significant impact on growth deficit. Nutritional intakes may partially affect growth. Furthermore, ethnicity should be considered when comparing RTT individuals' growth pattern to the RTT‐specific growth chart.
Technical and economic feasibility of an integrated ethanol and anthocyanin coproduction process using purple corn stover
Authors: Kurambhatti Chinmay , Kumar Deepak , Singh Vijay
Published: March 2021

The coproduction of high‐value anthocyanin extract in the cellulosic ethanol process would diversify the co‐product market, increase revenue, and potentially improve the economics of the process. The high anthocyanin concentration in the cob and structural carbohydrates in residual stover make purple corn stover an attractive source for anthocyanin and ethanol coproduction. This study aimed to develop simulation models for processes integrating ethanol production and anthocyanin extraction using purple corn stover, to evaluate their techno‐economic feasibility, and to compare their performance with the conventional ethanol production process using corn stover. The annual ethanol production for plants processing 2000 MT dry feedstock / day was 148.6 million L/year for the integrated processes compared with 222.6 million L/year for the conventional process. Anthocyanin production in the modified processes using dilute acid‐based and water‐based anthocyanin extraction processes was 1779 and 1099 MT/year, respectively. Capital investments for the integrated processes ($448.1 to $443.8 million) were higher than the conventional process ($371.9 million). Due to high revenue from anthocyanin extract, the ethanol production cost for the integrated process using acid‐based anthocyanin extraction ($0.36/L) was 34.5% lower than conventional ethanol production ($0.55/L). The ethanol production cost for the integrated process using water‐based anthocyanin extraction ($0.68/L) was higher than conventional ethanol production due to low ethanol and anthocyanin yields. The minimum ethanol selling price for the integrated process using acid‐based anthocyanin extraction ($0.65/L) was also lower than the conventional process ($0.72/L), indicating an improvement in economic performance. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
Flow management strategies for a connected purification process
Authors: Goebel Mathias , Rodrigues Rui , Pampel Lars , Rapp Johanna , Shultz Joseph , Cui Huanchun
Published: March 2021

This paper describes different flow management strategies for a connected purification process which includes two polishing steps, virus filtration and tangential flow filtration. Connecting these unit operations avoids introducing large intermediate product pool vessels in small manufacturing facilities. However, a connected‐downstream process requires an elaborate control strategy enabling multiple unit operations to function as a single unit. The key strategy to enable the connected‐downstream process is a robust management of flow disparities among unit operations. During a typical ultrafiltration step, product concentration increases as mass is added to the retentate tank, leading to a permeate flux decline. In a connected‐downstream process, the inlet stream is directly connected to the prior unit operation and any decrease in permeate flow rate could cause a flow disparity. Four different flow management approaches are proposed to manage potential flow disparities and their advantages and challenges are discussed. Bench‐scale results of these strategies are presented and evaluated.
Cyclobutadiene Rhodium Complexes as Catalysts for the Synthesis of Amides from Electron‐rich Arenes, Tosyl Azide and CO
Authors: Shvydkiy Nikita V. , Petrushina Tatiana N. , Perekalin Dmitry S.
Published: March 2021

Cyclobutadiene rhodium complexes [(C4R4)RhX]2 (R=Et, Ph; X=I, Cl) at 0.5 mol % loading catalyze the formation of aromatic amides from various indoles, tosyl azide, and carbon monoxide (1 atm). The reaction gives good yields of the target products (typically 60–85 %) and tolerates both donor and moderately acceptor substituents in the indoles (alkyl, OMe, Hal, COOMe, but not CN). The DFT calculations at the PBE/3ζ level revealed a new plausible mechanism for the reaction of TsN3 with CO via cycloaddition and formation of RhCON3 metallacycle, which is more favorable than the commonly assumed formation of nitrene intermediate.
Jens Weitkamp – in Memoriam
Authors: Kärger Jörg
Published: March 2021

Prof. Jens Weitkamp was a pioneer in the field of zeolite catalysis, especially for applications such as hydrocracking, isomerization, alkylation, but also selective ring opening of polynuclear aromatics. This is an extended version of the closing remarks delivered at the Symposium in honor of Professor Jens Weitkamp on February 11th, 2020, at the DECHEMA house, Frankfurt, Germany.
High‐density lipoprotein cholesterol levels are associated with major adverse cardiovascular events in male but not female patients with hypertension
Authors: Wang Xiaopu , Pei Junyu , Zheng Keyang , Hu Xinqun
Published: March 2021

Background

The relationship between high‐density lipoprotein cholesterol (HDL‐C) levels and major adverse cardiovascular events (MACEs) in hypertensive patients of different sexes is unclear.

Hypothesis

Sex differences in the relationship between HDL‐C levels and the risk of MACEs among hypertensive patients.

Methods

We performed a post‐hoc analysis of data obtained from the Systolic Blood Pressure Intervention Trial (SPRINT) and explored sex‐based differences in the relationship between HDL‐C levels and MACEs among hypertensive patients using Cox proportional hazards regression.

Results

A total of 9323 hypertensive patients (6016 [64.53%] men and 3307 [35.47%] women) were assessed using SPRINT data. MACEs occurred in 395 (6.57%) men and 166 (5.02%) women after a mean follow‐up of 3.26 years. When HDL‐C levels were used as a continuous covariate, each 10 mg/dl increase in HDL‐C levels decreased the risk of MACEs in men (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70–0.88; p < .0001). However, HDL‐C levels were not associated with MACEs in female hypertensive patients (HR, 1.02; 95% CI, 0.89–1.16; p = .7869). Compared with those in the first quartile, MACEs in the fourth quartile had the lowest risk among male patients (HR, 0.58; 95% CI, 0.41–0.82; p = .0023). Female patients in the fourth quartile of HDL‐C levels had an HR of 1.09 for MACEs (95% CI, 0.62–1.93; p = .7678). HDL‐C levels were not associated with the risk of MACEs among females.

Conclusion

Among elderly hypertensive patients, higher HDL‐C levels were associated with a lower MACE incidence in men but not in women. Unique identifier: NCT01206062.
Learning from East to West and vice versa: Clinical epidemiology of colorectal cancer in China
Authors: Winkels Renate M. , Kampman Ellen , Wu Ming
Published: March 2021

Cancer continues to be a significant health problem in China, and there is increasing attention to studies on cancer in China in the English‐language peer‐reviewed literature. The article discussed in this editorial reveals several interesting time trends in China for colorectal cancer epidemiology.
Statins and immunotherapy: Togetherness makes strength The potential effect of statins on immunotherapy for NSCLC
Authors: Rossi Alessandro , Filetti Marco , Taurelli Salimbeni Beatrice , Piras Marta , Rizzo Francesco , Giusti Raffaele , Marchetti Paolo
Published: March 2021

Background

Recent researches suggested that statins, beside their role in inhibiting endogenous cholesterol synthesis and in cardiovascular prevention, could influence several processes in cancer biology. In fact, a recent meta‐analysis demonstrated that statins could positively influence OS in lung cancer patients.

Aim

There is a lack of large cohort studies that could support a potential antineoplastic role of statins in clinical practice. We collected data from 162 patients treated with immunotherapy for Nonsmall Cell Lung Cancer (NSCLC) in first‐ and second‐line setting to investigate the impact of these drugs on survival parameters.

Methods and Results

In our observational study, we enrolled 162 patients who received immunotherapy for lung cancer between October 2015 and April 2020. We used descriptive statistics to analyze patients' baseline features. Tumor response was evaluated using RECIST version 1.1 guidelines. Uni and multivariate analysis were conducted to investigate the relationship between statin use and response to immunotherapy, using the χ2‐test. We used Kaplan‐Meier curves to estimate OS and PFS in statin and nonstatin users. We included 122 patients in the final analysis. Median PFS was 17.57 months in the statin group and 9.57 months in the nonstatin group, with a P = <.001. Moreover, median OS was superior in the statin‐users group, with a statistically significant difference (19.94 vs 10.94 months, P = <.001).

Conclusion

Although in our study, statin use positively correlates with PFS and OS in lung cancer patient treated with immunotherapy, these results require a further validation with randomized clinical trials.
High step‐up dc‐dc converter based on the differential connection of basic converters and switched‐capacitor cells
Authors: de Andrade Jessika M. , Coelho Roberto F. , Lazzarin Telles B.
Published: March 2021

This paper proposes a differential connection between the conventional boost and the mirrored SEPIC converters and the combination of them using switched‐capacitor cells. The integration results in a single stage power structure that provides high‐voltage gain and high efficiency. The article approaches a detailed static‐dynamic analysis and a comparison in relation to other structures presented in the literature. In addition, to corroborate the theoretical analysis and the operation stages of the proposed converter, a 200 W prototype, with a switching frequency at 50 kHz, an output voltage from 300 to 400 V and an input voltage of 20 V, is evaluated. An efficiency peak of 96.78% was reached at 100 W.
A hybrid two‐stage modular DC–DC converter with zero‐voltage switching
Authors: Nazih Yousef , Hossam‐Eldin Ahmed , Elserougi Ahmed
Published: March 2021

Conventional modular multilevel converters (MMCs) are widely used in high power applications due to their various astonishing advantages; however, they fail to achieve balanced capacitor voltage in DC operation. In this paper, a hybrid two‐stage modular DC–DC converter is proposed to solve the issue of unbalanced capacitor voltages. The proposed converter consists of a single‐phase half‐bridge MMC with half‐bridge submodules followed by a medium voltage valves‐based H‐bridge rectifier. The proposed converter is used in medium‐voltage applications such as feeding a DC‐load or interconnection between two DC grids of different voltage levels. The proposed configuration achieves successful DC–DC conversion with a low number of switches, a high conversion ratio with bidirectional power flow, low current stresses, soft switching across the second stage, and low switching losses. The operational concept and the control algorithm have been illustrated in detail. Finally, the effectiveness of the proposed DC–DC converter is evaluated based on simulation studies of MATLAB SIMULINK and a scaled‐down laboratory experimental test rig.
Odor identification impairment and cholinesterase inhibitor treatment in Alzheimer's disease
Authors: Motter Jeffrey N. , Liu Xinhua , Qian Min , Cohen Hannah R. , Devanand Davangere P.
Published: March 2021

Introduction

This study evaluated acute change in odor identification following atropine nasal spray challenge, and 8‐week change in odor identification ability, as a predictor of long‐term improvement in patients with mild to moderate Alzheimer's disease (AD) who received open‐label cholinesterase inhibitor treatment.

Methods

In patients with clinical AD, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Patients were then treated with donepezil for 52 weeks.

Results

In 21 study participants, acute atropine‐induced decrease in UPSIT was not associated with change in the Alzheimer's Disease Assessment Scale ‐ Cognitive Subscale (ADAS‐Cog) or Selective Reminding Test (SRT). Decline in odor identification performance from baseline to week 8 was indicative of a future decline in cognitive performance over 52 weeks.

Discussion

Change in odor identification with atropine challenge is not a useful predictor of treatment response to cholinesterase inhibitors. Short‐term change in odor identification performance needs further investigation as a potential predictor of cognitive improvement with cholinesterase inhibitor treatment.
Hypertrophic remodelling of retinal arterioles in patients with congestive heart failure
Authors: Jung Susanne , Kolwelter Julie , Bosch Agnes , Cífková Renata , Harazny Joanna M. , Ott Christian , Achenbach Stephan , Schmieder Roland E.
Published: March 2021

Aims

Analysis of microvascular parameters in the retinal circulation—known to reflect those in the systemic circulation—allows us to differentiate between eutrophic and hypertrophic remodelling of small arteries. This study aimed to examine microvascular changes in patients with congestive heart failure (CHF) and reduced as well as mid‐range ejection fraction.

Methods and results

Forty subjects with CHF underwent measurement of retinal capillary flow (RCF), wall‐to‐lumen ratio (WLR), vessel and lumen diameter, wall thickness, and wall cross‐sectional area (WCSA) of retinal arterioles of the right eye by scanning laser Doppler flowmetry (SLDF). Applying a matched pair approach, we compared this group with reference values of age‐matched controls from a random sample in the population of Pilsen, Czech Republic. There was no significant difference in RCF and WLR between the groups (RCF: P = 0.513; WLR: P = 0.106). In contrast, wall thickness and WCSA, indicators of hypertrophic remodelling, were higher in CHF subjects (WT: 15.0 ± 4.2 vs. 12.7 ± 4.2 μm, P = 0.021; WCSA: 4437.6 ± 1314.5 vs. 3615.9 ± 1567.8 μm2, P = 0.014). Similarly, vessel (109.4 ± 11.1 vs. 100.5 ± 14.4 μm, P = 0.002) and lumen diameter (79.0 ± 7.9 vs. 75.2 ± 8.5 μm, P = 0.009) were increased in CHF.

Conclusions

In CHF subjects, we observed hypertrophic remodelling of retinal arterioles indicative of similar changes of small resistance arteries in the systemic circulation. Microvascular structure and function assessed by SLDF may thereby represent a useful, non‐invasive method for monitoring of microvascular damage in patients with CHF and may offer innovative treatment targets for new CHF therapies.
Cognitive impairment as a determinant of response to management plans after heart failure admission
Authors: Huynh Quan L. , Whitmore Kristyn , Negishi Kazuaki , DePasquale Carmine G. , Hare James L. , Leung Dominic , Stanton Tony , Marwick Thomas H.
Published: March 2021

Aims

Cognitive impairment (CI) is highly prevalent in heart failure (HF), and increases patients' risks of readmission. This study sought to determine whether the presence and degree of CI could identify patients most likely to benefit from a HF disease management programme (DMP) to reduce readmissions.

Methods and results

A total of 1152 consecutive Australian patients admitted with HF (2014–2017) were prospectively followed up for 12 months. Of these, 324 patients who received DMP (1‐month duration, including post‐discharge home visits, medication reconciliation, exercise guidance and early clinical review) were matched (1:2 ratio) with 648 usual care patients. Cognitive function was assessed either on the day of or one day before discharge using the Montreal Cognitive Assessment (MoCA). Outcomes included readmission or death at 1, 3 and 12 months, and days at home within 12 months of discharge. Poorer cognitive function was associated with all adverse outcomes. Compared with usual care, DMP was associated with lower odds of 30‐day [odds ratio (OR) 0.60, 95% confidence interval 0.40, 0.91] and 90‐day (OR 0.53, 95% confidence interval 0.36, 0.77) readmission or death, and with 19 more days at home within 12 months, independent of HF therapy. The effect sizes of these associations were greater for patients with diminished cognition than those with normal cognition (interaction P = 0.036), and might have been more pronounced among those with mild CI compared with those with more severe CI (MoCA score 17–22; OR 0.42, 95% confidence interval 0.21, 0.87) at 30 days (OR 0.31, 95% confidence interval 0.16, 0.60 at 90 days). Patients with normal cognition had fewer events, irrespective of DMP.

Conclusions

Cognitive function may determine how HF patients respond to a DMP. Cognitive screening before implementation of a DMP may allow personalized plans for patients with different levels of cognitive function.
Human myeloid‐derived suppressor cell expansion during sepsis is revealed by unsupervised clustering of flow cytometric data
Authors: De Zuani Marco , Hortová‐Kohoutková Marcela , Andrejčinová Ivana , Tomášková Veronika , Šrámek Vladimír , Helán Martin , Frič Jan
Published: March 2021

Myeloid‐derived suppressor cells (MDSCs) are important regulators of immune processes during sepsis in mice. However, confirming these observations in humans has been challenging due to the lack of defined preparation protocols and phenotyping schemes for MDSC subsets. Thus, it remains unclear how MDSCs are involved in acute sepsis and whether they have a role in the long‐term complications seen in survivors. Here, we combined comprehensive flow cytometry phenotyping with unsupervised clustering using self‐organizing maps to identify the three recently defined human MDSC subsets in blood from severe sepsis patients, long‐term sepsis survivors, and age‐matched controls. We demonstrated the expansion of monocytic M‐MDSCs and polymorphonuclear PMN‐MDSCs, but not early‐stage (e)‐MDSCs during acute sepsis. High levels of PMN‐MDSCs were also present in long‐term survivors many months after discharge, suggesting a possible role in sepsis‐related complications. Altogether, by employing unsupervised clustering of flow cytometric data we have confirmed the likely involvement of human MDSC subsets in acute sepsis, and revealed their expansion in sepsis survivors at late time points. The application of this strategy in future studies and in the clinical/diagnostic context would enable rapid progress toward a full understanding of the roles of MDSC in sepsis and other inflammatory conditions.
Neurophysiological mechanisms of chiropractic spinal manipulation for spine pain
Authors: Gevers‐Montoro Carlos , Provencher Benjamin , Descarreaux Martin , Ortega de Mues Arantxa , Piché Mathieu
Published: March 2021

Together, neck pain and back pain are the first cause of disability worldwide, accounting for more than 10% of the total years lived with disability. In this context, chiropractic care provides a safe and effective option for the management of a large proportion of these patients. Chiropractic is a healthcare profession mainly focused on the spine and the treatment of spinal disorders, including spine pain. Basic studies have examined the influence of chiropractic spinal manipulation (SM) on a variety of peripheral, spinal and supraspinal mechanisms involved in spine pain. While spinal cord mechanisms of pain inhibition contribute at least partly to the pain‐relieving effects of chiropractic treatments, the evidence is weaker regarding peripheral and supraspinal mechanisms, which are important components of acute and chronic pain. This narrative review highlights the most relevant mechanisms of pain relief by SM and provides a perspective for future research on SM and spine pain, including the validation of placebo interventions that control for placebo effects and other non‐specific effects that may be induced by SM.

Significance

Spinal manipulation inhibits back and neck pain partly through spinal segmental mechanisms and potentially through peripheral mechanisms regulating inflammatory responses. Other mechanisms remain to be clarified. Controls and placebo interventions need to be improved in order to clarify the contribution of specific and non‐specific effects to pain relief by spinal manipulative therapy.
Ammonia separation from wastewater using bipolar membrane electrodialysis
Authors: Mohammadi Mariam , Guo Hui , Yuan Pengyi , Pavlovic Vladimir , Barber John , Kim Younggy
Published: March 2021

Nitrogen pollution is a serious environmental challenge in natural water and thus selective ammonia separation in wastewater treatment is of great importance to decrease the nitrogen load to natural water systems. Bipolar membrane electrodialysis (BMED) is a relatively new ion exchange membrane technology that can be used for ammonia recovery from wastewater as a beneficial substance. A bench‐scale BMED stack with seven pairs of bipolar membrane (BPM) and a cation exchange membrane (CEM) was operated under various voltage applications to separate ammonia from dewatering centrate (liquid downstream from dewatering of anaerobically digested wastewater sludge). Ammonia in the wastewater was rapidly separated (up to 87% in 30 min) and recovered as ammonium hydroxide solution using the BMED stack. We found that the maximum rate of ammonium separation was governed by the concentration polarization near CEMs rather than water transport into BPMs. In addition, even with the significantly high organic level in dewatering centrate (408 mg/L as total suspended solids), high efficient ammonia separation was maintained over 8 repeated BMED operations without any pretreatment of the feed wastewater, indicating effective organic fouling control with regular chemical cleaning. Furthermore, BMED operation for 30 minutes at 5.0 V per cell pair was found to be ideal for high purity ammonium hydroxide production and low electrical energy consumption. Based on the high separation efficiency and low energy consumption, we suggest that BMED be further investigated as an attractive option for ammonia separation and recovery from wastewater.
Association between apathy and satisfaction with meaningful activities in older adults with mild cognitive impairment: A population‐based cross‐sectional study
Authors: Maruta Michio , Makizako Hyuma , Ikeda Yuriko , Miyata Hironori , Nakamura Atsushi , Han Gwanghee , Shimokihara Suguru , Tokuda Keiichiro , Kubozono Takuro , Ohishi Mitsuru , Tabira Takayuki
Published: March 2021

Objectives

This cross‐sectional study aimed to clarify the relationship between apathy, meaningful activities, and satisfaction with such activities of older adults with mild cognitive impairment (MCI).

Methods

We analyzed 235 older adults with MCI (≥65 years, mean age: 76.9 ± 6.4 years, women: 63.4%) who participated in a community‐based health check survey (Tarumizu Study 2018). MCI was defined as at least 1.5 SD below the reference threshold (age‐ and education‐adjusted score) on one or more of the computerized cognitive test including memory, attention, executive functions, and processing speed. Apathy symptoms were assessed using three of the 15 items of Geriatric Depression Scale. Participants selected meaningful activities from the 95 activities of the Aid for Decision‐Making in Occupation Choice and evaluated their satisfaction and performance.

Results

Apathy in MCI was prevalent by 23.8%. The categories of meaningful activities revealed no difference, with, or without apathy. Logistic regression analysis showed that activity satisfaction was significantly associated with apathy after adjusting for age, sex, education, instrumental activities of daily living, depressive symptoms, and MCI subtype (OR, 0.62; 95% CI, 0.44–0.88, p = 0.008).

Conclusions

Satisfaction with the activities that are deemed meaningful is associated with apathy among community‐dwelling older adults with MCI.
The Exosome‐Associated Tetraspanin CD63 Contributes to the Efficient Assembly and Infectivity of the Hepatitis B Virus
Authors: Ninomiya Masashi , Inoue Jun , Krueger Eugene W. , Chen Jing , Cao Hong , Masamune Atsushi , McNiven Mark A.
Published: March 2021

Currently, the hepatocellular trafficking pathways that are used by the hepatitis B virus (HBV) during viral infection and shedding are poorly defined. It is known that the HBV uses late endosomal and multivesicular body (MVB) compartments for assembly and release. The intraluminal vesicles (ILVs) generated within MVBs have also been implicated in the late synthesis stages of a variety of pathogenic viruses. We recently observed that the HBV within infected hepatocytes appears to associate with the tetraspanin protein CD63, known to be a prominent and essential component of ILVs. Immunofluorescence microscopy of HBV‐expressing cells showed that CD63 colocalized with HBV proteins (large hepatitis B surface antigens [LHBs] and hepatitis B core) and labeled an exceptionally large number of secreted extracellular vesicles of uniform size. Small interfering RNA (siRNA)–mediated depletion of CD63 induced a substantial accumulation of intracellular LHBs protein but did not alter the levels of either intracellular or extracellular HBV DNA, nor pregenomic RNA. Consistent with these findings, we found that markedly less LHBs protein was associated with the released HBV particles from CD63 siRNA‐treated cells. Importantly, the HBV viral particles that were shed from CD63‐depleted cells were substantially less infective than those collected from control cells with normal CD63 levels. Conclusion: These findings implicate the tetraspanin protein CD63 as a marker and an important component in the formation and release of infectious HBV particles.
Advances of polymer binders for silicon‐based anodes in high energy density lithium‐ion batteries
Authors: Zhao Yu‐Ming , Yue Feng‐Shu , Li Shi‐Cheng , Zhang Yu , Tian Zhong‐Rong , Xu Quan , Xin Sen , Guo Yu‐Guo
Published: March 2021

Conventional lithium‐ion batteries (LIBs) with graphite anodes are approaching their theoretical limitations in energy density. Replacing the conventional graphite anodes with high‐capacity Si‐based anodes represents one of the most promising strategies to greatly boost the energy density of LIBs. However, the inherent huge volume expansion of Si‐based materials after lithiation and the resulting series of intractable problems, such as unstable solid electrolyte interphase layer, cracking of electrode, and especially the rapid capacity degradation of cells, severely restrict the practical application of Si‐based anodes. Over the past decade, numerous reports have demonstrated that polymer binders play a critical role in alleviating the volume expansion and maintaining the integrity and stable cycling of Si‐based anodes. In this review, the state‐of‐the‐art designing of polymer binders for Si‐based anodes have been systematically summarized based on their structures, including the linear, branched, crosslinked, and conjugated conductive polymer binders. Especially, the comprehensive designing of multifunctional polymer binders, by a combination of multiple structures, interactions, crosslinking chemistries, ionic or electronic conductivities, soft and hard segments, and so forth, would be promising to promote the practical application of Si‐based anodes. Finally, a perspective on the rational design of practical polymer binders for the large‐scale application of Si‐based anodes is presented.

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